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Ethical and

Policy Issues 

in International

Research:

Clinical Trials 

in Developing

Countries

VOLUME II

COMMISSIONED

PAPERS AND 

STAFF ANALYSIS

Bethesda, Maryland

May 2001
The National Bioethics Advisory Commission (NBAC) was established by Executive Order 12975,

signed by President Clinton on October 3, 1995. NBAC’s functions are defined as follows: 

a) NBAC shall provide advice and make recommendations to the National Science and Technology

Council and to other appropriate government entities regarding the following matters: 

1) the appropriateness of departmental, agency, or other governmental programs, policies,

assignments, missions, guidelines, and regulations as they relate to bioethical issues arising

from research on human biology and behavior; and

2) applications, including the clinical applications, of that research.

b) NBAC shall identify broad principles to govern the ethical conduct of research, citing specific

projects only as illustrations for such principles. 

c) NBAC shall not be responsible for the review and approval of specific projects. 

d) In addition to responding to requests for advice and recommendations from the National Science

and Technology Council, NBAC also may accept suggestions of issues for consideration from

both the Congress and the public. NBAC also may identify other bioethical issues for the

purpose of providing advice and recommendations, subject to the approval of the National

Science and Technology Council.

National Bioethics Advisory Commission

6705 Rockledge Drive, Suite 700, Bethesda, Maryland 20892-7979

Telephone: 301-402-4242 • Fax: 301-480-6900 • Website: www.bioethics.gov

Cover photo, top right, courtesy of James V. Lavery
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Ethical and

Policy Issues 

in International

Research:

Clinical Trials 

in Developing

Countries

VOLUME II

COMMISSIONED

PAPERS AND 

STAFF ANALYSIS

Bethesda, Maryland

May 2001

ISBN 1-931022-14-3
Patricia Backlar

Research Associate Professor of Bioethics

Department of Philosophy

Portland State University

Assistant Director

Center for Ethics in Health Care

Oregon Health Sciences University

Portland, Oregon

Arturo Brito, M.D.

Assistant Professor of Clinical Pediatrics

University of Miami School of Medicine

Miami, Florida

Alexander Morgan Capron, LL.B.

Henry W. Bruce Professor of Law

University Professor of Law and Medicine

Co-Director, Pacific Center for Health Policy and Ethics

University of Southern California

Los Angeles, California

Eric J. Cassell, M.D., M.A.C.P.

Clinical Professor of Public Health

Weill Medical College of Cornell University

New York, New York

R. Alta Charo, J.D.

Professor of Law and Medical Ethics

Schools of Law and Medicine

The University of Wisconsin

Madison, Wisconsin

James F. Childress, Ph.D.

Kyle Professor of Religious Studies

Professor of Medical Education

Director, Institute for Practical Ethics

Department of Religious Studies

The University of Virginia

Charlottesville, Virginia

David R. Cox, M.D., Ph.D.

Scientific Director

Perlegen Sciences

Santa Clara, California

Rhetaugh Graves Dumas, Ph.D., R.N.

Vice Provost Emerita, Dean Emerita, and 

Lucille Cole Professor of Nursing

The University of Michigan

Ann Arbor, Michigan

Laurie M. Flynn

Senior Research and Policy Associate

Department of Child and Adolescent Psychiatry

Columbia University

New York, New York

Carol W. Greider, Ph.D.

Professor of Molecular Biology and Genetics

Department of Molecular Biology and Genetics

The Johns Hopkins University School of Medicine

Baltimore, Maryland 

Steven H. Holtzman

Chief Business Officer

Millennium Pharmaceuticals Inc.

Cambridge, Massachusetts

Bette O. Kramer

Founding President

Richmond Bioethics Consortium

Richmond, Virginia

Bernard Lo, M.D.

Director

Program in Medical Ethics

Professor of Medicine

The University of California, San Francisco

San Francisco, California

Lawrence H. Miike, M.D., J.D.

Kaneohe, Hawaii

Thomas H. Murray, Ph.D.

President

The Hastings Center

Garrison, New York

William C. Oldaker, LL.B.

Senior Partner

Oldaker and Harris, L.L.P.

Washington, D.C.

Co-Founder and General Counsel

NeuralStem Biopharmaceuticals Ltd.

College Park, Maryland

Diane Scott-Jones, Ph.D.

Professor

Psychology Department

Boston College

Chestnut Hill, Massachusetts

National Bioethics Advisory Commission

Harold T. Shapiro, Ph.D., Chair

President

Princeton University

Princeton, New Jersey
v

CONTENTS

The Challenge of Equivalent Protection............................................................. A-1

Bernard M. Dickens

University of Toronto

Attitudes and Experiences of U.S. and Developing Country Investigators

Regarding U.S. Human Subjects Regulations ..................................................... B-1

Nancy Kass and Adnan A. Hyder

Johns Hopkins University

The Relevance of Culture for Informed Consent in 

U.S.-Funded International Health Research........................................................C-1

Patricia A. Marshall

Loyola University Chicago

Comparative Analysis of International Documents Addressing 

the Protection of Research Participants...............................................................D-1

Staff Analysis

National Bioethics Advisory Commission

International Perspectives on Protecting Human Research Subjects ................. E-1

Jeremy Sugarman, Benjamin Popkin, Judith Fortney, and Roberto Rivera

Duke University
A-1

THE CHALLENGE OF

EQUIVALENT PROTECTION

Commissioned Paper

Bernard M. Dickens

University of Toronto
A-3

1. Introduction

Title 45 of the Code of Federal Regulations Part 46 (45 CFR § 46) addresses the protection of human 

subjects of biomedical and behavioral research, including “research conducted, supported, or otherwise

subject to regulation by the Federal Government outside the United States” § (46.101(a)). Part 46 regulates

the process of review of research proposals through Institutional Review Boards (IRBs) and substantive rules

required to be observed on such general matters as informed consent and such special matters as research

involving prisoners, children, and pregnant women. Part 46.101 provides in paragraph (g) that the policy 

on protection of human subjects “does not affect any foreign laws or regulations which may otherwise be

applicable and which provide additional protections to human subjects of research.”

§ 46.101(h) provides that:

[w]hen research covered by this policy takes place in foreign countries, procedures normally

followed in the foreign countries may differ from those set forth in this policy. [An example is

a foreign institution which complies with guidelines consistent with the World Medical

Assembly (sic) Declaration (Declaration of Helsinki amended 19891

) issued either by sovereign

states or by an organization whose function for the protection of human research subjects is

internationally recognized.] In these circumstances, if a Department or Agency head determines

that the procedures prescribed by the institution afford protections that are at least equivalent

to those provided in this policy, the Department or Agency head may approve the substitution

of the foreign procedures in lieu of the procedural requirements provided in this policy....

This intention to accommodate studies the policy covers that are conducted in a foreign country therefore

depends on a determination that “the procedures prescribed by the institution” afford human subjects at least

equivalent protections to those provided in the policy.

The reference to “procedures” repeats the policy’s recognition that “procedures normally followed” in foreign

countries “may differ from those set forth in this policy.” This raises the issue of whether equivalent protection

is focused only on matters of institutional review procedures, where the equivalent structure and functioning of

an IRB are required, or whether equivalence must extend beyond the process of review to include the substance

of the proposal to be reviewed, including, for instance, subjects’ informed and voluntary consent and appropriate

acquisition and research use of fetal tissues.

The example provided suggests the latter. The Declaration of Helsinki is established and periodically 

revised by the World Medical Association (WMA), described in the policy as the World Medical Assembly, 

perhaps confused with the World Health Organization’s governing body, the World Health Assembly. Most

recently revised in 1996, the Declaration of Helsinki is modestly entitled only as “Recommendations guiding

physicians...” and, in contrast to the WMA Declaration of Geneva, which “binds physicians,” provides in its

Introduction that “[i]t must be stressed that the standards as drafted are only a guide to physicians all over the

world,” and that physicians “are not relieved from criminal, civil and ethical responsibilities under the law of

their own countries.”

The procedural content of the Declaration of Helsinki is rudimentary. In its Basic Principles, Article 1.2

requires that a research protocol: 

should be transmitted for consideration, comment and guidance to a specially appointed 

committee independent of the investigator and the sponsor provided that this independent

committee is in conformity with the laws and regulations of the country in which the research

experiment is performed.
A-4

Departmental and Agency heads responsible for determining equivalent protection must therefore look beyond

the claim of a foreign institution that its review procedure conforms to the Declaration of Helsinki. Compliance

with the Declaration’s guiding recommendations and an accordingly constituted independent review committee’s

comments and guidance may be satisfied by procedures falling far short of the composition and standards of

operation expected of IRBs bound by the policy in the Federal Regulations.

The contrast may be mitigated to some degree by the substantive provisions of the Declaration of Helsinki.

These address conformity with generally accepted scientific principles, the requirement of prior animal studies,

qualifications and supervision of research personnel, prior risk-to-benefit assessment, subjects’ voluntary and

adequately informed consent, protection of vulnerable subjects and, for instance, preservation of privacy and

confidentiality. Since the policy illustrates equivalent protection through “the procedures prescribed by the

institution” by reference to the Declaration of Helsinki, whose procedural provisions are undeveloped, the 

conclusion may be drawn that equivalence addresses substantive principles of ethical conduct of research with

human subjects, and not only the process of the review itself.

Considerably closer to the Federal Regulations is review under the drug industry’s International Conference

on Harmonization (ICH) Guideline for Good Clinical Practice, operative since January 1997. The objective of

the Guideline is to provide a common standard for the European Union, Japan, and the United States to

facilitate the mutual acceptance of clinical trial data by regulatory authorities. The Guideline was developed

with consideration of additional countries including Australia, Canada, and the Nordic countries. Its provisions

closely reflect those of the Federal Regulations, and points of departure are so relatively minor that requirements

of equivalent protection may easily appear to be satisfied.

The introduction to the Declaration of Helsinki and its Basic Principles cited above both make explicit 

reference to the obligation to obey research host countries’ laws. The Federal Regulations are similarly subject

to legislative provisions and judicial and quasi-judicial interpretation in the United States. It is therefore 

relevant in an approach to equivalence briefly to consider as a model the body of countries’ domestic laws 

that governs matters materially affected by the laws of foreign jurisdictions, called Conflict of Laws or Private

International Law.

2. The Legal Model

The modern preoccupation with globalization, particularly in the field of commercial interaction and enterprise,

has deeply historical roots. The historic law of commerce, the lex mercatoria, in England also known as the Law

Merchant, was a code of rules covering foreign trade and traders that was declared to be of universal application.

It constituted an international trade law similarly applied in mercantile courts throughout medieval Europe,

and its concept has survived to modern times.2 Similarly, commonly observed maritime customs were founded

on Byzantine principles that were well established by the twelfth century and quite uniformly applied by 

maritime courts of the north and east Mediterranean and North Atlantic coasts. In England, the Law Merchant

was absorbed into the Common law during the seventeenth and eighteenth centuries, adding to Anglo-Saxon

customary law, the Common law, an enduring capacity to resolve within its own doctrines on conflict of laws

disputes involving alien and internationally recognized legal principles.

An initial issue is the respect given to judgments of other countries’ courts of law. A key approach is acceptance of the propriety of other countries’ legal procedures, such as the Continental inquisitorial trial process,

which differs from the Common law’s adversarial process. Similarly, when, for instance, English law made 10 or

more years’ practice at the Bar a precondition to judicial appointment, and 5 or more years’ experience on the

High Court bench a legal condition of elevation to appellate courts, judgments of Continental courts were 

recognized whose judges, immediately on graduation from schools of law, had directly entered the judicial
A-5

branch rather than the practicing or administrative branch of the legal profession. Countries do not enforce

other countries’ criminal or tax laws, but widely recognize foreign marriage laws. When, for instance, English

law required parental consent for the marriage of adolescent girls, Scottish law did not. Accordingly, elopements

of legal minors for marriage in Scotland were common, particularly to the first village on the main road

crossing the border, Gretna Green. However, only marriage in monogamous form is recognized, excluding 

matrimonial relief in marriages celebrated in polygamous form even when no second or later spouse exists.

Although U.S. states are constitutionally required to give other states’ legal processes full faith and credit,3 such

as the liberal laws in Nevada on marriage and divorce, a current challenge is recognition of same-sex marriages

legally recognized in Hawaii.

When another jurisdiction’s laws involve issues of judicial procedure, they may not only prevail but be 

unreviewable in another jurisdiction’s courts, except on human rights grounds; but rulings on matters of substance, such as polygamous marriage, are reviewable and may not prevail. Whether an issue is of procedure or

substance is a matter of classification according to each jurisdiction’s own domestic law. Jurisdictions usually

attempt to accommodate and apply others’ substantive rules. For instance, Common law jurisdictions divide

property into real property and personal property. Land itself is real property (“real estate”), but a lease over

land is personal property (“personalty”). Continental Civil law derived from Roman law divides property into

movable and immovable property, the latter including real estate and leasehold interests in land. When, for

instance, a Common law court is administering an estate including interests in foreign land, it applies the law

of the jurisdiction where the land involved is situated, treating leasehold interests according to the foreign 

law on immovable property rather than its own domestic law on personal property.

Countries are more easily disposed to accept substantive rules of other countries that are culturally and/or

religiously compatible. Hence, Gretna Green marriages are acceptable in England, but foreign marriages

monogamous in fact but celebrated in polygamous form are not. Difficulties concern recognition of divorces,

for instance, in Islamic (“tallack”) and Jewish (“get”) religious form where they are claimed as allowing subsequent nonbigamous marriages in Common law jurisdictions.

Some principles are considered of universal application, binding among all nations (“erga omnes”) that no

jurisdiction can violate, tolerate to be violated elsewhere, or agree with another state to allow to be violated.

One is that forced or otherwise involuntary marriage is not recognized. Another is that, since persons cannot

profit from their own wrongs, a person acquitted of murder in his own country because of the defense of

“honor” that excuses killing, for instance, an adulterous wife or a fornicating sister or daughter, cannot inherit

the victim’s assets located in a country that does not allow this defense.

3. The Model Applied to Research Ethical Review Procedures

The legal distinction between matters of process and of substance may be applied to determinations of 

equivalence in protection of human subjects of research. The policy under Federal Regulations may be satisfied

where a country’s equivalent of an IRB does not satisfy the criteria of membership or function laid out in 

45 CFR § 46.107 and § 46.108 respectively, provided that the substantive rules of subject protection are applicable. For instance, in countries with few experts in a particular area, some of whom are principal investigators,

no review committee may be capable of constitution whose member with relevant expertise does not have a

conflict of interest. Other members may want not only that person’s information, permissible to be given under 

§ 46.107(e), but also that person’s advice and judgment on whether the proposal is scientifically sound and

appropriate according to the state of development of the field. Accordingly, it may be acceptable that the

response to the conflict of interest be not the person’s exclusion from the review process, as required by 

§ 46.107(e), but due disclosure of the conflict. Similarly, in countries where it is considered unseemly for
A-6

women to discuss intimate matters of sex with men, the requirement in § 46.107(b) that both sexes be represented on a review committee may not be observed where such matters are in issue; women’s interests may be

communicated indirectly if, as is likely, there is an all-male review committee.

The policy itself refers to compliance with the Declaration of Helsinki as an alternative that a Department or

Agency head may determine to afford equivalent protections to those of the policy. However, the Declaration

does not require that procedures be written in the detail described in § 46.103(b)(4) and (5), and a particular

country’s laws or regulations may be similarly undemanding. As a recipient of U.S. funds, the institution will be

accountable for the means by which ethics review committees are composed and function, but the secretarial

support that underpins domestic IRBs may not exist.

A transcending concern, not confined to resource-poor countries, is that the prospect of receiving U.S. 

funding of research may be so enticing to academic and health care institutions that risks of physical injury or

discomfort, cultural offensiveness, and emotional insults to which prospective subjects may be exposed will be

undervalued by investigators and members of ethical review committees. Members who have no conflict of

interest in the classical sense of motives of personal enrichment or comparable self-interest may be inspired by

a conviction that pursuit of the investigation will enhance the well-being of populations for which they care,

the prestige of their institutions, and the careers of investigators in whom their institutions and countries have

made significant investments. Similarly, their optimism that a study will be highly advantageous may distort

their risk-to-benefit assessment.

The policy requires, in § 46.107(d), that each review committee “shall include at least one member who is

not otherwise affiliated with the institution and who is not part of the immediate family of a person who is

affiliated with the institution.” In stratified or racially or otherwise divided societies, independent-minded 

representative community members may be difficult for the institutions to identify. Community members they

attract may be inclined to be deferential in the presence of members of institutionally affiliated elites, who, 

in accordance with the policy itself, may outnumber them four to one. Nonaffiliated peers of institutional

members may serve in political, governmental, or similar social leadership roles and share other committee

members’ hopes for institutional advancement through U.S.-funded research.

Accordingly, it may be an act of faith for a Department or Agency head to determine that institutional 

procedures in some foreign countries “afford protections that are at least equivalent to those provided in this

policy,” as required by § 46.101(h). Unless particular proposals are also reviewed by IRBs in the United States,

confidence may have to be placed in foreign institutions’ conformity with substantive rules of ethical conduct

for protection of human subjects of research.

Unless U.S. funding agencies are prepared to undertake on-site inspection of foreign ethics review committees that have not already received a form of U.S. accreditation, some degree of uncertainty of equivalent 

protection appears inescapable. An approach may be for funding agencies to classify degrees of risk that studies

appear to present, separating risks to life or enduring health at one end of a spectrum from risks of cultural

insensitivity at the other, and apply a higher level of scrutiny to how well host institutions review studies 

classified to present graver risks than to studies of intermediate- or low-level risk.

4. Substantive Rules of Ethical Research

A concern that has erupted particularly since 1997 in the United States 4 and elsewhere regarding U.S.-funded

placebo-controlled studies has been their conduct in poor countries where sick subjects who are offered investigational products have no practical access to alternative therapeutic products that are available to treat their

conditions in more favored countries. An ethical requirement is that sick persons offered an investigational

product should have the option of access to alternative treatment available for the condition that appears to

affect them. The Declaration of Helsinki provides in Article II(3) that:
A-7

[i]n any medical study, every patient—including those of a control group, if any—should be

assured of the best proven diagnostic and therapeutic method. This does not exclude the use

of inert placebo in studies where no proven diagnostic or therapeutic method exists. 

The second sentence was added in the 1996 revision of the Declaration, for fear that the first sentence taken

alone would be understood to proscribe all placebo controls.

The ethical question nevertheless remains, of whether “the best proven...method” means the best that medical

science has to offer anywhere, or the best available to patients in their circumstances outside the study they 

are invited to join. It has been claimed to be exploitive of potential subjects’ deprivation that they be offered

randomization between treatment with an investigational product and with a placebo on the rationalization

that, in their circumstances outside the study, “no proven diagnostic or therapeutic product exists,” although a

product does exist in more favored circumstances. Critics claim that investigators are ethically obliged to afford

such subjects alternative access to “the best proven...method” that medical science has available. The fear is

that unproven products will be tested among disadvantaged and deprived populations, because their members’

randomization into the placebo arm of a study would not deprive them of any treatments they would 

otherwise have.

The claim that studies of investigational products in disadvantaged populations must provide subjects with

alternative access to best treatment medical science can offer may be based on a more vigorous ethical doctrine

than the Declaration of Helsinki itself provides. The Declaration may present an inadequate basis on which to

distinguish right from wrong conduct, not only because its distinction between therapeutic and nontherapeutic

research has been condemned as illogical and in need of revision,5 but also because the Declaration itself is 

presented only as recommendations guiding physicians. Nevertheless, the ethics of studies proposed among

deprived populations of less economically developed countries legitimately pose critical issues. They include

whether investigators in U.S.-funded studies abroad may behave in ways that investigators in the United States

may not, and whether the deprived populations enjoy “protections that are at least equivalent to those provided

in this policy,” as prescribed in § 46.101(h). The background fear is a breach of distributive justice, since 

products that disadvantaged populations bear the burden of testing are likely to be marketed in affluent 

countries and be unavailable to populations of poor countries that served as testing sites.

Developed countries themselves have subpopulations that are deprived of an adequate standard of diagnostic

and therapeutic care and can avail themselves only of care that falls far below “the best proven...method,” not

least in the United States. Studies that propose to target such subpopulations for placebo-controlled studies on

the basis that, for them, “no proven diagnostic or therapeutic method exists,” might have considerable difficulty

gaining IRBs’ acceptance as ethical. This poses the question whether studies of this nature proposed to be conducted in foreign countries can be measured by different standards that achieve subjects’ equivalent protection.

The better view appears to be that best proven methods are to be assessed by reference to local circumstances in a country as the baseline, rather than some objective, location-neutral standard of optimal care. As

Robert J. Levine has explained,6 resource-poor countries need studies that compare and contrast new investigational products with their usual standard of care, which may be nontreatment, rather than with an optimal

standard they cannot achieve or maintain. Conducting studies to contrast an investigational treatment with the

best standard in a resource-poor country would violate the principle of distributive justice, since research subjects in the host country would have few if any means to avail themselves of the treatment their risk-taking has

shown to be preferable. The beneficiaries would be patients in more affluent settings of developed countries,

which should therefore be the sites of studies testing unproven treatments against the optimum care available.

Accordingly, the “best method” may be taken to focus on what is best in the circumstances of a foreign country.

Local medical and related health care providers will be able to identify prevailing best care, and a local committee

can best accomplish the required striking of the risk-to-benefit balance in deciding whether to host a proposed

study of an investigational product.
A-8

For greater certainty, ethics review committees in host countries may be required to give more than passive

approval to studies proposed for U.S. funding and be required actively to explain, perhaps through committee

chairs, the benefits for their own communities they find to justify approval of individual proposals. That is,

Department or Agency head approval of the foreign procedure might be made conditional on receipt of satisfactory identification of the advantages the local committee finds for the domestic health care system.

5. Risk-to-Benefit Assessment

The Declaration of Helsinki acknowledges in the fourth paragraph of its Introduction that:

[i]n current medical practice most diagnostic, therapeutic or prophylactic procedures involve

hazards. This applies especially to biomedical research.

In its Basic Principles, the Declaration provides in paragraph I.5 that:

[e]very biomedical research project involving human subjects should be preceded by careful

assessment of predictable risks in comparison with foreseeable benefits to the subject or to

others. Concern for the interests of the subject must always prevail over the interests of science

and society.

Determinations of risk and of benefit, and of the excess of one over the other, can focus on various aspects of

each. Medical research is usually directed to medical advance and tends to be assessed by clinical indicators,

including a patient’s better preventive care, diagnosis, therapy, post-operative or post-intervention recuperation

and post-traumatic recovery. Similarly, risk tends to be judged clinically in medical terms, such as of death or

injury from known side-effects of medical interventions, or, for instance, of unanticipated idiosyncratic reactions

due to genetic, pharmacological, environmental, or other causes. Both risk and benefit may also be determined,

however, by reference to public health or epidemiological measures, such as reduced prevalence of infection in

a community or higher or lower mortality or morbidity or change in life expectancy. Criteria not directly

related to medical outcomes may also weigh in the balance between risk and benefit, such as quality of life

considerations, including individual capacity to discharge the functions of everyday life and to pursue particular

interests or goals. Qualitative research methodologies have come to be employed for some of these assessments.

Which benefits members of a population or community consider most material to their interests to pursue

and which risks most important to minimize or avoid may be most reliably determined by members themselves,

or by those closely familiar with their values and perceptions of need. Whether a proposed study concerns

interests that intended subjects consider at an intimate, personal level, at a family level, or at a communal

wider level, and which benefits may be pursued at what costs, and which values must be preserved by sacrifice

of others are to be determined by local assessment. Local authorities can determine, for instance, whether or

how well a proposed study serves local health care priorities and whether its conduct would impose acceptable

burdens on local resources of facilities, personnel, and, for instance, medications. Accordingly, a Department or

Agency head may approve “the substitution of the foreign procedures in lieu of the procedural requirements”

provided in the Federal Regulations where satisfied that assessments of benefits and risks can be made with

equivalent protection of intended subjects at the relevant country or local level.

This is subject to compliance with transcending minimum or core protective values, on analogy with the

legal perception that some principles are so fundamental that they are binding among all (“erga omines”).

Central among these is the principle that each individual proposed to be at personal risk in a study should be

able to give, or effectively deny, consent. The historic Nuremberg Code of 1947, which the 1964 Declaration of

Helsinki was developed to amplify and explicate outside the Code’s conditioning environment of outrageous

crimes against humanity, states as its first principle that: 

The voluntary consent of the human subject is absolutely essential.
A-9

The Code goes on to elaborate the principle by explaining that:

[t]his means that the person involved should have legal capacity to give consent; should be so

situated as to be able to exercise free power of choice, without the intervention of any element

of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion;

and should have sufficient knowledge and comprehension of the elements of the subject matter

involved as to enable him to make an understanding and enlightened decision.

The Code makes no mention of elements that are also considered critical to the ethical planning and conduct of research with human subjects, such as independent ethical review and, for instance, due preservation

of confidentiality and disclosure of its limits. The Declaration of Helsinki considerably advances the detail of

ethical conduct in research. Further, it addresses research with subjects incapable of making their own decisions or consent, reflecting the recognition that research extends beyond the exploitive sacrifice of vulnerable

subjects that framed the Nuremberg Code, to include research, such as with mentally disabled people and with

infants and children, that it is ethical to undertake and may be unethically discriminatory to deny.

A Department or Agency head may act under § 46.101(h) to approve review procedures for research conducted in foreign countries as providing equivalent protection of human subjects to that under the policy of

the Federal Regulations when satisfied that, however local considerations of benefit and risk are determined

and prioritized, basic requirements of subjects’ protection will be observed.

Issues of intercultural and international dissonance will arise that will have to be satisfactorily resolved in

the United States for funding of foreign studies. For instance, the appropriateness of placebo-controlled studies

abroad that would not easily be acceptable in the United States has already been raised. Similarly in some 

foreign settings, where studies, for instance, into women’s health are proposed, husbands may expect to decide

on their wives’ participation and perhaps to be able to bar their wives’ entry, when their wives may want to join

the studies in order to advance their health and self-determination. The prospect of local controversy over studies

the United States is prepared to fund abroad, and perhaps encourage, exposes the limits of the equivalent 

protection language of § 46.101. The focus on protection of human subjects, rather than on promotion of

health research that presumably motivates U.S. funding, reflects the origin of modern regulation of research

with human subjects. This lies in the Nuremberg Tribunal’s trials of “the Nazi doctors,” Henry Beecher’s 1966

exposure of research abuse in the United States, M.H. Pappworth’s 1968 publication on several countries’

mistreatment of “Human Guinea Pigs” and, for instance, revelation in the early 1970s of decades-long abuses 

in the Tuskegee Syphilis Study. Part 46 of the CFR is entitled “Protection of Human Subjects” because of the

emphasis on protection, and in the context of potential abuse, protection is best achieved through potential

subjects’ nonparticipation.

In recent years, however, the perception has revived that medical research that may endanger individual

subjects has the overall goal of advancing understanding and innovation in order to protect health and that sick

patients’ health cannot be advanced without the funding and appropriate conduct of medical research. That is,

medical research itself serves the goal of protection of health, and its undue denial, prevention, or obstruction

may prejudice health. This explains why promotion of research, for instance, into women’s health, and containment of HIV infection, is encouraged by U.S. funding.

The protection of human subjects is therefore less a goal in itself than a necessary means or condition of

promoting medical research designed to protect the long-term health of populations, some of whose members

will be invited to take the risks of becoming its short-term subjects. This is the basis on which Federal

Regulations have been amended in recent years, not to relax protections of individual subjects, but to facilitate

research on care, for instance, of patients with early childhood diseases and traumatic head injuries. The

requirement that research that takes place in foreign countries be conducted under equivalent protection to
A-10

that provided by IRBs is intended to promote ethical research, rather than to limit opportunities for research,

provided that it be conducted consistently with “any foreign laws or regulations which may otherwise be 

applicable.”7

The voluntary assumption of individual risk and the conscientious imposition of communal risk are the

conditions of advancing communal health through medical research. As suggested above, an approach may be

for Department and Agency heads to be required to classify risk levels in particular proposals for funding, to

require local ethics review committees to articulate the grounds of local benefit on which they have found 

proposals acceptable, and to maintain stricter scrutiny of grounds for local acceptance of studies that are 

classified as presenting higher levels of risk.

6. Foreign Research Protections Compromised by U.S. Requirements

The conventional concern to ensure equivalent protection of human subjects of research conducted abroad 

has been apprehension that their well-being may not be as securely protected as are the interests of subjects 

of research governed by the Federal Regulations. The U.S. Regulations have been shaped in response to 

experiences, perceptions, and accountabilities concerning persons vulnerable to research-related risks to which

governments abroad have not always been equally responsive. The Regulations also reflect U.S. sensitivity to

the distributive injustice that medical studies sponsored abroad by U.S. Federal Departments and Agencies may

achieve benefits for U.S. patients that populations abroad enjoy only disproportionately to the greater risks they

accepted. The criticism is that “[a]s is so often the case, the results will probably find their greatest application

in the developed world.”8

However, recent political developments have created the possibility that foreign populations may find that

pursuit of their interests under their local laws and regulations is compromised by provisions that originate in

the United States. In 1974, the U.S. Agency for International Development (USAID) initiated a policy that 

prohibits U.S. funding for “information, education, training or communication programs that seek to promote

abortion as a method of family planning.”9 Between 1984 and 1993, this prohibition was interpreted to cover

all abortion except in cases of rape, incest, and danger to a woman’s life. Late in 1999, omnibus appropriations

legislation enacted to release funds toward payment of U.S. arrears to the United Nations had an attached prohibition of U.S. family planning funding of foreign nongovernmental organizations (NGOs) if, even with their

own funds, they perform abortions, except in cases of forcible rape, incest, or danger to life. Funding is also

prohibited if they engage in activities or efforts to alter the abortion laws or governmental policies of foreign

countries, including their own, although they may give counseling about abortion and refer women to other

organizations for services. In 2000, these prohibitions govern about $345 million in USAID family planning

assistance for foreign NGOs.

Where foreign NGOs seek such funds for research projects that fall under 45 CFR § 46, the question arises

whether their subjects have equivalent protection to that enjoyed by U.S. subjects. In the United States, the

capacity of NGOs to perform and fund abortions is constitutionally protected and activity and efforts to alter

laws are similarly protected, for instance, under rights of free speech, and to political participation in civil 

society and the democratic process. Further, in medical professional ethics, the Code of Medical Ethics that 

the American Medical Association adopted in 1980 provides that “[a] physician shall respect the law and also

recognize a responsibility to seek changes in those requirements which are contrary to the best interests of the

patient.”10 Physicians’ ethical and legal responsibilities of advocacy on behalf of their patients11 are an important

element of patients’ protection.

Foreign NGOs seeking to promote access to family planning services, particularly in poor countries, may

find the prospect of eligibility for U.S. funding of research programs too attractive to forgo. They are clearly

bound by prohibitions of their local law, but where this permits abortion they may accept the limits on

expenditure of their own money for abortion services, for instance, on contraceptive failures, on which 
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U.S. funding is conditioned. They may similarly forgo their lawful and democratic rights to inform their own 

governments of the health burdens women bear due to untimely pregnancies, such as those that are too closely

spaced, which access to lawful, safe abortion would relieve. They may also forgo statistical and other demonstrations of how frequently and at what cost the alternative to prohibited lawful abortion is—not childbirth,

but unskilled and self-induced unlawful abortion. In short, foreign NGOs attracted to seek U.S. funds for 

family planning research may find that they have to discontinue and forgo activities that, in the United States,

would be considered protective of research subjects who, in the course of research programs, experience

health-endangering pregnancies, including those whose continuation endangers the health of their dependent

children.

If a Department or Agency head determines that subjects of foreign NGO family planning research enjoy 

at least equivalent protection to that available for them under U.S. law, particularly when a research subject 

has a health-endangering pregnancy, the NGO may become ineligible for USAID funding. However, refusal of

such a determination will also result in ineligibility, although the inferior protection is a result of U.S. policy, 

for instance, in barring NGO funding of abortion from its own funds when the procedure is lawful and therapeutically indicated in a subject’s health interests. Department or Agency heads may, however, consider the 

prohibitive attachment to the 1999 appropriations legislation to be an enacted derogation from 45 CFR § 46.

Accordingly, such heads may determine foreign procedures to “afford protections that are at least equivalent

to those provided in this policy” under § 46.101(h), except in so far as the 1999 enactment prevents such 

protections from being offered. The Federal Regulations, authorized under the Public Health Service Act,

should be construed as subject to subsequent legislation restricting research funding capacity, even when its

effect is to compromise protections that foreign subjects of research would otherwise enjoy in their own 

countries, provided that local committees knowingly accept funding on this condition.

7. Compliance with Both U.S. and Foreign Requirements

Under § 46.101(a), the Federal policy on Protection of Human Subjects “includes research conducted, supported, or otherwise subject to regulation by the Federal Government outside the United States.” It does not

necessarily follow from compliance with the procedure under § 46.101(h) for ensuring equivalent protection of

subjects outside the United States to that available in the United States that research conducted and reviewed

outside the United States will not be liable in addition to IRB review within the United States. Where U.S. 

institutions’ personnel conduct research abroad, such as their faculty members, research staff, and students, 

the institutions’ terms of employment and student regulations may require submission of research protocols to

local IRBs. This is consistent with international requirements. For instance, the International Ethical Guidelines

for Biomedical Research Involving Human Subjects, issued in 1993 by the Council for the International

Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization, provides 

in Guideline 15, on obligations of sponsoring and host countries, that:

Externally sponsored research entails two ethical obligations:

■ An external sponsoring agency should submit the research protocol to ethical and scientific review

according to the standards of the country of the sponsoring agency, and the ethical standards applied

should be no less exacting than they would be in the case of research carried out in that country.

■ After scientific and ethical approval in the country of the sponsoring agency, the appropriate authorities 

of the host country, including a national or local ethical review committee or its equivalent, should satisfy

themselves that the proposed research meets their own ethical requirements.12
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The CIOMS Guidelines “are designed to be of use, particularly to developing countries, in defining national

policies on the ethics of biomedical research, applying ethical standards in local circumstances, and establishing

or redefining adequate mechanisms for ethical review....”13 Guideline 15 reflects the supposition of research

sponsorship by a more economically developed country, such as the United States, and a developing host

country. In 1991, the CIOMS also produced its International Guidelines for Ethical Review of Epidemiological

Studies. These contain a comparable provision on externally sponsored research to that in its 1993 Guidelines,

and include the explanation that:

[i]t is in the interest of the host country to require that proposals initiated and financed 

externally be submitted for ethical approval in the initiating country, and for endorsement 

by a responsible authority of the same country, such as a health administration, a research

council, or an academy of medicine or science.14

Advice that the host country should require study approval in the initiating country relates to the legal

model of Conflict of Laws and the principle of Renvoi. By this principle, country A respects the law of country

B and applies it to an issue involving the jurisdiction of country B, but refers not to country B’s domestic law

but to country B’s doctrine on private international law, or Conflict of Laws. By this, country B may conclude

that the governing law on the issue is the domestic law of country A. Accordingly, country A applies its own

domestic law, not in disregard of country B’s law but because that law requires country A to do so. Whether 

a judge in country A refers to the domestic law of country B or to its doctrine on Conflict of Laws may be 

governed by precedent, but where not, the judge will be influenced by parties’ advocacy and argument.

The research application of this principle arises when a foreign country, such as a developing country, has

no pharmaceutical or medical device regulatory authority or regulations of its own, but only a law providing

that, for a drug or device to be imported and used in its territory, the drug or device must satisfy the laws and

regulations of its country of origin. This will usually be a more economically and technologically developed

country. Accordingly, when a product of U.S. manufacture is proposed for research or use in the host country,

that country’s own rules require only that U.S. domestic provisions be observed, including those on the

protection of human research subjects.

This approach may be ethically unsatisfactory to U.S. authorities. The Commentary on Guideline 15 of the

1993 CIOMS guidelines notes that:

[c]ommittees in the host country have the special responsibility to determine whether the

goals of the research are responsive to the health needs and priorities of the host country.

Moreover, because of their better understanding of the culture in which the research is proposed to be carried out, they have special responsibility for assuring the equitable selection of

subjects and the acceptability of plans to obtain informed consent, to respect privacy, to maintain confidentiality, and to offer benefits that will not be considered excessive inducements to

consent.15

When host country authorities simply provide that approval of a research proposal by an IRB in the United

States, according to 45 CFR § 46, is adequate for local purposes, a Department or Agency head may determine

that local potential subjects have not been afforded at least equivalent protection to that specified in § 46,

because its criteria have not been applied to such subjects’ special circumstances by committees and personnel

with relevant knowledge. Accordingly, it may be recommended that equivalent protection cannot be determined unless an adequately composed ethics review committee in the host country has assessed and approved

a proposal.

As against this, a Department or Agency head may claim to be satisfied that the particular facts of a case

show that a study raises no special considerations of local health goals, needs or priorities, nor cultural concerns
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regarding informed and free consent, privacy, or confidentiality. Local acceptance of IRB approval according to

the substance of § 46 may therefore be proposed as appropriate, and to offer local subjects of the study not

simply equivalent but identical protection to that required in U.S. domestic policy. This assessment is more 

easily made when the foreign site of a study is culturally, economically, and otherwise comparable to the United

States. However, more immediately comparable countries, such as Australia, Canada, the United Kingdom, and

those of Western Europe, have their own regulatory rules and agencies, and their institutions would be unlikely

to be able to delegate approval of studies liable to be locally reviewed to U.S.-based IRBs, even though local

review processes and principles are similar to those under 45 CFR § 46. For drug studies, the ICH Guideline

for Good Clinical Practice goes far to unify standards of review in the European Union, Japan, the United

States, and several comparable countries.

The real issues that Department or Agency heads face arise in more exotic and less economically developed

countries where health needs and cultural traditions are unlike those of the U.S. mainstream. If there is a 

comparable community among the diverse populations of the United States through which an IRB can gain

adequate input to apply § 46 with faithful reflection of the health priorities, resources, and cultural values 

and sensitivities relevant to the foreign site, and if a relevant host country institution is able to endorse the

authenticity of IRB exposure to indigenous conditions, a Department or Agency head may consider it acceptable

to forgo specific local review. 

It may remain unclear, however, whether foreign acceptance of U.S.-based IRB approval is influenced 

primarily by the incentive of gaining U.S. research funds. It therefore appears necessary to require local review,

according to satisfactory processes and substantive principles at least as detailed as provided in the Declaration

of Helsinki or the CIOMS 1993 Guidelines. U.S. residents with special familiarity with the circumstances of

foreign countries may advise U.S.-based IRBs accordingly, but cannot be accepted to replace review conducted

in the country in which prospective research subjects live. Conditioning funding on local review appears 

ethically necessary.

8. Research Monitoring

The Achilles’ heel of much research with human subjects is monitoring investigators’ compliance with the

scientific and ethical undertakings of a protocol. When significant resources are available, investigators’ practices may be kept under credible scrutiny. Governmental agencies in the United States can make investigators

aware that they are liable to be made to account for compliance with scientific, ethical, and fiscal terms of

approval of their studies. Similarly, in significant drug, biological product, and comparable studies, sponsors

may establish independent data monitoring boards that keep studies under surveillance in order to ensure the

integrity of subject inclusion and exclusion practices, and, for instance, enforce or develop stopping rules,

marking points in data acquisition and analysis at which studies would be prematurely ended, or their inclusion,

exclusion, and informed consent criteria re-evaluated in light of evolving knowledge of safety and efficacy of

outcomes. However, unless governments fund independent review inspectorates for studies they sponsor or, for

instance, drug companies allocate an adequate proportion of the several hundreds of millions of dollars they

budget for product testing to monitoring of research practices, monitoring may be doubtful.

The purpose and very meaning of “monitoring” may be unclear. Governments may monitor because they are

accountable, often through political departmental heads, for the fiscal and wider integrity of projects they fund,

and want to avoid funding of projects that cause injury and other harm. Drug manufacturers require monitoring of investigators in order to ensure the reliability of scientific data for submission for marketing approval and

for quality control of products, as well as to identify and limit injuries to subjects. If a potentially marketable

product is harmful, however, they want that harm to become manifest in scientifically rigorous studies, so that,

for instance, risks of and contraindications to use are known. That is, a purpose of testing an unproven product
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or therapy is to determine the extent to which it can be used effectively and safely and the extent to which it

may cause harm. If testing on human subjects proves the harm of the product or therapy, compensation should

be available to victims of that harm to restore them to the condition in which they would otherwise have been,

in so far as monetary or other compensation can.

Monitoring may focus narrowly on the process of giving potential recruits information about the purpose

and particularly the risks of a study for human subjects and ensuring that consent was freely given and neither

coerced nor improperly induced. Coercion may arise, for instance, when a patient’s consent is requested by a

person on whose good will the patient feels dependent for care or comfort, and undue inducement when a

financial or other reward exceeds the gratification that comes from altruism and converts an act of commitment

to improved health care into selfish pursuit of personal advantage. Subjects’ comprehension and freedom of

consent can be monitored by observance of the processes of their recruitment, or, for instance, by asking them

by what understanding and choice they came to participate in a study.

A wider view of monitoring may focus on how subjects were medically and otherwise managed, how data 

of their treatment and responses were recorded, and, for instance, of interim assessment of study outcomes, to

ensure compliance with research protocols and identification and appropriate responses to adverse and other

unexpected incidents. However, monitoring of adverse incidents shows a limit and potential dysfunction of

protective monitoring by IRBs and their foreign equivalents.

By virtue of their composition, review committees include nonspecialists in the field of inquiry and nonscientists. Their understanding of whether a reported adverse incident is grave or minor, expected or unexpected, or study related or nonstudy related will often depend on information they receive from others. Those

others may be fellow review committee members with relevant interpretive skills, but will not uncommonly 

be the investigators themselves. When review committee members depend for their comprehension of the 

significance of an isolated adverse event on how the investigators assess it, they are not monitoring the investigators. Lay members of review committees do not credibly protect human subjects when they depend on

investigators’ opinions of whether, for instance, in light of an adverse event, study recruitment or exclusion 

criteria should be amended or consent information or procedures should be changed. Members may ask 

investigators pertinent questions, such as whether the incident under enquiry reflects other incidents reported

in the scientific literature or in anecdotal accounts, but usually depend on more specialized information than

they alone possess to determine whether investigators’ responses and proposals, particularly on maintenance 

or amendment of the protocol, are appropriate.

Even if review committee members could make reliable independent, individual assessments of an adverse

incident, they may be unavailable, or, for instance, may have acquired a preclusive conflict of interest. They

may have retired or otherwise left the institution that constituted the review committee, or they may be on

leave. Despite obstacles to individual service on review committees, however, some feasible assurance of monitoring may be achievable. When review is entrusted to an institutional standing committee, the institution may

accept responsibility to provide that its members will review adverse incidents as they arise and subject investigators to periodic review of compliance with their protocols and perhaps to liability without prenotification to

random review of their practices and record keeping. Committee members may rotate, so that responsibilities

for monitoring fall on members who were not necessarily involved in initial review of protocols, and they will

not be engaged full time in committee work. Their task will be to ensure that people with appropriate skills and

time undertake more detailed scrutiny of investigators’ performance, such as scientific or other administrative

staff who serve committees and make factual reports for committee members’ evaluation. When institutions

responsible for the conduct of research give assurances of monitoring of this nature, Department or Agency

heads may find that subjects of research have protection comparable to that provided in the U.S. policy.

Although review committees and committee administrations are responsible for monitoring, they do not

necessarily have to devise the means to do so. When submitting their protocols for review, investigators should
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be asked what means of independent monitoring of their conduct they propose. Review committees are not

bound to accept these proposals and may make alternative or additional requirements. These may be for more

frequent reviews of safety and efficacy, or, for instance, more independent monitors. Investigators may be

required to include budget items for monitoring in their financial plans, and U.S. funding agencies should

expect project funding applications to include such items and related administrative charges to cover monitoring conducted by or on behalf of ethics review committees. Ensuring necessary monitoring by feasible means 

is a protective responsibility both of host countries and institutions and of U.S. sponsors. Reimbursement of

costs of conducting ethics reviews is often an important issue, especially in impoverished host institutions and

countries, that includes but transcends monitoring.

9. A New Code of International Practice?

When it is apprehended that review of research protocols in foreign countries is not conducted by appropriate

procedures or fails adequately to apply governing principles, it is tempting to offer specific guidance on the

minimum review procedures required as a condition of U.S. funding and key principles of protecting subjects

from various types of harms and wrongs, including physical, psychological, cultural, confidential, and dignitary, that must be shown to be respected. In the United Kingdom, the Nuffield Council on Bioethics observed

in October 1999 that:

[o]ne of the main responses of sponsoring agents and donors from developed countries to

these difficulties in achieving local ethical review has been to draw up additional guidelines

and to try and [sic] ensure that studies with developing country partners are adequately

reviewed. Despite such efforts, great difficulties remain with effective and efficient implementation of the Guidelines in some developing countries. This situation is unlikely to improve

without raised awareness and an increase in open discussion. The development of increased

capacity in scientific research partnerships may need to expand to support expertise and 

experience in ethical review.16

There is no scarcity of international guidelines on bioethics. In December 1999, a 20-page, small-print 

publication identified 62 intergovernmental and nongovernmental international agencies that had produced

guidelines on a wide variety of bioethical topics and 29 miscellaneous international texts produced by ad hoc

tribunals, congresses, and the like, beginning with the 1947 Nuremberg Code.17 This Code, with the amended

Declaration of Helsinki, the CIOMS 1991 and particularly the 1993 Guidelines and the ICH Guideline, are 

perhaps the best-known international documents on the ethics of biomedical research with human subjects.

The Nuremberg Code ranks as international despite its exclusively U.S. origins because, like the classical

Hippocratic Oath, there is widespread acceptance of its overarching inspiration, rather than of each of its

detailed provisions. The Declaration of Helsinki and the CIOMS 1993 Guidelines have attracted a volume of

criticism, however, and proposals for their reform are in active contention. Among national codes, the U.S.

CFR on Protection of Human Subjects, 45 CFR § 46, is the basis upon which many other national codes have

been developed, some refining its principles or trying to re-express them in less formidable, intimidating, and

legalistic form.

All of the international and many of the leading national codes and guidelines are easily accessible in 

developing countries in print and electronic formats, so it is appropriate to wonder whether another expression

of their key features is required, or helpful, and, indeed, whether a new version proposed as a condition of 

U.S. funding of research might be counterproductive. The expression “ethical imperialism” is already current 

in bioethical discourse, and it might be unhelpful to risk its embodiment in a document. Nevertheless, the

Nuffield Council asked whether there is a need for a better guide than exists and how it might be developed.

The last of the 68 paragraphs of its discussion paper states that:
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[t]here is clearly a very considerable distance between the broadly based principles outlined 

in international guidance and the practical issues being considered by local research ethics

committees reviewing individual protocols. Is the most appropriate way forward to produce

‘intermediate’ guidelines to link these two levels of ethical assessment and if so, should they be

generated by national or international bodies?18

The Council perhaps indicated its own answer in its paper’s closing sentences:

The recent debate has stimulated a number of bodies including the Nuffield Council on

Bioethics, the World Health Organization, the U.S. National Bioethics Advisory Commission

and the U.S. National Institutes of Health to consider some of the issues arising from sponsorship of developing country clinical research by developed countries. The importance of

bringing these initiatives together to form coherent guidance has already been acknowledged

by many of the bodies concerned.19

Beyond possible international collaboration to develop coherent guidance on applying the broadly based

principles expressed in existing guidelines to the details and implications of individual protocols are initiatives,

international, national, or both, to train personnel in developing countries to lead and guide ethical review 

procedures in their own institutions and countries. An initial task may be to train the trainers, identifying

younger persons of appropriate (but diverse) educational backgrounds who could become their countries’

resource personnel in interpreting international guidelines on matters of substance and in constituting 

adequately composed and staffed committees to conduct ethical review procedures. 

Such trainees should be provided with opportunities, as their practical experience grows in their home 

settings, to collaborate in the refinement of guidelines prepared predominantly in developed countries, to

accommodate the particular needs, values, and sensitivities of their own countries and regions, and to explain

the impact of prevailing guidelines on promotion of research and protection of research subjects in their 

countries. They should be facilitated to work with their counterparts in the United States and other developed

countries that fund foreign research to adjust regulations for the protection of research subjects to mutual satisfaction and to guide their colleagues at home in their observance. By their contributions, based on experience

both of published research guidelines and the circumstances of their own countries, common understandings

might be developed between funding agencies and recipient institutions of what research is appropriate and

what protections of human subjects are feasible and convincing to funders and recipient institutions alike.

The approach of training personnel to equip developing countries to undertake ethical review of research

proposals received impetus on March 13, 2000, when the Fogarty International Center in Bethesda, Maryland,

in partnership with many of the National Institutes of Health Institutes, announced its proposal to fund an

International Bioethics Education and Career Development award to allow graduates to attend “advanced study

courses that primarily focus on the internationally relevant aspects of the ethical, legal and social principles

guiding the responsible conduct of research in developing countries, particularly on scientific integrity and the

protection of the interests of research participants.” The focus on research in low- and middle-income nations

would facilitate training of graduates primarily from those nations to become national leaders in the protection

of research subjects and promotion of studies that meet national needs.

Reinforcement for recommending funding of the training of such graduates comes from the need to address

the criticism that prevailing international research guidelines have emerged from narrow, privileged, and inadequately experienced origins. The Declaration of Helsinki is not alone in warranting the recent observation of its

reform process, presented from the perspective of HIV vaccine trials, that:

a look at the participants lists of virtually all major meetings which discussed proposed changes

to the Declaration shows a marked absence of patient representatives...from developing countries.
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Often developing country delegates to such meetings were actually Western researchers working in such countries or they were developing country government representatives with no

known expertise relating to clinical trials or research ethics.20

Although Western agencies and personnel may propose training individuals in developing countries to 

conduct research, this does not necessarily mean that these individuals will be equipped to determine for 

themselves under what conditions research should be internationally funded and conducted in their countries,

with due regard for ethical values and the protection of research subjects. An improved process of guideline

development, with educated, authentic international collaboration, may resolve several of the conflicts that 

currently beset the funding of foreign research. Training developing country personnel for such collaboration

appears a prudent and timely investment, supporting the integrity of funding and receiving agencies alike. 

Notes

1 Further amended in 1996.

2 Nottage, L., 2000, “The Vicissitudes of Transnational Commercial Arbitration and the Lex Mercatoria: A View from the Periphery,”

Arbitration International 16:53–78. 

3 U.S. Constitution, Article IV(1).

4 Angell, M., 1997, “The Ethics of Clinical Research in the Third World,” New England Journal of Medicine 337:847–849; Lurie, P.,

and Wolfe, S.M., 1997, “Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus

in Developing Countries,” New England Journal of Medicine 337:853–856.

5 Levine, R.J., 1996, International Codes and Guidelines for Research Ethics: A Critical Appraisal. In The Ethics of Research in

Human Subjects: Facing the 21st Century, ed. J.Y. Vanderpool, 235–259. Frederick, MD: University Publishing Group.

6 Levine, R.J., 1998, “The ‘Best Proven Therapeutic Method’ Standard in Clinical Trials in Technologically Developing Countries,”

IRB 20(1):5–9.

7 § 46.101(g).

8 Angell, M., 2000, “Investigators’ Responsibilities for Human Subjects in Developing Countries,” New England Journal of Medicine

342:967–969, 968.

9 Policy Determination No. 56 A.I.D. Policies Relative to Abortion-Related Activities 2 (1974); see now 48 CFR § 752.7016 (b)

(1996).

10 American Medical Association, 1980, Principles of Medical Ethics; Principle III.

11 See Wickline v. State, 239 Cal. Rptr. 810 (Cal. Ct. App. 1986).

12 Council for International Organizations of Medical Sciences (CIOMS), 1993, International Ethical Guidelines for Biomedical

Research Involving Human Subjects, 43. Geneva: CIOMS.

13 Ibid., 7.

14 CIOMS, 1991, International Guidelines for Ethical Review of Epidemiological Studies, 23 para. 49. Geneva: CIOMS.

15 CIOMS, 1993, 44. 

16 Nuffield Council on Bioethics, 1999, The Ethics of Clinical Research in Developing Countries: A Discussion Paper, 11 para 33.

London: Nuffield Council.

17 Fluss, S.S., December 1999, “International Guidelines on Bioethics,” Supplement to the [European Forum for Good Clinical Practice]

EFCGP News.

18 Nuffield Council on Bioethics, 20 para 68.

19 Ibid.

20 Schüklenk, U., and Ashcroft, R., 2000, “International Research Ethics,” Bioethics 14:158–172, 170.
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ATTITUDES AND

EXPERIENCES OF

U.S. AND DEVELOPING

COUNTRY INVESTIGATORS

REGARDING U.S. HUMAN

SUBJECTS REGULATIONS

Commissioned Paper

Nancy Kass and Adnan A. Hyder

Johns Hopkins University
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Acknowledgments

We would like to thank the human subjects health researchers from the United States and all participatingcountries for their valuable contributions. Their input made this report a rich response to the National

Bioethics Advisory Commission’s (NBAC’s) request for an insight on the issues related to international research

ethics and to U.S. human subjects regulations. We are grateful for the input and review by colleagues at various

points in the study: Chris Beyrer, Ruth Faden, Steven Goodman, Andrea Ruff, Carl Taylor, and Peter Winch.

Liza Dawson’s and Noreen Teoh’s management and coordination of the two studies on a daily basis were

invaluable and deeply appreciated. We would also like to thank other members of our research team—Nabeela

Ali, Kim Ashburn, Sekhar Bonu, Agha Nabeel Khan, Nilsa I. Loyo-Berrios, and Salman Wali—for their contributions toward the qualitative and quantitative analyses of the collected data. The website survey design, 

programming, and maintenance of databases would not have been possible without the generous support 

of the Johns Hopkins School of Public Health’s Information Systems Department, notably that of Nicole

Pennington. For research and other assistance, we also wish to thank the following individuals: Nicole Aaron,

Joan Atkinson, Alison Bateman, Ashley Bourland, Teresa Callison, Katherine Cheung, Sourou Gbangbade, 

Lisa Jones, Dede Orraca, Velma Pack, Irvin Pan, V. Prachi Setty, Shawn Storer, Prabhav Tella, and Tonya Walker.

We are grateful for the ongoing support, advice, and guidance from NBAC consultants and staff: Ruth Macklin,

Elisa Eiseman, Eric Meslin, and Alice Page.

Executive Summary

In recent years, controversies have erupted concerning the ethics of biomedical research sponsored by wealthy

nations and conducted in resource-poor countries, generating bitter debates and dozens of editorial articles.

However, little empirical research has been conducted on the ethics of research in developing countries, and

thus little information has been available about the extent and nature of ethical problems encountered by

researchers or the application of U.S. human subjects protections to research in these resource-poor settings.

This project is the first large-scale study of researchers’ experiences with ethics issues and human subjects 

regulations in the developing world. The results presented in this report should help to identify the key ethical

issues and problems encountered by researchers working in resource-poor countries and suggest mechanisms

to address these concerns. It is our hope that this report will be useful not only for current policy deliberations,

but also to set the stage for further empirical investigation and thoughtful analysis of international research

ethics.

This research project was undertaken at the Johns Hopkins University in 1998–2000 to investigate the attitudes and experiences of U.S. and developing country researchers regarding ethics issues and human subjects

regulations in developing country research. This project was a collaborative effort between two investigators at

Johns Hopkins School of Public Health: Dr. Nancy Kass of the Department of Health Policy and Management

and Bioethics Institute and Dr. Adnan Hyder of the Department of International Health. Dr. Kass’ study

entailed surveying U.S. investigators who work in developing countries, while Dr. Hyder’s consisted of parallel

methods applied to developing country investigators.

The project involved collection of qualitative data in the form of focus groups and interviews and quantitative data from a mailed survey. Focus group participants were asked open-ended questions about informed

consent; about Institutional Review Board (IRB)/ethics board review, both in the United States and in the host

country; about ethics issues in their research; and about recommendations for changes in the U.S. regulations.

The first focus groups conducted during this study provided qualitative data to help guide the design of the

survey instrument, which was largely identical for both the U.S. and international surveys. The topics covered

in the survey were the design of the index study; reasons for conducting this study outside the United States;
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informed consent; U.S. and host country IRB/ethics board review; researcher attitudes regarding U.S. and other

human subjects regulations; ethics issues in international research; and recommendations for changes in U.S.

policy and guidelines.

For the U.S. survey, investigators were contacted at a variety of U.S.-based institutions, including academic,

military, private nonprofit, private industry, and government. For the international survey, samples were drawn

from membership lists of several international professional organizations relating to biomedical research. For

both U.S. and international respondents, e-mail was the initial mode of contact for inviting researchers to

respond to the survey, which was available on a password-protected website for these respondents. Follow-up

mailings were sent through U.S. mail or by courier, and these respondents received a printed version of the

survey. The data collected are extensive, including the results of a total of more than 500 completed surveys

and 13 focus groups. The findings can be only summarized in this report. (See Appendix A for the U.S. focus

group guide and Appendix B for the survey developed for U.S. researchers.)

The collective experiences of researchers in this study demonstrate that consideration of ethics is a part of

the culture of international research that is seen as an essential component of conducting scientific investigations. Almost all studies described by researchers underwent review either in the United States, in the host

country, or in both; the vast majority of researchers felt that, despite procedural difficulties, U.S. regulations

sometimes or always ensure high ethical standards in research; informed consent is practiced by almost all

researchers, who believe it to be an essential feature of the research; and researchers frequently stated that the

informed consent process provided opportunities to discuss ethics issues with staff. At the same time,

researchers noted significant concerns regarding oversight of international research. Current U.S. regulations

and IRBs, they believed, emphasize procedural rather than substantive matters of ethics, such as focusing on

consent forms rather than on participant understanding. Also, IRBs give little attention to what is owed participants during or after a study. Researchers also felt that U.S. ethics boards require a better understanding of the

local contexts of developing countries and that international boards should have a better understanding of

ethics. These findings are summarized below.

Informed Consent

There were several major findings in the area of informed consent. Researchers from both the United States and

from developing countries demonstrated a commitment to the essential elements of consent, namely informing

participants about the research and ensuring that their participation was voluntary. Researchers in both groups,

however, asserted that the procedural requirements for informed consent—in particular, written consent

forms—are no guarantee of participant understanding and, in some cases, impede the process of explaining a

research study. The use of written consent forms for documentation of informed consent was seen as inappropriate by many respondents, especially when used in populations of low literacy. In addition, many respondents reported that in some settings participants felt threatened by the process of signing documents. Other or

additional mechanisms were suggested and used for documenting consent, such as oral consent with a witness

or a researcher signature. Researchers from both the United States and from developing countries described the

use of a variety of methods for educating participants and stressed that the disclosure process must be tailored

to fit the community. The vast majority of both U.S. and international researchers felt that more flexibility

should be allowed in methods of documenting consent. 

Respondents also believed that the complexity and legal language often required on consent forms by U.S.

IRBs was a barrier to participant understanding. Respondents in both the United States and the international

survey felt that the consent forms often served as legal protection for the researchers and their institutions

rather than as protection for the research participants. 

Researchers believed that improving participant understanding of research was the appropriate goal, in spite

of the challenges involved. Respondents described situations in which potential study participants did not
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share Western concepts of health and disease, and researchers, both from the United States and other countries,

used creative methods to elucidate biomedical concepts and to convey the essential information about their

research studies to potential participants. In many cases, an extensive period of community education and 

discussion took place before a research study began. Most researchers (65 percent of U.S. and 83 percent of

international) were in favor of incorporating tests of participant understanding into protocols, although only 

16 percent of U.S. and 27 percent of international researchers actually had done so in practice.

Investigators often described seeking permission or approval from community leaders in areas where a study

will be conducted. This approval was seen as essential to the success of the research and as a precursor to any

individual consent process. The majority of international respondents and a fifth of the U.S. respondents felt

that such approval should be a requirement for conducting research in settings where this is appropriate.

International researchers were more likely than U.S. researchers to believe that the consent process is too

focused on the individual rather than on the family or the community (66 percent versus 23 percent), and

many in both groups (47 percent of international and 37 percent of U.S. researchers) believed that the cultural

norms of the study population were inconsistent with individual decisionmaking. Some researchers described

how many residents of resource-poor communities look to their physicians to make medical decisions for them

and are not accustomed to selecting their own treatments. Also, participants may not distinguish between

research and clinical care, although the vast majority of U.S. and international researchers believed that their

study participants were aware that they were participating in a research study. Researchers frequently described

the difficulty of achieving voluntary participation in a setting lacking basic medical care and other services and

where the research involves some direct benefit for participants. Most researchers (about 60 percent of each

group) felt that participants joined their studies because of the benefits provided.

The vast majority of researchers, both U.S. and international, viewed the consent process as valuable in 

educating participants about their research projects. Participants expressed support for using informed consent

procedures in all types of research, with more rigorous standards for participant understanding and documentation of consent being used in higher risk studies.

Risks, Benefits, and Study Design

Researchers struggled with issues surrounding the need to balance benefit for study participants with benefits

for a larger community. This tension is present in all research, but it is made more acute by the conditions of

poverty and by the lack of basic medical care found in many developing countries. Questions of study design

and risk-benefit assessment were covered in both focus group and survey questions.

Only 12 percent of U.S. respondents and 5 percent of the international respondents reported that their 

studies entailed greater than minimal risk for study participants. In the U.S. survey, studies labeled greater than

minimal risk were more likely to be questioned by IRBs regarding several issues, including risk, participant 

voluntariness, and the relevance of the research to the host country. Researchers with studies of greater than

minimal risk were also more likely to report that some potential participants refused to enroll after learning

about the study. It is reassuring that riskier studies are being scrutinized more closely by IRBs and by potential

participants. Also, while the majority of all respondents believed that participants enrolled in their studies

because of the benefits provided, researchers with riskier studies were more likely to report that participants

overestimated the benefits they would receive. Better education about the nature of the research is needed to

eliminate false hopes among study participants.

Many focus group respondents described different types of benefits afforded to participants, including free

medical care, health screening or diagnostic tests, and cash reimbursements for travel expenses. Several focus

group respondents expressed that, given the poverty of the setting and the lack of access to good medical care,

it is understandable that potential participants are eager to join studies. Most researchers (about 60 percent of

each group) said that medical care provided was not locally available outside the study. 
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For more than half of both the U.S. and international respondents, the low background levels of medical

care in many settings created problems in determining what treatment to give to control groups. In focus

groups, a number of respondents stated that locally available medical care should be considered the acceptable

standard for control groups. In the survey, the majority of respondents (77 percent of international and 78 percent of U.S.) believed that the “standard of care” issue should be decided on a case-by-case basis. In general,

researchers mentioned the need to balance concern for the well-being of study participants with the overall

goal of gaining knowledge through the research that will benefit larger numbers of people. 

In addition to difficult questions regarding control groups, researchers grappled with decisions about providing participants with medical care unrelated to the study question. In some cases, medical conditions were

discovered during the course of the study, and treatment was provided; in other cases, unrelated care was not

provided, while in still other cases, research could not be carried out because the medical care costs would

have been prohibitive. Respondents described difficulty determining how much medical care unrelated to the

study question was appropriate and feasible, and many mentioned that the U.S. IRBs seemed poorly informed

and ill-equipped to help address these questions. 

A key question in the design of a U.S.-funded project conducted in a developing country is the rationale 

for carrying out the study in a poor country rather than in the United States. Seventy-three percent of both

U.S. and international researchers expressed a commitment to addressing global inequalities in health, and in

some cases this commitment was associated with efforts to provide benefits to study communities after the

research had concluded. U.S. respondents even more frequently mentioned as a reason the prevalence of 

disease in the host country (83 percent), and slightly less often the relevance of the intervention being tested

(69 percent). Some practical concerns were also listed, such as lower cost or more rapid enrollment of participants. Interestingly, international researchers were more likely than U.S. researchers to believe that U.S.-funded

research was conducted in their countries for pragmatic reasons, such as the need for marketing approval in

that country (25 percent of international versus 12 percent of U.S. researchers) or U.S. strategic interests in the

region (49 percent of international and 32 percent of U.S.). For both groups, however, these reasons were listed

least often, compared to other reasons for working in developing countries.

In focus groups, some respondents described how they chose the countries for their research. Some 

pharmaceutical researchers made candid remarks about the ease of access to large numbers of patients; in the

case of HIV research, researchers sought patients who had not had prior drug treatment. Several pharmaceutical

researchers commented that completing their clinical trials rapidly was one of their main concerns, given the

time pressure under which they work. Some of these respondents mentioned that the products being tested

would not be available to the host countries after the research, but that the benefits provided to the study participants during and after the trial (which were otherwise not available) justified, in their minds, the conduct 

of the research in the resource-poor setting.

In addition to benefits provided during the research, researchers were asked what benefits accrued to host

communities and countries after the research has ended. In the survey, roughly 40 percent of both U.S. and

international researchers were conducting intervention studies. Of the U.S. researchers, 67 percent had plans to

provide the intervention to some developing country residents at the conclusion of the study, while 92 percent

of international researchers had such plans. Most often, for both U.S. and international respondents, the intervention was or would be provided to the study population; in some cases it was or would be provided to larger

groups, such as the study community or the entire country. In the U.S. survey, the interventions being provided

to the entire country were more likely to involve funding by the host country government. It would be valuable

to study further those cases where the interventions were made widely available to see if useful models for

negotiation and funding could be derived from these cases and if those interventions entailed lower cost, 

available infrastructure, or mechanisms for producing the intervention in the host country.
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While the majority of international intervention studies had plans in place for distributing successful interventions, many researchers in the U.S. survey commented that this should not be a requirement for projects

conducted in developing countries. International respondents were more insistent that such arrangements

should be a prerequisite for conducting research; in the survey, three-quarters of the international respondents

and half of the U.S. respondents agreed with this principle. In written comments at the end of the survey, many

U.S. researchers remarked that an absolute requirement to provide an intervention would be an impediment to

much research and would ultimately be more harmful to resource-poor countries. Furthermore, many stated

that funding agencies would never be willing to fund research that entailed providing treatment at the end of

the study. But the numerous plans in place to provide post-study interventions demonstrate that, in many

cases, such arrangements are valued and are feasible. Many international focus group respondents expressed a

strong belief that effective interventions should be implemented in the host countries and that U.S. or other

foreign sponsors have an obligation to give something back to the countries that hosted their research projects. 

Capacity building was discussed extensively by both international and U.S. researchers. U.S. researchers 

frequently said that their research depended upon effective collaborations with developing country scientists

and that appropriate study design and communication with study communities could not be accomplished

without these liaisons. Similarly, international respondents saw themselves as a crucial bridge between their

own countries and Western researchers, because they are familiar with the political and cultural contexts of

their own societies and are also well versed in the practice of biomedical research. Several international respondents expressed a sense of responsibility toward their home countries, to ensure that appropriate research is

conducted and that ethical standards are followed. The majority of both U.S. and international researchers

reported that developing country colleagues were involved in every step of the research process, from grant

writing to recruitment of participants. Developing country scientists, however, were much less likely to participate in the more intellectual tasks, such as grant writing and data analysis, and were more likely to be involved

in field operations. Both U.S. and international researchers mentioned a need for developing country scientists

to be given opportunities to develop more substantive skills, particularly in the area of grant writing. The ability

to procure funding for research projects through grant writing would enable developing country researchers to

gain more control of the research agenda and to design and to conduct the studies in their own countries.

Both U.S. and international respondents also felt that ethics review should be a part of capacity building 

and that host countries with more experience in ethics review became more capable in this regard. Several

respondents suggested specific training for ethics review for developing country IRBs. 

A further element of capacity building is deciding which study-related resources will be left in the host

country at the conclusion of the research. While practically all researchers left behind some type of resource,

the nature of these resources ranged from medical equipment and supplies to buildings and water systems 

to better trained personnel. Many respondents stressed the fact that resources are only significant if trained 

personnel are on hand to utilize them. 

Review and Oversight

The final topic in this report is oversight of research, including both U.S. and developing country IRB/ethics

board review and the regulations and guidelines in place governing such review. The vast majority (91 percent)

of studies reported by U.S. respondents underwent U.S. IRB review, and most, but not all, reported that a host

country IRB also reviewed the study. In the international survey, significantly fewer (55 percent) of U.S.-funded

studies underwent U.S. IRB review; of those studies that were not reviewed, two-thirds were funded by U.S.

nonprofit organizations and one-third were funded by U.S. private companies. Although 97 percent of U.S.

researchers said that U.S. regulations sometimes or always ensure high ethical standards in research, both U.S.

and international researchers saw a great need for improved functioning of U.S. IRBs and a need for more
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appropriate regulations with regard to developing country research. The issues raised by U.S. IRBs tended to 

be procedural in nature, such as the need for translations of consent forms and for letters of approval from

developing country representatives. Less often, issues relating to fundamental ethics concerns were raised. U.S.

focus group participants reiterated this theme, stating that many times U.S. IRBs were excessively bureaucratic

and unhelpful in addressing true ethical dilemmas in their research. Comparison of host country IRB review

with U.S. IRB review in the U.S. survey showed that similar issues were raised by both boards. In focus groups,

however, U.S. researchers pointed out that developing country IRBs are crucial to ensuring that the research 

is conducted appropriately and that it is relevant to the country’s needs and sensitive to local cultural and 

political conditions.

U.S. researchers expressed frustration with U.S. IRBs that did not seem to understand the realities of life in

developing countries imposing inappropriate and unrealistic requirements. Sixty-six percent of the U.S. and 

58 percent of the international researchers felt that U.S. IRBs were more concerned with politics than with 

protecting the interests of research subjects, and the vast majority of both groups of researchers felt that U.S.

IRB regulations were insensitive to local cultural norms and traditions outside the United States. Researchers

from both groups suggested in focus groups that for U.S. IRBs, education was needed in the realities of life in

developing countries.

The vast majority of U.S. and international researchers felt that developing country investigators sometimes

or always relied on U.S. human subjects regulations for guidance, while 77 percent of international and 64 percent

of U.S. researchers felt that use of international guidelines was more appropriate than U.S. rules and regulations.

Ethics review in the host country was highly valued by most respondents: 85 percent of international and

77 percent of U.S. researchers felt that a developing country review should be required for all studies in those

countries; both U.S. and international respondents in focus groups noted that more ethics training is needed

for host country review boards. Most researchers reported that host country review had occurred at a collaborating institution, and a minority reported review at the national or provincial level. About one-third of the

IRBs, researchers believed, were established because of the U.S. regulations requiring local ethics review. Sixtythree percent of international and 79 percent of U.S. researchers believed that host country ethics boards were

more concerned with politics than with protecting research subjects. In focus group discussions, international

researchers commented on the establishment and evolution of IRBs and ethics review capacity in their countries. Countries and regions that had more experience with research also had more experienced and effective

review boards. Many respondents mentioned that host country review boards may be reviewing the science as

well as or instead of the ethics of a proposal, while some commented that political considerations and financial

gain were at stake in some host country reviews. Several international respondents commented that host country

governments, as well as IRBs, need to be educated about ethics review and ethical issues in research. 

A number of international respondents mentioned that there is currently no monitoring by IRBs or other

agencies to ensure that research studies are actually being carried out according to the approved protocols.

Examples were given where studies were conducted without appropriate follow-up procedures, and respondents remarked that there was no method of enforcing the guidelines set forth by the IRBs.

Another consideration raised by both U.S. and international researchers was the need for funding to support

the work of host country IRBs. Since educated professionals are in great demand in many developing countries,

these professionals may be taking time away from their many other responsibilities to serve on ethics boards,

often with no compensation for time or travel expenses. In addition, funds often are needed for practical functions, such as computers, photocopiers, or other office equipment. A strong majority of all researchers agreed

that U.S. funding agencies should support host country IRBs (85 percent of international and 70 percent of

U.S. researchers concurred).

In the U.S. survey and in focus groups, extensive discussion was generated on the topic of Single Project

Assurances (SPAs). SPAs have the aim of ensuring that an ethics board is constituted in the host country
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according to U.S. guidelines and performs a review based on principles laid out in the U.S. regulations.

Researchers who spoke on the topic of SPAs almost uniformly criticized the SPA process as time-consuming,

overly bureaucratic, insulting to foreign governments, and ineffectual in ensuring an adequate ethics review or

in protecting research subjects. Several focus group participants mentioned that the procedure was considered

insulting and imperialistic by many developing country governments. In addition, because the SPA is tied to

the funding for a project, new SPAs need to be obtained when funding changes, but not when protocols

change. Also, researchers described interactions with staff from the National Institutes of Health’s (NIH’s) Office

for Protection from Research Risks (OPRR) that revealed the agency’s lack of experience and knowledge of

developing country conditions. Respondents had no objection to the principle or goal of a substantive ethical

review to be carried out in the host country, but felt that the SPAs did little or nothing to further this goal. Half

of the U.S. respondents and 29 percent of the international researchers felt that the SPA procedure should be

eliminated. 

Recommendations

Based on our findings, we offer the following recommendations: 

1. Informed consent is central to the research process and is supported by developed and developing country researchers

as a leading principle.

Quantitative and qualitative data from both projects suggest that researchers agreed overwhelmingly that

informed consent is important and necessary in the conduct of research. Researchers described it as both a

means to educate participants about the study and to raise ethics issues with study staff.

2. There should be greater flexibility in the means of informing participants about research and in the methods of 

documenting consent in international and collaborative research.

While clearly valuing informed consent, many researchers were frustrated with how narrowly consent requirements have been interpreted by most U.S. IRBs. For these researchers, the goal of informing participants is not

negotiable, but the means for doing so should be flexible. Methods generally should be sensitive to cultural

norms and levels of literacy in the local community, and researchers in their applications to IRBs/ethics boards

should justify their choice of methods.

3. Tests of understanding should be incorporated into research studies.

Respondents to our survey and focus group participants overwhelmingly thought that participant understanding

was the appropriate goal for informed consent procedures. Ultimately, research can go forward only if participants

understand what the research entails. While there was overwhelming support for trying to assess participants’

understanding, most researchers admitted that they had never conducted such a test themselves. Regardless of the

methods used for consent, the test of understanding will reveal the success or failure of efforts to communicate

the study’s procedures, risks, and benefits to the study population.

4. All research studies concerning any topic, if they involve human subjects, should be reviewed by an appropriate ethics

board, although review should be streamlined based on a study’s level of risk.

There may be cases where reviews are hastened to meet a deadline or a waiver granted after preliminary review

(for secondary data analysis or extremely low-risk studies), but all studies, regardless of topic and method,

need to be reviewed. The notion that studies pertaining to social sciences, especially anthropological sciences,

and those involving qualitative research methods do not need to be reviewed must be negated. Some of the

most sensitive issues of human interactions are raised in such studies, and risks arising from breaches of confidentiality, particularly in certain countries, can literally be life threatening. 
B-10

Rather than determine whether review should occur based on a study’s discipline or method, IRBs should

streamline their review based on the level of risk. Riskier studies should have more rigorous and detailed

reviews and should similarly require more justification from researchers, more thorough consent processes, 

and a higher threshold of participant understanding.

5. Studies involving international collaborations need to be reviewed in both/all countries.

All studies that involve collaborative research must be reviewed in both the United States and the host country.

The United States has certain cultural and legal standards that require certain practices or approaches; host

country boards are expected to be more cognizant of appropriate methods for informing participants, to be

more aware of certain types of risks that would be overlooked by U.S. boards, to be more aware of what level

of benefit is realistic to provide, and to be more attuned to the health priorities of their own countries.

6. U.S. IRBs should gain greater expertise in the realities of life in a developing country.

Many U.S. researchers expressed frustration with unrealistic requirements raised by their U.S. IRB that, to

them, revealed their IRB’s ignorance about field realities in a developing country. Having someone on the U.S.

IRB with international experience is helpful or having, instead, an outside consultant to provide guidance can

begin to address this problem. Moreover, even a short “in-service” training for U.S. IRB members and staff on

how local conditions and/or beliefs might affect issues of research review, consent, expectations, or host IRB

working conditions would be helpful.

7. Host country ethics boards should gain additional experience in ethics.

Many U.S. researchers voiced concerns that host country boards had little familiarity with ethics. Thus, when

ethics boards convened, they focused on other issues where they felt more comfortable, such as the scientific

design or the budget. While researchers should consider providing mechanisms for ethics training along with

other types of training to their colleagues, funding agencies similarly should devise mechanisms for increasing

ethics capacity in local countries.

8. Collaborative research studies should be monitored at periodic intervals to ensure that procedures stated in the 

protocol are being carried out as planned.

While IRBs and collaborating institutions can require certain ethical principles to be upheld in the design 

and planning of a research project, if the plans are not carried out as promised, the safety and interests of the

study participants can be compromised. A mechanism must be put in place to ensure that appropriate study

procedures actually are followed.

9. Capacity building should be integral to any study.

Research collaborations occur between rich and poor countries, not only because poor countries cannot afford

to finance the studies, but often because there are not enough people trained locally to design, collect, and 

analyze data. It should be the U.S. researcher’s goal to encourage capacity building during every research 

collaboration, such that ever-increasing proportions of study staff are local residents.

10.The study population or community must benefit as a consequence of the study, and mechanisms to ensure this must

be discussed and/or developed as part of the study proposal.

All researchers, especially international researchers, overwhelmingly agreed that the study population must

benefit as a consequence of research conducted within that community. They also encouraged the exploration

of mechanisms to ensure that the benefits of research actually reach these people and promoted the inclusion

of such discussions in the early stages of thinking about research. 
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Researchers believed, however, that consideration of future benefit should not be their responsibility alone.

Innovative mechanisms must be devised for encouraging researchers to engage donors and aid agencies or 

service delivery organizations in discussions about realistic interventions before a study is initiated. Although

researchers do not need to shoulder this responsibility alone, it still may not be appropriate for funders to 

support research where no one is taking responsibility for working on future access to effective health 

interventions.

A. Introduction

This report describes a research project at the Johns Hopkins University School of Public Health on human

subjects regulations and ethical issues in developing country research that was commissioned by NBAC. The

project involves the collection of information from researchers both in the United States and in developing

countries who are involved with human subjects research in developing countries to ask about their experiences

with U.S. regulations and guidelines and with ethical issues in their research. The project is an important component of the information being used by NBAC in making policy recommendations concerning international

research. The sample of U.S. investigators and their developing country collaborators has direct experience

with the application of human subjects protections to international research and is aware of the benefits and

limitations of these regulations in practice. 

To our knowledge, this is the first federally funded comprehensive study of researchers’ attitudes and 

experiences in international research ethics. In 1994, Lane Porter and Lawrence Gostin of Georgetown

University, Washington, D.C., wrote a report entitled “The Application of United States Protection of Human

Subjects Regulations and Ethical Principles to United States Funded or Conducted HIV-Related Research in

Foreign Countries” (Porter and Gostin 1994). The authors sought information through personal communications, interviews, and letters of inquiry from U.S. researchers, U.S. administrators, host country administrators,

and host country researchers. The number of respondents was small—20 substantive narrative responses, with

12 quantitative responses. The report was not officially published, and it is unclear if its recommendations were

formally used within the federal structure.

Porter and Gostin’s study covered three issues: legal and ethical issues, practical issues, and special characteristics of HIV-related research. The section on legal and ethical issues was the most comprehensive and was

organized further into eight areas: informed consent, confidentiality, establishment of local review boards,

application of U.S. legal and ethical requirements, legal and ethical conflicts in collaboration, ethical reasons 

for foreign research, vulnerable populations, and research benefits and distributive justice.

A small-scale survey study was conducted by Alison Wichman and colleagues of the Office of Human

Subjects Research at NIH, published in 1997 (Wichman, Smith, Mills, and Sandler). They surveyed 55 U.S.

investigators working on collaborative research regarding the use of international SPAs. The response rate was

80 percent, and several of the findings of the study are pertinent to the current project.

There was strong concurrence (93 percent) among the researchers surveyed that U.S. investigators bear

some responsibility for the protection of human subjects who participate in their research projects in other

countries, even if they have no direct contact with these subjects. The researchers by and large placed a high

value on IRB review in the country hosting the research project; 84 percent felt that on-site review was important in international collaborative studies. Agreement was not as strong (64 percent) that provision of educational materials about IRBs in collaborators’ native languages would improve the system, and fewer than half

the researchers (43 percent) considered that use of international guidelines such as the Council of International

Organizations for Medical Sciences (CIOMS) would be more appropriate for international collaborative projects.

Almost three-quarters (73 percent) of the respondents reported that researchers in other countries had refused

the opportunity to collaborate because they did not want to negotiate an SPA.
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Wichman and colleagues noted that the number of respondents to the survey was small and that the survey

suggested some possible drawbacks of the current system, including inhibition of international collaborative

research; difficulties in fostering good working relations among researchers; and an unfounded belief that the

current international SPA process is fulfilling its important, intended goals.

In a review of the literature, no other empirical studies were found on the subject of researchers’ experiences

with human subjects regulations and ethical guidelines in international research ethics. Many of the recent

publications in this arena are editorial pieces, and approximately 60 percent of the articles address the issue of

HIV/AIDS, especially in Africa. Relatively little has been written about the interaction of Western clinical

research ethics with non-Western cultural norms and how conflicts that might arise from cultural differences

are being resolved.

This study consisted of two components: a study of U.S. investigators who work in developing countries

and a parallel study of developing country researchers, some of whom have experience working on U.S.-

funded projects. Quantitative and qualitative methods of data collection were used, through the conduct of a

self-administered written survey and focus groups and in-depth interviews. In both methods, participants were

queried on informed consent procedures; ethical reviews both in the United States and in developing countries;

availability of interventions; ethical challenges faced by researchers; and U.S. and international ethical rules and

guidelines.

U.S. investigators from four different sectors were included in this project: academic, military, government,

and private industry. The investigation of developing country researchers’ attitudes and opinions in this exploration is seen as an integral component of the study. The purpose of this effort is to gain an insight into their

perspectives on research ethics, as they work on projects funded by U.S. sources or in collaboration with U.S.-

based investigators. It is recognized that there are cultural, socio-economic, and governmental differences in

these settings, which may affect the conduct of research. Such realities, which should be identified, may not be

apparent even to U.S. researchers with experience in developing countries. The agenda, objectives, motives,

and interests of developing country researchers may be different from those of their collaborating U.S. investigators in conducting a specific research project. These differences in perspective and actions made it essential

to include a study of developing country researchers as well as those from the United States. 

Results from the developing country component are presented in a separate section from those of the United

States. Comparison of the two study groups is presented in a separate section, followed by recommendations

for changes in U.S. policies regarding international research, based on the data in this study.

The main purpose of this data collection was to provide NBAC with a broad range of opinions and experiences relating to human subjects regulations in international research. Data has also been collected concerning

the nature of ethical issues that researchers confront in developing country collaborations and their own recommendations about how human subjects regulations could best protect the interests of research participants in

resource-poor settings. It is our hope that NBAC’s recommendations for changes in U.S. policies and regulations will be more appropriate and effective based on the extensive data on researcher experiences presented in

this report.

B. Methods

B.1 Methods Used for the Study of U.S. Investigators

There were two sources of data for the survey of U.S. investigators. Focus groups were conducted with 

U.S.-based researchers who conduct research in developing countries, and a written survey was distributed 

to similar researchers. Both focus groups and survey methods were reviewed and approved by the Office of

Management and Budget (OMB) under the Paperwork Reduction Act and by the Johns Hopkins School of
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Public Health Committee for Human Research, the IRB of this division of the university. The methodology for

each form of data collection is described in this section.

B.1.1 Focus Groups

Focus groups were convened with researchers in four employment sectors: academia, the U.S. government, the

U.S. military, and the pharmaceutical industry. All but one focus group were homogeneous with regard to the

sector from which participating researchers were drawn. There were seven groups in total: one with academic

researchers, one with military, two with government agency employees, two with private industry researchers,

and one mixed group. Focus group participants were recruited through professional contacts and through

referrals at different institutions. Researchers were eligible to participate in a focus group if they had experience

conducting human subjects research in developing countries. 

In each focus group, confidentiality procedures were described to participants, and their consent was

obtained for participation and for recording the session. Participants were informed that data would be

reported without using names of individuals or institutions and that broad, region names (e.g., continent)

would be substituted for country names where appropriate, to protect confidentiality. 

The Focus Group Guide

The focus group guide consisted of open-ended questions that were asked in every group. Then, consistent

with focus group methodology, additional, follow-up questions were asked spontaneously based on participant

responses and focus group discussion. The questions on the focus group guide were based on the stated

interests of the funder (NBAC) on the literature concerning international research ethics, and, iteratively, the

guide was modified after each focus group discussion if new ideas were raised by participants. Topics covered

in the guide included informed consent procedures, U.S. and host country ethics review, developing country

collaboration, attitudes about existing U.S. human subjects regulations, and types of ethics issues that arise in

their work. Focus group participants also were asked to make recommendations concerning whether any

changes should be made to current U.S. human subjects regulations. A court stenographer was present during

every meeting to create a written transcript of the discussion. Participants received no compensation for their

participation, other than refreshments. 

Analysis

Focus group transcripts were read in their entirety by three members of the research team to identify relevant

themes. Transcripts were then coded by two members of the team according to the major themes and subthemes identified. Coded data were entered into one of two software packages: NUD*IST and Atlas/ti®. Data

then were summarized according to each theme. 

B.1.2 Written Survey

Survey Design

The survey instrument was designed based on the literature concerning international research ethics and using

qualitative information generated in focus groups. The survey was reviewed by NBAC commissioners as well as

by epidemiologists, international health researchers, and ethicists from academic, government, and/or private

industry institutions, and it was revised accordingly. Limited pilot testing was conducted to determine the

amount of time required to complete the survey. The final survey was professionally typeset and printed in a

booklet and was transferred to a website by information systems staff of the Johns Hopkins University.

Sampling Frame 

There were multiple sources of names for the survey’s overall sampling frame. The first source used was the

CRISP (Computer Retrieval of Information on Scientific Projects) database of NIH. The CRISP database contains the principal investigator’s name and institution, the fiscal year of funding, and an abstract describing the
B-14

research of NIH-funded projects. This database was searched systematically, using developing country names as

search terms one by one to compile a list of NIH-funded grantees whose projects were in developing countries.

Each abstract identified was then read and coded for eligibility. Eligible research was defined as a “developing

country research project involving human subjects.” Laboratory studies were included only if they involved 

primary collection of human tissue samples in a developing country; otherwise they were excluded. To define

“developing country,” a developing country list was taken from a 1996 World Health Organization (WHO)

report, “Investing in Health Research and Development” (WHO 1996). There were 252 potential respondents

from this CRISP list, most of whom were university-based researchers. 

University-based researchers also were recruited through university websites for descriptions of faculty

research projects. Universities were selected based on their reputation for conducting international health

research and/or their having received funds from the NIH’s Fogarty International Center (FIC). Searching 

university websites yielded 269 researchers who had described some type of human subjects research in 

developing countries. 

The remainder of the sample was recruited through personal contacts. A professional contact in the U.S.

military, Dr. Edward Lane, Deputy Director of Navy Medical Research and Development, provided the names 

of commanding officers of U.S. and overseas research centers, who were contacted and informed of the survey.

These commanding officers then forwarded names and e-mail addresses of researchers in their command who

they felt would be relevant survey respondents. There were 23 respondents in this group. 

Similarly, professional contacts at two federal agencies provided names and e-mail addresses of researchers

willing to be contacted about the survey project. Eighty-five U.S. government intramural researchers were on

this list. Federal government intramural researchers also appeared, although in relatively small numbers, in the

NIH CRISP database described above.

Forty-six surveys were provided to personal contacts at three pharmaceutical companies for distribution to

relevant researchers. In addition, the names of 52 researchers with private industry affiliations were obtained

from the membership list of an internationally oriented professional association. 

Additional respondents were referred by professional contacts at several different organizations and institutions, resulting in 139 additional names to the list of potential respondents from universities and 74 from private

nonprofit research groups. One professional university-based contact provided a list of potential respondents,

representing a variety of institutional affiliations. There were 34 names in this group. 

Survey Distribution

For all potential respondents for whom we had an e-mail address, initial contact was made by e-mail. A 

disclosure letter was sent describing the project, the survey itself, and the confidentiality procedures. Included

in the disclosure letter was the website address for the electronic version of our survey, along with a unique ID

code for each respondent to use when logging in. Researchers who did not fill out the survey online were sent

a paper disclosure letter and paper copy of the survey by U.S. mail, approximately four weeks after the initial

e-mail had been sent. Following this mailing, two reminder e-mails were sent, as was a second paper copy by

U.S. mail.

The first 362 respondents were also asked to provide the name and contact information of a project director

or project coordinator on their staff who had coordinated one of their developing country projects. When

paper copies of the survey were mailed to primary respondents, a second copy of the survey was included for

the project director and was marked as such. A specific ID code was used for project director surveys in order

to track the response from this group. After receiving a limited number of surveys from project directors, this

strategy was discontinued, and, thereafter, primary respondents received one survey and were not asked for

contact information regarding their staff.
B-15

Incentives to Survey Respondents

A U.S. $25 incentive was offered to respondents if they filled out and returned the survey either online or by

paper copy. Respondents were eligible to receive the U.S. $25 if they answered all the “required” questions on

the survey (approximately half of the questions), which were marked in color on the website and with bold

numerals on the paper copy. A statement at the top of each page of the survey reminded respondents that they

must fill out all required questions to receive the U.S. $25. At the end of the survey, respondents were asked to

provide a mailing address on a separate sheet for receiving the U.S. $25 check. The payment was available to

all respondents except those who work for the federal government and those who are forbidden by law to

receive outside remuneration for services related to their employment.

Confidentiality Procedures

The survey itself does not ask respondents for their names, addresses, or institutions, and data are identifiable

only by ID number. In addition, in order to protect respondent confidentiality, specific steps were taken when

receiving both website and paper copies of the survey. In the case of paper copies, the name and mailing

address at the end of the survey (provided to receive the U.S. $25 reimbursement) were separated from the

paper copy prior to any data editing or data entry and were stored in a separate file for subject reimbursement.

For website surveys, the names and addresses provided for reimbursement were printed separately from any

part of the survey data and were not included in the data transferred to STATA® for statistical analysis. For

purposes of survey follow-up, a master list of ID numbers, names, e-mail addresses, and mailing addresses 

was maintained in our address database, which was kept separate from our survey responses database. Once

recruitment and survey follow-up were complete, ID numbers were removed from the address database so that

survey data could never be linked with identifiers

Qualitative Data from Survey

At the end of the written survey, researchers asked two open-ended questions. The first question was whether

they wished to elaborate on any of the closed-ended survey questions that they felt required more detailed

responses; the other asked them to describe changes that they would make to the existing U.S. policy and 

regulations regarding human subjects research in developing countries. 

Data from United Nations Human Development Indicators, Human Development Report

In order to assess the relevance of the host country’s level of development for collaboration and capacity building and other ethical issues, the United Nations Development Programme (UNDP) Human Development Index

(HDI) was incorporated into the survey database, after data collection had been completed (UNDP 1999). 

The HDI is a composite index consisting of life expectancy at birth, adult literacy rate, and adjusted per capita

income. Each country reported by researchers as the site of their index study was assigned the appropriate 

HDI value (data obtained from the UNDP website). The new variable, HDI, was used in statistical analyses to

determine if different levels of development were associated with other survey variables of interest.

Statistical Analysis

The database containing website responses was created using Microsoft Access 2000. Every week, new data

were received from the website and converted into STATA®, Version 6. For quality control, data from the 

website were checked, and errors with skip patterns and/or incorrect codes were corrected during data 

cleaning. Participants who logged in to the website but answered three or fewer sections of the survey were

excluded from the analysis. After these records were deleted, 190 records were included from the website.

Data from mailed surveys were entered manually using EPI-INFO, Version 6.04b. For quality control three

steps were used: 

i. Data editing: Surveys received through the U.S. mail were checked for errors before being entered in the

data set. A “Data Editing Protocol” was used to ensure uniformity among data editors. The surveys were
B-16

checked for errors in skip patterns. If unanswered questions were found, the codes for missing values were

assigned, and each survey response was circled in red to facilitate data entry.

ii. Data entry: Once the surveys were edited, they were entered into the data set. A “Data Entry Protocol” was

created for data quality control purposes, to ensure consistency among data entry staff and to minimize

errors. Additionally, legal values and skip patterns were programmed in the data entry file to reject invalid

entries. 

iii.Double data entry: As the final step for quality control, all data were entered twice, by two different data

entry staff. Data were entered in two different files, then a validation test was performed using EPI-INFO.

The validation test compared the files and reported differences. When differences were observed, the Data

Manager checked the original record in question and corrected the data set appropriately. A total of 138 surveys were received as paper copies and entered in the EPI-INFO file. Once errors were fixed, the data was

transferred to STATA® format, and appended to the database that contained the data from the web. The

final data set contained 328 records.

Data Analysis

Statistical analysis was conducted using STATA®, Version 6. Descriptive, univariate statistics were generated 

for all survey variables. Bivariate analyses were conducted for all demographic variables by the other survey

variables, as well as for multiple other comparisons of interest. To evaluate differences in proportions, the 

Chi-square, Fisher Exact test (if fewer than five in cells) were used, and p-values were generated to evaluate

levels of statistical significance. Risk ratios and 95 percent confidence intervals were presented as the measure

of strength and direction of the association. Stratified analysis was conducted to identify confounding effect or

effect modification. Finally, multiple logistic regression models were used for multivariate analysis to predict

certain outcomes of interest.

B.2 Methods Used for the Study of Developing Country Researchers

The study involved collection of both qualitative and quantitative data from developing country researchers

with human subjects health research experience. The quantitative arm of the project was a (written) selfadministered survey. The qualitative data collection was a series of in-depth interviews and focus groups 

conducted with developing country health researchers. Both methods of data collection were reviewed and

approved by OMB under the Paperwork Reduction Act and by the Johns Hopkins School of Public Health

Committee for Human Research, the IRB of this division of the university.

Quantitative (Survey)

Slightly more than 500 developing country health researchers working with human subjects were invited to

participate in the survey, which was made available through a website that could be accessed by the researchers,

who were given individual identification codes. E-mail attachment and hard copy versions of the survey were

also made available to the researchers. The survey consisted of 9 sections with a total of 169 questions, covering IRB reviews; informed consent; relationships with collaborators; availability of interventions; ethical issues;

U.S. and international rules and guidelines; description of the researchers’ research studies (and experiences);

and their recommendations.

Qualitative

Eight in-depth interviews and six focus group meetings were held with researchers from developing countries.

They were questioned about their experiences with human subjects research regulations and with ethical issues

in their research work collaborating with the United States and other countries. Their recommendations for

change in U.S. regulations and policy concerning international research were also sought.
B-17

B.2.1 Quantitative Data Collection

Sample

In the process of identifying developing country researchers, the phrase “developing countries” requires explicit

definition. Although it is a widely used concept in international health discourse, this term has both very general

and specific meanings. In general, it refers to the group of countries marked by poverty, high burden of disease,

and poor socio-economic development. It is often used synonymously with less industrialized third world and

poor countries. Specifically, the term “developing country” may refer to an income-based social or demographic

definition that allocates a country in that category. Each of these definitions is available in the literature and has

its own perceived benefits. 

For the purposes of this study, a developing country has been defined using the criteria adopted by the

WHO’s Ad Hoc Committee on Health Research Relating to Future Intervention Options (WHO 1996), a global

effort to evaluate health research and development needs that represents an appropriate reference for purposes

of the current survey. The definition used by this committee was based on the demographic development of the

country, and this same definition has since been used in the Global Burden of Disease and Injury Study

(Murray and Lopez 1996) as well. A list of these countries is included as Appendix C.

Tens of thousands (if not more) of developing country health researchers work with human subjects. It is

neither possible to enumerate such a universe nor to assess it with a statistically representative sample. For the

purposes of this study, we intended to secure a “measurable universe” of developing country researchers who

could be expected to reasonably represent the true universe. A sample from such a list would then comprise

the sample for the survey.

Because no single database lists all such developing country researchers, multiple information sources were

used. A number of key organizations were identified based on their work with developing country researchers.

Information was then obtained from these organizations to construct a master list of researchers. These organizations included the following:

1. The International Clinical Epidemiology Network (INCLEN)

2. The Council on Health Research for Development (COHRED)

3. Scientists for Health and Research for Development (SHARED)

4. Health Systems Trust (HST)

INCLEN was originally an organization for clinical epidemiologists largely from the developing world, but

has since expanded to incorporate other sectors of public health. Members of INCLEN, especially those who

are faculty, are mostly involved with human subject research on health issues. Many of the members work with

international (including U.S.) collaboration and have established clinical epidemiology units that conduct 

continuing research in these countries. 

COHRED continued the work of the global commission of the same name, which put forth the concept of

“essential national health research.” It focuses efforts at the national level for the development and implementation of health research agendas in the developing world. COHRED staff come from the health research community and are usually active in human subjects research. A majority of COHRED’s database of approximately 

four thousand addresses are of researchers living in the Southern Hemisphere.

SHARED is a public-access repository of health research in the developing world. It contains information, by

country and topic, on health research projects in many parts of the developing world. It covers the description

of the project, personnel, collaborators, and funding sources. 

HST is an independent nongovernmental organization (NGO) in South Africa. HST focuses on research,

equity, and essential national health research and collaborates with international groups, including COHRED

and SHARED. A total of 31 researchers’ names were downloaded from the HST website, representing a relatively

small portion of the Master List.
B-18

Each of these organizations provides a different perspective to the database, contributing to the diversity of

researchers who have experience with laboratory, public health, behavioral, and clinical research. Together,

these organizations also provide a wide coverage of different regions of the world, all of them focused on the

developing world. 

Other organizations contacted include the Global Forum for Health Research and the WHO Special Program

for Research and Training in Tropical Diseases. Due to several constraints, their databases could not be used for

this study.

INCLEN, COHRED, and SHARED, the three major organizations from whom we obtained our list of

researchers (either directly or through their websites), were informed of the purpose of the project and of our

intent to disseminate the survey to their members. We received approval from all three organizations to contact

the researchers for the survey.

A master list was created from these databases after duplicate names, nonhealth researchers’ names, and

those without e-mail addresses were removed. If there were more than two researchers from the same department of the same institute or organization, they were randomly deleted as well. To our knowledge, this was the

first time such a list of developing country researchers had been constructed. 

For this study, all the developing countries were divided into three regions—Asia, Africa, and Latin

America—according to their geographical location. One of the goals of the study was to ensure adequate 

representation from all regions of the developing world. 

Survey Design

The survey instrument used for developing country researchers parallels the questionnaire developed for U.S.

researchers, with appropriate modifications. (See Appendix D.) It contains similar themes for which information

is requested from the researcher to enhance the comparability of the two surveys. 

The survey is divided into 9 sections with a total of 167 closed-ended questions and 2 open-ended questions

and covered the following topics: 

Section A Description of researcher’s experience 

Section B Description of a research index study and U.S. IRB review 

Section C Developing country IRBs and other ethical review 

Section D Consent

Section E Relationship with collaborators 

Section F Ethical issues in international research 

Section G Ethical guidelines and regulations in human subjects research 

Section H Recommendations 

Section J Researcher demographics

Survey Data Collection

In collaboration with the Johns Hopkins University’s Information Systems Department, a website version of the

survey was designed and tested. The U.S. and developing country surveys were first launched on the Internet

on November 18, 1999. All of the selected researchers were informed via e-mail about the survey, and each

researcher was given a specific ID code in order to log in. Completed surveys submitted via the Internet were

automatically sent to the Johns Hopkins University’s Information Systems Department and collected in a

Microsoft Access 2000 database. Those researchers who preferred to complete the survey as an e-mail attachment or as a hard copy version were provided with those versions.

A random selection of 350 developing country researchers from the Master List was first contacted via e-mail

to participate in the survey. Of these, 108 were returned undeliverable, and only 242 e-mail invitations presumably reached their destination. Due to the high volume of undeliverable e-mails and very poor response

within the first two weeks, the decision to sample the entire Master List was taken. Several weeks later, a second
B-19

batch of new 320 developing country researchers (the remaining names on the Master List) were contacted via

e-mail to participate in the survey, of which 84 e-mail invitations were returned undelivered. 

A reminder e-mail message was sent to all the researchers whose e-mail was delivered three weeks following

the first invitation to participate. In addition, the researchers were informed that e-mail attachments and hard

copies of the survey were also available. Regular monitoring of the incoming responses indicated that further

efforts would be required to reach a satisfactory response level. As a result, a decision was made to send hard

copies of the surveys to each researcher who had not yet responded to the survey (in any form, but not including those whose e-mails were undelivered).

Survey data collection occurred for five months (November 18, 1999, to April 17, 2000). During that time,

a total of 57 other additional developing country researchers were contacted to complete the survey. These

researchers were referred by U.S. researchers who were participating in the U.S. survey. Five surveys were also

completed by African researchers attending a Johns Hopkins international research ethics course in Malawi in

March 2000. A total of 540 researchers were contacted to respond to the survey.

Respondents were reimbursed U.S. $25 as an expression of gratitude for their time and effort in completing

the 26-page survey.

Confidentiality Procedures

The survey does not request respondents’ names, addresses, or institutions. Data collected are identifiable only

through assigned ID numbers. Names and mailing addresses at the end of the survey (required to mail the U.S.

$25 reimbursement) were separated from the completed surveys before data cleaning and data entry began.

Separate files were kept for reimbursement of the survey respondents. Likewise, personal information (names

and addresses) were separated from the surveys completed from the website before analysis began. Once reimbursements were completed, ID numbers were removed from the address database to prevent survey data from

being linked with individual survey respondents.

Statistical Analysis

Entries from the website surveys were stored in a Microsoft Access database, while hard copies of the surveys

received were entered into an EPI-INFO 6.04b database. Both of these databases were transferred and merged

using STATA® software. 

Data editing (cleaning) was done using STATA®. Surveys in which three or fewer sections were completed

were considered incomplete and were not used for data analysis. Codes were written in STATA® as “do” files

for data editing and to fix skip patterns. All data were entered twice by two separate individuals for crosschecking, and corrections were made as appropriate by checking original survey entries.

After removing those surveys that were considered incomplete, a total of 203 surveys were used for the

analysis. Overall, results from 37.6 percent of those invited to complete the survey were used as the final data

set (203 surveys out of 540).

Data exploration and interpretation were done through frequency distribution for each variable. Cross tabs

were run by 1) U.S.-funded studies, 2) educational status/profession of the researchers, 3) gender, 4) IRB 

membership, 5) employer, and 6) other variables of interest. To measure the strength of association between

different variables, Chi Square test and p-values were calculated. 

B.2.2 Qualitative Data Collection

Qualitative data were gathered regarding the opinions, experiences, and concerns of developing country investigators on the ethics of research involving human subjects. The primary purpose of this data is to provide

empirical evidence to support, illustrate, and potentially explain certain quantitative findings and to illuminate

areas of disagreement among respondents. This qualitative data will describe the range and depth of feelings

and attitudes of developing country investigators and provide context and dimension to the numeric survey

data. 
B-20

Data Sources

Three separate data sources are integrated in this analysis: 6 focus group discussions; 8 in-depth interviews;

and 78 responses to open-ended questions included in the survey questionnaires. Brief descriptions of these

data sources follow. 

The focus group discussions represent the primary source of data and were conducted from August 1999

through March 2000. A semi-structured field guide was developed by investigators and the research team to

cover all major topics of interest, including informed consent, local and U.S. IRB and ethics review processes,

specific concerns regarding ethics in research, and recommendations for improving review processes (see

Appendix E). The field guide was reviewed by and assessed for coherence and comprehension among

researchers from both the United States and developing countries. Project staff members trained in qualitative

data collection techniques facilitated each session. Facilitators covered all questions included in the field guide

and were also able to probe relevant topics or themes that emerged during the discussions that were of particular

importance to the study. An observer was also present in each focus group to take notes on the flow of discussion

and on participants’ reactions as indicated by their body language and facial expressions. 

In-depth interviews were conducted from August 1999 through March 2000 using a field guide similar to the

one used in the focus group discussions (see Appendix F).The interviewer covered all of the questions in the

field guide and also asked questions not included in the guide in order to probe particular relevant topics that

emerged during the interview. 

In both the focus groups and the in-depth interviews, consent was obtained using a written and signed consent form. Lunch and parking passes were provided for focus group participants, but no other compensation

was offered. Typically, the focus group discussions lasted 90 minutes, and the interviews took about an hour.

Responses to two open-ended questions appearing at the end of the quantitative survey are also included in

this analysis. These two questions ask the respondents to elaborate on any of the survey questions that they felt

required more detailed responses and to describe the changes they would make to the existing U.S. policies on

human subjects research. The responses were all hand written or typed directly onto the survey instruments by

the respondents themselves. 

Comments from the survey questionnaires have also been integrated into this analysis. These comments

generally addressed issues raised in the survey. In one case, the typed comments are actually responses to the

two survey questions previously described.

Sampling

Focus group and interview participants were identified through snowball sampling, a technique used in qualitative research where one or more informants are identified for the study and are asked to name others who

would be appropriate study participants (Bernard 1994). This technique is used in research among unique

groups of people who are likely to know one another. The only criterion for participant selection was that he 

or she have experience in research involving humans subjects.

Six focus group discussions and eight individual in-depth interviews were conducted. Two of the focus

groups and five of the in-depth interviews were conducted in Asia. The remaining four focus groups were held

in Baltimore at the Johns Hopkins University, and three in-depth interviews were conducted at the WHO headquarters in Geneva. All interviews and focus group discussions were tape recorded and later transcribed for

analysis using the textual data analysis software program, Atlas/ti®. Biographical data were collected from each

focus group participant to provide a demographic description of respondents, and this is included in the analysis.

The data described here are grouped into sections by major topic areas of discussion (Sections D.2 through

D.5). Specific codes for analysis were created based on these topic areas. Relevant recommendations suggested

by respondents are reported at the end of each section. A brief description of the demographic characteristics 

of focus group participants is included in Section D.1. All country names have been removed to protect the

identity of the respondents. References to specific countries have been categorized into one of three world

regions: Africa, Asia, and Latin America/Caribbean, and these appear in brackets. Text in brackets was also

added in certain quotations in order to clarify meaning. 
B-21

C. Results of the Study of U.S. Researchers

C.1 Description of Our Sample

C.1.1 Focus Group Participants

Seven focus groups were conducted in this study, with a total of 43 participants. Of these 43 participants, 

28 percent were employed by government, 21 percent by universities, 9 percent by the U.S. military, 37 percent

by private industry, and 2 percent by other types of institutions. A demographic data form was completed by

39 out of 43 respondents. Of these 39 respondents, 69 percent were men and 31 percent were women, and the

average age was 46. Seventy-seven percent of respondents currently had a research project in a developing

country, while 15 percent had a project within the last five years, and for 3 percent their last project was more

than five years ago. 

Researchers had an average of 8.2 years of experience working in developing countries and worked in an

average of 2.7 countries. Thirty-one percent described their role as principal investigator or co-investigator, 

44 percent were project directors, while 21 percent had other roles, such as administrator, medical monitor,

sponsor, or human subjects contact. Focus group participants used different research methodologies and/or 

disciplines in their studies; they could categorize their studies in multiple ways on our data collection form.

The majority (79 percent) conducted clinical trials, 38 percent used observational studies, and 31 percent used

community-based interventions, while fewer used behavioral studies (13 percent). More than one funding

source for studies often was checked. Funding sources included U.S. government funding (46 percent), U.S.

military (13 percent), U.S. private company (47 percent), U.S. nonprofit (8 percent), non-U.S. government

source (10 percent), and bilateral or international organizations, such as the Pan American Health Organization

(PAHO) or the WHO (13 percent).

C.1.2 Written Survey Respondents

A total of 966 researchers were contacted about the written survey, and 51 were determined to be ineligible to

complete it, because they did not conduct human subjects research in developing countries. Out of the remaining 915 researchers, 302 responded, resulting in an overall response rate of 33 percent. Ten submitted surveys

with fewer than three sections completed out of ten and were excluded from the final data set. An additional

26 completed surveys were received from project directors who responded after being offered a survey by a

principal investigator. The final data set consisted of 328 surveys. Table C.1.1 lists response rate by employment sector. As this table shows, the response rate is significantly lower for those in the private for-profit and

private nonprofit employment sectors. If these groups are excluded, the response rate is 39 percent.

More than half (63 percent) of the surveys 

were received via the project website; the remaining 

37 percent were received as paper copies.

Table C.1.2 lists the demographic characteristics 

of respondents. Thirty-five percent of respondents

were female, and almost half were in the 40 to 49 

age group. Respondents were also asked about their

research experience. The median number of years

researchers conducted research in developing countries was nine. Most researchers (67 percent) spent

more than half their time conducting research, and

55 percent had worked on at least five developing country projects.

Twenty-three percent of respondents currently or previously were members of an IRB. Most respondents 

(60 percent) had resided in a developing country for six months or longer at one point. Most respondents were

currently conducting research in a developing country (87 percent). Most of those who were not currently

working in a developing country had been involved in such a project within the past five years (70 percent).

Overall, only 4 percent of respondents had not been working in a developing country within the last five years. 

Table C.1.1: Response Rate by Employer

Number Response Rate

Government 136 51.2%

Military 25 54.2%

Private nonprofit 102 19.6%

Private for-profit 104 12.1%

University 598 34.2%
B-22

C. 2 Informed Consent and Disclosure

C.2.1 Disclosure and Documentation

Researchers in our study used a variety of methods

for informed consent and disclosure. Table C.2.1

lists all methods in order of likelihood of being used.

Seventy-six percent of the U.S. researchers in our

sample used written informed consent (requiring a

signature, thumbprint, or equivalent) in their studies.

However, 100 percent of those in the military and 

of the respondents who work for pharmaceutical/

biotechnology companies obtained written informed

consent, compared with approximately 70 percent 

of those in universities or other nonprofit private

organizations. Generally, researchers age 50 or older

were less likely to use written consent than younger

researchers (68 percent versus 81 percent, p = .02)

but were more likely to use oral consent and community meetings and to seek permission from a 

village leader. Researchers funded by any U.S. source

were twice as likely to use written methods as

researchers funded by other sources.

As can be seen in Table C.2.2, researchers were

more likely to use written consent with higher literacy populations, but even among the lowest literacy

population (defined as at least 80 percent of the

population is illiterate), 60 percent of researchers

still used written consent. 

Among those who did not use written consent,

92 percent used another method or methods

instead, including engaging in a question/answer

session with participants (69 percent), holding a

community meeting (51 percent), seeking approval

Table C.1.2: Demographic Characteristics

of Survey Respondents (n = 328)

Gender Percent

Female 35

Male 65

Age 

<40 22

40-49 47

>=50 31

Employer

University 62

Government agency 22

Private nonprofit research institution 8

Military 4

Pharmaceutical/biotech 3

Other 1

Degree

MD, DDS, MBBS, MBChB 52

PhD, ScD, DrPH, PharmD 51

MPH, MS, MA, MHS 46

Other 26

How many studies (total) in developing

countries have you been involved in?

One 12

2-4 33

5-10 27

>10 28

In what regions of the developing

world have you conducted research?

Africa 60

Asia 57

South America 37

Central America/Mexico 28

Caribbean 20

Pacific Islands 6

Other 6

Table C.2.1: Methods Used to Inform

Participants and/or to Document Consent

for the “Index” Research Project, in Order

of Likelihood of Being Used

Method % Who Used

This Method

Written informed consent, requiring a 

signature, thumbprint, or equivalent 76

Explanation and question and answer 

session with participants (either 

individually or in groups) 74

Community meeting to describe the study 44

Approval from a village or community 

leader 42

Oral consent with a witness signature 40

Test of participant understanding of 

research before enrollment 16

In research with adults, approval or 

consent from another family member 14

Pictorial description of study or study

procedures 7

Video to explain study 2
B-23

from a village leader (51 percent), obtaining oral consent with witness signature (38 percent), and seeking consent from another family member (13 percent). Even among those who obtained written consent, 89 percent

used at least one other method to explain the study. Seventy-five percent engaged in a question/answer session,

41 percent had a community meeting, 40 percent also sought oral consent with witness signature, 39 percent

sought approval from a village leader, and 14 percent sought consent from another family member. Female

researchers were 1.9 times as likely as male researchers to explain the study and engage in a question/answer

session with participants (p = .03).

Individual researchers volunteered through 

comments other methods that they used, including

obtaining consent only after a discussion had

occurred among family members; information sheets

for participants; stories in the local press about the

study; and a focus group discussion among potential

participants. One researcher described hiring a public

relations firm to develop posters and pamphlets to

describe their study and to deflect misunderstandings

about their study intervention. Many researchers 

also described in the survey that they had used oral

disclosure without witness signature to explain their

studies; therefore, our finding that oral disclosure was used by 40 percent of respondents is surely an underestimate, since our question asked only about oral disclosure with witness signature.

There was extensive discussion in focus groups, as well as in written comments on the survey, concerning

written consent. Some researchers described written consent as having an inherent tension in serving to protect

both the subject and the investigator and/or institution. Some researchers disclosed that their IRBs required

written consent. Others described the difficulties of writing consent forms that include enough detail to satisfy

U.S. regulations, but that are also written at an accessible reading level. Many researchers described negotiating

the consent form language back and forth between U.S. IRBs and host country boards, especially with regard to

the legal language and references to indemnity and health insurance typically required by U.S. boards: 

The stateside IRB and the NIH both expect consent forms that are narrowly delineated. And

the developing country...IRB doesn’t want anything to do with them. It’s an anathema. The

same way that the legalese, denial of responsibility for something that goes wrong is equally an

anathema....The United States, instead of acknowledging that, willfully signs on to consent

forms that have ten pages of legal jargon that many of us can’t understand in the United States,

let alone anybody overseas. So we constantly pervert the process with the conscious assent of

the NIH and our own IRBs. 

Fifty-two percent reported on the survey that legal language required on consent forms was not meaningful to study participants, although 37 percent also believed that local staff shortened consent procedures.

Researchers believed that staff were more likely to shorten consent procedures in lower literacy study populations than they were for populations with higher rates of literacy (45 percent versus 29 percent, p = .06). 

At the same time, one researcher described in a focus group the “intellectual and moral comfort” of having a

signed consent form from a participant; another said it was helpful in challenges from the media. In the survey,

29 percent thought the consent process raised distrust among participants, although 82 percent agreed that the

consent process creates a good opportunity to raise ethics issues among study staff.

In general, researchers voiced concern with a blanket requirement of written consent. One respondent wrote

the following in the comments at the end of the survey:

Table C.2.2: Literacy Rate of Population

by Use of Written Consent

% of Study Population % of Researchers Using

That Is Literate Written Consent

<20% 60

20-60% 67

>60-90% 82

>90% 86

n = 245; p = 0 .01
B-24

In [Latin American country], particularly those with limited reading ability are very hesitant

about signing things. This is not a procedure typically followed by native researchers. Our

insistence on informed consent was seen as culturally insensitive but was accepted out of

understanding of our needs to satisfy our funding agency and government regulations

(bureaucracy was certainly understood). More useful than this, I think, was the brochure we

created, complete with an official project seal, that described the project, the institutions, and

related services in the area that might be contacted. Also, afterwards, we gave each participant

a certificate which seemed to be quite appreciated.

A focus group participant revealed, similarly:

In some places, in some cultures, you don’t sign an informed consent. It really freaked them

out...once I wanted to enroll the patient for a tuberculosis treatment protocol. And I explained

to him that it was very straightforward. There is no placebo. And I could see he was profoundly

disturbed to sign the informed consent. And then he asked me, ‘When am I going to die?’ I

said, ‘Why are you saying that?’ ‘Well, you asked me to sign all these papers.’ And to him, it

was a sign that he was so ill that the written thing in the Muslim culture is something very

strong: It’s the will. It’s the testimony at the end.

Another researcher said his or her subjects were worried that signing would mean they could never immigrate

to the United States—that this would bring them to the attention of U.S. courts. Other researchers more generally voiced their belief that relying on written consent as the means to educate participants simply made no

sense:

So we get it translated into [local language] and back translated and it’s delivered. And we field

test it and we check it for its understandability, and we negotiate back and forth with [name of

institution] here first to make sure it’s acceptable to them. Then we send it out in the field and

we get lots of thumb prints and signatures on that page. And everybody at [institution] is very

happy...and the OPRR is happy with the way it’s read to the patients verbatim....But the

process is not clearly obtaining consent. 

Another respondent recalled an ethicist saying that it was unethical to attempt to extract a signed consent form

from someone who is marginally literate or illiterate, with a thumb print. The researcher went on to say, “We

need to drive that message home here. I think our IRBs overseas understand this issue much more clearly than

people do in the United States.” Others similarly described situations in which their U.S. IRB had required

written consent initially until the ethics board from the host country insisted that it was inappropriate locally.

Twenty-three percent of researchers believed the consent process is focused too much on the individual.

There were lengthy discussions in all focus groups about the efforts researchers made to educate the study

community prior to implementation of their projects. One researcher commented that U.S. IRB review focuses

too narrowly on the process researchers engage in with individual participants and generally overlooks the

extent to which they also engage in community-wide education and disclosure:

When things go through the IRB here, it’s a simplistic view of the whole consent procedure,

because we just write up what the individual is going to hear, and in fact one does so much

more. We do a lot more with the community education, discussion with community leaders.

You sort of go all of the way through the system and then the final thing is, when the person 

is going to get their intervention, you have this one-on-one interaction, but here is all of this

other stuff that surrounds it. You kind of say it in your application a little bit. But that process

doesn’t really get captured.
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Another researcher described his or her process for informing a community and discussing with a community a

potential research project:

From a moral perspective, unrelated to regulation issues...we spend an enormous amount of

time talking to communities well in advance of the study about what we’re going to do, what’s

involved, participation, nonparticipation, willingness to get involved, ability to say no. That

goes on both at the community level and the individual level at the time of the study. And 

we spend a lot of effort to hear what the community is saying and then to disseminate...

information at the end of the study about what the results were.

Another agreed that “the community discussion groups are actually providing a better level of ethical review

than some of the actual formally constituted IRBs.”

One researcher discussed the importance of having a local liaison, who is from the local community, but also

is educated and can communicate with researchers, to introduce the study to the community and to continue

to serve as a liaison throughout the study:

And they identified a local person who became educated but speaks the native languages and

grew up in the villages themselves. And all research is done through him. They actually call

him the master. They have a very high level of respect for this guy. You go with him to the 

village, and he formally greets the village chiefs. You see him perform a culturally defined 

give and take answers, asking them about their wives and their children, and has there been

enough rain and how are the locusts, etc., etc. And [he] moves over to the subject of research

and [it] is all done in a very culturally appropriate fashion.

In general, researchers said they wanted more flexibility. Informed consent was viewed as a valuable goal,

“trying to genuinely get people to understand what you’re doing so that they can make the right decision,”

but methods used to help participants understand and to document consent should be more flexible. Indeed,

85 percent of researchers agreed in the survey that U.S. regulations should allow more flexibility in ways of

documenting informed consent, a belief that was raised numerous times in the qualitative findings. One

focus group participant suggested a menu of choices from which investigators may select the most appropriate

methods for disclosure and documentation of consent.

From one setting to another, even within the same country, what makes sense in one place

makes no sense at all in another. The bottom line is that most of these issues need to be dealt

with on a case-by-case basis, and specific requirements as opposed to general guidelines are

likely to create unintended new sets of problems for international research. 

Another researcher wrote, similarly:

I would just recommend that they have more flexibility and regard for local norms and practices, think more about the spirit of the law rather than the letter of the law. The atmosphere

of paranoia that currently exists in the United States encouraging participants and regulators to

assume that investigators are dishonest predators until proven otherwise is not necessarily

something that needs to be exported.

Another recommended that the consent procedure be conceptualized as a communication process where materials and information are conveyed over time and in different formats. Overall, researchers should be required

to demonstrate that they “have a process in place designed to protect the subject,” not that they have a consent

form. Other researchers suggested that consent forms and consent processes be piloted. They suggested that a
B-26

small amount of grant funds be released before the IRB approval was complete in order to determine what will

work best locally. On the survey, 61 percent of researchers agreed that some research funds for piloting consent

forms should be released before final IRB approval is obtained. 

Generally, respondents thought the level of risk involved in study participation should determine the type 

of consent required. Several recommended a more informal, oral consent process for lower risk, observational,

or epidemiological studies: “I would not relax the requirements for testing potentially risky interventions like

vaccines and new drugs, but I would argue for considerable flexibility for epidemiological and observational

studies that pose very low levels of risk.” Related, essentially half (48 percent) of researchers agreed on the 

survey that “formal individual consent should not be necessary for observational studies.” At the same time,

respondents thought that whatever system is implemented, accountability must be ensured through monitoring

and site visits:

A key aspect of a safe study is having a site visit to make sure that the consent process is not

being inappropriately abbreviated, observe the procedures for confidentiality and to get feedback from participants. However, so much money and time are wasted on the bureaucratic

details that this is neglected.

C.2.2 Understanding

Eighty-seven percent of researchers believed that their study participants were aware they were in a research

study, although 57 percent thought participants did not understand the concept of a placebo. Not surprisingly,

77 percent of researchers working in lower literacy populations believed their participants did not understand

the concept of placebo, compared with 43 percent of researchers who worked with higher literacy populations

(p < .001). Regression analysis revealed that researchers are five times as likely to believe populations of low 

literacy do not understand the concept of placebo (p = .004) and were four times as likely to shorten consent

procedures with populations they believed did not understand the concept of placebo (p = .008).

Several researchers remarked on the difficulty of explaining placebos or control groups to participants, not

simply because there might not be comparable words in local languages, but because many populations have

no prior experience with such concepts:

Culturally it’s very difficult for them to understand how your doctor, who is supposed to want

good for you, could propose you to take nothing. It defeats the principles of medicine to some

extent. And you know you go a long way to try to explain that. And then the informed consent becomes very artificial when the very basis of the study design is not understood, and the

purpose of it is not understood. 

Western notions of science may be unfamiliar to participants. Frequently there are no words for “science,”

“research,” or “virus” in the local language. Researchers described the difficult process of explaining complex

biomedical information in ways that were relevant and meaningful to participants:

The concept of immunology, an immune response, that there’s something in your blood that is

going to attack bacteria and viruses which you also don’t have a concept for. I always wonder,

when you do a consent form, and you first are explaining the idea that there are these things

that are in your food and our air that you are ingesting, or you get from sex, and they are

coming into your body and invading it, and then your body has these things that are attacking

it. How much can someone really focus on the consent form, when they have this whole new

idea that there’s this battle going on in their bloodstream?....We try to use, for example like

immune cells, we talk about people who guard houses...it’s a particular kind of watchman [in

your body].
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Another voiced a similar sentiment:

Informed consent is a joke. It is not possible to claim a person who has never heard of a 

bacteria or virus is informed about what a vaccine or drug is doing or how their participation

fits into any such study. The protection these people have is only from a) the ethics of the

investigators; and b) the developing country review boards.

And another researcher wrote the following at the end of the survey:

Another [challenge] we are facing is the advances in science needing to be translated into 

consent forms (i.e., telling an African village that their blood will be used to analyze the 

parasites’ DNA for genetic mutations that confer resistance). 

Another researcher pointed out, however, that excluding subjects for this reason also has problems:

In many African languages, there is no word for ‘research’ or ‘science.’ The word used is generally the same as the word for ‘medicine.’ There is no concept of an experiment, placebos, etc.,

and despite the best translation of the most simply worded consent form, many adult subjects

still have no understanding of the difference between being a research subject and receiving

medical treatment. This should not be a reason to exclude these people from research; in fact,

they are often the population who will benefit most from the research and the only population

in whom the studies can be done, e.g., persons at risk of naturally acquired malaria or other

tropical diseases.

Many participants thought the informed consent process should focus more on participants’ understanding,

since they believed this was the core of informed consent. On the survey, 65 percent thought formal mechanisms to test participants’ understanding should be built into a study’s design, although only 16 percent

reported that they had included tests of understanding in their own studies. HIV/AIDS researchers were twice

as likely to use tests of understanding as other researchers (49 percent versus 24 percent, p = .001). In multivariate analysis, researchers with at least five years’ experience were three times as likely to use a test of understanding as those with less experience (p = .01). A focus group participant said: 

Maybe we should not be documenting consent, but documenting understanding of the 

consent process. What really might protect [institution] as an institution and funding agency 

is documentation that people participating in the study actually understand it.

C.2.3 Voluntariness and Decisionmaking

Seventy-two percent of researchers said that, after hearing about the study, some participants refused to participate. Female researchers were significantly more likely to report that some potential participants refused as

were male researchers (81 percent versus 66 percent, p = .009), and participants were more likely to refuse

participation in randomized (p = .005) or prospective studies (p = .003). Of some concern is that researchers

working with lower literacy populations were less likely to report that participants refused. Specifically, 81 percent of researchers working in higher literacy populations said some potential participants refused, compared

with 65 percent of researchers working in lower literacy populations (p = .01). Eighty-eight percent of

researchers engaged in studies they called more than minimal risk had some potential participants refuse, 

compared with 69 percent of researchers engaged in studies they called minimal risk (p = .07). In regression

analysis, female researchers were three times as likely to have participants refuse (p = .006), and researchers

engaged in more than minimal risk studies were four times as likely to have participants refuse (p = .04). Those

conducting randomized trials were 2.4 times as likely to have participants refuse (p = .03). However, literacy

was no longer significant in regression models. 
B-28

In terms of who made the decision about participation, 37 percent of researchers believed cultural norms

where they work are inconsistent with the practice of individual decisionmaking. Those working with Muslim

populations were more likely to report that cultural norms are inconsistent with the practice of individual 

decisionmaking than those working with other populations (46 percent versus 31 percent, p =. 01), as were

those working with populations practicing a local indigenous religion (44 percent versus 33 percent, p =. 05).

As stated above, 42 percent of researchers sought approval from a village or community leader for studies,

although our data do not show how integral this was to individual participants’ own decisions. Similarly, 

14 percent of researchers conducting research with adults sought approval or consent from another family

member. In regression models, researchers working with participants practicing a local indigenous religion

were four times as likely to say that the religious or cultural norms of the community were inconsistent with

individual decisionmaking, and those who had held a community meeting were 6 times as likely and those

who had sought approval from another family member were 12 times as likely to believe that cultural norms

were inconsistent with individual decisionmaking. Somewhat surprisingly, those who used pictorial descriptions

and those who sought approval from a village leader were less likely to say cultural norms were inconsistent

with individual decisionmaking. 

In focus groups, there was much discussion about the degree to which individuals made decisions independently and/or autonomously and the degree to which others were involved in decisions or made decisions

on behalf of participants:

In [African country] and in other areas of sub-Saharan Africa where I’ve worked, [informed

consent] is a communal process, and the last one who is involved is the family, the parent, and

by the time you’ve gone through the chief and the elders and the village, the process is already

well in motion....Their whole approach to decisionmaking is communally based...our IRBs

and the NIH both have no clue of this as far as I can tell.

Another researcher described a similar situation, but also emphasized that the individual remains an important

decisionmaker:

If you go to countries like [West African country], you have the chief of the village, of the

tribe....You can go to the individual after you have explained, and it takes a long time to 

educate these chiefs. Not to short cut them, that could be a mistake. To short cut the State if

you work in [Asian country] or to short cut the chief of the tribe [in Africa], but to respect this

hierarchy in this country and to educate them, to say that the individuals are important for the

pharmaceutical company or for our institutions etc. And you explain to them this informed

consent. Then they can explain this informed consent to their people without exerting pressure. And the best evidence of that is when the people refuse. That’s a good sign. They are able

to refuse, they are free to refuse.

Some researchers pointed out that leaders who are influential in decisionmaking do not always have the best

interests of their subordinates in mind:

Remember that those communities have internal hierarchies of sex and class, too, so that what

is in the leader’s best interests may not be in the individual men’s or women’s best interests.

Another researcher described conducting research in a political context in which rights were not guaranteed,

thus potentially compromising the voluntariness of research:

This concept of the consent of the individual, rights, and individual decisionmaking doesn’t

exist. And this is a country that has been under authoritative rule for a long, long time. And

people do what they are told, and people are told what to do.
B-29

Clearly, where one conducts research is relevant to the question of whom to approach for permission. One

researcher reported that in some settings, he or she had felt it imperative to go through village leaders; in other

areas, he or she had “laid low, trying to avoid the gaze of the community leaders and state or national politics.

Had we been noticed there, the tremendous corruption would have destroyed the study.” Another researcher

had a similar experience, and was troubled by it:

The [Asian country] government has basically told us that it is doubtful that we will receive

‘official permission’ to conduct our trial. However, it has become clear that they will not object

if it is done ‘clandestinely.’ We feel this is a real ethical dilemma (at least from the U.S.A. 

perspective), though it is not so viewed by our host collaborators. We have not yet made a

decision on how/where to go.

Finally, researchers believed economic realities of participants’ lives sometimes compromised the voluntariness of their participation:

If the patient has no other drug choices or has no drug choices, period, and you’re coming 

in with an acceptable drug, and you have a 50 percent chance of getting the experimental

drug...it’s very difficult to say that they’re making a true informed consent to participate in 

the study and they’re not just trying to get the drug.

Indeed, 68 percent of researchers believed that participants joined their studies “because of the desire for compensation, medical care, or other benefits.” However, only 10 percent of researchers reported their U.S. IRBs

had raised in the study’s review that voluntariness of participation could be compromised due to the incentives

or medical care provided by the study; 7 percent said the host country board had raised this concern.

C.3 Study Design, Risks, and Benefits

Because the ethics of a study are integrally related to its design, we asked researchers to describe what topics

they were studying in their research, what methods they were using, who comprised their sample, and why

they were conducting research in a developing country. We asked them questions about how much risk and

benefit they felt were inherent to their studies and the degree to which this was relevant to study subjects and

review boards

C.3.1 Study Design: Topic, Method, Sample, and Reason for Being in a Developing Country

In the written survey, respondents were asked to answer multiple questions about an “index study,” defined as

the developing country study on which they had spent the most time in the last five years. As can be seen in

Table C.3.1, these index studies most often were investigating questions related to infectious diseases other

than HIV/AIDS; to HIV/AIDS; or to reproductive health. Half of the researchers categorized their studies as

observational or descriptive, 28 percent said they were conducting randomized, controlled trials, and 13 percent were conducting a community-based intervention study. In a separate question, researchers were asked if

they were conducting an intervention study, and 39 percent said that they were. The majority of researchers

said the discipline of their study was epidemiology (67 percent), followed by behavioral science (18 percent),

and microbiology (17 percent). 

In order to explore the relationship between level of development of the host country and other variables of

interest, HDI data from the UNDP 1999 Human Development Report were added to the survey database.

These data are published by UNDP and are available on the UNDP website. The HDI indicator is a composite

of life expectancy at birth, adult literacy rate, combined enrollment ratio, and adjusted per capita income. This

development indicator was used in our statistical analyses to determine if there are relationships between level

of development of the host country and other variables of interest. Overall, most index studies (72 percent )

took place in countries with medium HDI scores1 according to UNDP, while 23 percent occurred in countries
B-30

with low HDI scores, and 4 percent were in countries with high HDI scores. An additional 4 percent

could not be classified because HDI values were not

listed for those particular countries. For further

analysis, the HDI levels of countries where the index

studies occurred were categorized as low or high,

using the 50th percentile of the HDI scores represented (0.632) as the cutoff point between low and

high. The topics of the index studies were associated

with the HDI level of the countries where the studies

were carried out. (See Table C.3.2.)

We were interested in why researchers chose 

to conduct their research in a developing country

and asked this question in some focus groups.

Researchers frequently mentioned a commitment to

addressing health priorities in developing countries,

including addressing diseases prevalent in the 

developing world and testing interventions that

would be affordable for those resource-poor 

countries that needed them. One researcher said:

And I would say for most of us in the

field the goal that we have is to prevent those [tropical disease] deaths.

That’s probably the ultimate humanitarian goal that we feel that motivates

us going to work in the mornings. So

we’re trying to develop a vaccine.

Researchers also mentioned the need to find a study

population that is appropriate to answer the particular research question at hand—in some cases, a 

population that has not had access to treatment 

previously:

We also look at incidence rates of HIV. I

think that’s what really pulled us into

[African country], is that there is such 

a great—a high incidence of HIV there,

it seemed like the right place to do

research. I think also there are considerations in terms of what types of patient

populations you are looking for....I

think also, in HIV we’re looking for

naïve patients, and most of the patients

in [African country], they are not

treated and they’re all available to us.

Table C.3.1: Location, Topic, Method, and

Discipline of Index Study (n = 327)

Study Location Percent

Africa 32

Asia 25

South America 14

Pacific Islands 10

Central America/Mexico 10

Other 6

Caribbean 4

Study Topic (Respondents could 

check more than one topic)

Infectious disease, non-HIV/AIDS 37

HIV/AIDS 27

Reproductive health 21

Cultural practices/behaviors 19

Chronic disease 15

Other 15

Nutrition 14

Genetics 13

Environmental health 12

Vaccine development/testing 9

Perinatal health/birth defects 9

Health systems/services 8

Injury 2

Study Methods (Respondents could 

check more than one method)

Observational/descriptive study 51

Prospective study 39

Randomized controlled trial 28

Case-control study 20

Qualitative methods 16

Operational research/program evaluation 15

Community-based intervention 13

Other 9

Study Discipline (Respondents could 

check more than one discipline)

Behavioral Science 18

Epidemiology 67

Microbiology 17

Clinical Care 14

Health Services Research 9

Other 28
B-31

One focus group respondent mentioned that procedural difficulties in obtaining U.S. government clearance

played a role in determining where she conducted her research:

You only work in select countries where you know you [have an assurance]. And you just

don’t even work elsewhere. That’s one of the big criteria I use nowadays when I’m trying to

decide where to do research, and that’s not the way it should be. Because, if anything, the 

people who need it most are the people you’re not going to.

Other researchers mentioned other pragmatic reasons as well. This researcher, from private industry, described

the need to balance the goals of his or her company’s marketing division with a need to complete the research

quickly, as well as a personal commitment to the ethical conduct of research: 

...the commercial folks will have their input, because from their perspective, the best premarketing of any drug is doing clinical trials. So from their perspective, they would like us to

use certain countries that they see has a good, you know, long-term outcome for the company.

Our perspective is a little bit different. We try to take their advice and want to try to help, 

but we’re looking at sites that can actually do the research ethically and can do the research

efficiently, because we tend to be guided more by timelines. If we say that we’re going to 

complete enrollment by X day, well, that might be nice to use country X, but knowing their

Ministry of Health systems or knowing how slow they are, that might be a blockade for us to

complete in a timely fashion.

Another pharmaceutical researcher was particularly candid about the reasons many private industry groups

conduct studies in resource-poor countries:

The vast majority of the trials I have done in the third world possibly are dose response trials.

Developing the profile of the knowledge on the drug to get profit and benefit elsewhere. That’s

extremely clear. There is not a question about that. I’m sure the simple fact that the pharmaceutical industry is a profitable business with all the drugs that we use just tells me that. It’s

not a charitable business. It’s a Wall Street hardcore business. And doing clinical trials in the

third world sometimes may be motivated by a variety of reasons. In general, the vast majority

Table C.3.2: Likelihood of Study Topic or Discipline Being Conducted in Host

Country with Low Versus High HDI Level

Lower HDI Upper HDI

Study Topic or Discipline (< 0.632) (> 0.632) P-Value

Infectious disease, non-HIV/AIDS 62% 38% 0.001

HIV/AIDS 64% 36% 0.002

Chronic disease 21% 55% < 0.001

Genetics 33% 67% 0.02

Environmental health 31% 69% 0.02

Health systems/services 71% 29% 0.03

Reproductive health 62% 38% 0.05

Perinatal health/birth defects 73% 27% 0.01

Behavioral science 66% 34% 0.005

Health services research 76% 24% 0.003

Qualitative methods 69% 31% 0.003
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is access to the patient in large numbers and a faster rate. And sometimes the third argument,

nevertheless, is also at a cheaper price....

In the survey, researchers were asked to select one or more options from a menu of reasons for conducting

research in a developing country as opposed to in the United States. As shown in Table C.3.3, the top reasons

why researchers conducted their studies in developing countries were that the prevalence of the disease in

question was greater in the host country (83 percent), researchers had an interest in addressing global inequalities in health (73 percent), the host country researchers asked for U.S. collaboration (72 percent), and the

intervention being tested was more relevant to the host country (70 percent).

Due to limited numbers of survey respondents from the private sector, it was not possible to do statistical

comparisons between the reasons of public versus private sector researchers. Comparisons among those who

listed their employer as government, university, or military showed little difference in the percentage who

answered “yes” to each of the reasons listed. Those conducting intervention studies were less likely to say that

their studies were relevant for U.S. strategic interests in the study region (21 percent, compared to 39 percent

for nonintervention studies, p = .0005) and were more likely to say that marketing approval for the drug/device

will be sought in host country (17 percent versus 6 percent, p = .017). Those with intervention studies were

not significantly different from those in nonintervention studies in their likelihood of checking “interest in

addressing global inequalities in health.”

The research topic, as one might expect, was associated with the reasons researchers gave for conducting

their research in a developing country. Researchers listed “prevalence of disease is higher” more frequently

when their study topic was infectious disease (95 percent versus 75 percent for noninfectious disease, p < .001),

and less frequently when their topic was chronic disease (60 percent versus 88 percent, p < .001) or genetics

(66 percent versus 76 percent, p = .002). Compared to those investigating other topics, researchers involved 

in infectious disease research were more likely to state “interest in addressing global health inequalities” as a

reason (80 percent versus 70 percent, p = .05), as were those doing health systems research (96 percent versus

71 percent, p = .013). Those studying chronic diseases were more likely to say the study is less expensive to

conduct in the developing country (63 percent versus 30 percent, p < .001). Those studying environmental

health were more likely to say it is easier to identify a cohort (79 percent versus 59 percent, p = .059), while

vaccine researchers were more likely to list marketing approval as a reason (40 percent versus 8 percent, p < .001).

Table C.3.3: Reasons for Conducting a Study in a Developing Country, in Order of

Likelihood of Being Mentioned (Respondents could list more than one reason)

Total Number Who

Reason Answered This Question % Yes

Prevalence of disease in question is much greater in the host country than 

in the United States 277 83

Interest in addressing global inequalities 263 73

Host country researchers asked for U.S. collaboration 260 72

Intervention being tested more relevant to host country than to United States 213 70

Easier to identify a cohort of patients relevant to research 218 62

Recruitment of patients more rapid in host country than in United States 219 47

Other reasons 166 47

Less expensive to do study in host developing country than in United States 214 36

Research question relevant to U.S. strategic interests in the region 234 32

Marketing approval for drug or device will be sought in host country 191 12
B-33

We further compared the reasons why researchers worked in countries with a low development index,

according to UNDP HDI indicators. Researchers working in countries with a low HDI level were more likely 

to explain why they work in a developing country in terms of the disease prevalence, relevance of interventions

to the population, and interest in global health inequalities, whereas researchers in higher HDI countries were

more likely to mention that marketing approval for an intervention would be sought. (See Table C.3.4.)

Forty percent of researchers admitted that the

research priorities of their funding agency were 

“not congruent with the top priorities of the developing country.” This did not differ by the HDI level 

of the country where they were conducting their

research. Thirty percent of U.S. IRBs and 23 percent

of host country review boards questioned the relevance of the study to the developing country. U.S.

IRBs were particularly likely to raise the relevance 

of the study to the host country for genetic studies

(43 percent versus 20 percent, p=.01). 

C.3.2 Assessing Risks and Benefits

Risk

In the survey, respondents were asked to categorize

the “index study” as minimal risk or greater than

minimal risk. Relatively few studies (12 percent) 

were described as greater than minimal risk; however, 24 percent of the intervention studies were classified as

greater than minimal risk, compared to 5 percent of the nonintervention studies (p < .001). Researchers who

used either randomized controlled trials or community-based interventions were more likely to describe their

studies as greater than minimal risk than researchers using any other method (29 percent versus 4 percent, 

p < .0001). Studies involving clinical care (29 percent versus 9 percent, p < .001) and randomized controlled

trials (28 percent versus 6 percent, p < .001) were more likely than other studies to be categorized as greater

than minimal risk, while observational/descriptive studies were less likely to be categorized this way (8 percent

versus 16 percent, p = .02). Eighteen percent of HIV/AIDS research was classified as greater than minimal risk,

compared with 9 percent of non-HIV research (p = .03). Greater than minimal risk studies were more likely to

be conducted in settings with lower background standards of care; 65 percent of researchers conducting greater

than minimal risk studies said the standard of care was lower in the host country, creating difficulties establishing

procedures for the control group, compared with 48 percent of those conducting minimal risk studies (p = .08). 

One focus group participant described the risks faced by potential study participants in a clinical study for a

serious illness:

And the first study I ever did, mortality was the primary variable, so I’ve done a number of

studies...where death is the primary outcome which jacks it up quite a bit in terms of its 

visibility. And right now, we are contemplating a vaccine trial...where death in infants was the

primary outcome variable. So that’s one type of study. [There are studies] where an adverse

outcome from the drug is a reasonable expectation and an adverse outcome from the disease

itself is a reasonable expectation....

Even fewer of the studies that involved children were classified as greater than minimal risk. Out of the 142

studies that enrolled children, 8 percent were classified as greater than minimal risk, compared to 15 percent 

of studies that did not enroll children (p = .05). Studies that enrolled children also were more likely to be 

Table C.3.4: Reason to Do Study in 

Two Categories of Countries Based 

on Human Development Index 

(HDI-1 lower half, HDI-2 upper half)

Reason To Do Study

in Host Country % Yes P- Value

HDI-1 HDI-2

Prevalence of disease is higher 92 74 <0.001

Intervention more relevant 

for developing country 83 52 <0.001

Marketing approval will 

be sought 7 17 0.027

Interest in addressing global 

inequalities 82 64 0.002
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conducted in lower HDI countries (57 percent were in lower HDI countries versus 43 percent in higher HDI

countries, p = .03), as were studies that enrolled infants (62 percent lower HDI versus 38 percent higher 

HDI countries, p = .007). Studies with infants, however, were no more likely to be classified as risky than 

studies with other populations. One respondent in a focus group commented that standards for doing research

with infants in another industrialized country were different from those in the United States. Whereas in the

United States, regulations require that greater than minimal risk research with children only be done when

there are potential benefits for those children in the trial, other countries may have different guidelines. Our

survey data do not include sufficient information for analyzing risk/benefit ratios for each index study, thus we

cannot assess risks and benefits specifically for studies involving children that were reported in the survey.

Forty-nine percent of researchers reported that the index study “gathered potentially sensitive or stigmatizing

information about participants (e.g., HIV status, domestic violence).” Researchers conducting work in lower

HDI countries were even more likely to say their studies gathered potentially sensitive information (57 percent

versus 43 percent, p = .01). Those studying HIV/AIDS also were more likely to gather potentially sensitive

information (91 percent versus 30 percent, p < .001), as were those studying cultural practice/behavior 

(71 percent versus 44 percent, p < .001), and reproductive health (67 percent versus 44 percent, p = .001).

One researcher described how serious a risk a breach of confidentiality could be:

Our [project] in [African city] is right next to the fever hospital, which is the big hospital of

fevers of unknown origin. Of course, anybody that’s HIV positive basically winds up there.

And we do the test for HIV positivity. If it comes back, the only person it goes to is, it must be

signed by [senior official of the research project]. And then it goes directly to the Minister of

Health, and then that person disappears. And it is very difficult...[HIV cases] are actually very

unusual in [African country] because there is very little because most of these people are taken

out of society...there is only one thing that happens; they go to jail, and they are not heard of

any more.

Another respondent commented at the end of the survey that his or her research involved collection of 

sensitive information that was sometimes questioned by study participants:

In general, this survey focused on medical research, specifically research on interventions or

drugs that might benefit the population. Most of my research is more behavioral or demographic in nature where sensitive questions are asked but there is not a specific intervention or

drug that can be offered to individuals. We frequently get questions from respondents about

why we need to know sensitive information, but without a specific treatment to offer them, I

don’t feel we can really respond. 

As described earlier, a trend was observed for more researchers engaged in greater than minimal risk studies 

to have some participants refuse enrollment, compared with researchers engaged in minimal risk research 

(88 percent versus 69 percent, p = .07). However, researchers engaged in studies where they gathered potentially sensitive information were no more likely to have participants refuse than other researchers.

Benefit

There are three types of benefits that might be provided in the context of a study: benefits to the individual 

or community during the study itself, provision of the study intervention or other benefits after the study is

over, and capacity building. The first of these, provision of benefits in the context of the study itself, will be

addressed here; the other two topics will be addressed in Section C.4, Obligations to Subjects, Communities,

and Countries.

Benefits provided directly to study participants may take several forms. The experimental intervention 

itself may be seen as a benefit, or the control intervention, if any, may be beneficial. Interventions provided to
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experimental and/or control groups may include treatment or services that generally are not available to individuals in that setting. Decisions concerning what to provide are related to the design of the study itself and

must satisfy both ethical and scientific standards. In addition, researchers in resource-poor areas often need to

make decisions about what benefits to provide to study participants that are unrelated to the study questions. This

latter type of benefit raises ethical questions about how much care to provide for unrelated health problems—that

is, what obligation researchers have to offer general care and treatment for humanitarian reasons. These benefits

differ in that they may not need to meet criteria for answering a scientific question, although, in some cases,

they too can affect study outcomes. Both categories of benefits can be inducements for potential participants to

join a research project.

Unfortunately, our survey did not include questions on what level or type of benefit researchers provided

during the study, although other questions related to benefit were asked. Overall, 63 percent of researchers 

and 74 percent working in low HDI countries reported that it was true or sometimes true that “medical care

provided to participants in this study generally is not available to local population outside the study.” Fifty-two

percent of researchers said that it was true or sometimes true that “the standard of medical care in the host

country may be much lower than that of [the] funding country, creating difficulties in establishing appropriate

procedures for the control group.” For studies in lower HDI countries, 64 percent agreed, compared to 36 percent

in higher HDI countries (p < .001). Those whose topic was HIV/AIDS were more likely than others to agree that

local standards made it difficult to establish control group procedures (71 percent versus 42 percent, p < .001).

In focus groups, participants discussed the challenges in determining how much medical care to provide to

participants. This arose in the context of determining what types of study interventions to provide to control

groups and also in determining what medical care to provide that was unrelated to the research question. 

Seventy-eight percent of researchers thought that standard of care issues should be decided on a case-by-case

basis, and many focus group participants thought that locally available care was appropriate for control groups.

Indeed, researchers in focus groups devoted much discussion to how they had grappled with establishing

appropriate procedures for control groups in terms of both scientific and ethics implications. In some cases,

researchers discussed how offering treatment to control groups makes it impossible to measure the outcome 

of interest—in this case, mortality rates:

Let’s say we develop a vaccine that can prevent death. Well, it has to be tested. We have to find

out, ‘Does it prevent death?’...So, we come into this knowing that without exception if we

bring simply a physician with [an effective drug treatment] into a community...we essentially

stop death due to [this disease]....So we cannot measure that end point if we intervene.

Cannot measure it. The [effective intervention] is easy; it is cheap. In the course of HIV you’re

dealing with major financial restrictions. But for us to field the physician, [the effective intervention], costs pennies or just relatively little. So we need to go into a village...we need to give

vaccine or some placebo vaccine or some other vaccine in a randomized way to several hundred or several thousand children. We have to just leave them and see what happens. Measure

the mortality rate. But with a very small amount of effort, we could prevent mortality altogether. We could prevent those children from dying. So I have no answers to this question,

but I would just put this out as a painful example of the kind of ethical dilemmas that we face.

In one case, a researcher described the study participants as being unwilling to participate in a controlled trial

because they believed the intervention to be efficacious:

We had some pilot data which suggested that putting an untrained volunteer to visit each

house once or twice a week just to look for kids who were sick would reduce the incidence of

severe malaria by 75 or more percent....And to nail that down, we wanted to do a control
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study. And the people in the village were so impressed by what was happening in terms of the

decrease in malaria, they said they would not permit a controlled study because they were

convinced this was efficacious, and they didn’t want us to do a controlled study in their village.

In survey comments, a respondent similarly addressed the tension between consideration of the needs of the

study population versus the need to gather adequate data to answer the research question:

Generalized rules may or may not apply under different circumstances. For example, when we

research in nutrition, it is very difficult to justify a ‘placebo’ given that nutritional deficiencies

are very common in developing countries where research is being done. However, there is a

need to determine if a nutritional intervention will have a measurable health impact on the

population or not, and whether nutrition programs should be based on adequate researchbased evidence of a benefit.

There was extensive discussion in focus groups about how researchers should determine how much medical

care should be provided to participants for conditions unrelated to the study topic. One researcher described

how he or she had received no guidance from the IRB on this and instead discussed it with host country 

collaborators: 

We were doing lead surveys, and we looked for anemia and side effects of lead, and you find

anemia and then you’re looking at parasite burdens. And where do you stop?...And as far as

the IRB is concerned, all you have to do, at least from our study, is refer them to what they

would normally have which is someone at the local clinic....We know the local clinic is not

going to do anything....Now we’re launching this whole parasite screening thing which is 

not part of what we were doing initially....We talked with our collaborators and said what’s

basically the right thing to do here....We decided we couldn’t leave these kids there with likely

huge parasite burdens.

In the context of HIV (or any other serious, chronic disease) the issue becomes only more complex, since 

any experimental or control treatments are needed for the long term. Thus, this researcher suggested that 

interventions that are short term and feasible should be provided during a study, but interventions that should

realistically be continued indefinitely after the study is over should perhaps not be provided if they would be

withdrawn when the study ends: 

A lot of times what they...I’m thinking specifically of the HIV issue. They [local IRB] don’t

want us to come in and start...offering something just for specific people in a research study

that they are going to get for three to six months and then have it taken away from them. It’s

different than, say, treating somebody with an obvious case of severe malaria where you’re 

benefiting them, and it may be a longer-term benefit. But to go in and give AZT for three

months...during the duration of a study and then walk away with it...what are you really 

providing for them?...a lot of times...they don’t want us to go in and interfere with what their

local norm is for that. I think in terms of treatment of the specific treatable disease, if the 

medication is available, and it’s really a resource issue, and we’re willing to provide the

resource...a lot of times...the local folks will come down...and say, ‘You’ve got the mechanism

to treat it, go ahead and treat it.’ I mean they do that in the [African country] studies where

they provide the anti-malarials free of charge if they identify somebody with it. It’s one of the

benefits to the study.

Another researcher described the difficulty in determining how much medical care should be provided for 

conditions unrelated to the research:
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If you make the diagnosis of something, what is your obligation to that individual? You may

be doing him a service by making a diagnosis, but are you obligated then to incur several

thousands of dollars worth of medical care and costs? Who is obligated to do what and where

do you draw the lines? Sometimes, depending on the situation, we’ve paid for care that we’re

sure is totally unrelated to the event, but the perception is still there, and as the investigator

that’s discretion that we have to be able to use.

Another focus group member, on the other hand, described following children with asymptomatic disease

without treating them:

The two aspects of those studies that are the most relevant, one, that human studies follow

children who are judged to be asymptomatically infected but they’re followed without treatment, which is, indeed, the national policy of that country and the policy of WHO for Africa,

but is quite at variance with the way most American IRBs would think of proceeding, [while

being] totally in line with [what] the African investigators think of following the studies of 

disease. But it does and has created tensions in the IRB review process.

This same respondent also mentioned providing medical care for study participants for unrelated medical 

conditions:

A second example which [another researcher] alluded to, is the big difference between a

restrictive focus on a disease which is so typical in the United States and Europe. I go in to

study abnormalities of the left toe, and if they are on the right toe, I ignore them. But if you 

go into a village and there are sick people, if you want to continue to work in that village, you

have to provide some recourse, especially if that village is in an area where medical care is

either totally unavailable or extremely hard to get.

Sometimes researchers performed health screening that was not related to the study question as a service to the

community: 

Another aspect of the studies is sometimes the studies involve children. We go into schools

and perform a school health survey and at the same time collect samples for them so it’s a

more extensive health screening than they would normally get. The results are provided to the

school health doctors, and they act on them, treat the children for parasites. We screen them

for parasites and other diseases, so there is an element of service that’s provided, and at the

same time we get the samples that we need.

That potential participants might be unduly influenced to join a study because of the study benefits was 

discussed frequently in focus groups. Virtually all the comments on this topic conveyed the message that study

participants do in fact join studies because of the benefits provided and that these studies generally provide

benefits that are not otherwise available. In the survey, 64 percent of researchers thought “participants join

because of the desire for compensation, medical care or other benefits,” while 33 percent thought that “participants have unrealistic hopes about personal benefit from participation.” Researchers conducting studies related

to HIV/AIDS were particularly likely to say their participants joined for compensation, medical care, or other

benefits (77 percent versus 60 percent, p = .005), and those in lower HDI countries were more likely to have

unrealistic expectations for personal benefit, according to researchers (60 percent versus 40 percent in higher

HDI countries, p = .023). Participants in riskier studies were also more likely to have unrealistic hopes; 44 percent of researchers conducting greater than minimal risk studies said that study participants had unrealistic

hopes about study benefits, compared to 28 percent for minimal risk studies (p = .039).
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The types of benefits vary from study to study. One focus group participant commented on changes in 

hospital care during his study:

I’m the chairman of the data management safety board and serve 1,500 children for a new

treatment for [infectious disease]. What happens—it’s happened to all of us, I’m sure—is 

you go in, you go into a community and based on the hospital record, the mortality rate of

[infectious disease] is 33 percent. The moment you go in there and you are doing certain

things, the mortality goes to 12 percent. The moment you leave, the mortality goes back up 

to 33 percent, so, of course, they’d be out of their minds not to participate in such a study

because the quality of care is completely different.

Another researcher commented that studies involving drug treatments were frequently the only means for 

participants to receive any treatment:

It must be very difficult from the patient perspective to give a truly independent informed 

consent when, in fact, what you’re consenting to is to take something versus nothing. Where 

is the choice? And I think you can’t fix that. You can’t make treatment available for everybody

so that your experimental agent is a truly deliberate choice where they have a real viable 

alternative outside of the study.

As will be discussed in the next section regarding obligations and justice, the question of whether or to what

degree the benefit to individuals in the study justified conducting the study in a resource-poor country was

raised by some researchers. This investigator, from a pharmaceutical company, believed that although his drug

would never be available to the country in the future, it provided significant short-term benefit to the individuals

who participated in the study, given that they otherwise had no access to therapies: 

I’ve come to the same level of acceptance, that is, if I look at what the alternative to going to a

country where only a small number of individuals who will actually participate in the study

will benefit. If the alternative is that no one goes to that country, that no one benefits, to me it’s

an easy choice. As long as the study is itself ethical and has appropriate safeguards and so

forth, I don’t...consider it to be exploitation of individuals to offer them something that some

would say well, it’s coercive because if you don’t go there, they get nothing. Because to me the

consequence or the logical conclusion is that therefore it’s more ethical for you not to go there

and let them die of their HIV.

C.4 Obligations to Subjects, Communities, and Countries

The previous sections addressed issues inherent to the ethical treatment of research participants before and

during study enrollment. This chapter will explore the obligations of researchers and sponsors to subjects and

communities after a research protocol has concluded, as well as the relationships of researchers with developing country colleagues. Three topics will be covered in this section: the degree to which interventions tested

and proven efficacious through studies should be made available to participants, communities, and countries

after the study is over—and under what conditions; collaborative arrangements between U.S. and developing

country researchers; and capacity building—the development of the host country’s capacity for conducting

research or delivering health care based on resources and skills gained through collaboration with the United

States.

C.4.1 Future Access to Interventions Tested in Studies

Thirty-eight percent of respondents overall and 47 percent working in lower HDI countries were conducting

intervention studies. A small number (5 percent) of respondents did not answer any questions about intervention
B-39

studies; this group when examined was significantly more likely to have fewer than five years’ experience 

working in developing countries, but was otherwise similar to those who did respond to questions about 

interventions in terms of gender, age, source of funding, and whether their study was completed or ongoing. 

Among those conducting an intervention study, 53 percent said their intervention already was efficacious,

11 percent said it was not, and 31 percent did not yet know. Researchers who said their intervention was 

efficacious or did not yet know were asked if they planned to provide the intervention, if successful, to any

groups within the host country at the conclusion of the study, or if they had already done so. The majority 

(67 percent) of those respondents who said that their intervention was, or might be, efficacious, said the intervention would be provided to “study participants or to any other host country residents at the conclusion of

the study,” while 20 percent did not know if it would be provided (see Table C.4.1). There was no significant

difference in the likelihood of providing the intervention for those researchers whose index study had concluded compared to those whose study was ongoing. However, those researchers who did not yet know if their

intervention was efficacious were less likely to say that it would be provided (52 percent versus 75 percent, 

p = .03). Of those who said they would provide the intervention, 9 percent said they would provide it for less

than one year, 35 percent said two to five years, 28 percent said more than five years, while an additional 28

percent said they did not know how long it would be provided. Forty-three percent said it would be provided

after the study was over to the study population, while 29 percent said it would be provided to the entire host

country. Researchers studying HIV/AIDS and researchers studying reproductive health were more likely to say

the intervention would be provided in the future than those studying other topics. Those who provided the

intervention, compared to those who did not, were more likely to say that one of the reasons for conducting

their study was “interest in addressing global inequalities in health” (85 percent versus 50 percent, p = .021).

Fifty-three percent of researchers agreed that “Research to test an intervention should not be carried out in a

developing country unless the intervention, if found to be successful, will be made available to that country at

the conclusion of the study.” It is of note, however, that those actually conducting an intervention study were

less likely to agree with this than those not conducting an intervention study (46 percent versus 58 percent, 

p = .04). In a different question, 27 percent of researchers believed that “international policy regarding research

should require researchers to establish a mechanism for continuing delivery of medical care after completion of

the study.”

The topic of future provision of interventions arose frequently in qualitative data. One researcher said at the

end of the survey: 

I agree with the notion...that formal steps be taken to insure certain actions after the study 

is completed (i.e., availability of drug or procedure studied to the study population/host 

population if benefit shown; reporting of findings to community; attempt to maintain or 

continue health services that were introduced to the community as part of the study, etc.).

Another agreed that benefits should flow to the host countries, but said that capacity building should occur

in all cases, in case specific interventions are not provided:

Simply put, the benefits of research conducted in developing countries should also be made

available to developing countries at affordable rates as soon as those benefits become apparent.

It would be very useful to make involvement of local researchers at any level available [and]

part of each research project in order to improve training and education, and therefore at 

the very least these educational...experiences may be the only benefits derived by the local

populations.
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Others, while agreeing in principle that interventions should be provided in the future, believed that, in

reality, this can be challenging. One respondent was concerned that a requirement for funding interventions

indefinitely would put a halt to some types of research projects, due to the difficulty in obtaining funds for

ongoing care:

And the issue of what medical care to provide after the study is a thorny one—research can

lead to suggested improvements in medical care but the funding of such improvements, and

building of the management skills required to implement them, cannot be the focus of the

research. This requirement means that for practical purposes, chronic illnesses cannot be

researched since no research funding agency would agree to fund the treatment indefinitely.

Table C.4.1: Provision of Intervention in the Future

Percent of Studies

Percent reporting the intervention was or will be provided, if successful, to study 

participants or to any other host country residents at the conclusion of the study. 67

To whom was (or will) the intervention be provided? 

(Respondents could check more than one option) Percent of Studies

Entire study population 43

Community from which the study population comes 42

Placebo or control group of study 29

Entire host country 29

Certain regions of host country 26

Other 14

What parties were (or will be) part of the arrangement to provide the intervention? 

(Respondents could check more than one option) Percent of Studies

Host country research team 71

Host country government, including Ministry of Health 60

Host country institution (e.g., university, NGO, clinical center) 46

U.S. research team carrying out this study 44

U.S. institution carrying out this study 28

U.S. funding agency for this study 22

International agency (e.g., WHO, United Nations Children’s Fund [UNICEF]) 21

Private for-profit company 10

Other 9

Private foundation 7

How was (or will) the intervention be paid for? 

(Respondents could check more than one option) Percent of Studies

Research grant for this study 35

International agency 29

Host country government 20

U.S. funding agency for this study 23

U.S. institution carrying out this study 20

Host country institution 17

Private for-profit company 12

Other 12

Private foundation 8
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Another researcher voiced a similar sentiment:

There is the issue of scope, in both place and time—for how long should the intervention be

implemented with outside assistance? Should it cover the original study population, the whole

country, or what? I feel strongly that only interventions which have a hope of being replicable

in the prevailing conditions should be tried in the first place—that’s where the economic work

should come in, and at the very beginning, not as an add-on. No research funding agency

would accept funding with a blank check for implementation of the intervention at the end.

The concern about funding was heard from another researcher as well:

These goals are usually but not always desirable if funding is available. No funding mechanism

that I know of will guarantee such action. Therefore this requirement would ban almost all

research in developing countries for whom it is the most beneficial even if many cannot benefit from the results. This is a case of best being the mortal enemy of good. I am very concerned

that this kind of ‘feel good’ regulation will constrain research that is useful to poor people in

developing countries.

Another respondent felt that researchers should not be the ones responsible for guaranteeing future access:

I don’t think that you can hold investigators responsible for the standard of medical care after

the study is over—however, there should be thought in design whether the intervention, if

effective, is feasible.

Another researcher also wondered about the limits of a researcher’s responsibility:

What is the horizon of responsibility of the investigator; is it specifically to those who are participating in a trial that the investigator is seeing on a regular basis and has personal contact

with, or does it go to all of the people in the community, all of the people with that particular

condition, and not only now, but in the future? So where does one’s responsibility lie?...We

were concerned about development of interventions that would be of value to the rest of the

community, to the rest of the country, perhaps to the rest of the world. I find these kinds of

situations very difficult to come to simple answers.

Another researcher voiced that future provision of interventions would be easier if drug prices could be lowered: 

I believe the issues of providing medical care and testing interventions in a developing country

that may never be available there is a complex one. I think the answer does not lie in prohibiting

research on interventions that will not be available but on changing the way drugs and other

interventions are marketed. The current flap about AZT in Africa is a perfect case in point—

the answer isn’t that we shouldn’t test AZT in Africa but that drug companies should not be

allowed to protect their huge profit margins at the cost of blocking a South African drug 

company from producing AZT at a cost that Africa can afford. Changes in IRB aren’t going 

to change the power of big business interests in the United States.

Another participant mentioned that successful interventions are frequently not implemented because of cost,

even when the cost is relatively cheap by U.S. standards:

There was actually a couple of years back a study from [African country] on use of bed nets

that demonstrated substantial reduction in under five mortality from use of impregnated bed

nets. The conclusion of the study was that this is a very nice study, but the [African country
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citizens] cannot afford to use bed nets. I found that distressing on almost every plain, but I

think it raises the fundamental issue of where are the ethics of equity within countries and

among countries; what are the cost issues, affordability issues?

Other researchers raised the more philosophical question of what defines “effective” in an intervention trial: 

The issue of what level of ‘effectiveness’ of an intervention should trigger replication of the

intervention has not been addressed. ‘Effectiveness’ is not a yes/no question. If an intervention

reduces transmission of say HIV by 10 percent, should it be implemented? What if another

intervention might produce a 15 percent reduction, but the researchers are obliged to implement the 10 percent effective intervention?

As described briefly in Section C.3, researchers working on HIV/AIDS studies faced complicated challenges

in providing care for their participants, because care for HIV needs to be ongoing, is expensive, and often

needs to be modified over time to adequately control the disease. Thus, an HIV study that provides drugs

invariably involves the question of what drugs will be available to participants after the study is over. One

researcher had reached an agreement for providing medications to study participants:

And the other thing is we are to negotiate, probably in [African country], one of the first

requests I got is meds for life for the participant. And of course, it’s not acceptable. Because it

could be completely considered as an incentive to participate in whatever the research. You

know, it’s like buying a patient basically for the rest of his life....And that creates an impossibility

on the budget side that we cannot afford to pay combination therapy for all the patients in the

clinical trial forever. On the other hand, you’ve really got to find a solution because you can’t

put them on a therapy that would be ridiculous and stupid and really not helping anybody. 

So that is a struggle....We basically reach an agreement and some of the investigators refused

and we didn’t work with them. We said, the rule was set a priori that we would supply the

medication for the patient and provide all medication and for an unlimited period of time as

long as [the drugs] work....And we define the criteria for what is a response. That means an

additional cost.

Another participant indicated that the local IRBs were opposed to providing HIV treatment that would be

withdrawn when the study ended. In contrast, short-term treatments for diseases such as malaria provided 

during a research study may be more effective and beneficial. Other researchers, however, believed that controversies surrounding HIV/AIDS therapies were an example of “AIDS exceptionalism” and that many other

interventions that would save many more lives, such as providing clean water to prevent diarrheal diseases in

infants, were not being advocated. 

One focus group participant described an example of research not being conducted because of concerns that

the treatment being tested would not be available at a later date:

We were going to look at an intervention using an [experimental drug] ...and we had made

arrangements to be able to provide antiretroviral drugs in those countries where they weren’t

routinely available, in this case [African country]. So the study design, those patients would

get antivirals, everybody, for as long as they were felt to be of benefit even beyond the study,

and that randomization would be to [experimental drug]. Well, the issue was, well, we’re not

sure that that is a treatment that would be available ever in that country, which is the type of

statement that people make without much perspective, I think, on how things do change over

time. In the HIV field we’ve heard this for CD4 counts, we’ve heard it for viral load monitoring. And then you see those things all come into place. So it’s sort of an anticipation of the
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worst case scenario that at times ends up with research not being done in a developing country that I think could be of value to the country, doesn’t put anyone at excessive risk, and, you

know, has the ability to learn about the big question much more quickly.

The same researcher felt that availability of the intervention was important, but that it was essential to recognize that there might be a time lapse between successful trial results and widespread implementation of the

intervention. His research team had made a commitment to provide treatment indefinitely to study participants

after the conclusion of the study:

I would feel uncomfortable if I thought there was no chance what we were doing would be of

benefit to that country. It doesn’t have to be a benefit to that country the day the study ends.

The day the study ends, though, I do think that all the participants in the trial should have the

benefit of whatever was found to be the best therapy....We had made provisions for them not

to just get [experimental treatment], but to get the [existing treatment] they were going to be

placed on...indefinitely. In the [African country] piece of the study, there was only going to be

300 patients. So we had arrangements of [pharmaceutical company] for [existing treatment],

we had arrangements with [another pharmaceutical company] for [another existing treatment].

We had done everything we needed to do. 

One researcher described submitting a manuscript for publication from an intervention study he had conducted in Africa. The editors of the journal to which he had submitted his paper challenged the ethics of the

study, stating that the population of the country would never have access to this drug and that the benefit of

the scientific knowledge would only accrue to the funding country, the United States. The investigator

responded to this criticism:

[Our response] was that the individual subjects who participate in this study did get benefit,

because part of it was in order to evaluate the drug, everyone needed to be treated with the

active drug to start with to clear up an infection and then they would have the protection from

symptomatic [disease] for some period of time after treatment before they get a new infection.

So everyone did benefit. And those who were randomized for the active [treatment] had 

continuing benefit for the 12 weeks for the randomized section of the study.

One respondent mentioned that in his or her study the “intervention” in question involved an enhancement of

medical services, which may be difficult to maintain after the conclusion of the study: 

Our ‘intervention’ involves case finding activities, more extensive lab work than is normally

provided, and the procurement of additional medication required to treat cases found.

Medication is provided through the same government system it is normally provided through.

However, it is my understanding that the involvement of researchers in normal public health

activities has resulted in increased efficiency of medication procurement. These ‘interventions’

are not the focus of the study, but merely provide the cases for study. However, the improvement in health care provision experienced by the local population is unlikely to outlive the

study....I’m concerned that the community will feel abandoned when the study ends and that

this will negatively impact their trust of the local public health system which has been providing

the enhanced services paid for by research funds. Also, study personnel have taken on reporting

responsibilities for the communicable disease involved. When the study ends, reporting is

likely to decrease dramatically unless the responsibility/awareness is thoughtfully transferred

back to local providers.
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In terms of dissemination of study findings, 62 percent of respondents believed that data from developing

country studies should be made directly available to the study population. In comments, one researcher

remarked that the form and manner of releasing data are significant:

Release of data to the subject populations is a meaningless ‘feel good’ activity unless it is

released to somebody who can use it for this or another similar population’s benefit, and it is

transmitted in such a form that it can be understood and is ‘actionable’ (identifies opportunities

for action). Releasing data to subjects in such a way that it may result in detrimental outcomes

to them or to others is not uncommon and is reprehensible. Thus, if data release is to be

required, the way this is to be done must also be required so that it leads to a useful result. 

C.4.2 Collaborative Arrangements

Researchers were asked about the involvement of host country researchers in different aspects of the research

process, from grant writing and study design to manuscript preparation and authorship of papers.

Table C.4.2 reveals that developing country investigators are very heavily involved in U.S.-funded research

projects conducted in their countries. At the same time, they are most likely to be involved in procedural tasks,

such as recruiting participants or obtaining consent, and are less likely to be involved in substantive issues,

such as grant writing and data analysis. One respondent noted, “I have observed that many American

researchers inappropriately exclude foreign colleagues from authorship. This engenders resentment among 

foreign colleagues.” However, survey data indicated that 97 percent of U.S. researchers did include developing

country colleagues as authors on papers. Another respondent wrote that developing country researchers were

often excluded from the more intellectual work:

Emphasis should be given to more input from researchers of developing countries involved 

in the study. U.S. investigators have all the power, since they had the idea for the study, they

wrote the grant....They therefore assume that they need to control all aspects of the study. It is

sometimes like a paternal-son relationship. Also, it is sometimes visible that the local investigator

is restricted to what he can do. The study sometimes will not teach them to become more

independent, to learn how to write their own grant, even a small one.

Researchers with fewer than five years of experience

conducting research in developing countries were 

less likely to involve developing country scientists in

almost all tasks asked about on the survey. Researchers

who were university employees were more likely 

than government or military employees to report that

host country scientists participated in grant writing

(62 percent versus 36 percent, p < .001). Those 

who were employed by public sector or nonprofit

institutions, compared to those in private for-profit

institutions, were more likely to include host country

colleagues in study design (89 percent versus 55 percent, p = .001) and in data analysis (73 percent versus

18 percent, p < .001). 

In addition, researchers whose projects received 

at least one source of funding from a developing

country, compared to those who did not, were more

Table C.4.2: Research Tasks in Which

Developing Country Scientists Were

Involved

Developing country researchers 

were/are included in the following 

research tasks: % Yes

Recruitment of participants 98

Training of research personnel 94

Listed as authors on papers 97

Changes in study design 94

Consent discussions with participants 94

Initial study design 87

Drafting manuscripts 83

Drafting consent form 82

Data analysis 69

Grant writing 53
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likely to include host country scientists in grant writing (77 percent versus 48 percent, p < .001), in study

design (97 percent versus 85 percent, p = .01), and in data analysis (85 percent versus 66 percent, p = .006).

Countries with higher HDI were more likely to have researchers included in grant writing (60 percent versus

47 percent for lower HDI, p = .03.)

Researchers in focus groups frequently referred to the importance of having a good relationship with 

developing country collaborators. Researchers repeatedly stated that addressing ethical and cultural concerns 

in their research could only be accomplished successfully if a healthy relationship existed between the United

States and host country scientists: 

The people you work with is the most important thing to getting anything done overseas. If

you wanted to do something, and you go there and you say, ‘I want to do this,’ I mean, that’s a

hopeless situation. You have to—it’s a long-term—it’s certainly not a short-term thing. It takes

a long time to develop relationships and understanding and trust and all those sorts of things.

That’s been invaluable in what we’ve done.

Another said, similarly:

It has to be a collaboration. You have to go into the country, get some sense of the country, get

some sense of who you feel comfortable working with in the country and what the norms are

in it. And once you do that, then it is very easy, because you basically hand off a lot of things

to the people in the country.

C.4.3 Capacity Building

Ninety-four percent of respondents reported that at least one “capacity building” resource remained in the host

country after their index study was over. Table C.4.3 lists which resources investigators said remained in the

host country.

Studies conducted in lower HDI countries were

significantly more likely to leave behind medical, 

laboratory, office, or pharmaceutical supplies; buildings and other facilities; and power equipment, water 

systems, or motor vehicles. 

Studies funded by the U.S. government were more

likely to leave behind computers or data management

systems. Studies with any source of U.S. funding

were more likely to leave behind “power generating

equipment, water systems, or motor vehicles,” and

those with any source of funding from the developing

country were more likely to report that a health care

or research infrastructure will be left behind.

One researcher mentioned that there are sometimes economic benefits to the entire community

where the study is situated:

Table C.4.3: Resources or Research

Infrastructure That Will Remain After 

the Study Has Ended

Percent 

Resource of Studies

Personnel trained in study 98

Medical, laboratory, or office equipment 90

Computer or data management systems 80

Medical laboratory, office, or 

pharmaceutical supplies 78

Organizational structure for health care 

or research 68

Buildings, laboratory facilities, or 

renovation 50

Power equipment, water systems, or 

motor vehicles 43

Other 12
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We’re just doing a study in [Asian country] in some God forsaken spot in the middle of no

place. We’re hiring everybody. We’re building a place to do that. People are getting income

during that period. That’s coercion. It’s positive. It’s positive for them...you are inducing them

to do this for reasons that are independent of the execution of the study, but if you go away,

their life is going to be worse.

One researcher, finally, believed that part of capacity building should be helping to enhance host countries’

capacity for ethics review:

I think it’s a good thing to promote ethical review of research in all countries, and if they 

don’t have that capacity, to develop that....What I’m saying is make an offer for capacity building—we do it with everything else. That’s part of it, is try to do capacity building technology

transfer...a bilateral partnership so that both parties are educated about issues for both sides.

C.5 Review and Oversight

C.5.1 U.S. Review of Research

Ninety-one percent of researchers said their studies had undergone review by a U.S. IRB. The majority of 

studies (63 percent) had been reviewed by one IRB, and the remainder had been reviewed by two or more

IRBs. For 42 percent of researchers, it took at least three months to receive approval from the IRB. Nine percent

of researchers reported having ever abandoned a research project because it was impossible to get U.S. IRB

approval, despite modifications.

Although more than 90 percent of researchers underwent IRB review in the U.S., only two out of the nine

pharmaceutical researchers surveyed had their studies approved by a U.S. IRB. However, 100 percent of 

pharmaceutical researchers, as described below, underwent both Ministry of Health and ethics board review 

in the host country, and 100 percent, as described earlier, used written informed consent in their studies. One

hundred percent of researchers from the U.S. government and the U.S. military had their studies reviewed by 

a U.S. IRB. Tables C.5.1 and C.5.2 show whether a study underwent U.S. IRB review according to the

researcher’s employer and the study’s sponsor.

Table C.5.3 lists the issues raised in review of studies by U.S. IRBs. U.S. IRBs were most likely to raise the

need for local language consent forms (66 percent) and letters from developing country officials (65 percent).

Close to half (45 percent) also asked about the cultural appropriateness of study procedures, and 30 percent

raised the relevance of the research to the developing country. Only 4 percent questioned whether the study

was too risky. These numbers already exclude studies for which researchers said the issue (e.g., placebos) was

not applicable. However, what our data cannot discern is whether IRBs did not raise a topic when applicable

because researchers had addressed the issue adequately in their protocol submission or because the IRB overlooked it.

Table C.5.1: Percent of Studies Undergoing Review by U.S. IRB, Host Country

Ministry of Health, or Host Country Ethics Board, by Researcher’s Employer

Reviewed by Reviewed by

Reviewed by Host Country Host Country

Employer U.S. IRB Ministry of Health Ethics Board

University 91% 72% 84%

U.S. government agency (nonmilitary) 100% 86% 97%

U.S. military 100% 100% 92%

Pharmaceutical/Biotech 22% 100% 100%
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Researchers engaged in certain types of studies or in certain contexts were more likely to have particular types

of issues raised in U.S. IRB review. For example, the 12 percent of researchers engaged in studies they classified

as more than minimal risk were more likely to report whether their U.S. IRB raised whether the intervention

was too risky (18 percent versus 2 percent, p < .001), appropriateness of procedures for the control group 

(35 percent versus 15 percent, p = .02), the use of placebos (32 percent versus 7 percent, p <.001), whether

voluntariness would be compromised because of the benefits provided (25 percent versus 8 percent, p = .005),

the relevance of the research question to the developing country (59 percent versus 27 percent, p < .001), the

availability of the intervention after the study was over (52 percent versus 17 percent, p < .001), the complexity

of the language on the consent form (66 percent versus 42 percent, p = .01), and the need for a local language

consent form (84 percent versus 63 percent, p = .02). Similarly, those conducting randomized trials were more

likely to be asked about the use of placebos, the availability of the intervention after the study was over, and

the complexity of the consent form. Studies focusing on HIV/AIDS or on vaccines also were more likely to be

Table C.5.2: Percent of Studies Undergoing Review by U.S. IRB, Host Country

Ministry of Health, or Host Country Ethics Board, by Source of Funding of Study

Reviewed by Reviewed by

Reviewed by Host Country Host Country

Source of Funding U.S. IRB Ministry of Health Ethics Board

U.S. government (nonmilitary) 97% 74% 89%

U.S. military 100% 100% 95%

U.S. private company 91% 86% 95%

U.S. non-profit (foundation, NGO, etc) 91% 73% 71%

Bilateral or international organization (United 

States Agency for International Development 

[USAID], WHO, UNICEF, PAHO) 88% 91% 85%

Table C.5.3: Percent of Researchers Reporting Issues Raised by Their U.S. IRB(s) and

by the Developing Country Ethics Boards in Order of Likelihood of Being Raised

Raised by

Developing

Raised by Country Ethics 

U.S. IRB(s) Board(s)

Issue % Yes % Yes 

Need for local language consent form 66 50 

Need for letters of approval from developing country representatives 65 31 

Complexity of language on consent form 45 38 

Cultural appropriateness of study procedure 48 29

Relevance of research question to country where research is conducted and/or rationale 

for doing study outside the United States 30 23 

Availability of intervention (if successful) to host country after study is over 23 25 

Appropriateness of procedures for control group 18 17 

Confidentiality protections for participants were not adequate 14 8

Use of placebos 12 12

Participant voluntariness may be compromised because of benefits study provides 10 7

Political considerations 7 14 

Intervention was considered too risky 4 4
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asked about the availability of the intervention after the study was over, and vaccine researchers were also more

likely to be asked about the cultural appropriateness of study procedures.

Researchers reporting that they worked in areas where “the standard of medical care may be much lower

than in the funding country, creating difficulties in establishing appropriate procedures for the control group”

were indeed more likely than others to be asked by their U.S. IRB about the appropriateness of procedures for

the control group (30 percent versus 14 percent, p = .02). Researchers were more likely to be questioned about

the cultural appropriateness of study procedures for studies where they believed that religious/cultural norms

of the population were inconsistent with individual decisionmaking (57 percent versus 44 percent, p = .02). 

Only 20 percent of index studies had Data Safety and Monitoring Boards (DSMBs). Studies classified by

researchers as greater than minimal risk were significantly more likely to have DSMBs (50 percent versus 

15 percent, p < .001), as were those funded by a U.S. pharmaceutical company (50 percent versus 17 percent,

p < .001) or a European pharmaceutical company (72 percent versus 18 percent, p < .001). Randomized 

controlled trials, logically, were more likely to have a DSMB (55 percent versus 4 percent, p < .001), as were

studies involving clinical care (35 percent versus 17 percent, p = .008). Almost half (45 percent) of those with

DSMBs said the DSMB had raised ethics issues in their reviews, but there was no significant difference between

greater than minimal and minimal risk studies in the likelihood of ethics issues being raised. Studies in lower

HDI countries, however, were more likely to have ethics issues raised by DSMBs (76 percent versus 44 percent

for upper HDI countries, p = .03). 

Thirty-two percent of researchers said U.S. regulations were never flexible when they needed to be, and 

only 2 percent said they always were flexible when they needed to be (Table C.5.4). Almost all respondents 

(94 percent) said U.S. IRBs sometimes or always were insensitive to local cultural norms, and 66 percent said

U.S. IRBs sometimes or always were more concerned with politics than with protecting the interests of subjects;

and yet 97 percent said that current U.S. regulations sometimes or always ensure high ethical standards.

In written comments and in focus groups, researchers requested more flexibility in requirements from 

their U.S. IRBs and better education of IRBs to the conditions and realities of life in a developing country.

Representative of so many researchers, one respondent said, “I think IRB chairmen should be required to do

international site visits so they can see the realities of what they ask!” Another said:

The IRB guidelines at my university are so narrowly defined that they didn’t apply in any way

to developing countries. I don’t think there was a single member of the committee who had

ever been in a developing country. They wanted me to include a phone number people could

call with complaints when the closest phone to my project site was an hour’s drive through the

mountains and my subjects didn’t have cars. The members of the Board had no clue how to

make adaptations for people who can’t read or write. It was a joke.

Another researcher similarly described being required to include the phone number and name of the chancellor

of his or her university. Still another said: 

The U.S.-based IRB that I must use has essentially no experience with conditions and realities

of life, medical care, and research in developing countries. Their actions often seem more

focused on avoiding potential litigation than on protecting research subjects and very often

make decisions that perpetuate bad public health situations overseas because of a poor 

understanding of realities.

One focus group respondent said, similarly:

I would say most of the people who are [on] IRBs here have never put their feet in those countries. They really don’t know anything about the real life in these countries....If the target is to
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improve the welfare of these people, we have probably to find some compromise and be more

flexible between the concept of the individual rights and the feasibility not to miss the target in

the field with different cultures.

Indeed, some researchers suggested that the lack of flexibility actually impedes public health: 

Institutional IRB regulations are quite strict and many times impossible to meet. This has

caused many studies to not be conducted in developing countries....My feeling is that we 

have gone too far into rules and regulations and that many studies benefiting study groups 

are being abandoned because of the strict regulations. In the long term it is people like those

included in a study population...that suffer, because the research is not being conducted.

Some researchers wanted more flexibility regarding particular requirements that originate in the United States

but that they feel are inappropriate in developing countries. One example was provided by a researcher in a

focus group of his U.S. institution requiring pregnant women to have the father of the unborn child sign a consent form for the woman’s own HIV testing. The alternative, according to the U.S. IRB, was having the woman

sign a statement that this researcher felt was no better:

To raise this issue, you know, to have a woman sign ‘this child’s father is not reasonably 

available or the child is a product of rape,’ or I forget the third one, is really pretty bizarre.

Particularly if you’re talking about HIV testing where in some countries that’s a really big deal.

You don’t want your husband to know that you are getting HIV tested. There are real consequences for the woman for that. It’s really inappropriate for us to be really forcing that issue.

C.5.2 Host Country Review

Seventy-seven percent of researchers reported that their studies had been reviewed by the host Ministry of

Health and 87 percent by a host country ethics board. Of those reviewed by a host country ethics board, 84 percent were reviewed by the ethics board of the collaborating institution, 51 percent by a national board, and 16

percent by a state or provincial board. See tables C.5.1 and C.5.2 for a comparison of which boards reviewed

respondents’ studies, by the respondent’s employer and research sponsor. Only 5 percent of studies overall

were not reviewed in the host country by either the Ministry of Health or an ethics board. However, 12 percent

Table C.5.4: Researchers’ Beliefs/Attitudes about U.S. and International Human

Subjects Regulations and Guidelines

Options %Always %Sometimes %Never

U.S. human subjects regulations are flexible where they need to be. 2 65 32

Developing country collaborators rely on U.S. ethics regulations for guidance. 13 78 9

U.S. IRBs are more concerned with politics than they are with protecting the interests 

of research subjects. 10 56 34

The current U.S. rules and regulations governing human subjects ensure high ethical 

standards in research. 27 68 3

U.S. IRB regulations are insensitive to local cultural norms and traditions outside 

the United States. 20 74 6

Developing country IRBs are more concerned with politics than they are with 

protecting the interests of research subjects. 3 76 21

Developing country IRBs have voiced concerns to me about the costs associated 

with the IRB carrying out its work. 6 20 74

National guidelines in developing countries are effective in protecting research subjects. 9 86 5
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of studies funded by a U.S. or developing country nonprofit or NGO were not reviewed by either the host

country Ministry of Health or a host country ethics board. All researchers whose studies were not reviewed by

either the Ministry of Health or a host country ethics board were employed by U.S. universities. U.S. pharmaceutical company researchers were significantly more likely to have had their studies approved by a national

ethics board than other researchers (78 percent versus 49 percent, p = .03) and were slightly more likely to

report that host country review was required for them. Researchers believed 29 percent of the time that the

developing country ethics board had been established because of U.S. human subjects regulations. Half of the

studies took two months or less to be approved in-country, although 12 percent took more than six months to

be approved by local boards. Six percent reported having ever had to abandon a research project because it was

impossible to get developing country IRB approval, despite modifications.

Table C.5.3 shows which issues were raised by the host country ethics board. Issues most likely to be raised

were whether there was a local language consent form (50 percent), the complexity of the form (38 percent),

the need for a letter of approval from the host country representative (31 percent), and the cultural appropriateness of study procedures (29 percent). In general, each possible review topic was less likely to be raised by

the host country board than by the U.S. IRB, according to researchers. The exception was the issue of availability

of the intervention after the study was over, which was equally likely to be raised by host country boards and

U.S. IRBs. Host country boards were most likely to question future availability for HIV/AIDS and vaccine studies.

Political considerations also were most likely to arise with HIV/AIDS and vaccine studies. Researchers engaged

in genetic studies were more likely to be asked by host boards about the relevance of the research question to

the developing country (24 percent versus 10 percent, p =.008), and researchers working on perinatal health

issues were more likely to be questioned by host country boards about their confidentiality procedures (25 percent versus 7 percent, p =.02) and about whether voluntariness could be compromised because of benefits 

provided (36 percent versus 7 percent, p < .001).

Whereas, as described earlier, studies classified by researchers as more than minimal risk had more issues

raised in U.S. IRB review than did lower risk studies, the only issue raised more frequently in developing country review for more than minimal risk studies was the use of placebos (25 percent versus 9 percent, p =.02). 

Respondents recognized the importance of local reviews, particularly with regard to their ability to raise 

concerns about cultural issues, and 77 percent thought a developing country ethical review should be required

for all studies. Overall, 95 percent of researchers believed national guidelines in developing countries are sometimes or always effective in protecting research subjects. Researchers in focus groups also voiced their belief

that local boards were in the best position to make ethical judgments regarding the welfare and needs of their

communities:

As much authority as possible should reside in local ethical review boards. Our [Asian country]-based ethical review board that has members from the Ministry of Health and general 

citizenry is vastly more qualified to pass judgment on a protocol to be executed in [Asian

country] than a U.S.-based committee.

This same respondent added that local boards also may be more likely to consider the relevance of the study to

their country’s health priorities.

These host international review boards are often interested in supporting research that is relevant to their perceived needs, and they’re suspicious of studies which...may be to study some

sort of drug which the local people of that country will not be able to purchase.

Researchers questioned the success of host country IRBs having community representation, however. In the

survey, 50 percent of researchers thought there was inadequate community representation on local ethics
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boards. We heard similar comments in focus groups, often emphasizing that in some countries, persons of 

differing backgrounds and/or class are unaccustomed to interacting with one another:

OPRR expects that the IRB...at least have some representation of the community in which

you’re going to do studies. And traditionally in institutions’ committees, whether they be IRBs

or other types of committees in institutions in a place like [Asian country] are usually made up

with people who run the thing or they’re well-to-do/upper middle class community, and not

necessarily representative of the lower class in the communities in which the studies are being

done. And there’s some resistance and some confusion about our insistence that there be 

representatives of commercial sex workers and STD patients sitting in the same room with

each other, first of all and secondly, I’m sure the group dynamics in that situation, even with

representation of the community at risk would make you wonder whether there’s true representation, even if they’re sitting at the same table, or whether they feel comfortable expressing

their views.

Overall, researchers had varying experiences with host country IRBs, and several remarked how, in the years

they have been conducting research, host country reviews had evolved from being a stamp of approval from

one authority, such as the Ministry of Health, to a more rigorous and structured committee process. Still, just as

researchers reported that they thought U.S. IRBs needed to learn more about the realities of life in developing

countries, they believed host country IRBs needed to learn more about ethics. Ninety-one percent said developing country collaborators sometimes or always rely on U.S. ethics regulations for guidance. In a focus group,

one participant said:

I would like to see more initiative in development and implementation of ethics education and

training in developing countries. The dialogue on this is dominated by the United States. It is

not up to us to determine what is best for them.

One respondent suggested that a training grant could be established for academic institutions to work with

local IRBs to provide education, training, and general IRB support. One researcher said, “Some of them do

really quite a decent job, just as you would want them to be. And there are others that are completely rubber

stamps, and nothing else....Yes, there’s an IRB, [but] I don’t have any faith that there was any real review.” One

was quite concerned by this:

[Local IRB members] may be people that are not all equipped intellectually, culturally, scientifically to deal with the issues you are asked to deal with. And therefore, you introduce a false

sense of security and conformity with the rule, with the letter, when the spirit is actually

vacant.

Another researcher said:

In some cases, the developing country ethical review is actually a process of seeking permission to conduct research, and no ethical questions are raised at all. Developing country review

boards are often more concerned about the financial aspects of the study than about ethics.

Another researcher reported that in the country where he or she was working, there still was no IRB, and the

Ministry of Health believed that ethics review was not important. Thus, “our approval came in the form of a

letter from the Director of the Division of Epidemiology and no IRB process was undertaken.”

In the survey, 79 percent of researchers believed that developing country IRBs sometimes or always are 

more concerned with politics than they are with protecting the interests of research subjects. Another voiced

the following concern:
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Some of the potential risks/ethics violations or cutting of corners can be perpetrated by collaborating investigators in other countries because the incentives to them (status, publications,

foreign travel) to get the data collected are substantial enough as to be coercive. I don’t know

how policies and regulations could be written around this problem but I think it is not a trivial

issue.

By contrast, another researcher had a different experience:

Our current project in [African country]...they didn’t have an IRB, but they made an IRB

according to the NIH guidelines, and I was afraid that it was going to be a rubber stamp, but it

turned out they had questions.... They actually raised issues and had questions that we had to

address, and it was healthy....I think going through an IRB review establishes questions and

then going through the process provides a cover for us and for that institution in case some

kind of trouble occurs.

Twenty-six percent of researchers reported that developing country IRBs have voiced concerns to them about

the costs associated with the IRB carrying out its work, and 70 percent believed funding agencies should 

provide funding to support the work of developing country IRBs. One researcher said:

Foreign IRBs have no budget and will tell you, why should they use their time to meet U.S.

OPRR regulations when no funds are provided for salary, secretarial, DHL, office, notification,

etc?

Some researchers, however, were concerned about potential conflicts of interest when providing funding for the

host country IRB. One researcher described his or her experience: 

Our research group has borne the responsibility for developing and maintaining an IRB in

[Caribbean country]. This has been burdensome for us and at some level represents a conflict

of interest. Our institutional IRB (as well as WHO and OPRR) have not been very realistic

about the difficulties associated with ethical review in other countries.

C.5.3 SPAs and the OPRR

Sixty percent of researchers obtained an SPA for their studies, and 66 percent of those funded by the U.S. 

government had obtained an SPA. Those funded by any U.S. source were more likely to have an SPA than

those not funded by a U.S. source (65 percent versus 19 percent, p < .001). For the majority of researchers,

obtaining the SPA took three to six months, and for close to 20 percent it took more than six months. Six 

percent of researchers said they had ever abandoned a study because it was impossible to get an SPA. The

majority of researchers (65 percent) did not find the SPA process valuable, and 49 percent thought the 

requirement should be eliminated. Not surprisingly, those for whom obtaining the SPA took at least three to 

six months were significantly more likely to believe that the SPA requirement should be eliminated than those

who obtained their SPA more quickly (62 percent versus 41 percent, p = .003).

Twenty-one percent reported that they encountered resistance on the part of developing country officials 

in agreeing to an SPA; related, 24 percent reported encountering resistance on the part of developing country

officials to U.S. requirements for IRB composition. 

The formation of an IRB board according to U.S. standards does nothing to assure appropriate

review....The check of having the Board look like a U.S. Board seems to be designed to assuage

consciences here rather than to get at the real issue of whether the protocol will be reviewed

by members who are truly objective and include a ‘member of the community’ who can

provide input into the study.
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SPAs often became a heated topic during focus groups and were also mentioned more than any other topic in

the open-ended comments researchers volunteered at the end of their surveys. One respondent wrote:

The SPA process is burdensome to U.S. and developing country investigators. I have 

personally had to apply for three individual SPAs for the same project in order to satisfy the

administrative structure of the project. This led to more than a six-month delay in providing

our international collaborators with appropriate reimbursement.

Researchers often mentioned that the SPA requirement was duplicative at best and not designed to protect 

subjects at worst. They believed SPAs involved additional bureaucracy with little additional protection of 

subjects. One researcher wrote at the end of his or her survey: 

In my experience, if local review has been done, the assurances add no additional protection

for human subjects (OPRR employees do not seem to have international experience).

Ministries of Health are sometimes offended that the U.S. is dictating policy and the composition

of ethics review boards in their countries. Furthermore, the delays in obtaining clearance often

prevent researchers from addressing real public health issues in real time.

Another researcher had a similar reaction:

In my experience they have not been very useful in terms of awareness regarding ethical

issues. The guidelines and filling out of forms in this structured way is EXTREMELY difficult

in developing countries. Mostly, it raises questions and in some way resentments. In many

ways the requirements are just signed without being read, mostly because they are so 

cumbersome and complicated.

One researcher described how the act of signing a paper for collaborating agencies or government officials

sometimes was met with resistance. Another researcher described that in areas of war or political conflict, the

SPA requirement makes research impossible, since assurances require governmental signatures:

I’ve had people just dying, whole villages getting wiped out by African trypanosomiasis. 

We can’t work there [African country], because we can’t get an assurance, because there’s no

government.

Multiple researchers felt that the strict imposition of procedural and administrative dictates was inappropriate:

“The United States dictating how another sovereign nation should behave in the operation of medical research

is a bit arrogant and colonialistic;” “It is humiliating to ask bodies in other countries to accept U.S. rules;” or

“U.S. rules should not rule other countries. SPAs should be eliminated. Most countries get offended by having

to be certified.” Sometimes the rules inherent to the SPA process simply seemed irrational to researchers:

I converted an NIH R29 grant into an R01 grant. Because the funding mechanism changed, 

I had to get a new SPA for essentially the same protocol, and the awarding of the grant was

delayed for many months....On the other hand, I have a five-year contract that may ultimately

support testing vaccines in Africa. I got an SPA for the first protocol executed under this 

project, an observational study. No additional assurance will be required by OPRR for this

project, even for totally different protocols with much greater levels of risk.

In general, focus group discussions revealed that researchers believed SPAs had a bureaucratic, rather than

ethics, focus, requiring original signatures of narrowly delineated officials. One respondent described a lengthy

delay in starting his or her project because someone signed on the wrong line of a document. Fundamentally,

one researcher shared, it indicated that the oversight of research has turned into a “sad” state of affairs where
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researchers are spending the vast majority of their time attending to the paperwork requirements of oversight

rather than the true ethics considerations:

I think one of the sad things is that I think in general the investigators... really want to do

what’s right, and they really care about the ethics and the research that they’re doing. And, yet,

if you look at how much time on the average protocol in an international setting you spend on

the ethics of it, versus how much you spend getting your assurance in place, getting the consent form down to an eighth grade level even though it’s going to be translated into another

language....So you spend so much time doing that. I would say probably less than 10 percent

of the time is being spent on ethical issues, and the remainder of the time gets spent on paperwork, on exercises that don’t protect human rights or human relations, human subjects. And I

think that what’s happening is that people are trying to now find ways to circumvent the IRB

process, not because of the ethical issues but because of the paperwork, because of the assurances....And some projects are just not being done.

Others suggested that some researchers find current regulatory requirements so cumbersome that they now

try calling their research by a different name, in order to avoid having to follow the regulations:

It’s like find a loophole in this so that it’s not research....that’s not helping your human subjects. In fact it’s just facilitating people to do an end run around the whole process. So then

you have no review. Oh, well, we’re just going to provide treatment to some people as part of a

program and call it [something else] instead of research. And then you have no review of that

process. So, in fact...these OPRR regs and everything may...encourage people to go around the

whole process.

One researcher said that the SPA application package from OPRR meant the end of his or her research collaboration: “I’ve sent it to some countries, and it’s the last I’ve heard of them, places where you’ve been cultivating

research for months and months.” Another said: 

Our project almost ended. If we had not had a relationship before then, it would have ended. 

I was told it [OPRR regulations] was insulting. I was told it was being imperialistic: ‘Didn’t I

think they were moral people?’

Several other researchers also objected to the rigidity with which U.S. guidelines or rules needed to be followed in other countries. One researcher described two recent examples where host country colleagues reacted:

“‘You know, maybe that’s the way you do it in the West, but that’s not the way we do it here.’” Another said: 

Rigid enforcement of U.S. regulations in another country or culture, however well meaning 

or politically correct, is a form of cultural imperialism and is often resented by [the] local 

population.

Many researchers were concerned that the staff at OPRR who reviewed SPA applications had inadequate

experience in international settings. Some respondents recommended taking SPA reviewers to field study sites

so they could see first-hand the conditions of the research. One researcher, however, suggested modifying,

rather than eliminating, the process:

Develop greater flexibility in the assurance process. This process should respect [the] scientific,

intellectual, and ethical integrity of IRBs in developing countries. Allow foreign IRBs to have

and maintain multiple project assurances [MPAs]. An IRB in a foreign country may start with

an SPA but graduate to an MPA if it demonstrates that it can maintain standards acceptable to
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[the] United States. For some countries where there are many ongoing projects and the

research infrastructure is well developed, this would make the process more efficient by 

reducing the need for a separate SPA for each project reviewed by the same committee. 

Sixty-four percent believed international guidelines (e.g., CIOMS) should be used instead of U.S. rules and 

regulations, and 83 percent believed the composition of ethics review boards used in developing countries

should not be dictated by U.S. regulations. One researcher said: 

I would like to see a U.S. policy that encourages developing countries to develop their own

requirements. I believe that this would lead to a greater impact locally by implementation of

requirements that they developed themselves.

There were general comments and recommendations concerning the future direction of international

research ethics and oversight. One researcher asked from where moral authority arises:

One can hear a perspective in a place like [Asian country] and maybe also in other developing

country communities where the issue of consent or ethics or decisions about morality are

really deferred to other people in a community. And so the idea of having an autonomous

opinion about morality or ethics of a particular study for instance, really depends on who you

are, whether you feel you have that moral authority or not, but whether you feel it’s appropriate

for you to make those decisions. So decisionmaking about issues like this I think are quite

complex and may not fit the usual ideas we have of autonomy in our society.

And finally, two researchers talked about the fragility of trust and the potential for our regulatory framework

to destroy that trust:

We’ve suddenly tried to bureaucratize, that ‘we trust you’ issue....We’re losing that and I’m not

sure how to recapture it, but I think that’s one of things we need to learn from our colleagues

overseas is that they’re trying to tell us something about trust, and then we do have to get our

cultures in agreement...and that’s the richness, I think, of collaborative research—we have to

decide together what is an acceptable level of ethical behavior, and then how do we document

that or how do we assure that.

Another wrote: 

The concept of ‘ethics’ should not be restricted to the narrow issue of protection against

research risks. The NBAC must find a mechanism to view international research as a partnership, not as an exploiter/exploited relationship. The NBAC should actively try to explain the

ethical framework as one of joint problem solving, and should do everything in its power to

facilitate this noble enterprise. As it stands now, the ethical community is at serious risk of

becoming marginalized and irrelevant to what is an exciting new era of trust, cooperation, 

and the alleviation of human suffering world-wide.

C.6 Discussion

C.6.1 Informed Consent

There were several important findings from both quantitative and qualitative data regarding informed consent.

Researchers overwhelmingly use written informed consent, even when they believe it does not make sense to

do so; researchers believe the consent process is an important means of educating participants about the study,

although they want more flexibility in their methods to explain their research and document consent; and
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researchers believe more attention should be given in the consent process to participant understanding, even

though few researchers thus far have tested participant understanding themselves.

Given the educational and cultural contexts in which these researchers work, it was striking that as many 

as 76 percent of them reported obtaining written informed consent in their studies. Of note, the older the

researchers were, the less likely they were to use written consent. Even when working in the lowest literacy

populations (at least 80 percent of the study population illiterate), 60 percent of researchers still obtained written consent, although almost all researchers who used written consent also used at least one other method to

explain their studies to participants. Indeed, researchers described in focus groups and in comments creative

and multiple mechanisms for explaining research, ranging from focus groups and community meetings to

brochures and media campaigns. Researchers overwhelmingly believed that the consent process provided an

opportunity to discuss ethics issues with field staff, and host country staff were almost universally involved in

explaining studies and seeking consent from participants.

The vast majority of researchers (85 percent) wanted more flexibility in methods of documenting informed

consent. We have no way to know from our data whether the IRBs that reviewed the projects in question actually require written consent universally or whether they allow flexibility in certain situations, and investigators

did not know this either. And yet, if the IRBs had more flexibility, one must wonder why they did not ask

whether written consent was the most appropriate method to use. In some situations, researchers revealed that

it was OPRR, in negotiating a SPA, that had required the written consent, or required that written consent

forms grow in length from a couple of pages to more than five. Clearly, the U.S. Code of Federal Regulations

does allow exceptions to written consent in certain situations. Presumably an experienced IRB would allow 

(or even require) researchers to use alternative methods when written consent either would be meaningless

(e.g., when the population is illiterate) or when it would create more harms than benefits (e.g., when the 

purpose of signing the paper was significantly misunderstood or caused tremendous anxiety). 

Written consent is the norm in domestic and international research, and it was the belief of most of our

researchers that they had to use this method, even when it seemed ridiculous to them to do so. A recommendation that derives from this is that the new Office for Human Research Protections should reiterate more

explicitly to both researchers and IRBs that, although written consent should remain the norm for most human

subjects research, exceptions to written consent are allowed by current regulations and in some instances are

morally preferable. It is a disservice to the intent of the regulations to obtain written consent in contexts where

it is meaningless; in such situations, IRBs and researchers must consider broadly alternative methods to inform

potential participants about the study and to document consent.

Many researchers suggested that IRBs expand their examination of a study’s consent procedures from a

seemingly exclusive focus on the individual researcher-participant interaction, to greater attention to the multiple methods researchers use to introduce the study to the community as a whole and/or to the family. As one

researcher put it, after months of informing the community about the research, talking to leaders, and holding

community meetings, to then be asked only how he was informing the individual participant indicated a lack

of awareness of the process by which participants were informed. 

Many researchers used oral consent with a witness signature to document consent. A related approach that

we did not ask about is oral consent with the researcher’s signature, whereby the researcher signs a form attesting that he or she explained the study to the participant and the participant voluntarily agreed to enroll. One

researcher recommended that IRBs require researchers to use one or more methods from a “menu of choices”

to reinforce within the research community that researchers must be thoughtful and considered about which

methods of informing and documenting consent are most appropriate for their target population and should 

justify why they have selected a particular method. 

Researchers further suggested that consent methods should be targeted to the study’s design and level of

risk. That is, some of them recommended that observational studies often should not require formal individual
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consent and that higher risk studies should receive more scrutiny and have more rigorous requirements for

consent and for understanding than lower risk studies. A clear recommendation is that researchers who have

used diverse methods of informing or documenting consent should share their strategies and outcomes with

colleagues and IRBs.

Certainly, many researchers referred to the tension between the presumed legal and ethics purposes of consent forms and procedures. On the one hand, informed consent was interpreted by researchers to be an ethics

exercise, to ensure that their participants understand what they are being asked to do before deciding whether

to participate. On the other hand, some of the requirements, like signatures or indemnity language, were seen

as legal protection for themselves or their institutions. One focus group member suggested that if institutions

need what researchers viewed as legal protection, this should be separated from consent procedures, so that

procedures to protect subjects would be distinct from procedures to protect institutions. 

Assessing participant understanding is significantly more challenging than drafting a consent form or 

engaging in alternative methods to inform participants. Researchers who were not required to perform such

tests and who spent considerable time fulfilling other ethical requirements may have lacked time to address 

this issue. Also, it is difficult to know what elements of a study to ask participants about or how much understanding is sufficient, although the threshold certainly would vary with the study’s risk. Only 16 percent of 

our respondents said they had used a test of understanding, despite the repeated assertion in focus groups that

understanding was the relevant element of an ethical consent procedure and despite the fact that 65 percent of

researchers agreed that “a mechanism to measure participants’ understanding should be built into any research

study.”

That this area is challenging simply means that more empirical and conceptual work must be conducted 

to learn which methods to assess understanding seem most effective and what types of outcomes are most

appropriate. An ethics challenge will always exist, however, in that certain concepts, despite broad and creative

techniques to inform participants, and despite tests of understanding, are likely to still not be understood, or

not understood the way Western researchers understand them. Concepts like DNA mapping, immunology,

placebos, or randomization will be completely foreign to some individuals, and despite the most creative

efforts, they will remain incomprehensible. Researchers and IRBs, then, must make the difficult balancing decision of whether the public health problem in question is important enough to warrant the conduct of research

where participants have a less than complete understanding (assuming that they are protected from harm) or

whether research will not be allowed in areas where participants cannot give consent with full understanding.

In terms of voluntariness, it is reassuring that researchers consistently reported that some numbers of 

participants refused participation. While this does not verify whether participants accurately understood the

research, it does suggest that at least some knew that participation was not required. It is disconcerting, however, that refusals were less likely among populations of lower literacy, and of note that female researchers were

more likely to have some participants refuse than male researchers. It is hard to interpret from our limited data

the ethics implications of the involvement of village leaders or other family members in participants’ decision 

to enroll and that these practices occurred more often in countries with lower HDI scores. That others are

involved is not necessarily an indication that individual participants were denied independent choice, nor is 

it necessarily a sign that the choice made was an inappropriate or harmful one. Nonetheless, more empirical

work should be conducted on the meaning of individual choice in different cultures, particularly in relation to

gender, class, and political empowerment. 

C.6.2 Study Design, Risks, and Benefits

A key survey question focused on why researchers were conducting their studies in developing countries rather

than in the United States. Researchers could answer this question by selecting one or more reasons from a list

provided. The most common reasons selected were that disease prevalence was higher, researchers had an
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interest in addressing global inequalities in health, and host country collaborators asked for U.S. collaboration.

Researchers also listed practical concerns, such as ease in identifying a relevant cohort, faster recruitment, and

cheaper cost. Researchers who worked in lower HDI countries were even more likely to mention disease prevalence, relevance of intervention to the local community, and interest in global health inequalities. 

In focus groups, some candid remarks were made by private industry researchers describing why their

research was conducted in resource-poor areas. These justifications were practical, relating to faster recruitment

of participants and, in HIV research, access to patients who had not had prior therapy. It is noteworthy that

several of the private industry researchers in focus groups mentioned that completing a clinical trial quickly

was one of their primary goals, based on the short timelines set for them by their employers. Several private

industry researchers voiced their belief that, while the host countries were unlikely to be able to afford the new

drugs that were being tested in their studies in the future, it was ethical to carry out the studies there because

individual participants received some benefit during the study. In analyzing the survey data, it was not possible

to make statistical comparisons between private and public sector researchers, due to very limited numbers of

private sector respondents. 

In the survey, relatively few (12 percent) of our respondents classified their research as greater than minimal

risk, although 24 percent of researchers conducting intervention research classified their research this way, and

researchers conducting randomized controlled trials or HIV/AIDS research were more likely to call their

research greater than minimal risk. We have no means to objectively classify researchers’ studies in terms of

their level of risk, although it is possible that researchers, so close to their work, sometimes underestimate risk.

At the same time, because IRBs and ethics boards rarely questioned researchers about risk in study review, it

was clear that they were not concerned that researchers were underestimating risk. 

Of note, researchers working with children were less likely to call their research greater than minimal risk.

Although we asked researchers about the risk involved in their studies, we did not ask about potential clinical

benefits that may result from study participation, and thus we cannot assess the risk/benefit ratio for studies

reported in the survey that included children or infants. U.S. regulations require that greater than minimal 

risk research with children be conducted only when the children enrolled are likely to benefit directly, and 

the CIOMS guidelines specify certain conditions for conducting research with children, including determining

that the purpose of the research is to obtain knowledge relevant to the health needs of children and that the

research could not be conducted in adults and balancing any potential risks of the research with potential

direct benefits for the children in the research study. In this survey, the norms for conducting research with

children in developing countries have not been explored, while in focus groups, researchers mentioned that

ethical guidelines for conducting research with children vary between industrialized countries. Further investigation of standards and practices regarding research with children in both industrialized and developing

countries is warranted. 

It is evident that the vast disparity in resources and background conditions between the U.S. and developing

countries creates ethical challenges in the area of risks and benefits, in several ways. First, potential study participants may feel they have no choice but to join a research protocol, even a risky one, if it offers the chance 

of benefits unavailable outside the study. Moreover, in relatively deprived background situations, participants

may be more vulnerable to misunderstanding the likelihood of personal benefit, out of their desperation and

need for any type of health care. Most survey respondents (64 percent) felt that study participants joined their

index project because of benefits obtained; and researchers in focus groups reiterated this theme. Seventy-six

percent of researchers with greater than minimal risk studies stated that participants joined for benefits, and

even 62 percent of those in minimal risk studies said the same. At least two focus group respondents felt that

the direct benefits obtained by individual participants in a research project were sufficient justification for doing

the research in a resource-poor setting, even if it did compromise voluntariness, and even if the treatments

would not be available to the host country as a whole. 
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This raises questions about the degree to which voluntariness is compromised in such a setting and about

the justification for doing research in populations that will not receive the larger benefit of access to successful

treatments or research results. Certainly, since 30 percent of researchers generally and 44 percent of researchers

conducting greater than minimal risk studies believed that their participants had unrealistic hopes about study

benefits, further efforts to ensure participant understanding of study protocols must be implemented. 

Second, this disparity in resources between rich and poor countries makes it difficult to establish procedures

for control groups. Researchers repeatedly expressed concern about the appropriate treatments for control

groups. Fifty percent of the survey respondents who had a control group stated that the standard of care was

lower in the host country, creating difficulty in establishing appropriate treatment for the control groups.

Furthermore, 78 percent of researchers believed that the issue of what standard of care to provide to study 

participants should be decided on a case-by-case basis. Several researchers commented that they believed it 

was ethical to offer study participants less than the best-known treatment in a controlled trial, if the best treatments were not locally available and if the study was addressing questions relevant to the needs of the study

community. Determining the right standard to provide to control groups can be particularly challenging in HIV

research. Most HIV drugs are very costly, making them prohibitive for most resource-poor countries and for 

the budgets of many research projects as they are currently constructed. In addition, the chronic nature of the

disease demands that treatment be ongoing, and deciding when, if ever, study benefits should end becomes

problematic. Also, even if drugs could be provided, they often require a health care infrastructure for testing

and monitoring that is not available. 

Third, this disparity in resources raises questions about what other treatments or care, unrelated to the study

itself, researchers should provide to participants and/or to the larger community and for how long. This was a

lengthy topic of discussion in several focus groups. In situations where study participants lack basic care, they

often turn to the research team to address their health needs. Researchers described difficulty in determining

how much care to provide, and, in some cases, they received little guidance from their U.S. IRBs in determining

what was appropriate. Researchers sometimes found that a study could not be conducted in a particular population because the medical care costs would be overwhelming, and the researchers felt they could not conduct

the study without providing this supplemental care. In some cases the medical needs of the population were

not evident until after the study had been initiated. One researcher commented that IRB members may have

assumed that medical care was locally available when it was not. From researchers’ comments, it appeared that

funding agencies and IRBs had no clear policy about the issue of medical care unrelated to the research question.

Finally, there is a tension between the desire to directly benefit the study population and the need or desire

to gain scientific knowledge to eventually benefit larger numbers of people. While this tension exists in all

research, it is heightened in resource-poor settings, since participants’ likelihood of receiving comparable benefit

outside the study is significantly less than it might be in other settings. This tension is further heightened in

countries with lower human development indicators. Indeed, researchers described struggling with the question

of whose benefit is paramount: study participants or a larger community, such as all those who suffer from 

particular disease. Many researchers stated that their primary motivation for working in developing countries

was to contribute to long-term health benefits for these countries and to reduce global inequities in health;

nonetheless, every researcher must face the practical dilemma of how to balance the acquisition of such knowledge with the health needs of the individual participants. Virtually all the researchers in focus groups expressed

concern for the well-being of the study participants, but also described limitations of time, money, and infrastructure, as well as scientific goals, that sometimes circumscribed their efforts to provide benefits to individual

participants. 

Data from this project, both from surveys and focus groups, indicate that U.S. researchers are acutely aware

of and are often quite troubled by these ethical issues. The challenge, of course, is how to respond to them.
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That researchers are sensitive to the ethics dilemmas is an important first step. Raising awareness among IRBs,

as described earlier, about the realities of life in a developing country and raising awareness of ethics issues

among host country boards also should help. Ultimately, however, the ethics issues raised by a study that is

providing care that is considerably better than care that is or will be provided in the surrounding community

raises larger challenges than can be solved simply by educational interventions. Much greater attention should

be devoted to these ethics issues at a policy level so that coherent policies can be developed concerning what

researchers should provide to participants in terms of standards of care for control treatments and in terms of

unrelated medical care.

C.6.3 Obligations to Participants, Communities, and Countries

While most researchers in our study agreed in principle that effective study interventions should be provided

after a study ends, many voiced concern that the practical realities can make this problematic. Researchers

raised issues involving who will pay to implement successful interventions, how adequate infrastructure can 

be established to deliver interventions, how equitable selection of recipient populations or groups can be

accomplished, for how long future benefits should be provided, and more. In the written survey, researchers

with intervention studies were asked a series of questions about their plans to provide the intervention, if successful, to any groups in the host country at the conclusion of the research. More than half of the respondents

with successful interventions were planning to provide them to at least some groups at the end of the study.

Thus, although providing interventions can be costly and difficult, arrangements already are being made to do

so in many cases. Some of the interventions were being provided only to study participants, but 29 percent

were provided to the entire host country. Host country governments, logically enough, were more likely to be

involved in the plans to distribute the intervention to the entire country than in other plans; international 

agencies were more likely to be involved in providing the intervention in lower HDI countries. 

It is notable that researchers who provided the intervention were more likely to say that they were conducting

the study to address global inequalities in health. In two cases, researchers in focus groups reported having

made specific plans to provide expensive drugs to study participants at the end of the study, although the drugs

would not be made widely available in the host country. In general, researchers expressed the sentiment that

providing interventions was a laudable goal, but that the economic realities of resource-poor countries made 

it impossible to accomplish on a broad scale. Fifty-three percent of researchers agreed that research should not

be carried out in a developing country unless the intervention will be made available after the study, although

many felt that imposing a precondition that interventions must be provided if research is to be carried out

would prohibit much useful research that would have the potential to benefit poor communities in the

developing world. 

Some details of the arrangements to provide interventions were not obtained in the written survey, such as

whether the intervention researchers were testing was a short-term or long-term one, its cost, and whether it

required an accompanying infrastructure, all of which are related to the feasibility of future implementation 

and may have affected whether or not researchers provided their intervention. One respondent stated that 

high drug prices, particularly for HIV drugs, were a major obstacle in providing access to treatments in

resource-poor areas and that this problem could never be resolved by ethics committees. 

Other respondents noted that the utility of the intervention itself—for example, a new drug—hinged upon

the infrastructure that was available in the host country. In many cases adequate infrastructure for health care

does not exist, and providing an intervention would require large scale improvements in the health system. 

A few researchers mentioned the magnitude of the economic problems faced by resource-poor countries and

stated that individual researchers were not in a position to address these inequities. At the same time, it was

clear that U.S.-funded research did sometimes lead to lasting improvements in health care in the host countries. Many researchers said that they would welcome such improvements, but would be disturbed by policies
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that put a halt to U.S. research projects that did not result in immediate widespread implementation of interventions, since in the end, they believe, this would be more harmful to resource-poor countries.

Fewer participants (27 percent) agreed that international policy should require researchers to establish a

mechanism for continuing delivery of medical care after completion of the study. It is not clear whether

researchers believed this question was referring to the ongoing provision of study-related interventions or to

the provision of general medical care unrelated to the intervention. Medical care unrelated to the research question may be seen by researchers as a responsibility of the host country and international agencies rather than

that of the U.S. research team. Many researchers felt that the global inequalities in health care and economic

resources were too great to be addressed adequately by individual research projects in developing countries.

However, many felt that it was desirable to continue medical care and other services that had been set up in

host countries, if reasonable mechanisms, other than a requirement imposed on researchers themselves, could

be developed to support this.

In sum, although most researchers expressed concern for a blanket requirement that all U.S.-funded

research provide successful interventions to host countries’ communities, many interventions, in fact, are being

provided, and many researchers are taking steps to accomplish this goal. This is another area that deserves 

further inquiry regarding the mechanisms and policies that can address the goal of providing benefits to those

communities in resource-poor countries that have participated in research projects, without halting or encumbering the research process.

Separate from research products, U.S.-sponsored research can, and should, include capacity building in

developing countries for health care and research activities, including the enhancement of human capacity.

Focus group participants frequently mentioned that collaboration with, and respect for, the host country

researchers was essential to well-designed and appropriate international research. Several researchers described

relationships they had with in-country colleagues for many years. Consistent with this, U.S. researchers with

less experience were less likely to involve their colleagues in a number of the research tasks. 

The survey results revealed a hierarchy of research tasks that involved collaboration, from more intellectual

tasks, such as grant writing and data analysis, to field operations, such as recruitment of study participants and

training of research personnel. Developing country colleagues were more often included in the field operations

than in the intellectual work, although a significant number were included in both. The lowest level of participation by developing country scientists was in grant writing; those projects that included some developing

country funding, logically enough, were more likely to involve host country scientists in the grant writing

process. One respondent remarked in survey comments that U.S. researchers often had a paternalistic attitude

towards their developing country colleagues and that host country scientists were not allowed to develop skills,

such as grant writing, that would enable them to work independently. Grant writing is one area in particular in

which more extensive capacity building seems warranted; developing country scientists who could obtain

funding could gain more control of the research and could direct the research towards goals relevant to their

country’s needs.

Capacity building also involves resources for health care or research infrastructure, which may be left in 

the host country at the conclusion of the study. The vast majority (94 percent) of survey respondents said that

some resources remained, ranging from medical equipment, organizational structure, and computers to bettertrained personnel. Studies conducted in lower HDI countries were more likely to leave behind resources such

as buildings or power equipment than studies in higher HDI countries, and studies with some developing

country funding were more likely to leave organizational structure. Focus group participants commented that

equipment and supplies are only useful if the technical expertise is left behind to utilize them. In 68 percent of

the index studies, organizational structure was left behind; however, funding may not exist to carry on research

or health care activities. 
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One survey respondent described enhanced public health surveillance and procurement of medication in his

or her study that would not be maintained at the conclusion of the research; another described better hospital

treatments for a life-threatening disease, which reduced the mortality rate during the study. These researchers

mentioned their concern that at the conclusion of the research, conditions would revert to their previous state.

Thus, in some cases, the benefits of research may be short lived if sustained efforts are not made after study

completion to continue collaborative relationships and to continue to build the human and material capacity of

host country communities. 

C.6.4 Oversight and Research Review

Overall, 91 percent of studies were reviewed by a U.S. IRB, 87 percent were reviewed by a host country ethics

board, and 77 percent were reviewed by the host country Ministry of Health. Indeed, only 5 percent of studies

were not reviewed by any board. That almost all studies received outside ethics review suggests that, in the 

relatively short period since U.S. regulations and international guidelines governing human subjects research

have been in place, the idea that studies should receive prior review from an outside committee has become a

standard practice. 

Our small sample of researchers from the pharmaceutical industry were significantly less likely to have their

studies reviewed by a U.S. IRB, but in every case their studies were reviewed in the developing country. In

focus groups, pharmaceutical researchers from two companies commented that their company policy required

local (host country) review at each study site, but did not require U.S. IRB review. The requirement for local

IRB review fulfills Food and Drug Administration (FDA) requirements, which companies must follow when

submitting clinical data to the FDA for drug approval. It should be noted FDA regulations are the only ones

applicable to private industry, since private companies are exempt from the Common Rule2

, which requires

U.S. IRB review for projects carried out outside the United States. 

While outside and prior ethics review has become standard practice, it is less clear what the content of 

that review is. From researchers’ reports of which issues were raised in review of their studies, it is clear that

procedural issues are far more likely to be raised by U.S. and to a lesser degree host country boards than are

substantive issues. U.S. IRBs were most likely to ask researchers about the need for a local language consent

form (again, despite the questionable appropriateness of written consent), for letters of approval from developing country representatives, and about the complexity of language on consent forms. The substantive issue

addressed most frequently was whether the research question was relevant to the host country (or why the

study was being conducted in the host country), although this issue was raised with fewer than one-third of

researchers. 

Lagging further behind was the future availability of the intervention to the host country (addressed by 

23 percent of IRBs) and issues of design, such as the appropriateness of procedures for the control group and

whether the intervention might be too risky, addressed by only 4 percent of IRBs. Of course, that an IRB did

not raise an issue might have meant that the researcher had addressed the issue adequately before submitting

the protocol; alternatively, our findings suggest that IRBs truly are better equipped or more schooled in discerning

procedural issues, such as whether or not a local language consent form has been submitted, which certainly

are easier for IRB staff or reviewers to ascertain through such means as a check list. These are items that can be

gleaned from U.S. regulations and then easily noted to be present or absent in each study. Such items do not

require as much training or experience in real research ethics; thus, a more sophisticated analysis of the adequacy

of the materials presented by a researcher from human subjects perspective need not occur. 

Certainly, some number of procedural requirements are inevitable and appropriate in even the most sophisticated of reviews. Moreover, one could argue that procedural issues apply to all studies, and particular substantive issues will apply only to particular studies, so of course the likelihood of procedural issues being raised

should be higher than each individual substantive issue. On the other hand, we asked respondents to report
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whether the IRB had raised an issue only if the issue (e.g., adequacy of the intervention provided to the control

group) was relevant to their own study. Fortunately and appropriately, IRBs were significantly more likely to

raise substantive issues with the 12 percent of studies investigators classified as greater than minimal risk. For

such studies, issues from the appropriateness of interventions for the control group to whether the study was

too risky were more likely to be addressed by U.S. IRBs. 

U.S. IRBs also were more likely to ask about issues that researchers themselves thought were relevant to 

the study. For example, researchers who reported in the survey that they believed that the standard of care 

in the host country was lower than that of the funding country—and that this made it difficult to establish 

procedures for the control group—indeed were more likely to be asked about the adequacy of control group 

interventions by the IRB. Of course, from our retrospective survey, one does not know whether the U.S. IRB

brought this issue to the researcher’s attention, whether the researcher brought it to the attention of the IRB, or

whether both the researcher and IRB independently believed the issue was relevant.

Host country boards, like U.S. IRBs, asked about the need for a local language consent form more than any

other issue. Host country boards, however, were less likely to ask about all issues than the U.S. IRB, with the

exceptions of the availability of the intervention after the study was over and the appropriateness of using

placebos, which were asked equally often. It is possible that host country boards raised fewer issues because

they generally reviewed studies only after U.S. IRBs had approved them and researchers had cleared up issues

of concern; however, it is possible that because the host country review was submitted by the respondent’s

developing country colleague, the U.S. researcher was not fully aware of all of the issues raised. Or, it might 

be that developing country boards are truly less likely to raise a variety of issues in their reviews. Certainly

researchers believed developing country ethics boards needed additional training in ethics and that host country

boards often raised scientific or budgetary issues rather than ethical issues. Certainly, ethics capacity building

can be part of the general capacity building in which researchers participate as part of research collaborations. 

The FIC of the NIH recently released for the first time a request for proposals to provide long-term ethics

training to developing country scientists, presumably to address this need. It is less clear how U.S. IRBs or the

new OPRS will learn more about the realities of international health work, as was also suggested. Short of

requiring extensive travel, one possibility is to require someone with substantial experience in developing

countries to review studies, as is required for research with prisoners or with Native American populations.

Further, even a small amount of required continuing education for IRB members and staff could provide 

statistics about typical distances from phones or health clinics, the likelihood of having a car, typical literacy

rates, or even the frequency with which in-country ethics boards meet and the operating budgets of local 

ethics boards.

It is important to emphasize that U.S. researchers believed strongly in the importance of host country

review, and 77 percent believed it should be required for all studies. Researchers reported that it is during the

host country review that culturally relevant concerns are likely to be raised. Indeed, in our survey, cultural

appropriateness of study procedures was the second most likely issue to be raised by host country ethics

boards. Several researchers further commented that when a thorny ethics dilemma arises (e.g., what standard 

of care should be used or what study end point is appropriate), it is the host country that should decide. 

An issue that raised considerable emotional response in focus groups involved SPAs, which currently are

required for all federally funded researchers and/or those otherwise required to follow the Common Rule when

they work in developing countries. Most would agree that the intent of the SPA requirement is good: SPAs 

are designed to ensure that a host country board reviewed the study and that the composition of the board 

was both varied and legitimate. The SPA requirement is a way to make sure that a single person, such as a coinvestigator, or even a government official, did not simply write a letter approving the study. The requirement,

further, was designed to ensure that the host country review was an ethics review, rather than one based on
B-64

financial or political considerations. While these goals are laudable and appropriate, the system in execution,

according to our respondents, generally has been a failure. 

First, there was consensus that the process for obtaining an SPA is excessively bureaucratic. Whereas all

other ethics and design decisions and negotiations occur locally between the United States and the host country researchers and institutions, to obtain an SPA, the U.S. federal government must become involved. This not

only delays the process significantly, but more importantly from an ethics perspective, it brings individuals into

the mix who, according to our respondents, in general have less familiarity with both particular research settings

and international health research than the other parties already providing external review. 

Several researchers wondered, in focus groups, why their U.S. IRB cannot decide the adequacy of the host

country board if there are generic concerns about composition. Many researchers used the word “ridiculous”

when describing current SPA requirements and cited issues such as the need for original signatures from narrowly specified officials in the host country or the need for a completely new SPA every time a new or followup study is conducted between the same institutions or in conjunction with the same ethics board that already

had been sanctioned by OPRR and granted an SPA. Of little surprise, then, 65 percent of researchers believed

the SPA process was not valuable, and half thought it should be eliminated. 

Not only did researchers believe that the SPA added little to the ethical conduct of their research, they further

were concerned that it offended their colleagues, a practical and a moral concern. From a practical perspective,

gaining trust and interpersonal familiarity can take months or years and is essential to the smooth execution of

a cross-national collaborative project. Outside requirements that threaten this relationship, because they are

offensive or “imperialistic,” to quote our respondents, clearly impede the research process. Arguably more

important, however, from a moral perspective, a goal of U.S. and international guidelines is to respect persons

and communities. While it is appropriate, according to our researchers, for U.S. guidelines to require host

country review and to require that certain elements (such as evaluations of risk and benefit or appropriateness

of consent procedures) constitute that review, to delineate too precisely the composition of boards or the types

of people who have authority over their procedures can be disrespectful of how other countries conduct their

work. Requiring other countries to follow certain procedures seemed to be more offensive to our respondents’

colleagues, they reported, than requiring that certain substantive areas be covered in a review. If our government

is concerned about the adequacy of ethics capacity in some developing countries, specifying who can sign off

on the board’s composition is not the answer. 

Many researchers in both focus groups and the survey recommended allowing developing country boards

international guidelines (such as CIOMS) rather than having to follow U.S. regulations. The majority of respondents (64 percent) thought international guidelines should be used; only 7 percent disagreed. 

Researchers’ global comments regarding IRB review and SPAs overlapped, as one would expect, with their

comments regarding informed consent. Informed consent was a significant part of research review, so when

researchers asked for greater flexibility in how to inform participants or how to document consent, they often

more broadly expressed the desire for greater flexibility in the review process. Researchers again requested 

flexibility both in how IRBs interpret federal guidelines and in the guidelines themselves. 

In general, researchers voiced strong interest in and support for the spirit of ethics guidelines—that is, to

protect the interests of research subjects and their communities. However there was widespread concern that

the regulations themselves and their interpretation by IRBs often failed to adequately protect populations in

developing countries and, in fact, impeded the process of conducting research that meets substantive ethical

standards. 
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D. Results of the Study of Developing Country Researchers

D.1Description of Developing Country Researchers and Their Work

D.1.1 Quantitative Research Component

Demographic information pertaining to participants in the developing country survey is shown in Figure D.1.1.

More males (68 percent) comprised our sample as compared to females, and a little more than half (53 percent)

of the respondents were less than 45 years of age. The majority of our survey respondents were physicians

(M.D.s) or equivalent (69.3 percent) and were employed by universities (62 percent). Forty-four percent of 

the researchers were members of an IRB/ethics board at either the national/state or local level. Three-quarters

(74 percent) of IRB members were male. In addition, more than half (63 percent) of the IRB members are older

researchers (>45 years of age).

In order to determine their level of experience, the researchers were asked about the numbers of years they

have been involved in conducting research in developing countries, the average time they spend on research,

and the number of studies they have conducted. About half of them (53 percent) had fewer than ten years of

research experience in developing countries, while the other half had more than ten years of experience.

Eighty-one percent of the researchers had conducted more than five research studies, while fewer researchers

spent more than half of their time conducting research. 

In our survey sample, most of the researchers (37 percent) were conducting studies in Asia, followed by

Africa (29 percent) (see Figure D.1.2). 

To explore the types of studies being conducted, their topics, and the methodological approaches that are

being used to investigate those topics, we asked the researchers to provide information about their work. 

Those researchers who had been involved in a research project and had received funds from the United States

and/or who had collaborated with U.S. investigators were asked to identify that project as the “index study.”

Researchers who were neither involved in U.S.-funded studies nor had collaboration with U.S. researchers were

Figure D.1.1. Socio-Demographic Information on Researchers Male Female Non-MD Member Non-Member University Non-University <45 Yr >45 Yr

<10 Yr

>10 Yr

<50 Yr

>50 Yr

MD

Gender Age Education Employer IRB Membership Experience Time Spent

of Research on Research

80

70

60

50

40

30

20

10

0

Percent
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asked to identify a research project they had been

working on for the past five years that would be

labeled the “index study.”

Researchers were asked to provide information

regarding their respective index studies. The results

of these questions are shown in Table D.1.1. Almost

one-third (31 percent) of the studies involved 

infectious diseases excluding HIV/AIDS, and nearly

45 percent of the studies were conducted on infectious diseases including HIV/AIDS. Twenty-seven

percent of the studies addressed issues in health 

systems/services research, and a quarter of the studies

(24 percent) in chronic disease research. Only 5 percent were related to vaccine development and testing.

In response to the question regarding the discipline of the study, nearly half (52 percent) of the

studies were related to epidemiology, while one-third

(30 percent) were in health systems research and 

24 percent in clinical care. Anthropology and behavioral studies were also included in nearly one-third

of the responses. 

Among the various methodological approaches

being used to carry out different studies, 53 percent

of the respondents were conducting observational

and descriptive studies. Twenty-eight percent were

prospective studies, while 27 percent were labeled as

Figure D.1.2. Regions of the

Developing World Where Health

Researchers Conducted Research

(Researchers could check more than

one region) (n = 200)

Pacific 

Islands

1%

Caribbean

Latin 5%

America

8%

South

America

20%

Africa 29%

Asia

37%

Table D.1.1: Information on the

Developing Country Researchers’ Index

Studies (Respondents could check

more than one option)

Number of 

Topic of the Study Responses Percent

Infectious disease, 

non-HIV/AIDS 61 31

Health systems/services 52 27

Chronic disease 46 24

Cultural practices/behavior 40 21

Reproductive health 35 18

HIV/AIDS 28 14

Nutrition 25 13

Environmental health 23 12

Injury 11 6

Other 9 5

Vaccine development/testing 9 5

Perinatal health/birth defects 9 5

Genetics 8 4

Number of 

Discipline of the Study Responses Percent

Epidemiology 103 52

Health Services Research 60 30

Clinical Care 47 24

Behavioral Science 34 17

Microbiology 28 14

Anthropology 23 12

Psychology/Mental Health 14 7

Other 10 5

Ethics 6 3

Number of 

Method of the Study Responses Percent

Observational/descriptive study 105 53

Prospective study 56 28

Randomized controlled trial 54 27

Qualitative methods 53 27

Operational research/program 

evaluation 41 21

Community-based intervention 40 20

Case-control 36 18

Other 8 4

Cross-sectional study 7 4
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“randomized controlled trials” that are liable to be

clinical in nature. Twenty-seven percent of the

reported studies used qualitative methods. 

The survey gathered information about the source

of funds being provided to carry out the index studies

(Table D.1.2). Developing country governments

funded 35 percent of the studies, followed by international organizations, which provided funds for 25

percent of the studies. Developing country sources

funded a large number of the studies, whereas the

private sector (any source) funded fewer studies

overall.

U.S.-funded studies comprised an important group

for the purpose of our study. Studies having one or

more than one sources of U.S. funding were defined

as U.S.-funded studies. It excluded bilateral organizations. Forty-four percent of the studies were

funded by one or more than one U.S. sources (Table

D.1.3). U.S. nonprofit organizations were the largest

funding source amongst the U.S.-funded studies. 

The relationship of the source of funding

(whether U.S. or non-U.S.) with the topic of the

study was further explored and is displayed in

Figure D.1.3. More (74 percent) studies on

HIV/AIDS were funded by U.S. sources than by 

non-U.S. sources (p = .001). Of all the health 

systems studies, 69 percent were funded by nonU.S. agencies and 31 percent by U.S. sources 

(p = .024). More (54 percent) of the studies on

infectious diseases (excluding HIV/AIDS) were

funded by U.S. agencies (p = .05). Forty-one percent

of the studies on reproductive health were funded

by non-U.S. sources, and 59 percent had U.S. 

funding (p = .046).

Researchers were also asked to provide information about the study population. The responses are

shown in Table D.1.4.

The largest number of studies was conducted on

nonpregnant women (78 percent), followed by men,

who were involved in 66 percent of the studies.

Fewer studies enrolled infants. The majority of the

studies involved participants who were Christians

(71 percent), followed by Muslims and local indigenous religions. Nearly half of the respondents said

that their study population had 6 to 12 years of 

formal schooling, and 4 percent of the studies

involved populations who were university educated.

D.1.2 Qualitative Research Component

Focus group respondents for the developing country

study were nearly equally male and female, 19 

(53 percent) and 17 (47 percent) respectively. The

majority of respondents had primary citizenship 

in developing countries (89 percent), followed by 

8 percent with U.S. citizenship, and 1 percent had

citizenship in other developed countries. Half of 

the respondents were aged 32 to 43 years, with 

all respondents under the age of 65. Respondents 

conducted different types of research with many

reporting observational studies and communitybased intervention studies (see Table D.1.5).

Table D.1.2. Sources of Funding for the

Study (Multiple answers question)

Number of 

Source Responses Percent

Developing country 

government 69 35

International organization 

(WHO, PAHO, etc) 49 25

U.S. nonprofit 

(foundation, NGO) 42 21

U.S. government (nonmilitary) 36 18

Bilateral organization 

(USAID, etc) 35 18

European government 

(nonmilitary) 25 13

Developing country nonprofit 

(foundation, NGO) 18 9

U.S. private company 14 7

European nonprofit 12 6

Developing country private 

company 12 6

Other 10 5

U.S. military 7 4

European private company 7 4

Table D.1.3: U.S. Versus Non-U.S.-

Funded Research

Funding Percent of Studies

Non-U.S. 56

U.S. 44
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A total of 68 percent of respondents were currently

involved in research. Of the 12 respondents not 

currently involved in research, 7 had done some

research in the past five years and 5 had last been

involved in research over five years ago. The majority

of respondents had between eight and ten years of

research experience involving human subjects.

Slightly more than half of the respondents reported

functioning in the role of principal investigator 

on research projects, while 29 percent served as 

co-investigator. Three global regions were most 

frequently mentioned as the sites of research 

activities (see Table D.1.6).

Various sources for research funding were

reported (see Table D.1.7).

Figure D.1.3. U.S. Versus Non-U.S.-Funded Research (n = 199)

Infectious Diseases HIV/AIDS** Health Systems** Chronic Diseases* Reproductive Health**

(excluding HIV)*

80

70

60

50

40

30

20

10

0

Topic of the Study

Percent

*p<0.1

**p<0.05

U.S.

Non-U.S.

Table D.1.4: Information on Index Study

Participants

Groups Number (%) Yes

Nonpregnant women 152 (78)

Men 128 (66)

Pregnant women 92 (47)

Children 1 to 5 years 83 (43)

Infants (younger than 1) 48 (25)

Religion Number (%) Yes

Christian 139 (71)

Muslim 77 (39)

Local indigenous religion 52 (26)

Buddhist 36 (18)

Hindu 28 (14)

Don’t know 15 (8)

Animist 10 (5)

Jewish 9 (5)

Other 7 (4)

None 17 (7)

Education Number (%) Yes

6 to 12 years of formal schooling 94 (51)

1 to 6 years of formal schooling 64 (35)

No formal education 11 (6)

University educated 7 (4)

Other/don’t know 9 (5)

Table D.1.5: Types of Research

Study Design Frequency (%)

Clinical trials 14 (38)

Observational studies 24 (65)

Community-based studies 21 (57)

Behavioral studies 17 (46)

Anthropological studies 8 (22)
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For 78 percent of the respondents, their primary

employer was located in a developing country, while

the remaining 22 percent had primary employers

located in the United States. Half of the respondents

identified their primary employer to be a university.

Other primary employers included government

agencies and research institutions (see Table D.1.8). 

D.2 Informed Consent

D.2.1 Results from the Survey

The requirement for obtaining voluntary, informed

consent from human subjects study participants is a

fundamental aspect of research ethics. This section

covers the area of informing and obtaining informed

consent from study participants in the developing

countries. The results are based on the survey 

questionnaire completed by developing country

researchers. 

Disclosure

Survey participants were asked about the different

methods they used to inform participants on their

research studies. Three out of four (77 percent) of

the developing country researchers used explanations, as well as question and answer sessions with

participants, either individually or in groups, as a

way to inform and/or to obtain consent for study

participation (Table D.2.1). Only one out of five

researchers used pictorial descriptions of the study

or study procedures to inform the participants.

Academic researchers tend to use pictorial descriptions more (27 percent) than nonacademic

researchers (11 percent, p = .017). Only a small 

percentage (4 percent) of the survey respondents

stated that they used videos to explain the study. 

Half (50 percent) used community meetings 

to describe their studies, although a majority 

(63 percent) agreed that where appropriate, community leaders’ approval should be required by 

U.S. IRBs, in addition to individual informed 

consent (see Table D.2.4 on Recommendations).

Table D.1.6: Research Sites

Research Location Frequency (%)

Asia 21 (54)

Africa 12 (32)

Latin America/Caribbean 5 (14)

Table D.1.7 Funding Sources for

Research

Funding Source Frequency (%)

U.S. government 9 (26)

U.S. military 2 (6)

U.S. private company 2 (6)

U.S. nonprofit, foundation, NGO 11 (32)

Non-U.S. government 8 (23)

Non-U.S. private company 1 (3)

Non-U.S. nonprofit 7 (20)

Bilateral organization 14 (40)

Other funding 7 (21)

Table D.1.8: Primary Employers

Primary employer Frequency (%)

University 50%

Government agency 20%

Private nonprofit research institute 11%

Private for-profit research institute 6%

Independent consultant 3%

Table D.2.1: Methods Used to Inform

Participants and/or to Document Consent

for the “Index” Research Project, in

Order of Likelihood of Being Used 

Option % Yes

Explanation and question and answer session with

participants (either individually or in groups) 77

Written informed consent, requiring a signature, 

thumbprint, or equivalent 62

Community meeting to describe the study 50

Approval from a village or community leader 49

Other methods 36

Oral consent with a witness signature 33

Test of participant understanding of research 

before enrollment 27

Pictorial description of study or study procedures 20

In research with adults, approval or consent 

from another family member 19

Video to explain study 4
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In their studies, 27 percent of researchers had tested participants’ understanding of the research study before

enrollment (Table D.2.1). When asked for their recommendations, a very high percentage (84 percent) of them

recommended that a mechanism to measure participants’ understanding should be built into any research

study.

More than half (58 percent) of the researchers disagreed that the formality of going through the informed

consent process raises distrust in study participants. Nonacademic researchers were more likely to disagree 

(70 percent) with this statement than academic researchers (48 percent, p = .019).

More than half (58 percent) of the survey respondents agreed that some potential participants declined to

enroll after learning about the study (Table D.2.2). One-third (32 percent) of all survey respondents disagreed

that some potential participants declined enrollment after learning about the study. 

Informed Consent Procedures

Written Consent. The survey respondents were asked about the methods of informing participants and/or 

documenting consent (Table D.2.1). Sixty-two percent of the researchers in our sample used written informed

consent, requiring a signature, thumbprint or equivalent. However, a higher percentage of physicians in the

sample used written informed consent (68 percent), whereas only 47 percent of nonphysicians used it (p = .014).

IRB members were noted to use written consent more often (69 percent) than non-IRB members (55 percent),

in their research studies (p = .062). When the population of study participants is less than 20 percent literate,

written informed consent was obtained from only a third (33 percent). When the population’s literacy rate is

over 20 percent, written informed consent was obtained from two-thirds (65 percent, p = .023).

Shortening or Simplifying Consent Procedures. Half (49 percent) of the researchers disagreed that local

staff shortened or simplified the consent procedures compared to the original protocol, while 35 percent

agreed (Table D.2.2). Sixteen percent of the researchers were neutral on the question. Academic researchers

were more likely to agree (45 percent) than other types of researchers (24 percent) that local staff shortened or

simplified the consent procedures (p = .025). When the population of study participants is less than 20 percent

literate, over 60 percent of the researchers agree or strongly agree that local staff shortened the consent procedures, versus 32 percent, when the population’s literacy rate is over 20 percent (p = .001).

Table D.2.2: Responses to Statements Regarding Consent in Index Studies

% Strongly

% Strongly Disagreed

Agreed and and

Option Agreed % Neutral Disagreed

The informed consent process is focused too much on the individual rather 

than on the family and/or community. 66 10 24

Participants often do not understand the concept of placebo. 50 24 26

Study participants are usually aware that they are in a research study. 84 10 6

The consent process is an important means of educating participants about 

the study. 94 3 3

The consent process provides an opportunity to discuss ethics issues with 

field staff. 89 6 5

After learning about the study, some potential participants declined enrollment. 58 10 32

The formality of going through the informed consent process raises distrust 

in study participants. 27 15 58

Local staff shortened or simplified the consent procedures compared to the 

original protocol. 35 16 49

Legalistic language was required on consent forms that was not meaningful to 

study participants. 29 9 62
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A very high percentage (89 percent) of the researchers agreed that the consent process provides an opportunity

to discuss ethical issues with the field staff (Table D.2.2). 

Oral Consent. One-third (33 percent) of the researchers used oral consent with a witness signature (Table

D.2.1). Older researchers (> 45 years of age) (39 percent) tend to use oral consent with witness signatures

more than younger researchers (25 percent, p = .054).

Approval from the Village or Community Leader. Half (49 percent) of the researchers sought approval

from a village or community leader as a method for informing participants and/or documenting consent for

their specific research studies (Table D.2.1). Nonphysician researchers sought approval from the village or 

community leader more often (60 percent) than physician researchers (44 percent, p = .051). Those researchers

who did not obtain written informed consent were also more likely to obtain approval from village or community

leaders (69 percent) than those who did obtain written informed consent (50 percent, p = .015).

Consent from Another Family Member. In research with adults, one out of five (19 percent) of the

researchers obtained consent from another family member (Table D.2.1). It is interesting to note that only half

as many IRB member researchers (13 percent) used this method, compared to non-IRB member researchers 

(26 percent, p = .063). Those researchers who did not obtain written consent from the study participants were

more likely to obtain consent from another family member (28 percent) than those who did obtain written

informed consent (11 percent, p = .008).

Overall, two-thirds (66 percent) of the researchers perceived the informed consent process as being focused

too much on the individual rather than on the family and/or community (Table D.2.2). Among the researchers,

most academic researchers (73 percent) said it is too focused on the individual, while fewer (55 percent) of

nonacademic researchers agreed on the same issue (p = .019).

Forty-seven percent of the survey respondents said it is true or sometimes true that religious beliefs and/or

cultural norms of study populations were inconsistent with the practice of individual decisionmaking (Table

D.2.3). When the researchers identified their study populations as being of the Muslim faith, a higher percentage (59 percent) stated that it was true or sometimes true that the religious beliefs and/or cultural norms were

inconsistent with the practice of individual decisionmaking. In contrast, 36 percent of the researchers who

identified their study populations as being of other faiths reported that it was true or sometimes true that the

religious beliefs and/or cultural norms were inconsistent with the practice of individual decisionmaking 

(p = .004).

Table D.2.3: Responses to Ethical Issues in International Research

% True and 

Option Sometimes True

Medical care provided to participants generally is not available outside the study. 61

Study gathered potentially sensitive information about participants. 58

Study participants have unrealistic hopes about personal benefits from study participation. 55

The standard of medical care in the host country may be much lower than that of funding country, 

creating difficulties in establishing appropriate procedures for the control group. 66

Participants join because of the desire for compensation, medical care, or other benefits. 63

Research priorities of funding agency are not congruent with priorities of developing country. 58

Treatment or intervention being tested is unlikely to be available to most citizens of developing country 

in the foreseeable future. 48

Inadequate community representation on the local IRBs/ ethics boards. 61

Religious beliefs and/or cultural norms of study population are inconsistent with the practice of individual 

decisionmaking. 47

Ethics issues are rarely discussed with field staff on this research project. 39
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Study Participants’ Understanding of Informed Consent

Almost all respondents (94 percent) agreed that the consent process is an important means of educating participants about the study (Table D.2.2). A high percentage (84 percent) of them also said that the study participants are usually aware that they are in a research study (Table D.2.2). Eighty-nine percent of researchers not

employed by universities and 79 percent of researchers employed by universities said that study participants

are usually aware that they are in a research study (p = .036).

Concept of Placebo. Half of the survey respondents (50 percent) agreed that study participants often did

not understand the concept of placebo. Twenty-six percent disagreed while 24 percent of them were neutral.

Older researchers (> 45 years of age) were twice as likely (67 percent) to say that participants often do not

understand the placebo concept than younger researchers (<45 years of age) (34 percent, p = .006) 

Sixty-two percent of the respondents disagreed that legalistic language required on the consent forms was

not meaningful to study participants (Table D.2.2). As many as half (51 percent) of the academic researchers

and three-quarters (75 percent) of the nonacademic researchers disagreed that the legalistic language required

on the consent forms was not meaningful to study participants (p = .021).

Researchers’ Perception of Study Participants. Slightly more than half (55 percent) of the researchers

stated that it was true or sometimes true that the research study participants had unrealistic hopes about 

personal benefits from participating in the study. Sixty-three percent of them said it is true or sometimes true

that participants joined because of the desire for compensation, medical care, or other benefits.

Recommendations

Survey respondents were asked for their recommendations in the area of informing and obtaining consent from

study participants. Responses from all the researchers versus only those whose studies are/were funded by the

United States are compared in Table D.2.4.

The key recommendations based on the survey sample in the areas of disclosure and informed consent are

as follows:

1. The majority (72 percent) of survey respondents preferred that human subjects regulations allow more 

flexibility in ways of documenting informed consent (e.g., nonwritten methods), while 20 percent disagreed.

For those researchers who have been funded by the United States, 77 percent of them agreed that human

subjects regulations should allow more flexibility.

2. For observational studies, 40 percent overall and one-third (32 percent) of U.S.-funded developing country

researchers agreed that formal individual consent should not be necessary. 

3. Sixty-three percent of respondents agreed that where appropriate, U.S. IRBs should require the approval of

community leaders, in addition to individual informed consent.

4. Most of them (84 percent) agreed that a mechanism to measure participants’ understanding should be built

into any research study.
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D.2.2 Results from Qualitative Research

Disclosure, Voluntary Participation, and Informed Consent

The topic of informed consent consistently generated a great deal of discussion throughout these interviews.

Informed consent is a fundamental element of U.S. guidelines and regulations for research and must be implemented by U.S. researchers worldwide. Although the cultural and structural contexts of research vary greatly

across countries and within countries, some common themes emerged in the data. Generally, respondents 

considered there to be three separate issues in the informed consent process:

■ Community and potential participant education.

■ Documentation.

■ Level of participant understanding.

Many respondents felt that education of the study community and potential study participants about research

and making the concepts of the research project understandable to them was critical in gaining informed 

consent. U.S. regulations for the documentation of consent were discussed at length. 

Informing the Community. Community and individual education was viewed as fundamental, as this

respondent remarked:

...for individual consent, I feel it is right for every individual to know what type of research is

going on. And I feel that for any group that is going to decide, there should be [an] adequate

time interval, when they would be educating the people as to what they will be carrying out,

and what they are likely to benefit and what they may not benefit for it, before they come in to

carry out the procedures of research.

Table D.2.4: Recommendations

Developing Country Researchers 

Developing Country Researchers* (U.S. Funded)**

% % % % Strongly

Strongly Strongly Strongly Disagree

Agree and Disagree and Agree and and

Recommendations n Agree % Neutral Disagree n Agree % Neutral Disagree

Human subjects regulations should 

allow more flexibility in ways of 

documenting informed consent 

(e.g., nonwritten methods). 187 72 8 20 82 77 4 19

Formal individual consent should not 

be necessary for observational studies. 189 40 15 45 81 32 17 51

Where appropriate, community 

leaders’ approval should be required 

by U.S. IRBs, in addition to individual 

informed consent. 189 63 16 21 81 64 12 24

A mechanism to measure participants’

understanding should be built into 

any research study. 188 84 11 5 82 84 10 6

*Survey respondents from developing countries 

**Survey respondents from developing countries whose index studies are/were funded by the United States.
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Several respondents described lengthy consent processes that involved meeting with village leaders and community members to explain the proposed study, which was not required by any U.S. guidelines or regulations.

However, one respondent described a specific phase of the study that was the pre-study community education

component required by the study sponsor, NIH. Researchers were required to go into the study community

seven days in advance of implementing the study and meet with community leaders and talk with potential

study participants about the research and the proposed study. 

Several respondents explained a process that was used to communicate difficult medical concepts to 

members of the study community. One respondent said: 

I gathered around 22 representatives of community and talked to them, they all listened 

attentively. When I came back I knew I was unable to reach them. So I decided there is 

something wrong with the way I approached them. I requested them to gather again, meanwhile, I prepared myself and educated myself and tried to explain in their own language by

giving examples of things which are of their own interest...how water is necessary for growing

crops and similarly water is necessary otherwise the child gets dehydrated...before plowing

you prepare the land and then put seed in it so that the yield is healthy and plenty, in case of

your children do you prepare your women for childbirth to have a healthy baby...this is how 

I made myself and my team acceptable in the village.

In gaining informed consent, one salient issue was that it should be done in a culturally appropriate manner.

Although the written and signed consents seemed to be more difficult to execute in many study communities,

the overall concept of consent seemed to be consistent with local cultural practices, as this respondent

explained:

...it’s [informed consent] a cultural practice and part and parcel of our cultural norm, that you

introduce yourself and tell them why you have come.

Respondents emphasized the importance of following local social norms and cultural customs during the

recruitment of study volunteers, even if it is a time-consuming process. This was of high priority and concern

for some respondents. In one university, students are graded on how well they dress and interact with the

study population. Another respondent remarked:

...if you do not conduct yourself [in] what is a socially accepted way, they will kick you out. 

I mean it is as simple as that. So, if you go there you have to follow the accepted norms in that

society and explain what you want to do.

Informing the community is held as the critically important component in gaining informed consent. As one

respondent remarked, the standard that is always used is individual informed consent. But because so few 

participants are really familiar with research, getting informed consent was viewed as depending on how well

the individual and the community were educated about the study. Individual consent is the end result of a lot

of conscious and unconscious “community consultation.” As this respondent commented: 

People get information through the media and through what other people in the community

are talking about, although the aim is for individual consent. 

Standards of Disclosure

Disclosure of medical information was not discussed at great length. One respondent mentioned this issue in

terms of the discomfort of the disclosure of medical diagnosis for which there was no local treatment available.
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Disclosure of HIV test results was mentioned as being provided with pre- and post-test counseling. Another

respondent disclosed cancer diagnoses gradually over a period of time, as was culturally more appropriate. 

More often, disclosure was described in terms of communicating the risks and benefits of research participation to potential study volunteers. Full disclosure to study volunteers was perceived to influence the success of

not only the current study, but also future research projects. As one respondent stated: 

In [African country] we see it as a very essential complement of any successful research

because be it at, the community level or in the hospital, rumors spread very fast.

Misinformation goes around very rapidly, so to have any successful research, we think it 

is important to be transparent and to get the patient to understand exactly what they need 

to go through. So for us it’s a must. 

Several respondents mentioned that poorly supervised recruitment efforts or staff who receive monetary 

incentives for achieving recruitment quotas could result in a failure to communicate all aspects of the study.

This situation created negative consequences for present and future research efforts. In one case, study participants wanted to leave the study early because they were not made fully aware that blood would be drawn on a

monthly basis. As this respondent stated:

...so right at the beginning I would try to explain that [negative consequences]...because

other people who are participating [recruiters] were more interested in recruiting that person

and would tell them the positive side of participating and not mention the negatives. 

Another respondent described incompetence in adherence to regulations among data collectors and admitted: 

In certain situations the forms are just handed over to data collectors and they are not supervised. The problem arises when the next round of data collection starts and false hopes are

raised.

This was true of hospital settings as well, where written consent forms are given to the patient, but are typically

just signed without being read or without any explanation given by the provider. Although specific risks and

benefits may be included in the consent form, the consent process in those cases is reduced to “just getting a

signature.”

Voluntary Participation

Several respondents made very clear statements that participants understand that study participation is 

voluntary. This respondent expressed concern that respondents are told explicitly about the voluntary nature 

of study participation:

One of the important things...is, including in the consent forms is that it’s a moral obligation

thing. Like we have to say, and this is my own feeling, that if you do not answer the question

and if you refuse to on the interview...don’t feel bad about it. Sometimes they do that...it’s I

don’t have time or I don’t have energy. So this is something which is not in the regular consent

forms.

Another respondent agreed: 

It is on us to make, to let them know that [study participation is voluntary] because if you

don’t make it clear, then they’re tied to this stuff, which is not good. 

Several respondents also mentioned cultural and structural barriers to voluntary participation. Two respondents

commented on specific cultural factors:
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...if you’re coming from the government system or from the university, and you turn up and

you’re doing research, traditionally people are very receptive anyway for visitors. So they

extend [to] you that traditional hospitality and they will answer questions without...hesitation. 

You know in our country, people feel that they are morally bound not to refuse a guest. We

assure them that if they refuse, their reputation will not fall in our eyes. 

A situation was described of how voluntary participation was not allowed in a study among military conscripts.

The data collection was conducted in one large room where military conscripts were present with their superiors

who initially did not allow conscripts to leave without participating in the study. This respondent related the

experience:

...we somehow negotiate[d] with the superiors to let them walk out if they don’t want to 

participate in the study. 

One respondent raised a concern regarding local policy and informed consent. In this particular case, a U.S.

organization was conducting large national demographic surveys in two African countries. This work is typically organized and implemented through the national statistical offices most often found as a nondepartmental

entity or within departments dealing with economics, finance, or planning. Most developing countries have

such offices, and they are responsible for gathering certain information that is used for statistical purposes.

Providing this information is considered mandatory by the government. The problem arose in two countries

where the national statistical offices felt that the information included in this national survey was within their

legal mandate for gathering data to be used for statistical purposes. A consent form was implemented in 

gathering the survey data; however, all references to the data collection as being voluntary were deleted from

the consent form. When blood was drawn as part of the survey for gathering information on biomarkers, the

entire consent form was permitted including the statements that participation was voluntary. 

Documentation

Written Consent. Respondents felt it important for study participants to provide consent, but found it difficult

to fulfill U.S. consent documentation requirements. The concept of the written consent form was new in most

study communities and has only reached familiarity in settings where people regularly participate in research.

One of the most salient problems with informed consent was the amount and detail of information required to

be included in written consent forms. These statements reflect the concern of most respondents: 

I found that the consent document as required in this country. I mean it lists so many 

subheadings, that for a lot of situations in which we are doing research, people generally 

find it irrelevant. They will either grant you consent or not.

You are kind of complicating the whole situation by ...go[ing] into depth about asking 

permission and all of that.

Respondents reported using written consent forms of up to eight to ten pages in length. Generally respondents

felt the required content made consent forms too complicated and detailed. Some study participants were

described as being intimidated and frightened by official-looking written documents. However, one respondent

suggested that the NIH regulations had “very clear guidelines” that “they were able to translate...into a rural

culture.” Another respondent disagreed with this and explained that condensing the consent form to even one

page does not address all barriers:

But that doesn’t make any difference if you’re dealing with an illiterate person. That’s the case

for more than 60 percent of the population of [Caribbean country]. Even though we have 

one-page informed consent, that doesn’t make any difference.
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Illiteracy was the concern of several respondents:

In many parts of endemic areas, [a] relatively high percentage of local people are illiterate.

Thus asking for written consent is unfair.

Several respondents felt that the consent form regulations focused on the legal protection of investigators or

universities and were being applied in locations that do not have a legal framework similar to the United States

to sustain or guide the process. As one respondent said regarding these procedures, “It is driven by the

American system.” Another respondent commented that there were no answers for study participants when

they asked about the confusing language of “giving up legal rights” found in the consent form. The complexity

of written consent forms can unfairly exclude people from participating in research:

...it’s making it difficult for people and I even question the ethics of it. By making the form so

complicated, are we preventing people who should have a right to participate from participating

because they cannot read or interpret that lengthy, you know [consent form]....We are excluding

people because of that, and they should have a right to participate too. So we need to look 

at that. 

Several respondents, who felt that these forms should not be used in lieu of a thorough ethical review, 

commented on the emphasis on legal protection in the consent form requirements. These respondents felt 

that consent forms should not excuse ethics violations or take on what is the responsibility of the review

boards. One participant commented: 

I think institutional review boards must review the ethics of studies and not necessarily the

unethics [unethical aspects] of the study with a piece of paper [consent form] saying we told

the patients...it must be reviewed to see if it’s ethical....

Verbal Consent. Many respondents felt that in certain situations, using an oral consent process was more

appropriate than using a written consent form. In order to provide the necessary and sufficient information so

that people could understand and make a decision, many respondents felt that this could only be done verbally:

Informed consent for me is not giving a paper and then sign. We have to explain because

when we explain what does it really mean, like you have explained to me right? What is the

objective of the research, what you have come [for], what is the benefit there or no benefit

there, what is his right or her right or whether he can say, yes or no, so given all the explanation and description what you’re really going to do so that he or she can form an opinion of

whether he or she wants to participate....

The typical verbal consent process described in the data involved the study staff reading a written consent 

form or a disclosure statement to the study volunteer followed by discussion and an opportunity for the study 

volunteer to clarify information and ask questions. The person may or may not sign the form, in some cases a

thumbprint is used, and often there is no record of the consent. Several respondents reported having the staff

person as a witness who signs the consent form stating that the study volunteer understood the conditions of

the study and agreed to participate. Some respondents describe this oral consent process as an opportunity to

not only “explain”’ and “clarify” the conditions and implications of the study but also, as one respondent said:

It’s a great venue to teach, to really educate people, especially with HIV disease...it gives you

an opportunity to really sit one on one almost like counseling....

Other respondents described the time-consuming process of talking and discussing the study with potential

volunteers over a long period of time before they decide whether or not to participate. 
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Verbal consent was a very appropriate technique for many respondents in the settings, where literacy levels

are low and verbal exchanges and discussion are the cultural norm. Respondents commented that written 

consent forms possibly were more appropriate in some settings, such as urban areas, and for intervention 

studies versus observational studies or for epidemiological studies that do not cover sensitive topics. As one

respondent noted:

In a noninterventional study it is more important to sit with people or individuals and explain

to them verbally rather than signing a document.

Heated debates were reported among respondents who had to deal with the inappropriateness of the written

consent forms in some of their study communities. In conducting a national survey, one respondent reported

this issue was resolved by using the written consent form as the goal, while allowing study staff to adapt this to

their settings, using verbal consent as necessary. Respondents referred to “formal” and “informal” consent, but

no clear definition of these terms emerged in the data. 

Signed Consent. Many respondents felt that the signed consent form, regardless of how well the issues 

of the study are explained, verbally or in writing, created suspicion and discomfort among potential study 

volunteers and actually served to deter research participation. There are several reasons for this, including a

history of political unrest and conflict, as this respondent explained:

...this is mainly because of the history that our country has gone through with sometimes

repressive regimes...if you sign any document...somebody could use it against you at a 

certain point. 

In some countries signing a document is synonymous with potential harm, while in other countries, it is associated with property, and signing a consent form may be misconstrued as signing away a home or land. Other

respondents stated that when a document is signed it signifies that there is distrust between the two parties or

that the document refers to something legal to which the person is now bound. Several respondents reported

that study participants were willing to answer any questions for the study but were reluctant and unwilling to

sign the consent form. There may be other, more specific cultural meanings attached to the act of signing one’s

name that were not mentioned here. 

Level of Risk and Consent Requirements. One respondent commented on her ten years of research 

experience and the differing requirements of consent by local ethics review committees that she has observed.

Different types of studies were required to have different types of consent. Clinical trials required written and

signed consent forms; community-based interventions and trials required verbal consent which could be 

documented, but signatures were not required; and, until recently, observational studies did not require 

documentation of informed consent. 

Social Science Research. Two respondents were particularly concerned about social science research being

conducted to gather data on sensitive personal topics without the use of consent forms. According to one

respondent, there has been “gross indifference to ethics and self-regulation” in the social sciences. One of these

respondents recognized a need to develop ethical guidelines for social science research “to protect participants

and uphold their dignity.”

Research Versus Program. Others questioned the development-oriented programs that are not research 

per se but that have conducted surveys or evaluations without using consent forms:

I don’t know how like somebody should know like the World Bank or the WHO, UNICEF,

when these organizations conduct studies....I know there’s a lot of studies conducted by or

sponsored by these organizations and I’ve never seen consent forms.
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Communal and Surrogate Consent

While the U.S. ethical guidelines emphasize individual autonomy, in many developing countries, emphasis is

on the collective well-being of the community, and reaching community consensus is paramount. One respondent

commented on this fundamental cultural difference:

There are a lot of cultural differences...my experience of research in the United States is very

limited. However, there people are more concerned about what they will get out of it and once

you explain it to them that there will be no immediate benefit, they are a bit disappointed 

initially. The basic difference I think is that in [the] United States, an individual can make a

decision on his own.

Seeking approval or permission for the study from community leaders or through the established hierarchy of

leadership was critically important in some study communities. Although this was often not a requirement of

investigators per U.S. guidelines, it was a critical step in gaining access to the community. Several respondents

described the process of meeting with village leaders to explain and discuss the details of the proposed study.

The leaders discussed and asked questions, and when they reached a consensus, they would either grant or

deny permission for the research to be implemented in their community. 

Once the village leaders gave their permission, the investigators could comfortably approach individuals for

their participation. Individuals could refuse to participate despite their community leaders’ approval of the

project. Regarding this process one respondent said:

...if you’ve had all of the authorizations from the Ministry of Health, and locally you read

everything to them (community leaders) and they understand what you’re going to do in the

community, then they sign the consent. But if you’re going to individual consent, you are

going to scare people. But as long as local leaders are giving consent, then every program is

complete, because they explain everything to the subjects. 

Government approval was mentioned by one respondent as being particularly effective in gaining community

and religious leaders’ permission for the study:

But what we do, successfully what we have been doing is when we launch a study, we take the

permission from the general health or general family planning, and he sends a letter to all of

the district levels [down]...to the lowest hierarchy of the [local] health facility.

Other respondents disagreed with the process of communal consent. While they recognized the importance 

of community leaders’ involvement and awareness of the study, they did not feel community leaders should

provide consent. As this respondent remarked:

It may be appropriate or sufficient to ensure community leaders are informed of the research

rather than requiring their approval. In communities where leadership could either be aligned

to prevailing politics or/and biased towards men, such a requirement may not fulfill the ethical

aims as intended. 

Another respondent felt that the protection of individual rights and particularly rights of minorities and 

women is made difficult in settings where surrogate or communal consents are culturally promoted. One

respondent suggested the way around protecting the autonomy of individuals, but still seeking permission 

from community leaders, is to ask for signed consent from individual participants or from a third party where

literacy is low:
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The way around that could be to, you know, to...have a consent. Read up [the consent form]

to individuals [and] have a third person as [a witness] who can then sign the form for the

individual. But I...wouldn’t think it would be enough to just use the community leader’s 

permission to go ahead and do the study.

Another respondent disagreed with this and felt that true informed consent will take years of community 

education and exposure to research: 

I would agree with you, but we are talking about meantime. Meantime. Like for example, in

[African country] meantime, if you have to do a research, I think it would be okay to go ahead

and just get consent from the leaders. But for personal autonomy in the long run you have to

educate the people in terms of their rights... You can’t actually expect someone on an individual

level to actually give, what is called informed consent...I mean, otherwise, [you are] just 

getting a signature, really.

Surrogate Consent. Individual consent is not culturally appropriate in some settings where individual decisionmaking is not the norm. Surrogate consent was a particularly poignant issue for women. In many cultures

women are in a position of little to no decisionmaking power within their household. This has been an important

concern in some countries and has been raised on local ethics review boards. A respondent described this 

specific incident:

I think in our society husband’s permission is very important so that should somehow be

made part of the regulations. Well, we had this experience that we took permission from the

woman, conducted the interview and at that time the woman did not think it was important

to get the husband’s permission. But later she had lots of trouble with her husband and her

mother-in-law. After that we explicitly asked for husband’s permission.

Legal advice was sought in one case to determine whether or not a husband or a son could provide permission

for their wife or mother to have surgery. In another example, a respondent explained how a video of a puppet

show on breastfeeding to be shown to mothers in the community had to be performed for community leaders

before the study was implemented to provide proof that it included nothing that was culturally inappropriate.

Only after permission was granted was the video shown to the mothers. 

The inappropriateness of individual consent was also mentioned in the context of conducting research

among the elderly. One respondent provided the example of a study on Alzheimer’s disease in which participants

were recruited door-to-door. In this particular host country, the elderly are cared for by their relatives and

rarely live alone. The family, in a sense, serves to protect their elderly relatives. Surrogate consent was the only

acceptable method for gaining informed consent in this context:

In [Asian country] you find very few elderly living alone. At the time we were doing the study

probably something like two to five percent. Five percent is even too high. It is like two to

three percent were living alone. So, therefore, when you not knock on the house and there is

an older person, the consent is given by family and relatives, not by that older person. And

they decide whether to let you or to allow that older person to answer questions. So, you have

to explain to them what you are doing.

While all participants felt it was important to protect human subjects rights, they also recognized that these

particular cultural issues should be addressed in designing appropriate consent processes. 

One respondent related the idea of communal consent to a group of peer investigators with whom he would

conduct HIV research. Investigators were intimidated by HIV disease, which carried an enormous stigma in the

host country, as in many other parts of the world. After presenting the study and allowing investigators to 
B-81

discuss and ask questions, the discomfort and fear of researching and talking about HIV was reduced. The

respondent also felt that because a local and not a Western investigator conducted the presentation, the 

information was more easily accepted.

Level of Understanding

Most respondents felt it unrealistic to think that study participants will be able to comprehend all of the details

of the study. It is very clear among respondents that the idea of the consent form is useless unless the person

understands it. These two respondents commented as follows: 

...informed consent means nothing if the participant has not understood it. Otherwise it is

just a piece of paper. It is just rubbish. 

Is it meaningful? As a tool to improve research...but not all of the patients understand in our

city, a big university hospital. 

Respondents generally felt that broad concepts should be communicated without confusing participants with

too much technical or medical information that unnecessarily raises their anxiety. Again, the educational

process was emphasized as one respondent said:

I think informed consent is the most difficult part of research. It is also the most sensitive. It

depends on how well you educate the patient and how much awareness there [is]....

Another respondent described a long process of recruitment of couples for a study. She visited each family’s

house individually, returning several times to answer questions and provide explanation before the couples

made a decision. She commented that this took a great deal of time but that “it was important that they understand” what study participation entailed. The education component was important.

Several respondents did think that it was possible for study participants to have an acceptable level of

understanding to be involved in the study. A respondent stated:

It doesn’t take a whole lot of research that someone should get a Ph.D. to understand some of

these things. You just need to explain in the vernacular, what research is so they understand

what they are getting into. 

One respondent felt that there should be an assessment of the level of understanding of the participant before

introducing the consent form. This respondent commented as follows: 

I think...it [informed consent] is extremely important, informed consent has a place in

research because the people that in my case....I would take a skin snip or blood or remove

nodules from people and they need to understand the relationship between those nodules and

blindness. I need to go through the life cycle of whatever you’re doing with the patients to that

point so that they understand...So we find out that they know what we want and they know

what to get from it [study participation]. Once that is established, then informed consent 

[documentation] is absolutely important.

Another respondent described the process of trying to explain complex biomedical information using language

and concepts comprehensible to participants. This respondent said: 

Working with HIV was really very difficult to put all of that information down there. So we

had to break it down really like...although it wasn’t...very accurate, you know...to talk about

retroviruses and even clinicians themselves don’t know what you’re talking about, so we had

to break it down.
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Many respondents discussed the difficulty of explaining placebo and control arms and the logic behind applying them in study designs. Study participants generally wanted to receive the intervention and did not understand the concept of “placebo.”

Barriers to Autonomy. While the decision to participate in research is preferably an informed and

autonomous one, social and contextual factors greatly influence decisionmaking. In many societies, patients

defer to their doctor in health care decisions. Several respondents described this situation: 

...I think in our culture people expect when they go to a doctor or a medical person, the

medic knows best...and the whole notion of questioning or arguing with their doctor is just

[for] a very, very small elite that is highly educated and so on that actually starts to do that.

But I will say a lot of the people they go to the doctor they say, okay, you are the doctor. You

decide for me what is best. 

...in my experience, most of the times the patients tell me to decide for themselves which is

very common in my society....Some people tell you what to do. You’re not as an individual

empowered to decide on your own or to steer yourself. So it’s the mentality, which is different.

I think most of the times or at least half of the times the patient feels like it should be better

for him or her; otherwise the physician wouldn’t suggest [it]. 

In [Asian country], many of the patients, most [studies are] done by doctors, many of the

patients, when they are talking to the doctor,...[they think] this person is definitely trying to

do something good for us. He’s like a God.

In some countries, the lack of awareness among health officials presented a barrier to providing education and

informed consent. This respondent described the attitudes of local health authorities: 

...if you are providing health service, it’s good for the person. They don’t have to say, yes, I

agree that I want to participate in this...it’s [informed consent] seen as an inconvenience and

that the people you are dealing with don’t know what you’re talking about anyway, so let it go.

That climate of opinion isn’t there yet, and that’s part of the work we need to do is to make

them aware. 

One respondent remarked that research staff often encouraged people to stay in the study because they 

consider this their job responsibility:

Sometimes those who that were working on the project, I mean not ourselves as the main

researcher, but the others that came, it was their duty to keep them in the research and to 

convince them to stay in the research. That is their task.

Conducting research in poor communities is challenging for investigators in explaining the benefits of the

study to people who have more immediate needs, such as access to potable water. These respondents feel 

constrained by informed consent guidelines: 

It is restrictive. Researchers have reacted to it. In [Asian country] at times you are spending 

so much time telling why you are here etc., it’s not that we are coercive. Half the time the 

challenge is to convince the people that this research is needed, as they do not see any benefit. 

To tell the truth the researcher[s] are least concerned about consent and more concerned about

acceptability. You have to go with your heart tied, that I need this information for the greater

good. Our agenda is different from the agenda of the woman being interviewed. She will see

less utility of interview over feeding her kids or animals. 
B-83

Recommendations

Documentation. The most frequently mentioned recommendations involved flexibility in applying guidelines

for informed consent documentation. Where written consent forms are not applicable, verbal consent should

be acceptable. Although several respondents felt it was advisable to have written consent forms for therapeutic

interventions considered to be invasive procedures, such as drug trials, in areas of high levels of illiteracy, a 

verbal consent procedure should be acceptable. 

Respondents recommended the application of various innovative techniques for community education and

informed consent such as videos, small group discussions, and the use of visual aids. One participant recommended, particularly in studies regarding family planning or reproductive health issues, providing information

to potential participants and allowing them to take a few days to discuss it with significant others before

returning to give their individual consent.

The issue of the content of the consent form should be revisited, with an emphasis on broad concepts and

general explanations of the risks and benefits involved in study participation and the conditions and responsibilities of study participants and the investigators. At least one respondent recommended that host country

investigators develop consent forms. Local religious beliefs, level of education, cultural norms, and legal needs

should also be considered. The appropriate local language should be used in writing consent forms, with a

focus on translating concepts, not individual words that have no meaning in certain cultural settings, such as

“blood pressure” and “cholesterol.” Several respondents recommended that written consent forms should be no

more than one or two pages long. 

In terms of requiring signed consent, many respondents opposed this as a requirement in cases other than

for surgery or invasive procedures. The only recommendation offered was to have a third party witness the 

participant’s consent and sign the form for the study participant. Several respondents recommended a short

assessment of the level of understanding of each individual of their role and basic concepts of the study at the

completion of study participation. 

Autonomy and Consent. Communal or familial consent versus individual consent requires substantial

exploration. Cultural, political, and social factors are important in examining this issue. Several respondents

cautioned against advocating for the necessity of community leaders’ approval of the study due to their political

or personal interests that could potentially not be in the best interest of the community. However, the majority

of respondents advocated a review of the cultural sensitivity of guidelines regarding communal and surrogate

consent. 

Respondents also suggested multilevel education activities for individual, community, and government 

officials to raise awareness of research and related ethical issues and principles. Implementing a pre-study 

community education phase where members of the study community have an opportunity to receive and 

discuss information about the proposed research with study investigators was also recommended.

Personal autonomy in decisionmaking was sometimes viewed as a long-term goal in research, but others

suggested that the IRB should find ways “to increase the ability of persons to make competent and autonomous

decisions.” At the government level, education and training for health officials and researchers alike was recommended. A general discussion of the philosophy and purpose of informed consent was recommended for

developing country officials and investigators before writing specific guidelines at the local level regarding this

process.
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D.3 Risks and Benefits

D.3.1 Results from Survey

One of the challenging ethical issues in international research is whether a research design that could not be

implemented in the sponsoring industrialized country can be ethically justified in the host country where the

research is carried out. In the survey, developing country researchers were asked about reasons for the study

being carried out in the host (developing) country as opposed to in the United States. All of the survey respondents’ answers were compared with answers of those respondents whose studies are/were funded only by U.S.

sources, as shown in Table D.3.1.

Overall, 66 percent of the developing country researchers who completed the survey agreed that prevalence

of disease in question is much greater in the host country than in the United States. Sixty-four percent of those

developing country researchers whose index studies were funded by the United States agreed on the same

question. A much higher percentage (88 percent) of nonphysicians versus 59 percent of physicians stated that

prevalence of disease in question is much greater in the host developing country than in the United States 

(p = .040).

Seventy-six percent of the survey respondents agreed that the intervention being tested is more relevant to

the host country than to the United States. Seventy-seven percent of the U.S.-funded developing country

researchers agreed. A much higher percentage of nonuniversity respondents (89 percent) versus university

respondents (67 percent) agreed that the intervention being tested is more relevant to the host country than 

to the United States (p = .053).

Table D.3.1: Reasons for the Study Being Carried Out in the Host (Developing)

Country as Opposed to in the United States 

Developing Country

Developing Country Researchers 

Researchers* (U.S. Funded)**

Question Number (n) % Yes Number (n) % Yes

Prevalence of disease in question is much greater in the host country 

than in the United States 80 66 63 64

Intervention being tested more relevant to host country than to the 

United States 82 76 62 77

Easier to identify a cohort of patients relevant to research 69 55 54 54

Recruitment of patients more rapid in host country than in the 

United States 60 52 49 53

Less expensive to do study in host developing country than in the 

United States 60 62 47 60

Host country researchers asked for U.S. collaboration 85 69 66 67

Research question relevant to U.S. strategic interests in the region 70 49 55 45

Marketing approval for drug or device will be sought in host country 53 25 41 24

Interest in addressing global inequalities 80 71 63 71

*Survey respondents from developing countries. 

**Survey respondents from developing countries whose index studies are/were funded by the United States. In the survey questionnaire,

although only those researchers who received U.S. funds for their index studies were asked to respond to this question, additional numbers

of researchers also responded to the question. It is possible that U.S. funding may have been involved as part of bilateral funding or other

arrangements that could not be determined from the survey data. The responses are to be based on index studies, and it is possible that

responses may have been given based on general experiences and personal opinions.
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Over half (55 percent) of the respondents agreed that it was easier to identify a cohort of patients relevant 

to research in the host country. Fifty-four percent of the U.S.-funded developing country researchers agreed. 

Half (52 percent) of the respondents also agreed that recruitment of patients is more rapid in the host country

than in the United States. Fifty-three percent of U.S.-funded developing country researchers agreed. About 

one-third (62 percent) of the survey respondents agreed that it is less expensive to do the study in the host

developing country than in the United States. Sixty percent of the survey respondents with U.S.-funded studies

agreed.

Sixty-nine percent of the developing country researchers agreed that they asked for U.S. collaborations.

Similarly, 67 percent of the U.S.-funded developing country researchers also asked for U.S. collaborations. Half

(49 percent) of the respondents agreed that the research question is relevant to U.S. strategic interests in the

region. Forty-five percent of U.S.-funded developing country researchers agreed. Sixty-three percent of the

female survey respondents agreed, while a smaller percentage (41 percent) of male survey respondents agreed

that the research question is relevant to U.S. strategic interests in the region (p = .098).

One-quarter (25 percent) of the survey respondents (as well as 24 percent of the U.S.-funded researcher

respondents) agreed that marketing approval for the drug or device would be sought in the host country. More

than twice as many (38 percent) of IRB-member respondents agreed versus 17 percent of non-IRB member

respondents that marketing approval for drugs or devices will be sought in the host country (p = .115).

Seventy-one percent of the respondents agreed that interest in addressing global inequalities was one of 

the reasons for the study being carried out in the host country as opposed to in the United States. The same

percentage of U.S.-funded developing country researchers also agreed. It is of statistical significance that as

many as 94 percent of nonphysician respondents versus physician respondents (64 percent) agreed that interest

in addressing global inequalities was one of the reasons for the study being carried out in the host country as

opposed to in the United States (p = .016).

Standard of Care in Host Country

Sixty-one percent of the respondents agreed that it is true or sometimes true that medical care provided to 

participants generally is not available outside the study (Table D.2.3 in Section D.2). Almost three-quarters 

(74 percent) of the U.S.-funded researchers said it was true or sometimes true versus half (52 percent) of the

non-U.S. funded researchers that medical care was generally not available outside the study (p = .031). A

higher percentage (65 percent) of male respondents agreed versus female respondents (49 percent) that medical

care provided to participants within the study generally was not available to local populations outside the study

(p = .084). 

Two-thirds (66 percent) of the developing country researchers agreed that it is true or sometimes true that

the standard of medical care in the host country may be much lower than that of the funding country, creating 

difficulties in establishing appropriate procedures for the control group. Fifty-five percent of the respondents

said that it is true or sometimes true that study participants have unrealistic hopes about personal benefits from

study participation. 

Sixty-three percent agreed that it is true or sometimes true that study participants join because of the desire

for compensation, medical care, or other benefits. Response of male survey respondents differed significantly

from the female respondents. Sixty-eight percent of the male respondents versus 58 percent of female respondents stated that it is true or sometimes true that study participants join for the benefits (p = .033).

Slightly more than half (58 percent) of the respondents agreed that it is true or sometimes true that research

priorities of funding agency are not congruent with priorities in developing country. Half (48 percent) of the

respondents said that it is true or sometimes true that treatment or intervention being tested is unlikely to be

available to most citizens of the developing country in the foreseeable future. For those researchers whose index

studies are related to HIV/AIDS, they appear to be more optimistic. As many as 82 percent of them disagree,
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compared to the other researchers working on other issues (53 percent), that the treatment or intervention

being tested is unlikely to be available to most citizens of the developing countries in the future (p = .034).

Recommendations

Survey respondents were asked for their recommendations in the area of standard of medical care for the study

participants and availability of intervention if research is found to be successful. Responses from all the

researchers versus only those whose studies are/were funded by the United States are compared in Table D.3.2.

Seventy-seven percent of the developing country researchers agreed or strongly agreed that the issue of what

standard of medical care to provide to study participants should be decided on a case-by-case basis, while 

16 percent disagreed. Similarly, 77 percent of U.S.-funded researchers agreed, while 19 percent disagreed.

More than three-fourths (78 percent) of the developing country researchers agreed that research to test an

intervention should not be carried out in a developing country unless the intervention, if found to be successful, will be made available to that country at the conclusion of the study.

D.3.2 Results from Qualitative Research

Access to Health Care

Local health care services in study communities are typically described as “not functioning,” “understaffed,”

and “lacking in supplies.” Several respondents remarked that people must seek care outside of the communities

where they live, often at a great distance. Family planning services are often not readily available in the community, particularly access to a broad range of family planning methods. 

Some respondents claimed there was an underutilization of services due to “lack of awareness” and poor

quality of care. Lack of utilization of health care services in one country was explained as due in part to village

health workers selling pharmaceuticals from shops adjacent to their homes or the health center. Often, community members preferred purchasing these drugs to seeking care at the health center because the health center

itself often did not have pharmaceuticals in stock. In terms of HIV, antiretrovirals and other more basic drugs

used in the treatment of HIV and AIDS are typically inaccessible. In some countries, only the wealthy upper

class are able to purchase HIV medications including antiretroviral therapies. 

Table D.3.2: Recommendations

Developing Country Researchers 

Developing Country Researchers* (U.S. Funded)**

% % Strongly % % Strongly

Strongly Disagree Strongly Disagree

Agree and and Agree and and

Recommendations n Agree % Neutral Disagree n Agree % Neutral Disagree

The issue of what standard of medical 

care to provide to study participants 

should be decided on a case-by-case 

basis. 182 77 7 16 79 77 4 19

Research to test an intervention 

should not be carried out in a 

developing country unless the 

intervention, if found to be successful, 

will be made available to that country 

at the conclusion of the study. 187 78 9 13 81 32 17 51

*Survey respondents from developing countries.

**Survey respondents from developing countries whose index studies are/were funded by the United States.
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Relevance of Research

Respondents generally felt that research should not be conducted without giving something back to the study

community. A respondent expressed this point as follows:

At times you have to do this kind of study with controls for the benefit of the people at large.

To me the real issue is working in a community and later pulling out of it. You benefit from

the community but what had you given them in return.

While most respondents acknowledged that much of the research benefits the “greater good” and not the 

individual, some questioned who the “greater good” might represent. These respondents strongly opposed

research in resource-poor countries that will only benefit those living in developed countries:

U.S. investigators should not be allowed to test hypotheses in developing countries that would

tend to benefit primarily subjects in the United States. The justice principle of ethics would be

violated. The argument that a technology, be what it may be, has already diffused and is

already standard therapy in the United States is just not acceptable.

This debate was most often illustrated through examples of drug trials and drug companies conducting what

some respondents considered unethical research. Another respondent remarked:

I know that’s being very radical, but the point is that there are drugs that are dumped on

developing countries. There are things that are done wrongly to people, and you don’t know

what the effect is down the line. Are they carcinogenic? Are they toxic? Nobody knows, and

they just bring it. If they’re doing drug clinical trials and if the Ministry [of Health], you bring

your drug, I’ll ask you, did you try these drugs on your own people? If they say no, then don’t

bring it here, period. 

Compensation and Incentives

Medical Care Compensation. Many respondents acknowledged that people who do not have access to health

care, who have less education, and who are poor want to participate in the research so that they may receive

health care or other services. By participating in studies, they hope to gain access to at least some benefit for

themselves or their families, as this respondent said:

...the low income class they really don’t know what is going on...they [are] willing to 

answer whatever it is. Or if that’s a treatment [that] might help them but doesn’t cost any

money, they don’t care. Just to go through the benefits of whatever...is offered. But when 

the thing goes to a high level of...socioeconomic level with education, you might get more

questions...and...they might be unwilling to participate.

Other respondents agreed and felt that providing medical care as an incentive was undoubtedly coercive:

...I don’t think the informed consent forms add anything or do anything ethical to the whole

research process because if a mother is in the hospital and to bring their child....What do they

tell them? What do you have to say? Treat the children. They wouldn’t bring them there in the

first place. How would they refuse to take any form of treatment they are offering to them? It’s

hypocrisy, I think. I think researchers ought to think about what they are doing and then do it

with the interest of the patient at hand rather than go through some bureaucratic process and

call it informed consent. 
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...I don’t think it mattered to the people [initiating consent forms]. They just wanted help and

they expected that they would be investigated and they would get assistance somehow.

Despite these opinions, generally, respondents did feel that medical care was an acceptable incentive, or rather

benefit, for study participation. Many respondents viewed the provision of medical care including diagnostic

testing, as acceptable incentives for study participation:

What we have done in terms of incentives in the project is provide medication...to the people

in their communities. We provide more clinics to the people.

One of the things that—we went to do research, but one of the things that we had to do was

really establish a lab where we were providing diagnosis, just diagnosis and screening and confirmation of HIV disease to anyone who wanted it, and that was, you know, kind of part of an

incentive for, you know, participating in the study.

However, at least one respondent did not agree that receiving knowledge of a positive test result for syphilis, in

that case, could be considered an incentive, because the disease cannot be treated locally and the clinic referral

is meaningless.

When respondents were asked if they knew why people participated in their studies, it was found that most

did not typically document this information. However, several respondents felt that study volunteers willingly

participated in research knowing that it would not directly benefit them beyond gaining some new information

or, as in one case, an opportunity to socialize with their friends and neighbors.

For many respondents this broadened the discussion to the more difficult issue of determining the limits of

treatment of infections or health problems unrelated to the study that are diagnosed during the study. Several

respondents shared experiences of procuring treatment or the funding to make medications available to treat

infections diagnosed during the study. One respondent researching diabetes was concerned about whether

study volunteers would be able to access health care when the study ended. Medical supplies were given to

study volunteers, but the research staff also provided their personal telephone numbers so study participants

could reach them in case of emergency. 

Monetary Incentives. Monetary compensation for travel to the study site or for loss of income from paid

work or other costs incurred in relation to study participation was acceptable to most respondents. However,

several individuals spoke out against distributing monetary incentives to study participants. As one respondent

explained:

They want to see taps in their houses with running water but we do not pay them anything.

We never pay for anything. I am dead against that, but some organizations are paying.

Another respondent stated that this was a national level concern because many community-based organizations

provide services similar to those of the studies, but do not offer monetary incentives to participants. In the long

run, monetary incentives were viewed as jeopardizing the activities of community-based organizations. Financial

incentives were used in some studies, but the amount of the incentive was so low that it was not used as an

incentive per se, but rather to cover the costs of study participation. 

Study Staff Incentives. Providing incentives for study staff was typically not commented on, as it seems

staff are generally not offered any incentive for recruiting study volunteers. However, one participant reported

this to be a very controversial topic in his country where study staff have been provided monetary bonuses for

recruiting volunteers. This has created a “conflict of interest” for study staff who have low incomes and who

genuinely feel that participation in the study is “the right thing” for the volunteer. In their eagerness to recruit

volunteers, the conditions of participation were not clearly explained. When some of the volunteers wanted to

leave the study early, the staff who feared losing their bonuses persuaded the volunteers to stay. 
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Standard of Care

The term “standard of care” was used by many respondents in discussing the issue of the best treatment locally

available. As this respondent explains, the best treatment available is typically less than what is available in the

United States and often is no treatment at all: 

I think the central issue is ‘standard of care.’ Is there a global standard of care, which is

decided upon the best evidence available or is the standard of care flexible and dependent on

what is the usual practice in a particular country. This is a very difficult issue. For instance in

[African country] the government policy would probably support the use of antiretrovirals to

prevent mother-to-child transmission of HIV, however, the usual practice is to do nothing

because of cost. However, the affluent minority would be given state-of-the-art prophylaxis by

their private physicians. This is complicated by the fact that standards of practice in different

industrialized countries are different—more anti-retroviral use in the United States versus in

the United Kingdom, for instance. I would argue that there is a global standard of care—the

best therapy or prevention that is available. 

This same respondent also felt that the ethical issues change—that they are dynamic, as the nature of the

research changes. 

Another respondent remarked on the potential barriers to research if investigators are required to provide

the best-known treatment for study participants. Screening for HIV in countries where most people do not

have access to care would be prohibited as this respondent commented:

...it is seen as an issue of North and South. They have no therapy, but you must provide it

because you are doing research in that country. It gets to ridiculous limits. You know you

might say, well, we can’t ever screen for HIV in any country where therapy is not available. 

It’s a very confusing and contentious issue.

Respondents also mentioned experiences with IRBs raising the issue of the level of care available in treating

specific diagnoses. One respondent reported that a study on anemia was rejected by the local IRB because local

treatment was not available. In this case a pamphlet was prepared describing the management of anemia by

eating locally available foods. However, these foods were not normally consumed in this population, and the

respondent in part related the rejection of the study to a lack of trust. 

Another researcher described a nutrition study in which acutely malnourished patients had been recruited

in order to have a more representative sample of the population, rather than recruiting only stable patients. A

high incidence of death at the initiation of the study caused the U.S. sponsors to halt the study to investigate.

Because the hospital had no respirators to provide intensive care to these patients, there were more deaths than

what is typically seen in U.S. hospital settings. If the study had taken place in the United States, the patients

could have been put into an intensive care unit and possibly have been saved with the help of a respirator. As

this respondent explained:

If you don’t have a ventilator, does that mean you do not do any research or

interventions....No, I believe some of the work that you did and were able to publish 

has actually tremendously improved case management for many of those children....

This respondent felt that although the best-known treatment was not available for study participants, results of

the study were beneficial to many children locally. 
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Another respondent agreed that requiring the best-known treatment prohibited research from occurring:

We can’t do diabetes research in the developing world because we can’t provide kidney 

transplants for diabetic neuropathy. It’s a silly standard.

A distinction was made in one focus group between prevention and intervention research. Several respondents

contended that provision of the best-known treatment should not be an issue in prevention studies. One

respondent could not screen for pediatric HIV because the country did not have pediatric HIV treatment 

available. The respondent felt that any requirement for best-known care would be too limiting for prevention

research, where best prevention is the focus of study and not best treatment.

One respondent suggested that a unilateral requirement for treatment standards could not be applied in all

countries, but that a case-by-case review was more appropriate:

But my feeling is that there is no standard procedure that applies to all countries. You really

have to go to the country and then see what happens and see how things go in a particular

place.

Clinical Trials and Control Trials

A great deal of debate has been sparked by recent AZT and placebo drug trials in developing countries aimed

at preventing mother-to-child transmission of HIV. Respondents made emotional comments in regard to these

debates and were clearly concerned with how these issues are resolved. One respondent felt that the complexities

of drug trials in developing countries have yet to be fully and honestly debated. 

Many feared exploitation of unwitting populations who did not know the circumstances of their participation or who were used as “guinea pigs” for the benefit of those living in developed countries:

I think the researchers from economically developed countries should apply the same rules

and regulations as they apply in their own countries. I think if they are not doing that, they

are not doing justice. Lots of drug trials [that] are being carried out in sub-Saharan Africa and

in other developing countries are not ethical. I think it’s beyond ethics and totally unjustified.

Others argued that control trials are necessary to discover unknown benefits of drugs and is an opportunity to

research the “second best” drugs while the best-known treatments remain economically out of reach: 

I am aware of the...criticism of studies not using best standard of care in control groups....

Applying this standard to developing country research [when treatment is aimed at citizens of

that and similar countries] prevents them benefiting from second best which might be a big

improvement on nothing at all.

Several respondents expressed concern that developing country nations are able to define for themselves what

they want from research and what they can accept. Each country has its own values and needs in regard to

research participation: 

...you cannot resolve the points of confusion for countries. They really have to understand

what their needs are in relation to research.

Several respondents described how both intervention and control groups would receive the intervention when

the study was over. Specific examples provided by respondents included studies in education and communication involving counseling, training, and nutritional education. However, one respondent was concerned that

the control arm in one study was not going to receive treatment. Another respondent noted how their study

was halted more than once because the intervention was proving to be so effective that it was unethical to 

continue withholding treatment from the control group.
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One respondent said that the issue of how to treat the control arms of studies did emerge in discussions

among investigators, but that he was opposed to using controls:

A couple of times this issue was raised in our department. I personally feel the controls 

are unacceptable.

In terms of drug trials, another respondent did not oppose placebo-controlled trials: 

I am aware of the Angell/Lurie criticism of studies not using best standard care in control

groups. I feel this is making the best the enemy of the good. If applied widely this principle

prevent[s] testing of cheaper, i.e., affordable, almost as good as the best, interventions. And it

prevents them being evaluated against usual care, which is often nothing.

Other respondents did not necessarily oppose control trials but did raise issues of informed consent and the

importance of ensuring participants understand the conditions of the controlled trial: 

I think participants should be clearly told we are not sure about the benefits [and] that’s why

we are doing the research.

Another respondent felt control trials were acceptable, but asked: 

...controls benefit [the] greater good, but what do you leave [with the] study participants?

Another respondent felt that providing some benefit to the study community was absolutely necessary:

I believe every research must have an intervention to follow. After our last research when we

analyzed the problems of the community there were so many that we could not deal with

them. For instance, we went to the community and women’s group told us that two women

died last month, I would immediately think of providing antenatal care to women rather then

walking out of the communities without any follow up services [which] is unethical.

This same respondent felt that pre-study agreements are critical in providing benefits to the study community.

The interventions described by this respondent were not necessarily the treatments under investigation, but are

interventions selected for implementation by the study team based on available resources and the expertise of

the participating investigators and needs of the community. 

Several respondents commented on the lack of control over the drug trials the pharmaceutical industry is

conducting in developing countries. One respondent thought the “pharmaceutical industry is very strong and

important” in the United States and therefore more loosely controlled. This respondent commented:

Pharmaceutical industry puts pressure on researchers to conduct research on their drugs 

and we are acting as guinea pigs for the first world. This industry is actively participating in

unethical research which could never be carried out in other developed countries or the

United States.

Some felt that the United States did nothing to stop unethical research even when it was aware that it was 

taking place. This respondent commented as follows:

...before AZT was found to be useful in preventive perinatal transmission, it was not thought

that it was a useful single drug for HIV-infected individuals, but there were areas that were

using that and they’re not doing it on their own. They had somebody that was providing them

with the drugs. So when I go to some of the meetings...where the head of USAID is saying,

Well, a list of the official legal vaccines that we know of...that really disturbs me because it

means there are some unofficial or unethical things happening and it’s a huge problem for

[African country]....
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Recommendations

Compensation and Incentives. Many respondents had very clear concerns in regard to how the community

will benefit from research, particularly the study participants themselves. Monetary incentives were not recommended except at low enough levels to be considered as compensation to cover the costs of study participation and not as the primary reason for participation. One participant suggested “more creative, nonmonetary

incentives” need to be developed for study participants, particularly in areas of poverty or low employment.

Providing monetary incentives to research staff also was not recommended due to the potential for conflict of

interest. 

Study Design. There were dissenting opinions on the ethics of using control and placebo arms in research

in resource-poor countries. Some felt that these arms were important in discovering second-best treatments

while others warned of the potential to treat people as guinea pigs. Generally, respondents felt that the intervention under investigation had to be relevant to the population and that there needed to be some provision 

of direct benefit to the study population. Respondents also felt that the control groups should receive the intervention at the completion of the study. Some respondents felt there should be specific requirements regarding

these issues, while others felt that a case-by-case review was more appropriate.

Much of the disagreement regarding benefits to the study community related to drug trials and use of 

control or placebo arms. One respondent felt that U.S. guidelines should include special restrictions for U.S.

researchers conducting research in developing countries that could not be conducted in the United States. 

The respondent explained that the restrictions should not result in prohibition, but that a set of processes

should be required to justify the research. Another respondent recommended restricting drug testing in 

developing countries to only those drugs that previously have been tested in a developed country. 

There also was a discrepancy between the responsibilities in terms of treatment during the study for treatment intervention research and prevention intervention research. Several respondents argued that requiring the

best-known available treatment for prevention studies is not appropriate. 

Pre-Study Agreements. A pre-study process was recommended for determining which interventions will be

provided to the study community after the study is completed. Specific organizations providing these services

or interventions should be included in the pre-study agreement negotiations. 

Cultural Sensitivity. Two respondents mentioned cultural insensitivity among researchers involved in a

study on breastfeeding and breast cancer, respectively. In both cases, respondents felt that the investigators

lacked awareness of the significance and meaning of the breast within their particular cultural setting. The

respondents called for more cultural awareness on the part of the investigators in designing and implementing

their studies.

In terms of study design, the issue of religion was raised in one focus group and is an example of how 

contextual factors were considered in developing a study. Investigators were concerned with whether or not

drawing blood would break the fast during Ramadan. A group of Islamic scholars was consulted to resolve 

the issue.
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D.4. Obligations to Subjects, Communities, and Countries

D.4.1 Results from Survey

This section covers the issues related to the conclusion of research studies. Based on the survey findings, the

section addresses the implementation of interventions after research studies are completed and capacity building

and partnerships between the sponsors of the study and the developing country researchers.

Research Priorities

Fifty-eight percent of the developing country researchers responded true or sometimes true that “research 

priorities of outside funding agencies that are funding the study are not congruent with top priorities of the

developing country” (Table D.2.3). Among those researchers funded by the United States, 55 percent of them

responded true or sometimes true on the same question. These responses relate to either the reality of the 

situation or a perception of the researchers’ priorities.

Intervention Studies as Human Subjects Health Research

Less than half (44 percent) of the developing country researchers described their “index study” (on the survey

questionnaire) as being an intervention study. Among physician respondents, almost half (48 percent) of them

had intervention studies as part of their human subjects research. Only 30 percent of those researchers who

were nonphysicians had intervention studies (p = .032). Of those researchers with intervention studies, almost

all (94 percent) of the respondents reported that their particular studies had shown the intervention to be 

efficacious.

Implementation of Interventions After Research Studies

Most (92 percent) of the developing country researchers responded “yes” to the question “Was the intervention

provided, or, will it be provided, if successful, to study participants or any other host country residents at the

conclusion of the study?” Six percent responded “don’t know,” while 2 percent responded “no.”

To the question, “To whom was (or will) the intervention be provided?” the responses are as follows 

(Table D.4.1):

For the above groups of respondents, a difference (p < .10) was found upon further analysis by type of

researcher (i.e., by gender, age, and IRB/non-IRB membership status) for the “entire study population” category.

The differences are presented in Table D.4.2.

Table D.4.1: To Whom Was (or Will) the

Intervention be Provided? (Respondents

could check more than one option)

Group Percent

Community from which the study 

population comes 38

Entire study populations 32

Certain regions of host country 28

Entire host country 22

Placebo or control group of study 20

Others 8
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To the question, “What parties were (or will be)

part of the arrangement to provide the intervention?”

the responses leaned heavily towards host country

categories (Table D.4.3). The researchers identified

the host country institution (55 percent), the host

country government (53 percent), and the host

country research team (47 percent) as the parties

who were/will be part of the arrangement to 

provide the intervention. 

Further analysis was made among the survey

respondents regarding host country government

arranging for the provision of the intervention. The

results indicated that 72 percent of nonuniversity

respondents said the host country government did 

or will do so, while a smaller percentage (43 percent)

of university respondents say the host country 

government did or will arrange for provision of the

intervention (p = .080).

The U.S.-funded researchers (19 percent) were

more likely to state that the “foreign institution carrying out the study” should be involved in arranging

the provision of intervention than non-U.S.-funded

researchers (3 percent, p = .096).

The developing country respondents were also

asked the question, “How long was (or will) the intervention be provided?” Their responses are organized

in descending order in Table D.4.4.

Fifty percent of non-IRB members indicated that

the intervention was (or will be) provided from two

to five years, whereas 50 percent of IRB members

indicated that the intervention was (or will be) 

provided for more than five years (Table D.4.5).

Table D.4.2: If the Intervention in the Research Study was Successful, Will It be

Provided to the Entire Study Population?

Gender of Survey Respondents % Yes % No P-Value

Female (n = 16) 50 50 0.057

Male (n = 38) 24 76

Age of Survey Respondents % Yes % No P-Value

45 years or less (n = 26) 19 81 0.075

Greater than 45 (n = 25) 44 56

IRB Member/Nonmember % Yes % No P-Value

Members (n = 25) 44 56 0.066

Nonmembers (n = 29) 21 79

Table D.4.3: What Parties Were (or Will

Be) Part of the Arrangement to Provide

the Intervention? (Respondents could

check more than one option)

Category Percent

Host country institution 55

Host country government 53

Host country research team 47

International agency (e.g., WHO, UNICEF) 24

Foreign funding agency for this study 19

Foreign research team carrying out this study 14

Foreign institution carrying out this study 10

Other 7

Private foundation 5

Private for-profit agency 3

Table D.4.4: How Long Was (or Will) the

Intervention Be Provided?

Duration of Post-Research Intervention Percent

Two to five years 39

Greater than five years 33

Less than one year 26

Other 2
B-95

Among respondents employed by nonuniversity

settings, the majority (53 percent) stated that the

intervention was (or will be provided) for more 

than five years (Table D.4.6). In contrast, most 

(44 percent) of the university-employed respondents

stated that the intervention would be provided for

two to five years; one-third (33 percent) of them

stated that it would be provided for less than a year.

Only 23 percent of them said the intervention would

be provided for more than five years.

The developing country researchers responded to

the question, “How was (or will) the intervention be

paid for?” as shown in Table D.4.7. The host country

government (46 percent), followed by the research

grant for the study (39 percent), was mentioned

most often as being the source of funding for the

intervention. Upon further analysis, statistical 

significance was found between IRB members 

(64 percent) and non-IRB members (31 percent)

stating that host country government would pay for

the interventions (p = .014).

The above data suggest optimism in the provision

of interventions at the conclusion of the study to

study participants or any other host country residents.

However, the researchers appear less optimistic when

asked if the treatment or intervention being tested

will be made available for most citizens of the country in the foreseeable future (Table D.2.3). Almost

half (48 percent) of them agree that it is true or

sometimes true that the treatment or intervention

being tested is unlikely to be available for most 

citizens of the country in the foreseeable future.

Capacity Building and Partnerships with

Developing Country Researchers

The Involvement of Developing Country

Researchers in Research Tasks. According to 

the developing country researchers, they participate

in various research tasks with foreign research 

collaborators. The tasks are ranked according to 

perceived level of involvement (see Table D.4.8). 

In terms of involving field staff on the topic of ethics

issues, 39 percent said that it is true or sometimes

true that it was rarely discussed. See Section D.6.5

and Section E.4 for further discussions on this topic.

Table D.4.5: IRB Versus Non-IRB 

Survey Respondents on Duration of

Intervention Provision 

IRB Members/ <1 year 2-5 years >5 years Other

Nonmembers

Members (n = 24) 25 25 50 0

Nonmembers

(n = 24) 29 50 17 4

p = .050

Table D.4.6: University- Versus

Nonuniversity-Employed Survey

Respondents on Duration of Intervention

Provision

University/ <1 year 2-5 years >5 years Other

Nonuniversity

Nonuniversity 

employed (n = 17) 18 23 53 6

University 

employed (n = 30) 33 44 23 0

p = .069

Table D.4.7: How Was (or Will) the

Intervention Be Paid for? (Respondents

could check more than one option)

Source of Funding Percent

By host country government 46

By research grant for this study 39

By foreign funding agency for this study 25

By host country institution 21

By international agency 11

By private foundation 9

Other 7

By private for-profit company 5

By foreign institution carrying out this study 4
B-96

Resources and Research Infrastructure for Host

Countries. As many as 92 percent of the developing

country researchers say that some of the resources or

research infrastructure established for their studies

will remain in the developing country after the study

has ended. The type of resources and infrastructure

are ranked in descending order in Table D.4.9.

Recommendations

Survey respondents were asked for their recommendations in the area of intervention implementation 

at the conclusion of research studies. Responses from

all the researchers versus only those whose studies

are/were funded by the United States are compared 

in Table D.4.10.

Three-fourths (77 percent) of the developing

country researchers agreed that the issue of what

standard of medical care to provide to study participants should be decided on a case-by-case basis.

Eighty percent of the U.S.-funded developing country

researchers agreed.

Eighty percent of the respondents agreed that

researchers should be required to make data from the

research study directly available to study populations

after the study is over. A slightly higher percentage

(87 percent) of U.S.-funded developing country

researchers agreed that researchers should be required

to make data from the research study directly available to study populations after the study is over.

Seventy-eight percent of the respondents agreed

that research to test an intervention should not be

carried out in a developing country unless the intervention, if found to be successful, will be made available to that country at the conclusion of the study.

The same percentage of U.S.-funded developing

country researchers agreed.

Seventy-nine percent of the respondents agreed

that international policy regarding research should

require researchers to establish a mechanism for 

continuing delivery of medical care after completion

of the study. Seventy-five percent of U.S.-funded

developing country researchers agreed.

Table D.4.8: Developing Country

Researchers Were/Are Included in the

Following Research Tasks

Option % Yes

Listed as authors on papers 95

Training of research personnel 92

Change in study design 87

Drafting manuscripts 86

Initial study design 86

Data analysis 86

Recruitment of participants 86

Drafting consent form 84

Consent discussions with participants 84

Grant writing 72

Table D.4.9: Resources or Research

Infrastructure That Will Remain After the

Study Has Ended

Question % Yes

Will some of the resources or research 

infrastructure established for this study 

remain in the developing country after the 

study has ended? 92

Personnel who were trained or who acquired 

skills on this research project 95

Medical, laboratory, or office equipment 90

Computers or data management system 86

Medical, laboratory, office, or pharmaceutical 

supplies 79

Organizational structure for health care 

or research 70

Power generating equipment, water system, 

or motor vehicles 48

Buildings, laboratory facilities, or renovations 44

Other 37
B-97

D.4.2 Results from Qualitative Research

Provision of Effective Intervention

Generally, as mentioned in the previous section, “cowboy research,” where researchers go into a community,

collect data, and leave, is not acceptable:

They [study participants] need to be informed and something needs to go back to them. You

can’t just do the research and take the results and run. Intervention has to come through, and

this is happening now.

However, the issue of requiring implementation of interventions found to be effective during the study was

debated. Some respondents felt that effective interventions should be implemented in the study community

after completion of the study, as this respondent stated:

...I give an example of [study in an African country]...where they...found that treating STDs

can reduce HIV 42 percent...but after that what has really happened? Has the government 

got the money to...implement the findings? What do we really need from these countries

[developed countries]...the drugs for treating STDs and the training...you can provide international presentation and publication but so what?

Table D.4.10: Recommendations

Developing Country Researchers 

Developing Country Researchers* (U.S. Funded)**

% % Strongly % % Strongly

Strongly Disagree Strongly Disagree

Agree and and Agree and and

Recommendations n Agree % Neutral Disagree n Agree % Neutral Disagree

The issue of what standard of medical 

care to provide to study participants 

should be decided on a case-by-case 

basis. 182 77 7 16 79 80 5 15

U.S. researchers should be required 

to make data from research study 

directly available to study populations 

after study is over. 176 80 13 7 76 87 9 4

Research to test an intervention 

should not be carried out in a 

developing country unless the 

intervention, if found to be 

successful, will be made available 

to that country at the conclusion 

of the study. 187 78 9 13 81 78 9 13

International policy regarding research 

should require researchers to establish 

a mechanism for continuing delivery 

of medical care after completion of 

the study. 185 79 12 9 80 75 14 11

*Survey respondents from developing countries 

**Survey respondents from developing countries whose index studies are/were funded by the United States.
B-98

One respondent felt that an essential part of a “research contract” between the government and the researchers

should be to make the product of the research available to the study volunteers if proven effective:

As an example for HIV vaccine, I wouldn’t be surprised if we finally get a very good

result...we should have some kind of consent that says this vaccine...should be available first

for those people...for free because they...risk their life in something they don’t know. 

One respondent suggested provision of the intervention be written into the guidelines as a requirement:

It should be made a requirement that research involving testing of drugs and other 

interventions, if found efficacious, the participating populations should be among the first

ones to benefit, at affordable costs.

However, another respondent felt that this was beyond the scope of research and that providing effective 

interventions was a policy decision of the Ministry of Health or host country government: 

We think more or less to do the research and hand the results to the Ministry and it’s their

objective to implement and mandate....

Economic Feasibility

The feasibility of making effective vaccines available was considered low unless some pre-study negotiation 

had been achieved. In terms of other interventions, such as information, education, and communication interventions aimed at preventing maternal mortality, respondents felt these decisions were up to their governments

to provide the funding. Some respondents felt that their role was limited to making national health policy 

recommendations, not funding decisions. Several others spoke of potential funding sources with private donors

or research institutions. Others mentioned built-in research funding to implement successful interventions.

Respondents in one focus group agreed that typically after the study is completed, all interventions end. 

Another respondent agreed that interventions should be made available to the study community, but 

cautioned:

This is an issue that needs to be studied further to see how it can be implemented. It is indeed

important for equity and justice. However, it is difficult to require this for ERB/IRB approval in

the case of new drugs/tools, having little idea yet of its efficacy, market price, etc. This needs

continuing negotiation and discussion as the study proceeds. At least, if found efficacious, the

new drug/tool should be made available to the study community.

The quality of the health care delivery system and efforts in changing government policy were also mentioned

as considerations in the provision of effective treatment:

We can never be sure that an intervention would be available all over the country, even 

successful. It depends on the cost of drugs, government policy [national] and health system

possibilities to do it. We have to test interventions that make sense for the country where 

they are done but availability after the results depends on our common fight as a society to

implement those [interventions].

In terms of HIV, the drugs are more expensive. Several respondents felt that it was not realistic economically for

studies to provide the drugs for an unlimited time period. This respondent remarked:

...our general...what we call opinions from us as locals [local investigators] from local 

countries, we actually thought it [provision of effective intervention] was quite unreasonable

because you couldn’t, we couldn’t—even if you gave the drugs during the study, but you

couldn’t continue giving the drugs after the study. 
B-99

Recommendations

Respondents clearly felt there is a need for the study community to benefit from the research. Whether or not

to make the provision of effective interventions a requirement was debated. In some cases, respondents felt it

was prohibitively costly to provide the treatment, particularly in HIV research. Other respondents mentioned

that the decision to provide effective interventions in the study community was a public heath policy decision

that should be made by the host country government and not the investigators themselves. 

Pre-study agreements were clearly recommended where provision of the intervention is considered. One

respondent felt that such “contract” agreements require continuous negotiation, particularly in terms of providing

drugs or vaccines that were proven effective.

D.5 International Collaborative Research

D.5.1 Results from Survey

This section covers the survey findings in the area of U.S. as well as developing country (host) IRBs and human

subjects research regulations.

U.S. IRBs Versus Developing Country IRBs

The developing country researchers were asked to respond to the frequency in which the U.S. IRBs raised the

following issues, as well as the frequency with which the same issues were raised by the developing country’s

IRBs or ethics board in its review of the same index study (Table D.5.1).

Table D.5.1: Comparison of Responses to Issues Raised by U.S. IRB(s) vis-à-vis

Issues Raised by Developing Country IRB(s)

Raised by

Developing Test of

Raised by U.S. Country IRB(s) Statistically

IRB(s) in Its or Ethics Board Significant

Review of the in Its Review of Difference

Index Study the Index Study

Option % Yes % Yes P-Value

Relevance of research question to country where research is 

conducted and/or rationale for doing study outside the United States 52 54 0.8426

Complexity of language on consent form 64 45 0.0699

Cultural appropriateness of study procedure 63 59 0.6876 

Need for local language consent form 84 58 0.0065

Need for letters of approval from developing country representatives 79 47 0.0011

Intervention was considered too risky 15 11 0.4656

Appropriateness of procedures for control group 50 39 0.3254 

Confidentiality protections for participants were not adequate 42 18 0.0045

Participant voluntaries may be compromised because of benefits 

study provides 20 24 0.6446 

Use of placebos 22 26 0.6949 

Availability of intervention (if successful) to host country after 

study is over 46 54 0.4832 

Political considerations 17 16 0.9052

Others 8 12 0.000
B-100

In comparing issues raised by U.S. IRBs versus those raised by developing country IRBs or ethics boards, 

significant differences (p < .01) were observed in the response of the researchers on the following three issues:

■ The need for local language consent forms.

■ The need for letters of approval from developing country representatives.

■ Confidentiality protections for participants.

Further analyses were conducted to determine whether or not there was statistical significance depending 

on the various categories of the researchers (e.g., age, gender, university/ nonuniversity employed, physician/

nonphysician, and IRB/non-IRB member). Significant findings are reported below. 

Need for Local Language Consent Forms. The issue of the need for local language consent form was

brought up by 84 percent of the U.S. IRBs versus 58 percent by developing country IRBs or ethics boards 

(p = .0065) (Table D.5.1). With regard to developing country IRBs or ethics boards, one-third (30 percent) of

the researchers over 45 years of age disagreed that there is a need for a local language consent form, whereas

slightly more than half (55 percent) of those researchers age 45 or less disagreed (p = .006). 

Need for Letters of Approval from Developing Country Representatives. The need for letters of

approval from developing country representatives was brought up more often (79 percent) by U.S. IRBs than

the local IRBs or ethics boards (47 percent) (p = .0011) (Table D.5.1). With regard to developing country IRBs

or ethics boards, older researchers (>45 years of age) were more likely (59 percent) than younger researchers

(35 percent) to agree that the local IRBs/ethics boards raise the issue of needing letters of approval (p = .015).

In addition, nonacademic researchers (60 percent) were more likely to agree than academic researchers 

(38 percent) on the same issue (p = .020).

Confidentiality Protections for Participants. The U.S. IRBs raised the issue of confidentiality protections

for participants not being adequate, more often (42 percent) than by the developing country IRBs/ethics boards

(18 percent, p = .0045). On the issue of confidentiality protections for the participants being inadequate, only

10 percent of the researchers funded by the U.S. stated that it was brought up by the developing country IRB

or ethics board reviews of their studies. A much higher percentage (25 percent) of non-U.S. funded researchers

said the same issue was brought up (p = .042).

Other issues that arose during developing country IRB reviews only that were noted to be significant are as 

follows:

Appropriateness of Procedures for Control Group. Forty-four percent of the older researchers (>45 years

of age) versus 15 percent of younger researchers said that issues related to the appropriateness of procedures

for control groups were brought up during their index studies (p = .001).

Use of Placebos. On this issue, a significant difference was observed between researchers over age 45 versus

researchers 45 or less. As many as 41 percent of the older researchers said the placebo use was brought up by

the developing country IRB or ethics board review. Only 6 percent of researchers 45 or younger said the same

issue was brought up (p < .001).

Availability of Intervention (If Successful) to Host Country After Study Is Over. When the research

studies involved vaccine development and/or testing, all five researchers (100 percent) stated that the issue of

availability after the study was brought up by the country’s IRB or ethics board review (p = .058). No statistical

significance was found regarding the same issue, by the U.S. IRB. When the research studies were on health

systems or services, 80 percent of the time the availability of intervention was brought up by the country’s IRB

or ethics board review (p = .010).

Political Considerations. When the research studies involved HIV/AIDS, political considerations were

raised 35 percent of the time (p = .016). No further information on the nature of this issue was available from

the survey. 
B-101

U.S. Human Subjects Regulations

Table D.5.2 describes the developing country researchers’ experiences and attitudes regarding U.S. and international human subjects regulations and guidelines. Thirty-seven percent of the survey respondents said that

U.S. human subjects regulations were “never” flexible where they needed to be, while 7 percent said they were

“always” flexible, and 56 percent said “sometimes.” More than half (57 percent) of the developing country

researchers agreed (“sometimes” or “always”) that U.S. IRBs were more concerned with politics than with protecting the interests of research subjects, while 43 percent disagreed. Seventy-seven percent of the researchers

responded that “sometimes” U.S. IRB regulations are insensitive to local cultural norms, while 6 percent

responded “always” (cumulative percentage is 83 percent for “sometimes” and “always”). No association was

found when the researchers were further classified by gender, age, physician/ nonphysician, IRB/non-IRB 

member, U.S./non-U.S. funded, or academic/nonacademic.

A very small percentage (6 percent) of the researchers agreed that they have ever had to abandon a research

project because it was impossible to get U.S. IRB approval, despite modifications. 

Single Project Assurance. Forty-four percent of the survey respondents had index studies that are/were

funded by the United States. Based on those who responded, from this category, 44 percent reported that they

did obtain SPAs (p = .72). According to the majority (almost three-quarters) of them, it took between one and

six months to obtain the SPA. Only 2 percent of the researchers agreed that they have ever had to abandon a

research project because it was impossible to obtain an SPA. A small percentage (15 percent) of these survey

respondents (n = 26) encountered resistance on the part of developing country officials to agreeing to a SPA

(Table D.5.3). At the same time, as many as 84 percent of them (n = 25) considered the SPA process to be 

valuable in ensuring that a developing country ethics review was carried out.

Besides SPAs, 12 percent of the researchers reported that they encountered resistance on the part of developing

country officials to U.S. requirements for (host country) IRB composition (Table D.5.3).

In the area of DSMBs, all the researchers who have studies involving greater than minimal risk (n = 3) stated

that they had a DSMB (p = .015). (See Table D.5.4 for additional information.)

Table D.5.2: Researchers’ Beliefs/Attitudes About Ethical Guidelines and Regulations

in Human Subjects Research

Options % Always % Sometimes % Never

U.S. human subjects regulations are flexible where they need to be. 7 56 37

Developing country collaborators rely on U.S. ethics regulations for guidance. 14 77 9

U.S. IRBs are more concerned with politics than they are with protecting the interests 

of research subjects. 3 54 43

The current U.S. rules and regulations governing human subjects ensure high 

ethical standards in research. 59 36 5

U.S. IRB regulations are insensitive to local cultural norms and traditions outside 

the United States. 6 77 17

Developing country IRBs are more concerned with politics than they are with 

protecting the interests of research subjects. 3 60 37

Developing country IRBs have voiced concerns to me about the costs associated 

with the IRB carrying out its work. 7 38 55

National guidelines in developing countries are effective in protecting research subjects. 21 71 8
B-102

Despite the relatively high percentages of agreements that U.S. human subjects regulations are not

flexible, are concerned with politics, and are insensitive to local cultural norms, there are also higher

agreements of the positive contributions of the regulations. As much as 59 percent of the developing

country researchers responded “always,” while 36

percent responded “sometimes” (combined percentage of 95 percent), that the current U.S. rules and

regulations governing human subjects ensure high

ethical standards in research. Over three-quarters of

the researchers (77 percent) relied on U.S. ethics regulations for guidance “sometimes,” while 14 percent

said “always” (cumulative percentage for “always” and “sometimes” is 91 percent). A much higher percentage (97

percent) of academic respondents said that developing country collaborators rely on U.S. ethics regulations for

guidance “sometimes” or “always” versus 81 percent of nonacademic respondents (p = .018).

Host Country (Developing Country) Human Subjects Regulations

The developing country researchers were equally critical of their countries’ IRBs as they were of the U.S. IRBs,

when asked if their IRBs are more concerned with politics than they are with protecting the interests of research

subjects. Sixty-three percent of them agreed (“sometimes” or “always”). (Fifty-nine percent of them had agreed

about U.S. IRBs, on the same issue.) Nonphysician researchers as a group were more critical about their 

countries’ IRBs on this issue (82 percent) (“sometimes” and “always” combined) than the physician researchers

(57 percent) (“sometimes” and “always” combined) (p = .008). 

When asked whether the developing country IRBs have voiced concerns about the costs associated with an

IRB in carrying out its work, 45 percent (cumulative percentage for “always” and “sometimes”) of researchers

stated that it has been brought up. The majority of the researchers (92 percent) agreed that “sometimes” or

“always” the national guidelines in the developing countries are effective in protecting research subjects. 

Seventeen percent of the researchers responded that they have had to abandon a research project because it

was impossible to get developing country IRB approval despite modifications. In contrast, only 6 percent of

them reported having to abandon their project because it was impossible to obtain U.S. IRB approval. More

IRB-member researchers (62 percent) had to abandon their research because it was impossible to get developing

country IRB approval despite modifications, compared to 38 percent of researchers who are not IRB members

(p = .029) (Table D.5.5).

Table D.5.3: SPA Information

Option % Yes % No

Encountered resistance on the 

part of developing country 

officials to agreeing to an SPA 

(n = 26) 15 85

Encountered resistance on the 

part of developing country 

officials to U.S. requirements 

for IRB composition (n = 25) 12 88

Considered the SPA process 

valuable in ensuring that a 

developing country ethics 

review was carried out (n = 25) 84 16

Table D.5.4: DSMB Information

Question % Yes % No % Don’t Know

Study had a DSMB (n = 84) 22 58 20

Ethic issues arose in DSMB review of study (e.g., medical care offered to 

participants)? (n = 19) 37 58 5

% Never % Sometimes % Always

Aware of results of DSMB meetings (n = 18) 17 33 50
B-103

IRB and Ethics Review at the National or 

Local Level

Forty-four percent of the survey respondents reported

that their studies did not undergo review by the

Ministry or Department of Health in the country

where the research is/was conducted (Table D.5.6).

Twenty-five percent of the respondents also reported

that their studies did not undergo some type of ethics

review by an IRB, ethics board, or Ministry/Department

of Health in the country. Further analyses show that a

potential 15 percent (28 studies) of the studies being

described in the survey were neither reviewed by the

Ministry/Department of Health nor by any IRB/ethics

board. Of these studies that were neither reviewed 

by the Ministry/Department of Health nor by any 

IRB/ethics board, 36 percent (10 studies) were

funded by the United States.

Source of Ethics Review Requirements. Of those researchers whose index studies are/were funded by the

U.S., 69 percent of them responded that the developing country ethics review was required by U.S. institutions/

regulations (p = .001) (Table D.5.7). Further, 95 percent of this category of researchers reported that the 

developing country ethics review was required by developing country institutions/regulations.

Table D.5.5: Developing Country IRB

Approval

Have you ever had to 

abandon a research 

project because it was 

impossible to get 

developing country 

IRB approval despite 

modifications? Yes No

IRB member % 62 38

Non-IRB member % 40 60

p = .029

Table D.5.6: Developing Country IRBs and Other Ethics Review

Studies That Did Not Undergo Reviews % n

The study did not undergo review by the Ministry/Department of Health in the country 

where the research is/was conducted. 44 82

The study did not undergo some type of ethics review by an IRB, ethics board, or 

Ministry/Department of Health in the country where the research is/was conducted. 25 46

Studies that were neither reviewed by the Ministry/Department of Health nor by any 

IRB/ethics board. 15 28

Studies that were neither reviewed by the Ministry/Department of Health nor by any 

IRB/ethics board and were funded by the United States. 36 10

Table D.5.7: Source of Ethics Review Requirements

U.S.-Funded Researchers

Question n % Yes % No

Was any of this developing country ethics review required by U.S. 

institutions/regulations? 55 69 31

Was any of this developing country ethics review required by developing country 

institutions/regulations? 61 95 5
B-104

Types of Studies and Ethics Review. Compared to other study methods, half (52 percent) of the anthropological studies did not undergo any type of ethical review by an IRB, ethics board, or Ministry of Health 

(p = .002) (Table D.5.8). In addition, 11 percent of studies conducted by researchers in clinical care also did

not undergo ethical review (p = .016); 18 percent of epidemiological studies did not undergo ethics review

(p = .013).

The following types of research studies did not undergo ethical review: 39 percent of health systems/services

types of research studies (p = .013); 14 percent of infectious disease (but non-HIV/AIDS) research studies 

(p = .016); and 7 percent of HIV/AIDS studies (p = .017) (Table D.5.9).

In the country where the research was conducted,

the respondents stated that the study was reviewed

by the following institutions (Table D.5.10):

Note that the majority of studies (92 percent) were

being reviewed at the local institution level. In terms

of community representation, 61 percent of the

researchers say that there is inadequate community

representation on the local IRBs/ethics boards. 

Table D.5.8: Developing Country IRBs and Other Ethics Review

Did this study undergo some type of ethics review by an IRB,

ethics board, or Ministry of Health in the country where the research

is/was conducted? Response of the Researchers

% Yes % No P-Value

Discipline of index study: epidemiology 82 18 0.013

Discipline of index study: clinical care 89 11 0.016

Discipline of index study: anthropology 48 52 0.002

Table D.5.9: Developing Country IRBs and Other Ethics Review

Did this study undergo some type of ethics review by an IRB,

ethics board, or Ministry of Health in the country where the research

is/was conducted? Response of the Researchers

% Yes % No P-Value

Topic: infectious diseases, non-HIV/AIDS 86 14 0.016

Topic: HIV/AIDS 93 7 0.017

Topic: health systems/services 61 39 0.013

Table D.5.10: Developing Country IRBs

and Other Ethics Review

Percent of Responses

Review Board % Yes % No

A national IRB /ERB (n = 115) 49 51

State/provincial IRB/ERB 

(n = 93) 27 73

Collaborating local institution 

IRB/ERB (n = 130) 92 8

Other in-country ERB 

(n = 70) 14 86
B-105

Recommendations

Survey respondents were asked for their recommendations in the areas of U.S. IRBs, developing country IRBs,

SPAs, ethical reviews and international guidelines. Responses from all the researchers versus only those whose

studies are/were funded by the U.S., were similar when compared (Table D.5.11).

The majority (85 percent) of survey respondents agreed that research funding agencies should provide 

funding to support the work of developing country IRBs. More than three-quarters (77 percent) of the survey

respondents recommended that international guidelines (e.g., CIOMS) should be used instead of U.S. rules 

and regulations. According to 85 percent of the developing country researchers, a developing country ethical

review should be required for all studies. Ninety-two percent of them also stated that the composition of ethics

review boards used in developing countries should not be dictated by U.S. regulations. Forty-six percent were

neutral, while 28 percent agreed and 26 percent disagreed that the SPA requirement should be eliminated.

Seventy percent of the researchers agreed that some research funds for piloting consent forms should be

released before final IRB approval is obtained. 

Table D.5.11: Recommendations

Developing Country Researchers 

Developing Country Researchers* (U.S. Funded)**

% % Strongly % % Strongly

Strongly Disagree Strongly % Disagree

Agree and and Agree and Neutral and

Recommendations n Agree % Neutral Disagree n Agree 1 Disagree

Research funding agencies should 

provide funding to support the work 

of developing country IRBs. 191 85 7 8 82 89 6 5

International guidelines (e.g., CIOMS) 

should be used instead of U.S. rules 

and regulations. 171 77 22 1 75 76 23 1

A developing country ethical review 

should be required for all studies. 190 85 6 9 81 89 2 9

The composition of ERBs used in 

developing countries should not be 

dictated by U.S. regulations. 191 92 7 1 82 85 14 1

The SPA requirement should be 

eliminated. 116 28 46 26 82 26 41 33

Some research funds for piloting 

consent forms should be released 

before final IRB approval is obtained. 182 70 21 9 54 70 18 12

*Survey respondents from developing countries 

**Survey respondents from developing countries whose index studies are/were funded by the United States.
B-106

D.5.2 Results from Qualitative Research

Local National IRBs in Host Country

Adequacy and Effectiveness. Respondents felt that a local institutional review process was necessary for

regulating research and was described as bringing “some sanity to the researchers.” However, the perceived

functioning of these review systems varied greatly. Some countries do not have local IRBs, while others have

well-established IRBs that have been in operation for many years: 

Most of the issues did not arise at the local review because they were already addressed in 

the application. My institution has a strong ethics board, which has been active for several

decades. Thus, formal ethics review is an essential part of the tradition and teaching in

research.

Respondents felt that local IRBs were strengthened over time as they gained experience and exposure to various

research and ethical issues. Several respondents described the process of building up the IRB. This respondent

commented as follows: 

Once we got it set up in the university then we moved on to the Ministry [of Health] and it

took a while....I’m not saying that all Ministry people are bad, but some people...[the government] took money from, these researchers, and turned their backs, so whatever happens to the

patients, they don’t care too much.

This same respondent felt that these issues are beginning to be dealt with now: 

In [African country] there was no ethics or research committee by the time I got there and

when there were a lot of researchers coming from abroad and calling themselves researchers

who just came to the country and they did what they wanted to do and left. It took a while 

for us to push the government to the point [of addressing the situation]. The university first

approached the issue. Once we had it set in the university we moved on to the Ministry and 

it took a while and there are many, many reasons for that. This has been addressed in most

African developing countries by now because the patient is extremely important.

One respondent remarked that other than official IRBs, there were many private advocacy organizations that

served minorities groups, human rights, and women, among others. These groups were vigilant of research

activities and the protection of human subjects. 

Urban areas where university or research institutions are generally located were more likely to have established review processes that were better functioning and more effective than in rural regions. Outside of larger

cities there was reportedly less familiarity with the IRB process and the government had more difficulty in 

regulating research. However, where there is a history of research or more recent research activity, there is 

more capacity and familiarity with the process. Several respondents mentioned that IRBs are “routine” for 

rural districts where research activity has been at a high level. Any investigator arriving in those areas will be

required to go through a review process, but rural districts with less research activity do not share in this level

of experience with the local IRB process and do not know how to advise incoming investigators. Other respondents noted that although their local university has an established review system, investigators, both nationals

and non-nationals, who are not aware of its existence, bypass it. Some of these respondents also felt that

research was in its infancy in their country, that ethical considerations are not taken seriously, and that review

processes are sometimes simply ignored. Other respondents also felt that seeking ethical approval was the

investigator’s responsibility, particularly for projects to be implemented in rural districts where review processes

are not well established. 
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Several respondents felt the review process at the government level was slowed considerably by bureaucratic

procedures: 

...when it gets to the Ministry [of Health] it just drags on forever. So you have to follow it all

the time because the committee will tend to not meet regularly and you have to push the chair

person to call a meeting...it takes four to six months. 

Citing a long history of research in collaboration with a U.S. university, one researcher referred to the “tradition

of research” that exists at the university level, but is absent at the government level Ministry of Health, which

was described as: 

...More concerned about the money than [whether the study is] for the people or not.

Frustration was frequently expressed over the inadequacy of the national governments to regulate research and

to enforce ethical guidelines for all research projects implemented within national boundaries. This respondent

commented: 

...Institutions that have universities attached to it and have a lot of people that have been outside and are [also] used to the developing world system, it’s more probable that you will have

something comparable to what you have in the developed nations...moving from those cities

that have universities and just set up a collaboration with some private medical practitioner or

some small group somewhere...you might find...that they have no control at all, and that is a

huge problem for the government. 

Another respondent explained that when they began research in the early 1980s in (a Caribbean country), the

Ministry of Health had a review board, but its role and mission were unclear, and it operated without guidelines. A regional research institution, which already had an IRB and served several countries in the region,

began to review proposals for the respondent’s projects sponsored by the United States. This was a feasible

solution for the investigators so that they could fulfill U.S. requirements of local IRB approval. Such creative

solutions with partnering and twinning of institutions could be effective in the design phase of research. 

Emphasis of Review. Most participants reported their university review boards as serving dual functions of

both technical and ethical review. One participant remarked that U.S. investigators have been rebuked at the

questioning of local IRBs on the technical merit of their studies because their expectation is that the review will

be based solely on ethical concerns. But as this respondent said, the philosophy behind the dual role of the

local IRB is that you cannot have ethical research without “good science.”

Ethical review of study proposals has been a more recent occurrence in some countries, a process many

respondents described to have developed within the last ten years. In some countries the local review continues

to emphasize scientific, political, or funding concerns versus ethical considerations: 

They [local IRBs] are not really concerned about ethical issues, they are looking [at] technical

[issues]. And you know, and who [is] giving you money, how much are you getting....But now

[we need to look at] the ethical aspects, what people are doing, is it right.

Particular instances were mentioned of IRBs considering the political sensitivity of the potential proposals primarily, while the scientific and ethical aspects of the study are judged secondarily. Generally, funding concerns

were more often associated with governmental IRBs than university IRBs. Several respondents mentioned the

political nature of local IRB decisionmaking. One respondent remarked:

...it is a political approval. It is not an approval that is about ethics. It was more about whether

we would be spies or we would be real researchers that would benefit [Asian country]. 
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In resource-poor countries, the issue of corruption and “kickbacks” for government officials was a concern in

establishing and, particularly, in enforcing standards for research ethics at the national level. These concerns

were relevant for all respondents. One respondent expressed their concern that external organizations took

advantage of the resource-poor countries in that they could dictate what they wanted by finding government

officials that they could control. Where specific regulations do exist, enforcement of those regulations is a 

problem. Several participants specifically referred to pharmaceutical companies looking for new markets for

their drugs:

...they [pharmaceutical companies] get an institution somewhere that has a half-controlled

person that would be willing to just take them in and do...whatever kinds of studies they

want to do. 

...the companies when they want to market the new drug in a new market...they would promote those trials, and for them to get into the market was to get the approval of the Ministry

of Health and then find collaborators at the universities and then move on. 

Other participants felt that the lack of standards or guidelines came from their government officials’ lack of

familiarity with principles of ethics, scientific expertise, or commitment to developing or enforcing ethical

guidelines because of the strong desire to build links with international organizations. One respondent 

commented: 

...they would have anything any foreign government body would require, so that they would

make a link with [Asian country] or WHO...but in terms of who is running these bodies and

who is controlling what’s really happening, you will be amazed. It is mostly people who have

no idea about this. They just know it is a word. So if it’s human rights abuses, it will be OK,

we won’t abuse anyone. That is the context. 

Several respondents felt that the unequal power relationships between the United States and developing countries created a paternalistic environment in which to negotiate the terms of research. When the United States

brings funding, a research proposal, and specific technical expertise necessary for implementing a study, the

developing country governments have difficulty in refusing the opportunity. Given these power differentials,

respondents felt that decisionmaking regarding research was unfairly influenced:

The biggest problem in developing countries is that our poverty puts us in a situation [where]

the beggar has no choice.

Composition of Review Boards. The composition of review boards was mentioned in a few cases and

included scientists, lawyers, faith leaders, doctors, and community members. One respondent remarked that

the local university IRB would not approve research proposals unless a community representative is serving 

on the review board. 

The issue of community representatives was important to another respondent who said it would ensure

diversity and democratic composition of the board. In the university setting, one respondent mentioned the

issue of conflict of interest. It was customary to have both departmental and nondepartmental faculty review

each proposal to reduce the possibility for conflicts of interest to arise. Some of the respondents served on

review boards, and several commented on the difficulty in finding appropriate individuals with adequate

familiarity with ethics and enough experience to serve on review boards. It is frequent that the review boards

are set up ad hoc to satisfy the requests of U.S. donors or collaborators, which is found to be “paternalistic” by

some respondents, particularly in areas that already have established IRBs. One respondent had the experience

of an ad hoc committee being set up because the composition of the local IRB was “not equal to that in U.S.

institutions.” This respondent added that this created a problem because the U.S. IRB felt that the local IRB 

was not “appropriate.”
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External Influence. External influence in the establishment of review processes was met with both support

and skepticism. Several respondents felt that high-quality review processes could be developed through learning

and borrowing from external review systems. As one respondent stated:

I guess you learn from outsiders how research is conducted and then try to apply those 

standards to our situation....

This was reiterated by another respondent, who described the process of starting with no guidelines at the 

university and having to build a system for ethics review:

I think if we are both self-directed and also directed by the requirements of any agency, you

learn from it the right way....Initially it was very difficult for us as there was no board. We 

had to take our guidelines from various agencies, the [local] college...NIH, [local research

institution]....We had to go through four IRBs. There was no regulating body. 

Others clearly felt that while the review process was important, they were critical of external regulations. As

one participant explained:

So the thing for us [as] a country [is that] we don’t really care about the other country’s

approval...we really want to make [sure] that everything is OK according [to] our standards

and not with the outside standard because they might have another agenda to pursue. 

This reflects the same skepticism of how effective external review requirements are in protecting human 

subjects in the consent process. 

However, several respondents saw these “outsiders” as positive forces in motivating change for better

research through more control over the type and quality of research conducted in their respective countries.

Two participants mentioned specific examples of how their governments were guided and motivated by WHO

and NIH to establish a process of review for research proposals in their respective countries. They felt that

these external organizations served as catalysts in prompting their governments and universities to improve

standards in research: 

...it was WHO that was...behind the whole study....And they were very insistent that they

cannot start the study or do anything without being invited by the Ministry of Health....And

they try to push and empower them....

Other respondents said that while the NIH guidelines were “comprehensive” and provided a good “basic 

format,” some of the regulations are irrelevant and do not apply in their particular setting. Respondents 

felt there were distinctions between the U.S. cultural context and that of other countries, making some 

requirements irrelevant. 

Several respondents commented on the lack of monitoring of research in the field. Review systems are

important, but where activities are not monitored, efforts of the IRBs are negated:

Now, what this mechanism does is to have on paper something that is acceptable. That doesn’t

mean that that’s the way it is going to be implemented. As to what happens out there in the

field, nobody knows, because there is no mechanism for follow-up to make sure that people

are doing what they put down on paper.

In some cases, the sheer number of IRBs requiring approval complicated the process. Each research institution,

donor organization, national government, and collaborator’s institution has requirements and boards, each 

with several steps of approval depending on the level of risk involved for study participants, the number of 

collaborators involved, and the level of collaboration. Considerable time was reportedly spent in seeking IRB
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approvals. Another respondent felt that the IRBs were too stringent and that some of their requests were quite

“illogical.”

Gaining IRB approval was described as faster and easier for international organizations than for individuals

or for local NGOs because negotiations are said to occur at higher levels. One respondent felt it was advisable

to gain funding before seeking local approval because the local clearance will depend on whether or not the

project has financial support.

Capacity Building. One cultural dimension discussed by some respondents was that of the local power

dynamics and hierarchies in the government. For one participant, it was important to sensitize U.S. investigators

and donors to the “power structures” of the government so that they deal with the government officials who

are not corrupt and are making decisions in the citizens’ best interest. 

However, more often participants emphasized capacity building of government officials as the important

issue, sensitizing them to ethical concerns and broadening their understanding of how they can be active 

players in regulating the type of research implemented in their country. 

The main issue for most participants was not one of speaking to the “right people” in the government, but

rather one of raising awareness and empowering the government to take ethical issues under their control, to

negotiate the terms of the research, and to actively protect their communities. Many referred to this capacity

building as their responsibility as investigators who have been “trained outside,” but who also have local 

cultural knowledge in developing appropriate ethics guidelines for their particular setting and in building the

capacity of their local governments to deal with donors in negotiating research proposals: 

Where I think we have a role to play from developing countries not to be persuaded...not to

be taken off by monetary matters. We need to take the interest of the people and the country

at heart...it’s our duty who know how to do this type of research to guide the country to make

sure that whoever comes to do research...does it the way the government wants it to be done,

the country wants it to be done.

These respondents felt that not only do they have familiarity with Western ideas, they also have an understanding and knowledge of their own cultures. As investigators with this dual knowledge, including an understanding

of the local health care situation, many saw themselves as responsible for raising awareness of ethical principles

and adapting them to their cultural setting. In this way, they are able to build the capacity of their governments

to actively participate in research regulation within the local and national governments in particular, but also at

the university level.

One respondent described research as “a very new [option] for recent medical school graduates in [Asian

country].” While there is a dependency on outside researchers to conduct research, this respondent felt a

strong obligation among them to develop capacity in the country where the research is conducted: 

Whenever you are doing research in a developing country, you have to have the mentality 

that we are going there because the research capacity is not there so we are going to develop

something when we leave there is something left there...and also not carrying out the research

but the reporting and the presenting and also the...capacity building it’s not there.

The publication and dissemination of study results was also considered an important area of training for 

developing country researchers. Respondents wanted to be equally included in the publication and presentation of study results. Other respondents felt that this was already integrated into collaborative research activities

and reported having been involved in the research process from the study design to the dissemination of results.

Providing training of local health providers in how to diagnose, treat, or otherwise provide specific care was

also considered a key issue in capacity development.
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Another area of capacity development mentioned repeatedly throughout the discussions was infrastructure.

Many respondents felt it very necessary to begin to provide physical structures and equipment, particularly laboratories for diagnostic testing, in the country where the research is being implemented. Respondents viewed

this as a way to offer something back to the study communities after completion of the study. This has been a

point of conflict between sponsors and collaborators, as this respondent commented:

...I find unless you are the collaborating body or the government forces your donors or 

sponsors think of things that they can leave behind after the study, or benefits during the

study that would benefit your own people, its very difficult. Its very generic...that way of

thinking, and some of them actually accept your suggestion, but some are...like, Oh we know

what we should leave behind after the study that can help you...it would be nice if they

would ask.

One respondent felt that donors should send laboratory equipment directly to developing country study 

sites instead of providing the money to procure the equipment. Another respondent included provision of

infrastructure in the “ground rules” agreed to by the collaborators before the study began: 

I like people to come and take samples, but after a few years I want the work to be done at

home because not only are we getting the treatment, we are [getting] people trained to be able

to do the work and carry on the work when I’m not there or somebody else is not there. 

For another respondent, capacity development included the relationships that had been established between

health workers and the researchers. This respondent described how health workers continue visiting the

researchers “every now and then as they have the confidence” to interact with the researchers as a direct result

of their involvement in a study. Several respondents made comments regarding the actions of their local government IRBs in stopping research activities that were viewed as unethical. One respondent discussed how the

government refused a drug trial testing the effectiveness of Aquamarine as a birth control method. Another

respondent related a case where the Ministry of Health rejected the research proposal of an investigator who

falsely claimed to have found a cure for AIDS.

U.S. IRB Review

U.S. Regulations. U.S. guidelines were generally thought to be acceptable in terms of their basic premises.

This respondent remarked:

...it [present U.S. human subjects regulations] is all right in principle and in spirit, as they

want to protect the rights of the participants.

However, several respondents viewed U.S. guidelines as inappropriate because they are based on the U.S. legal

system and issues originating from concerns of protection and liability that are only relevant in the United

States. Respondents typically felt that the manner in which these guidelines were applied should reflect the 

cultural and social distinctions found across all countries: 

It is offensive that U.S. funding agencies impose IRB requirements on developing countries

that exist because of tort liability concerns in the United States...as if other countries were

additional states of the United States. Protection of research subjects is, or should be, of 

paramount concern everywhere, but the individual nature of that protection as practiced in

the United States is not necessarily the best model for other social/cultural settings.

This same respondent also felt that instead of U.S. institutions focusing on a U.S. review, they should rather

ensure a proper, relevant, and complete local review. Others charged that their local review processes were

highly functioning and adequate, as one respondent noted:
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...at least at my university the IRB, etc., procedures are by no means inferior to those in the

United States, and it is not necessary for them to be superceded or made consistent with U.S.

regulations.

Another respondent agreed: 

There are too many review boards. The U.S. and developing country’s national review boards

duplicate the work as they have similar guidelines by and large. 

The need for multiple approvals created difficulty in coordinating review schedules and funding cycles. If local

IRBs do not meet regularly, there may be a considerable time lag between getting approval and start of funding.

Conflict was noted in trying to seek local approval first, making changes per the U.S. IRB process and then

having to return to the local IRB to seek approval again. Some felt that IRB regulations were too stringent and

impeded important research. 

Respondents frequently mentioned that U.S. guidelines were applied unequally to research conducted

within the U.S. and outside the United States. One respondent did not feel it was appropriate for studies that

are not approved for implementation in the United States to seek approval in countries outside the United

States.

One respondent felt that the U.S. government or U.S. universities seeking local approval before a study may

be implemented is “healthy.” Similarly, others felt that the local IRB having the last review approval was more

appropriate because they were more familiar with the local cultural landscape and what would work best in

terms of specific consent processes and seeking permission from the local community. Another important issue

in this regard is reviewers’ understanding the level of health care available in the local setting. One respondent

remarked that there is a

...need for a broader knowledge of the health system, availability of treatment, and resources

in the host country [which] should be reviewed before making negative decisions about

important research impossible to develop without international funding.

Ethical Responsibility. Respondents identified individual researchers, donors, and local and U.S. governments

as having a role in maintaining ethical standards. As one respondent noted: 

I find the process as mandated by the NIH overly bureaucratic...the SPA is a good example....I don’t think the process...adds anything to the safety of studies. While I appreciate the

need for standards, in the end the only guarantee for protecting human subjects are the

researchers and the research team. 

Donors were viewed as having a role in maintaining ethical standards in research by providing education 

and allowing government officials to negotiate their ethical concerns and needs. This respondent referred to

capacity building with government officials and encouraged discussion of ethical concerns and issues with the

local IRB for a more meaningful review process:

There are a lot of donors who will strictly deal with only the government and the government

will get away with pure murder because part of the problem is they don’t even understand

it...they’re [the donors] surprised when you have the Ministry of Health who does not

know...about a live virus...given in a vaccine...He doesn’t [Ministry official] care a hoot, but

he’s interested in getting a kickback...we’re talking about developing countries...if he is able

to line his pockets he will do that...some of those kinds of information [ethical issues] should

be getting to the government...let them filter through their hierarchy so that at least they will
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begin to ask questions, they will know that they can bargain for incentives, bargain for making

the vaccines available if we participate in the studies, be active participants....A lot of them

[Ministry officials] are really very positive.

Another respondent felt that collaborators shared in the responsibility to maintain ethical standards:

Along the same lines, I think that the responsibility should not be solely on the developing

country researchers, but on the collaborators as well because a lot of things, researchers in

developing countries are low with money, I mean, the funds are low, and so they lose interest

in the people they’re treating, but I think collaborators should also have some level of credibility.

Monitoring. Several respondents felt that the United States did not pursue investigation or take any action

against ethics violations of which it was fully aware:

[The] United States should also—to the extent possible—curb unethical research done by

U.S.-based firms which do not follow existing U.S. and international policies and regulations.

Respondents related examples of ethics violations, which ranged broadly from physicians not participating in

the training for implementing the study intervention to failing to treat the placebo arms of a control trial once

the study concluded. In this latter example, after the study ended, the investigators not only did not treat the

placebo control group but also did not acknowledge their departure to the Ministry of Health. 

Another incident involved data collection on Lassa fever and at the same time, but unknown to the study

volunteers, on HIV. The HIV data was published in a well-known journal without the knowledge, much less

consent, of the study participants. In another case, a respondent commented that the government allowed for

an HIV drug trial to be conducted. When controversy over the study created attention and debate in the 

community, the government was not able to defend its decision and could not rescind approval. Another

respondent provided a particularly disturbing example of a Norplant study where implants were left in 

research participants’ arms with no follow-up care provided after the study was completed. 

One of the ethical concerns voiced by several respondents was the need for better enforcement of guidelines

and monitoring of research as it is implemented to ensure review board recommendations are carried out:

My humble submission is that there is no dearth of rules and regulations but there is no

enforcement, the rules have to be implemented...So what I am trying to say is that there is 

so much talk on ethics and [the] third world is all the time exploited. 

Several respondents made clear references to enforcement of the recommendations made by IRBs:

As to what happens out there in the field, nobody knows, because there is no mechanism for

follow-up to make sure that people are doing what they put down on paper.

Sometimes the ethical board clearances are a mere formality and paperwork. Therefore a

method should be devised to evaluate the process of clearance and the actual execution of the

recommendations of the ethical board.

Cultural, political and economic pressures often greatly influence decisionmaking about research. Several

respondents suggested that a monitoring system is needed to ensure that the changes suggested by the review

boards are implemented in the field, as this respondent commented: 

Ways should be found to monitor U.S. research collaborators about details of their research

activities in developing countries. Sometimes some of their activities go beyond what was

approved by the IRBs in areas that might be unethical. The issues of carrying away human

samples and their use should also be discussed.
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One respondent commented that the current review system could be made a more culturally appropriate

process by paying attention to the basic principles of ethics and justice, more specifically, the distribution of

justice: 

I think there is no hard and fast rule. We have to respect our subjects. To my mind, the real

issue is the exploitation or taking advantage of the decency of poor people. The issue is of 

distribution of benefits, power, money, and position.

Recommendations

Capacity Building

Workshops, discussion groups, and seminars were recommended for researchers in both developed and 

developing countries to raise awareness of ethics in research. U.S. funding was also suggested for supporting

the establishment of local IRBs and developing ethics guidelines. One respondent suggested that specific funds

should be included in research project grant money to support IRB reviews. Scholarships for researchers in

developing countries to study bioethics should be made available to ensure ethical research is conducted.

Regular and wider dissemination of results was suggested, which includes the participation of developing

country collaborators in the publications and presentations of data. Other capacity building was recommended

in terms of providing infrastructure and training in advanced scientific research methods. A very general

recommendation was mentioned by one respondent to identify and include investigators from developing

countries in all aspects of research.

One of the most frequent recommendations from respondents is that guidelines remain flexible and adaptable for application in diverse cultural settings and allow for integration of local policy, particularly in terms of

informed consent. Many respondents recommended the establishment of a national, independent regulatory

body that could develop guidelines for regional application. These respondents suggested the Ministry of

Health take on this responsibility of forming the regulatory body and developing guidelines. Appointing an IRB

representative from within the Ministry who could be the contact for U.S. IRBs was another recommendation

from one respondent. 

U.S. IRB

Many respondents recommended allowing more flexibility in the application of U.S. guidelines. Coordination

with developing country IRBs should be compulsory for U.S. researchers. An individual from a developing

country should be included on U.S. IRB committees. Equal application of developed country standards of

ethics for research within both developed and developing countries was also suggested. One respondent called

for the reduction in the level of coercive tactics used by drug companies to market their products, but did not

provide specific details. One respondent suggested integrating peer review into the proposal review process.

Another respondent suggested an attempt should be made to understand study participants’ perspectives on

being involved in research and to integrate their experiences into developing national guidelines for the local IRB. 

An ethical “commissar” should be appointed in the United States for each developing country or region, and

a counterpart should be identified in the Ministry of Health of all countries. After these “commissars” develop a

“common language,” then all projects could have these professionals conduct the basic work between the local

and U.S. IRBs. 

Gender perspectives should be integrated into the ethics of research, including adding a woman’s health

activist to IRB committees. One respondent did not recommend that representatives from the religious community serve on IRB committees. 

Several participants felt that the ethical clearance and the informed consent process are symbolic, with 

no real enforcement by the ethics review board for the implementation of the recommended changes. The
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establishment of a monitoring system to evaluate whether or not the study is implemented as it was proposed

and to enforce implementation of IRB changes was recommended by several respondents. Other respondents

suggested the application of international guidelines instead of U.S. guidelines.

D.6 Discussion of International Results

D.6.1 General

This empirical work reflects the expressed attitudes and opinions of the 203 researchers who were surveyed in

the developing world and the 37 additional scientists who participated in focus group discussions or in-depth

interviews. This work clearly has some limitations, especially with respect to the sample of researchers surveyed

and the domains of inquiry covered in the survey. Yet, this first attempt to explore input from the developing

world has provided a much-needed insight into the assumptions and myths that have been taken for granted

in the ethical discourse within the developed world—especially in the United States. The analysis contained

herein is intended to demonstrate the potential implications of the nature and application of ethical rules and

regulations—primarily U.S. guidelines—in a developing world setting. It helps to further our understanding

about the many issues that plague those in developing countries who are involved in research—researchers,

health professionals, participants, observers—and about how these issues are viewed by those who conduct

research.

The diversity in attitudes, opinions, and experiences that emerged reflect the complexity of ethical issues 

in health research. Across countries, there are tremendous differences in culture, medical practices, politics, 

and religion. Even within countries, these differences can create a challenging context within which to apply

standard guidelines for ethics. The notion of applying a single set of guidelines universally has the potential of

stereotyping cultures, which may have negative consequences for research. One of the most prevalent concerns

among respondents to this survey was the need for flexibility in applying guidelines so that they can be

adapted to specific settings. 

In general, respondents did not criticize the basic premise underlying the present set of U.S. guidelines for

international health research. However, respondents were concerned about how those guidelines have been

applied and about the mechanisms needed to make them more relevant to other countries. The need for 

flexibility repeatedly emerged in the data. While opinions seemed most vocal regarding drug trials, specific 

recommendations typically focused on practical changes in operational elements, as further described below. 

D.6.2 Informed Consent

Disclosure

One of the issues traditionally thought of as a challenge by health researchers is the extra burden posed by the

informed consent process and the inherent risk of losing potential research participants through that process. A

majority of the survey participants agreed that there is a risk of losing potential participants upon disclosure of

study details (whether randomized controlled trials or observational studies) in an informed consent process.

However, participants did not feel that the informed consent process promoted wider mistrust in the study

population, indicating that these researchers are willing to conduct the informed consent process even though

some risks are involved. University-based researchers were more likely to agree with the issue of informed 

consent raising distrust than were nonuniversity researchers, which may be reflective of their perception within

the academic centers or a consequence of the nonuniversity researchers being closer to the communities. Or, it

may be based on the experiences of academic researchers. In any case, further exploration of this issue may be

warranted in future studies.

The basic premise of individual informed consent seemed to coincide with the cultural values of most of the

respondents and their respective research settings. Community and individual education were emphasized as
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important in gaining true informed consent, and many respondents were concerned that people need to truly

understand what was involved in study participation. Full disclosure of the relevant risks and benefits was an

essential element in ensuring informed consent and in protecting the integrity of the research and the credibility

of the investigators. However, this appears to be a trend that has evolved from earlier research practices in

which full disclosure was not always the norm. Several examples of previous recruitment efforts, which did not

include full disclosure of risks and benefits, were described, a practice that reportedly could not be repeated in

the current climate of greater sensitivity toward ethical research. 

Procedures

Despite the oft-quoted “hesitancy” of using written and signed informed consent in the developing world, 

the majority (nearly two-thirds) of the survey respondents indicated that this was the most common form of

informed consent procedure used in their index studies. This was used appropriately and significantly more

often in populations defined by medium to high literacy (>20 percent) as compared to low literacy populations.

In addition, the use of community meetings and approvals from leaders was also common in index studies for

nearly half the respondents. This is reflective of several possible trends:

■ That the process of written and signed consent is being thrust upon research participants by ethical 

guidelines and rules that the local researchers must follow.

■ That there are secular trends occurring in these countries along with social and economic development, 

and that the hesitancy for a written and signed consent may be an historical carry-over.

■ That local researchers actually supported the implementation of this form of consent procedure and have

convinced community leaders to lend their support to the process.

In any particular developing country, a mixture of these and other factors may be at play. The appeal for greater

flexibility in applying ethical guidelines and more legitimate options for informed consent would tend to indicate that the first option may be close to reality. However, it is likely that the actual prevalence of the perceived

hesitancy to written informed consent is decreasing and that both the local populations and researchers are

becoming more accustomed to the concept, even if this trend is catalyzed by external guidelines. This may be 

a case of “exporting” standards to the developing world over time.

Participants in the qualitative research arm of this study expressed a measured perception on this issue.

They considered written consent forms, in general, to be appropriate in studies involving therapeutic interventions, especially those that were invasive (higher risk), such as surgery or the administration of drugs. For

lower risk studies and observational studies, the perception was that they typically have not followed strict

informed consent procedures. Serious concerns were raised regarding the ethics of social science research,

health program evaluation, and development oriented projects that are not required to obtain consent from

participants, particularly when sensitive topics are covered in data collection. In considering research of lower

risk not involving sensitive subjects, respondents felt some kind of consent process was still necessary, with

verbal consent mentioned as a possible option. 

Where illiteracy is high, verbal consent with or without a signature should be acceptable. However, it was

suggested that verbal consent with a third party witness’ signature would preserve the individual consent

process without requiring the individual participants’ signature. The distinctions made between informed 

consents that are written alone, written and signed, oral alone, or oral and signed reflect the great concern

among developing country researchers in this area. Obtaining signatures, as an independent activity for

informed consent, was often considered inappropriate and difficult to obtain in many situations. Such

sensitivities to obtaining signatures in developing world communities must be reflected in the search for a

wider menu of choices for informed consent in research that is compatible with U.S. ethical guidelines.
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The use of nonwritten media for informed consent was limited to less than one-third of reported cases, and

the use of high technology media was rare, reflecting the capacity development of local researchers in these

countries to conduct such procedures, as well as the availability of technology for use in research. Further

analysis revealed that academic (university-based) researchers were significantly more likely to use such media

than their nonuniversity colleagues, and senior (>45 years of age) researchers had more experience with such

methods. This is consistent with their exposure to research projects and the availability of resources over their

professional careers.

Testing of participants’ understanding prior to informed consent was reported to occur in less than a third 

of the cases. There may be a need to increase the importance given to this process, regardless of the exact 

procedure used for informed consent. In fact, the need for testing such understanding is further enhanced in

countries where informed consent procedures may be considered imposed by external guidelines, or new for

the local situation. Under these conditions, the effectiveness of the procedures and their validity need to be

evaluated, especially if background conditions—illiteracy and poverty—make the population more vulnerable.

As mentioned by focus group participants, if informed consent procedures do not promote enhanced understanding and truly informed decisionmaking, then they are not achieving their intended purpose. 

It was also disturbing to note that a minority of the survey respondents felt that research staff interfered in

the informed consent process by shortening or simplifying the consent forms. This was expressed by a significantly greater proportion of university-based researchers, as compared to nonuniversity based researchers.

Although significantly more researchers working with populations with higher literacy (>20 percent) agreed

with the statement, the numbers of studies in low literacy populations were small. This may also reflect the

inadequacy of the consent forms and the discomfort of field staff in using them without additional modifications. The length, tense, phrases, and use of language may all play a role; however, this issue was not explored

further in the survey. On the other hand, the conduct of research staff, especially field staff, such as interviewers,

is critical to both the scientific and ethical integrity of the project. As a result, any undue actions on their part

within the context of research need to be carefully monitored. There may be potential here for the development

of guidelines for research staff that could accompany the main research ethical guidelines.

Substantive Issues

Much has been said in the literature on ethical guidelines about the imposition of Western values on the 

developing world. In this context, one of the most commonly noted examples is the individual orientation of

the informed consent process. A large majority (two-thirds) of the survey respondents in this current study

support this notion as well. Academic researchers (university-based) were significantly more likely to consider

the informed consent process as focused on the individual than were nonacademic respondents. This corresponds to the report that community approval procedures were used in nearly half of the cases, although we

do not know whether they were used by the researcher on his or her own accord or as a result of specific 

ethical guidelines. Both community and individual consent can be accommodated by the combination of both

procedures within the same study and mandated by ethical guidelines. This strategy will avoid the perceived

stress on individual informed consent only, while still providing the same opportunity for each person to

respond to the study. 

The use of cultural and religious beliefs to support the notion that individual decisionmaking is not 

compatible with societies in developing countries is still reported by nearly half of the survey respondents.

However, the other half were either not convinced or disagreed with that statement, making it difficult to reach

a conclusion. Studies done in areas of Muslim faith were more likely to agree with the individual orientation 

of informed consent. Suffice it to say that the notion of individual decisionmaking is being currently used in

health research in the developing world and may need to be strengthened within the context of community 

and family consent. Even for observational studies, the notion that individual informed consent may not be

necessary was supported by less than half of the survey respondents. 
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In further analysis of the survey data, it was found that physician respondents used written informed 

consent more and community consent less than nonphysician respondents. This appears to be consistent 

with the individually oriented medical care that doctors provide and with their practice of taking consent for

therapeutic regimes from one patient at a time. This potentially makes them more comfortable with individual

consent even within the research context. It could also be the result of the greater exposure of these physicians

to Western practices and a familiarity with the notions of individual consent. This is also a reflection of the

scarcity of trained and skilled professionals in developing countries where it is very common for physicians to

be health researchers for a smaller portion of their time. In other words, the concept of a full-time health

researcher who gains all of his or her livelihood from that pursuit is rare in these countries.

Level of Understanding

Comprehension and understanding by participants of research is essential for a complete informed consent

procedure. Respondents view the procedure as an opportunity for dialogue with both the participants and the

research staff. This presents informed consent as an education tool within the research enterprise and enhances

the value to the community where research is being conducted. This is a very creative and appropriate view of

informed consent, as it also presents an opportunity for providing some benefit to the community.

Researchers report that participants are mostly aware that they are involved in a research study and also

dispelled the notion that the overall language used in informed consent forms may be too difficult—a hindrance to understanding by participants. This may be a reflection of the involvement of developing country

researchers within collaborative projects where their input in the development of the local consent form and

any subsequent translation creates a more appropriate form. Despite this general understanding, research 

participants were thought to have “unrealistic hopes” regarding the research projects in terms of personal gain

of any nature. These viewpoints are quite compatible with anecdotal experience within the developing world,

where despite an understanding of health processes, impoverished conditions cause people to hope for some

personal health gain. A strong desire for some relief from the challenging circumstances of every day life is held

by people, despite a presentation of facts to the contrary.

Conveying specific information was considered challenging within the informed consent process. Technical,

biomedical information was difficult to explain, particularly in areas where the local language did not have words

for terms such as “research” or “virus.” Understanding of other biomedical concepts by research participants, 

such as use of placebos (this was not related to literacy level of study population), was also acknowledged to

be challenging by the majority of the respondents. Senior researchers (>45 years of age) were significantly more

likely to agree with this observation than their younger colleagues, which may reflect their longer experience 

or their firmly held beliefs based on their experiences. Overall, this phenomenon in a community may have

culture-specific variations depending on the understanding of the nature and the use of placebos for therapeutic

purposes in such settings. 

Voluntariness

The respondents, especially in focus group discussions, expressed the concern that the informed consent

process must allow for voluntary decisions. The communal context of health issues, presence of strong family

influences, deep social traditions, and previous provider-patient interactions, often create situations in which

individual voluntariness may be compromised in a research context. Thus, refusal of persons to participate in

research studies was considered a proxy for some expression of voluntariness. Researchers described situations

(in focus group discussions) where the social rules of hosting visitors or the established rapport between

patients and local physician-researchers made refusal very difficult for potential research participants.

Examples of national censuses and demographic/health surveys were quoted to illustrate how participation

in “research” can sometimes be mandated by law and do not involve voluntary consent. One can argue that the
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primary intent of a census is not research; rather, it can be used for research once completed. In the specific

case quoted by one researcher, a census was a rare entity in two countries, and participation in a health survey

was mandated by the government and involved a consent form without expression of voluntariness.

Demographic/health surveys may be used for the same purposes as a census but are often conducted to get 

a better understanding of the disease burden, especially in children and women. Countries mandating participation in such surveys may need to revisit this issue based on the nature and type of information collected.

This is an area for further empirical work with nations and organizations that are involved in the conduct of

demographic/health surveys. 

Recommendations

The recommendations expressed by researchers from the developing world call for more flexibility in the 

procedures for documenting and practicing informed consent within human subjects regulations. This is

consistent with the call for requiring community leader’s consent, as well as individual informed consent, both

of which are considered important. Thus, the notion of informed consent as a principle is strongly supported,

and its flexible application at both individual and community level is also supported. This empirical evidence

dispels some of the assumptions that informed consent itself may either not be acceptable in the developing

world or that the ethical principle of respect for autonomy may not be as universally held. However, the

evidence strongly urges ethical guidelines to include more options for “acceptable” forms of informed consent,

which are appropriate for diverse national situations and cultures. 

An overwhelming support for testing participants’ understanding was recommended by these researchers.

This is an issue that may be seriously considered for any future modifications in the U.S. ethical guidelines.

Such a “check” is also consistent with the scientific side of research, where the notions of pilot testing and 

certifying methods and design issues are quite prevalent. Therefore, formal inclusion of such a requirement 

into guidelines may be quite acceptable. Exploration of innovative techniques, such as video, small group discussion, and visual aids, should also be recommended for participants’ understanding and for seeking informed

consent. Translation of written consent forms should emphasize the basic concepts of the study in order to

ensure greater understanding of the fundamental aspects of research.

It is important to note that the recommendations described above were supported by even higher proportions of those developing country researchers who had received funding from U.S.-based sources. This lends

greater credibility to their potential implications for the U.S. ethical guidelines. 

D.6.3 Risks and Benefits

Survey respondents categorized their index studies as “minimal” risk for participants in the overwhelming

majority of cases (>90 percent). The participants in these index studies included men, women, pregnant

women, children, and infants, and there was no relationship between the level of risk and type of participants.

All of the “greater than minimal risk” index studies were reported in populations with medium to high literacy

levels (>20 percent literacy). In general, the index studies are diverse and hopefully reflective of the vast

majority of low-risk studies done in the developing world. 

The survey also queried respondents on the sensitive nature of the information in their index studies. 

Half of the respondents indicated that their index study gathered sensitive information and that there was 

no association between the level of risk and the sensitivity of information gathered in the index study. The

majority of studies for HIV/AIDS were reported to gather sensitive information as compared to one-fifth of the

non-HIV/AIDS index studies. The interpretation of the word “sensitive,” personal and professional concepts 

of sensitive information, and the examples written in the survey next to the question (HIV-positive status,

domestic violence) may have influenced these responses. However, in general, the impression that emerges is

that studies done in developing countries, especially those dealing with HIV/AIDS, are handling information

considered “sensitive” and the need for appropriate ethical evaluations is very relevant. 
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Burden of Disease

One domain of inquiry within the survey dealt with the reasons for conducting the index study (the reference

study—on the basis of which the respondents answered several domains of questions). The majority of respondents agreed with each one of the reasons written for conducting the study in a developing country: greater 

relevance to the country in question, interest in global inequalities, and requests by host country researchers

were the most frequently cited reasons. This set of responses is a reassuring picture from the potential notion

that the West thrusts all research on the developing world and is irrelevant to the local situation. 

However, there may be some difficult response issues creeping in this section as evidenced by the following

observations:

■ Two-thirds agreed that addressing “global inequalities” was the reason for conducting research; physician

responders were significantly less likely to agree to this statement. In a generic way, this could be considered

true at some level in any research within the developing world; on the other hand, the generation of a

research project specifically to address these inequalities seems unlikely in such a majority of cases. Most

research projects would tend to arise from an interest on specific topics or discipline-related questions. The

continuing stark global inequalities, even within research investments and research utilization, make this

point very relevant (Hyder 1999a). 

■ Half agreed that a research study was conducted because it was relevant to U.S. strategic interests in the

region. A trend was noticed that female respondents were more likely to agree with this statement, compared

to male respondents. This reason was included in the menu of reasons for the respondent to consider, as it

is not related to either the science of the research study or to the health issue under investigation—making it

an important reason to note. Nonhealth and nonscientific reasons should not govern the conduct of health

research, specifically if they reflect concerns of only one country. However, this question could have been

answered from a variety of different perspectives—health research, broader science, geo-political, economic—

and it is difficult to assess which one each respondent used in defining “strategic.” It may also have been

viewed as a provocative statement, and the respondents may not have wanted their experiences to be labeled

under such a category. 

Further analysis of this data revealed that those researchers funded by U.S.-based sources had the same pattern

of response as the overall sample of researchers. In other words, the source of funding did not affect the way

respondents perceived or responded to such issues, making these findings more widely applicable.

A significant finding was that marketing approval being sought for a drug or product in the host country

was found to be a reason for conducting the research in only a minority of the cases. Even among those studies

that tested interventions (n = 27), less than 30 percent were stated to be done for this reason. This could indicate

one of the following:

■ Generally, marketing approvals do not form a substantial component of research portfolios for academic or

nonacademic, nonprofit researchers in the public or private sectors. This is also indicated by the portfolios

of survey respondents, such that 30 percent were predominantly involved with health systems research, for

example.

■ Research before marketing is not traditionally done in the developing world.

■ Marketing approval is not required in these countries, as the laws and regulations either are not stringent or

approvals in other countries can be used to bring drugs on the market.

■ These drugs will not be sold in these countries after the end of research, at least in the short- to mediumterm, and, therefore, the need for market research does not exist. This is held true by the time-lag in 

making drugs and vaccines available in the developing world after their approval in the developed world 

(Hyder 1999b).
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It is likely that although a mixture of these factors may play a role, the last bulleted item above has the greatest

impact on the health and development of the people in the developing world.

Types of Care and Treatment Available in the Host Country

The nature and content of health care available in the developing world generally leaves a lot to be desired.

This is consistent with countries’ level of health and economic development and the extent of the infrastructure

available. This situation presents a multitude of ethical challenges in a research setting, two of which are 

supported by the majority of respondents to this survey:

■ Medical treatment made available within a study setting is not usually available in the country.

■ The difference between the standard of care in the country of study and the donor country is usually 

significant, making the selection and treatment of controls a very challenging task.

Those researchers funded from U.S.-based sources were found to support these opinions more than nonU.S.-funded researchers. These statements also confirm the source of debate in recent literature and emphasize

the stark inequalities between nations, although they do not provide insight into potential solutions. (Lurie and

Wolfe 1997; Angell 1997). 

Medical treatment available during a study is one form of benefit to those involved in the study (limited to

those who actually receive it; for example, in the “treatment” arm of a randomized controlled trial). Treatment

of conditions found during the study but not related to the research question may or may not be available during the study. These potential “benefits” have the advantage of giving something back to generally impoverished

communities. On the other hand, they are usually not sustainable over the long term (post-study) and may be

important enough to the local community to be considered “incentives” for participation in the study. 

Differences between standards of care are relevant to intervention trials with control groups. The nature of

the “control” has to be determined (or the comparative regimen) based on an understanding of the standard 

of care. Interpretations of international guidelines such as CIOMS (1991 and 1993) were taken to mean that

the best-known treatment globally be applied to the controls. In recent years, especially with the conduct of

HIV/AIDS trials, the notion of best-available standard has been propagated. In either event, the use of any 

standard needs justification on ethical grounds. 

Issues such as this one prompted discussions of pre-study agreements in focus group settings. The intent of

such agreements was considered to support the provision of benefits to the study population and community.

Details of such pre-study agreements were not explored in this current work. 

In focus group discussions, a unilateral requirement for the best-known standard of care was generally 

considered inappropriate, due to the range of available therapies and the variation in clinical practice from one

country to another. More importantly, it was stated that the level of treatment during the study needs to reflect

what was typically available so that interventions could be tested for that particular setting. Where best-known

treatment is not available and will not be feasible for some time, respondents generally felt that the second best

interventions should be researched. This was a contentious issue, and some felt that developing country IRBs

needed to clarify their research needs and develop their capacity to advocate benefits for their communities.

This issue highlights the need for additional global debate between nations on health research and subsequent

benefits. 

Incentives and Compensation

Despite procedures of informed consent and information about studies, participants tend to have unrealistic

hopes about personal benefits. Although it was acknowledged that providing medical care to people living in

very poor conditions may be considered coercive, medical care was typically thought to be an acceptable incentive for study participation and, in fact, a benefit for study participants who would otherwise not have access to

medical care. 
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Monetary incentives, other than for reimbursing costs of study participation, were not recommended by the

respondents, who expressed the concern that the value of any reimbursements should be appropriate to the

local setting. New forms of nonmonetary incentives, particularly for poor and unemployed individuals participating in research, were recommended. In addition, any incentives for recruiters and research staff were

strongly rejected and were viewed as a possible source of conflict of interest.

Background Conditions

Research is a precious enterprise in resource-poor settings, one that requires careful justification. A decade ago,

a global call was made to ensure that research in the developing world was relevant and essential to the needs

of such countries and to develop a mechanism for more equity in development (COHRED 1990). This requires

that donors and countries jointly agree on research agendas, which has not been the norm in most cases. As a

result, half of the respondents agreed with the statements that the priorities of funding agencies and countries

often differ and that the products of research are not likely to be available in the country where research is

being conducted. The conduct of research in a country where the research topic is not a priority (if national

priorities have been defined) by political leverage of donors needs to be contested, based on the above rationale

(COHRED 2000). The priorities of the local institutions involved in research, the national health research

agenda, and priorities of donors and those of the foreign research institution may all differ, creating further

complexities. Thus, any piece of research may fall within the priorities of one or more of these stakeholders

and yet be outside the realm of others. Regardless of such categorization, an ethical review process should be

able to identify the relevancy and potential benefits of a proposed study to the population of concern. 

Recommendations

A majority of the respondents promoted the notion of reviewing studies on a case-by-case basis to evaluate the

standard of medical care provided during the study. Four-fifths of those researchers funded by U.S. sources also

supported this notion. This indicates that the issue is important enough to these researchers to warrant specific

attention in an ethical review process of studies. Whether this reflects a suggestion towards defining standards

of medical care or a discomfort with pronouncing a fixed rule to this effect is difficult to judge. Qualitative

explorations also indicated a recommendation to further evaluate the potential use of pre-study agreements

regarding the care to be provided during and after the study. Such mechanisms would allow for a careful consideration of issues related to the provision of benefits in the early planning phases of a study. This would assist

with the study-population interaction, as the expectations from the study would become explicit and transparent.

D.6.4 Obligations to Subjects, Communities, and Countries

In the survey sent to developing country researchers, they were asked to focus on a specific study that they 

are most involved with or have been involved with within the past five years. In questions pertaining to a 

specific study that involved external collaboration, fewer than half of the respondents were focusing on studies

that involved testing an intervention—which could be a drug, a treatment option, a treatment method, or a

public health intervention. Of these respondents, a very high percentage indicated that the intervention being

tested had been shown to be efficacious, and nearly all (>95 percent ) indicated that the intervention will be

provided to “the study participants or any other host country residents at the conclusion of the study.” This

comes as a surprise finding, and these numbers must be carefully interpreted.

It is clear that intervention testing is less common in the developing world, than other types of research. The

results indicate that the respondents involved in intervention research:

■ Were generally part of successful intervention studies.

■ Were of the opinion that the intervention would be provided to the study participants and their community;

fewer indicated that the intervention would be available to other parts of the country; female respondents,
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those who were over the age of 45 years, and those who were members of IRBs were more likely to suggest

that the intervention would be provided to the entire study population. No significant differences were

found between the source of funding, the topic, or the discipline of research.

■ Thought that provision of the intervention would be done by stakeholders within the host country—the

researchers (themselves), their institutions, and the government; nonacademic researchers were more likely 

to indicate the role of government in this process than academic respondents. 

■ Responded that the intervention would be available for more than two years, in most instances.

■ Reported that it would be paid for by both the host country government and the research institution, on the

one hand, and the research grant, on the other; respondents who were members of IRBs were significantly

more likely to indicate that the national governments would have to pay for the intervention, compared to

those who were not members of IRBs.

■ Reported that a minority (<17 percent) of all the intervention studies were funded by any private sector

source; moreover, of those funded by the private sector, only half were intervention studies. These numbers

indicate that the U.S., European, and developing country private sector are funding very few studies 

(<14 percent) in the developing world and that they do fund intervention and nonintervention studies.

This depicts a situation that is contrary to the expectation and experience usually described in the literature

and one that is also different from the facts about intervention availability in the developing world. 

In considering the intervention studies that are conducted in the developing world, some very important

issues emerge as a result of these findings, including the following:

■ Studies may yield positive results (in terms of efficacious interventions) in many cases, and as such the consequences of such findings need to be addressed in the design and ethical review of these studies. In other

words, prior to the initiation of studies, such outcomes need to be anticipated and a response prepared. 

■ There is a great desire expressed by developing country researchers to provide the products of research to

the populations of concern to them—the study participants, the communities within which the studies have

been conducted, and the national populace. These products could range the whole gamut of therapeutic and

diagnostic options interpreted to be an “intervention,” including those within the public health domain. 

■ The reported high prevalence of actual provision may therefore be colored by this spectrum of interpretation.

Thus, interventions such as bed nets for malaria, vitamin A for malnutrition, and oral rehydration therapy

that have been provided in several parts of the developing world would be included with other options,

such as new drugs for hypertension or new vaccines for childhood diseases. Since the former types of 

interventions would tend to dominate the research scene in the developing world, the positive statements

reported by the researchers become more consistent with what is known of current health care delivery. 

■ With the above proviso regarding delivery of interventions, only one-fifth of the researchers reported that a

placebo or control group received the intervention after completion of the study. Again, this seems to indicate the fact that randomized controlled trials with placebo groups were experienced by fewer developing

country researchers than other types of study design (<28 percent). A similar proportion reported that the

intervention was provided or would be provided to the whole country. Interpreting this is difficult, since, on

the one hand, the provision of an efficacious intervention to the whole nation should be of concern from the

beginning of the research enterprise. On the other hand, however, the actual provision of any intervention

country-wide is a huge undertaking, and it is unclear how these researchers can be so sure or how they can

commit to it. 
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■ Even if the interventions are provided, the responsibility of providing them in most cases excludes the 

foreign stakeholders, the research team, institution, and donor. This reflects the lack of responsibility in this

action that is faced currently by external agencies that conduct research in the developing world. Similarly

the private sector has been largely left out in the responses to this survey as being active in the provision of

interventions (the private sector funded less than one-fifth of the reported studies overall). These facts are

important for the development of appropriate mechanisms that allow for a more equal sharing of responsibilities for providing the products of research in such settings. Leaving the burden on local agencies and

national governments is impractical and futile and leads to the current lack of provision seen in the developing world. As mentioned by a researcher from Asia in one of the focus groups: “Even cheaper interventions

are sometimes not feasible [in our settings].”

■ On a similar note, the reported instances of intervention provision were at least in part paid for by institutions within the developing country. It is likely that such provision involved a multitude of funding sources,

and yet there is a hint of an undue burden on the country within which the research is conducted. A small

minority of the respondents indicated that an international agency was involved in the financing of the intervention provision, which is a surprising finding, as there is an assumption that often it is the international

agencies that pick up the tab for financing interventions in the developing world. Again, there is a trend of

enhanced burden on developing countries themselves to pay for these interventions when they are in no

position to do so in the first place. It is interesting to note that there was a higher trend for U.S.-funded

respondents to indicate that the foreign institution would be involved with financing the intervention, than

those not funded by the United States. 

■ Time is of essence within the health care industry, and commitments to population health are not to be held

for only the short term. As a result, the commitment to provide interventions needs to be done on a longer

term and sustained basis. Initiation of this process may be time-limited, as the intrinsic capacity of these

countries is further developed to respond to situations themselves. Two-thirds of respondents indicated that

the intervention, when provided, was done for less than a five-year period. 

These researchers believe, in general, that the products of research are unlikely to reach developing country

populations; they appear to see the national governments and the research institutions as the bearers of this

responsibility; and they consider the products of research to be a public health policy decision to be handled

by the Ministry of Health or other such agencies.

Recommendations

The survey section on recommendations evoked a set of responses that further affirms the notion that respondents

value and believe that the products of research need to reach the study population. This was further categorized

as an explicit agreement on the part of a majority of respondents to the following:

■ Data from the study, need to be made directly available to the study population; U.S.-funded researchers

demonstrated a trend of agreeing to this issue more often than non-U.S.-funded researchers. Participants in

focus groups further agreed by stating that any data emerging from studies should be in a “usable” format for

both the people and the policymakers.

■ The conduct of research needs to be questioned if the results of that research will not be available to the

developing country; this is a further reiteration of opinions expressed at various points in the survey to the

same effect.
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■ Mechanisms to enhance and facilitate the transfer of results need to be seen as a component of the research

enterprise; this promotes the concept of planning for such a transfer of benefits at the start of the study; 

furthermore, it promotes the notion that ethical guidelines need to make explicit this requirement for

demonstrating such a mechanism.

Analysis of these responses from those researchers funded by U.S.-based sources and the qualitative arm of 

this study both revealed complete consistency with these statements, only revealing even higher proportions.

These findings are very significant as an expression of the beliefs and desires, as well as the practice of health

researchers in the developing world. They need to be operationalized within international and U.S. ethical

guidelines.

D.6.5 International Collaborative Research

IRB Review Results: Local and United States

The nature of true collaborative research means that the studies are reviewed in all of the countries within the

collaboration. As a result, exploring the issues raised during reviews in the United States and in the host country

provides an insight into the nature of such review processes. The types of issues raised indicate both the process

of review and its recollection by the respondent. 

In responding to their impressions of the ethical reviews conducted in the United States, developing country

researchers indicated that the type and complexity of documentation related to the study was raised in a high

percentage of cases; these include issues relevant to the letters of approval and informed consent forms. Procedural issues, such as selection of control groups, were also raised by U.S. IRBs; while others, such as political

issues, were raised less often. Respondents who were IRB members demonstrated a trend to be more likely to

state that the issue of the intervention being too risky was raised; while nonphysicians were more likely to state

that the issue of participant voluntariness was raised.

These results are more interesting when compared to the issues reportedly raised by developing country

IRBs. In general, respondents indicated that most issues were raised more often by the U.S. IRB than the developing country IRB. This was especially related to informed consent processes and the protection of confidentiality,

where statistically significant differences were found. Other issues were either raised equally by both IRBs, or

the differences were small. Senior researchers (>45 years of age) were more likely to state that issues related to

consent forms, approval letters, controls, and placebos were raised by developing country IRB’s. U.S.-funded

researchers were more likely to state that issues related to relevancy of the research and confidentiality were

raised. Cultural appropriateness of the study was reportedly raised by both IRBs; in the international component, women researchers were more likely than men to report this issue (as being raised by the developing

country IRB). 

These findings may occur for several reasons:

■ Developing country respondents actually experience U.S. IRBs raising more of each issue; this could be due

to the greater experience of U.S. IRBs in conducting such reviews (and therefore a greater ability to detect

issues) or their ability to compare procedures with standards used in the United States (and therefore identify

differences). Developing country IRBs may have had less experience in conducting such reviews or may lack

any set standards for comparison.

■ Respondents recall the U.S. IRB comments more than they recall those of developing country IRB review.

This could be the result of paying more attention to understanding U.S. IRB comments and responding to

them; or it could reflect their own internal sensitivity to the critique of the U.S. IRB.
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■ The U.S. IRB review may have been the first to occur chronologically, and, therefore, it may have had more

issues to critique. This could also relate to the fact that issues pertaining to letters, language, and consent

were significantly more frequent, as these comprise common procedural issues in proposals. Subsequent

reviews in the developing world, therefore, were conducted upon a more developed proposal, with several

of the issues already addressed.

■ The additional experience, with seniority of age, seems to make older researchers more likely to note issues

raised by the local IRBs; this may also be due to their knowledge of the local IRB experiences of colleagues

and other projects.

■ U.S.-funded researchers are clearly consistent with their heightened awareness of specific issues, even from

their local IRBs, potentially reflecting their earlier experience with U.S. IRBs. Greater sensitivity to local IRBs

was also mentioned in one of the focus group discussions.

■ Women researchers displayed a tendency to indicate that the issue of cultural acceptability of research has

been raised by an IRB review.

Although it is difficult to generalize from such a recalled response, it is important to note that:

■ On the one hand, a review of the ethical aspects of a study are being done in both the United States and the

host country, which comprise both substantive and process issues covering a wide spectrum of ethical questions. This upholds the impression that such reviews are being conducted on both sides with serious intent. 

■ On the other hand, the fact that such issues were reportedly raised is a proxy way of saying that they were

presumably addressed. This is the more critical issue at stake: What happened after these questions were

asked from the research team? The survey itself did not address this issue, and we can only presume that a

satisfactory response was given to the IRBs by the researchers and that the response was then implemented. 

The last point feeds into an important issue that was also raised during focus group discussions. The IRB

reviews only determine in principle and on paper what should happen, since usually, there is no monitoring 

or evaluation of the studies after the ethical review process. This often creates a dilemma for those researchers

who know that what they write to the committee will subsequently need some (slight) “modification” procedures

once field work actually begins. 

Focus group discussion revealed that there was little communication between local IRBs and U.S. IRBs.

Appointing an IRB representative within the Ministry of Health was suggested to encourage communication

and to provide a contact person for the U.S.-IRBs. Similar representatives were suggested from U.S. IRBs so 

that these individuals could work together with a more open exchange. Several respondents felt that the

responsibility of establishing the IRB system should fall upon those who have been “trained outside,” who have

an understanding of the ethical principles on which U.S. guidelines are based, and who are also intimately

familiar with the local culture. Building collaborative partnerships between local and U.S. investigators was also

recommended in curbing the corruption of local IRBs by powerful countries or industries. Local universities

should emphasize the importance of ethics among their students and faculty by establishing a university IRB, 

if one does not exist, and by insisting on project review and approval. However, one respondent cautioned that

local researchers who have been trained in Western countries are as “delineated from our own cultural setting

as any foreigner would be.”

IRB Review: United States

A very interesting finding in the survey pertained to U.S. IRB reviews of studies. Nearly 40 percent of reportedly

U.S.-funded studies were not reviewed by a U.S. IRB. Although respondents whose studies were not U.S.-

funded were not supposed to respond to this question, one-fourth of the respondents to this question fell in

this category, and approximately 45 percent of non-U.S. funded studies were reviewed by a U.S. IRB. 
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U.S.-funded studies were defined to be those with at least one source of funding being labeled as a U.S.

source, but excluding bilateral organizations. So, if a study received funds from a USAID office (considered a

bilateral organization), in a country, for example, the study may not have gone through a U.S. review process

and may be controlled within that country only. Similarly, studies that were not labeled as U.S.-funded may

have included funds from USAID (under the bilateral organization category) and therefore have undergone 

U.S. IRB review. The classification of sources of funding did not distinguish between USAID and other bilateral

organizations, and this may be a source of potential misclassification in the survey.

In order to better understand this potential misclassification, the 30 studies that were reported to be U.S.

funded and not reviewed by a U.S. IRB and the 10 studies that were not U.S.-funded and yet reviewed by a

U.S. IRB were further explored for sources of funding. It was found that only 3 of the 30 studies and 5 of the

10 studies, respectively, were in the “bilateral organization” category. Excluding this potential misclassification

still leaves these questions: Why were 27 of the studies that were U.S.-funded not reviewed by a U.S. IRB?

Why did five studies not funded by U.S. sources still undergo U.S. IRB review? 

■ Is this an error by the respondents? Could it be either a recall error or a mistake made while completing the

survey? For example, did they forget to check off the U.S. course of funding for the five studies? Or has the

check for a U.S. source of funding been made in error or from mistaken knowledge?

■ Were the 27 U.S.-funded studies not reviewed in the “exempt” category for IRB review (which is only 

given after a “review”) but considered to be “not reviewed” by the respondent? Or were they funded and/or

conducted on an “informal” basis and thus “slipped through” the system? Or, is it that the U.S. funds were

routed in a very indirect manner through many intermediaries so that it would be considered a “subcontract”

and be subsumed within an original IRB review?

■ Regarding the five non-U.S. funded studies that reportedly underwent a U.S. IRB review: Were they incorporating some form of U.S. input, such as technical assistance, equipment, or personnel, so that the U.S.

collaborators had to submit the proposal for a U.S. review? Or were they part of a larger study that was

reviewed and funded by the United States (although the specific component that the respondent worked 

on was considered separate by him/her)?

It is difficult to predict which of the above played a greater role, and the survey itself is limited in providing

additional explanations. It is clear that the system of ethical review is imperfect and that the process of

appropriate review needs to be improved (as well as the content of the review).

IRB Review Process: Local

Slightly more than half the studies reported undergoing a review by a governmental body. This may have 

been an ethical review or a general review (although the pre-question instructions referred to an ethical review,

the actual question in the survey did not mention the word ethical for this question only). Although this did

not vary between those studies funded by U.S. and those not funded by U.S. sources, nearly 40 percent of

U.S.-funded studies were not reviewed at this level. 

Two-thirds of the participants reported having an in-country ethical review, and again there was no significant

difference between U.S. and non-U.S. funded projects. Local IRB reviews were most frequent, indicating that

some form of an ethical review committee was either developed or already in place in these institutions for

such a review. The high prevalence of this phenomenon is refreshing. Studies pertaining to the topics of infectious diseases and HIV/AIDS were more likely to be reviewed, while those dealing with health systems and

health services were less likely to have had an in-country review. Along the same lines, studies in the fields of

epidemiology, microbiology, and clinical care were more likely to have undergone review, while those under

anthropology were less likely to have been reviewed. 
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One-fourth of the respondents indicated that the specific study they were thinking of had no ethics review

in the country where the research was conducted. Similarly, nearly half the respondents indicated that their

index study did not have a Ministry/Department of Health review in the host country. Further analysis indicated

that 15 percent of the studies did not undergo even one review in the host country—either a Ministry/Department 

of Health review or an IRB review at any level—regardless of the source of funding. Of those funded by U.S.

sources, one-fifth did not receive an ethical review within the country. The survey was limited in further analysis of this issue, because no alternatives were provided to explore the reasons why a review was not done. For

these studies, where no ethical review was conducted in the countries, what happened? It is possible that:

■ The respondents stringently looked at the three options in the question—“IRB, ethics board, or Ministry of

Health”—and somehow decided that the ethical review entity did not fit in with these categories?

■ The studies were reviewed and given “exemptions” and, therefore, the respondent did not report that

review? Or were considered “exempt” by the researchers?

■ The studies in question were only reviewed by the collaborating institution in the West?

■ The studies were not reviewed at all?

It is clear that the last two options are very serious and need to be investigated further. A situation in which

studies are not reviewed in either the host or the donor country would be unacceptable. Qualitative explorations also indicated that there are a number of studies that were reported to have escaped the attention of or

need for ethics reviews in these countries. Focus group participants indicated that sometimes studies funded

within the country by bilateral or international organizations, especially those related to the social sciences, 

did not undergo standard review processes. There may be a special need to further explore the ethical review

processes of social science and anthropology studies.

The result of an IRB review process is affected by the guidelines that are followed, the procedures for review,

and the composition of the IRB. Some of the most important representatives on an IRB are those who represent

civil society, and it is here that the respondents expressed a weakness in local IRBs, with two-thirds reporting

inadequate community representation on IRBs. Younger respondents and those not funded by U.S. sources

were more likely to agree with this statement. Community participation has long been known as an essential

component for the success of any health program; and, indeed, for any health research when considered in its

entirety. The notion that health research should be responsive to the needs of the communities in which it is

conducted and be respectful of their way of life was expressed by these respondents. As a result, one of the

mechanisms to promote this is to empower communities to evaluate the research process. Thus, community

members serving on IRBs are but one way to gain this input, while community dialogue, permission, and formal

feedback mechanisms represent other ways. 

It was interesting to note that there were significantly more respondents who were members of IRBs among

those who reported that a study had to be abandoned as a result of lack of IRB approval in a developing country.

This may be due to the fact that:

■ These members were more likely to acknowledge the abandoned study (may or may not be as a consequence

of recall);

■ Their participation in an IRB may be related to their experience (over time) and desire to learn more about

the ethical review process; or

■ They may have interpreted this question in a more generic fashion to indicate that there are research studies

that are rejected.

Further exploration of this issue with IRB members would constitute an interesting qualitative research project.
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The process of ethical review, however faulty in both the United States and the developing world, did not

prevent a large majority of the research work from moving forward. This is an important finding for proponents (often researchers themselves) who view ethical review processes as potential “barriers” to research. Only

6 percent of the responses indicated that a project had been abandoned due to the lack of an ethical approval

from the U.S. IRB, while 19 percent indicated the same for the developing country IRB (this difference is not

statistically significant). None of these was related to the sensitivity of the information gathered in the study. In

all, 22 percent of those respondents who answered both questions (n = 93) indicated that they had to abandon

their research projects because it was impossible to get an IRB approval from either the developing country or

the United States or both. 

These percentages may include some cases that were unfairly judged or the victims of overburdened 

bureaucracies and long time lags, but it is also likely that there were studies that should not have been permitted

from an ethical viewpoint. Thus, the idea that all (100 percent) studies should be approved after modification,

assumes that all scientific questions are worth asking. Under a different assumption, that good science is a 

prerequisite for good ethics, there will always be poorly asked questions or questions that cannot be answered

within the acceptable realm of ethical trials. Therefore, there will always be a small percentage of research 

proposals that will not be able to obtain ethical clearances for these reasons. What this “small” percentage is,

whether it varies by country, research topics, and the nature of IRBs, and other related questions would require

a more detailed exploration than can be provided here.

U.S. Regulations: Application to the Developing World

In evoking their opinions about the applicability of U.S. ethical guidelines to developing country research, 

the survey asked respondents to review their entire working experience. In addition, the survey offered the 

category of “sometimes” as a response, which caused the majority of responses to be in this category. We could

interpret the “sometimes” to mean that the respondent agrees upon an issue but that he or she wants to be 

less categorical than “always” and therefore marks “sometimes.” On the other hand, it could also be that the

respondent feels that, in some cases at least, these issues would be true and therefore marks “sometimes.”

In relation to the U.S. ethical guidelines, the most positive opinion expressed was when half of the participants agreed that the current U.S. ethical guidelines always ensure high ethical standards. This was also the

only case in this section (Section G) of the survey where the majority of responses were not in the “sometimes”

category. Up to three-fourths commented on the insensitivity of U.S. guidelines to local cultures, while more

than half of the respondents expressed the fact that political considerations were affecting the guidelines at least

some of the time. The responses to these statements did not vary by source of funding, gender, age, professional

qualifications, or affiliations of the respondent. 

These opinions are important to construe that:

■ The issue of cultural sensitivity, although it may be expressed in the guidelines, is being consistently

reported as a weakness within the U.S. ethical guidelines as enforced in or viewed by the developing world;

this is an easily modifiable issue within the guidelines, and a renewed stress within the guidelines on appropriate cultural sensitization in developing countries would make an impact on this opinion.

■ Politics is viewed as playing a role in the functioning of the U.S. IRB; this is a serious perception, although it

relies heavily on the interpretation of the word “politics.” The work of U.S. IRBs should not be viewed by

more than half of developing country respondents as even sometimes being influenced by any issues that are

not ethical or scientific in nature, because this opens the door for differential application of guidelines based

on other U.S. interests. NBAC will have to be creative in exploring the operational implications of this finding and how the guidelines can respond to this concern in creating a new “standard” for the working of U.S.

IRBs, where this issue is explicitly addressed. The current survey offers little additional insight into this

potentially important issue.
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In relation to developing country ethical guidelines, as opposed to those of the U.S., only one-fifth expressed

the opinion that they are “always” able to protect research subjects. This lower proportion reflects a mixture of

their absolute opinion, as well as their relative comparison with the United States (since these questions were

also placed together in the same section of the survey). It is important to note that the fact that ethical guidelines in developing countries exist and are able to offer some protection to research subjects is different from

the generally held opinion that such guidelines are entirely worthless. However, the low percentage of support

is of concern, especially when compared to the larger agreement for the effectiveness of U.S. guidelines.

Respondents who were IRB members were more likely to support the working of the national guidelines than

were non-IRB members, and this seemed consistent with their proximity to the development or application of

such national guidelines. Similarly, the role of political considerations in the review process was also expressed

and with surprisingly similar proportions as with U.S. IRBs. 

Another hypothesis that was tested in this survey was the issue of costs associated with running IRBs. It was

thought that the cost of such operations may be a limiting factor in developing countries. Therefore, the survey

explored whether this issue had been raised with the researchers by their local IRBs. More than half reported

that it was “never” the case. However, the presence of a significant proportion, although a minority, expressing

that it had been raised indicates that it may well be an issue in some cases and needs to be explored in circumstances where it will prevent a fair and appropriate ethical review. This reflects the generally poor availability of

infrastructure and support in developing countries. 

Capacity Development

The notion of helping resource-poor countries develop their capacities in health research is integral to the 

practice of true collaborative research. The efforts at capacity development may take several forms:

■ Intentional

■ Formal training (degrees, certifications)

■ Teaching for research (formal/informal)

■ Availability of resources (library/Internet/journals)

■ Provision of equipment (laboratory, computers)

■ Capital development (buildings, rooms, laboratories)

■ Unintentional

■ Educational processes in the conduct of research

■ Scientific dialogue

■ Exposure to new methods and technologies

■ Availability of networks/contacts

Each of these is important for the developing world scientists; however, this survey only asked about the 

intentional elements of capacity development. 

Building Up People

Survey respondents in general rated their own involvement in the process of research very highly. More than

three-fourths of respondents indicated that they participated in tasks from planning of the study to writing of

papers, and from field tasks to data analysis. In the great majority of cases, the research projects lead to training

opportunities for local investigators. Although very refreshing to read, these results would be interesting to

compare with the reports from U.S. investigators to explore any differences in reporting. The results could

mean that:

■ The developing country researchers are being involved comprehensively in the research process, such that

they have the opportunity for capacity development.
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■ The researchers perceive themselves to be involved in such tasks and are made to feel involved, although

their actual contribution may or may not be significant; this paternalistic interpretation needs to be verified by

comparison between the U.S. and the international survey components of this project.

■ The focus of the training may be on the investigators (perhaps as according to the need of the project) and

limited to technical issues (again, as according to requirement).

■ Formal training in research ethics was not commonly stated, suggesting that this could be an area where

explicit attention needs to be given, such that it becomes equally important in developing local capacities.

■ Noninvestigators, field, and other staff may have received less opportunity for training, and even informal

dialogue on ethical issues was not very common; this could mean that unless specific training programs are

built into research projects, staff members may have to rely on informal strategies for individual capacity

development.

Qualitative work provided another feeling of unequal power relationships between countries of the “North”

and those of the “South.” In many cases, grants originate in the developed country and are then presented to

developing country investigators. Respondents felt that investigators from developing countries should be

involved in grant writing, to reduce the potential for coercion of governments to accept research opportunities

that they find difficult to refuse, particularly when the project is already funded. These unequal power relationships create difficult situations for developing countries in which to negotiate the terms of research. Cultural,

social, political, religious, and economic factors must be considered in designing studies in resource-poor 

countries. Additionally, for health research, investigators must have a clear understanding of the health care 

system in the host country. 

Infrastructure

Nearly all the researchers indicated that there would be some infrastructure left behind at the conclusion of

research in the developing country. Equipment and pharmaceutical supplies were the most frequently reported

of these items. In addition, two-thirds reported that organizational plans and processes were also part of the

package left behind after conclusion of research. It is important to note that:

■ Although the primary intention of developing such infrastructure would have been to ensure success of the

research project, it still contributes to an increase in available resources, since the materials are left behind.

■ When done unintentionally as a consequence of convenience or to avoid cost of re-shipment, leaving behind

such equipment, for example, may not ensure proper utility. The presence of trained personnel to use and

service it and the need for supplies to maintain it are all important and may need to be planned as part of

the project, if capacity development is important for the external team.

■ The notion that a research project could leave an “organizational plan or structure” for health care or

research is very interesting. This may be referring to a learning process within local institutions of how to

conduct a research trial, or it may refer to a health systems study that provides insight into how health 

services should be organized. In either case, these are only suggestions, and potential plans would require

intra-national discussions at high levels, including policy debates, prior to any consideration of being

applied in the country. It is possible that some of these reported cases did reach that stage of development,

but it is unlikely that the majority did so. Therefore, interpreting this statement conservatively would be

more appropriate. It also provides a hint that a significant proportion of these studies could therefore relate

to health systems and health services (30 percent or so were under this heading) even though they may be

categorized under a different topical heading (so that a study on cholera could be categorized under the 
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discipline of microbiology, but if it yields tips on how the health system should respond to cholera, it would

be subsumed within this statement).

Recommendations

The survey was able to return to the issue of collaborative international research in the recommendation section,

yielding specific insights into the similar and often unified thinking of developing country researchers regardless of their geographic and disciplinary backgrounds. 

Although the statement that local IRBs may have urgent cost issues did not strongly bear out, researchers

nevertheless agreed that local IRBs need to be financially supported. This is in line with a sympathetic attitude

towards their colleagues (or themselves) working on IRBs in a setting where the opportunity cost of voluntary

work is very high. Disagreeing with such a positive statement is difficult, although more male respondents were

likely to disagree than female respondents.

Respondents to the survey recommended that international guidelines, rather than U.S. guidelines, would

serve them better. This is a very important statement that requires careful interpretation along with a consideration of the following:

■ Earlier statements regarding the usefulness of U.S. ethical guidelines were supported by an overwhelming

majority of these same respondents; therefore, this cannot mean that they are entirely unhappy with U.S.

guidelines.

■ It could relate to the fact that they are unhappy with some specific issues within the U.S. ethical guidelines

(such as their insensitivity to local cultures) and that the international guidelines do better on those specific

issues.

■ The application of U.S. guidelines may be more cumbersome (or viewed as such) than the potential 

application of international guidelines; by intent, the former are for U.S. interests and the latter are based 

on a multicountry perspective.

■ Although the U.S. guidelines serve as well, it would be more “politically correct” to have international 

rather than U.S.-based guidelines. Any guidelines deemed “international” would presumably have been

developed by an international collaborative activity and could also be amenable to input from the 

international community. 

■ The wording of the statement made the respondent compare the U.S. ethical guidelines with the CIOMS

guidelines, since that was the only example quoted within the question. Even if the expressed preference is

for the CIOMS guidelines only, it still underscores the fact that a preference is being expressed for a more

“international” guideline than a uni-national one.

A common thread in these potential interpretations is that despite the fact that respondents feel that U.S.

guidelines work, they would prefer to use other guidelines. 

The need for a local/national ethical review of every study in the developing world has been stated in earlier

sections as well, and it received an overwhelming approval at various points in the survey. The minority who

disagreed with this premise may be those researchers who have had negative experiences with local IRBs, those

with research projects they feel do not require an ethics review, or those who feel that the capacity for such

review does not exist in their countries. Nonphysicians were more likely to disagree with this statement than

were physician respondents. Further qualitative exploration with these few researchers would be enlightening.

Similarly, the composition of the IRB board, which is also controlled by U.S. ethical guidelines, was found 

to be dictatorial. An overwhelming majority reported that the U.S. guidelines should not determine the composition, although U.S.-funded respondents were significantly less likely to agree with this statement. Physician
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respondents also demonstrated a trend of being less likely to agree with this statement. Again, this may 

be seen as an expression of the preference that issues should not be controlled by one entity—U.S.-based ethical

guidelines. Rather, a more international standard should be adopted. We can hypothesize that the issue is that a 

single source of guidelines is presented, in this case U.S. ethical guidelines, and that the response would have

been similar had the survey presented a different single source for guidelines, for example, guidelines from the

United Kingdom. The issue is the difference between guidelines from one country being applied elsewhere as

opposed to guidelines that stem from a collaborative standard.

D.6.6 Commentary on the Entire Study’s Recommendations

The survey ended with a general recommendation section, the components of which have already been analyzed

within the main issues discussed above. Although each statement of recommendation was developed by the

authors, each is open to interpretation by the respondents, and each varies from positive to negative in tone,

the results provide important messages for the U.S. bioethics community. All but two of the recommendations

were supported by at least a two-thirds majority, with most higher. This calls for serious consideration of these

issues in further analysis of U.S. ethical guidelines as they are used and applied in internationally sponsored

research. 

One of the most critical appeals is expressed in the call for studies the benefits of which reach the study

population after they end. The context of scarcity in the developing world, the abject poverty of all types of

resources, and the righteous needs of the people make this call more poignant. Research is questionable under

any circumstance and needs to be justified based on the scientific question at hand; under these circumstances,

it becomes even more necessary to balance the risks and benefits and to make certain that the benefits are tangible

and are received. 

Moreover, this recommendation is very appropriately coupled with the call for exploring and developing

mechanisms to ensure that populations actually receive benefits and represents recognition of the great challenge

that such a demand poses upon all stakeholders in the research enterprise. And yet, it needs to be seen as an

essential component of ethical research at some level. Therefore, it is now a challenge for U.S. ethical guidelines

(as it is for other national and international guidelines) to devise more precise and innovative mechanisms to

address this issue of providing benefit during and after research. The intent is not to develop loopholes where

such responsibility is displaced or avoided. Rather, the intent is to develop creative solutions that allow for a

predetermined process to occur and for the benefits to flow to the deprived communities. At the same time, the

need to look at this issue collectively and fairly for all parties is central to the success of any potential solution.

E. Comparative Results of U.S. and International Components

This section of the report will explore the differences and similarities between the responses received from

researchers in the United States and those from the developing world. The intent is to consider potential 

reasons for such observations and offer policy recommendations based upon them. 

E.1 The Samples

A comparison of the respondents in the United States and international components of this study reveals that

the two samples are comparable in terms of gender and age. (See Table E.1.1). International researchers are

more likely to have been involved in at least five studies in a developing country over their careers, although

this may be because all of their work, one would assume, was international according to our definition. That is, 

the two groups of researchers may have been involved in equal numbers of projects overall, but some of the

studies conducted by the United States may not have been in developing countries. 
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U.S. researchers were more likely to be involved currently in an international research project (the index

study), more likely to have worked on the index study for more than two years, and more likely to spend over

50 percent of their time on research. Some of these differences are an artifact of the differences in sampling

strategies between the U.S. and international projects, but others may be true differences between U.S. and

Table D.6.1: Summary of Recommendations from Survey of Developing Country

Researchers

Main Issue Recommendations Explanatory Notes

1. More flexibility in documenting informed consent 1. Going beyond written to other forms

2. Informed consent may or may not be required in 2. Split support for this issue on a specific

observational studies study design

3. Community approval should be required 3. As appropriate

4. Testing of participants understanding prior to joining 4. Important to note for guideline revision

research should be required

1. Standard of care should be decided on case-by-case basis 1. Care provided during research study

2. No research unless benefits of research can be provided 2. Strong support for this overall premise

afterwards**

1. Study data should be provided to study population 1. Feedback to community from researchers

directly after study ends

2. Mechanism to continue delivery of medical care 2. Part of planning the study and its

afterwards should be required** consequences

1. Funding for developing country IRBs should be provided 1. Addressing donors and research investors

2. International guidelines should be used instead of U.S. 2. CIOMS stated in the question as an 

ethical guidelines example

3. Developing country ethical review should be required 3. Very high support for this process

4. Composition of developing country IRBs should not 4. As a requirement from the U.S., this is

depend on U.S. guidelines rejected

5. The SPA requirement should or should not be 5. Few respondents and split decision

eliminated

6. Funds for pilot testing should be released prior to 6. Currently not usually done

full/complete ethical approval

*Recommendations overlap for these issues.

**Important overall impressions supported by 80 percent of respondents.

Informed consent

Risks and 

benefits*

Obligations to

subjects and

communities*

International 

collaborative

research

Table E.1.1: Demographics

Gender % U.S. % International P-Value

Female 35 32 .53

≥50 years old 31 31 .95

Working on index study currently 82 67 <.001

Worked on index study >2 years 73 53 <.001

Role on index study 

• Principal Investigator 80 73 .04

• Project Coordinator 20 27

Have worked on ≥ 5 studies 55 81 <.001

Spends > 50% of time on research 67 27 <.001

Past or current member of IRB 23 44 <.001
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international researchers. This U.S. project recruited participants heavily through the NIH-CRISP database,

which includes researchers who currently or recently were funded for research by the NIH. Thus, one would

expect more currently funded researchers in the sample. Moreover, additional recruitment was conducted

through personal contacts who were asked to identify professionals who conduct research in developing countries. Thus, one might expect these contacts to have identified researchers conducting projects currently. The

international sample, by contrast, was constructed based on membership lists of four international professional

organizations. It is assumed that it will take some time and experience for a developing country researcher to

become part of an international database and to have collaborative projects, lending support to the finding that

these respondents are more experienced, while society membership does not necessarily imply that a member

has research ongoing. Most of both sets of researchers were the principal investigators of their index studies,

although this was somewhat more likely to be true for U.S. investigators.

In general, health professionals in the developing world are not dedicated solely to research. The same individuals likely have multiple roles—including clinical practice, teaching, and administration—and, therefore,

the amount of time that they dedicate to research inevitably is less compared to their counterparts in the

United States. The lack of trained professionals in developing countries often means that the few people who

have the requisite skills to conduct major research projects typically perform several functions, as required by

the needs of the country or institution. 

It must be remembered when comparing characteristics of research projects and attitudes of investigators

from the international and the U.S. surveys that our two samples of researchers were not literally one another’s

counterparts or colleagues, nor were they necessarily referring to the same studies, and, indeed, international

respondents may not have been referring to research that was collaborative with the United States at all in

many instances. Thus, where responses differ, both sets of responses may be accurate reflections of research

experiences of two different groups of respondents. At the same time, it is also possible that there are significant differences in attitude, opinions, or values held by U.S. versus developing researchers as a whole, which

deserve careful consideration.

It is also important to note that the U.S. researchers are likely to be more homogenous than the international

respondents in many relevant respects. The former are from one country working within the general rules,

guidelines, and cultural norms of a single nation. International researchers, on the other hand, represent

researchers from three continents and dozens of countries following a wide variety of rules and guidelines

within their nations and dealing with many other international or Western ethical guidelines. As a result, the

within-sample diversity would be much higher in the international sample than in the U.S. sample. This qualification is critical as we discuss the comparative analysis, since this provision colors the statements we will

make that refer to the international group as a unified entity. However, the diversity also is a strength in terms

of documenting a more comprehensive range of relevant experiences and views. 

As described in Sections B.1 and C.3, data from the UNDP Human Development Report (UNDP 1999) was

incorporated into the survey database in order to facilitate analysis of selected survey variables in comparison

with a UNDP development indicator. The indicator variable, HDI, also was used to compare international and

U.S. survey data. Table E.1.2 shows the percentage of index studies in countries with different development 

levels, for the U.S. and international surveys. The U.S. survey more often reported index studies in countries

with low HDI scores (“low” human development was defined by UNDP as <500), and more often intervention 

studies were carried out in those countries as well. Using two categories of HDI level, with a cutoff point of

682, these differences were statistically significant; the U.S. survey had a greater percentage of studies in lower

HDI, compared to the international survey (50 percent versus 41 percent, p = .05) and the same was true for

intervention studies (59 percent versus 41 percent, p = .02).
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E.2 Informed Consent

Respondents to both the U.S. and international 

surveys were asked to answer questions related to the

process and outcomes of informed consent in their

index studies.

Methods for Informing Participants and

Documenting Consent. U.S. respondents were more

likely to have used written informed consent in their

studies than the international researchers and were

more likely to use written consent than any other

method (see Table E.2.1). These differences may

reflect U.S. researchers following the requirements 

of U.S. ethical guidelines for documenting informed

consent. While most international researchers used written consent (62 percent), even more (77 percent)

reported using an explanation of the study to participants followed by a question/answer session. International

focus group participants reported their own use of verbal consent in many cases. International researchers were

more likely than U.S. respondents to use pictorial descriptions to inform research participants and were more

likely to say they checked participants’ understanding prior to their enrollment, something that both groups

articulated should be done much more often; it was a minority of both groups, however, that actually used

such a test. 

Beliefs About the Consent Process. The overwhelming majority of both groups thought that the consent

process is an important means of educating participants about the study, although international respondents

were even more likely to agree with this (94 percent versus 82 percent, p < .001). International focus group

members were particularly likely to raise the issue that the consent process served as a valuable opportunity to

provide health education and counseling more broadly to patients. Furthermore, international researchers were

significantly more likely to agree that the consent process is too focused on the individual (66 percent versus

23 percent, p < .001; see Table E.2.2) and that the religious/cultural beliefs of the study population are inconsistent with individual decisionmaking (47 percent versus 37 percent, p = .04; see Table E.3.1). Both groups were

more likely to believe that religious and cultural beliefs are inconsistent with individual decisionmaking if their

index study was carried out in a lower HDI country. International researchers obtained consent from a family

member in 20 percent of studies, while U.S. researchers did so in 14 percent of studies; however, it is interesting to note that international respondents who used written consent or who were IRB members were significantly less likely to obtain consent from family members, suggesting that perhaps in some cases international

researchers had adopted a more “Western” model of consent processes. 

Overall, international researchers were significantly more likely than U.S. researchers to agree that, in addition to individual informed consent, U.S. IRBs should require community leaders’ approval (63 percent versus

32 percent, p < .001). In focus groups, U.S. respondents seemed to feel that host country colleagues and IRBs

understood when community approval should be obtained much better than they (the researchers) or the 

U.S. IRBs. One U.S. researcher said that no U.S. IRB would ask him to talk to the village chief before going into

the village. U.S. researchers often admitted their “cultural ignorance” on this issue, or that “our culture doesn’t

understand a community the way [South American country] does.” International researchers also raised in

focus groups the discrepancy between the U.S. emphasis on individual rights and the community or family

level decisionmaking processes of developing countries. Most international researchers in focus groups, however,

thought that although community consent was important, individual consent should also occur.

Table E.1.2: HDI Levels of Countries

Where Index Studies Were Conducted 

HDI Levels of

Countries <500 500-800 <800

U.S. survey,

% of all index studies 23 73 4

International survey, 

% of all index studies 13 83 4

U.S. survey, 

% of intervention studies 30 68 3

International survey, 

% of intervention studies 17 77 5
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International researchers may have used written consent as much as they did because it was required of them

in their collaborative projects, or they had grown accustomed to it through their experience with collaborative

research, or because in certain settings they felt that it was appropriate. Both U.S. and international respondents were more likely to use written consent in higher HDI countries, and researchers from both groups who

used written consent forms also used other methods to inform participants. For example, among researchers

who used written consent in their index study, 75 percent of U.S. and 69 percent of international also used an

explanation and question/answer session, and 41 percent of U.S. and 45 percent of international researchers

also used a community meeting to describe the study. Our data clearly suggest that both groups believe that

nonwritten methods may be more appropriate in certain contexts, or should be an integral accompaniment to

written consent. 

Table E.2.1: Different Methods of Informing Participants and/or Documenting

Consent Used for the Research Project

International

U.S. Survey Survey

Option % Yes % Yes P-Value

Written informed consent, requiring a signature, thumbprint, or equivalent 76 62 .001

Pictorial description of study or study procedures 7 20 <.001

Oral consent with a witness signature 40 32 .1

Community meeting to describe the study 44 51 .1

Approval from a village or community leader 42 49 .2

In research with adults, approval or consent from another family member 14 20 .1

Explanation and question and answer session with participants 

(either individually or in groups) 74 77 .6

Video to explain study 2 4 .3

Test of participant understanding of research before enrollment 16 27 .01

Table E.2.2: Percent Agreeing or Strongly Agreeing with Various Statements

Regarding Consent in an Index Study

International

U.S. Survey Survey

Option % Yes % Yes P-Value

The informed consent process is focused too much on the individual rather than 

on the family and/or community. 23 66 <.001

Participants often do not understand the concept of placebo. 57 51 .6

Study participants are usually aware that they are in a research study. 87 84 .2

The consent process is an important means of educating participants about the study. 82 94 <.001

The consent process provides an opportunity to discuss ethics issues with field staff. 82 89 .03

After learning about the study, some potential participants declined enrollment. 72 58 .001

The formality of going through the informed consent process raises distrust in study 

participants. 29 27 .7

Local staff shortened or simplified the consent procedures compared to the original 

protocol. 37 35 .9

Legalistic language was required on consent forms that was not meaningful to study 

participants. 52 29 <.001
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Although international researchers were significantly more likely to use a test of understanding with participants, international and U.S. researchers were equally likely to believe that many of their participants do not

understand placebos (over 50 percent reported this in both surveys). The two groups were equally likely to

believe that, in general, their participants were aware they were in a research project. About one-fourth of each

group believed that the consent process raised distrust among participants, and both groups reported in focus

groups that consent forms included too much technical information, which can induce anxiety among participants. U.S. researchers were significantly more likely to believe that the legal language in consent forms is

meaningless for participants (52 percent versus 29 percent, p < .001), but it may well be that the international

researchers actually put less of that legal language into their forms. Indeed, in focus groups, U.S. researchers

devoted considerable attention to their frustration with consent forms having an increased focus on legal protection for investigators and institutions. International investigators mentioned in focus groups that the legal

framework inherent to the U.S. consent process does not exist outside the United States and is inappropriate.

In terms of voluntariness, it is interesting that so many more U.S. researchers reported that some of their

participants had refused to participate (72 percent versus 58 percent, p = .001). It could be that the consent

processes used in U.S. research projects more clearly distinguished the research from clinical activity and/or

emphasized the voluntariness of participation; it is also possible that developing country investigators had

closer relationships with study communities that may have facilitated acceptance of the research.

E.3. Assessing Risks and Benefits

Only 12 percent of U.S. researchers and only 5 percent of international researchers (p = .01) classified their

index studies as entailing greater than minimal risk. It is not clear from this finding whether the number 

of risky studies truly differed or whether researchers’ perceptions of risk varied instead. Indeed, it is quite 

conceivable that risk was underestimated by both groups of researchers.

In terms of benefit, approximately 60 percent of both international and U.S. researchers agreed that the 

care provided to participants in studies generally is not available outside of the study (Table E.3.1). Those in

the international survey were significantly more likely to believe that this made it difficult to establish appropriate

interventions for control groups (67 percent versus 52 percent, p = .01), and that participants had unrealistic

hopes about personal benefits from participation (55 percent versus 33 percent, p < .001). It is interesting to

note that developing country scientists more often agreed with statements about ethical issues arising from the

disparities in levels of medical care between sponsor and host countries. Since the samples of U.S. and international respondents are not literally each others’ collaborators—that is, they were not referring to the same index

studies, it is possible that international respondents more often worked in areas where the available medical

care was inadequate, thus creating ethical challenges in study design. It also should be noted that the international survey had higher percentage of studies involved in clinical care (24 percent versus 14 percent for U.S.,

p = .005) and therefore possibly more likely to encounter difficulties in determining appropriate levels of 

treatment, although international researchers were less likely to work in the lower HDI countries. In addition,

perhaps international researchers had a higher sensitivity to the needs of study participants for medical care or

a greater sense of responsibility for providing care that was not locally available.

An exploration of the reasons for conducting U.S.-funded research in developing countries revealed a set of

interesting differences between the U.S. and international respondents (Table E.5). As stated above, the index

studies referred to by each group of respondents are different studies, and, therefore, differences observed in

responses may reflect different characteristics of those studies; alternatively, the respondents may have different

perceptions regarding similar research projects. It should also be noted that the response rate differed for each

of the reasons listed for conducting the research in the host country; between 10 percent and 30 percent of the

respondents did not answer a given question and were excluded from calculations. While both U.S. and international researchers frequently listed relevance of the intervention, global inequalities in health, and developing
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country requests for collaboration as reasons for conducting the study in the host country, U.S. researchers

were much more likely to state that disease prevalence in the host country was a relevant factor. International

respondents who were funded by the United States were as likely as U.S. respondents to work on topics where

one might expect disease prevalence to be relevant, such as infectious diseases other than HIV (about 38 percent

of each group) or HIV/AIDS studies (approximately 25 percent of each group). International researchers, whom

one can assume often conducted their research in their home countries, may not have focused on the difference

in disease prevalence between the United States and their own country, since they were working, presumably,

on health problems that affected their home nation. 

A more notable finding is that international researchers were much more likely than U.S. researchers to believe

that the index study was located in the host country because of several pragmatic reasons: cheaper cost, relevance to U.S. strategic interests in the region, and the need to obtain marketing approval for drugs or devices.

While it is a minority (25 percent) of international respondents who listed marketing approval as a reason for

the index study to be carried out in a developing country, almost half checked U.S. strategic interests, and more

than half (63 percent) checked cheaper cost as reasons for conducting the study in the host country. It may be

that differences in the types of index studies reported by international researchers, compared to U.S. researchers,

relate to these practical issues. For example, a greater percentage of studies in the international survey were

funded by private companies (16 percent versus 10 percent of U.S.); some of these studies may have been 

carried out in developing countries for practical reasons, as mentioned by some U.S. focus group respondents.

Also, international respondents’ perceptions of the reasons for conducting research in developing countries 

may differ from those of U.S. respondents, even for similar studies. Although the practical reasons listed do 

not a priori exclude consideration of the health needs of the developing country, these health needs may not 

be addressed by research that is driven by financial or strategic motives. 

It is important to note that three-quarters of both groups of respondents said they were conducting research

in developing countries because they were interested in addressing global inequalities in health. This noble 

reason clearly motivates researchers around the world. The degree to which they feel they are able to provide

the fruits of their research to local communities after studies are over, however, will be addressed in the next

section.

Table E.3.1: Reasons for the Study Being Carried Out in the Host (Developing)

Country as Opposed to in the United States (“% of yes” by the researchers in 

developing countries)

International

U.S. Survey Survey

Question % Yes % Yes P-Value

Prevalence of disease in question is much greater in the host country than in the 

United States 83 66 .001

Interest in addressing global inequalities 73 73 .9

Host country researchers asked for U.S. collaboration 72 70 .7

Intervention being tested more relevant to host country than to the United States 69 76 .3

Recruitment of patients more rapid in host country than in the United States 47 53 .4

Less expensive to do study in host developing country than in the United States 36 63 <.001

Easier to identify a cohort of patients relevant to research 61 56 .4

Research question relevant to U.S. strategic interests in the region 32 49 .01

Marketing approval for drug or device will be sought in host country 12 25 .01
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E.4 Obligations to Communities and Participants

Our surveys addressed two aspects of obligations and collaborations: one related to what role international

researchers had in collaborative research and how much capacity building U.S. researchers engaged in; the other

was how studies addressed continuing to provide care or interventions to study participants or communities

after the study was over. 

In terms of responsibilities within research collaborations, as shown in Table E.4.1, both U.S. and international researchers reported that international researchers are likely to be involved in most aspects of the research.

More than 90 percent of researchers in both samples agreed international researchers are involved in training

of research personnel and are listed as authors on papers. More than 80 percent of both said international

researchers are involved in the initial study design, changes in study design, recruitment of participants, 

consent discussion with participants, and drafting of manuscripts. There were significant differences, however.

U.S. researchers were most likely to say that their international colleagues were involved in procedural tasks

(such as recruitment, consent discussions, and staff training) and less likely to say they were involved in more

substantive tasks like grant writing and data analysis. International researchers, while also less likely to mention

grant writing as a task with which they were involved, still reported themselves significantly more involved in

that task than did the U.S. researchers (72 percent versus 53 percent, p < .001). They also reported themselves

more involved in data analysis than did the U.S. researchers (86 percent versus 69 percent, p < .001), and somewhat less likely to be involved in recruitment or consent discussions. 

It is possible that the index studies described by the two groups differ, on average, in the level of developing

country scientist involvement with specific tasks. On the other hand, it also could be true, at least in part, that

U.S. researchers underestimate how involved their colleagues are in substantive matters, or developing country

researchers overestimate their involvement. An important future study would be to recruit researchers who

were paired in terms of actually serving as the U.S. and international counterparts for the same studies. This

and many other study comparisons would be further clarified by such a design.

In terms of capacity building more broadly, researchers were asked whether resources or research infrastructure would remain after the study had ended. Over 90 percent of both groups answered “yes” to this question.

The type of capacity or resources that were improved or remained after study completion differed little between

the groups.

Table E.4.1: Developing Country Researcher Were/Are Included in the Following

Research Tasks

International

U.S. Survey Survey

Option % Yes % Yes P-Value

Initial study design 87 86 .8

Grant writing 53 72 <.001

Change in study design 94 88 .03

Recruitment of participants 98 86 <.001

Drafting consent form 82 84 .7

Consent discussions with participants 94 84 .001

Training of research personnel 94 92 .4

Drafting manuscripts 83 87 .4

Data analysis 69 86 <.001

Listed as authors on papers 97 95 .2
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Thirty-nine percent of U.S. researchers and 44 percent of international researchers reported conducting an

intervention study. They then were asked whether the intervention was provided to participants or communities

after the study was over, if the intervention proved efficacious. International researchers were more likely to

answer “yes” to this question (92 percent versus 67 percent, p = .009), although the majority of both groups

answered positively. U.S. intervention studies were more likely to be ongoing (82 percent versus 64 percent, 

p = .008); the data from the U.S. survey indicated that U.S. researchers were less likely to say that they would

provide the intervention if they did not yet know if it was efficacious, although they were no more or less likely

to describe plans to provide it if the study was ongoing. Logically enough, more U.S. intervention studies were

funded by the U.S. government (71 percent versus 19 percent, p < .001) and fewer were funded by the developing country government (18 percent versus 33 percent, p = .02). Funding levels were similar for bilateral and

international organizations. Many more of the U.S. intervention studies were HIV studies (35 percent versus

15 percent of international intervention studies, p = .002), and fewer were chronic disease studies (9 percent

versus 24 percent, p = .004); the most frequent topic for each group was infectious diseases, non-HIV (41 percent of U.S. and 34 percent of international intervention studies.) International intervention studies were much

more likely to be health services research (31 percent versus 10 percent, p < .001). It is possible that many of

the international studies that provided an intervention were in fact interventions already being implemented

through the existing health system, where the health system itself was the focus of study. We lack further

details to clarify this point. Also, the higher percentage of HIV studies in the U.S. group may be related to a

diminished likelihood (compared to the international group) of providing the intervention after the study,

although in the U.S. survey, HIV studies were more likely to provide interventions than studies on other topics.

Both groups report a similar percentage of intervention studies classified as operational research/program 

evaluation (25 percent of U.S. and 28 percent of international). These program evaluation studies could be 

providing interventions as part of a health program, rather than as a post-study benefit.

It is also possible that international researchers are more likely to report providing successful interventions

after study completion because they are more likely to work on problems that are relevant to the policy priorities of their home countries and governments; they may be better situated to influence local policy implementation since they are more likely to know and work with (or are themselves) government officials. Also it is

possible that, by virtue of being more likely to live amidst the health problems in question, they are much

more committed to advocacy to change local conditions. Consistent with this, international researchers were

significantly more likely to believe that research to test an intervention should not be done in a developing

country unless the intervention, if successful, will be made available to the country at the conclusion of the

study (78 percent versus 53 percent, p < .001) and to believe that international policy regarding research

should require researchers to establish mechanisms for continuing delivery of medical care after the completion

of the study (79 percent versus 27 percent, p < .001). International researchers were more likely than U.S.

researchers to believe that interventions would not be available to most citizens of the host country (48 percent

versus 33 percent, p = .01); thus, perhaps they felt a greater need for policies to address this gap. U.S.

researchers, while supporting the principle that benefits should accrue to those populations and countries

where research was carried out, frequently expressed concern in survey comments about the difficulty in

obtaining funding for providing ongoing interventions and medical care.

The strong commitment of many researchers to providing the benefits of research to developing country

populations is very significant. This reflects an inherent desire on the part of these researchers to make health

research a benefit to the populations within which it is conducted both during the study and after it is completed. Clearly, additional mechanisms need to be developed to support such intentions within collaborative

health research. 

Another important difference is that international researchers were significantly more likely than U.S.

researchers to believe that the research priorities of outside funding agencies were not congruent with the
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developing country’s priorities (58 percent versus 39 percent, p < .001; Table E.4.2), although it is interesting

to note that only 40 percent of the international researchers who received U.S. funding believed this to be true.

The fact that international researchers questioned the priorities of the funding agencies is consistent with a

commitment on their part to promote research that addresses the health needs of the developing country 

populations and consistent with a critical view of research driven by financial or strategic motives, which was

frequently expressed in international focus groups.

E.5 Review and Oversight

E.5.1 U.S. IRB Review

Both the U.S. and international surveys asked respondents about the U.S. and host country IRB review of 

their research. The percentages of studies that underwent different types of review are shown in Table E.5.1.

International respondents whose index study received U.S. funding (n = 86) were asked if their study was

reviewed in the U.S.; it is quite striking that only 55 percent reported U.S. IRB review, while 96 percent of

U.S.-funded studies reported in the U.S. survey had such review. Nineteen respondents, or 22 percent of those

who had U.S. funding, did not answer the question about U.S. IRB review and were not included in the 

calculations. It is not clear why essentially half of the U.S.-funded studies in the international survey were not

reviewed in the United States. Of those 30 U.S.-funded studies that did not undergo U.S. IRB review, 7 percent

had funding from the U.S. government, 67 percent from U.S. nonprofits, and 30 percent from U.S. private

companies. There were 14 international studies that received U.S. private company funds, and 82 percent of

them had no U.S. IRB review. As noted in section C.5, U.S. private companies conducting studies either inside

or outside the United States are not necessarily required by U.S. law to undergo ethics review in the United

Table E.4.2: Ethics Issues in International Research

U.S. International

% True or % True or

Sometimes Sometimes

Option True True P-Value

Medical care provided to participants in this study generally is not available to local 

population outside the study. 63 61 0.6

Study gathered potentially sensitive or stigmatizing information about participants. 49 58 0.08

Study participants have unrealistic hopes about personal benefit from study 

participation. 33 55 <0.001

The standard of medical care in the host country may be much lower than that of 

funding country, creating difficulties in establishing appropriate procedures for 

control group. 52 67 0.01

Participants join because of the desire for compensation, medical care, or other 

benefits. 68 64 0.3

Research priorities of the outside agency that is funding the study are not congruent 

with top priorities of developing country funding. 39 58 <0.001

Treatment or intervention being tested is unlikely to be available to most citizens of 

developing country in the foreseeable future. 33 48 0.01

There is inadequate true community representation on the local IRBs/ethics boards 

for this study. 50 62 0.04

Religious beliefs and/or cultural norms of study population are inconsistent with the 

practice of individual decision-making. 37 47 0.04

Ethics issues are rarely discussed with field staff on this research project. 24 39 <0.001
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States, although if they submit clinical data to the FDA, they must undergo IRB review at each study site,

including study sites in developing countries. Also, it is possible that the international respondents in the survey were not always aware that a U.S. IRB review had taken place, especially if such review occurred prior to

developing country review or before their involvement with the study protocol. Even so, it is probable that a

number of studies reported by international researchers truly did not receive any U.S. IRB review, which is

cause for concern. Out of the studies that had reported U.S. IRB review, 32 percent reported no ethics review

in the host country and thus were not reviewed by any board; this represents 6 percent of all the index studies

in the international survey. 

It was notable that for each IRB issue mentioned in the survey, international respondents were more likely 

than U.S. researchers to state that the U.S. IRB had raised the issue. (Table E.5.2). This difference was statistically significant (p < .05) for the relevance of research to host country, confidentiality issues, control group 

procedures, and availability of intervention after study. These findings suggest that the U.S. IRB review and role

may be perceived differently by both groups of respondents. International respondents, for example, perceive

that the U.S. IRB raised these issues more, or are more sensitive to multiple issues being raised about their

Table E.5.1: Percentage of Index Studies Undergoing IRB Reviews

IRB Reviews: All Studies, Regardless of Source of Funding

U.S. Survey: International Survey:

Board Percent Reviewed Percent Reviewed P-Value

Ministry of Health (host country) 77 56 <0.001

Any ethics review (host country) 87 75 0.001

National IRB (host country) 51* 49* 0.7

State/provincial IRB 16* 27* 0.03

Collaborating institution IRB 84* 92* 0.03

Other board 7* 15* 0.03

U.S.-Funded Studies Only, in Both International and U.S. Surveys 

(U.S.-funded is defined as any study that reported at least one source of funds from the United States.

Does not include bilateral organizations as a U.S. source.)

U.S. Survey: International Survey:

Board Percent Reviewed Percent Reviewed P-Value

U.S. IRB 96 55 <0.001

Ministry of Health (host country) 76 58 0.002

Any ethics review (host country) 89 79 0.02

National IRB (host country) 51* 43* 0.3

State/provincial IRB 17* 25* 0.2

Collaborating institution IRB 84* 98* 0.004

Other board 6* 12* 0.2

*Percentages refer only to those who responded positively to the question about any ethics review; those who did not undergo ethics review

were excluded from further calculations.
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studies. Indeed, international researchers, presumably having less experience with U.S. IRBs, may have had 

different expectations, and may have remembered all of the concerns raised, whereas U.S. researchers may have

forgotten some of the concerns that seemed to them routine. It also is possible, since our two samples, again,

were referring to different studies, that the studies truly differed in their need to have issues raised, although 

we assume that such individual variation would be neutralized over the large samples for each group. On the

other hand, U.S. IRBs may indeed give more scrutiny to developing country researchers than they do to U.S.

researchers, or U.S. researchers may have been able to appear before their IRBs and address concerns before

ever receiving the formal comments from the IRB.

E.5.2 Host Country IRB Review

Respondents in both the international and the U.S. survey were asked about review by the host country

Ministry of Health and by ethics boards. In the international survey, those studies conducted in lower HDI

countries were more likely to have Ministry of Health review (67 percent versus 47 percent, p = .009). For

those whose index study was reviewed by one or more ethics board, respondents were asked to identify the

type of board or boards that were involved, as shown in Table E.5.1. U.S. researchers significantly more often

reported Ministry of Health review and ethics review in the host country than did international researchers.

This was true overall and also true when U.S.-funded studies in each group were compared. For those who 

did undergo host country ethics review, both international and U.S. researchers were most likely to report that

the host country IRB that reviewed their study was associated with the collaborating institution, and next most

likely to report that a national IRB had conducted the review, although the international researchers had an

even higher percentage of studies being reviewed by collaborating institutions compared to the U.S. researchers

(98 percent versus 84 percent, p = .004). International researchers were also more likely to have studies reviewed

by provincial boards, compared to U.S. researchers. International respondents who are working within the

countries may prefer to seek approvals from provincial boards, even for collaborative projects, due to familiarity

with people and processes and potentially fewer bureaucratic procedures.

It is interesting to note the discrepancy in host country IRB review between the U.S. and the international

survey. International researchers report host country review significantly less often than U.S. researchers, even

for U.S.-funded studies (79 percent in the international survey versus 89 percent for the U.S. survey, p = .02).

In the case of U.S.-funded research, U.S. regulations would require a host country review to be conducted in

most cases, and, in fact, when FDA regulations apply, the host country review is the only one that is required.

Presumably all studies that received U.S. funds, reported either in the U.S. or in the international survey, would

have been governed by some U.S. regulations, either the Common Rule or those of FDA. It is not clear if the

studies that were not reviewed in either survey gained an exemption from review, and, if so, on what basis. 

More than three-quarters of the respondents from both groups felt that developing country ethics review

should be required for all studies, although international researchers felt so even more frequently (85 percent

versus 77 percent, p = .03). At the same time, developing country researchers were more likely to feel that

community representation was inadequate on local boards (62 percent versus 50 percent, p = .04).

In comparing the responses from both surveys on the outcomes of the review done in the host country,

international respondents (as in the previous section) were more likely to suggest that all issues had been

raised. This global trend was significant for issues related to the relevance of the study to the host country, 

cultural appropriateness, approvals, control procedures, confidentiality issues, voluntariness, and availability 

of intervention. The reasons for this difference probably are similar to the reasons suggested above for why

international researchers reported a greater likelihood of issues being raised for them by the U.S. IRB. 

If the U.S. IRB or the local IRB would tend to review collaborative projects more stringently, then both

groups should reflect it in the responses. The fact that there is the same differential in response (international

greater than U.S.) for both reviews is indicative of issues that pertain to the international respondents and their
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characteristics. In general, there has been an historical tendency for the few trained researchers, especially

physician-researchers, to do their work without much question in the developing world. At the same time, the

processes of peer review, group critique of proposals and papers, and the expectation that people can question

and challenge senior researchers is a relatively new phenomenon in many parts of the developing world. As a

result, the IRB review processes may be a source of greater consternation and concern for developing country

researchers, as compared to the U.S. respondents. In addition, the heightened sensitivities of the international

researchers would affect their response to such critique and their recall of such processes as well. These findings

would partly explain the result discussed in the previous section and this section.

International researchers were more likely to agree that funding agencies should provide funding to support

the work of developing country IRBs (85 percent versus 70 percent, p < .001) and to report that developing

country IRBs had raised concerns to them about the costs associated with IRB operations (44 percent versus 

26 percent, p < .001, Table E.5.3). These are consistent with the notion that volunteering time for such activities

is much more difficult and has a greater opportunity cost in the developing world than in developed countries;

it is likely that developing country researchers would be more acutely aware of these issues than their U.S. 

colleagues.

Table E.5.2: Comparison of Responses to Issues Raised by U.S. IRB(s) vis-à-vis

Issues Raised by Host Country Ethics Board

Raised by Host Country

Raised by U.S. IRB Ethics Board

According to According to According to According to

U.S. International to U.S. International

Researchers Researchers Researchers Researchers

Options % Yes % Yes P-Value % Yes % Yes P-Value

Relevance of research question to 

country where research is conducted 

and/or rationale for doing study 

outside the United States 30 52 .02 23 55 <.001

Complexity of language on consent 

form 45 64 .05 29 59 <.001

Cultural appropriateness of study 

procedure 48 63 .1 38 45 .2

Need for local language consent form 66 84 .03 50 58 .2

Need for letters of approval from 

developing country representatives 65 79 .1 31 47 .005

Intervention was considered too risky 4 15 .01 4 10 .03

Appropriateness of procedures for 

control group 18 50 <.001 17 39 <.001

Confidentiality protections for 

participants were not adequate 14 42 <.001 8 18 .004

Participant voluntariness may be 

compromised because of benefits 

study provides 10 20 .09 7 24 <.001

Use of placebos 12 22 .2 12 26 .006

Availability of intervention 

(if successful) to host country after 

study is over 23 46 .01 25 54 <.001

Political considerations 7 17 .09 14 16 .6
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In comparing countries with different development levels, using combined data from the U.S. and international surveys, it seems that ethics review capacity, at least on the surface, is not associated with HDI levels of

the host country. Index studies in countries with lower HDI levels were not any less likely to have undergone

host country ethics review (about 82 percent overall); this review was more often carried out by a national IRB

in the lower HDI countries compared to higher HDI countries (63 percent versus 39 percent, p < .001), and

less often by a provincial IRB (14 percent versus 23 percent, p = .05) or an IRB at a collaborating institution

(79 percent versus 92 percent, p < .001). Also, respondents reported that IRBs were formed because of U.S.

regulations with the same frequency for low and high HDI countries (about one-quarter of the cases overall).

On the other hand, lower HDI countries took significantly longer to complete host country ethics review (53

percent of studies took greater than three months, compared to 37 percent of studies in higher HDI countries,

p = .003), which may be a disincentive to conduct research in these countries. Also, 13 percent of respondents

whose index study was in a lower HDI country reported they had ever abandoned a research project due to

difficulty in obtaining developing country IRB approval, compared to 6 percent of those who worked in higher

HDI countries (p =.03). Respondents more often reported that host country IRBs were more concerned with

politics than with protecting research subjects in lower HDI countries (80 percent versus 66 percent, p = .003),

and less often reported that host country collaborators relied on U.S. ethics regulations for guidance in lower

HDI countries (87 percent versus 94 percent for higher HDI countries, p = .01), although the percentage of

respondents who believed that national guidelines are sometimes or always effective in protecting research subjects was the same for those who conducted their index study in low or high HDI countries (about 94 percent

of each group). 

In terms of IRB review, lower and higher HDI countries showed similar percentages for most issues that

could be raised by IRBs, with a few exceptions. Lower HDI countries’ IRBs more often brought up the need for

letters of approval (45 percent versus 28 percent, p = .002) and the potential for voluntariness to be compromised (17 percent versus 10 percent = .06). While the letters of approval are a procedural matter, the issue of

voluntariness may indicate a real concern for the well-being of the potential research participants. In general, it

is not clear if there are any differences of substance in terms of host country ethical review between poorer and

richer nations, or if procedural difficulties may arise more often in some cases due to lack of resources to fund

IRBs or other government bureaucracies. In addition, our survey data does not include information about

national guidelines that might have been applied in different countries where research was conducted; this

topic deserves further inquiry.

Generally, international researchers were more likely to agree that international guidelines should be used

instead of U.S. rules and regulations to govern collaborative research in developing countries, although the

majority of both sets of researchers agreed with this recommendation (77 percent versus 64 percent, p = .001),

and some U.S. researchers commented in focus groups that international guidelines would be more appropriate.

This is likely to be the result of a number of factors, including a resistance to the idea that other countries

should be held accountable to rules emanating from a single nation, to real concerns about the lack of flexibility

in application, to a preference for a more international approach to the ethics of research.

In comparing researchers’ attitudes towards human subjects regulations (Table E.5.3), it can be seen that

both international and U.S. researchers were critical of the current U.S. regulations and of IRBs, both in the

United States and in the host countries. However, the vast majority of both groups also said that U.S. human

subjects regulations sometimes or always ensure high ethical standards in research. This apparent paradox can

be explained if we postulate that researchers in general find that the regulations do provide protection to

research participants, but that the protection could better be achieved through more flexible and culturally

appropriate mechanisms. It should be added that those researchers who said that the regulations “sometimes”

ensure high ethical standards are also implying that “sometimes” the regulations do not provide this assurance. 
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In focus groups, U.S. researchers commented that some procedural requirements, for example, lengthy 

consent forms, actually impede the substantive part of research ethics, such as ensuring adequate participant

understanding.

E.6 Summary

There are broad areas of agreement, on the whole, between U.S. and international researchers, as well as 

significant differences. In general, both groups of researchers expressed strong commitment to ethics principles

in their research, while at times expressing frustration with procedural requirements or difficulties of interpretation of ethics guidelines in different countries and cultures. Both U.S. and international respondents felt that

U.S. guidelines could be significantly improved by becoming more flexible and more culturally appropriate.

Both groups expressed strong commitment to the elements of informed consent, namely, participant understanding and voluntary participation in research. In focus groups, both groups said that IRBs in the United

States and in developing countries need to be educated, the former about realities of life in the developing

world, and the latter with regard to ethics and ethics review.

Researchers in both surveys were asked if they agreed or disagreed with a series of recommendations about

the conduct of international collaborative research and the human subjects regulations that govern such

research. A strong majority of both international and U.S. researchers recommended support for developing

country review processes, including requiring developing country review for all studies, supporting developing

country IRBs with funding, and not imposing on developing country ethics boards the U.S. requirements for

IRB composition. International respondents were less likely than U.S. researchers to agree that the SPA requirement should be eliminated, which may indicate that fewer of them had experience with SPAs or that those who

had dealt with SPAs had not experienced the considerable frustration with the process that U.S. researchers

expressed in survey comments and in focus groups. A majority of both groups, and international respondents

even more frequently than U.S. respondents, supported the use of international ethical guidelines such as

CIOMS rather than U.S. rules and regulations for human subjects research.

Table E.5.3: U.S. and International Human Subjects Regulations and Guidelines

U.S. International

Researchers, Researchers,

% Sometimes % Sometimes

Option or Always or Always P-Value

U.S. human subjects regulations are flexible where they need to be. 68 63 .4

Developing country collaborators rely on U.S. ethics regulations for guidance. 91 91 .9

U.S. IRBs are more concerned with politics than they are with protecting the 

interests of research subjects. 66 58 .2

The current U.S. rules and regulations governing human subjects ensure high 

ethical standards in research. 97 95 .6

U.S. IRB regulations are insensitive to local cultural norms and traditions 

outside the United States. 94 83 .001

Developing country IRBs are more concerned with politics than they are with 

protecting the interests of research subjects. 79 63 .001

Developing country IRBs have voiced concerns to me about the costs 

associated with the IRB carrying out its work. 26 44 <.001

National guidelines in developing countries are effective in protecting 

research subjects. 95 92 .1
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Concerning informed consent, a strong majority of both groups supported increased flexibility in documenting consent, although international researchers were less likely to recommend this than U.S. researchers. A

majority of both groups recommended the measurement of participant understanding of research projects and

the release of funds before IRB review so that researchers can pilot consent forms with study populations.

Both international and U.S. respondents supported the idea that the level of medical care provided to study

participants should be decided on a case-by-case basis. Expressions by members of both groups in focus group

discussions indicated that this aspect of study design was ethically problematic and that there was no clear 

consensus about what should be required of researchers. Some researchers in both groups felt that the level of

medical care that would be available locally should be considered reasonable for control groups, even when

that care would be considered grossly insufficient in the country that sponsored the research. 

Table E.6.1: Recommendations

U.S. International

% Strongly % Strongly

Agree or Agree or

Recommendations Agree Agree P-Value

U.S. regulations should allow more flexibility in ways of documenting 

informed consent. 85 72 .001

Formal individual consent should not be necessary for observational studies. 48 39 .05

Where appropriate, community leaders’ approval should be required by U.S. 

IRBs, in addition to individual informed consent. 32 63 <0.001

A mechanism to measure participants’ understanding should be built into any 

research study. 65 83 <0.001

Research funding agencies should provide funding to support the work of 

developing country IRBs. 70 85 <0.001

International guidelines (e.g., CIOMS) should be used instead of U.S. rules 

and regulations. 64 77 .003

A developing country ethical review should be required for all studies. 77 85 0.03

The composition of ERBs used in developing countries should not be dictated 

by U.S. regulations. 83 92 0.004

The SPA requirement should be eliminated. 49 29 <0.001

The issue of what standard of medical care to provide to study participants 

should be decided on a case-by-case basis. 78 77 .8

Some research funds for piloting consent forms should be released before 

final IRB approval is obtained. 61 70 .04

U.S. researchers [international survey: ‘researchers’] should be required to 

make data from research study directly available to study population after Not

study is over. 62 80 calculated

Research to test an intervention should not be carried out in a developing 

country unless the intervention, if found to be successful, will be made 

available to that country at the conclusion of the study. 53 78 <0.001

International policy regarding research should require researchers to establish 

a mechanism for continuing delivery of medical care after completion of 

the study. 27 79 <0.001
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More than half of U.S. researchers and more than three-quarters of international researchers believed that

research to test an intervention should not be carried out in a developing country unless that intervention will

be made available to the host country. International respondents, both in the survey and in focus groups, 

mentioned the need to provide benefits of research to host countries and were often adamant that this should

be required. U.S. researchers, on the other hand, were more tepid in their approach to this issue, due to their

concern about funding difficulties and their opinion that needed and useful research would not take place if

requirements for providing research products became financially overwhelming and that such requirements

should not be their sole responsibility. The survey data regarding interventions show that more than half of

U.S. and almost all international researchers are providing successful interventions to some residents of study

communities, and sometimes to larger groups, at the conclusion of their research projects, but it is not clear

from the survey data what types of interventions are being provided, at what cost, and what the required 

infrastructure might be.

There was less agreement between U.S. and international researchers concerning the provision of medical

care generally after a research protocol has ended; more than three-quarters of international respondents but

only 29 percent of U.S. respondents felt that researchers should be responsible for establishing this ongoing

care. In survey comments, many U.S. researchers remarked that although they supported the principle of providing ongoing benefits to developing countries, funding for continuation of medical care could be problematic. 

In general, the majority of both international and U.S. researchers support significant changes to policies

and ethics guidelines for international collaborative research, with international respondents being even more

likely to advocate for change. The substantial agreement by the more than 500 researchers who participated in

this project on the majority of these recommendations makes these findings particularly notable. The experiences of these researchers, from diverse countries and backgrounds, provide valuable insight into the current

workings of ethics review processes in international collaborative research and point toward constructive

changes in this area.

F. Conclusion

F.1 Limitations of the Study

F.1.1 Sample Issues

This study has two components—the U.S. project and the international project. While we use the general

terms “U.S. researchers” and “international researchers” or “developing country researchers” throughout this

report, it is important to acknowledge that some developing country scientists, of course, are employed by 

U.S. institutions and may have been included in the U.S. sample. Similarly, some U.S. or European nationals

probably were among our international respondents. We are aware that this misclassification exists; however,

we expect that it constitutes only a small minority of the respondents. 

Sampling for both components of the survey was subject to selection bias. Comprehensive lists of researchers

who conduct health-related research in developing countries, unfortunately, do not exist in any country. Hence,

different methods to assemble a respondent pool were utilized for this study that varied in how systematic they

were. For the U.S. survey, the CRISP database was assumed to be a reasonable source of investigators who were

funded by the NIH. While probably a fair assumption, a number of researchers known to the investigators as

NIH grant recipients did not appear on our lists. Also, much international research is conducted through funding sources other than the NIH. Therefore, we began assembling lists of potentially eligible researchers through

U.S. university websites. While this additional strategy yielded many additional respondents, our response rate

decreased considerably, perhaps because our new method was overly inclusive and surveys were sent to many
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researchers who were not eligible but never returned a survey explaining their ineligibility. Further, given that

no lists comparable to the CRISP database exist for the other sectors (U.S. government researchers, U.S. military,

or private industry), we had to rely solely on a few personal contacts within each sector to help us identify 

relevant researchers. The likely result of such convenience sampling in our study is the creation of a pool of

respondents that does not fully represent the universe of U.S.-based researchers who work in developing 

countries. However, it is hoped that the researchers selected through this wide number of sources, contacts,

and sectors reduces the impact of this problem to some extent. 

A major limitation of the U.S. survey is the limited number of responses from researchers within the pharmaceutical industry, despite repeated attempts to include larger numbers. Our sponsor for this project, NBAC,

met several times with leaders from PhARMA, the pharmaceutical industry trade organization, who unfortunately declined participation in the study. We also made several attempts to contact international health

researchers at various U.S.-based pharmaceutical companies to describe our study and evoke interest in participation. While several individual researchers sounded willing to participate, when we approached their public

relations divisions, as was required, we generally were denied access to researchers. Thus, we relied on existing

personal contacts at a handful of companies to help identify individual researchers willing to participate in 

the study. It is perhaps worth noting that this distinction between the researchers and the public relations or

marketing division of pharmaceutical companies was a distinction made by researchers themselves in our focus

groups. That is, pharmaceutical researchers in focus groups described confronting ethics issues that other

researchers had raised—including how to achieve adequate participant understanding; how to determine

appropriate standards of care; and what should be left behind after the study was over—but referred to pressure

from their marketing divisions to conduct research more quickly and/or to engage in procedures that researchers

found troubling.

For the international survey, there similarly were no comprehensive global lists of developing country health

researchers. For the purposes of this survey, the objective was to construct a “reasonable” sample of developing

country researchers. The absence of a sampling frame or defined universe made this issue more challenging. As

a result, the list of respondents was generated de novo for this study from professional organizations, U.S. survey

respondents, and attendees of an international research ethics workshop. Furthermore, only those researchers

who had e-mail contacts were included initially, due to time, economy, and ease of contact. Later, additional

surveys were sent by courier and the U.S. global mail system, and about one-third of the responses were

received in hard copy.

Since we made our survey available on an Internet website, this decision to begin with e-mail contacts 

facilitated reaching potential international respondents who could complete the survey online. Indeed, more

than two-thirds of the 210 surveys were completed via the website. The survey took approximately 30 to 

45 minutes to complete. For many researchers in developing countries, it is expensive to stay online for long

periods, and frequent disconnection is common. This may have discouraged some researchers from completing

the survey, which is obvious from a large number of incomplete responses. Besides the cost of staying online

(relative to the U.S. researchers), other possible impediments to completing the survey included inconvenience/

difficulty in accessing the Internet, type of Web browser being used, low computer memory, or other computer/

technical problems.

Ideally, this study would have been designed by identifying index international collaborative studies and

then surveying both the U.S. and international researchers from the same study. This would have allowed us to

make comparisons between the two samples more directly.
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F.1.2 Survey Instrument Issues

The survey questionnaire consists of 169 closed-ended questions and 2 open-ended questions (see Appendices

B and D). As such there were the generic issues that plague any survey instrument. For example, closed-ended

questions limit the initial choice of answers for each question (although an “other” category is present), because

the respondent is confined to checking off one answer when he/she may prefer to elaborate. 

The survey was based on two major approaches to asking questions in order to elicit the attitudes and opinions of researchers on ethics guidelines: questions seeking their experiences and questions seeking their opinions. Responses based on an index study depend on the specific study that the researcher has selected, which

may or may not be representative of the usual experience of the researcher. However, our premise is that the

more than 200 (developing countries) or 300 (U.S.) responses will result in a wide spectrum of responses that

together will mirror the experiences of researchers in the field. 

As with many studies, we realized that the survey instrument failed to ask certain key questions. For

example, we never asked what benefits researchers actually provided in their studies, despite asking them their

opinions about how much benefit should be provided and whether IRBs questioned the degree of benefit they

were providing. Further, although we asked researchers many questions concerning whether particular issues

were raised by their IRB/ethics boards during study review, we cannot know from the questions we asked

whether a board not raising a particular issue meant that the board did not think of it, or whether the issue had

been adequately addressed by the investigator in the protocol submitted. Nonetheless, despite this limitation,

the fact that certain issues were asked by IRBs more often than others is revealing.

Further, while our researchers’ experiences spanned many countries, diverse research topics, and different

study designs, every situation and country is unique. While we referred to all research in developing countries

as eligible research, the level of development among countries varies widely and does so in ways integrally 

relevant to many of our outcomes of interest. As one of our participants said: 

I would certainly spend a little time defining what type of country. Because I know that Brazil

and Argentina, to me are not third world countries. You go to Burkina Faso, you’re going to

see a third world country. So I think it is going to be difficult to lump them all into one bag as

third world country or underdeveloped or whatever you want to use....So the conditions in

these different places will be important to use existing structure to [categorize] one as nearly

like in the United States, to something that is in the Middle Ages. And that is clearly difficult

to make a policy when you deal with such a diversity of situations. 

F.1.3 Qualitative Data Collection

Seven focus groups were held for the U.S. projects, while six were convened for the international project, of

which two were held in the developing world. Eight additional in-depth interviews were conducted for the

international project in Geneva and Pakistan. Additional groups undoubtedly would have enriched the qualitative

data and enhanced our ability to draw conclusions from it more confidently.

As with all qualitative data, broad comparisons should be made with caution. The data collected here reflect

the thoughts and experiences of those who were purposively sampled and do not a represent a probability-based

sample of investigators. 

The majority of investigators from developing countries were recruited and interviewed in the United States.

These investigators likely vary in their experiences and training from those developing country investigators

who were not accessible to the project. Investigators who have the opportunity to visit, work, or study in the

United States could be inherently different than the investigators who do not share this background. Ideally, all

data collection would have been conducted in developing countries; however, financial and logistical constraints

made this impossible. The majority of in-depth interviews were conducted in one developing country alone.

Findings could be influenced to some extent by the over-sampling of one country. 
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A total of four different Hopkins researchers facilitated the focus groups and conducted in-depth interviews

of the developing country investigators. Each researcher brings his or her own individual perspective and interpretation of data, which potentially elicited varied responses. Greater reliability could have been obtained

through consistency in data collection by using the same interviewer or facilitator. 

The participants in the focus group discussions were less homogenous than that of the U.S. focus groups.

Among developing country investigators, participants may have been entirely unknown to one another, perhaps

restricting the level of comfort for some. Participants from developing countries were associated in varying

capacities with a variety of research institutions and organizations throughout the world. This level of familiarity

could have affected the depth and detail of discussion and the openness of individual participants’ responses.

Furthermore, the topic of discussion and questioning was possibly more pertinent to the U.S. investigators relative to the developing country investigators. This system of ethical review affects virtually every U.S. investigator

whether through their academic institution, funding mechanisms, or employer. By contrast, a developing country

researcher is required to work under the rules and regulations as put forth by his own government and is 

possibly not required on any level to be involved in U.S. regulations regarding research. 

Further, if time had permitted, it would have been helpful to conduct qualitative work again after our quantitative data collection. There were several findings in the quantitative survey that could have been elucidated

through qualitative interviews with researchers, and, indeed, researchers were asked in the survey to indicate

their willingness to complete a follow-up interview, and many agreed. While such follow-up may be done in

the future, it is not included in this report, because of time limitations. 

F.2 Project Recommendations

This study is the first large-scale survey of U.S. and international researchers regarding ethics in international

health research. As such, it can provide some data on researchers’ experiences and opinions regarding informed

consent, obligations during and after a study is conducted, and ethics review and oversight. It is our hope that

this study can begin to fill the void of the lack of data that have been available to support or refute normative

claims regarding how, ethically, international health research should be conducted. We hope this study will

provide data useful to policymakers regarding whether and how current regulations should be modified, where

the educational goals should be directed, and how IRBs and researchers can further their clearly shared goals of

conducting sound scientific research that protects and furthers participants’ welfare and respects them and their

interests. 

Based on our findings, we make the following series of recommendations:

1. Informed consent is central to the research process and is supported by developed and developing country researchers

as a leading principle.

Quantitative and qualitative data from both projects suggest that researchers agreed overwhelmingly that

informed consent is important and necessary in the conduct of research. Researchers described it as important

in and of itself and also as a means to educate participants about the study and raise ethics issues with study

staff.

2. There should be greater flexibility in the means of informing participants about research and in the methods of 

documenting consent in international and collaborative research.

While clearly valuing informed consent, many researchers were frustrated with how narrowly consent requirements have been interpreted by most U.S. IRBs. One researcher suggested as an alternative a “menu of choices”

from which researchers could choose. Others suggested that multiple methods be used in the same study (a

practice employed by many of our respondents) and that all methods should be explained to the IRB, not just
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the written one. Clearly, for our researchers, the goal of informing participants is not negotiable, but the means

for doing so should be flexible. Specifically, written consent should not be required universally, and IRBs

should ask researchers what multiple methods they plan to use and why. Methods of documentation should

range from participant signature (written consent) to researcher or witness signature for oral consent procedures, depending on relevant characteristics of the study population. Methods generally should be sensitive to

cultural norms and levels of literacy in the local community, and researchers in their applications to IRBs/ethics

boards should justify choice of methods.

3. Tests of understanding should be incorporated into research studies.

Respondents to our survey and focus group participants overwhelmingly thought that participant understanding

was the appropriate goal for informed consent procedures. Ultimately, research only can go forward if participants

understand what the research entails. While there was overwhelming support for trying to assess participants’

understanding, most researchers admitted they had never conducted such a test themselves. One reason for

this may be that doing so is difficult; another may be that it is not part of current regulations or guidelines.

Incorporating assessments of participant understanding—whether through a formal quiz or through more

informal questions about key concepts—into guidelines, codes, and IRB applications would increase the likelihood that this procedure would be followed more frequently. Ultimately, regardless of the methods used for

consent, the test of understanding will reveal the success or failure of efforts to communicate the study’s 

procedures, risks, and benefits to the study population.

4. All research studies concerning any topic should be reviewed by an appropriate ethics board if they involve human

subjects, although review should be streamlined based on a study’s level of risk.

There may be cases where reviews are hastened to meet a deadline or a waiver granted after preliminary review

(for secondary data analysis or extremely low-risk studies), but all studies, regardless of topic and method,

need to be reviewed. The notion that studies pertaining to social sciences, especially anthropological sciences,

and those involving qualitative research methods need not be reviewed is inappropriate. Some of the most sensitive issues of human interactions are raised in such studies, and risks arising from breaches of confidentiality,

particularly in certain countries, can literally be life threatening. 

Rather than determine whether review should occur based on a study’s discipline or method, IRBs should

streamline their review based on the level of risk. Riskier studies should have more rigorous and detailed

reviews, more justification from researchers, more thorough consent processes, and a higher threshold of 

participant understanding. 

All studies need to be reviewed, regardless of the source of funding. Donor agencies—private, international,

national, nongovernmental—all are within the purview of ethical reviews. Therefore, bilateral agencies working

within countries fund research, and such studies need to be reviewed as well.

5. Studies involving international collaborations need to be reviewed in both/all countries.

All studies that involve collaborative research must be reviewed in both countries—the United States and the

host country. The United States has certain cultural and legal standards that require certain research practices

or approaches; at the same time, host country boards are expected to be more cognizant of appropriate methods

culturally for informing participants, to be more aware of certain types of risks that would be overlooked by

U.S. boards, and to be more aware of what level of benefit to provide is realistic. 

6. U.S. IRBs should gain greater expertise in the realities of life in a developing country.

Many U.S. researchers expressed frustration with unrealistic requirements raised by their U.S. IRB that, to

them, revealed their IRB’s ignorance about field realities in a developing country. Examples included requiring
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phone numbers, often of U.S. officials, to be included on consent forms, or requiring multiple revisions and

new approvals of a study from host country ethics boards that might not have the resources to copy protocols

for all members, not to mention bring them in from all over the country for another meeting. Having someone

on the U.S. IRB with international experience is helpful, or having, instead, an outside consultant to provide

guidance can begin to address this problem. Moreover, even a short “in-service” training for U.S. IRB members

and staff on how local conditions (from rates of electricity or phone service to cultural or religious norms)

and/or beliefs might affect issues of research review, consent, expectations, or host IRB working conditions

would be helpful.

7. Host country ethics boards should gain additional experience in ethics.

Many U.S. researchers voiced concerns that host country boards had little familiarity with ethics. Thus, when

ethics boards convened, they focused on other issues that felt more comfortable, such as the scientific design or

the budget. Increasing ethics capacity of local boards is mentioned in the CIOMS guidelines as an appropriate

task for researchers to undertake, although we are not suggesting here that this should be the responsibility

solely of researchers. While researchers should consider providing mechanisms for ethics training to their colleagues along with other types of training, funding agencies similarly should devise mechanisms for increasing

ethics capacity in local countries, such that countries are better equipped to determine for themselves how

guidelines are best drafted and interpreted for their setting, or whether studies are providing appropriate levels

of care.

8. Collaborative research studies should be monitored at periodic intervals to ensure that procedures stated in the 

protocol are being carried out as planned. 

While IRBs and collaborating institutions can require certain ethical principles to be upheld in design and 

planning of a research project, if the plans are not carried out as promised, the safety and interests of the study

participants can be compromised. A mechanism must be put in place to ensure that appropriate study procedures actually are followed.

9. Capacity building should be integral to any study.

Research collaborations occur between rich and poor countries, not only because poor countries cannot afford

to finance the studies, but often because there are not enough people in the poorer country who are trained 

in study design and data collection and analysis. It should be the U.S. researcher’s goal to encourage capacity

building during every research collaboration, such that higher and higher proportions of study staff are local

residents. Sometimes this will mean funding graduate training of collaborators; other times it will mean providing

short-term, in-country training on specific topics such as laboratory techniques or consent procedures.

Particular attention should be paid to increasing the developing country researchers’ training and role in substantive tasks, such as data analysis and grant writing. Researchers should conceive of their role as facilitating

host countries’ capacity to eventually conduct most of their research independently and should aim for such

capacity development as one of the most significant benefits a study can provide. 

10.The study population or community must benefit as a consequence of the study, and mechanisms to ensure this must

be discussed and/or developed as part of the study proposal.

Researchers, especially international researchers, overwhelmingly agreed that the study population must benefit

as a consequence of research conducted within that community. They also encouraged the exploration of

mechanisms to ensure that the benefits of research actually reach these people and promoted the inclusion of

such understanding in the early stages of thinking about research. This recommendation emerges from both 

an overarching philosophical stance that can be gleaned from the respondents regarding the conduct of

research in impoverished settings and also a very operational element in their opinions on research planning

and implementation. 
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Researchers believed, however, that consideration of future benefit should not be their responsibility alone.

Innovative mechanisms must be devised for encouraging researchers to engage donors, aid agencies, or service

delivery organizations in discussions about realistic interventions before a study is initiated. Possible mechanisms might include requiring discussion in a grant proposal about prospects for future implementation;

including a professional from a donor agency on study sections for international health research; encouraging

IRBs to incorporate questions related to future access in their review; or offering continuation grants for implementation and infrastructure creation to support research interventions shown to be successful. This does not

necessarily mean that studies cannot go forward without guarantees of future access; however, it does mean

that studies cannot go forward where researchers have given no thought to how realistic future implementation

is and how it could be actualized. While researchers do not need to shoulder this responsibility alone, it still is

not appropriate for funders to support research where no one is taking responsibility for working on future

access to effective health interventions.

Notes

1 According to UNDP, development levels are defined as follows: High human development is greater than .800 HDI, medium is

.500 to .800 HDI, and low is less than .500 HDI. Source: UNDP website, www.undp.org.

2 Federal regulations regarding protection of human subjects in research, 45 CFR 46, are referred to as the Common Rule, and, in

general, are applicable to all research with human subjects that receives U.S. federal government funding. Private companies that do

not receive such funding would not be bound by these regulations, but in cases where clinical data is to be used for drug approval

in the United States, regulations for clinical research set forth by the Food and Drug Administration must be followed.

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Bernard, R.H. Research Methods in Anthropology: Qualitative and Quantitative Approaches. Thousand Oaks, CA: Sage

Publications, 1994.

Commission on Health Research for Development. Essential National Health Research: A Link for Equity in Development. Geneva,

1990.

The Council on Health Research for Development (COHRED). Learning Brief No. 5: Negotiations for National Research: Making

Priorities Matter. Prepared by A.A. Hyder, 2000 (www.cohred.ch). 

Hyder, A.A. Priorities in Health Research and Development: Correcting the 10/90 Disequilibrium (Chapter 3). In The 10/90 Report

on Health Research. Geneva: Global Forum for Health Research, 1999a.

Hyder A.A. The Health and Poverty Interaction: Old Problem, New Perspectives (Chapter 5). In The 10/90 Report on Health

Research. Geneva: Global Forum for Health Research, 1999b.

Lurie, P., and Wolfe, S.M. Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus

in Developing Countries. New England Journal of Medicine 337:853–855, 1997.

Murray, C.J.L., and Lopez, A. The Global Burden of Disease and Injury. Boston, MA: Harvard University Press, 1996.

Porter, L., and Gostin, L. The Application of United States Protection of Human Subjects Regulations and Ethical Principles to

United States Funded or Conducted HIV-Related Research in Foreign Countries. Georgetown University, 1994. Unpublished.

United Nations Development Programme (UNDP). Human Development Report 1999. Human Development and Human Rights.

New York and Oxford: Oxford University Press, 1999 (www.undp.org). 

Wichman, A., Smith, J., Mills, D., and Sandler, A.L. Collaborative Research Involving Human Subjects: A Survey of Researchers

Using International Single Project Assurances. IRB 19:11–6.

World Health Organization (WHO) Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in

Health Research and Development. Geneva, September 1996.
B-157

APPENDIX A

Focus Group Guide

I. Introductions: [Go around the room]

1. What do you do? 

2. What countries have you worked in? For how long?

3. Generally, what types of studies?

II. U.S. Review of Studies

1. Generally, do your studies need to go through an ethics review (IRB or equivalent)?

2. If so, is that at your institution, or elsewhere (where)? Other layers of approval necessary?

3. How well did that process work? How meaningful an ethics review?

4. Substance of review: Were you asked mostly about administrative details or about issues you thought

related to human subjects protections and ethics?

III. In-Country Review of Studies

1. Generally, do your studies need to go through an ethics review in the host country before you start a

study? 

2. If so, how many in-country IRBs or ethics boards did you need to go through? Is ethics review separate

from or combined with scientific review? 

3. Did boards exist or did they need to be established for your study? Because of U.S. requirement or not?

Was composition or procedures of board influenced by U.S. regulations?

4. Generally, how well did process work? How meaningful an ethics review?

5. Substance of review: Were you asked mostly about administrative details or about issues you thought

related to human subjects protections and ethics?

IV. Informed Consent Procedures

1. Did you get/seek informed consent from individual participants? From other individuals (relatives)?

Communities? Others?

2. How was informed consent handled (written, oral, groups)? 

3. How meaningful do you think the informed consent process was?

4. Were you faced with cultural differences in how consent procedures should be implemented? 

4.1 Did U.S. regulations require you to do anything you thought was culturally inappropriate?

5. How foreign is the concept of informed consent:

5.1 How foreign a concept is research?

5.2 Do doctors/providers usually DISCLOSE much about diagnoses, etc., to patients? 

5.3 Do patients usually have CHOICES or MAKE DECISIONS in their own medical care? 
B-158

V. Ethics Issues That Arise

1. What kinds of ethics issues have arisen in your studies?

2. How did you try to resolve them?

3. (Examples:)

3.1 Didn’t think participants understood.

3.2 What intervention to provide to comparison group.

3.3 Providing additional benefits (e.g., more health care) to participants.

VI. After Study Ended

1. Dissemination of intervention after study ended?

2. Interventions you studied ever implemented in country?

3. Was implementation discussed before study was initiated?

VII. Overall Recommendations

1. How should U.S. ethics regulations be modified?

2. Should there be in-country IRBs? 

3. How best to protect vulnerable, poor, uninformed participants?

4. What recommendations would you make?
B-159

APPENDIX B

Survey of U.S. Researchers’ Experiences 

with and Attitudes Towards 

Human Subjects Regulations
Survey of U.S. Researchers’ 

Experiences with 

and Attitudes towards 

Human Subjects Regulations

A survey conducted by the U.S. National Bioethics Advisory Commission

Please direct questions concerning this survey to: 

Nancy E. Kass, Sc.D. Liza Dawson, Ph.D.

(410) 955-0310 or (410) 614-0208

nkass@jhsph.edu usethics@jhsph.edu

Bioethics Institute

Johns Hopkins School of Hygiene and Public Health

624 N. Broadway, Room 351, Baltimore, MD 21205

Public reporting burden for this collection of information is estimated to average 30 minutes per response,

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data

needed, and completing and reviewing the collection of information. An agency may not conduct or sponsor, and

a person is not required to respond to, a collection of information unless it displays a currently valid OMB control

number. Send comments regarding this burden estimate or any other aspect of this collection of information,

including suggestions for reducing this burden, to: NIH, Project Clearance Office, 6701 Rockledge Drive, MSC

7730, Bethesda, MD 20892-7730, ATTN: PRA (0925-0472*). Do not return the completed form to this address. 

OMB no. 0925-0472

Expiration date 9/30/2000

Revised 11-15-99
A Introduction

This survey is designed to collect information from researchers based in the

U.S. (not necessarily of U.S. origin) who have carried out research involving

human subjects in developing countries. If you have not conducted research in

a developing country, please do not complete this survey.

Please Note: In order to receive the $25 payment for completing the 

survey you must fill out every question with a black dot ●.

A1 Are you currently involved in a study in the Yes (Please skip to question A2) . . . . . . . 1 ❍

developing world that requires human subjects? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

A1a If no, have you been involved in a study Within the past five years . . . . . . . . 2 ❍ 

in the developing world that requires More than five years ago . . . . . . . . . . 3 ❍

human subjects: Never (Please do not complete this survey) .1 ❍

If your answer to question A1a. is “never” please 

do not complete this survey. Thank you for your time.

A2 How many years total have you been conducting 

human subjects research in developing countries? __________ Years

A3 How many studies (total) in developing countries 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

have you been involved in? 2 to 4 . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

5 to 10 . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 10 . . . . . . . . . . . . . . . . 4 ❍

A4 In what regions of the developing world have Asia . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

you conducted research? (Check all that apply) Africa . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Pacific Islands . . . . . . . . . . . . . . . . . . 3 ❍

South America . . . . . . . . . . . . . . . . . 4 ❍

Central America/Mexico . . . . . . . . . 5 ❍

Caribbean . . . . . . . . . . . . . . . . . . . . . 6 ❍

Other (Please specify) . . . . . . . . . . . . 7 ❍

A5 During the last year, in what country have you U.S.A. . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

lived most of the time? Country where research 

is conducted . . . . . . . . . . . . . . . . 2 ❍

Another country . . . . . . . . . . . . . . . . 3 ❍

2
3

B Developing Country Research Project

Please think about the developing country study on which you have spent the

most time in the last five years. We will refer to this study as the “index

study”. Please think of this “index study” in answering the following questions:

B1 In what country was/is this study?

B2 To date, how long have you been working Less than 1 year . . . . . . . . . . . . . . . . 1 ❍

on this study? 1 to 2 years . . . . . . . . . . . . . . . . . . . . 2 ❍

2 to 5 years . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 5 years . . . . . . . . . . . . . 4 ❍

B3 Is the study still ongoing (data collection Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

and/or analysis)? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B4 What topic(s) is/was this study investigating? Infectious disease, non-HIV/AIDS . 1 ❍

(Check all that apply) HIV/AIDS . . . . . . . . . . . . . . . . . . . 2 ❍

Chronic disease . . . . . . . . . . . . . . . 3 ❍

Vaccine development/testing . . . . . 4 ❍

Nutrition . . . . . . . . . . . . . . . . . . . . 5 ❍

Cultural practices/behavior . . . . . . . 6 ❍

Injury . . . . . . . . . . . . . . . . . . . . . . . 7 ❍

Genetics . . . . . . . . . . . . . . . . . . . . . 8 ❍

Environmental Health . . . . . . . . . . 9 ❍

Health Systems/Health Services . . . 10 ❍

Reproductive Health . . . . . . . . . . . 11 ❍

Perinatal Health/Birth defects . . . . 12 ❍

Other (Please specify) . . . . . . . . . . . 13 ❍

B5 Which discipline(s) best describes this study? Behavioral science . . . . . . . . . . . . . . 1 ❍

(Check all that apply) Epidemiology . . . . . . . . . . . . . . . . . . 2 ❍

Microbiology . . . . . . . . . . . . . . . . . . 3 ❍

Clinical care . . . . . . . . . . . . . . . . . . . 4 ❍

Health Services research . . . . . . . . . . 5 ❍

Psychology/Mental Health . . . . . . . . 6 ❍

Anthropology . . . . . . . . . . . . . . . . . . 7 ❍

Ethics . . . . . . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . .9 ❍

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
4

B6 Which of the following methodological Randomized controlled trial . . . . . . . 1 ❍

approaches are you using in this study? Observational/descriptive study . . . . 2 ❍

(Please check all that apply) Prospective study . . . . . . . . . . . . . . . 3 ❍

Case-Control . . . . . . . . . . . . . . . . . . 4 ❍

Community-based intervention . . . . 5 ❍

Operational research/

program evaluation . . . . . . . . . . . 6 ❍

Qualitative methods . . . . . . . . . . . . . 7 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . 9 ❍

B7 In your opinion, what level of risk does this Minimal Risk . . . . . . . . . . . . . . . . . . 1 ❍

study involve for participants? Greater than minimal risk . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B8 What is (are) the source(s) of funding for U.S. government (non-military) . . . . 1 ❍

this study? (Please check all that apply) U.S. military . . . . . . . . . . . . . . . . . . . 2 ❍

U.S. private company . . . . . . . . . . . . 3 ❍

U.S. non-profit (foundation, NGO) . 4 ❍

Developing country government . . . 5 ❍

Developing country 

private company . . . . . . . . . . . . . 6 ❍

Developing country non-profit 

(foundation, NGO) . . . . . . . . . . . 7 ❍

European government (non-military) 8 ❍

European military . . . . . . . . . . . . . . . 9 ❍

European private company . . . . . . . .10 ❍

European non-profit 

(foundation, NGO) . . . . . . . . . .11 ❍

Bilateral organization 

(SIDA, USAID, etc.) . . . . . . . . .12 ❍

International organization 

(WHO, PAHO, UNICEF, etc.) .13 ❍

Other (Please specify) . . . . . . . . . . . .14 ❍

B9 Which of the following best describes your Project Coordinator . . . . . . . . . . . . . 1 ❍

role in this study? Co-investigator . . . . . . . . . . . . . . . . . 2 ❍

Principal investigator . . . . . . . . . . . . 3 ❍

Other (Please specify) . . . . . . . . . . . . 4 ❍
B10 Are you or any of your colleagues conversant Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

in a language or dialect of the study participants? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Not applicable . . . . . . . . . . . . . . . . . 9 ❍

B11 Which of the following groups are included in Non-pregnant women . . . . . . . . . . . . 1 ❍

the study? (Please check all that apply) Pregnant women . . . . . . . . . . . . . . . . 2 ❍

Men . . . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Children 1 to 15 . . . . . . . . . . . . . . . . 4 ❍

Infants (younger than 1) . . . . . . . . . . 5 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B12 What is (are) the religious affiliation(s) of Local indigenous religion . . . . . . . . . 1 ❍

study participants? (Please check all that apply) Buddhist . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Muslim . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Hindu . . . . . . . . . . . . . . . . . . . . . . . . 4 ❍

Animist . . . . . . . . . . . . . . . . . . . . . . 5 ❍

Jewish . . . . . . . . . . . . . . . . . . . . . . . . 6 ❍

Christian . . . . . . . . . . . . . . . . . . . . . 7 ❍

None . . . . . . . . . . . . . . . . . . . . . . . . .9 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

Other (Please specify) . . . . . . . . . . 10 ❍

B13 What level of education is predominant in No formal education . . . . . . . . . . . . . 1 ❍

the study population? 1 to 6 years of formal schooling . . . . 2 ❍

6 to 12 years of formal schooling . . . 3 ❍

University educated . . . . . . . . . . . . . .4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . 5 ❍

B14 What percentage of the study population Less than 20% . . . . . . . . . . . . . . . . . 1 ❍

is literate? 20% to 60% . . . . . . . . . . . . . . . . . . . 2 ❍

60 to 90% . . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 90%. . . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B15 On average, each year, how many weeks do 2 weeks or less . . . . . . . . . . . . . . . . . 1 ❍

you spend at the research site of this 2 to 8 weeks . . . . . . . . . . . . . . . . . . . 2 ❍

“index study”? Greater than 8 weeks . . . . . . . . . . . . 3 ❍

5
6

B16 In your opinion, what were the reasons this study was carried out in the host (developing)

country as opposed to in the U.S.? Don’t Not

Yes No know applicable

a Prevalence of disease in question is much 1 ❍ 2 ❍ 8 ❍ 9 ❍

greater in the host developing country 

than in the U.S.

b Intervention being tested more relevant 1 ❍ 2 ❍ 8 ❍ 9 ❍

to host country than to U.S.

c Easier to identify a cohort of patients 1 ❍ 2 ❍ 8 ❍ 9 ❍

relevant to research question (e.g., 

patients without prior treatment history)

d Recruitment of patients more rapid in 1 ❍ 2 ❍ 8 ❍ 9 ❍

host country than in U.S.

e Less expensive to do study in host 1 ❍ 2 ❍ 8 ❍ 9 ❍

developing country than in the U.S.

f Host country researchers asked for U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

collaboration

g Research question relevant to U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

strategic interests in the region

h Marketing approval for drug or device 1 ❍ 2 ❍ 8 ❍ 9 ❍

will be sought in host country

i Interest in addressing global inequalities 

in health 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)

The following questions relate to review by Institutional Review Boards

(IRBs). Institutional Review Boards are formally constituted human subjects

research ethics review boards.

B17 Did your study undergo IRB review in the U.S.? Yes (Please continue) . . . . . . . . . . . . . . 1 ❍

No (Please skip to question B20) . . . . . . 2 ❍

Don’t know (Please skip to question B20) .8 ❍

Not applicable

(Please skip to question B20) . . . . . . . .9 ❍
7

B17a How many U.S. IRBs reviewed your study? One . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

Two . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Three . . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Four . . . . . . . . . . . . . . . . . . . . . . . . . 4 ❍

Five . . . . . . . . . . . . . . . . . . . . . . . . . 5 ❍

Six . . . . . . . . . . . . . . . . . . . . . . . . . . 6 ❍

Greater than 6 . . . . . . . . . . . . . . . . . 7 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B18 Please indicate if any of the following issues were raised by the U.S. IRB(s) in its review of this

index study protocol. Don’t Not

Yes No know applicable

a Relevance of research question to country 

where research is conducted and/or rationale 

for doing study outside the U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Complexity of language on consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Cultural appropriateness of study procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Need for local language consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Need for letters of approval from developing 

country representatives 1 ❍ 2 ❍ 8 ❍ 9 ❍

f Intervention was considered too risky 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Appropriateness of procedures for control group 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Confidentiality protections for participants 

were not adequate 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Participant voluntariness may be compromised 

because of benefits study provides 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Use of placebos 1 ❍ 2 ❍ 8 ❍ 9 ❍

k Availability of intervention (if successful) to 1 ❍ 2 ❍ 8 ❍ 9 ❍

host country after study is over

l Political considerations 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)

m Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)
B19 How long did it take to obtain U.S. IRB Less than 1 month . . . . . . . . . . . . . . 1 ❍

approval for this research? 1 to 2 month . . . . . . . . . . . . . . . . . . 2 ❍

3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

More than 6 months . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

The following questions concern documents which are sometimes required by U.S. federal

regulations. The term Single Project Assurance (SPA) refers to a written document signed

by government officials in the country in which the research is conducted. This document

is intended to assure that an institution collaborating with U.S. researchers agrees to follow

specific ethical review procedures mandated by U.S. federal regulations.

Thinking of the same “index” research project, please answer the following questions.

B20 Did you obtain a Single Project Assurance (SPA) Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

for this project? No (Please skip to question B25) . . . . . . 2 ❍

Don’t know 

(Please skip to question B25) . . . . . . . 8 ❍

Not Applicable 

(Please skip to question B25) . . . . . . . 9 ❍

If you did not obtain an SPA, please skip to question B25.

B21 How long did it take to obtain the SPA? Less than 1 month . . . . . . . . . . . . . . 1 ❍

1 to 2 months. . . . . . . . . . . . . . . . . . 2 ❍

3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 6 months . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B22 Did you encounter resistance on the part of Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

developing country officials to agreeing to No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

an SPA? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . .9 ❍

B23 Did you encounter resistance on the part of Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

developing country officials to U.S. requirements No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

for IRB composition? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

8
B24 Did you consider the SPA process valuable Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

in ensuring that a developing country ethics No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

review was carried out? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

B25 Did this study have a Data Safety and Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

Monitoring Board (DSMB)? No (Please skip to section C) . . . . . . . . . 2 ❍

Don’t know (Please skip to section C) . . 8 ❍

If this study did not have a Data Safety and Monitoring Board, 

please skip to section C.

B26 Were you made aware of results of Never . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

DSMB meetings? Sometimes . . . . . . . . . . . . . . . . . . . . 2 ❍

Always . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . 9 ❍

B27 Did ethics issues arise in DSMB review of the Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

study (e.g., medical care offered to participants)? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

9
C Developing country IRBs and other ethical review

We would like to find out about your experiences with ethical review in

developing countries. The term “developing country IRB” refers to ethics

boards in the country where research is conducted.

C1 Did your study undergo review by the Ministry Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

or Department of Health in the country where No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

the research is/was conducted? Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

Not applicable . . . . . . . . . . . . . . . . . .9 ❍

C2 Did this study undergo some type of ethics review Yes (Please continue) . . . . . . . . . . . . . . 1 ❍

by an IRB, ethics board or Ministry of Health in No (Please skip to section D) . . . . . . . . . 2 ❍

the country where the research is/was conducted? Don’t know (Please skip to section D) . . .8 ❍

Not applicable (Please skip to section D) .9 ❍

C2a In the country where research was conducted, was your study reviewed by the following:

Don’t Not

Yes No know applicable

a. A national IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

b. State/provincial IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

c. Collaborating/local institution 

IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

d. Other in-country ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

(If yes, please specify)

C3a Was any of this developing country ethics review Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

required by U.S. institution/regulations? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . .9 ❍

C3b Required by developing country institution/ Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

regulations? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . .9 ❍

10

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
11

C4 Please indicate if any of the following issues arose during any of the developing country IRB or 

ethics board reviews of this study Don’t Not

Yes No know applicable

a Relevance of research question to country 

where research is conducted and/or 

questioned why research done outside U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Cultural appropriateness of study procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Complexity of language on consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Need for local language consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Need for letters of approval from developing 

country representatives 1 ❍ 2 ❍ 8 ❍ 9 ❍

f Intervention was considered too risky 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Appropriateness of procedures for control group 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Confidentiality protections for participants 

were not adequate 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Participant voluntariness may be compromised 

because of benefits provided through study 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Use of placebos 1 ❍ 2 ❍ 8 ❍ 9 ❍

k Availability of intervention (if successful) to 

host country after study is over. 1 ❍ 2 ❍ 8 ❍ 9 ❍

l Political considerations 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

m Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

C5 How long did it take to obtain all developing Less than 1 month . . . . . . . . . . . . . . 1 ❍

country ethics board or IRB approval for 1 to 2 months . . . . . . . . . . . . . . . . . . 2 ❍

this research? 3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

More than 6 months . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

C6 For this index study, was one or more developing Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

country IRB or ethics boards established because No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

of the US requirements? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable. . . . . . . . . . . . . . . . . 9 ❍
12

D Consent

Thinking of the same “index” research study, please answer the following

questions about the informed consent process.

D1 Which of the following methods of informing participants and/or documenting consent did you 

use for this research project? (Please check all that apply)

Don’t Not

Yes No know applicable

a Written informed consent, requiring a 

signature, thumbprint, or equivalent 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Pictorial descriptions of study or study 

procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Oral consent with a witness signature 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Community meeting to describe the study 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Approval from a village or community 

leader 1 ❍ 2 ❍ 8 ❍ 9 ❍

f In research with adults, approval or 

consent from another family member 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Explanation and question and answer 

session with participants (either individually 

or in groups) 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Video to explain study 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Test of participant understanding of 

research before enrollment 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Other methods 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
Thinking of the same “index” study, please indicate if the following statements

apply. (Please check one response for each statement)

Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

D2 The informed consent process 

is focused too much on the 

individual rather than on the 

family and/or community. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D3 Participants often do not understand the concept of a placebo. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D4 Study participants are usually aware 

that they are in a research study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D5 The consent process is an 

important means of educating 

participants about the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D6 The consent process provides an 

opportunity to discuss ethics issues 

with field staff. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D7 After learning about the study, 

some potential participants 

declined enrollment. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D8 The formality of going through 

the informed consent process 

raises distrust in study participants. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D9 Local staff shortened or simplified 

the consent procedures compared 

to the original protocol. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D10 Legalistic language was required 

on consent forms which was not 

meaningful to study participants. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

13
14

E Relationship with developing country

Thinking again about the “index” study, please respond to the following

statements about developing country involvement in your project.

E1 Developing country researchers were/are included in the following research tasks:

(Please check one response for each statement)

Don’t Not

Yes No know applicable

a initial study design 1 ❍ 2 ❍ 8 ❍ 9 ❍

b grant writing 1 ❍ 2 ❍ 8 ❍ 9 ❍

c changes in study design 1 ❍ 2 ❍ 8 ❍ 9 ❍

d recruitment of participants 1 ❍ 2 ❍ 8 ❍ 9 ❍

e drafting consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

f consent discussions with participants 1 ❍ 2 ❍ 8 ❍ 9 ❍

g training of research personnel 1 ❍ 2 ❍ 8 ❍ 9 ❍

h drafting manuscripts 1 ❍ 2 ❍ 8 ❍ 9 ❍

i data analysis 1 ❍ 2 ❍ 8 ❍ 9 ❍

j listed as authors on papers 1 ❍ 2 ❍ 8 ❍ 9 ❍

E2 Will some of the resources or research infra- Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

structure established for this study remain in the No (Skip to question E3) . . . . . . . . . . . . 2 ❍

developing country after study has ended? Don’t know (Skip to question E3) . . . . . 8 ❍

Not Applicable (Skip to question E3) . . 9 ❍

E2a If E2 answer is “Yes”, please check all that apply

Don’t Not

Yes No know applicable

a. Personnel who were trained or who 

acquired skills on this research project 1 ❍ 2 ❍ 8 ❍ 9 ❍

b. Medical, laboratory, or office equipment 1 ❍ 2 ❍ 8 ❍ 9 ❍

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
Don’t Not

Yes No know applicable

c. Medical, laboratory, office, or 

pharmaceutical supplies 1 ❍ 2 ❍ 8 ❍ 9 ❍

d. Computers or data management system 1 ❍ 2 ❍ 8 ❍ 9 ❍

e. Buildings, laboratory facilities or renovations 1 ❍ 2 ❍ 8 ❍ 9 ❍

f. Power generating equipment, water system, 

or motor vehicles 1 ❍ 2 ❍ 8 ❍ 9 ❍

g. Organizational structure for health care 

or research 1 ❍ 2 ❍ 8 ❍ 9 ❍

h. Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)

E3 Is this index study an intervention study? Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

No (Skip to section F) . . . . . . . . . . . . . 2 ❍

Don’t know (Skip to section F) . . . . . . . 8 ❍

Not Applicable (Skip to section F) . . . . 9 ❍

E4 Has the study shown the intervention to be Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

efficacious? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

No (Skip to section F) . . . . . . . . . . . . . . 2 ❍

Not Applicable (Skip to section F) . . . . 9 ❍

E5 Was the intervention provided, OR will it be Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

provided, if successful, to study participants No (Skip to section F) . . . . . . . . . . . . . . 2 ❍

or to any other host country residents at the Don’t know (Skip to section F) . . . . . . . 8 ❍

conclusion of the study? Not Applicable (Skip to section F) . . . . 9 ❍

E6 To whom was (or will) the intervention be Placebo or control group of study . . . 1 ❍

provided? Entire study population . . . . . . . . . . .2 ❍

Community from which 

the study population comes . . . . .3 ❍

Certain regions of host country . . . . .4 ❍

Entire host country . . . . . . . . . . . . . .5 ❍

Other (Please specify) . . . . . . . . . . . . .6 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

15
E7 What parties were (or will be) part of the U.S. research team 

arrangement to provide the intervention? carrying out this study . . . . . . . . . 1 ❍

(Please check all that apply) U.S. institution 

carrying out this study . . . . . . . . ..2 ❍

U.S. funding agency for this study . . .3 ❍

International agency 

(e.g. WHO, UNICEF) . . . . . . . . .4 ❍

Host country research team . . . . . . . .5 ❍

Host country government, 

including Ministry of Health . . . . 6 ❍

Host country institution 

(e.g. university, NGO, 

clinical center) . . . . . . . . . . . . . . 7 ❍

Private for-profit company . . . . . . . . .9 ❍

Private foundation . . . . . . . . . . . . . .10 ❍

Other (Please specify) . . . . . . . . . . . 11 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

E8 How long was (or will) the intervention be Less than one year . . . . . . . . . . . . . . 1 ❍

provided? Two to five years . . . . . . . . . . . . . . . . 2 ❍

Greater than 5 years . . . . . . . . . . . . . 3 ❍

Other (Please specify) . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

E9 How was (or will) the intervention be paid for? By research grant for this study . . . . . 1 ❍

(Please check all that apply) By U.S. institution 

carrying out this study . . . . . . . . .2 ❍

By U.S. funding agency 

for this study . . . . . . . . . . . . . . . . 3 ❍

By international agency . . . . . . . . . . 4 ❍

By host country government . . . . . . . 5 ❍

By host country institution . . . . . . . . 6 ❍

By private for-profit company . . . . . . 7 ❍

By private foundation . . . . . . . . . . . . 9 ❍

Other (Please specify) . . . . . . . . . . . 10 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

16
F Ethical issues in international research

The following statements have been made by some researchers in discussing

research in developing countries. Thinking of the “index” study, please indicate

whether you think these statements are True, Sometimes True, or False.

Sometimes Don’t Not

True True False know applicable

F1 Medical care provided to participants in 

this study generally is not available to 

local population outside the study. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F2 Study gathered potentially sensitive or 

stigmatizing information about participants 

(e.g., HIV+ status; domestic violence). 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F3 Study participants have unrealistic hopes 

about personal benefit from study participation (e.g. think their disease will be cured). 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F4 The standard of medical care in the host 

country may be much lower than that of 

funding country, creating difficulties in 

establishing appropriate procedures for 

the control group. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F5 Participants join because of the desire for 

compensation, medical care or other 

benefits. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F6 Research priorities of the outside agency 

that is funding the study are not congruent 

with top priorities of developing country. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F7 Treatment or intervention being tested 

is unlikely to be available to most 

citizens of developing country in the 

foreseeable future. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

17

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
Sometimes Don’t Not

True True False know applicable

F8 There is inadequate true community 

representation on the local IRBs /ethics 

boards for this study. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F9 Religious beliefs and/or cultural norms of 

study population are inconsistent with the 

practice of individual decision-making. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F10 Ethics issues are rarely discussed with field 

staff on this research project. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

18
G. U.S. and international human subjects

regulations and guidelines

These are general statements about U.S. regulations and about ethical review

in developing country research. Thinking of all the developing country

projects you have worked on, not just the “index case,” please answer the

following questions about ethics regulations and guidelines.

Some- Don’t Not

Never times Always know applicable

G1 U.S. human subjects regulations are 

flexible where they need to be. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G2 Developing country collaborators rely 

on U.S. ethics regulations for guidance. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G3 U.S. IRBs are more concerned with 

politics than they are with protecting 

the interests of research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G4 The current U.S. rules and regulations 

governing human subjects ensure high 

ethical standards in research. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G5 U.S. IRB regulations are insensitive to 

local cultural norms and traditions 

outside the U.S. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G6 Developing country IRBs are more 

concerned with politics than they 

are with protecting the interests of 

research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G7 Developing country IRBs have voiced 

concerns to me about the costs 

associated with the IRB carrying out 

its work. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G8 National guidelines in developing 

countries are effective in protecting 

research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

19

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
Don’t Not

Yes No know applicable

GA1 Have you ever had to abandon a research project 

because it was impossible to get U.S. IRB approval 

despite modifications? 1 ❍ 2 ❍ 8 ❍ 9 ❍

GA2 Have you ever had to abandon a research project 

because it was impossible to obtain an SPA? 1 ❍ 2 ❍ 8 ❍ 9 ❍

GA3 Have you ever had to abandon a research project

because it was impossible to get developing country 

IRB approval despite modifications? 1 ❍ 2 ❍ 8 ❍ 9 ❍

20
H Recommendations

Please indicate if you agree with any of the following statements. Also, feel free

to elaborate on these or any other questions in the final section of the survey.

Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

H1 U.S. regulations should allow 

more flexibility in ways of 

documenting informed consent 

(e.g. non-written methods). 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H2 Formal individual consent 

should not be necessary for 

observational studies. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H3 Where appropriate, community 

leaders’ approval should be required by U.S. IRBs, in addition 

to individual informed consent. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H4 A mechanism to measure participants’ understanding should 

be built into any research study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H5 Research funding agencies 

should provide funding to 

support the work of developing 

country IRBs. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H6 International guidelines (e.g., 

CIOMS) should be used instead 

of U.S. rules and regulations. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H7 A developing country ethical 

review should be required for 

all studies. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H8 The composition of ethics review 

boards used in developing 

countries should not be 

dictated by U.S. regulations. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H9 The single project assurance 

(SPA) requirement should 

be eliminated. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

21

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

H10 The issue of what standard of 

medical care to provide to study 

participants should be decided 

on a case-by-case basis. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H11 Some research funds for piloting 

consent forms should be 

released before final IRB 

approval is obtained. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H12 U.S. researchers should be 

required to make data from 

research study directly available 

to study population after study 

is over. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H13 Research to test an intervention 

should not be carried out in a 

developing country unless the 

intervention, if found to be successful, will be made available 

to that country at the conclusion 

of the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H14 International policy regarding 

research should require 

researchers to establish a 

mechanism for continuing 

delivery of medical care after 

completion of the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

22
J Finally, please give us more information

about yourself

J1 Gender: Female . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

Male . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

J2 Age: ______________ Years

J3 Degree(s) (Please check all that apply): MD, DDS, MBBS, MBChB . . . . . . . 1 ❍

Ph.D., ScD., DrPH, or PharmD . . . . 2 ❍

RN, CNP, CNM, LPN, NP . . . . . . . . 3 ❍

MPH, MS, MA, MHS . . . . . . . . . . . 4 ❍

BS or BA . . . . . . . . . . . . . . . . . . . . . 5 ❍

Other (Please specify) . . . . . . . . . . . . 6 ❍

J4 What type of institution is your primary employer? University . . . . . . . . . . . . . . . . . . . . . 1 ❍

Government agency (non-military) . 2 ❍

Military . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Private for-profit research 

institute/organization . . . . . . . . . 4 ❍

Private non-profit research 

institute/organization . . . . . . . . . . 5 ❍

Pharmaceutical/biotech . . . . . . . . . . 6 ❍

Independent consultant . . . . . . . . . . 7 ❍

Other (Please specify) . . . . . . . . . . . 8 ❍

J5 Where is your primary employer located U.S. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

(headquarters)? Other industrialized country. . . . . . . 2 ❍

Developing country . . . . . . . . . . . . . 3 ❍

J6 What percentage of your work is spent on 

research as compared with teaching, clinical care,

administration, or other work? ______________ % 

23

Please Note:

In order to receive the $25 payment for completing the survey you must 

fill out every question with a black dot ●.
J7 Are you, or have you been in the past, a member Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

of an Institutional Review Board? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

J7a Have you ever resided in a developing nation for Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

6 months or more at a time? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

J8 Please elaborate on any of the questions that you feel require more detailed responses.

J9 Please describe changes that you would make to the existing U.S. policy and regulations 

regarding human subjects research in developing countries.

24
J10 Would you be willing to participate in a half hour in-depth interview with one of our project

team to discuss these issues? Transcripts of interviews will not contain your name or institution,

and specific place names will be replaced with region names where necessary, to protect your

confidentiality.

❍ Yes

❍ No

Please provide us with a mailing address on the last page of this booklet, where we may send

you a $25 check for completing the survey. Any contact information you give us will be

separated from the completed survey, so that your survey responses will remain confidential.

Thank you for your participation

25
K Contact Information

Please provide us with a mailing address where we may send you a $25 check

for completing the survey. Any contact information you give us will be

separated from the completed survey, so that your survey responses will

remain confidential.

Name ____________________________________________________________

Address ____________________________________________________________

City ____________________________________________ State ____________

Zip/Country Code __________________________________________________

Country____________________________________________________________

26
B-187

Demographically Developing

Countries:

China

India

Other Asia and Islands (OAI):

American Samoa

Bangladesh

Bhutan

Brunei Darussalam

Cambodia

Cook Islands

Fiji

French Polynesia

Guam

Indonesia

Johnston Island

Kiribati

Korea, Democratic People’s

Republic of

Korea, Republic of

Lao, People’s Democratic

Republic

Macao

Malaysia

Maldives

Marshall Islands

Mauritius

Micronesia, Federated States of

Midway Island

Mongolia

Myanmar

Nauru

Nepal

New Caledonia

Niue

Northern Mariana Islands

Palau

Papua New Guinea

Philippines

Pitcairn Island

Reunion

Seychelles

Singapore

Solomon Islands

Sri Lanka

Taiwan, China

Thailand

Tokelau Island

Tonga

Tuvalu

Vanuatu

Viet Nam

Wake Island

Wallis and Futuna Islands

Western Samoa

Sub-Saharan Africa (SSA):

Angola

Ascension

Benin

Botswana

Burkina Faso

Burundi

Cameroon

Cape Verde

Central African Republic

Chad

Comoros

Congo

CÔte d’Ivoire

Djibouti

Equatorial Guinea

Eritrea

Ethiopia

Gabon

Gambia, The

Ghana

Guinea

Guinea-Bissau

Kenya

Lesotho

Liberia

Madagascar

Malawi

Mali

Mauritania

Mayotte

Mozambique

Namibia

Niger

Nigeria

Rwanda

Saint Helena

Sao Tome and Principe

Senegal

Sierra Leone

Somalia

South Africa

Sudan

Swaziland

Tanzania, United Republic of

Togo

Tristan de Cunha

Uganda

Zaire

Zambia

Zimbabwe

Latin America and the

Caribbean (LAC):

Anguila

Antigua and Barbuda

Argentina

Aruba

Bahamas, The

Barbados

Belize

Bolivia

Brazil

British Virgin Island 

Cayman Islands

Chile

Colombia

Costa Rica

APPENDIX C
B-188

Cuba

Dominica

Dominican Republic

Ecuador

El Salvador

Falkland/Malvinas Islands

French Guiana

Grenada

Guadeloupe

Guatemala

Guyana

Haiti

Honduras

Jamaica

Martinique

Mexico

Montserrat

Netherlands Antilles

Nicaragua

Panama

Paraguay

Peru

Puerto Rico

Saint Kitts and Nevis

Saint Lucia

Saint Vincent and the Grenadines

Suriname

Trinidad and Tobago

Turks and Calcos Islands

Uruguay

U.S. Virgin Islands

Venezuela

Middle Eastern Crescent

(MEC):

Afghanistan

Algeria

Armenia

Azerbaijan

Bahrain

Cyprus

Egypt

Former Spanish Sahara

Georgie

Iran, Islamic Republic of

Iraq

Israel

Jordan

Kazakhstan

Kuwait

Kyrgyzstan

Lebanon 

Libyan Arab Jamahiriya

Malta

Morocco

Oman

Pakistan

Qatar

Saudi Arabia

Syrian Arab Republic

Tajikstan

Tunisia

Turkey

Turkmenistan

United Arab Emirates

Uzbekistan

West Bank and Gaza

Yemen

Source:

WHO Ad Hoc Committee on Health

Research Relating to Future Intervention

Options. Investing in Health Research and

Development. World Health Organization,

Geneva, Switzerland, September 1996.
B-189

APPENDIX D

Survey of Developing Country 

Researchers’ Experiences with 

and Attitudes Towards 

Human Subjects Regulations
Survey of Developing Country

Researchers’ Experiences with 

and Attitudes towards 

Human Subjects Regulations

A survey conducted by the U.S. National Bioethics Advisory Commission

by

Adnan A. Hyder, MD, MPH, PhD

Department of International Health

The Johns Hopkins University School of Hygiene and Public Health

Baltimore, MD, USA

ethics@jhsph.edu

Please direct questions concerning this survey to Dr. A Hyder

Public reporting burden for this collection of information is estimated to average 30 minutes per response,

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data

needed, and completing and reviewing the collection of information. An agency may not conduct or sponsor, and

a person is not required to respond to, a collection of information unless it displays a currently valid OMB control

number. Send comments regarding this burden estimate or any other aspect of this collection of information,

including suggestions for reducing this burden, to: NIH, Project Clearance Office, 6701 Rockledge Drive, MSC

7730, Bethesda, MD 20892-7730, ATTN: PRA (0925-0472*). Do not return the completed form to this address. 

OMB no. 0925-0472

Expiration date 9/30/2002

ID Code No. _____________
A Introduction

This survey is designed to collect information from researchers who have

carried out research involving human subjects in developing countries. If you

have not conducted research in a developing country, please do not complete

this survey.

A1 Are you currently involved in a study in the Yes (Please skip to question A2) . . . . . . . 1 ❍

developing world that requires human subjects? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

A1a If no, have you been involved in a study Within the past five years . . . . . . . . 2 ❍ 

in the developing world that requires More than five years ago . . . . . . . . . . 3 ❍

human subjects: Never (Please do not complete this survey) .1 ❍

If your answer to question A1a. is “never” please 

do not complete this survey. Thank you for your time.

A2 How many years total have you been conducting 

human subjects research in developing countries? __________ Years

A3 How many studies (total) in developing countries 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

have you been involved in? 2 to 4 . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

5 to 10 . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 10 . . . . . . . . . . . . . . . . 4 ❍

A4 In what regions of the developing world have Asia . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

you conducted research? (Check all that apply) Africa . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Pacific Islands . . . . . . . . . . . . . . . . . . 3 ❍

South America . . . . . . . . . . . . . . . . . 4 ❍

Central America/Mexico . . . . . . . . . 5 ❍

Caribbean . . . . . . . . . . . . . . . . . . . . . 6 ❍

Other (Please specify) . . . . . . . . . . . . 7 ❍

A5 During the last year, in what country have you

lived most of the time? 

2
3

B Developing Country Research Project

We would like to find out about your experience with a developing country

research study on which are currently working or have worked in the last five

years. If you conducted human subjects research more than five years ago,

please proceed to Section G (skip Sections C, D, E & F)

B0 In the last five years, have you either collaborated with U.S. investigators on a research project, 

OR received U.S. funds directly for your research?

Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍ No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

If “Yes,” thinking of a project which has If “No,” please consider the project on 

involved either direct U.S. funding or which you have spent the most time 

U.S. collaboration, please answer the fol- during the last five years, and respond to 

lowing questions about the study. We will the following questions. We will refer to 

refer to this study as the “index study.” this study as the “index study.”

B1 In what country was/is this study?

B2 To date, how long have you been working Less than 1 year . . . . . . . . . . . . . . . . 1 ❍

on this study? 1 to 2 years . . . . . . . . . . . . . . . . . . . . 2 ❍

2 to 5 years . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 5 years . . . . . . . . . . . . . 4 ❍

B3 Is the study still ongoing (data collection Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

and/or analysis)? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B4 What topic(s) is/was this study investigating? Infectious disease, non-HIV/AIDS . 1 ❍

(Check all that apply) HIV/AIDS . . . . . . . . . . . . . . . . . . . 2 ❍

Chronic disease . . . . . . . . . . . . . . . 3 ❍

Vaccine development/testing . . . . . 4 ❍

Nutrition . . . . . . . . . . . . . . . . . . . . 5 ❍

Cultural practices/behavior . . . . . . . 6 ❍

Injury . . . . . . . . . . . . . . . . . . . . . . . 7 ❍

Genetics . . . . . . . . . . . . . . . . . . . . . 8 ❍

Environmental Health . . . . . . . . . . 9 ❍

Health Systems/Health Services . . . 10 ❍

Reproductive Health . . . . . . . . . . . 11 ❍

Perinatal Health/Birth defects . . . . 12 ❍

Other (Please specify) . . . . . . . . . . . 13 ❍
4

B5 Which discipline(s) best describes this study? Behavioral science . . . . . . . . . . . . . . 1 ❍

(Check all that apply) Epidemiology . . . . . . . . . . . . . . . . . . 2 ❍

Microbiology . . . . . . . . . . . . . . . . . . 3 ❍

Clinical care . . . . . . . . . . . . . . . . . . . 4 ❍

Health Services research . . . . . . . . . . 5 ❍

Psychology/Mental Health . . . . . . . . 6 ❍

Anthropology . . . . . . . . . . . . . . . . . . 7 ❍

Ethics . . . . . . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . .9 ❍

B6 Which of the following methodological Randomized controlled trial . . . . . . . 1 ❍

approaches are you using in this study? Observational/descriptive study . . . . 2 ❍

(Please check all that apply) Prospective study . . . . . . . . . . . . . . . 3 ❍

Case-Control . . . . . . . . . . . . . . . . . . 4 ❍

Community-based intervention . . . . 5 ❍

Operational research/

program evaluation . . . . . . . . . . . 6 ❍

Qualitative methods . . . . . . . . . . . . . 7 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . 9 ❍

B7 In your opinion, what level of risk does this Minimal Risk . . . . . . . . . . . . . . . . . . 1 ❍

study involve for participants? Greater than minimal risk . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B8 What is (are) the source(s) of funding for U.S. government (non-military) . . . . 1 ❍

this study? (Please check all that apply) U.S. military . . . . . . . . . . . . . . . . . . . 2 ❍

U.S. private company . . . . . . . . . . . . 3 ❍

U.S. non-profit (foundation, NGO) . 4 ❍

Developing country government . . . 5 ❍

Developing country 

private company . . . . . . . . . . . . . 6 ❍

Developing country non-profit 

(foundation, NGO) . . . . . . . . . . . 7 ❍

European government (non-military) 8 ❍

European military . . . . . . . . . . . . . . . 9 ❍

European private company . . . . . . . .10 ❍

European non-profit 

(foundation, NGO) . . . . . . . . . .11 ❍

Bilateral organization 

(SIDA, USAID, etc.) . . . . . . . . .12 ❍

International organization 

(WHO, PAHO, UNICEF, etc.) .13 ❍

Other (Please specify) . . . . . . . . . . . .14 ❍
B9 Which of the following best describes your Project Coordinator . . . . . . . . . . . . . 1 ❍

role in this study? Co-investigator . . . . . . . . . . . . . . . . . 2 ❍

Principal investigator . . . . . . . . . . . . 3 ❍

Other (Please specify) . . . . . . . . . . . . 4 ❍

B10 Are you or any of your colleagues conversant Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

in a language or dialect of the study participants? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Not applicable . . . . . . . . . . . . . . . . . 9 ❍

B11 Which of the following groups are included in Non-pregnant women . . . . . . . . . . . . 1 ❍

the study? (Please check all that apply) Pregnant women . . . . . . . . . . . . . . . . 2 ❍

Men . . . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Children 1 to 15 . . . . . . . . . . . . . . . . 4 ❍

Infants (younger than 1) . . . . . . . . . . 5 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B12 What is (are) the religious affiliation(s) of Local indigenous religion . . . . . . . . . 1 ❍

study participants? (Please check all that apply) Buddhist . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Muslim . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Hindu . . . . . . . . . . . . . . . . . . . . . . . . 4 ❍

Animist . . . . . . . . . . . . . . . . . . . . . . 5 ❍

Jewish . . . . . . . . . . . . . . . . . . . . . . . . 6 ❍

Christian . . . . . . . . . . . . . . . . . . . . . 7 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

v None . . . . . . . . . . . . . . . . . . . . . . . . .9 ❍

Other (Please specify) . . . . . . . . . . 10 ❍

B13 What level of education is predominant in No formal education . . . . . . . . . . . . . 1 ❍

the study population? 1 to 6 years of formal schooling . . . . 2 ❍

6 to 12 years of formal schooling . . . 3 ❍

University educated . . . . . . . . . . . . . .4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Other (Please specify) . . . . . . . . . . . . 5 ❍

B14 What percentage of the study population Less than 20% . . . . . . . . . . . . . . . . . 1 ❍

is literate? 20% to 60% . . . . . . . . . . . . . . . . . . . 2 ❍

60 to 90% . . . . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 90%. . . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

5
6

B15a On average, each year, how many weeks do 2 weeks or less . . . . . . . . . . . . . . . . . 1 ❍

you spend at the research site of this 2 to 8 weeks . . . . . . . . . . . . . . . . . . . 2 ❍

“index study”? 2 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

More than 6 months . . . . . . . . . . . . . 4 ❍

If the study you are describing received U.S. funds, either directly or 

through collaboration, please continue. If not, please skip to section C.

B16 In your opinion, what were the reasons this study was carried out in the host (developing)

country as opposed to in the U.S.? Don’t Not

Yes No know applicable

a Prevalence of disease in question is much 1 ❍ 2 ❍ 8 ❍ 9 ❍

greater in the host developing country 

than in the U.S.

b Intervention being tested more relevant 1 ❍ 2 ❍ 8 ❍ 9 ❍

to host country than to U.S.

c Easier to identify a cohort of patients 1 ❍ 2 ❍ 8 ❍ 9 ❍

relevant to research question (e.g., 

patients without prior treatment history)

d Recruitment of patients more rapid in 1 ❍ 2 ❍ 8 ❍ 9 ❍

host country than in U.S.

e Less expensive to do study in host 1 ❍ 2 ❍ 8 ❍ 9 ❍

developing country than in the U.S.

f Host country researchers asked for U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

collaboration

g Research question relevant to U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

strategic interests in the region

h Marketing approval for drug or device 1 ❍ 2 ❍ 8 ❍ 9 ❍

will be sought in host country

i Interest in addressing global inequalities 

in health 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)
7

The following questions relate to review by Institutional Review Boards

(IRBs). Institutional Review Boards are formally constituted human subjects

research ethics review boards.

B17 Did your study undergo U.S. IRB review? Yes (Please continue) . . . . . . . . . . . . . . 1 ❍

No (Please skip to question B20) . . . . . . 2 ❍

Don’t know (Please skip to question B20) .8 ❍

Not applicable

(Please skip to question B20) . . . . . . . .9 ❍

B17b Are you familiar with or have knowledge of the Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

U.S. review process for this study? No (Please skip to section C) . . . . . . . . . 2 ❍

If you are familiar with the U.S. IRB review process for this 

study, please continue. If not, please skip to section C.

B18 Please indicate if any of the following issues were raised by the U.S. IRB in its review of this

index study protocol. Don’t Not

Yes No know applicable

a Relevance of research question to country 

where research is conducted and/or rationale 

for doing study outside the U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Cultural appropriateness of study procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Complexity of language on consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Need for local language consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Need for letters of approval from developing 

country representatives 1 ❍ 2 ❍ 8 ❍ 9 ❍

f Intervention was considered too risky 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Appropriateness of procedures for control group 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Confidentiality protections for participants 

were not adequate 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Participant voluntariness may be compromised 

because of benefits study provides 1 ❍ 2 ❍ 8 ❍ 9 ❍
Don’t Not

Yes No know applicable

j Use of placebos 1 ❍ 2 ❍ 8 ❍ 9 ❍

k Availability of intervention (if successful) to 1 ❍ 2 ❍ 8 ❍ 9 ❍

host country after study is over

l Political considerations 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

m Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)

B19 How long did it take to obtain U.S. IRB Less than 1 month . . . . . . . . . . . . . . 1 ❍

approval for this research? 1 to 2 month . . . . . . . . . . . . . . . . . . 2 ❍

3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

More than 6 months . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

B20–24. The following questions concern documents which are sometimes required by

U.S. federal regulations. The term Single Project Assurance (SPA) refers to a

written document signed by government officials in the country in which the

research is conducted. This document is intended to assure that an institution

collaborating with U.S. researchers agrees to follow specific ethical review

procedures mandated by U.S. federal regulations.

Thinking of the same “index” research project, please answer the following questions.

B20 Did you obtain a Single Project Assurance (SPA) Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

for this project? No (Please skip to question B25) . . . . . . 2 ❍

Don’t know 

(Please skip to question B25) . . . . . . . 8 ❍

Not Applicable 

(Please skip to question B25) . . . . . . . 9 ❍

If you did not obtain an SPA, please skip to question B25.

8
B21 How long did it take to obtain the SPA? Less than 1 month . . . . . . . . . . . . . . 1 ❍

1 to 2 months. . . . . . . . . . . . . . . . . . 2 ❍

3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

Greater than 6 months . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

B22 Did you encounter resistance on the part of Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

developing country officials to agreeing to No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

an SPA? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . .9 ❍

B23 Did you encounter resistance on the part of Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

developing country officials to U.S. requirements No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

for IRB composition? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

B24 Did you consider the SPA process valuable Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

in ensuring that a developing country ethics No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

review was carried out? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

B25 Did this study have a Data Safety and Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

Monitoring Board (DSMB)? No (Please skip to section C) . . . . . . . . . 2 ❍

Don’t know (Please skip to section C) . . 8 ❍

If this study did not have a Data Safety and Monitoring Board, 

please skip to section C.

B26 Were you made aware of results of Never . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

DSMB meetings? Sometimes . . . . . . . . . . . . . . . . . . . . 2 ❍

Always . . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . 9 ❍

B27 Did ethics issues arise in DSMB review of the Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

study (e.g., medical care offered to participants)? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable . . . . . . . . . . . . . . . . . 9 ❍

9
C Developing country IRBs and other ethical review

We would like to find out about your experiences with ethical review in

developing countries. The term “developing country IRB” refers to ethics

boards in the country where research is conducted.

C1 Did your study undergo review by the Ministry Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

or Department of Health in the country where No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

the research is/was conducted?

C2 Did this study undergo some type of ethics review Yes (Please continue) . . . . . . . . . . . . . . 1 ❍

by an IRB, ethics board or Ministry of Health in No (Please skip to section D) . . . . . . . . . 2 ❍

the country where the research is/was conducted? Don’t know (Please skip to section D) . . .8 ❍

Not applicable (Please skip to section D) .9 ❍

C2a In the country where research was conducted, was your study reviewed by the following:

Don’t Not

Yes No know applicable

a. A national IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

b. State/provincial IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

c. Collaborating/local institution 

IRB/ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

d. Other in-country ethics review board 1 ❍ 2 ❍ 8 ❍ 9 ❍

(If yes, please specify)

C3-1 Was any of this developing country ethics review Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

required by U.S. institutions/regulations? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . .9 ❍

C3-2 Required by developing country institutions/ Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

regulations? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not applicable . . . . . . . . . . . . . . . . . .9 ❍

10
11

C4 Please indicate if any of the following issues arose during any of the developing country IRB or 

ethics board reviews of this study Don’t Not

Yes No know applicable

a Relevance of research question to country 

where research is conducted and/or 

questioned why research done outside U.S. 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Cultural appropriateness of study procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Complexity of language on consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Need for local language consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Need for letters of approval from developing 

country representatives 1 ❍ 2 ❍ 8 ❍ 9 ❍

f Intervention was considered too risky 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Appropriateness of procedures for control group 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Confidentiality protections for participants 

were not adequate 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Participant voluntariness may be compromised 

because of benefits provided through study 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Use of placebos 1 ❍ 2 ❍ 8 ❍ 9 ❍

k Availability of intervention (if successful) to 

host country after study is over. 1 ❍ 2 ❍ 8 ❍ 9 ❍

l Political considerations 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

m Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)

C5 How long did it take to obtain all developing Less than 1 month . . . . . . . . . . . . . . 1 ❍

country ethics board or IRB approval for 1 to 2 months . . . . . . . . . . . . . . . . . . 2 ❍

this research? 3 to 6 months . . . . . . . . . . . . . . . . . . 3 ❍

More than 6 months . . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

C6 For this index study, was one or more developing Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

country IRB or ethics boards established because No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

of the US requirements? Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

Not Applicable. . . . . . . . . . . . . . . . . 9 ❍
12

D Consent

Thinking of the same “index” research study, please answer the following

questions about the informed consent process.

D1 Which of the following methods of informing participants and/or documenting consent did you 

use for this research project? (Please check one response for each statement.)

Don’t Not

Yes No know applicable

a Written informed consent, requiring a 

signature, thumbprint, or equivalent 1 ❍ 2 ❍ 8 ❍ 9 ❍

b Pictorial descriptions of study or study 

procedures 1 ❍ 2 ❍ 8 ❍ 9 ❍

c Oral consent with a witness signature 1 ❍ 2 ❍ 8 ❍ 9 ❍

d Community meeting to describe the study 1 ❍ 2 ❍ 8 ❍ 9 ❍

e Approval from a village or community 

leader 1 ❍ 2 ❍ 8 ❍ 9 ❍

f In research with adults, approval or 

consent from another family member 1 ❍ 2 ❍ 8 ❍ 9 ❍

g Explanation and question and answer 

session with participants (either individually 

or in groups) 1 ❍ 2 ❍ 8 ❍ 9 ❍

h Video to explain study 1 ❍ 2 ❍ 8 ❍ 9 ❍

i Test of participant understanding of 

research before enrollment 1 ❍ 2 ❍ 8 ❍ 9 ❍

j Other methods 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please describe)
Thinking of the same “index” study, please indicate if the following statements

apply. (Please check one response for each statement)

Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

D2 The informed consent process 

is focused too much on the 

individual rather than on the 

family and/or community. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D3 Participants often do not understand the concept of a placebo. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D4 Study participants are usually aware 

that they are in a research study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D5 The consent process is an 

important means of educating 

participants about the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D6 The consent process provides an 

opportunity to discuss ethics issues 

with field staff. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D7 After learning about the study, 

some potential participants 

declined enrollment. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D8 The formality of going through 

the informed consent process 

raises distrust in study participants. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D9 Local staff shortened or simplified 

the consent procedures compared 

to the original protocol. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

D10 Legalistic language was required 

on consent forms which was not 

meaningful to study participants. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

13
14

E Relationship with Collaborators

If your “index case” involved collaboration with foreign researchers, please

complete this section. If not, please skip to E3.

Thinking again about the “index” study, please respond to the following

statements about developing country involvement in your project.

E1 Developing country researchers were/are included in the following research tasks:

(Please check one response for each statement)

Don’t Not

Yes No know applicable

a initial study design 1 ❍ 2 ❍ 8 ❍ 9 ❍

b grant writing 1 ❍ 2 ❍ 8 ❍ 9 ❍

c changes in study design 1 ❍ 2 ❍ 8 ❍ 9 ❍

d recruitment of participants 1 ❍ 2 ❍ 8 ❍ 9 ❍

e drafting consent form 1 ❍ 2 ❍ 8 ❍ 9 ❍

f consent discussions with participants 1 ❍ 2 ❍ 8 ❍ 9 ❍

g training of research personnel 1 ❍ 2 ❍ 8 ❍ 9 ❍

h drafting manuscripts 1 ❍ 2 ❍ 8 ❍ 9 ❍

i data analysis 1 ❍ 2 ❍ 8 ❍ 9 ❍

j listed as authors on papers 1 ❍ 2 ❍ 8 ❍ 9 ❍

E2 Will some of the resources or research infra- Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

structure established for this study remain in the No (Skip to question E3) . . . . . . . . . . . . 2 ❍

developing country after study has ended? Don’t know (Skip to question E3) . . . . . 8 ❍

Not Applicable (Skip to question E3) . . 9 ❍

E2a If E2 answer is “Yes”, please check all that apply

Don’t Not

Yes No know applicable

a. Personnel who were trained or who 

acquired skills on this research project 1 ❍ 2 ❍ 8 ❍ 9 ❍

b. Medical, laboratory, or office equipment 1 ❍ 2 ❍ 8 ❍ 9 ❍
Don’t Not

Yes No know applicable

c. Medical, laboratory, office, or 

pharmaceutical supplies 1 ❍ 2 ❍ 8 ❍ 9 ❍

d. Computers or data management system 1 ❍ 2 ❍ 8 ❍ 9 ❍

e. Buildings, laboratory facilities or renovations 1 ❍ 2 ❍ 8 ❍ 9 ❍

f. Power generating equipment, water system, 

or motor vehicles 1 ❍ 2 ❍ 8 ❍ 9 ❍

g. Organizational structure for health care 

or research 1 ❍ 2 ❍ 8 ❍ 9 ❍

h. Other 1 ❍ 2 ❍ 8 ❍ 9 ❍

(Please specify)

E3 Is this index study an intervention study? Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

No (Skip to section F) . . . . . . . . . . . . . 2 ❍

Don’t know (Skip to section F) . . . . . . . 8 ❍

Not Applicable (Skip to section F) . . . . 9 ❍

E4 Has the study shown the intervention to be Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

efficacious? No (Skip to section F) . . . . . . . . . . . . . . 2 ❍

Don’t know . . . . . . . . . . . . . . . . . . 8 ❍❖

Not Applicable (Skip to section F) . . . . 9 ❍

E5 Was the intervention provided, OR will it be Yes . . . . . . . . . . . . . . . . . . . . . . . . . . .1 ❍

provided, if successful, to study participants No (Skip to section F) . . . . . . . . . . . . . . 2 ❍

or to any other host country residents at the Don’t know (Skip to section F) . . . . . . . 8 ❍

conclusion of the study? Not Applicable (Skip to section F) . . . . 9 ❍

E6 To whom was (or will) the intervention be Placebo or control group of study . . . 1 ❍

provided? (Please check all that apply) Entire study population . . . . . . . . . . .2 ❍

Community from which 

the study population comes . . . . .3 ❍

Certain regions of host country . . . . .4 ❍

Entire host country . . . . . . . . . . . . . .5 ❍

Other (Please specify) . . . . . . . . . . . . .6 ❍

Don’t know . . . . . . . . . . . . . . . . . . . .8 ❍

15
E7a What parties were (or will be) part of the Foreign research team 

arrangement to provide the intervention? carrying out this study . . . . . . . . . 1 ❍

(Please check all that apply) Foreign institution 

carrying out this study . . . . . . . . . 2 ❍

Foreign funding agency for this study . 3 ❍

International agency 

(e.g. WHO, UNICEF) . . . . . . . . . 4 ❍

Host country research team . . . . . . . 5 ❍

Host country government, 

including Ministry of Health . . . . 6 ❍

Host country institution 

(e.g. university, NGO, 

clinical center) . . . . . . . . . . . . . . 7 ❍

Private for-profit company . . . . . . . . 9 ❍

Private foundation . . . . . . . . . . . . . 10 ❍

Other (Please specify) . . . . . . . . . . . 11 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

E8 How long was (or will) the intervention be Less than one year . . . . . . . . . . . . . . 1 ❍

provided? Two to five years . . . . . . . . . . . . . . . . 2 ❍

Greater than 5 years . . . . . . . . . . . . . 3 ❍

Other (Please specify) . . . . . . . . . . . . 4 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

E9a How was (or will) the intervention be paid for? By research grant for this study . . . . . 1 ❍

(Please check all that apply) By foreign institution 

carrying out this study . . . . . . . . .2 ❍

By foreign funding agency 

for this study . . . . . . . . . . . . . . . . 3 ❍

By international agency . . . . . . . . . . 4 ❍

By host country government . . . . . . . 5 ❍

By host country institution . . . . . . . . 6 ❍

By private for-profit company . . . . . . 7 ❍

By private foundation . . . . . . . . . . . . 9 ❍

Other (Please specify) . . . . . . . . . . . 10 ❍

Don’t know . . . . . . . . . . . . . . . . . . . 8 ❍

16
F Ethical issues in international research

The following statements have been made by some researchers in discussing

research in developing countries. Thinking of the “index” study, please indicate

whether you think these statements are True, Sometimes True, or False.

Sometimes Don’t Not

True True False know applicable

F1 Medical care provided to participants in 

this study generally is not available to 

local population outside the study. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F2 Study gathered potentially sensitive or 

stigmatizing information about participants 

(e.g., HIV+ status; domestic violence). 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F3 Study participants have unrealistic hopes 

about personal benefit from study participation (e.g. think their disease will be cured). 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F4 The standard of medical care in the host 

country may be much lower than that of 

funding country, creating difficulties in 

establishing appropriate procedures for 

the control group. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F5 Participants join because of the desire for 

compensation, medical care or other 

benefits. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F6 Research priorities of outside funding agencies

that are funding the study are not congruent 

with top priorities of developing country. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F7 Treatment or intervention being tested 

is unlikely to be available to most 

citizens of country where research is 

conducted in the foreseeable future. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

17
Sometimes Don’t Not

True True False know applicable

F8 There is inadequate true community 

representation on the local IRBs /ethics 

boards for this study. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F9 Religious beliefs and/or cultural norms of 

study population are inconsistent with the 

practice of individual decision-making. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

F10 Ethics issues are rarely discussed with field 

staff on this research project. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

18
G. Ethical guidelines and regulations in

human subjects research

Thinking of all the developing country projects you have worked on, not just

the “index case,” please answer the following questions about ethics

regulations and guidelines.

If you have NEVER received U.S. funds directly or collaborated on a 

research project with a U.S. institution, please skip to question G6.

General statements about U.S. regulations and about ethical review in developing country research.

Please indicate how much you think the following general statements are accurate when describing the

application of U.S. human subjects regulations to research in developing countries.

Some- Don’t Not

Never times Always know applicable

G1 U.S. human subjects regulations are 

flexible where they need to be. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G2 Developing country collaborators rely 

on U.S. ethics regulations for guidance. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G3 U.S. IRBs are more concerned with 

politics than they are with protecting 

the interests of research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G4 The current U.S. rules and regulations 

governing human subjects ensure high 

ethical standards in research. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G5 U.S. IRB regulations are insensitive to 

local cultural norms and traditions 

outside the U.S. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

19
The following questions concern ethics review in developing countries.

Don’t Not

Yes No know applicable

GA1 Have you ever had to abandon a research project 

because it was impossible to get U.S. IRB approval 

despite modifications? 1 ❍ 2 ❍ 8 ❍ 9 ❍

GA2 Have you ever had to abandon a research project 

because it was impossible to obtain an SPA? 1 ❍ 2 ❍ 8 ❍ 9 ❍

Don’t Not

Yes No know applicable

G6 Developing country IRBs are more 

concerned with politics than they 

are with protecting the interests of 

research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G7 Developing country IRBs have voiced 

concerns to me about the costs 

associated with the IRB carrying out 

its work. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

G8 National guidelines in developing 

countries are effective in protecting 

research subjects. 1 ❍ 2 ❍ 3 ❍ 8 ❍ 9 ❍

Don’t Not

Yes No know applicable

GA3 Have you ever had to abandon a research project

because it was impossible to get developing country 

IRB approval despite modifications? 1 ❍ 2 ❍ 8 ❍ 9 ❍

20
H Recommendations

Please indicate if you agree with any of the following statements. Also, feel free

to elaborate on these or any other questions in the final section of the survey.

Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

H1 Human subjects regulations 

should allow more flexibility in 

ways of documenting informed 

consent (e.g. non-written methods). 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H2 Formal individual consent 

should not be necessary for 

observational studies. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H3 Where appropriate, community 

leaders’ approval should be required by IRBs, in addition 

to individual informed consent. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H4 A mechanism to measure participants’ understanding should 

be built into any research study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H5 Research funding agencies 

should provide funding to 

support the work of developing 

country IRBs. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H6 International guidelines (e.g., 

CIOMS) should be used instead 

of U.S. rules and regulations. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H7 A developing country ethical 

review should be required for 

all studies. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H8 The composition of ethics review 

boards used in developing 

countries should not be 

dictated by U.S. regulations. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H9 The single project assurance 

(SPA) requirement should 

be eliminated. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

21
Strongly Strongly Don’t Not

Agree Agree Neutral Disagree Disagree know applicable

H10 The issue of what standard of 

medical care to provide to study 

participants should be decided 

on a case-by-case basis. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H11 Some research funds for piloting 

consent forms should be 

released before final IRB 

approval is obtained. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H12a Researchers should be required 

to make data from research study

directly available to study 

population after study is over. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H13 Research to test an intervention 

should not be carried out in a 

developing country unless the 

intervention, if found to be successful, will be made available 

to that country at the conclusion 

of the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

H14 International policy regarding 

research should require 

researchers to establish a 

mechanism for continuing 

delivery of medical care after 

completion of the study. 1 ❍ 2 ❍ 3 ❍ 4 ❍ 5 ❍ 8 ❍ 9 ❍

22
J Finally, please give us more information

about yourself

J1 Gender: Female . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

Male . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

J2 Age: ______________ Years

J3 Degree(s) (Please check all that apply): MD, DDS, MBBS, MBChB . . . . . . . 1 ❍

Ph.D., ScD., DrPH, or PharmD . . . . 2 ❍

RN, CNP, CNM, LPN, NP . . . . . . . . 3 ❍

MPH, MS, MA, MHS . . . . . . . . . . . 4 ❍

BS or BA . . . . . . . . . . . . . . . . . . . . . 5 ❍

Other (Please specify) . . . . . . . . . . . . 6 ❍

J4 What type of institution is your primary employer? University . . . . . . . . . . . . . . . . . . . . . 1 ❍

Government agency (non-military) . 2 ❍

Military . . . . . . . . . . . . . . . . . . . . . . 3 ❍

Private for-profit research 

institute/organization . . . . . . . . . 4 ❍

Private non-profit research 

institute/organization . . . . . . . . . . 5 ❍

Pharmaceutical/biotech . . . . . . . . . . 6 ❍

Independent consultant/

self employed . . . . . . . . . . . . . . . . 7 ❍

Other (Please specify) . . . . . . . . . . . 8 ❍

J5 Where is your primary employer located U.S. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

(headquarters)? Other industrialized country. . . . . . . 2 ❍

Developing country . . . . . . . . . . . . . 3 ❍

J6 What percentage of your work is spent on 

research as compared with teaching, clinical care,

administration, or other work? ______________ % 

23
J7 Are you, or have you been in the past, a member Yes . . . . . . . . . . . . . . . . . . . . . . . . . . 1 ❍

of an Institutional Review Board? No . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ❍

J8 Please elaborate on any of the questions that you feel require more detailed responses. 

(Please identify the question number specifically)

J9 Please describe changes that you would make to the existing U.S. policy and regulations 

regarding human subjects research in developing countries.

24
J10 Would you be willing to participate in a half hour in-depth interview with one of our project

team to discuss these issues? Transcripts of interviews will not contain your name or institution,

and specific place names will be replaced with region names where necessary, to protect your

confidentiality.

❍ Yes

❍ No

Telephone Number ________________________________________

25
K Contact Information

Please provide us with a mailing address where we may send you a US $25

payment for completing the survey. Any contact information you give us will

be separated from the completed survey, so that your survey responses will

remain confidential.

Name ____________________________________________________________

Address ____________________________________________________________

__________________________________________________________________

City ____________________________________ Country___________________

Thank you for your participation

26
B-217

APPENDIX E

Focus Group Guide

I. Introductions

1. What do you do?

2. What countries have you worked in? For how long?

3. Generally, what types of studies? 

4. Were your studies done in collaboration with American researchers? Researchers from other countries?

II. In-Country Review of Studies

1. Generally, do your studies need to go through an ethics review in your country before you start a study?

2. If so, how many in-country IRBs or ethics boards did you need to go through? Is ethics review separate

from or combined with scientific review?

3. Did boards exist or did they need to be established for your study? Because of U.S. requirements or not?

Was composition or procedures of the board influenced by U.S. regulations?

4. Generally, how well did the process work? How meaningful was the ethics review?

5. Substance of review: were you asked mostly about administrative details, or about issues you thought

related to human subjects’ protections and ethics?

III. U.S. (or other countries’) Review

1. Generally, do your studies need to go through an ethics review (IRB or equivalent) by your collaborator’s

country, such as the United States?

2. If so, is that at your collaborator’s institution, or elsewhere (where)? Other layers of approval necessary?

3. How well did that process work? How meaningful an ethics review?

4. Substance of review: were you asked mostly about administrative details, or about issues you thought

related to human subjects protections and ethics?

IV. Informed Consent Procedures

1. Did you get/seek informed consent from individual participants? From other individuals (relatives)?

Communities? Others?

2. How was informed consent handled (written, oral, groups)? 

3. How meaningful do you think the informed consent process was?

4. Were you faced with cultural differences in how consent procedures should be implemented?

4.1 Did U.S. regulations (or other regulations) require you to do anything you thought was 

culturally inappropriate?

5. How foreign is the concept of informed consent?

5.1 How foreign a concept is research?

5.2 Do doctors/providers in your country usually DISCLOSE much about diagnoses, treatments, etc., 

to patients?

5.3 Do patients usually have CHOICES or MAKE DECISIONS in their own medical care?
B-218

V. Ethics Issues That Arise

1. What kinds of ethics issues have arisen in your studies?

2. How did you try to resolve them?

3. (Examples:)

3.1 Didn’t think participants understood.

3.2 What intervention to provide to comparison group.

3.3 Providing additional benefits (e.g., more health care) to participants.

VI. After Study Ended

1. Dissemination of intervention after study ended?

2. Interventions you studied ever implemented in your country?

3. Was implementation discussed before study was initiated?

VII. Overall Recommendations

1. How should U.S. ethics regulations be modified?

2. Should there be in-country IRBs?

3. How best to protect vulnerable, poor, uninformed participants?

4. What recommendations would you make?
B-219

APPENDIX F

Experiences and Attitudes of Developing Country Investigators 

Regarding U.S. Human Subjects Regulations:

Interview Outline

I. Description of research

■ How long have you been conducting research in your country? 

■ What kinds of research topics do you investigate in your country?

■ How many research projects do you have ongoing at the moment?

■ What is the source of funding for these studies?

■ How many of these projects involve collaboration between U.S. and non-U.S. institutions?

II. Experiences with human subjects review committees

■ If you have collaborated with American researchers, do all of those projects undergo U.S. IRB review?

■ What kinds of issues have been raised in U.S. IRB reviews?

■ Do you find U.S. IRB review helpful in addressing your research issues, or not?

■ Does/did U.S. IRB require your country’s ethics review?

■ Was there (or is there) an ethics review in your country?

■ In your country, was an ethics review board or IRB set up specifically for your study?

■ What kinds of issues have been raised in your country’s ethics review?

■ Please comment on your experiences with human subjects review committees from other countries 

(e.g., the United Kingdom, Sweden) in comparison with your experience of U.S. IRBs.

III. Approval and consent issues

■ Do you have to seek approval for your research from your Ministry of Health or other government officials?

■ Do you seek approval from community or village leaders for the study? And if so, can you elaborate?

■ Can you describe how the consent process was developed?

■ What methods of informing participants do you use?

■ Do you have any assessment of the effectiveness of these methods? Please describe.

■ Are there difficulties in communicating biomedical research concepts to potential participants?

■ Regarding decisionmaking, in your perception, are there cultural differences between your country’s 

communities and American communities?

■ Regarding the signing of documents, in your perception, are there cultural differences between your 

country’s communities and American communities?

■ Are the study participants literate, for the most part?
B-220

IV. Ethics issues

■ How would you describe the background economic conditions in the study community?

■ How would you describe the medical care available to the community?

■ Did your study provide participants with medical care or benefits not generally available to others in 

the community?

■ How did you decide which benefits or care, if any, would be provided through your study?

■ When the study is over, is there medical care or research infrastructure left in the country? 

■ Why do people join the study?

■ Are there sensitive issues (e.g., HIV status) raised by study participation?

■ What was your role as the research collaborator in the project?

■ Who will have access to the data from the study?

■ If the intervention is successful, do you think it will be implemented in your country?

■ What do you consider to be important ethics issues in your research?

V. Recommendations

■ What kind of changes would you recommend to U.S. human subjects regulations?

■ What kind of policies would be helpful generally?

■ Do you think researchers in the United States or in developing countries need training in ethics?

■ In your opinion, what are some key issues that members of U.S. human subjects review committees 

need to be made aware of regarding the conduct of research in your country?

■ What do you think is an effective way to address ethics issues that currently are not addressed by 

regulations?

■ Do you think international guidelines can be helpful for ethical issues in conducting research in 

your country?
C-1

THE RELEVANCE

OF CULTURE FOR

INFORMED CONSENT

IN U.S.-FUNDED

INTERNATIONAL

HEALTH RESEARCH

Commissioned Paper

Patricia A. Marshall

Loyola University-Chicago
C-3

I. Introduction

The current research agenda of the President’s National Bioethics Advisory Commission (NBAC) includes

analyzing and developing recommendations on the federal oversight system of U.S.-funded national and

international research on human subjects and on the complex ethical and legal issues in U.S. federally and

privately funded international research. The overall goal of this research agenda is to examine the adequacy

and appropriateness of U.S. human subjects protections as they apply to research in other countries. Findings

from this research will assist the Commission in determining the necessity of changes in federal regulations

and policies and the development of recommendations for changes, if they are warranted.

One component of this broad initiative concerns the relevance of cultural context for processes involved in

the application of informed consent to research in U.S.-funded international health investigations. The purpose

of this specific project is to examine cultural beliefs and values regarding the meaning and expression of

informed consent in U.S. biomedical and behavioral international health research. Particular attention will be

given to the articulation of individual and social agency in the process of obtaining informed consent from

individuals participating in research. 

Project Summary

This project was initiated in January 1999. Initially, three specific objectives were outlined:

1. Review literature relevant to definitions of personhood and the expression of autonomy in cross-cultural

context, with attention to their implications for the application of informed consent to research.

2. Conduct key informant interviews with scholars in the field and investigators who have been or are 

currently participating in biomedical and behavioral international research. 

3. Conduct a case study of ethical issues involved in obtaining approval for the implementation of an ongoing

investigation of hypertension in Nigeria, with special focus on the application of informed consent from

human subjects. 

Two changes were made in the proposed objectives during the development and implementation of the 

project goals. First, key informant interviews with scholars and investigators who are involved in international

research (objective number 2) were not implemented. Drs. Nancy Kass and Adnan Hyder, as consultants to

NBAC’s initiative on international research ethics, have conducted focus groups with investigators to explore

their concerns about ethical issues related to health research in international settings. The data gathered in

these focus groups include information on informed consent and institutional review of protocols by ethics

committees. Moreover, Dr. Kass and her colleagues will be conducting a large-scale survey with U.S. investigators

on challenges related to ethical issues in the implementation of international research; in-depth interviews will be

conducted with a small number of the individuals surveyed. Adnan Hyder is implementing a similar project with

investigators from other countries. It is unlikely that the key informant interviews with scholars and investigators

that I originally proposed would contribute substantially to the information gathered in these projects. 

Second, the case study was designed initially to examine ethical issues associated with the implementation

of a population-based genetic epidemiological study of hypertension in Nigeria. However, the case study

was broadened to include genetic epidemiological studies on breast cancer and diabetes mellitus. This 

decision was made because the U.S. researchers with whom I worked on the case study are involved in ongoing

large-scale collaborative investigations of these three diseases in Nigeria. The researchers, here in the United

States and in Nigeria, work as a team on these three projects. Interviews were conducted with six investigators,

five physicians and one psychologist, ten research assistants, and three research participants involved in the

three studies. During interviews, it was common for individuals to discuss ethical challenges related to more

than one of the projects. 
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Work Completed

1. A review of the literature on informed consent with attention to cultural factors that influence its interpretation

and application in international research.

2. A case study of ethical issues involved in obtaining approval for the implementation of research examining

the genetic and environmental determinants of hypertension, breast cancer, and diabetes mellitus in 

Nigeria, with special focus on the application of informed consent with human subjects. The case study 

was implemented during April 1999.

The literature review and the findings from the case study are reported in the following two sections.

II. Informed Consent in International Health Research

A. Historical Background: Research Ethics and Informed Consent

Societal concerns with ethical issues surrounding human experimentation were heightened following World

War II during the Nuremberg Trials (Annas and Grodin 1992). These proceedings, which judged medical

experiments conducted by Nazis on concentration camp prisoners, resulted in the Nuremberg Code for ethical

conduct in scientific research. An important aspect of the Nuremberg Code was its commitment to informed

consent in research involving human subjects (Katz 1972). The World Medical Association’s Declaration of

Helsinki in 1964 reiterated concerns for voluntary and informed consent to research, as have subsequent

guidelines such as those prepared by the World Health Organization (WHO) and the Council of International

Organizations of Medical Sciences (CIOMS) (ICH 1996; WHO/CIOMS 1993).

In the United States, in 1972, public reports of governmental research on untreated syphilis among 

low-income African American men in Alabama emphasized the absence of voluntary participation and the

unwillingness of researchers to disclose the availability of a treatment (Jones 1981). Public outrage concerning

the Tuskegee experiment prompted the appointment of a panel by the Department of Health, Education, and

Welfare to review the study, and, in 1974, the National Research Act was passed. This act established the

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The

Belmont Report, published in 1978 by the National Commission, described basic ethical principles regarding

research with human subjects; this document recognized that informed and voluntary consent for research 

subjects is a vital dimension of the principle of respect for persons (U.S. National Commission for the

Protection of Human Subjects of Biomedical and Behavioral Research 1978).

Currently, throughout the world, institutional ethics committees have been established to provide oversight

and approval for proposals to conduct studies involving human subjects (Brody 1998). In the United States, in

1966, the Public Health Service required the establishment of ethics committees at research institutions. Final

regulations concerning policies governing research on human subjects were issued in 1981 by the Department

of Health and Human Service (DHHS) (U.S DHHS 1981) and reissued a decade later (U.S. DHHS 1991). The

federal mandates were clear: Any research involving human subjects that is funded by a Department agency,

with certain exemptions, must be evaluated by an Institutional Review Board (IRB). Initially, eight criteria for

IRB approval were outlined, including 1) a sound research design; 2) protection of privacy and confidentiality; 

3) equality in treatment of subjects; 4) consideration of risks/benefits; 5) monitoring of data collection; 

6) informed consent; 7) documentation of informed consent; and 8) a statement indicating that participation 

in the research is voluntary and that withdrawing from the study will not result in harm or penalty. Six 

additional criteria must now be addressed for particular projects.
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IRBs have had a profound impact on the regulation of research with human subjects (Faden and Beauchamp

1986; Levine 1986; Veatch 1987). While there is consensus about the general purpose of IRBs, significant

problems remain in the application of the review process. One issue concerns the selection of committee 

members (Veatch 1987). Committees are required to include representatives from nonscientific fields and from

the community, but most are dominated by scientists who are responsible for reviewing the research protocols

of colleagues and friends. Two issues become apparent. First, questions regarding professional competence arise

in determining who is qualified to judge the professional merit of protocols. Second, professional bias may be

an obstacle to objectivity regarding determination of harm to research subjects. The strong value placed on 

promoting scientific research among most IRB representatives may outweigh the concerns of a community 

representative. Moreover, lay members may experience psychological pressure to reach consensus and therefore

they may be inclined to accept the arguments of a “professional.” Additional problems center around which

studies fall under the guidelines set by IRBs. Research that is perceived to involve minimal risk to subjects is

exempt from review. The problem, of course, is one of interpretation regarding the judgment of “minimal risk.”

Similar issues arise in the implementation of research ethics committees in international settings and may be

particularly challenging where there are no clear institutional directives concerning membership criteria or

committee responsibilities. In non-Western and developing countries, investigators (Christakis 1988, 1992;

Christakis and Panner 1991; Goodgame 1990; Lane 1993; Levine 1991, 1993, 1996, 1998, 1999; Loue,

Okello, and Kawuma 1996; Marshall, Koenig, Grifhorst, and Van Ewijk 1998) have called attention to the

problematic development of appropriate standards for ethical conduct in scientific research. Lane (1993), 

for example, describes the development of a code of research ethics in Egypt; she argues that the social and

cultural context of biomedical research in Egypt will influence the interpretation and application of generally

accepted principles of research. Similarly, Loue, Okello, and Kawuma (1996), in their discussion of strategies

for developing a Ugandan code of research ethics, suggest that, while ethical principles governing research are

relevant to investigations in Uganda, their adoption and implementation must reflect the circumstances and

cultural context that are unique to the Ugandan setting. 

Despite overwhelming agreement regarding the duty to obtain informed consent and the importance of 

ethical review boards, practices associated with the consent process and review of scientific protocols remain

problematic (Moreno, Caplan, Wolpe, et al. 1998). For example, in their recommendations for updating IRB

protection for human subjects, Moreno and his associates argue that existing IRB guidelines do not take into

account the significant changes in recent years associated with multisite and multinational trials; they suggest

that IRBs should monitor the entire research process and outcome and that IRB members should have more

training. Some investigators (Katz 1984) argue that neither patients nor communities involved in research

understand adequately the risks associated with their participation or whose interests are served by research

agendas. Indeed, recent public controversies, such as the trials conducted in developing countries testing the

efficacy of less expensive alternatives to standard antiretroviral therapy for reducing perinatal transmission of

HIV, call attention to inconsistent interpretations and applications of national and international ethical guidelines governing research (Angell 1997; Levine 1999; Lurie and Wolfe 1997; Varmus and Satcher 1997). 

B. Factors Influencing Informed Consent to Scientific Research

Requirements for informed consent to research appeal to and are justified by the principle of respect for persons.

National and international guidelines for ethical conduct in scientific research identify specific requirements for

informed consent including the following three key elements: the provision of information, comprehension of

information, and voluntariness in regard to participation (Brody 1998; Weisstub 1998). Adequate information

for potential subjects must include a description of research purposes and a clear delineation of risks and

benefits. Voluntary participation in research depends upon the respondent’s ability to understand not just the
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meaning of the research, but the impact it may have on his or her life. The offer of excessive financial compensation, bribes, or unrealistic promises may constitute coercion, especially if the subject is vulnerable because of

social factors such as poverty or ethnic background. Moreover, the voluntary nature of participation in research

is influenced significantly by the implicit or explicit power of investigators and the institutions they represent.

Voluntariness in informed consent may be inhibited when there are social status and social class differences

between investigators and potential subjects—differences based on gender, age, education, income level, 

religious affiliation, and ethnic identity. 

A number of factors influence approaches to implementing informed consent—the nature of the research,

the cultural context of the research project, communication issues that influence comprehension of information, and discrepancies in social power between subject and researcher. In international health research, the

challenges associated with implementing informed consent are heightened because of language barriers that

may inhibit effective communication, particularly regarding the translation of scientific or medical concepts and

differences in beliefs about who may provide consent to participate in research.

The following discussion of factors influencing the process of informed consent is organized around three

issues: 1) comprehension of information; 2) language barriers; and 3) location of decisional authority to provide consent to research.

Comprehension of Information. An individual’s decision to accept treatment or to participate in scientific

research is influenced by his or her comprehension of information and the meaning attached to the information

communicated. In clinical settings, a summary of studies conducted in the United States over a 20-year period

(1965–1985) on patient-clinician interaction found that patient satisfaction was associated with “partnershipbuilding”—behavior such as facilitating conversations with patients and positive nonverbal behaviors; patient

recall also was associated with the clinician’s communication of information and more positive talk during the

interaction (Roter, Hall, and Katz 1988; Hall, Roter, and Katz 1988). It is likely these same skills are found to

promote effective communication in investigational consent discussions because they are the types of behavior

that encourage trust—an essential aspect of decisionmaking in consent to research (Kass, Sugarman, Faden,

and Schoch-Spana 1996). Tests of behavioral decision theory in experimental and natural settings demonstrate

that individuals rarely conform to scientific rational models in making decisions (Elstein and Holzman, et al.

1987; Kahneman and Tversky 1981). Rather, choices often are made based on incomplete or inconsistent

information, the strength of someone’s ability to persuade, and past experiences that are relevant to the decision.

In medical research, particularly complex trials involving randomization or the use of placebos, investigators

must explain sophisticated scientific concepts (Davis, Holcombe, Berkel, Pramanik, and Divers 1998; Geller,

Strauss, Bernhardt, and Holtzman 1997; Olver, Buchanan, Laidlaw, and Poulton 1995). Studies have shown

repeatedly that information included in informed consent documents is difficult for patients or potential

research subjects to understand (Goldstein, Frasier, Curtis, Reid, and Kreher 1996; Grossman, Piantadosi, and

Covabey 1994; Jubelirer 1991; Taylor, Bezjak, Hunter, and Fraser 1998). Most consent forms are written on a

college or graduate school level, yet the average reading ability in the United States is significantly lower than

that (Meade and Howser 1992; Miles and Davis 1995; Ogloff and Otto 1991), and in many resource-poor

nations, illiteracy rates are high. In a study designed to test patients’ comprehension of a standard versus a 

simplified consent form (seventh-grade reading ability) for a “hypothetical” randomized clinical trial, Davis 

and associates (Davis, Holcombe, Berkel, Pramanik, and Divers 1998) found that low levels of literacy were

associated with a preference for the simplified consent. However, comprehension was low with both forms.

Thus, Davis et al. suggest that simply lowering readability level does not result in increased comprehension.

Despite low levels of comprehension due to ineffective disclosure practices (Andrews 1997) or a patient’s

inability to understand, most individuals view participation in scientific research favorably (Cassileth, Lusk,

Miller, and Hurwitz 1982; Kemp, Skinner, and Toms 1984). 
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Application of informed consent with culturally diverse populations or in international settings is often

problematic (Barnes, Davis, Moran, Portillo, and Koenig 1998; Christakis 1988; Ekunwe and Kessel 1984; 

El-Sadre and Capps 1992; Ijsselmuiden and Faden 1992; Kaufert and O’Neil 1990; Levine 1991; Marshall,

Koenig, Grifhorst, and VanEwjik 1998). For example, in a study of informed consent in clinical practice in

Bangalore, India, investigators found that doctors believed it was difficult to obtain consent from illiterate

patients, and nearly a third of the 148 patients and 60 doctors interviewed believed that provision of information could sometimes be harmful (Sriram, Kishore Kumar, Jayaprakash, Sriram, and Shanmugham 1991). 

In a study of informed consent for an influenza vaccine for children in The Gambia, 90 percent of the 189 

consenting parents knew the purpose of the vaccine was to prevent disease, but only 10 percent understood

the placebo control design; the primary motivation for consenting was to receive the vaccine (Leach, Hilton,

Greenwood, Manneh, Dibba, Wilkins, and Mulholland 1999). Freeman (1994) describes the work of the

Indian Health Service in developing models of consent forms that are informative and understandable to

American Indian and Alaskan Natives considering participation in research; these models emphasize brevity,

clarity, and comprehensible formatting.

Language Barriers. Communication between health researchers and potential subjects may be difficult to

achieve when the relationship extends across cultural boundaries. Misunderstandings and miscommunication

about scientific research are more likely to occur when patients and practitioners speak different languages. The

translation of informed consent documents from English to another language may be especially difficult if there

are no equivalent expressions for particular concepts. In Nigeria, for example, investigators involved in genetic

epidemiological research with Yoruba-speaking patients report that there are no Yoruba words for “genotyping”

or “candidate gene.”

Linguistical barriers may be reduced through the use of an interpreter, but potential problems remain

(Barnes, Davis, Moran, Portillo, and Koenig 1998; Kaufert and O’Neil 1990; Marshall 1992a; Marshall, Koenig,

Grifhorst, and VanEwjik 1998). An investigation requiring a translator creates a dual problem for health

researchers (Marshall 1991). First, the investigator depends on the translator to communicate the research

objectives correctly and effectively; second, the investigator depends on the translator to actually follow

through with the consent, which means relaying the information and requesting participation in the study. In

situations where a translator is used, consent can only be assumed if the respondent agrees to participate. 

Translators are often thought to act as straightforward interpreters of information exchanged between health

providers or researchers and patients. This perspective minimizes the complexities of the process of interpretation, where the translator must negotiate not only language, but also cultural and contextual factors (Carrillo,

Green, and Betancourt 1999; Kaufert and O’Neil 1990; Koenig and Gates-Williams 1995; Marshall 1992b;

Marshall and Koenig 1996). Moreover, if family members or friends are used for translation, there may be a

tendency for them to camouflage, exaggerate, or minimize information (Putsch 1985). Some of the problems

associated with medical interpretation include the inability to easily translate equivalent expressions across 

languages; paraphrasing that results in omissions or erroneous substitutions of terms; varying levels of comprehension among participants in the interaction; and the influence of conflicting cultural beliefs and values

among participants. Drawing on their research with Native Canadian medical interpreters in Winnipeg hospitals,

Kaufert and O’Neil (1990) argue that interpreters have a significant impact on medical interactions and their

outcomes. They suggest that, in addition to mediating the explanatory models of illness held by clinicians and

patients, Native interpreters often introduce their own beliefs and personal agendas into the interaction. Kaufert

and O’Neil (1990) emphasize the dynamic nature of the interaction. They describe the triad that exists between

the patient, interpreter, and clinician, in which the process of feeding information back and forth results in a

restructuring of both the patient’s and the provider’s understanding of the medical problem. 
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It is inevitable that interpreters exercise some degree of control over the communication between researchers

and potential study participants. Their influence on communication is articulated through the role of gatekeeping; interpreters make crucial decisions about the selection of information to communicate, the terminology

used to express concerns, and the simplification of information to suit particular interactions (Barnes, Davis,

Moran, Portillo, and Koenig 1998). The modification of the message that researchers wish to give to potential

subjects, and conversely, the response of individuals to questions, have serious implications for the informed

consent process. 

Wasongarz, Carter, Barnes, and Koenig (1995), as part of an ongoing ethnographic study of end-of-life 

decisionmaking among culturally diverse patients terminally ill with cancer, explored the way in which medical

interpreters influenced decisions such as resuscitation, the limitation of treatments, and the completion of a

Durable Power of Attorney for Health Care. Although this study does not address informed consent to research,

the findings are applicable to an investigational context. These investigators challenge the assumption that

interpreters are simply conduits of information between patients and providers. Results of their analysis suggest

that interpreters modified language in order to make patients feel more comfortable about their diagnosis and

prognosis. Translators were also found to influence the communication process by acting as cultural brokers,

patient advocates, and counselors. For example, referring to her practice of modifying the words of the

provider, one interpreter stated, “When I translated ‘death,’ I usually would avoid using the word ‘death.’

For Chinese patients, I would use ‘letting go,’ ‘sleeping,’ ‘stop eating rice,’ and other words to substitute the

word ‘death’” (Wasongarz, Carter, Barnes, and Koenig 1995:13). The investigators suggest that perhaps the

interpreter changes the word “death” not only to ease the emotional burden of the patient, but also to ease 

the discomfort the interpreter feels when telling the patient that he or she is dying. Wasongarz and associates

(1995) call attention to another process of modification in which translators expand upon what the physician

says in order to communicate a technical medical procedure in culturally appropriate terms. They report that 

a Cantonese interpreter spent 15 minutes explaining a lumbar puncture to a patient; the oncologist had 

communicated this in one sentence. 

Language barriers represent only one dimension of effective communication in international investigations.

Cultural norms governing the structure and content of discourse in medical encounters are also vitally important (Barnes, Davis, Moran, Portillo, and Koenig 1998; Kaufert, and O’Neil 1990; Koenig and Gates-Williams

1995; Marshall and Koenig 1996). Beliefs and expectations concerning “appropriate” discourse in medical

interactions—what is discussed, the timing of the conversation, who is present at the conversation, and who

participates in the discussion—influence deliberation over ethical issues such as disclosure of information and

confidentiality.

Autonomy and Locus of Decisional Authority. Who has the authority to provide consent for participation 

in research? Beliefs about personhood, individual autonomy, and decisional capacity are embedded within the

social and cultural patterns of family ties and community obligations. In the United States, where personal

autonomy is emphasized, patients are expected to make decisions for themselves or through designated 

surrogates. However, in many non-Western settings, religious or tribal leaders or a patient’s extended family

may play a significant role in decisions concerning health care and health research (Barry 1988; Barry and

Molyneux 1992; DeCraemer 1983; Hall 1989; Levine 1991; Marshall, Thomasma, Bergsma 1994; Marshall,

and Koenig 1996; Marshall, Koenig, Grifhorst, and VanEwjik 1998). Cultural differences in beliefs about the

nature of personhood and the location of decisional authority for consent have been problematic for investigators conducting international health research.

In her discussion of AIDS research in Africa, for example, Barry (1988) describes the challenge of translating

the concept of autonomy in areas where personhood is defined by one’s tribe, village, or social group. In these

situations, tribal elders, community leaders, religious authorities, or family members of the research subject
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may need to be approached before obtaining consent from individuals. In an early report on consent for smallpox vaccination research in five areas of West Africa, investigators (Henderson et al. 1973) found that compliance with the decisions of tribal leaders in particular areas was the strongest factor influencing a community’s

receptivity to the program. In 1980, Ajayi identified numerous social obstacles to achieving informed consent

to research in Nigeria according to the criteria mandated by the Helsinki Declaration; his discussion called

attention to the importance of cultural beliefs concerning respect for community and family elders. In Uganda,

more recently, Loue, Okello, and Kawuma (1996) note that, according to Ugandan civil law, an 18-year-old

male living at home has the legal right to make his own decisions; it is customary, however, for the son to

obtain his father’s consent prior to entering into any obligation or contract, including participation in research.

Additionally, without the consent of their partner, Ugandan women often refuse to make a decision regarding

their own or their child’s participation in research.

In their examination of informed consent practices associated with an influenza vaccine trial in The Gambia,

Leach and his colleagues (1999) report that parental consent for a child’s participation conformed generally to

Western notions of autonomous decisionmaking. Parents sought the advice of health workers, families, and

friends, but only 1 percent of the 189 parents involved traditional or religious leaders in their decision.

However, 10 percent of the urban parents compared to 25 percent of the rural parents agreed that the village

chief should have some input in making the decision to participate in the influenza vaccine trial. Moreover, all

of the mothers from one entire village refused to participate in the research. None of these women agreed to be

interviewed, but an elderly woman who was respected in the community made the following statement: “The

mothers of this village don’t want MRC [the United Kingdom Medical Research Council] affairs. MRC is fond 

of taking blood samples from babies who will then eventually die or continuously suffer....All the mothers and

fathers, including the village chief, do not want MRC and we have agreed that nobody should accept your

interview” (Leach, Hilton, Greenwood, Manneh, Dibba, Wilkins, and Mulholland 1999). The investigators

argue that, in this case, the women may have been too frightened to refuse individually. The results of this

study suggest that international codes of informed consent, emphasizing individual choice, are appropriate, 

but in particular settings, input from community leaders may be necessary.

Negotiating informed consent with the designated authorities in health research with non-Western populations

requires investigators to move beyond narrow definitions of personhood, autonomy, and “self” determination. 

A number of scholars (Angell 1988; Newton 1990) have suggested that the application of Western ethical 

standards to scientific research conducted in developing countries with divergent cultural norms may be 

construed as a form of ethical imperialism. Nevertheless, as Angell (1988) and others (see e.g., Barry 1988;

Christakis 1992; Christakis and Panner 1991; Ekunwe and Kessel 1984; Ijsselmuiden and Faden 1992; Levine

1991, 1993, 1996; Macklin 1998, 1999; Marshall 1992b; Marshall, Koenig, Grifhorst, and VanEwjik 1998)

point out, while ethical relativism demands cultural sensitivity to local customs, investigators are never authorized to conduct research without regard to potential harm and without attempts to be informative throughout a

project’s implementation. In particular, scholars (see e.g., Angell 1997; Lurie and Wolfe 1997; Macklin 1998,

1999) have cautioned against an ethical relativism that would permit the exploitation of populations in nonWestern settings in research that would not be allowed in the investigator’s home country. In his development

of a model for the negotiation of value differences relevant to science and health in a multicultural world, Baker

(1998a, 1998b, 1998c) levels a strong critique against those who embrace moral fundamentalism—the idea

that certain ethical principles are applicable cross-culturally (Beauchamp 1998; Macklin 1998, 1999). The

struggle to respect the unique identity of culturally diverse communities and simultaneously to develop internationally applicable policies that respect the rights of individuals who may be vulnerable in scientific research

remains problematic.
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Overall, official international policies governing human subjects research promote cultural sensitivity in

obtaining informed consent without losing sight of the importance of individual autonomy and freedom of

choice (see e.g., ICH 1996; WHO 1998; WHO/CIOMS 1993). Brody (1998) contends that guidelines such as

those espoused by WHO/CIOMS (1993) strengthen a commitment to transcending cross-cultural differences

by mandating that research subjects from developing countries be told everything that would be told to

research subjects in an industrialized country and that they be advised of their right of refusal. Thus, a tribal

chief, village elder, or community leader may express approval of a research agenda, but sensitivity to cultural

customs is secondary to honoring individual choice (Macklin 1999). Paradoxically, community “consent” to

research may work either for or against the welfare of community members. In situations where research may

benefit individuals or the broader community, approval from local authorities would not be problematic.

However, in cases where the research is of questionable value or where the health and welfare of individuals is

at risk, approval from local authorities could actually threaten community well-being.

III. Case Study: Ethical Review of Research Protocols and Informed

Consent in Genetic Epidemiological Studies of Hypertension, Breast

Cancer, and Diabetes Mellitus in Nigeria

A. Description of Case Study

The purpose of this case study is to document issues and challenges surrounding the process of institutional

ethical review and the application of informed consent in studies funded by the United States (National

Institutes of Health [NIH]) being conducted in Lagos, Ibadan, and Igbo-Ora, Nigeria, on the genetic and 

environmental determinants of hypertension, Type II diabetes, and breast cancer. These studies are part of the

NIH-funded collaborative research of the Chronic Disease Network. Genetic epidemiologists and physicians at

Loyola University of Chicago and physicians at the University Teaching Hospital in Lagos and the University

College Hospital in Ibadan have been actively engaged in these studies for more than ten years.

The case study was implemented April 4–15, 1999. Interviews were conducted with 19 individuals in

Nigeria: 5 physician/researchers, 1 psychologist/researcher, 10 research assistants, and 3 research participants.

These in-depth interviews took place in individual and group settings. A team meeting of researchers involved

in the Type II diabetes study in Lagos was also observed. Information obtained during interviews was recorded

by hand and transcribed; when possible, interviews were audio-taped and transcribed. Ethnographic field notes

were also recorded.

In-depth interviews were conducted using a modified version of the Interview Guideline for Researchers

developed by Dr. Jeremy Sugarman and members of Family Health International. This interview guide was

designed for Dr. Sugarman’s project involving site visits to eight countries to talk with investigators about their

experience with ethical issues related to the conduct of internationally funded health research (see, also in this

volume, Sugarman, Popkin, Fortney, and Rivera, International Perspectives on Protecting Human Research

Subjects). Data gathered during informal discussions with individuals were recorded in field notes.

Topics addressed in the interviews and informal discussions included the following: 1) formal structures for

ethical review of research protocols; 2) experience with the ethical review process; 3) challenges associated with

obtaining approval for implementation of the study; 4) issues surrounding the application of informed consent;

5) ethical issues involved in the process of data collection; and 6) the experience of informed consent from the

perspective of the research subjects. Interviews lasted approximately 60 to 90 minutes.

IRB approval for this study was obtained from Duke University. The Nigerian case study was included as an

amendment to the NBAC consultation project being implemented by Dr. Sugarman at Duke University.
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Results of this case study cannot be generalized because of the small sample size, the unique circumstances

of the study protocol, and the individual experiences of those involved in the implementation of the process of

ethical review and informed consent. However, the purpose of the case study is not to produce generalizable

results, but to generate questions and problems for further consideration and research.

B. Description of Research Projects

Hypertension Studies. In 1991, investigators received an NIH grant for the International Collaborative Study

of Hypertension in Blacks to examine the social and environmental determinants of the gradient of hypertension risk in West Africa, the Caribbean, and the United States. By 1994, this study had enrolled and examined

over 10,000 men and women ages 25 to 74 years from West Africa—Nigeria (with urban and rural sites—

Ibadan, Idere, and Igbo-Ora); Cameroon (with urban and rural sites); the Caribbean—Barbados, Jamaica, 

and St. Lucia; the United Kingdom—Manchester (primarily migrants from the Caribbean); and the United

States—Maywood, Illinois. Participants in this study had blood draws and physical examinations as well as

interviews on family history of hypertension, medical history, and environmental risk factors for hypertension.

Collectively, the investigators have three additional NIH-funded research projects to study the genetic and

environmental determinants of blood pressure and hypertension in populations of the African Diaspora with

study sites in Nigeria, Jamaica, and the Chicago area. These ongoing genetic epidemiology studies so far have

enrolled and examined over 400 families in Nigeria (Ibadan and Igbo-Ora), 200 families in Jamaica (Spanish

Town), and over 300 African American families from the Chicago metropolitan area. These families have been

extensively characterized both at the molecular level (using candidate gene and genome wide scan approaches)

and at the phenotypic levels with special emphases to the renin-angiotensin system in relation to hypertension

and blood pressure regulation. Participants undergo blood draws and physical examinations and interviews on

family history of hypertension, medical history, and environmental risk factors for hypertension. Findings from

these family studies have formed the basis for several publications regarding the genetic epidemiology of common complex diseases in multiple African origin populations. 

Breast Cancer Studies. This project is an ongoing international collaboration between Nigerian and U.S.

investigators to study breast cancer genetics in blacks of African descent. The main objective of this research is

to identify high-risk alleles on two continents (Africa and North America). In Nigeria, over 200 breast cancer

patients have been enrolled in the study. Although this study is being implemented at the University College

Hospital in Ibadan, many patients come from other villages and cities because resources for cancer treatment

are not available in their home towns. The University College Hospital is a referral center for breast cancer

patients in this area. The study has provided useful information regarding the genetic epidemiology of breast

cancer in Nigerian women. For example, in Nigeria, the peak age of incidence of breast cancer is 43 years, at

least a decade earlier than in Anglo Americans. Fewer than 0.5 percent of U.S. breast cancer cases are younger

than 30, compared to 12 percent in Nigeria. 

The Diabetes Mellitus Study. This international collaborative study, initiated in 1997, examines genetic 

and environmental determinants of Type II diabetes in Nigeria (three sites: Enugu, Ibadan, Lagos) and Ghana

(two sites: Accra and Kumasi). The investigators are using an affected-sib pairs study design. One spouse of

either affected sibling is enrolled as the control. Participants undergo blood draws and a complete physical

examination. In addition, they are interviewed once during the study. To date, 250 affected pairs of siblings 

and 200 case controls have been enrolled. 

C. Institutional Ethical Review at Nigerian Study Sites

Nigerian investigators collaborating with foreign researchers must seek approval from local research ethics 

committees established at the institution sponsoring the research (e.g., universities, hospitals, and clinics).
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There is considerable variation in the implementation of the process for ethical review between institutions. In

Lagos, the diabetes mellitus study was reviewed by the research ethics committee at the University Teaching

Hospital. There are approximately nine members on this committee. The hypertension and breast cancer studies

were reviewed by the research ethics committee at the University of Ibadan through the University College

Hospital. Approximately ten members are included on this committee. Committee members at the University

Teaching Hospital in Lagos and the University College Hospital in Ibadan include faculty from various clinical

and basic science departments, one faculty member from a nonscience department, and community members.

D. Results of Interviews

Data were analyzed using standard techniques for qualitative research (Bernard 1994; Denzin and Lincoln

1994). In order to facilitate the integration of the final NBAC report, the major categories and themes are outlined following the scheme devised by Drs. Kass and Hyder in their analysis of focus group data: informed 

consent; other issues relating to respect for persons; host country IRBs; and moral responsibility and justice

issues. Four of the Kass/Hyder study categories are not included, because information on these topics was 

not systematically obtained (standard of care; U.S. IRBs; Office for Protection from Research Risks; defining

research). However, a thematic category addressing cultural beliefs about disease etiology and western biomedical treatments was added. These issues are discussed briefly, with examples from the interviews to illustrate concerns that were raised. Recommendations from the respondents on strategies to resolve dilemmas in

the application of the ethical review process and informed consent follow the report of findings for each

thematic category.

Hereafter, the terms “investigator” and “researcher” refer to the physicians and psychologist interviewed, and

the term “research assistant” refers to the research assistants working on the three different studies.

1. Informed Consent

Ethical challenges associated with obtaining and documenting informed consent were primary concerns for all

of the investigators and research assistants interviewed. Although this concern is not unique to research being

conducted in international settings, investigators involved in collaborative international research may encounter

significant challenges in their efforts to obtain informed consent because of cultural traditions, language barriers,

and structural factors surrounding the implementation of research. Five issues associated with the consent

process are addressed below: 1) informing participants and participant understanding; 2) disclosure of risk; 

3) autonomy and locus of decisional authority; 4) documentation; and 5) voluntariness

Informing Participants and Participant Understanding. A common concern expressed by the investigators and research assistants was the difficulty associated with language barriers. Translating an English consent form into Yoruba is often problematic because particular words may have no Yoruba equivalent. Moreover,

Nigerian investigators and research assistants interviewed suggested that the U.S. consent forms tend to be

lengthy and include information that may be confusing or alarming to patients. Additionally, the complexity of

consent forms produced for patients in the United States may hinder the translation from English to Yoruba. 

When investigators were asked about the process of translating an English document to Yoruba, they often

discussed problems associated with back translation (translating a document from one language to another 

and then having an independent native speaker back translate the document into the original language). One

physician noted the following:

Concepts are very important...we may not have the equivalent words...[and it’s hard] to 

communicate concepts...the second [problem] is when you read the direct translation 

[from English to Yoruba] it sounds funny...it’s grammatically correct, but it sounds funny.
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In this same group interview, another physician added that the direct translation may not be “culturally 

appropriate.” Several physicians reported an incident that occurred in which an English consent form was

translated into Yoruba, and then back translated by language experts at the university in Ibadan. When the

final document was used with potential subjects in the field, individuals had difficulty understanding it. It 

was necessary to revise the consent once more, so that it could be used effectively with subjects.

Investigators and research assistants also expressed concern about the difficulties associated with translating

genetic concepts into Yoruba. A physician involved in the diabetes mellitis study in Lagos reported the following:

We have to translate the informed consent to the local language. You tend to lose some 

quality because some words don’t have counterparts in Yoruba...like ‘genotyping’...[or other

words that have to do with] biotechnology...like ‘candidate genes.’ It’s difficult to get that

across....You have to go through this elaborate explanation process on how inheritance is 

governed...what factors are responsible for inheritance and how those factors can mediate 

the transmission [of certain diseases]. 

Another physician reported a similar frustration: “There’s no point saying ‘genotyping’ when he doesn’t speak

English! It’s rubbish! There’s no word in Yoruba for it!” A third physician reported that “...the issue of interpretation [and] translation...is so difficult...there is no Yoruba word for ‘gene.’”

One of the obstacles that investigators and research assistants identified is the relative lack of information

and public education on issues such as informed consent in medical research, and more specifically, on medical

issues such as genetic testing and screening. A physician involved in the breast cancer study noted that:

In the United States, [people] may pick up information [on breast cancer, on genetic risks, 

on the genome project]...from the media...but here...[people are not that familiar with these

things].

A physician involved in the diabetes study reported that the amount of time it takes to go through the consent

process is directly related to an individual’s educational background and his or her level of understanding

regarding some of the difficult medical concepts. However, when asked if research participants understand the

concept of inheritability, a physician replied, “To a large extent, yes...I think because of the prevalence of sickle

cell anemia they have some familiarity with inheritability.”

In a discussion with a physician involved in the diabetes research and one of his patients who is participating in the study, I asked the patient directly how the concept of “genes” was explained to him. He did not

understand my question. The following interaction occurred between me and the physician when the patient

could not respond:

Physician: “...it was explained [genotyping]...he blocked it out [because it is not meaningful to him].”

Marshall: “How do you explain it?”

Physician: “I say genes are what you inherit from your mother and your father. They understand that—

[that genes refer to] what comes from your mother and father...to make you who you are. If you

ask him that way then he’ll understand what you’re talking about.”

Marshall: “Does anyone ask what a gene is?”

Physician: “Yes, and I tell them it’s what comes from their parents when they are born....”

Despite the patient’s inability or reluctance to describe what he was told about “genes” or the concept of

“inheritence,” when the physician asked the patient to tell me what he was told about the study, the patient

gave a very concise and detailed response indicating that he understood the basic purpose of the research and

what procedures would be done:
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You told me my brother also has diabetes [my brother was seen for a number of years for 

diabetes]...[You said] we are making a study on family diabetes. [If]...you have a brother or three

brothers [with diabetes...then we want to talk with you about a study]....Then he examined

me...[he said]...some people in America are suffering from diabetes too, and they are trying [to

understand how it works in families]. I said I would go to great lengths to be a participant in

the study...to help fellow Nigerians and beyond, to enable [the doctors to know more]...he said

he would take care of me medically by supplying drugs and he sends me to the eye specialist

to take care of my eyes....He said that [he would] be testing my fasting blood...[and that there

would be] urine tests, weight checks [and checks on my] electrolytes....

The importance of educating individuals and the community about the study and its specific purpose and

procedures was mentioned by all those interviewed. Investigators and research assistants noted that education

should begin at the community level, as indicated by the following interaction with several researchers who

discussed the process involved in community entry and community education:

Researcher 1: “You approach some person as a contact person...you often start with the local governance...we

need to obtain permission from them and we need their help to get to community leaders...they

need to work with community leaders...we spend time discussing [the study]...you have to

explain [it] fully.”

Researcher 2: “They are clear headed, they will sift it [sort it through]....”

Researcher 3: “They educate [help educate the others].”

Researcher 1: “If anything bad happens they lose face, and when you lose face you lose it, not only you, your

children and your generation...people have the memory of an elephant.”

In regard to educating individuals about the study, the investigators and research assistants described the

importance of allowing potential participants time to discuss the study with family members or others in the

community. Many also mentioned that it is very helpful to have something written such as an information sheet

or a brochure for people to take home with them. The following interaction with breast cancer researchers

illustrates this point:

Researcher 1: “The [consent] process is not so bad....There is a need for continual evaluation of the consent

process...[it’s] important to allow patients time to think about the study and discuss it with their

family.”

Researcher 2: “So if they had information that they could take home [maybe that] would improve [their

understanding].”

Marshall: “You mean something like a brochure?”

Researcher 1: “Our consent says [asks them] do they want to have it read to them.....They might be able to

read [themselves]...[or they can] get their children [to read it].”

Researcher 3: “[It would be good to have] something that explains what is cancer [the brochure] and what are

the advantages and disadvantages of having the gene test.”

A research assistant working on the hypertension study reiterated the importance of discussing the study

with family members for some individuals:

Usually [what we focus our education on] depends upon what part [of the consent] they don’t

understand. Like they might say what [are the] benefits for me....We explain that they might

not personally benefit, but others may say, ‘what’s in it for me?’...Others say, ‘I need to talk to

the head of the family.’
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In summary, the investigators and research assistants interviewed expressed serious concerns about difficulties associated with the translation of the consent forms from English to Yoruba. Specifically, they noted 

difficulties with the translation of words for which there are no Yoruba equivalents and with communicating difficult scientific concepts in the field of genetics. They also stressed the importance of educating both the community and individual participants. They noted that education at the community level may begin long before

the project is initiated through extensive interaction with community leaders in which local people are invited

to participate in discussions of the study goals and strategies for implementation. 

Disclosure of Risks in Informed Consent. Investigators and research assistants commented specifically 

on the informed consent documents for the genetic research and what they perceived to be the inclusion of

extraneous, irrelevant, or culturally inappropriate information. They called attention to the emphasis placed 

on explaining the potential risks to study participants, noting that in the United States there is much greater

concern about communicating the possibility of harm to research subjects. One physician said that patients

may be alarmed by addressing all possible risks associated with the research:

Look, [say] you’ve been my patient for 30 years. [A patient might say] ‘You’re telling me I’m

going to faint when you take my blood? Why are you telling me I’m going to die?’...I look at

what are the essential parts [of informed consent]. You introduce the subject...make sure you

know what we are trying to achieve, what will be done to the patient, what participation in

the study will require of him, the risks and benefits to him...you have to talk about both...

[but] if I make a mountain out of a molehill [then it’s not going to work]. There are not many

risks [in this study]...so I’d scare them if [I talked a lot about risks].

Another physician made a similar point:

I said it [the informed consent document] was fine for America, but it could be counterproductive here...it needs to be adapted to us. You don’t say ‘I’m going to give you a ride in the

car’...you could have an accident or a stroke...you need to say ‘I’m going to get you there.’

Maybe, ‘I’m going to get you there safely’ and then maybe, ‘God forbid we will not have an

accident.’ Think positive! I had to think of my environment [when adapting the informed 

consent document].

When asked about differences between the United States and Nigeria concerning beliefs about what potential

subjects might want to know regarding risks, a physician described the experience of a resident obtaining consent for surgical procedures:

[In the United States, we say things like]...‘You may die...this may not benefit you.’ I had a 

resident who was keen on informed consent. She would tell patients that they could die. [She

would tell them this] pre-op [before they went into surgery]...and they would say, ‘Why are you

telling me I could die!?’ They [the patients] thoroughly abused her. We [Nigerians] don’t like

to talk about it. It makes it more important...it distorts the importance [of the risk of dying].

Physicians working on the breast cancer study held a focus group with breast cancer patients not involved

in the study to learn more about what kinds of concerns they would have about participating in the research. 

A research assistant on this project stated the following:

Most had a common perspective...[they would participate] even if the research did not benefit

them, they were willing to participate as long [as] we could give them reassurances [that they

would not be harmed]...[then] they had no concerns.
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The physician and research assistants involved in the breast cancer project also reported that focus group 

members expressed some anxiety about the use of blood:

They want to know the importance of taking blood, and [we say] that it is to look at the 

mutations in the blood.

Many of the investigators and research assistants interviewed indicated that patients might be fearful about

risks associated with blood draws. As the following interaction with an investigator suggests, one of the concerns that patients have relates to how the loss of blood will affect their ability to function: 

Marshall: “How do you communicate the risks involved in the study?”

Researcher: “...[we] tell them about the procedures...[that we will be] drawing blood. They know that by

taking blood...[it might] involve some discomfort.”

Marshall: “Do the patients ask questions?”

Researcher: “Yes, [they want to know] if the amount of blood will affect how they function afterwards.”

More information on concerns related to blood draws is reported in the section on cultural beliefs that impact

the informed consent process.

A number of investigators mentioned challenges associated with communicating the concept of risk to

potential subjects, noting that in Nigeria many people are not exposed to the extensive media attention given to

health risks in the United States. The following interaction with a physician (Researcher 1) and two research

assistants (Researchers 2, 3) illustrates this point:

Researcher 1: “In the United States, the community is pretty literate. [They know whether] something is a

risk...I think what people [here] don’t understand is what risk is...like...here is an example...a

woman says ‘What are my chances [of surviving cancer]?’ I might say that 85 percent are alive

five years later and she’ll say, ‘So I have a risk of dying of 15 percent?’ and I say no...[and

explain]....They are illiterate [about risk]....We [in Nigeria] are not yet at the stage where [concepts of risk] are more common knowledge.”

Researcher 2: “[It’s difficult] to communicate what is a gene test...why we’re doing it—genetic testing.”

Researcher 1: “The advantage [in the United States] is the amount of [media] information is more....Some

patients here deny the risk of cancer...maybe their religious group says [to them] ‘God says I

can’t have cancer.’ At that level, it’s difficult to get through [the idea] of genetic risk. We need to

develop [a] literature [for patients]. It’s easy to say, ‘We’ll send [you] the results of the clinical trials

[for example, something from the drug company]. [But] it’s very sophisticated [information]. 

We need to develop appropriate educational brochures [to provide] information for patients.”

Researcher 3: “[It is hard] to come down to their level. You have to explain it right.”

Many investigators and research assistants emphasized the importance of the patient’s trust in his or her

physician and the impact this has on the patient’s willingness to participate in a proposed research project. 

The investigators called attention to the power they have because of their professional status and authority. 

One physician, describing his influence over patients, said pointedly, “Look, I am in a commanding position

[because I am their doctor].” This physician noted that one of his patients was eager to participate and not 

concerned about risks associated with the study because of their relationship and because of the patient’s 

experience working in the radiology department of the hospital for 36 years:

Now, he has experience [with the hospital, with health care issues] so he will play down 

the risks.
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The patient supported his physician’s claims, saying:

I have known him [the doctor] for a few years. I agree to follow him. He said he is going to

make me well...and that he will give me drugs [for my diabetes]....Nothing will happen to me

[in the study]....There is nothing to fear [about the blood draw].

Community trust in the research team was emphasized by many of the investigators and research assistants.

When asked during an interview if patients were concerned about risks associated with the study, one research

assistant noted the following:

Yes...but if you assure them [that risks are minimal]...[then it’s usually okay]...and since they

know us in the community then they trust us.

In summary, information included in informed consent documents about risks associated with study procedures was a major concern for investigators and research assistants. They believe that in the United States there

is a much greater emphasis on reporting risks. Additionally, they highlighted the importance of trust between

the physician and patient and the powerful effect this has on an individual’s willingness to participate in a

study, regardless of the risks involved. 

Autonomy and Locus of Decisional Authority. An important area of concern for the investigators and

research assistants was the issue of individual consent, as it is generally expressed in the West, and the notion

of community consent, as it is understood in settings like Nigeria, particularly in the more rural areas. One

physician noted that, “Life here is still very communal. The basic unit is not the nuclear family, but the

extended family.”

The investigators, research assistants, and two of the rural study participants interviewed provided a description of what is meant by obtaining consent to conduct a study from community leaders, specifically, local tribal

Chiefs. In the following transcript, a physician from the city of Lagos describes this process:

Researcher: “To enter [a] community you need to carry that community along with you. There are imperatives....[You must communicate] with the Chief and his council and some others from the community [community leaders]....The individualism that exists in the West does not exist here. I

cannot go to a village and start doing something. I need to go to the local leader...the Chief [I

might go to him] with kola nuts or whiskey...they [Chiefs] appreciate it, they expect it.”

Marshall: “Do you go to the Chief by yourself, or with others?”

Researcher: “[You] go with local people and they do the introduction and sometimes you might not even

speak the local language...[and they explain the study, what it is about, what is needed] and then

he says ‘Fine, you can do this.’ Then he goes to the local people and says Dr. X is here to do this,

give him cooperation.”

Marshall: “Can you tell me more about community consent? How that works?”

Researcher: “There are really two levels. One is community and the other is individual. [The community

consent is somewhat like getting approval from the IRB...you can’t do the research without

approval.] When you leave [the Chief], the Chief is expected to open households, so there is

really another level of consent [in between]...the Chief and council, the household head, then

the individual.”

Marshall: “If the Chief approves, then how will the community respond?”

Researcher: “Most of the time they agree [to participate], when you have the conversation with the Chief and

[he communicates to] household heads. You are likely to get approval.”
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A similar description of community consent and the importance of obtaining approval from local tribal 

leaders was given by investigators, research assistants, and research participants at the rural sites. For example,

according to a member of the research team in Ibadan, “Community consent is very important in Igbo-Ora 

and Idere.” In a group discussion with team members in Igbo-Ora, investigators and research assistants were

asked how the chief communicates his approval or disapproval of the research project to the local population.

A research assistant explained, “You know, we have sub-Chiefs. These [senior Chiefs] will take it to their 

household heads and from there [the household heads] will take it to each family. The other way is with a town

crier.” When asked how the information is communicated through a town crier, this individual replied as follows: 

That person [the town crier] goes to the street [to the neighborhoods or maybe the town 

center] and he has a big bell, a gong, and he bangs on it and people in the neighborhood 

will come and he’ll announce [the message] and then go to a different neighborhood. 

In some cases, the town crier might go to 20 or 30 locations to make his announcement. Members of the

research team were asked what the town crier actually says in these announcements. A research assistant said,

“It goes in the form of an instruction from the Chief [like...he’ll explain the study] and say ‘We want people to

cooperate with them’ [the researchers].”

When asked if a Chief will usually approve of studies, a research assistant involved with the rural study sites

reported, “It could go either way, but [in the hypertension study] the case was well presented and in general

these people are well educated and especially when there [is evidence of concern for] the good of the community, there is usually approval.” Another research assistant agreed, adding, “Especially when they know [you],

when they are associated with medical management.” This theme was also addressed by a third research assistant who commented on the fact that the Chief and the local community are likely to be receptive to a study,

“When they are familiar [with us].” Nevertheless, as the following statement made by one of the physicians

indicates, respect for individual autonomy is still considered to be very important:

Don’t get it wrong, even if a [big leader] says [yes]...an individual can still say no.

A similar statement was made by another research assistant:

You have your own self opinion, so you can think on your own. Some people like it, 

some don’t.

However, when asked specifically if anyone goes against the Chief’s decision, one research assistant replied,

“Usually not many, but [sometimes].” Acknowledging the power of the Chief’s permission to conduct a study,

another research assistant reported: 

Some people couldn’t be bothered [with the study]...but it [the study] would not be successful

at all without his [the Chief’s] approval.

When the issue of obtaining permission from a household head to participate in a study was explored with

one research assistant, she reported that:

[They] might need permission, but some are buying time. Some don’t know for sure if they

want to join the study [and they want to talk to the household head about it]. If they ask you

to come back the next day and then you go back and they say the head of the house is gone

for a week or something then you know they are not interested.

Several investigators discussed the practice of gift exchange between the local Chief and the researchers 

proposing a study. The following interaction addresses this issue:
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Researcher 1: “Usually, if the Chief thinks that it [the study] is beneficial they will give you a gift.”

Marshall: “What kind of gifts?”

Researcher 2: “A goat, a chicken....The tradition is that when you go to see the ruler, you bring a whiskey or a

brandy, or kola nuts, but not because it’s research, but because it’s what you do anytime you visit

at all [visit the Chief]. In the southwest you don’t have to give but [here] it would be considered

[appropriate to give a gift].”

All of the investigators and research assistants interviewed commented on differences between the rural and

urban areas regarding the importance of obtaining permission from local community leaders such as tribal

chiefs. When asked if the process of obtaining consent in urban settings was different from the consent process

in rural settings, one of the physicians stated the following: 

Yes, because people [in urban areas] immigrated from various parts of Nigeria, so they, to a

large extent, they can decide what to participate [in] and what not to. But in particular households, if the head of the household does not agree then they might not be able [to participate].

Another physician agreed with this assessment:

In the rural area, community consent is stronger than the urban area. In Ibadan, some neighborhoods have traditional [leadership], some modern, some have a traditional Chief and the

community structure still holds.

Many of the investigators and research assistants interviewed called attention to the need for foreign

researchers to understand cultural traditions concerning the importance of the community and extended family

relationships when implementing a study in Nigeria. A physician noted pointedly, “You need to respect local

ethics.” A physician involved in the breast cancer study noted that cancer patients often need the approval of

the husband to participate. He emphasized that, in these cases, the woman’s individual consent was essential,

but that their research team supported a patient’s wish to discuss the study with her husband and other family

members. Indeed, most investigators and research assistants reported strategies that accommodated and

encouraged discussion regarding study participation with family members. In the hypertension study, for 

example, the study is described to patients and they are given information to take home. An appointment is 

set for a later date to meet with the patient and obtain his or her consent.

Commenting on Western and non-Western views about ethics in relation to research, another physician

stated:

There are concepts that are universal, but you need to address the local context....There is an

inherent assumption that foreign ethical standards are superior.

One physician remarked that: 

I think there is a third alternative [to using local standards or foreign standards of ethics].

When foreign researchers work in my country then there should be a hybridization of both

local standards and international standards. What is most important from my perspective

would be the rights of the individual even if the client is not aware of these issues.

In summary, in Nigeria, in addition to obtaining informed consent from individual study participants, investigators working in some areas, particularly the more rural areas, must negotiate permission to conduct the

study from local community leaders, including tribal Chiefs. Findings from this case study indicate the need for

developing a strategy for informed consent that provides the opportunity to respect individual autonomy while

simultaneously showing deference for local traditions that demand particular attention to community elders. In
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the United States and elsewhere, researchers often pursue the support of community representatives in areas

where studies are being implemented. In some cases, interactions with these community leaders might involve

obtaining permission to conduct the study. However, the notion of community “consent” as it is expressed in

Nigeria, differs significantly from practices associated with community involvement in the United States. In

Nigeria, especially in rural areas and urban communities where traditional relationships are strong, there exist

well-defined protocols for obtaining permission from a tribal Chief to conduct a study. While the investigators

and research assistants interviewed in this case study emphasized that individuals have the right to refuse to

participate in a study even if a local leader has approved it, they suggest that most people will participate once

the study is endorsed. Thus, upholding the internationally agreed-upon standard for individual voluntary 

consent may be challenging for persons who are vulnerable because of their gender or their status in their

extended household or local community. 

Documentation. Many of the investigators and research assistants commented on problems related to

requirements for documentation of informed consent by U.S. funding agencies. They were particularly concerned about two issues: first, the length and complexity of informed consent documents; and second, the

need for written consent. These issues were perceived as obstacles for those attempting to obtain consent from

potential study participants. They were also viewed as possible impediments to participant understanding. 

For example, one physician called attention to the problem of overwhelming individuals with too much 

information for them realistically to be able to understand:

Apart from the sheer amount [of information], the content of the information...[it’s] too

much...[and it’s] not meaningful to have so much information presented to the patient. We 

go for the principles. It’s confidential, it’s voluntary, and [we talk about] risks and benefits. 

The difference [between what we would do and what we have to do to meet the U.S. requirements] lies in the amount of background and scientific information you put in there [the

informed consent document].

In his discussion of the ineffectiveness of lengthy documents and the barriers to effective communication they

create, another investigator stated:

At the end of the day, you can’t read a five-page document, so you need to make it smaller...

[you use] bullets [you highlight the important parts].

Expressing similar concerns about the complexity of long documents that attempt to describe concepts that

may be hard for some people to comprehend, a physician reported:

It’s not so much that it’s not necessary [the information]. It’s just that they can’t take all the

information] when their level of education is low.

In addition to concerns about the length and complexity of consent forms, many investigators and research

assistants described some of the difficulties surrounding requirements for written consent, particularly among

people who cannot read or write. One researcher noted the confusion that is sometimes expressed by individuals

who do not comprehend the need for their written signature in order to participate in a study:

Some [patients] don’t understand why we have informed consent. Sometimes [they ask] ‘Why

are you asking me to sign?’ They accept [the study] without needing to sign in writing.

When asked if he thought patients are less likely to participate if written consent is required, one physician

replied:

They won’t refuse to participate but [they] may refuse to sign [a written consent]....They will

[sign] after [we] explain it, that it [signing] is important, that it shows they understand [the

study and what they are consenting to].
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In a group interview, a research assistant noted that, “When people cannot read and write, then you get verbal consent [or get thumbprint].” Investigators and research assistants agreed that sometimes individuals may

have some anxiety about writing their signature or placing their thumbprint on a formal document because of

uncertainties about how the document may be used against them. As one of the research assistants indicated,

“They can get very suspicious.” An investigator concurred:

Even if they use a thumbprint, they [can] get suspicious. They can’t read so they wonder why

[you need their thumbprint]. It’s a big fear...the issue [has to do with] government documents.

[It’s threatening] because they don’t know what they are signing or what they might be ‘giving

away.’

A perception that individuals may be concerned about signing a document was also expressed by a physician

who noted that formality of the process might be intimidating for some people:

That formal process they consider unnecessary and sometimes they might [feel] threatened if

they have to sign [a written consent form]. [They might feel] there’s more to it than [simply

the study].

The challenges of meeting U.S. requirements for documentation of informed consent in international studies

is particularly problematic when study participants are illiterate and if they are reluctant to formalize a document with their signature or thumbprint because of previous experiences that resulted in their victimization

(e.g., loss of personal property or land) when “legal” documents were used against them.

Voluntariness. All of the investigators and research assistants interviewed recognized the importance of

obtaining individual voluntary consent to participate in scientific research. Several issues were raised concerning

challenges to voluntary consent, including a person’s ability to comprehend the goals of the study and the risks

involved and the vulnerability of patients to incentives such as the provision of money, drugs, or medical treatment. Investigators and research assistants also expressed concern about the power and authority of researchers

because of their professional background and social status and the affect this power has on obtaining voluntary

consent in research. A final challenge to voluntary consent noted by investigators and research assistants was

the impact of community pressure to participate in a study if it has been sanctioned by community elders such

as tribal Chiefs. 

When asked what he thought the strongest challenges were in obtaining informed consent from prospective

study participants, a physician noted:

The strongest challenge is philosophical...that I’m [actually] getting informed consent, that

participation is voluntary and that you’ve informed them to the point they can give informed

consent.

Another physician stated:

[You need to make sure to say] you are free to say no. I believe that anyone can understand

those [basic] elements in the consent.

The issue of professional power and patient vulnerability in relation to voluntary consent in medical

research was mentioned by many of the investigators and research assistants interviewed. For example, in his

discussion of patients’ understanding of the consent process, a physician suggested that it might be beneficial

to have a focus group to learn more about what would increase their level of comprehension. He highlighted

the power that investigators have in influencing voluntary participation because of their status and authority:
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What I would really like to do is administer an informed consent [document] to different people and then bring them together and ask what they felt about it and how they could be better

informed about it, and how we could be more involved in insuring that the point where we

got their signature they actually understand what you have explained without the ‘White Coat’

syndrome, without the power [issue].

The following observation made by a physician speaks directly to the vulnerability of patients and their 

reluctance to question or challenge physicians when the possibility of becoming involved in a clinical research

project is raised:

By the time a patient comes into the clinic or hospital he is a changed person. He is vulnerable,

just hoping [he will be okay]. The thing that we have to establish is that the human rights perspective is very different in Nigeria and the United States and that modulates your response. 

If you haven’t been brought up to question or challenge...[but to] accept circumstances, then I

think there is [less willingness to challenge].

Several investigators called attention to the need for patients to understand that they could withdraw from

the study, even after they agreed to participate. Despite the inclusion of this information in the consent discussion, researchers indicated that it was rare for individuals to withdraw from clinical studies, as noted by one of

the physicians:

Once they agree, they don’t drop out...except if they feel you have not met your own 

obligations, for example, then you may find that people are ‘turned off.’

Another investigator agreed, noting that as long as an individual receives medical treatment, it is unlikely they

will drop out of the study:

[One of the most important aspects of informed consent is to tell the person] that he doesn’t

have to participate, that he can pull out at any stage. [But] when a person is followed up and

given free treatment, they do not want to pull out of they study. [For example, this patient’s

brother was also in the study but he has not been back for follow up.] Some patients, if they

are only on a diet, they don’t come around again. But if they are on drugs, then they usually

don’t back out of the study. The early patients, in Phase I [of the research], I don’t see them so

much [because the study part is over, the free treatment is over].

Many of the investigators and research assistants interviewed discussed the issue of providing inducements

such as money, free drugs, medical care, or supplemental vitamins and medical supplies and the impact this

may have on voluntary participation in scientific research. One physician indicated that because patients are

informed fully of the study goals and what they receive if they agree to join a study, then there should not be a

problem:

Right now, the present state is adequate...[there is] no hiding of facts from them, [and there is]

not anything that would be an inducement [to participate].

The following interaction between two physicians calls attention to the issue of trust and incentives to participate

in the research:

Researcher 1: “The need to recognize their privacy [is important]...patients need to trust you. We need to give

them a choice [and] there [are not] going to be any inducements.”
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Researcher 2: “The issue of inducements can be very subtle. [Sometimes] a patient [may] think that what she

is doing is [trying] to please me, so sometimes you have got to be very professional. They are

not used to it. Then you may come across as cold. If you come across as friendly [then it’s easier

for them].”

When asked about modifications of the consent form to accommodate the local context, a physician commented on the issue of incentives:

Physician: “Occasionally we do [need to modify it]. There are several cultural things, for example, we don’t

as a rule offer incentives. We offer incentives, but we don’t include it in the informed consent.”

Marshall: “Why is that?”

Physician: “Because the needs are different [in different communities]. We tailor the document to fit the

needs of the community. For example, [when] we do studies in Ibadan, we say you will come

[to the clinic] and we’ll take some samples [e.g., tests], and we say we’ll provide transportation

fees and refreshments and vitamin supplements. In the rural area, we say we’re doing this study

so we can understand health care [whatever the problem is]. We offer explanations and we

might give them vitamin supplements [but they may not need transportation, etc.].”

Several physicians noted that offering money as an incentive to participate in studies could be considered

coercive under certain conditions:

Researcher 1: “Someone who offers $5.00 a week [to participate in their study], it could be coercive.”

Researcher 2: “In the hypertension study in Maywood [U.S.], they offer money. But here we can’t do that

because it would be coercive because people would be so poor [they would participate no 

matter what]. We do offer incentives [for example, vitamins, drugs, transportation], but we 

don’t tell them [they are incentives]....The real issue is this, if people participate, then it’s as if 

it’s only those people who need the money. They may feel obliged to do something, even if they

are not. [They might think] ‘I’ll have a desire to please you because I feel obligated’ [because of

the money].”

Researcher 1: “So you don’t drop me from the study or from the source of my money...instead of offering

money we offer tablets or public health, or referrals [to other doctors].”

When asked about the impact of a study being sanctioned by community leaders such as tribal Chiefs on

individual voluntary participation, a physician replied:

It’s important, but it’s difficult to measure what is voluntary. The scenario I just described,

when you have a central command system [the Chief...and council], and when you come with

what is perceived as an improvement to their life, it would be difficult [to know if consent is

voluntary] if the central command [Chief] says it [is good]. 

The importance of comprehension for voluntary consent was recognized by many of the investigators and

research assistants. One research assistant working on the hypertension study emphasized how potential study

participants are encouraged to take the consent form home to study it if they can read or to find someone who

can read it for them if they cannot: 

We tell them [to find] someone to read [the consent if they don’t read]...if they read [then they

can do it themselves]...so we [tell them] we didn’t force you. So they can take it to someone

even if they don’t read and then talk it over and then sign [with us later]. Most of the time this

is what they do.
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In summary, the investigators and research assistants agreed that an individual’s voluntary participation was

essential in conducting medical research. They emphasized the importance of personal trust in a physician or

investigator and the powerful influence this has on a patient’s willingness to participate. They also highlighted

the potential for coercion through the offer of monetary inducements and the provision of drugs, medical treatments, or other supplies. Finally, comprehension was considered key to an individual’s ability to voluntarily

consent to a study. Investigators and research assistants mentioned strategies developed to reinforce voluntary

consent such as explaining the study to a patient and encouraging him or her to review the consent form and

discuss the project with family members. 

2. Other Issues Related to Respect for Persons

Disclosure of Medical Information to Participants. The issue of disclosing or withholding medical information was discussed by several of the investigators and research assistants. They acknowledged that this is 

an important issue for physicians providing medical care when family members feel strongly about protecting

loved ones from what they perceive as emotionally distressing information. For example, a physician and

research assistants involved in the breast cancer study reported that often family members are reluctant to tell 

a patient that he or she has cancer because it is such a serious condition. One physician described an incident

in which a woman from a “high positioned family” did not know that she was being treated for breast cancer

because she was not told. However, most of the investigators indicated that they did not encounter problems

associated with medical disclosure in the genetic epidemiological studies they were conducting. They emphasized that it would be impossible to obtain voluntary consent from an individual without fully informing them

of the relevant medical information.

Confidentiality. The promise to respect privacy and confidentiality was perceived as an essential ingredient

of the informed consent discussion among the investigators and research assistants interviewed. Many

researchers commented on the tight-knit communities, neighborhoods, and families in Nigeria and the impact

this can have on an individual if information about participation in a study is inadvertently disclosed. In the

following interaction, for example, research assistants suggest that patients may be concerned about others

learning their medical status or test results:

Researcher 1: “Before we get informed consent, [we explain the study] and they may have concerns about

[how] it will affect other family members. Sometimes [they want to know tests results], and we

don’t have the results yet. They might be concerned about [whether] we are going to leak the

information about the tests outside the family.”

Researcher 2: “[They are concerned about] privacy.”

Marshall: “Are they concerned about privacy in the family?”

Researcher 2: “Sometimes they want to keep it from the [village].”

Researcher 1: “I think it’s the community...they don’t want the community to know.”

In another group discussion, research assistants stated similar concerns about respecting patient confidentiality:

Researcher 1: “Yes [confidentiality is important]. They don’t want anyone to know in the neighborhood [that

they are sick...or maybe that they are involved in the study].”

Researcher 2: “If they want to say something private they call you outside.”

Several investigators and research assistants noted that the importance of confidentiality varies depending

upon the nature of the specific study. One physician observed that in research on more controversial issues

such as HIV/AIDS, maintaining confidentiality was absolutely critical:
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[The importance of confidentiality] depends on the study. If I was doing a study on sexuality,

then if you want to get quality information, you need confidentiality all the time. For example,

if it was a study on HIV [confidentiality is essential]. But [with something like the diabetes

family study] then confidentiality is not so important. It depends on [medical] conditions that

have bearing on one’s integrity. For example, in this society, we like to think there are no

homosexuals or lesbians...[in these cases] you have to be careful!

Another investigator described the importance of confidentiality in relation to stigma that might be attached to

the disease being studied:

[With] sickle cell anemia, it’s serious. The thing is, even if you said you discovered a possible

cure, everyone would try it [no matter what] because it [the disease] is so stressful. Most

affected families are dislocated. Because [it’s so hard]...they have some terrible social and 

psychological problems. Some families break up because you have to have a healthy child

[sometimes you might need another wife to produce another child—hopefully without sickle

cell]. So a lot depends on the condition and how it is viewed. Hypertension doesn’t carry that

kind of stigma.

One of the patients involved in the diabetes study recognized that some people might be concerned about 

privacy in relation to their medical condition or participation in a research project, but he claimed that he was

not worried about this issue:

I have nothing to hide....I fill out the questionnaire....I want to speak for diabetes [I want to

do everything possible to make people feel more free to come forward when they are sick with

diabetes].

A physician commented on the need to explain confidentiality to potential research subjects in a way that

communicates clearly what is meant:

The word ‘confidentiality’ [may be] too much for some patients to understand. So it’s important

to use language that they understand, like ‘Information about you will not be spread around.’

3. Host Country IRBs

Nigerian investigators discussed administrative issues regarding the process of obtaining approval from ethical

review committees. Several investigators commented on the difficulties of responding to the requirements of

funding agencies in the United States and at local Nigerian institutions. They said it was particularly frustrating

to try to respond to what they perceived as inconsistent requirements for ethical review. A physician in Lagos

reported difficulties at many levels: dealing with the informed consent document itself, having to “fight with

Washington” to change the consent form, and then going through the process of making the form useful and

appropriate for his patients in Nigeria. In addition to adapting the consent document, this investigator was

frustrated with the administrative aspects of the process including the amount of paperwork and committee

negotiations: 

I had to produce all the documents for [our] IRB. They said it cannot be summarized. [I had

to make nine copies] for our IRB. I photocopied the entire document and sent it to the Chair

[of the IRB]. I told them in Washington I’m going to have problems [with the consent document]. [I revised it, then sent to our IRB.] I put it in the best language I could. 

He noted that his office had to bear the burden of the expense of making the copies for the IRB and assembling

the documents. This was difficult given the few resources available for copying and the lack of administrative

assistance.
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When asked whether they had encountered substantive problems in the review process with their local

IRBs, the investigators reported that the most serious challenges were making accommodations in the informed

consent. One physician observed:

No [we did not have difficulties]. We met the informed consent [requirements] and they

approved it. The protocol was no problem. We had to modify the informed consent, based on

our experience with patients.

Another physician indicated that dealing with the local IRB was not difficult, but that addressing the concerns

of Washington was more problematic:

With the IRB here [in Nigeria] there were no problems. But we did have administrative issues

with Washington, requests for modification of the informed consent [documents].

Several physicians expressed concerns about the possibility of overlooking some of the suggested modifications for consent forms because of the routing back and forth between U.S. and host researchers and their

IRBs, in addition to the U.S. funding agency. One physician described a situation in which they received IRB

approval for conducting a study from their institutional IRB. He went on to explain, “We sent it to [our colleagues in the United States] who sent it to NIH. They looked at the original consent [not ours] and they

wanted modifications on the original.” The U.S. investigators modified the consent form and sent it back to

their Nigerian colleagues who, according to the investigator, “gave it to the [local] IRB who approved it and

sent it back to NIH.” In situations like this, the physician questioned whether all of the modifications would

finally make it into the consent form actually used with patients because it would have gone through so

many iterations and levels of review.

Investigators reported that IRB requirements in the United States called for a more precise and formal way of

communicating information about a study. One physician said pointedly:

In the West...the language is too exact and legalistic.

Other investigator respondents suggested that regulatory agencies in the United States should make a greater

investment in the IRBs of host countries through training and the provision of materials and resources in order

to facilitate the smooth and effective review and implementation of research projects. Some researchers believed

that governmental funding agencies in the United States were often more interested in protecting themselves

from litigation, rather than in promoting high standards of ethical conduct. The following interaction between

several physicians illustrates some of the frustration with attempting to respond to requirements that appear to

be too “legalistic:”

Researcher 1: “They should deal more with the local IRB [more attention should be given to the local IRB].”

Researcher 2: “Especially in a collaborative study because this is when it gets really crazy with NIH.

Researchers from Ibadan send in a consent, and the NIH looks at it [and says] ‘see page 3, line 5’

and they are not in Ibadan. [The communication] is almost in a legalistic language.”

Researcher 1: “They [the NIH] are more interested in avoiding litigation.”

4. Moral Responsibility and Justice Issues

Many of the investigators interviewed expressed concern about issues related to human rights and the implementation of research in nations such as Nigeria that are resource poor. Investigators identified social and structural impediments that may hinder the effective application of what are considered to be international ethical

standards. One physician described the profound influence of poverty on an individual’s capacity to choose

freely and autonomously to participate in research:
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Because of the scarcity of everything [in Nigeria], to be talking about a choice [is questionable]...in the United States, you can ask questions, you can ask for a second opinion, but that

doesn’t happen here. We are challenged by [our] culture, by poverty, by lack of literacy, by

education of what basic rights a person has...[the] power [of these factors] is too awesome.

A physician commented specifically on the unequal access to resources between host country and U.S. collaborators that encourages a posture of acceptance to comply with what might be perceived as unnecessary or

culturally inappropriate requirements in order to conduct a research project. He was particularly troubled

about the rigorous standards of conduct applied to countries such as Nigeria when they were associated with

an unwillingness to follow through with study evaluation or support at the completion of a project:

There is the American system which requires us to do ‘xyz’ and that happens because they

don’t want to be responsible for things beyond the study. We are happy to do it because of the

resources we get, apart from what’s being asked. Also, there is the power issue in the donorrecipient relationship. If someone says here is $50,000 to do what you really want to do but

before I give it to you have to [fulfill these requirements], fine....[But] there may not be followup or monetary [investment beyond the study] or evaluation. And no one really knows how

we are applying [the regulations].

During individual and group interviews, investigators raised questions about the moral responsibility that

researchers have to study participants and the communities in which the research is conducted. They also 

considered the implications of their research agendas for national priorities. The investigators recognized the

stronger emphasis placed on individual rights in Western than in non-Western nations. In commenting on this

issue, one of the respondents emphasized that it was not necessary to polarize respect for the individual and

respect for the community, noting instead that both are essential and that in certain places in Nigeria it would

be virtually impossible to conduct ethical research without acknowledging the importance of individual 

autonomy within the context of community. In his discussion of the application of foreign and local ethical

standards, a physician suggested that both are significant, but that individual rights are paramount:

I think there is a third alternative [to using local standards or foreign standards of ethics].

When foreign researchers work in my country, then there should be a hybridization of both

local standards and international standards. What is most important from my perspective

would be the rights of the individual even if the client is not aware of these issues.

5. Cultural Beliefs About Disease Etiology and Biomedical Procedures

Cultural beliefs about disease etiology and the use of body tissue such as blood for harmful purposes were

thought to influence the informed consent process. The investigators and research assistants interviewed

emphasized the importance of understanding, respecting, and accommodating cultural traditions concerning

perceptions about the nature and cause of disease, beliefs about sorcery, and social relationships within the

extended families that may affect recruitment practices and informed consent. In his reflections on the need for

foreign investigators to respect the culture of the Yoruba people, a physician noted the following:

The way the informed consent is presented must be sensitive to the culture of the people. 

The Yoruba, despite different religious views, tend to view life and death as a continuum, so

death doesn’t have that sense of finality that it has in the West. When [you are] talking about

chronic disease and terminal illness, so much is influenced by cultural elements...expressions
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of religious [beliefs] and so on. Those influences are very strong, even though they don’t find

everyday expression.

Another physician commented on patients’ beliefs about chronic illness and its affect on an individual’s 

willingness to participate in the genetic epidemiological studies:

In this study, no one refused [to participate], because we’re dealing with a small number of

people [so far]. It’s not our patients who tend to [refuse]...but their siblings [who might]

refuse. They are reticent. Most people don’t know how to deal with chronic disease. Most 

people feel...[it can] be cured, so in the face of overwhelming disease they go into denial. They

believe it shouldn’t be happening...[They are] using traditional methods for a cure before they

come to you. They believe that the diabetes will go away, so accepting to participate in a

chronic disease study is like accepting defeat.

In some cases, cultural beliefs concerning the cause and treatment of disease may differ radically from

Western views about underlying disease etiology. When asked if he thought patients understood the nature of

the research, for example, a physician said:

To a large extent, yes, but communication within the power structure of the conversation [is

important]. It’s difficult for one to say if what you are saying is acceptable to the other, or

understood so they can make a decision. Indeed, what I worry about is whether we are really

informing them. We are talking to a society that does not believe in the germ theory of disease

so it’s difficult to explain. 

When asked to give an example, this physician replied:

If [a relative] dies suddenly they might believe the person was killed by sorcery. That’s a very

widely pervasive belief system. When you come from that background, when you talk

about...meningitis or malaria...which is common...you spend a lot of time educating them...or

you can use other people to educate them, to persuade them [so they understand the study].

Many of the investigators and research assistants described patients’ concerns related to beliefs about the use

of sorcery to inflict illness and disease on individuals. In describing beliefs about the cause of hypertension, for

example, a physician noted that some of his patients think that it might be due to sorcery:

Some people ask us what causes hypertension...whether it’s inherited or whether it’s caused by

someone thinking something [as in sorcery].

Similar views were expressed by research assistants in their description of patients’ understanding of the etiology

of hypertension:

Researcher 1: “Some people think it’s a new problem [hypertension] and we explain it’s not. [They think it’s

new] because people would suddenly [get sick] and people did not know [that it was finally

symptomatic].”

Researcher 2: “People did not know and would think it was caused by black medicine and they would drink

alcohol [and do other things that might not be good for them].”

Many of the investigators and research assistants described patients’ fears that blood drawn for laboratory

tests could be used to practice sorcery against them, as indicated in this observation made by a physician:
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When you collect biological specimens [such as blood], people believe you can bewitch 

people. If you need 10 ml [of blood], you can’t say that. You need to say [we will collect a]

tablespoon or teaspoon. [But] people don’t want to hear that.

A research assistant agreed, saying:

There are concerns about drawing too much blood. People are worried about the affect on

their health, and also what you are going to do with it [some might think it could be used for

sorcery]. 

The power associated with blood and the implications for study procedures involving blood draws was

mentioned repeatedly by many investigators and research assistants. The importance of cultural beliefs and 

values surrounding blood are revealed in the following interaction with three investigators:

Researcher 1: “When blood spills on the hand, or floor, or anywhere, patients get upset and [say] ‘That much

[blood]!?’ because [the blood] spreads.”

Researcher 2: “We think about blood in Yoruba in terms of sacrificial [rituals] or slaughter, but human blood is

much different to deal with in a neutral fashion.”

Researcher 3: “In fact, it can never be neutral because it’s alive.”

Investigators and research assistants highlighted beliefs concerning the negative impact of taking what is

believed to be large amounts of blood for testing. Researchers attempt to minimize the amount of blood necessary for study tests, as one of the physicians suggests:

[Patients say] ‘You are taking so much blood from me and how will it affect me?’ And I say,

‘You shouldn’t worry, you have so much and we are only taking just a little from you.’ We try

to explain in simple language what we do with the blood and that we will not use it in any

other way outside of the tests.

Several investigators and research assistants reported that patients are concerned about replacing the blood

that is taken for laboratory tests, as indicated in the following interaction between research assistants:

Researcher 1: “[They are] concerned...about how to replace the blood.”

Researcher 2: “[They] ask for a drug to [help] replace it [the blood], or [they ask] for money for food.”

Researcher 1: “But they will not ask for it directly...only indirectly.”

Researcher 3: “[They will say], ‘How are you going to replace [the blood]?”

Although investigators and research assistants reported that only a small number of patients refused to 

participate in the genetic studies because of questions concerning the use of their blood, they all agreed that

beliefs about the potential harm associated with the misuse of blood specimens could be a consideration in 

the decisionmaking process. The following interaction between two physicians illustrates the profound impact

these beliefs may have on informed consent and the successful implementation of a research project:

Researcher 1: “[Some] concepts are completely alien to people. For example, if you tell someone you are going

to take some blood, or you say they are going to die in the process [of doing the study], no one

can accept that. When you take someone’s body fluid, some people think you are taking a person’s goodness and that can [bring them] harm, even without you having done anything.”

Researcher 2: “This is especially true with blood.”
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Researcher 1: “Psychologically, people may begin to feel strange. We went to a do a village study on anemia

and we took [a very small amount] of blood from each child. After [we obtained] consent from

everyone, a mother came [to us] after a few days and said her children could not participate in

the study. [It happened in 1992], and this is a village where we’d been for years.”

Researcher 2: “[News spreads] and the study had to stop because other mothers pulled out [after they heard

that the one mother pulled her children out].”

Many of the investigators and research assistants commented on the importance of educating and reassuring

potential participants about the purpose for drawing blood and how it might be used. A physician noted:

[There is a problem] with blood drawing...[people may be] hesitant because of the amount of

blood. Most people believe that blood is so precious that any amount could be wasted. You

have to allay their fears and explain that the amount is insignificant.

An individual’s experience with blood draws and his or her educational background are believed to influence response to the need for blood tests associated with the genetic studies. Indeed, one of the patients was

asked during the interview if he had any questions about the study for the researchers when they obtained

informed consent from him. He replied:

I don’t ask any questions about the blood because I work here and I am familiar with what

they do with the blood. I am satisfied [with the study...with what happens to me...to my

blood].

Other cultural factors that influence recruitment strategies and informed consent are normative social practices associated with marriages involving multiple wives. In genetic epidemiological studies, investigators may

want to enroll family members who are genetically related to each other. When a man has more than one wife,

but researchers only want to recruit the wife who is genetically important to the study, they must navigate the

potentially disruptive social consequences for extended family households. The following interaction in a group

discussion illustrates this point:

Researcher 1: “[Speaking of recruiting individuals for the control sample] The wife of one of the patients, she

came willingly, but she’s motivated.”

Researcher 2: “This type of control is easier [to recruit] because they have experience [with diabetes...they are

more familiar with the problems].”

Researcher 1: “We need one control per family.”

Researcher 2: “[You might] go to a family and a man has three wives and you go to the youngest. She doesn’t

have kids yet, so theoretically she is not genetically related. So according to the requirements [it’s

not necessary to recruit her]. But you create a social problem...so we do it as a service [test her

for diabetes]. So if [there is a perception] that [it will be a problem in the family if the youngest

one is left out—the one with no children yet] go ahead and include her.”

Researcher 3: “But the senior wife may refuse [because of her age, or her husband may be concerned about her

age, her health and not want her tested].”

Researcher 2: “Try to explain why she’s a better control than the younger wife...she may understand why it’s

better to have the 60 year old rather than the [younger wife]...but no arm twisting!”

In summary, investigators and research assistants reported a number of cultural beliefs that may impact the

informed consent process and someone’s willingness to participate in scientific research. Specifically, beliefs

about the cause and expression of diseases such as hypertension and diabetes and beliefs about the practice of
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sorcery and the power of body fluids and tissues were identified as factors that influence a potential subject’s

comprehension of the study goals and their decision concerning participation. Moreover, social traditions such

as marriage customs in which men have more than one wife were also recognized as factors in recruiting 

participants for genetic epidemiological studies.

IV. Recommendations

Investigators and research assistants were asked about recommendations for changes in regulations for the ethical

review of research protocols, including requirements for informed consent and documentation. The following

recommendations include strategies used to overcome some of the obstacles they have encountered in their

research along with suggestions for future modifications in the implementation of policy governing ethical

review of research.

A. Informed Consent

Informing Participants and Participant Understanding. Investigators and research assistants expressed serious

concerns about difficulties associated with communication and comprehension in obtaining consent from 

participants. Specifically, they noted difficulties with the translation of English words for which there are no

equivalents and with communicating difficult scientific concepts. Additionally, they suggested that in the

United States, consent forms tend to be lengthy and complex and often include information that may be 

confusing to patients. 

In their recommendations, investigators and research assistants stressed the importance of educating both

the community and individual participants about the study and its specific purpose and procedures. They

noted that education at the community level may begin long before the project is initiated through extensive

interaction with community leaders in which local people are invited to participate in discussions of the study

goals and strategies for implementation. Community education should not be seen as a single event, but rather

as an ongoing process in which the community is kept aware of research activities and findings. Maintaining 

an open and interactive dialogue at the community level could take a variety of forms including, for example,

holding regularly scheduled meetings with local community leaders or tribal elders or distributing a newsletter

that provides information about the research project and its study team.

In regard to educating individuals about the study, the investigators and research assistants recommended

instituting strategies that allow participants time to discuss the study with family members or others in the

community. They noted that it is very helpful to have something written, such as an information sheet or a

brochure for people to take home with them. If patients do not read themselves, this gives them an opportunity

to find someone to read the information to them. Another recommendation is to establish a process for

informed consent that takes place over several encounters, not one. In the hypertension study, for example, 

the study is first explained to individuals at the clinic. They are provided with the consent form, and an

appointment is made to visit them at home at a later date. Consent for the study is obtained at the second

meeting. 

Another option for ensuring that potential subjects understand the nature and purpose of the study is to

assess their comprehension through a process of requesting feedback from them concerning the study goals

and risks. This could be accomplished by simply asking individuals to tell the person obtaining informed 

consent what is understood to be the purpose of the study and the risks involved. Investigators and research

assistants also emphasized that it would be important to get feedback on the crucial dimensions of voluntariness,

confidentiality, and the possibility of withdrawing from the study at any time.
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Disclosure of Risks in Informed Consent. Information included in informed consent documents about risks

associated with study procedures was a major concern for investigators and research assistants. They recognize

that in the United States there is much greater emphasis on communicating every possible harm to research

subjects. They noted that the language regarding risks is often extraneous, irrelevant, or culturally inappropriate.

They recommended that host country investigators should be allowed greater freedom to determine how to

report risks in a way that is culturally sensitive and appropriate without diminishing the significance of the

potential harms. They also emphasized the importance of providing strong reassurances about the procedures

in place to minimize risks to individuals.

Autonomy and Locus of Decisional Authority. Researchers working in some areas must negotiate

permission to conduct a study from local community leaders, including tribal Chiefs, in addition to obtaining

informed consent from individual study participants. Investigators and research assistants interviewed

emphasized the need for developing strategies for informed consent that respect individual autonomy while

simultaneously showing deference for local traditions that demand particular attention to community elders.

Well-defined protocols for obtaining permission from community elders to conduct a study exist in Nigeria 

and other countries where community approval is required. Foreign investigators should accommodate these

traditional community protocols. However, upholding the internationally agreed-upon standard for individual

voluntary consent may be challenging for persons who are vulnerable because of their gender or their status in

their extended household or local community. Investigators and research assistants recommended that patients

should be given considerable reassurances about their ability to refuse to participate and to withdraw if they

choose. Educating patients about study objectives and the informed consent process was considered to be an

essential aspect of reinforcing respect for individual autonomy in the context of community sanctions that may

encourage participation.

Documentation. Investigators and research assistants were concerned about two issues regarding requirements for documentation of informed consent by U.S. funding agencies: first, the length and complexity of

informed consent documents; and second, the need for written consent. They called attention to the problem

of overwhelming individuals with too much information for them to realistically comprehend. The challenges

of meeting U.S. requirements for documentation of informed consent in international studies is particularly

problematic when study participants are illiterate and if they are reluctant to formalize a document with their

signature or thumbprint because of previous experiences that resulted in their victimization such as losing 

personal property or land when “legal” documents were used against them. Investigators recommended that

regulatory agencies should allow greater freedom in developing consent forms that address the essential aspects

of the study and ethical standards for voluntary consent. 

Voluntariness. Four issues were raised concerning challenges to voluntary consent: 1) a person’s ability to

comprehend the goals of the study and the risks involved; 2) the vulnerability of patients to incentives such as

the provision of money, drugs, or medical treatment; 3) the power investigators have to influence a person’s

decision to participate because of their professional authority and social status; and 4) the impact of community

pressure to participate in a study if it has been sanctioned by community elders such as tribal Chiefs. 

Recommendations include the following: 1) establishing methods to ensure that individuals understand 

the study goals and procedures, such as providing thorough explanations of the research project; 2) providing 

written information about the study that individuals could read or have read to them; 3) requesting feedback

that demonstrates comprehension; 4) providing considerable opportunities for discussion with family members

or others; and 5) devising a process of informed consent that takes place over several encounters rather than

one. Investigators and research assistants also recommended offering incentives to participate that are not 

coercive given the sociocultural and economic environment. Educational efforts to increase individual and

community knowledge about the importance of voluntary consent were recommended to diminish the impact

of community sanctions.
C-33

B. Other Issues Related to Respect for Persons

Disclosure of Medical Information to Participants. The investigators and research assistants interviewed 

agreed that it would be impossible to obtain voluntary consent from an individual without fully informing him

or her of the relevant medical information. They acknowledged that disclosing or withholding medical information may be a consideration for physicians providing medical care when family members feel strongly about

protecting loved ones from distressing news. Nevertheless, they recommended that there should be no deviation

from the current standard regarding full disclosure of information in the consent discussion for participation in

research.

Confidentiality. Respect for privacy and confidentiality was perceived as an essential ethical practice in the

conduct of research. Investigators and research assistants commented on the possible negative consequences for

individuals if information about someone’s medical condition or study participation is inadvertently disclosed.

Specifically, they noted concerns about stigmatization in relation to certain types of illness and disease, such as

HIV/AIDS. They recommended that study participants should be provided with clear explanations and ongoing

reassurances (if necessary) about procedures in place to protect individual privacy.

C. Host Country IRBs

Investigators discussed two primary issues regarding the process of obtaining approval from local ethical review

committees. First, investigators commented on the difficulties of responding to what often are perceived as

inconsistent requirements of funding agencies in the United States and at local Nigerian institutions. Second,

investigators noted administrative difficulties associated with the bureaucracy and management of local IRBs.

Recommendations address capacity building for IRBs in host countries. Investigators suggest that regulatory

agencies should develop and provide training workshops for IRB committee members and that there should 

be a greater financial investment in providing materials and resources in order to facilitate the smooth and

effective review and implementation of research projects. Another recommendation concerns the possibility of

instituting and maintaining collaborative relationships between foreign and local IRBs.

D. Moral Responsibility and Justice Issues

Investigators expressed concern about issues related to human rights and the implementation of research in

nations such as Nigeria that are resource poor. Social and structural impediments that may hinder the effective

application of what are considered to be international ethical standards were identified. These include factors

such as poverty, illiteracy, and in some countries, the presence of dictatorial or authoritarian governmental

regimes that seriously diminish the expression of individual freedom. Another factor concerns the unequal

access to resources between host country and U.S. collaborators that may encourage a willingness to comply

with what might be perceived as unnecessary or culturally inappropriate requirements in order to conduct a

research project. 

While investigators acknowledged that these issues are daunting for individual researchers to address, they

recommended that every attempt should be made to encourage the protection of basic human rights, particularly in relation to enabling voluntary consent to participation in research. They recommended that host country

investigators should be included at all levels in the design and implementation of research projects. They also

recommended that host and foreign collaborators should consider carefully issues related to standard of care

and commitments of researchers to provide treatment for study participants once the project has ended. 

E. Cultural Beliefs About Disease Etiology and Biomedical Procedures

Cultural beliefs about disease etiology and the use of body tissue such as blood for harmful purposes were

thought to influence the informed consent process. Additionally, social traditions such as marriage customs 

in which men have more than one wife were also recognized as factors in recruiting participants for genetic

epidemiological studies. 
C-34

In their recommendations, the investigators and research assistants emphasized the importance of understanding, respecting, and accommodating cultural traditions concerning perceptions about the nature and

cause of disease, beliefs about sorcery, and social relationships within the extended families that may affect

recruitment practices and informed consent. Specifically, they suggested that foreign researchers should become

knowledgeable about local customs, traditions, and beliefs that are relevant to the study goals. They recommended that potential research subjects should be provided with thorough explanations about the medical

conditions being researched. Strategies for implementing this recommendation include 1) allowing time in the

consent discussion for questions about the particular problem; 2) providing written information to participants

that they could read themselves or have read to them; and 3) ensuring that ample opportunities are available

for discussion of the study with family members or others (this may include obtaining consent in a two-step

process in which the study is explained and, at a later time, consent is obtained).

V. Conclusions

Results of the review of the literature and findings from the case study of genetic epidemiological research

being conducted in Nigeria suggest a number of obstacles to informed consent in international scientific 

investigations and ethical review of protocols at host country institutions. Although concerns about ethical

challenges to informed consent are not unique to research being conducted in international settings, investigators involved in collaborative studies may encounter difficulties because of cultural traditions and structural

factors that influence the implementation of research. 

The challenges associated with the application of informed consent are heightened in international settings

because of language barriers that may inhibit effective communication, particularly regarding the translation of

scientific concepts. Differences in beliefs about who has the authority to give permission to participate in

research may also create obstacles to obtaining individual voluntary consent. Securing study approval from

community leaders, tribal elders, or household heads is no substitute for individual consent, regardless of the

cultural setting. Nevertheless, it would be naive to assume that an individual is free from community pressures

or social customs regarding decisional authority. Thus, it is imperative to devise strategies for ensuring, to the

degree possible, that potential research subjects comprehend adequately the goals and risks associated with the

study and that their decision to participate is a choice, not a mandate.

Investigators and research assistants interviewed for the case study question the relevance of human subject

regulations that seem to be impediments to conducting ethically sound research. Specifically, they noted stringent requirements for including information on consent forms that may be superfluous, culturally inappropriate,

confusing and, in some cases, unnecessarily alarming for potential subjects. For example, in the United States,

the inclusion of a detailed description of all possible risks, regardless of how minimal, is emphasized. Moreover,

U.S. consent forms often are lengthy and complex. The investigators and research assistants noted that this

gives the appearance that funding agencies are more concerned about shielding themselves from future litigation

rather than protecting the individuals actually involved in studies. Thus, as Kass and Hyder (1999) and

Sugarman (1999) observe in their preliminary analyses of data collected in focus groups and interviews with

researchers involved in international studies, regulations serve bureaucratic purposes but do not necessarily

assist investigators in meeting ethically acceptable standards of conduct.
C-35

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D-1

COMPARATIVE ANALYSIS

OF INTERNATIONAL

DOCUMENTS ADDRESSING

THE PROTECTION OF

RESEARCH PARTICIPANTS

Staff Analysis

National Bioethics Advisory Commission
D-3

Introduction

This chart compares the texts of 25 documents that address the protection of research participants. The first

seven documents were developed by various international organizations and provide general guidance:

■ The Nuremberg Code (1947)

■ Declaration of Helsinki (2000)

■ Council of Europe – Convention for the Protection of Human Rights and Dignity of the Human Being with

Regard to the Application of Biology and Medicine (1997)

■ Council for International Organizations of Medical Sciences (CIOMS) – International Ethical Guidelines for

Biomedical Research Involving Human Subjects (1993)

■ Council for International Organizations of Medical Sciences (CIOMS) – International Guidelines for Ethical

Review of Epidemiological Studies (1991)

■ International Conference on Harmonisation (ICH) – Harmonised Tripartite Guideline, Guideline for Good

Clinical Practice (1996)

■ UNAIDS – Ethical Considerations in HIV Preventive Vaccine Research (2000)

The remaining 18 documents come from countries around the world and provide regulations or guidance 

specific to that country:

■ Australia – National Statement on Ethical Conduct in Research Involving Humans (1999)

■ Brazil – Resolutions 196/1996, 251/1997, and 292/1999 (1996–1999)

■ Canada – Tri-Council Policy Statement, Ethical Conduct for Research Involving Humans (1998)

■ China – Guidelines on Ethical Review of Medical Research (1998)

■ Denmark – Act on a Scientific Ethical Committee System and the Handling of Biomedical Research Subjects

(1992)

■ Finland – Decrees 494/1998 and 986/1999 (1992–1999)

■ France – Law 88-1138 Regarding the Protection of Persons Agreeing to Biomedical Research (1988)

■ India – Indian Council of Medical Research (ICMR), Ethical Guidelines on Biomedical Research Involving

Human Subjects (2000)

■ Netherlands – Law Regarding Medical-Scientific Research on Humans (1998)

■ New Zealand – Health Research Council (HRC), Guidelines on Ethics in Health Research (1997)

■ South Africa – Medical Research Council (MRC), Guidelines on Ethics for Medical Research (1993)

■ Thailand – Rule of the Medical Council on the Observance of Medical Ethics (1995)

■ Uganda – Guidelines for the Conduct of Health Research Involving Human Subjects in Uganda (1997)

■ United Kingdom – Medical Research Council (MRC), Guidelines for Good Clinical Practice in Clinical Trials

(1998)

■ United Kingdom – Medical Research Council (MRC), Interim Guidelines for Research Involving Human

Participants in Developing Societies, Ethical Guidelines for MRC-Sponsored Studies (1999)

■ United States – Food and Drug Administration (FDA)

■ United States – Common Rule

■ United States – Agency for International Development (USAID)

This chart is not intended to provide an exhaustive analysis of all 25 documents. Rather, it attempts to highlight similar and different provisions contained within them. 
D-4

Explanation of Chart Headings

The chart is divided into six parts:

Part 1. Informed Consent and Disclosure 

Informed Consent Process: One of the key protections for human participants participating in research is the

informed consent process. Every document has specified a need for the informed consent process. 

Voluntariness of Consent: All research participants should have the legal capacity to give their free and voluntary consent and not be subject to coercion or undue inducement by researchers to give consent. The language

in the documents reflect these concerns and attempt to delineate what is and what is not acceptable conduct. 

Disclosure to Research Participants: Essential to the informed consent process is the amount and type of

information that is disclosed to research participants prior to the start of the research study. The documents

include provisions that 1) require researchers to disclose certain elements to research participants and 

2) address a number of related concerns. 

Documentation and Other Protections: Although most organizations and countries require written informed

consent, the documents have language requiring varying degrees of documentation which is reflected in the

chart.

Exceptions and Waivers: Most documents have specified that exceptions and waivers to the informed 

consent requirements should be granted based on the type of research study being conducted, and have

included language in each document to reflect this concern.

Privacy and Confidentiality: The availability of powerful computers and the Internet has made accessing 

and sharing data less difficult. As a result, privacy and confidentiality concerns have become more prevalent.

Several documents have directly addressed this concern.

Part 2. Assessing Risks and Benefits

Risk/Potential Benefit Analysis: The other of the twin protections for human participants in research is 

independent review of the harms and benefits of the research. Every document has language that defines the

boundaries of acceptable risk to research participants and explains the process of assessing predictable harms

and foreseeable benefits.

Part 3. Selection of Participants and Distribution of Risks and Potential Benefits

Distributive Justice: In this context, distributive justice has been divided into three separate categories that vary

in focus. The first column includes provisions that prohibit the exclusion of certain groups from participating in

a research study. The second column includes provisions that require the equitable distribution of harms and

benefits among research participants. The third column includes provisions that require the equitable distribution of harms and benefits within and among communities. 

Special Protections: Almost every document has specified special groups that require additional protections

which have been incorporated into each document.

Part 4. Study Design Considerations

Prior Ethical and/or Scientific Review by Independent Body: The United States relies on the Institutional

Review Board (IRB) system to oversee protection of research participants at the local level. Other organizations

and countries have similar oversight mechanisms in place, which are reflected in the provisions of the documents.
D-5

Level of Treatment: The phrase “best proven diagnostic and therapeutic method” in the Declaration of

Helsinki has generated considerable discussion as to its meaning and implementation. Some documents have

either included similar language or referred to this phrase in the Declaration of Helsinki. 

Providing Research Results to Research Participants: This column refers not to publishing research results

in a peer-reviewed scholarly journal but to informing research participants, the local research community, and

the affected community-at-large of the research results.

Part 5. Obligations to Research Participants

Treatment and Compensation for Injured Research Participants: Many documents have provisions

(although varying in specificity) that require researchers and/or sponsors to provide compensation and 

treatment for research participants who are injured during the course of a research study.

Duty Owed to Research Participants During/After Trial: Several documents have provisions that explicitly

state the duty that researchers owe to research participants and the larger community during the course of and

after the conclusion of a research study.

Successful Products Made Reasonably Available: Several documents have provisions that researchers should

consider providing a therapeutic intervention to study participants after the research study has ended.

Part 6. Legal Considerations

Equivalent Protections (Harmonization of Standards): As the documents indicate, the scope of protection

for research participants at the international level is uneven, but attempts continue to harmonize these standards. For example, the International Conference on Harmonization (ICH) has made strides in developing a

common standard for the European Union, Japan, and the United States to facilitate the mutual acceptance of

clinical data. Other documents have provisions that attempt to provide equivalent protections when research is

conducted elsewhere.

Research and Review of Research Conducted in Other Countries: For international research projects, 

several documents require ethical review in both the country where the sponsor is located and in the country

where the research is to be carried out.

Have Force and Effect of Law?: The documents use a variety of words such as principle, guideline, law, 

and regulation. After reading the compliance and/or enforcement provisions contained in each document and

consulting outside experts, it was determined whether each document carried the same weight as the law of 

a particular country or group of countries.

Covers Privately-Funded Research?: The legal and ethical scope of each document is limited by the authority

granted to it. For example, United States regulations only cover federally-funded research, while the law in

Uganda explicitly covers all research regardless of whether it is publicly or privately funded.

Table Abbreviations

These are the abbreviations used in the table: CER = Committee on Ethics in Research; DSMB = Data Safety

Monitoring Board; GCP = Good Clinical Practice; HRC = Health Research Council; HREC = Human Research

Ethics Committee; IEC = Independent Ethics Committee; IND = Investigational New Drug Application;

IRB = Institutional Review Board; IRC = Institutional Review Committee; MOPH = Ministry of Public Health;

MRC = Medical Research Council; NHMRC = National Health and Medical Research Council; REB = Research

Ethics Board; RCT = Randomized Controlled Trial; UNCST = Uganda National Council for Science and

Technology
PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers ConfidentialityPrinciple 1 Principle 1 Principle 1

Nuremberg Code “The voluntary consent “... the person involved “... the person involved ... NOT MENTIONED NOT MENTIONED NOT MENTIONED(1947) of the human subject is should have legal should have sufficient

absolutely essential ...” capacity to give consent; knowledge and

should be so situated as comprehension of theto be able to exercise elements of the subjectfree power of choice, matter involved, as towithout the intervention enable him to make anof any element of force, understanding andfraud, deceit, duress, enlightened decision ...”over-reaching, or other ulterior form of 

constraint or coercion ...”

Principle 20 Principle 23 Principle 22 Principle 22 Principle 22 Principle 26

Declaration of “The subjects must be “When obtaining “... each potential subject “...After ensuring that the “...If the consent “... Every precaution should

Helsinki (2000) volunteers and informed informed consent for must be adequately subject has understood cannot be obtained in be taken to respect the

participants in the the research project the informed of the aims, the information, the writing, the non-written privacy of the subject, theresearch project.” physician should be methods, sources of physician should then consent must be formally confidentiality of the patient’s

particularly cautious if funding, any possible obtain the subject’s documented and information and to minimize

the subject is in a conflicts of interest, freely-given informed witnessed.” the impact of the study on the

dependent relationship institutional affiliations consent, preferably in subject’s physical and mental

to him or her or may of the researcher, the writing.” integrity and on the personalityconsent under duress ...” anticipated benefits and of the subject.”

potential risks of the study and the discomfort 

it may entail ...”

Article 5 Article 5 Article 16(v) Article 8 Article 10

Council of Europe “An intervention ... may NOT MENTIONED “... This person shall “... the necessary consent “When because of an “Everyone has the right to

(1997) only be carried out after beforehand be given as provided for ... has emergency situation the respect for private life in

the person concerned has appropriate information been given expressly, appropriate consent relation to information aboutgiven free and informed as to the purpose and specifically and is cannot be obtained, any his or her health.”

consent to it ... The nature of the intervention documented ...” medically necessaryperson concerned may as well as on its intervention may be “Everyone is entitled to knowfreely withdraw consent consequences and risks. carried out immediately any information collectedat any time.” The person concerned for the benefit of the about his or her health.

may freely withdraw health of the individual However, the wishes of theconsent at any time.” concerned.” individuals not to be so

informed shall be observed.

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

continued Article 16(iv) Article 9 “.... restrictions may be placed

Council of Europe “... persons undergoing “The previously by law on the exercise of the(1997) research have been expressed wishes related rights ... in the interests of the

informed of their to a medical intervention patient.”rights and safeguards by a patient who is not,prescribed by law for at the time of thetheir protection.” intervention, in a state to 

express his or her wishes shall be taken into 

account.”

Guideline 1 Guideline 4 Guideline 2 Guideline 3 Commentary on Guideline 12

Council for “... the investigator “Subjects may be paid “Before requesting an obligations of Guideline 1 “The investigator must 

International must obtain the for inconvenience and individual’s consent to investigators regarding “When the research establish secure safeguards

Organizations informed consent of the time spent, and should participate in research, informed consent: design involves no more of the confidentiality of of Medical Sciences prospective subject ...” be reimbursed for the investigator must documentation of than minimal risk ... and research data. Subjects should(CIOMS) (1993) expenses incurred, in provide the individual consent it is not practicable to be told of the limits to the

Guideline 3 connection with their with the following obtain informed consent investigators’ ability

obligations of participation in research; information, in language from each subject ... the to safeguard confidentiality

investigators regarding they may also receive that he or she is capable ethical review committee and of the anticipatedinformed consent: free medical services. of understanding: may waive some or all of consequences of breaches ofcontinuing consent However, the payments (9 criteria)” the elements of informed confidentiality.”

should not be so large or consent ...”

Guideline 8 the medical services so Guideline 3“Before undertaking extensive as to induce obligations of Guideline 9research involving prospective subjects to investigators regarding “For several types of 

subjects in consent to participate in informed consent: epidemiological researchunderdeveloped the research against their necessary information, individual informedcommunities, whether in better judgment opportunity to ask consent is eitherdeveloped or developing (“undue inducement”) ...” questions impracticable or

countries, the inadvisable. In suchinvestigator must ensure (see Guideline 3) cases the ethical review that: ... every effort will committee should

be made to secure the determine whether it isethical imperative that ethically acceptable tothe consent of individual proceed withoutsubjects be informed ...” individual informed

consent ...”

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers ConfidentialityPrinciple 1 Principle 10 Principle 1 Principle 2 Principle 3

Council for “When individuals “Prospective subjects “... Consent is informed NOT MENTIONED “An investigator who “An ethical issue may arise

International are to be subjects of may not feel free to when it is given by a proposes not to seek when occupational records,Organizations of epidemiological studies, refuse requests from person who understands informed consent has medical records, tissue samples,Medical Sciences their informed consent those who have power the purpose and nature the obligation to explain etc. are used for a purpose for(CIOMS) (1991) will usually be sought ...” or influence over them ... of the study, what to an ethical review which consent was not given ...

Investigators are expected participation in the study committee how the study Individuals ... should normally

Principle 2 to explain to the ethical requires the person to do would be ethical in its be told that their data might

“An investigator who review committee how and to risk, and what absence ...” be used in epidemiological

proposes not to seek they propose to neutralize benefits are intended studies ... when such 

informed consent has such apparent influence.” from the study.” information is to be used, 

the obligation to explain it is understood that to an ethical review Principle 11 investigators will minimize 

committee how the study “Individuals or disclosure of personally 

would be ethical in its communities should not sensitive information.”

absence ...” be pressured to

participate in a study. Principle 26

Principle 5 However, it can be hard “... investigators should make

“When it is not possible to draw the line between arrangements for protecting

to request informed exerting pressure or the confidentiality of such dataconsent from every offering inappropriate by, for example, omittingindividual studied, the inducements and creating information that might lead toagreement of a legitimate motivation ... the identification of individualrepresentative of a To determine the ethical subjects, or limiting access tocommunity or group propriety of such the data, or by other means ...”

may be sought, but the inducements, they mustrepresentative should be be assessed in light of thechosen according to the traditions of the culture.”nature, traditions and political philosophy of Principle 12

the community or group. “It is acceptable to repay

Approval given by a incurred expenses ...

community representative Similarly, promises ofshould be consistent with compensation and care

ethical principles ...” for damage, injury or

loss of income should not be considered 

inducements.”

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers ConfidentialityPrinciple 2.9 Principle 4.8.3 Principle 4.8.2 Principle 4.8.8 Principle 4.8.15 Principle 2.11

International “Freely given informed “Neither the investigator, “... The subject ... should “... the written informed “In emergency situations, “The confidentiality of records

Conference on consent should be nor the trial staff, shall be informed in a timely consent form should be when prior consent of that could identify subjectsHarmonisation obtained from every coerce or unduly influence manner if new information signed and personally the subject is not should be protected, respecting

(ICH) (1996) subject prior to clinical a subject to participate or becomes available that dated by the subject ... possible ... enrollment of the privacy and confidentiality

trial participation.” to continue to participate may be relevant to the and by the person who the subject should require rules in accordance with 

in a trial.” subject’s willingness to conducted the informed measures described in the the applicable regulatory

Principle 4.8.1 continue participation in consent discussion.” protocol and/or elsewhere, requirement(s).”

“In obtaining and the trial.” with documenteddocumenting informed approval/favourable

consent, the investigator... Principle 4.8.5 opinion by the IRB/IEC,

should adhere to GCP “The investigator ... to protect the rights,

and to the ethical should fully inform the safety, and well-being ofprinciples that have their subject ... of all pertinent the subject and to ensureorigin in the Declaration aspects of the trial ...” compliance withof Helsinki ...” acceptable regulatory

Principle 4.8.6 requirements.”

Principle 4.8.9 “The language used ... 

“If a subject is unable should be as non-technical

to read ... an impartial as practical and shouldwitness should be be understandable to thepresent during the subject ...”entire informed consent discussion ...” Principle 4.8.7

“Before informed consent may be obtained, the investigator ... should provide the subject ... ample time and opportunity to inquire about details ... and to decide whether or not toparticipate in the trial ...”Principle 4.8.1020 elements for written informed consent form

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers ConfidentialityGuidance Point 12 Guidance Point 10 Guidance Point 9

UNAIDS “Independent and “The research protocol “The nature, magnitude, NOT MENTIONED NOT MENTIONED NOT MENTIONED

(2000) informed consent ... should outline the and probability of all

should be obtained from benefits that persons potential harms resultingeach individual while participating in HIV from participation in abeing screened for preventive vaccine trials HIV preventive vaccine

eligibility for participation should experience as a trial should be specified

in an HIV preventive result of their in the research protocolvaccine trial and before participation. Care should as fully as can be

s/he is actually enrolled be taken so that these are reasonably done ...”in the trial ... Informed not presented in a wayconsent, with pre- and that unduly influences Guidance Point 12

post-test counselling, freedom of choice in “Independent and

should also be obtained participation.” informed consent basedfor any testing for HIV on complete, accurate,status conducted before, Guidance Point 12 and appropriately

during, and after the “... Efforts should be conveyed and understood

research.” taken to ensure information should be

throughout the trial that obtained from eachparticipants continue to individual ...”

understand and toparticipate freely as the 

trial progresses ...”

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Part 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers ConfidentialityPrinciple 1.7 Principle 1.7(b) Principle 1.7(a) Principle 1.9 Principle 1.11 Principle 1.19

Australia “Before research is “... obtaining consent “... obtaining consent “... research must be so “It is ethically acceptable “... research must strive

(1999) undertaken ... the should involve the should involve provision designed that each to conduct certain types to ensure that the privacy,

consent of the exercise of a voluntary to participants, at their participant’s consent is of research without confidentiality and cultural 

participants must be choice to participate.” level of comprehension, clearly established, obtaining consent from sensitivities of the participants

obtained ...” of information about whether by a signed participants in some and/or the collectivity are

Principle 1.10 the purpose, methods, form, return of a survey, circumstances, for respected ...”

Principle 1.8 “The consent of a person demands, risks, recorded agreement for example, the use of 

“A person may refuse to to participate in research inconveniences, interview or other de-identified data in Principle 12.11

participate in a research must not be subject to discomforts, and sufficient means ... In epidemiological research, “In a clinical trial ... (a) data

project and need give no any coercion, or to any possible outcomes of some circumstances and observational research in management should complyreasons nor justification inducement or influence the research ...” some communities, public places, or the use with relevant privacy

for that decision.” which could impair its consent is not only a of anonymous surveys.” requirements ...; (b) if data are

voluntary character.” Principle 1.12 matter of individual of a confidential nature,

“A participant must be agreement, but involves confidentiality must be

Principle 12.6(a) free at any time to other properly interested observed; (c) data and records

“An HREC must examine withdraw consent to parties ... In such cases must be preserved ... asthose aspects of the further involvement in the researcher needs to prescribed by laws of thebudgets of clinical trials the research. If any obtain the consent of all Commonwealth, the relevantwhich raise ethical consequences may arise properly interested State or Territory or nationalissues ... It should be from such withdrawal, parties before beginning policies or guidelines ...”

satisfied that payment advice must be given to the research.”in money or kind would participants about these Principle 18.1

not cause researchers to before consent to “An HREC must be satisfied

apply pressure to involvement in the that a research proposalindividuals so as to research is obtained.” conforms to all relevant

obtain their consent to Commonwealth, State orparticipate.” Territory privacy legislation

or codes of practice.”

Principle 18.2“An HREC must be satisfied that, where a research proposal involves the collection, storage, disclosure, or other use of personal information, the privacy of persons to whom that information relates is protected ...”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

Brazil (1996–1999)

Resolution No. 196/1996III.1.a“Ethics in research signifies freely given and informed consent of target-individuals and the protection ofvulnerable groups andthe legally disabled(autonomy) ...”III.3.h“Research involvinghuman subjects 

... must

... have the freely givenand informed consent ofthe research subject ...”IV“... research must onlybe carried out afterinformed consent hasbeen freely given by the prospective researchsubjects 

... who have

expressed their agreement to participate inthe research ...”

IV.3.e“... in communities with a different culture,including Indigenouscommunities, prior consent must be obtainedfrom the community,through its leaders, without foregoing, however, efforts to obtainindividual consent.”

Resolution No. 196/1996II.11“Freely given andinformed consent 

—

agreement of the researchsubject 

... without flaws

(simulation, fraud, orerror), dependency, subordination, or intimidation, after a completeand detailed explanationabout the nature of theresearch, its objectives,methods, foreseen benefits, potential risks 

...

set forth in a term ofconsent, authorizing thesubject’s voluntary participation in the research.”

IV.3.b“... freedom of consentmust be particularlyguaranteed to those individuals who, althoughadults and capable, areexposed to specific conditioning or to the influence of authority 

...

ensuring them completefreedom to participate,or not, in the research,without any retaliation.”IV.3.f“... when the merit of theresearch depends on somerestriction of informationto the subjects, such factmust be duly stated andjustified by the researchers... The data obtained 

...

cannot be used for purposes other than thosecontemplated ...”

Resolution No. 196/1996IV.1“Accessible languagemust be used in providing the prospective subjects informationabout the research,always including the following: (9 elements)”V.7“... The form used inobtaining the freelygiven and informed consent of the researchsubjects must not contain any clauseexempting the researcherfrom responsibility ordepriving any individualof his/her legal rights,including the right toseek an indemnity forinjury resulting from theresearch.”

Resolution No. 196/1996IV.2.c“The terms of freelygiven and informed consent must 

... be

signed by or identifiedwith the fingerprint ofeach and every researchsubject ...”

Resolution No. 196/1996IV.3.c“... in the event it isimpossible to record the freely given andinformed consent of the research subject,such fact must be dulydocumented, with anexplanation of the causes and the technicalopinion of theCommittee for Ethics in Research ...”

Resolution No. 196/1996III.3.i“Research involving humansubjects 

... must 

... plan 

procedures that will ensureconfidentiality and privacy,protection of the image and non-stigmatization of the research subjects, guaranteeing that the information obtained will not be used to the detrimentof individuals and/or communities ...”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

Canada (1998)

Article 2.1(a)“Research ... may beginonly if (1) prospectivesubjects ... have beengiven the opportunity togive free and informedconsent about participation, and (2) their freeand informed consenthas been given and ismaintained throughouttheir participation in theresearch.”

Article 2.2“Free and informed consent must be voluntarily given, without manipulation,undue influence, orcoercion.”Section 1.C1“... There is a similarthreshold regardingundue or excessive offersof benefit. As an offer of payment in relation to research participationexceeds the normalrange of benefits open to the research subject, it is increasingly likely to amount to an undueincentive for participation.”Article 2.4(d)“An assurance thatprospective subjects arefree not to participate,have the right to withdraw at any timewithout prejudice to pre-existing entitlements,and will be given continuing and meaningful opportunitiesfor deciding whether or not to continue toparticipate.”

Article 2.4“Researchers shall provide to prospectivesubjects ... full and frank disclosure of allinformation relevant tofree and informed consent. Throughout the free and informedconsent process, theresearcher must ensurethat prospective subjectsare given adequateopportunity to discussand contemplate their participation. (5 elements)”Commentary to Article 2.4“Research subjects 

...

may have cultural valuesdifferent from those of theresearcher 

... researchers

must clearly explain thenature and goals of theresearch 

... in a manner

appropriate for theprospective subjects’

cultural settings.”

(see Table 1 

—

additional informationthat may be required for some projects)

Article 2.1(b)“Evidence of free andinformed consent by the subject ... shouldordinarily be obtained inwriting. Where writtenconsent is culturallyunacceptable, or wherethere are good reasonsfor not recording consent in writing, the procedures used toseek free and informedconsent shall be documented.”

Article 2.1(c)“The REB may approve a consent procedurewhich does not include,or which alters, some orall of the elements ofinformed consent ... orwaive the requirementsto obtain informed consent, provided thatthe REB finds and documents that: (5 criteria)”Article 2.8“... research involvingemergency health situations shall be conducted only if itaddresses the emergencyneeds of individualsinvolved, and then onlyin accordance with criteria established inadvance of such researchby the REB. The REBmay allow research that involves healthemergencies to be carried out without the free and informedconsent of the subject ...if ALL of the followingapply: (6 criteria)”

Article 3.1“... researchers who intend tointerview a human subject tosecure identifiable personalinformation shall secure REBapproval for the interviewprocedure used and shallensure the free and informedconsent of the interviewee ...”Article 3.2“... researchers shall secureREB approval for obtainingidentifiable personal information about subjects.Approval for such researchshall include such considerations as: (8 considerations)”Article 3.3“If identifying information isinvolved, REB approval shallbe sought for secondary uses of data. Researchers may gain access to identifyinginformation if they havedemonstrated to the satisfaction of the REB that:(3 elements)”(see Articles 3.4, 3.5, 3.6)

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

China (1998)

Article 15“... only when theinformed consent signedby human subject isobtained, it can bejudged that the humansubject consents to participate ... when theprocedure or conditionof the research ischanged, the changemust be explained tohuman subjects in detail,and the consent must beobtained again fromthem.”

Article 17“Researcher should commit to give certaincompensation or freemedical services tohuman subjects, but the amount or servicesshould not constitute an inducement ...”Article 15“The researcher shouldrespect human subjects... must not use cheating, threat andother undue means tohuman subjects ...”

Article 15“The researcher shouldrespect human subjects.Sufficient time should begiven to human subjectsto ask questions or give answers ... must

provide adequate andrelevant information andknowledge to humansubjects and give themadequate time to consider, and then askthem to make decisionof whether to consent toparticipate ...”

Article 10“All biomedical research involvinghuman subjects mustobtain written informed consent from humansubjects ...”

NOT MENTIONED

Article 18“Perfect confidential measuresmust be taken to the researchmaterials. The researcher must not disclose anythinginvolving the privacy ofhuman subjects to media ...”

Denmark (1992)

Act No. 503 § 8Section 1“As a part of their evaluation of the committees will have to secure that: ... theirfree and explicit consentwill be obtained andgiven in writing.”

Act No. 503 § 8Section 5“If research subjectsreceive a salary or otherremuneration in returnfor their participation inthe study, the committeewill have to approvesuch remuneration and to control that it is not influencing theconsenting improperly.”

Act No. 503 § 8Section 1“As a part of their evaluation of the committees will have to secure that: ... thepatients or healthy volunteers participatingin the project will beinformed in writing and verbally about itscontent, foreseeable risks and advantages ...”Act No. 503 § 8 Section 4“As a part of their evaluation of the committees will have to secure that: ... it isobvious from the information sheets, that patients and healthyvolunteers ... at anytime can retract theirconsent.”

Act No. 503 § 8 Section 1“As a part of their evaluation of the committees will have to secure that: ... theirfree and explicit consentwill be obtained andgiven in writing.”

NOT MENTIONED(no exceptions orwaivers are permitted inDanish legislation)

NOT MENTIONED(Danish Council of Ethics has separate report entitled“Protection of PersonalSensitive Information”)

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

Finland (1992–1999)

Statute No. 488/1999Section 6“Medical research onpersons may not be conducted without theresearch subject’sinformed consent inwriting ...”

Statute No. 488/1999Section 21“No payment shall bemade for participating in the research to theresearch subjects 

...

However, an appropriateremuneration may bepaid in respect ofexpenses or loss of earnings or for any other inconvenience suffered as the result of the research.”

Statute No. 785/1992Section 5“A patient shall be giveninformation 

.... related

to his/her treatment thatare significant whendecisions are made onthe treatment given tohim/her 

... Health care

professionals should tryto give the informationin such a way that thepatient can understand it ...”

Statute No. 488/1999Section 6“Research subjects shallhave their rights, thepurpose and nature ofthe research and the procedures it involvesproperly explained tothem. The potential risksand harm shall also beproperly explained tothem. This informationshall be given so thatresearch subjects are in a position to give theirinformed consent asregards issues connectedwith the research thathave a bearing on theirdecision-making.”“Research subjects shallbe entitled to withdrawtheir consent at anypoint prior to the completion of theresearch. They shall beinformed of this rightbefore the start of theresearch.”

Statute No. 488/1999Section 6“Medical research onpersons may not be conducted without theresearch subject’sinformed consent inwriting ...”

Statute No. 488/1999Section 6“... Exceptions to thismay be made where consent cannot beobtained owing to theurgency of the matterand the patient’s state ofhealth and the measureis expected to be ofimmediate benefit to thepatient’s health ...”

Statute No. 785/1992Section 13“The information in patientdocuments is confidential.”“Health care professionals 

...

shall not give information in patient documents to outsiders without a writtenconsent of the patient.”Statute No. 488/1999Section 23“... Confidential informationobtained in the course ofactivities 

... and relating to

research plans, personal information concerning otherpersons, their state of health,personal circumstances orfinancial status or business or trade secrets, must not bedisclosed to a third party.”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

France (1988)

Title II, Article L. 209–9“... The investigator shall inform the personwhose consent is soughtthat he is entitled torefuse to participate inresearch and to revokehis consent at any timewithout incurring anypenalty ...”

Title I, Article L. 209–8“Biomedical researchshall not give rise to anyfinancial considerationother than reimbursement of expensesincurred ...”

Title II, Article L. 209–9“Before biomedicalresearch is conducted on a person, his free,informed, and expressconsent shall beobtained by the investigator ... who shall inform the personof: (3 elements)”

Title II, Article L. 209–9“... Consent shall begiven in writing, or, if it cannot be given inwriting, shall be witnessed by a thirdparty ... wholly independent of theinvestigator and or thesponsor.”

Title II, Article L. 209–9“... in biomedicalresearch to be carriedout in emergency situations ... the protocolsubmitted for the opinion of theCommittee ... may dispense with obtainingthe consent of the participant and requirethat only the consent ofany next of kin presentbe obtained ...”

NOT MENTIONED

India (2000)

General Principle 2“...The principles ofinformed consent andvoluntariness are cardinal principles to beobserved throughout ...the nature and form ofthe consent ... shalldepend upon the degreeand seriousness of theinvasiveness into theconcerned human subject’s person and privacy, health and life ... and the overall

purpose and the importance of theresearch.”

General Ethical Issue 1“For all biomedicalresearch involvinghuman subjects, theinvestigator must obtain the informed consent of the prospective subject ...”

General Principle 2“... research subjects are fully apprised of theresearch and the impactand risk of such researchon the research subjectand others; and ... retain

the right to abstain fromfurther participation inthe research irrespectiveof any legal or otherobligation ...”

General Ethical Issue 2 “The investigator has a duty to: exclude the possibility of unjustifieddeception, undue influence and intimidation; seek consent only afterprospective subject isadequately informed ...;not use intimidation in any form which invalidates informedconsent ...”

General Principle 3“[research subjects are] kept fully apprisedof all the dangers arising in and out of theresearch so that they can appreciate all thephysical and psychological risks as well as moral implications of the research ...”General Ethical Issue 3“... the investigator mustprovide the individualwith ... information inthe language he or she is able to understandwhich should not onlybe scientifically accuratebut should also be sensitive to their socialand cultural context: (15 elements)”

General Ethical Issue 3“The investigator has aduty to: ... obtain from

each prospective subjecta signed form as an evidence of informedconsent (writteninformed consent)preferably witnessed by a person not relatedwith the trial ...”

General Ethical Issue 1“When research designinvolves no more thanminimal risk ... the

Institutional EthicsCommittee may waiveoff some of the elementsof informed consent.Waiver of informed consent could also beconsidered during 

conditions of emergency.”

General Principle 4“... the identity and records of the human subjects ...are as far as possible kept confidential ...”General Ethical Issue 4“The investigator must safeguard the confidentialityof research data, which mightlead to the identification ofthe individual subjects.”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

continuedIndia (2000)

General Ethical Issue 2“The investigator has aduty to: communicatewith prospective subjectall the information necessary for informedconsent. There shouldnot be any restriction onsubject’s right to ask anyquestions related to thestudy ...”

General Ethical Issue 4 “Subjects may be paidfor the inconvenienceand time spent, andshould be reimbursedfor expenses incurred ...They may also receivefree medical services.However, paymentsshould not be so large or the medical servicesso extensive as to induceprospective subjects toconsent to participate in research against theirbetter judgement(inducement).”

General Ethical Issue 8Special Concern 5“The nature, magnitude,and probability of allforeseeable harms resulting from participation in a collaborativeresearch programmeshould be specified inthe research protocoland explained to theparticipants as fully ascan be reasonably done.”

Netherlands (1998)

Article 6.1a“Performing scientificresearch is prohibited ...if the experimental subject is of adult age ... without writtenpermission from theindividual involved.”Article 6.4“... The potential subject will be grantedsufficient time to makean informed decisionregarding the requestedpermission based on thisinformation.”

Article 3f“A commission may only grant a positivedecision on a researchprotocol if ... it is reasonably plausible that the compensation to be paid to the experimental subject isnot disproportionallyinfluential in the granting of approval for participation in theresearch ...”Article 5“Performing scientificresearch on experimentalsubjects about whom areasonable assumptionexists that they are not free to decide to participate in it ... is prohibited ...”

Article 6.3“Before permission isrequested, those who areperforming the researchensure that the personwhose permission isrequired receives writteninformation concerning:(4 elements)”Article 6.4“The information will be provided in such away that it is reasonablycertain that the partiesinvolved will completelyunderstand its contents ...”Article 6.5(researchers must informchildren under the age of 12 

... about the

research “in a manner in keeping with theircomprehension level”)

Article 6.1a“Performing scientificresearch is prohibited ...if the experimental subject is of adult age ...without written permission from theindividual involved.”

Article 6.2“If the scientific researchcan be carried out underan emergency situationin which the permissionrequired ... cannot begranted, and may benefitthe person ... actions forcarrying it out may takeplace without permissionas long as the circumstance that makes itimpossible to grant permission arises.”

Article 12“Those who are performingthe scientific research willensure that the personal life of the experimental subject is protected as much as possible.”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

continuedNetherlands (1998)

Article 9“... ensure that theexperimental subjectmay refer to a physicianindicated in the researchprotocol who is notinvolved in carrying out the research forinformation and adviceregarding the research.”Article 11“... ensure that theexperimental subject isinformed in good time... about the course ofthe research ...”

New Zealand (1997)

Chapter 3–Part A“In most cases researchconstitutes a health care procedure and, assuch, written informedconsent will be requiredunless there are goodreasons to the contrary.”

Chapter 3–Part B“Any payment ... to a

research participant ...which is an inducementto participate in researchis unacceptable.”

Chapter 3–Part A“... The participants’consent must be voluntary and not influencedby financial reward ...

or by duress in any manner ...”

Chapter 3–Part A“... Participants must beable to withdraw fromthe investigation at anytime without waiver ofany rights and withoutgiving reasons ...”

Chapter 4–Part B“Subjects have the rightto receive, in languagethat they will easilyunderstand, informationabout proposed researchin which they have beeninvited to participate.”Chapter 3–Part A“Elements of informedconsent include but are not limited to: ...Information about theproposed research being comprehensively,properly and appropriately given, includingany likely outcomes ofparticipation in theresearch ...”

Chapter 3–Part A“In most cases researchconstitutes a health care procedure and, assuch, written informedconsent will be requiredunless there are goodreasons to the contrary.”

Chapter 3–Part A“If consent is notobtained in writing thejustification should begiven to the reviewingethics committee, andthe circumstances underwhich consent wasobtained should berecorded. Ethics committees will berequired to consider ifthe circumstances areappropriate ones inwhich to waive writtenconsent.”

Chapter 3–Part C“6. The right of the researchsubject to safeguard his or her integrity must always berespected. Every precautionshould be taken to respect theprivacy of the subject and tominimise the impact of thestudy on the subject’s physical

and mental integrity and onthe personality of the subject.”

Chapter 6–Part A“The Health InformationPrivacy Code 1994 (HIPC) is the starting point for anyconsideration of the privacyissues which arise in healthresearch.”

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Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

South Africa (1993)

Chapter 8“For consent to be validit should be offered voluntarily and be based on adequateunderstanding, with dueregard to the patient’slanguage and culture.”

Chapter 6“There should ... be no coercion, overt orcovert, of anyone to volunteer for research,whether the pressure befinancial, for academic oremployment advantage,for job security, or forother reasons.”Chapter 9■ Inducements to

healthy volunteers

■ Inducements directed

towards patients

■ Offer of otherwise

unobtainable treatment

■ Offer of superior care

and attention

Chapter 7“The patient should beassured that if he agreesto participate in theresearch he will remainfree to withdraw at anytime, that no reasonneed be given for thewithdrawal, and thatwithdrawal will beaccepted without question, without incurring displeasureand without any disadvantage to futurecare.”Chapter 8“If there is more thanminimal risk, thesemeasures are mandatory:a subject informationsheet [8 elements]; time to reflect; ... aresponsible third partymay act as an adviser to the patient ...”

Chapter 8“Where comprehensionof the research by thesubject is not straightforward ... the simpleprocedure of seekingoral consent after an oral explanation mayneed to be supported byadditional measures ...If there is more thanminimal risk, thesemeasures are mandatory:... written consent ...witnessed consent maybe a useful alternative inpatients with impairedcapacity to comprehend.”

Chapter 8“There are some circumstances in whichit is justifiable to initiateresearch without theconsent of the patient.Prior approval of theResearch EthicsCommittee must beobtained in all cases.”Chapter 8“Some research is without intrusiveness orrisk and may justifiablybe conducted withoutthe patient’s consent ...”

Chapter 7“Investigators should be aware of the dangers of releasing confidential information about patientsparticipating in a study to any third party, unless thepatient ... has consented to this.”Chapter 11“It is essential that informationabout a patient acquired inthe course of research shouldbe regarded as completelyconfidential ... Sensible 

precautions should be takento preserve confidentiality.”

Chapter 19“The records of thepatient/subject should at all times be treated as confidential.”

Thailand (1995)

# 4“The subject ... musthave agreed to the studyby signing the consentform after being properlyinformed. The consentform should follow theMOPH requirement.”

NOT MENTIONED

# 6“Researchers have to explain clearly to potential subjects: (5 elements)”# 10“Subjects ... are free towithdraw the consent toparticipate in the study.The withdrawal will notaffect any entitlement tothose treatments thatmay be required undernormal circumstances.”

# 4“The subject ... musthave agreed to the studyby signing the consentform after being properlyinformed. The consentform should follow theMOPH requirement.”

NOT MENTIONED NOT MENTIONED

D-19
PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

Uganda (1997)

III.E.(4)“Informed consent willbe sought from eachindividual prospectiveresearch participant ...”IV.A.“... no investigator mayinvolve a human beingas a subject in researchunless the investigatorhas obtained the legallyeffective informed consent of the individualresearch participant ... a community leader may not consent to the participation of community members ...”(9 required and 6optional elements)IV.H.(3)privacy exception to written informed consent form

IV.A“... An investigator shallseek such consent undercircumstances that provide the prospectiveresearch participant ...sufficient opportunity toconsider whether or notto participate and thatminimize the possibilityof coercion or undueinfluence ...”

IV.A“.... The information ...shall be in languageunderstandable to theresearch participant ...whether it is conveyedorally or in writing ...”

III.E.(5)“Informed consent will be appropriatelydocumented ...”IV.H.(1)“... informed consentshall be documented by the use of a writteninformed consent formapproved by the IRC andsigned by the researchparticipant ...”

IV.H.(3)“An IRC may waive therequirement for theinvestigator to obtain asigned consent form ifthe IRC finds that theonly record linking theresearch participant andthe research would bethe consent documentand the principal risk to the participant wouldbe potential harm resulting from a breachof confidentiality ...”

IV.A.(1)“Basic elements of informedconsent include the following.These elements must beincluded in the informationprovided to each research participant in order for theconsent to be valid.(e) a statement describing the extent, if any, to whichconfidentiality of the research participants will be maintained.”

United Kingdom(1998)

Principle 2.9“Freely given informedconsent should beobtained from every participant prior to clinical trial participation.”Principle 3.1.10“The proposal states thatfreely given informedconsent will be soughtfrom every participantprior to clinical trial participation wheneverpossible.”

Principle 2.9“Freely given informedconsent should beobtained from every participant prior to clinicaltrial participation.”

Principle 3.1.9“... all potential trial participants will beinformed whenever possible of the possiblebenefits and known risksof the intervention ...and of the possibilitythat there are unknownrisks.”Principle 5.4.6“Appropriate informationshould be provided in aform which is readilyaccessible and at a level

Principle 5.4.2“The participant’s 

consent to participateshould be obtainedthrough signing anappropriate consentform ...”

Principle 5.4.3“In the case of childrenup to the age of 18,mentally incapacitatedindividuals who cannotgive informed consentand the unconscious,particular considerationsapply ...”

Principle 2.11“The confidentiality of records that could identifyparticipants should be protected, respecting the privacy and confidentialityrules in accordance with the applicable regulatoryrequirement(s).”

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

continuedUnited Kingdom(1998)

Principle 5.4.2“Whenever possible, all participants ... mustgive their consent to participate in the trial onthe basis of appropriateinformation and withadequate time to considerthis information and askquestions.”

which will enable aninformed decision by the trial participants ...regarding participationin the trial.”Principle 5.4.5“The participants ...must be made awarebefore consenting to participate that they arefree to withdraw withoutobligation at any timeand that such an actionwill not adversely affectany aspect of their care.”

United Kingdom(1999)*

General Principle 4“The research must normally be done onlywith the full andinformed consent of theindividual participants;particular restrictionsand safeguards arerequired when this is not possible ...”

General Principle 5“There must be neither inducement nor coercion; for certaintypes of non-therapeuticresearch participantsmay be recompensed for their expense, time,and inconvenience.”

Specific Consideration 8“Special care should betaken to obtain validinformed consent fromparticipants ... in particular, all prospectiveparticipants must fullyunderstand that theirparticipation is entirelyvoluntary and that theyare free to refuse to participate or withdrawat any time without lossof any entitlement.”

Specific Consideration 8“... A permanent personalised record of consent should beretained, although thisneed not necessarily be in the form of a signature.”

NOT MENTIONED*(see footnote)

NOT MENTIONED*(see footnote)

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,1992, apply to research conducted in developing societies ... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on the

ICH Harmonised Tripartite Guideline for Good Clinical Practice.”

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

United StatesFood and DrugAdministration (FDA)Title 21 Code of Federal Regulations 

21 CFR § 50.20“... no investigator mayinvolve a human beingas a subject in research... unless the investigatorhas obtained the legallyeffective informed consent of the subject ...”21 CFR § 50.23(a)“The obtaining ofinformed consent shallbe deemed feasibleunless ... both the investigator and a physician who is nototherwise participatingin the clinical investigation certify in writing all of the following: (4 criteria)”

21 CFR § 50.20“... An investigator shallseek such consent onlyunder circumstances thatprovide the prospectivesubject ... sufficientopportunity to considerwhether or not to participate and that minimize the possibilityof coercion or undueinfluence ...”

21 CFR § 50.20“... The information thatis given ... shall be inlanguage understandableto the subject ...”21 CFR § 50.25(a)–(b)8 required and 6 optionalelements for informedconsent21 CFR § 50.25(c)“The informed consentrequirements ... are notintended to preempt any applicable ... lawswhich require additionalinformation to be disclosed for informedconsent to be legallyeffective.”

21 CFR § 50.27“... informed consentshall be documented by the use of a writtenconsent form approvedby the IRB and signedand dated by the subject ... at the time of consent.”

21 CFR § 50.23(a)exception from generalrequirements(4 required elements)21 CFR § 50.24exception from informedconsent requirements foremergency research

21 CFR § 56.111(a)(7)“... there are adequate provisions to protect the privacy of subjects and tomaintain the confidentiality of data.”

United StatesCommon Rule**Title 45 Code of Federal Regulations

45 CFR § 46.116“... no investigator mayinvolve a human beingas a subject in research... unless the investigatorhas obtained the legallyeffective informed consent of the subject ...”45 CFR § 46.116(d)“An IRB may approve a consent procedurewhich does not include,or which alters, some orall of the elements ofinformed consent ... orwaive the requirementsto obtain informed consent provided the IRBfinds and documentsthat: (4 criteria)”

45 CFR § 46.116“... An investigator shallseek such consent onlyunder circumstances thatprovide the prospectivesubject ... sufficientopportunity to considerwhether or not to participate and that minimize the possibilityof coercion or undueinfluence ...”

45 CFR § 46.116“... The information thatis given ... shall be inlanguage understandableto the subject ...”45 CFR § 46.116(a)–(b)8 required and 6 optional elements for informed consent45 CFR § 46.116(e)“The informed consentrequirements ... are notintended to preempt any applicable ... lawswhich require additionalinformation to be disclosed for informedconsent to be legallyeffective.”

45 CFR § 46.117(a)“... informed consentshall be documented bythe use of a written consent form approved bythe IRB and signed bythe subject ...”

45 CFR § 46.117(b)

“... the consent formmay be either of the following: (1) A writtenconsent form thatembodies the elementsof informed consent ...(2) A short form writtenconsent document stating that the elementsof informed consent ...have been presentedorally to the subject ...”

45 CFR § 46.116(c)“An IRB may approve a consent procedurewhich does not include,or which alters, some orall of the elements ofinformed consent ...”

45 CFR 46.111(a)(7)“... there are adequate provisions to protect the privacy of subjects and tomaintain the confidentiality of data.”

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A.

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PART 1. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Informed Disclosure DocumentationConsent Voluntariness to Research and Other Exceptions Privacy andProcess of Consent Participants Protections and Waivers Confidentiality

United States Agency forInternationalDevelopment (USAID)Title 22 Code of Federal Regulations

22 CFR § 225.116“... no investigator mayinvolve a human beingas a subject in research... unless the investigatorhas obtained the legallyeffective informed consent of the subject ...”22 CFR § 225.116(d)“An IRB may approve a consent procedurewhich does not include,or which alters, some orall of the elements ofinformed consent ... orwaive the requirementsto obtain informed consent provided theIRB finds and documentsthat: (4 criteria)”

22 CFR § 225.116“... An investigator shallseek such consent onlyunder circumstances that provide the prospective subject ... sufficientopportunity to considerwhether or not to participate and that minimize the possibilityof coercion or undueinfluence ...”

22 CFR § 225.116“... The information thatis given ... shall be inlanguage understandableto the subject ...”22 CFR §225.116(a)–(b)8 required and 6 optional elements for informed consent22 CFR § 225.116(e)“The informed consentrequirements ... are notintended to preempt any applicable ... lawswhich require additionalinformation to be disclosed for informedconsent to be legallyeffective.”

22 CFR § 225.117(a)“... informed consentshall be documented by the use of a writtenconsent form approvedby the IRB and signed by the subject ...”

22 CFR § 225.116(c)“An IRB may approve a consent procedurewhich does not include,or which alters, some orall of the elements ofinformed consent ...”

22 CFR § 225.111(a)(7)“... there are adequate provisions to protect the privacy of subjects and tomaintain the confidentiality of data.”

D-23
Principle 5

Nuremberg Code (1947) “No experiment should be conducted, where there is an a priori reason to believe that death or disabling injury will occur ...”

Principle 6“The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.”Principle 5

Declaration of Helsinki (2000) “In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the 

interests of science and society.”

Principle 7“In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and burdens.”Principle 16“Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in 

comparison with foreseeable benefits to the subject or to others...”

Principle 17“Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks involved have 

been adequately assessed and can be satisfactorily managed...”

Principle 18“Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and 

burdens to the subject...”

Principle 19“Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research.”Article 2

Council of Europe (1997) “The interests and welfare of the human being shall prevail over the sole interest of society or science.”

Article 16(ii)“Research on a person may only be undertaken if all the following conditions are met ... the risks which may be incurred by that person are not disproportionate to the potential benefits of the research ...”Commentary on Guideline 14

Council for International Organizations “The Declaration of Helsinki forbids the imposition of unwarranted risks on human research subjects. Article I.4 requires that ‘the importance is inof Medical Sciences (CIOMS) (1993) proportion to the inherent risk to the subject.’ ... The Declaration of Helsinki, Article I.7 ... requires forgoing research involving human subjects unless

‘the hazards involved are believed to be predictable,’ and ... Article I.5 ... requires that clinical testing ‘be preceded by careful assessment of predictable 

risks in comparison with foreseeable benefits to the subject or to others.’Principle 19

Council for International Organizations of “... Investigators will inform ethical review committees and prospective subjects of perceived risks, and of proposals to prevent or mitigateMedical Sciences (CIOMS) (1991) them. Investigators must be able to demonstrate that the benefits outweigh the risks ...”

PART 2. Comparative Analysis of International Documents Addressing the Protection of Research Participants

Risk/Potential Benefit Analysis

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Principle 2.2

International Conference on Harmonisation “Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject (ICH) (1996) and society ...”

Principle 2.3“The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.”Guidance Point 9

UNAIDS (2000) “The nature, magnitude, and probability of all potential harms resulting from participation in a HIV preventive vaccine trial should be specified 

in the research protocol as fully as can be reasonably done, as well as the modalities by which to address these, including provision for the 

highest level of care to participants who experience adverse reactions to the vaccine, compensation for injury related to the research, and referral 

to psycho/social and legal support, as necessary.”

Guidance Point 10“The research protocol should outline the benefits that persons participating in HIV preventive vaccine trials should experience as a result of their participation ...”Principle 1.3

Australia (1999) “... the ethical principle of beneficence is expressed in researchers’ responsibility to minimise risks of harm or discomfort to participants in 

research projects.”

Principle 1.6“The proportion of burdens for any research participant will vary. In clinical research, where patient care is combined with an intent to 

contribute to knowledge, the risks of participation must be balanced by the possibility of intended benefits for the participants ...”

Principle 1.14“All research proposals must be so designed as to ensure that any risks of discomfort or harm to participants are balanced by the likely benefit 

to be gained.”

Principle 12.2(c)“An HREC must consider all aspects of the design of a clinical trial and be satisfied that where the research is therapeutic, and is therefore intended and likely to be of direct benefit to participants, there is an acceptable balance between the risks and benefits of the trial.”Resolution No. 196/1996

Brazil (1996–1999) III.1.b

“Ethics in research signifies weighing risks and benefits, both actual and potential, individual and collective (beneficence), making a commitment to maximize benefits and minimize distress and risks.”III.1.c“Ethics in research signifies ensuring that predictable injury will be prevented (non-maleficence).”III.3.d“Research involving human subjects ... must ... always favour the probability of foreseen benefits, rather than predictable risks.”

PART 2. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Risk/Potential Benefit Analysis

D-25
contined V.1

Brazil (1996–1999) “Despite potential risks, research involving human subjects will be admissible provided that: a) it is highly probable that it will generate 

knowledge that will permit understanding, preventing, or attenuating a problem that affects the well-being of the research subjects ...; 

b) the risk is justified by the importance of the expected benefit; and c) the benefit is greater than or equal to other, already established prevention, diagnosis or treatment alternatives.”

V.2“Research without direct benefit to individuals must include conditions easily tolerated by the research subjects, considering their physical, 

psychological, social, and educational status.”

Resolution No. 251/1997I.4“... the dignity and well-being of the research subject must prevail over any other interests, whether economic, scientific, or of the community.”

(see page i.6)

Canada (1998) “... subjects are participants in the development of a research project ... such collaboration entails an active involvement by research subjects, and ensures 

both that their interests are central to the project or study ... researchers and research subjects may not always see the harms and benefits of a research project in the same way.” (see page i.7)

Section 1.C1“If potential subjects can reasonably be expected to regard the probability and magnitude of possible harms implied by participation in the 

research to be no greater than those encountered by the subject in those aspects of his or her everyday life that relate to the research then the research can be regarded as within the range of minimal risk ...”

Article 1.5(a)“The REB shall satisfy itself that the design of a research project that poses more than minimal risk is capable of addressing the questions being 

asked in the research.”

Article 1.6“The REB should adopt a proportionate approach based on the general principle that the more invasive the research, the greater should be the care in assessing the research.”

China (1998) NOT MENTIONED

Act No. 503 § 8 Section 1

Denmark (1992) “As part of their evaluation of the committees will have to secure that: the risks, that might be connected with implementation of a project, 

have been meticulously judged and that they not in themselves or in relation to the foreseeable advantages of the project have an unjustifiable 

magnitude ...”Statute No. 488/1999Section 4

Finland (1992–1999) Weighing up benefits and harmful effects

“In medical research the interests and well-being of the research subject shall always be put before any benefits to science or society. Measures 

shall be taken to prevent any risks or harmful effects to the research subject, as far as possible.”“Research subjects may be exposed only to measures where the expected health or scientific benefit is unequivocally greater than the potential 

risks or harm to the research subject.”

PART 2. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Risk/Potential Benefit Analysis

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Title I, Article L. 209–2

France (1988) “Biomedical research may not be conducted on human beings if ... the foreseeable risk to participants in the research is disproportionate to the 

anticipated benefit for them or to the value of such research ...”

Title IV, Article L. 209–14“Biomedical research without direct therapeutic objectives may not entail any foreseeable risk to the health of participants ...”General Principle 5

India (2000) “... due care and caution is taken at all stages ... to ensure that the research subject ... [is] put to the minimum risk, suffer[s] from no 

irreversible adverse effects and ... benefit[s] from and by the research or experiment ...”

General Ethical Issue 8Special Concern 3“Careful consideration should be given to protect the dignity, safety and welfare of the participants when the social contexts of the proposed 

research can create foreseeable conditions for exploitation of the participants or increase the vulnerability to harm and the steps to be taken to 

overcome these should be described.”Article 3c

Netherlands (1998) “A commission may only grant a positive decision on a research protocol if ... it is reasonably plausible that there will be a proportional ratio of 

burden and risk upon the experimental subject in the research ...”Chapter 3–Part C

New Zealand (1997) “4. Biomedical research involving human subjects cannot legitimately be carried out unless the importance of the objective is in proportion to 

the inherent risk to the subject.”“5. Every biomedical research project involving human subjects should be preceded by careful assessment of predictable risks in comparison 

with foreseeable benefits to the subject or to others.”Chapter 5

South Africa (1993) “A key decision in the assessment of proposed research is whether the risk or inconvenience caused to the patient is justifiable in relation to the 

value of the information sought.”

Chapter 5“The Research Ethics Committee needs to do more than a mere risk/benefit analysis in deciding whether research is justifiable. A proper 

assessment of whether the risk to the patient seems to be outweighed by the probable benefits can only be arrived at if the Research Ethics 

Committee itself has a proper regard for the comfort and safety of the individual participant.”# 7

Thailand (1995) “Researchers should select methods of study which will cause minimal impact on the subject’s physical and mental health.”

I.B.(7)

Uganda (1997) “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves

than those ordinarily encountered in daily life or during the performance of routine physical or psychological examination or tests.”

III.E.(1)“Risks to subjects are minimized (a) by using procedures which are consistent with sound research design and which do not unnecessarily expose

the research participants to risk and (b) ... by using procedures already being performed on the subjects for diagnostic or treatment purposes.”

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Risk/Potential Benefit Analysis

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contined III.E.(2)

Uganda (1997) “Risks to research participants are reasonable in relation to anticipated benefits ... and the importance of the knowledge that may reasonably be 

expected to result. In evaluating risks and benefits the UNCST should consider only those risks and benefits that may result from the research ... The UNCST should also consider possible long-range effects of applying knowledge gained in the research as among those research risks that 

fall within the purview of its responsibility.”Principle 2.2

United Kingdom (1998) “Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial 

participant and society.”

Principle 2.3“...the rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science 

and society.”

Principle 6.6.1“In all the deliberations of the TSC the rights, safety and wellbeing of the trial participants are the most important considerations and should 

prevail over the interests of science and society. The TSC should ensure that the protocol demands freely given informed consent from every trials

participant. The TSC should look closely at the patient information provided and advise the investigators on its completeness and suitability.”General Principle 3

United Kingdom (1999)* “The potential and known risks of the research to the participants must be taken into account by participant and investigator as well as the 

potential benefits of the research to the participants or others.”

Special Consideration 5“The balance of risks and benefits is that pertaining to the circumstances and setting of the study.”21 CFR § 50.3(k) and 21 CFR § 56.102(i)

United States “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves

Food and Drug Administration (FDA) than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

Title 21 Code of Federal Regulations 21 CFR § 56.111(a)(1)

“Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily 

expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.”

21 CFR § 56.111(a)(2)“Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research ... The IRB should not consider possible long-range effects of applying knowledge gained in the research ... as among those research risks that fall within the purview of its responsibility.”

PART 2. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Risk/Potential Benefit Analysis

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,

1992, apply to research conducted in developing societies ... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on theICH Harmonised Tripartite Guideline for Good Clinical Practice."

D-28
45 CFR § 46.102 (i)

United States “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves

Common Rule** than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

Title 45 Code of Federal Regulations 45 CFR § 46.111(a)(1)

“Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily 

expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.”

45 CFR § 46.111(a)(2)“Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably 

be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research ... The IRB should not consider possible long-range effects of applying knowledge gained in the research ... as among those research risks that fall 

within the purview of its responsibility.”22 CFR § 225.102(l)

United States “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves

Agency for International Development than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

(USAID)

Title 22 Code of Federal Regulations

PART 2. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Risk/Potential Benefit Analysis

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A. 

D-29
PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants 

Distributive Justice

1 2 3 Special Protections

Nuremberg Code (1947) NOT MENTIONED NOT MENTIONED

Principle 2“The experiment shouldbe such as to yield fruitful results for thegood of society ...”

NOT MENTIONED

Declaration of Helsinki (2000) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Principle 8economically and medically disadvantagedhuman subjects unable to give or refuse consenthuman subjects who give consent under duresshuman subjects who will not benefit personally from the researchhuman subjects in research that is combined with carePrinciple 24legal incompetencephysical or mental incapacitylegally incompetent minorPrinciple 25minor child

Council of Europe (1997) NOT MENTIONED NOT MENTIONED

Article 3“Parties, taking intoaccount health needsand available resources,shall take appropriatemeasures with a view toproviding, within theirjurisdiction, equitableaccess to health care ofappropriate quality.”

Article 6protection of persons not able to consentArticle 7protection of persons who have a mental disorderArticle 17protection of persons not able to consent to research

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

D-30
PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Distributive Justice

1 2 3 Special Protections

Council for International Organizations of Medical Sciences (CIOMS) (1993)

Commentary onGuideline 11“Women in most societieshave been discriminatedagainst with regard totheir involvement inresearch ... A general policy of excluding fromsuch clinical trials womenbiologically capable ofbecoming pregnant isunjust in that it depriveswomen as a class of persons of the benefits of the new knowledgederived from the trials.Further, it is an affront to their right of selfdetermination.”

Guideline 10“Individuals or communities to be subjects of researchshould be selected insuch a way that the burdens and benefits of the research will beequitably distributed ...”

NOT MENTIONED

Guidelines 5–7children; persons with mental or behavioural disorders; prisonersGuideline 8research involving subjects in underdeveloped countries Guideline 11selection of pregnant or nursing women as research subjects 

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

Council for International Organizations of Medical Sciences (CIOMS) (1991)

NOT MENTIONED NOT MENTIONED

Principle 42“... Potential benefits and harm should be distributed equitablywithin and among communities that differon grounds of age, gender, race, or culture,or other variables.”

Principle 43vulnerable and dependent groups

International Conference on Harmonisation (ICH) (1996)

NOT MENTIONED NOT MENTIONED NOT MENTIONED

Principle 4.8.12“When a clinical trial ... includes subjects who can only beenrolled in a trial with the consent of the subject’s legally 

acceptable representative ... the subject should be informed

about the trial to the extent compatible with the subject’s 

understanding and, if capable, the subject should sign and personally date the written informed consent.”

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PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Distributive Justice

1 2 3 Special Protections

UNAIDS (2000)

Guidance Point 17“... women should beincluded in clinical trialsin order to verify safety,immunogenicity, andefficacy from theirstandpoint ...”Guidance Point 18“... children should beincluded in clinical trialsin order to verify safety,immunogenicity, andefficacy from theirstandpoint ...”

NOT MENTIONED

Guidance Point 4“... the desired outcomeof the research protocolshould potentially benefit the populationfrom which the researchparticipants are drawn.”

Guidance Point 7“Where relevant, the research protocol should describe thesocial contexts of a proposed research population (country orcommunity) that create conditions for possible exploitation orincreased vulnerability among potential research participants,as well as the steps that will be taken to overcome these and protect the dignity, the safety, and the welfare of the participants.”Guidance Point 8“... the choice of study populations for each trial phaseshould be justified in advance in scientific and ethical termsin all cases, regardless of where the study population is found.Generally, early clinical phases of HIV vaccine research shouldbe conducted in communities that are less vulnerable to harmor exploitation, usually within the sponsor country ...”Guidance Point 13“Special measures should be taken to protect persons whoare, or may be, limited in their ability to provide informedconsent due to their social or legal status.”Guidance Point 17“... During such research, women should receive adequate information to make informed choices about risks to themselves, as well as to their fetus or breastfedinfant, where applicable.”Guidance Point 18“... Efforts should be taken to design vaccine developmentprogrammes that address the particular ethical and legal considerations relevant for children, and safeguard their rights and welfare during participation.”

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

Australia (1999) NOT MENTIONED NOT MENTIONED NOT MENTIONED NOT MENTIONED

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PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Distributive Justice

1 2 3 Special Protections

Brazil (1996–1999)

Resolution No.196/1996III.3.j“... Vulnerable individuals or groupsshould not be researchsubjects when thedesired information canbe obtained from fullycapable individuals,unless the research is to directly benefit thevulnerable individualsor groups ...”

Resolution No.196/1996III.1.d“Ethics in research signifies social relevanceof the research, with significant advantages to the research subjectsand minimization of theburden to vulnerableindividuals, which guarantees equal consideration of allinterests involved andpreserves the sociohumanitarian purposeof research (justice andequality).”

Resolution No.196/1996III.3.m“Research involvinghuman subjects ... must... guarantee that, whenever possible, research in communities is translated into benefits whoseeffects continue to be felt after the research is concluded ...”Resolution No.292/1999IV“The burden and benefits arising from the investigation [coordinated abroad or withforeign participation]and the research resultsmust be distributed fairly among the partsinvolved and should beclearly set forth in theprotocol.”

Resolution No. 196/1996III.1.a“Ethics in research signifies freely given and informed consentof target-individuals and the protection of vulnerable groupsand the legally disabled (autonomy) ...”III.3.u“Research involving human subjects ... must ... take into

account, in research carried out in women in the reproductiveage or pregnant women, the evaluation of risks and benefits,as well as possible interference with the fertility, pregnancy,embryo, or fetus, labor, puerperium, nursing and the newborn.”

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

Canada (1998)

Commentary to Article 2.1“The requirement of freeand informed consentshould not disqualifyresearch subjects who are not proficient in the language used byresearchers from theopportunity to participatein the potential research.”(see Articles 5.1, 5.2(women), 5.3 (incompetent persons))

(see page i.6) (see page i.6)

Article 2.5research involving incompetent individualsArticle 2.64 minimum requirements to obtain informed consent from incompetent individualsArticle 2.7“... the researcher shall seek to ascertain the wishes of the individual concerning participation ...” where “... the legally

incompetent individual understands the nature and consequences of the research ...”

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Denmark (1992) NOT MENTIONED NOT MENTIONED NOT MENTIONED

PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Distributive Justice

1 2 3 Special Protections

China (1998) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Article 11childrenArticle 12mental patientsArticle 16pregnant or nursing women

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

Finland (1992–1999) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Statute No. 488/1999Section 7 (persons not able to consent)Section 8 (minors)Section 9 (pregnant women and nursing mothers)Section 10 (prisoners)

France (1988) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Title I , Article L. 209–4pregnant or nursing womenTitle I, Article L. 209–5persons deprived of liberty (solicitation)Title I, Article L. 209–6minors, mentally ill, critically ill (solicitation)Title II, Article L. 209–10minors

India (2000) NOT MENTIONED

General Principle 3“Such human subjectsshould be selected sothat the burdens andbenefits of the researchare distributed withoutarbitrariness, discrimination or caprice.”

General Principle 8“... the research orexperiment and its subsequent applicativeuse are conducted tobenefit all human kindand not just those whoare socially better off but also the least advantaged; and in particular,the research subjectsthemselves.”

General Ethical Issues 5Research involving pregnant or nursing women, children, andvulnerable groups

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Uganda (1997) NOT MENTIONED

III.E.(3)“The selection ofresearch participants isequitable ...”

NOT MENTIONED

II.E.(8)“When some or all of the research participants are likely to be vulnerable to coercion or undue influence, additional safeguards have been included in the study to protect the rights and welfare of these research participants.”IV.B–IV.Gpregnant women; children; prisoners; soldiers; mentally ill andbehaviorally disordered; refugees

PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Distributive Justice

1 2 3 Special Protections

Netherlands (1998) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Article 4.1“Performing scientific research with experimental subjectswho have not reached 18 years of age, or who are not in acondition to assess their interests reasonably, is prohibited.This prohibition does not apply to scientific research that may also benefit the experimental subjects involved or to scientific research that cannot be performed with the cooperation of the experimental subjects from the category to which the experimental subject belongs for whom the risks and burdens are minimal.”Article 6.1 b–dminorsArticle 6.7“If ... the experimental subject is not competent to give 

permission, those who are competent in his place may withdraw it at any time without explanation ...”

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

New Zealand (1997) NOT MENTIONED NOT MENTIONED NOT MENTIONED NOT MENTIONEDSouth Africa (1993) NOT MENTIONED NOT MENTIONED NOT MENTIONED

Chapter 6Special Groups (including women, children, the elderly, the mentally handicapped, prisoners, and students)

Thailand (1995) NOT MENTIONED NOT MENTIONED NOT MENTIONED NOT MENTIONED

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United Kingdom (1999)* NOT MENTIONED NOT MENTIONED NOT MENTIONED

PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

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1 2 3 Special Protections

United Kingdom (1998)(Guidance Notes are available on theInternet at:http://www.mrc.ac.uk/Clinical_trials/ct_gn.html)

Guidance Notes“We require that, in full proposals, any proposed lower andupper age limits for trialparticipants should bejustified on scientificgrounds. Normally, forexample, there shouldbe no upper age limit on recruitment.Similarly, exclusion onthe grounds of gendershould be justifiable on scientific grounds.”

Principle 5.4“The principles ofinformed consent in thecurrent version of theHelsinki Declaration 

....

and those laid out in the 13 principles at the beginning of thisdocument should beimplemented in allRCTs.”*

NOT MENTIONED

Principle 5.4.3children, mentally incapacitated persons who cannot give fullinformed consent, unconscious

United States Food and Drug Administration (FDA)Title 21 Code of Federal Regulations

NOT MENTIONED

21 CFR § 56.111(a)(3)“Selection of subjects isequitable ...”

NOT MENTIONED

21 CFR § 56.111(a)(3)“... the IRB ... should be particularly cognizant of the specialproblems of research involving vulnerable populations ...”21 CFR § 56.111(b)“When some of the subjects ... are likely to be vulnerable tocoercion or undue influence additional safeguards have beenincluded in the study to protect the rights and welfare ofthese subjects.”

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,

1992, apply to research conducted in developing societies 

... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on the

ICH Harmonised Tripartite Guideline for Good Clinical Practice.”

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NOT MENTIONED
PART 3. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

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1 2 3 Special Protections

DISTRIBUTIVE JUSTICE Column 1: provisions that prohibit the exclusion of certain groups from participating in a research study ■ Column 2: provisions that require the equitable distribution of harms and 

benefits among research participants ■ Column 3: provisions that require the equitable distribution of harms and benefits within and among communities

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate 

United StatesCommon Rule**Title 45 Code of Federal Regulations 

regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A. 

NOT MENTIONED

45 CFR § 46.111(a)(3)“Selection of subjects isequitable ...”

NOT MENTIONED

45 CFR § 46.111(a)(3)“... the IRB ... should be particularly cognizant of the specialproblems of research involving vulnerable populations ...”45 CFR § 46.111(b)“When some of the subjects ... are likely to be vulnerable tocoercion or undue influence additional safeguards have beenincluded in the study to protect the rights and welfare ofthese subjects.”

United States Agency for International Development(USAID)Title 22 Code of Federal Regulations

NOT MENTIONED

22 CFR § 225.111(a)(3)“Selection of subjects isequitable ...”

NOT MENTIONED

22 CFR § 225.111(a)(3)“... the IRB ... should be particularly cognizant of the specialproblems of research involving vulnerable populations ...”22 CFR § 225.111(b)“When some of the subjects ... are likely to be vulnerable tocoercion or undue influence additional safeguards have beenincluded in the study to protect the rights and welfare ofthese subjects.”

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PART 4. Comparative Analysis of International Documents Addressing the Protection of Research Participants

Prior Ethical and/or Scientific Review Providing Research Resultsby Independent Body Level of Treatment to Research Participants

Nuremberg Code (1947) NOT MENTIONED NOT MENTIONED NOT MENTIONEDDeclaration of Helsinki (2000)

Principle 13“The design and performance of each experimental procedure involving humansubjects should be clearly formulated in anexperimental protocol. This protocol shouldbe submitted for consideration, comment,guidance, and where appropriate, approvalto a specially appointed ethical review committee, which must be independent ofthe investigator, the sponsor or any otherkind of undue influence. This independentcommittee should be in conformity with thelaws and regulations of the country in whichthe research experiment is performed...”Principle 14“The research protocol should always containa statement of the ethical considerationsinvolved and should indicate that there iscompliance with the principles enunciated in this Declaration.”

Principle 29“The benefits, risks, burdens and effectivenessof a new method should be tested againstthose of the best current prophylactic, diagnostic, and therapeutic methods. Thisdoes not exclude the use of placebo, or no treatment, in studies where no provenprophylactic, diagnostic or therapeuticmethod exists.”

NOT MENTIONED

Council of Europe (1997)

Article 16(iii)“The research project has been approved by the competent body after independentexamination of its scientific merit and multidisciplinary review of its ethical acceptability ... ”

NOT MENTIONED NOT MENTIONED

Council for International Organizations of Medical Sciences (CIOMS) (1993)

Guideline 14“All proposals to conduct research involvinghuman subjects must be submitted forreview and approval to one or more independent ethical and scientific reviewcommittees ...”

Commentary on Guideline 14“... as required by the Declaration of Helsinki,Article III.3, ‘every patient — including those of a control group, if any — should be assuredof the best proven diagnostic and therapeuticmethod.’ Therefore, if there is already anapproved and accepted drug for the conditionthat a candidate drug is designed to treat, placebofor controls usually cannot be justified.”

NOT MENTIONED

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Prior Ethical and/or Scientific Review Providing Research Resultsby Independent Body Level of Treatment to Research Participants

Council for International Organizations of Medical Sciences (CIOMS) (1991)

Principle 33“The requirement that proposals for epidemiological studies be submitted to independent ethical review applies irrespective of the source ...”Principle 40“... Scientific review and ethical review cannot be considered separately; a study that is scientifically unsound is unethical inexposing subjects to risk ... and achieving

no benefit in knowledge ...”

NOT MENTIONED

Principle 13“Part of the benefit that communities, groups,and individuals may reasonably expect fromparticipating in studies is that they will be toldof findings that pertain to their health ...Research findings and advice to communitiesshould be publicized by whatever suitablemeans are available ...”

International Conference on Harmonization (ICH) (1996)

Principle 2.6“A trial should be conducted in compliancewith the protocol that has received priorIRB/IEC approval/favorable opinion.”

Principle 2.1“Clinical trials should be conducted in accordance with the ethical principles thathave their origin in the Declaration ofHelsinki, and that are consistent with GCPand the applicable regulatoryrequirement(s).”Principle 4.3.2“During and following a subject’s participation in a trial, the investigator/institution

should ensure that adequate medical care isprovided to a subject for any adverse events... related to the trial.”

NOT MENTIONED

UNAIDS (2000)

Guidance Point 5“To ensure the ethical and scientific qualityof the proposed research, its relevance to the affected community, and its acceptanceby the affected community, community representatives should be involved in anearly and sustained manner in the design,development, implementation, and distribution of results of HIV vaccineresearch.”

Guidance Point 11“As long as there is no known effective HIVpreventive vaccine, a placebo control armshould be considered ethically acceptable in a phase III HIV preventive vaccine trial.However, where it is ethically and scientifically acceptable, consideration should begiven to the use in the control arm of a vaccine to prevent a relevant condition apart from HIV.”

Guidance Point 2“... other knowledge and benefits resultingfrom HIV vaccine research should be madeavailable as soon as possible to all participantsin the trials in which it was tested ...”

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Prior Ethical and/or Scientific Review Providing Research Resultsby Independent Body Level of Treatment to Research Participants

continuedUNAIDS (2000)

Guidance Point 6“HIV preventive vaccine trials should only be carried out in countries and communitiesthat have appropriate capacity to conductindependent and competent scientific andethical review.”Guidance Point 15“A plan for monitoring the initial and continuing adequacy of the informed consentprocess and risk-reduction interventions,including counselling and access to prevention methods, should be agreed upon beforethe trial commences.”

Guidance Point 16“Care and treatment for HIV/AIDS and itsassociated complications should be providedto participants in HIV preventive vaccine trials, with the ideal being to provide thebest proven therapy, and the minimum toprovide the highest level of care attainable in the host country in light of circumstanceslisted ...A comprehensive care package

should be agreed upon through a host/community/sponsor dialogue which reachesconsensus prior to initiation of a trial ...”

Australia (1999)

Principle 1.13“Every research proposal must demonstratethat the research is justifiable in terms of itspotential contribution to knowledge ...”Principle 1.16“Research projects involving humans mustbe reviewed by a Human Research EthicsCommittee (HREC) and must not be undertaken or funded unless and until approvalhas been granted.”Principle 12.2“An HREC must consider all aspects of thedesign of a clinical trial ...”

Principle 12.2(b)“An HREC must consider all aspects of thedesign of a clinical trial and be satisfied thatthere is a scientifically valid hypothesis beingtested which offers a realistic possibility thatthe interventions being studied will be atleast as effective as standard treatment.”

Principle 1.18“... Normally, research results should be madeavailable to research participants.”

Brazil (1996–1999)

Resolution No. 196/1996III.3.r“Research involving human subjects ... must

... guarantee the absence of conflicts ofinterest between the researcher and theresearch subjects or sponsor of the researchproject.”

VII.13.a“[The Committee for Ethics in Research will]review all protocols of research involvinghuman subjects, including multicentreresearch; the CER will be responsible for all

NOT MENTIONED 

Resolution No. 196/1996III.3.n“... When it is ... beneficial to foster orencourage changes in practices or behaviors in the interest of a community, the researchprotocol must include, whenever possible,provisions to communicate such benefits tothe individuals and/or communities.”

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continuedBrazil (1996–1999)

decisions pertaining [to] the ethics of theresearch to be developed by the institution,so as to ensure the integrity and rights ofvolunteers participating in said research.”

VII.14“The ethical review of each and every proposal of research involving human subjectscannot be dissociated from the scientificanalysis of said proposal ...”

Canada (1998)

Article 1.1(a)“All research that involves living human subjects requires review and approval by an REB ... before the research is started ... ”Article 1.2“The institution in which research involvinghuman subjects is carried out shall mandatethe REB to approve, reject, propose modifications to, or terminate any proposedor ongoing research involving human subjects ...”Article 1.13(a)“Ongoing research shall be subject to continuing ethics review.”Article 4.1“Researchers and REB members shall disclose actual, perceived or potential conflicts of interest to the REB. REBs should develop mechanisms to address and resolve conflicts of interest.”

Article 7.4“The use of placebo controls in clinical trialsis generally unacceptable when the standardtherapies or interventions are available for aparticular patient population.”

(see pages 6.3 and 6.4)

China (1998) NOT MENTIONED NOT MENTIONED NOT MENTIONED

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Denmark (1992)

Act No. 503 § 6 Section 1“Every biomedical research project whichincludes research on: live human subjects... has to be notified to the regional committee within the area, where the person responsible for the project works.”Act No. 503 § 7 Section 1“Projects ... must not be initiated until they have been subject to a scientific ethicalevaluation and a permission to start has been given by the regional committee ...”Act No. 503 § 7 Section 3“Dealing with projects, of which a clinicaltrial of medicinal products is a part, andthus covered by the Medicines Act, theregional committee submits its report on the scientific ethical evaluation of the projectto the National Board of Health ... The

National Board of Health gives the finallicense to initiate the project.”

Act No. 503 § 7 Section 4“If no consensus can be reached in judging agiven project in a regional committee, or ifthe committee finds that the project bringsup questions of a principal character, theproject will have to be referred to the CentralCommittee.”

NOT MENTIONED NOT MENTIONED

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Finland (1992–1999)

Statute No. 488/1999Section 3“Before any research ... is undertaken, 

the ethics committee shall have given afavourable opinion on the research plan.”

Statute No. 488/1999Section 17“Ethics committees shall be responsible forprior evaluation of research projects anddelivering opinions on them. Projects shallbe considered by the ethics committee of theregion where the person in charge of theresearch is based or of the region where theresearch is to be principally conducted ...”Statute No. 986/1999Section 1“The research plan shall be submitted for the opinion of the ethics committee ... tothe ethics committee of the hospital districtin whose area the person responsible for the research operates and in whose area themajor part of the research is to be carriedout ...”

Statute No. 785/1992Section 3“Every person who stays permanently inFinland is without discrimination entitled tohealth and medical care required by his stateof health within the limits of those resourceswhich are available to health care at the timein question ... The patient has a right to

qualitatively good health care and medicalcare ... The mother tongue of the patient,

his/her individual needs and culture have to be taken into account according to possibilities in his/her medical care andother treatment.”

NOT MENTIONED

France (1988)

Title III, Article L. 209–12“Before conducting research on humanbeings, the investigator shall submit his proposal for the opinion of the AdvisoryCommittee for the Protection of Participantsin Biomedical Research ...”

NOT MENTIONED NOT MENTIONED

India (2000)

Ethical Review Procedures“It is mandatory that all proposals on biomedical research involving human subjectsshould be cleared by an appropriately constituted Institutional Ethics Committee(IEC) ... to safeguard the welfare and the

rights of the participants.”

NOT MENTIONED

General Principle 2“The principles of informed consent and voluntariness are cardinal principles to beobserved throughout ... so that research subjects are continually kept informed of anyand all developments in so far as they affectthem and others.”

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Netherlands (1998)

Article 2.2 a–b“A positive decision must be obtained onthis research protocol: from a recognizedcommission [for the purpose of testingresearch protocols in agreement with what isdefined in or by virtue of this law] 

...; from

the central commission [for medical and scientific research] when it involves a decisionof an administrative nature [or] scientificresearch 

.... that an involved experimental

subject may not benefit and whereby his/hercondition is changed deliberately ...”

NOT MENTIONED NOT MENTIONED

South Africa (1993)

Chapter 4“All medical research involving healthy people and patients should be subject toindependent ethical review and this shouldbe accomplished by a Research EthicsCommittee.”Chapter 13“It is recommended that Research EthicsCommittees should require investigators in charge of approved research projects tosubmit a brief report of progress at leastannually ...”

Chapter 10“Where the administration of effective treatment is important for the future well-beingof the patient, it is ethical for a controlledtrial to be undertaken only if, at the outset,the investigator does not know whether thetrial treatment is more or less effective thanthe standard treatment with which it is to becompared (or than no treatment at all in thecase of a placebo-controlled study).”Chapter 10“Withholding effective treatment for a limited,stipulated period, whether or not it is substituted by a placebo, can sometimes beacceptable in order to validate a technique of measurement or confirm the sensitivity ordiscrimination of a therapeutic trial design.This can only be acceptable if no long-termharm to the patient can reasonably be foreseen by the applicant and the ResearchEthics Committee.”

Chapter 12“In studies which involve any sustained co-operation on the part of the patient it isgood practice to make arrangements to informparticipants of the outcome of the research inbroad terms, and to combine this with a letterof thanks or small gift in the case of children.”

New Zealand (1997)

Chapter 1–Part A“... ethical approval from an accreditedethics committee must be obtained beforeHRC funding for any research proposal maycommence.”Chapter 2–Part A“... every application for funding received bythe HRC is required to have been reviewedby an accredited ethics committee.”

Chapter 3–Part E“When the administration of effective treatment is important for the well-being of the patient, a controlled trial can only be undertaken where there is genuine uncertainty about whether the trial treatmentis more effective (or has less risk) than thestandard treatment with which it is beingcompared.”

Chapter 2“... investigators should ensure that the results of their research and an account of the methods employed are adequately andappropriately disseminated in a manner accessible to the research participants ...”Chapter 4–Part B“... the results of any investigation should beappropriately disseminated in a full and frankmanner [to research participants].”

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Thailand (1995)

# 1“The MOPH is responsible for reviewing ethical issues in the medical research whichmeet the following criteria: (1) conducted by the MOPH’s personnel or organizations,or conducted in geographical areas underresponsibility of the MOPH; (2) requested by other organizations for ethical review; (3) requiring national authority approval.”

NOT MENTIONED NOT MENTIONED

Uganda (1997)

V.C.(2)“Pre-clinical studies that provide sufficientdocumentation of the potential safety of thepharmaceutical product ... are a prerequisiteto a clinical trial ...”

NOT MENTIONED NOT MENTIONED

United Kingdom (1998)

Principle 2.6“A trial should be conducted in compliancewith the protocol that has received priorEthical Committee favourable opinion.”Principle 3.1.11“Any necessary approval has been, or will be, obtained from the relevant ethicaland regulatory bodies before the trial’s

implementation.”

Principle 5.2.1“Any material amendments or alterations toor deviations from the protocol ... must haveapproval of the relevant ethics committees ...before their implementation.”

Principle 5.3.1“The ... Declaration of Helsinki is the accepted basis for clinical trial ethics andmust be known and implemented by thoseengaged in research involving human participants. The personal integrity and welfare of the trial participants is the ultimate responsibility of the doctor responsible for their care.”

Principle 5.4.8“... Where feasible, trial participants shouldalso be notified of progress with the trial andthe eventual outcome of the trial.”

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United Kingdom (1999)*

General Principle 1“The research must be of potential scientificor practical value; it must address an important question relevant to Council’s

overall objectives, and be feasible and well-designed.”

General Principle 6“The research should be done only with theapproval of an independent research ethicsbody ...”Specific Consideration 7“Local ethical review of research proposals isrequired to judge the ethical acceptability ofthe research in accordance with the customsand traditions of the particular community.”

Specific Consideration 6“The Helsinki principle II.3 — ... bestproven diagnostic and therapeutic method...

— should take into account the available

and feasible health care in the particulardeveloping country. (The fact that a treatment tested in a trial may not currently beaffordable to the local population should not in itself necessarily be a reason to preclude the study on ethical grounds, butthe information given to patients should setout the position unequivocally.)”

Specific Consideration 9“In anticipation of any beneficial results oftherapeutic research, there should be normallydiscussion in advance with relevant parties inthe developing society about the disseminationof those results to study participants and localinhabitants, and about subsequent availabilityof the relevant product to local inhabitants.”

United StatesFood and Drug Administration (FDA)Title 21 Code of Federal Regulations 

21 CFR § 56.103“Any clinical investigation which must meetthe requirements for prior submission ... tothe Food and Drug Administration shall notbe initiated unless that investigation hasbeen reviewed and approved by, and remainssubject to continuing review by, an IRB ...”21 CFR § 56.109“An IRB shall review and have authority to approve, require modifications in (tosecure approval), or disapprove all researchactivities ...”21 CFR § 312.22(b)“The amount of information on a particulardrug that must be submitted in an IND toassure the accomplishment of the objectives... depends upon such factors as the noveltyof the drug, the extent to which it has beenstudied previously, the known or suspectedrisks, and the developmental phase of thedrug.”

NOT MENTIONED NOT MENTIONED

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,

1992, apply to research conducted in developing societies ... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on theICH Harmonised Tripartite Guideline for Good Clinical Practice.”

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United StatesCommon Rule**Title 45 Code of Federal Regulations 

45 CFR § 46.103(b)“ ... the research has been reviewed andapproved by an IRB provided for in theassurance, and will be subject to continuingreview by the IRB ...”45 CFR § 46.109(a)“An IRB shall review and have authority to approve, require modifications in (tosecure approval), or disapprove all researchactivities ...”

NOT MENTIONED NOT MENTIONED

United States Agency for International Development(USAID)Title 22 Code of Federal Regulations

22 CFR § 225.103(b)“ ... the research has been reviewed andapproved by an IRB provided for in theassurance, and will be subject to continuingreview by the IRB ...”22 CFR § 225.109(a)“An IRB shall review and have authority to approve, require modifications in (tosecure approval), or disapprove all researchactivities ...”

NOT MENTIONED NOT MENTIONED

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A. 

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Nuremberg Code (1947) NOT MENTIONED

Principle 7“Proper preparations should be made andadequate facilities provided to protect theexperimental subject against even remotepossibilities of injury, disability, or death.”Principle 10“During the course of the experiment, thescientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe ... that acontinuation of the experiment is likely toresult in injury, disability, or death to theexperimental subject.”

NOT MENTIONED

Declaration of Helsinki (2000) NOT MENTIONED

Principle 1.7“... Physicians should cease any investigationif the hazards are found to outweigh thepotential benefits.”

Principle 30“At the conclusion of the study, every patiententered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identifiedby the study.”

Council of Europe (1997)

Article 24“The person who has suffered undue damage resulting from an intervention isentitled to fair compensation according tothe conditions and procedures prescribed by law.”

Article 3“Parties, taking into account health needsand available resources, shall take appropriate measures with a view to providing ...equitable access to health care of appropriatequality.”

NOT MENTIONED

Council for International Organizations of Medical Sciences (CIOMS) (1993)

Guideline 13“Research subjects who suffer physical injury as a result of their participation areentitled to such financial or other assistanceas would compensate them equitably for any temporary or permanent impairment or disability. In the case of death, theirdependents are entitled to material compensation. The right to compensationmay not be waived.”Commentary on Guideline 13accidental injury; equitable compensation; obligation of sponsor to pay

Commentary on Guideline 2“If the investigator is a physician, the subjectmust be told clearly whether the investigator willact ... both as an investigator and a physician tothe subject ... an investigator who agrees to actas physician-investigator undertakes all of thelegal and ethical responsibilities of the subject’sprimary-care physician.”Commentary for Guideline 15“When indicated, sponsors should also providefacilities and personnel to make necessaryhealth-care services available to the populationfrom which research subjects are recruited ...”

Guideline 8“Before undertaking research involving subjects in underdeveloped communities,whether in developed or developing countries,the investigator must ensure that:■ persons in underdeveloped countries will

not ordinarily be involved in research thatcould be carried out reasonably well indeveloped communities;

■ the research is responsive to the health

needs and the priorities of the community in which it is to be carried out...”

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Treatment and Compensation for Duty Owed to Research Participants Successful Products MadeInjured Human Participants During/After Trial Reasonably Available

continuedCouncil for International Organizations of Medical Sciences (CIOMS) (1993)

Commentary to Guideline 8“If any product is to be developed ... clear understanding should be reached ... about what the

community is to expect and what can or cannot beprovided during and at the close of the research.Such understanding must be reached before theresearch has begun, to ensure that the research is

truly responsive to the priorities of the community.”“As a general rule, the sponsoring agency shouldensure that, at the completion of successful testing,any product developed will be made reasonablyavailable to inhabitants of the underdevelopedcommunity in which the research was carried out ...”Commentary to Guideline 15“... the sponsoring agency should agree in advanceof the research that any product developed throughsuch research will be made reasonably available tothe inhabitants of the host community or countryat the completion of successful testing ...”

Council for International Organizations of Medical Sciences (CIOMS) (1991)

Principle 47“Compensation is difficult when it is notappropriate to make monetary payments ...When harm results from a study, the bodythat has sponsored or endorsed the studyshould be prepared to make good the injury,by public apology or reparation.”

Principle 16“... the expectation in the community ... thatit will be provided with health care ... shouldnot be frustrated and where people needhealth care, arrangements should be made to have them treated ...”

NOT MENTIONED

International Conference on Harmonisation (ICH) (1996)

Principle 4.8.4“None of the oral and written information ...should contain any language that causes thesubject ... to waive or to appear to waive anylegal rights, or that releases or appears torelease the investigator, the institution, thesponsor ... from liability for negligence.”Principle 5.8compensation to subjects and investigators

Principle 4.3.2“During and following a subject’s participation in a trial, the investigator/institution

should ensure that adequate medical care isprovided to a subject for any adverse events... related to the trial.”

NOT MENTIONED

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UNAIDS (2000)

Guidance Point 9“The nature, magnitude, and probability of all potential harms resulting from participation in a HIV preventive vaccine trialshould be specified in the research protocolas fully as can be reasonably done, as well as the modalities by which to address these,including provision for the highest level ofcare to participants who experience adversereactions to the vaccine, compensation forinjury related to the research, and referral to psycho/social and legal support, as necessary.”

Guidance Point 3"Strategies should be implemented to buildcapacity in host countries and communitiesso that they can practice meaningful selfdetermination in vaccine development, canensure the scientific and ethical conduct ofvaccine development, and can function asequal partners with sponsors and others in a collaborative process.”Guidance Point 14“Appropriate risk-reduction counselling and access to prevention methods should be provided to all vaccine trial participants,with new methods being added as they arediscovered and validated.”Guidance Point 16“Care and treatment for HIV/AIDS and itsassociated complications should be providedto participants in HIV preventive vaccine trials ...”

Guidance Point 2“Any HIV preventive vaccine demonstrated to be safe and effective ... should be madeavailable as soon as possible to all participantsin the trials in which it was tested, as well as to other populations at high risk of HIVinfection ...”

Australia (1999)

Principle 12.7“An HREC must be satisfied, before approving a clinical trial, that arrangementsexist to ensure adequate compensation toparticipants for any injury suffered as aresult of participation in the trial.”

Principle 12.10“It may be unethical for a researcher to continue a trial if: (a) there are or have beensubstantial deviations from the trial protocol;(b) side effects of unexpected type, severity,or frequency are encountered; (c) as the trial progresses, one of several treatments orprocedures being compared proves to be somuch better, or worse, than other(s) thatcontinuation of the trial would disadvantagesome of the participants.”

NOT MENTIONED

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Brazil (1996–1999)

Resolution No. 196/1996V.5“The researcher, the sponsor, and the institution must assume full responsibilityfor providing comprehensive care to theresearch subjects, as regards complicationsand injury resulting from foreseen risks.”V.6“Research subjects that suffer any type ofinjury resulting from their participation inthe research, regardless of such injury havingbeen foreseen in the terms of consent, ornot, have the right to receive comprehensivemedical care, as well as an indemnity.”

Resolution No. 196/1996III.3.q“Research involving human subjects ... must... ensure the research subjects the requiredfollow-up, treatment, or orientation, inscreening surveys ...”III.3.s“... Studies sponsored by external organizations must also respond to trainingneeds in Brazil, so that the country be ableto independently develop similar projects.”V.3“If the main researcher perceives any risk orinjury to the health of the research subjects... he/she must interrupt the research immediately. Likewise, as soon as the advantage of a method under study has been demonstrated, the project must beinterrupted and all research subjects must be offered the benefits of the best regime.”

Resolution No. 196/1996III.3.p“Research involving human subjects ... must... ensure the research subjects the benefitsresulting from the research project, in terms ofsocial return, access to procedures, productsor research agents.”III.3.s“Research involving human subjects ... must... submit evidence, in case of research conducted abroad or with external cooperation, ofcommitments and advantages to the researchsubjects and to Brazil, which will result fromthe implementation of the research ... ”Resolution No. 251/1997IV.1.m“... Access to the medicine being tested must be assured by the sponsor or by theinstitution, researcher, or promoter ... in theevent its superiority to the conventional treatment is proven.”

Canada (1998) NOT MENTIONED

Commentary to Article 1.14“... researchers should ensure the benefits of their research are available in the host country. Benefits may ... take the form of information-sharing, training for local personnel both in the host country and inCanada, or health care or similar services.”(see pages 6.3 and 6.4)

Commentary to Article 7.2“The REB should also examine (1) the issue ofcontinuing access after the trial, (2) the treatments... or, (3) if impossible, the provisions taken toensure adequate replacement.”

China (1998)

Article 19“Those human subjects who got temporaryor permanent harm owing to participating [in] the research should get treatment andfinancial compensation; if the death ofhuman subject is caused, his/her familyshould get compensation. Any research, any institution or any individual must notdeprive this right from human subjects.”

Article 17“Researcher should commit to give certaincompensation or free medical services tohuman subjects ...”

NOT MENTIONED

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Denmark (1992) NOT MENTIONED NOT MENTIONED NOT MENTIONEDFinland (1992–1999) NOT MENTIONED

Statute No. 785/1992Section 6“The patient has to be cared in mutualunderstanding with him/her. If the patientrefuses certain treatment or measure, he/shehas to be cared according to possibilities inanother medically acceptable way in mutualunderstanding with him/her.”Statute No. 785/1992Section 10“A patient who is not satisfied with thehealth care or medical care and the relatedtreatment received by him/her has the rightto make a complaint on the matter to thedirector responsible for health care in thehealth care unit in question ...”Statute No. 785/1992Section 3“Every person who stays permanently inFinland is without discrimination entitled tohealth and medical care required by his stateof health within the limits of those resourceswhich are available to health care at the timein question ... The patient has a right to

qualitatively good health care and medicalcare ... The mother tongue of the patient,his/her individual needs and culture have to be taken into account according to possibilities in his/her medical care andother treatment.”

NOT MENTIONED

France (1988)

Title I, Article L. 209–7“In the case of biomedical research withoutdirect therapeutic benefit, the sponsor shallbe subject to strict and vicarious liability toprovide full compensation for the harmfulconsequences of research suffered by a participant ... In all biomedical research, thesponsor shall take out an insurance policycovering his own civil liability ...”

NOT MENTIONED NOT MENTIONED

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India (2000)

General Principle 3“Each research shall include an inbuiltmechanism for compensation for the humansubjects either through insurance cover orany other appropriate means to cover allforeseeable and unforeseeable risks by providing for remedial action and comprehensive after-care, including treatment duringand after the research or experiment ...”General Ethical Issue 7“Research subjects who suffer physical injuryas a result of their participation are entitledto financial or other assistance to compensate them equitably for any temporary orpermanent impairment or disability ... Thesponsor whether a pharmaceutical company,a government, or an institution, shouldagree, before the research begins, to providecompensation for any physical injury forwhich subjects are entitled to compensationor agree to provide insurance coverage for an unforeseen injury whenever possible.”

General Principle 12“... there is a general and positive duty on all persons conducting, associated or connected with any research entailing theuse of a human subject to ensure that boththe letter and the spirit of these guidelines,as well as any other norms, directions, andguidelines 

... are scrupulously observed and

duly complied with.”

NOT MENTIONED

Netherlands (1998)

Article 7.1“The scientific research will only be performed if, at the time the research begins,insurance is in place covering damages fordeath or injury to the experimental subjectcaused by the research ...”Article 7.4“The manner in which the first paragraph isto be executed is established in the researchprotocol.”Article 7.5“If the party performing the scientificresearch is responsible for death or injurydamages vis-à-vis the experimental subject,then the party sponsoring the scientificresearch is also responsible ...”Article 7.6“... The injured party who has no insurancein place ... has toward a governmental service, institution, or company the rights whichhe would otherwise have in accordance ...with regard to the insurer.”

Article 10“If the scientific research proceeds along acourse that is less favorable for the experimental subject than that which is providedin the research protocol, the individual whois carrying out the research is to inform theexperimental subject at once ... Until a closerpositive decision is granted, the performanceof the research will be suspended unless thehealth of the experimental subject does notallow suspension or cessation.”

NOT MENTIONED

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New Zealand (1997)

Chapter 5–Part G“... where personal injury results from medical error or medical mishap that occursin a clinical trial the personal injury shallconstitute medical misadventure only wherethe trial

—(a) (i) Has been approved by an

ethics committee accredited by the HRC or the Director-General of Health, and (ii) The ethics committee has certified that it is satisfied that the trial is not conducted 

principally for the benefit of the manufactureror distributor of the medicine or item inrespect of which the trial is carried out; or(b) The person has not agreed, in writing, to participate in the trial.”Chapter 5–Part H“Where personal injury results from negligence during a non-approved clinicaltrial, or a clinical trial conducted by a manufacturer or distributor principally forthe purpose of testing or proving a product,the injured person will have a right to suefor common law damages 

... it will be 

necessary for the researcher that all parties(including the researcher, the manufacturer,the distributor and the host institution) areadequately insured to meet any potential liabilities.”

NOT MENTIONED NOT MENTIONED

South Africa (1993)

Chapter 14“It is recommended that researchers or sponsors of research take out professionalindemnity insurance to cover them againsteventual liability for claims arising fromresearch activities.”Chapter 14“In the event of any significant injury, the patient should be entitled to receivecompensation regardless of whether theremay or may not have been negligence orlegal liability on any other basis.”Chapter 19“In the event of injury sustained by apatient/volunteer during the course of a clinical trial, compensation should be paidwithout the patient/volunteer having beenrequired to prove mala fides, negligence orincompetence.”

Chapter 10“In trials where the consequences of onetreatment being found to be more effectivethan others could have profound implicationsfor the future health of participants, the trialshould be terminated as soon as evidencehas accumulated from enough patients toestablish the point.”Chapter 11“It is important that the ordinary requirements 

— medical and other 

—

are not neglected as a consequence of theinvolvement in research, and that the identity of the person in overall clinicalcharge of the patient’s care is clear.”

Chapter 10“The arrangements, if any, for continuing tosupply the superior treatment, if any, after the end of the study should be known at thebeginning of the study, and declared to allpotential participants. Any special arrangements should be honoured. Participants donot have the right to claim ongoing treatmentwith a new unlicensed medicine unless specialarrangements have been made at the time ofthe trial.”

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Thailand (1995) NOT MENTIONED

# 5“... Command facilities are required for thesafe and efficient treatment of the subjectwhen needed.”#8“Each activity involving human subjectsmust be conducted under caution based onmedical standards. Any methods found toindicate potential hazards to the subjectsmust be ceased.”# 9“Researchers must report to the Committeeor the monitor/DSMB in case of seriousadverse reaction as determined in theGuidelines for Good Clinical Practice(GCP).”

NOT MENTIONED

Uganda (1997)

V.D.(6)“The investigator must provide evidence of insurance to cover claims of injuries, disabilities, or death of a clinical trial participant that has resulted from participation in a clinical trial.”V.E.(6)“The sponsor is responsible for providingcompensation or indemnity in the event of trial-related serious injury, disability, or death ...”

V.D.(3)“The investigator must provide adequate andsafe medical or dental care ... to participantsduring the clinical trial ... and must ensurethat the appropriate medical care and follow-up procedures are maintained afterthe trial for a period of time ...”

V.D.(4)“The investigator must provide assurancesthat, if the investigational product is found tobe beneficial, the investigator will make everyeffort to ensure its provision, without charge,to participants in the trial following the conclusion of the trial. In addition, the investigator shall make a reasonable effort tosecure the product's availability to the localcommunity in which the research occurred.”

United Kingdom (1998)

Principle 5.4.12“The participant should have access to information about the procedures for obtaining compensation and treatment following harm through negligence ornon-negligence as a direct result of participating in the trial.”

Principle 2.7“The medical care given to, and medicaldecisions made on behalf of, participantsshould always be the responsibility of a qualified physician, or, when appropriate, a qualified dentist.”Principle 5.3.1“... The personal integrity and welfare of thetrial participants is the ultimate responsibilityof the doctor responsible for their care.”

NOT MENTIONED

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continuedUnited Kingdom (1998)

Principle 6.10“The MRC ... accepts responsibility for itssponsorship of the trial, and as such wouldgive sympathetic consideration to claims for any non-negligent harm suffered by individuals as a result of participating in thetrial ... the Council is unable to insure andthus cannot offer advance indemnity coverfor participants in MRC-funded studies.”

Principle 5.3.2“The medical care given to, and medicaldecisions made on behalf of, participantsshould always be the responsibility of a qualified physician, or, when appropriate, aqualified dentist or other qualified healthcare professional ...”Principle 6.10.3“Where studies are carried out in a hospital,the hospital continues to have a duty of care to the patient being treated within thathospital, whether or not that patient is participating in an MRC-supported study.”Footnote to Principle 2“In the UK there may be situations where itwould be appropriate for other qualified healthcare professionals, such as midwives etc. to beresponsible for patient care.”

United Kingdom (1999)* NOT MENTIONED NOT MENTIONED

Specific Guideline 9“In anticipation of any beneficial results oftherapeutic research, there should normally bediscussion in advance ... about subsequentavailability of the relevant product to localinhabitants.”

United StatesFood and Drug Administration (FDA)Title 21 Code of Federal Regulations 

21 CFR § 50.20“.. No informed consent .... may include any exculpatory language through which the subject of the representative is made towaive or appear to waive any of the subject’slegal rights, or releases or appears to releasethe investigator, the sponsor, the institution,or its agents from liability for negligence.”

NOT MENTIONED

21 CFR § 312.34“In case of a serious disease, a drug ordinarilymay be made available for treatment use ...during Phase 3 investigations or after all clinical trials have been completed ...”(see 21 CFR § 812.36 — medical devices)

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,

1992, apply to research conducted in developing societies ... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on theICH Harmonised Tripartite Guideline for Good Clinical Practice.”

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United StatesCommon Rule**Title 45 Code of Federal Regulations 

45 CFR § 46.116“.. No informed consent .... may include any exculpatory language through which the subject of the representative is made towaive or appear to waive any of the subject’slegal rights, or releases or appears to releasethe investigator, the sponsor, the institution,or its agents from liability for negligence.”

NOT MENTIONED NOT MENTIONED

United States Agency for International Development(USAID)Title 22 Code of Federal Regulations

22 CFR § 225.116“.. No informed consent .... may include any exculpatory language through which the subject of the representative is made towaive or appear to waive any of the subject’slegal rights, or releases or appears to releasethe investigator, the sponsor, the institution,or its agents from liability for negligence.”

NOT MENTIONED NOT MENTIONED

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A. 

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Nuremberg Code (1947) NOT MENTIONED NOT MENTIONED NO YESDeclaration of Helsinki (2000)

Principle 9“Research Investigators should beaware of the ethical, legal and regulatory requirements for researchon human subjects in their owncountries as well as applicable international requirements. Nonational ethical, legal or regulatoryrequirement should be allowed toreduce or eliminate any of the protections for human subjects setforth in this Declaration.”

NOT MENTIONED NO YES

Council of Europe (1997)

Article 26“No restrictions shall be placed on the exercise of the rights andprotective provisions ... other thansuch as are prescribed by law andare necessary in a democratic society ...”Article 27“None of the provisions ... shall be interpreted as limiting or otherwise affecting the possibilityfor a Party to grant a wider measureof protection with regard to theapplication of biology and medicinethan is stipulated ...”

NOT MENTIONED NO

Article 23“The parties shall provide appropriate judicial protection to prevent or to put a stop to anunlawful infringement of the rightsand principles set forth ... at shortnotice.”Article 25“Parties shall provide for appropriatesanctions to be applied in the eventof infringement of the provisions ...”

YES

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Council for InternationalOrganizations of Medical Sciences(CIOMS) (1991)

Principle 48“Such a study implies two ethicalobligations: the initiating agencyshould submit the study protocol toethical review, in which the ethicalstandards should be no less exactingthan they would be for study carriedout in the initiating country; theethical review committee in the hostcountry should satisfy itself that the proposed study meets its ownethical requirements.”Principle 51“Investigators must comply with theethical rules of the funding countryand host country ...”

Principle 49“It is in the interest of the hostcountry to require that proposalsinitiated and financed externally be submitted for ethical approval in the initiating country ...”

NO YES

Council for InternationalOrganizations of Medical Sciences(CIOMS) (1993)

Guideline 15“Externally sponsored researchentails two ethical obligations ...

An external sponsoring agencyshould submit the research protocolto ethical and scientific reviewaccording to the standards of thecountry of the sponsoring agency,and the ethical standards appliedshould be no less exacting than theywould be in the case of research carried out in that country.”

Guideline 8“Before undertaking research involving subjects in underdeveloped communities, whether indeveloped or developing countries,the investigator must ensure that ...the proposals for the research havebeen reviewed and approved by anethical review committee that hasamong its members or consultantspersons who are thoroughly familiarwith the customs and traditions ofthe community.”Guideline 15“Externally sponsored researchentails two ethical obligations ...After scientific and ethical approvalin the country of the sponsoringagency, the appropriate authoritiesof the host country, including anational or local ethical review committee or its equivalent, shouldsatisfy themselves that the proposedresearch meets their own ethicalrequirements.”

NO

Commentary for Guideline 14“Ethical review committees generallyhave no authority to impose sanctionson investigators who violate ethicalstandards in the conduct of researchinvolving human subjects. However,they should be required to report toinstitutional or governmental authorities any serious or continuingnoncompliance with ethical standards ... Sanctions imposed by institutional, governmental, professional or other authorities possessing disciplinary power shouldbe employed as a last resort ...”

YES

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International Conference on Harmonisation (ICH) (1996)

Introduction“The objective ... is to provide a unified standard for the EuropeanUnion, Japan and the United Statesto facilitate the mutual acceptance of clinical data by the regulatoryauthorities in these jurisdictions.”

NOT MENTIONED YES

(certain member states of theEuropean Union, Japan, Russia,Hungary, and Poland have adoptedICH-GCP as national law; theUnited States, Canada, India and thePhilippines have adopted ICH-GCPas official guidance)

Principle 5.20.1“Noncompliance with the protocol,SOPs, GCP, and/or applicable regulatory requirement(s) ... shouldlead to prompt action by the sponsor to ensure compliance.”(in practice, the local health authority or drug regulatory authority may require inspections to ensure compliance)Principle 5.20.2“If the monitoring and/or auditingidentifies serious and/or persistentnoncompliance, the sponsor shouldterminate the investigator’s/institution’s participation in the trial.When ... participation is terminatedbecause of noncompliance, thesponsor should notify promptly the regulatory authority(ies).”

DEPENDS

UNAIDS (2000) NOT MENTIONED

Guidance Point 5“To ensure the ethical and scientificquality of the proposed research, itsrelevance to ... and its acceptanceby the affected community, community representatives shouldbe involved in an early and sustained manner in the design,development, implementation, and distribution of results of HIVvaccine research.”

NO YES

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Australia (1999)

Principle 12.3“An HREC, before granting approvalto a clinical trial, must be satisfiedthat the protocol conforms to: (a) this Statement; (b) the 

...

Declaration of Helsinki; (c) where 

relevant, the CPMP/ICH Note for

Guidance on Good Clinical Practice 

...

and the ISO 14155 Clinical

Investigation of Medical Devices

and the requirements of the TGA[Therapeutic Goods Administration];and (d) any requirements of relevantCommonwealth or State/Territorylaws.”

Principle 1.21“Where research is conducted in an overseas country under the aegis of an Australian institution or organization, the research mustcomply with the requirements ofthis Statement as well as the lawsand guidelines of that country.”

YES

Preamble“The NHMRC requires all institutionsor organisations that receive NHMRCfunding for research to establish aHuman Research Ethics Committee(HREC) and to subject all researchinvolving humans ... to ethical reviewby that committee. The NHMRCexpects this Statement to be used as the standard for that review ...”(in practice, the National Statementhas been comprehensively endorsedas the national standard for the ethical review of research involvinghumans. However, non-compliancewith the National Statement is notan issue of legality or illegality)

YES

Preamble“... this Statement is recommended for use by any individual, institution or organisation conducting researchinvolving humans as an inclusive, reliable and informative guide to theethical considerations relevant to thereview of that research. This wouldinclude any research involving humansundertaken by industry.”

Brazil (1996–1999)

Resolution No. 196/1996III.3.s“... The protocol must comply withthe requirements of the Declarationof Helsinki and include 

... an

authorization issued in the countryof origin. The Committee for Ethicsin Research will require compliancewith its own ethical parameters ...”

Resolution No. 292/1999II“In all research [coordinated abroador with foreign participation], it ismandatory: to set forth the responsibilities, rights, and obligationsthrough an agreement of the partsinvolved (in the research).”VII“In preparing the (research) protocol, special attention must be given to the presentation of 

...

approval document issued by theCommittee on Research Ethics orequivalent institution in the countryof origin that will promote or alsoexecute the project.”

Resolution No. 196/1996III.3.l“Research involving human subjects... must 

... respect the cultural,

social, moral, religious, and ethicalvalues, as well as the mores andhabits, when research involves communities.”

YES YES

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Canada (1998)

Commentary to Article 1.14“Rules pertaining to research abroadshould be created and interpreted inthe spirit of the Helsinki Accords andsubsequent documents that encouragethe free movement of researchers acrossnational boundaries.”Commentary to Article 7.2“Clinical investigators undertakingresearch intended for use in seekingregulatory approval for pharmaceuticalsshould also generally respect the ICHGuidelines which were developed bythe United States, Europe and Japanand have been adopted by Canada.”

Article 1.14“Research to be performed outsidethe jurisdiction or country of theinstitution which employs theresearcher shall undergo prospectiveethics review both (a) by the REBwithin the researcher’s institution;and (b) by the REB, where suchexists, within the legal responsibilityand equivalent ethical and procedural safeguards in the country or jurisdiction where the research is to be done.”

YES

Introduction“The Councils will consider funding (or continued funding) only to individuals and institutions which certify compliance with this policyregarding research involving humansubjects.”(note that, although the Councilsare prepared to withhold funds from institutions that do not complywith the Policy Statement, noncompliance is not an issue of legalityor illegality)

YES(academic institutions are applyingthe Policy Statement to all research,irrespective of the funding source.An average of 60–80% of health

research conducted at academicinstitutions is sponsored by industry) 

Denmark (1992) NOT MENTIONED

Recommendation No. 4“... Danish biomedical researchprojects in foreign countries including developing countries are not required to be notified to a scientific ethical committee 

...

However, the scientific ethical committee system is, if requested,willing to conduct an advisory ethical evaluation of biomedicalresearch projects carried out byDanish researchers in a developingcountry in accordance with the fundamental recommendation bythe World Health Organization(WHO).”“Danish biomedical research projectsthat are solely conducted in a developing country are handled on an advisory base by the CentralScientific Ethical Committee towhom the research protocol shall be submitted. A scientific ethicalevaluation shall also be performedin the developing country in question according to local regulations.”

YES

Act No. 503 § 17 Section 1“Anyone that initiates a projectagainst § 6, § 7, § 14, sections 2, 3,

4 and 55, and § 15 can be punished

with fine or ordinary imprisonment.”

YESAct No. 503 § 7 Section 1“[Every biomedical research projectwhich includes research on liveborn human subjects] must not be initiated until they have been subject to a scientific ethical evaluation and a permission to start has been given by the regionalcommittee ...”

China (1998) NOT MENTIONED NOT MENTIONED NOT MENTIONED NOT MENTIONED

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continuedDenmark (1992)

“The ... Danish biomedical researchprojects conducted both in Denmark

and in a developing country shall be

evaluated according to the Act on ascientific ethical committee systemand the handling of biomedicalresearch projects.”

Finland (1992–1999)

Statute No. 488/1999Section 17“... For the purposes of deliveringopinions, ethics committees shallexamine whether the research planhas taken account of ... internationalobligations covering the status ofresearch subjects and the rules andguidelines that govern medicalresearch ...”

NOT MENTIONED YES

(see e.g. Statute No. 488/1999,Section 27)

YES

Statute No. 488/1999Section 1“This Act applies to medicalresearch carried out on persons ...save as otherwise provided in law.”

France (1988) NOT MENTIONED NOT MENTIONED YES

Title III, Article L. 209–12“... The Minister may at any timesuspend or prohibit biomedicalresearch if there is a risk to public health or a breach of the provisions ...”Title III, Article L. 209–13“Medical Inspectors of Health andPharmaceutical Inspectors of Healthshall be empowered to ensure thatthe provisions ... are compliedwith.”

NOT MENTIONED

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India (2000)

General Ethical Issue 8Special Concern 7“Guidelines, rules, regulations, andlaws of all countries participating in collaborative research projectsshould be respected, especially byresearchers in the host country andthe sponsor country.”

Statement of Specific Principlesfor Clinical Evaluation of Drugs ... Specific Principle 1“The proposed trial should be carried out, only after approval ofthe Drugs Controller General ofIndia ... All the guiding principlesshould be followed irrespective of whether the drug has been developed in this country or abroador whether clinical trials have beencarried out outside India.”

YES NOT MENTIONED

Netherlands (1998) NOT MENTIONED NOT MENTIONED YES

Article 33.1“Parties who do not comply with the prohibition contained in Article 6,first paragraph, will be punishedwith a prison sentence of a maximumof one year or a monetary fine ...”Article 33.2“Parties who do not comply withthe obligation to fulfill article 2, firstparagraph or second paragraph ...or who do not comply with theobligation contained in article 29,will be punished by being takeninto custody for a maximum of sixmonths or will be required to pay a monetary fine ... Those who disobey the prohibitions containedin articles 4 and 5 and parties whocarry out scientific research withouta protocol on which a positive decision has been received willreceive the same penalty.”Article 39“... the law will be enforced foraccurate execution on the part of allministries, authorities, universitiesand officials concerned.”

YES

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Equivalent Protections Research and Review Have Force and Covers Privately Funded(Harmonization of Standards) Conducted in Other Countries Effect of Law? Research?

New Zealand (1997) NOT MENTIONED

Chapter 4–Part B“Practices and beliefs of an ethnicand/or religious nature must be fully respected. Research must beundertaken in a culturally sensitiveand appropriate manner, in full discussion and partnership with theresearch participants whatever theirethnicity or religious affiliation ...”Chapter 4–Part H“Any investigator participating ininternational collaborative researchwhose project is funded ... by theHRC will require ethical approvalfrom an accredited New Zealandethics committee for the research.Research conducted overseas havinghuman ... involvement will alsorequire ethical approval from anethics committee (or equivalentbody) in the country concerned ...Any international collaborativeresearch project, whether funded by HRC or not, which involvesinvestigations in New Zealand or its territories, will be required toundergo ethical review by anaccredited ethics committee withinNew Zealand.”

YES NO

South Africa (1993) NOT MENTIONED

Chapter 1“The basic ethical assumption inmedical research is the autonomy ofthe individual within the broadercontext of human relations. Thesocial and cultural environmentshould be taken into considerationin all circumstances. Patients should be treated as human beingsin the context of their social, political, economic and religiousenvironments ... This is of paramount importance for medicalresearch in an African context.”

NO NOT MENTIONED

D-65
PART 6. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Equivalent Protections Research and Review Have Force and Covers Privately Funded(Harmonization of Standards) Conducted in Other Countries Effect of Law? Research?

Thailand (1995) NOT MENTIONED NOT MENTIONED YES

# 11“The Ethics Committee has the right to set any future guidance orregulation as deemed necessary.”

YES

Uganda (1997)

I.A.3“Research covered by this policymay take place in a foreign country.The procedures enumerated in theserules may differ from those followedin the foreign country. In suchinstances, if the procedures requiredin the foreign country provide atleast the equivalent protection asthose provided by these rules, thesubstitution of the foreign country’s

procedures may be approved. Thissubstitution is not, however,required by these rules.”

NOT MENTIONED YES

I.C.1“Each institution which is engagedin research that is covered by this policy shall provide writtenassurance to the Uganda NationalCouncil on Science and Technology(UNCST) and the Uganda NationalHealth Research Organisation(UNHRO) when it is established,that it will comply with the requirements ...”III.F“The UNCST shall have authority totemporarily suspend or permanentlyterminate approval of research thatis not being conducted in accordancewith the UNCST’s requirements or that has been associated with unexpected serious harm to researchparticipants ...”VI.B“Failure to comply with the provisions ... may result in termination of the research, fine,imprisonment, and/or deportation.”

YES

I.B.1“An institution means any entity or

agency, whether public or private.”

I.C.1“Each institution which is engagedin research that is covered by thispolicy shall provide written assurance to the Uganda NationalCouncil on Science and Technology(UNCST) and the Uganda NationalHealth Research Organisation(UNHRO) when it is established,that it will comply with the requirements ...”

United Kingdom (1998)

Principle 2“The principles for Good ClinicalPractice in MRC-funded trials arethe same as those laid down in theICH Harmonised Tripartite Guidelinefor Good Clinical Practice ...”

NOT MENTIONED NO

Introduction“The Council expects that this framework for good practice will be implemented in all MRC-funded trials thatinvolve human participants, includingall trials involving medicinal products.”

NO

D-66
PART 6. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Equivalent Protections Research and Review Have Force and Covers Privately Funded(Harmonization of Standards) Conducted in Other Countries Effect of Law? Research?

United Kingdom (1999)* NOT MENTIONED

Specific Consideration 7“Local ethical review of researchproposals is required to judge theethical acceptability of research inaccordance with the customs andtraditions of the particular community ...”

NO NO

United StatesFood and Drug Administration(FDA)Title 21 Code of Federal Regulations 

21 CFR § 312.120(c)(1)“Foreign clinical research is requiredto have been conducted in accordance with the ethical principlesstated in the Declaration of Helsinkior the laws and regulations of thecountry in which the research wasconducted, whichever represents thegreater protection of the individual.”(see 21 CFR § 814.15–medical

devices)

(see 21 CFR § 312.120

and 21 CFR § 814.15)

YES YES

(if it involves FDA regulated products)

United StatesCommon Rule**Title 45 Code of Federal Regulations 

45 CFR § 46.101(h)“When research covered by this policy takes place in foreign countries, procedures normally followedin the foreign countries to protecthuman subjects may differ fromthose set forth in this policy ... theprocedures prescribed by the institution afford protections that areleast equivalent to those provided inthis policy ... may [be substituted]in lieu of the procedural requirements provided in this policy.”

NOT MENTIONED YES DEPENDS

(all privately funded research conducted at institutions, whosemultiple project assurance (MPA)requires adherence to the CommonRule for “all research conducted at

that institution,” is covered)

* “The MRC’s key principles, which are underpinned by the Declaration of Helsinki and outlined in Responsibility in Investigations on Human Participants and Material and on Personal Information,1992, apply to research conducted in developing societies ... In addition, investigators are expected to follow the MRC Guidelines for Good Clinical Practice in Clinical Trials, which are based on the

ICH Harmonised Tripartite Guideline for Good Clinical Practice.”

** The Federal Policy for the Protection of Human Subjects, also known as the Common Rule, is found at 45 CFR Part 46, Subpart A. Many federal agencies that conduct research involving humanparticipants, including the Department of Health and Human Services (DHHS) and the Agency for International Development (USAID), are signatories to the Common Rule. Note that DHHS haspassed regulations that include not only Part A but also Parts B, C, and D which address special protections for pregnant women, prisoners, and children. Likewise, USAID has passed separate regulations found at 22 CFR Part 225 which mirror 45 CFR Part 46, Subpart A. 

D-67
PART 6. Comparative Analysis of International Documents Addressing the Protection of Research Participants continued

Equivalent Protections Research and Review Have Force and Covers Privately Funded(Harmonization of Standards) Conducted in Other Countries Effect of Law? Research?

United States Agency for InternationalDevelopment (USAID)Title 22 Code of Federal Regulations

22 CFR § 225.101(h)“When research covered by this policy takes place in foreign countries, procedures normally followedin the foreign countries to protecthuman subjects may differ fromthose set forth in this policy ... theprocedures prescribed by the institution afford protections that areleast equivalent to those provided inthis policy ... may [be substituted]in lieu of the procedural requirements provided in this policy.”

NOT MENTIONED YES DEPENDS

(all privately funded research conducted at institutions, whosemultiple project assurance (MPA)requires adherence to the CommonRule for “all research conducted at

that institution,” is covered)

D-68
E-1

INTERNATIONAL

PERSPECTIVES ON

PROTECTING HUMAN

RESEARCH SUBJECTS

Commissioned Paper

Jeremy Sugarman, Benjamin Popkin, Judith Fortney, 

and Roberto Rivera

Duke University
E-3

Executive Summary

By conducting focused site visits to countries in which research funded by the United States has been conducted, this project illuminates some of the ways in which U.S. human subjects protections and

research practices may affect local investigators and others involved in the research enterprise. To obtain

these perspectives, conversations with local researchers and members of committees charged with oversight

of research were conducted in eight countries (Chile, Guatemala, Haiti, Kenya, Mexico, Taiwan, Thailand, 

and the United Kingdom).

Overall, there seems to be a high degree of commitment to conducting ethically sound research as well as

much consonance between the values of foreign researchers and U.S. guidelines. However, researchers with

whom we spoke commonly expressed concern that despite its importance in conducting research, the review

process is unnecessarily burdensome—that is, it is time consuming and often difficult. At times, the specific

procedures outlined in U.S. regulations regarding how this review should take place and how it should be 

documented pose substantial challenges, due to limited staffing, space, and resources. Local researchers and

those charged with the oversight of research sometimes perceived that there is little flexibility in applying 

U.S. regulations in the face of cultural variability.

Similarly, while local researchers generally support the need to obtain consent for research, in some settings,

cultural barriers exist (such as a tendency to withhold information about certain diagnoses or procedures) to

obtaining individual informed consent. Nonetheless, even where such challenges to the informed consent

process were absent, widespread concern was expressed that U.S. regulations regarding informed consent place

undue emphasis on detailed documentation that seems to serve U.S. needs rather than local needs. In one

instance, the documents themselves posed a risk to subjects. Although, arguably, Institutional Review Boards

(IRBs) could properly waive the need for written consent in such situations, this approach can be difficult to

implement in international collaborative research. 

Despite some discordance between local and U.S. approaches, local researchers and those charged with the

oversight of research tended to see this discordance not as one that poses irreconcilable conflicts, but as one

that provides opportunities for negotiation and compromise. However, local researchers and IRB members 

perceived that their well-intentioned offers for negotiation and compromise can be met with a lack of trust in

local investigators, institutions, and IRB members.

Although exploratory, this project makes it possible to provide some recommendations to investigators, 

IRB members, regulators, and sponsors regarding ways to enhance the protection of human subjects in 

international collaborative research, such as the following: 

1. Work with local colleagues to make the research relevant to local issues and priorities.

2. In designing research, assess whether any relevant cultural barriers (such as whether placebos are culturally

appropriate) exist to conducting research in a given location. 

3. Develop informed consent documents in collaboration with local colleagues, paying special attention to

potential problems in translation of particular concepts.

4. Exercise a degree of flexibility with regard to written consent documents, which may be awkward for

research participants unaccustomed to receiving documentation of any important transaction.

5. Develop means of simplifying requirements for documentation that retain the ability to audit, both for the

oversight of research (initial review, direct oversight, and continuing review) and for informed consent. 

6. Consider having a local ombudsman available to answer subjects’ concerns about the study as well as their

rights as research subjects.
E-4

7. Encourage international discussion about the role of trusting the integrity of local investigators and those

charged with the oversight of research to adopt and enforce mechanisms for ensuring that the rights and

interests of human subjects are protected. 

8. Provide education and training for local investigators and IRB members about U.S. regulatory requirements

that include information about the rationale for those regulatory requirements.

Background

The National Bioethics Advisory Commission (NBAC) has been charged with examining selected ethical and

legal issues in international research conducted and/or supported by the United States. In order to meet this

charge, NBAC has initiated several projects to assist in deciding whether changes in federal regulations and

policies are warranted, and if so, to develop recommendations for such changes.

By conducting focused site visits to countries in which research funded by the United States has been 

conducted, this project illuminates some of the ways in which U.S. human subjects protections and research

practices may affect local investigators and others involved in the research enterprise. These perspectives were

obtained through a series of visits to eight countries and involved conversations with local researchers and

members of committees charged with the oversight of research. 

Methods

The project was approved by the Duke University Medical Center (DUMC) IRB. Site visits were conducted in

eight countries: Chile, Guatemala, Haiti, Kenya, Mexico, Taiwan, Thailand, and the United Kingdom. Sites were

selected according to three main criteria. First, investigators who are now or have in the past been affiliated with

DUMC or Family Health International (FHI) and have conducted internationally funded research were identified. Among this group, senior staff then identified those researchers with significant experience in international

collaborative research who would be most able to provide informed responses relating to the project domains

(described below). Next, a preliminary list of sites was selected to achieve a balanced geographic distribution.

Finally, because of the significant time and financial constraints inherent to the project, most of the final sites

selected for inclusion were among those to which travel by FHI personnel on unrelated business was already

scheduled.

Once all of these factors were taken into account, a key respondent in each country was identified and

asked to facilitate project staff in gaining an appreciation of how U.S. human subjects protections are perceived

as well as their consonance with local values and concerns. To provide as complete a picture as possible, key

respondents then identified others who could provide additional perspectives and information. Oral informed

consent to participate in this project was obtained from individuals before they were engaged in formal

discussions.

Standardized discussion guidelines were developed for use in conversations with local investigators, those

involved in the local oversight of research, and those who obtain informed consent for research. The guidelines

covered several domains including experiences with U.S. regulations regarding research (e.g., how they

function, who carries them out, and a review of the standard U.S. elements of informed consent); how U.S.

regulations correspond to international investigators’ own moral rules and how situations of conflict are reconciled; and recommendations for changes or improvements in current U.S. regulations and research practices.

Following three initial site visits by senior project staff, minor modifications were made to the discussion 

guidelines. The final guidelines are included as appendices to this paper.
E-5

Based on the experiences garnered during the initial three visits by senior staff, a training session was

developed for staff who would make the subsequent site visits. The training session covered study domains;

use of discussion guidelines; information to be included in trip reports and site visit reports; and intended

application of study results. 

Site visitors prepared a brief trip report as well as a more extensive site visit report. Each site visitor attended

at least one of two group debriefing sessions (in person, and in one case by telephone). These sessions focused

on uncovering general themes as well as other information that might not have been included in individual site

visit reports. The debriefing sessions were tape recorded and transcribed. Then, site visit guidelines, site visit

reports, and transcripts from the group debriefing sessions were reviewed to identify themes that emerged as a

result of the site visits. 

Findings

The findings from this project are reported according to the major themes that emerged: informed consent;

IRBs; justice; research design; contrasting approaches to oversight; and trust. In this report, the term IRB is

used to refer to local committees charged with reviewing and overseeing the conduct of research, recognizing

that in international research, these committees commonly have different names, such as Research Ethics

Committee or Ethics Committee.

In interpreting these findings, it is essential to note that the design of this project makes it inappropriate to

generalize about the research practices of specific countries. In addition, because the ethical issues that arise in

research can be controversial, it is essential to protect the confidentiality of key respondents and others with

whom discussions were held. Accordingly, details that might provide a richer picture of the issues encountered

are necessarily omitted from this report.

Informed Consent

The topic of informed consent engendered significant interest. In general, those who participated believed 

that it was important to obtain informed consent comprised of the basic elements outlined in U.S. regulations.

For example, one IRB member mentioned that a “person must understand 100 percent what the research is

about—must be able to say in her/his own words what the study is about. No coercion, pressure. Freedom to

leave [the] study. That information [should] be given at the ‘right/best’ moment—not when the woman is in

labor, for example.”

However, frequent comments were made about the legalistic nature of U.S. guidelines for informed consent

and the fact that they seem more oriented towards protecting institutions, researchers, and sponsoring agencies

rather than research participants. For example, one person commented that “[c]onsent forms should protect

participants (up to a point) not the provider.”

There were also reports of investigators having difficulty translating the concept of informed consent to

potential research participants, because of cultural practices and expectations. In addition, the process of 

documenting informed consent according to U.S. regulations seems to create a substantial amount of difficulty.

In one study, it was described ironically as placing research participants at risk. Each of these issues will be

described in greater detail.

The concept of individual consent. The concept of informed consent is challenging in some settings

because of different attitudes and levels of concern about individual versus family decisionmaking; perceived

expectations about telling the truth concerning certain diagnoses, treatments, and the details of research; and

the degree of regard for women’s roles in decisionmaking. 
E-6

In some settings, the notion of individual informed consent can seem inappropriate, because important 

decisions are often made in conjunction with families or are even left to communities. For instance, investigators

in one country repeatedly noted that patients who might be asked to enroll in a medical study would be 

skeptical of an investigator who did not involve the family in the decisionmaking process. In another country, 

a research project ultimately included a multistep consent process beginning with community consent and 

followed by individual parental consent for research involving children. Finally, village elders were invited to sit

in on sessions with children, because of community suspicions that children might be abducted and used as

servants or be subject to having their organs harvested. 

In one country, complete information about medical diagnoses and prognoses is withheld routinely from

patients with certain diseases, such as cancer. Consequently, obtaining valid informed consent (for either treatment or research participation) can be difficult or impossible. While these patients are sometimes enrolled in

research, family members may be asked to provide permission in lieu of consent even when the patient retains

adequate decisionmaking capacity.

Consent documents. Although there was broad agreement that the basic elements of informed consent are

important, repeated concerns were expressed about the amount of detail that was expected to be provided in

consent documents according to U.S. standards. U.S. consent forms are viewed universally as too long, too

detailed, and too complex. As recorded by one site visitor, “The process should be shorter. Information should

be shorter.” Some researchers questioned the need to include highly technical information, such as the pharmacological pathways of drugs. Others indicated that detailed consent forms might lead to a perception of

exploitation, because providing detailed information to patients in some settings is uncommon. Similarly, there

may be a perception among potential participants that complex forms would not be used unless the research in

question involved substantial risk. One site visitor recounted the beliefs of an investigator regarding a lengthy

consent document: “Nobody reads it, and it will just scare away individuals who would have participated in

the study.”

Investigators and those charged with overseeing research told stories about awkward translations of consent

documents. According to an investigator in one study, “[t]he informed consent [form] had to be changed many

times; in our culture the wording was not as strong as in the U.S. proposed wording.” At another site, in a

study that required a careful assessment of frequency of vaginal intercourse, the term coitus was translated to

“with your husband,” yet this may have led to an incomplete measure of the frequency of vaginal intercourse

with all partners. 

At times, working with U.S. IRBs on clarifying these issues has been difficult. One IRB chair was especially

unhappy over a project funded by the National Institutes of Health in which a U.S. IRB insisted on retaining

what the local IRB believed was inappropriate wording. Specifically, in this study the U.S. IRB wanted to retain

a clause indicating that the participant would “pay for care even in the case of an adverse event.” However,

even though in the country in which the research was proposed, this clause was inappropriate because health

care is provided at no charge, no flexibility was permitted in creating a local form that did not include this text.

As a result, participation in the study was discontinued. A similar concern was expressed about inflexibility in

changing terminology to refer to a midwife rather than a doctor, even though the appropriate clinician in the

local setting was a midwife.

Avoiding such conflicts should not be difficult. As local researchers in one setting mentioned, “[we] are presented with informed consent documents already finished by the sponsors, and there is almost no opportunity

to change them.” These researchers concluded that they should participate in the development of informed

consent forms.

In contrast to the standard practice of including contact information for someone in the United States in the

consent form, most local investigators and IRB members believed that the contact person listed on the consent
E-7

form should be a citizen of the country in which the research was being conducted and who was located in

that country. However, some favored including the names of both a local contact person and someone in the

country of the sponsoring organization.

Documenting consent. In an occasional setting, documenting individual consent itself was seen as inappropriate. For instance, in one project involving many illiterate subjects, although thumbprints might be considered

to be an appropriate means of documenting individual consent, local investigators did not use such an approach

because it was too closely related to past police tactics and was believed to frighten potential research participants. In another setting where guerilla warfare was ongoing, the use of written informed consent posed a risk

to participants because these documents linked them to particular institutions. This point was summarized by

a site visitor: “Signing a form in this country means ‘asking for trouble;’ whereas signing a form in the United

States means ‘self-protection.’”

Institutional Review Boards

Researchers and IRB members viewed the process of conducting local IRB review as important. Nevertheless, 

in some cases, the goal of IRB review in protecting human subjects seems lost amidst concerns about meeting

U.S. regulations regarding appropriate procedures and the emphasis on documentation of these procedures. 

As indicated in a conversation with one investigator, “Everyone is in agreement that the patient’s well-being is

of [the] utmost concern, and everyone’s goal is to look out for [the] subject—but IRBs ultimately shouldn’t

interfere with the research process. IRBs in [the] United States [are] looking out for legal protection of [their]

institution—they lose sight of the subject’s protection. This is not the way things work [here].”

In some settings, there seem to be impediments to implementing IRB review as stipulated in U.S. regulations. These include lack of resources to support comprehensive oversight that includes detailed documentation; concerns regarding the composition and function of IRBs; and the need for training of IRB members and

investigators. 

Resources. Conducting meaningful IRB review requires substantial resources that may not be available in

some settings. In many poor countries where physicians are considerably overburdened, it is difficult to

encourage their participation on IRBs. Yet, some members are very dedicated despite the burden on their time

and the opportunity cost. 

Shortage of office space and a lack of computers add to the difficulty of conducting some of the administrative work expected of IRBs. Compounding this problem is the fact that U.S. regulations can require substantially greater documentation of the entire oversight process than is the local norm (and with documentation

requirements that may differ by sponsor). In addition, maintaining detailed records of IRB meetings and

informed consent forms is difficult, particularly when resources for this work are not made available. In one

research institution that does not have secure storage areas, it has been difficult to find sufficient room to retain

documentation for the length of time that is sometimes required or expected. When faced with office shortages

for existing staff and faculty, maintaining secure storage areas for files that may or may not ever be reviewed

seems to be a low priority or a misallocation of resources. Finally, some observers mentioned that they face a

conflict concerning the need to spend resources without this being recognized by sponsors. 

Composition and function. Although many investigators know about U.S. federal requirements for the

composition and function of IRBs, in some settings, “[l]ocal IRBs are not constituted according to these requirements, [and are] comprised of only physicians without community representatives.” Further, some local and

national IRBs seem to have operated without written guidelines, whereas others have very explicit guidelines.

In some places without such guidelines, efforts are under way to develop them. In one IRB, members do not

know each other and do not meet. They also do not know if the studies are followed up or even approved.

This is not a national requirement, but is apparently done for historical reasons or perhaps because of the 

personality of the IRB chair.
E-8

Training. In many settings, U.S. regulations are not well known, and there may also be a good deal of 

confusion regarding which U.S. guidelines should be followed (e.g., those of the Department of Health and

Human Services or those of the Food and Drug Administration). Furthermore, it is often difficult for international researchers and IRB members to keep apace with changing U.S. regulations. 

Clearly, however, investigators and IRB members expressed a desire to learn about the U.S. regulatory

approach. One group created the following list:

■ Training of IRB members.

■ Exchanges between U.S. and overseas IRBs.

■ Dissemination of U.S. regulations.

■ Need for more information/education/training for researchers and IRB members.

IRB members cited a similar list:

■ More involvement of local IRBs in the development of informed consent.

■ Need for training/information for IRB members and researchers.

■ Dissemination of U.S. federal regulations.

■ Development of local guidelines.

Justice

Considerations of justice abound in international research, yet in these site visits, comments related to justice

focused on the responsibility to subjects once research has been completed and the importance of incorporating

local priorities into the selection of study topics for international collaborative research based on their relevance

in the United States and in the host country. For example, a site visitor summarized that while it was understood that “Foreign donors want to address issues that are important to them, [they] should involve issues that

are of interest to local people too. [The] study must have relevance to local people and humanity in general.”

Similarly, IRBs need to evaluate research questions to make sure they are relevant for the population. Such a

task would seem to require collaboration in the design of international research. In the words of one IRB

member, “[f]oreign research must be genuinely collaborative, not a facade [of] collaboration.”

Research Design

In some settings, explicit interest was expressed in having a role in research design. Of particular interest were

stories regarding local perceptions concerning cultural barriers to randomization and the use of placebos.

While local investigators understood the scientific rationale for using these techniques, they spoke of conflicts

arising from cultural expectations on the part of patient-subjects. 

In one setting, local researchers were dedicated to conducting a Phase III randomized, placebo-controlled

trial, but were unable to engage patients in the study by using a standardized informed consent process. The

investigators believed that obtaining informed consent was a barrier to the trial because participants in that 

setting did not expect physicians to be uncertain about which “treatment” was appropriate, regardless of the

scientific uncertainty involved. These investigators deliberated extensively about the appropriate course of

action, verifying the need for data obtained from a randomized trial and the need for consent. They entertained

the possibility of conducting a pre-randomized study, but decided against doing so, because they believed it to

be unethical. Ultimately, the trial was abandoned in favor of a Phase II trial. 
E-9

In another setting, local researchers indicated that if a trial involves the use of a placebo, it is simply not

included in the informed consent process. According to an IRB member, the “...community would not like

placebo, but they don’t know....” Moreover, since there is no direct translation of the term placebo in the local

language, it is apparently translated in such a way that it might be misleading. Thus, research participants in

this study were left without accurate information. 

Contrasting Approaches to Oversight

Local researchers and those charged with the oversight of research reflected on the possibility of contrasting

approaches to oversight in collaborative international research. Some suggested that local and national standards should prevail over U.S. approaches because they more adequately reflect cultural expectations than do

international guidelines. Others argued that foreign researchers had an obligation to use their own standards

when conducting research abroad. For example, one investigator said that “Researcher[s] from abroad should

not carry out research [that would be considered] repugnant in his/her own culture in a second country.” Still

others believed that there are, or should be, universal principles that should be applied internationally and that

the implementation of these principles must be sensitive to local needs. That is, international guidelines

“should leave room for compromise...valid standards for everyone...not be too specific.”

Although faced frequently with contrasting approaches to oversight from local and U.S. guidelines, such

contrasts were not viewed as representing conflict. Rather, these situations generally prompted a search for

negotiation and compromise. As indicated by a site visitor, one investigator mentioned that “he’s never seen a

conflict which couldn’t be resolved; it comes down to understanding local cultures.”

Nevertheless, a site visitor noted that in certain situations there is “[a] perception of a double standard, 

U.S. agencies do research [in this region]...that would not be possible in the United States because of ethical

problems....[Also] an economic imposition: if you do not do it our way you will not get the money.”

Some investigators emphasized that collaborative research involves continuing discussion and review and

that there is a need to attend not only to meeting U.S. regulations, but also to respecting local regulations and

expectations. One group of investigators expressed “a need for cultural communication” and made the following

recommendations: 

■ Need for more involvement of local researchers.

■ Need for education on use/meaning of the regulations.

■ Need for clear definition of concepts.

■ Need for agencies to understand the difference between a language problem and a substance problem.

Trust

IRB members and researchers questioned frequently the extent to which U.S. sponsoring institutions appeared

to distrust the integrity of local researchers. Yet, “Trust is the basic component.” Furthermore, the degree of

inflexibility expressed by U.S. regulatory approaches is viewed as disrespectful, if not offensive, particularly by

researchers and institutions with a great deal of experience and long-term relationships with American sponsors

and research institutions.

Local investigators perceived some differences between the amount of trust inherent to collaborative 

research with U.S. sponsors compared to other governments. One site visitor observed that when “working

with European Community, [Investigators are] only required to sign that they’ll follow...guidelines of

Helsinki...i.e., much less red tape, no inappropriate forms, and more trust and respect for them as researchers

and as ethical moral beings.”
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Comments

Through a series of international site visits, much can be learned about how U.S. regulations and research 

practices are perceived and how these regulations correspond to international investigators’ own moral rules.

Nevertheless, these results should be interpreted with several limitations in mind:

1. The primary respondents in this study had extensive experience conducting research and were therefore

aware of generally accepted international approaches for protecting human research subjects. Therefore,

these respondents may have already decided to accept the U.S. regulatory approach, even if they had 

cultural reservations about doing so. 

2. It is possible that site visitors may have been guided to colleagues with an interest in ethics. 

3. Because of the high profile of this study, the information obtained may be overly positive. 

4. The perspectives of research subjects are absent from this study. 

5. Official local policies, procedures, laws, and regulations that guide the conduct of research with human 

subjects were beyond the scope of this study and thus were not analyzed. 

6. These qualitative data were derived in a fashion that does not permit making generalizations about 

international research in general, or even for all research in specific countries. 

Although many of these limitations might be overcome in subsequent evaluations using both qualitative and

quantitative techniques, several of the findings from this study provide new, rich, and important information. 

Overall, there seems to be a high degree of commitment to conducting ethically sound research as well as

much consonance between the values of foreign researchers and U.S. guidelines. However, researchers with

whom we spoke commonly expressed concern that the review process is burdensome in that is it time consuming

and often difficult, despite its importance in conducting research. At times, the specific procedures outlined in

U.S. regulations regarding how this review should take place and how it should be documented pose substantial

challenges because of lack of staffing, space, and resources. Local researchers and those charged with oversight

of research sometimes perceived that there is almost no flexibility in those procedures in the face of cultural

variability.

Similarly, while local investigators generally support the need to obtain consent, in some settings, there 

are cultural barriers (such as a tendency to withhold information about certain diagnoses or procedures) to

obtaining individual informed consent. Nonetheless, even where such challenges to the informed consent

process were absent, widespread concern was evident that U.S. regulations regarding informed consent place

undue emphasis on detailed documentation that seems to serve U.S. rather than local needs. In one instance,

the documents themselves posed a risk to subjects. Although arguably IRBs could properly waive the need for 

written consent in such situations, this approach can be difficult to implement in international collaborative

research.

Despite some discordance between U.S. and local approaches, local researchers and IRB members tended

not to view the discordance as one that posed irreconcilable conflicts. Rather, they were considered to be

opportunities for negotiation and compromise. However, local researchers and IRB members perceived that

their well-intentioned offers for negotiation and compromise can be met with a lack of trust in local investigators, institutions, and IRB members. 
E-11

Recommendations

Although exploratory, this project makes it possible to offer some recommendations to investigators, IRB 

members, regulators, and sponsors regarding ways to enhance the protection of human subjects in international

collaborative research: 

1. Work with local colleagues to make the research relevant to local issues and priorities.

2. In designing research, assess whether any relevant cultural barriers (such as whether placebos are culturally

appropriate) exist to conducting research in a given location. 

3. Develop informed consent documents in collaboration with local colleagues, paying particular attention to

potential problems in the translation of particular concepts.

4. Exercise a degree of flexibility regarding written consent documents that may be awkward for research 

participants who are unaccustomed to receiving documentation of any important transaction.

5. Develop ways to simplify documentation requirements that retain the ability to audit, both for the oversight

of research (initial review, direct oversight, and continuing review) and for informed consent. 

6. Consider having a local ombudsman available to address subjects’ concerns about the study and their rights

as research subjects.

7. Encourage international discussion about the role of trusting the integrity of local investigators and those

charged with the oversight of research to adopt and enforce mechanisms for ensuring that the rights and

interests of human subjects are protected. 

8. Provide education and training for local investigators and IRB members about U.S. regulatory requirements

that include information about their rationale.
E-13

Appendix A

National Bioethics Advisory Commission

Assessment of the Impact of U.S. Federal Ethics

Regulations on Research in Other Countries

Implemented by

Duke University

Family Health International

SITE VISIT GUIDELINES FOR

IRB MEMBERS AND MEMBERS OF 

NATIONAL ETHICS COMMITTEES

Site Visit Guidelines for IRB and National Ethics Committee Members

The purpose of our conversation is to learn about the impact of research that is funded by the United States.

Foreign funding can influence research in many ways, but we are mainly interested in the impact on various

ethical issues. What we learn from this may be used to modify U.S. policies. Your comments and recommendations will be kept confidential, and your name will not be used in our reports. 

Have you any questions before we start?

[Write down questions.] 

Do you consent to discussing these issues with me? 

Yes ■ No ■

I have a consent form here that we need to go through before we start. [OBTAIN CONSENT.] 

Would you like to have a signed copy of it?

Yes ■ No ■

IDENTIFICATION NUMBER 1 
E-14

Site Visit Guidelines for IRB and National Ethics Committee Members

Ask the Respondent about his or her background–who s/he represents on the IRB/NEC (law, clergy, consumer,

researcher, etc). Find out who appointed the Respondent and why s/he thinks s/he was asked. Find out

whether s/he serves on any other IRBs (currently or formerly), and how long s/he has served on this one. How

are members appointed? Is there any special training for members?

Learn as much as you can about this IRB/NEC. What is the committee’s role? Ask about number of members,

frequency of meetings, whether documents are sent for review in advance, whether decisions are made by vote

or by consensus, and if by vote whether a simple majority is required. Ask how many proposals are reviewed

per year. For NEC members, are biomedical issues other than those involving research examined by the 

committee?

Ask about the nature and source of the guidelines used by this IRB/NEC. Please cover the following:

■ Are there written guidelines, and do all members of the IRB/NEC and all researchers have a copy?

■ Who wrote the guidelines—this IRB/NEC, a national committee, another body? Were they adapted from

other guidelines (which)?

■ Does the IRB/NEC follow up studies that they have approved? How are regulations enforced?

IDENTIFICATION NUMBER 1 
E-15

Determine what procedures researchers must go through to get ethics approval for research. Determine if 

there are differences depending on whether the source of funding is local, bilateral (e.g., U.S.), multilateral

(e.g., WHO), private (e.g., pharmaceutical), or public (e.g., government agencies). How does this IRB/NEC

relate to others in the process? Are there multiple steps in review? If so, what are they? Ask for detailed 

descriptions, and take extensive notes. Ask the Respondent how burdensome s/he feels this process is and

whether s/he feels the process is good and/or necessary.

Is the documentation of the IRB/NEC process different for research funded from different sources? If so, how?

Now we want to learn about areas of similarity and discrepancies or conflicts between different sets of ethical

guidelines and how they are resolved. Ask about differences of opinion/rules between

■ Individual committee members.

■ Researchers and local IRB.

■ Researchers and national guidelines.

■ National guidelines and those of the funding or collaborating agency.

Write down all examples, and for each determine whether this happened on this committee or another. 

Ask the Respondent what, in his or her opinion, are the most common sources of similarities and differences

regarding ethical issues in research. Although the focus here is on agreement and disagreement between

national and international ethical standards, local situations are also instructive. [Write down the responses.] 

IDENTIFICATION NUMBER 1 
E-16

When the Respondent has finished, ask about each of the following if it HAS NOT ALREADY BEEN 

MENTIONED:

■ Diagnostic testing and screening (probe: confidentiality, treatment availability, informing of test results).

■ Experimental treatments.

■ Use of placebos.

■ Payment for iatrogenically caused injury or disease.

■ Use of animals.

■ Randomization.

■ Other.

Sometimes local scientific communities feel that U.S. regulations for informed consent for research participation

are inappropriate to their situation. Please tell what you feel are the most important components of informed

consent. Explain.

When the Respondent is finished, ask how s/he feels about the importance of the following IF NOT ALREADY

MENTIONED:

■ Purpose of research.

■ Risks of procedure/drug/contraceptive.

■ Benefits of procedure/drug/contraceptive.

■ Effectiveness of procedure/drug/contraceptive.

■ Voluntary nature of participation.

■ Freedom to drop out.

■ Confidentiality.

■ Burden of participation.

■ Name of person to contact with questions or problems.

■ Payment.

IDENTIFICATION NUMBER 1 
E-17

Now ask about any examples of complaints on the part of study participants about their treatment in the

course of their participation. Ask whether the IRB was involved in the resolution. Ask about the process of 

resolution of complaints and the final outcomes. Does the Respondent feel the complaints were justified? 

Did they lead to any change in IRB or institutional procedures or policies? 

Ask the Respondent to give examples of how this committee made research projects more ethical or participants in research projects safer. Learn if any of these examples involved internationally funded research.

Ask the Respondent to make recommendations to enhance resolving conflicts or discrepancies between 

different sets of ethical guidelines and making external guidelines function more effectively.

Explain that all research is governed by some code of ethics. Then read the Respondent the following two 

sentences and ask which one more closely reflects his or her own thinking:

■ When foreign researchers and funders work in your country, they should use your local standards of ethics.

■ When foreign researchers and funders work in your country, they should use the same standards of ethics as

they use in research in their own country.

Ask the Respondent to elaborate on his or her answer.

Ask the Respondent if there are any other topics related to the subject of ethical conduct of research that s/he

would like to discuss.

IDENTIFICATION NUMBER 1 
E-18

DUKE UNIVERSITY MEDICAL CENTER

CONSENT FOR RESEARCH

Respondent:_________________________

International Research: Case Studies

(Protocol Number: 1869-98-12ER)

Form M30

We are asking you to take part in a research study sponsored by the National Bioethics Advisory Commission.

PURPOSE OF THE STUDY

The purpose of the study is to document the effect that American research regulations have when applied in

international settings. You are being asked to participate because of your experience with research studies that

take place in foreign countries but are funded by the U.S. government. The results of this study will help

inform U.S. policymakers about ways in which current regulations may need to be modified to help ensure 

the adequate and appropriate protection of participants in international research.

PROCEDURES

If you agree to be in this study, you will be interviewed about your experience with international research. 

POTENTIAL RISKS

There are no physical risks associated with participation in this study. However, there is a small risk to your

privacy by responding to the interviewer’s questions and by sharing information about your experiences. In

order to preserve the confidentiality of your responses to the interview, an identification number will be

assigned to you. A list linking your name and identification number will be maintained in a secure location,

accessible only by the study’s technical monitor located at FHI.

ANTICIPATED BENEFITS

Information gathered during this interview will be reported to those charged with formulating policies and 

regulations governing federally funded research. Your responses will help inform policymakers of the possible

effects that changes to U.S. research regulations may have upon foreign-based researchers and any individuals

involved in their research studies.

Your participation in this study is entirely voluntary. You may refuse to answer any questions posed to you 

during this interview.

“I have read the above and have been given the opportunity to discuss it and ask questions. I have been

informed that I may contact Benjamin Popkin, the FHI technical monitor, at (919) 544-7040, ext 229, 

to answer any questions I may have during the investigation and that I may contact the Office of Risk

Management at (919) 684-3277 for any questions regarding my rights as a research subject. I agree to 

participate as a subject with the understanding that I may withdraw at any time.”

Name of person obtaining consent

Date Signature of person obtaining consent

IDENTIFICATION NUMBER 1 
E-19

Appendix B

National Bioethics Advisory Commission

Assessment of the Impact of U.S. Federal Ethics

Regulations on Research in Other Countries

Implemented by

Duke University

Family Health International

SITE VISIT GUIDELINES FOR

PERSONS WHO OBTAIN INFORMED CONSENT

Site Visit Guidelines for Persons Who Obtain Informed Consent

The purpose of our conversation is to learn about the impact of research that is funded by the United States.

Foreign funding can influence research in many ways, but we are mainly interested in the impact on various

ethical issues. What we learn from this may be used to modify U.S. policies. Your comments and recommendations will be kept confidential, and your name will not be used in our reports. 

Have you any questions before we start?

[Write down questions.] 

Do you consent to discussing these issues with me? 

Yes ■ No ■

I have a consent form here that we need to go through before we start. [OBTAIN CONSENT.] 

Would you like to have a signed copy of it?

Yes ■ No ■

IDENTIFICATION NUMBER 1 
E-20

Site Visit Guidelines for Persons Who Obtain Informed Consent

What is his or her professional background? How did s/he get involved in clinical research? Did s/he receive

any special training?

Ask the Respondent about his or her understanding of the details of the studies s/he is or has worked on. For

each project, make sure you cover the following topics:

■ The sponsor.

■ The purpose of the research.

■ How participants are recruited.

■ Policies for withdrawing from the study.

■ Risks.

■ Benefits.

■ Additional burden due to research.

■ To whom participants would turn if they think they are not being properly treated in the study.

Ask the Respondent 

■ What s/he believes is the most important information to give study participants.

■ Whether there is information not on the consent form that s/he would give participants. Specify.

■ Whether there is information on the consent form that is not necessary. What is it?

IDENTIFICATION NUMBER 1 
E-21

IDENTIFICATION NUMBER 1 

Ask the Respondent about his or her general perceptions about informed consent. Be sure to cover

■ Whether study participants seem to desire additional information about the studies in which they 

participate. 

■ Whether most participants seem to understand what they are getting into when they agree to join a 

research study. 

■ If participants do not understand, why might that be? 

■ Recommendations for improving the informed consent process.

Explain that all research is governed by some code of ethics. Then read the following two sentences to the

Respondent and ask which one is closest to his or her own thinking:

■ When foreign researchers and funders work in your country, they should use your local standards of ethics.

■ When foreign researchers and funders work in your country, they should use the same standards of ethics 

as they use in research in their own country.

Ask the Respondent to explain why s/he feels this way.

Ask the Respondent if there are any other topics related to the subject of ethical conduct of research that s/he

would like to discuss.
E-22

DUKE UNIVERSITY MEDICAL CENTER

CONSENT FOR RESEARCH

Respondent:_________________________

International Research: Case Studies

(Protocol Number: 1869-98-12ER)

Form M30

We are asking you to take part in a research study sponsored by the National Bioethics Advisory Commission.

PURPOSE OF THE STUDY

The purpose of the study is to document the effect that American research regulations have when applied in

international settings. You are being asked to participate because of your experience with research studies that

take place in foreign countries but are funded by the U.S. government. The results of this study will help

inform U.S. policymakers about ways in which current regulations may need to be modified to help ensure 

the adequate and appropriate protection of participants in international research.

PROCEDURES

If you agree to be in this study, you will be interviewed about your experience with international research. 

POTENTIAL RISKS

There are no physical risks associated with participation in this study. However, there is a small risk to your

privacy by responding to the interviewer’s questions and by sharing information about your experiences. In

order to preserve the confidentiality of your responses to the interview, an identification number will be

assigned to you. A list linking your name and identification number will be maintained in a secure location,

accessible only by the study’s technical monitor located at FHI.

ANTICIPATED BENEFITS

Information gathered during this interview will be reported to those charged with formulating policies and 

regulations governing federally funded research. Your responses will help inform policymakers of the possible

effects that changes to U.S. research regulations may have upon foreign-based researchers and any individuals

involved in their research studies.

Your participation in this study is entirely voluntary. You may refuse to answer any questions posed to you 

during this interview.

“I have read the above and have been given the opportunity to discuss it and ask questions. I have been

informed that I may contact Benjamin Popkin, the FHI technical monitor, at (919) 544-7040, ext 229, 

to answer any questions I may have during the investigation and that I may contact the Office of Risk

Management at (919) 684-3277 for any questions regarding my rights as a research subject. I agree to 

participate as a subject with the understanding that I may withdraw at any time.”

Name of person obtaining consent

Date Signature of person obtaining consent

IDENTIFICATION NUMBER 1 
E-23

Appendix C

National Bioethics Advisory Commission

Assessment of the Impact of U.S. Federal Ethics

Regulations on Research in Other Countries

Implemented by

Duke University

Family Health International

SITE VISIT GUIDELINES FOR

RESEARCHERS

Site Visit Guidelines for Researchers

The purpose of our conversation is to learn about the impact of research that is funded by the United States.

Foreign funding can influence research in many ways, but we are mainly interested in the impact on various

ethical issues. What we learn from this may be used to modify U.S. policies. Your comments and recommendations will be kept confidential, and your name will not be used in our reports. 

Have you any questions before we start?

[Write down questions.] 

Do you consent to discussing these issues with me? 

Yes ■ No ■

I have a consent form here that we need to go through before we start. [OBTAIN CONSENT.] 

Would you like to have a signed copy of it?

Yes ■ No ■

IDENTIFICATION NUMBER 1 
E-24

Site Visit Guidelines for Researchers

Ask the Respondent about the nature of his or her research. Be sure to cover the following topics:

■ Type of research (bench, clinical trials, epidemiology, service delivery, etc.). 

■ The substantive area (family planning, STDs, HIV/AIDS, oncology, etc.).

■ Whether the Respondent has a current research project(s).

■ How extensive the Respondent considers his or her experience with international collaborative research, as

well as national research conducted with external funding and local funding. 

Ask the Respondent whether s/he plays a role in other aspects of research.

Yes ■ No ■

If yes, which roles:

■ Chair of IRB.

■ Member of IRB.

■ National ethics committee member.

■ Person who obtains informed consent.

■ Participant in research.

■ Other, explain _________________________________________________________________________.

Now ask about sources of funding. The point is to get the variety of sources and the extensiveness of experience.

■ Number and type of different donors on current projects.

■ Approximate value of current projects.

■ Number and type of different donors on projects in the last five years.

■ Approximate value in last five years.

IDENTIFICATION NUMBER 1 
E-25

What is the general procedure that the Respondent must follow for a protocol to undergo ethical review and

receive approval? How did s/he learn about this process?

Does this process vary according to the source of funding (i.e., funding source is local, bilateral [e.g., U.S.],

multilateral [e.g., WHO], private [e.g., pharmaceutical], or public [e.g., government agencies])? 

Yes ■ No ■ How?

Ask the Respondent how burdensome s/he feels this process is and whether s/he feels the process as it 

currently exists is good and/or necessary. Ask the Respondent for personal recommendations as to how to

improve this process.

Write down all examples that this Respondent can give you about any differences in ethical guidelines 

(i.e., between individual researchers, researchers and local IRB, researchers and national guidelines, national

guidelines and those of funding or collaborating agency) with which they or their colleagues have had direct

experience. If it was with a colleague, ask if it would be okay to talk with that person. Obtain contact information and record it on the next to last page (which is otherwise blank), which will be removed before processing.

IDENTIFICATION NUMBER 1 
E-26

Learn how any moral differences that surfaced during the research review and approval process were resolved.

What reviews and committees were involved? What was the resolution? How long did it take? Was the scientific design of the study jeopardized? Did the research proceed as planned? Was the Respondent satisfied with

the resolution?

[NOTE: This refers to the process of resolution.]

Ask the Respondent what, in his or her opinion, are the most common sources of similarities and differences

regarding ethical issues in research. Although the focus here is on agreement and disagreement between

national and international ethical standards, local situations are also instructive. [Write down the responses.]

[NOTE: This refers to substantive areas of research or techniques.]

When the Respondent has finished, ask about each of the following IF THEY HAVE NOT ALREADY BEEN

MENTIONED:

■ Diagnostic testing and screening (Probe: confidentiality, treatment availability, informing of test results).

■ Experimental treatments.

■ Use of placebos.

■ Written consent.

■ Payment for iatrogenically caused injury or disease.

■ Use of animals.

■ Other methods of seeking approval or consent.

■ Randomization.

■ Other.

IDENTIFICATION NUMBER 1 
E-27

IDENTIFICATION NUMBER 1 

Is the documentation of the IRB process different for research funded from different sources? Please elaborate on

your answer.

Sometimes local scientific communities feel that U.S. regulations for informed consent for research participation are inappropriate to their situation. Please say what you feel are the most important components of

informed consent. Explain.

When the Respondent has finished, ask how s/he feels about the importance of the following IF THEY HAVE

NOT BEEN MENTIONED:

■ Purpose of the research.

■ Risks of procedure/drug/contraceptive.

■ Benefits of the procedure/drug/contraceptive.

■ Effectiveness of the procedure/drug/contraceptive.

■ Voluntary nature of participation.

■ Freedom to drop out.

■ Confidentiality.

■ Burden of participation. 

■ Name of person to contact with questions or problems.

■ Payment for participation.
E-28

Now ask about any examples of complaints on the part of study participants about their treatment in the

course of their participation. Ask about the process of resolution of complaints and the final outcomes. Does

the Respondent feel the complaints were justified? Did they lead to any change in institutional procedures or

policies?

Ask the Respondent to make recommendations to enhance the current method for resolving differences or 

discrepancies between different sets of ethical guidelines and making external guidelines function more 

effectively.

Explain that all research is governed by some code of ethics. Then read the Respondent the following two 

sentences and ask which one more closely reflects his or her own thinking:

■ When foreign researchers and funders work in your country, they should use your local standards of ethics.

■ When foreign researchers and funders work in your country, they should use the same standards of ethics

that they use in research in their own country.

Ask the Respondent to elaborate on his or her answer.

Ask the Respondent if there are any other topics related to the subject of ethical conduct of research that s/he

would like to discuss.

IDENTIFICATION NUMBER 1 
E-29

Ask the Respondent if there are colleagues who have experienced conflicts or discrepancies in ethical guidelines

relevant to their work. 

You may use the rest of the page to make contact and scheduling notes. They will be removed before these 

discussion notes are processed.

IDENTIFICATION NUMBER 1 
E-30

DUKE UNIVERSITY MEDICAL CENTER

CONSENT FOR RESEARCH

Respondent:_________________________

International Research: Case Studies

(Protocol Number: 1869-98-12ER)

Form M30

We are asking you to take part in a research study sponsored by the National Bioethics Advisory Commission.

PURPOSE OF THE STUDY

The purpose of the study is to document the effect that American research regulations have when applied in

international settings. You are being asked to participate because of your experience with research studies that

take place in foreign countries but are funded by the U.S. government. The results of this study will help

inform U.S. policymakers about ways in which current regulations may need to be modified to help ensure 

the adequate and appropriate protection of participants in international research.

PROCEDURES

If you agree to be in this study, you will be interviewed about your experience with international research. 

POTENTIAL RISKS

There are no physical risks associated with participation in this study. However, there is a small risk to your

privacy by responding to the interviewer’s questions and by sharing information about your experiences. In

order to preserve the confidentiality of your responses to the interview, an identification number will be

assigned to you. A list linking your name and identification number will be maintained in a secure location,

accessible only by the study’s technical monitor located at FHI.

ANTICIPATED BENEFITS

Information gathered during this interview will be reported to those charged with formulating policies and 

regulations governing federally funded research. Your responses will help inform policymakers of the possible

effects that changes to U.S. research regulations may have upon foreign-based researchers and any individuals

involved in their research studies.

Your participation in this study is entirely voluntary. You may refuse to answer any questions posed to you 

during this interview.

“I have read the above and have been given the opportunity to discuss it and ask questions. I have been

informed that I may contact Benjamin Popkin, the FHI technical monitor, at (919) 544-7040, ext 229, 

to answer any questions I may have during the investigation and that I may contact the Office of Risk

Management at (919) 684-3277 for any questions regarding my rights as a research subject. I agree to 

participate as a subject with the understanding that I may withdraw at any time.”

Name of person obtaining consent

Date Signature of person obtaining consent

IDENTIFICATION NUMBER 1 
ISBN 1-931022-14-3