December 2011

MORAL SCIENCE

Protecting Participants in 

Human Subjects Research

Presidential Commission

for the Study of Bioethical Issues
Updated edition June 2012
MORAL SCIENCE

Protecting Participants in 

Human Subjects Research

Presidential Commission

for the Study of Bioethical Issues

Washington, D.C.

December 2011

http://www.bioethics.gov
MORAL SCIENCE Protecting Participants in Human Subjects Research

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ABOUT THE PRESIDENTIAL COMMISSION FOR 

THE STUDY OF BIOETHICAL ISSUES

The Presidential Commission for the Study of Bioethical Issues (the Commission) 

is an advisory panel of the nation’s leaders in medicine, science, ethics, religion, 

law, and engineering. The Commission advises the President on bioethical issues 

arising from advances in biomedicine and related areas of science and technology. 

The Commission seeks to identify and promote policies and practices that 

ensure scientific research, health care delivery, and technological innovation are 

conducted in a socially and ethically responsible manner.

For more information about the Commission, please see http://www.bioethics.gov.
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CONTENTS

Letter of Transmittal to the President.................................................................... v

Letter from the President to the Commission....................................................... vi

Members of the Commission............................................................................... vii

Commission Staff and Consultants .................................................................... viii

Acknowledgements............................................................................................... ix

Executive Summary ..............................................................................................1

Improving Accountability.................................................................................6

Treating and Compensating for Research-Related Injury..................................8

Creating a Culture of Responsibility: Human Research Protections as 

Professional Standards......................................................................................9

Respecting Equivalent Protections.................................................................. 10

Promoting Community Engagement.............................................................. 11

Justifying Site Selection .................................................................................. 12

Ensuring Ethical Study Design....................................................................... 13

Promoting Current Federal Reform Efforts..................................................... 14

Following Up.................................................................................................. 15

CHAPTER 1: Introduction.................................................................................... 17

The Need to Assess the Contemporary Environment ...................................... 21

Research Across Borders .................................................................................23

Contemporaneous Reviews of the Human Subjects Protection System ...........25

About this Report...........................................................................................26

CHAPTER 2: Assessing the Current System .........................................................29

The Scope and Volume of Federal Human Subjects Research .........................33

Current Rules.................................................................................................40

Conclusion .....................................................................................................42

CHAPTER 3: Further Analysis and Recommendations ........................................43

Commission Recommendations .....................................................................46

1. Improving Accountability.........................................................................46

2. Treating and Compensating for Research-Related Injury............................56

Ethical Justification for Compensation...................................................56

Reparations for Unethical Research .......................................................62

Designing a System of Compensation ...................................................64
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3. Creating a Culture of Responsibility: Human Research Protections as 

Professional Standards ............................................................................. 70

4. Respecting Equivalent Protections............................................................. 74

5. Promoting Community Engagement.........................................................78

6. Justifying Site Selection............................................................................82

7. Ensuring Ethical Study Design ................................................................88

Towards a Middle Ground on Study Design .......................................... 91

(1) Treatment Standards ................................................................... 91

(2) Methodological Constraints........................................................93

(3) Risk Minimization......................................................................94

8. Promoting Current Reform Efforts ...........................................................96

Ensuring Risk-Based Protections............................................................96

Streamlining IRB Review of Multi-Site Studies .....................................98

Improving Informed Consent ................................................................99

Clarifying and Harmonizing Regulatory Requirements and 

Agency Guidance................................................................................. 100

Data Collection to Enhance Adverse Event Reporting ......................... 100

9. Following Up ........................................................................................ 102

Endnotes........................................................................................................... 105

Appendices........................................................................................................ 139

Appendix I: Human Subjects Research Landscape Project: 

Scope and Volume of Federally Supported Human Subjects Research .......... 140

Appendix II: Human Subjects Research Landscape Project Methods............ 163

Appendix III: U.S. Treatment/Compensation for Treatment Methods.......... 184

Appendix IV: International and Transnational Requirements for 

Treatment and Compensation for Research Injuries...................................... 186

Appendix V: International Research Panel.................................................... 191

Appendix VI: Guest Speakers....................................................................... 192
Presidential Commission for the Study of Bioethical Issues

President Barack Obama

The White House

1600 Pennsylvania Avenue, NW

Washington, DC 20500

Dear Mr. President:

On behalf of the Presidential Commission for the Study of Bioethical Issues, we present to you 

this report, “Moral Science: Protecting Participants in Human Subjects Research.”

In response to your request of November 24, 2010, the Commission oversaw a thorough review 

of current regulations and international standards to assess whether they adequately protect human 

participants in federally funded research, no matter where it occurs.

The Commission held four multi-day, public meetings. Speakers addressed a range of U.S. and 

international policies and norms, and provided perspectives from a wide array of professional 

and institutional organizations. At your request, we sought the advice of international experts and 

appointed the International Research Panel, a subcommittee of the Commission. Finally, the 

Commission solicited information from the public and it received over three hundred comments.

The Commission concludes that current regulations, which apply to a diverse and wide-ranging 

portfolio of research, generally appear to protect people from avoidable harm or unethical treatment. 

However, because of the currently limited ability of some governmental agencies to identify basic 

information about all of their human subjects research, the Commission cannot say that all federally 

funded research provides optimal protections against avoidable harms and unethical treatment. 

Many of our most important advances derive from research that involves human participants. 

It is essential, therefore, that critical research of this sort adheres to the highest ethical practices to 

ensure, as best as possible, that those who volunteer to participate in studies for the benefit of others 

are protected. Thus, the Commission offers 14 recommendations to improve the current system.

The Commission Members are honored by the trust you have placed in us and we are grateful 

for the opportunity to serve you and the nation in this way.

Sincerely,

Amy Gutmann, Ph.D. James Wagner, Ph.D.

Chair Vice-Chair

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1425 New York Avenue, NW, Suite C-100, Washington, DC 20005

Phone 202-233-3960 Fax 202-233-3990 www.bioethics.gov
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PRESIDENTIAL COMMISSION FOR THE STUDY OF BIOETHICAL ISSUES

AMY GUTMANN, PH.D., CHAIR

President and Christopher H. Browne

Distinguished Professor of Political Science, University of Pennsylvania

JAMES W. WAGNER, PH.D., VICE CHAIR

President, Emory University

YOLANDA ALI, M.B.A.

Michael J. Fox Foundation

Founder’s Council; 

Emory Neurosciences

Community Advisory Board

ANITA L. ALLEN, J.D., PH.D.

Henry R. Silverman Professor of Law 

And Professor of Philosophy 

University of Pennsylvania Law School

JOHN D. ARRAS, PH.D.

Porterfield Professor of Biomedical

Ethics, Professor of Philosophy,

University of Virginia

BARBAR A F. ATKINSON, M.D.

Executive Vice Chancellor,

University of Kansas Medical Center; 

Executive Dean, University of 

Kansas School of Medicine

NITA A. FAR AHANY, J.D., PH.D.

Leah Kaplan Visiting Professor in 

Human Rights, Stanford Law School

Associate Professor of Law; 

Associate Professor of Philosophy

Vanderbilt University

ALEXANDER G. GARZA, M.D., M.P.H.

Assistant Secretary, Office of Health

Affairs; Chief Medical Officer, 

Department of Homeland Security

CHRISTINE GR ADY, R.N., PH.D.

Acting Chief of the Department of 

Bioethics, National Institutes of 

Health Clinical Center

STEPHEN L. HAUSER, M.D.

Robert A. Fishman Distinguished 

Professor and Chair of the Department 

of Neurology, University of California, 

San Francisco

R AJU S. KUCHERLAPATI, PH.D.

Paul C. Cabot Professor, Department 

of Genetics, Harvard Medical School; 

Professor, Department of Medicine, 

Brigham and Women’s Hospital

NELSON L. MICHAEL, M.D., PH.D.

Colonel, Medical Corps, U.S. Army; 

Director, Division of Retrovirology; 

Walter Reed Army Institute of Research; 

U.S. Military HIV Research Program

DANIEL P. SULMASY, M.D., PH.D., FACP

Kilbride-Clinton Professor of Medicine 

and Ethics, Department of Medicine 

and Divinity School; Associate Director, 

The MacLean Center for Clinical Medical 

Ethics, University of Chicago
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PRESIDENTIAL COMMISSION FOR THE STUDY OF BIOETHICAL ISSUES 

STAFF* AND CONSULTANTS

Executive Director

Valerie H. Bonham, J.D.

Deputy Director

Debbie Banks Forrest, M.P.P.

Communications Director

Hillary Wicai Viers, M.S.J.

Senior Advisors

Paul Lombardo, Ph.D., J.D.

Jonathan D. Moreno, Ph.D.

Jeremy Sugarman, M.D., M.P.H., M.A.

Research Staff

Eleanor Celeste, B.A. 

Tom Cinq-Mars, B.A.

Brian C. Eiler, J.D.

Michelle Groman, J.D.

Chris Havasy, Sc.B.

Holly Fernandez Lynch, J.D., 

M. Bioethics

Debra Mathews, Ph.D.

Eleanor E. Mayer, J.D., M. Bioethics

Anne Pierson, J.D.

Elizabeth Pike, J.D.

Cary Scheiderer, Ph.D

Kayte Spector-Bagdady, J.D., 

M. Bioethics

Victoria Wilbur, B.A.

Consultants

Burness Communications

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

Committee and Staff Affairs

Svetlana Cicale, M.S.

Judith E. Crawford

Esther E. Yoo, B.A.

Fellows and Interns

Adebukola J. Awosogba, M.A.

Michael Grippaldi, B.S.

Magdalina Gugucheva, B.A.

Casey Nicol, B.S.

Tuua Ruutiainen, B.A.

Michael Tennison, M.A.

David Tester, Ph.D.

Jennifer Therrien, B.S.

Ilana Yurkiewicz, B.S. 

*Includes former and part-time staff
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ACKNOWLEDGEMENTS

The Commission is grateful to the many individuals who contributed their 

time, energy, and expertise to this report. The Commission offers its particular thanks to the exceptional speakers who travelled great distances to 

participate in the Commission’s public meetings. It thanks also the dedicated 

department and agency employees who shared their experience, expertise, and 

insight with the Commission.

The Commission also extends its gratitude to the members of the subcommittees whose advice shaped the direction of this report. We thank the members 

of the International Research Panel for their reflections and unique knowledge of human subjects protection standards and practices in international 

research, and the members of the Empirical Advisory Group, who advised the 

Commission on how to analyze and interpret data on the scope of scientific 

studies currently supported by the federal government.

Finally, the Commission is enormously indebted to the members of its 

talented staff for their dedicated research, and thoughtful insights on human 

subjects protection in a short period of time. The Commission extends 

special thanks to Executive Director Valerie Bonham, and Senior Advisors 

Jonathan Moreno and Jeremy Sugarman. Furthermore, the Commission 

is particularly grateful to staff lead Michelle Groman for her tireless and 

extraordinary efforts on its behalf to ensure a comprehensive assessment of 

this important topic.
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EXECUTIVE SUMMARY
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Human research serves to ensure the safety of new medicines, establish 

tolerable exposure levels for environmental and workplace hazards, 

and determine the effectiveness of new interventions in public health, education, and countless other fields. Without volunteers, these studies would be 

impossible to conduct. Recognizing society’s responsibility to protect human 

subjects of research from avoidable harm and unethical treatment, President 

Barack Obama asked the Presidential Commission for the Study of Bioethical 

Issues (the Commission) to conduct a thorough review of current regulations 

and international standards to assess whether they adequately protect human 

subjects in federally supported scientific studies, no matter where they occur. 

The Commission’s review confirmed that the federal government supports 

a diverse and wide-ranging portfolio of research, which includes activities 

funded directly, or by award or sub-award, throughout the world. Support 

for medical and public health research predominates, but the federal government also supports a large volume of human subjects research in other fields, 

including social and behavioral sciences and education. 

Sound scientific experimentation is rooted in uncertainty and volunteers 

cannot be immunized from all physical or psychological risks. However, in 

order for research with human beings to be ethical, human subjects must 

be volunteers who give their informed consent, who are treated fairly and 

respectfully, who are subjected only to reasonable risks from which proportionate humanitarian benefit can be obtained, and who are not treated as 

mere means to the ends of others. (Some carefully specified and regulated 

exceptions to informed consent are based on the incapacity of some subjects 

or the very low risk of the experiments, provided that all the other conditions—including fair and respectful treatment—hold.)1

In the absence of these ethical constraints, tragic results may follow. 

Many prior abuses of human subjects are now carefully documented, and 

some informed the development of today’s federal human subjects protection system. Eighteen federal departments and agencies require adherence 

to a uniform regulatory floor for human subjects research, known as the 

“Common Rule,” which generally requires informed consent, independent 

ethical review, and the minimization of avoidable risks. These standards apply 

to all research funded by these departments and agencies, regardless of where 
EXECUTIVE SUMMARY

3

it occurs. The Food and Drug Administration applies essentially the same 

standards to all research conducted in support of seeking U.S. marketing 

approval for drugs, devices, and biologics; regardless of the source of funding. 

These rules reflect widely accepted principles of ethics. These principles are 

rooted in longstanding values that find expression in many sources of moral 

philosophy; theological traditions; and codes, regulations, and rules. They are 

the bulwark of ethically sound science, or “moral science,” as the Commission 

terms it. Each generation may re-examine how these principles are contextually applied and understood. And, their application or implementation may 

vary depending on the level of risk that a subject faces. Medical research that 

poses risk of physical injury rightly raises more concerns than does routine 

social survey research, for example. Nonetheless, the same ethical principles 

govern all of these activities, and serve as enduring guideposts that must not 

be ignored. 

The public has a right to expect researchers to abide by rules that satisfy 

these principles. Researchers themselves benefit from public confidence when 

they conform to these rules; and with public esteem they earn the ability to 

conduct potentially important research with public support. Without such 

earned confidence, research participation may be threatened and critical 

research jeopardized. More than these measurable effects, society risks irretrievably losing sight of what is inherently owed to fellow human beings and 

those who deserve special protection by virtue of their willingness to participate in experiments designed to benefit others and advance scientific and 

social progress. 

From time to time society revisits the rules applied to research with human 

subjects and the implementation of guiding ethical principles. The need for 

reassessment may arise from challenges presented by novel scientific advances, 

a perceived mismatch between ethical principles and their implementation, or 

revelations of abuse. When President Obama charged the Commission with 

undertaking this review of contemporary human subjects protection standards, he recognized the sacred trust and responsibility that we as a society 

have to ensure that human research subjects are protected from harm and 

unethical treatment.2

 The immediate catalyst to action came from newly 

discovered evidence of unethical activities by U.S. scientists in Guatemala 
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in the late 1940s. The Commission’s findings and ethical assessment of those 

events, documented in its report “Ethically Impossible” STD Research in Guatemala 1946 to 1948, illustrate how the quest for scientific knowledge without 

regard to relevant ethical standards can blind researchers to the humanity of 

the people they enlist into research.3

For this review, the first of its kind by a national bioethics commission in 

a decade, the President asked the Commission to complete its work in nine 

months. Recognizing the increasing involvement of foreign sites and partners 

in human subjects research, the Commission organized a panel of international experts, the International Research Panel (the Panel), consisting of 

experts in bioethics and biomedical research from 10 countries: Argentina, 

Belgium, Brazil, China, Egypt, Guatemala, India, Russia, Uganda, and the 

United States.4

 The Panel, led by Commission Chair Amy Gutmann, held 

three day-long meetings to discuss research standards and practices around 

the globe. In their discussions, Panel members drew upon their individual 

expertise and decades of experience conducting research and developing 

policy to protect human subjects. 

In attempting to assess the current depth and breadth of the federally funded 

human research enterprise, the Commission quickly learned there is no ready 

source that comprehensively describes its basic characteristics, such as level 

of funding, or number of studies, subjects, or geographic locations. Instead, 

what exists are isolated pockets of information and some descriptive summaries. To better understand, and enable the public to know the scope and 

volume of “scientific studies supported by, the Federal Government,” the 

Commission therefore asked each Common Rule agency to provide limited, 

project-specific information on human subjects research supported in Fiscal 

Year 2010, and to identify trends, if possible, the same information back 

through Fiscal Year 2006. 

The Commission collected basic, project-level data about human subjects 

research, including study title, number and location of sites, number of 

subjects, and funding information. These data were compiled into the 

Commission’s “Research Project Database,” and analyzed as part of its 

Human Subjects Research Landscape Project (see further discussion below 

and Appendices I and II). Among other things, the Commission learned that 
EXECUTIVE SUMMARY

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the federal government supported more than 55,000 human subjects research 

projects around the globe in Fiscal Year 2010, mostly in medical and healthrelated research, but also in other fields such as education and engineering. 

The Commission also learned that many federal departments and agencies 

have no ready means to identify basic information about the research they 

support (e.g., location of study sites) or link funding information with studylevel data. 

The Commission convened an Empirical Advisory Group, comprised of 

experts in bioethics, statistics, clinical trial management, and qualitative 

research, to assist in analysis and interpretation of the Human Subjects 

Research Landscape Project and suggest future empirical work that could be 

conducted to evaluate the current human subjects protection system.

In sum, the Commission concludes that current regulations generally appear 

to protect people from avoidable harm or unethical treatment, insofar as is 

feasible given limited resources,5

 no matter where U.S.-supported research 

occurs. This conclusion is fully consistent with, and also qualified by, the 

large yet incomplete set of information made available to the Commission in 

the time available to carry out its charge. Specifically, the Commission found:

The current U.S. system provides substantial protections for the health, 

rights, and welfare of research subjects and, in general, serves to “protect 

people from harm or unethical treatment” when they volunteer to participate as subjects in scientific studies supported by the federal government. 

However, because of the currently limited ability of some governmental 

agencies to identify basic information about all of their human subjects 

research, the Commission cannot conclude that all federally funded 

research provides optimal protections against avoidable harms and unethical treatment. The Commission finds significant room for improvement 

in several areas where, for example, immediate changes can be made to 

increase accountability and thereby reduce the likelihood of harm or 

unethical treatment. 

In reaching this conclusion, the Commission believes that the ethical principles for human subjects research should not—indeed must not—vary 

depending on the source of funding or location of the research.6

 While the 

specific methods of implementing the ethical principles of human subjects 
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research are likely to differ, the principles should not. Ethical principles 

provide the foundation for the rules and regulations that govern human 

subjects research as well as lay the groundwork upon which everyone who 

conducts human subjects research must stand. 

There is no way to eradicate all risk of harm, particularly in some types of 

medical and translational research, but the Commission found several 

important areas where improvement or refinement of the current system 

is both possible and desirable. It offers guidance and reflection in eight 

specific areas, all ripe for action or advancement now. Chief among these, 

the Commission finds that accountability can and should be refined through 

improving access to basic information about the scope and volume of human 

subjects research funded by the government. It also draws a bright line 

affirming the view of most bioethicists and others, including the majority of 

nations supporting human subjects research around the globe, that human 

subjects should not individually bear the costs of care required to treat 

harms resulting directly from that research. The Commission also calls on 

the federal government to respect the equivalent protections offered by international partners and exercise its longstanding authority to recognize these 

protections when available. 

The Commission’s review of the current system comes while the government is 

already considering systematic reform through revision of the Common Rule. 

Some of the proposed reforms offer useful means to improve upon current 

practices. Although the Commission was not asked to undertake a comprehensive assessment of the proposed reforms, it did examine the published 

ideas and offers several overarching comments to further these reform goals. 

Improving Accountability

Science requires substantial societal investment, putting it in competition 

with other important activities that also contribute to the public good. The 

public therefore has the right to accountability in the use and management 

of resources allocated to the pursuit of scientific knowledge for the common 

good. The need for accountability is all the more heightened when publicly 

funded research also depends on the participation of human subjects. In 
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carrying out President Obama’s charge to assess the degree to which current 

federally funded research protects human subjects from harm or unethical 

treatment, the Commission encountered a significant challenge in ascertaining federal investment in human subjects research. Internal department or 

agency-specific systems to track human subjects research are generally available, although they vary widely in the basic information they maintain and 

differ considerably in the information they can readily retrieve or make available publicly or online. To accurately track and assess the volume and scope 

of human subjects research and to determine whether protections are in place, 

there must be better data and more ready availability of information.

Recommendation 1: Improve Accountability through Public Access

To enhance public access to basic information about federal governmentfunded human subjects research, each department or agency that supports 

human subjects research should make publicly available a core set of data 

elements for their research programs—title, investigator, location, and 

funding—through their own systems or a trans-agency system. The Office 

for Human Research Protections or another designated central organizing 

agency should support and administer a central web-based portal linking to 

each departmental or agency system. This should not preclude the prospective development of a unified federal database that may ultimately be more 

cost-effective and efficient.

The Commission also encourages additional research into the effectiveness 

of human subjects protection standards to obtain empirical data through 

which to assess such protections. Such data could, for example, illuminate 

issues pertinent to research site selection or assist in promoting the effectiveness of community engagement—both topics the Commission believes 

could use improvement.

Recommendation 2: Improve Accountability through Expanded Research

To evaluate the effectiveness of procedural standards embedded in current 

human subjects protection regulations, the federal government should 

support the development of systematic approaches to assess the effectiveness of human subjects protections and should expand support for research 

related to ethical and social consideration of human subjects protection.
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Treating and Compensating for Research-Related Injury

Those who sponsor or engage in human subjects research have an ethical obligation to protect those who volunteer as research subjects. Almost all other 

developed nations have instituted policies to require treatment, or compensation for treatment, for injuries suffered by research subjects. The Panel advised 

the Commission to recommend that the United States establish a system to 

assure compensation for the medical care of human subjects harmed in the 

course of biomedical research. However, the Commission believes that before 

altering the current approach to compensation for injuries sustained during 

federally funded research, the nature and scope of harms that remain unaddressed must be assessed. 

Recommendation 3: Treating and Compensating for Research-Related Injury

Because subjects harmed in the course of human research should not individually bear the costs of care required to treat harms resulting directly 

from that research, the federal government, through the Office of Science 

and Technology Policy or the Department of Health and Human Services, 

should move expeditiously to study the issue of research-related injuries 

to determine if there is a need for a national system of compensation or 

treatment for research-related injuries. If so, the Department of Health 

and Human Services, as the primary funder of biomedical research, should 

conduct a pilot study to evaluate possible program mechanisms.

The Commission stresses that it is important to recognize the limits of 

current models for providing compensation, like the National Vaccine Injury 

Compensation program, and also the various means by which the government may satisfy the ethical obligation to compensate individuals who suffer 

research-related injuries in a federally funded study. While there are systems 

already in place for some government research, the Commission recommends a study to evaluate future options and outlines many questions to be 

considered. It also recognizes that several national bodies have made similar 

recommendations in the past. Given the seriousness of the ethical concern, 

and these past efforts, the Commission encourages the government to follow 

up publicly with its response.
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Recommendation 4: Treating and Compensating for Research-Related 

Injury Follow Up

The Commission recognizes that previous presidentially appointed bioethics 

commissions and other duly appointed advisory bodies have made similar 

recommendations regarding compensation or treatment for research-related 

injuries; yet no clear response by the federal government has been issued. 

Therefore, the federal government, through the Office of Science and Technology Policy or the Department of Health and Human Services, should 

publicly release reasons for changing or maintaining the status quo.

Creating a Culture of Responsibility: Human Research Protections as 

Professional Standards

The Commission heard from a wide range of research professionals that the 

procedural requirements of human subjects regulations are often viewed as 

unwelcome bureaucratic obstacles to conducting research. The density of some 

of these requirements can obscure their justification and routinized interpretation can create distance between the underlying ethical principles and 

how they are viewed and implemented by institutional review boards and the 

research community. The Commission too recognizes that there is often a 

fundamental distinction between ethical principles (and the personal responsibilities that must be exercised to effect them), and procedural or policy 

strategies to apply and implement these principles. While tension between 

principles and procedures is, in some ways, perennial, the Commission 

believes that specific steps can be taken now to deflect the tilt that some see 

favoring process over principle. Two of these recommendations are directed to 

government specifically, and a third more generally relates to education and 

the duty to all engaged in the research enterprise.

Recommendation 5: Make the Ethical Underpinnings of Regulations 

More Explicit

To promote a better understanding of the context and rationale for applicable 

regulatory requirements, the Department of Health and Human Services or 

the Office of Science and Technology Policy should ensure that the ethical 

underpinnings of regulations are made explicit. This goal is also instrumental 

to the current effort to enhance protections while reducing burden through 

reform of the Common Rule and related Food and Drug Administration 
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regulations. (See Promoting Current Federal Reform Efforts below.) Following 

the principle of regulatory parsimony, regulatory provisions should be rationalized so that fundamental, core ethical standards are clearly articulated.

Recommendation 6: Amend the Common Rule to Address Investigator 

Responsibilities

The Common Rule should be revised to include a section directly addressing 

the responsibilities of investigators. Doing so would bring it into harmony 

with the Food and Drug Administration regulations for clinical research 

and international standards that make the obligations of individual 

researchers more explicit, and contribute to building a stronger culture of 

responsibility among investigators. 

Recommendation 7: Expand Ethics Discourse and Education

To ensure the ethical design and conduct of human subjects research, 

universities, professional societies, licensing bodies, and journals should 

adopt more effective ways of integrating a lively understanding of personal 

responsibility into professional research practice. Rigorous courses in 

bioethics and human subjects research at the undergraduate as well as 

graduate and professional levels should be developed and expanded to 

include ongoing engagement and case reviews for investigators at all levels 

of experience.

Respecting Equivalent Protections

Research supported by the federal government is subject to the same regulatory requirements domestically as well as internationally. Research 

collaborators and partners in other countries who are funded or supported 

by Common Rule agencies file an assurance that they will comply with these 

requirements, regardless of overlapping or more protective standards that may 

exist in the country where the research is conducted. At the same time, U.S. 

regulations governing the protection of human research subjects delineated 

in the Common Rule have long permitted U.S. departments and agencies 

supporting or conducting research to recognize and accept procedures from 

foreign countries that may differ from those delineated in U.S. regulations 

as long as they provide “protections that are at least equivalent” to those in 

the Common Rule. Yet U.S. departments and agencies have rarely, if ever, 
EXECUTIVE SUMMARY

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exercised the authority to accept any foreign country’s procedures as equivalent. Instead they sometimes insist that all U.S. procedural details must 

be met, in all cases, regardless of the effectiveness or similarity of foreign 

requirements. This insistence on both the spirit and letter of U.S. regulatory constraint fails to recognize or respect that many nations today have 

systems to protect human subjects that are as good, or perhaps more stringent, 

than our own. Despite numerous efforts to clarify or resolve the meaning 

and interpretation of “equivalent protections,” no comprehensive policy has 

emerged for determining when equivalent protections exist.

Recommendation 8: Respect Equivalent Protections

The federal government, through the Office for Human Research Protections, 

should adopt or revise the 2003 Health and Human Services Equivalent 

Protections Working Group’s articulation of the protections afforded by 

the specific procedural requirements of the Common Rule. It should use 

these requirements to develop a process for evaluating requests from foreign 

governments and other non-U.S. institutions to determine if their laws, 

regulations, and procedures can be recognized as providing equivalent 

protections to research subjects. 

Promoting Community Engagement

The Panel directed the Commission’s attention to the value of community 

engagement and demonstration of respect for cultural differences that are 

compatible with the ethical conduct of human subjects research. These values 

are applicable to research conducted both domestically and abroad. Effective community engagement provides an additional layer of safeguards by 

providing the community with opportunities to thoroughly weigh and accept 

or reject the risks and benefits of research activities, discover possible implications of research that might have unintended consequences to the host 

community, and independently debate the effectiveness of research protections. Interactive and ongoing dialogue between communities and research 

teams allows for the integration of community norms, beliefs, customs, and 

cultural sensitivities into research activities. The guidelines enumerated in 

the Joint United Nations Programme on HIV/AIDS and the AVAC Good 

Participatory Practice Guidelines, for example, provide a standardized framework for implementing community engagement activities across a wide range 
MORAL SCIENCE Protecting Participants in Human Subjects Research

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of research. The Commission believes these, and related documents, should be 

evaluated and guidance provided by the government on effective community 

engagement strategies for all human subjects research.

Recommendation 9: Promote Community Engagement

The federal government, through the Office for Human Research Protections 

and authorized research funders, should support further evaluation and 

specification of the Joint United Nations Programme on HIV/AIDS and 

the AVAC Good Participatory Practice Guidelines with the aim of providing 

a standardized framework for those community engagement practices that 

would further the protection and ethical treatment of human subjects in all 

areas of research. Research should be conducted to prospectively evaluate 

the effectiveness of this framework and strengthen it after it is developed.

Justifying Site Selection

Careful selection of sites for research is important for two sets of reasons. 

First, the ethical criteria for how subjects must be treated narrows the selection of sites to those that allow for the ethical treatment of subjects. Second, 

as the Belmont Report states, “selection of research subjects needs to be scrutinized in order to determine whether some classes are being systematically 

selected because of their easy availability, their compromised position, or their 

manipulability, rather than for reasons directly related to the problem being 

studied.” Thus, careful examination of site selection is extremely important 

and critical to ensuring that research is done ethically and participants are 

protected from harm or unethical treatment. Some domestic and international settings present challenges that increase concern about exploitation 

of human subjects. One proposed strategy for minimizing the potential of 

exploitation when research is done in low-income communities—whether 

domestic or international—is to ensure that the proposed study is responsive 

to the medical, as well as other, needs of the local community or communities. The ethical requirement of responsiveness to local communities needs to 

be further developed and implemented for responsiveness to become a clearly 

justified criterion for site selection.
EXECUTIVE SUMMARY

13

Recommendation 10: Ensure Capacity to Protect Human Subjects

Funders of research should determine that researchers and the sites that 

they propose to select for their research have the capacity—or can achieve 

the capacity contemporaneously with the conduct of the research—to 

support protection of all human subjects. 

Recommendation 11: Evaluate Responsiveness to Local Needs as a Condition 

for Ethical Site Selection

The federal government, through the Office for Human Research 

Protections and federal funding agencies, should develop and evaluate 

justifications and operational criteria for ethical site selection, taking into 

consideration the extent to which site selection can and should respond to 

the needs of a broader community or communities. The Office for Human 

Research Protections should produce, and other agencies should consider 

developing, guidance for investigators.

Ensuring Ethical Study Design

Study design, particularly in clinical research, is another area where concerns 

about exploitation have arisen in the past. The Commission reviewed issues 

surrounding use of placebo and other comparator arms in randomized clinical 

trials conducted in locations that do not have access to the highest standard 

of care. It found consensus around a “middle ground” to guide researchers 

designing clinical trials that expose subjects to interventions or conditions 

that may not be viewed as the best available standard of care but nonetheless provide potential for benefit to the local population. The Commission’s 

proposed framework, rooted in the thinking that has developed in the literature over several decades, provides a pathway to ensuring that research subjects’ 

interests are protected.

Recommendation 12: Ensure Ethical Study Design for Control Trials

When assessing how to reconcile the requirements of rigorous study design 

with the interests of research subjects, a nuanced approach is recommended 

that permits subjects to receive a placebo or an active agent that otherwise might not represent the “best-proven” approach when the site selected 

is ethically justifiable and the following conditions are met: a) the “bestproven” intervention is not known to be the best for a particular population 
MORAL SCIENCE Protecting Participants in Human Subjects Research

14

due to local infrastructural, behavioral, genetic, or other relevant circumstances; and b) the scientific rationale and the ethical justification for the 

study design have undergone careful review to ensure all of the following: 

i) use of placebo or other comparators is of limited duration; ii) subjects are 

carefully monitored; iii) rescue measures are in place should serious symptoms develop; and iv) there are established withdrawal criteria in place for 

subjects who experience adverse events. 

Promoting Current Federal Reform Efforts

The Commission commends efforts already underway to reform federal policy 

for the protection of human subjects and recommends that these efforts 

be advanced. In particular, the Commission endorses the following proposals 

presented in the Advance Notice of Public Rulemaking issued in July 2011 

by the Office of the Secretary of the Department of Health and Human 

Services (HHS) in coordination with the Office of Science and Technology 

Policy (OSTP). 

Recommendation 13: Promoting Current Federal Reform Efforts

The Commission supports the federal government’s proposed reforms to:

a) Restructure research oversight to appropriately calibrate the level and 

intensity of the review activities with the level of risk to human subjects;

b) Eliminate continuing review for certain lower-risk studies and regularly 

update the list of research categories that may undergo expedited review;

c) Reduce unnecessary, duplicative, or redundant institutional review board 

review in multi-site studies. Regardless of the process used to review and 

approve studies, institutions should retain responsibility for ensuring that 

human subjects are protected at their location as protection of human 

subjects includes much more than institutional review board review. 

The use of a single institutional review board of record should be made 

the regulatory default unless institutions or investigators have sufficient 

justification to act otherwise;

d) Make available standardized consent form templates with clear language 

understandable to subjects;
EXECUTIVE SUMMARY

15

e) Harmonize the Common Rule and existing regulations of the Food and 

Drug Administration, and require that all federal agencies conducting 

human subjects research adopt human subjects regulations that are 

consistent with the ethical requirements of the Common Rule; and

f) Work toward developing an interoperable or compatible data collection 

system for adverse event reporting across the federal government. 

Following Up

The Commission recognizes that several of these recommendations have 

been made by presidentially appointed bioethics commissions and other 

duly appointed government advisory bodies in the past, and it found no 

clear response by the federal government to many of them. For example, a 

number of commissions, including the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, the National 

Bioethics Advisory Commission, the Presidential Commission for the Study 

of Ethical Problems in Medicine and Biomedical and Behavioral Research, 

and the President’s Advisory Committee on Human Radiation Experiments, 

made recommendations endorsing compensation for subjects for injuries 

arising from research.7

 Both National Bioethics Advisory Commission and 

Advisory Committee on Human Radiation Experiments recommended recognition of equivalent protections.8

 In addition, National Bioethics Advisory 

Commission addressed many of the same issues raised in the recommendations in this report, such as community engagement, ethics training, and 

the importance of an expanded research agenda addressing human researchrelated issues.9

Recommendation 14: Responding to Recommendations

The Commission recommends that the Office of Science and Technology 

Policy or another appropriate entity or entities within the government 

respond with changes to the status quo or, if no changes are proposed, 

reasons for maintaining the status quo with regard to the recommendations below. Possible departments or agencies to lead the efforts include 

the Department of Health and Human Services, the Office for Human 

Research Protections, and the National Institutes of Health, as well as other 

funders and regulators. 
MORAL SCIENCE Protecting Participants in Human Subjects Research

16

Table ES.1 Recommendation Follow-up Summary

RECOMMENDATION 

NUMBER†

SUMMARY OFFICE

1 Increase accountability through online access to basic 

human subjects research data.

OHRP/all departments and 

agencies that support human 

subjects research

2 Support the development of systematic approaches to 

assess the effectiveness of human subjects protections 

and expand support for research related to ethical and 

social consideration of human subjects protection.

OHRP/all departments and 

agencies that support human 

subjects research

3 Study research-related injuries to determine if there 

is a need for a national system of compensation or 

treatment for research-related injuries because subjects 

harmed in the course of human research should not 

individually bear the costs of care required to treat 

harms resulting directly from that research.

OSTP/HHS

4 Publicly release reasons for changing or maintaining 

the status quo regarding compensation or treatment for 

research-related injuries.

OSTP/HHS

5 Explicate the ethical underpinnings for human subjects 

protection requirements. 

HHS/OSTP

6 Add responsibilities of investigators to the Common Rule. HHS/OSTP

8 Adopt or revise the 2003 Department of Health and 

Human Services Equivalent Protections Working 

Group’s analysis and develop a process for evaluating 

requests from foreign governments and other non-U.S. 

institutions for determinations of equivalent protections.

OHRP

9 Support further evaluation of the UNAIDS/AVAC 

Guidelines to provide a standardized framework for 

community engagement practices across research fields.

OHRP

11 Support research to develop and evaluate justifications 

and operational criteria for ethical site selection.

OHRP/all departments and 

agencies that support human 

subjects research

13 Develop proposed regulations to reform the current 

Common Rule. 

OSTP/OHRP

14 Follow up. OSTP/other appropriate entity

† Listed here are recommendations directed to the federal government only.

A response need not be unduly lengthy or be provided by a single department, agency, or division, but the public should know whether the federal 

government intends to move forward, and if so in what way, with any or all of 

these recommendations. (See Table ES.1 for a summary of recommendations 

directed towards the federal government.)
17

CHAPTER 1

Introduction
MORAL SCIENCE Protecting Participants in Human Subjects Research

18

Research is not only important as a means of advancing knowledge; it is 

also a core component of America’s growth and prosperity in human 

health, energy, defense, education, and countless other components of daily 

life. Social progress depends on new discoveries and new ways of thinking 

about old problems. Yet, as the philosopher Hans Jonas observed, “society 

would indeed be threatened by the erosion of those moral values whose loss, 

possibly caused by too ruthless a pursuit of scientific progress, would make its 

most dazzling triumphs not worth having.”10

The relationship between scientific progress and morality is not a new concern 

in the United States. Writing nearly 200 years before Jonas, and in the midst 

of the hard work of building the new nation, Benjamin Franklin reflected 

that “[t]he rapid progress true science now makes, occasions my regretting 

sometimes that I was born so soon.” He continued:

“It is impossible to imagine the height to which may be carried, in 

a thousand years, the power of man over matter . . . . Agriculture 

may diminish its labor and double its produce; all diseases may by 

sure means be prevented or cured, not excepting even that of old 

age, and our lives lengthened at pleasure even beyond the antediluvian standard. O that moral science were in as fair a way of 

improvement, that men would cease to be wolves to one another, 

and that human beings would at length learn what they now 

improperly call humanity!”11

Surely Franklin would not be wholly satisfied in how far our society or the 

world has progressed in conquering “wolfish humanity,” and neither should 

society. Yet Franklin and the other American founders believed that the 

values of individual freedom of speech, conscience, and inquiry—along 

with a dedication to pursuing the common good—held great promise for a 

republic dedicated to progress in both science and morality, and that science 

and morality inform one another by challenging dogmatism in either realm. 

What Franklin called “moral science” is what we would today call “ethics.”12

Franklin clearly intended that “moral science” (ethics) should inform empirical science. Thus, using a contemporary play on Franklin’s phrase, one can 

say that the challenge of “moral science” (i.e., pursuing science in a morally 

justified manner) is one that every generation must take up again.13
INTRODUCTION I

19

There is no more acute instance of this challenge than research involving 

human subjects, upon which knowledge and discovery often depend. Human 

research subjects, in most cases, must be informed volunteers who are willing 

to allow their bodies or personal information to be used by researchers to 

craft new hypotheses, infer plausible explanations and predictions, and test 

theories.14 Pursuit of these goals sometimes offers no direct prospect of benefit 

to the human research subject. Early stage translational research serves to 

test physiological effects or biological functions of new drugs and medical 

interventions but is not necessarily designed to benefit subjects. Sometimes 

research subjects experience serious adverse health effects as a result of participation in trials.15 Research in other fields, including housing, social work, and 

criminology, typically poses fewer physical risks, but may pose substantial 

social, psychological, and economic risks for human subjects. Such research 

also aims to improve the lives of later generations without offering any direct 

or measurable benefit to those who participate as research subjects. 

Regardless of whether research offers the prospect of direct benefit to human 

subjects, long-standing ethical principles constrain the unfettered pursuit of 

knowledge. For research with human subjects to be ethical, volunteers must 

be treated fairly and with respect, subjected only to reasonable risks from 

which proportionate humanitarian benefit can be obtained, and not treated 

as mere means to the ends of others. Experimentation is rooted in uncertainty, 

and human subjects cannot be immunized from all physical risks. Nonetheless, these stated boundaries dictate that anticipated and avoidable harms 

must be eliminated, informed consent must be obtained in most cases, and 

the burdens and benefits of research must be equitably shared.

From time to time, society has been reminded of the need to revisit the rules 

applied to research with human subjects. The need for reassessment might 

arise from challenges emerging from novel scientific advances or from a 

perceived mismatch between ethical principles and how they are implemented 

in practice. Revelations of abuses also have been a driving force in reconsideration of the policies and procedures for protecting the subjects of research.

In the past few years, several factors have converged to compel a contemporary 

review of human subjects protection policies and practices. The Presidential 

Commission for the Study of Bioethical Issues (the Commission) initiated this 
MORAL SCIENCE Protecting Participants in Human Subjects Research

20

review in response to a charge from President Obama to undertake “a thorough 

review of [current] human subjects protection to determine if Federal regulations and international standards adequately guard the health and well-being 

of participants in scientific studies supported by the Federal Government.”16

This request came paired with the President’s charge to conduct an investigation of new revelations about medical research supported by the United 

States and conducted in Guatemala between 1946 and 1948. Some of that 

research involved the deliberate exposure of people to sexually transmitted 

diseases (STDs) without their consent. Subjects, including soldiers, prisoners, 

psychiatric patients in a state-run institution, and commercial sex workers, 

were exposed to syphilis, gonorrhea, and chancroid. Serology diagnostic 

testing involved the previous four groups as well as children, U.S. Servicemen 

stationed in Guatemala, and leprosarium patients. In October 2010, President Obama expressed “deep regret” to the President of Guatemala for this 

research, and affirmed the federal government’s “unwavering commitment to 

ensure that all human medical studies conducted today meet exacting” standards for the protection of human subjects.17

The results of the Commission’s investigation into the Guatemala experiments were released in September 2011 in its report, “Ethically Impossible” 

STD Research in Guatemala from 1946 to 1948, the findings of which are 

summarized below.18 That report provided a historical account and ethical 

assessment of the Guatemala experiments. It uncovered and contextualized as 

much as could be known about experiments that took place nearly 65 years 

ago. It also aimed to inform current and continuing efforts to protect the 

rights and welfare of the subjects of U.S.-sponsored or -conducted research. In 

“Ethically Impossible,” the Commission recognized that U.S. and international 

policies and practices governing human subjects research have evolved in the 

time since the Guatemala experiments from an informal set of principles, 

based primarily on medical ethics and the doctor-patient relationship, to a 

highly structured oversight system codified in regulation and statute. 

However, the uncovering of the 1940s STD studies in Guatemala prompted 

President Obama to ask whether such unethical research could be conducted 

in today’s research environment using U.S. federal funds. When the President 

asked the Commission to undertake this review of human subjects protection 
INTRODUCTION I

21

standards, he recognized, as do we all, the sacred trust and responsibility that 

society has to ensure that human research subjects are protected from harm 

and unethical treatment.19

The Need to Assess the Contemporary Environment

Since the 1940s, the research enterprise and the system of protection for 

human subjects have continuously evolved. Abuses uncovered in the 1960s 

and 1970s led to the development of the current U.S. regulations for the 

protection of human subjects. These regulations combine with longstanding 

professional norms and obligations to map the ethical boundaries for research 

today. For federally funded research, the rules have remained largely 

unchanged since at least 1991. For some agencies, the regulations are even 

older. For example, explicit Department of Health and Human Services 

(HHS; then the Department of Health, Education, and Welfare) policy 

requirements began in 1953 with the opening of the National Institutes of 

Health (NIH) Clinical Center (the agency’s internal research hospital).20 They 

expanded with statutory requirements for informed consent in Food and 

Drug Administration (FDA) regulated clinical trials and other HHS policy 

requirements in the 1960s, and were further modified with the regulations for 

government-sponsored medical research promulgated in 1972.21

Regarding the changing 

geography of clinical research, 

“[w]e are seeing a massive shift 

in the conduct of research....

[W]hat we are seeing is a large 

shift in economics and finance 

occurring at a setting in which 

the marketing of medical 

products has become global 

in every respect.” 

Dr. Robert M. Califf, Vice Chancellor 

for Clinical Research, Duke University

Professor of Medicine, Duke University 

Medical Center, Director, Duke 

Translational Medicine Institute, 

speaking to the Commission on 

March 1, 2011.

The decades that have elapsed since the first 

national bioethics commission began an 

evaluation of U.S. human subjects protections in 1974 have seen dramatic changes in 

the research enterprise and further development of our system for protecting human 

subjects.22 Research beyond public health and 

medicine, in social science and related fields, 

can involve thousands of research subjects 

through increasingly accessible survey tools 

and methodologies that expand experimental 

rigor.23 Much like the globalization of business and other sectors of our economy and 

culture, research with human subjects is now 

a global enterprise (see Figure 1.1). 
MORAL SCIENCE Protecting Participants in Human Subjects Research

22

Figure 1.1: National Institutes of Health. Map of All Studies in ClinicalTrials.gov. (n.d.). Retrieved from 

http://www.clinicaltrials.gov/ct2/search/map/click?map.x=322&map.y=305 (accessed December 5, 2011).

In the health sector, large-scale, multi-site, and multi-national clinical trials 

and management by contract research organizations (third parties to whom 

research sponsors outsource many of the administrative needs for research) 

are just two markers of this increasingly decentralized enterprise. Biomedical research is rapidly and inexorably 

expanding internationally.24 It increasingly 

addresses diseases more prevalent in other, 

sometimes developing, nations. Treatment naïve subjects (those not yet exposed 

to myriad pharmaceutical interventions), 

larger study populations, and the need to 

perform research in certain countries for 

both marketing and scientific purposes, 

further explain decisions to locate research 

in international settings.25 With the exception of the goals of product marketing, 

these factors are relevant to both publicly 

and privately funded research activities. 

“Looking at the change in global 

clinical trials, I think many people 

have rightly said that pendulum is 

swinging from where the majority 

of clinical trials were done in 

North America and Western 

Europe, to the point now where 

they are being done all over, to 

the point where they are going 

to be done in other parts of the 

world....” 

Dr. Murray M. Lumpkin, Deputy 

Commissioner for International Programs, 

FDA, speaking to the Commission on 

May18, 2011.
INTRODUCTION I

23

Research Across Borders

Recognizing the increasing involvement of foreign sites and partners in 

human subjects research, the Commission organized the International 

Research Panel (Panel), consisting of experts in bioethics and biomedical 

research hailing from 10 countries: Argentina, Belgium, Brazil, China, 

Egypt, Guatemala, India, Russia, Uganda, and the United States.26 The Panel, 

chaired by Commission Chair Amy Gutmann, met on three day-long occasions to discuss research standards and practices around the globe. In their 

discussions, Panel members drew upon their individual expertise and decades 

of experience conducting research and developing policy to protect human 

subjects.

The Panel presented its findings and recommendations, which focused on 

biomedical research, to the Commission in its report, Research Across Borders: 

Proceedings of the International Research Panel of the Presidential Commission 

for the Study of Bioethical Issues.

27 The Panel reached consensus on several 

issues. The United States and many other nations, the members agreed, have 

made significant progress in developing measures to protect human subjects 

in research over the last 50 years. Still, the rules, standards, and practices 

inside and outside the United States continue to vary greatly.28 The Commission’s research on international standards confirmed these findings.

The Panel concluded that researchers must demonstrate respect for human 

subjects and their communities in all phases of study design and implementation, and wherever research occurs. Recognizing different cultural 

standards and practices through community engagement that are compatible with the ethical treatment of human subjects is an important way of 

demonstrating respect across national boundaries, just as it is an important 

way of demonstrating respect within a diverse society. The Panel also stressed 

the importance of ongoing international dialogue between the United States 

and international bodies. As many within the United States and international 

partners have said before, the Panel agreed that U.S. and foreign investigators 

would benefit from clarification of the U.S. regulatory exception for foreign 

“protections that are at least equivalent to those” in the United States (“equivalent protections” found at 45 C.F.R. § 46.101(h)), and how it can be applied.
MORAL SCIENCE Protecting Participants in Human Subjects Research

INTERNATIONAL COLLABORATION: 

RV144 TRIAL 

Working with the Thai Ministry of 

Public Health (MOPH), U.S. and Thai 

researchers tested an HIV vaccine 

(RV144) that showed a 31.2% 

efficacy rate in preventing HIV 

transmission in a study sponsored 

by the U.S. Army and primarily 

funded by NIH.

The Panel considered this case 

study in its proceedings and focused 

its attention on the collaboration 

between the two countries. Of note, 

the vaccine developers guaranteed 

from the outset that, if the vaccine 

proved effective, Thailand would get 

it at a discount, as well as rights to 

manufacture it locally. In addition, 

naming a Thai MOPH official as one 

of the principal investigators in the 

study assured the Thai government 

that its interests would be honored.

Source: Presidential Commission for the 

Study of Bioethical Issues. (September 2011). 

Research Across Borders: Proceedings of 

the International Research Panel of the 

Presidential Commission for the Study of 

Bioethical Issues, pp. 50-53. Washington, 

DC: Presidential Commission for the Study 

of Bioethical Issues; AVAC (2010). AVAC 

Report 2010: Turning the Page, p. 25. AVAC. 

Retrieved from http://www.avac.org/ht/a/

GetDocumentAction/i/28305. 

The Panel proposed increased accountability by expanding access to public 

information about research.29 “Greater 

efforts are needed,” the Panel concluded, 

“to enhance transparency, monitor 

ongoing research, and hold researchers 

and institutions responsible and accountable for violations of applicable rules, 

standards, and practices.” Specifically, the 

Panel suggested that the government 

require all greater than minimal risk 

research to be registered and results 

reported in a system such as ClinicalTrials.gov (a federally sponsored on-line 

registry of most clinical trials conducted 

in or outside of the United States).30

The Panel also highlighted one of the 

widest disparities between the United 

States and other nations—many other 

countries provide greater protection for 

human subjects by ensuring treatment 

for research-related injuries or compensation for the costs of research-related 

treatment. The Panel noted that most 

other developed countries require sponsors, investigators, or others engaged 

in research to provide such treatment 

or reimbursement free of charge to the 

subject. The Commission’s research reached similar conclusions (see Appendix 

IV). In light of these facts, and the strong ethical case for such protection, the 

Panel recommended that the federal government explore whether revision of 

its rules is needed to ensure compensation for the medical costs of researchrelated injuries.31

24
INTRODUCTION I

25

Finally, the Panel echoed a view voiced by many of the guest speakers and 

individuals who provided written comments to the Commission. Reflecting 

what might be called “process fatigue,” the group endorsed ongoing efforts 

to harmonize and clarify existing rules to better protect human subjects over 

creating new rules.32

The Panel’s findings and recommendations gave the Commission important insight into the practice of human subjects research internationally and 

appreciation of the capacity of the current system to protect human subjects 

from harm and unethical treatment domestically as well as internationally. 

Furthermore, the Panel reinforced a conclusion the Commission reached in 

its own research—namely, that the ethical principles constraining pursuit 

of knowledge with human subjects apply regardless of where research takes 

place or who funds it.33 Procedural differences can, and sometimes should, 

affect the implementation of these principles, but the fundamental ethical 

foundations and boundaries of ethically sound research apply to all domestic, 

international, public, and private research.

Contemporaneous Reviews of the Human Subjects Protection System

Shortly after the Commission began its work in this area, the Office of the 

Secretary of HHS, in coordination with the White House Office of Science 

and Technology Policy (OSTP) issued an Advance Notice of Proposed Rulemaking, signaling the intent to consider comments on how to modernize 

the U.S. regulations governing human subjects research to make them more 

effective. This ANPRM, issued July 26, 2011, notes that the current HHS 

regulations34 also signed onto by 17 other federal departments and agencies 

(i.e. the Common Rule), were developed more than 20 years ago, “when 

research was predominantly conducted at universities, colleges, and medical 

institutions, and each study generally took place at only a single site.”35

In addition to changes over time in who is conducting research and where, 

the ANPRM also notes other trends in an evolving research enterprise, 

such as the expansion of health services research, research in the social and 

behavioral sciences, and research involving databases, the Internet, biological 

specimens, and genomics. The ANPRM sought comments on “how to better 

protect human subjects who are involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.”36
MORAL SCIENCE Protecting Participants in Human Subjects Research

26

Thus, in undertaking its review in response to the President’s charge, the 

Commission also considered aspects of the ANPRM for which it could make 

an informed contribution and reviewed ongoing efforts to modernize and 

clarify existing rules.

About this Report

President Obama gave the Commission nine months to thoroughly investigate the activities in Guatemala and, following the appointment of the 

Panel in March 2011, nine months to complete this contemporary review. 

The Commission held four multi-day, public meetings to address the President’s requests. Meeting speakers addressed a range of U.S. and international 

policies, rules, regulations, and publicly enunciated principles, providing 

perspectives from a wide array of professional and institutional organizations. 

The Commission also participated in deliberative discussion with members 

and the audience. It received more than 300 comments on this work.37

In the course of its review, the Commission studied human subjects research 

protections around the globe. A brief summary of some of those standards is 

made readily available through the website of the Office for Human Research 

Protections. The Commission also asked federal departments and agencies 

for information about their policies and practices to protect human research 

subjects.38 Department and agency liaisons provided extensive information 

concerning relevant policies used during the planning, execution, and oversight of research. They also provided valuable practical insight into how each 

department or agency supports and conducts research, as well as the efforts 

they take to ensure that human subjects are protected.

The Commission’s deliberations took into account the work of numerous 

preceding bodies. The 1995 Final Report of the Advisory Committee on Human 

Radiation Experiments offered 18 detailed and thoughtful recommendations 

regarding past abuses and remedies for participants injured in governmentsponsored scientific studies as well as empirically based ways to improve 

protection for human subjects in current and future studies. These included 

specific recommendations for ongoing debate through public fora.39 Many of 

these recommendations have since been implemented, and all of them raised 

important considerations to guide the Commission in its work.
INTRODUCTION I

27

In 2001, the National Bioethics Advisory Commission issued a comprehensive report on the existing system to protect human research subjects that 

included more than 30 specific recommendations; it also issued a report on 

research in international settings with 28 recommendations.40 In 2003, the 

Institute of Medicine (IOM) issued Responsible Research: A Systems Approach 

to Protecting Research Participants, with recommendations to extend the oversight system to all research, regardless of funding source or research setting.41

Additional IOM recommendations focused on the duties and functions of 

Institutional Review Boards, conflict of interest rules, the informed consent 

process, compensation for research-related injuries, levels of ethics review, 

and the need for quality improvement. Foreshadowing a perspective that the 

Commission heard repeatedly in this investigation, and voiced previously in 

the context of synthetic biology, IOM Chair Daniel Federman wrote, “[w]e 

do not, however, urge a permanent accretion of new regulations and bureaucracy.”42 Rather, Federman urged periodic reexamination of the problems and 

challenges facing the oversight system to better appreciate its appropriateness 

in “minimiz[ing] harm while enabling the benefits of progress to emerge.”43

Also during the last decade, the Secretary’s Advisory Committee on Human 

Research Protections (SACHRP), which advises the Secretary of HHS, has 

provided extensive guidance to the government on human subjects research 

protections and practices, including but not limited to recommendations 

regarding current rules for research involving children, prisoners, and other 

vulnerable populations; informed consent practices; community engagement; 

regulatory burden; and the need for harmonization of human subjects regulations.44 Collectively, all of this work assisted the Commission.

In Chapter 2, the Commission provides its response to the question of 

whether current protections are adequate to protect subjects from harm or 

unethical treatment. Chapter 3 includes further findings and recommendations. Additional background material appears in the appendices.
MORAL SCIENCE Protecting Participants in Human Subjects Research

28
29

CHAPTER 2

Assessing the Current System
MORAL SCIENCE Protecting Participants in Human Subjects Research

30

President Obama charged the Commission to determine whether “current 

rules for research participants protect people from harm or unethical 

treatment, domestically as well as internationally” and to undertake “a thorough review of human subjects protection to determine if federal regulations 

and international standards adequately guard the health and well-being of 

participants in scientific studies supported by the federal government.”45 In 

making this request the President sought assurance that the rules governing 

federal research today adequately guard against the abuses perpetrated by the 

U.S. Public Health Service in Guatemala in the 1940s. The President also 

asked for assurance that current rules protect people from harm or unethical 

treatment, no matter where in the world U.S.-supported research occurs.

In its previous report, “Ethically Impossible” STD Research in Guatemala from 

1946 to 1948, the Commission detailed how researchers in the 1940s failed to 

protect subjects from harm and unethical treatment in research supported by 

the Public Health Service and the government of Guatemala.46 In that case, 

investigators enrolled people in studies that involved intentional exposure to 

STDs without informing them of risks or seeking their consent. The study 

design, and the investigators’ actions in executing it, relied on flawed methodology and failed to minimize risks or maximize benefits for the majority 

of subjects and the community. Investigators intentionally hid information 

from the subjects, the public, and others who might have questioned their 

methods or aims. 

In 1946, when the research in Guatemala began, no federal laws, regulations, guidelines, or explicit international standards protected human subjects 

from these abuses. However, professional standards for physicians that had 

been promulgated by the American Medical Association, and the researchers’ 

own conduct in a previous U.S.-based STD trial that they had conducted in 

1943 and 1944, demonstrated their awareness that participants should not be 

exposed to undue risk and should be informed volunteers. Given these facts, 

the Commission concluded that many of the investigators and others in the 

chain of command supporting the research failed to protect subjects from 

harm and unethical treatment and did not abide by ethical constraints that 

they knew applied to their work. 
ASSESSING THE CURRENT SYSTEM II

31

Since the 1940s, however, major changes in the oversight and practice 

of research with human subjects have created a vastly different world for 

researchers and subjects alike. Federal laws, regulations, and guidelines; 

numerous transnational standards; and many similar laws and guidelines in 

other countries, enumerate and impose specific provisions to protect human 

subjects. Today’s federal rules reflect the now widely and long-recognized view 

that researchers must demonstrate respect for all human research subjects, 

including minimizing the risks and maximizing the benefits of research before 

it begins and respecting each person’s right to give his or her informed consent 

or its moral equivalent. These norms also are reflected in the terms of international human rights treaties, such as the International Covenant on Civil and 

Political Rights, to which the United States is a signatory.47 Americans, like 

many people and nations, hold these norms to be fundamental moral duties 

owed to every person, each of whom is entitled to respect by virtue of their 

unique status as moral agents. 

Federal statutes and regulations require informed consent from volunteers, independent ethical review, equitable subject selection, confirmation 

of scientific validity, and minimization of risks to subjects, among other 

essential limits.48 The Common Rule extends these requirements to most 

federally funded scientific studies regardless of where they occur.49 In addition, FDA regulations for protecting human subjects apply to all clinical 

research on drugs, including biologics, and devices, regardless of the source 

of funding (i.e. public or private sources).50 (See Figure 2.1.) The history of 

SCIENTIFIC STUDIES WITH HUMANS:

FEDERAL PROTECTION OF HUMAN SUBJECTS IN RESEARCH

FDA-regulated research supported by 

Common Rule agencies

FDA

Applies to privately 

and federally 

funded research 

involving drugs, 

biologics, and 

devices.

Common Rule

Applies to research 

supported 

by 18 federal 

departments and 

agencies.

Not federally 

funded and 

not subject to 

FDA rules

Federally funded 

and not subject 

to FDA rules or 

the Common Rule

Figure 2.1: Federal Protection of Human Subjects in Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

32

these rules, which have evolved over several decades, is well documented. 

Together, they extend to most, although not all, research conducted in the 

United States and nearly all research funded with public monies outside of 

the country.51

Regulatory standards are not the sole or sufficient means to ensure that human 

subjects are protected from harm or unethical treatment. There are long and 

distinguished philosophical traditions, traceable in Western traditions, for 

example, to Aristotle’s moral psychology and to a Kantian ethics of acting 

out of moral duty, that emphasize the need to cultivate individual moral character.52 For research, this focus on virtuous character translates into a focus on 

the internal ethical motivation of individual investigators, not only the rules 

and regulations that externally motivate investigators toward compliance. 

Although there are disagreements about how much reliance should be placed 

on the virtuous researcher, and although there are notorious instances in 

which virtue alone has not sufficed as a bulwark of research protections, it is 

undeniable that any compliance regimen is more effective and efficient when 

researchers have internalized a strong sense of personal responsibility as part 

of their professional calling. A strong sense of personal responsibility that 

supports research ethics may emerge from the individual’s own moral sensibility, but it also can and should be cultivated through an education that 

effectively emphasizes the importance of ethics and a keen sense of social 

responsibility in professional life.

Professional standards for research today, as the Commission details in 

Chapter 3, are available but limited. Existing guidelines are found in the 

codes of conduct of numerous professional societies, universities, and 

pharmaceutical companies.53 Embedded in these codes are the principles of 

respect for persons, beneficence, and justice, as demonstrated by the inclusion 

of safeguards such as standards for risk balancing, disclosure of investigator 

funding source, and independent review of payments to human subjects and 

investigators. Provisions calling for registration of clinical trials and publication of study results provide for greater transparency. Review requirements 

also seek to ensure scientific rigor and subject safety in trial design.54 The 

Pharmaceutical Researchers and Manufacturers Association (PhRMA) and 

many of its affiliates promote general professional standards of conduct.55
ASSESSING THE CURRENT SYSTEM II

33

AstraZeneca is one organization that explicitly characterizes the conduct of 

research ethics as a professional standard.56 Various federal agencies provide 

protections in addition to those in the Common Rule or FDA rules. These 

include conflict of interest regulations to guide investigators in disclosure 

practices and privacy rules that ensure researchers comply with confidentiality requirements of the Health Insurance Portability and Accountability Act 

(HIPAA) Privacy Rule.57

With well-recognized rules (including regulations and professional standards) 

for consent, prospective review, scientific validity, and minimization of risks 

now in place, there is a starting point to answer the question of whether 

research subjects are adequately protected from harm and unethical treatment. However, having adequate rules in place does not, in and of itself, 

ensure that those rules are well implemented or, that they therefore provide 

adequate protection for human subjects. A far more extensive analysis than 

is possible now would assess whether these rules are sufficiently understood 

and implemented given the scope and volume of human subjects research 

supported or conducted by the federal government today. 

The Scope and Volume of Federal Human Subjects Research

Faced with the need to assess all scientific studies with humans supported 

by the government, the Commission found that the scope and volume of 

federally supported scientific studies involving human subjects is broad and 

not easily identified. Available information about U.S.-funded research is 

sporadic, with no single listing of human subjects research available inside 

or outside of the government. Public information on research in medicine 

and health is generally more accessible than information on research in other 

sectors, such as education, justice, or engineering. But, overall, systemic information is very limited. 

Given these limitations, the Commission sought to collect basic, projectlevel data about human subjects research, including study title, number and 

location of sites, number of subjects, and funding information directly from 

each Common Rule department and agency.58 These data were compiled into 

its Research Project Database, and analyzed as part of its Human Subjects 

Research Landscape Project (see further discussion in Chapter 3 and Appendices I and II). 
MORAL SCIENCE Protecting Participants in Human Subjects Research

34

The Commission’s data collection efforts show that federally supported 

human subjects research is occurring around the globe and with an enormous 

investment by the federal government.59 Over 55,000 human subjects research 

projects (awards and individual studies) were supported in Fiscal Year 2010, 

mostly in medical and health-related research, but also in other fields such as 

education and engineering. The Commission’s direct request for information 

from Common Rule departments and agencies revealed that some lack the 

means to readily identify what human subjects research they support. For 

example, some lack a straightforward way, such as the ability to sort relevant 

records in internal systems, to identify human subjects research projects. 

Short of reaching down into the operating components of departments and 

agencies and to individual program officers, which several agencies did to 

support the Commission’s efforts, many agencies have no means to identify 

even basic information about agency-supported human subjects research.60

With over six months to gather and submit project data, some departments 

and agencies were unable to respond fully to the Commission’s request.

These systemic problems notwithstanding, the Commission found that 

the federal government supported approximately 55,386 human subjects 

research projects in Fiscal Year 2010. HHS supported almost half of all projects, approximately 26,651, with NIH supporting the largest percentage of 

HHS research by far, approximately 23,891 projects, or 89.6 percent of HHS 

studies and 43 percent of all federal studies. (See Figures 2.2, 2.3, and Tables 

2.1 and I.4.) Data from earlier years, though less complete, show that the 

total number of human subjects projects is rising but the distribution among 

departments and agencies is fairly steady. HHS is the largest supporter of 

research with human subjects and, within it, NIH is the primary funder. (See 

Tables 2.1, I.4, I.9, and I.10.)
ASSESSING THE CURRENT SYSTEM II

35

Human Subjects Projects by Department/Agency, FY10†

Other 

DOE 363

USDA 272

DOJ 216

NASA 136

USAID 62

DOT 56

EPA 46

DOC 23

HUD 18

SSA 13

DHS 10

CPSC 1

DOD

7,084

NSF

3,051

VA

15,415

ED

1,969

HHS

26,651

†

 “Projects” include awards and individual studies. The CIA did not submit project-level data to the Commission’s database because 

these data are confidential (although not classified). Departments/agencies that appear italicized reported that they were unable to 

provide complete data. See Appendix II for additional details. 

Figure 2.2 

Human Subjects Projects by HHS Unit, FY10†

CDC

1,317

FDA

200

NIH

23,891

AHRQ

898

IHS

251

Other 

HRSA 35

OAH 31

OPA 16

ASPR 12

†

 “Projects” include awards and individual studies. See Appendix II for additional details.

Figure 2.3
MORAL SCIENCE Protecting Participants in Human Subjects Research

36

Table 2.1 Human Subjects Projects Over Time†

DEPARTMENT/

AGENCY 

FY06 FY07 FY08 FY09 FY10 MEAN

HHS 25,275 25,700 25,168 26,512 26,651 25,861

VA 16,763 16,731 16,706 16,383 15,415 16,400

DOD 6,518 6,557 6,886 6,279 7,084 6,665

NSF 1,820 2,271 2,627 2,988 3,051 2,551

ED 222 1,145 1,199 1,296 1,969 1,166

DOE 407 368 371 348 363 371

USDA 118 122 220 201 272 187

DOJ 120 118 86 140 216 136

NASA 83 104 121 133 136 115

USAID 159 157 106 64 62 110

DOT 26 26 35 47 56 38

EPA 36 41 43 21 46 37

DOC 21 26 34 27 23 26

DHS‡ N/R 22 30 24 10 22

SSA 15 18 17 14 13 15

HUD 7 11 7 18 18 12

CPSC 1 1 2 1 1 1

CIA§ N/R N/R N/R N/R N/R N/R

Total 51,591 53,418 53,658 54,496 55,386

† “Projects” include awards and individual studies. “N/R” means that the data were not reported to the Commission.

Departments/agencies that appear italicized reported that they were unable to provide complete data. See Appendix 

II for additional details. ‡ DHS reported that there “are no earlier data” than FY07. § The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified). 

It is no surprise that HHS, and NIH within it, supports the largest volume of 

human subjects research. Research with humans is critical to advancing many 

fields and chief among these is medicine and health. NIH has led development of human subjects protection standards for more than 50 years since the 

opening of its Clinical Center in 1953.61
ASSESSING THE CURRENT SYSTEM II

37

SOCIAL, BEHAVIORAL, AND ECONOMIC 

SCIENCE RESEARCH METHODS

Laboratory Experiments – measure effects 

of social or physical manipulation in a 

controlled setting

Field Experiments – measure effects of 

social or physical manipulation in a real 

world setting

Observations of Natural Behavior – 

document descriptions of real world 

behavior

Interviews – 1) Unstructured: gather open 

ended, qualitative data; 2) Semistructured: 

gather qualitative data on a specific topic; 

3) Structured: gather quantitative data on 

a specific topic

Secondary Data Analyses – analyze 

existing data for another research purpose

Source: Coleman, C. et al. (2005) The Ethics and 

Regulation of Research with Human Subjects. Newark, 

NJ: LexisNexis.

Less well known is information 

about the volume of research 

supported outside of HHS. The top 

five supporters of research with 

human subjects in Fiscal Year 2010, 

based on projects reported, were 

HHS, followed by the Department 

of Veterans Affairs (15,415), Department of Defense (7,084), National 

Science Foundation (3,051), and 

Department of Education (1,969). 

(See Table 2.1.) Research funded in 

these departments and agencies 

includes some medical/healthrelated research, but also largely 

includes research in other fields, like 

education and engineering. 

Sub s t a nt i a l hu m a n s ubje c t s 

research programs are also in 

place at the Department of Justice, 

the Department of Agriculture, 

and the Department of Energy. Here again, some of the research includes 

health-related activities, for example, measuring health effects of new technologies, but much relates to program and policy evaluation.62 (See Table 2.2.) 

Although it is difficult to precisely quantify the proportion of health-related 

research, by relying on the mission of the departments and agencies—an 

imperfect but preliminary measure—approximately 42,066 projects were 

medical or health-related, and 13,320 projects were in other fields, including 

education and engineering.
MORAL SCIENCE Protecting Participants in Human Subjects Research

38

Table 2.2 Examples of Non-Clinical Human Subjects Research

Department of Housing 

and Urban Development 

(HUD)

Observational Studies Illuminate Environmental Effects on Health

A HUD-supported observational study examined whether a neighborhood’s 

environment influences the health of its inhabitants. Researchers randomly assigned 

some participants living in public housing to receive vouchers to move to lower 

poverty areas, and found that moving to an area with lower poverty has a modest, but 

potentially significant, impact on the incidence of obesity and diabetes in residents.

Department of Energy 

(DOE)

International Research Improves Radiation Protection Standards

Through the Radiation Effects Research Foundation (RERF), which is co-sponsored by 

the U.S. and Japanese governments, the DOE studies the long-term health impacts 

resulting from radiation exposure from the atomic bombs detonated in Hiroshima 

and Nagasaki in 1945. The RERF research has yielded improved radiation 

protection standards that are now employed worldwide.

Department of Justice 

(DOJ)

New Technologies Improve Safety By Preventing Injury

DOJ supported a study to monitor the use of conducted energy devices or CEDs (e.g., 

Taser stun guns). Comparing safety outcomes of law enforcement agencies that 

deployed CEDs to those of agencies that did not, researchers found that the former 

had improved safety outcomes compared to the latter.

Sources: Ludwig, J., et al., (2011). Neighborhoods, obesity, and diabetes – A randomized social experiment. The 

New England Journal of Medicine 365(16),1509-1519; Radiation Effects Research Foundation: A Cooperative JapanUS Research Organization. (2007). [Foundation website]. Retrieved from http://www.rerf.or.jp/index_e.html; Police 

Executive Research Forum. (September 2009). Comparing safety outcomes in police use-of-force cases for law 

enforcement agencies that have deployed Conducted Energy Devices and a matched comparison group that have not: A 

quasi-experimental evaluation. Report submitted to the National Institute of Justice. Washington, D.C.: Police Executive 

Research Forum. Retrieved from http://www.policeforum.org/library/use-of-force/CED%20outcomes.pdf.

The Commission found, for some departments and agencies, that it was 

difficult to obtain comprehensive, country-specific data on where research 

is occurring. Some agencies limit support to domestic research and some 

lack authority to operate internationally. For example, the Department of 

Transportation and HHS’s Indian Health Service, with 56 and 251 projects 

respectively reported for Fiscal Year 2010, limited their support to studies 

in the United States. (See Tables I.7 and I.8.) For these funders, all research 

occurred in the United States. By contrast, some departments and agencies 

did not identify specific countries in which research occurs. For example, 

readily available records were sometimes limited to saying whether work is 

“foreign” or “domestic,” and some departments or agencies did not report 

where work is occurring with certainty. (See Figure 2.4. and Tables I.7 and 

I.8.) However, for those that did report country-specific information, the 

Commission found that U.S.-government research was occurring in at least 

117 countries around the globe in Fiscal Year 2010 and on each inhabited 
ASSESSING THE CURRENT SYSTEM II

39

continent. About 4.6 percent of the 55,386 Fiscal Year 2010 governmentsupported projects included at least one international component (site or data 

collection); 65.1 percent were entirely domestic; and 30.3 percent did not 

report a site country. (See Table I.7.) In HHS, approximately 7.7 percent of 

the 26,651 Fiscal Year 2010 projects included at least one international 

component (site or data collection); 88.3 percent were entirely domestic. (See 

Table I.8.)

† Human Subjects Projects by Location, FY10

Unknown‡

16,785

Domestic

36,046

Domestic and Foreign

1,624

Foreign

931

† “Projects” include awards and individual studies. The CIA did not submit project-level data to the Commission’s database because 

these data are confidential (although not classified), but did indicate to the Commission that all of its human subjects research 

takes place in the United States. See Appendix II for additional details. 

‡

 Over 90 percent of “unknown” studies were reported by the VA, which explained that normally its human subjects research takes 

place in the United States.

Figure 2.4

When considering responsibility for research, an important distinction exists 

between the government’s support for intramural human subjects research 

(i.e., conducted directly by governmental personnel and at governmental facilities) and extramural human subjects research (i.e., conducted by academic 

investigators or others supported through agency grant, contract, or other 

mechanism). (See Tables I.2, I.3, I.5, and I.6.) Generally, departments and 

agencies have a far more direct line of authority and responsibility for the 

conduct of intramural research. It is, in a sense, “their” work. Extramural 
MORAL SCIENCE Protecting Participants in Human Subjects Research

40

research, by contrast, is conducted by individuals outside of the government, although they are funded by the government and, for contract-funded 

research, operate at the behest and with specific guidance from the government. The proportion of intramural and extramural projects across the 

Common Rule departments and agencies varies greatly. But, generally, based 

on total number of projects, the government’s extramural research portfolio, 

comprising around 54 percent of the government’s total research efforts, is 

more extensive than its intramural portfolio. In Fiscal Year 2010, the federal 

government directed extramural awards to approximately 3,100 institutions, 

about 200 of which are located outside the United States. (See Table I.13.) 

Funding to these approximately 3,100 institutions totaled about $16.7 billion. 

(See Table I.9.) 

Current Rules

Knowing the scope and volume of research is a prerequisite for assessing 

whether the current system is adequate for protecting human subjects from 

harm or unethical treatment, but another critical determinant is whether the 

investigators and researchers conducting this research understand and abide 

by the ethical rules and constraints applicable to their work. 

The Common Rule agencies have various civil methods to enforce their 

regulations. (See Table 2.3.) Within HHS, the Office for Human Research 

Protections (OHRP) evaluates complaints and conducts compliance oversight 

site visits and not-for-cause surveillance evaluations of institutions. OHRP 

does not conduct investigations of noncompliance regarding research solely 

conducted or supported by agencies other than HHS. Those other agencies are 

responsible for directly investigating allegations of noncompliance in research 

they support. 
ASSESSING THE CURRENT SYSTEM II

41

Table 2.3 Examples of Agency Enforcement Authorities

AGENCY LEAD ENFORCEMENT AUTHORITY

Health and Human Services Office for Human Research Protections

Central Intelligence Agency Human Subject Research Panel

Department of Defense Director, Defense Research and Engineering

Department of Veterans Affairs Research Compliance Officers; Office of Research Oversight

National Aeronautics and Space Administration Chief Health and Medical Officer

Sources: Department of Health and Human Services, Office of the Assistant Secretary for Health, Office for Human 

Research Protections. Program Description; Letter from V. Sue Bromley, Associate Deputy Director, CIA, to Amy 

Gutmann, Chair, Presidential Commission for the Study of Bioethical Issues. (May 16, 2011); DOD Directive 3216.02, 

Protection of Human Subjects and Adherence to Ethical Standards in DOD-Supported Research, sec. 4.10, March 25, 

2002; VHA Handbook 1058.01: Research Compliance Reporting Requirements, para. 6; VHA Directive 1058, The Office 

of Research Oversight. www1.va.gov/vhapublications/ViewPublication.asp?pub_ID=1825. NASA. (2007).NASA Policy 

Directive: Protection of Human Research Subjects. June 14. Retrieved from http://nodis3.gsfc.nasa.gov/npg_img/N_

PD_7100_008E_/N_PD_7100_008E__main.pdf.

Recent reviews of OHRP’s enforcement actions show that noncompliance 

often involves violations related to the IRB initial review process and IRB 

approval of informed consent documents.63 The identified violations were 

overwhelmingly procedural, with a much smaller percentage of the violations 

reflecting substantive concerns such as a failure to obtain informed consent 

(8 percent of violations).64 These data offer a snapshot of the ways that institutions have failed to comply with regulations. Given the volume of research 

HHS supports, these results suggest that there is room for improvement, but 

that the incidence of serious harm or unethical treatment is fairly low.

Once a database of federally sponsored human subjects research is readily 

available, there are various methods that could be useful to assess investigators’ specific understanding of ethical requirements and practices on the 

ground. For example, a project-by-project assessment could be undertaken 

using a sample of recent federally supported projects in order to determine 

how individuals and organizations conducting human subjects research 

currently apply federal regulations and international standards. Such an 

assessment could identify the practical ethical challenges facing researchers 

and the organizations that oversee them. Document review of agency IRB 

records, structured interviews with research team members and other stakeholders, as well as site visits, could bring far more specific information than is 

now readily available. Given limited information and time, the Commission 
MORAL SCIENCE Protecting Participants in Human Subjects Research

42

did not undertake these actions, but it encourages future reviewers and 

policymakers to consider them.

Conclusion

Existing evidence suggests both that the rules governing federal research 

today adequately guard against abuses analogous to those perpetrated in 

Guatemala in the 1940s and that current regulations generally appear to 

protect people from avoidable harm or unethical treatment, insofar as is 

feasible given limited resources, no matter where U.S.-supported research 

occurs. This conclusion, set forth more fully below, is both consistent with 

and also qualified by the large, yet incomplete, set of information made available to the Commission in the time available to carry out its charge. 

The Commission concludes, however, that improvement of the current system 

is both possible and desirable. In Chapter 3, the Commission describes those 

areas where improvements are warranted at this time. With these improvements, or response from policymakers to explain to the public as to why they 

are not justified, the abuses of the past can be left firmly in the past. There 

is no way to eradicate all risk of harm, particularly in some types of medical 

and translational research, but the current system, with the improvements 

suggested here, can become one in which we can all be more confident. 

In sum, the Commission finds:

The current U.S. system provides substantial protections for the health, 

rights, and welfare of research subjects and, in general, serves to “protect 

people from harm or unethical treatment” when they volunteer to participate as subjects in scientific studies supported by the federal government. 

However, because of the currently limited ability of some governmental 

agencies to identify basic information about all of their human subjects 

research, the Commission cannot say that all federally funded research 

provides optimal protections against avoidable harms and unethical treatment. 

The Commission finds significant room for improvement in several areas 

where, for example, immediate changes can be made to increase accountability and thereby reduce the likelihood of harm or unethical treatment. 
43

CHAPTER 3

Further Analysis and Recommendations
MORAL SCIENCE Protecting Participants in Human Subjects Research

44

I

n several important ways, the current regulatory and professional system 

for the protection of human research subjects can and should be strengthened. Ethical standards, at least as reflected in current regulations, are 

sometimes seen as a barrier or burden rather than as an integral part of 

the web of respectful human relationships.65 Society as a whole often lacks 

adequate information with which to hold researchers and research funders 

accountable for the work that they do. And, despite the fact that science itself 

is founded on the expansion and exchange of human knowledge, there are 

insufficient data available to assess the soundness of current human subject 

protections or their accessibility and responsiveness to stakeholders and the 

general public. 

The Commission identified several areas for improvement, including:

1) increasing accountability; 

2) helping those who are harmed as a result of research participation;

3) respecting equivalent protections of international partners;

4) promoting a culture of responsibility;

5) evaluating site selection and the justification for chosen study designs; and 

6) engaging communities at all levels of research.

Some of these recommendations include specific suggestions for government 

action and others are directed more broadly to the community of research 

investigators, scientists, and others involved in protecting human subjects 

from harm and unethical treatment. The Commission also offers endorsement and comments on several of the proposed reforms published by HHS 

and OSTP in the ANPRM to reform the Common Rule issued in July 2011.66

The Commission’s attempts to understand the full range of human subjects 

research conducted or supported by the federal government highlighted the 

difficulty of performing such an inquiry. Thus, recommendations are offered 

on increasing accountability of research programs. Review of existing regulations, guidelines, and professional standards; combined with testimony 

received about the challenges of linking procedural requirements to ethical 
FURTHER ANALYSIS AND RECOMMENDATIONS III

45

principles; underscored the need to focus on a variety of means to further 

cultivate and reinforce a culture of responsibility among researchers.

In examining the current system to ensure that subjects are protected from 

harm or unethical treatment, the Commission also identified a set of important 

ethical questions about study design and site selection that remain unsettled, 

yet possible to address in the context of particular research endeavors. Ethical 

considerations for the choice of study design include a range of issues, such 

as ascertaining to whom the benefits of the trial accrue, and determining 

whether the interests of the subjects and their communities are properly 

weighed and balanced in relation to the distribution of risks and benefits. 

Study design and methods cannot be justified by the importance of research 

alone. Certain study designs—such as comparing placebos to experimental 

interventions through a controlled trial—raise ethical concerns when existing 

alternative treatments can be effective in the communities where the research is 

intended to occur, unless a strictly defined set of conditions can be met under 

which comparison is justified. Engaging with relevant communities prior to 

beginning research may be one important step for researchers to show respect 

and sensitivity to cultural norms relevant to protecting human subjects. 

The globalization of biomedical and behavioral research has at times outpaced 

the thoughtfulness with which decisions can or should be made about the 

selection of research sites, a decision that should never be simply a matter 

of efficiency or expediency. Ethical concerns inherent in moving research 

across international borders need further careful specification. Many issues 

are unlikely to be unique to international research; they also arise domestically when, for example, research is undertaken in resource-poor or culturally 

distinct settings. It is recognized that taking research to specific sites that 

are less expensive because of lower costs associated with care or recruitment, 

or because of the relative ease of identifying populations with the condition 

under study who might be treatment naïve does not necessarily mean the 

research is ethically unacceptable. But when the circumstances of selecting 

research sites suggest the possibility or appearance of exploitation and failure 

to respect individual human dignity or appropriate community interests, site 

selection—both domestic and international—needs to be examined more 

carefully than it has been at times in the past.67
MORAL SCIENCE Protecting Participants in Human Subjects Research

46

Finally, it has long been agreed, as a matter of principle, that respectful treatment of those who volunteer as research subjects should include medical 

treatment for injury, however rare, without charge to subjects. While people 

may disagree on the extent to which medical expenses should be paid and 

by whom, the notion that research subjects should not be made worse off as 

a result of volunteering to advance science and society is generally uncontroversial. The just distribution of burdens suggests that individuals should 

not be forced to bear the costs of injuries they suffer to advance collective 

well-being. But here, as in much of life, the devil lies in the details. The 

Commission recognizes that there are variable policies and practices in place 

now to insulate subjects from bearing medical treatment costs and believes 

that the federal government should undertake further study to determine 

whether, and if so how, a government-wide policy could be developed.

The recommendations in this report are intended to enhance and strengthen 

the current system. They include some overarching issues applicable to 

research in any sector and several other issues that, while focused largely 

on details of health research, have important implications for how human 

subjects are protected. The Commission’s recommendations, if implemented, 

will help to ensure that the well-being and rights of research subjects are 

protected, promote professionalism, better integrate ethical responsibilities 

among researchers, and serve to increase society’s confidence that research 

volunteers are not subjected to avoidable harm or unethical treatment. In 

short, these recommendations offer tools to aid the practice of ethically sound 

research. There of course can be no guarantor of perfection or final word in 

this complex realm. Just as the President asked the Commission to examine 

our country’s understanding and application of fundamental ethical principles for the protection of human subjects in research today, future generations 

will need to re-evaluate their contemporary application of these principles in 

the context of their own time. 

Commission Recommendations

1. Improving Accountability

The need for greater accountability among all federal supporters of research 

emerged as a crucial, and imminently remediable, issue among the Commission’s overarching concerns. Contemporary tools for public access to 
FURTHER ANALYSIS AND RECOMMENDATIONS III

47

information offer mechanisms to enhance accountability. Expanded support 

for research into the methods and processes of human subjects protection 

offers the opportunity to further assure that human subjects are protected 

from harm or unethical treatment.

Science requires substantial societal investment, putting it in competition 

with other important activities that may contribute to the public good. Therefore, and especially for publicly funded research, the public has the right to 

accountability in the use and management of the resources allocated to the 

pursuit of scientific knowledge for the common good. Moreover, public scrutiny can offer the opportunity for responsible officials and scientists to gain a 

better understanding of the values and preferences of the public whose good 

they ultimately serve. As subject matter experts may sometimes fail to appreciate all implications of their work, substantive contributions by others, not 

directly engaged, may provide unexpected and positive contributions. 

However, the rationale for accountability is not merely one rooted in the 

contingencies of public funding. Modern science is grounded in the enlightenment values of democratic participation and public demonstration, so that 

access to insights about the nature of the universe is not limited to only a 

small fraction of society. Over the last 200 years—and especially in recent 

decades—science has developed into an increasingly collaborative activity 

among teams that are often geographically distant, each taking responsibility 

for an aspect of a complex body of work. Peer review, which is an integral 

and longstanding practice in decisions about both funding and publication of 

research, is another element that crucially contributes to accountability and 

exemplifies the fact that science is a communal activity. Making research more 

transparent can help to improve its quality, reduce the chances for unnecessary duplication, and inform determinations of scientific merit and reasonable 

risk in human subjects research. Systems for making research information 

publicly available should take into account privacy and intellectual property 

concerns, and conform to applicable statutory and regulatory constraints. 

Scientific and lay communities have increasingly advocated for public 

access to information about federally sponsored biomedical research activities. Insufficient access to research information allows studies and results to 

be hidden and can result in injuries to human subjects, wasted resources, 
MORAL SCIENCE Protecting Participants in Human Subjects Research

48

EXAMPLES OF CLINICAL TRIAL REGISTRIES 

AROUND THE WORLD

Australia and New Zealand – 

http://www.anzctr.org.au/

Brazil – http://www.ensaiosclinicos.gov.br/

China – http://www.chictr.org/en/

Cuba – http://registroclinico.sld.cu/

European Union – 

https://www.clinicaltrialsregister.eu/

Germany – 

https://drks-neu.uniklinik-freiburg.de/drks_web/

India – http://www.ctri.in/

Iran – http://www.irct.ir/

International Standard Randomised Controlled 

Trial Number Register – http://www.isrctn.org/

Japan – http://rctportal.niph.go.jp/en/index

Netherlands – 

http://www.trialregister.nl/trialreg/index.asp

Pan Africa – http://www.pactr.org/

South Korea – http://ncrc.cdc.go.kr/cris/index.jsp

Sri Lanka – http://www.slctr.lk/

Source: World Health Organization. (n.d.). Members of the WHO 

Registry Network. Retrieved from http://www.who.int/ictrp/

network/primary/en/index.html.

and unethical exposure to 

unnecessary risk.68 Federal 

law since 1997 has required 

public and online access 

to limited, basic information about clinical trials 

involving drugs for serious or 

life-threatening conditions, 

whether publicly or privately 

funded.69 Congress expanded 

these requirements in 2007 

to cover most clinical trials of 

drugs and devices and public 

access to basic results of these 

trials through the government 

website, ClinicalTrials.gov.70

The International Federation 

of Pharmaceutical Manufacturers Associations and the 

State of Maine promulgated 

policies mandating public 

access to certain clinical 

trial information, and the 

World Health Organization 

developed a voluntary international clinical trial registry 

platform in which many countries participate.71 Several countries maintain 

their own national registries a well.72

The Declaration of Helsinki now states that “[e]very clinical trial must be 

registered in a publicly accessible database before recruitment of the first 

subject.”73 Federal law has also mandated online public access to basic information about federally funded grant and contract research. For example, 

USASpending.gov was implemented by the Federal Funding Accountability 

and Transparency Act to create a publicly accessible, online database of all 

federal contracts and grants over $25,000; cataloguing details such as the 
FURTHER ANALYSIS AND RECOMMENDATIONS III

49

funding agency, the recipient, project site, and a description of the project’s 

subject matter.74 Recovery.gov is a similar site that allows the public to track 

use of funding made available specifically under the American Recovery and 

Reinvestment Act.75

Despite these several and promising recent developments in making 

information about research publicly available, more can be done. Only “applicable” clinical trials must be registered in ClinicalTrials.gov, yet human 

subjects research encompasses a much broader range of study types. Biomedical research alone comprises first-in-human and other early phase trials, 

natural history studies, and physiological studies that are not among those 

required to be registered. Research with human subjects also includes, for 

example, social, behavioral, and economic research conducted by federal 

departments and agencies such as the Department of Education, the National 

Science Foundation, and the Department of Justice. Indeed, the National 

Science Foundation and Department of 

Education were among the top five federal 

supporters of human subjects research (by 

number of projects) in Fiscal Year 2010. 

(See Table I.1.) And, databases such as 

USASpending.gov and Recovery.gov track 

federal grants and contracts generally, not 

those related to research—much less human 

subjects research—specifically.

CLINICALTRIALS.GOV

ClinicalTrials.gov contains 

information about nearly all 

federally and privately funded 

clinical trials investigating new 

drugs or devices, except phase I 

drug and device trials and 

certain types of post-market 

surveillance. Registration of 

covered studies in ClinicalTrials.

gov is mandated by statute.

Publicly available data at 

ClinicalTrials.gov includes: 

the trial’s sponsor; the title, 

description, and design of the 

study; locations where the 

study is conducted; and contact 

information for the trial facility. 

Clinicaltrials.gov does not collect 

funding information.

Source: Food and Drug Administration 

Amendments Act § 801, 42 U.S.C. § 282 

(j) (2007).

Other notable efforts to enhance accountability and access to information about 

human subjects research are also underway. 

For example, “Health Research Web,” initiated by the Council on Health Research 

for Development, an international nongovernmental organization whose primary 

objective is to strengthen research for 

health and innovation, compiles information on studies taking place around the 

world, as well as information about IRBs 

and research ethics committees, countries’ 
MORAL SCIENCE Protecting Participants in Human Subjects Research

50

governance policies, and other useful data.76 In 2008, Congress required that 

NIH-funded investigators submit their publications to PubMed Central, an 

electronic publicly accessible database.77 And, in accordance with the America 

Competes Act, OSTP, in late 2011, requested public input on recommendations on approaches for “encouraging broad public access to unclassified 

digital data that result from federally funded scientific research” and “broad 

public access to the peer-reviewed scholarly publications that result from 

federally funded scientific research.”78

Department- or agency-specific systems to track human subjects research are 

also available, though they vary widely. Some are centralized, publicly available databases. For example, the Department of Energy’s Human Subjects 

Research Database provides a wide range of protocol-level information 

about Department of Energy-supported human subjects research, including 

funding for and number of subjects involved in specific studies.79 NIH maintains RePORTER, a database listing information about all NIH grants and 

contracts such as funding amount, funding organization and location, and 

project abstract.80 Other departments and agencies lack such systems. For 

example, as part of its review, the Commission learned that some agencies are 

unable to link information about human subjects research projects to funding 

information in any systematic way. Other agencies maintain numerous 

internal databases, but cannot relate or de-duplicate among them.

Comparability of existing agency-specific databases is also limited. The data 

elements contained in each database reflect individual agency priorities and 

resources. For example, NIH’s RePORTER database, provides online access 

to award-level rather than project-level data, and includes information on all 

research—not just human subjects research. Therefore it can be difficult to 

readily distinguish information on specific human subjects studies.

In an effort to collect information on the scope, volume, and type of research 

funded by the federal government, the Commission requested from departments and agencies limited, project-specific information; such as study title, 

performance country (or countries), number of subjects (if available), and 

funding information; that it deemed necessary to assess the adequacy of 

protections in scientific studies supported by the federal government. For its 

Human Subjects Research Landscape Project, the Commission asked each 
FURTHER ANALYSIS AND RECOMMENDATIONS III

51

department and agency covered by the Common Rule to provide data that 

they maintain and have readily available. Some elements were particularly 

difficult for many agencies to report, such as a study’s number of subjects 

and whether the study was exempt from IRB review.81 Each department and 

agency asked for data provided some information about its human subjects 

research portfolio to the Commission. Some were able to respond fully (or 

almost fully) with each of these variables, while others provided more limited 

information. (See Appendices I and II.)

As technical computing and data sharing capabilities have evolved, and the 

public is increasingly able to access information about the research that it 

supports, accountability in research can be increased. While access to information alone does not ensure that human subjects will be protected from 

harm or unethical treatment, making information related to human subjects 

research readily available across department and agency supporters will 

contribute to the protection of human subjects by enabling further scrutiny 

and accountability. Knowing where research occurs will enable interested 

members of the public to raise appropriate questions on, for example, site 

selection or research design. It will enable accrediting organizations and 

oversight officials to readily identify basic details about research within their 

jurisdiction.82 And it will enable funders to more easily monitor their own 

portfolio to identify what work they do with human subjects and where more 

resources or attention may be needed. 

The Panel also recommended that information on all research that is more 

than minimal risk be made publicly available through an online tool.83 Given 

the existing requirements already in place for online access to information 

about many clinical trials posing more than minimal risk, the Commission does not single out this kind of research for special treatment. Rather, 

it recommends that a core, minimal data set on all federally funded research 

with human subjects should be made publicly available. 

Existing systems—both agency-specific and government-wide—provide a 

foundation from which agencies can develop and improve their own systems 

to be utilized as publicly available databases. It may be particularly important 

that departments and agencies collect sufficiently detailed data for individual 

projects to be identified and categorized. Aggregate data do not provide 
MORAL SCIENCE Protecting Participants in Human Subjects Research

52

information that would enable members of the public, including fellow 

researchers, to identify individual projects, understand where research may 

be duplicative (therefore imposing unnecessary risks on human subjects), or 

assess if research subjects are adequately protected. A core set of data elements 

about each project is necessary to provide a baseline description of federally 

supported human subjects research and changes over time, and to allow for 

compilation across departments and agencies. This core set of data elements 

should include at least: 1) title, 2) principal investigator and institutional affiliation, 3) location of research activities, and 4) funding source and funding 

amount.84 Where possible, the nature of the research study or abstract of 

the study and number of participants should also be included. For clinical 

research, an “NCT” number, assigned to projects registered in ClinicalTrials.

gov, if available, should be included to facilitate accountability by linking to 

other readily available information already maintained by the government. 

The Commission considered whether a new, central, government-wide database of this information should be developed. Because of cost and capital 

investments required, the Commission recommends instead that each 

department and agency should make core data publicly available either by 

developing or improving upon its own systems to make information publicly 

available or release information through a trans-agency system. For agencies 

without existing systems today, data could be submitted to ClinicalTrials.

gov or another existing online registry, provided the core data elements are 

available.85 The Commission endorses registration and reporting results of all 

human clinical research including early phase studies and all privately funded 

research. Certainly it will be easier if the public can access as much information as possible through an existing and widely recognized mechanism such 

as ClinicalTrials.gov. Moreover, information submitters may find it easier to 

rely on this existing system rather than having to prepare information for 

multiple databases. 

Creation of a central government web-based portal rather than a single 

government-wide database would enable department- or agency-level systems 

to be centrally accessible, leverage department- or agency-specific systems 

already in place, permit variability among agencies (e.g., differences in 

mission, research types, and recordkeeping practices), and provide opportunities for innovation and flexibility. A central web portal linking to each 
FURTHER ANALYSIS AND RECOMMENDATIONS III

53

department or agency’s system should be created and administered by OHRP 

or another designated agency. OHRP “provides leadership in the protection of 

the rights, welfare, and wellbeing of subjects involved in research conducted 

or supported by the U.S. Department of Health and Human Services,”86 and 

also occupies a prominent role in human subjects protection governmentwide.87 Thus, maintenance of a central web portal for research information 

access is consonant with OHRP’s mission. As above, however, recommendation of a portal mechanism is not intended to preclude the prospective 

development of a unified federal database if it is ultimately more cost-effective 

and efficient to do so and it is not intended to discourage use of available 

mechanisms that may make it easier for the public to obtain information 

efficiently. 

Accordingly, the Commission recommends: 

Recommendation 1: Improve Accountability through Public Access

To enhance public access to basic information about federal governmentfunded human subjects research, each department or agency that supports 

human subjects research should make publicly available a core set of data 

elements for their research programs—title, investigator, location, and 

funding—through their own systems or a trans-agency system. The Office 

for Human Research Protections or another designated central organizing 

agency should support and administer a central web-based portal linking to 

each departmental or agency system. This should not preclude the prospective development of a unified federal database that may ultimately be more 

cost-effective and efficient.

In addition to making core information available and more transparent for 

public scrutiny, the Commission finds that data are essential to determining 

whether current policies are meeting their intended goals. Contemporary 

federal policies regarding human subjects protection are generally based on 

sound ethical principles and many include procedural mechanisms that are 

intended to satisfy them. Determining the extent to which these procedures 

actually serve to protect human subjects depends, at least in part, upon empirical evidence. Today, there are limited data that demonstrate the effectiveness of 

particular procedures and no agreed upon metrics by which to measure them.88
MORAL SCIENCE Protecting Participants in Human Subjects Research

54

Empirical and conceptual bioethics research synergistically play important roles in protecting human subjects. The need for empirical research in 

bioethics is well established. Descriptive data can inform and test normative 

work in bioethics.89 It amplifies the force of conceptual bioethics activity, such 

as the development and delineation of ethical principles, by enabling such 

work to more closely map onto real-world situations and provide concrete 

solutions and recommendations. “[E]mpiric bioethics research serves [at least] 

three essential functions . . . : 1) debunking widely held but erroneous views; 

2) assessing the importance of ethical concerns; and 3) facilitating the realization of certain ethical values.”90 The latter functions can help determine the 

extent to which contemporary research policies manifest abstract values and 

ethical principles as well as tangible human subject potections. 

“The near-term priorities have 

certainly emphasized the 

importance for mission-related 

bioethics initiatives and training 

initiatives. The longer-term 

goal is to try to do more to 

integrate bioethics into the 

full spectrum of biomedical 

research. Not having this as 

a separate discipline but one 

that is fully connected with 

what is going on in the 

laboratories and the clinics.”

Dr. Francis Collins, Director, NIH, 

(2011). Bioethics Research at the NIH. 

Presentation to PCSBI, February 28, 

2011. Available at: http://bioethics.gov/

cms/node/187. 

Recognizing the value of empirical research to advancing human subjects 

protection, Dr. Francis Collins, NIH Director, detailed for the Commission 

his agency’s expanding research agenda in this area. Remarking that NIH 

Institutes and Centers have devoted roughly $50 million per year to research 

in bioethics, according to the most recent survey, Dr. Collins noted that the 

largest program, garnering $18 million per year, resides in the National 

Human Genome Research Institute, as its 

Ethical, Legal, and Social Implications 

Program. This program has been investigating the implications of genetic and 

genomic research for the last 17 years. 

During the two-year period following 

passage of the American Recovery and 

Reinvestment Act, NIH f unded 21 

bioethics Challenge Grants, which are noteworthy for the short time period and the 

especially competitive funding and review 

process. Set aside in the budget of the Office 

of the Director is $5 million for institutes 

that propose projects that fit the bioethics 

research and training agenda. A bioethics 

taskforce, comprised of representatives from 

25 Institutes and Centers, has reviewed the 
FURTHER ANALYSIS AND RECOMMENDATIONS III

55

results of NIH investment in bioethics research and is now entering a second 

phase and developing a strategic plan for the future of bioethics research at 

NIH. This strategic plan is certain to include initiatives to “integrate bioethics 

into the full spectrum of biomedical research,” making it part and parcel of 

the scientific process instead of a separate discipline.91

Still, there remains a dearth of knowledge about the actual efficacy of 

human subjects protections. Given this, the Commission recommends that 

the federal government support an expanded operational research agenda to 

study the effectiveness of human subjects protections. Research and evaluation designed to identify and measure protections afforded by Common 

Rule procedures could also inform understanding and implementation of 

the Common Rule’s equivalent protections provision, evaluate the effectiveness of implementing guidelines for community engagement, and assist in 

clarifying the justifications underlying research-site selection, all of which are 

areas the Commission believes can be improved (see Respecting Equivalent 

Protections, Promoting Community Engagement, and Justifying Site Selection, 

below). Accordingly, the Commission recommends that the federal government continue to support and consider expanding its support for systematic 

assessment of current human subjects protection standards.

Recommendation 2: Improve Accountability through Expanded Research

To evaluate the effectiveness of procedural standards embedded in current 

human subjects protection regulations, the federal government should 

support the development of systematic approaches to assess the effectiveness of human subjects protections and should expand support for research 

related to ethical and social consideration of human subjects protection.

Taken together, these recommendations aim to make more data publicly 

available in a coordinated way, enable periodic independent evaluation of the 

scope and volume of federal human subjects research, and support ongoing 

empirical study of human subjects protection standards. With them, the 

public will be better informed about federal research with human subjects, 

domestically as well as internationally, and will have greater opportunity to 

hold researchers and other officials engaged in the research process accountable for the work that they do. 
MORAL SCIENCE Protecting Participants in Human Subjects Research

56

2. Treating and Compensating for Research-Related Injury

Ethical Justification for Compensation

Those who sponsor or engage in human subjects research have an ethical 

obligation to protect people who volunteer as research subjects. Just as health 

services researchers speak of both primary and secondary forms of prevention, 

the Commission understands the duty to provide “protection” to encompass 

two important kinds of duties—primary and secondary protection.92

Lifeguards, for instance, have a duty to protect swimmers in both a primary 

and a secondary sense. They are obliged to protect swimmers from drowning 

risks, and to rescue those who begin to drown. Similarly, researchers should 

protect subjects from exposure to undue risk and limit or reverse the harm 

subjects may experience as a result of their participation in the research by 

assuring the provision of appropriate medical care.

The duty to protect only concerns risks that can be avoided or remedied. One 

can only protect against risks that can be reasonably foreseen and avoided or 

risks due to states of affairs that can be identified and modified. Some risks 

cannot be avoided, and there can be no duty to protect against such risks in a 

primary sense. Some harms cannot be remedied, and there can be no duty to 

protect against such harms in a secondary sense.

In thinking about whether there is an ethical justification for providing treatment or some form of compensation for the medical costs of research-related 

injuries, two important facts about the risks of research must be considered: 

•	 First, for the most part, the benefits of such research redound to the common 

good, while the risks are almost entirely borne by the subjects.93

•	 Second, some risks of human subjects research are unavoidable and often not 

readily foreseeable. This unforeseeable nature of some of the risk is part of the 

ethical justification for undertaking human subjects research in the first place.

Many have argued that there is a duty to provide medical care for subjects 

harmed by their participation in research.94 This Commission is not the first to 

study the question of compensation for injuries incurred in the course of research 

participation. The Presidential Commission for the Study of Ethical Problems in 

Medicine and Biomedical and Behavioral Research in 1982 and NBAC in 2001 

explored this issue and called on the government to study the feasibility and 
FURTHER ANALYSIS AND RECOMMENDATIONS III

57

need for requiring treatment or compensation for medical costs in the United 

States.95 The Institute of Medicine in 2002, also recommended that “organizations conducting research should compensate any research participant who is 

injured as a direct result of participating in research, without regard to fault.”

Over the last several decades, almost all other developed nations, and many 

transnational standard-setting bodies, have instituted policies to require 

researchers or sponsors to provide treatment or compensation for treatment 

for research subjects’ injuries.96 (See Table 3.1.) The Commission’s Panel 

recommended to the Commission that the United States should establish a 

system to assure compensation for the medical care of subjects harmed in the 

course of biomedical research.97

Table 3.1 International Requirements for Treatment of Research-Related Injury

COUNTRY POLICY

Belgium Requires subjects receive treatment for injury and compensation for death.

Denmark Establishes fund ensuring treatment for injury and additional compensation for 

pain and suffering, spouse or partner, loss of earnings, loss of earning capacity, 

loss of dependency for children, and injury to a person’s feelings or reputation.

Finland Establishes fund ensuring subjects receive treatment for injury and additional 

compensation for pain and suffering, disability, and economic loss.

Uganda Requires that subjects receive treatment for injury and compensation for any 

resultant impairment, disability, or handicap.

Brazil Requires that subjects receive comprehensive medical care for injury to the 

physical, psychic, moral, intellectual, social, cultural, or spiritual dimensions of 

the human subject.

GUIDANCE DOCUMENT RECOMMENDATION

CIOMS, International Ethical 

Guidelines for Biomedical Research 

Involving Human Subjects

Recommends that subjects receive both treatment for injury, recommends 

compensation for resulting disabilities.

International Conference on 

Harmonisation, Guideline for Good 

Clinical Practice

Recommends that subjects receive treatment for injury, and recommends 

compensation for resulting injuries in accordance with applicable regulatory 

requirements.

Institute of Medicine, Responsible 

Research: A Systems Approach to 

Protecting Research Participants

Recommends that subjects receive compensation that includes at least the cost 

of medical care and rehabilitation.

Sources: Belgium: Annex No. 1 Law of May 7, 2004 Concerning Experiments on the Human Person. Denmark: The Danish 

Liability for Damages Act (2005, amended 2006 and 2007). Finland: Pharmaceutical Injuries Insurance: General Terms 

and Conditions (2007). Uganda: Ugandan National Council for Science and Technology. (2007). National Guidelines 

for Research Involving Humans as Research Participant. Kampala: UNCST. Retrieved from http://www.uncst.go.ug/

dmdocuments/Guideline,%20Human%20Subjects%20Guidelines%20Marc.pdf; Hungary: Act XCV of 2005 on Medicinal 

Products for Human Use and on the Amendment of Other Regulations Related to Medicinal Products. (2005). Brazil: Rules 

on Research Involving Human Subjects. (2003). Council for International Organizations and Medical Sciences and World 

Health Organization. (2002). International Ethical Guidelines for Biomedical Research involving Human Subjects. Geneva: 

World Health Organization. ICH/GCP: International Conference on Harmonisation. (1996). Guideline for good clinical 

practice E6(R1). June 10. Retrieved from http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/

Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf; Institute of Medicine. (2002). Responsible Research: A Systems Approach 

to Protecting Research Participants. Washington, D.C.: National Academies Press.
MORAL SCIENCE Protecting Participants in Human Subjects Research

58

The primary argument in favor of providing care or costs for care of researchrelated injuries involves the principles of justice and fairness. Those who agree 

to take part in human subjects research accept the risks of this research, and 

place their bodies and sometimes even their lives on the line. For taking on 

the unavoidable risks of bodily injury that are inherent in such research, 

subjects often receive little or no monetary benefit and often no promise of 

any direct therapeutic benefit, particularly in early phases of clinical research. 

Society benefits from research subjects’ acceptance of these risks, so it seems 

fair that they are protected from some of the ameliorable harms that they 

may sustain as a result of their participation. This is sometimes described as 

an argument against “free-riders.”98 Those who benefit have an obligation in 

fairness toward those who experience harms. 

Unintended harm is inevitable in the course of human subjects research. 

Human subjects who are harmed as a consequence of participation in research 

should not individually bear the costs of medical care for such harms. This 

is true whether the harm results from a foreseen risk about which they are 

informed as part of the informed consent 

process or from a wholly unforeseen risk. 

Treatment or compensation for the cost 

of medical care is appropriate as an act of 

benevolent regard for individuals’ willingness to participate in an enterprise of 

important benefit to the public.

“I think compensation is the great 

leveler, and ... I think if the 

victim is harmed through no fault 

of his or her and through no fault 

of the researcher, I think there 

has got to be [compensation].”

Mr. Feinberg drew a contrast 

with the current tort system, 

noting that a compensation 

program, if implemented, should 

be an “efficient streamlined 

system that can reach resolution 

in months, not years,” noting 

that the current system is 

“often not very efficient.” 

Kenneth R. Feinberg, J.D., Administrator 

of the Gulf Coast Claims Facility and 

Special Master of the September 11 

Victim Compensation Fund. (2011). 

Presentation to the PCSBI, November 17. 

Available at: http://bioethics.gov/cms/

meeting-seven.

The primary argument against this view 

has been the assertion that there is a freely 

undertaken assumption of risk on the part 

of subjects volunteering for human research. 

If they understand the risks and benefits 

and still freely consent to participate, so the 

argument goes, then they have no claim, 

in justice, for compensation for any harms 

that befall them as a result of their participation in the research. This argument is 

steeped in legal history and expressed in 

the doctrine of volenti non fit injuria (those 
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59

who consent cannot claim injury).99 Because 

society permits research subjects to consent 

freely and accept the risks of research, then 

it is claimed that society should permit 

subjects to consent freely and accept the 

risk of doing so without expectation of free 

medical care or compensation for any harm 

caused by their participation.100

“We need human subjects for 

the simple reason you can’t 

try new therapies on lots of 

people that you haven’t tested. 

So we have to have human 

subjects. And there’s going to 

be an unavoidable, ineliminable 

burden that this places on some 

human beings. . . . [W]e have to 

be very careful that we spread 

this risk fairly[.]” But, “doing 

it without a safety net is not 

required. You can do the science 

and provide a safety net. . . . 

[T]here’s no excuse for imposing 

that on subjects whereas there 

is a perfectly good excuse for 

imposing the burden of being a 

research subject, namely you 

can’t do research without it.”

Daniel Wikler, Ph.D., Mary B. Saltonstall 

Professor of Population Ethics, 

Professor of Ethics and Population 

Health, Department of Global Health and 

Population, Harvard University. (2011). 

Compensation for Research-Related 

Injury. Presentation to the PCSBI, 

November 17, 2011. Available at: 

http://bioethics.gov/cms/node/391.

There are several arguments against the view 

that a human subject’s free and informed 

consent to participate in research qualifies 

as assumption of all risks related to research 

participation. This conclusion rests on a 

fallacious conf lation of avoidable and 

unavoidable risks. Society does not permit 

subjects to consent to any and all research 

risks, but requires instead a prior determination by an IRB that foreseeable risks are 

minimized or eliminated.101 IRBs carry out 

this duty of primary protection by prohibiting research that involves undue risk, 

regardless of whether an individual may 

freely consent to accept those risks. IRBs 

permit subjects to consent and accept 

unavoidable risks when the benefits of the research outweigh the perceived 

risks of harm. But many research risks are not reasonably foreseeable or 

cannot be avoided; this is one of the very reasons why research is conducted. 

While the nature of research at times requires the acceptance of unavoidable 

physical and psychological risks, to which society permits subjects to freely 

expose themselves, this fact does not mandate that society must permit 

subjects also to accept avoidable risks before, during, or after research. Among 

the risks that can be avoided is the cost of medical treatment for unavoidable 

injuries. Protecting human subjects from bearing the costs of medical treatment for illness or injury from participation, that is identifiable and 

ameliorable through medical care, comes under the category of secondary 

protection and the duty to assist such subjects arises again.102
MORAL SCIENCE Protecting Participants in Human Subjects Research

60

A just society can protect persons from undue risks. A society that values 

individual freedom and autonomy can consistently determine that some 

arrangements are inherently unfair and unjust. It can also determine that 

some parties are particularly vulnerable and not in the best position to make 

individual determinations that would protect them from undue risk. Society 

makes such a determination in preventing subjects from enrolling in clinical 

trials that are too risky, and charges IRBs with making that determination on 

a routine basis. If research subjects are entitled to such primary protection, 

they should also be extended secondary protection if they are harmed as a 

result of their participation.

The paradigmatic example of this sort of research circumstance is the typical 

Phase I trial of a new but traditional cytotoxic oncologic agent that holds 

promise in animal studies but has not yet been tried in human beings. The 

purpose of such a study is to determine toxicity and tolerability in human 

beings. The subjects enrolling in such trials are typically patients with 

advanced malignancies for which all standard therapeutic options have failed. 

Such studies pose risk and hold very little promise of therapeutic benefit 

for those who volunteer as subjects. The risks are largely unforeseeable and 

unavoidable. These subjects are vulnerable, often desperate, holding out hope 

for individual benefit even though informed that the probability of individual 

benefit is small. Even if an individual’s own motives are not altogether altruistic, the results of such trials nonetheless redound to the common good. Even 

negative trials contribute to our common scientific understanding. To say to 

such persons that they are volunteering for the common good but that they 

must bear full financial responsibility for medical care needed to treat any 

harms that ensue as a direct result of their participation seems grossly unfair.

Nor does the argument for compensation depend on the untenable assumption that research is conducted always and only to benefit the general public. 

The argument instead is that voluntary acceptance of risk by human subjects, 

which advances the interest of the biomedical research enterprise, warrants 

benevolent and just responses. Even when the motives of the investigators and 

sponsors are not solely to advance the common good, the fact remains that 

the research enterprise does redound to the common good regardless of the 

motives of the investigators. Moreover, human subjects are explicitly recruited 

to volunteer for research, even in the for-profit sector, under the assumption 

that their efforts are at least partly intended to advance the common good. 
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61

Still another objection to compensating research subjects might be that 

the presumption that subjects are volunteers is naïve: some research today, 

it may be claimed, comes closer to the market conditions of laborers and 

employers freely contracting, with both primarily motivated by personal 

gain. This is the model of the research subject as “wage-earner,”103 which 

some commentators have explicitly endorsed.104 Adopting the wage-earner 

model full-throttle, however, actually enhances the case for compensation 

on the basis of justice, rather than undermining it. If research subjects are 

employees, and employees in a dangerous job, then how can they be justly 

excluded from a form of worker’s compensation that is available to other 

employees in other industries? Clearly any harm caused to their health by 

virtue of their participation in the research would be “work-related” injuries 

that ought to entitle them to compensation.

Whichever model one chooses for understanding the relationship between 

human research subjects, investigators, and sponsors, justice argues for 

a system that assures that research subjects who suffer medical, dental, or 

psychiatric harms directly caused by their participation in research ought not 

to bear the costs of treatment for these harms all by themselves.

Moral considerations other than justice also argue for treatment or compensation for treatment of research-related injuries. To the extent that human 

subjects research is biomedical and conducted by physicians, nurses, dentists, 

clinical psychologists, and other health care professionals, then professional 

ethical commitments to the principles of beneficence and non-maleficence 

also support a system of compensation for those harmed by research. One 

might argue that clinician-investigators who know that at least some individuals will inevitably be harmed by their human subjects research ought not 

to engage in such research unless they can be assured that there is a system in 

place to care for those harmed by research so that their duties of beneficence 

and non-maleficence can be fulfilled.

Finally, general utility also argues for such a system. Potential human research 

subjects may be more likely to agree to serve if they know they will be taken 

care of in the event that they are harmed as a direct result of their participation. In an era in which the recruitment of adequate numbers of research 

subjects continues to be a major challenge, this could be significant. 
MORAL SCIENCE Protecting Participants in Human Subjects Research

62

Further, if there is a growing commitment toward harmonization of policies 

and recognition of equivalent protections, the fact that federally sponsored 

human subjects research differs substantially in its policy towards compensation for human subjects who are harmed in the course of research could 

prove a significant barrier. Domestically, private sponsors of human subjects 

research have voluntarily committed to assuring such protections to research 

subjects, and internationally, many other countries require this. Harmonization and equivalent protections could be well-served were the federal 

government either to prove that such a system already exists in a rigorous 

(even if inchoate and patchwork) fashion, or to adopt a more formal and 

transparently comprehensive system of compensation. 

The Commission concludes that ethics requires that subjects harmed in the 

course of human subjects research ought not individually bear the costs of 

care required to treat qualified harms resulting directly from that research.105

Such a conclusion does not, however, specify what an optimal system to carry 

out this ethical mandate would look like. Some serious considerations include 

the scope of any possible coverage, the delineation of qualified harms, mechanisms for determination of causation and qualification, relation to the tort 

system, the need for any special public or private insurance, and how the 

current nonsystematic approach to this issue functions in practice. A distinction also needs to be made between compensation for the costs of needed care 

resulting from harms due to participation in morally justifiable research and 

reparations for unethical research.

Reparations for Unethical Research

The foregoing discussion concerns treatment or compensation to treat harms 

sustained as a result of participation in trials that are ethically justified. The 

Commission finds that it is important to distinguish this from possible reparations for unethical and exploitative research.

The above discussion focused on compensation (or restitution) through 

providing medical care or the funds to remunerate participants in human 

subjects research for the direct costs of medical care for injuries that have 

proximately resulted from their participation in research. The Commission 

argues that these costs should not be borne by the subjects themselves. Under 

the presumption that these injuries were the result of ethically acceptable 

research and could not reasonably have been prevented but instead resulted 
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63

directly from the uncertainties associated with the experimental intervention 

(and which justified undertaking the research project in the first place), the 

investigators cannot be held ethically blameworthy for such injuries.

Thus, treatment or compensation/restitution for the costs of treatment, is 

justified by distributive or corrective justice and by duties of beneficence. It 

is also justified by the primary duty of professional caregivers to do no harm. 

For example, someone who enrolls in an ethically approved and conducted 

clinical trial, who suffers from pneumonia caused by the trial drug but who 

lacks health insurance to pay for treatment, therefore could merit treatment 

or compensation for treatment costs. Likewise, someone currently enrolled 

in an ethically designed and ethically conducted U.S.-sponsored trial carried 

out overseas who develops a severe side effect and needs health care but has 

no independent means to obtain treatment, such as insurance for health care, 

could likewise merit treatment or compensation for the costs to treat the 

research-related harm.106

Reparation, by contrast, calls for acknowledgment of wrongdoing and 

contrition, along with actual or symbolic repayments for wrongdoing. The 

Commission uses the term reparation in this context to describe the expression of regret for wrongs done to victims of unethical human subjects 

research. Such individuals need not have been harmed physically or psychologically, and may not even be alive. Likewise, the individual perpetrators of 

the unethical research may no longer be alive to be held directly accountable. 

However, once unethical research has come to light, the institutional sponsors of such unethical research bear some responsibility to make amends 

for past institutional wrongdoing or that of their former agents. As such, a 

formal apology, compensation for any identifiable living individuals harmed 

by such research, or symbolic gestures of contrition such as the establishment 

of charitable foundations or institutions related to the future prevention of 

such harms may also be appropriate in some cases.107

Compensation might be part of reparation. For example, an individual 

who was enrolled in the infamous Public Health Service’s “Tuskegee Study 

of Untreated Syphilis in the Negro Male” (Tuskegee Syphilis Study) from 

1932-1972, and now, still alive, needs treatment for tertiary syphilis, might 

deserve compensation as part of an overall program of reparation.108 Reparation, however, need not include compensation. For example, in 1997, 
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64

President William Jefferson Clinton apologized to the families of those who 

were enrolled in the Tuskegee Syphilis Study, and the United States provided 

funds for the establishment of the Tuskegee University National Center for 

Bioethics as an act of reparation.109 President Obama’s swift apology to the 

people of Guatemala for the U.S. Government’s sponsorship of the 1946-1948 

STD studies was similarly an important act of reparation, or moral repair.

Designing a System of Compensation 

The Commission recommends that the federal government undertake a 

careful assessment to address how best to satisfy the ethical obligation to 

compensate individuals who suffer research-related injuries as a result of 

volunteering in a federally funded study. The nature and extent of injury, 

the type of research in which the injury is occurring, and the costs of injury 

to subjects, investigators, and society have not been systematically studied. 

When the scope and nature of compensation for research-related injuries is 

determined, it will be possible to address adequately the practical questions 

associated with treatment and compensation.

The questions to be addressed in such an assessment include: To what extent 

do established (and emerging) public and private health insurance programs 

contribute to compensating individuals for research-related injuries? What 

types of injuries are compensated? How is it best to establish causal links 

between research protocols and medical problems? How should research 

subjects in foreign countries be compensated? Should there be limits placed 

on the time, amounts, and categories of compensation?

The Commission was informed and advised about the advantages and disadvantages of various means by which the current system offers treatment or 

compensation for treatment for some research subjects. These means include: 

civil tort liability, institutional self-insurance and commercial insurance, 

individual health insurance, government benefit programs like Medicare, and 

direct treatment paid or provided by agencies directly (and as a term and 

condition of a research award). As a general matter, the tort system works 

well for many types of intentional and accidentally caused injuries. Some 

alternatives that selectively pre-empt the tort system, such as the National 

Vaccine Injury Compensation Program (which the Panel proposed as a model 

for consideration), have been established to take into account the particular 
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65

circumstances under which compensation is due.110 The Commission, accordingly, advises of the importance of carefully considering the variation among 

federally sponsored human subjects research in order to determine the 

optimal system for compensation.111

Today, several federal departments and agencies provide treatment or compensation for treatment when research subjects are injured. The Departments of 

Defense and Veterans Affairs both provide care for research-related injuries. 

The Department of Veterans Affairs’ regulations require that it provides care 

for all research-related injuries, even in those studies considered minimal 

risk.112 The Department of Defense provides health care services from military treatment facilities for subjects injured in the course of research, but no 

compensation (i.e., payment) for injuries.113 The NIH Clinical Center provides 

short-term care but no long-term care or financial compensation for injury.114

These programs essentially “self-insure” for treatment or costs of treatment.115

Personal insurance or government programs such as Medicare also pay the 

costs for treatment for some injuries arising from research.116 (See Table 3.2.)

Table 3.2 U.S. Treatment/Compensation for Treatment Methods

INSTITUTION TYPE OF POLICY

NIH Clinical Center Provides short-term care during the trial, but no long term care or financial 

compensation.

NASA Provides compensation for injuries arising from intramural research through its 

worker’s compensation system; directs principal investigators for extramural research 

to provide compensation through “insurance, worker’s compensation, or the like.” 

Medicare Medicare covers “reasonable and necessary items and services used to diagnose and 

treat complications arising from participation in all clinical trials.” Medicare serves as 

a secondary payer for these costs. 

University of Washington Self-insurance: no-fault program that provides up to $10,000 for out-of-pocket costs 

and write-off of care provided at University of Washington Medicine.

Private clinical trial 

insurance providers 

(e.g.: RJ Ahmann Company)

Covers a number of different types of liability, including: general liability, latent injury 

liability, and incidental medical malpractice liability.

Sources: National Institutes of Health. (2006). Sheet 6—Guidelines for Writing Informed Consent Documents, retrieved 

from http://ohsr.od.nih.gov/info/sheet6.html (accessed November 23, 2011); NASA. (2004). NASA Procedural 

Requirement 7100.1 – Protection of Human Research Subjects, secs. 9.1.4, 11.6, and Appendix B, Revalidated July 

7, 2008; Centers for Medicare and Medicaid Services. Medicare Coverage—Clinical Trials: Final National Coverage 

Decision. Retrieved from: https://www.cms.gov/clinicalTrialPolicies/Downloads/finalnationalcoverage.pdf; Centers 

for Medicare and Medicaid Services. (2010, May 26). Clinical trials and liability insurance (including self-insurance), 

no-fault insurance, and workers’ compensation. Retrieved from: http://www.cms.gov/MandatoryInsRep/Downloads/

AlertClinicalTrailsNGHP.pdf; Moe, K.E., Director and Assistant Vice Provost For Research, University of Washington. 

(2011). University of Washington Human Subjects Assistance Program. Presentation to the PCSBI, November 17. 

Retrieved from http://bioethics.gov/cms/meeting-seven; RJ Ahmann Company. (n.d.). What You Need to Know About 

Insuring Your Clinical Trials. Retrieved from http://www.rja.com/clinical-trial-insurance-liability-minneapolis-mn/.
MORAL SCIENCE Protecting Participants in Human Subjects Research

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Some academic centers that receive federal funds for research with human 

subjects also provide treatment and cover medical costs for research-related 

injuries. These are established through institutional self-insurance and 

commercial insurance schemes. For example, since 1972 the University of 

Washington health care system has administered a university-wide system of 

treatment and compensation for treatment of research-related injuries. This 

system, self-funded through the institution’s operating budget, provides up to 

$10,000 for out-of-pocket expenses and for treatment at University of Washington facilities.117

Sometimes component programs of federal departments and agencies 

require awardees to provide for treatment of research-related injuries or carry 

insurance to cover treatment costs. The National Aeronautics and Space 

Administration directs principal investigators seeking funding for research 

conducted outside of its facilities to provide compensation for injury “by 

means of insurance, worker’s compensation, or the like” and may fail to 

approve research because such a provision is not included in a protocol.118 The 

National Human Environmental Effects Research Laboratory (funded by the 

Environmental Protection Agency) promises to provide up to $5000 to cover 

costs for treatment of research-related injuries.119 Costs for insurance are paid 

by the government as part of research awards.120

FDA guidance directs research investigators as part of their duties to protect 

the rights, safety, and welfare of subjects and to provide both “reasonable 

medical care...for medical problems arising during participation in [a] trial 

that are, or could be, related to the study intervention,” and “reasonable 

access to needed medical care, either by the investigator or by another identified, qualified individual (e.g., when the investigator is unavailable, or when 

specialized care is needed).”121

Most industry-based clinical research sponsors carry insurance to compensate 

individuals injured in research trials. In discussion and written comments 

to the Commission, representatives from PhRMA and the Biotechnology 

Industry Organization, trade groups representing pharmaceutical and 

biotechnology companies respectively, explained that good business practice, 

as well as legal obligations, require their member companies to carry insurance to cover the costs of research-related injuries.122
FURTHER ANALYSIS AND RECOMMENDATIONS III

67

No authoritative sources exist by which to determine whether all individuals 

for whom compensation for research-related injuries is warranted are both 

adequately and quickly compensated for their medical care. Consequently, 

in order to fulfill the President’s aim of ensuring that all human subjects 

are adequately protected in federally supported research, the Commission 

finds that further study into any shortfalls of the existing system and the 

utility of alternative systems of compensation is necessary. The Commission recognizes that it would be unwise to alter or supplant the country’s 

current approach to compensation for research-related injuries without first 

gauging the nature and scope of harms that remain unaddressed. A careful 

and timely study, however, will enable the government to address the practical questions associated with whether or how to develop a better overall 

system or a supplementary set of approaches to the current system that optimally assures compensation.

For example, the government may decide that a study of alternative 

approaches to compensation should take into account considerations such as 

deterrence, loss spreading, and internalization of risk.123 These considerations 

raise questions about where the burden of compensation is best placed. For 

example, how much (if any) of the burden of compensation should be placed 

on research sponsors to create and sustain incentives for ensuring the highest 

possible level of protection of human research subjects consistently with 

preserving the incentives and capacity for research? Are researchers themselves in the best position to internalize some or all of those costs, that is, 

to price some or all of the costs of compensation—including insurance and 

administrative costs—into their research programs? Because researchers play 

an essential role in advancing biomedical research and discovery, an effective 

compensation system should not unnecessarily burden them or impede their 

ability to undertake novel research programs that advance scientific progress 

and discovery. The Commission is recommending a study to help the government determine what constitutes a manageable cost of compensation and who 

should bear these costs.

Alternative, complementary, or supplementary models to the status quo 

that merit consideration range from case-by-case compensation by insured 

or self-insured research sponsors and institutions, to a more centralized 

governmental system of compensation for research subjects (analogous to 
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68

the current National Vaccine Injury Compensation program), to the creation 

of wholly new institutions or system-wide requirements (that specify what 

constitutes adequate standards of compensation). Some compensation 

programs preempt state tort remedies, while others do not. Statutes such as 

the National Childhood Vaccine Injury Act and the legislation that established the Workers Compensation fund preempt state tort remedies.124 The 

study that the Commission recommends should explicitly consider whether 

federal preemption of state tort remedies is necessary or desirable for any 

new (or revised) compensation model, whose goal is to ensure coverage of all 

qualified research-related injuries. The study should also consider whether 

a single and predictable model of compensation is more or less burdensome 

to researchers and secure for subjects than a piecemeal approach, the overarching ethical goal being to ensure that research participants who are injured 

by research—whether by foreseeable or wholly unexpected injuries—receive 

adequate medical care for their injuries.

The Commission’s deliberations found that National Childhood Vaccine 

Injury Act model or other strict liability models may not be appropriate for 

human subjects research, and could be difficult to apply in a wide range of 

research settings. Many retrospective federal systems of compensation—such 

as the September 11th Victim Compensation Fund—are not appropriate 

models: they have been responses to disastrous events that called for a coordinated unique national response.125 The National Childhood Vaccine Injury 

Act, which is a prospective model of compensation, was also a response to 

concerns of vaccine manufacturers about the risk-benefit ratio of producing 

vaccines in light of the substantial civil liability they were then facing and 

could continue to face.126

The Commission thinks it important to recognize the limits of these models 

in the course of considering the optimal means (which are likely to be plural, 

rather than singular) of ensuring appropriate compensation for researchrelated harms. A study should take into account the differences between 

the conditions of being recruited and volunteering for the kind of experimental research that may later result in harm and being a subject who uses 

an approved, manufactured product that later results in harm. Similarly, 

designing a system of retrospective compensation for harms sustained by 
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69

many people during a single involuntary event, for example the September 

11th Victim Compensation Fund, differs from designing a prospective 

program for compensating people harmed by having volunteered to assist the 

common good. 

Comparing possible clinical compensation schemes to vaccine compensation schemes may provide useful insight. For example, clinical research often 

occurs in environments where research subjects are asked to take medicines 

or other interventions outside of the clinical setting. Vaccines are administered in a clinical setting where one can be certain that the vaccine was 

administered, when it was given, and to what individual. A relatively small 

number of signature adverse events arise from vaccines, and when one of 

those adverse events occurs, the vaccine more likely than not caused the 

injury. The side effects that arise from clinical research trials may not be as 

limited or as predictable. There are a large number of research protocols and 

a wide range of medical interventions, each of which may produce a variety 

of adverse events.

Any system of compensation needs to define a standard or standards for when 

an injury would become a treatable or compensable event.127 Such standards 

could turn on the nature or the severity of the injury, and whether side effects, 

including those that follow an effective therapeutic intervention—such as 

anticipated or unanticipated side effects—should constitute a compensable 

event. Moreover, a standard or standards should articulate what is needed to 

show that the research caused the injury.

Recommendation 3: Treating and Compensating for Research-Related Injury

Because subjects harmed in the course of human research should not individually bear the costs of care required to treat harms resulting directly 

from that research, the federal government, through the Office of Science 

and Technology Policy or the Department of Health and Human Services, 

should move expeditiously to study the issue of research-related injuries 

to determine if there is a need for a national system of compensation or 

treatment for research-related injuries. If so, the Department of Health 

and Human Services, as the primary funder of biomedical research, should 

conduct a pilot study to evaluate possible program mechanisms.
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Recommendation 4: Treating and Compensating for Research-Related Injury 

Follow Up

The Commission recognizes that previous presidentially appointed bioethics 

commissions and other duly appointed advisory bodies have made similar 

recommendations regarding compensation or treatment for research-related 

injuries; yet no clear response by the federal government has been issued. 

Therefore, the federal government, through the Office of Science and Technology Policy or the Department of Health and Human Services, should 

publicly release reasons for changing or maintaining the status quo.

3. Creating a Culture of Responsibility: Human Research Protections as 

Professional Standards

The most fundamental obligation of research involving human subjects is 

to protect the rights and welfare of individuals who offer themselves for the 

good of both science and society and, in some cases, for the hope of personal 

benefit. As persons, research subjects possess an inviolability that rules out 

treating them as mere means to the ends of others, including others who 

may be suffering from a disease or in need of medical care. But, in helping to 

advance research, human subjects sometimes place themselves in a position of 

informational asymmetry, where they must rely on the expertise and wisdom 

of researchers, reviewers, funding institutions, and, at times, their own physicians to ensure that a research study in which they enroll is designed and 

deployed with their rights and welfare in mind. 

Respecting the interests of subjects is often more complicated than it might 

appear. Despite comprehensive (and what some describe as overly burdensome) regulations, a number of competing interests may make it difficult for 

researchers to recognize or exercise objective ethical judgment in practice.128

For example, in clinical trial design researchers may struggle with trade-offs 

between high quality science—which offers the possibility of developing 

future means to prevent, treat, or reverse disease—and the immediate best 

interests of subjects.129 So too, financial and nonfinancial conflicts of interest, 

or the appearance of these conflicts, have received increasing attention in the 

last decade. When manifest, they can lead to harm and unethical treatment 

and jeopardize participant and public trust in the research system.130
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As early as 1966, physician Henry Beecher introduced the idea that the best 

protection for subjects is the enlightened and ethically sensitive conscience of 

the investigator. In addition to the requirement of informed consent, Beecher 

described “the presence of an intelligent, informed, conscientious, compassionate, responsible investigator” as offering the best protection for research 

subjects.131 In his view, a system of external regulation was unnecessary 

because properly educated and virtuous clinician-researchers would know to 

do the right thing based on their keenly honed internal compasses. In spite of 

Beecher’s preference for an enlightened conscience over the sometimes-heavy 

hand of regulation, a number of highly publicized research scandals, some 

identified by Beecher himself, in the last century demonstrated the need for 

external regulation.132

While a separate source of oversight in the form of regulations and enforcement is an indispensable complement to a culture of virtuous investigators, 

the optimal system for human subjects protection is a dual system of external 

regulatory checks and internal embodiment of appropriate professional norms, 

such as respect for persons. In developing such a system, care must be taken 

to ensure that external safeguards are not so onerous as to dampen the desire 

and commitment to develop an internal ethical identity. Ideally, researchers 

should view the norms of research ethics as a legitimate and necessary part 

of their mission as scientists. In this regard, the principle of regulatory parsimony, which the Commission developed more fully its report, New Directions: 

The Ethics of Synthetic Biology and Emerging Technologies, must be acknowledged in concert with regulatory necessity.133 Only by balancing compulsory 

and voluntary checks can a lively personal sense of professional ethics develop.

Ethics in a professional practice should be seen as strict standards that are 

simultaneously self-imposed by the relevant profession and expected by the 

society it serves, similar to any other practice standards or standards of care. 

Rather than a matter of only regulatory compliance, professional ethics are 

an integral part of what it means to be a profession in the public service. 

Professional standards correlate with ethical duties toward subjects and with 

the privileges of office and cannot be waived or ignored for expediency, 

convenience, perceived interests of the many at the expense of the few, or 

the allegedly superior demands of science. Researchers must view compliance 

as a shared duty stemming not only, or even primarily, from regulation, but 
MORAL SCIENCE Protecting Participants in Human Subjects Research

72

instead from their collective professional responsibility to the subjects of their 

research and the public that supports their research mission.

Today, many sources exist to describe useful professional norms. For example, 

PhRMA, of which many of the major pharmaceutical research and biotechnology companies are members, has released a code entitled PhRMA’s 

Principles on Conduct of Clinical Trials and Communication of Clinical Trial 

Results.

134 The goal of this code is to uniformly assist member companies in 

the ethical conduct of clinical trials. Many member companies have also 

adopted their own code of conduct to promote professional standards.135

In order for researchers to understand, internalize, and embrace critical 

ethical requirements for research with human subjects, these obligations need 

to be seen as strict professional standards that accompany and justify the 

privileges of office. Throughout their professional training, researchers should 

learn and adopt these standards as a condition of acceptance into the professional discipline entrusted to undertake research with fellow human beings.136

Funding agencies and research institutions should commit to creative, flexible, and innovative educational approaches, such as case studies combined 

with rigorous ethical analysis, undergraduate and graduate level mentoring, 

and even senior researcher “coaching,” both in science and in ethical treatment of subjects by master researchers.137 A shift towards teamwork and away 

from individual blame in research institutions may also facilitate the discussions 

“Education regarding research 

and research participation 

is critically important for 

all stakeholders including 

institutional leadership, 

IRBs, investigators and 

research staff, policymakers, 

sponsors, research subjects 

and the general public.”

Letter from Barbara E. Bierer, Chair, 

Secretary’s Advisory Committee 

on Human Research Protections 

(SACHRP), to Kathleen Sebelius, 

Secretary of Health and Human 

Services. (August 5, 2011). Retrieved 

from http://www.hhs.gov/ohrp/

sachrp/commsec/commentspcsbi.

pdf.pdf.

that will promote a culture of responsibility.138

The aim should be to both intellectually 

engage researchers and instill a sense of ethical 

responsibility as an integral part of professionalism. Success in achieving this aim could 

avert the resentment of learning “modules” 

that many well-motivated researchers currently 

view as an insulting waste of time.139

As important as it is to teach rigorously 

the ethics of protecting human subjects to 

professionals, it is at least as important to 

teach the increasingly important and wellresearched subject of bioethics—including 

research ethics—at all levels, including the 
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73

undergraduate level. Bioethics is a universally important subject, fully consonant with a liberal arts and sciences education, and as such it should not be 

taught first, let alone only, at the professional-school level. Human subjects 

are drawn from the general citizenry, not only or mainly from the ranks of 

medical professionals and researchers. Citizens will benefit from knowing their 

rights as human subjects, and accountability will be better served if citizens are 

educated to hold accountable the researchers, IRBs, funders, and others in the 

research enterprise. The Commission recommends the development and expansion of rigorous courses in bioethics and human subjects research tailored to 

students at different levels of education. A proven effective method of teaching 

ethics is to combine scholarship on the subject with case studies—such as the 

STD experiments in Guatemala—to engage students in deliberations about 

what they would and should do in these and analogous circumstances.140 Like 

the Panel, the Commission strongly recommends that ethics education play an 

increasingly central role in advancing research ethics.141

The Commission recommends that specific training in research ethics be 

focused not simply on the system of regulations but also on the ethical principles animating them. Professional societies, universities, and accrediting 

organizations need to promote standards not as legal burdens relegated to 

compliance departments but as expectations enforced by the community of 

scientists as well as oversight officials. Regulators should explicate the ethical 

rationale for requirements reflecting these standards in order to foster a strong 

sense of professional responsibility. 

Accordingly, the Commission offers the following recommendations: 

Recommendation 5: Make the Ethical Underpinnings of Regulations 

More Explicit

To promote a better understanding of the context and rationale for applicable 

regulatory requirements, the Department of Health and Human Services or 

the Office of Science and Technology Policy should ensure that the ethical 

underpinnings of regulations are made explicit. This goal is also instrumental 

to the current effort to enhance protections while reducing burden through 

reform of the Common Rule and related Food and Drug Administration regulations. (See Promoting Current Federal Reform Efforts below.) Following the 

principle of regulatory parsimony, regulatory provisions should be rationalized 

so that fundamental, core ethical standards are clearly articulated.
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Recommendation 6: Amend the Common Rule to Address Investigator 

Responsibilities

The Common Rule should be revised to include a section directly addressing 

the responsibilities of investigators. Doing so would bring it into harmony 

with the Food and Drug Administration regulations for clinical research 

and international standards that make the obligations of individual 

researchers more explicit, and contribute to building a stronger culture of 

responsibility among investigators. 

Recommendation 7: Expand Ethics Discourse and Education

To ensure the ethical design and conduct of human subjects research, 

universities, professional societies, licensing bodies, and journals should 

adopt more effective ways of integrating a lively understanding of personal 

responsibility into professional research practice. Rigorous courses in 

bioethics and human subjects research at the undergraduate as well as 

graduate and professional levels should be developed and expanded to 

include ongoing engagement and case reviews for investigators at all levels 

of experience.

4. Respecting Equivalent Protections

Clinical research has increasingly become a global enterprise. The number 

of privately sponsored clinical trials being conducted around the world has 

grown dramatically, as has the number of multinational and collaborative 

research projects sponsored or supported by the federal government.142 Most, 

but not all, human subjects research supported by the federal government is 

subject to the same regulatory requirements—either the Common Rule and/

or FDA regulations—regardless of where it is conducted. Research collaborators and partners in other countries funded or supported by Common Rule 

agencies must file an assurance that they will comply with Common Rule 

requirements. At the same time, the regulations delineated in the Common 

Rule have long permitted U.S. departments and agencies supporting or 

conducting research to recognize and accept procedures from foreign countries that may differ from those delineated in U.S. regulations as long as they 

provide “protections that are at least equivalent” to those in the Common 

Rule. Yet U.S. departments and agencies have rarely, if ever, exercised the 
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75

authority to accept any foreign country’s procedures as equivalent. In some 

cases U.S. procedural requirements even conflict with individual country 

requirements, and controversy remains regarding the processes or criteria to 

determine equivalence of protections.143

The Common Rule applies to “research conducted, supported, or otherwise 

subject to regulation by the Federal Government outside the United States”;144

and states that the policy “does not affect any foreign laws or regulations 

which may otherwise be applicable and which provide additional protections 

to human subjects of research.”145 The Common Rule also gives authority to 

a department or agency to approve the substitution of procedures utilized by 

foreign countries that differ from those delineated in the Common Rule if 

the department or agency determines that those procedures “afford protections that are at least equivalent” to those in the Common Rule.146 Since the 

time when U.S. federal regulations and the Common Rule were first written, 

many countries have developed their own regulations and laws regarding the 

protection of human research subjects and some have even adopted laws or 

guidelines based on the International Conference on Harmonization Good 

Clinical Practice Guidelines or on the Common Rule itself. In some cases, 

other countries’ laws and regulations are even more extensive than those 

found in the Common Rule.

One way of demonstrating respect for foreign collaborators and partners in 

research, a goal articulated by the Panel, is to develop and employ a process 

“Recognizing equivalent 

protections would minimize 

the problem of U.S. insistence 

on procedural standards that 

may not offer more effective 

ethical safeguards for human 

subjects, or that may preclude 

research in countries where it 

could improve public health.”

The International Research Panel of the 

PCSBI (2011, September). Research 

Across Borders: Proceedings of the 

International Research Panel of the 

PCSBI. Washington, D.C.: PCSBI, p. 9.

for determining when protections delineated in foreign laws and regulations are 

equivalent to U.S. regulations.147 In addition, as noted by SACHRP, allowing 

recognition of equivalent protections could 

reduce the burden on U.S. IRBs without 

reducing, and perhaps even enhancing, 

human subject protections.148 Furthermore, 

this process will facilitate ongoing internat ion a l d ia log ue be t we en U. S. a nd 

international bodies, the importance of 

which the Panel also highlighted in its 

recommendations to the Commission.149
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The issue of whether and how to recognize “equivalent protections” offered 

by non-U.S. collaborators and researchers is not new. NBAC recommended 

in 2001 that the U.S. government “identify a set of procedural criteria and a 

process for determining whether the human participants protection system 

of a host country or a particular host country institution has achieved all 

the substantive ethical protections.”150 Also in 2001, the U.S. Office of the 

Inspector General, citing the increasing volume of international collaborative 

research, recommended that OHRP address how to “better assess whether 

other nations’ laws and practices afford equivalent protections to those that 

apply to human subjects participating in clinical trials in the U.S.”151

Two years later, in 2003, an internal HHS working group made several useful 

recommendations and proposed a framework for developing criteria to determine equivalent protections. The first step in its framework is to articulate 

the specific protections embodied in the Common Rule. The working group 

noted that the Common Rule is primarily procedural and does not articulate 

either the ethical basis for its required procedures or the actual protections 

that its procedures provide. The working group identified seven protections 

it thought the Common Rule does afford, including that it: 1) establishes 

expectations of ethical conduct and due diligence in review and performance 

of research within the institution; 2) ensures adequate independence and 

authority of the IRB/Research Ethics Committee; 3) protects from biased and 

arbitrary decisions in research ethics review; 4) ensures sufficient quality and 

comprehensiveness of research ethics review; 5) ensures review and oversight 

are commensurate with risk and the vulnerability of the study population; 6) 

protects from unnecessary or unjustified risk throughout the study; and 7) 

ensures voluntary participation after adequate disclosure of study information. 

Importantly, the working group observed that “the protections embodied in 

the [Common Rule]...generally represent broad and complex aims, each of 

which might be satisfied in a variety of different ways through a variety of 

procedures.”152

Despite this 2003 HHS report and a 2005 Federal Register notice calling for 

public comment on the proposals,153 OHRP has not finalized or employed 

criteria or process for determining equivalent protections. In fact, a 2006 

Federal Register Notice on Interpretation of Assurance Requirements reiterated 
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77

the requirement that all who receive U.S. federal research funds, including 

those outside the United States, follow the exact procedures delineated in the 

Common Rule.154 United Kingdom government officials in 2007 formally 

requested a determination from HHS regarding the equivalence of protections afforded by United Kingdom procedures for human subjects protection, 

and other countries are also interested in gaining recognition of “equivalent 

protections” for their system.155 Yet to date OHRP has not formally recognized any country’s protections as equivalent. 

The federal government does recognize the adequacy of some foreign human 

subjects protections standards as part of its program to license new drugs 

and devices for use in the United States. FDA regulations for clinical investigations supporting new drug or device marketing applications specify 

requirements, similar to those found in the Common Rule, for informed 

consent, IRB review, and other standards to protect human subjects. FDA 

accepts data from foreign studies that comply with certain international 

standards for human subjects protection (such as those that abide by “good 

clinical practice,” the Declaration of Helsinki, or certain host country regulations), rather than with FDA’s exact regulatory procedures.156 Thus, the 

development of a system for recognizing equivalent protections under the 

Common Rule can draw from the experiences of FDA.157

Given this history, and the prominent way that recognizing equivalent protections demonstrates respect for communities (a safeguard discussed further 

below), the Commission recommends:

Recommendation 8: Respect Equivalent Protections

The federal government, through the Office for Human Research Protections, should adopt or revise the 2003 Health and Human Services 

Equivalent Protections Working Group’s articulation of the protections 

afforded by the specific procedural requirements of the Common Rule. It 

should use these requirements to develop a process for evaluating requests 

from foreign governments and other non-U.S. institutions to determine 

if their laws, regulations, and procedures can be recognized as providing 

equivalent protections to research subjects. 
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5. Promoting Community Engagement

The Panel directed the Commission’s attention to the value of community 

engagement and the demonstration of respect for cultural differences that are 

compatible with the ethical conduct of human subjects research. The term 

“community engagement” means many things. It includes but is not limited 

to:  community based participatory research, which is a term of art for studies 

designed to engage communities and researchers as equal partners, studying 

health issues in community settings, using communities or community entities as a unit of study or unit of randomization, engaging communities in 

defining research priorities, engaging communities in shaping a particular 

study to their needs, as well as community “consent,” community advisory 

boards, community outreach for recruitment, and community monitoring of 

study progress.158

In the United States, community advisory boards include, for example, the 

Framingham Heart Study Ethics Advisory Board, which enables participants 

and community members from the town of Framingham, Massachusetts, to 

advise researchers conducting the decades old NIH-funded epidemiological 

study on proposed research design and methods.159 Community advisory 

boards are required for each research site in the HIV Vaccine Trials Network, 

a group of NIH-funded researchers working across the globe to find a vaccine 

for HIV led by researchers at the University of Washington.160 And recent 

guidance from the Centers for Disease Control and Prevention, the Health 

Resources and Services Administration, and NIH contains comprehensive 

discussion of how public health researchers and others can engage community 

partners in their work.161

The values underlying calls for community engagement are applicable to 

research conducted both domestically and abroad. Effective community 

engagement provides an additional layer of safeguard by providing the 

community with opportunities to more thoroughly weigh and accept or reject 

the risks and benefits of research activities, discover possible implications of 

research that might have unintended consequences to host communities, and 

independently evaluate the effectiveness of research protections.162 Interactive and ongoing dialogue between the communities engaged in research and 

the research team allows for the integration of community norms, beliefs, 

customs, and cultural sensitivities with the research activities. 
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Community engagement should provide ongoing two-way communication 

between community partners with research funders, teams, and national 

regulatory authorities. As discussed by the Panel, such communication serves 

as a local mechanism of accountability for the researchers and can also create 

a mutual sense of partnership that facilitates realizing the goals of the research 

project. In the event that communication reveals conflicting ethical values 

among partners regarding how to conduct the research, the partners can 

engage in a mutually acceptable process of conflict resolution. 

Over the past few decades, there has been a growing international consensus 

on the principles underlying the ethical conduct of biomedical research. 

Although there remains some variation in their content, internationally 

recognized documents converge on several themes that are generally compatible with the idea of accommodating community norms in human subjects 

research, but only to the extent that those norms do not conflict with the 

principles that are essential to protecting individual subjects and otherwise making human subjects research ethical.163 To this point, the Panel 

recognized, however, that “researchers cannot—and should not—accept 

uncritically everything that a community recommends or requests.”164 For 

example, several international documents admit the possibility that it may be 

both necessary and desirable for researchers to use a mechanism other than a 

written document to obtain individual informed consent in some communities, but they rule out substitution of the collective consent of a community, 

community leader, or a spouse for the consent of any adult who is capable of 

giving his or her individual consent.165

Valuing community engagement during human subjects research around the 

globe is a relatively recent phenomenon. This is seen especially in international guidance documents. Although the topic is tangentially discussed in 

the Council for International Organizations of Medical Sciences (CIOMS) 

2002 International Ethical Guidelines for Biomedical Research Involving Human 

Subjects, CIOMS focuses its guidelines on responsiveness to the health needs 

and priorities of host countries, and the ethical acceptability of the study 

for the host country requiring “a thorough understanding of a community’s 

customs and traditions.”166 The Declaration of Helsinki also includes provisions 

regarding the health needs and priorities of host countries, but no mention is 

explicitly made of community engagement standards.167
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Still, these principles are beginning to 

emerge with more force in transnational 

documents. The 2007 Joint United Nations 

Programme on HIV/AIDS UNAIDS and 

World Health Organization (WHO) guidance document, Ethical Considerations in 

Biomedical HIV Preventative Trials, and 

the companion UNAIDS/AVAC Good 

Participatory Practice Guidelines168 explicitly 

include community engagement principles. 

Nor has the lack of international guidance 

stopped the incorporation of community engagement principles in a piecemeal 

fashion by individual entities. For example, 

in addition to U.S. examples cited above, 

research ethics bodies in Australia and 

Canada have created documents outlining 

the importance of community engagement to ethical human subjects research, 

specifically focusing on aboriginal and other minority communities.169

Despite a dearth of explicit formulations for community engagement by international organizations, proposals for a common framework for community 

engagement in biomedical research have appeared in the literature over the 

past decade.170 Still, there remains a lack of sufficiently detailed and extensive 

empirical information on the successful implementation of community 

engagement strategies for biomedical research and even less information for 

research in other spheres.171

In 2011, UNAIDS and AVAC published a new edition of their guidelines 

to provide trial funders, sponsors, and researchers with systematic guidance 

on how to effectively engage with stakeholders on the design and conduct of 

biomedical HIV prevention trials.172 This publication provides a roadmap to 

implement community engagement based on principles of respect, mutual 

understanding, integrity, transparency, accountability, and community stakeholder autonomy. 

“Why does this matter? Well, it 

matters not just for the conduct 

of a single trial. It matters for 

the ways trials can take place 

in a long-term process with 

communities over many different 

types of research endeavors. 

It really comes down to ‘how 

do we create the trust and 

respect for the research 

process that researchers 

and clinicians have, but 

communities often don’t 

for lack of their input and 

engagement throughout 

the process.’”

Mitchell Warren, Executive Director, 

AVAC: Global Advocacy for HIV 

Prevention. (2011). Presentation to 

PCSBI, August 30. Retrieved from http://

bioethics.gov/cms/node/319.
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The UNAIDS/AVAC Good Participatory Practice Guidelines call for execution of community engagement through a set of activities, including use of 

community advisory boards, the development of community communication 

processes, discussion of post-trial access to beneficial research products or 

outcomes, and access to care for discovered medical illnesses. (See Figure 3.1.) 

These guidelines, however, were developed specifically for HIV prevention 

research rather than for human subjects research more generally. They should 

be prospectively evaluated for applicability to human subjects research beyond 

HIV prevention. 

Layers of Biomedical HIV Prevention Trial Stakeholders

Global Stakeholders

National Stakeholders

Broader Stakeholders

Community Stakeholders

Trial Participant

CBOs • participant’s family • friends • schools • colleagues • peers • trial site staff

ol cal rel gi oi us institutions • traditional leaders • community advisory boards • local health service prov di ers

NGOs • local policymakers • local media • medical professionals

national NGOs • parliamentarians • ministries of health • media • regulatory bodies • ethical review committees • funders • sponsors

international NGOs • trial sponsors and networks • WHO/UN AIDS • international organizations • international foundations • funders

Examples

Source: UNAIDS/AVAC. (2011). Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials. UNAIDS: 

Geneva. Retrieved from http://www.avac.org/gpp (accessed November 21, 2011).

Figure 3.1
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To further develop operational guidelines for the protection and ethical treatment of human subjects through the means of community engagement, the 

Commission recommends that:

Recommendation 9: Promote Community Engagement

The federal government, through the Office for Human Research Protections and authorized research funders, should support further evaluation 

and specification of the Joint United Nations Programme on HIV/AIDS and 

the AVAC Good Participatory Practice Guidelines with the aim of providing 

a standardized framework for those community engagement practices that 

would further the protection and ethical treatment of human subjects in all 

areas of research. Research should be conducted to prospectively evaluate the 

effectiveness of this framework and strengthen it after it is developed.

6. Justifying Site Selection

Careful selection of research sites is important for two sets of ethical considerations. First, the ethical criteria for how subjects must be treated narrows the 

selection of sites to those that allow for the protection and ethical treatment 

of subjects. Second, site selection implicates other important considerations 

of fairness and justice. With regard to the ethical treatment of subjects, as the 

Belmont Report recognizes, “selection of research subjects needs to be scrutinized in order to determine whether some classes are being systematically 

selected because of their easy availability, their compromised position, or their 

manipulability, rather than for reasons directly related to the problem being 

studied.”173 With regard to the second set of ethical considerations, the report 

continued, “whenever research supported by public funds leads to the development of therapeutic devices and procedures, justice demands that these not 

provide advantages only to those who can afford them and that such research 

should not unduly involve persons from groups unlikely to be the beneficiaries 

of subsequent applications of research.”174

Certain domestic and international settings present particular concern about 

possible exploitation of human subjects. Alan Wertheimer has observed that 

explicit concern for “exploitation” in research is pronounced in cases involving 

vulnerable populations and studies in low- and middle-income countries.175

U.S. history contains examples of the failure to treat human subjects ethically in no small part because subjects were chosen for their vulnerability 
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83

rather than for the sake of potentially benefiting them or members of their 

community. One prominent example where the site and the subjects selected 

for research signaled a willingness to exploit vulnerable and poor members of 

a minority population for the purported benefit of others was the Tuskegee 

Syphilis Study. In retrospect, some defenders of this research argued that 

subjects received some benefits through annual medical check-ups and minor 

health treatments otherwise unavailable to them, but indubitably these “benefits,” standing alone, were far outweighed by the total neglect to treat the 

syphilis176 and by the pervasive deceptions that defined this study.177

The STD experiments funded by the Public Health Service in Guatemala 

during the 1940s are another prominent example of how sites may be chosen 

for the vulnerability of available subjects, in this case, prisoners, psychiatric 

patients, sex workers, and conscripted soldiers. The U.S. researchers exploited 

the easy availability, compromised position, and manipulability of these 

Guatemalan subjects, and they benefited 

from the willingness of some Guatemalan 

officials and researchers to cooperate with 

and support the experiments. 

“The Guatemala research 

targeted some of the most 

vulnerable groups in any society 

(prisoners, conscripted soldiers, 

institutionalized psychiatric 

patients, and children), and 

also was conducted in an 

underdeveloped country with 

pervasive social inequalities that 

exacerbated their vulnerabilities. 

Such populations are given 

special protections in modern 

society because of their limited 

abilities to protect their own 

interests...In the Guatemala 

experiments the most vulnerable 

populations appear to have been 

targeted specifically because 

of their inability to protect 

themselves or to have others 

represent their interests.” 

PCSBI. (2011, September). “Ethically 

Impossible” STD Research in Guatemala 

from 1946-1948. Washington, D.C.: PCSBI.

Decisions about research site selection 

involve consideration of many factors related 

to scientific opportunities and possibilities, as well as ethical considerations. When 

conducted according to the highest ethical 

and scientific standards, human subjects 

research across national borders can serve 

important scientific ends and yield life-saving 

and life-enhancing benefits for participating 

subjects and the communities in which they 

live.178 An expanding number of publicly and 

privately funded research projects are multinational, involving numerous collaborating 

researchers and institutions, and are taking 

place in hundreds of sites in multiple countries; therefore, attention to the ethics of site 

selection is more important than ever. Some 

reasons for site selection are worrisome—for 
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example, choosing a site because of the availability of vulnerable, treatment 

naïve subjects, lower regulatory burdens, and limited plans for making the 

experimental treatment available to its population. Similarly, choosing domestic 

or international sites where systems for protecting human subjects are not in 

place, are insufficient or inexperienced, or allow for the conduct of research that 

would not pass scrutiny elsewhere elevate concerns about exploitation and the 

possibility of unethical treatment. 

The Commission strongly affirms that the same ethical principles that apply 

to domestic research should also be applicable on the international front. We 

should assess globally based research, including research in developing countries, by the same high ethical standards that we apply to domestic research 

and research in developed countries. Three longstanding and widely accepted 

principles relevant to the ethics of human subjects research are 1) do not treat 

people as mere means to the ends of others by doing research without their 

consent, 2) treat all individuals fairly and with respect, and 3) do not subject 

people to harm or the risk of harm, even with their consent, unless the risk is 

reasonable and there is a proportionate humanitarian benefit to be obtained.179

These three fundamental principles do not change depending on the location 

of a study, the type of research, or the funding source. Nor are these principles 

of ethical research exclusively applicable to human subjects research in medicine or health. Because the most prominent examples of past abuses are found 

in biomedical research, and scholars’ attention to site selection focuses on this 

area, the Commission directs this discussion of site selection to health-related 

research. However, the principled position staked out here can and should be 

extended beyond biomedical research.

The primary goal of biomedical research is the production of generalizable 

knowledge that will elucidate information about human health and illness 

and facilitate the design and application of preventive, diagnostic, or therapeutic interventions to meet the needs of future patients. Individual subjects 

of the research themselves may benefit by receiving medical attention in a 

study, and communities may benefit through the development of their health 

care infrastructures or if the fruits borne of a study are made available to 

them. Myriad risks comprise the burdens of research, including risks to physical health, mental health, privacy, confidentiality, social status, and economic 

productivity. Research that places a significant burden on subjects and/or 
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85

their communities can constitute ethically impermissible exploitation unless 

the risks are offset by an adequate level of benefit, including type and quantity 

of benefit. Research in low-income countries raises particular concern that 

communities with limited access to needed health care will accept the risks of 

research but derive benefits that are disproportionately low in relation to the 

risks involved—or that they will be enrolled in research to answer questions 

that will only benefit those in richer countries.180

These concerns lead to the Commission’s second set of reasons for calling 

attention to the issue of site selection: minimizing exploitation and promoting 

fairness and justice. One proposed strategy for minimizing the potential of 

exploitation when research is done in domestic or international low-income 

communities is to ensure that the proposed study is responsive to the health 

needs and priorities of the local community. Several international codes of 

ethics incorporate this broad criterion. For example, the CIOMS’ 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects

provide that, when conducting research in resource-limited areas, sponsors and 

investigators are responsible for responding to the “health needs and the priorities” of the subject population as well as ensuring that they can benefit from 

the research.181 When research involves vulnerable or disadvantaged groups, 

the Declaration of Helsinki similarly holds that the justifiability of the research 

hinges on its responsiveness to local health needs and priorities.182

Generally speaking, responding to the health needs and offering benefits to a 

population may be an appropriate way to minimize the possibility of exploitation and promote fairness. The Universal Declaration on Bioethics and Human 

Rights (UDBHR), adopted by the General Conference of UNESCO in 2005, 

also emphasizes the importance of responsiveness to host communities, stating 

that “transnational health research should be responsive to the needs of host 

countries, and the importance of research contributing to the alleviation of 

urgent global health problems should be recognized” (Article 21). NBAC 

recommended that a developing country should only be selected as a research 

site when the proposed study responds to the host country’s health needs 

(Recommendation 1.3).183 Yet the concept of responsiveness is highly abstract 

and needs further specification before it can be operationalized; further, many 

more specific operational definitions that can be gleaned from the literature on 

responsiveness have been subject to strong counterarguments.184 Prevalence of 
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disease, for example, may be important in evaluating responsiveness, though 

it surely is insufficient as an indicator of burden of disease. Less common and 

even less burdensome diseases may be important health needs amenable to 

answers through good research. Understanding responsiveness as requiring 

research to respond to health priorities may provide a disincentive to research 

other important health problems. In this way, it could readily, albeit unintentionally, let the perfect—approving only ethically sound research that serves 

the highest health priorities of a poor community or country—become the 

enemy of the good—approving all ethically sound research that serves some 

health need.185

How to first effectively define and then implement the criterion of responsiveness remains an unsettled issue among scholars and practitioners.186 Who has 

the capacity and legitimate authority to define what research is adequately 

responsive to a community, and how best to prioritize that community’s 

health needs, are two critically important questions that remain in need of 

further careful examination. Precisely how any developed criteria of responsiveness to health needs apply to both publicly and privately funded research 

is yet a third question that cries out for further consideration. What is clear, 

however, with regard to the ethics of site selection is that all human subjects 

research should be performed in sites where the researchers are both willing 

and able to conduct their research in a way that protects human subjects from 

avoidable harm and unethical treatment. Enforcing this ethical mandate will 

also go a long way toward minimizing, even if not eliminating, the threat of 

unjustifiable exploitation. 

Another important consideration in site selection, which enables ethical 

research to be conducted in under-served communities both domestically 

and internationally, embraces the values of well-functioning collaborations 

and well-established infrastructure for conducting ethical research and 

high-quality science, as well as assurance that the site has or can obtain the 

necessary infrastructure, resources, and oversight structure to ensure that 

research subjects will be treated ethically. With ample capacity to conduct 

research, robust oversight and enforcement mechanisms, and a strong ethical 

framework for human subjects protection comes the expectation in international research that the host country is well positioned to participate in 

scientifically valid research and adequately protect subjects in that research. 
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87

In considering the adequacy of infrastructure and ethical oversight across 

national lines, many questions arise, including: Are potential research subjects 

available and can they be fairly selected from the local population? Does the 

design of the trial match the capabilities of the possible site, in terms of facilities, staffing, and other assets to execute the study or can capacity be built to 

enable the conduct of the study without unreasonable diversion of limited 

resources? Is the site selection compatible with ensuring that protections for 

human subjects are equivalent or superior to those in the country originating 

the research, including mechanisms for evaluating and ensuring an acceptable 

balance of risks and benefits for the subjects, independent review of the trial 

design, informed consent, and fair compensation for research-related injury?

Careful examination of site selection is critical to ensuring that subjects in 

research are protected from avoidable harm or unethical treatment. The duty 

to ensure ethical site selection lies first with the researchers who conduct 

research. Generally, they are closest to the ground and able to judge conditions in the host community and country. Sponsors and funders too retain 

responsibility and should not initiate or approve research in locations where 

ethical site selection cannot be assured. Funders and sponsors may consider 

relying on determinations of duly constituted and independent IRBs and their 

equivalent bodies internationally. For example, a “just in time” certification, 

of the sort some agencies currently employ for institutional certification of 

IRB review could be developed to address the adequacy of site selection as 

well.187 But funders and sponsors should not allow IRB or ethics committee 

representations to override or replace their own responsibility. In many cases, 

IRBs will have little influence over site selection, as study site decisions may be 

made far in advance of IRB review. Each actor in the funding, conduct, and 

oversight of human subjects research can, and should, exercise their discretion 

and authority to consider the ethics of site selection.

Recommendation 10: Ensure Capacity to Protect Human Subjects

Funders of research should determine that researchers and the sites that 

they propose to select for their research have the capacity—or can achieve 

the capacity contemporaneously with the conduct of the research—to 

support protection of all human subjects. 
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In addition to the absolute requirement to choose research sites where human 

subjects can and will be protected and treated ethically (and the implied 

prohibition on not choosing sites that cannot ensure this protection), other 

important considerations in site selection include how responsive to the health 

needs of a larger community a research project must be once human subjects 

are assured protection and ethical treatment. This issue raises complex 

questions of distributive justice in a non-ideal world where incentives to 

do publicly or privately funded human subjects research are often not well 

aligned with the locations that have the greatest needs for such research.188

Recognizing that some of these questions remain unsettled and knowing 

that they will benefit from further research and analysis, the Commission 

concludes that the government should lead an effort to focus on them and 

develop more concrete guidance for researchers, funders, and IRBs.

Recommendation 11: Evaluate Responsiveness to Local Needs as a Condition 

for Ethical Site Selection

The federal government, through the Office for Human Research 

Protections and federal funding agencies, should develop and evaluate 

justifications and operational criteria for ethical site selection, taking into 

consideration the extent to which site selection can and should respond to 

the needs of a broader community or communities. The Office for Human 

Reseach Protections should produce, and other agencies should consider 

developing, guidance for investigators.

7. Ensuring Ethical Study Design 

The scientific design of human subjects research, especially clinical research, 

becomes a subject of ethical concern when rigorous design elements (e.g., 

placebo controls, assignment to treatment arms, randomization, and blinding) 

raise the question of whether scientific advance is being placed ahead of 

human subjects protection.189 For example, when subjects are assigned to a 

particular treatment or control group to receive an intervention known or 

strongly suspected to be inferior to other treatments available in other arms 

of the study or existing outside the study altogether, critics raise doubts about 

whether the rights or well-being of these subjects are compromised. Several 

controversial cases in the last 20 years have polarized the medical community 

into sharply opposed camps on this issue.190
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DIFFERING VIEWS

“Placebo Orthodoxy”

Comparing an experimental drug 

to a placebo ensures scientific 

validity and accurate measurements 

of drug efficacy. Thus, it is ethical 

to use placebos as controls, 

even when alternative, approved 

therapies exist.

“Active-Control Orthodoxy”

Placebos are never ethical if an 

alternative, approved therapy exists, 

and the best available alternative 

must be used as the control.

“Middle Ground”

A placebo-controlled trial can 

sometimes be considered ethical 

if certain methodological and 

ethical standards are met. If these 

standards cannot be met, then 

the use of placebos in a clinical 

trial is unethical.

Emanuel, E.J., and F.G. Miller. (2001). The 

Ethics of Placebo-Controlled Trials—A Middle 

Ground. New England Journal of Medicine

345(12), 915-919.

Among the most discussed of these cases 

was a series of trials undertaken in the 

1990s to gauge the safety and effectiveness of a short course of A ZT (an 

antiretroviral drug) in preventing the 

perinatal infection of children with HIV. 

The active arm receiving A ZT was 

compared to a control arm receiving a 

placebo (i.e., an inactive agent). The 

proponents of these trials contended that 

a placebo control was necessary in order 

to develop efficiently a scientifically validated, safe, and effective prophylaxis 

against HIV infection in children and 

noted that the use of the known effective 

method was not feasible in the test locations.191 Critics argued strenuously that 

other designs (e.g., involving active 

controls and equivalency studies) were 

both scientifically reliable and ethically 

mandatory. They argued that those who 

designed, approved, and carried out such 

placebo-controlled trials were responsible 

for hundreds of preventable deaths.192

Similar debates arise when human 

subjects are engaged in controversial 

procedures, for example “washout periods” that involve withdrawal of current 

medications for such serious conditions as depression or psychosis in order to 

avoid confusion with the effects of new drugs.193 Also controversial, “challenge 

studies” involve intentional exposure to pharmacologic agents or circumstances to induce disease or symptoms for further study.194

Regarding the ethics of placebo-controlled clinical trials, differences remain 

and disagreements continue, but consensus is emerging.195 In particular, 

Ezekiel Emanuel and Franklin Miller have proposed a “middle ground” for 

ethical clinical research,196 largely supported by this report. Many ethicists 

and ethical codes have concluded that placebo-controlled trials can be ethical, 
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provided certain criteria are met, including (but not limited to) these conditions: that withholding a proven treatment will cause only minimal harm to 

the subjects; that using an established intervention would not yield reliable 

results; and that the study is responsive to the needs of the host country. 

NBAC and CIOMS, for example, suggest giving the control arm of the trial 

the “worldwide best” treatment available as a default rule, with exceptions 

permitting a lower standard based on factors such as necessity, potential harm, 

affordability, and relevance of the research question to the host community.197

The current Declaration of Helsinki, however, specifies that new interventions 

should be tested against the “best current proven” intervention, restricting the 

permissibility of placebo-controlled trials.198

In highlighting this emerging consensus, the Commission begins with the 

maxim that in research “good ethics begins with good science.”199 Every clinical trial starts either within a context of controversy, wherein investigators 

disagree as to the relative merits of, for example, new drug A and old drug 

B; or a context of uncertainty wherein investigators do not know which drug 

is better. Clinical trials are designed specifically to help resolve such controversy and uncertainty. If they are poorly designed and lack scientific rigor, 

studies cannot contribute to the resolution of such questions and the medical 

community will potentially ignore the results. Scientifically flawed studies 

have no social value, and if they have no social value there is no benefit to 

exposing subjects to any risk through participation. Ethical research must 

therefore be based upon a firm foundation of good (i.e., rigorous) science.

The unfettered demand for scientific and methodological rigor still can raise 

ethical concerns about whether subjects are being treated with sufficient deference to their status as moral agents worthy of equal concern and respect, 

persons should never be reduced to “mere means” for the benefit of others. 

For example, designing a placebo-controlled trial for a life-threatening illness 

such as HIV/AIDS might be thought to violate “clinical equipoise,”200 which 

would ethically necessitate a genuine controversy or uncertainty among the 

expert medical community about the net benefit of each intervention being 

compared (including a placebo/no treatment at all). With convincing evidence 

and consensus within the medical community that, for example, drug A is 

better than drug B, then a design giving some human subjects drug A and 

others drug B, under the principle of clinical equipoise, would be unethical.201
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Different commentators describe the nature of this perceived ethical flaw in 

different ways.202 Some argue that researchers who knowingly withhold the 

best-proven treatment from subjects violate their “therapeutic obligation,” 

which is grounded in the physician-patient relationship.203 Others, owing at 

least in part to the fact that much human subjects research is not conducted 

by physicians (e.g., social scientists), locate the source of this duty elsewhere, 

such as in the subjects’ status as equal and inviolable moral agents.204 For 

example, critics of the perinatal AZT trials argued that a placebo-controlled 

trial exposed pregnant women and their children to an excessive risk of harm 

or death.205 They charged too that when citizens of rich and prosperous 

countries receive the best-proven treatments, but people in lower and middle 

income nations receive “short course” treatments or placebos in clinical trials, 

this creates a morally pernicious “double standard.”206 This concern becomes 

even more problematic when the research is not “responsive” to the health 

needs of the host country.207

Towards a Middle Ground on Study Design

In the last section, the Commission discussed some ethical considerations that 

go into selecting research sites which must be considered in designing studies 

as well.208 Furthermore, the Commission offers the following specific criteria 

for evaluating methods and risks of study design.

(1) Treatment Standards

As a matter of biological effectiveness and safety, treatments proven best for 

populations in the developed world are not always best for populations in 

the developing world. For example, genetic differences between population 

groups may make the best-proven treatment generally unsuitable for some, 

and variability in underlying health status may make some populations more 

vulnerable to side effects than others. Also, differences in the medical and 

logistical infrastructure of a developing host country may render the effective deployment of a best-proven intervention difficult or even impossible in 

practice. For example, the best possible comparator drug for the control arm 

might require refrigeration unavailable in a country lacking reliable electrical 

power, or the drug might need to be delivered intravenously in a country 

without the medical resources necessary for such delivery.209
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The standard of care available to subjects in a control group need not be 

the best-proven, especially when there is uncertainty about whether such a 

standard would be best for the local population under study. Thus, in spite 

of the rhetorical appeal of the “no double standards” objection, it has become 

increasingly evident that trial designs offering human subjects an intervention 

that falls short of the best-proven approach can pass moral muster without 

relying on moral relativism (which would underlie an objectionable double 

standard), provided that certain rigorous conditions are met. 

First, any application of clinical equipoise must carefully and scrupulously 

take into account local context. This does not, however, mean that the appropriate measure of the standard of care for determining ethical study design 

should be the level of access currently afforded to the study population. The 

so-called “local de facto” standard permits the deployment of placebos in 

control groups whenever the local “standard of care” is in fact no care at 

all.210 But to call “no treatment” due to impoverished health care budgets 

the local “standard of care” is to distort the meaning of standard of care as a 

guiding medical norm.211

Recognizing that meaningful debate on this issue continues, the Commission 

finds that the optimal standard lies between the “best-proven” and “local de 

facto” interpretations: for example, a standard of care that would or should 

be optimal for a certain population; given their health needs and the level of 

available medical and logistical infrastructure, cultural practices, genetics, 

and economic capacity to sustain treatment into the future.

The Commission recognizes too that a rigid insistence upon a best-proven 

standard could have the unintended consequence of precluding meaningful 

research and achievable health reforms in relatively poor host countries. As 

Zulfiquer Bhutta, a well-known pediatrics expert, has noted, major progress in 

treating newborns with suspected sepsis has recently been achieved in India, 

but such progress would have been unlikely had the best-proven standard 

of care, intravenous antibiotics, been ethically required of the researchers. 

Instead, the researchers were able to compare an intervention against the local

standard of care and conclude that the intervention was both accessible to the 

population and more effective than the local standard.212
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(2) Methodological Constraints

Second, the scientific design of a trial must be adequate to yield usable 

results. Absent this, results will not be credible and human subjects would 

have been exposed to risk unnecessarily. However, there is disagreement 

about the level of confidence required for sound science and adequate trial 

design. Some insist that a placebo-controlled, double-blinded, randomized trial is the gold standard for testing new interventions or treatments. 

Others regard insistence upon such a design as counter-productive, and an 

inappropriate dismissal of potential trial results that may be somewhat less 

conclusive but obtainable without the potentially unacceptable ethical costs 

of a placebo-controlled trial.213

The Commission does not need to take sides in this debate to agree that 

the results of clinical trials must be amenable to definitive interpretation. 

As Robert Temple and Susan Ellenberg, clinical trial experts from the FDA, 

have pointed out, it is highly desirable that the meaning and significance of 

studies be contained within the study itself.214 Ideally, one should not have to 

rely on results outside of a trial to interpret a single trial’s results. In placebocontrolled trials, this additional outside evidence is not required because the 

study itself can show that the intervention being tested is better than no intervention. But in some designs, for example “equivalency” designs (trying to 

show that the intervention being studied is at least as good as an intervention 

already being employed), previous studies demonstrating the effectiveness of 

the intervention already being employed in a similar population are required. 

Temple and Ellenberg describe this as the problem of “assay sensitivity.” 

Absent a placebo control or independent evidence taken from outside the 

trial that the intervention already being employed is effective, researchers will 

be unable to interpret the study’s results.215 This sort of design is appealing, 

however, because it does not subject trial subjects to the medical risks of a 

placebo control. It is, however, logistically and economically more challenging 

because it requires the recruitment of more subjects for trials of longer duration and greater expense.216

Similar worries concern equivalency trials wherein the new drug is expected

to perform less well than the established standard, as in the perinatal AZT 

trials, but there are compelling policy reasons to find an alternative to the 
MORAL SCIENCE Protecting Participants in Human Subjects Research

94

standard. In the perinatal AZT trials, the short course AZT was expected to 

be somewhat less effective than the “076 protocol” (the best-proven standard 

at the time), but also much less expensive and therefore more affordable in 

developing countries.217 Indeed, the goal of the short course trials was to find 

an affordable and implementable regimen to prevent perinatal HIV transmission in developing countries, not to find the best such intervention worldwide. 

In such a context, designing a trial that would compare the established 076 

protocol against short course regimens without a placebo control would have 

suffered from the same problem of assay sensitivity described above. If the new 

drug regimen had shown to be somewhat less effective than the best-proven 

standard, what would the researchers have learned? The intuitive answer 

is that the researchers would have learned that the new drug protocol was 

comparable to the best-proven standard and thus possibly a good candidate 

for public health funding; but without a comparator to judge how effective, 

decisions about adopting the intervention would be uninformed.

(3) Risk Minimization

Third, although study designs that do not use the best-proven therapy for a 

given condition in a given population can sometimes be justified for methodological reasons, such designs nonetheless can place subjects at risk of harm. 

An additional ethical constraint requires researchers to minimize the amount 

of harm to which subjects might be exposed.

Subjects receiving less than the optimal standard of care should not be 

subjected to substantially increased risk of mortality, serious morbidity, or 

severe discomfort. An example of a problematic study falling into the latter 

category was a placebo-controlled study of the anti-emetic drug, Ondansetron, which was being introduced as a remedy for nausea and vomiting 

associated with cancer chemotherapy.218 At the time of the study, there were 

a number of approved anti-emetic drugs that were effective and had been 

shown in previous trials to be superior to placebo, yet subjects in the placebo 

arm of the Ondansetron study experienced extreme vomiting following their 

chemotherapy. Such a study was arguably unethical because subjects in the 

control arm experienced serious side effects, even if it had methodological 

advantages over an active control design comparing Ondansetron against 

another approved anti-emetic.
FURTHER ANALYSIS AND RECOMMENDATIONS III

95

Trials of psychiatric drugs in which some subjects receive less than the standard of care provide examples of increased risks of mortality and serious 

morbidity. Because depressed patients may be at risk for suicide, denying them 

effective treatment within a control group could place them at increased risk 

of death. Likewise, patients who are abruptly weaned from an anti-psychotic 

regimen during the washout phase of a new anti-psychotic trial might be 

placed at increased risk of new and possibly exacerbated psychotic episodes.

IRBs should scrutinize the elements of study design as a distinct focus of 

their review. Study designs that pose risks to subjects by departing from the 

current standard of care in control groups should be explicitly justified in the 

research protocol, and the anticipated additional risks to subjects should be 

proportional to the expected degree of individual or social benefit. Subjects 

who might be exposed to additional risks should be carefully examined for 

special vulnerabilities before trials begin, and their clinical course should be 

carefully monitored throughout the duration of the trial so that they can be 

taken off study, if necessary, to address emerging threats to their lives, health, 

or comfort.

The Commission finds, then, that some research designs in which control arm 

subjects receive less than the best-proven treatment can be ethically justified 

if the above criteria are all applied and clearly met. Importantly, contrary to 

some of the critics of the short-course perinatal HIV trials, the Commission 

has concluded that good ethical reasons can be found for permitting some 

of these trials and that one need not resort to any intellectually or morally 

questionable theory of ethical relativism in order to do so.

Recommendation 12: Ensure Ethical Study Design for Control Trials

When assessing how to reconcile the requirements of rigorous study design 

with the interests of research subjects, a nuanced approach is recommended that permits subjects to receive a placebo or an active agent that 

otherwise might not represent the “best-proven” approach when the site 

selected is ethically justifiable and the following conditions are met: 

a) the “best-proven” intervention is not known to be the best for a particular population due to local infrastructural, behavioral, genetic, or other 

relevant circumstances; and b) the scientific rationale and the ethical justification for the study design have undergone careful review to ensure all of 
MORAL SCIENCE Protecting Participants in Human Subjects Research

96

the following: i) use of placebo or other comparators is of limited duration; 

ii) subjects are carefully monitored; iii) rescue measures are in place should 

serious symptoms develop; and iv) there are established withdrawal criteria 

in place for subjects who experience adverse events. 

8. Promoting Current Reform Efforts

Federal efforts to reform the current human subjects research protections 

system are already underway. In July 2011, the HHS Secretary and the OSTP 

Director published an ANPRM entitled Human Subjects Research Protections: 

Enhancing Protections for Research Subjects and Reducing Burden, Delay, and 

Ambiguity for Investigators, soliciting comments on possible revisions to the 

Common Rule and other provisions of the current system of protection for 

human research. Specifically, the ANPRM asks for public comment on “how 

current regulations for protecting human subjects who participate in research 

might be modernized and revised to be more effective.”219

The ANPRM includes many thoughtful proposed revisions to human 

subjects protections. The Commission generally supports the objectives of the 

ANPRM and the goal of better protecting human subjects while reducing 

burden, delay, and ambiguity for investigators.220 Several sections in the 

proposed reforms specifically are of interest to the Commission, and several 

topics are of particular relevance to the Commission’s charge from the President. Moreover several of the recommendations made above, such as the 

recommendation to develop specific regulatory directions for investigators, 

could be included as part of the current reform effort and the Commission 

urges the government to consider doing so.

Ensuring Risk-Based Protections

Currently under the Common Rule, review of human research studies is 

undertaken by a convened IRB for all studies involving more than minimal 

risk to subjects or more than minor changes from previously reviewed 

work.221 Studies involving no more than minimal risk or minor changes 

in previously approved research may be reviewed by a single IRB member 

through “expedited review” if the category of research appears on a published 

list of activities eligible for expedited review.222 Additionally, six categories 

of studies are “exempt” from IRB review altogether.223 OHRP guidance 
FURTHER ANALYSIS AND RECOMMENDATIONS III

97

recommends—but does not require—

that review of exempt studies be done by 

someone other than the investigator in 

order to confirm that the study has been 

appropriately classified as exempt.224

“The current regulations 

governing human subjects 

research were developed 

years ago when research was 

predominantly conducted at 

universities, colleges, and 

medical institutions, and each 

study generally took place at 

only a single site. Although 

the regulations have been 

amended over the years, they 

have not kept pace with the 

evolving human research 

enterprise, the proliferation 

of multi-site clinical trials 

and observational studies, 

the expansion of health 

services research, research 

in the social and behavioral 

sciences, and research involving 

databases, the Internet, and 

biological specimen repositories, 

and the use of advanced 

technologies, such as genomics. 

Revisions to the current human 

subjects regulations are being 

considered because OSTP and 

HHS believe these changes 

would strengthen protections 

for research subjects.”

Subjects Research Protections: 

Enhancing Protections for Research 

Subjects and Reducing Burden, Delay, 

and Ambiguity for Investigators, 76 Fed. 

Reg. 44,512 (July 26, 2011).

The current system has been criticized as 

“not adequately calibrating the review 

process to the risk of research.”225 Furthermore, many IRBs review minimal risk 

studies at convened meetings out of concerns 

for regulatory and institutional liability, 

rather than through expedited review. 

Accordingly, many social and behavioral 

scientists have argued that their research is 

over-regulated in the current system.226

In its first report, New Directions: The 

Ethics of Synthetic Biology and Emerging 

Technologies, the Commission elucidated 

the principle of intellectual freedom and 

responsibility, and its corollary principle 

of regulatory parsimony. These principles 

reflect the fact that scientific discoveries 

and advancements depend on the intellectual freedom of researchers coupled with 

the responsibility of individuals and institutions to use their creative potential in 

morally responsible ways. Regulatory oversight must be limited to that which is truly 

necessary to ensure justice, fairness, security, and safety while pursuing the public 

good. Consequently, the Commission supports reforming research review 

to appropriately calibrate the evaluation with the level of risk to human 

subjects. This reform also would accomplish the vital goal of allowing 

IRBs and institutions to focus their efforts and limited resources on studies 

involving higher risk. The Commission endorses the ANPRM in its goal of 
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98

eliminating continuing review for certain lower-risk studies and to regularly 

update the list of research categories or activities that may undergo expedited review. 

Also elucidated in New Directions, the principle of public beneficence 

encourages maximizing public benefits and minimizing public harm, and 

the principle of responsible stewardship reflects a shared obligation among 

members of the domestic and global communities to act in ways that demonstrate concern for those who are not in a position to represent their own 

interests. Both of these principles applied to human subjects research demand 

a thorough and more complete review of studies deemed to be greater than 

minimal risk to subjects. These principles also encourage a lesser regulatory 

burden on investigators conducting minimal risk research so that important 

work is not delayed through unnecessary regulatory processes and so that 

IRBs can focus their resources on reviewing higher risk protocols. 

For exempt research, expanded and called “excused” in the ANPRM, the 

Commission agrees with the proposal to adopt a registration system as a 

reasonable strategy to track this research, provided that institutions responsible for this research retain the flexibility to require a higher standard of 

independent review of exempt status. Just as with determinations concerning 

independent review of minimal risk research, which the Common Rule 

currently allows to be made by expedited review,227 decisions about exemption 

should be made without full IRB review so long as they are not limited solely 

to the discretion of the individual investigator. Data from projects, such as the 

“Exempt Wizard” currently being studied through the Federal Demonstration 

Partnership, will be useful in evaluating how registration protects subjects of 

exempt research.228

Streamlining IRB Review of Multi-Site Studies

While the current Common Rule regulations do not require IRB review by 

each institution involved in a multi-site study, in many—if not most—cases 

individual institutions229 and IRBs independently review research protocol 

and informed consent documents.230 This sometimes results in hundreds of 

individual reviews and, if the protocol is revised, multiple re-reviews at each 

site. This process is time consuming, logistically burdensome, and often duplicative for both the IRBs as well as the investigators, and there is little evidence 
FURTHER ANALYSIS AND RECOMMENDATIONS III

99

that multiple reviews improve human subjects protections. In addition, IRBs 

do not always reach the same conclusions on important issues. 

The Commission supports reducing time consuming duplicative IRB review 

where duplication serves no purpose to improve protections. Reducing 

unnecessary burdens to research is encouraged by the principles of intellectual freedom and responsibility and regulatory parsimony. Multiple reviews 

can unnecessarily delay important research, result in costly and problematic 

alterations to protocols and study designs, cause burdensome requirements to 

clear minor changes, and in some cases even jeopardize the integrity of the 

science. In addition, reducing burdens and barriers to effective IRB review 

helps speed research discoveries from the bench to the bedside and thereby 

effectuates the principle of public beneficence by improving public health 

and overall societal well-being. Although the ideal of a single IRB of record 

for such studies should be pursued as the ANPRM describes, the Commission believes it should not be mandated. In some situations, institutions and 

investigators have unresolved concerns about liability, regulatory enforcement, 

and implementation of a single Institutional Review Board of record, which 

should not be ignored.

Improving Informed Consent

The Common Rule requires legally effective informed consent from all 

research subjects in studies subject to the Rule, unless that requirement is 

waived by an IRB in accordance with pre-specified regulatory criteria.231

However, the ANPRM notes that “consent forms may frequently fail to 

include some of the most important pieces of information that a person would 

need in order to make an ‘enlightened decision’ (to quote the Nuremberg Code) 

to enroll in a research study. Rather than presenting the information in a way 

that is most helpful to prospective subjects—such as explaining why someone 

might want to choose not to enroll—the forms often function as sales documents, instead of as genuine aids to good decision-making.”232

The principle of responsible stewardship requires citizens and their representatives to think and act collectively for the common good. The government, 

in collaboration with institutions and investigators, should refocus on the 

importance of the process of informed consent lest the procedures, ostensibly 

derived from ethical principles, serve to obscure the values they were intended 
MORAL SCIENCE Protecting Participants in Human Subjects Research

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to implement. If both the government and institutions take a step back and 

concentrate on that which ensures actual informed consent, they may start to 

unravel the impediments to the process overall. That said, much like streamlining IRB review, regulating informed consent procedures must be done with 

great care and should be informed by data concerning what is and is not 

effective in achieving such consent. The Commission encourages the development of flexible guidelines and procedures for obtaining informed consent, 

especially in social and behavioral sciences as well as in epidemiology, public 

health, and quality improvement research since the issues in these kinds of 

research are often different than those in more classic pharmaceutical trials.

Clarifying and Harmonizing Regulatory Requirements and Agency Guidance

Although the Common Rule is widely seen as a single, comprehensive standard for protecting human subjects in research across the federal government, 

departments and agencies vary in their implementation of it233 and some 

funders of research have not adopted it at all.234 The ANPRM acknowledges 

the importance of improving the consistency of guidance on the protections 

of human subjects across federal departments and agencies.235

The Panel recommended to the Commission in its Research Across Borders

report that “continued efforts to harmonize and guide interpretation of rules 

should be made a priority over creating new rules.”236 The Panel acknowledged 

that new rules may be needed to harmonize existing U.S. rules, but any additions should be clear, sound, and streamlined. Furthermore, harmonization 

would add clarity to the U.S. oversight process, particularly for international 

clinical trials.

The principle of responsible stewardship espouses the clarity, coordination, 

and accountability of regulations across the government called for both by the 

ANRPM and the Panel, and reinforces the compelling case for consistency, 

to the extent feasible, among all federal departments and agencies supporting 

human subjects research. 

Data Collection to Enhance Adverse Event Reporting

The ANPRM also discusses the standardized collection of safety data, specifically adverse events, and suggests changes to improve the real-time, prompt 

collection of such data.237 These proposed changes include using a streamlined 
FURTHER ANALYSIS AND RECOMMENDATIONS III

101

set of data elements to satisfy most agency reporting requirements and implementing a prototype of a web-based, federal-wide portal, already in use by 

several agencies, to which institutions can submit safety data.238

This concept of centralized human subjects research data collection is also 

reflected in one of the Panel’s recommendations to the Commission, further 

discussed in Improving Accountability above, enumerating that “[t]o enhance 

transparency and accountability, governments should consider requiring all 

greater than minimal risk research to be registered and results reported.”239

The Commission recognizes that different agencies have different systems, 

but efforts should be made to report some common data elements in a 

unified system.

In sum, the ANPRM is an encouraging and important step forward in 

ensuring that human subjects in federally sponsored research are protected 

from harm and unethical treatment. Many of the ethical principles the 

Commission has previously articulated find reflection in the current 

proposals. The Commission expressly endorses several of the specific proposals 

contained in the ANPRM.

Recommendation 13: Promoting Current Federal Reform Efforts

The Commission supports the federal government’s proposed reforms to:

a) Restructure research oversight to appropriately calibrate the level and 

intensity of the review activities with the level of risk to human subjects;

b) Eliminate continuing review for certain lower-risk studies and regularly 

update the list of research categories that may undergo expedited review;

c) Reduce unnecessary, duplicative, or redundant institutional review board 

review in multi-site studies. Regardless of the process used to review and 

approve studies, institutions should retain responsibility for ensuring that 

human subjects are protected at their location as protection of human 

subjects includes much more than institutional review board review. 

The use of a single institutional review board of record should be made 

the regulatory default unless institutions or investigators have sufficient 

justification to act otherwise;
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d) Make available standardized consent form templates with clear language 

understandable to subjects;

e) Harmonize the Common Rule and existing regulations of the Food and 

Drug Administration, and require that all federal agencies conducting 

human subjects research adopt human subjects regulations that are 

consistent with the ethical requirements of the Common Rule; and

f) Work toward developing an interoperable or compatible data collection 

system for adverse event reporting across the federal government. 

9. Following Up

The Commission recognizes that many of these recommendations have been 

made previously by presidentially appointed bioethics commissions and other 

duly appointed government advisory bodies over the past two decades, yet it 

found no clear response by the federal government to many of these recommendations. A primary example concerns compensation for research-related 

injuries, which was recommended by President Clinton’s Advisory Committee 

on Human Radiation Experiments in 1995. Writing only six years later, in 

Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries, NBAC again called for the “adequate care and compensation to 

participants for injuries directly sustained during research.” Other commissions have more modestly recommended an investigation of the need for 

compensation of human subjects for injury in research trials.240

Recommendation 14: Responding to Recommendations

The Commission recommends that the Office of Science and Technology 

Policy or another appropriate entity or entities within the government 

respond with changes to the status quo or, if no changes are proposed, 

reasons for maintaining the status quo with regard to the recommendations below. Possible departments or agencies to lead the efforts include the 

Department of Health and Human Services, the Office for Human Research 

Protections, and the National Institutes of Health, as well as other funders 

and regulators. 
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103

Table 3.3 Recommendation Follow-Up Summary

RECOMMENDATION 

NUMBER†

SUMMARY OFFICE

1 Increase accountability through online access to basic 

human subjects research data.

OHRP/all departments and 

agencies that support human 

subjects research

2 Support the development of systematic approaches to 

assess the effectiveness of human subjects protections 

and expand support for research related to ethical and 

social consideration of human subjects protection.

OHRP/all departments and 

agencies that support human 

subjects research

3 Study research-related injuries to determine if there 

is a need for a national system of compensation or 

treatment for research-related injuries because subjects 

harmed in the course of human research should not 

individually bear the costs of care required to treat 

harms resulting directly from that research.

OSTP/HHS

4 Publicly release reasons for changing or maintaining 

the status quo regarding compensation or treatment for 

research-related injuries.

OSTP/HHS

5 Explicate the ethical underpinnings for human subjects 

protection requirements. 

HHS/OSTP

6 Add responsibilities of investigators to the Common Rule. HHS/OSTP

8 Adopt or revise the 2003 Department of Health and 

Human Services Equivalent Protections Working 

Group’s analysis and develop a process for evaluating 

requests from foreign governments and other non-U.S. 

institutions for determinations of equivalent protections.

OHRP

9 Support further evaluation of the UNAIDS/AVAC 

Guidelines to provide a standardized framework for 

community engagement practices across research fields.

OHRP

11 Support research to develop and evaluate justifications 

and operational criteria for ethical site selection.

OHRP/all departments and 

agencies that support human 

subjects research

13 Develop proposed regulations to reform the current 

Common Rule. 

OSTP/OHRP

14 Follow up. OSTP/other appropriate entity

† Listed here are recommendations directed to the federal government only.

A response need not be unduly lengthy or provided by a single department, 

agency, or division. The Commission knows that analyzing and implementing (or not) the recommendations contained herein may involve work 

with multiple agencies across the government, and may also involve public 

engagement and legal processes, such as rulemaking or statutory change. 
MORAL SCIENCE Protecting Participants in Human Subjects Research

104

The Commission is asking that the public be informed whether the federal 

government intends to move forward, and if so in what way, with any or all 

of these recommendations.

The Commission’s point, simply put, is to assist all members of society to 

understand the response of those entrusted with policymaking on its behalf 

to these specific recommendations. Repeatedly during its review, Commission members, guest speakers, and members of the public asked “what will 

the next ‘Guatemala’ be?” For many, this question related to concern about 

what future generations will see as “ethically impossible” in our own practices. While it is difficult to know what future generations will think, it 

is clear that they will be aided in their assessment by clear articulation of 

what this generation, through its authorized policymakers, thinks and, most 

importantly, how it acts.
ENDNOTES
MORAL SCIENCE Protecting Participants in Human Subjects Research

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1 Exemptions to the individual informed consent requirements permit surrogate consent of 

children and adults who cannot consent, automation of processes in emergency settings, and 

notification to or exemption from informed consent requirements for very low risk research.

2 Memorandum from President Barack Obama to Dr. Amy Gutmann, Chair, Presidential 

Commission for the Study of Bioethical Issues (PCSBI). (November 24, 2010). Retrieved 

from http://bioethics.gov/cms/sites/default/files/news/Human-Subjects-Protection-Letterfrom-President-Obama-11.24.10.pdf.

3 PCSBI. (2011, September). “Ethically Impossible” STD Research in Guatemala from 1946-

1948. Washington, DC: PCSBI.

4 The President expressly charged the Commission to engage with international experts. 

Memorandum from President Barack Obama, op cit. Retrieved from http://bioethics.

gov/cms/sites/default/files/news/Human-Subjects-Protection-Letter-from-PresidentObama-11.24.10.pdf. (“In fulfilling this charge, the Commission should seek the insights 

and perspective of international experts . . . .”). 

5 In a world of unlimited resources one could devote more funds and personnel to create 

myriad systemic checks on research with human subjects. Abuses or adverse events tied to 

human error, no matter how infrequent they may be, would surely be reduced, and those 

tied to design could also diminish. 

6 See also The International Research Panel of the PCSBI (2011, September). Research Across 

Borders: Proceedings of the International Research Panel of the Presidential Commission for the 

Study of Bioethical Issues. Washington, DC: PCSBI, p. 4.

7 Advisory Committee on Human Radiation Experiments (ACHRE). (1995). Final Report 

of the Advisory Committee on Human Radiation Experiments. New York: Oxford University 

Press; National Bioethics Advisory Commission (NBAC). (2001). Ethical and Policy Issues 

in International Research: Clinical Trials in Developing Countries. Bethesda, MD: NBAC; 

National Commission for the Protection of Human Subjects of Biomedical and Behavioral 

Research. (1976). Research Involving Prisoners (DHEW Publication No. (OS) 46-131). 

Washington, DC: Department of Health, Education, and Welfare (DHEW); President’s 

Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral 

Research. (1982). Compensating for Research Injuries. Washington, DC: DHEW.

8 Equivalent Protections Working Group. (2003). Report of the Equivalent Protections Working 

Group. Washington, DC: Department of Health and Human Services (HHS); NBAC. 

(2001). Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries. Bethesda, MD:  National Bioethics Advisory Commission.

9 NBAC, Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries, op. cit; NBAC. (2001). Ethical and Policy Issues in Research Involving Human 

Participants. Bethesda, MD: NBAC.

10 Jonas, H. (1969). Philosophical reflections on experimenting with human subjects. 

Daedalus: Journal of the American Academy of Arts and Sciences, 98, 245.

11 Franklin, B., and J. Sparks. (1839). The Works of Benjamin Franklin: Vol. VIII. Boston, MA: 

Hilliard, Gray, and Company, p. 418.
ENDNOTES IV

107

12 Franklin, of course, employs the term “moral science” in the usage of the day, namely, as 

the science of morality. For the Commission, the term is synonymous with ethically sound 

science. In the spirit of the Enlightenment, philosophers like Frances Hutchison and Jeremy 

Bentham, so influential in the thinking of the American Founders, wanted to find an 

empirical or “naturalistic” grounding for morality. A still more provocative matter, to which 

Franklin’s musing alludes only indirectly, is the question whether progress in “Experimental 

Researches into Nature” might also somehow make experimental science more ethically 

sound. It is a question that has preoccupied Americans ever since and the answer has 

vacillated. For example, by the middle and late 19th century the idea that experimental 

science and moral science co-evolved was prevalent among public intellectuals, including 

academics and clergy. But confidence that that is the case seems to have waned in our own 

time. For further discussion of these principles, see, e.g., Emanuel, E.J., Wendler, D., and C. 

Grady. (2000). What makes clinical research ethical? JAMA, 283, 2701-2711; PCSBI. (2011, 

September); “Ethically Impossible” STD Research in Guatemala from 1946-1948. Washington, 

DC: PCSBI (describing long-standing ethical traditions for medical research); The National 

Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 

(1979). The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 

Subjects of Research (DHEW Publication OS 78-0012). Washington, DC: Department of 

Health, Education, and Welfare, pp. 4-6 (describing principles of autonomy, beneficence and 

justice); World Medical Association. (2008). Code of Ethics of the World Medical Association: 

Declaration of Helsinki. Ferney-Voltaire, France: World Medical Association.

13 Franklin made strenuous attempts to contribute to medical science. He engaged in 

electrotherapy experiments with persons suffering from paralysis, at their request. 

Unfortunately, as he himself noted, his efforts failed to produce a cure. Franklin, B. (1769). 

Experiments and Observations on Electricity made at Philadelphia in America (4th ed.). 

London: David Henry, pp. 359-361. Anticipating the importance of data for validating 

public health interventions, Franklin also compiled statistics on the effectiveness of 

smallpox vaccination. Franklin’s belief in reason and public demonstration as a corrective to 

dogmatism led him to participate in a French commission that engaged in experiments to 

disprove the “animal magnetism” claims of Franz Anton Mesmer’s medical cult. Whether 

Franklin obtained the consent of the experimental subjects, which included members of his 

own household, is unknown. Gensel, L. (2005). The medical world of Benjamin Franklin. 

Journal of the Royal Society of Medicine, 98(1), 534-538.

14 Normally, informed consent must be obtained prospectively from each subject. In some 

research, like that involving anonymous information or information that is de-identified 

under the HIPAA Privacy Rule (45 C.F.R. §164.512), or that involving minimal risk, certain 

routine surveys and other low-risk categories, current regulations do not require informed 

consent. See 45 C.F.R. §§ 46.101(b), 46.116(c)-(d). Generally, these exclusions have not been 

controversial and, for many, they reflect society’s expectations.  A few poignant examples 

demonstrate how complicated decisions about informed consent can be.  For example, in 

testimony to the Commission, Carletta Tilousi, a member of the Havasupai tribe from the 

southwestern United States, described the pain and suffering she and others in her tribe 

experienced when informed consent was not sought from them for secondary research use 

of data and samples. Tilousi, C., Member of the Havasupai Tribe. (2011). Community 

Engagement—Needs, Models and U.S. Actions. Presentation to the PCSBI, August 30, 
MORAL SCIENCE Protecting Participants in Human Subjects Research

108

2011. Retrieved from http://bioethics.gov/cms/node/319 (accessed December 5, 2011). Under 

current law, “what constitutes adequate informed consent is unsettled.  Federal regulations 

require informed consent when identifiable biospecimens are collected for research purposes, 

but such regulations provide little guidance on how to obtain informed consent for future, 

unspecified uses.”  See Mello, M.M., and L.E. Wolf. (2010). The Havasupai Indian tribe 

case—Lessons for research involving stored biologic samples. New England Journal of 

Medicine, 363(3), 205.     

15 Lemonick, M.D., and A. Goldstein. (2002, April 22). At your own risk. TIME. Retrieved 

from http://www.time.com/time/magazine/article/0,9171,1002263,00.html (accessed 

December 2, 2011) (describing the 2001 death of a healthy woman following participation 

in an early-stage asthma treatment study); Suntharalingam, G., et al. (2006). Cytokine 

storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. The New England 

Journal of Medicine, 355, 1018-1028. (describing a 2006 Phase 1 drug trial that hospitalized 

six otherwise healthy men with multiple organ system failure due to unknown properties of 

the chemical agent).

16 Memorandum from President Barack Obama to Dr. Amy Gutmann, Chair, PCSBI. (2010, 

November 24). Retrieved from http://bioethics.gov/cms/sites/default/files/news/HumanSubjects-Protection-Letter-from-President-Obama-11.24.10.pdf.

17 Read-out of the President’s Call with Guatemalan President Colom. (2010, October 1). 

Retrieved from http://www.whitehouse.gov/the-press-office/2010/10/01/

read-out-presidents-call-with-guatemalan-president-colom. 

18 PCSBI, “Ethically Impossible,” op cit.

19 Memorandum from President Barack Obama to Dr. Amy Gutmann, op cit.

20 This policy required “voluntary agreement based on informed understanding” from 

all research subjects, written consent when a physician deemed the research “unusually 

hazardous,” and, beginning in 1954, written consent was required from all “healthy, 

‘normal’ subjects of research.” ACHRE, op cit.; it is not, however, the earliest known federal 

policy requiring informed consent from subjects. See PCSBI, “Ethically Impossible,” op cit. 

(discussing policy decision requiring informed consent in prison research in 1945); ACHRE, 

op cit. (discussing the evolution of policies across the federal government for consent and 

other human subjects protections in the 1940s through the 1970s).

21 See Drug Amendments of 1962, Public Law No. 87-781 (1962), codified at 21 U.S.C. 355 

(requiring informed consent in certain FDA-regulated research); 21 C.F.R. 50 (same); 

National Research Act of 1974, Public Law No. 93-348 (1974), codified at 42 U.S.C. 218 

(requiring informed consent and independent review in HHS-sponsored research). See also 

ACHRE. (1995), op cit., pp. 64-67, 83-129, 171-195.

22 Coleman, C., et al. (2005). The Ethics and Regulation of Research with Human Subjects. 

Newark, NJ: LexisNexis. Before the National Commission, the Department of Health, 

Education and Welfare convened the Tuskegee Syphilis Study Ad Hoc Advisory Panel in 

1972. This Panel found that the men involved in the Tuskegee study had not been informed 

of the actual purpose of the study, had been mislead, and thus had been unable to provide 

informed consent. The Panel concluded that the study was “ethically unjustified” and 

recommended stopping the study immediately. A month later, the study was terminated. 
ENDNOTES IV

109

CDC. (2011, June 15). U.S. Public Health Service Syphilis Study at Tuskegee. Retrieved 

from http://www.cdc.gov/tuskegee/timeline.htm (accessed December 5, 2011).

23 Citro, C.F., Ilgen, D.R., and C.B. Marrett, (eds.). (2003). Protecting Participants and 

Facilitating Social and Behavioral Sciences Research. Washington, DC: The National 

Academies Press, pp. 45-53.

24 Glickman, S.W., et al. (2009). Ethical and scientific implications of the globalization of 

clinical research. The New England Journal of Medicine, 360(8), 816-823.

25 Office of the Inspector General (OIG). (2010, June). Challenges to FDA’s Ability to Monitor 

and Inspect Foreign Clinical Trials (OEI-01-08-00510). Retrieved from http://oig.hhs.gov/oei/

reports/oei-01-08-00510.pdf.

26 PCSBI, Research Across Borders, op cit., p. 2.

27 PCSBI, Research Across Borders, op cit. Public comments on the report were solicited through 

a notice in the Federal Register, at Commission meetings, and through the Commission’s 

website. Request for Comments on Research Without Borders: Proceedings of the 

International Research Panel of the Presidential Commission for the Study of Bioethical 

Issues, 76 Fed. Reg. 55,914 (Sept. 9, 2011).

28 “[Rules] may be interpreted or implemented differently as a result of complex cultural, 

political, and economic influences.” Ibid, pp. 5-6.

29 Ibid, pp. 8-11.

30 See www.clinicaltrials.gov for more information. See also the section on Improving 

Accountability.

31 Ibid, p. 11.

32 Ibid, pp. 8-11. For example, as discussed in recent regulatory reform efforts, multiple IRBs 

for multi-site studies might actually be leading to weaker protections for subjects than fewer 

reviews with greater responsibility on the part of the IRBs involved. Subjects Research 

Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, 

and Ambiguity for Investigators, 76 Fed. Reg. 44,513 (July 26, 2011); Boscheck, R., et al. 

(2008). Strategies, Markets and Governance: Exploring Commercial and Regulatory Agendas. 

Cambridge: Cambridge University Press, p. 285 (using the term “process fatigue” to reflect 

the burden of the proliferation of monitoring mechanisms associated with EU constitutional 

governance).

33 PCSBI, Research Across Borders, op cit., p. 4.

34 45 C.F.R. Parts 46, Parts A through D, 160, and 164 and, through the Food and Drug 

Administration (FDA) at 21 C.F.R. Parts 50 and 56. Other federal departments and agencies 

joined HHS in adopting a uniform set of rules for the protection of human subjects, the 

“Common Rule,” identical to subpart A of 45 C.F.R. part 46 of the HHS regulations. See 

more extensive discussion of the current regulations in the section on Promoting Current 

Reform Efforts.

35 Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing 

Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 44,512-44,530 (July 26, 2011). 

36 Ibid., p. 44,512.
MORAL SCIENCE Protecting Participants in Human Subjects Research

110

37 Request for Comments on Human Subjects Protections in Scientific Studies, 76 Fed. Reg. 

11,482 (March 2, 2011).

38 Bartlett, E. E. (2008). International analysis of institutional review boards registered with 

the Office for Human Research Protections. Journal of Empirical Research on Human 

Research Ethics, 3(4), 49-56; Bhutta, Z. A. (2002). Ethics in international health research: A 

perspective from the developing world. Bulletin of the World Health Organization,114-120; 

Glickman, S. W., et al. (2009). Ethical and scientific implications of the globalization of 

clinical research. The New England Journal of Medicine, 360(8), 816-823; Lansang, M. A., 

and F.P. Crawley. (2000). The ethics of international biomedical research. British Medical 

Journal, 321(7264), 777-778; McCarthy, J., Wilenzick, M., and C. Cuenot. (2010). The 

globalization of clinical trials – Challenges, opportunities and a path forward. International 

In-house Counsel Journal, 3(11), 1-13; Office for Human Research Protections, U.S. 

Department of Health and Human Services. (2012). International Compilation of Human 

Research Standards. Retrieved from http://www.hhs.gov/ohrp/international/intlcompilation/

intlcompilation.html (accessed December 7, 2011). The Commission is especially grateful 

to Edward E. Bartlett, PhD, International Human Research Liaison, Office for Human 

Research Protections and the International Working Group for providing guidance and 

assistance in understanding human subjects protections around the globe. The Commission 

reached out to the heads of the 18 federal agencies and departments that have adopted 

the Common Rule. They are: (1) Department of Agriculture (USDA); (2) Department of 

Commerce (DOC); (3) Department of Defense (DOD); (4) Department of Education 

(ED); (5) Department of Energy (DOE); (6) Department of Health and Human Services 

(HHS); (7) Department of Homeland Security (DHS); (8) Department of Housing 

and Urban Development (HUD); (9) Department of Justice (DOJ); (10) Department 

of Transportation (DOT); (11) Department of Veterans Affairs (VA); (12) Agency for 

International Development (USAID); (13) Consumer Product Safety Commission (CPSC); 

(14) Environmental Protection Agency (EPA); (15) National Aeronautics and Space 

Administration (NASA); (16) National Science Foundation (NSF); (17) Social Security 

Administration (SSA); and (18) the Central Intelligence Agency (CIA). 

39 ACHRE. (1995). Final Report of the Advisory Committee on Human Radiation Experiments.

New York, NY: Oxford University Press.

40 NBAC. (2001). Ethical and Policy Issues in Research Involving Human Participants. Bethesda, 

MD: NBAC; NBAC. (2001). Ethical and Policy Issues in International Research: Clinical Trials 

in Developing Countries. Bethesda, MD: NBAC.

41 Institute of Medicine (IOM). (2003). Responsible Research: A Systems Approach to Protecting 

Research Participants. Washington, DC: National Academies Press.

42 See generally, PCSBI. (2010, December). New Directions: The Ethics of Synthetic Biology and 

Emerging Technologies. Washington, DC: PCSBI, p. 17. (as with synthetic biology, “Ongoing 

assessment and review is required in several areas to avoid unnecessary limits on science”); 

PCSBI, Research Across Borders, op cit., pp. 8-11; “The stacking of regulations within and 

across agencies and countries increases the burden without any benefit to the subjects and in 

many cases results in increases costs and decreased research productivity.” DeCrappeo, A.P., 

President, Council on Governmental Relations. (2011). Comments submitted to the PCSBI, 

May 2, 2011.
ENDNOTES IV

111

43 IOM, op cit., p. 9.

44 Bierer, B.E., Chair, Secretary’s Advisory Committee on Human Research Protections 

(SACHRP). (2011). Comments submitted to PCSBI, August 5, 2011. Retrieved from http://

www.hhs.gov/ohrp/sachrp/commsec/commentspcsbi.pdf.pdf (accessed December 2, 2011). 

45 Memorandum from President Barack Obama to Dr. Amy Gutmann, op cit.

46 PCSBI, “Ethically Impossible,” op cit.

47 See, e.g., International Convention on Civil and Political Rights, adopted and opened for 

signature Dec. 16, 1996, 999 U.N.T.S. 171. Note, however, that although the ICCPR Article 

7 guarantees that “[n]o one shall be subjected to torture or to cruel, inhuman or degrading 

treatment or punishment. In particular, no one shall be subjected without his free consent to 

medical or scientific experimentation,” the United States has ratified the treaty, but reserved 

articles 1-27 as non-self-executing. Consequently, there is no private right of action, or 

recourse to the U.S. state or federal courts, for violating Article 7. 138 Cong. Rec. S. 4781.

48 Some U.S. states also impose one or more of these standards on all research within their 

borders. Schwartz, J. (2001). Oversight of Human Subject Research: The Role of the 

States. In H. Shapiro, et al. (Eds.), Ethical and Policy Issues in Research Involving Human 

Participants. (pp. M1-M20). See also Cal. Health and Safety § 24175 (2010). (mandating 

that, with very narrow exceptions, no person shall be subjected to any medical experiment 

unless the informed consent of such person is obtained); Md. Code Ann., Health-Gen § 

13-2002(a) (2011). (adopting the Common Rule as a matter of state law, stating, “A person 

may not conduct research using a human subject unless the person conducts the research 

in accordance with the federal regulations on the protection of human subjects”); Va. 

Code Ann. §§ 32.1-162.18, 32.1-162.19 (2011). (requiring for the performance of human 

subjects research (1) “informed consent must be obtained” and (2) that research and research 

proposals be subjected to the review of a human subject review committee). State law 

sometimes mandates additional protections; Common Rule regulations do not preempt state 

or local laws that provide additional protections for human subjects. 45 C.F.R. § 46.101(f). 

49 See generally 45 C.F.R. pt. 46, Subpart A. The policy is known as the Common Rule because 

it was promulgated jointly in 1991 as a single set of regulations by 15 different departments 

and agencies. Since 1991, three additional departments and agencies have signed onto it. See

Federal Policy for the Protection of Human Subjects (“Common Rule”), 56 Fed. Reg. 28003 

(June 18, 1991). Institutions must certify that proposed research with human subjects, that 

is subject to the regulations, has been reviewed and approved by an IRB. The regulations 

set forth specific requirements for IRB membership, as well as criteria for IRB approval of 

research. IRBs are empowered to approve, require modifications of, or disapprove covered 

research activities, and are required to conduct continuing review of ongoing research at 

least annually. They also have authority to suspend or terminate approval of research not 

conducted in accordance with the IRB’s requirements or that has been associated with 

unexpected serious harms to subjects. Institutions must provide written assurance to the 

agency sponsoring the research that they will comply with the Common Rule. They must 

adopt a statement of principles for protecting human subjects; designate a responsible IRB; 

retain information on IRB membership; establish written procedures for IRB review and 

reporting unanticipated problems, noncompliance, and suspension or termination of IRB 

approval. 45 C.F.R. pt 46, Subpart A.
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50 FDA has not adopted the Common Rule per se, but has its own regulations for human 

subjects protection. Like the Common Rule FDA regulations require informed consent 

and independent review. The regulations also specify safety data and other details that must 

be provided for FDA review prior to initiation of most clinical investigations, describe the 

responsibilities of sponsors and investigators, set forth standards to help assure that studies 

will be acceptable to support marketing approval in order to avoid exposing subjects to 

unwarranted burden and risk, and address conflicts of interest. 21 C.F.R. pt. 50, pt. 56, pt. 

312, and pt. 812.

51 See also Congressional Research Service. (2005). CRS Report for Congress: Federal 

Protection for Human Research Subjects- An Analysis of the Common Rule and the HIPAA 

Privacy Rule. June 2. Retrieved from http://www.fas.org/sgp/crs/misc/RL32909.pdf (accessed 

December 6, 2011); Faden, R.R. and T.L. Beauchamp. (1986). A History and Theory of 

Informed Consent. New York, NY: Oxford University Press; Porter, J.P. and G. Koski. (2008). 

Regulations for the Protection of Humans in Research in the United States: The Common 

Rule. In E.J. Emanuel, et al. (Eds.). The Oxford Textbook of Clinical Research Ethics. New 

York: Oxford University Press, (pp. 156-167). State law also regulates certain research outside 

the reach of federal law, though not all states regulate human subjects research. Those that 

do, generally follow the example of federal law, with a focus on independent prior review 

and legally effective informed consent. For example, New York, one of the earliest adopters 

of relevant state law, mandates that “no human research may be conducted in this state 

in the absence of the voluntary informed consent subscribed to in writing by the human 

subject.” N.Y. Public Health Law § 2442 (Consol. 2011). Notably, New York law defines 

“human research” as “any medical experiments, research, or scientific or psychological 

investigation, which utilizes human subjects,” which, unlike federal law, brings both privately 

and publicly funded human research activities under its purview. N.Y. Public Health Law 

§ 2441 (Consol. 2011). New York law also requires institutions that conduct or propose to 

conduct human research to establish a human research review committee. That committee 

reviews research and approves “a statement of principle and policy,” issued by the institution 

conducting or authorizing human research, “in regard to the rights and welfare of human 

subjects in the conduct of human research.” N.Y. Public Health Law § 2444 (Consol. 2011). 

See also Va. Code Ann. § 32.1-162.20 (2011); MD Code Ann., Health–Gen. §13-2002 

(2011); MD Code Ann., Health–Gen. §13-2001 (2011). By contrast to New York, Virginia, 

and Maryland, California does not require prior review by a research ethics committee, but 

requires that subjects be given an “experimental subject’s bill of rights” and provides civil 

and criminal penalties for those who negligently or willfully fail to obtain informed consent. 

Cal Health & Safety § 24170-24179.5 (2010). Additionally, some states have also chosen to 

regulate in particular areas—including human cloning, genetic research, and stem cells—or 

to provide additional protections for certain classes of research participants—including 

research with prisoners, children, patients in psychiatric facilities, individuals in facilities for 

the developmentally disabled, or fetuses. See, e.g., Va. Code Ann. §§ 32.1-162.22 (2011).

52 See e.g., Aristotle. (1999). Nicomachean Ethics. T. Irwin, (Ed.). Indianapolis, IN: Hackett 

Publishing; Kant, E. (1998). Groundwork of the Metaphysics of Morals. Gregory, M. (Ed.). 

Cambridge: Cambridge University Press; Pellegrino, E.D. and D.C. Thomasma. (1993). The 

Virtues in Medical Practice. New York, NY: Oxford University Press, pp. 3-29. 
ENDNOTES IV

113

53 See e.g., American Society for Investigative Pathology (ASIP). (2011). ASIP By Laws. 

February Retrieved from http://www.asip.org/gov/documents/bylaws.PDF; Glaxo-Smith Klein. 

(2010). GSK Corporate Responsibility Report. Retrieved from http://www.gsk.com/

responsibility/downloads/GSK-CR-2010-Report.pdf; Yale University. (2010, May 1). 

Policy 1360: Human Research Protection. Retrieved from http://www.yale.edu/policy/1360/

1360.pdf.

54 See e.g., AstraZeneca. Code of Conduct. Retrieved from http://www.astrazeneca.com/

Responsibility/Code-policies-standards; PhRMA. (2011, July). PhRMA Principles on Conduct 

of Clinical Trials: Communication of Clinical Trial Results. Retrieved from http://www.phrma.

org/sites/default/files/105/042009_clinical_trial_principles_final.pdf.

55 Bayer. (2011, January 20). Bayer: Science for a Better Life Mission and Values. Retrieved from 

http://www.bayer.com/en/mission---values.aspx; Bristol-Myers Squibb. (2010). Bristol-Myers 

Squibb Standards of Business Conduct and Ethics. Retrieved from http://www.bms.com/

Documents/ourcompany/SBCE_2010.pdf; Novartis. (2001, June). Novartis Code of Conduct. 

Retrieved from http://www.corporatecitizenship.novartis.com/downloads/business-conduct/

code_of_conduct.pdf; PhRMA, op cit.; Sanofi-Aventis. (2011, August 19). Sanofi US Code of 

Business Conduct. Retrieved from http://www.sanofi.us/l/us/en/layout.jsp?scat=DD8ABF97-

8898-4629-8CBF-931915609029 (Note: actual document not publicly available.).

56 AstraZeneca, op cit., (stating that the key issues in the code address the fundamental 

principle that members must “conduct clinical research in a manner that recognizes the 

importance of protecting the safety of and respecting research participants”).

57 Responsibility of Applicants for Promoting Objectivity in Research for which Public Health 

Service Funding is Sought and Responsible Prospective Contractors. 76 Fed. Reg. 53,256 

(August 25, 2011). (to be codified at 42 C.F.R. pt. 50, 45 C.F.R. pt. 94); Standards for 

Privacy of Individually Identifiable Health Information, 45 C.F.R. pt. 160 and pt. 164.

58 See Appendix II (explaining data collection methods).

59 The Human Subjects Research Landscape Project includes research that was not reported 

because it is classified or because of national security concerns. Classified research is 

generally not disclosed to the public. However, such research must undergo review by an 

IRB. For example, at DOD an IRB must have at least five members, one of whom must be 

non-governmental, and classified research may never be approved using expedited review 

procedures. Office of the Under Secretary of Defense. (2011). Research Regulatory Oversight 

Office, Human Research Protection Program, Operating Instruction. Retrieved from: http://

home.fhpr.osd.mil/Libraries/DoDD-RROO/Signed_OI_17_June_2011.sflb.ashx. CIA 

and DHS are subject to similar rules aligning with the Common Rule requirements of IRB 

review and prohibiting expedited review of classified research. Executive Order 12333, Sec. 

2.10; Letter from V. Sue Bromley, CIA, to Dr. Amy Gutmann, PCSBI. (May 16, 2011); 

DHS. (2007). DHS Management Directive 026-04: Protection of Human Subjects, May 25, 

2007. Retrieved from www.dhs.gov/xlibrary/assets/foia/mgmt-directive-026-04-protectionof-human-subjects.pdf.
MORAL SCIENCE Protecting Participants in Human Subjects Research

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60 See Tables I.17, I.18, and I.19 (showing low response rates from some agencies for number of 

subjects, exempt/non-exempt status, and number of sites). Similarly, DHS for example, did 

not provide funding data because “it would be overly burdensome, and in many cases not 

feasible, to obtain the requested award information [e.g., award ID and total award amount] 

for the years requested by the Commission and align the human subject research data with 

the DHS award information obtained through OMB [i.e., USASpending.gov]).” Letter from 

Richard Legault, DHS, to Valerie Bonham, PCSBI. (2011, September 29). ED also could 

not link a significant portion of extramural funding information to study-level data, but is 

working to improve by developing grant and contract management systems designed “to 

enable coordinated implementation of [ED human subjects protection regulations] as part 

of the broader grant and contract management system.” Jeffery Rodamar, ED, to Michelle 

Groman, PCSBI. (2011, September 6). E-mail Correspondence. DOD also could not readily 

link funding data to nearly all of their reported studies. Michelle Groman, PCSBI, to Patty 

Decot, DOD. (2011, October 27). Email Correspondence.

61 Honey, K. (2011). True dedication to clinical research: The Clinical Center of the National 

Institutes of Health receives the 2011 Mary Woodard Lasker Award for Public Service. 

Journal of Clinical Investigation, 121(10), 3778-3781.

62 Silver, H. et al. (2011). Social and Behavioral Science Research in the FY 2012 Budget. 

In AAAS Report XXXVI: Research & Development FY 2012. pp. 205-213. Retrieved from 

http://www.aaas.org/spp/rd/rdreport2012/12pch19.pdf; Kobor, P., Wurtz, S., and D. 

Johnson. (1999). Behavioral and Social Sciences in the FY2000 Budget. In AAAS Report 

XXIV: Research & Development FY 2000. Retrieved from http://www.aaas.org/spp/rd/xxiv/

chap20.htm.

63 For example, a violation of IRB approval of informed consent may include a lack of a 

statement describing the extent to which confidentiality of records identifying the subject 

will be maintained. See generally Office of Human Research Protections (OHRP). (2011). 

2011 Determination Letters. Retrieved from http://www.hhs.gov/ohrp/compliance/letters/

index.html.

64 Borror, K., et al. (2003). A review of OHRP compliance oversight letters. IRB: Ethics & 

Human Research, 25(5), 1. (reviewing OHRP compliance letters issued between October 1, 

1998 and June 20, 2002); Weil, C., et al. (2010, March-April). OHRP compliance oversight 

letters: An update. IRB: Ethics & Human Research, 32(2), 1-6 (reviewing OHRP compliance 

letters issued between August 1, 2002 and August 31, 2007).

65 Porter, J.P. and G. Koski, op cit., pp. 156-167. 

66 Human Subjects Research Protections: Enhancing Protections for Research Subjects and 

Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 44,512 (July 26, 2011).

67 Concerns such as these are one factor motivating the promulgation of international human 

rights treaties ensuring universal rights to bodily integrity and health. See e.g., International 

Convention on Civil and Political Rights, adopted and opened for signature Dec. 16, 1996, 

999 U.N.T.S. 171; International Covenant on Economic, Social, and Cultural Rights, 

adopted and opened for signature Dec. 16, 1996, 993 U.N.T.S. 3. 
ENDNOTES IV

115

68 Dieppe, P. (2004, October 14). Lessons from the withdrawal of rofecoxib. British Medical 

Journal, 329, 867-868; Saul, S. (2008, April 15). Ghostwriters Used in Vioxx Studies, Article 

Says. New York Times. Retrieved from http://www.nytimes.com/2008/04/15/business/15cndvioxx.html?pagewanted=all (last accessed December 6, 2011); Harris, G. (2010, February 

19). Research Ties Diabetes Drug to Heart Woes. New York Times. Retrieved from http://

www.nytimes.com/2010/02/20/health/policy/20avandia.html?pagewanted=all (last accessed 

December 6, 2011); Steinbrook, R. (2004). Public registration of clinical trials. New England 

Journal of Medicine, 351(4), 315-317.

69 Food and Drug Modernization Act of 1997 § 113, 42 U.S.C. § 282(i) (2011).

70 Food and Drug Administration Amendments Act of 2007 § 801, 42 U.S.C. § 282(j) (2011).

71 Me. Rev. Stat. Ann. tit. 22, § 2700-A (2011); International Federation of Pharmaceutical 

Manufacturers & Associations. (2005); Patients and Physicians To Gain Easy Access To 

Clinical Trials Information Via New Ifpma Search Portal [Press release].  Retrieved from 

http://clinicaltrials.ifpma.org/clinicaltrials/fileadmin/files/pdfs/EN/CTP_Release_0_EN.pdf

(last accessed December 6, 2011); World Health Organization. (2005). Resolutions and 

Decisions: Ministerial Summit on Health Research. Retrieved from https://apps.who.int/gb/

ebwha/pdf_files/WHA58/WHA58_34-en.pdf (last accessed December 6, 2011).

72 See Research Across Borders, op cit., p. 10. Australian New Zealand Clinical Trials Registry. 

(2011). Retrieved from http://www.anzctr.org.au/; Ministerio da Saude. Registro Brasileiro 

de Ensaios Clinicos. (n.d.). Retrieved from http://www.ensaiosclinicos.gov.br/ (accessed 

December 6, 2011); National Institute of Medical Statistics (Indian Council of Medical 

Research). (2011). Clinical Trials Registry – India. Retrieved from http://ctri.nic.in/

Clinicaltrials/login.php (accessed December 6, 2011). 

73 World Medical Association (WMA).  (2008). WMA Declaration of Helsinki – Ethical 

Principles for Medical Research Involving Human Subjects. Article 19. Retrieved from 

http://www.wma.net/en/30publications/10policies/b3/index.html.

74 OMB Memorandum from Vivek Kundra to the Heads of Departments and Agencies. (June 

1, 2009). Guidance on Data Submission under the Federal Funding Accountability and 

Transparency Act (FFATA). Retrieved from http://www.whitehouse.gov/sites/default/files/

omb/assets/memoranda_fy2009/m09-19.pdf (last accessed December 6, 2011); Public Law 

No. 109-282, as amended by section 6202(a) of Public Law 110-252 (see U.S.C. 6101 note).

75 American Recovery and Reinvestment Act of 2009, Public Law No. 111-5 § 3001(c)(4), 42 

U.S.C. § 300jj-11(c)(4) (2011). 

76 COHRED: Council on Health Research for Development. (2011). Retrieved from http://

www.cohred.org/ (accessed December 6, 2011).

77 Consolidated Appropriations Act of 2008, Division G, Title II, Public Law No. 110-161; 

NIH. (2008). Revised Policy on Enhancing Public Access to Archived Publications Resulting 

from NIH-Funded Research. Retrieved from http://grants.nih.gov/grants/guide/notice-files/

NOT-OD-08-033.html (accessed November 29, 2011). (“The Director of the National 

Institutes of Health shall require that all investigators funded by the NIH submit or have 

submitted for them to the National Library of Medicine’s PubMed Central an electronic 

version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made 
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publicly available no later than 12 months after the official date of publication: Provided, 

That the NIH shall implement the public access policy in a manner consistent with 

copyright law.”). For more information see http://publicaccess.nih.gov/policy.htm (accessed 

December 6, 2011). 

78 Request for Information: Public Access to Peer-Reviewed Scholarly Publications Resulting 

From Federally Funded Research, 76 Fed. Reg. 68,518-68,520 (Nov. 4, 2011). The 

government’s recognition of openness and transparency as a tool for accountability is well 

documented. See Presidential Memorandum – Managing Government Records, (2011, 

November 28). Retrieved from http://www.whitehouse.gov/the-press-office/2011/11/28/

presidential-memorandum-managing-government-records (directing agencies to 

make records more available and accessible to the public); Statement of Cass Sunstein, 

Administrator of the Office of Information and Regulatory Affairs of the Office of 

Management and Budget. (November 28, 2011). We Can’t Wait: Bringing Records 

Management into the Twenty-first Century. Retrieved from http://www.whitehouse.

gov/blog/2011/11/28/we-cant-wait-bringing-records-management-twenty-first-century-0

(describing how agency information “provide[s] a prism through which future generations 

will view, understand and learn from the actions of the current generation); The Open 

Government Partnership—National Action Plan for the United States of America. (2011, 

September 20). Retrieved from http://www.whitehouse.gov/sites/default/files/us_national_

action_plan_final_2.pdf. For more information on existing disclosure requirements, see, 

e.g., Office of Management and Budget: Open Government website. Retrieved from http://

www.whitehouse.gov/omb/open.

79 See DOE Human Subjects Research Database (HSRD). Retrieved from http://www.orau.

gov/HsrdReport/ (accessed December 6, 2011). The HSRD database includes information on 

all research projects involving human subjects that are not exempt by their local Institutional 

Review Board (IRB). The data is reported to the DOE by the project’s principal investigator 

on an annual basis, and project data is available back to 1995. 

80 See Research Portfolio Online Reporting Tools (RePORTER), NIH. Retrieved from 

http://projectreporter.nih.gov/reporter.cfm (accessed December 6, 2011).

81 The Commission recognizes that in many cases agencies may not have access to this 

information when research is funded through grant or contract but conducted by third 

parties. NIH. (2011). NIH Grants Policy Statement. October 1, 2011. Retrieved from http://

grants.nih.gov/grants/policy/nihgps_2011/nihgps_2011.pdf. (demonstrating the arms 

length nature of awards, it states “[o]verall responsibility for successfully implementing an 

NIH grant is a shared responsibility of the [program director]/[principal investigator], the 

[authorized organization representative], and the research administrator. As key members of 

the grant team, they respectively lead the scientific and administrative aspects of the grant.). 

82 AAHRPP. (2011). AAHRPP Our Mission, Vision, and Values. Retrieved from http://www.

aahrpp.org/www.aspx?PageID=5 (accessed December 6, 2011); IOM. (2003). Exploring 

Challenges, Progress, and the New Models for Engaging the Public in the Clinical Research 

Enterprise: Clinical Research Roundtable Workshop Summary. Washington, DC: The National 

Academies Press, pp. 44-45.

83 PCSBI, Research Across Borders, op cit., p. 10.
ENDNOTES IV

117

84 Public evaluation of research results is also important. The Commission recognizes the 

programs already in place to accomplish this. See discussion in Improving Accountability 

section of this report regarding NIH public access programs, clinicaltrials.gov, and grantwide proposals to require free online access to published results of federally funded research.

85 ClinicalTrials.gov today collects most of the elements the Commission specifies. It includes 

1) title, 2) principal investigator and institutional affiliation, 3) collaborating institutions, 4) 

location of research activities, and 5) federal funding source. See http://www.clinicaltrials.

gov/ for more information. Reliance on this existing program may be impractical for all 

agencies as it is oriented to biomedical research, but the Commission encourages its use to 

consolidate reporting requirements and simplify public access.

86 OHRP. About OHRP. (n.d.). http://www.hhs.gov/ohrp/about/index.html (accessed 

December 6, 2011).

87 For example, OHRP manages the Federalwide Assurance system. See OHRP. (2011, June 

17). Federalwide Assurance for the Protection of Human Subjects. Retrieved from http://

www.hhs.gov/ohrp/assurances/assurances/filasurt.html (accessed December 6, 2011). 

88 Abbott, L., and C. Grady. (2011). A systematic review of the empirical literature evaluating 

IRBs: What we know and what we still need to learn. Journal of Empirical Research on 

Human Research Ethics, 3-19; Emanuel, E.J. (2002). The relevance of empirical research 

for bioethics. In Stepke, F.L. and L.A. Corbinos (Eds.), Interfaces Between Bioethics and the 

Empirical Social Sciences. Buenos Aires, Argentina: World Health Organization. Letter from 

Barbara E. Bierer, Chair, SACHRP, to Kathleen Sebelius, Secretary, HHS. (August 5, 2011). 

Retrieved from http://www.hhs.gov/ohrp/sachrp/commsec/commentspcsbi.pdf.pdf (“There is 

an inadequate evidence base to inform regulation and best practices in many areas of human 

subjects protections. Increased federal support for research to enhance this evidence base is 

essential to facilitate improvements in human subjects research regulations and practices.”).

89 Sugarman, J., and D. Sulmasy. (Eds.) (2001). Method in Medical Ethics. Washington, DC: 

Georgetown University Press, 2nd edition.

90 Emanuel, E.J. (2002). The relevance of empirical research for bioethics. In F.L. Stepke and 

L.A. Corbinos (eds.), Interfaces Between Bioethics and the Empirical Social Sciences. Buenos 

Aires: World Health Organization.

91 Collins, F., Director, NIH. (2011). Bioethics Research at the NIH. Presentation to PCSBI, 

February 28, 2011. Retrieved from http://bioethics.gov/cms/node/187 (accessed December 6, 

2011).

92 The majority of the discussion that follows applies directly to medical research. The majority 

of physical and psychological harms that arise in human subjects research appear in this 

arena. Insofar as such harms arise in other fields of human subjects research, however, the 

Commission believes that the ethical arguments for treatment or compensation for treatment 

extend as well.

93 Some might object that invoking the common good is unjustified because subjects of 

research are often motivated to participate for reasons other than an altruistic desire to serve 

the common good. This, however, would not vitiate the fact that whatever the motive of 

the subjects, they do, in fact, contribute to the common good through their participation in 

research and this fact is morally significant.
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118

94 Indeed, the DHEW went so far as to draft regulations requiring that institutions receiving 

funds from DHEW have in place “mechanisms to provide compensation for individuals 

who suffer injury as the result of their participation as subjects in biomedical or behavioral 

research,” but these regulations were never enacted. DHEW. (1979). Draft Protection of 

Human Subjects: Proposed Regulations on Compensation of Human Subjects Injured in 

Biomedical and Behavioral Research.

95 Neither body went beyond treatment or medical costs in their recommendations. NBAC. 

(2001, August). Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries. Bethesda, MD; Mastroianni, A., Faden, R., and D. Federman. (Eds). Appendix 

D: Compensation Systems for Research Injuries. In Institute of Medicine, Women and Health 

Research: Ethical and Legal Issues of Including Women in Clinical Studies, Vol. I. Washington, 

DC: National Academy Press, pp. 243-252; Pike, E. (In press). Recovering from research: 

A No-fault proposal to compensate injured research participants. American Journal of Law 

and Medicine. Retrieved from http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1923817; 

Presidential Commission for the Study of Ethical Problems in Medicine and Biomedical 

and Behavioral Research. (1982). Compensating for Research Injuries. Washington, DC: 

Department of Health, Education, and Welfare; Scott, L. (2003). Research-related injury: 

Problems and solution. The Journal of Law, Medicine and Ethics, (31)3, 421-422. (which 

touches on the history of compensation). 

96 Institute of Medicine (IOM). (2002). Responsible Research: A Systems Approach to Protecting 

Research Participants. Washington, DC: National Academies Press, p. 193. Act No. 885 

of September 20, 2005 (as amended by Act No. 1545 of December 20, 2006 and Act No. 

523 of June 6, 2007). The Liability for Damages Act. Copenhagen: Patientforsikringen. 

Retrieved from http://www.patientforsikringen.dk/en/Love-og-Regler/Lov-om-klage-ogerstatningsadgang/Behandlingsskader.aspx (accessed December 6, 2011); Act. No. 24 of 

January 21, 2009. The Right to Complain and Receive Compensation within the Health 

Service. Copenhagen: Patientforsikringen. Retrieved from http://www.patientforsikringen.

dk/en/Love-og-Regler/Lov-om-klage-og-erstatningsadgang/Lægemiddelskader.aspx (accessed 

December 2, 2011); Council for International Organizations and Medical Sciences (CIOMS) 

and World Health Organization. (2002). International Ethical Guidelines for Biomedical 

Research involving Human Subjects. Geneva: World Health Organization; France. Code 

de la Santé Publique. Arts. L. 1121-7, L. 1121-10, L. 1142-22 (dedicated to the insurance 

and compensation of research subjects). Retrieved from http://www.legifrance.gouv.fr/

(accessed December 2, 2011); International Conference on Harmonisation. (1996, June). 

Guideline for good clinical practice E6(R1). Retrieved from http://www.ich.org/fileadmin/

Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.

pdf; Ministry of Health of China. (2007). Interim Measures for Guidelines on Ethical Review 

of Biomedical Research Involving Human Subjects. Retrieved from http://www.chinaphs.

org/bioethics/regulations_&_laws.htm#_Toc161968266 (accessed December 6, 2011); 

Uganda National Council for Science and Technology. (2007, March). National Guidelines 

for Research Involving Humans as Research Participants. Kampala, Uganda: UNCST; World 

Health Organization. (2005). Handbook for good clinical research practice (GCP): guidance 

for implementation; Many less developed nations also require treatment or compensation for 

treatment. These include: Brazil, India, the Philippines, and Uganda; Brazil. (1987). National 

Health Council. Resolution No. 196/96. Decree No. 93933 of January 14, 1987; Indian 
ENDNOTES IV

119

Council of Medical Research. (2006). Ethical Guidelines for Biomedical Research on Human 

Participants. New Delhi, India: Director General of the Indian Council of Medical Research; 

Philippine Council for Health Research and Development. (2000). National Guidelines for 

Biomedical/Behavioral Research. Taguig, Metro Manila. 

97 PCSBI, Research Across Borders, op cit., p. 11. The Panel suggested that the “United States 

should implement a system to compensate research subjects for research-related injuries.”

98 Schaefer, G.O., Emanuel, E.J., and A. Wertheimer. (2009). The obligation to participate in 

biomedical research. The Journal of the American Medical Association, 302(1), 67-72.

99 Nolan, J.R. and J.M. Nolan-Haley. (1990). Deluxe Black’s Law Dictionary: Sixth Edition. 

St. Paul, MN: West Publishing Co.

100 Weisbard, A.J. (1987). The role of philosophers in the public policy process: A view from the 

President’s Commission. Ethics, 97(4), 780.

101 Other examples where society does not permit informed volunteers to assume risks include 

the medical education context. Wikler, D., Professor of Ethics and Population Health, 

Harvard University. (2011). Compensation for Research-Related Injury. Presentation to 

PCSBI, November 17, 2011. Retrieved from http://bioethics.gov/cms/node/391 (accessed 

December 6, 2011).

102 In other words, there are unforeseeable and/or unavoidable risks that are part of the nature of 

human subjects research and must be borne by someone if medical science is to progress. But 

it does not follow from this fact that good science and a social safety net are incompatible.

103 The Commission does not endorse the view of research subjects as “wage-earners,” however, 

because if volunteers were treated as “wage-earners,” the research would violate the 

prohibitions on “undue inducement.” 45 C.F.R. Part 46. 

104 Dickert, N. and C. Grady. (1999). What’s the price of a research subject? Approaches to 

payment for research participation. The New England Journal of Medicine, 341(3), 198-203.

105 This Commission goes further than past commissions in stating unequivocally that injured 

research subjects should not bear the financial costs of research injuries. After intensive study, 

the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical 

and Behavioral Research (1982) ultimately recommended only that “a small experiment 

be undertaken” to “determine the need for, and practical feasibility of, a compensation 

program”—a recommendation that was reiterated by ACHRE in 1995 and NBAC in 2001. 

No action was taken in response to this series of recommendations. ACHRE, op cit.; NBAC. 

(2001, August). Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries (2001). Bethesda, MD: NBAC; Presidential Commission for the Study of Ethical 

Problems in Medicine and Biomedical and Behavioral Research. (1982). Compensating for 

Research Injuries. Washington, DC: Department of Health, Education, and Welfare.

106 The University of Washington, for example, offers treatment to human research subjects 

injured overseas at their facility in Seattle or through reimbursement (restitution) to 

individuals who receive treatment overseas. Moe, K.E., Director and Assistant Vice Provost 

for Research, University of Washington. (2011). University of Washington Human Subjects 

Assistance Program. Presentation to PCSBI, November 17, 2011. Retrieved from http://

bioethics.gov/cms/meeting-seven.
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120

107 In this regard, the Commission recognizes the research and analysis into questions of 

reparations and remedies produced by ACHRE. See ACHRE. (1995). Final Report of the 

Advisory Committee on Human Radiation Experiments. New York, NY: Oxford University 

Press, pp. 512-522 (providing an example of carefully parsed recommendations for different 

groups affected by the radiation experiments depending on their particular circumstances); 

Memorandum from Advisory Committee Staff to the Members of the Advisory Committee 

on Human Radiation Experiments. (December 12, 1994). Discussion Memo on Proposed 

Remedies and Guidelines. Retrieved from http://www.gwu.edu/~nsarchiv/radiation/dir/

mstreet/commeet/meet9/brief9/tab_g/br9g1.txt (discussing possible remedies available 

for those affected by the human radiation experiments). See also Brooks, R.L., ed. (1999). 

When Sorry Isn’t Enough: The Controversy over Apologies and Reparations for Human Injustice. 

New York: New York University (discussing a number of examples of reparations, and 

developing a “theory of redress” based on the concepts of human injustice and human 

rights); Randelzhofer, A., and C. Tomuschat, eds. (1999). State Responsibility and the 

Individual: Reparation in Instances of Grave Violations of Human Rights. Cambridge, MA:  

Kluwer Law International (addressing in particular claims for reparations under a several 

international covenants and agreements, including the European Convention on Human 

Rights); Schonsteiner, J. (2007). Dissuasive measures and the “society as a whole”: A working 

theory of reparations in the Inter-American Court of Human Rights. American University 

International Law Review, 23, 127-164 (examining reparations as implemented by a 

particular international body).

108 During the Tuskegee Syphilis Study, 600 African American men with syphilis were enrolled 

in a decades-long observational study of disease progression without receiving readily 

available and proven treatment. DHEW. (1973). Final Report of the Tuskegee Syphilis Study Ad 

Hoc Advisory Panel. Retrieved from http://biotech.law.lsu.edu/cphl/history/reports/tuskegee/

tuskegee.htm (accessed December 6, 2011); Jones, J.H. (1993). Bad Blood: The Tuskegee 

Syphilis Experiment. New York, NY: The Free Press. Most of the actors in that infamous 

research are now deceased. Reverby, S. (2009). Examining Tuskegee: The Infamous Syphilis 

Study and Its Legacy. Chapel Hill, NC: University of North Carolina Press.

109 Clinton, W.J. (1997, July 16). Remarks by the President in Apology for Study Done in 

Tuskegee. The White House. Washington, DC. Retrieved from http://clinton4.nara.gov/

New/Remarks/Fri/19970516-898.html.

110 PCSBI, Research Across Borders, op cit., p. 11.

111 An individual injured as a result of research participation can sue for damages through the 

tort system. Claims may be brought on a range of intentional, negligence, strict liability 

and products-liability theories. See, e.g., Morreim, E.H. Medical research litigation and 

malpractice tort doctrines: Courts on a learning curve. Houston Journal of Health Law and 

Policy, 4, 1-86. Subjects may, for example, allege they did not give fully informed consent 

when exposed to certain adverse events from research, and thereby bring an intentional tort 

claim of battery against research sponsors. See, e.g., Morreim, E.H. (2004). Litigation in 

clinical research: Malpractice doctrines versus research realities, Journal of Law, Medicine 

& Ethics, 32, 474-481. Subjects could also allege negligence, which is the more typical 

malpractice-based action. To succeed on a civil claim of negligence, individuals who are 

injured must prove that the research sponsors violated a duty of reasonable care or a medical 
ENDNOTES IV

121

standard of care—e.g., by failing to obtain fully informed consent or to minimize the risks of 

dangerous research—and that doing so caused and proximately caused physical or emotional 

injury. Ibid, p. 475; Pike, E. (In press). Recovering from Research: A No-Fault Proposal to 

Compensate Injured Research Participants. American Journal of Law and Medicine. Retrieved 

from http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1923817; Injured research subjects 

may have difficulty recovering under strict liability; the restatement governing products 

liability for drugs and devices requires that risks of harm be foreseeable, a standard that 

injured research subjects may have difficulty satisfying. See Restatement (Third) of Torts: 

Prod. Liab. § 6(c) (1998) (strict products liability for drugs and devices turns on whether the 

risks of harm were foreseeable); Restatement (Third) of Torts: Prod. Liab. § 6, Comment 

g (1998) (“Imposing liability for unforeseeable risks can create inappropriate disincentives 

for the development of new drugs and therapeutic devices.”). See also Hufft v. Horowitz, 4 

Cal. App. 4th 8, 21 (1992) (arguing that the use of the strict liability standard with regards 

to pharmaceutical drugs and devices would be against the public interest because of the 

potential for stifling valuable biomedical research). Moreover, subjects injured as a result of 

participating in federally conducted research may have difficulty recovering due to other 

legal barriers. Pike, E. R. (In press). Recovering from Research: A No-Fault Proposal to 

Compensate Injured Research Participants. American Journal of Law and Medicine. Retrieved 

from http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1923817

112 VA. (2010). VHA Handbook 1200.05, para.31(a)(10)(b) and para. 60. October 15. 

The treatment guarantee is limited to research studies approved by a VA Research & 

Development Committee and conducted under the supervision of VA employees; it does not 

apply to injuries resulting from noncompliance by a subject or to research conducted for VA 

under a contract with an individual or non-VA institution.

113 See 32 C.F.R. 108.4(i); DOD. (2002, March 25). Department of Defense Directive: 

Protections of Human Subjects and Adherence to Ethical Standards in DOD-supported 

Research 3216.02, sec. 5.3.4. DOD. (2007, December 3). Department of Defense Instruction 

6000.08, sec. 6.2.4. DOD-Department of the Army. (1990, January 25). Army Regulation: 

Research and Development- Use of Volunteers as Subjects of Research 70-25, sec. 3-1(k); 

DOD-Department of the Army. (1989, September 1). Army Regulation: Medical Services-

-Clinical Investigation Program 40-38, sec. 3-3(j) and Appendix C; DOD-Department of 

the Navy. (2006, November 6). Human Research Protection Program SECNAV Instruction 

3900.39D, sec. 6(a)(5); DOD-Office of the Under Secretary of Defense (Personnel and 

Readiness), Research Regulatory Oversight Office, Human Research Protection Program, 

Administrative Instruction, sec. 12.2.3, p.17; DOD-Air Force Research Laboratory. (2005, 

May 5). Air Force Instruction: Protection of Human Subjects in Research 40-402, sec. 3.3.2.

114 OHRP. (2006). Sheet 6—Guidelines for Writing Informed Consent Documents. Retrieved 

from http://ohsr.od.nih.gov/info/sheet6.html (accessed December 6, 2011).

115 The federal government also essentially self-insures for civil liability. The Federal Tort Claims 

Act was enacted in 1948. Under the FTCA, the U.S. Government can be found liable 

for a tort, “in the same manner and to the same extent as a private individual under like 

circumstances.” The U.S. Government cannot, however, be liable for punitive damages. 28 

U.S.C. § 2674.
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122

116 In 2010, Medicare provided guidance indicating that Medicare was consider the “secondary 

payer” in the event of other provision for compensation associated with clinical trial injury, 

and as a result, that compensation must be exhausted first before Medicare can be billed for 

care associated with injuries arising from clinical trials. Centers for Medicare and Medicaid 

Services. (n.d.). Medicare Coverage—Clinical Trials: Final National Coverage Decision. 

Retrieved from https://www.cms.gov/clinicalTrialPolicies/Downloads/finalnationalcoverage.

pdf; Centers for Medicare and Medicaid Services. (2010, May 26). Clinical trials and 

liability insurance (including self-insurance), no-fault insurance, and workers’ compensation. 

Retrieved from http://www.cms.gov/. Furthermore, Medicare covers routine costs arising 

from “qualifying clinical trials,” such as conventional care that would be provided even if 

the patient were not enrolled in a clinical trial. Centers for Medicare and Medicaid Services 

(CMS). (n.d.). Medicare Coverage—Clinical Trials: Final National Coverage Decision. 

Retrieved from https://www.cms.gov/clinicalTrialPolicies/Downloads/finalnationalcoverage.

pdf; CMS. (2010, May 26). Clinical Trials and Liability Insurance (Including SelfInsurance), No-Fault Insurance, and Workers’ Compensation. Retrieved from http://www.

cms.gov/MandatoryInsRep/Downloads/AlertClinicalTrailsNGHP.pdf. See also IOM. 

(2000). Extending Medicare Reimbursement in Clinical Trials. Washington, DC: National 

Academy Press.

117 In the last five years, the program has written off approximately $250,000 in healthcare costs 

for care in the UW system and paid about $8,000/year in out-of-pocket compensation. Moe, 

K.E., Director and Assistant Vice Provost for Research, University of Washington. (2011). 

University of Washington Human Subjects Assistance Program. Presentation to the PCSBI, 

November 17. Retrieved from http://bioethics.gov/cms/meeting-seven (accessed December 

6, 2011); The Committee on Human Research, The Human Research Protection Program, 

University of California San Francisco. (2006). UCSF Guidance on Research Topics and 

Issues. Retrieved from http://www.research.ucsf.edu/chr/Guide/chrH_Injury.asp (accessed 

December 6, 2011); Wake Forest University Health Sciences Institutional Review Board. 

(2007). Research Related Injury. Retrieved from http://www.wakehealth.edu/WorkArea/

linkit.aspx? LinkIdentifier=id&ItemID=2126 (accessed December 6, 2011) (describing other 

institutional compensation programs). 

118 NASA provides compensation for subjects through its worker’s compensation system in 

the event of injury related to intramural research (i.e., research performed at NASA, using 

NASA equipment or facilities, or where a NASA employee or on-site contractor serves as 

the principal investigator). See NASA. (2004). NASA Procedural Requirement 7100.1 – 

Protection of Human Research Subjects, secs.9.1.4, 11.6, and Appendix B, Revalidated July 

7, 2008.

119 The language in the consent form is as follows: “All forms of medical research, diagnosis, 

and treatment involve some risk of injury or illness. Despite our high level of precaution, you 

may develop an injury or illness due to participating in this study. If you develop an injury or 

illness determined by the on duty physician to be due to your participation in this research, 

the EPA will reimburse your medical expenses to treat the injury or illness up to $5000.” 

See EPA. (2009, June). Guidance for Human Subjects Research in the National Exposure 

Research Laboratory, EPA 600/R-10/175, sec. 4.1.2.
ENDNOTES IV

123

120 See NIH. (2011, October). Grants Policy Statement. Retrieved from http://grants.nih.gov/

grants/policy/nihgps_2011/nihgps_2011.pdf (noting that “insurance usually is treated as 

an F&A [Facilities and Administration] cost. In certain situations, however, where special 

insurance is required as a condition of the grant because of risks peculiar to the project, 

the premium may be charged as a direct cost if doing so is consistent with organizational 

policy. Medical liability (malpractice) insurance is an allowable cost of research programs 

at educational institutions only if the research involves human subjects. If so, the insurance 

should be treated as a direct cost and assigned to individual grants based on the manner in 

which the insurer allocates the risk to the population covered by the insurance.”).

121 “During a subject’s participation in a trial, the investigator . . . should ensure that reasonable 

medical care is provided to a subject for any adverse events, including clinically significant 

laboratory values, related to the trial participation. . . . Subjects should receive appropriate 

medical evaluation and treatment until resolution of any emergent condition related to the 

study intervention that develops during or after the course of their participation in a study, 

even if the follow-up period extends beyond the end of the study at the investigative site.” 

FDA. (2009, October). Guidance for Industry, Investigator Responsibilities — Protecting the 

Rights, Safety, and Welfare of Study Subjects, p. 7. Retrieved from www.fda.gov/downloads/

Drugs/GuidanceComplianceRegulatory Information/Guidances/UCM187772.pdf.

122 Biotechnology Industry Organization (BIO). (2011). Comments submitted to PCSBI, 

October 28, 2011. (“In the private sector, sponsors are required to obtain clinical trial 

insurance to pay for medical expenses for injured trial participants.”); Francer, J.K. Assistant 

General Counsel, PhRMA. (2011). Presentation to PCSBI, November 16. Retrieved from 

http://bioethics.gov/cms/node/389; Medford, R.M., Chairman and President of Salutria 

Pharmaceuticals. (2011). Presentation to PCSBI, November 16. Retrieved from http://

bioethics.gov/cms/node/389. 

123 See Calabresi, G. (1961, March). Some thoughts on risk distribution and the law of torts. Yale 

Law Journal, 70, 449-553; Latin, H.A. (1985, May). Problem-solving behavior and theories of 

tort liability. California Law Review, 73, 677-746. 

124 The National Childhood Vaccine Injury Act of 1986, Public Law 99-660, 100 Stat. 3743. 

November 14, 1986; Federal Employees’ Compensation Acts Amendments of 1966, Public 

Law 89-488, 80 Stat. 252. July 4, 1966. 

125 Air Transportation Safety and System Stabilization Act, Public Law 107-42, 115 Stat. 230. 

September 22, 2001 (establishing the 9/11 Fund). 

126 Neraas, M.B. (1988). The National Childhood Vaccine Injury Act of 1986: A solution to the 

vaccine liability crisis? Washington Law Review, 63, 149. 

127 For example, a varied system could be left open to a range of reasonable standards. The 

National Childhood Vaccine Injury Act sets forth two standards, one of which claimants 

must satisfy to obtain compensation: claimants requesting compensation for injuries 

listed in the Vaccine Injury Table have a rebuttable presumption of causation, while 

claimants requesting compensation for an off-Table injury must prove causation in fact by a 

preponderance of the evidence. See, e.g., Little, E.A. (2007). The role of special masters in 

off-table vaccination compensation cases: Assuring flexibility over certainty. Federal Circuit 

Bar Journal, 16, 356-57.
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124

128 Porter, J.P. and G. Koski, (2008). Regulations for the protection of humans in research in 

the United States: The Common Rule. In E.J. Emanuel, et al. (Eds.). The Oxford Textbook 

of Clinical Research Ethics. New York, NY: Oxford University Press (pp. 156-167). (stating 

that “imposition of federal regulations to achieve these goals is not considered necessary 

or appropriate by some in the research community... the enthusiasm for these processes is 

dampened by the logistical, administrative, and regulatory burdens they necessarily entail, 

rather than by lack of concern for ethical conduct or well-being of research subjects.”).

129 Brock, W. (2008). Philosophical Justifications of Informed Consent in Research. In E.J. 

Emanuel, et al. (Eds.). The Oxford Textbook of Clinical Research Ethics. New York, NY: 

Oxford University Press (pp. 606-612) (stating “there is always an inherent conflict of goals 

between researchers and participants, a conflict between participants’ typical goal of securing 

their wellbeing and the researchers’ goal of producing knowledge.”). 

130 NIH promulgated new conflict of interest rules in the summer of 2011 citing a need 

based on the increased percentage of research funding by industry, complications created 

by multidisciplinary research teams that involve a larger number of researchers, and 

the increasingly complexity of growing ties between industry and academia. American 

Association of Medical Colleges and Association of American Universities.  (2008).  

Protecting Patients, Preserving Integrity, Advancing Health: Accelerating the Implementation of 

COI Policies in Human Subjects Research; IOM. (2009). Conflict of Interest in Medical Research, 

Education, and Practice.  Washington, DC: National Academies Press; Responsibility of 

Applicants for Promoting Objectivity in Research for which Public Health Service Funding 

is Sought and Responsible Prospective Contractors, 76 Fed. Reg. 53256 (Aug. 25, 2011). (to 

be codified at 42 C.F.R. pt. 50 and pt. 94). 

131 Beecher, H.K. (1966). Ethics and clinical research. New England Journal of Medicine,

274(24), 1354-1360.

132 Prior to promulgation of the Common Rule and other human subjects protections, a 

number of incidents, some deeply disturbing and tragic, demonstrated that relying on 

investigators alone could not ensure a consistent baseline level of safety and respect for the 

interests of research subjects. In 1963, at the Jewish Chronic Disease Hospital in Brooklyn, 

22 elderly patients were injected, without their consent, with live cancer cells. This protocol 

had no relation to the patients’ medical care, and later investigations revealed that consent 

was not sought precisely because researchers wanted to avoid the possibility that patients 

would refuse. See Arras, J. (2011). The Jewish Chronic Disease Hospital Case: A Tragedy in 

Research Ethics. In E.J. Emanuel, et al. (Eds.). The Oxford Textbook of Clinical Research ethics.

New York, NY: Oxford University Press (pp. 73-79); Coleman, C.H. et al (2005). The Ethics 

and Regulation of Research with Human Subjects. Newark, NJ: Lexis Nexis. p. 39; Between 

1956 and 1971, a study at the Willowbrook State School sought to better understand the 

natural history of hepatitis, and the effects of gamma globulin in treating it, by injecting and 

inoculating the physically and cognitively impaired residents of the institution with the virus. 

Coleman, op cit. Later public scrutiny of this work raised deep concerns about the quality 

of consent provided, although, several prominent medical journals weighed in at the time 

commending the researchers for their “judicious use of human beings,” and for benefitting 

the children by “infecting them under carefully controlled conditions and [giving] them 

expert attention.” Coleman, op cit. (quoting The Journal of the American Medical Association 
ENDNOTES IV

125

and the New England Journal of Medicine). Beecher was of course aware of the Brooklyn and 

Willowbrook cases and cited them in his landmark 1966 paper. Though he rejected “rigid 

rules” to govern investigator conduct, his own argument demonstrates the inadequacy of 

relying alone on the virtue of individual investigators. Though Beecher was wrong about 

the need for external constraints, he was decidedly right about the need for an internalized 

professional ethic. The ethical rationale the researchers voiced at the time was that these 

children would have become infected regardless because of the frequency of infection in the 

institution and lack of any known antidote. Similar and distressingly inadequate rationales 

were used to justify the infamous Tuskegee Study, in which impoverished African-American 

sharecroppers were misled and deliberately denied treatment for syphilis so that members 

of the U.S. Public Health Service could study the natural history of the disease. Reverby, S. 

(2009). Examining Tuskegee: The Infamous Syphilis Study and Its Legacy. Chapel Hill, NC: 

University of North Carolina Press.

133 Through encouraging regulatory parsimony, the Commission recommended “only as much 

oversight as is truly necessary to ensure justice, fairness, security, and safety while pursuing 

the public good.” PCSBI. (2010, December). New Directions: The Ethics of Synthetic Biology 

and Emerging Technologies. Washington, DC: PCSBI.

134 PhRMA. (2011, July). PhRMA Principles on Conduct of Clinical Trials: Communication of 

Clinical Trial Results. Retrieved from http://www.phrma.org/sites/default/files/105/042009_

clinical_trial_principles_final.pdf.

135 For example, AstraZeneca has its own code of conduct. AstraZeneca. (2011, February). 

Code of Conduct. Retrieved from http://www.astrazeneca.com/Responsibility/

Code-policies-standards.

136 The Commission recognizes that the phrase “research profession” encompasses many 

different roles. Researchers may be trained in medicine, laboratory science, statistics or other 

fields, each of which has a unique professional culture that provides its members with varying 

instruction in research ethics. The disciplinary diversity endemic in the modern research 

enterprise underscores the need to develop shared professional norms for all who are trusted 

to do research on human subjects.

137 As Atul Gawande discusses in The New Yorker: “There was a moment in sports when 

employing a coach was unimaginable—and then came a time when not doing so was 

unimaginable. We care about results in sports, and if we care half as much about results 

in schools and in hospitals we may reach the same conclusion...We could create coaching 

programs not only for surgeons but for other doctors, too—internists aiming to sharpen 

their diagnostic skills, cardiologists aiming to improve their heart-attack outcomes, and all 

of us who have to figure out ways to use our resources more efficiently. Gawande, A. (2011, 

October 3). Personal Best. The New Yorker. Some of the federal government funding agencies 

currently require ethics training for researchers. For example, NIH requires training in 

the protection of human subjects through NIH-based training or free web-based tutorial 

in human subjects research. NIH. (n.d.). Grants Policy Statement – Part II: Terms and 

Conditions of NIH Grant Awards, Subpart A, Chapter 4.1.15.5. Retrieved from http://grants.

nih.gov/grants/policy/nihgps_2011/nihgps_2011.pdf.

138 Geller, G., et al. (2010). Beyond “compliance”: The role of institutional culture in promoting 

research integrity. Academic Medicine, 85(8), 1296-1302.
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139 For example, see Dr. Ronald Bayer’s talk before the Commission. “I, like everyone else at the 

Mailman School of Public Health have to take an online test to guarantee that I have read 

the right things and understand the right things...I have to tell you, it is the most insulting 

experience to sit in front of a screen, to download a text and then a series of questions to 

which there is only one right answer, and if God forbid you think that there may be an 

ambiguity or an uncertainty, you get the answer wrong. They have to learn something, spit 

it back and give the right answer, and if you don’t get a good enough score, you can’t do 

research, you have to take the test again.” Bayer, R., Professor of Sociomedical Sciences, 

Columbia University. (2011). Implementing Federal Standards – Ethics Issues. Presentation 

to PCSBI, May 19, 2011. Retrieved from http://bioethics.gov/cms/node/229 (accessed 

December 6, 2011).

140 Arras, J.D. (1991, February). Getting down to cases: The revival of casuistry in bioethics. 

Journal of Medicine and Philosophy, 16(1), 29-51; Coutts, M.C. (1991). Teaching ethics in 

the health care setting. Kennedy Institute of Ethics, Scope Note 16. Retrieved from http://

bioethics.georgetown.edu/publications/scopenotes/sn16.pdf; Macrina, F. L. and C. L. 

Munro. (1995). The case-study approach to teaching scientific integrity in nursing and the 

biomedical sciences. Journal of Professional Nursing, 11(1), 40-44. The Commission also plans 

to enlist experts to develop the Guatemalan case study into a teaching resource that could be 

used at the undergraduate level.

141 PCSBI, Research Across Borders, op cit., p. 9.

142 For example, between 1999 and 2003, Congress doubled the NIH’s budget for research and 

development from a 1998 level of $13.6 billion to $27.3 billion. Office of Legislative Policy 

and Analysis. (n.d.). Doubling the NIH Budget in the 107th Congress. Retrieved from http://

olpa.od.nih.gov/legislation/107/pendinglegislation/doubledec.asp (accessed December 6, 

2011). In 2011, the NIH budget was $31.2 billion for research and development. While many 

of these funds are dedicated to research without human subjects, a proportionate increase 

has attached for human subjects research. See NIH. (n.d.). NIH Data Book. Retrieved from 

http://report.nih.gov/nihdatabook (accessed December 6, 2011). See also, for privately 

funded research, Glickman, S. W., et al. (2009). Ethical and scientific implications of the 

globalization of clinical research. The New England Journal of Medicine, 360(8), 816-823; 

Office of the Inspector General. (2001). The Globalization of Clinical Trials: A Growing 

Challenge in Protecting Human Subjects. Boston, MA: HHS. Retrieved from http://oig.hhs.

gov/oei/reports/oei-01-00-00190.pdf.

143 For example, United Kingdom regulations delineate different requirements for continuing 

review than U.S. regulations do, but may protect research subjects just as well. See, e.g., 

Neaton, J., et al. (2010). Regulatory impediments jeopardizing the conduct of clinical trials 

in Europe funded by the National Institutes of Health. Clinical Trials, 7, 705-718.

144 45 C.F.R. § 46.101(a).

145 45 C.F.R. § 46.101(g).

146 45 C.F.R. § 46.101(h).

147 PCSBI, Research Across Borders, op cit., p. 8.
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127

148 SACHRP to The Honorable Kathleen Sebelius. (October 13, 2011). Recommendations 

relative to the Department’s recent Advance Notice of Proposed Rulemaking (ANPRM). 

Washington, DC; Letter from Barbara E. Bierer, Chair, SACHRP, to Kathleen Sebelius, 

Secretary, HHS (August 5, 2011). Retrieved from http://www.hhs.gov/ohrp/sachrp/

commsec/commentspcsbi.pdf.pdf (“The lack of determinations of ‘equivalence’ – and of 

acceptable methods to determine ‘equivalence’ – has led to circumstances in which U.S.-

based researchers and research institutions must insist on foreign entities’ and foreign 

researchers’ strict adherence to what can seem, to them, confusing and even impenetrable 

U.S. regulations and guidance documents. The solution is for the equivalent standard 

regulation to be implemented, as recommended by the Equivalent Protections Working 

Group, the National Bioethics Advisory Commission, and others.”)

149 PCSBI, Research Across Borders, op cit., p. 8.

150 NBAC. (2001). Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries. Bethesda, MD.: NBAC, p. 89.

151 OIG. (2001). The Globalization of Clinical Trials: A Growing Challenge in Protecting Human 

Subjects. Boston, MA: HHS. p. 21. Retrieved from http://oig.hhs.gov/oei/reports/oei-01-00-

00190.pdf.

152 Equivalent Protections Working Group. (2003). Report of the Equivalent Protections Working 

Group. Washington, DC: HHS, p. 9. Retrieved from http://www.hhs.gov/ohrp/international/

epwgreport2003.pdf.

153 Protection of Human Subjects, Proposed Criteria for Determinations of Equivalent 

Protection. 70 Fed. Reg. 15,322-15,327 (March 25, 2005).

154 Protection of Human Subjects: Interpretation of Assurance Requirements. 71 Fed. Reg. 

38,645-38,646 (July 7, 2006).

155 Davies, S., Director General of Research and Development and Chief Scientific Adviser 

for the Department of Health and NHS. (2011). Comments submitted to the PCSBI, 

May 13, 2011. Speaking with the Commission in March 2011, bioethicist Eric Meslin 

described the reaction in Canada to the failure to exercise equivalent protections authority. 

Meslin, E., Director, Indiana University Center for Bioethics. (2011). Social Justice and 

Ethics Issues. Presentation to the Presidential Commission of the Study of Bioethical Issues, 

March 1. Retrieved from http://bioethics.gov/cms/node/161. (“My own home country of 

Canada has an interesting conversation with the U.S. all the time about why it has to satisfy 

FDA and NIH rules when the Tri-Council policy is arguable as good as or better than [U.S. 

rules].”) 

156 21 C.F.R. § 312.120(a)(1); 21 C.F.R. § 814.15; FDA, Guidance for Industry: Acceptance of 

Foreign Clinical Studies (March 2001), Retrieved from http://www.fda.gov/downloads/

RegulatoryInformation/Guidances/ucm124939.pdf (accessed December 2, 2011) (this 

guidance was superseded by 21 C.F.R. § 312.120 in 2008, but remains applicable to device 

clinical trials). FDA policy for foreign clinical trials is nuanced. FDA will not accept data 

from foreign studies that do not conform to good clinical practice in support of drug 

marketing applications, but it will examine such data. 21 C.F.R. §312.120(a)(2). Moreover, 

an applicant for marketing may seek a waiver of “any applicable requirements” (i.e., including 

the consent and independent review requirements) provided the applicant shows one of 
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128

the following: 1) why meeting the requirements is unnecessary or cannot be achieved, 2) 

an alternative course of action that satisfies the purpose of the requirement, or 3) other 

information that justifies a waiver. 21 C.F.R. § 312.120. The FDA, in turn, may grant a 

waiver “if it finds that doing so would be in the interest of the public health.”

157 It may also draw upon the experience of USAID, which recognizes that the standards 

established by the United Nations agencies, such as WHO, as “at least equivalent,” and in 

guidance, sets forth three elements that, if met, could also result in a finding of equivalence. 

22 C.F.R. §225.101(h); USAID. (2006, December 26). Protection of Human Subjects in 

Research Supported by USAID; A Mandatory Reference for ADS Chapter 200. Section 5. 

Retrieved from http://www.usaid.gov/policy/ads/200/200mbe.pdf (accessed December 2, 2011).

158 Horowitz C.R., Robinson M., and S. Seifer. (2009). Community-based participatory 

research from the margin to the mainstream: Are researchers prepared? Circulation, 

119(19), 2633-2842. (explaining that such research “provides a structure and mechanism 

for collaboration and rigorous research, using well-established or emerging methods, with 

a community focus” and that it “challenges researchers to list to, learn from, solicit and 

respect et contributions of, and share power, information and credit for accomplishments 

with the groups that they are trying to learn about and help.”) at 2634; UNAIDS/AVAC. 

(2007). Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials. 

UNAIDS: Geneva; PCSBI, Research Across Borders, op cit., p. 7; Clinical and Translational 

Science Awards Consortium and Community Engagement Key Function Committee 

Task Force on the Principles of Community Engagement. (2010). Principles of Community 

Engagement 2d ed. Bethesda, MD: NIH, pp. 7-17. Retrieved from http://www.atsdr.cdc.gov/

communityengagement/.

159 For further information on the Framingham Heart Study Ethics Advisory Board, see 

http://www.framinghamheartstudy.org/about/index.html (accessed December 6, 2011). 

160 For further information on the community advisory boards of the HIV Vaccine Trials 

Network, see http://www.hvtn.org/community/cab.html. See also National Institute of 

Allergy and Infectious Diseases (NIAID). (2009). Community Recommendations Working 

Group of Community Partners and NIAID, Recommendations for Community Involvement 

in National Institute of Allergy and Infectious Diseases HIV/AIDS Clinical Trials Research. 

Retrieved from http://www.hvtn.org/community/CAB_Recommendations_Certified.

pdf (describing the requirements for community advisory boards in certain NIH-funded 

trials); NIH. (2004). RFA AI-05-001: Leadership for NIH/AIDS Clinical Trials Networks. 

Retrieved from http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-05-001.html (program 

announcement detailing requirements for community advisory boards, community input 

and community representation to include training and education and resources required 

to meet community goals); Woodsong, C., and Q.A. Karim. (2005). A model designed to 

enhance informed consent: Experiences from the HIV Prevention Trials Network. American 

Journal of Public Health, 95(3), 412–419. 

161 Clinical and Translational Science Awards Consortium and Community Engagement Key 

Function Committee Task Force on the Principles of Community Engagement. (2010). 

Principles of Community Engagement, 2d ed. Bethesda, MD: NIH. Retrieved from http://

www.atsdr.cdc.gov/communityengagement/.

162 E.g., the RV144 trial discussed in Chapter 1. 
ENDNOTES IV

129

163 UNAIDS/WHO. (2007). Ethical Considerations in Biomedical HIV Preventative Trials. 

UNAIDS: Geneva; CIOMS. (2009). International Ethical Guidelines for Epidemiological 

Studies. CIOMS: Geneva; Nuffield Council on Bioethics. (2002, April). The Ethics of 

Research Related to Healthcare in Developing Countries, p. 77. Retrieved from http://www.

nuffieldbioethics.org/sites/default/files/Ethics%20of%20research%20related%20to%20 

healthcare%20in%20developing%20countries%20I.pdf.

164 PCSBI, Research Across Borders, op cit., p. 8. 

165 CIOMS. (2009). International Ethical Guidelines for Epidemiological Studies. Geneva: 

CIOMS; Nuffield Council on Bioethics. (2002, April). The Ethics of Research Related to 

Healthcare in Developing Countries. Retrieved from http://www.nuffieldbioethics.org/

sites/default/files/Ethics%20of%20research%20related%20to%20healthcare%20in%20

developing%20countries%20I.pdf. 

166 CIOMS. (2002). International Ethical Guidelines for Biomedical Research Involving Human 

Subjects. Geneva: CIOMS. p. 31.

167 WMA. (2008). The Declaration of Helsinki. Ferney-Voltaire, France: WMA.

168 UNAIDS; UNAIDS/AVAC. (2007). Good Participatory Practice Guidelines for Biomedical 

HIV Prevention Trials. Geneva: UNAIDS; UNAIDS/WHO. (2007). Ethical Considerations 

in Biomedical HIV Preventative Trials. Geneva. 

169 Australia National Health and Medical Research Council. (1991). Guidelines on ethical 

matters in aboriginal and Torres Strait Islander research. Canberra: Commonwealth of 

Australia. Retrieved from http://www.nhmrc.gov.au/guidelines/publications/e11; Medical 

Research Council of Canada, Natural Sciences and Engineering Council of Canada, 

and Social Sciences and Humanities Research Council of Canada. Chapter 9: Research 

Involving the First Nations, Inuit, and Métis peoples of Canada. In Social Sciences and 

Humanities Research Council of Canada. (2010). Tri-Council Policy Statement: Ethical 

Conduct for Research Involving Humans, 2d ed. Ottawa: Public Works and Government. 

Retrieved from http://www.pre.ethics.gc.ca/english/policystatement/introduction.cfm. 

Several of the Common Rule agencies also have policies related to community engagement. 

USAID requires both community involvement and community benefit for any USAIDsupported research. USAID. (Draft, unpublished). Protection of Human Subjects In Research 

Supported by USAID. Attached to e-mail correspondence from Lee Claypool, Bureau for 

Global Health, USAID, to Valerie H. Bonham and Michelle Groman. (2011, June 23). 

The Indian Health Service (IHS) requires Area IRBs to, “determine and appraise the effect 

of research projects on the tribal organizations and Indian communities involved.” Indian 

Health Service (IHS). (n.d.). Indian Health Manual. Part 1, ch.7, sec 1-7.5 (E) Retrieved from 

http://www.ihs.gov/ihm/index.cfm?module =dsp_ihm_pc_p1c7. In addition, the IRBs must 

assess the potential benefits of the proposal for the overall health of American Indians 

and Alaskan Natives.

170 Lavery, J.V., et al. (2010). Towards a framework for community engagement in global 

health research” Trends in Parasitology, 26, 279-283; Tindana, P.O., et al. (2007). Grand 

challenges in global health: Community engagement in research in developing countries. 

PLoS Medicine, 4(9), e273; Weijer, C., and E. J. Emanuel. (2000). Protecting communities 

in biomedical research. Science, 289, 1142-1144.
MORAL SCIENCE Protecting Participants in Human Subjects Research

130

171 Lavery, J.V., op cit. 

172 UNAIDS/AVAC. (2011), op cit.

173 The National Commission for the Protection of Human Subjects of Biomedical and 

Behavioral Research. (1978). The Belmont Report: Ethical Principles and Guidelines for 

the Protection of Human Subjects of Research. Washington, DC: Department of Health, 

Education, and Welfare, DHEW Publication OS 78-0012, p. 9.

174 Ibid, p. 10.

175 See Wertheimer, A. (2008). Exploitation in clinical research. In Emanuel, E.J., et al. (Eds.). 

The Oxford Textbook of Clinical Research Ethics. New York, NY: Oxford University Press, pp. 

201-210.

176 While there was no real effective treatment for syphilis when the study began in 1932, by 

1943 it had been demonstrated that penicillin had the potential to be used as a curative 

agent for syphilis. 

177 The Commission here focuses on the issues of justice. See Brandt, A.M. (1978). Racism 

and research: The case of the Tuskegee syphilis study. The Hastings Center Report, 8(6), 

21-29; King, P.A. (1998). Race, justice, and research. In J.P. Kahn, A.C. Mastroianni, and J. 

Sugarman (Eds.). Beyond Consent: Seeking Justice in Research. New York: Oxford University 

Press, pp. 88-110. (both describing the injustice perpetrated in that case). But, it recognizes 

too that the deception and the lack of any informed consent represented grave ethical 

violations as well.

178 Robert M. Califf, M.D., Vice Chancellor for Clinical Research, Duke University, Professor 

of Medicine, Duke University Medical Center, Director, Duke Translational Medicine 

Institute. (2011). Presentation to the PCSBI, March 1. Retrieved from http://bioethics.gov/

cms/meeting-four; Lawrence Corey, M.D., President and Director, Fred Hutchinson Cancer 

Research Center. Principal Investigator, HIV Vaccine Trials Network, Professor, Laboratory 

Medicine and Medicine, University of Washington. (2011). Presentation to the PCSBI, 

March 1. Retrieved from http://bioethics.gov/cms/meeting-four. 

179 PCSBI. (2011, September). Ethically Impossible. Washington, DC: PCSBI, pp. 94-96. 

(discussing these fundamental principles).

180 Emanuel, E.J., et al. (2004). What makes clinical research in developing countries ethical? 

The benchmarks of ethical research. The Journal of Infectious Diseases, 189, 930-937; 

London, A.J. (2008). Responsiveness to host community health needs. In E.J. Emanuel, 

et al (Eds.). The Oxford Textbook of Clinical Research Ethics. New York, NY: Oxford 

University Press, pp. 737-744.

181 Council for International Organizations and Medical Sciences and World Health 

Organization. (2002). International Ethical Guidelines for Biomedical Research involving 

Human Subjects, Guideline 3 and Guideline 10. Geneva: World Health Organization. 

Guideline 3 states, in part, “The health authorities of the host country, as well as a national 

or local ethical review committee, should ensure that the proposed research is responsive to 

the health needs and priorities of the host country and meets the requisite ethical standards.” 

Guideline 10 states, “Before undertaking research in a population or community with limited 

resources, the sponsor and the investigator must make every effort to ensure that: the research 
ENDNOTES IV

131

is responsive to the health needs and the priorities of the population or community in which 

it is to be carried out; and any intervention or product developed, or knowledge generated, 

will be made reasonably available for the benefit of that population or community.”

182 WMA. (2008). The Declaration of Helsinki, Article 17. Ferney-Voltaire, France: WMA.

183 NBAC. (2001). Ethical and Policy Issues in International Research: Clinical Trials in Developing 

Countries, Recommendation 1.3. Bethesda, MD: NBAC.

184 Ibid; London, A.J., op cit. 

185 Ibid.

186 Shah, S., Wolitz, R., and E.J. Emanuel. (2011). Refocusing the Responsiveness Requirement. 

Bioethics. doi: 10.1111/j.1467-8519.2011.01903.x. 

187 Just-in-time procedures allow specific elements of an application for an NIH grant to be 

submitted later in the application process, such elements may include certification of IRB 

approval if appropriate, or evidence of compliance with the education requirements to 

protect human research participants.  See, e.g., NIH. (2011). NIH Grants Policy Statement, 

Section 2.5.1: Just-in-Time Procedures. Retrieved from http://grants.nih.gov/grants/policy/

nihgps_2011/nihgps_ch2.htm#just_in_time_procedures; NSF. (2011). Grant Proposal 

Guide, January 2011. Retrieved from http://www.nsf.gov/pubs/policydocs/pappguide/

nsf11001/gpgprint.pdf; Kelly, P.A., and M.L. Johnson. (2005). Just-in-time IRB review: 

Capitalizing on scientific merit review to improve human subjects research compliance. IRB: 

Ethics and Human Research, 27(2), 6-10.

188 Glickman, S.W., et al. (2009). Ethical and scientific implications of the globalization of 

clinical research. New England Journal of Medicine, 360(8), 816-823.

189 This section focuses on clinical research because it is the subset of research that most often 

raises concerns about study design. The principles and conclusions described herein may have 

utility for other fields, however, and the Commission reiterates its view that the fundamental 

ethical constraints on research with human subjects apply regardless of location, funding, 

or category. Implementation and understanding of ethical principles may vary across these 

spheres, however.

190 For example, in 2000, Discovery Labs proposed a placebo-controlled Phase 3 trial to test 

the efficacy of a “me-too” surfactant (for the treatment of respiratory distress syndrome in 

premature infants) called Surfaxin in Latin America. Surfactants used for respiratory distress 

syndrome had been shown to decrease infant mortality by 34 percent; however none were 

available in the communities where the study was to be located. The infants in the active arm 

of the proposed trial were to receive Surfaxin, whereas all infants, including in the control 

arm, were to receive endotracheal tubes, ventilators, and antibiotics. In a case study on the 

topic, FDA official Robert Temple asked “why, if everyone in a trial is better off because of 

participation, and no one is denied anything otherwise available to them, the trial is not 

ethically acceptable?” Consumer advocates Peter Laurie and Sidney Wolfe countered that 

“[t]he ethical obligation of the researcher is to obtain needed scientific information in the 

manner most protective of the health of his or her study participants. Given the proven, 

life-saving effectiveness of other surfactants, a placebo-controlled trial could not satisfy this 

requirement, and an active-control trial was mandatory.” Lavery, J.V., et al. (Eds.). (2007). 
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132

Ethical Issues in International Biomedical Research: A Casebook. New York, NY: Oxford 

University Press, pp. 153-159.

191 Ellenberg, S.S. and R. Temple. (2000). Placebo-controlled trials and active-control trials 

in the evaluation of new treatments: Part 1: Ethical and scientific issues. Annals of Internal 

Medicine, 133(6), 455-463. (arguing that “placebo-controlled trials may be ethically 

conducted even when effective therapy exists, as long as patients will not be harmed by 

participation and are fully informed about their alternatives”); Satcher, D. and H. Varmus. 

(1997). Ethical complexities of conducting research in developing countries. New England 

Journal of Medicine 337: 1003-1005.

192 Angell, M. (1997). Ethics of clinical research in the Third World. New England Journal of 

Medicine, 337, 847-849; Lurie, P. and S. Wolfe. (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.

193 Appelbaum, P.S. (1996). Drug-free research in schizophrenia: An overview of the 

controversy. IRB: A Review of Human Subjects Research, 18(1), 1-5. 

194 While some have argued that challenge studies are per se unethical, see Weyers, W. (2003). 

The Abuse of Man: An Illustrated History of Dubious Medical Experimentation. New York, NY: 

Ardor Scribendi, p. 9. (“The best interest of individual human beings and the principle of 

preventing harm were never violated more openly than through experiments that employed 

inoculation, that is the deliberate infection of persons with pathogenic organisms for the 

expressed purpose of producing disease.”), the Academy of Medical Sciences has argued that 

challenge studies are not unique in nature, ethically-speaking, from other study methods and 

may be conducted in an ethical manner under the same ethical standards that govern clinical 

drug trials. The Academy of Medical Sciences (2005, July). Microbial Challenge Studies of 

human volunteers. London: The Academy of Medical Sciences.

195 The Commission recognizes that progress has been made by both scholars and the research 

community in carefully charting the contours of this middle ground, in a way that indicates 

not only where agreement has been forged but also where disagreements remain. Emanuel, 

E.J., and F.G. Miller. (2001). The ethics of placebo-controlled trials—a middle ground. 

New England Journal of Medicine, 345, 915-919; Kimmelman, J., Weijer, C., and E. Meslin. 

(2009). Helsinki discords: FDA, ethics, and international drug trials. The Lancet, 373(9657), 

13-14. Speaking with the Commission in March 2011, philosopher Dan Brock supported 

a middle ground driven by professional mores in this arena. (“[T]he example that we have 

talked about, the standard of care example, is one where I am not sure who has the authority 

to make the law but there could be developed a consensus on a process to evaluate the 

standard of care in different countries and then a consensus that if Merck wants to come in or 

Pfizer wants to come in and do studies there, it has to meet this middle ground that we were 

talking about.”) Brock, D., Director, Division of Medical Ethics, Harvard Medical School. 

(2011). Social Justice and Ethics Issues. Presentation to the Presidential Commission of the 

Study of Bioethical Issues, March 1. Retrieved from http://bioethics.gov/cms/node/161.

196 Emanuel, E.J. and F.G. Miller, op cit.

197 CIOMS. (2002). International Ethical Guidelines for Biomedical Research Involving Human 

Subjects, Commentary on Guideline 11, pp. 56-59. Retrieved from http://www.cioms.ch/
ENDNOTES IV

133

publications/layout_guide2002.pdf; NBAC. (2001, August). Ethical and Policy Issues in 

Research Involving Human Participants, Recommendation 2.2 and 28. Bethesda, MD: NBAC.

198 WMA. (2008). The Declaration of Helsinki. Ferney-Voltaire, France: WMA. The 2008 

Declaration permits some exceptions. It requires that “the benefits, risks, burdens and 

effectiveness of a new intervention must be tested against those of the best current proven 

intervention, except in the following circumstances: (1)The use of placebo, or no treatment, 

is acceptable in studies where no current proven intervention exists; or (2) Where for 

compelling and scientifically sound methodological reasons the use of placebo is necessary 

to determine the efficacy or safety of an intervention and the patients who receive placebo 

or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care 

must be taken to avoid abuse of this option.” See Ibid, Section C(32). By way of background, 

in 2000, the Declaration stated that a new method of treatment should be tested against 

the “best current...methods” of treatment. (There is also a consistent exception in the 

Declaration for when no method of intervention exists.) Concerns were raised that requiring 

the “best current” method of treatment in all studies was over-inclusive and would rule out 

many important clinical trials. For these reasons, in 2002, the WMA approved a “Note of 

Clarification” to their position on placebo-controlled trials stating that a placebo-controlled 

trial might be ethically acceptable if placebo was necessary for “compelling and scientifically 

sound methodological reasons,” or the method under investigation was for a minor condition 

and those subjects receiving placebo would not be exposed to “any additional risk of serious 

or irreversible harm.”

199 Gutmann, A., PCSBI Chair. PCSBI Meeting 7, November 16, 2011. Retrieved from http://

tvworldwide.com/events/bioethics/111116; Hyder, A.A., et al. (2004). Ethical review of 

health research: A perspective from developing country researchers. Journal of Medical Ethics,

30, 68-72; Lemmens, T. (1999). In the name of national security: Lessons from the Final 

Report on the Human Radiation Experiments. European Journal of Health Law, 6(7), 7-23.

200 Angell, M., op cit.

201 See Walach, H. et al. (2006) for the difference between “equipoise” and “clinical equipoise:” 

“[e]quipoise...means that there is no preference based on systematic knowledge for a 

treatment over an alternative or no treatment. Clinical equipoise...refers to the notion that 

there is honest disagreement about the optimal treatment among the medical community 

or between important sectors of the community. Walach, H., et al. (2006). Circular instead 

of hierarchical: methodological principles for the evaluation of complex interventions. BMC 

Medical Research Methodology, 6, 29.

202 Commentators have differing views not only about the ethical source of clinical equipoise but 

also about its scope or the nature of its demands. 

203 Freedman, B. (1990). Placebo-controlled trials and the logic of clinical purpose. IRB: A 

Review of Human Subjects Research, 12(6), 5-6.

204 London, A. J. (2007). Clinical equipoise: Foundational requirement or fundamental error? 

In Steinbock, B. (Ed.) The Oxford Handbook of Bioethics. New York, NY: Oxford University 

Press, pp. 571-596; Kukla, R. (2007). Resituating the principle of equipoise: Justice and 

access to care in non-ideal conditions. Kennedy Institute of Ethics Journal, 17(3), 171-202.
MORAL SCIENCE Protecting Participants in Human Subjects Research

134

205 In their view, an active study design comparing the already validated longer course of AZT 

treatment (the 076 protocol) against the shorter (and less expensive) course designed for 

deployment in the developing world was the only ethical option. See Angell, M. op cit.; 

Lurie, P. and S. Wolfe, op cit.; Connor, E.M, et al. (1994). Reduction of maternal-infant 

transmission of human immunodeficiency virus type 1 with zidovudine treatment. New 

England Journal of Medicine, 331, 1173-80. By contrast, Alex London believes that the critics 

of the short course AZT trial harbor an excessively narrow conception of what factors should 

be held in equipoise (i.e. just mortality data or a larger ‘portmanteau’ conception of equipoise 

that would include local differences such as sustainability, culture, or genetics). London, A. J. 

(2007). Clinical equipoise: Foundational requirement or fundamental error? In Steinbock, B. 

(ed.) The Oxford Handbook of Bioethics. New York, NY: Oxford University Press, pp. 571-596.

206 Hearkening back to Aristotle’s famous dictum that those who are equal in relevant respects 

should receive equal treatment, these critics argued that giving human subjects from poor 

countries a placebo while their better off counterparts in Europe and the United States 

received the full course of AZT constituted a profound moral injustice. In the critics’ 

view, the only theoretical perspective that could possibly justify such disparate treatment 

of patients suffering from the same condition was a dubious “moral relativism” according 

to which what’s true ethically for people at one time and place might differ radically from 

what’s ethically true for people in other circumstances. According to such a view, people 

in rich countries might maintain very high standards of appropriate treatment for research 

subjects, standards which were “true for them,” while people in poor countries might well 

embrace much lower standards of acceptable treatment that were true for them. Another 

way to put this objection is to say that mere differences in socio-economic status should not 

count as morally relevant considerations in the design of clinical trials. See Macklin, R., 

Professor of Bioethics, Department of Epidemiology and Population Health, Albert Einstein 

College of Medicine. (2011). Presentation to PCSBI, August 30, 2011. Retrieved from http://

bioethics.gov/cms/node/321; Angell, M. (1988). Ethical imperialism?: Ethics in international 

collaborative clinical research. New England Journal of Medicine, 319, 1081-1083; Annas, G. 

J. and M. A. Grodin. (1998). Human rights and maternal-fetal HIV transmission prevention 

in Africa. American Journal of Public Health, 88(4), 560-563.

207 See Justifying Site Selection section above.

208 See Justifying Site Selection section above.

209 Many of these population-specific and infrastructure deficiencies were on display in the 

midst of the original perinatal AZT trials. The global state of the art, the 076 protocol, called 

for intravenous delivery of the drug not just at the time of birth but also well before and 

well after. This was an enormous problem in poor African countries where the first contact 

between pregnant women and the health system would usually take place just shortly before 

birth. That protocol also assumed that the women under study would not be breastfeeding 

their newborns and would instead be relying on infant formula, but this proviso would 

have forced these mothers to dilute the formula powder with water from contaminated local 

sources, thus placing their newborn children at grave risk for life-threatening diarrhea. And 

there were also legitimate worries expressed at the time that AZT might well have harmful 

side effects on women who were already plagued with iron deficiencies. On top of all these 

concerns, there was the fact that the 076 protocol, then currently costing roughly $1,000 

per case, was obviously unsustainable economically in the countries hosting the trial, most 
ENDNOTES IV

135

of which spent less than $10 per person per year from their meager public health budgets.  

See Dabis, F., et al. (1999). 6-month efficacy, tolerance, and acceptability of a short regimen 

of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte 

d’Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME 

Study Group. Diminution de la Transmission Mère-Enfant. Lancet, 353, 786-792; Crouch, 

R.A., and J.D. Arras. (1998). AZT trials and tribulations. Hastings Center Report, 28, 26-34; 

Wendler, D., et al. (2004). The standard of care debate: Can research in developing countries 

be both ethical and responsive to those countries’ health needs? American Journal of Public 

Health, 94, 923-928.

210 London, A. J. (2000). The ambiguity and the exigency: Clarifying ‘standard of care’ 

arguments in international research. Journal of Medicine and Philosophy, 25(4), 379-385.

211 The inadequacy of this purported standard is amply demonstrated by the fact that the U.S. 

Public Health Service researchers could have cited it as a justification for giving no treatment 

to poor African-American subjects in the infamous Tuskegee Study, for whom medical 

treatment for syphilis was made unavailable, both before and after the advent of penicillin.

212 Bhutta, Z. A. (2002). Ethics in international health research: A perspective from the 

developing world. Bulletin of the World Health Organization, 80, 117-120. 

213 See Hellman, S., and D.S. Hellman. (1991). Of mice and not men: Problems of the 

randomized clinical trial. New England Journal of Medicine, 324, 1585-1589; Relton, C., et al. 

(2010). Rethinking pragmatic randomised controlled trials: Introducing the “cohort multiple 

randomised controlled trial” design. British Medical Journal, 340, c1066; Truog, R.D. (1992). 

Randomized clinical trials: Lessons from ECMO. Clinical Research, 40(3), 519-522.

214 See “A well-designed study that shows superiority of a treatment to a control (placebo or 

active therapy) provides strong evidence of the effectiveness of the new treatment, limited 

only by the statistical uncertainty of the result. No information external to the trial is needed 

to support the conclusion of effectiveness.” Ellenberg, S.S., and R. Temple. (2000). Placebocontrolled trials and active-control trials in the evaluation of new treatments: Part 1: Ethical 

and scientific issues. Annals of Internal Medicine, 133(6), 455-463.

215 For example, researchers run a trial designed to test the equivalence of drug A (the established 

standard treatment worldwide) against drug B (a new drug that is hopefully as effective but 

also less expensive, or with fewer side effects, etc.) In this trial, drug B proves to be as effective 

as drug A in a head to head comparison without a placebo control. Although the intuitive 

conclusion to draw is that both A and B are equally effective, this might reflect a false positive 

error. Unless there are good reasons to believe that drug A, the established drug, was indeed 

effective in the specific population under study in the trial, it could be that neither drug was 

effective—i.e., that both were equally ineffective. Temple, R., and S.S. Ellenberg, op cit. 

216 Makuch, R., and M. Johnson. (1989). Issues in planning and interpreting active control 

equivalence studies. Journal of Clinical Epidemiology, 42, 503-511; Senn, S. (1993). Inherent 

difficulties with active control equivalence studies. Statistics in Medicine 12(24), 2367-2375; 

Temple, R. and S.S. Ellenberg, op cit.

217 Anderson, J.R. (2001). Perinatal transmission and HIV: An unfinished success story. The 

Hopkins HIV Report, pp. 2-6.
MORAL SCIENCE Protecting Participants in Human Subjects Research

136

218 Emanuel, E. and F.G. Miller. (2001). The ethics of placebo controlled trials: A middle 

ground. New England Journal of Medicine, 345, 915-919; Cubeddu, L.X., et.al. (1990). 

Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea 

and vomiting. New England Journal of Medicine, 322, 810-860.

219 Human Subjects Research Protections: Enhancing Protections for Research Subjects and 

Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,512 (July 

26, 2011).

220 In addition, the Commission submitted comments to OSTP and the Secretary on October 

24, 2011. Amy Gutmann, Chair, and James Wagner, Vice-Chair, to the Honorable John 

Holdren, Assistant to the President for Science and Technology and Director, OSTP, and the 

Honorable Kathleen Sebelius, Secretary, HHS. October 24, 2011.  

221 45 C.F.R. § 46.101.

222 45 C.F.R. § 46.110.

223 45 C.F.R. § 46.101.

224 OHRP. (2003, August). Guidance on Expedited Review Procedures. Retrieved from http://

www.hhs.gov/ohrp/policy/exprev.html. 

225 Human Subjects Research Protections: Enhancing Protections for Research Subjects and 

Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,513 (July 

26, 2011).

226 Ibid.

227 45 C.F.R. § 46.110.

228 Brako, L., Assistant Vice President, University of Michigan, et al. (2011). Federal 

Demonstration Partnership (FDP) Current Initiatives for Reducing Burden of Regulatory 

Compliance [Powerpoint]. Presentation to the Secretary’s Advisory Committee on Human 

Research Protections, March 8, 2011. Retrieved from http://www.hhs.gov/ohrp/sachrp/

mtgings/mtg03-11/20110308fdp_.pdf. The FDP is a cooperative initiative consisting of 10 

federal agencies and approximately 120 other recipients of federal funds (mostly academic 

institutions). 

229 45 C.F.R. § 46.114.

230 Human Subjects Research Protections: Enhancing Protections for Research Subjects 

and Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,513 

(July 26, 2011).

231 45 C.F.R. § 46.116.

232 Human Subjects Research Protections: Enhancing Protections for Research Subjects 

and Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,513 

(July 26, 2011).

233 A recent example of discord between the adaptation of the Common Rule among differing 

agency signatories is EPA’s recent proposed rule on human subjects research involving 

pesticides, a final rule for which is due out in December 2011. Revisions to EPA’s Rule on 

Protections for Subjects in Human Research Involving Pesticides. 76 Fed. Reg. 22, 5735, 
ENDNOTES IV

137

5755 (Feb. 2, 2011). See also, Sean E. Peters, U.S. Nuclear Regulatory Commission, to 

Valerie Bonham (2011, November 9). E-mail Correspondence.

234 For example, the Nuclear Regulatory Commission funds human subjects research but has 

not signed onto the Common Rule. Letter from Brian W. Sheron, Director, Office of Nuclear 

Regulatory Research, NRC, to Valerie H. Bonham, Executive Director, PCSBI. (November 

9, 2011). Scientific Studies Supported by the U.S. Nuclear Regulatory Commission. 

235 Human Subjects Research Protections: Enhancing Protections for Research Subjects 

and Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,513 

(July 26, 2011).

236 PCSBI. (2011, August). Research Across Borders. Washington, DC: PCSBI, p. 11.

237 Human Subjects Research Protections: Enhancing Protections for Research Subjects 

and Reducing Burden, Delay, and Ambiguity for Investigators, 76 Fed. Reg. 143, 44,513 

(July 26, 2011).

238 Ibid.

239 PCSBI, Research Across Borders, op cit., p. 10.

240 In 1977, the Task Force on the Compensation of Injured Research Subjects produced a 

report finding that subjects involved in research supported by the U.S. Public Health Service 

should be compensated for injury going above and beyond that caused by any underlying 

illness that the subject might be experiencing. Secretary’s Task Force on the Compensation 

of Injured Research Subjects. (1977). Final Report. Washington, D.C.: Department of 

Health, Education, and Welfare. HEW Secretary Caspar Weinberger convened the Task 

Force in 1975 in response to a memorandum from Theodore Cooper, M.D., Acting Assistant 

Secretary for Health, which outlined several ways in which the issue of compensation for 

research-related injury might be addressed. Memorandum from Theodore Cooper, Acting 

Assistant Secretary for Health, to Caspar Weinberger, Secretary of DHEW. February 25, 

1975 (describing possible responses including: requiring grantees and contractors to provide 

assurance that they would compensate subjects injured in the course of research; establishing 

a no-fault compensation fund to compensate subjects for research-related injury; defining 

research subjects as federal employees for the purposes of the Federal Employees Worker’s 

Compensation Act, 5 U.S.C. 8101 et seq.; and developing a federal “re-insurance” program 

that would provide assistance to institutions that were insured or self-insured if their 

liability went over a certain fixed amount). See also the Presidential Commission for the 

Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. (1982). 

Compensating for Research Injuries. Washington, D.C.: U.S. Government Printing Office 

(recommending that HHS conduct a pilot study to determine the need for and feasibility of 

creating a program to provide compensation for injured research subjects).
MORAL SCIENCE Protecting Participants in Human Subjects Research

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139

APPENDICES
MORAL SCIENCE Protecting Participants in Human Subjects Research

140

Appendix I: Human Subjects Research Landscape Project: Scope and 

Volume of Federally Supported Human Subjects Research

Table Title

I.1 Departments/Agencies and HHS Operating Divisions

I.2 Extramural Human Subjects Projects Over Time

I.3 Intramural Human Subjects Projects Over Time

I.4 HHS Human Subjects Projects Over Time

I.5 HHS Extramural Human Subjects Projects Over Time

I.6 HHS Intramural Human Subjects Projects Over Time

I.7 Location of Human Subjects Projects Over Time

I.8 Location of HHS Human Subjects Projects Over Time

I.9 Total Extramural Award Funding (Human Subjects Projects) Over 

Time

I.10 Total HHS Extramural Award Funding (Human Subjects Projects) 

Over Time

I.11 Top 20 (of 117) Human Subjects Project Site Countries 

by Number of Projects, FY10

I.12 Top 20 (of 68) Extramural Awardee Institution Countries 

by Number of Human Subjects Projects, FY10 

I.13 Location of Unique Extramural (Human Subjects Projects) Awardee 

Institutions, FY10

I.14 Proportion of Extramural Human Subjects Projects with 

Known Award Amounts 

I.15 Proportion of Human Subjects Projects with Known Site Country 

I.16 Proportion of HHS Human Subjects Projects with Known 

Site Country 

I.17 Proportion of Human Subjects Projects with Known Subject Count

I.18 Proportion of Human Subjects Projects with Known Exempt/

Non-exempt Status

I.19 Proportion of Human Subjects Projects with Known Number of Sites
APPENDIX I: V

141

Table I.1 Department/Agencies and HHS Operating Divisions

Departments and Agencies that Received Data Request

DEPARTMENT/AGENCY ABBREVIATION

Agency for International Development USAID

Central Intelligence Agency CIA

Consumer Product Safety Commission CPSC

Department of Agriculture USDA

Department of Commerce DOC

Department of Defense DOD

Department of Education ED

Department of Energy DOE

Department of Health and Human Services HHS

Department of Homeland Security DHS

Department of Housing and Urban Development HUD

Department of Justice DOJ

Department of Transportation DOT

Department of Veterans Affairs VA

Environmental Protection Agency EPA

National Aeronautics and Space Administration NASA

National Science Foundation NSF

Social Security Administration SSA

HHS Operating Divisions

UNIT ABBREVIATION 

Agency for Healthcare Research and Quality AHRQ

Assistant Secretary for Preparedness and Response ASPR

Centers for Disease Control and Prevention CDC

Centers for Medicare & Medicaid Services CMS

Food and Drug Administration FDA

Health Resources and Services Administration HRSA

Indian Health Service IHS

National Institutes of Health NIH

National Vaccine Program Office NVPO

Office of Adolescent Health OAH

Office of Population Affairs OPA

Substance Abuse and Mental Health Services Administration SAMHSA

Scope and Volume of Federally Supported Human Subjects Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

142

Table I.2 Extramural Human Subjects Projects Over Time†

DEPARTMENT/

AGENCY 

FY06 FY07 FY08 FY09 FY10 MEAN

HHS 21,676 21,491 20,929 22,309 22,322 21,745

DOD 2,976 2,946 2,925 1,890 2,107 2,569

NSF 1,820 2,271 2,627 2,988 3,051 2,551

ED 222 1,145 1,199 1,296 1,969 1,166

USDA 68 75 178 167 231 144

DOJ 95 107 74 125 188 118

USAID 159 157 106 64 62 110

DOE 88 70 72 60 52 68

EPA 29 29 35 17 40 30

DHS‡ N/R 19 30 23 10 22

NASA 8 15 17 23 26 18

SSA 10 18 17 14 13 14

HUD 7 11 7 18 18 12

DOT 4 8 11 18 19 12

DOC 11 8 13 10 10 10

CPSC 0 0 0 0 1 0

VA 0 0 0 0 0 0

CIA§ N/R N/R N/R N/R N/R

Total 27,173 28,370 28,240 29,022 30,119

†

 “Extramural” includes projects conducted solely extramurally and projects with an extramural component. 

“Projects” include awards and individual studies. “N/R” means that the data were not reported to the Commission. 

Departments/agencies that appear italicized reported that they were unable to provide complete data. See Appendix II 

for additional detail. ‡

 DHS reported that there “are no earlier data” than FY07. Mean is of reported years.

§

 The CIA did not submit project-level data to the Commission’s database because these data are confidential (although 

not classified).
APPENDIX I: V

143

Table I.3 Intramural Human Subjects Projects Over Time†

DEPARTMENT/

AGENCY 

FY06 FY07 FY08 FY09 FY10 MEAN

VA 16,763 16,731 16,706 16,383 15,415 16,400

HHS 3,599 4,209 4,239 4,203 4,329 4,116

DOD 3,542 3,611 3,961 4,389 4,977 4,096

DOE 319 298 299 288 311 303

NASA 75 89 104 110 110 98

USDA 50 47 42 34 41 43

DOT 22 18 24 29 37 26

DOJ 25 11 12 15 28 18

DOC 10 18 21 17 13 16

EPA 7 12 8 4 6 7

CPSC 1 1 2 1 0 1

DHS‡ N/R 3 0 1 0 1

SSA 5 0 0 0 0 1

USAID 0 0 0 0 0 0

ED 0 0 0 0 0 0

HUD 0 0 0 0 0 0

NSF 0 0 0 0 0 0

CIA§ N/R N/R N/R N/R N/R N/R

Total 24,418 25,048 25,418 25,474 25,267

†

 “Projects” include awards and individual studies. “N/R” means that the data were not reported to the Commission. 

Departments/agencies that appear italicized reported that they were unable to provide complete data. See Appendix II 

for additional detail. ‡

 DHS reported that there “are no earlier data” than FY07. Mean is of reported years.

§

 The CIA did not submit project-level data to the Commission’s database because these data are confidential (although 

not classified).

Scope and Volume of Federally Supported Human Subjects Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

144

Table I.4 HHS Human Subjects Projects Over Time†

UNIT FY06 FY07 FY08 FY09 FY10 MEAN

NIH 22,396 23,210 22,709 24,028 23,891 23,247

CDC 1,739 1,387 1,380 1,334 1,317 1,431

AHRQ 668 634 598 655 898 691

IHS 254 277 238 239 251 252

FDA 90 103 122 192 200 141

HRSA 47 51 50 43 35 45

OAH‡ x x x x 31 31

NVPO 61 14 39 0 0 23

OPA 12 16 22 17 16 17

ASPR 8 8 10 4 12 8

CMS 0 0 0 0 0 0

SAMHSA 0 0 0 0 0 0

Total 25,275 25,700 25,168 26,512 26,651

†

 “Projects” include awards and individual studies. See Appendix II for additional detail.

‡

 OAH was established in 2010. Mean is of reported years.
APPENDIX I: V

145

Table I.5 HHS Extramural Human Subjects Projects Over Time†

UNIT FY06 FY07 FY08 FY09 FY10 MEAN

NIH 20,632 20,526 19,922 21,255 21,006 20,668

AHRQ 562 550 517 574 830 607

CDC 277 251 289 310 304 286

FDA 67 66 71 93 74 74

HRSA 44 47 46 40 31 42

OAH‡ x x x x 31 31

NVPO 61 14 39 0 0 23

OPA 12 16 22 17 16 17

IHS 13 13 13 16 18 15

ASPR 8 8 10 4 12 8

CMS 0 0 0 0 0 0

SAMHSA 0 0 0 0 0 0

Total 21,676 21,491 20,929 22,309 22,322

†

 “Extramural” includes projects conducted solely extramurally and projects with an extramural component. 

“Projects” include awards and individual studies. See Appendix II for additional detail. ‡

 OAH was established in 2010. Mean is of reported years.

Scope and Volume of Federally Supported Human Subjects Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

146

Table I.6 HHS Intramural Human Subjects Projects Over Time†

UNIT FY06 FY07 FY08 FY09 FY10 MEAN

NIH 1,764 2,684 2,787 2,773 2,885 2,579

CDC 1,462 1,136 1,091 1,024 1,013 1,145

IHS 241 264 225 223 233 237

AHRQ 106 84 81 81 68 84

FDA 23 37 51 99 126 67

HRSA 3 4 4 3 4 4

ASPR 0 0 0 0 0 0

CMS 0 0 0 0 0 0

NVPO 0 0 0 0 0 0

OAH‡ x x x x 0 0

OPA 0 0 0 0 0 0

SAMHSA 0 0 0 0 0 0

Total 3,599 4,209 4,239 4,203 4,329

† “Projects” include awards and individual studies. See Appendix II for additional detail. ‡ OAH was established in 2010. Mean is of reported years.
V

147

Table I.7 Location of Human Subjects Projects Over Time†

DEPARTMENT/

AGENCY 

LOCATION FY06 FY07 FY08 FY09 FY10

CIA‡

Domestic N/R N/R N/R N/R N/R

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

CPSC

Domestic 1 1 2 1 1

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

DHS§

Domestic N/R 20 26 23 10

Foreign N/R 2 4 1 0

Mixed N/R 0 0 0 0

Unknown N/R 0 0 0 0

DOC

Domestic 21 26 34 27 23

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

DOD

Domestic 2,451 4,904 4,775 5,082 6,787

Foreign 203 379 368 255 265

Mixed 2 6 5 8 30

Unknown 3,862 1,268 1,738 934 2

DOE

Domestic 391 356 356 334 348

Foreign 14 10 13 12 14

Mixed 2 2 2 2 1

Unknown 0 0 0 0 0

† “Projects” include awards and individual studies. “Mixed” means projects with both domestic and foreign 

components. “N/R” means that the data were not reported to the Commission. Departments/agencies that appear 

italicized reported that they were unable to provide complete data. See Appendix II for additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified), but the agency did advise the Commission that all of its human subjects research 

takes place in the United States. § DHS reported that there “are no earlier data” than FY07.

APPENDIX I: Scope and Volume of Federally Supported Human Subjects Research

continued
MORAL SCIENCE Protecting Participants in Human Subjects Research

148

DEPARTMENT/

AGENCY 

LOCATION FY06 FY07 FY08 FY09 FY10

DOJ

Domestic 118 118 86 140 215

Foreign 0 0 0 0 1

Mixed 0 0 0 0 0

Unknown 2 0 0 0 0

DOT

Domestic 26 26 35 47 56

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

ED

Domestic 114 1,067 1,104 1,151 1,538

Foreign 0 6 30 65 115

Mixed 0 0 0 0 0

Unknown 108 72 65 80 316

EPA

Domestic 32 39 37 20 44

Foreign 4 2 6 1 2

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

HHS

Domestic 24,176 23,173 22,303 23,633 23,539

Foreign 370 401 474 503 481

Mixed 654 854 1085 1,375 1,577

Unknown 75 1,272 1,306 1,001 1,054

HUD

Domestic 7 11 7 18 18

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

NASA

Domestic 74 104 120 132 133

Foreign 0 0 1 1 1

Mixed 0 0 0 0 0

Unknown 9 0 0 0 2

† “Projects” include awards and individual studies. “Mixed” means projects with both domestic and foreign 

components. “N/R” means that the data were not reported to the Commission. Departments/agencies that appear 

italicized reported that they were unable to provide complete data. See Appendix II for additional detail.

Table I.7 Location of Human Subjects Projects Over Time†
V

149

DEPARTMENT/

AGENCY 

LOCATION FY06 FY07 FY08 FY09 FY10

NSF

Domestic 1,820 2,271 2,626 2,984 3,049

Foreign 0 0 1 4 2

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

SSA

Domestic 15 18 17 14 13

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

USAID

Domestic 26 28 20 15 14

Foreign 126 121 82 44 45

Mixed 7 8 4 1 3

Unknown 0 0 0 4 0

USDA

Domestic 111 118 193 198 258

Foreign 4 3 5 2 5

Mixed 1 1 17 1 4

Unknown 2 0 5 0 5

VA¶

Domestic 0 0 0 0 0

Foreign 0 0 0 0 0

Mixed 0 1 2 4 9

Unknown 16,763 16,730 16,704 16,379 15,406

All

Domestic 29,383 32,280 31,741 33,819 36,046

Foreign 721 924 984 888 931

Mixed 666 872 1115 1391 1624

Unknown 20,821 19,342 19,818 18,398 16,785 

Total 51,591 53,418 53,658 54,496 55,386

† “Projects” include awards and individual studies. “Mixed” means projects with both domestic and foreign 

components. “N/R” means that the data were not reported to the Commission. Departments/agencies that appear 

italicized reported that they were unable to provide complete data. See Appendix II for additional detail. ¶ Although most VA research normally takes place in the United States, VA did not have data to assure the 

Commission that all of its research for which it did not specify a site country took place domestically. 

APPENDIX I: Scope and Volume of Federally Supported Human Subjects Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

150

Table I.8 Location of HHS Human Subjects Projects Over Time†

UNIT LOCATION FY06 FY07 FY08 FY09 FY10

AHRQ

Domestic 668 634 598 655 893

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 5

ASPR

Domestic 2 3 4 1 4

Foreign 2 0 0 2 0

Mixed 1 2 0 0 0

Unknown 3 3 6 1 8

CDC

Domestic 1,637 1,264 1,182 1,078 1,077

Foreign 85 104 177 235 220

Mixed 16 17 21 21 20

Unknown 1 2 0 0 0

CMS

Domestic 0 0 0 0 0

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

FDA

Domestic 85 102 121 191 200

Foreign 2 1 1 1 0

Mixed 0 0 0 0 0

Unknown 3 0 0 0 0

HRSA

Domestic 45 50 50 43 35

Foreign 0 0 0 0 0

Mixed 2 1 0 0 0

Unknown 0 0 0 0 0

IHS

Domestic 254 277 238 239 251

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

† “Projects” include awards and individual studies. “Mixed” means projects with both domestic and foreign 

components. See Appendix II for additional detail.
V

151

UNIT LOCATION FY06 FY07 FY08 FY09 FY10

NIH

Domestic 21,473 20,827 20,088 21,409 21,033

Foreign 281 296 296 265 261

Mixed 635 834 1,064 1,354 1,557

Unknown 7 1,253 1,261 1,000 1,040

NVPO

Domestic 0 0 0 0 0

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 61 14 39 0 0

OAH‡

Domestic x x x x 30

Foreign x x x x 0

Mixed x x x x 0

Unknown x x x x 1

OPA

Domestic 12 16 22 17 16

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

SAMHSA

Domestic 0 0 0 0 0

Foreign 0 0 0 0 0

Mixed 0 0 0 0 0

Unknown 0 0 0 0 0

All

Domestic 24,176 23,173 22,303 23,633 23,539

Foreign 370 401 474 503 481

Mixed 654 854 1,085 1,375 1,577

Unknown 75 1,272 1,306 1,001 1,054 

Total 25,275 25,700 25,168 26,512 26,651

† “Projects” include awards and individual studies. “Mixed” means projects with both domestic and foreign 

components. See Appendix II for additional detail. ‡ OAH was established in 2010. 

APPENDIX I: Scope and Volume of Federally Supported Human Subjects Research
MORAL SCIENCE Protecting Participants in Human Subjects Research

152

Table I.9 Total Extramural Award Funding (Human Subjects Projects) Over Time (in $)†

DEPARTMENT/

AGENCY 

FY06 FY07 FY08 FY09‡ FY10‡

CIA§ N/R N/R N/R N/R N/R

CPSC 0 0 0 0 612,662

DHS¶ N/R 0 0 0 0

DOC 1,575,482 819,419 1,735,902 1,609,793 3,389,309

DOD 162,285 0 0 0 0

DOE 46,865,718 52,400,201 44,218,307 46,772,089 34,528,425

DOJ 51,306,495 57,291,788 33,820,452 63,808,343 113,365,616

DOT 5,268,756 20,410,017 3,304,967 14,373,087 4,125,572

ED 151,777,538 611,483,875 705,112,958 802,093,966 1,120,977,802

EPA 27,280,526 14,764,372 43,740,633 18,018,128 22,252,025

HHS 12,140,348,243 13,025,906,747 11,727,308,402 13,543,732,524 14,172,966,147

HUD 3,863,530 7,196,379 3,570,404 10,889,720 15,503,513

NASA 2,075,000 3,100,000 3,822,000 4,858,000 6,583,124

NSF 475,612,817 639,525,864 774,954,954 998,513,105 1,013,447,119

SSA 33,676,780 31,367,788 31,078,994 23,642,888 16,039,115

USAID 39,023,094 34,526,585 36,113,044 30,310,172 32,660,180

USDA 18,859,721 25,786,633 81,409,010 58,552,343 98,614,148

VA 0 0 0 0 0

Total 12,997,695,985 14,524,579,668 13,490,190,027 15,617,174,158 16,655,064,757

† The total, de-duplicated funding amount was calculated as described in the methods. “N/R” means that the data 

were not reported to the Commission. Departments/agencies that appear italicized reported that they were unable to 

provide complete extramural funding data. See Appendix II for additional detail. ‡ FY09 and FY10 funding includes American Recovery and Reinvestment Act (ARRA) funding. § The CIA did not submit project-level data to the Commission’s database because these data are confidential (although 

not classified). ¶ DHS reported that there “are no earlier data” than FY07.
V

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Table I.10 Total HHS Extramural Award Funding (Human Subjects Projects) 

Over Time (in $)†

UNIT FY06 FY07 FY08 FY09‡ FY10‡

AHRQ 103,132,977 85,009,499 84,190,585 108,927,568 501,164,798

ASPR 1,295,992,119 1,333,999,855 329,190,000 254,329,277 372,039,662

CDC 0 7,213,883 7,213,883 0 840,000

CMS 0 0 0 0 0

FDA 12,840,244 16,527,562 14,048,750 13,008,554 16,947,213

HRSA 24,066,586 28,774,579 28,678,683 25,630,790 24,879,696

IHS 1,935,769 1,794,339 1,906,226 2,384,267 3,055,331

NIH 10,684,023,688 11,547,265,574 11,251,479,555 13,136,308,827 13,206,860,106

NVPO 15,994,885 2,275,174 6,320,016 0 0

OAH§ x x x x 44,018,655

OPA 2,361,975 3,046,282 4,280,704 3,143,241 3,160,686

SAMHSA 0 0 0 0 0

Total 12,140,348,243 13,025,906,747 11,727,308,402 13,543,732,524 14,172,966,147

† The total, de-duplicated funding amount was calculated as described in the methods. Departments/agencies that 

appear italicized reported that they were unable to provide complete extramural funding data. See Appendix II for 

additional detail. ‡ FY09 and FY10 funding includes American Recovery and Reinvestment Act (ARRA) funding. § OAH was established in 2010.

APPENDIX I: Scope and Volume of Federally Supported Human Subjects Research
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Table I.11 Top 20 (of 117) Human Subjects Project Site Countries by Number of 

Projects, FY10†

SITE COUNTRY USAID CIA‡ CPSC USDA DOC DOD ED DOE HHS

United States 17 N/R 1 262 23 6,858 1,538 349 25,121

Canada 2 22 1 3 86

Peru 1 69 4 1 14

Kenya 8 1 10 3 53

Egypt 61 3

South Africa 13 5 2 30

United Kingdom 2 14 3 28

Uganda 12 1 28

India 8 7 25

China 1 2 10 2 21

Thailand 12 1 1 16

Australia 1 8 15

Bangladesh 4 1 19

Brazil 3 3 16

Tanzania 4 1 5 8

Malawi 5 1 11

Indonesia 1 11 1

France 5 3 4

Mexico 1 1 1 4 3

Sweden 6 2 4

Foreign 1,557

Blank or N/A¶ 5 2 316 1,054
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APPENDIX I: Scope and Volume of Federally Supported Human Subjects Research

DHS HUD DOJ DOT VA EPA NASA NSF SSA TOTAL

United States 10 18 215 56 9 44 133 3,049 13 37,716

Canada 1 2 117

Peru 1 90

Kenya 75

Egypt 64

South Africa 1 51

United Kingdom 1 48

Uganda 41

India 40

China 36

Thailand 1 31

Australia 24

Bangladesh 24

Brazil 1 1 24

Tanzania 1 19

Malawi 17

Indonesia 13

France 12

Mexico 2 12

Sweden 12

Foreign 1,557

Blank or N/A¶ 15,406§ 2 16,785

†

 “Projects” include awards and individual studies. Departments/agencies that appear italicized reported that they 

were unable to provide complete extramural funding data. See Appendix II for additional detail ‡

 “N/R” means that the data were not reported to the Commission. The CIA did not submit project-level data to the 

Commission’s database because these data are confidential (although not classified), but the agency did advise the 

Commission that all of its human subjects research takes place in the United States. §

 Although most VA research normally takes place in the United States, VA did not have data to assure the Commission 

that all of its research for which it did not specify a site country took place domestically. ¶

 “Blank” and “N/A” mean that the department/agency did not report a site country. See Appendix II for additional detail.
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Table I.12 Top 20 (of 68) Extramural Awardee Institution Countries 

by Number of Human Subjects Projects, FY10†

INSTITUTION COUNTRY TOTAL

United States 29,142

Canada 94

United Kingdom 34

Australia 19

China 16

South Africa 15

Bangladesh 14

Germany 11

India 11

New Zealand 11

France 10

Netherlands 10

Switzerland 10

Brazil 9

Kenya 9

Sweden 9

Israel 8

Peru 8

Uganda 7

Thailand 6

Invalid, N/A, or Unknown‡ 607

† “Projects” include awards and individual studies. See Appendix II for additional detail. ‡ “Invalid” means that text other than an institution name was entered in the “Institution 

name” column; “N/A” means that an institution name field was left blank; and “Unknown” 

means that the location of the awardee institution could not be determined with certainty, 

e.g., if an individual was listed as the awardee.
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Table I.13 Location of Unique Extramural (Human Subjects Projects) Awardee 

Institutions, FY10†

LOCATION TOTAL

United States 2,867

Foreign 189

Invalid, N/A, or Unknown‡ 60

Total 3,116

† “Projects” include awards and individual studies. See Appendix II for additional detail. ‡ “Invalid” means that text other than an institution name was entered in the “Institution name” column; “N/A” means 

that an institution name field was left blank; and “Unknown” means that the location of the awardee institution could 

not be determined with certainty, e.g., if an individual was listed as the awardee.

Table I.14 Proportion of Extramural Human Subjects Projects with Known Award Amounts†

DEPARTMENT/AGENCY FY06 FY07 FY08 FY09 FY10

CIA‡ N/R N/R N/R N/R N/R

CPSC — — — — 1.000

DHS§ N/R 0.000 0.000 0.000 0.000

DOC 1.000 1.000 1.000 1.000 1.000

DOD 0.001 0.000 0.000 0.000 0.000

DOE 1.000 1.000 1.000 1.000 1.000

DOJ 1.000 1.000 1.000 1.000 1.000

DOT 1.000 1.000 1.000 1.000 1.000

ED 0.468 0.789 0.791 0.776 0.585

EPA 1.000 1.000 1.000 1.000 1.000

HHS 0.986 0.988 0.985 0.984 0.986

HUD 1.000 1.000 1.000 1.000 1.000

NASA 1.000 0.867 1.000 0.957 1.000

NSF 1.000 1.000 1.000 1.000 1.000

SSA 1.000 1.000 1.000 1.000 1.000

USAID 1.000 1.000 1.000 1.000 1.000

USDA 1.000 1.000 1.000 1.000 1.000

VA — — — — —

Weighted Average 0.875 0.878 0.876 0.912 0.892

† “Extramural” includes projects conducted solely extramurally and projects with an extramural component; “Projects” 

include awards and individual studies; “Known” means “Total Award $” is not N/A, NULL, or an “invalid” $0, i.e., 

a $0 indicating that the Department/Agency cannot link funding and project data. “—” means that the proportion 

is undefined because the denominator is 0. “N/R” means that the data were not reported to the Commission. See 

Appendix II for additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified). § DHS reported that there “are no earlier data” than FY07.

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Table I.15 Proportion of Human Subjects Projects with Known Site Country†

DEPARTMENT/AGENCY FY06 FY07 FY08 FY09 FY10

CIA‡ N/R N/R N/R N/R N/R

CPSC 1.000 1.000 1.000 1.000 1.000

DHS§ N/R 1.000 1.000 1.000 1.000

DOC 1.000 1.000 1.000 1.000 1.000

DOD 0.407 0.807 0.748 0.851 1.000

DOE 1.000 1.000 1.000 1.000 1.000

DOJ 0.983 1.000 1.000 1.000 1.000

DOT 1.000 1.000 1.000 1.000 1.000

ED 0.514 0.937 0.946 0.938 0.840

EPA 1.000 1.000 1.000 1.000 1.000

HHS 0.997 0.951 0.948 0.962 0.960

HUD 1.000 1.000 1.000 1.000 1.000

NASA 0.892 1.000 1.000 1.000 0.985

NSF 1.000 1.000 1.000 1.000 1.000

SSA 1.000 1.000 1.000 1.000 1.000

USAID 1.000 1.000 1.000 0.938 1.000

USDA 0.983 1.000 0.977 1.000 0.982

VA 0.000 0.000 0.000 0.000 0.001

Weighted Average 0.596 0.638 0.631 0.662 0.697

† “Projects” include awards and individual studies; “Known” means the entry in the “Site Country” field is not N/A, 

NULL, or blank. Note that a response of “Foreign” is considered “Known” in this report. “N/R” means that the data 

were not reported to the Commission. See Appendix II for additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential (although 

not classified). § DHS reported that there “are no earlier data” than FY07.
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Table I.16 Proportion of HHS Human Subjects Projects with Known Site Country†

UNIT FY06 FY07 FY08 FY09 FY10

AHRQ 1.000 1.000 1.000 1.000 0.994

ASPR 0.625 0.625 0.400 0.750 0.333

CDC 0.999 0.999 1.000 1.000 1.000

FDA 0.967 1.000 1.000 1.000 1.000

HRSA 1.000 1.000 1.000 1.000 1.000

IHS 1.000 1.000 1.000 1.000 1.000

NIH 1.000 0.946 0.944 0.958 0.956

NVPO 0.000 0.000 0.000 — —

OAH‡ x x x x 0.968

OPA 1.000 1.000 1.000 1.000 1.000

Weighted Average 0.997 0.951 0.948 0.962 0.960

† “Projects” include awards and individual studies; “Known” means the entry in the “Site Country” field is not N/A, 

NULL, or blank. Note that a response of “Foreign” is considered “Known” in this report. “—” means that the 

proportion is undefined because the denominator is 0. See Appendix II for additional detail. ‡ OAH was established in 2010. 

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Table I.17 Proportion of Human Subjects Projects with Known Subject Count†

DEPARTMENT/AGENCY FY06 FY07 FY08 FY09 FY10

CIA‡ N/R N/R N/R N/R N/R

CPSC 1.000 1.000 1.000 1.000 1.000

DHS§ N/R 0.000 0.000 0.000 0.000

DOC 0.857 0.846 0.853 0.852 0.870

DOD 0.000 0.001 0.005 0.005 0.005

DOE 0.867 0.905 0.908 0.914 0.950

DOJ 0.125 0.161 0.291 0.164 0.097

DOT 0.577 0.346 0.429 0.404 0.411

ED 0.000 0.000 0.000 0.000 0.000

EPA 0.167 0.220 0.256 0.143 0.000

HHS 0.073 0.075 0.083 0.084 0.085

HUD 0.000 0.000 0.000 0.000 0.000

NASA 0.108 0.144 0.215 0.203 0.787

NSF 0.000 0.000 0.000 0.000 0.000

SSA 1.000 1.000 1.000 1.000 1.000

USAID 0.126 0.121 0.179 0.375 0.403

USDA 0.525 0.492 0.350 0.398 0.706

VA 0.000 0.000 0.000 0.000 0.000

Weighted Average 0.046 0.046 0.050 0.051 0.055

† “Projects” include awards and individual studies; “Known” means the entry in the “# Participants” field is not N/A, 

NULL, or blank. “N/R” means that the data were not reported to the Commission. See Appendix II for additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential (although 

not classified). § DHS reported that there “are no earlier data” than FY07.
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Table I.18 Proportion of Human Subjects Projects with Known Exempt/

Non-exempt Status†

DEPARTMENT/AGENCY FY06 FY07 FY08 FY09 FY10

CIA‡ N/R N/R N/R N/R N/R

CPSC 0.000 0.000 0.000 0.000 0.000

DHS§ N/R 1.000 1.000 1.000 1.000

DOC 1.000 1.000 1.000 1.000 1.000

DOD 0.666 0.878 0.901 0.854 0.839

DOE 1.000 1.000 1.000 1.000 1.000

DOJ 0.467 0.432 0.512 0.414 0.472

DOT 0.385 0.269 0.200 0.277 0.268

ED 0.910 0.130 0.158 0.164 0.396

EPA 1.000 1.000 1.000 1.000 1.000

HHS 0.033 0.035 0.035 0.036 0.041

HUD 0.714 0.909 0.857 0.944 0.722

NASA 1.000 1.000 1.000 1.000 1.000

NSF 1.000 1.000 1.000 1.000 1.000

SSA 1.000 0.444 1.000 1.000 1.000

USAID 0.000 0.000 0.000 0.000 0.000

USDA 0.873 0.893 0.959 0.980 0.801

VA 0.000 0.000 0.000 0.000 0.000

Weighted Average 0.154 0.184 0.201 0.190 0.213

† “Projects” include awards and individual studies; “Known” means the entry in the “Exempt or Non-Exempt” field 

is not N/A, NULL, or blank. “N/R” means that the data were not reported to the Commission. See Appendix II for 

additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified). § DHS reported that there “are no earlier data” than FY07.

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Table I.19 Proportion of Human Subjects Projects with Known Number of Sites†

DEPARTMENT/AGENCY FY06 FY07 FY08 FY09 FY10

CIA‡ N/R N/R N/R N/R N/R

CPSC 1.000 1.000 1.000 1.000 0.000

DHS§ N/R 0.000 0.000 0.000 0.000

DOC 1.000 0.923 0.941 0.926 1.000

DOD 0.000 0.012 0.008 0.028 0.006

DOE 0.998 0.997 0.997 0.997 1.000

DOJ 0.200 0.203 0.337 0.214 0.241

DOT 0.500 0.308 0.371 0.404 0.482

ED 0.000 0.000 0.000 0.000 0.000

EPA 0.472 0.512 0.907 0.429 0.217

HHS 0.001 0.001 0.000 0.000 0.001

HUD 0.000 0.000 0.000 0.000 0.000

NASA 0.892 1.000 0.909 0.872 0.985

NSF 0.000 0.000 0.000 0.000 0.000

SSA 0.933 0.944 1.000 1.000 1.000

USAID 0.547 0.688 0.755 0.875 0.403

USDA 0.864 0.877 0.832 0.846 0.816

VA 0.000 0.000 0.000 0.000 0.000

Weighted Average 0.015 0.017 0.017 0.018 0.017

† “Projects” include awards and individual studies; “Known” means the entry in the “# Sites [per country]” field is not N/A, 

NULL, or blank. “N/R” means that the data were not reported to the Commission. See Appendix II for additional detail. ‡ The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified). § DHS reported that there “are no earlier data” than FY07.
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Appendix II: Human Subjects Research Landscape Project Methods

In order to respond to President Obama’s charge, the Commission recognized 

that a critical first step would be to define and understand the landscape 

of “scientific studies supported by the Federal Government.” Finding no 

comprehensive publicly available source for this information, the Commission asked the 18 federal departments and agencies that have adopted the 

Common Rule—and therefore were likely to support scientific studies with 

human subjects—to provide basic project-level data for department/agencysupported human subjects research in Fiscal Year 2006 to Fiscal Year 2010. 

These agencies are listed in Table I.11

 and an overview of the Human Subjects 

Research Landscape Project is displayed in Figure II.1. 

Commission Chair, Dr. Amy Gutmann, wrote to department/agencies 

regarding this request in early spring 2011. An example of the letter is 

provided in Figure II.2. As necessary, Commission staff clarified the data 

request with contacts at departments/agencies. The Commission asked departments/agencies to provide only data they maintained and that was readily 

available so that the Commission could respond to President Obama’s charge 

in a timely manner. A summary of responsive data received is included in 

Table II.1.

Database and Electronic Data Collection Tools

The Commission engaged a contractor, SRA International, Inc. (SRA), to 

develop 1) an electronic data collection tool to assist departments/agencies 

in gathering data, 2) a website through which department/agencies could 

submit data (www.bioethics-rpd.net), and 3) a database in which to store 

these data, called the “Research Project Database” (RPD). The Commission, 

through SRA, also established a Help Desk to provide technical assistance to 

departments/agencies.

The Commission provided departments/agencies with the option to collect 

their data either in Microsoft Excel or XML format, and provided templates 

and instructions for each. (The data fields and instructions are listed in Table 

II.2.) These data collection tools were equipped with built-in data validations 

so that departments/agencies could pre-screen their data prior to upload to 

the RPD. 
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Registered department/agency users could access the password-protected RPD 

website to upload, delete, or review submitted data. Department/agency users 

uploaded data in a separate file for each fiscal year. The system validated all 

data fields upon upload, for example, to confirm that each “Study ID” (i.e., 

unique study identification number) was unique in a single fiscal year (and, 

therefore, that each study was listed only once per year). If data fields were 

found to have errors, the system provided the department/agency with an 

automated report explaining the errors encountered during the data validation along with a request to resubmit the data. If a department/agency did not 

enter “Site Data” (i.e., site country, number of sites per country, and number 

of participants per country) or “Other Federal Funding Data” (i.e., source of 

other federal funding and other federal funder identifier, such as an award 

number), the system displayed “warnings” asking the department/agency 

to either add these data, or to confirm that these data were not maintained 

or readily available. The department/agency could then add these data and 

resubmit, or confirm that these data were not maintained or readily available 

to bypass the warnings and submit the file as-is. 

If a department/agency supported no human subjects research in a given fiscal 

year, Commission staff asked for written confirmation of that fact.2

Uploaded data were stored in an SRA-hosted SQL Server database. The original uploaded Excel and XML documents were also stored and retained on 

an SRA server. Following the data collection period, SRA exported the entire 

data set from the RPD into three “comma separated values” (.csv) files. The 

export process and naming conventions are detailed in Table II.3. Data were 

organized in three separate tables: (i) “study records” that provides projectlevel data; (ii) “site records” that captures Site Data; and (iii) “other federal 

funding records” that captures Other Federal Funding Data. A unique ID 

field common to all three tables allowed for linkage among them. 

In the Human Subjects Research Landscape Project, the term “project” refers 

to a single line of data entered by a department/agency, whereas “study” 

refers to an individual human subjects research protocol or activity; and 

“award” refers to an extramural award, such as a grant or contract, which 

may fund more than one “study.” The Commission defined “project” broadly 

in order to accommodate different department/agency record-keeping 
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APPENDIX II: Human Subjects Research Landscape Project Methods

systems. Although study-level data were preferred, some departments and 

agencies provided award-level data for extramural human subjects research. 

Additional definitions are listed in Table II.2.

Data Cleaning

Generally, if department/agency data passed the system’s validations, the 

Commission accepted these submissions as-is. Nonetheless, minimal data 

cleaning was performed to facilitate analyses, which is detailed below.

In the SQL database, SRA performed one cleaning task:

•	 Incorrect “unit” names. Departments/agencies could specify individual 

“units” for data submission. For example, NASA submitted data for four 

units: Ames Research Center, Johnson Space Center, Kennedy Space Center, 

and Langley Research Center. In total, six submitted files incorrectly omitted 

a unit designation. SRA corrected these unit names in the SQL database.

Prior to initial analysis of the data, consultant statisticians, Norman P. Ross, 

M.S., Ph.D. and Philip Kalina, M.A., ran a number of checks on the data 

tables, including making sure that:

•	 All variables were in columns and observation records were in rows;

•	 There was one unique id for each project record; and

•	 All missing data had been identified and the appropriate code had been 

inserted in missing data cells.

Once the data were screened and checked, statisticians performed a comprehensive data cleaning process on the analytical database to remove anomalies 

that could be detected through statistical screening; for example, looking for 

missing values and contradictions within or between records, duplicates, and 

outliers. Before final analysis, the data were further cleaned as follows: 

•	 Projects removed from the analysis dataset. Some departments/agencies 

noted in the “Other Comments” field that they were unable to delete or 

remove records from their data submissions. Based on a manual review of 

these comments, a small number of awards (eight) were moved out of the 

analysis dataset. 
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•	 Addition of data submitted after close of the database. HHS-ASPR 

supplemented its data submission after the database was closed. So that all 

data submitted to the Commission were accounted for in its analysis, these 

data were added to the SQL database and provided as a supplemental export 

to the statisticians to incorporate into the analysis dataset. In addition, one 

agency (Agricultural Research Service [USDA-ARS]) inadvertently uploaded 

the same FY06 file for two different units. When brought to its attention, 

USDA-ARS deleted the duplicate file and submitted corrected data after 

the database closed. These data were provided as a supplemental export to 

the consultant statisticians to incorporate into the analysis dataset. Finally, 

although DOD submitted aggregate data before the database closed, it 

submitted project-level data to the database after it was closed. These data 

also were provided as a supplemental export to the consultant statisticians to 

incorporate into the analysis set. 

•	 Units combined. In the interest of simplifying and presenting data, some 

units were combined before analysis. The specific changes were:

•	 Within USDA, all units starting with “ARS” were combined into one 

unit, Agricultural Research Service.

•	 Within HHS, all units starting with “IHS” were combined into one 

unit, Indian Health Service.

•	 Within HHS, all units starting with “National Institutes of Health” 

were combined into one unit, National Institutes of Health. NIH data 

were submitted in several parts due to limitations on the number of 

rows of data that could be entered into the Excel template. Because these 

divisions were arbitrary and not reflective of actual functional operating 

units, they were combined.

•	 Within DOJ, all units starting with “OJP” were combined into one unit, 

Office of Justice Programs.

•	 Within VA, all units were ignored. Like NIH, VA submitted its data 

in several parts due to limitations on the number of rows of data that 

could be entered into the Excel template. Because these divisions were 

arbitrary and not reflective of actual functional operating units, they 

were combined.
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APPENDIX II: Human Subjects Research Landscape Project Methods

•	 Within DOD, all units were ignored under the same reasoning.

•	 Study classification. Where not apparent from department/agency data 

submissions, Commission staff asked for clarification about whether the 

submitted data were award level (i.e., each line of data corresponded an 

award) or study level (i.e., each line of data submitted corresponded to a 

single study). An additional column, “Study or Award Level,” was added 

to the analysis dataset. Valid entries for this column were A (Award), S 

(Study), Q (Equivalent, where one award always supports a single study), U 

(Unclassifiable), and I (Intramural). 

•	 Site country data. A few departments/agencies were able to state that 

all projects for which no country data were submitted took place in the 

United States.3

 These records were updated, and blanks were replaced with 

“United States.”

•	 Awardee institution names. Departments/agencies submitted “Award 

Institution” names in a variety of formats (e.g., with differences in 

abbreviations, misspellings, etc.). Commission staff conducted a manual 

review of institution names and corrected obvious typographical errors and 

standardized institution names.

•	 Awardee institution countries. Awardee institution countries were manually 

added to the analysis dataset based on publicly available sources. If the 

awardee institution country could not be determined with certainty, 

the country was assigned a value of “Unknown.” If a value other than 

an institution name was found in the “Award Institution” field (e.g., a 

department/agency mistakenly entered an abstract in this column), the 

country was assigned a value of “Invalid.” If “N/A” had been entered in the 

institution name column, the country was assigned a value of “N/A.”

•	 Total extramural award amount. “N/A” was not an accepted response 

in the “Total Award $ in FY” field. Because some department/agencies 

indicated that, although they entered “0” in the Total Award field, these 

data, in fact, were not available,4

 a new column, titled ExtraAwardFundVal0 

(i.e., indicating whether “0” in the Total Award field was a “valid” 0 or an 

indication that data was not available) was added to the analysis dataset, 

where acceptable values were Y (Yes), N (No), and U (Unknown).
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•	 Extramural/intramural/both indication clarification. NSF initially classified 

all projects as “both” in the “Intramural or Extramural” field (i.e., with 

both intramural and extramural components), but later clarified that all 

reported projects are extramural. This change was made accordingly in 

the analysis dataset.5

•	 Duplicate awards. Instances appeared in the database where, for a given fiscal 

year, a department/agency submitted lines of study-level data with identical 

award IDs and total award amounts. This is not necessarily indicative of an 

error, as a single award can fund multiple studies. Commission staff checked 

the affected awards in a publicly available database, USASpending.gov. If the 

award amount in the RPD matched the award amount in USASpending.gov, 

it was assumed that the award amount in the database did indeed reflect the 

total award amount and should not inadvertently be counted twice when 

making overall funding calculations. Because of these concerns, extramural 

funding tabulations were run in two ways: (i) by adding all total award 

amounts; and (ii) by adding all total award amounts except those identified 

as duplicates through the above process. 

Following these cleaning processes, a final dataset was ready for analysis, tabulation, and statistical report generation. 

Data Analysis

Following completeness and accuracy checks, the .csv files were read into 

a Microsoft Access database for analysis. The tables produced (included in 

Chapter 2 and Appendix I to this report) are based on descriptive tabulations 

and computations of relevant summary data. The descriptive summaries and 

tabulations presented provide a broad “landscape” view of the human subjects 

research activities being undertaken by participating departments/agencies 

both in the United States and in other countries. Tabulations were provided 

for Fiscal Year 2006 to Fiscal Year 2010 for all departments/agencies that 

provided data. 
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APPENDIX II: Human Subjects Research Landscape Project Methods

Empirical Advisory Group

The Commission convened the Empirical Advisory Group (EAG) to assist the 

Commission with its empirical work, comprised of two Commission members 

and six outside experts in bioethics, statistics, clinical trials, and qualitative research (listed in Table II.4). The EAG met on multiple occasions to 

discuss the Human Subjects Research Landscape Project and other empirical 

approaches that might be used to inform the Commission’s response to the 

President’s charge. The EAG advised the Commission concerning analysis 

and interpretation of the Human Subjects Research Landscape Project data.

Limitations

The Human Subjects Research Landscape Project provides information 

that characterizes human subjects research projects supported by the federal 

government. While these data are extensive, they must be interpreted with 

some limitations in mind. These limitations include: 

The information was reported by departments/agencies and was not independently audited or verified. As such the completeness of reporting cannot 

be verified.6

Each department/agency determined what constituted “relevant” work, which 

may have contributed to reporting bias as well as difficulty in comparing 

data across departments/agencies. The Commission asked departments/agencies to report all human subjects research projects, but definitions of “human 

subjects research” can vary across departments/agencies.7

Not all departments/agencies provided all of the information requested. 

Accordingly, there may be distorted estimates of some summary statistics 

(e.g., total number of studies, funding/award information), further complicating making meaningful comparison within and between departments/

agencies as well as comparisons over time. In addition, NIH provided two 

sets of intramural data retrieved from two different databases (IMPACII 

and Protrak), which have overlaps. Without looking through both sets of 

data individually, NIH could not be sure of the extent of the overlap or eliminate overlaps.8

 Thus, NIH intramural projects may thus be over-reported in 

these analyses. 
MORAL SCIENCE Protecting Participants in Human Subjects Research

170

A single extramural award can fund multiple studies. Thus, a department/

agency’s total extramural funding, calculated by summing relevant “Total 

Award $” fields, is likely an overestimate to the extent that the award funding 

reported may fund more projects than the single project listed.9

 Moreover, 

because some departments/agencies submitted award-level data and others 

submitted project-level data, the number of “projects” reported in the database is likely an underestimate of the total number of human subjects studies 

supported by the government because some projects may correspond to 

awards that fund more than one study.

The Human Subjects Research Landscape Project does not provide a robust 

understanding of research that was not reported because it is classified or because 

of national security concerns.10
V

171

Endnotes

1 Because HHS is the largest government supporter of human subjects research, the Human 

Subjects Research Landscape Project results are often presented in more detail for HHS 

Operating Divisions. Table I.1 also lists the HHS Operating Divisions that responded to the 

Commission’s data request.

2 E-mail Correspondence: Theron Pride, DOJ, to Michelle Groman, PCSBI. (2011, August 2 

and 2011, September 13); Phillip Smith, IHS, to Michelle Groman. (2011, September 20); 

Lori Putman, DOT, to Michelle Groman, PCSBI. (2011, October 17); Mark Grabowsky, 

NVPO, to Michelle Groman, PCSBI. (2011, October 3); Jeffery Rodamar, ED, to Michelle 

Groman, PCSBI. (2011, September 6); Richard Legault, DHS, to Michelle Groman, PCSBI. 

(2011, September 15); Mala Adiga, DOJ, to Michelle Groman, PCSBI. (2011, August 9; 

2011, September 7, 2011; and 2011, September 12); MJ Fiocco, DOT, to Michelle Groman, 

PCSBI. (2011, August 26); Krista Fletcher, SAMHSA, to Michelle Groman, PCSBI. (2011, 

August 2); Amy Farb, OAH, to Michelle Groman, PCSBI. (2011, August 5); Memorandum 

from Jacquelyn White, CMS, to Dawn Smalls, CMS, Request from the Presidential 

Commission for the Study of Bioethical Issues for Information on Human Subjects Scientific 

Research OS#071220111044, July 26, 2011.

3 E-mail Correspondence: Valerie Bonham, PCSBI, to Kevin Neary, HUD. (2011, October 

7); Alan Trachtenberg, IHS, to Michelle Groman, PCSBI. (2011, September 28); Barbara 

DeCausey, CDC, to Michelle Groman, PCSBI. (2011, October 14). Preeti Kanodia, 

HRSA, to Michelle Groman, PCSBI (2011, November 8). NIH explained that for awards 

to domestic institutions, it reported “United States” in the site country field; for awards to 

foreign institutions, it reported the name of the awardee country in the site country field; and 

for awards to domestic institutions that have a foreign component; it reported “United States” 

and “Foreign” in the site country field. Sarah Carr, NIH, to Michelle Groman, PCSBI. 

(2011, October 5). E-mail Correspondence. Thus, NIH projects understood as “foreign” 

(as opposed to “mixed,” or with foreign and domestic components) represent direct awards 

to foreign institutions. Where a project reported no Site Data, a placeholder site record was 

created with blank values for country, sites, and participants. In addition, duplicate site 

records were removed from the analysis dataset; a small number of almost-exact duplicates 

were removed upon agency confirmation. Francis Chesley, AHRQ, to Michelle Groman, 

PCSBI. (2011, November 2). E-mail Correspondence.

4 Some departments/agencies and units indicated that they could not link some or all protocollevel data with extramural funding data. Letter from Richard Legault, DHS, to Valerie 

Bonham, PCSBI. (September 29, 2011). E-mail Correspondence: Michelle Groman, PCSBI, 

to Patty Decot, DOD. (2011, October 27); Jeffery Rodamar, ED, to Michelle Groman, 

PCSBI. (2011, September 6); Rhondalyn Cox, FDA, to Michelle Groman, PCSBI. (2011, 

August 5 and 2011, October 14); Barbara DeCausey, CDC, to Michelle Groman, PCSBI. 

(2011, October 13); Jeffrey Hill, NASA, PCSBI. (2011, August 2).

5 Michelle Groman, PCSBI, to Myron Gutmann, NSF. (2011, October 24). E-mail 

Correspondence.

6 For example, it cannot be stated with certainty that if the same project was reported in several 

fiscal years that the award amount, number of participants, etc., listed in each fiscal year data 

APPENDIX II: Human Subjects Research Landscape Project Methods
MORAL SCIENCE Protecting Participants in Human Subjects Research

172

set was the amount/number specific to that fiscal year or if the totals were repeated year after 

year. Similarly, for awards where ARRA funding was indicated, it is unclear whether the 

reported award amount is entirely or partially ARRA funded.

7 Other terms may be defined differently by different agencies as well, such as “extramural” 

and “intramural.”

8 Sarah Carr, NIH, to Valerie Bonham, PCSBI. (2011, October 5). E-mail Correspondence.

9 Total extramural funding was calculated by summing relevant “Total Award $” fields rather 

than relevant “Total Extramural Study $” fields because the mean response rate for this latter 

variable was less than 17 percent.

10 For example, the CIA did not submit project-level data to the RPD because “the application 

by the C.I.A. of certain research results may implicate intelligence sources and methods, 

and thus cannot be discussed in the public domain.” Letter from V. Sue Bromley, Associate 

Deputy Director, Central Intelligence Agency to Amy Gutmann, Ph.D., Chair, Presidential 

Commission for the Study of Bioethical Issues. (November 15, 2011). The CIA confirmed 

that all CIA-sponsored human subjects research is conducted in the United States – not 

abroad.  CIA personnel also met with Commission staff to discuss the CIA’s human subjects 

research portfolio and made records available to appropriately cleared Commission staff. In 

addition, the Department of Energy provided de-identified data about three human terrain 

mapping projects that have not been accounted for in the RPD.
APPENDIX II: Human Subjects Research Landscape Project Methods V

173

Figure II.1 Human Subjects Research Landscape Project Overview

COMMISSION DEPT/AGENCY SRA STATISTICIANS EAG

March

2011

Dec.

2011

PREPARATION

Identify Common 

Rule depts/agencies

Request dept/

agency liaisons

Data request

Work with SRA to 

develop tools for 

data upload

Work with dept/

agency liaisons to 

clarify data request

Work with 

Commission 

staff to clarify 

data request

Initial data 

collection

Develop XML and 

Excel tools

Develop web 

interface

Develop and 

maintain SQL 

database

Establish 

help desk

DATA GATHERING

Respond to dept/

agency questions

Collect data via 

XML or Excel

Respond to dept/

agency questions

Dept/agency users 

register for RPD 

website

Files uploaded to 

the RPD by dept/

agency users

ANALYSIS

Work with 

statisticians 

to clean and 

analyze data

Data cleaning

Export data Receive .csv 

export from SRA

Advise 

Commission about 

data analyses and 

interpretation Data checks

Export data to 

Microsoft Access

Additional data 

cleaning 

Statistical analysis 

and tabulations
MORAL SCIENCE Protecting Participants in Human Subjects Research

174

Figure II.2 Sample Letter from Dr. Amy Gutmann to Department/Agency Liaison
175

APPENDIX II: Human Subjects Research Landscape Project Methods V
MORAL SCIENCE Protecting Participants in Human Subjects Research

176

Table II.1 Responsive Data Received†

DEPARTMENT/

AGENCY

UNIT DATA SUBMITTED TO RPD

FY06 FY07 FY08 FY09 FY10

Agency for 

International 

Development

Y Y Y Y Y

Central Intelligence 

Agency

N N N N N

Consumer Product 

Safety Commission

Y Y Y Y Y

Department of 

Agriculture

Agricultural Research Service Y Y Y Y Y

Economic Research Service Y Y Y Y Y

National Institute of Food and Agriculture Y Y Y Y Y

Department of 

Commerce

Y Y Y Y Y

Department of 

Defense

Y Y Y Y Y

Department of 

Education

Institute for Educational Sciences Y Y Y Y Y

Office for English Language Education N-None N-None N-None N-None N-None

Office for Elementary and Secondary Education N N N N Y

Office for Innovation and Improvement N N N N Y

Office for Postsecondary Education 

(including Fulbright-Hays fellowships)

Y Y Y Y Y

Office of Planning, Evaluation & 

Policy Development

N N N N Y

Office of Safe and Drug Free Schools N N N N Y

Office for Special Education and Rehabilitative 

Services (including National Institute for 

Disability and Rehabilitation Research)

N Y Y Y Y

Office for Vocational and Adult Education N N N N N

Department of 

Energy

Y Y Y Y Y

† “Y” indicates that the department/agency or unit submitted data to the RPD for the given fiscal year. “N-None” 

indicates that the department/agency or unit informed the Commission that it did not support human subjects research 

in the given fiscal year. “N” indicates that the department/agency or unit did not submit data to the RPD for the given 

fiscal year. The CIA did not submit project-level data to the Commission’s database because these data are confidential 

(although not classified). Letter from V. Sue Bromley, Associate Deputy Director, CIA to Amy Gutmann, Ph.D., Chair, 

PCSBI. (November 15, 2011). ED did not upload data as summarized here, but also reported that “OESE, OII, OPEPD and 

OVAE have very few studies that fall under the Common Rule.” Jeffery Rodamar, ED, to Michelle Groman, PCSBI. (2011, 

September 14). E-mail Correspondence. DHS reported that it had “no earlier data” than FY07. Richard Legault, DHS, to 

Michelle Groman, PCSBI. (2011, September 15). E-mail Correspondence.
177

APPENDIX II: Human Subjects Research Landscape Project Methods V

DEPARTMENT/

AGENCY

UNIT DATA SUBMITTED TO RPD

FY06 FY07 FY08 FY09 FY10

Department of 

Health and Human 

Services

Agency for Healthcare Research and Quality Y Y Y Y Y

Assistant Secretary for Preparedness and 

Response

Y Y Y Y Y

Centers for Disease Control and Prevention Y Y Y Y Y

Centers for Medicare and Medicaid Services N-None N-None N-None N-None N-None

Food and Drug Administration Y Y Y Y Y

Health Resources and Services Administration Y Y Y Y Y

Indian Health Service‡ Y Y Y Y Y

National Institutes of Health Y Y Y Y Y

OASH National Vaccine Program Office Y Y Y N-None N-None

Office of Adolescent Health§ N-None N-None N-None N-None Y

Office of Population Affairs Y Y Y Y Y

Substance Abuse & Mental Health Services 

Administration

N-None N-None N-None N-None N-None

Department of 

Homeland Security

N Y Y Y Y

Department of 

Housing and Urban 

Development

Office of Healthy Homes & Lead Hazard Control Y Y Y Y Y

Office of Policy Development and Research Y Y Y Y Y

Department of 

Justice

Bureau of Prisons Y Y Y Y Y

Federal Bureau of Investigation Y Y Y Y Y

Office of Community Oriented Policing Services N-None N-None N-None N-None N-None

Office of Justice Programs¶ Y Y Y Y Y

Office on Violence Against Women N-None N-None N-None N-None N-None

‡

 Within IHS, the Billings Area Office did not support human subjects research in FY09.

§

 Because it is a “new” office, OAH did not have FY06-FY09 data to report. Amy Farb, OAH, to Michelle Groman, 

PCSBI. (2011, August 5). E-mail Correspondence. OAH. About the Office of Adolescent Health. Retrieved from 

http://www.hhs.gov/ash/oah/about-us/ (last accessed December 8, 2011) (“OAH was established through the 

Consolidated Appropriations Act of 2010, within the Office of the Assistant Secretary for Health.”). ¶

 Within OJP, the Bureau of Justice Assistance did not support human subjects research in FY07, FY08, or FY10 

and the Office of Victims of Crime did not support human subjects research in FY06.

continued
178

MORAL SCIENCE Protecting Participants in Human Subjects Research

Table II.1 Responsive Data Received†

DEPARTMENT/

AGENCY

UNIT DATA SUBMITTED TO RPD

FY06 FY07 FY08 FY09 FY10

Department of 

Transportation

Federal Aviation Administration Y Y Y Y Y

Federal Highway Administration Y Y Y Y Y

Federal Motor Carrier Safety Administration N-None Y Y Y Y

Federal Railroad Administration Y Y Y Y Y

Maritime Administration N-None N-None N-None N-None N-None

National Highway Traffic Safety Administration†† Y Y Y Y Y

Research and Innovative Technology 

Administration

Y N-None Y Y Y

Department of 

Veterans Affairs

Y Y Y Y Y

Environmental 

Protection Agency

Y Y Y Y Y

National 

Aeronautics 

and Space 

Administration

Ames Research Center Y Y Y Y Y

Johnson Space Center Y Y Y Y Y

Kennedy Space Center Y Y Y Y Y

Langley Research Center Y Y Y Y Y

National Science 

Foundation

Y Y Y Y Y

Social Security 

Administration

Y Y Y Y Y

†

 “Y” indicates that the department/agency or unit submitted data to the RPD for the given fiscal year. “N-None” 

indicates that the department/agency or unit informed the Commission that it did not support human subjects 

research in the given fiscal year. “N” indicates that the department/agency or unit did not submit data to the RPD for 

the given fiscal year. The CIA did not submit project-level data to the Commission’s database because these data are 

confidential (although not classified). Letter from V. Sue Bromley, Associate Deputy Director, CIA to Amy Gutmann, 

Ph.D., Chair, PCSBI. (November 15, 2011). ED did not upload data as summarized here, but also reported that “OESE, 

OII, OPEPD and OVAE have very few studies that fall under the Common Rule.” Jeffery Rodamar, ED, to Michelle 

Groman, PCSBI. (2011, September 14). E-mail Correspondence. DHS reported that it had “no earlier data” than FY07. 

Richard Legault, DHS, to Michelle Groman, PCSBI. (2011, September 15). E-mail Correspondence. †† NHTSA data for FY06-FY09 does not include information about safety-related studies involving human 

subjects. Lori Putnam, DOT, to Michelle Groman, PCSBI. (2011, December 1). E-mail Correspondence.
179

APPENDIX II: Human Subjects Research Landscape Project Methods V

Table II.2 Data Fields and Instructions

FIELD INSTRUCTIONS

1. Study ID# Enter a unique study identification number such as IRB or institute protocol number, IND number, 

or other unique identifier assigned by the Department/Agency. Note that award number is 

acceptable here but, because it is requested separately, an alternative identifier is preferred. NCT 

number is also acceptable here but, if available, should be provided in the “NCT#” field as well.

2. NCT# 

[N/A is option]

Enter NCT number, if available. For trials entered in ClinicalTrials.gov, ClinicalTrials.gov 

assigns a unique NCT identifier of the form NCTxxxxxxxx where each x is a numeric digit. 

Enter N/A if the Department/Agency does not maintain this data, or it is not readily available.

3. Title of Study Enter the title of the study, as maintained by the Department/Agency. “Title of Study” is 

intended to be as specific as possible, with protocol title preferred. Award title may be 

substituted for protocol title when necessary. It is understood that an award may support 

more than one protocol.

4. Abstract 

[N/A is option]

Enter the study or award abstract if it is readily available. Enter N/A if the Department/

Agency does not maintain this data, or it is not readily available.

5. PI(s) Enter the name or names of the study’s principal investigator(s). Names may be provided 

in any format, and can be separated by a “,” or “;”.

6. Year X of Y 

[N/A is option]

Enter the duration of the study, for example, “Year 2 of 4.” “X” should be entered in 

reference to the fiscal year for which the Department/Agency is reporting. That means, 

for example, that a study reported in FY06 as “Year 2 of 4,” would be reported in FY07 as 

“Year 3 of 4.” Enter N/A if the Department/Agency does not maintain this data, or it is not 

readily available. If the full duration of the study is unknown, enter N/A for “Y.”

7. Exempt or Non-Exempt 

[Ex/N] 

[N/A is option]

Enter Ex if the study is human subjects research “exempt” from 45 CFR 46 or applicable 

agency regulations. Enter N if the study is non-”exempt.” Enter N/A if the Department/

Agency does not maintain this data, or it is not readily available.

8. Total # Sites 

[N/A is option]

Enter the total number of locations where the study is being conducted, which may not 

correspond to where the approving IRB is located. Enter N/A if the Department/Agency 

does not maintain this data, or it is not readily available. 

9. Site Country 

[N/A is option]

Enter all countries in which the study is being conducted. Enter each country in a separate row. 

Enter N/A if the Department/Agency does not maintain this data, or it is not readily available. 

10. # Sites 

[Per Country] 

[N/A is option]

Enter the total number of locations where the study is being conducted in the listed 

country. Enter N/A if the Department/Agency does not maintain this data, or it is not 

readily available. 

11. # Participants 

[Per Country] 

[N/A is option]

Enter the total number of participants in the listed country in the relevant fiscal year. There 

is no need to list participants for each site within the country separately. Enter N/A if the 

Department/Agency does not maintain this data, or it is not readily available. 

12. ARRA Funded by 

Reporting Entity? 

[Y/N]

Enter Y if Department/Agency funding (if any) for the study is from American Recovery 

and Reinvestment Act (ARRA) funds. Enter N if Department/Agency funding (if any) for the 

study is not from American Recovery and Reinvestment Act (ARRA) funds.

13. Other Fed Funding? 

[Y/N] 

[N/A is option]

Enter Y if this study was funded in the reported fiscal year by another federal funder, in 

whole or in part. Enter N if this study was not funded in the reported fiscal year by another 

federal funder, in whole or in part. Enter N/A if the Department/Agency does not maintain 

this data, or it is not readily available.

14. Source of Other Fed 

Funding?

If this study was funded in the reported fiscal year by another federal funder, in whole or in 

part, select the Department/Agency that is the source of that federal funding. If more than 

one, enter each Department/Agency that is the source of other federal funding in a separate 

row. Select “Other” if the Department/Agency that is the source of other federal funding is 

not listed in the drop-down menu and, if known, enter its name in the “Other Comments” field. 

If this study was not funded in the reported fiscal year by another federal funder, in whole 

or in part, leave blank.
MORAL SCIENCE Protecting Participants in Human Subjects Research

180

Table II.2 Data Fields and Instructions

FIELD INSTRUCTIONS

15. Other Fed Funder 

Identifier

[N/A is option]

If this study was funded in the reported fiscal year by another federal funder, in whole or in 

part, enter a study identification number assigned to the study by the Department/Agency 

that is the source of other federal funding, such as award number or IRB protocol number, 

if known and readily available. Enter N/A if not known or readily available.

If this study was not funded in the reported fiscal year by another federal funder, in whole 

or in part, leave blank.

16. Other Non-Fed 

Funding? 

[Y/N] 

[N/A is option]

Enter Y if this study was funded in the reported fiscal year by another non-federal funder, in 

whole or in part. A non-federal funder could be, for example: foreign, state, or local governments 

or university, industry, non-profit, or philanthropic organizations. Enter N if this study was not 

funded in the reported fiscal year by another non-federal funder, in whole or in part. Enter N/A 

if the Department/Agency does not maintain this data, or it is not readily available.

17. Intramural or 

Extramural 

[I/E/B]

Enter I if the study is considered intramural by the Department/Agency. Enter E if the 

study is considered extramural by the Department/Agency. “Intramural,” generally, means 

internal agency research programs. “Extramural,” generally, means research supported 

by the Department/Agency through grant, cooperative agreement, contract, interagency 

agreement of any type, and “other transaction authority,” e.g., 10 U.S.C. 2371 (DOD). For 

studies funded with both intramural and extramural monies, enter B.

18. Total Intramural 

Study $ in FY from 

Reporting Entity 

[N/A is option]

If intramural, enter the Department/Agency’s intramural funding of the study in the 

reported fiscal year. Do not include funding from other federal or non-federal sources. 

This may be “0.” If the Department/Agency does not track total study funding by project, 

aggregate amounts by fiscal year are acceptable, e.g., laboratory or program. Please 

provide an explanation in the “Other Comments” field. Enter N/A if the Department/Agency 

does not maintain this data, or it is not readily available.

If extramural, leave blank.

19. Award ID# If extramural, enter unique identification number assigned to the award by the 

Department/Agency. “Award” means grant, cooperative agreement, contract, interagency 

agreement of any type, and “other transaction authority,” e.g., 10 U.S.C. 2371 (DOD).

If intramural, leave blank.

20. Award Institution If extramural, enter the name of the institution receiving the award.

If intramural, leave blank.

21. Award Title If extramural, enter the title of the award, as maintained by the Department/Agency.

If intramural, leave blank.

22. Total Award $ in FY If extramural, enter the amount of award extramural funding in the reported fiscal year.

If intramural, leave blank.

23. Total Extramural 

Study $ in FY from 

Reporting Entity 

[N/A is option]

If extramural, enter the Department/Agency’s extramural funding of the study in the reported 

fiscal year. Do not include funding from other federal or non-federal sources. This may be “0.” 

Enter N/A if the Department/Agency does not maintain this data, or it is not readily available.

If intramural, leave blank.

24. Direct Award $ in FY 

[N/A is option]

If extramural and “Total Study $” is not given, enter the amount of direct award funding in 

the reported fiscal year. Enter N/A if the Department/Agency does not maintain this data, 

or it is not readily available.

If “Total Study $” is given, leave blank. If intramural, leave blank.

25. Indirect Award $ in FY

[N/A is option]

If extramural and “Total Study $” is not given, enter the amount of indirect award funding 

in the reported fiscal year. Enter N/A if the Department/Agency does not maintain this 

data, or it is not readily available.

If “Total Study $” is given, leave blank. If intramural, leave blank.

26. Other Comments Enter any necessary explanations, as well as any additional information that may be 

helpful to the Commission about the listed study.

If no other comments, leave blank.
181

APPENDIX II: Human Subjects Research Landscape Project Methods V

Table II.3 SRA Methodology

SPREADSHEET FIELD DATABASE FIELD VALUE AS STORED IN 

DATABASE

VALUE FOR ANALYSIS

(INVERSE OF VALUE 

STORED)

Values as Stored in Database

Study ID# StudyID As supplied As supplied

NCT # NCT As supplied As supplied

Title of Study Title As supplied As supplied

Abstract Abstract As supplied As supplied

PI(s) PI As supplied As supplied

Year X Year_X Integer => As Supplied; N/A 

=> NULL

Integer => As Supplied; 

NULL => N/A

Year Y Year_Y Integer => As Supplied; N/A 

=> NULL

Integer => As Supplied; 

NULL => N/A

Exempt or Non-Exempt Exempt Ex => 1; N => 0; 

N/A =>NULL

1 => Ex; 0 => N; 

NULL =>N/A

Total # of Sites Sites Integer => As Supplied; N/A 

=> NULL

Integer => As Supplied; 

NULL => N/A

ARRA Funded by 

Reporting

Arra Y => 1; N => 0 1 => Y; 0 => N

Other Fed Funding Other_Fed_Funding Y => 1; N => 0; N/A => 

NULL

1 => Y; 0 => N; NULL => 

N/A

Other Non-Fed Funding Other_NonFed_Funding Y => 1; N => 0; N/A => NULL 1 => Y; 0 => N; NULL => N/A

Intramural or 

Extramural

Funding_Type As Supplied As Supplied

Total Intramural Study 

$ in FY

Intramural_Funding IF FUNDING TYPE == 

E => NULL

IF FUNDING TYPE == 

I,B {Money Value => As 

Supplied, without dollar 

formatting; N/A => NULL}

IF FUNDING TYPE == 

E => NULL

IF FUNDING TYPE == 

I,B {Money Value => As 

Supplied; NULL => N/A}

Award ID# Award_ID IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

Award Institution Award_Inst IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

continued
Table II.3 SRA Methodology

MORAL SCIENCE Protecting Participants in Human Subjects Research

182

SPREADSHEET FIELD DATABASE FIELD VALUE AS STORED IN 

DATABASE

VALUE FOR ANALYSIS

(INVERSE OF VALUE 

STORED)

Values as Stored in Database

Award Title Award_Title IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

IF FUNDING TYPE == I => 

NULL

IF FUNDING TYPE == E,B => 

As Supplied

Total Award $ in FY Total_Funding IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == 

E,B {Money Value => As 

Supplied, without dollar 

formatting; N/A => NULL}

IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == 

E,B {Money Value => As 

Supplied; NULL => N/A}

Total Extramural Study 

$ in FY from Reporting 

Entity

Extramural_Funding IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == 

E,B {Money Value => As 

Supplied, without dollar 

formatting; N/A => NULL}

IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == 

E,B {Money Value => As 

Supplied; NULL => N/A}

Direct Award $ in FY Direct_Funding IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == E,B 

and EXTRAMURAL_FUNDING 

== N/A => { Money Value => 

As Supplied, without dollar 

formatting; N/A => NULL}

IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == E,B and 

EXTRAMURAL_FUNDING == 

N/A => {Money Value => As 

Supplied; NULL => N/A}

Indirect $ in FY Indirect_Funding IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == E,B 

and EXTRAMURAL_FUNDING 

== N/A => {Money Value => 

As Supplied, without dollar 

formatting; N/A => NULL}

IF FUNDING TYPE == I 

=> NULL

IF FUNDING TYPE == E,B and 

EXTRAMURAL_FUNDING == 

N/A => {Money Value => As 

Supplied; N/A => NULL}

Other Comments Comments As Supplied As Supplied
183

APPENDIX II: Human Subjects Research Landscape Project Methods V

Table II.4 Empirical Advisory Group

Robert M. Califf, MD

Vice Chancellor for Clinical Research

Duke University Medical Center

Director, Duke Translational 

Medicine Institute

Ruth Faden, Ph.D., M.P.H.

Philip Franklin Wagley Professor 

of Biomedical Ethics 

Director, Johns Hopkins Berman 

Institute of Bioethics

Professor, Department of Health Policy 

and Management

Johns Hopkins Bloomberg 

School of Public Health

Professor, Department of Medicine 

Johns Hopkins School of Medicine

Kenneth A. Getz, M.B.A.

Founder and Board Chair

The Center for Information and Study 

on Clinical Research Participation

Senior Research Fellow

Tufts Center for The Study of 

Drug Development

Tufts University Medical School

Christine Grady, R.N., Ph.D.*

Acting Chief of the Department of Bioethics

National Institutes of Health 

Clinical Center

Philip W. Lavori, Ph.D.

Professor, Health Research and Policy

Stanford School of Medicine

Bernard Lo, M.D.

Professor of Medicine

Director, Program in Medical Ethics

University of California San Francisco

National Program Director, Greenwall 

Faculty Scholars Program in Bioethics

Kathleen M. MacQueen, Ph.D., M.P.H.

Senior Scientist, Behavioral & 

Social Sciences

Coordinator of Interdisciplinary 

Research Ethics

FHI 360

Daniel P. Sulmasy, M.D., Ph.D.*

Kilbride-Clinton Professor of Medicine 

and Ethics, Department of Medicine and 

Divinity School

Associate Director, The MacLean Center 

for Clinical Medical Ethics

University of Chicago

* Commission member
MORAL SCIENCE Protecting Participants in Human Subjects Research

184

Appendix III: U.S. Treatment/Compensation for Treatment Methods

Department of Defense

Title 32: National Defense, Part 108 

- Health Care Eligibility Under the 

Secretarial Designee Program and 

Related Special Authorities (2010)

DOD Instruction Number 6000.08 

(2007)

“Because subjects may be injured while participating in CI research, for 

research involving more than minimal risk as determined by the IRB having 

jurisdiction over the study, include in every intramural (in-house) CIP 

protocol an arrangement for treatment of any research-related injuries. 

Such arrangement in the protocol may be that all subjects are eligible DoD 

healthcare beneficiaries, that they are granted Secretarial designation as 

DoD healthcare beneficiaries under applicable Service regulations, or that 

specific obligations for such treatment have otherwise been undertaken.” 

Section 6.2.4 (2007).

Department of Veterans Affairs

38 CFR §17.85 (2002)

“VA medical facilities shall provide necessary medical treatment to a 

research subject injured as a result of participation in a research project 

approved by a VA Research and Development Committee and conducted 

under the supervision of one or more VA employees.” Part 17 Sec. 17.85(a).

Medicare

Program Memorandum 

Intermediaries/Carriers: Claims 

Processing Instructions for Carriers, 

DMERCS, Intermediaries and Regional 

Home Health Intermediaries (RHHIs) 

for Claims Submitted for Medicare 

Beneficiaries Participating in Medicare 

Qualifying Trials (2000)

“This NCD states that Medicare covers: ... 2) reasonable and necessary 

items and services used to diagnose and treat complications arising from 

participation in all clinical trials.” Background.

“Routine costs DO include (and are therefore covered): ... Items and 

services that are medically necessary for the diagnosis or treatment of 

complications arising from the provision of an investigational item or 

service.” Clinical Trial Services that Qualify for Coverage Section 2.

National Aeronautics and Space 

Administration

NASA Procedural Requirements 

7100.1 Protection of Human Research 

Subjects (Revalidated 7/7/08)

“The PI may ensure that the subject or the subject’s beneficiaries receive 

compensation by means of insurance, worker’s compensation, or the like in 

the event that the subject suffers illness, disease, injury, loss, or death as a 

direct result of the research. The lack of this provision may serve as a basis 

for disapproval of the research. Such provisions for compensation shall be 

required for all studies performed at a NASA Center, uses NASA equipment 

or facilities, or for which a NASA employee or on-site contractor is the 

principal investigator.” Section 9.1.4.

National Institutes of Health

Sheet 6 - Guidelines for Writing 

Informed Consent Documents (2006)

The Clinical Center of the NIH will provide short-term medical care for any 

injury resulting from your participation in research here. ... In general, 

no long-term medical care or financial compensation for research-related 

injuries will be provided by the National Institutes of Health, the Clinical 

Center, or the Federal Government. Section 4(s).

University of California Los Angeles

Guidance and Procedure: Treatment 

and Compensation for Research 

Related Injury (last updated July 26, 

2011)

“The University of California will provide to any injured subject any and all 

medical treatment reasonably necessary for any injury or illness which a 

human subject suffers as a direct result of participation in an authorized 

University activity covered by University policy on the protection of 

human subjects in research or reimburse the subject for the costs of such 

treatment, except when the injury or illness is a consequence of a medical 

research procedure which is designed to benefit the subject directly. 

University of California Policy on Treatment and Compensation for Injury in 

Research 1.
V

185

University of Washington

Human Subjects Manual, Section VII

“The University’s policy on compensation for adverse events to human 

subjects is intended primarily to provide necessary medical care to subjects 

who sustain bodily injury as a direct result of participation in a research 

project.” Section VII(G).

Wake Forest University

Research Related Injury 

Operational Policy and Procedure 

(last revised 2007)

“It is the position of the Wake Forest University School of Medicine 

(WFUSM) Institutional Review Board (IRB) that for any research study it 

approves and determines to be of greater than minimal risk, provisions 

must be made for the coverage of reasonable costs for the necessary 

treatment for illnesses, adverse events or injuries that results from 

medications, devices, interventions, procedures, or tests that the 

research study subject would not have been exposed to had he or she not 

volunteered to participate in the research study.” Research Related Injury.

“For research studies of greater than minimal risk that are industry 

sponsored, provisions must be made for the coverage of reasonable costs 

for the necessary treatment for illness, adverse events or injuries that 

results from medications, devices, interventions, procedures, or tests that 

the research study subject would not have been exposed to had he or she 

not volunteered to participate in the research study protocol.” Research 

Related Injury 2. [Bold added]

“The Wake Forest University School of Medicine maintains limited liability 

insurance coverage to provide for the treatment of research related injuries 

that occur as a result of participation in non-sponsored research (e.g. NIH 

or Departmental).” Research Related Injury 3. [Bold added]

Appendix III: U.S. Treatment/Compensation for Treatment Methods
MORAL SCIENCE Protecting Participants in Human Subjects Research

186

Appendix IV: International and Transnational Requirements for 

Treatment and Compensation for Research Injuries

Australia 

Note for Guidance on Good Clinical Practice 

CPMP/ICH/135/95 (2000) 

National Statement on Ethical Conduct in Human 

Research (2007)

Institutions must be satisfied that sponsors of trials have made 

the indemnity or insurance and compensation arrangements 

required by CPMP/ICH Note for Guidance on Good Clinical Practice 

[recommending that care be provided, and that compensation be 

provided in accordance with local requirements], ISO 14155 Clinical 

Investigation of Medical Devices [requiring disclosure of provisions 

made for compensation] and the TGA. Art. 3.3.24 (2007).

Austria 

Austrian Drug Law (2009) 

Federal Act on Medical Devices (as amended 2011)

The sponsor must have personal injury insurance to cover any 

injuries that may be caused to life or health of the subject by the 

tests carried out in the clinical trial and for which the clinical 

investigator too would be liable if at fault. Art. 47(1) (2011). 

Belgium 

Law Relating to Experimentation on Humans, 

Chapter XVII (Responsibility and Insurance) 

(2004)

Before commencing the experiment, the sponsor shall enter into 

an insurance contract which covers this liability, and the liability 

of every person intervening in the trial, irrespective of the nature 

of the affiliation between the intervening person, the sponsor and 

the subject. Art. 29.2.

Bosnia/Herzegovina 

Medicinal Products and Medical Devices Act 

(2008)

Prior to commencement of the testing, the legal entity performing 

the clinical testing of the medical device and the sponsor of the 

clinical testing shall insure their liability against any possible 

damages which might be caused to the participant or participants 

in the clinical trial. Art. 116.

Brazil 

Rules on Research Involving Human Subjects 

(Res. CNS 196/96 and others) (2003)

The researcher, the sponsor and the institution must assume full 

responsibility for providing comprehensive care to the research 

subjects, as regards complications and injury resulting from 

foreseen risks. Art. V.5.

Bulgaria 

Law on the Medicinal Products in Human 

Medicine (2007, amended through 2011) 

The contracting authority and the principal researcher shall have 

insurance covering their liability for property or non-property 

damages to the study subjects caused in or on the occasion of 

the conduct of the clinical test. Art. 91. 

Canada 

Tri-Council Policy Statement: Ethical Conduct for 

Research Involving Humans (2010)

The information generally required for informed consent includes: 

... (j) information about any payments, including incentives for 

participants, reimbursement for participation-related expenses 

and compensation for injury. Art. 3.2.

China 

Good Clinical Practice (Board Order No. 3) (2003)

The sponsor should provide insurance for the subjects 

participating in clinical trials so that injured subjects do not bear 

the cost of treatment and so they may receive corresponding 

economic compensation. Art. 43.

CIOMS* 

Council for International Organizations of 

Medical Sciences (CIOMS), International Ethical 

Guidelines for Biomedical Research Involving 

Human Subjects (2002)

Investigators should ensure that research subjects who suffer 

injury as a result of their participation are entitled to free 

medical treatment for such injury and to such financial or other 

assistance as would compensate them equitably for any resultant 

impairment, disability or handicap. Guideline 19.

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: Convention 

on Human Rights and Biomedicine (1997) 

Additional Protocol to the Convention on Human 

Rights and Biomedicine concerning Biomedical 

Research, Article 13, CETS No. 195 (2005)

The person who has suffered damage as a result of participation 

in research shall be entitled to fair compensation according to the 

conditions and procedures prescribed by law. Art. 31 (2005). 

* International standard setting body + Supranational European body
187

Appendix IV: International and Transnational Requirements for Treatment V

continued

Croatia 

Clinical Trials and Good Clinical Practice (2003)

The Central Ethics Committee, in the approval process of clinical 

testing, will determine: the existence of insurance compensation 

in case of injury, death or treatment of subjects that is related to 

clinical trials. Art. 12.

Declaration of Helsinki - World Medical 

Association*

 

59th WMA General Assembly Seoul, Korea (2008)

The protocol should include information regarding ... provisions 

for treating and/or compensating subjects who are harmed as a 

consequence of participation in the research study. Section B.14.

Denmark 

The Danish Liability for Damages Act (2005, 

amended 2006 and 2007) 

Danish Act on the Right to Complain and Receive 

Compensation within the Health Service (2009)

Compensation shall be paid pursuant to the provisions of this Part 

to patients or the bereaved families of patients who suffer injury 

in Denmark in connection with examination, treatment or the like 

carried out... Individuals taking part in biomedical trials that do 

not form part of the diagnosis or treatment of their illness shall 

have the same status as patients. Part 3 §§19(1), (2) (2009).

Estonia 

Medicinal Products Act (2004; amended most 

recently in 2010) 

Conditions and Procedure for Conducting Clinical 

Trials of Medicinal Products, Regulation No. 23 

of the Minister of Social Affairs (2005)

The sponsor of a clinical trial of a medicinal product shall 

guarantee the trial subjects health insurance protection in the 

event of damage to health related to the trial. §90(9) (2004). 

European Union+ 

Directive 2001/20/EC of the European 

Parliament and of the Council (2001)

A clinical trial may be undertaken only if, in particular: ... (f) 

provision has been made for insurance or indemnity to cover the 

liability of the investigator and sponsor. Art. 3.2(f).

Finland 

Patient Injuries Act (586/1986; amendments up 

to 1100/2005 included) (amendments through 

2005)

The Patient Injuries Board is responsible for issuing 

recommendations for decisions on individual claims at the 

request of a claimant... and for issuing, when requested by a 

court or one of the parties involved, statements on compensation 

claims which are being processed in court. Section 11a(1).

France 

Biomedical Research (Loi Huriet-Sérusclat), 

Articles L1121-1 to L1126-7 (2004)

Requires that entities both private (e.g. industry, individuals, or 

private institutions) and public (government or nongovernmental 

institutions) serving as sponsors must obtain insurance to cover 

the costs for all damages or injuries arising from the performance 

of the trial. 

Germany 

Medicinal Products Act (The Drug Law) (2009) 

The clinical trial of a medicinal product may only be conducted on 

human beings if and as long as: ... 8. in the event that a person 

is killed or a person’s body or health is injured during the course 

of the clinical trial, an insurance policy which provides benefits, 

even when no one else is liable for the damage, exists .... Section 

40(1).

Hungary 

Act XCV of 2005 on Medicinal Products for 

Human Use and on the Amendment of Other 

Regulations Related to Medicinal Products 

(2005)

The sponsor of a clinical trial shall obtain sufficient liability 

insurance coverage for any damages that may occur in 

connection with the clinical trial from an insurance company 

that is established or has a branch in any Member State of the 

European Economic Area ... . The liability insurance policy shall 

afford sufficient cover for any and all potential claims for damage 

in connection with the clinical trial. Section 3(5).

* International standard setting body + Supranational European body

and Compensation for Research Injuries
MORAL SCIENCE Protecting Participants in Human Subjects Research

188

Iceland 

Regulation on Clinical Trials of Medicinal 

Products in Humans No. 443 (2004)

Subjects participating in a clinical trial of a medicinal product 

must be sufficiently insured against conceivable damage to their 

health resulting from the trial. The principal investigator or, as the 

case may be, the investigator shall be responsible for ensuring 

satisfactory insurance coverage. Art. 5.

ICH Harmonised Tripartite Guideline: 

Guideline For Good Clinical Practice E6(R1)*

 

International Conference on Harmonisation 

of Technical Requirements for Registration of 

Pharmaceuticals for Human Use (1996)

During and following a subject’s participation in a trial, the 

investigator/institution should ensure that adequate medical care 

is provided to a subject for any adverse events ... related to the 

trial. Art. 4.3.2. 

The sponsor’s policies and procedures should address the costs 

of treatment of trial subjects in the event of trial-related injuries 

in accordance with the applicable regulatory requirement(s). 

Art. 5.8.2.

India 

Ethical Guidelines for Biomedical Research on 

Human Participants (2006)

The sponsor whether a pharmaceutical company, a government, 

or an institution, should agree, before the research begins, in the 

a priori agreement to provide compensation for any physical or 

psychological injury for which participants are entitled or agree 

to provide insurance coverage for an unforeseen injury whenever 

possible. Chapter III, Section VI.

Institute of Medicine*

 

Responsible Research: A Systems Approach to 

Protecting Research Participants (2002)

Organizations conducting research should compensate 

any research participant who is injured as a direct result 

of participating in research, without regard to fault. 

Compensation should include at least the costs of medical 

care and rehabilitation, and accrediting bodies should include 

such compensation as a requirement of accreditation. 

Recommendation 6.8.

Ireland 

Statutory Instruments, S.I. No. 190 of 2004, 

European Communities (Clinical Trials on 

Medicinal Products for Human Use) (2004)

In preparing its opinion, the ethics committee shall consider, 

in particular, the following matters: ... (k) the provision made 

for indemnity or compensation in the event of injury or death 

attributable to the clinical trial; (l) any insurance or indemnity 

to cover the liability of the investigator and sponsor.... Part 3, 

Section 13(6).

Israel 

Guidelines for Clinical Trials in Human 

Subjects (2006)

A commercial company entering into an agreement with a 

medical institution and/or Investigator to conduct a clinical trial 

shall insure its legal liability pursuant to the laws of Israel against 

claims filed by clinical trial participants and/or third-party claims 

in connection with the clinical trial, whether during the course of 

the trial or thereafter. Appendix 2.

Italy 

Minimum Requirements for Insurance Policies 

to Protect the Subjects Participating in Clinical 

Trials of Medicines (2009)

The clinical trial sponsor must submit to the ethics committee a 

certificate of insurance. ... The insurance policy must provide 

coverage to specific compensation for injuries. Arts. 1.1, 1.2.

Japan 

Pharmaceutical Administration and Regulations 

in Japan (2011)

Insurance coverage and other measures required for 

compensation in cases of trial-related injury must be undertaken 

beforehand. Chapter 3, page 101.

* International standard setting body + Supranational European body
continued

Appendix IV: International and Transnational Requirements for Treatment V

189

Latvia 

Cabinet Regulation No. 289: Regulations on 

Conducting Clinical Trials and Non-Interventional 

Studies and Labeling of Investigational 

Medicinal Products, and Procedure for 

Conducting Inspections on Compliance with the 

Requirements of Good Clinical Practice (2010)

The sponsor shall ensure that provisions have been made for 

insurance and indemnity to cover the liability of the investigator 

and sponsor. The sponsor is not responsible for a deliberate or 

accidental injury to a subject caused by the investigator or other 

individuals involved in the clinical trial. Art. 22.

Lithuania 

Principal Investigators and Biomedical 

Research Customers in Civil Liability Insurance 

Rules (2000)

Liability Compulsory Insurance Regulations govern the principal 

investigators and biomedical research customers’ compulsory 

insurance contract, the conditions of the contract, the parties - 

the insurer and the insured, the pre-contractual and contractual 

rights and obligations, and the insured person’s rights and 

obligations. Art. I.1.

Macedonia (Republic of) 

On the Manner and the Procedure for 

Clinical Trials on Medicinal Products and the 

Documentation (2009)

The application for granting approval for the clinical trial of 

the medicinal product referred to in Paragraph 1 of this Article 

shall contain: ... 14. evidence that the trial subjects had been 

insured by the applicant in case of occurrence of damage to 

the investigator’s health (damage or death of the trial subject). 

Section II(7), Art. 24.

Netherlands 

Rules for Compulsory Insurance in Medical 

Research Involving Human Subjects (2003)

Medical Research Involving Human Subjects 

Act (WMO) (2006)

The trial shall not be conducted unless at the time of its 

commencement a contract of insurance has been entered into 

covering losses due to death or injury resulting from the trial. 

Such insurance need not cover injury which is inevitable or 

almost inevitable, given the nature of the trial. Section 7.1.

New Zealand 

Health Research Council: Guidelines on Ethics 

in Health Research (2002, revised 2005) 

Injury Prevention, Rehabilitation, and 

Compensation Act (2001, amended 2007)

The Injury Prevention, Rehabilitation, and Compensation Act 

2001 (IPRC Act), provides cover for treatment injuries caused 

as part of a clinical trial where an accredited ethics committee 

has approved the trial and is satisfied that the trial was not to 

be conducted principally for the benefit of the manufacturer or 

distributor of the medicine or item being trialed. Art. 5.6 (2005).

Philippines

Philippine Council for Health Research 

and Development, National Guidelines for 

Biomedical/Behavioral Research (2000) 

National Ethical Guidelines for Health 

Research (2006)

The investigator shall provide the following information to the 

potential subject, using language that can be understood: ... w. 

That treatment will be provided free of charge for specified types 

of research-related injury or for complications associated with 

the research, the nature and duration of such care, the name 

of the organization or individual that will provide the treatment, 

and whether there is any uncertainty regarding funding of such 

treatment; x. In what way, and by what organization the subject 

or the subject’s family or dependents will be compensated for 

disability or death resulting from such injury (or, when indicated, 

that there are no plans to provide such compensation). Art. I.2 

(2006).

Poland

Pharmaceutical Law of 6 September 2001 

(amended through 2008)

The Bioethics Committee shall consider, in particular: ... (9) the 

level of the indemnity or compensation in the event of injury or 

death attributable to participation in the clinical trial. Art. 37r(2).

Russia

On Medicinal Products, Federal Law No. 86-FZ 

(2006) 

The legal basis for conducting clinical trials of medicinal products 

consists of the following documents: 5) civil liability insurance of 

persons carrying out clinical trials of the drug. Article 38.1 

* International standard setting body + Supranational European body

and Compensation for Research Injuries
MORAL SCIENCE Protecting Participants in Human Subjects Research

190

Singapore

Medicines (Clinical Trials) Regulations (2000)

The subject is entitled to a full and reasonable explanation of the 

following: ... (j) any compensation and treatment available to 

the subject in the event of injury arising from participation in the 

clinical trial. Art. 14(1).

Slovakia

On Healthcare, Healthcare-Related Services 

and on the of Certain Laws, Act No. 576/2004 

Coll. (2004)

The instructions prior to informed approval must contain 

information on ... (h) measures intended for ensuring adequate 

compensation in the case of damage of the health of the research 

participant in connection with his/her participation in this 

research. Art. 27(2).

South Africa

Guidelines on Ethics for Medical Research: 

General Principles (2002)

In the event of significant injury, the participant should be entitled 

to receive compensation regardless of whether or not there was 

negligence or legal liability on any other basis. Art. 10.6.2.2.

South Korea

Guideline for Korean Good Clinical Practice 

(2000)

If required by the applicable regulatory requirement(s), the 

sponsor shall provide insurance or shall indemnify (legal and 

financial coverage) the investigator/the institution against 

claims arising from the trial, except for claims that arise from 

malpractice and/or negligence. Art. 32.

Spain

Royal Decree 223/2004 of 6 February Regulating 

Clinical Trials with Medicinal Products (2004)

Law 14/2007, of 3 July, on Biomedical Research 

(2007)

A clinical trial with investigational medicinal products may only 

be undertaken if insurance or other financial cover has previously 

been taken out to include any trial-related injury or loss occurring 

to the person in whom it is to be conducted... . Art. 8(1) (2004).

Switzerland

SR 812.214.2 Ordinance on Clinical Trials of 

Therapeutic Products (2010)

The developer is liable for injuries to a research subject in the 

context of a clinical trial through insurance to cover liability. Arts. 

7(1), 7(2).

Taiwan

Human Research Ethics Policy Guidelines (2007) 

Medical Care Act (2009)

In the case that violation by juridical persons in medical care 

results in damage or injury, the offender shall be responsible for 

compensation. Art. 112 (2009).

Uganda

National Guidelines for Research Involving 

Humans as Research Participants - Uganda 

National Council for Science and Technology 

(2007)

Research participants shall be entitled to compensation when 

the injury is classified as ‘Probably’ or ‘Definitely’ related 

to their participation in the research project. Sponsors shall 

ensure that research participants who suffer injury as a result 

of their participation in the research project are entitled to free 

medical treatment for such injury and to such financial or other 

assistance as would compensate them equitably for any resultant 

impairment, disability or handicap. Art. 7.5.

Ukraine

On Medicines, No. 3323-VI (2011)

The sponsor of the clinical trial shall, prior to its performance, 

make an Agreement on Insurance of Health and Life of the 

Patient (the Volunteer), according to the procedure envisaged by 

the legislation. Art. 8.

United Kingdom

The Medicines for Human Use (Clinical Trials) 

Regulations, 2004 No. 1031 (2004)

In preparing its opinion, the committee shall consider, in 

particular, the following matters... (i) provision for indemnity or 

compensation in the event of injury or death attributable to the 

clinical trial. Art. 15(5)(i).

* International standard setting body + Supranational European body
V

191

Appendix V: International Research Panel

Members

Amy Gutmann, Ph.D., Chair*

President and Christopher H. Browne

Distinguished Professor of Political 

Science, University of Pennsylvania

John D. Arras, Ph.D.*

Porterfield Professor of Biomedical Ethics

Professor of Philosophy

University of Virginia

Julius Ecuru, B.Sc., M.Sc., Dip. IRE.

Assistant Executive Secretary

Uganda National Council for Science

and Technology, Kampala-Uganda

Christine Grady, R.N., Ph.D.*

Acting Chief of the Department of Bioethics

National Institutes of Health 

Clinical Center

Dirceu Bartolomeu Greco, M.D., Ph.D. 

Professor, Internal Medicine

School of Medicine

Federal University of Minas Gerais

Belo Horizonte, Brazil

Unni Karunakara, M.B., B.S., Dr.PH.

Assistant Clinical Professor, Heilbrunn

Department of Population & Family Health

Mailman School of Public Health

Columbia University

Nandini K. Kumar, M.B.B.S., D.C.P., 

M.H.Sc.

Former Deputy Director General Sr. 

Grade (Scientist F)

Investigator NIH project on Bioethics

National Institute of Epidemiology, India

Sergio G. Litewk a, M.D., M.P.H.

Research Assistant Professor

Director International Programs

CITI Program Latin American 

Coordinator

University of Miami

Luis Manuel López Dávila, M.D., M.Soc.

Sc., M.A.

Researcher of the Year 2009

Medical School Professor, and Committee on 

Bioethics in Health Research Staff Member

Universidad de San Carlos de Guatemala

President and Founder of Oxlajuj N’oj 

Foundation

Adel Mahmoud, M.D., Ph.D.

Professor in Molecular Biology and 

Public Policy

Woodrow Wilson School of Public and 

International Affairs

Princeton University

Nelson L. Michael, M.D., Ph.D. *

Colonel, Medical Corps, U.S. Army

Director, Division of Retrovirology

Walter Reed Army Institute of Research

U.S. Military HIV Research Program

Peter Piot, M.D., Ph.D.

Director and Professor of Global Health

London School of Hygiene &

Tropical Medicine, UK

Huanming Yang, Ph.D.

Professor & President

BGI (Beijing Genomics Institute), China

Boris Yudin, Ph.D.

Corresponding Member of the Russian 

Academy of Sciences, Professor of Philosophy

M. Lomonosov’s Moscow State University

*Commission member
192

Appendix VI: Guest Speakers

Ronald Bayer, Ph.D.

Professor and Co-Chair, Center for the 

History and Ethics of Public Health, 

Mailman School of Public Health,

Columbia University

David A. Borasky, Jr., M.P.H., C.I.P.

IRB Manager, Office of Research 

Protection, RTI International

Dan W. Brock, Ph.D. 

Frances Glessner Lee Professor of Medical 

Ethics, Department of Global Health 

and Social Medicine; Director, Division of 

Medical Ethics, Harvard Medical School

Robert M. Califf, M.D. 

Vice Chancellor for Clinical Research, 

Duke University; Professor of Medicine, 

Duke University Medical Center;

Director, Duke Translational 

Medicine Institute

Connie Celum, M.D., M.P.H.

Professor of Medicine; Professor of 

Global Health; Adjunct Professor 

of Epidemiology; Director, 

International Clinical Research 

Center, Department of Global Health, 

University of Washington

Lawrence Corey, M.D. 

President and Director, Fred Hutchinson 

Cancer Research Center; Principal 

Investigator, HIV Vaccine Trials 

Network; Professor, Laboratory 

Medicine and Medicine, 

University of Washington

Francis P. Crawley

Executive Director, Good Clinical Practice 

Alliance – Europe (GCPA)

Ezekiel J. Emanuel, M.D., Ph.D.

Diane v.S. Levy and Robert M. Levy 

University Professor and Vice Provost for 

Global Initiatives, Center for Bioethics, 

University of Pennsylvania

Kenneth R. Feinberg, J.D.

Administrator of the Gulf Coast Claims 

Facility and Special Master of the 

September 11 Victim Compensation 

Fund (2001-2004)

Dafna Feinholz, Ph.D.

Chief of the Bioethics Section, 

Division of Ethics of Science and

Technology, Sector for Social 

and Human Services, United

Nations Educational, Scientific 

and Cultural Organization

(UNESCO)

Joseph J. Fins, M.D., F.A.C.P.

E. William Davis, M.D., Jr. Professor 

of Medical Ethics; Chief, Division of 

Medical Ethics; Professor of Medicine, 

Professor of Public Health, and 

Professor of Medicine in Psychiatry,

Weill Cornell Medical College

Jeffrey K. Francer

Assistant General Counsel, PhRMA

Roger I. Glass, M.D., Ph.D. 

Director, Fogarty International Center; 

Associate Director for International 

Research, National Institutes of Health

Susan E. Lederer, Ph.D. 

Robert Turell Professor of History 

of Medicine and Bioethics; 

Chair, Medical History and Bioethics

University of Wisconsin School of 

Medicine and Public Health

MORAL SCIENCE Protecting Participants in Human Subjects Research
193

Sergio Litewka, M.D., M.P.H.

International Programs Director; 

Research Assistant Professor,

University of Miami Ethics Programs

Murray M. Lumpkin, M.D., M.Sc.

Deputy Commissioner for 

International Programs, U.S. Food 

and Drug Administration (FDA)

Ruth Macklin, Ph.D. 

Professor of Bioethics, Department of 

Epidemiology and Population Health, 

Albert Einstein College of Medicine

Russell M. Medford, M.D., Ph.D.

Chairman and President of 

Salutria Pharmaceuticals

Jerry Menikoff, M.D., J.D.

Director, Office for Human Research 

Protections, U.S. Department of Health 

& Human Services

Eric M. Meslin, Ph.D. 

Director, Indiana University Center for 

Bioethics; Dean (Bioethics), IU School 

of Medicine; Professor of Medicine, 

Medical and Molecular Genetics, 

Public Health, and Philosophy; Director, 

Indiana University-Moi University 

Academic Research Ethics Partnership

Karen E. Moe

Director & Assistant Vice Provost 

for Research, University of Washington 

Human Subjects Division 

Linda Nielsen, J.D.

Vice President, European Group on 

Ethics in Science and New Technologies 

(EGE); Professor of Global Law 

and Governance, University of 

Copenhagen, Denmark

Maurizio Salvi, Ph.D.

Policy Advisor (Ethics) to the President of 

the European Commission; Head of the 

EGE Secretariat; Member of the Bureau

of European Policy Advisors (BEPA)

Robert Temple, M.D. 

Deputy Center Director for Clinical 

Science, Center for Drug Evaluation 

and Research; Acting Director, Office 

of Drug Evaluation I, U.S. Food and 

Drug Administration (FDA)

Carletta Tilousi 

Member, Havasupai Tribal Council

Havasupai Tribe 

Johannes J. M. van Delden, M.D., Ph.D.

President, Council for International 

Organizations of Medical Sciences (CIOMS); 

Professor of Medical Ethics, Utrecht

University Medical Center

Mitchell Warren 

Executive Director, AVAC: Global 

Advocacy for HIV Prevention

Daniel Wikler, Ph.D.

Mary B. Saltonstall Professor of Population 

Ethics, Professor of Ethics and Population 

Health, Department of Global Health and 

Population, Harvard University

John R. Williams, Ph.D.

Consultant, World Medical Association 

(WMA); Adjunct Professor, Department 

of Medicine, University of Ottawa; 

Adjunct Research Professor, Department of 

Philosophy, Carleton University (Ottawa)

Appendix VI: Guest Speakers V


Presidential Commission for the Study of Bioethical Issues

1425 New York Avenue NW, Suite C-100

Washington, D.C. 20005

(202) 233-3960

www.bioethics.gov