Ethical and 

Policy Issues 

in Research 

Involving 

Human 

Participants

SUMMARY

Bethesda, Maryland

August 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

ISBN 1-931022-18-6
National Bioethics Advisory Commission

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 Bioethics

Law School and Medical School

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

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

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

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

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 & 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

*Resigned on May 10, 2001

Harold T. Shapiro, Ph.D., Chair

President Emeritus and Professor of Economics and Public Affairs

The Woodrow Wilson School of Public and International Affairs

Princeton University

Princeton, New Jersey

National Bioethics Advisory 

Commission Staff and Consultants

Executive Director

Eric M. Meslin, Ph.D.*

Project Director

Marjorie A. Speers, Ph.D. 

Research Staff

Douglas Berger, M.Litt., Program Analyst** 

Glen Drew, M.S., J.D., Senior Research Policy Analyst

Elisa Eiseman, Ph.D., Senior Research Analyst

Ellen L. Gadbois, Ph.D., Senior Policy Analyst

Stu Kim, J.D., Program Analyst***

Kerry Jo Lee, Program Analyst* 

Ayodeji Marquis, Intern (June–August 2000) 

Debra McCurry, M.S., Information Specialist

Alice K. Page, J.D., M.P.H., Senior Policy Analyst*

Consultants

Burness Communications, Communications Consultant

Sara Davidson, M.A., Editor

Liza Dawson, Ph.D., Research Consultant

(December 2000–March 2001)

Debra DeBruin, Ph.D., Bioethics Consultant

(July–December 2000)

Kathi E. Hanna, M.S., Ph.D., Editorial Consultant

The Hill Group, Meeting Consultant

Tamara Lee, Graphic Designer

Administrative Staff

Nicole Baker, Administrative Technician

Jody Crank, Assistant to the Executive Director

Evadne Hammett, Administrative Officer

Margaret C. Quinlan, Office Manager

Sherrie Senior, Secretary

* Until July 2001

** Until June 2001

***Until November 2000

Introduction

Protecting the rights and welfare of those who volunteerto participate in research is a fundamental tenet of

ethical research. A great deal of progress has been made

in recent decades in changing the culture of research to

incorporate more fully this ethical responsibility into 

protocol design and implementation. In the 1960s and

1970s, a series of scandals concerning social science

research and medical research conducted with the sick

and the illiterate underlined the need to systematically and

rigorously protect individuals in research (Beecher 1966;

Faden and Beauchamp 1986; Jones 1981; Katz 1972;

Tuskegee Syphilis Study Ad Hoc Advisory Panel 1973).

However, the resulting system of protections that evolved

out of these rising concerns—although an improvement

over past practices—is no longer sufficient. It is a patchwork arrangement associated with the receipt of federal

research funding or the regulatory review and approval of

new drugs and devices. In addition, it depends on the voluntary cooperation of investigators, research institutions,

and professional societies across a wide array of research

disciplines. Increasingly, the current system is being

viewed as uneven in its ability to simultaneously protect

the rights and welfare of research participants and promote

ethically responsible research.

Research involving human participants has become a

vast academic and commercial activity, but this country’s

system for the protection of human participants has not

kept pace with that growth. On the one hand, the system

is too narrow in scope to protect all participants, while on

the other hand, it is often so unnecessarily bureaucratic

that it stifles responsible research. Although some reforms

by particular federal agencies and professional societies

are under way,1 it will take the efforts of both the 

executive and legislative branches of government to put

in place a streamlined, effective, responsive, and comprehensive system that achieves the protection of all

human participants and encourages ethically responsible

research.

Clearly, scientific investigation has extended and

enhanced the quality of life and increased our understanding of ourselves, our relationships with others, and

the natural world. It is one of the foundations of our 

society’s material, intellectual, and social progress. For

many citizens, scientific discoveries have alleviated the

suffering caused by disease or disability. Nonetheless, the

prospect of gaining such valuable scientific knowledge

need not and should not be pursued at the expense 

of human rights or human dignity. In the words of 

philosopher Hans Jonas, “progress is an optional goal,

not an unconditional commitment, and...its tempo...

compulsive as it may become, has nothing sacred about

it” (Jonas 1969, 245).

Since the 1974 formation of the National

Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research and the activities in

the early 1980s of the President’s Commission for the

Study of Ethical Problems in Medicine and Biomedical

and Behavioral Research, American leaders have consistently tried to enhance the protections for human

research participants. The research community has, in

large part, supported the two essential protections for

human participants: independent review of research

to assess risks and potential benefits and an opportunity for people to voluntarily and knowledgeably decide

whether to participate in a particular research protocol. 

1

Protecting Research Participants—

A Time for Change
2

Summary

The charter of the National Bioethics Advisory

Commission (NBAC), a presidential commission created

in 1995, makes clear the Commission’s focus: “As a first

priority, NBAC shall direct its attention to consideration

of protection of the rights and welfare of human research

subjects.” In our first five years, we focused on several

issues concerning research involving human participants,

issuing five reports and numerous recommendations

that, when viewed as a whole, reflect our evolving

appreciation of the numerous and complex challenges

facing the implementation and oversight of any system

of protections.2 The concerns and recommendations

addressed in these reports reflect our dual commitment

to ensuring the protection of those who volunteer for

research while supporting the continued advance of 

science and understanding of the human condition. This

report views the oversight system as a whole, provides 

a rationale for change, and offers an interrelated set of

recommendations to improve the protection of human

participants and enable the oversight system to operate

more efficiently.

Respecting Research Participants

Whether testing a new medical treatment, interviewing

people about their personal habits, studying how people

think and feel, or observing how they live within groups,

research seeks to learn something new about the human

condition. Unfortunately, history has also demonstrated

that researchers sometimes treat participants not as 

persons but as mere objects of study. As Jonas observed:

“Experimentation was originally sanctioned by natural

science. There it is performed on inanimate objects, and

this raises no moral questions. But as soon as animate,

feeling beings become the subject of experiment...this

innocence of the search for knowledge is lost and 

questions of conscience arise” (Jonas 1969, 219).

How, then, should people be studied? For over half a

century, since the revelations of medical torture under

the guise of medical experimentation were described at

the Nuremberg Trials,3 it has been agreed that people

should participate in research only when the study

addresses important questions, its risks are justifiable,

and an individual’s participation is voluntary and

informed.

The principles underlying the Belmont Report: 

Ethical Principles and Guidelines for the Protection of 

Human Subjects of Research (Belmont Report) (National

Commission 1979) have served for over 20 years as a

leading source of guidance regarding the ethical 

standards that should govern research with human 

participants in the United States. The Belmont Report

emphasized that research must respect the autonomy 

of participants, must be fair in both conception and

implementation, and must maximize potential benefits

while minimizing possible harms. The report’s recommendations provided a coherent rationale for the federal

policies and rules that created the current U.S. system of

decentralized, independent research review coupled with

some degree of federal oversight. But although the

Belmont Report is rightly hailed as a key source of guidance on informed consent, assessment of risk, and the

injustice of placing individuals (and groups) in situations

of vulnerability, the principles the report espouses and

the regulations adopted as federal policy 20 years ago

have often fallen short in achieving their overarching 

goal of protecting human research participants. Moreover, since the Belmont Report was published, additional

concerns have arisen that require much-needed attention

today.

Ensuring Independent Review of Risks

and Potential Benefits

A central protection for research participants is the 

guarantee that someone other than the investigator 

will assess the risks of the proposed research. No one

should participate in research unless independent

review concludes that the risks are reasonable in

relation to the potential benefits. In the United States,

the Institutional Review Board, or IRB, has been the

principal structure responsible for conducting such

reviews.

Independent review of research is essential because it

improves the likelihood that decisions are made free from

inappropriate influences that could distort the central

task of evaluating risks and potential benefits. Certainly,

reviewers should not have a financial interest in the

work, but social factors may be just as crucial. Reviewers

may feel constrained because they are examining the
National Bioethics Advisory Commission

3

work of their colleagues or their supervisors, and they

should not participate in protocol review unless they are

able to separate these concerns from their task. All

reviewers who themselves are members of the research

community should recognize that their familiarity with

research and (perhaps) their predilection to support

research are factors that could distort their judgment.

Truly independent and sensitive review requires more

involvement of individuals drawn from the ranks of

potential research participants or those who can 

adequately represent the interests of potential research

participants.

A critical purpose of independent review is to ensure

that risks are reasonable in relation to potential personal

and societal benefits. This is a precondition to offering

people the opportunity to volunteer, since informed 

consent alone cannot justify enrollment. When reviewed

for risks and potential benefits, research studies must be

evaluated in their entirety. Studies often include different

components, however, and the risks and potential 

benefits of each should also be examined separately, lest

the possibility of great benefit or monetary enticement in 

one component cause potential participants or IRBs to

minimize or overlook risk in another. No matter what

potential benefit is offered to individual participants or

society at large, the possibility of benefit from one 

element of a study should not be used to justify otherwise

unacceptable elements. 

In our view, IRBs should appreciate that for some

components of a study, participants might incur risks

with no personal potential benefit, for example, when a

nondiagnostic survey is included among the components

of a psychotherapy protocol or when placebos are given

to some participants in a drug trial. For these elements,

there should be some limitation on the amount of social

and physical risk that can be imposed, regardless of the

participants’ willingness to participate or the monetary

(or other) enticement being offered. Further, the possibility of some benefit from one element of a study should

not be used to justify otherwise unacceptable elements of

research whose potential benefits, if any, accrue, solely to

society at large. If aspects of a study present unacceptable

risks, protocols should not be approved until these elements are eliminated. If removing the risky component

would impair the study as a whole, then the entire study

should be redesigned so that each of its elements presents

risks that are reasonable in relation to potential benefits.

Other parts of studies can obscure risks, such as when

standard medical interventions are compared in a patient

population, leading some participants and researchers to

discount the risks because they are associated with

known therapies. It is essential that participants and

investigators not be led to believe that participating in

research is tantamount to being in a traditional therapeutic relationship. Regardless of whether there is the

possibility or even the likelihood of direct benefit from

participation in research, such participation still alters the

relationship between a professional and the participant

by introducing another loyalty beyond that to the participant, to wit, loyalty to doing good science. It is too often

forgotten that even though the researchers may consider

participants’ interests to be important, they also have a

serious, and perhaps conflicting, obligation to science.

Years of experience with the current system of 

independent review have demonstrated that there are

enduring questions about how to arrive at such impartial

judgments and how to go about deciding when potential

benefits justify risks that are incurred solely by participants or the community from which they come. In recent

years, increasing strains on the system have undermined

the practice of independent review. IRBs are overburdened by the volume of research coming before them,

a strain that is compounded by concerns about training

of IRB members and possible conflicts of interest. In

addition, the constantly changing nature of research 

challenges existing notions about what constitutes risks

and potential benefits. 

Because IRBs are so central to the current oversight

system, they need better guidance on how to review and

monitor research, how to assess potential benefits to

research participants and their communities, and how to

distinguish among levels of risk. This report provides

such guidance in the following areas: determining the

type of review necessary for minimal risk research; ensuring that research participants are able to make voluntary

decisions and are appropriately informed prior to giving

consent; providing adequate protections for privacy and

confidentiality; identifying appropriate measures needed
4

Summary

when participants are susceptible to coercion or are otherwise placed in vulnerable situations; and monitoring

ongoing research. In addition, the report recommends

that IRB members and staff complete educational and

certification programs on research ethics before being

permitted to review research studies. 

Obtaining Voluntary Informed Consent

Even when risks are reasonable, however, no one should

participate in research without giving voluntary

informed consent (except in the case of an appropriate authorized representative or a waiver). Investigators must make appropriate disclosures and

ensure that participants have a good understanding

of the information and their choices, not only at 

the time of enrollment, but throughout the research.

Engaging in this process is one of the best ways

researchers can demonstrate their concern and respect

for those they aim to enroll in a study. It also serves as the

best means for those who do not wish to participate to

protect themselves.4

Recommendations from our previous reports are reinforced in this report, which emphasizes the process of

providing information and ensuring comprehension

rather than the form of documentation of the decision to

give consent. Both the information and the way it is conveyed—while meeting full disclosure requirements—

must be tailored to meet the needs of the participants in

the particular research context. In addition, documentation requirements must be adapted for varying research

settings, and the criteria for deciding when informed

consent is not necessary must be clarified so that participants’ rights and welfare are not endangered.

The decision to participate in research must not only

be informed, it must be voluntary. Even when risks are

reasonable and informed consent is obtained, it may

nonetheless be wrong to solicit certain people as participants. Those who are not fully capable of resisting the

request to become participants—such as prisoners and

other institutionalized or otherwise vulnerable persons—

should not be enrolled in studies merely because they are

easily accessible or convenient. This historic emphasis on

protecting people from being exploited as research 

participants, however, has failed to anticipate a time

when, at least for some areas of medical research, people

would be demanding to be included in certain studies

because they might provide the only opportunity for

receiving medical care for life-threatening diseases.

Making Research Inclusive While

Protecting Individuals Categorized as

Vulnerable

Vulnerable individuals need additional protection in

research. Although certain individuals and populations

are more vulnerable as human participants than others,

people whose circumstances render them vulnerable

should not be arbitrarily excluded from research for 

this reason alone. This includes those viewed as more

open to harm (e.g., children), more subject to coercion

(e.g., institutionalized persons), more “complicated”

(e.g., women, who are considered more biologically complicated than men), or more inconvenient (e.g., women

with small children, who are viewed as less reliable

research participants due to conflicting demands on

time). Calling competent people intrinsically “vulnerable”

can be both insulting and misleading. It is not their 

gender or other group designation that exposes them to

injury or coercion, but rather their situation that can be

exploited by ethically unacceptable research. That is, it is

their circumstances, which are situational, that create the

vulnerability. At other times it is the intrinsic characteristics of the person—for example, children or those with

certain mental or developmental disorders—that make

them generally vulnerable in the research setting. 

The response, whenever possible, should not be to

exclude people from research, but instead to change the

research design so that it does not create situations in

which people are unnecessarily harmed. To do otherwise

is to risk developing knowledge that helps only a subset

of the population. To the extent that the results are not

generalizable, the potential societal benefits that justify

doing the research are attenuated. Research participants

must be treated equally and with respect. Whenever

possible, research should be designed to encourage

the participation of all groups while protecting their

rights and welfare.
National Bioethics Advisory Commission

5

To accomplish this, we recommend that rather than

focusing primarily on categorizing groups as vulnerable,

investigators and IRBs should also recognize and avoid

situations that create susceptibility to harm or coercion.

Such situations may be as varied as patients being

recruited by their own physicians; sick and desperate

patients seeking enrollment in clinical trials; participants

being recruited by those who teach or employ them; 

or studies involving participants with any characteristic

that may make them less likely to receive care and respect

from others (e.g., convicted criminals or intravenous drug

users). In these circumstances, rather than excluding

whole groups of people, researchers should design studies

that reduce the risk of exploitation, whether by using a

different method of recruitment, by using a recruiter who

shares the participants’ characteristics, or by some other

technique. This is not always easy. It requires researchers

to consider carefully their research design and the potential pool of participants. At times, it will mean anticipating

that otherwise seemingly benign situations may become

more complex because a particular participant or group

of participants will be unusually susceptible to harm or

manipulation in this situation. At other times, the nature

of the vulnerability may require using a different research

design. Ethical research does not avoid complexity.

Rather, it acknowledges the full range and realities of the

human condition.

Compensating for Harms

Despite all these precautions, however, some research

participants might be harmed. Participants who are

harmed as a direct result of research should be cared

for and compensated. This is simple justice. The fact

that they offered to participate in no way alters the view

that mere decency calls for us to take care of these 

volunteers. Unfortunately, this is a greater challenge than

it might appear. For those who endure harm while participating in research, it is often very difficult to separate

injuries traceable to the research from those that stem

from the underlying disease or social condition being

studied. For others, appropriate care and compensation

would be far beyond the means of the researchers, their

sponsors, and their institutions. Two decades ago, the

President’s Commission for the Study of Ethical Problems

in Medicine and Biomedical and Behavioral Research

called for pilot studies of compensation programs—a

recommendation that was not pursued. It is time to

reconsider the need for some type of compensation 

program and to explore the possible mechanisms that

could be used were one to be adopted. Regardless of 

individual motives, research participants are providing a

service for society, and justice requires that they be

treated with great respect and receive appropriate care 

for any related injuries. It should always be remembered

that it is a privilege for any researcher to involve human 

participants in his or her research.

Establishing a Comprehensive,

Effective, and Streamlined System

In the United States, government regulations, professional

guidelines, and the general principles highlighted in the

Belmont Report (1979) form the basis of the current system of protections. In the earliest stages of adoption, the

federal regulations were fragmented and confusing. Even

today, they apply to most—but not all—research funded

or conducted by the federal government, but have inconsistent and sometimes no direct application to research

funded or conducted by state governments, foundations,

or industry. They apply to medical drugs and devices and

vaccines approved for interstate sale, but not to some

medical innovations that would remain wholly within

state borders. And they apply to other research only

when the investigators and their institutions volunteer to

abide by the rules. 

A comprehensive and effective oversight system 

is essential to uniformly protect the rights and 

welfare of participants while permitting ethically and

scientifically responsible research to proceed without

undue delay. A fundamental flaw in the current oversight system is the ethically indefensible difference in the

protection afforded participants in federally sponsored

research and those in privately sponsored research that

falls outside the jurisdiction of the Food and Drug

Administration (FDA). As a result, people have been subjected to experimentation without their knowledge or

informed consent in fields as diverse as plastic surgery,
6

Summary

psychology, and infertility treatment. This is wrong.

Participants should be protected from avoidable

harm, whether the research is publicly or privately

financed. We have repeated this assertion throughout

our deliberations, and recommendations in this regard

appear in four previous reports (NBAC 1997; NBAC

1999a; NBAC 1999b; NBAC 2001).

In this report, we recommend that the protections of

an oversight system extend to the entire private sector for

both domestic and international research. A credible,

effective oversight system must apply to all research, and

all people are entitled to the dignity that comes with

freely and knowingly choosing whether to participate in

research, as well as to protection from undue research

risks. This is consistent with our 1997 resolution that 

no one should be enrolled in research absent the twin 

protections of independent review and voluntary

informed consent. 

Even when current protections apply, the interpretation of the federal regulations can vary unpredictably,

depending on which federal agency oversees the research.

Even the most basic, common elements of the federal

rules took a decade to develop into regulations, because

there was no single authority within the government to

facilitate and demand cooperation and consistency. There

still is no such single authority.5 This has slowed the diffusion of basic protections and made it almost impossible

to develop consistent interpretations of the basic protections or those relevant to especially problematic research,

such as studies involving children or the decisionally

impaired. Nor has there been a unified response to

emerging areas of research, such as large-scale work on

medical records and social science databases or on stored

human biological materials.

Today’s research protection system cannot react

quickly to new developments. Efforts to develop rules

for special situations, such as research on those who 

can no longer make decisions for themselves, have languished for decades in the face of bureaucratic hurdles,

and there is no reason to believe that efforts to oversee

other emerging research areas will be any more efficient.

In addition, the current system leaves people vulnerable

to new, virtually uncontrolled experimentation in

emerging fields, such as some aspects of reproductive

medicine and genetic research.

Indeed, some areas of research are not only uncontrolled, they are almost invisible. In an information age,

poor management of research using medical records,

human tissue, or personal interview data could lead to

employment and insurance discrimination, social stigmatization, or even criminal prosecution.6 The privacy and

confidentiality concerns raised by this research are real,

but the federal response has often been illusory. There is

almost no guidance and certainly no coordination on

these topics. The time has come to have a single source

of guidance for these emerging areas, one that would be

better positioned to effect change across all divisions of

the government and private sector, as well as to facilitate

development of specialized review bodies, as needed.

In this report we propose a new independent oversight office that would have clear authority over all

other segments of the federal government and extend

protections to the entire private sector for both

domestic and international research. A single office

would decide how to introduce consistency or reforms,

and only that office would develop mechanisms to provide specialized review when needed. We recognize the

challenges to such a proposal. For example, an independent office might lack the political support accorded

an existing cabinet-level department. Although assigning

one department, such as the Department of Health 

and Human Services (DHHS), the role of “first among 

equals” would allow it to advocate forcefully for uniform

rules across the government, without special provisions 

it would not have the authority to require other departments to comply, nor is it certain to escape the temptation to develop rules premised on a traditional,

biomedical model rather than the wider range of research

to be covered. 

Federal research protections should be uniform

across all government agencies, academe, and the 

private sector, but they should be flexible enough to

be applied in widely different research settings or to

emerging areas of research. Furthermore, any central

coordinating body should be open to public input, have

significant political or legal authority over research

involving human participants—whether in the public or

private sector—and have the support of the executive

and legislative branches of government.
National Bioethics Advisory Commission

7

Education as the Key to Promoting

Local Responsibility

Currently, federal protections depend on a decentralized

oversight system involving IRBs, institutions, investigators,

sponsors, and participants. We endorse the spirit and

intent of this approach, specifically its contention that

the ethical obligation to protect participants lies first

with researchers, their sponsors, and the IRBs that

review their research. Protecting research participants 

is a duty that researchers, research institutions, and 

sponsors cannot delegate completely to others or to the

government. In addition, merely adhering to a set of rules

and regulations does not fulfill this duty. Rather, it is

accomplished by acting within a culture of concern and

respect for research participants.

It is unrealistic to think that ethical obligations can be

fully met without guidance and resources. To help

researchers and IRBs fulfill their responsibilities, the 

federal government should promote the development

of education, certification, and accreditation systems

that apply to all researchers, all IRB members and

staff, and all institutions. These tools should help

researchers craft and IRBs review studies that pose few

problems and to know when their work requires special oversight. Today, investigators and IRBs are rightly

confused over issues as basic as which areas of inquiry

should be reviewed and who constitutes a human 

participant.

Education is the foundation of the oversight system

and is essential to protecting research participants. In all

of our reports, we have highlighted the need to educate

all those involved in research with human participants,

including the public, investigators, IRB members, institutions, and federal agencies. In Cloning Human Beings

(1997), we recommended federal support of public 

education in biomedical sciences that increasingly affect

our cultural values. In Research Involving Persons with

Mental Disorders That May Affect Decisionmaking Capacity

(1998), we called for practice guidelines and ethics education on special concerns regarding this population. In

Ethical and Policy Issues in International Research: Clinical

Trials in Developing Countries (2001), we recommended

measures to help developing countries build their 

capacity for designing and conducting clinical trials, for

reviewing the ethics and science of proposed research,

and for using research results after a trial is completed.

In this report, we again acknowledge the inadequacy

of educational programs on research ethics in the United

States. This deficiency begins at the highest level within

the federal oversight system and extends to the local 

level at individual institutions. We recommend that

investigators and IRB members and staff successfully

complete educational programs on research ethics and

become certified before they perform or review research,

that research ethics be taught to the next generation 

of scientists, and that research ethics be included in 

continuing education programs.

Clarifying the Scope of Oversight

Many areas of scientific inquiry are “research,” and many

of these involve human participants, but only some need

federal oversight, while others might be better regulated

through professional ethics, social custom, or other state

and federal law. For example, certain types of surveys and

interviews are considered research, but they can be well

managed to avoid harms without federal oversight, as the

risks are few and participants are well situated to decide

for themselves whether to participate. On the other hand,

certain studies of medical records, databases, and discarded surgical tissue are often perceived as something

other than human research, even when the information

retrieved is traceable to an identifiable person. Such

research does need oversight to avoid putting people at

risk of identity disclosure or discrimination without their

knowledge. Federal policies should clearly identify

the kinds of research that are subject to review and

the types of research participants to whom protections should apply. When research poses significant

risks or when its risks are imposed on participants 

without their knowledge, it clearly requires oversight.

However, meaningless or overly rigid oversight engenders

disdain on the part of researchers, creates an impossible

and pointless workload for IRBs, and deters ethically

sound research from going forward.
8

Summary

Ensuring That the Level of Review

Corresponds to the Level of Risk

Even within areas of research that need oversight, many

individual studies will involve little or no risk to participants. Although current federal policies allow for 

some distinction between research involving minimal

risk and research involving more than minimal risk, the

distinction operates mostly in terms of how the research

will be reviewed—that is, how procedures are to be 

followed. But the distinction should be based on how the

research is pursued, how the participants are treated, 

and how the work is monitored over time. Overall, the

emphasis should be on knowing how to protect participants rather than on knowing how to navigate research

regulations. Instead of focusing so much on the period

during which a research design is reviewed, oversight

should also include an ongoing system of education and

certification that helps researchers to anticipate and minimize research risks. Oversight should also make it easier

for researchers to collaborate with their colleagues here

and abroad without the burden of redundant reviews.

Research review and monitoring should be intensified

as the risk and complexity of the research increase

and at all times should emphasize protecting participants rather than following rigid rules. In addition,

the review process should facilitate rather than hinder

collaborative research among institutions and across

national boundaries, provided that participants are

protected.

Providing Resources for the Oversight

System

Creating a system that protects the rights and welfare 

of participants and facilitates responsible research

demands political and financial support from the federal

government as well as the presence of a central coordinating body to provide guidance and oversee education

and accreditation efforts. The oversight system should

be adequately funded at all levels to ensure that

research continues in a manner that demonstrates

respect and concern for the interests of research 

participants.

National Bioethics Advisory Commission

This report proposes 30 recommendations for changing the oversight system at the national and local

levels to ensure that all research participants receive the

appropriate protections. The adoption of these recommendations, which are directed at all who are involved in

the research enterprise, will not only lead to better protection for the participants of research, but will also serve

to promote ethically sound research while reducing

unnecessary bureaucratic burdens. Achieving these goals

will, in turn, restore the respect of investigators for the

system used to oversee research, support the public’s

trust in the research enterprise, and enhance public

enthusiasm for all research involving human beings. 

Scope and Structure of the Oversight

System

The entitlements due to all research participants of a

prior independent review of risks and potential benefits

and the opportunity to exercise voluntary informed consent are the most basic and essential protections for all

research participants. However, not all research participants receive these entitlements and not all are protected

by the existing oversight system. The commitment to

protect participants should not be voluntary, nor should

requirements be in place for only some human research.

Extending current protections to all research, whether

Summary of Recommendations
National Bioethics Advisory Commission

9

publicly or privately funded, and making uniform all 

federal regulations and guidance cannot be accomplished

within the current oversight system, in which no entity has

the authority to act on behalf of all research participants.

Thus, to facilitate the extension of the same protections

to all humans participating in research, a unified, comprehensive federal policy promulgated and interpreted

by a single office is needed. 

Recommendation 2.1: The federal oversight 

system should protect the rights and welfare 

of human research participants by requiring 

1) independent review of risks and potential 

benefits and 2) voluntary informed consent.

Protection should be available to participants in

both publicly and privately sponsored research.

Federal legislation should be enacted to provide

such protection.

Recommendation 2.2: To ensure the protection of

the rights and welfare of all research participants,

federal legislation should be enacted to create a

single, independent federal office, the National

Office for Human Research Oversight (NOHRO),

to lead and coordinate the oversight system. This

office should be responsible for policy development, regulatory reform (see Recommendation

2.3), research review and monitoring, research

ethics education, and enforcement. 

Recommendation 2.3: A unified, comprehensive

federal policy embodied in a single set of regulations and guidance should be created that would

apply to all types of research involving human

participants (see Recommendation 2.2).

Determining whether particular research activities

involving human participants should be subject to a federal oversight system has been a source of confusion for

some time. No regulatory definition of covered research

can be provided that has the sensitivity and specificity

required to ensure that all research activities that include

human participants that should be subject to oversight

are always included and all activities that should be

excluded from oversight protections are always excluded.

Clarification and interpretation of the definition of what

constitutes research involving human participants will

invariably be required if the oversight system is to work

effectively and efficiently. Moreover, there will always be

cases over which experts disagree about the research 

status of a particular activity. One of the important leadership roles the proposed oversight office should fulfill 

is that of providing guidance on determining whether 

an activity is research involving human participants and

is therefore subject to oversight. 

Recommendation 2.4: Federal policy should 

cover research involving human participants 

that entails systematic collection or analysis of

data with the intent to generate new knowledge.

Research should be considered to involve human

participants when individuals 1) are exposed to

manipulations, interventions, observations, or

other types of interactions with investigators 

or 2) are identifiable through research using 

biological materials, medical and other records,

or databases. Federal policy also should identify

those research activities that are not subject to

federal oversight and outline a procedure for

determining whether a particular study is or is

not covered by the oversight system.

The proposed federal office should initiate a process

in which representatives from various disciplines and

professions (e.g., social science, humanities, business,

public health, and health services) contribute to the

development of the definition and the list of research

activities subject to the oversight system. 

Level of Review

Although the definition of research involving human 

participants should be applied to all disciplines, the

risks differ both qualitatively and quantitatively across

the spectrum of research. Therefore, the oversight system

should ensure that all covered research is subject to basic

protections—such as a process of informed consent—

with the exceptions of the specified conditions for which

these protections can be waived, including protection of

privacy and confidentiality and minimization of risks.

Because the proposed oversight system may include

more research activities, it is more critical than ever that

review mechanisms and criteria for various types of
10

Summary

research are suited to the nature of the research and the

likely risks involved. More specific guidance is needed

for review of different types of research, including appropriate review criteria and IRB composition. For example,

procedures other than full board review could be used for

minimal risk research, and national level reviews could

supplement local IRB review of research involving novel

or controversial ethical issues. 

Recommendation 2.5: Federal policy should

require research ethics review that is commensurate with the nature and level of risk involved.

Standards and procedures for review should 

distinguish between research that poses minimal

risk and research that poses more than minimal

risk. Minimal risk should be defined as the 

probability and magnitude of harms that are 

normally encountered in the daily lives of the

general population (see Recommendation 4.2). 

In addition, the federal government should 

facilitate the creation of special, supplementary

review bodies for research that involves novel 

or controversial ethical issues. 

Education, Certification, and

Accreditation

Protecting the rights and welfare of research participants

is the major ethical obligation of all parties involved in

the oversight system, and to provide these protections, 

all parties must be able to demonstrate competence in

research ethics—that is, conducting, reviewing, or overseeing research involving human participants in an

ethically sound manner. Such competence entails not

only being knowledgeable about relevant research 

ethics issues and federal policies, but also being able to

identify, disclose, and manage conflicting interests for

institutions, investigators, or IRBs. Finally, the oversight

system must include a sufficiently robust monitoring

process to provide remedies for lapses by institutions,

IRBs, and investigators.

Recommendation 3.1: All institutions and sponsors

engaged in research involving human participants

should provide educational programs in research

ethics to appropriate institutional officials, investigators, Institutional Review Board members,

and Institutional Review Board staff. Among

other issues, these programs should emphasize

the obligations of institutions, sponsors,

Institutional Review Boards, and investigators 

to protect the rights and welfare of participants.

Colleges and universities should include research

ethics in curricula related to research methods,

and professional societies should include research

ethics in their continuing education programs. 

Recommendation 3.2: The federal government, 

in partnership with academic and professional

societies, should enhance research ethics 

education related to protecting human research 

participants and stimulate the development of

innovative educational programs. Professional

societies should be consulted so that educational

programs are designed to meet the needs of all

who conduct and review research. 

Educating all parties in research ethics and human

participant protections is effective only when it results in

the necessary competence for designing and conducting

ethically sound research, including analyzing, interpreting, and disseminating results in an ethically sound 

manner. Such competence, however, cannot be assumed

to follow from exposure to an educational course or program. As the complexion of research continues to change

and as technology advances, new and challenging ethical

dilemmas will emerge. And, as more people become

involved in research as investigators or in roles that are

specifically related to oversight, it becomes increasingly

important for all parties to be able to demonstrate

competence in the ethics of research involving human

participants. 

Although accreditation and certification do not

always guarantee the desired outcomes, these programs,

which generally involve experts and peers developing 

a set of standards that represents a consensus of best

practices, can be helpful in improving performance.

Therefore, the choice of standards for these programs and

the criteria for evaluating whether an institution has met

them are critically important. Accreditation and certification programs should emphasize providing education

and assuring that appropriate protections are in place,

while avoiding excessively bureaucratic procedures. 
National Bioethics Advisory Commission

11

Recommendation 3.3: All investigators, Institutional

Review Board members, and Institutional Review

Board staff should be certified prior to conducting

or reviewing research involving human participants.

Certification requirements should be appropriate

to their roles and to the area of research. The federal government should encourage organizations,

sponsors, and institutions to develop certification

programs and mechanisms to evaluate their effectiveness. Federal policy should set standards for

determining whether institutions and sponsors

have an effective process of certification in place. 

Recommendation 3.4: Sponsors, institutions, and

independent Institutional Review Boards should

be accredited in order to conduct or review research

involving human participants. Accreditation should

be premised upon demonstrated competency in

core areas through accreditation programs that

are approved by the federal government.

Assessing and Monitoring Compliance

Assessing institutional, IRB, and investigator compliance

can help to ensure that standards are being followed 

consistently. Current mechanisms for assessment include

assurances of compliance issued by DHHS and several

other federal departments, site inspections of IRBs conducted by FDA, other types of site inspections for participant protection, and institutional audits. In addition,

some institutions have established ongoing mechanisms

for assessing investigator compliance with regulations.

However, institutions vary considerably in their efforts

and abilities to monitor investigator compliance, from

those that have no monitoring programs to those that

conduct random audits. Assessing the behavior of investigators is an important part of protecting research participants and should be taken seriously as a responsibility

of each institution. Investigators, IRBs, and institutions

should discuss the many practical issues involved in

monitoring investigators as they conduct their research

studies and provide input into the regulatory process. 

Recommendation 3.5: The process for assuring

compliance with federal policy should be modified

to reduce any unnecessary burden on institutions

conducting research and to register institutions

and Institutional Review Boards with the federal

government. The assurance process should not

be duplicative of accreditation programs for 

institutions (see Recommendation 3.4). 

Recommendation 3.6: Institutions should develop

internal mechanisms to ensure Institutional

Review Board compliance and investigator 

compliance with regulations, guidance, and 

institutional procedures. Mechanisms should be

put in place for reporting noncompliance to all

relevant parties.

Managing Conflicts of Interest

A research setting that involves human participants 

necessarily creates a conflict of interest for investigators

who seek to develop or revise knowledge by enrolling

individuals in research protocols to obtain that knowledge. Overzealous pursuit of scientific results could lead

to harm if, for example, investigators design research

studies that pose unacceptable risks to participants,

enroll participants who should not be enrolled, or continue studies even when results suggest they should have

been modified or halted. Conflicts of interest can also

exist for IRB members or the institutions in which the

research will be conducted. Thus, it is important to

address prospectively the potentially harmful effects on

participants that conflicts of interest might cause. 

Organizations, particularly academic institutions,

should become more actively involved in managing

investigators’ and IRB members’ conflicts of interest and

increase their efforts for self-regulation in this arena. IRB

review of research studies is one method for identifying

and dealing with conflicts of interest that might face

investigators. By having IRBs review research studies

prospectively and follow an IRB-approved protocol,

investigators and IRBs together can manage conflict

between the investigators’ desire to advance scientific

knowledge and to protect the rights and welfare of

research participants. Financial and other obvious conflicts for IRB members, such as collaboration in a research

study, are often less difficult to identify and manage than

some of the more subtle and pervasive conflicts.
12

Summary

Guidance should be developed to assist IRBs in identifying

various types of conflict. 

Recommendation 3.7: Federal policy should define

institutional, Institutional Review Board, and

investigator conflicts of interest, and guidance

should be issued to ensure that the rights and

welfare of research participants are protected. 

Recommendation 3.8: Sponsors and institutions

should develop policies and mechanisms to 

identify and manage all types of institutional,

Institutional Review Board, and investigator 

conflicts of interest. In particular, all relevant

conflicts of interest should be disclosed to 

participants. Policies also should describe 

specific types of prohibited relationships. 

IRB Membership

Appropriate composition of IRB membership ensures

that research studies are reviewed with the utmost regard

for protecting the rights and welfare of research participants. Current federal regulations require that each IRB

have “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”

(45 CFR 46.107(d); 21 CFR 56.107(d)). The regulations

also require that each IRB include “at least one member

whose primary concerns are in scientific areas and at

least one member whose primary concerns are in nonscientific areas.” Some have raised the concern of

whether only 1 unaffiliated member on an IRB is sufficient to avoid institutional influence, especially when

IRBs have 15 to 21 members on average. In addition,

unaffiliated members do not have to be present for an IRB

to conduct review and approve research studies. Thus,

IRBs can approve research with only institutional representation present as long as a nonscientist and a quorum

are also present. IRBs should strive to complement their

membership by having clearly recognizable members

who are unaffiliated with the institutions, members who

are nonscientists, and members who represent the 

perspectives of participants. However, it is difficult to

require that IRBs increase the presence and participation

of more unaffiliated members to reduce the influence of

institutional interests on IRB decisionmaking, because

finding them can be difficult. Currently, there are no rules

or guidance that describe criteria for meeting the definition of an unaffiliated member, that specify how long

such members should serve, or that provide guidance

regarding under what circumstances they may be

removed or what payment should be provided.

Institutions should be careful to select unaffiliated members who are truly separated from the institution, except

for their role on the IRB. Procedures for the selection and

removal of unaffiliated members should be established in

a way that empowers the independent voices of those

members. In addition, providing reasonable payment to

IRB members who are otherwise unaffiliated with the

institution can be a valuable way to strengthen these

members’ role.

Recommendation 3.9: Federal policy should 

establish standards and criteria for the selection

of Institutional Review Board members. The 

distribution of Institutional Review Board 

members with relevant expertise and experience

should be commensurate with the types of

research reviewed by the Institutional Review

Board (see Recommendation 3.10). 

Recommendation 3.10: Institutional Review 

Boards should include members who represent

the perspectives of participants, members who

are unaffiliated with the institution, and members

whose primary concerns are in nonscientific

areas. An individual can fulfill one, two, or all

three of these categories. For the purposes of

both overall membership and quorum determinations 1) these persons should collectively

represent at least 25 percent of the Institutional

Review Board membership and 2) members from

all of these categories should be represented each

time an Institutional Review Board meets (see

Recommendation 3.9). 
National Bioethics Advisory Commission

13

Guidance for Assessing Risks and

Potential Benefits

In addition to protecting the rights and welfare of

research participants, it is equally important to protect

them from avoidable harm. Thus, an IRB’s assessment of

the risks and potential benefits of research is central to

determining whether a research study is ethically

acceptable. Yet, this assessment can be a difficult one to

make, as there are no clear criteria for IRBs to use in

judging whether the risks of research are reasonable in

terms of what might be gained by the individual or society.

IRBs should be able to identify whether a clear and

direct benefit to society or the research participants might

result from participating in the study. However, IRBs

should be cautious in classifying procedures as offering

the prospect of direct benefit. In fact, if it is not clear that

a procedure also offers the prospect of direct benefit, IRBs

should treat the procedure as one solely designed to

answer the research question(s). A major advantage of this

approach is that it avoids justifying the risks of procedures that are designed solely to answer the research

question(s) based on the likelihood that another procedure in the protocol would provide a benefit.

Recommendation 4.1: An analysis of the risks 

and potential benefits of study components

should be applied to all types of covered research

(see Recommendation 2.4). In general, each 

component of a study should be evaluated 

separately, and its risks should be both reasonable in themselves as well as justified by the

potential benefits to society or the participants.

Potential benefits from one component of a study

should not be used to justify risks posed by a

separate component of a study.

Minimal Risk

Determining whether a study poses more than minimal

risk is a central ethical and procedural function of the

IRB. The definition of minimal risk in federal regulations

(45 CFR 46.102(i); 21 CFR 56.102(i)) provides an

ambiguous standard by which risks involved in a

research study are compared to those encountered in

daily life. However, it is unclear whether this applies to

those risks found in the daily lives of healthy individuals

or those of individuals who belong to the group targeted

by the research. If it refers to the individuals to be

involved in the research, then the same intervention

could be classified as minimal risk or greater than minimal

risk, depending on the health status of those participants

and their particular experiences. According to this understanding, the standard for minimal risk is a relative one. 

This report recommends that IRBs use a standard

related to the risks of daily life that are familiar to the

general population for determining whether the level of

risk is minimal or more than minimal, rather than using

a standard that refers to the risks encountered by particular persons or groups. These common risks would

include, for example, driving to work, crossing the street,

getting a blood test, or answering questions over the 

telephone. Thus, research would involve no more than

minimal risk when it is judged that the level of risk is no

greater than that encountered in the daily lives of the

general population. 

Recommendation 4.2: Federal policy should 

distinguish between research studies that pose

minimal risk and those that pose more than 

minimal risk (see Recommendation 2.5). Minimal

risk should be defined as the probability and

magnitude of harms that are normally encountered

in the daily lives of the general population. If a

study that would normally be considered minimal

risk for the general population nonetheless poses

higher risk for any prospective participants, then

the Institutional Review Board should approve

the study only if it has determined that appropriate protections are in place for all prospective

participants.

Evaluating Vulnerability

All segments of society should have the opportunity to

participate in research, if they wish to do so and if they

are considered to be appropriate participants for a given

protocol. However, some individuals may need additional protections before they can fully participate in the

research study; otherwise they might be more susceptible
14

Summary

to coercion or exploitation. Individuals might be considered vulnerable within the research context because of

intrinsic characteristics (e.g., they are children or have

mental illness or retardation) or because of the situation in

which they find themselves (e.g., they are impoverished,

unemployed, or incarcerated). Recognizing various types

of vulnerability and providing adequate safeguards can

prove challenging for IRBs. 

Appropriate and specific safeguards should be established to protect persons who are categorized as vulnerable. Once safeguards are established, investigators 

should not exclude persons categorized as vulnerable

from research involving greater than minimal risk

because this would deprive them of whatever potential

direct benefits they might receive from the research and

deprive their communities and society from the benefit of

the knowledge such research might generate. 

Recommendation 4.3: Federal policy should promote the inclusion of all segments of society in

research. Guidance should be developed on how

to identify and avoid situations that render some

participants or groups vulnerable to harm or

coercion. Sponsors and investigators should

design research that incorporates appropriate

safeguards to protect all prospective participants.

Emphasizing the Informed Consent

Process

Rather than focusing on the ethical standard of informed

consent and what is entailed in the process of obtaining

informed consent, IRBs and investigators have followed

the lead of the federal regulations and have tended to

focus on the disclosures found in the consent form.

However, from an ethics perspective, the informed consent process, not the form of its documentation, is the

critical communication link between the prospective 

participant and the investigator throughout a study,

beginning when the investigator initially approaches the

participant. Informed consent should be an active

process through which both parties share information

and during which the participant at any time can freely

decide whether to withdraw from or continue to participate in the research. It is time to place the emphasis on

the process of informed consent to ensure that information is fully disclosed, that competent participants fully

understand the research in order to make informed

choices, and that decisions to participate or not are

always made voluntarily.

Recommendation 5.1: Federal policy should

emphasize the process of informed consent

rather than the form of its documentation and

should ensure that competent participants have

given their voluntary informed consent. Guidance

should be issued about how to provide appropriate

information to prospective research participants,

how to promote prospective participants’ comprehension of such information, and how to

ensure that participants continue to make

informed and voluntary decisions throughout

their involvement in the research.

Waiver of Informed Consent

Obtaining voluntary informed consent should not be a

requirement for every research study. In fact, waiving the

informed consent process is justifiable in research studies

that include no interaction between investigators and

participants, such as in studies using existing identifiable

data (e.g., studies of records) and in studies in which

risks generally are not physical. In these kinds of

research, risks are likely to arise from the acquisition, use,

or dissemination of information resulting from the study

and are likely to involve threats to privacy and breaches

in confidentiality. The criteria for waiving informed consent in such instances should be revised, so that if such

studies have protections in place for both privacy and

confidentiality, IRBs may waive the requirement for

informed consent. 

Recommendation 5.2: Federal policy should permit

Institutional Review Boards in certain, limited

situations (e.g., some studies using existing 

identifiable data or some observational studies)

to waive informed consent requirements if all of

the following criteria are met:

a) all components of the study involve minimal

risk or any component involving more than

minimal risk must also offer the prospect of

direct benefit to participants;
National Bioethics Advisory Commission

15

b) the waiver is not otherwise prohibited by

state, federal, or international law;

c) there is an adequate plan to protect the 

confidentiality of the data;

d) there is an adequate plan for contacting 

participants with information derived from

the research, should the need arise; and

e) in analyzing risks and potential benefits, 

the Institutional Review Board specifically

determines that the benefits from the knowledge to be gained from the research study 

outweigh any dignitary harm associated with

not seeking informed consent.

Documentation of Informed Consent

Although the federal regulations may have been intended

to reflect a legal standard for documentation of informed

consent, NBAC is aware of no case law in which a signed,

written consent form is required. To fulfill the substantive

ethical standard of informed consent, depending on the

type of research proposed, it may be more appropriate to

use other forms of documentation, such as audiotape,

videotape, witnesses, or telephone calls to participants

verifying informed consent and participation in the

research study.

Recommendation 5.3: Federal policy should

require investigators to document that they 

have obtained voluntary informed consent, but

should be flexible with respect to the form of

such documentation. Especially when individuals

can easily refuse or discontinue participation, or

when signed forms might threaten confidentiality,

Institutional Review Boards should permit 

investigators to use other means of verifying 

that informed consent has been obtained.

Protecting Privacy and Confidentiality

Privacy and confidentiality are complex and poorly

understood concepts in the context of some research.

Privacy refers to the ways and circumstances under

which investigators access information from participants.

Because privacy concerns vary by type and context of

research and the culture and individual circumstances of

participants, investigators should be well informed and

mindful of the cultural norms of the participants. In

addition, investigators should be aware of the various

research procedures and methods that can be used to

respect privacy. Needed is a clear, comprehensive regulatory definition of privacy along with guidance for 

protecting privacy in various types of research.

Like privacy concerns, concerns about confidentiality

vary by the type and context of the research. No one set

of procedures can be developed to protect confidentiality

in all research contexts. Thus, IRBs and investigators

must tailor confidentiality protections to the specific circumstances and methods used in each specific research

study. Further, IRBs and investigators are encouraged to

consider the use of strong confidentiality protections,

which can also reduce some of the violations associated

with privacy. A clear, comprehensive definition of confidentiality is needed, along with guidance for protecting

confidentiality in various types of research. 

Recommendation 5.4: Federal policy should be

developed and mechanisms should be provided

to enable investigators and institutions to reduce

threats to privacy and breaches of confidentiality.

The feasibility of additional mechanisms should

be examined to strengthen confidentiality 

protections in research studies.

Monitoring of Ongoing Research

Continual review and monitoring of research that is in

progress is a critical element of the oversight system.

Such review is necessary to ensure that emerging data or

evidence have not altered the risks/potential benefits

assessment so that risks are no longer reasonable. In addition, mechanisms are needed to monitor adverse events,

unanticipated problems, and changes to the protocol.

IRBs can do a better job in this area with the appropriate

guidance and some restructuring of the review and 

monitoring process. 

Currently, the requirement of continuing review is

overly broad. The frequency and need for continuing

review vary depending on the nature of research, with

some protocols not requiring continuing review. In

research involving high or unknown risks, the first few

trials of a new intervention may substantially affect what
16

Summary

is known about the risks and potential benefits of that

intervention. Even if the knowledge does not warrant

changes in study design, it may warrant changes in the

information presented to prospective and enrolled 

participants.

On the other hand, the ethics issues and participant

protections necessary in minimal risk research are

unlikely to be affected by developments from within or

outside the research—for example, research involving

the use of existing data or research that will no longer

involve contact with participants because it is in the data

analysis phase. Continuing review of such research

should not be required because it is unlikely to provide

any additional protection to research participants and

merely increases the burden of IRBs. However, because

minimal risk research does involve some risk, IRBs may

choose to require continuing review. In these cases, other

types of monitoring may be more appropriate, such as

assessing investigator compliance with the approved protocol or reporting of protocol changes and unanticipated

problems. Clarifying the nature of the continuing review

requirements would allow IRBs to better focus their

efforts on reviewing riskier research and would increase

protections for participants where they are most needed.

Recommendation 6.1: Federal policy should

describe how sponsors, institutions, and 

investigators should monitor ongoing research.

Recommendation 6.2: Federal policy should

describe clearly the requirements for continuing

Institutional Review Board review of ongoing

research. Continuing review should not be

required for research studies involving minimal

risk, research involving the use of existing data,

or research that is in the data analysis phase

when there is no additional contact with participants. When continuing review is not required,

other mechanisms should be in place for ensuring

compliance of investigators and for reporting

protocol changes or unanticipated problems

encountered in the research.

Recommendation 6.3: Federal policy should 

clarify when changes in research design or 

context require review and new approval by 

an Institutional Review Board.

Adverse Event Reporting

Assessing adverse events reports can be a major burden

for IRBs and investigators because of the high volume

and ambiguous nature of such events and the complexity

of the pertinent regulatory requirements. Investigators

have reported frustration in attempting to understand

what constitutes an adverse event, the required reporting

times, and to whom adverse events should be reported.

The regulations need to be simplified, and one set of 

regulations should be available for safety monitoring.

Regulations and guidance should be written so that

investigators and sponsors understand what constitutes

an adverse event, what type of event must be reported

within what time period, and to whom it should be

reported. In addition, regulations and guidance should

be clear regarding whose responsibility it is to analyze

and evaluate adverse event reports and should describe

the required communication and coordination channels

for these reports among IRBs and safety monitoring entities, such as Data Safety Monitoring Boards, investigators,

sponsors, and federal agencies.

Recommendation 6.4: The federal government

should create a uniform system for reporting and

evaluating adverse events occurring in research,

especially in multi-site research. The reporting

and evaluation responsibilities of investigators,

sponsors, Institutional Review Boards, Data

Safety Monitoring Boards, and federal agencies

should be clear and efficient. The primary concern

of the reporting system should be to protect 

current and prospective research participants.

Review of Cooperative or Multi-Site

Research Studies

One of the greatest burdens on IRBs and investigators 

is the review of multi-site studies. Requiring multiple

institutions to review the same protocol is unnecessarily

taxing and provides no additional protection to participants. In addition, such review poses problems in the 

initial stages of review as well as in the continual review

and monitoring stages and is especially problematic in

the evaluation of adverse events in clinical research.
National Bioethics Advisory Commission

17

Innovative and creative alternative mechanisms and

processes for reviewing protocols in multi-site research

are needed. To allow for such projects and to support a

change in the current system toward a more flexible

review system, federal policy should be clear about the

functions that must be performed, but be less restrictive

about who performs each function. 

Recommendation 6.5: For multi-site research, 

federal policy should permit central or lead

Institutional Review Board review, provided 

that participants’ rights and welfare are 

rigorously protected.

Compensation for Research-Related

Injuries

Participants who volunteer to be in a research study and

are harmed as a direct result of that study should be cared

for and compensated. However, no adequate database

exists that describes the number of injuries or illnesses

that are suffered by research participants, the proportion

of these illnesses or injuries that are caused by the

research, and the medical treatment and rehabilitation

expenses that are subsequently borne by the participants.

It may be argued that regardless of the magnitude of the

problem, the costs of research injuries should never be

borne by participants. If individuals are injured by

research participation, those who benefit from the

research (e.g., institutions and sponsors) bear some 

obligation to compensate those who risked and suffered

injury on their behalf. At this time, injured research 

participants alone bear both the cost of lost health and

the expense of medical care, unless they have adequate

health insurance or successfully pursue legal action to

gain compensation from the specific individuals or

organizations that were involved in conducting the

research. 

A comprehensive system of oversight of human

research should include a mechanism to compensate 

participants for medical and rehabilitative costs resulting

from research-related injuries. 

Recommendation 6.6: The federal government

should study the issue of research-related injuries

to determine if there is a need for a compensation

program. If needed, the federal government

should implement the recommendation of the

President’s Commission for the Study of Ethical

Problems in Medicine and Biomedical and

Behavioral Research (1982) to conduct a pilot

study to evaluate possible program mechanisms.

The Need for Resources

Adopting the recommendations made in this report will

generate additional costs for institutions, sponsors, and

the federal government (through the establishment of a

new federal oversight office). Sponsors of research,

whether public or private, should work together with

institutions carrying out the research to make the necessary funds available.

Recommendation 7.1: The proposed oversight 

system should have adequate resources to ensure

its effectiveness and ultimate success in protecting

research participants and promoting research: 

a) Funds should be appropriated to carry out the

functions of the proposed federal oversight

office as outlined in this report.

b) Federal appropriations for research programs

should include a separate allocation for 

oversight activities related to the protection 

of human participants.

c) Institutions should be permitted to request

funding for Institutional Review Boards and

other oversight activities.

d) Federal agencies, other sponsors, and institutions should make additional funds available

for oversight activities.

Future Research

This report raises many questions about ethical issues

that cannot be answered because of insufficient or

nonexistent empirical evidence. Current thinking about

ethical issues in research—such as analysis of risks and
18

Summary

potential benefits, informed consent, privacy and confidentiality, and vulnerability—would greatly benefit from

additional research. Deserving of more study, for example,

are questions regarding the development of effective

approaches for assessing cognitive capacity, for evaluating

what participants want to know about research, and for

determining how to ascertain best practices for seeking

informed consent. Clearer and more effective guidance

could be developed from a stronger knowledge base. In

general, understanding the ethical conduct of research

would be advanced by increased interdisciplinary discussion that would include biomedical and social scientists,

lawyers, and historians. 

Recommendation 7.2: The federal government, 

in partnership with academic institutions and

professional societies, should facilitate discussion

about emerging human research protection issues

and develop a research agenda that addresses

issues related to research ethics.

Notes

1 For example, the Office for Human Research Protections is

implementing a new process by which institutions assure future

compliance with human participant protections. The Institute of

Medicine has recently issued a report on accreditation standards

for IRBs (IOM 2001). Public Responsibility in Medicine and

Research has established training programs and has co-founded 

a new organization, the Association for the Accreditation of 

Human Research Protection Programs. 

2 To date, NBAC has issued five reports: Cloning Human Beings

(NBAC 1997), Research Involving Persons with Mental Disorders 

That May Affect Decisionmaking Capacity (NBAC 1998), Ethical Issues

in Human Stem Cell Research (NBAC 1999a), Research Involving

Human Biological Materials: Ethical Issues and Policy Guidance

(NBAC 1999b), and Ethical and Policy Issues in International

Research: Clinical Trials in Developing Countries (NBAC 2001).

3 United States v. Karl Brandt et al., Trials of War Criminals Before

the Nuremberg Military Tribunals Under Control Council Law 10.

Nuremberg, October 1946–April 1949. Volumes I–II. Washington,

D.C.: U.S. Government Printing Office.

4 There are, of course, some circumstances in which consent 

cannot be obtained and in which an overly rigid adherence to 

this principle would preclude research that is either benign or

potentially needed by the participant him- or herself. Thus, NBAC

endorses the current exceptions for research that is of minimal risk

to participants and for potentially beneficial research in emergency

settings where no better alternative for the participants exists.

NBAC also urges attention to emerging areas of record, database,

and tissue bank research in which consent serves only as a sign 

of respect and in which alternative ways to respect participants 

do exist (NBAC 1999b; 21 CFR 50.24). In a previous report, the

Commission made recommendations regarding persons who lack

decisionmaking capacity and from whom informed consent cannot

be obtained (NBAC 1998).

5 Porter, J., Testimony before NBAC. November 23, 1997.

Bethesda, Maryland. See McCarthy, C.R., “Reflections on the

Organizational Locus of the Office for Protection from Research

Risks.” This background paper was prepared for NBAC and is

available in Volume II of this report.

6 See Goldman, J., and A. Choy, “Privacy and Confidentiality in

Health Research” and Sieber, J., “Privacy and Confidentiality: 

As Related to Human Research in Social and Behavioral Science.”

These background papers were prepared for NBAC and are 

available in Volume II of this report. See also Ferguson v. City of

Charleston 121 S. Ct. 1281. (2001).
National Bioethics Advisory Commission

19

References

Beecher, H.K. 1966. “Ethics and Clinical Research.” New England

Journal of Medicine 274(24):1354–1360.

Faden, R.R., and T.L. Beauchamp. 1986. A History and Theory of

Informed Consent. New York: Oxford University Press.

Institute of Medicine (IOM). 2001. Preserving Public Trust:

Accreditation and Human Research Participant Protection Programs.

Washington, D.C.: National Academy Press.

Jonas, H. 1969. “Philosophical Reflections on Experimenting with

Human Subjects.” Daedalus 98:219–247.

Jones, J.H. 1981. Bad Blood: The Tuskegee Syphilis Experiment.

New York: The Free Press.

Katz, J. 1972. Experimentation with Human Beings. New York:

Russell Sage Foundation.

National Bioethics Advisory Commission (NBAC). 1997. Cloning

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Office.

———. 1998. Research Involving Persons with Mental Disorders 

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———. 1999a. Ethical Issues in Human Stem Cell Research. 3 vols.

Rockville, MD: U.S. Government Printing Office.

———. 1999b. Research Involving Human Biological Materials:

Ethical Issues and Policy Guidance. 2 vols. Rockville, MD: U.S.

Government Printing Office.

———. 2001. Ethical and Policy Issues in International Research:

Clinical Trials in Developing Countries. 2 vols. Bethesda, MD: 

U.S. Government Printing Office.

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Tuskegee Syphilis Study Ad Hoc Advisory Panel. 1973. Final

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and Welfare.


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