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44–389 CC 1997

OVERSIGHT OF NIH AND FDA: BIOETHICS AND

THE ADEQUACY OF INFORMED CONSENT

HEARING

BEFORE THE

SUBCOMMITTEE ON HUMAN RESOURCES

OF THE

COMMITTEE ON GOVERNMENT 

REFORM AND OVERSIGHT 

HOUSE OF REPRESENTATIVES

ONE HUNDRED FIFTH CONGRESS

FIRST SESSION

MAY 8, 1997

Serial No. 105–49

Printed for the use of the Committee on Government Reform and Oversight

(

(II)

COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT 

DAN BURTON, Indiana, Chairman 

BENJAMIN A. GILMAN, New York 

J. DENNIS HASTERT, Illinois 

CONSTANCE A. MORELLA, Maryland 

CHRISTOPHER SHAYS, Connecticut 

STEVEN SCHIFF, New Mexico 

CHRISTOPHER COX, California 

ILEANA ROS-LEHTINEN, Florida 

JOHN M. MCHUGH, New York 

STEPHEN HORN, California 

JOHN L. MICA, Florida 

THOMAS M. DAVIS, Virginia 

DAVID M. MCINTOSH, Indiana 

MARK E. SOUDER, Indiana 

JOE SCARBOROUGH, Florida 

JOHN B. SHADEGG, Arizona 

STEVEN C. LATOURETTE, Ohio 

MARSHALL ‘‘MARK’’ SANFORD, South 

Carolina 

JOHN E. SUNUNU, New Hampshire 

PETE SESSIONS, Texas 

MICHAEL PAPPAS, New Jersey 

VINCE SNOWBARGER, Kansas 

BOB BARR, Georgia 

ROB PORTMAN, Ohio 

HENRY A. WAXMAN, California 

TOM LANTOS, California 

ROBERT E. WISE, JR., West Virginia 

MAJOR R. OWENS, New York 

EDOLPHUS TOWNS, New York 

PAUL E. KANJORSKI, Pennsylvania 

GARY A. CONDIT, California 

CAROLYN B. MALONEY, New York 

THOMAS M. BARRETT, Wisconsin 

ELEANOR HOLMES NORTON, Washington, 

DC 

CHAKA FATTAH, Pennsylvania 

ELIJAH E. CUMMINGS, Maryland 

DENNIS J. KUCINICH, Ohio 

ROD R. BLAGOJEVICH, Illinois 

DANNY K. DAVIS, Illinois 

JOHN F. TIERNEY, Massachusetts 

JIM TURNER, Texas 

THOMAS H. ALLEN, Maine 

HAROLD E. FORD, JR., Tennessee 

———

BERNARD SANDERS, Vermont 

(Independent) 

KEVIN BINGER, Staff Director 

DANIEL R. MOLL, Deputy Staff Director 

JUDITH MCCOY, Chief Clerk 

PHIL SCHILIRO, Minority Staff Director 

SUBCOMMITTEE ON HUMAN RESOURCES

CHRISTOPHER SHAYS, Connecticut, Chairman 

VINCE SNOWBARGER, Kansas 

BENJAMIN A. GILMAN, New York 

DAVID M. MCINTOSH, Indiana 

MARK E. SOUDER, Indiana 

MICHAEL PAPPAS, New Jersey 

STEVEN SCHIFF, New Mexico 

EDOLPHUS TOWNS, New York 

DENNIS J. KUCINICH, Ohio 

THOMAS H. ALLEN, Maine 

TOM LANTOS, California 

BERNARD SANDERS, Vermont (Ind.) 

THOMAS M. BARRETT, Wisconsin 

EX OFFICIO

DAN BURTON, Indiana HENRY A. WAXMAN, California 

LAWRENCE J. HALLORAN, Staff Director and Counsel 

ANNE MARIE FINELY, Professional Staff Member 

R. JARED CARPENTER, Clerk 

CHERRI BRANSON, Minority Counsel 

(III)

C O N T E N T S 

Page 

Hearing held on May 8, 1997 ................................................................................. 1

Statement of: 

Caplan, Arthur, professor of bioethics, University of Pennsylvania; Benjamin Wilfond, professor of pediatrics, University of Arizona; Peter 

Lurie, professor of medicine, University of California-San Francisco; 

and Laurie Flynn, director, National Alliance for the Mentally Ill .......... 160

Raub, William, Deputy Assistant Secretary for Science Policy, Department of Health and Human Services; David Satcher, Centers for Disease Control and Prevention; Harold Varmus, Director, National Institutes of Health; and Mary Pendergast, Deputy Commissioner, Food 

and Drug Administration ............................................................................. 9

Letters, statements, etc., submitted for the record by: 

Caplan, Arthur, professor of bioethics, University of Pennsylvania, prepared statement of ........................................................................................ 164

Flynn, Laurie, director, National Alliance for the Mentally Ill: 

Information concerning ways to protect mentally ill research participants ....................................................................................................... 213

Prepared statement of ............................................................................... 198

Lurie, Peter, professor of medicine, University of California-San Francisco, prepared statement of ......................................................................... 188

Pendergast, Mary, Deputy Commissioner, Food and Drug Administration: 

Information concerning waiver of informed consent .............................. 155

Prepared statement of ............................................................................... 61

Raub, William, Deputy Assistant Secretary for Science Policy, Department of Health and Human Services, prepared statement of ................... 14

Satcher, David, Centers for Disease Control and Prevention, prepared 

statement of ................................................................................................... 25

Shays, Hon. Christopher, a Representative in Congress from the State 

of Connecticut, prepared statement of ........................................................ 3

Towns, Hon. Edolphus, a Representative in Congress from the State 

of New York, letters concerning the subject of Public Citizen’s news 

release ............................................................................................................ 115

Varmus, Harold, Director, National Institutes of Health: 

Information concerning clinical trials ...................................................... 144

Prepared statement of ............................................................................... 48

Wilfond, Benjamin, professor of pediatrics, University of Arizona, prepared statement of ........................................................................................ 179

(1)

OVERSIGHT OF NIH AND FDA: BIOETHICS 

AND THE ADEQUACY OF INFORMED CONSENT 

THURSDAY, MAY 8, 1997 

HOUSE OF REPRESENTATIVES, SUBCOMMITTEE ON HUMAN RESOURCES, COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT, Washington, DC. 

The subcommittee met, pursuant to notice, at 10:05 a.m., in room 

2247, Rayburn House Office Building, Hon. Christopher Shays 

(chairman of the subcommittee) presiding. 

Present: Representatives Shays, Snowbarger, Pappas, Towns, 

and Kucinich. 

Staff present: Lawrence J. Halloran, staff director and counsel; 

Anne Marie Finley, professional staff member; R. Jared Carpenter, 

clerk; and Cherri Branson, minority counsel. 

Mr. SHAYS. I call this hearing to order. Next week the President 

will formally apologize to the survivors of the 40-year Tuskegee experiment, a federally funded study in which black men were allowed to suffer and die of a curable disease—syphilis—in the name 

of scientific research. Last week, this subcommittee heard testimony from Gulf war veterans ordered to take a potentially toxic 

drug for an experimental use without being informed of any possible side effects. 

The road from Tuskegee to Baghdad is lined with other landmarks of scientific arrogance and human tragedy. Thalidomide, radiation experiments, the EZ measles vaccine trials—those notorious 

lapses in the protection of human research subjects and the complex ethical implications of emerging biomedical issues like cloning, 

gene therapies, and AIDS vaccine trials compel us to ask: How effective are current mechanisms to review ethical issues and detect 

violations of informed consent requirements? 

What needs to be done so patient protections keep pace with scientific advances? Do we need a permanent national panel to serve 

as the arbiter of biomedical ethics issues? Physicians have a moral 

duty to inform human research subjects of the foreseeable risks of 

participation, and a duty to minimize those risks. The discipline of 

bioethics has evolved from the Hippocratic oath to the Nuremberg 

Code to current national and international standards to protect the 

health and human dignity of all who submit themselves to help advance scientific knowledge. 

But the current system of bioethics review appears to be showing 

signs of age and disrepair. Multiple layers of review and enforcement provide a false sense of security that difficult issues are being 

confronted. The regulatory scheme lacks specific provisions to proVerDate 0ct 02 2002 09:43 Oct 05, 2002 Jkt 010199 PO 00000 Frm 00005 Fmt 6633 Sfmt 6633 W:\DISC\44389 44389
2

tect mentally ill, drug addicted and cognitively impaired persons 

involved in biomedical research. Local institutional review boards— the IRBs—considered the cornerstone of the entire bioethics review 

structure, are often hard-pressed to monitor research protocols and 

informed consent procedures on an ongoing basis. 

By one recent estimate, more than half the federally funded research projects inspected by the FDA between 1977 and 1995 failed 

in some way to inform research subjects fully of the experimental 

nature of the medical procedure. Multi-site research studies further 

challenge the capacity of local IRBs to control the research nominally under their purview. The National Institutes of Health— NIH—are charged with the potentially conflicting duties to fund research, conduct research, and enforce bioethics regulations. As a result, the NIH Office of Protection for Research Risks—the OPRR— faces both institutional barriers and logistic obstacles in attempting 

to police thousands of research projects. 

The third leg of what is supposed to be the national bioethics 

triad doesn’t even exist. Department of Health and Human Services—HHS—regulations call for a permanent ethics advisory 

board—the EAB—to advise the Secretary of bioethics issues. The 

EAB has been without members since 1979, supplanted by a series 

of temporary commissions to study particular bioethics problems. 

The latest, the National Bioethics Advisory Commission—the 

NBAC—was directed in 1995 to make their first priority protection 

of the rights and welfare of human research subjects. Only recently 

staffed, the commission has now been directed by the President to 

focus their attention on cloning, and will not review ethical issues 

arising from specific research projects. 

Given these constraints, can the NBAC function in the role envisioned by the permanent Ethics Advisory Board? The weakness of 

the current system became more apparent recently when the NIH 

had to convene an ad hoc panel to review serious ethical questions 

presented by a proposed randomized needle exchange study in 

Alaska. Intravenous drug users are at high risk of contracting hepatitis and AIDS. For some, participation in the study to increase 

the avoidable risk of getting hepatitis B, for which there is an effective vaccine. A series of reviews by the local IRB and NIH failed 

to correct that ethical deficiency or detect flaws in the proposed informed consent materials. 

This self-policing, self-validating, and in some ways self-satisfied 

system of bioethics review and enforcement may be vulnerable to 

institutional pressures to conform and to cronyism. Missing are the 

periodic evaluations and external oversight needed to maintain a 

rigorous bioethical review system. We begin our part of that external oversight today. And we look to our witnesses for suggestions 

to improve patient protections and informed consent procedures. At 

this time I would recognize the ranking member and an equal partner in this effort, Mr. Towns. 

[The prepared statement of Hon. Christopher Shays follows:]

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6

Mr. TOWNS. Thank you very much, Mr. Chairman. African-Americans have had a long and unhappy history of involuntary participation in medical studies. From 1932 to 1972, U.S. Public Health 

Service embarked on a 40-year study of African-American men who 

had contracted syphilis. Known as the Tuskegee Study, the Government agency withheld treatment and administration of a cure 

in order to study the effects of the disease on the black male. In 

the 1950’s, a University of Cincinnati Medical Center exposed 82 

charity ward patients to 10 times the amount of radiation that was 

known to be safe at the time. 

In this study on the effects of full body radiation, three-quarters 

of the patients in the study were low income black men and 

women. Their consent signatures had been forged. During the 

1970’s, one group of parents in Baltimore thought they were enrolling their boys in a free child program at John Hopkins University. 

During the course of these 3 years, NIH-funded study of 7,000 

boys, over 90 percent African-American, had their blood drawn. 

This blood was subjected to genetic testing without the knowledge 

or consent of any of the parents. 

This long and troubling history has made the African-American 

community extremely leery of medical research, and let me also 

add, the medical community. Although representing about 15 percent of the general population, they account for only about 2 to 4 

percent of volunteers in cancer prevention trials. For instance, 

overall, African-Americans have lower cancer survival rates than 

whites. However, blacks who participate in clinical trials have survival rates equal to those of whites. 

In some instances, this unwillingness to participate in trials may 

hamper later treatment. There is a lot of evidence that racial minorities and other vulnerable groups have been exploited doing 

medical research. I believe it is the powerlessness of these groups 

which make them targets for medical exploitation. Surely we cannot allow some members of this society to be sacrificed for the 

health and well-being of others. 

On the other hand, there’s evidence that research improves the 

overall health of the population. We must strike the right balance 

and ensure that any opportunity for exploitation is eliminated. 

Current Federal guidelines require the inclusion of women and minorities in clinical research to ensure that biomedical and behavior 

research findings are applicable to all populations. Therefore, the 

HHS, CDC, NIH, and FDA must ensure active recruitment of volunteers in minority communities. 

However, the Federal Government must also ensure that researchers and research facilities fairly represent the American people. Federal reviewers and local review boards should become suspicious when minorities seem to be purposely excluded or seem to 

be the exclusive subjects. We may be able to accomplish these modest goals by enacting additional safeguards to protect the rights of 

the patient. We may need to expand the membership on the institutional review boards, provide additional advocates for patients, 

include greater participation by those not associated with the research facilities and provide a Federal ombudsman specifically to 

receive questions or complaints of study participants. 

7

I hope that this hearing does not advocate eliminating Federal 

research support or placing regulatory restrictions on the receipt of 

Government funding for research that few institutions are able to 

meet. I don’t want to see that happen. I hope that we can use this 

opportunity today to build on the existing framework of the Federal 

regulations to improve our system for the benefit of all future patients and study participants. That’s what I hope to accomplish. 

Mr. Chairman, thank you for raising this important issue—and it 

is important. I look forward to working with you on this issue and 

hearing the testimony of today’s witnesses, to determine in terms 

of what we can do to correct the wrongs and to try to move forward 

by making them right. Thank you so much. 

Mr. SHAYS. I thank the gentleman. At this time the Chair recognizes Mr. Pappas, Congressman Pappas from New Jersey. 

Mr. PAPPAS. Thank you, Mr. Chairman. I want to thank you for 

calling this hearing and focusing on an issue that I think more and 

more Americans are becoming concerned about. The examples that 

both you and the ranking member, Mr. Towns, mentioned both 

about the Tuskegee experiment as well as that which some of our 

Persian Gulf war veterans may have experienced. I’ll just point out 

that the ends do not always justify the means. And there are many 

people in our country that have a great deal of concern that in 

folks’ overzealousness and excitement with regard to the advances 

that are being made in research that people could not necessarily 

just be helped by some of the research and advances that are taking place. So I welcome the opportunity to hear from the panelists 

here today. Thank you. 

Mr. SHAYS. I thank the gentleman. Congressman Kucinich of 

Ohio. 

Mr. KUCINICH. Thank you very much, Mr. Chairman and members of the committee. I want to thank the Chair for holding a 

hearing on this subject, join with Mr. Pappas’ comments, and also 

express my concern with my good friend Congressman Towns about 

the way in which minorities are treated on issues like this. The 

central concern of my constituents is, can public trust and confidence be maintained in such programs? We’re concerned about 

how risks are identified and how they’re communicated to human 

subjects. All of us clearly understand that medical technology and 

research is part of the unfolding of the possibilities for improved 

public health. 

But we also know that we have a moral and ethical responsibility 

to see to it that anyone participating in any type of experiment receives the information that they need so that they know what the 

risks are and that they know what their rights are. There are ethical issues that we’ll be reviewing today. And we want to see the 

extent to which violations of informed consent requirements, 

whether those requirements were ethical, or in fact rules and regulations may have been violated. It’s very clear this is an area of 

public policy that the Federal Government needs to step up to. 

A few years ago we had a couple of laws which regulated bioethics. The National Commission for the Protection of Human Subjects of Biomedical Research and also the President’s Commission 

for the Study of Ethical Providence in Medicine and Biomedical 

and Behavioral Research were established. Neither are in existence 

8

today. And with the exception of the common rule, which only applies to Federal agency, there’s no provision of U.S. law explicitly 

requiring informed consent and independent review of research involving human subjects. 

As we review the biomedical ethics questions here today I am 

confident that this committee with the cooperation of those who 

will be testifying will be able to lead the way to establishing some 

new standards which will derive from ethical considerations. And 

I’m very grateful, Mr. Chairman, that you have chosen this moment to bring this issue to the forefront. 

Mr. SHAYS. I thank the gentleman. And we are joined by the 

vice-chairman of the subcommittee, Mr. Snowbarger, who is from 

Kansas and would just as soon we get on with the hearing. So 

we’re going to do what we do at all our hearings. We swear in our 

witnesses, including any Member of Congress, who come and testify. So if you would stand and raise your right hands, we’ll swear 

you in. 

[Witnesses sworn.] 

Mr. SHAYS. Thank you. Note for the record that our witnesses 

have responded in the affirmative. And I will tell you who our witnesses are for the record. We have Dr. William Raub, acting executive director, National Bioethics Advisory Committee and Deputy 

Assistant Secretary, Department of Health and Human Services. 

We have Dr. David Satcher, Director, Center for Disease Control 

and Prevention. We have Dr. Harold Varmus, who is Director, National Institutes of Health. And we have Mary Pendergast, who is 

Deputy Commissioner, Food and Drug Administration. 

I would prefer that we go in the order that I mentioned our witnesses: Dr. Raub, Dr. Satcher, then Dr. Varmus, and then Ms. 

Pendergast. We’ll go in that order. And we don’t have our traditional clock. We have asked that you speak for about 5 minutes. 

But we do recognize that this is a very important subject. And we 

do want your testimony on the record. 

We will just deal with two housekeeping issues and ask unanimous consent that the members of the subcommittee be permitted 

to place any opening statement in the record and that the record 

remain open for 3 days for that purpose. And without objection, so 

ordered. I also ask unanimous consent that all witnesses be permitted to include their written statements in the record. And without objection, so ordered. 

Your testimony is important. And we want to make sure that we 

cover it. So if you go over, a little over the 5 minutes, we recognize, 

because this is a very important subject. I just say for the four witnesses that will be following, we’re happy to have you listen to 

some of the questions that are asked of the first panel and include 

them in your opening statements as well. So if you want to just 

make some notes and so on, that’s fine as well. So we’ll start with 

you, Dr. Raub, and welcome. 

Mr. RAUB. Thank you, Mr. Chairman. 

Mr. SHAYS. Maybe since you haven’t started it would make sense 

for us to vote and then come back. And then we won’t have the 

interruption. And I might say if we have any students here, we will 

allow students to sit in those first three seats there to give a little 

9

more room. So we’ll be back. We stand at recess. And we will 

hustle. 

[Recess.] 

Mr. SHAYS. I feel I have tremendous power with this. What I’d 

like to do, I understand that some of our witnesses have others 

who have accompanied them who might assist them in responding 

to questioning, which we actually would want to encourage. But we 

do need to swear them in. So if any of you have someone you would 

like to respond to a question, I think it would be good to take care 

of that now. So do any of you have a witness that might—— Mr. RAUB. Yes, we do. 

Mr. SHAYS. Would you identify who they might be? They can just 

stand where they are for now. Here’s what we’re going to have to 

do. We will swear all of you in. And then if you do testify for the 

recorder, we’ll then ask you to give your name then. Let’s do it that 

way. And I’ll try to remember faces. 

[Witnesses sworn.] 

Mr. SHAYS. Thank you very much. I really appreciate your cooperation in this regard. And then if you testify, if you would be 

prepared just to leave your full name and title for our recorder so 

he makes sure that he has it. Dr. Raub, we welcome your testimony and you’re on. 

STATEMENTS OF WILLIAM RAUB, DEPUTY ASSISTANT SECRETARY FOR SCIENCE POLICY, DEPARTMENT OF HEALTH 

AND HUMAN SERVICES; DAVID SATCHER, CENTERS FOR DISEASE CONTROL AND PREVENTION; HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH; AND MARY 

PENDERGAST, DEPUTY COMMISSIONER, FOOD AND DRUG 

ADMINISTRATION 

Mr. RAUB. Thank you, Mr. Chairman, and good morning. 

Mr. SHAYS. Good morning. 

Mr. RAUB. I’m the Deputy Assistant Secretary for Science Policy 

within the Office of the Assistant Secretary for Planning and Evaluation in the Department of Health and Human Services. I also 

serve as the acting executive director of the National Bioethics Advisory Commission, heretofore labeled as NBAC, pending completion of recruitment for that position. I appreciate this opportunity 

to present background information on NBAC and to describe its 

current activities. 

President Clinton established NBAC by Executive order dated 

October 3, 1995. The order describes that function as follows:

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

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

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

policies, assignments, missions, guidelines, and regulations as they relate to bioethical issues arising from research on human biology and behavior; and 

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

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

citing specific projects only as illustrations for such principles. 

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

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

National Science and Technology Council, NBAC also may accept suggestions of 

issues for consideration from both the Congress and the public. NBAC also may 

identify other bioethical issues for the purpose of providing advice and recommendations, subject to the approval of the National Science and Technology Council.

10

The order also indicates that NBAC will terminate on October 3, 

1997 unless extended prior to that date. 

The Assistant to the President for Science and Technology issued 

the charter for NBAC in July 1996. In describing the functions of 

NBAC the charter indicates the following:

As a first priority, the Commission will direct its attention to consideration of: 

A. Protection of the rights and welfare of human research subjects; and 

B. Issues in the management and use of genetic information including but not 

limited to human gene patenting.

Also in July 1996, the President appointed the members of 

NBAC. The chairman is Harold T. Shapiro, Ph.D., president of 

Princeton University. 

NBAC held its first meeting on October 4, 1996. Following a series of background presentations and a general discussion of the 

President’s charge to NBAC, Chairman Shapiro elected to create 

two subcommittees. The human subjects subcommittee, chaired by 

James Childress, Ph.D., of the University of Virginia, has the responsibility for examining the current system of protections for 

human research subjects with emphasis on determining whether 

research sponsors and performers are adhering to the so-called 

‘‘common rule’’—that is, a set of essentially identical regulations 

issued simultaneously by 16 agencies of the Federal Government 

on July 18, 1991—and whether the rule itself is adequate to assess 

the ethical issues associated with current and future research endeavors. The genetics subcommittee chaired by Thomas H. Murray, 

Ph.D., of Case Western Reserve University has responsibility for 

examining the management and use of genetic information with 

emphasis on the bioethical issues associated with the use of human 

tissue samples in genetics research. 

Each of the two subcommittees has held a series of meetings toward fulfillment of their respective tasks. They have identified information needs, discussed alternative strategies for meeting them, 

and set priorities for followup efforts by individual commissioners 

and/or NBAC staff. For example, as both subcommittees identify 

leading experts from relevant disciplines from whom they wish to 

receive oral and/or written testimony, NBAC staff make the requisite contractual and logistical arrangements. 

In addition, with respect to the assessment of the common rule, 

a DHHS staff group, with guidance from the human subjects subcommittee, is gathering pertinent information from the participating agencies so that the subcommittee and ultimately the full 

NBAC will have a strong data base and set of analyses to facilitate 

its assessment as to how well the system of protection for human 

research subjects is working. As I will describe in more detail in 

a few minutes, President Clinton’s request for a study of the legal 

and ethical issues associated with cloning technology added a substantial task to NBAC’s agenda, one that demands and is receiving 

intensive effort from all the commissioners. 

This unforeseen development cause both subcommittees to reformulate their work plans for this year with the view to making 

them less labor- and time-intensive than they otherwise would 

have been. Nevertheless, both subcommittees are intent upon important substantive contributions in their respective areas in a sufficiently timely manner so that by October 1997, the full NBAC can 

11

report findings and recommendations regarding human subjects 

protection and genetic testing over and beyond whatever findings 

and recommendations it provides within the next few weeks with 

respect to cloning. 

NBAC’s operating priorities for this year changed abruptly in the 

wake of the press announcements on February 23, 1997, that scientists in Scotland had cloned a lamb from a single cell from the 

mammary tissue of a 6-year-old ewe. The scientists’ research report 

appeared in that week’s edition of the scientific journal Nature. On 

February 24, President Clinton sent a letter to NBAC Chairman 

Shapiro, requesting that the National Bioethics Advisory Commission undertake a thorough review of the legal and ethical issues associated with the use of this technology—namely, cloning—and report back to him within 90 days with recommendations on possible 

Federal actions to prevent its abuse. 

Further, on March 4, President Clinton issued to the heads of executive departments and agencies a memorandum entitled, ‘‘Prohibition on Federal Funding for Cloning of Human Beings.’’ In that 

memorandum he mentioned his assignment to NBAC, noting that 

cloning technology offers the potential for enormous scientific 

breakthroughs that could offer benefits in such areas as medicine 

and agricultural while raising profound ethical issues, particularly 

with respect to its possible use to clone humans. 

Since February 25, NBAC has devoted an extraordinary effort toward fulfilling President Clinton’s request. The commissioners 

quickly developed a preliminary framework for the issues they 

wished to address and organized themselves into several informal 

working groups so that they initially could pursue various subsets 

of these issues in parallel. Then they identified within each issue 

area the specific topics for which they desired additional information, and they provided guidance to NBAC staff regarding leading 

experts in relevant scientific or professional disciplines who might 

be sources of or at least links to sources of such information. 

Using this guidance, NBAC staff contracted for a series of special 

analyses on a variety of topics including the state of the science related to cloning, the current array of State and local level statutes 

that might affect cloning and/or cloning related research, and the 

historical experience with moratoria associated with other areas 

where rapid scientific advances raised major ethical issues—that is, 

fetal research, gene therapy, and recombinant DNA research. 

Further, NBAC staff invited experts in science, religion, ethics 

and other relevant subject matter areas to address the commission 

directly and participate in indepth discussions of critical issues. 

Moreover, NBAC staff made special efforts to accommodate within 

each meeting agenda those members of the public who requested 

an opportunity to address the commission. To date the full NBAC 

has held three meetings largely or wholly devoted to the cloning assignment. 

Between meetings, the informal subgroups have pursued their 

respective assignments through special meetings, conference calls 

or e-mail exchanges, and the NBAC staff has maintained regular, 

often daily contact with Chairman Shapiro and the other commissioners in anticipation of their needs for assistance or in response 

to specific requests. The commissioners are optimistic that they can 

12

produce a thorough, well reasoned report to President Clinton on 

or about the end of this month. 

The NBAC charter assigns to the Department of Health and 

Human Services the responsibility for providing management and 

administrative support services for NBAC. Secretary Shalala initially delegated this responsibility to the Director, National Institutes of Health, who redelegated it to the Director, Office for the 

Protection from Research Risks. The Director, OPRR established 

the NBAC office, recruited the initial complement of staff, and participated with them and Chairman Shapiro in planning and implementation of the initial NBAC activities. 

During the fall 1996, the Director, NIH expressed concern that 

the organizational placement of the NBAC office could create the 

appearance of conflict of interest. That is, because NBAC inevitably 

will focus on many issues that fall within the purview of the OPRR, 

any NBAC assessments that relate to OPRR’s activities, whether 

favorable or otherwise, might lack credibility in the eyes of some 

observers. After weighing these concerns, Secretary Shalala, on November 1, 1996, reassigned responsibility for NBAC management 

and administrative support to the Assistant Secretary for Health, 

who in turn requested that I provide day to day oversight of the 

NBAC staff in my capacity as his science advisor. 

Subsequently, I also assumed the role of acting executive director, pending the recruitment of an appropriately qualified individual to fill this position on a regular basis. And I arranged for 

a DHHS staff member thoroughly experienced in working with advisory commissions to serve as Acting Deputy Director. The Department recently published the vacancy announcement for the position of NBAC executive director. The position is classified within 

the senior executive service, and, depending upon the qualifications 

of the individual selected, offers an annual salary in the range of 

$104,000 to $120,000 and possibility higher if the individual selected is a physician. 

We expect significant competition for this vacancy and look forward to receipt of applications by the deadline, June 4, 1997. The 

NBAC staff currently consists of eight full-time and four part-time 

individuals. As NBAC activities continue to evolve, future staffing 

needs will be assessed by the executive director in consultation 

with Chairman Shapiro and in context of available resources. 

The budget for NBAC this year is approximately $1.6 million. Almost half of those funds—$760,000—are being provided by agencies of the U.S. public health service, namely the NIH, the CDC, 

the FDA and the Agency for Health Care Policy and Research. The 

remainder of the funds—$850,000—are being provided by six other 

departments or agencies, namely the Department of Defense, the 

Department of Veterans Affairs, the Department of Energy, the Department of Agriculture, the National Aeronautics and Space Administration, and the National Science Foundation. The Office of 

Science and Technology Policy within the executive office of the 

President was instrumental in facilitating the arrangements for 

joint funding of NBAC. 

Mr. Chairman, I know that I speak for my colleagues as well as

13

myself in saying that we are eager to facilitate the work of NBAC 

as best we can, and that we feel privileged to work with this capable and dedicated group of commissioners. If you have questions I 

will be pleased to respond either now or for the record. 

[The prepared statement of Mr. Raub follows:]

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Mr. SHAYS. Thank you, Doctor. We’ll have questions when we’ve 

heard from everyone. But you’ll be asked questions about why the 

EAB couldn’t be doing this why would you be hiring someone in 

June when it’s going to come to a conclusion in October. To help 

sort that out for us. Dr. Satcher. 

Dr. SATCHER. Thank you, Mr. Chairman and members of the 

subcommittee. Let me say that I’m pleased to be able to join you 

for this very important discussion. I think recently I’ve had opportunities to testify before this subcommittee, dealing with issues 

such as the safety of the blood supply and the safety of the food 

supply in this country. I think those are very critical issues for us 

and I think today’s discussion of informed consent is equally critical. 

CDC is committed to protecting all persons who agree to participate in research studies. We make every effort to comply fully with 

the Title 45 Code of Federal Regulations, Part 46 for the protection 

of human subjects. 

Mr. SHAYS. Doctor, I’m going to just ask you to pause a second. 

Dr. SATCHER. Sure. 

Mr. SHAYS. But we’re kind of getting a ring. And I don’t know 

why. It’s not your fault. But I’m just wondering in the case of that 

mic, we’ll just pull it away and see if it’s—— Dr. SATCHER. OK. 

Mr. SHAYS. No. The mic will work—no pull away—just a little 

further. Yes. Maybe that will help. Let’s try it here. 

Dr. SATCHER. OK. 

Mr. SHAYS. You have such a nice-sounding voice, but we’re getting this little echo. 

Dr. SATCHER. Well, despite the commitment which we—— Mr. SHAYS. No. I think if you turn that mic away. Let’s turn it 

away. Let’s try that. Sorry. 

Dr. SATCHER. Despite our commitment and the fact that we 

make every effort to comply with Title 45 CFR, Part 46 for the protection of human subjects, we are, however, aware of incidents that 

indicate lapses in our efforts to protect individuals who have participated in research that we have conducted. I’m confident that 

the corrective actions that we have taken and that we continue to 

work on will continue to improve our protection of research subjects. I would like to address specifically two examples of these 

lapses. 

First, the EZ measles vaccine study. From 1989 to 1991, the 

United States experienced a measles epidemic with more than 

55,000 cases and more than 120 deaths, mostly in young children, 

many of them under 1 year of age. Many cases occurred in this age 

group that was considered too young to be vaccinated with the 

standard measles vaccine—Moraten. During the 1980’s, multiple 

studies conducted around the world indicated that another vaccine, 

the Edmonston-Zagreb [EZ] measles vaccine administered at 10- to 

100-fold greater potency than the standard dose for measles vaccine, was showing promising results in children under 12 months 

of age. Because of measles cases and deaths in children less than 

12 months of age in this country, CDC undertook a study, in May 

1990, of U.S. infants to determine whether results found in other 

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eral studies in other countries carried out by the World Health Organization. In fact, over 200 million doses of this [EZ] vaccine had 

been administered. And who had recommended it in cases like this. 

Beginning in June 1990, under the auspices of the Kaiser Foundation Research Institute and the Los Angeles County Health Department, approximately 1,500 children were enrolled and randomly allocated into five different study groups and received either 

higher or standard dosages of EZ vaccine and standard doses of the 

Moraten vaccine. The protocol for the study was reviewed and approved by the IRB at CDC prior to awarding a contract to Kaiser, 

and was later approved by the IRB at Kaiser. 

The parents or parent’s representatives for each child enrolled in 

the measles study signed the consent form which described the 

purpose of the study, the procedures to be followed, and the benefits and risks of participation. Thus, the parents of the children 

who participated in the study were aware that they were participating in a vaccine study. However, we later acknowledged that the 

consent form was deficient because the EZ measles vaccine was not 

identified clearly as experimental and parents were not given adequate description of the foreseeable risks of vaccination and alternative treatments. 

During the time the EZ measles study was being conducted data 

became available from a study in Senegal, West Africa suggesting 

lower survival in girls who received high potency measles vaccine 

compared to girls who received the standard potency vaccine. So 

October 1991, as additional information became available from a 

study of this same high potency measles vaccine in Haiti, suggesting that girls vaccinated with this level of potency were at increased risk of dying in the 2 or 3 years following the vaccination, 

CDC stopped all use of EZ vaccines in Los Angeles County in October 1991. 

Following the termination of the EZ measles vaccine study, all 

children who participated in the study were asked to enter a followup study to determine whether the vaccine had any adverse 

health effects. Parents were informed of the reason for the followup 

study, including the fact that some studies had found lower survival in those children who received high potency vaccine. To date, 

of all the children who have been evaluated, no child who took part 

in this study and received the high potency EZ vaccine has suffered 

a significant health problem that can be associated with the vaccine. 

And in fact, the death rate in the group of participants is no different from the rest of the population of children. In a thorough review of this study, the Office of Protection from Research Risks 

[OPRR] concluded in 1995 that the EZ measles vaccine study was 

scientifically and ethically justified, however, the consent form was 

deficient. In response to the recommendations from OPRR, a letter 

signed by Kaiser Permanente was sent in June 1996 covering the 

topics required by OPRR and approved by the IRB at both institutions. 

In addition, CDC and Kaiser sent a jointly signed letter of apology in September 1996, to the parents of the children enrolled in 

the trials. In this letter, an apology was made for the mistake on 

the consent form of the study, acknowledging that the parents who 

23

enrolled their children in the study were not adequately informed. 

The issue was informed consent. 

Now there is another example which I will discuss only briefly. 

And that has to do with the hepatitis A vaccine prior to its licensure. While the incidence of hepatitis A has declined substantially 

since 1950, more than 28,000 cases were reported to CDC in 1996. 

And we estimate that there are about 150,000 cases of hepatitis A 

in this country each year. American Indians have a rate of hepatitis A infection that is 20 times higher than for whites and African-Americans. 

It was anticipated that several American Indian communities in 

North and South Dakota would have hepatitis A epidemics during 

the early 1990’s. The prevention of hepatitis A has been somewhat 

problematic and has primarily relied on improvement in hygienic 

conditions. In the 1980’s a number of prototype hepatitis A vaccines were developed and offered the potential to control and prevent the disease. And let me say briefly, in South Dakota, before 

the hepatitis A trials were launched, there was informed consent 

on the part of the parents and assent on the part of children over 

the age of 7. 

In addition to the CDC Institutional Review Board, there was 

also a review by the Indian Health Service Institutional Review 

Boards. And the tribal councils in South Dakota also had to approve the study as this was the Pine Ridge Reservation in South 

Dakota. The study was approved in 1990 and over 500 children 

were enrolled in the study. But in this particular case there was 

concern expressed by many people early, so only one child was ever 

vaccinated in South Dakota. 

Later, however, in North Dakota on the Standing Rock Reservation—we also implemented a study with the consent of our IRB, 

the Indian Health Service Institutional Review Board, the tribal 

councils on the reservations, and, again, the parents and the children. The study began by enrolling 245 children and about 245 

children were vaccinated before the study was stopped. The study 

was stopped, again, because of concern expressed by people on the 

reservation that this was a study where about 60 percent of the 

participants were American Indians. And the concern was, why 

was the study being done on American Indians primarily. So the 

study was stopped after vaccinating 245 children. 

Later, in Thailand, based on some work done by others, it was 

demonstrated that the hepatitis A vaccine was in fact effective at 

preventing hepatitis A. Since that time, American Indians have 

been vaccinated against hepatitis A. And the epidemics that occurred every 5 to 7 years in the past seem to be under control. 

Our position is, and I think most who have reviewed these studies agree, that in the case of the hepatitis A—unlike the EZ vaccine—in the case of the hepatitis A there was full informed consent. Not only was it reviewed by the IRBs at CDC and the Indian 

Health Service, but also the tribal councils approved. However, I 

think what this points out—and I think it’s a very important point 

that some of you have made—is that because we were dealing with 

a minority population that often feels that it does not have access 

to the full value of medical therapy in this country, when a study 

24

disproportionately involves those populations, they often are suspicious. And I think most of us can understand why. 

So this study was stopped because of the suspicion of the members of the reservation that they were being selected out for a 

study. Today, everyone agrees that the hepatitis A vaccine is effective in preventing hepatitis A in a very high percentage of the 

cases. 

Mr. Chairman, I would like to say that there are two things that 

we would like to leave with you. No. 1, we believe that the systems 

that we have in place to protect the human subjects are better than 

they’ve ever been, but we don’t believe that they are good enough. 

We have invested significantly in upgrading our office of human 

subject protection. We review the consent forms, and we made sure 

that there is certain information in every consent form. We require 

that any researcher at CDC is trained in bioethics and the implications of serving on the institutional review board. And we’ve had 

several leadership director’s forums to discuss these issues. However, despite all these efforts, much remains to be done and we will 

continue to work to improve these systems. 

However, I think this will be relevant later this morning. There 

are certain ethical principles about which there will continue to be 

debate, especially when one ethical principle seems to compete with 

another. And hopefully we will have an opportunity to discuss that 

later. Thank you. 

[The prepared statement of Dr. Satcher follows:]

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Mr. SHAYS. I thank you. And we’ll be happy to have you bring 

it up if we don’t. Dr. Varmus. 

Dr. VARMUS. Thank you, Mr. Chairman. I want to join my colleagues in thanking you and your colleagues for conducting a hearing on this most important topic. Let me briefly introduce the colleagues who came with me today—four institute directors who have 

serious concerns about issues and cases that your staff has brought 

to our attention: Dr. Duane Alexander, Director of the National Institute of Child Health and Human Development; Dr. Anthony 

Fauci, Director of the National Institute of Allergy and Infectious 

Diseases; Dr. Steve Hyman, Director of the National Institute of 

Mental Health; and Dr. Alan Leshner, Director of the National Institute on Drug Abuse. I’m also accompanied by Dr. Wendy Baldwin, my deputy director for extramural research, who has administrative oversight over the Office for Protection from Research 

Risks. 

I’m going to talk briefly about protection of human subjects in research. I’ll begin with a very brief description of our system for protecting research volunteers and then briefly speak to some of the 

initiatives we have underway to improve the system. A much 

longer statement describing these activities will be submitted for 

the record. The forerunners for the current system that you will be 

hearing about are the Nuremberg Code, which was developed to 

provide standards for judging human experimentation by the 

Nazis, and the Declaration of Helsinki, which was issued in 1964 

by the World Medical Association. 

These statements establish the principles of autonomy, beneficence and justice that underline many of the activities we’ll be 

talking about. And as Dr. Satcher has just indicated, those principles are complex and sometimes even in opposition. 

The NIH issued its policies for the protection of human subjects 

in 1966 and these were then established by the Department as regulations in May 1974. 

Our regulations are not a set of rigid rules for determining 

whether research activity is right or wrong. Instead, they provide 

a framework for insuring that all serious efforts are made to protect the rights and the welfare of human research subjects. Responsibility for protection of human subjects is shared by a number of 

groups and institutions: the clinical investigator, the local institutional board—so-called IRB—in some cases a data and safety monitoring board, officials at the institutions that receive grants from 

the NIH and the CDC, as well as officials of the NIH. At each level 

of review, there is the authority to raise concerns about human 

subjects issues, to request further evaluation, and to suggest corrections of any identified problems. The Department’s Office for 

Protection from Research Risks—the OPRR—while lodged administratively at NIH, exerts extensive oversight over the entire process 

involving a number of departmental agencies, especially providing 

oversight at those sites at which the research is carried out, often, 

for example, through assurances of compliance with our regulations. 

A crucial part of the system is the requirement for informed consent, the topic of this hearing. The elements of informed consent 

are designed to ensure that before subjects enroll in a study, they 

46

are fully informed about the study, about their rights regarding 

participation, and about the full range of risks and benefits of participation. 

I want to speak briefly about the particular attention that needs 

to be paid to certain categories of research subjects. These are 

those people judged more likely than others to be vulnerable to coercion or undue influence to participate in a study. Our regulations 

contain specific protections for pregnant women, prisoners, children, and fetuses. And reviewers also are asked to pay particular 

attention to studies involving individuals with mental disabilities 

or reduced cognitive capacities, drug abusers and people who are 

economically or educationally disadvantaged. 

Now, we believe the system we have created is generally effective, but it’s not perfect. And occasionally, as you have heard, it 

seems to fail. For this reason we are continually working to enhance the system for protecting our subjects. I want to take a few 

final minutes to highlight a number of NIH activities that are 

aimed at making the system better. Many of these relate to the 

specific vulnerable populations I’ve just mentioned. 

First, the NIH in collaboration with the Department of Energy 

and the Department of Veterans Affairs has jointly issued a request for applications for original research regarding ‘‘Informed 

Consent in Research Involving Human Participants.’’ The goals are 

to test and develop alternative strategies that are relevant for diverse populations and to determine optimal ways to obtain informed consent. We have received more than 80 proposals at the 

time of the deadline for applications, and each of the three agencies 

has set aside funds in this fiscal year to support projects in response. 

Second, six NIH institutes will soon cosponsor a workshop to develop principles to guide informed consent in the case of subjects 

who may be cognitively impaired. The cosponsoring institutions are 

the National Institute of Mental Health, the National Institute on 

Drug Abuse, the National Institute of Neurological Disorders and 

Stroke, the National Institute on Aging, the National Institute of 

Alcohol Abuse and Alcoholism, and the National Institute on Child 

Health and Human Development. Three of those institutes are represented here today. This workshop has been in the planning stage 

for some time, and we hope to have it by next fall. 

Third, the advisory council of the National Institute on Drug 

Abuse recently has issued guidelines for research involving administration of drugs, especially drugs of misuse and abuse to human 

subjects. These guidelines for IRBs address the ethics of both 

human subject research in general and studies involving special 

populations. We’ve provided a copy of those guidelines to the subcommittee’s staff. The National Institute of Mental Health—

NIMH—has a number of additional activities underway. They have 

recently cosponsored a conference that addressed the specific ethical challenges involved in mental health research with children 

and adolescents. 

In collaboration with the National Alliance for the Mentally Ill, 

the NIMH has cosponsored a series of meetings to discuss ethical 

issues of medical research involving human subjects with mental 

illnesses. In addition, the NIH and the Office for Protection from 

47

Research Risks cosponsor annual regional workshops that focus on 

human subjects issues in mental health clinical research. The National Institute on Aging issued an announcement in the NIH 

Guide in October 1996 on implementation of policies for intervention studies, especially involving those subjects who may be mentally impaired. 

And as one final item, the Clinical Center at the NIH, together 

with OPRR and several NIH institutes, has pioneered the concept 

of durable power of attorney applied to research participation. This 

procedure allows individuals, while they are mentally competent, to 

identify someone to represent their best interest and to provide 

proxy informed consent should they later become cognitively impaired. 

Mr. Chairman, the people who volunteer to be research subjects 

are invaluable partners with us in the pursuit for new knowledge 

in medical science. Research investigators, research institutions, 

the NIH, and our partner agencies in the Department of Health 

and Human Services have a responsibility to protect those volunteers’ rights and welfare. We take that responsibility very seriously. Thank you, Mr. Chairman. I’ll be pleased to answer any 

questions you may have. 

[Note.—The ‘‘OPRR Reports, NIH, PHS, HHS, Protection of 

Human Subjects’’ can be found in subcommittee files.] 

[The prepared statement of Dr. Varmus follows:]

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Mr. SHAYS. Thank you, Dr. Varmus. Thank you. And Ms. 

Pendergast. 

Ms. PENDERGAST. Thank you, Mr. Chairman, members of the 

subcommittee. Good morning. 

Mr. SHAYS. Good morning. 

Ms. PENDERGAST. The Food and Drug Administration has put 

forward a longer written statement concerning the human subject 

protection system and the FDA’s bio-research monitoring program. 

This morning I would like to briefly describe to you our regulations 

concerning research in life or death emergency situations. 

Medical research is important. But the rights of human subjects 

in clinical trials are more important. Our attitude is grounded in 

the laws, in the ethical principles set forth in the post-World War 

II Nuremberg Code, in the Declaration of Helsinki, and above all 

in our conscious as individuals and as officials responsible for the 

protection of consumers and the public health. 

We fully believe that medical research, which is intrinsically hazardous, must be conducted with complete integrity, that it must not 

be carried out at the expense of human subjects, and the their informed consent is the bedrock protection of their rights and self-interest. Therefore, when we had to consider the possibility of research without informed consent, we approached the task with 

great caution. We were asked to explore this option because new 

technology makes possible products that hold out the promise of 

saving lives in emergencies that were regarded as hopeless only a 

few years ago: lives of people who are close to death, cannot communicate, and require immediate treatment but whose condition 

has no proven remedy. To make this type of critical research possible while providing the maximum protection for the patient, we 

conducted extensive, indepth consultations with leading ethics, 

legal, research, patient advocacy, and minority communities. 

With their assistance, and in cooperation with the National Institutes of Health, we issued in September 1995 a proposal that drew 

16 negative comments, mostly from individuals who believed that 

informed consent should never be waived under any circumstances 

whatsoever. The other 74 commenters were strongly supportive. 

They included the National Stroke Association, the Brain Injury 

Consortium, the National Head Injury Foundation, the American 

Heart Association Emergency Cardiac Care Committee, the American College of Emergency Physicians, and the Applied Research 

Ethics National Association. 

Our rule, Mr. Chairman, demands that informed consent be obtained whenever possible, but it also allows a waiver of informed 

consent in extremely limited emergency situations while safeguarding the subject’s rights with overlapping layers of protection. 

The basic preconditions of the waiver are that the subject’s life is 

threatened by an extremely serious condition, such as heart attack, 

stroke, or traumatic head injury; there is no proven or approved 

treatment; the intervention must be studied to determine what 

intervention is most beneficial; and informed consent of the subject 

or the legal representative is not feasible for several clearly defined 

reasons. 

If all of these preconditions are met, the IRB—the Institutional 

Review Board—can waive the consent requirement in a particular 

60

trial, but the subject’s rights are protected in other ways. The IRB 

must find that the research holds out the possibility of direct benefit to the subjects. We call this clinical equipoise. The FDA must 

engage in a heightened review. We apply higher standards than 

usual to this research. There must be public disclosure of the proposed study to the community in which the research will take 

place. And the Institutional Review Board must consult with that 

community. The community must be engaged in the question of 

whether or not the research should go forward in their community. 

There must be public disclosure when the study is done. And there 

must be an independent safety and monitoring board. Finally, the 

researchers must continue to search out family members, next of 

kin, legal representatives, so that they or the person who, if the 

person becomes conscious, can be told about this study and asked 

whether they want to continue with it. 

Mr. Chairman, these are merely the highlights of a complex system that is more fully described in my written statement. Let me 

close by assuring you that we and the many ethicists with whom 

we worked did our utmost to devise a system that exhaustively protects the subjects while saving their lives. The rules are too recent 

to pass any judgment on them. But we are committed to careful 

oversight of the rule’s used. And we will modify the rule if needed. 

Thank you for your attention. 

[The prepared statement of Ms. Pendergast follows:]

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Mr. SHAYS. Thank you. I think what I’d like to do is start with 

you, Ms. Pendergast. And what I would like you to do, if you don’t 

mind, if you would read your statement and put it in the record 

orally beginning on page 37. I think that’s where it begins. I’ll tell 

you where. This relates to the Desert Storm issue. And if you could 

start with the second paragraph. And if you just read that paragraph, I’d like that on the record. And then I’d like to ask you questions about it. 

Ms. PENDERGAST. The paragraph that begins ‘‘Under this regulation?’’ Mr. SHAYS. Yes. 

Ms. PENDERGAST. All right. We’re referring now to a regulation 

that the FDA promulgated in December 1991 regarding waivers of 

informed consent during military combat situations.

Under this regulation, waivers were granted for two products during Operation 

Desert Storm/Desert Shield: pyridostigmine bromide and botulinum toxoid vaccine. 

Although FDA had concluded that informed consent was not feasible, FDA did obtain the Department of Defense’s agreement to provide accurate, fair and balanced 

information to those who would receive the investigational products. To do this, the 

Department of Defense developed information leaflets on both products with FDA’s inputs and these leaflets received final FDA approval. 

Following the cessation of combat activities, the Assistant Secretary of Defense for 

Health Affairs notified the Commissioner in a March 1991 letter that the Department of Defense considered the two waivers granted under the interim rule to be 

no longer in effect. He also informed the Commissioner that the Department of Defense had ultimately decided to administer the botulinum toxoid vaccine on a voluntary basis. 

Since that time, the Presidential Advisory Committee on Gulf War Veterans Illnesses has recommended that we ‘‘solicit timely, public and expert comment on any 

rule that permits waiver of informed consent for use of investigational products in 

military exigencies.’’ Final report, page 52. FDA has carefully evaluated the committee’s recommendations as well as other information that has come to its attention. 

FDA has engaged in discussions within the Agency, with the Department of Defense, and with others on this important topic. As a result of these discussions, the 

Agency will solicit public comment in line with the committee’s report. The public 

comment will be directed towards whether the FDA should finalize the interim rule, 

modify it, or eliminate it completely.

Mr. SHAYS. Let me ask you this to start my questions: Did the 

Department of Defense violate the conditions of the FDA’s waiver 

of the informed consent requirement by not providing military personnel with information about the experimental drugs they were 

required to take? 

Ms. PENDERGAST. As a condition of the waiver, we did negotiate 

an agreement with them where they would provide information 

sheets to the soldiers so that the soldiers, while not being allowed 

to decide whether they wanted to take the drug, they at least knew 

what they were taking, what it’s risks were, what it’s purported 

benefits would be. Unfortunately, we are advised by the Defense 

Department that they did not give all soldiers those information 

sheets. 

Mr. SHAYS. So what is your answer to the question? 

Ms. PENDERGAST. It’s not clear to me that it’s a violation of the 

regulation, but it is a violation of our agreement. 

Mr. SHAYS. No. I asked is it a violation of the conditions of the 

FDA waiver. They didn’t inform. 

Ms. PENDERGAST. They didn’t. No. There’s no dispute about the 

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ument and one of the preconditions for the waiver. And I’m afraid 

I’d have to submit that for the record. 

Mr. SHAYS. The war took place 7 years ago. Basically, 6 years 

ago. And you’re telling me that the FDA still hasn’t determined 

whether or not the Department of Defense was in violation of the 

notification requirement as a condition of waiving the informed 

consent? 

Ms. PENDERGAST. No. I think that there’s no dispute about the 

facts. We know that the information sheets were not provided to 

all of the soldiers. 

Mr. SHAYS. OK. 

Ms. PENDERGAST. You’re asking me a different and more specific 

question. 

Mr. SHAYS. Well, I don’t think they were really provided to practically any of the soldiers. We’ve had eight hearings on the Gulf 

war. So this should show up on your radar screen. It’s not something you need to check now. You need to make a determination 

of whether they were in violation or not. And I’m asking a question 

that it seemed to me that you could have responded 2 years ago. 

And so I’m going to repeat the question. Are they in violation of 

the agreement that the FDA had? 

Ms. PENDERGAST. If you’ll give me one moment, sir? 

Mr. SHAYS. Sure. 

Ms. PENDERGAST. The actual requirement that the information 

being given to the soldiers is not contained as a precondition in the 

actual written waiver document. So as a technical matter, it could 

be disputed that they were in violation of the waiver agreement. 

However, and more importantly from the soldiers’ point of view and 

from our point of view, it was a promise that was not met. 

Mr. SHAYS. So you’re saying they promised to do it, but technically didn’t sign an agreement to do it? 

Ms. PENDERGAST. That’s my understanding, sir. 

Mr. SHAYS. What did they technically agree to? 

Ms. PENDERGAST. There were a number of things that they 

agreed to do basically. 

Mr. SHAYS. Not the promise, the technical. 

Ms. PENDERGAST. No. The technical agreement. What it is, is we 

have regulations that describe the responsibilities of anyone who is 

conducting an investigation. And they basically go to the control of 

the drug, recordkeeping with respect to the administration of the 

drug, and recordkeeping pertaining to the adverse events or not of 

the administration of the drug. So there is a basic set of requirements. Because it was war, we recognized at the time that not all 

of the standard requirements would be capable of being met. This 

isn’t administration in a hospital. 

The pyridostigmine would have been given out in field combat 

situations. So what we did is we limited their requirements to a 

more limited set of requirements pertaining to information. If the 

worst possible thing happened and our troops were exposed to 

chemical or biological weapons then there were lots of obligations 

that kicked in, in terms of finding out what happened and whether 

or not the administration——

Mr. SHAYS. Ms. Pendergast, this is kind of painful here. 

Ms. PENDERGAST. Yes. 

103

Mr. SHAYS. The soldiers did take the PB pills. They did take 

them. They were under orders to take the pills. The Army was allowed to order them to take the pills because the FDA made a determination that the pyridostigmine bromide—the PB pills would 

be allowed to be used for a use that it had not yet been licensed 

for. You are telling me that the Department of Defense promised 

but did not sign an agreement that they would inform. Is it conceivable that they FDA would have allowed our soldiers to be required to take these pills without their being informed, at least 

that they may have a bad chemical reaction, that this was an experimental pill for this use? Is it conceivable the FDA would allow 

our soldiers to not be informed? 

Ms. PENDERGAST. No, sir. As I indicated, we suggested and then 

worked with the Defense Department to create these information 

sheets so that the soldiers would have information——

Mr. SHAYS. They weren’t informed. And you’re telling me that 

they are technically not in violation of the consent because it was 

not a contracted, written agreement they promised to. But that was 

not part of the agreement technically. Was it part of the agreement 

technically that they would keep records? 

Ms. PENDERGAST. Yes, it was. 

Mr. SHAYS. OK. Did they keep records? 

Ms. PENDERGAST. They kept some records. In our judgment they 

did not keep sufficient records. 

Mr. SHAYS. So let me repeat my question. Were they in violation 

of the agreement? 

Ms. PENDERGAST. In that sense, yes. 

Mr. SHAYS. OK. So it terms of not informing our soldiers, they 

weren’t in violation technically, but they were clearly in technical 

violation as well as in the spirit in terms of not keeping records of 

who was given these drugs and so on. 

Ms. PENDERGAST. That is correct. 

Mr. SHAYS. OK. So what is the Department doing about that? 

What is your agency doing about it? 

Ms. PENDERGAST. Well, we’ve done a number of things. We have 

worked with the Defense Department to see if additional information could be provided to us. We have written them asking that if 

they have additional information on certain specific points that it 

be provided to us. In 1994, we sent them basically a ‘‘lessons 

learned’’ letter describing what was in our judgment the problems 

that we saw in the 1991 administration of the products and what 

could have been done better. And we are—as we indicate in our 

testimony—we are working to see whether or not this kind of a system worked and could work in the future differently or perhaps be 

abandoned. 

Mr. SHAYS. So what I’m basically to infer from what you’ve said 

is, clearly the spirit of the law—for them to get this waiver of informed consent, the spirit of the law was they were at least to inform the soldiers that this was an experimental drug first and that 

the spirit of the law was clearly to keep records, but technically 

they were not required to inform the soldiers, which blows my 

mind. And you’re saying technically they were required to keep 

records, which they didn’t. And you sent out a letter in 1994 and 

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they have ignored your interaction and communication and you’re 

satisfied? 

Ms. PENDERGAST. Sir, we’ve never said we were satisfied. We recognize that this did not go well. We are, if anything, disappointed 

that it didn’t go better. 

Mr. SHAYS. No. Disappointed isn’t good enough. Because this 

committee feels that some of our soldiers may have suffered severe 

physical problems as a result of taking an experimental drug in 

cases where maybe they took it after they were exposed to chemicals as opposed to before, and not knowing the relationship of when 

they should have taken these pills. So disappointed isn’t good 

enough for us. 

Ms. PENDERGAST. Let me explain. The law states quite clearly 

that informed consent may permissibly be waived if the obtaining 

of informed consent is not feasible or not in the best interest of the 

subject. That’s our law. It was written in 1962. 

Mr. SHAYS. Well, it was feasible. When they were given these 

pills, it was feasible to inform them. And that’s the least they deserved. 

Ms. PENDERGAST. At the time we wrote a regulation that addressed the question of whether or not informed consent was feasible in a military combat exigency, the testimony and the record 

at that time showed that the Defense Department indicated to us 

that during a military combat exigency, because of military command and in order to preserve the health and well-being, not just 

of the individual soldier, but of the other soldiers that would have 

to protect the soldier that had fallen as well as the troops as a 

whole, that informed consent was not feasible. The Food and Drug 

Administration accepted that representation. 

Mr. SHAYS. I understand why they may have decided not to allow 

for soldiers to consent. I have no sympathy whatsoever they 

couldn’t have informed the soldiers. And I am pained that after so 

many years have passed that you would concur in some way that 

they did not need to inform, that there was some military impossibility for informing. 

Ms. PENDERGAST. Sir, I have not made that representation. The 

Defense Department has to answer the question as to why it was 

unable to give them the information sheets. 

Mr. SHAYS. No. You have to enforce the requirements that they 

are technically required to. And have you enforced it? 

Ms. PENDERGAST. Yes. I believe we have. 

Mr. SHAYS. I wish you had just said ‘‘no’’ and we could have gone 

on. Because you haven’t you have sent out a letter. There will be 

no response from the audience, please. You have basically said you 

have sent out a letter. You have basically accepted and put on the 

record that military activity prevented them from even living up to 

the technical requirements and certainly the spirit. And I want to 

know specifically now, given that you said you are enforcing this, 

I want to know specifically what you’ve done to enforce their failure to live with the spirit and the technical requirement that they 

agreed to. 

Ms. PENDERGAST. As I indicated, we have expressed to the Defense Department in writing the problems we have found with 

their conduct of the administration of these drugs during Desert 

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Storm. And we have been working with the Defense Department 

and with others and the Presidential Commission on Gulf War 

Syndrome to ascertain what could be a better way of doing this. 

Mr. SHAYS. You’re talking about in the future. And I’m talking 

about the hundreds of thousands of soldiers who were sent into 

this conflict. And you have not told me how you have enforced their 

requirement. Have you asked for all their records? 

Ms. PENDERGAST. Yes. 

Mr. SHAYS. OK. How many have you received? 

Ms. PENDERGAST. I can’t tell you how many inches. 

Mr. SHAYS. Pardon me? 

Ms. PENDERGAST. I mean, we have received safety information 

and the other information that was required to be submitted under 

their investigational new drug exemption. As I indicated to you, it 

was not the type or quantity of information we would have hoped 

for——

Mr. SHAYS. That’s an understatement. 

Ms. PENDERGAST. We don’t disagree with you. This was war. 

This was the first time. And it didn’t work particularly well. We 

are in full agreement with you on that. 

Mr. SHAYS. This isn’t the first time the military has conducted 

themselves this way. And as long as they know the FDA is going 

to be a paper tiger with the military, they will continue to do this. 

They will continue to basically say ‘‘bug off.’’ And as far as I’m concerned that’s what they’ve said and that’s what you’ve accepted. 

And you have said under oath that they have sent you information, 

you have asked for information. So it’s just really important that 

you provide this subcommittee with specific requests and that you 

provide this subcommittee the results of what you requested. And 

we’ll just continue this later. 

I want to go on record as saying that I think this was an obvious 

question for me to ask you. I would have thought that you would 

have been very prepared to respond to it. And I think that if we 

didn’t ask these questions after having eight hearings on this issue, 

that we would be derelict in our duty. And so we are going to pursue this with the FDA. Because in my judgment the FDA allowed 

the military to do what they have to do in time of war, to have gotten a waiver from informed consent. 

They should have required that the troops technically, not just 

in spirit, be notified. And they should have made sure that it was 

being enforced. And the technical requirement of information, 

which is an outrage that it was not kept and data was not kept. 

And the FDA has not, in fact, really overseen this and sought to. 

And frankly, if you had said to me, we really blew it, just like the 

military, I could accept it. But you’re defending it. So now we’re 

going to pursue it. I have other questions for the other witnesses, 

but at this time I’m going to give Mr. Towns as much time as he’d 

like to consume. 

Mr. TOWNS. I yield to my colleague from Ohio. 

Mr. KUCINICH. Thank you very much, Mr. Towns, Mr. Chairman. 

I’m new to this subcommittee and to the Congress, but I have followed the Chair’s tireless efforts to get to the bottom of the Gulf 

War Syndrome. And it’s interesting to listen to this testimony, Mr. 

Chairman, with respect to the FDA’s non-supervisory status. I 

106

would like to ask the representative from the FDA, if she could answer this question? Since we’ve seen that the waiving of PB for 

military personnel in the Persian Gulf, waiving a consent for any 

reason can have serious consequences, do you agree that based on 

that experience there should be an immediate moratorium on waivers for any reason until some of the ethical problems that are being 

brought forward are addressed with comprehensive and stringent 

protocols for informed consent? 

Ms. PENDERGAST. Yes; basically I agree with you. There are no 

waivers in effect at this time, and haven’t been for a number of 

years. And the 1994 letter that we sent to the Defense Department 

was an indication that were there ever to be another waiver request considered—and there was no judgment made as to whether 

we would ever say yes again—but were we to even consider another waiver request, the specific standards would have to be much 

higher and more rigorous because of the failures. 

Mr. KUCINICH. So you’re saying this would never happen again? 

Is that what you’re saying? 

Ms. PENDERGAST. Not the way it happened this time. No. 

Mr. KUCINICH. And do you feel that the Department of Defense 

ran roughshod over the FDA here? 

Ms. PENDERGAST. It is difficult for us to say that. I think that 

the persons that we were dealing with were well-meaning. I also 

think that the FDA, which is an agency staffed with doctors and 

scientists, and not soldiers, has a very limited ability to secondguess what was going on in the Persian Gulf during the time of the 

war, and so—— Mr. KUCINICH. But when it comes to medical matters and matters related to bioethics, who should make the decision, a general 

or a doctor? 

Ms. PENDERGAST. There is an obligation on the part of the Defense Department to have doctors in charge of making sure that 

the troops received the drugs properly and that the information 

was given to them, and that adverse events were reported back to 

the FDA. Doctors had to be in charge. That was part of the system 

that was in place as we went forward to permit the Defense Department to administer these products. 

Mr. KUCINICH. So you’re saying military doctors made the decision? 

Ms. PENDERGAST. Military doctors. 

Mr. KUCINICH. But are they subject to review by the FDA? 

Ms. PENDERGAST. The military doctors basically had to report 

back to the FDA what they accomplished and what they failed to 

accomplish. And the reasons why the military doctors were able or 

unable to do particular things is a broader question of military logistics and chain of command during a theater of war. But from 

where we sat, we were talking to the military doctors who had obligations to do certain things and report back to the agency. 

Mr. KUCINICH. You know, one of the things, if I may, and I’ll let 

this go, Mr. Chairman, because I think that you’ve set the inquiry 

on a track that will eventually get the truth out, but something occurs to me about hearing this discussion. It’s very disturbing, because the whole idea of consent—in a way, it’s a matter of a time 

sequence. Troops are gathered to the Persian Gulf, they’re put in 

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staging areas, they’re engaged to the field. At some point along the 

way, even before people were sent out to the Persian Gulf, there 

was an understanding that they could run into an environment 

where nerve gas could be used. The idea of having PB came up, I’m 

sure, years before our troops went out there. And it just makes me 

wonder, Mr. Chairman, how this could have happened. 

Because we’re talking about a pick-up game, like a street basketball or street baseball game—everybody gets together and you 

make up the rules as you go along. People knew years before that 

if we were engaged in the Persian Gulf that nerve gas was a possibility. And for that reason it seemed to me that the exigencies of 

which we speak in combat are not a defensible argument for not 

providing informed consent. Because there was plenty of time to let 

anyone who would be in the Persian Gulf, Mr. Chairman—anyone 

who was going to be sent out there could have been told far in advance of being deployed to the field that they would be subject to 

taking a drug that could have certain consequences. 

But the uniformed personnel never had that opportunity. And 

that’s where I think the FDA has failed. And that’s where, also, I 

think the Department of Defense failed our enlisted men and 

women. So I sat in a hearing which the chairman called, and we 

listened to men and women who are the victims of Persian Gulf 

Syndrome—they weren’t told. So I have—I want you to know that 

I have a lot of respect for the role that the FDA plays in our society—I mean, to make sure that food and drugs that people consume are safe. 

It’s not a small matter. We all rely on it. It’s like a basic trust 

that we have. But in order to rescue that trust, the FDA needs to 

come forward with a comprehensive statement of what went wrong 

and what you intend to do to make sure it will never happen again. 

Because it’s very clear that there have been ethical breaches which 

undermine not only public trust but which have put human health 

on some kind of a foreign altar. And we ought never again be in 

a situation where this happens to our people. 

Ms. PENDERGAST. May I respond? 

Mr. KUCINICH. Please. 

Ms. PENDERGAST. I think, Congressman Kucinich, you raise an 

incredibly important point. One of the things that we are looking 

at now is the question of, having accepted the fact that war may 

happen, is it possible to obtain basically anticipatory consent from 

troops? As in the question of, if you were ordered to take it, would 

you take it? And then only field the people into war zones who are 

willing to say or whatever. But that’s a Defense Department question that I’m fully prepared—but that is the kind of debate that is 

going on. 

I think if you go back and look at fall 1990, this issue first came 

up when the Defense Department was preparing for war. And I 

think in the view of hindsight we know that there may have been 

better ways of doing it. But at the time, they were trying to basically protect their troops. And I would like to say that these two 

products—pyridostigmine bromide and botulinum toxoid—are products that, although not approved for this use, had been widely and 

extensively used by people. Pyridostigmine bromide is approved 

and has been since the 1950’s at doses 20 times higher than the 

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troops used. And people take it every day. And so we knew that 

it was a very safe product. Did we know it would work to protect 

them against nerve gas? No. Monkey trials showed it would. Did 

we know it would protect humans? No. But we had no way of 

knowing. Because it’s not ethical to give somebody a prophylactic 

drug and then expose them to nerve gas and if you’re wrong say, ‘‘Oh, I’m sorry.’’ You just died. So you can’t ethically test it. You 

do your best—— Mr. SHAYS. Excuse me. If the gentleman will—— Mr. TOWNS. It’s my time. I’ll yield. 

Mr. SHAYS. If it’s not ethical, then why did we do it to hundreds 

of thousands of our troops? 

Ms. PENDERGAST. Because based on the information we had, it 

was indisputably safe and—— Mr. SHAYS. No. But you just made a comment. 

Ms. PENDERGAST [continuing]. And we thought it was their best 

shot against nerve gas. You can’t ethically expose someone to nerve 

gas as part of a clinical trial. That is the point where it’s unethical. 

Nobody in the United States was ever going to expose our troops 

to nerve gas. The enemy was going to expose them. The question 

is what could we give our troops that would give them the best 

shot at making it through that adverse war time situation. We 

knew pyridostigmine bromide was safe. We had been giving it to 

people for 40 years. And we knew that in monkeys it had protected 

them against nerve gas. It was better than nothing. With respect 

to the botulinum—— Mr. SHAYS. Let me just say to you, if that’s the logic you used, 

then apply it to the private sector as well. And you don’t. I thank 

the gentleman for yielding. 

Ms. PENDERGAST. With respect to the botulinum toxoid, that botulinum toxoid is used routinely by the scientists at the Centers for 

Disease Control and by other public health officials. Again, you 

can’t ethically test biological and chemical weapons, even against 

volunteers. But that has been tested in animals. And it is used routinely by public health officials on themselves. Again, we though at 

the time that it was the best possible treatment or prophylaxis for 

our troops, that if we were going to war, if our children were going 

to war, we would want them to have that protection. 

Mr. SHAYS. I’m sorry. If the gentleman—— Mr. TOWNS. I yield further. 

Mr. SHAYS. No. I don’t—I can even accept that you would ultimately have done that. I cannot accept for the life of me that you 

would not have required technically under law to have informed 

the soldiers. That I cannot accept. And I cannot accept once the 

war had ended, that the FDA wouldn’t have been extraordinary 

vocal and active early on in making sure that records were kept. 

And if they weren’t kept that they heard big time from the FDA 

in such a way that they would never even want to consider doing 

something like that in the future. And frankly, the response of the 

FDA, the anemic response of the FDA, tells me that the military 

knows they can be comfortable to do it again. 

Mr. TOWNS. Let me move to another area, I think one even more 

basic. I’m concerned about the language used in some of these consent forms. It seems to me that you would have to be a person with 

109

a Ph.D., almost to understand the content of these forms. I know 

that there is an effort to provide simple verbal explanation. However, I wonder whether you can provide a simple written explanation? So why don’t I go to you, Ms. Pendergast, first, and then 

let others comment about it—because the consent form itself. 

Ms. PENDERGAST. I’m not sure which consent form you’re referring to. But it is one of the requirements of informed consent that 

it be written in a way that the subjects of the trial—the human 

volunteers—can understand it. So it has to be written—the regulations require that it be written in a way that the people who are 

receiving the information can understand it. 

Mr. TOWNS. How do we arrive at that particular form? You see, 

have you seen some of those forms, those consent forms? I mean, 

all of them—that you find that, in terms of the way they’re written, 

is just not clear. Just the average person would not be able to understand it. 

Ms. PENDERGAST. The institutional review boards that must review research before it is allowed to go forward looked at—— Mr. TOWNS. That’s another problem. Go ahead. I don’t want to 

cut you off. 

Ms. PENDERGAST. They’re the ones that are closest to the community where the research is going to take place. So we look to them 

for that—their job is to protect the human subjects. And their job 

is to stand in the shoes of the volunteers to make sure that the volunteers are treated properly. And they are asked to look at those 

consent forms and make sure that those consent forms are appropriate for the people in their community who will be subject to the 

research. Whether they do it right all the time or not—I’m sure 

they don’t. I’m sure mistakes are made. But if you look at the system, those are people who we turn to and say, is it in the right language, is it the right reading level, does it use too tough words, is 

it at the college level, should it be at the sixth grade or eighth 

grade reading level? Those are things that we turn to the institutional review boards to do. 

Mr. TOWNS. But you know, I think maybe if you make your answers a little shorter you might not have as many problems. 

Ms. PENDERGAST. Thank you. 

Mr. TOWNS. Because what you’re saying is, the review board— only CDC really—the review board—reflects the composition of the 

people that are going to be involved in the research. So why would 

you say—because that doesn’t make a difference. Because if you 

have people that are involved in the review board that do not reflect the people that are going to be in the study, then what good 

does that do? 

I don’t understand how you’re answering that. I can see CDC answering it that way, because there seems to be an effort to make 

certain that the people that are going to be in the study—actually 

that’s the people that would be on the review board. Now, that’s 

the only one I know—does anybody else? 

Dr. VARMUS. That’s true, also, Mr. Towns, of the review board 

that would review a proposal that’s being carried out under the 

terms of an NIH grant. Virtually all of our grants go to academic 

institutions and research institutions which have review boards at 

the institutions composed of people who represent the community—

110

diverse with respect to gender and race. They are asked to interpret the consent form to be sure that it is understandable by the 

subjects. Now you’re raising an important question, because if the 

language is too watered down you could argue that the study is not 

being adequately explained. 

We work with these institutions through the Office for Protection 

from Research Risks to try to provide guidance. We’ve had tremendous experience at our OPRR, and we work with our institutions 

to be sure that they can find the happy medium. 

Mr. TOWNS. Ms. Pendergast, can you say that? 

Ms. PENDERGAST. Yes. The same rules are true for all the research that the FDA regulates. The review boards have to have 

gender and racial diversity. There have to be representatives from 

the community. And if the research involves children or other vulnerable populations, experts from those fields should be consulted. 

Dr. SATCHER. Congressman Towns, let me——

Mr. TOWNS. Yes. Go ahead. 

Dr. SATCHER. I just briefly want to say two things. I think the 

issue of informed consent is a very difficult issue. And I’ve been 

struggling with it for at least—well, going back to the sickle cell 

research center in Watts in the early 1970’s, and I agree with Dr. 

Varmus. I think on the one hand, the critical issue is do people understand what you’re saying. On the other hand, are you including 

enough content so that they really are able to explore the substance of what’s going to go on with them. I think we just have to 

continue to struggle with this. I don’t think we have perfect informed consent forms. Or IRBs, for that matter. I think we continue to make sure that the institutional review boards reflect the 

community. And it is a continuing struggle. Because sometimes you 

get people because you think they reflect their community and you 

find out later that they don’t. 

Mr. TOWNS. Right. 

Dr. SATCHER. And then you put together an informed consent 

form, and then you find out sometimes the people don’t read them. 

A lot of us do that. Not just people who have trouble reading. But 

a lot of us sign things without taking the time to read them. So 

we’re struggling with all of those things. But what I think what 

we’re trying to do is to improve communication between our institutions and the public that we’re trying to serve. 

Mr. TOWNS. Right. Dr. Raub, do you want to comment? Thank 

you very much, Dr. Satcher. 

Mr. RAUB. I can add only in reinforcing my colleagues that the 

institutional review board is the first line of protection here. And 

every day they struggle with getting the message clear enough yet 

not so simplified that it misleads, and when they do explain a risk, 

explaining that risk in a way that is accurate without being so 

frightening or unnecessarily detailed as to mislead the subjects. 

There’s been the constant struggle over the last several decades especially in a very litigious society where every time the risk is not 

disclosed adequately it then creates legal problems. So I think each 

board must struggle with getting the information as simple and 

clear as possible without being inaccurate or misleading or otherwise exploiting the individuals involved. 

111

Mr. TOWNS. Right. Let me just sort of go back to something that 

was raised earlier. And I think that we have to be honest. I think 

that the chairman said something that I think that we need to 

really make certain that we put everything on the table. I’m concerned about the illusion of consents in certain circumstances. And 

of course, in the military or in prison, people are not free to say 

no. And I think we might as well go on and recognize this and 

admit it and let’s move on. And I think that that’s a fact. 

And I think that, the chairman raising his question—also the 

gentleman from Ohio—that there is no need to dance around those 

kind of issues. There are certain situations and certain circumstances where people cannot say no, not in the true sense of 

no. We have to recognize that and then determine in terms of what 

we might try to do to begin to work on those kinds of things in 

order to make certain that people’s rights are not violated. And I 

think that’s an open and honest kind of discussion. 

And I think that if we go about it any other way, I think that 

we’re not really being fair to ourselves and the time that we’re 

spending here together. So I want to lay that on the line, Ms. 

Pendergast, and to say to you that that’s what we have to acknowledge. That’s a fact. And of course—begin to deal with it. One more 

question, Mr. Chairman, and then I’m going to yield back, because 

I know that our time has been——

Mr. SHAYS. Mr. Kucinich will go after you. But you have more 

time. 

Mr. TOWNS. OK. Fine. I’m concerned about the HIV trials being 

conducted in Africa, in the Caribbean and in Asia. There are allegations that these trials would have never been conducted in the 

United States. On the other hand, there are those who say that if 

these trials are halted, it would be difficult to conduct future drug 

trials in Third World countries. I would like each of you to comment on where we should strike the balance when considering drug 

trials in other countries. 

Dr. SATCHER. Could I start? And the only reason I want to start 

is because that is the issue that I was referring to at the end of 

my testimony——

Mr. TOWNS. Yes. 

Dr. SATCHER [continuing]. When I mentioned that sometimes 

there can be, if you will, what seem to be competing ethical principles. I think the AZT trials in Africa and Thailand and some of 

the other places throughout the world that are being carried out by 

NIH and CDC are funded in this country but also carried out by 

the World Health Organization and the United Nations AIDS program are an example of that in many ways. And recently a group, 

Public Citizen, raised some of those issues. And I want to say that 

it’s a group that I respect. 

And I agree with them on most of the issues. I disagree on this 

particular one. I believe the AZT trials that we’re supporting and 

carrying out in Cote d’Ivoire and Thailand—and I’ll just speak to 

those two for CDC—in fact do meet ethical principles. The debate 

is whether, in fact, they would be conducted that way in this country. As you know, the 076 trials were carried out primarily in this 

country and in France—well-developed countries. And they reVerDate 0ct 02 2002 09:43 Oct 05, 2002 Jkt 010199 PO 00000 Frm 00115 Fmt 6633 Sfmt 6602 W:\DISC\44389 44389
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ceived long-term, high dose AZT treatment to prevent the spread 

of HIV from mother to child, sometimes 16–24 weeks of therapy. 

In the host countries where we’re conducting those trials, there 

is no AZT treatment which is now standard in this country and in 

France and some other places. And the reason that there is no AZT 

treatment has to do with cost and complexity of the 076 regimen. 

The international community has never accepted the 076 regimen 

as appropriate for developing countries. So what we did in working 

with our host countries in Cote d’Ivoire and Thailand was to respond to their concerns about AZT, their desire to implement AZT, 

but their recognition that they couldn’t do it the way we were doing 

it in this country. 

Now, the two ethical principles—No. 1, there is an ethical principle about when you enroll people in a study: Do you ever give any 

group less than what is the accepted standard of care? In this case, 

the accepted standard of care in this country is not the accepted 

standard of care in those countries. The other ethical principle is, 

do you respect the host country? Do you answer the questions that 

the host countries have? Do you conduct studies that you are going 

to be able to implement the outcome after the studies are over? 

And we have decided that in order to make a difference in those 

countries and to save lives we need to have the kind of studies in 

which we have a placebo control versus short-term AZT, like 3 to 

4 weeks, as opposed to the 16 to 24 weeks. And therefore, our studies are looking at: Can we make a difference using short-term AZT 

therapy that costs about $50 as compared to $800 to $1,000 for the 

076 approach that we use in this country, in countries where the 

average expenditures for health are $10 per capita. Those are the 

issues, I think, in the AZT trials. And that’s why they’re done differently. And those are the debates. I hope I’ve captured the essence of—— Mr. TOWNS. You have, but there are still some problems that I 

have. It is my understanding that when you have this going on, 

that the doctor who’s in charge of it is also responsible for the overall medical supervision for the patient. I’m not sure that’s safe. If 

I’m involved in research and I see a certain type of behavior that 

I think that somebody else should be able to evaluate and determine whether it should be continued or stopped. 

Dr. SATCHER. Right. 

Mr. TOWNS. I have so much invested in it as a person who’s providing the research, that I won’t stop even though I see signs 

that——

Dr. SATCHER. Exactly. I think it’s a very important point. These 

studies had to be approved by the CDC institutional review boards 

before they were funded. They also had to be approved by the host 

countries’ review boards, in Cote d’Ivoire and in Thailand. They 

have an oversight board. Not the physicians treating the patients, 

but a board of people constituted to look at the proposed studies 

and to answer the question: Are they appropriate for this population? The rules also say that they are to revisit those studies periodically and say, ‘‘Has anything changed in terms of benefits and 

risks? If so, then should we continue these studies?’’ One of the studies in Cote d’Ivoire, for example, we observed very 

early that there is a 10 percent still-birth rate among participants 

113

in the study. It turns out that whether people were receiving AZT 

or the placebo, they all—in that country there is a 10 percent rate 

of still-births among women who have HIV infection. So if we did 

not have the placebo group, we would not have known that. We obviously would have thought that it was the AZT that was causing 

the still-births. So I think the studies are organized in such a way 

and the oversight is done in such a way as to protect against the 

concern which you have. And I think it’s a valid concern. I think 

if we relied on the people who were just treating the patients to 

carry out these studies, I think you’re absolutely right. It would 

violate the rights of the patient. 

Mr. TOWNS. Any other comments? Yes? 

Dr. VARMUS. Mr. Towns, may I just comment briefly? I agree 

with many of the comments made by my colleague, Dr. Satcher. 

The issues that were raised by Public Citizen and that have been 

brought to your attention are not new ones. The 076 trials that 

demonstrated the efficacy of AZT in preventing maternal to infant 

transmission in this country and France were brought to conclusion. The World Health Organization organized a meeting in Geneva to consider the implications of those studies for the developing 

parts of the world where the transmission rate is, in fact, at its 

highest. 

It was generally agreed that in thinking about how we could 

translate the success of 076 to the other parts of the world where 

transmission was so frequent, we had to confront what is an evident fact to anyone who travels in many parts of the world: Namely what we in Europe and North America and other places receive 

from advanced medicine simply is not available nor affordable in 

those countries. The 076 trial was a very complex trial, and the 

methodology was very expensive and sophisticated. 

It was generally agreed by representatives of both developing 

and developed countries that any effort to carry out studies that 

would be effective and feasible in the developing world would have 

to involve studies that actually could be used. In fact, one injustice 

that could be perpetrated upon those countries would be to go there 

and do studies that were only applicable in parts of the world that 

could afford the therapies. 

There are many examples of that principle. It is one that is uncomfortable, because all of us would like to feel that the advanced 

medicine that is available to us could be available to all. But it’s 

a fact of life that it’s not. There are simple, cheap therapies that 

do work. A classical example is, as the trial carried out some years 

ago in Bangladesh, to ask whether oral hydration therapy for patients with cholera would work when we knew that in this part of 

the world intravenous hydration is effective. Well, intravenous hydration would not be a very feasible therapy in small villages. 

Oral rehydration works. It turns out, when the trial was done it 

was extremely beneficial. That’s a good example of why doing the 

appropriate trial can be of immense benefit. These are complex 

issues. We believe that the trials being carried out, which have 

been subjected to many review processes that Dr. Satcher has alluded to, have satisfied all the criteria for responsible review. 

Mr. TOWNS. Dr. Raub. 

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Mr. RAUB. I don’t believe I need to add any further detail to that. 

I share the basic principles that Dr. Satcher and Dr. Varmus have 

enunciated. 

Mr. TOWNS. Thank you. 

Dr. VARMUS. Mr. Towns, I would be pleased to provide for the 

record, if you would like, some letters that we have received from 

institutions both in African countries and in this country that are 

carrying out the collaborative work, who have responded to the letter from Public Citizen. I think you would find them reassuring. 

And I would be pleased to provide them for you, if you’d like. 

Dr. SATCHER. I just want to add one thing because I think there 

is another critical issue here. I don’t know all of the history behind 

some of the studies that have gone on, but I have visited Cote 

d’Ivoire and I know the people there and have worked with the 

people there in terms of what they really want to achieve from 

these studies. I know their concern about not being able to use 

AZT. I’ve met with the Minister of Health and the U.S. Ambassador there. 

We have funded the virology laboratory there. We are training 

people who in the future will be able to conduct studies like this 

and even more sophisticated ones in their own countries. I don’t 

want you to think that this is just a study that we’re going in, 

doing a study and coming out. Our commitment in these countries 

is to develop the kind of relationship that they will be able to 

buildupon. I think that’s happening. 

Certainly in Cote d’Ivoire. And I think it’s happening in Thailand. I’m going to visit there in July. But I think what we’re trying 

to do is to develop relationships that will be supportive and ongoing. And they’re doing the same thing. They’re visiting us, and in 

many cases contributing to what we’re trying to do in very useful 

ways. 

Mr. TOWNS. Mr. Chairman, I have a letter I’d like to add to the 

record, which is the subject of Public Citizen’s news release. And 

it says—it’s actually a letter to Dr. Varmus. And I’d like to include 

in the record—from Uganda Cancer Institute. So I’d like to make 

it a part of the record, as well. And it talks about, ‘‘I read with dismay and disbelief the above-mentioned documents regarding clinical trials in developing countries with special emphasis on those 

taking place in Uganda.’’ So I’d like to make this a part of the 

record. 

Mr. SHAYS. OK. 

[The letters referred to follows:]

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Mr. TOWNS. Thank you very much. 

Mr. SHAYS. Thank you. Mr. Kucinich. 

Mr. KUCINICH. I just have a quick question of Dr. Varmus. If 

NIH believes that only placebo controlled studies can provide answers to the questions most relevant in developing countries, why 

then is the NIH funding one Harvard study in Thailand in which 

no women will receive a placebo and all with receive anti-viral 

drugs? 

Dr. VARMUS. Well, we don’t believe that that is the only way to 

achieve results. Thailand, of course, is a somewhat different situation than some of the African countries we’re discussing today, because of the more—the stronger economy and the ability of the 

country to provide drugs that are more expensive and would be 

unaffordable in Africa. 

Mr. KUCINICH. And if it’s true that using placebo controls reduces 

the number of subjects needed to demonstrate statistical significance, why does NIH funded non-placebo controlled study in Thailand anticipate in enrolling fewer subjects than the U.N. AIDS program study in Tanzania, Uganda and South Africa? For example, 

you have, I think, 1,554 subjects in Thailand versus 1,900 in a 

combined U.N. AIDS study. 

Dr. VARMUS. 1,500 subjects being enrolled in Thailand. I’m not 

quite sure what the question is, Mr. Kucinich. 

Mr. KUCINICH. I’m asking why, if you are using placebo controls—if you’re saying that reduces the number of subjects that you 

need to have statistical significance—do you agree that you do 

that? 

Dr. VARMUS. Yes. 

Mr. KUCINICH. OK. Then why do you—why does this funded nonplacebo controlled study in Thailand anticipate enrolling fewer subjects than the study that’s going on with the U.N. AIDS program 

in Tanzania, Uganda, and South Africa. I’m trying to compare your 

policies with the other. 

Dr. VARMUS. I would have to look at the details of the protocols 

more closely to give you a direct answer to that question. I’d be 

happy to do that for the record. 

[The information referred to follows:]

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Mr. KUCINICH. OK. I’ll pass for now. 

Dr. SATCHER. I may have contributed to some of the confusion. 

There are two or three reasons why we feel the placebo control 

studies are important and I’ll just briefly mention them. You know, 

I mentioned what the countries are wanting to learn from these 

studies. One issue is safety. They want to be certain that AZT is 

safe as it relates to the mother and a developing fetus. And it’s a 

question that can only be answered by using, from our perspective, 

placebo controlled studies. We can’t answer it satisfactorily comparing short-term dose with a long-term dose of AZT. 

I gave one example of that. There are also complicated statistical 

reasons why we couldn’t answer that question using short-term 

AZT comparing it with long-term AZT. And so I think there are 

questions that the host countries have asked that we can only answer, certainly in Africa, by using the placebo controls. 

Mr. KUCINICH. Well, one quick followup based on this colloquy 

with Dr. Varmus. Did you say that using the placebo controls is not 

the only way to do a study? 

Dr. VARMUS. You can get information. It may be less reliable. It 

may take more enrollees. Again, I don’t know the details of the protocols you’re alluding to. One obvious reason why the study populations might differ in size is because of the frequency of infection 

or the prevalence of infection in those populations. 

Mr. KUCINICH. Do ethical considerations come up when you get 

into those matters? 

Dr. VARMUS. They might depending, again, on the availability of 

support systems to provide the drugs that might be used. 

Mr. KUCINICH. Would you advocate that the most ethical way always be used in designing your protocols? 

Dr. VARMUS. Well, I think you have to be clear about what the 

most ethical way is. 

Mr. KUCINICH. Yes, we do. That’s what we’re here. 

Dr. VARMUS. Yes. I know. But it can be difficult. It may vary 

from country to country. 

Mr. SHAYS. Gentlemen, we’re going to probably need to ask questions for another 30 minutes. We have a vote now. I’d like to say 

to the second panel it’s very unlikely that we would get to you before 1 o’clock. And so you may want to get something to eat. We’re 

going to have a vote and we’re going to come right back. We consider this an expert panel. 

Not to be compared to many others we have had. You are an excellent panel and we really want to get some things on the record. 

So we’re going to vote and come back. We may then end up with 

another vote 10 minutes later, and I apologize. But we’ll make the 

best of it. So I would just say to the second panel, if you’re back 

by 1 o’clock, we’ll begin with the second panel at 1 o’clock. I don’t 

think sooner. And so you don’t need to be here sooner. I want to 

be clear. Second panel does not need to be here before 1 o’clock. We 

stand at recess. 

[Recess.] 

Mr. SHAYS. Dr. Raub, let me start with you and ask why has 

HHS not abided by the regulations by making appointments to the 

Ethics Advisory Board? And it goes back a long ways. I’m not 

146

throwing stones here. But it goes back to 1979. I’d like the short 

reason. 

Mr. RAUB. I’ll do my best, sir. 

Mr. SHAYS. OK. 

Mr. RAUB. The Department believes that it is operating in conformance with both the law and the regulation with respect to the 

Ethics Advisory Board. The 1975 regulation did several interrelated things: It imposed strict limits on research with fetuses and 

with pregnant women; put an outright ban on in vitro fertilization 

research; and then defined a process for exceptions. And the Ethics 

Advisory Board, or boards, were the vehicle where exceptions could 

be considered to either the ban on in vitro fertilization research or 

the restrictions on research with fetuses and pregnant women. 

Mr. SHAYS. I had interpreted the Ethics Advisory Board had 

broad discretion over ethics in medicine, not limited to just a certain area. 

Mr. RAUB. The regulation is framed where the secretary has the 

discretion to have an ethics advisory board for specific tasks of that 

sort or for a broad set of issues. 

Mr. SHAYS. So it’s not one board that’s supposed to make a ruling 

on lots of different issues? 

Mr. RAUB. No, sir. The regulation allows for the possibility of 

several different boards. 

Mr. SHAYS. Or just one. 

Mr. RAUB. Or just one. 

Mr. SHAYS. Yes. But why would it be in our best interest to establish commissions and not have a board that is fully funded and 

has a staff. For instance, you’re getting an executive director, basically a replacement—you’re acting as the executive director, correct, of the commission? 

Mr. RAUB. Yes, sir. 

Mr. SHAYS. And I don’t understand why that would be a logical 

way to proceed. It seems too ad hoc to me. 

Mr. RAUB. OK. Well, one of the options available to the administration was to invoke the secretary’s authorities to create an ethics 

advisory board. And it could have addressed essentially the same 

agenda that the NBAC is. However, we view it as clearly more desirable for this to be a Presidential level commission, especially giving it the span of involvement of multiple agencies in the Government that are involved in research on human subjects. 

Mr. SHAYS. How many people are employed on this board? 

Mr. RAUB. There are 17 members of the board, 17 commissioners. 

Mr. SHAYS. Yes. 

Mr. RAUB. And the staff supporting it involves eight full-time 

staff and four who are part-time. 

Mr. SHAYS. Now, your testimony, I thought, said it continues or 

authorized until, what, October? 

Mr. RAUB. That is correct. 

Mr. SHAYS. What’s the logic of that? 

Mr. RAUB. The Executive order signed by the President covered 

2 years from the date of the President’s signature. And the Executive order allows that it expires on that date unless extended by 

an Executive order. 

Mr. SHAYS. Right. So what’s going to happen? 

147

Mr. RAUB. Well, the administration is now considering extending 

the NBAC charter via amendment to the Executive order because 

of the additional work load that has developed and because of the 

additional issues that have been identified. 

Mr. SHAYS. Well, it seems to me like a no-brainer that we need 

this work done. I don’t quite understand why this wouldn’t be a 

permanent board. In other words, when I’m looking to see what we 

have, we have basically local institutional review boards. We have 

those. We have the institutes of health and their boards and we 

have the Ethics Advisory Board not constituted. I see a gigantic 

void here. And you don’t see a big void? 

Mr. RAUB. Sir, I believe you’ll find many advocates within the 

Government as well as outside for the notion of a continuing body 

with functions similar to that of NBAC to address these issues just 

in the way you’re suggesting. Many are looking to the experience 

with NBAC as getting additional evidence and information as to 

the desirability of such a board. And I believe that’s one of the 

major issues under consideration right now. 

Mr. SHAYS. Why would someone take a job that basically they’re 

not guaranteed that they’re going to have it go until October? 

Mr. RAUB. I would share that concern, sir. And we’re hopeful 

that by the time we are ready to make a selection we will have had 

some resolution as to the extension of the board. 

Mr. SHAYS. OK. Dr. Satcher, what specific steps would your 

agency take to detect what is called the—I guess we call it the 

therapeutic illusion. Really, let me ask it in the way I think makes 

sense to me. Some testing is a healing agent, and you want to test 

whether it really succeeds in doing what it’s projected to do. Others 

you might just do testing for safety. How do you notify someone in 

a clinical trial that really all they’re doing—they may get sicker, 

we just want to know if it’s safe? What are the requirements that 

you feel have to be made ethically? 

Dr. SATCHER. Let me say that in most cases we’re asking both 

the efficacy and the safety question. It’s just, again——

Mr. SHAYS. But not always. And I want to be clear. The only reason I would participate in some kind of clinical test is the thought 

that I might get healed and I’m willing to take the chance. And 

you’re going to warn me of all the potential downsides and I’m still 

going to do it. But I want to know if there is a requirement to tell 

someone that along with talking about, well, this may not be safe 

here, there’s no promise that it’s going to help you? 

Dr. SATCHER. I think definitely we’re required. And the informed 

consent form should make that very clear, that they are involved 

in a study that may not benefit them personally at all. And if an 

informed consent form does not make that clear, then I would say 

that it’s inadequate. 

Mr. SHAYS. Dr. Varmus. 

Dr. VARMUS. Mr. Shays, I think you’re referring mainly to phase 

1 clinical trials for which NIH probably has more responsibility 

than the CDC. 

Mr. SHAYS. Right. 

Dr. VARMUS. Our consent forms do explicitly make clear that 

there is no intent to—no expectation of clinical benefit. This does 

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tion is that they will be testing here for safety. That will allow 

some determination of what doses might be used, and then you can 

proceed into a phase 2 trial. 

Mr. SHAYS. Are you suggesting, though, that there may still be 

the hope that the person has that this could result in some healing 

benefit? 

Dr. VARMUS. There is in some cases that possibility, but we 

stress to the patients in these very limited studies that the intent 

of the phase 1 is to establish safety and that they are performing 

a service through their participation and research. This is why we 

take these consent forms so seriously, particularly in that phase of 

the experimentation. 

Mr. SHAYS. Now, with the Office for Protection from Research 

Risk, that basically is an in-house. I’m trying to understand——

Dr. VARMUS. The OPRR——

Mr. SHAYS. I’m trying to deal with the issue of how you avoid a 

conflict of interest. You’re an independent ‘‘watch dog.’’ And yet, 

you’re basically providing for research. You’re involved in the whole 

ethics of whether it’s allowed, but you’re funding it. 

Dr. VARMUS. Well, let me address that issue, Mr. Shays. 

Mr. SHAYS. I’m sorry? 

Dr. VARMUS. Let me address that issue. 

Mr. SHAYS. OK. 

Dr. VARMUS. The OPRR does provide oversight for activities that 

are carried out by the NIH institutes and also by the CDC and 

FDA and other organizations within the Department. It has administrative housing and some administrative oversight from Dr. Baldwin’s office, the Office for Extramural Research. It’s important to 

remember that the office does not have any vested interest in seeing the research go forward in the sense that my office would be 

funding the research. The research is being funded by the CDC or 

by institutes, each of which has its own authorization and its own 

appropriation. It is the institutes that are responsible for funding 

those studies. So there really isn’t the conflict of interest that I 

think you’re——

Mr. SHAYS. I’m missing something. Because it’s the same organization. You’re just saying a division within the organization. 

Dr. VARMUS. Well, there is fiscal independence and a responsibility for funding a study that lies outside of the office of the director in which the administrative housing occurs. 

Mr. SHAYS. And you’re satisfied that that would meet an independent’s test? 

Dr. VARMUS. I think it does. As you heard from Dr. Raub, I was 

concerned about having the NBAC housed within the NIH because 

the NBAC is, of course, looking at much broader issues that establish the principles in which informed consent or protection of individuals of abuse of genetic information might be carried out. The 

OPRR is following regulations that were issued by the Department. 

And it’s governing compliance with already established rules and 

regulations. 

Mr. SHAYS. Doctor, do you believe that mentally ill individuals 

and those who are addicted should have a different protocol, should 

be covered explicitly by HHS regulations? 

149

Dr. VARMUS. Yes, but special care needs to be taken in overseeing studies that involve patients that may be cognitively compromised. I discussed that in my testimony. This is a very difficult 

issue, which accounts for the large number of studies and work 

shops and consultations that the institutes involved in such studies 

are involved in. 

Mr. SHAYS. With regard to Alzheimer’s patients, do you have 

written guidelines for informed consent? 

Dr. VARMUS. The National Institute on Aging, which has a major 

responsibility for such patients is working on such guidelines. They 

will be participating very actively in the upcoming work shop this 

fall in which we expect to confront the issue of consent in such patients as a special case study during the proceedings. 

Mr. SHAYS. Why wouldn’t have that already occurred? 

Dr. VARMUS. Attention has been given to it. But, of course, there 

is always the need to proceed further and evaluate what has been 

done. We were not oblivious to the fact that patients with cognitive 

disorders of aging present special problems. But we do believe that 

as we gain increased experience, we should be profiting from that 

by further contemplating the issue. 

Mr. SHAYS. This is an issue, Dr. Satcher that you have already 

addressed. But I want to just clarify it for when we write a report 

or recommend legislation. It deals with generally the issue that 

was being raised by my colleagues of trials done overseas. And I’m 

gathering that in Thailand the CDC is funding placebo control 

trials. 

Dr. SATCHER. Right. 

Mr. SHAYS. And the answer is yes to that. The NIH has another 

program where there’s no placebos. And I think I heard your response, which I’m not critical of, because I’m just—I may be critical 

of it, but it seems like an interesting issue to deal with; you’re saying that overseas some patients wouldn’t have gotten AZT anyway. 

Dr. SATCHER. That’s exactly right. 

Mr. SHAYS. Pardon me? 

Dr. SATCHER. It’s not the standard of care. 

Mr. SHAYS. Right. But isn’t there an incredible temptation that 

we have to be careful of, of suggesting that a lot of things, health 

care that people don’t get overseas—— Dr. SATCHER. Yes. I think you’re right. 

Mr. SHAYS. And it almost becomes your proving ground—the rich 

United States with all our good laws and all the medicine that’s 

available to American citizens. But overseas you can say, you 

wouldn’t have had this anyway, so you’re not losing anything. And 

I’m just curious how we sort that out. Because I think it’s potentially a dangerous road to travel. 

Dr. SATCHER. I think so. I think it’s a complex issue. And I think 

it has to be looked at just as you have described it. Let me say that 

there is an international community involved here, and it’s not just 

the United States. I think the U.N. AIDS program, which is very 

important in this, as well as the World Health Organization have 

both looked at the AZT regimen that we use in this country and 

that’s used in some European countries. 

I think the critical issue—and I think it’s referred to in the international guidelines for research—has to do with the host country 

150

and the extent to which the research is meeting the needs and interests of the host country and is going to result in benefit for the 

host country. I think these are really the key issues that we’re 

struggling with when we try to resolve the question that you raise 

which is so important—To what extent will the host country benefit from this study? To what extent are they asking the questions 

that your study is seeking to answer? 

Mr. SHAYS. Yes. 

Dr. SATCHER. History is very important as you know. And we 

were just talking earlier when you were away that the hepatitis B 

vaccine studies that were done in China in the early 80’s—very 

similar to what we’re discussing now in Africa and Thailand—a 

major problem in China—hepatitis B. We had the immune globulin 

in this country. It was a little different situation in terms of what 

we were able to afford and what was being used. However, that 

study was very important and of great interest to the Chinese. Of 

course it resulted in showing the efficacy and safety of the hepatitis 

B vaccine. 

It’s benefited China significantly, but it has also benefited us. 

And as you know now, it’s a major part of our vaccine regimen in 

this country. But it was done because of the interest of the Chinese 

primarily. The same thing is true here in terms of the short course 

of AZT therapy. Obviously, the interest of the people in the Ivory 

Coast and in Thailand is that we don’t feel that we can use the 076 

regimen. We would like to know if there’s another way we can use 

AZT to intervene to prevent the spread of AIDS from mother to 

child. Is there a cheaper way? Is it safe? Is it efficacious? 

Mr. SHAYS. I just want to highlight the issue, though, that it’s 

almost this imperialism of the United States of having one standard overseas and another standard here because we say, well, it’s 

a different culture, different society, different wealth, different 

standards. And then we can then end up doing things there that 

we would never conceive of doing here. 

Dr. SATCHER. I don’t think we should unless it’s in the interest 

of that country and unless that country is making it very clear that 

it’s in their interest and it responds to their questions. I understand your point. And I agree that there is a danger that we could, 

in fact, exploit other countries. 

Mr. SHAYS. OK. I’m going to ask the other two to followup. At 

the same time I’m just going to ask this question: Do infrastructure 

problems of malnutrition and poor water supply ultimately distort 

the finding of a clinical study that may give us a result different 

overseas than in the United States? But I’d like the first question—

I’d like all three of our other panelists to respond to the ethics of 

experiments overseas based on different laws overseas and based 

on lack of wealth that says that they would have been denied certain health care that they would get in this country. Dr. Raub. 

Mr. RAUB. Well, first of all, Mr. Chairman, I agree with your 

principle that we must be sensitive from the beginning and all 

through that what we may pursue with the best of intentions and 

compassion might somehow slip into being exploitive or imperialistic. And so that must be a caution all the way through. From 

my point of view I believe there are four principles that affect these 

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studies. My colleagues have spoken to them in various ways. But 

just very quickly. 

That the treatment that is involved, in the judgment of experts, 

have a reasonable chance of working; that the treatment be well 

matched to the health care system of that host country, that is 

something that could be adopted and become the standard of care 

if the results of the trial were sufficiently positive. Third, that the 

placebo control be used only when necessary, that is only when the 

historical information is so bad that it would be worthless and 

would not lead to either good science or an ethical study. Finally, 

that there be full participation of public health officials in that host 

country from the beginning, in terms as Dr. Satcher was indicating—the design of the studies and the implementation. 

I believe that those four principles can be held through with systematic use of IRBs and wherever possible to avoid the conflicts of 

interest. Then I think we have an excellent chance of doing things 

that are good both for the host country and this Nation. 

Mr. SHAYS. And I’m going to come back to the infrastructure 

issue and the malnutrition issue in a second. Dr. Varmus. 

Dr. VARMUS. Mr. Chairman, I don’t want to reiterate what has 

been said, but I also would point out that the issue of exploitation, 

which is that one that’s currently being addressed, presents a number of problems. Perhaps the most egregious of these, in my view, 

would be to carry out in a developing country a trial which only 

produced results that would be of benefit elsewhere and not in that 

country. That’s why the design of the studies we’re talking about 

need to be one that could lead to an outcome that would be beneficial to the country in which the study is being carried out. 

Mr. SHAYS. So that would be a primary determinate for all three 

of the panelists. Ms. Pendergast, do you want to comment on this 

issue? 

Ms. PENDERGAST. No. I would just reiterate the comments of my 

colleagues. I think we all recognize that this is an incredibly complex ethical and scientific question that reasonable minds can and 

do debate. And I think that the debate is healthy. And I think it 

behooves us all to continue to critically explore these issues to 

make sure that we are on and stay on the proper path. 

Mr. SHAYS. OK. It’s my intention to end at 1 o’clock. Dr. Varmus, 

you have to be over there at 1 o’clock? 

Dr. VARMUS. I believe so. Yes. 

Mr. SHAYS. OK. We’ll make sure you have a car ride over and 

get you over there unless you have 10 people with you. 

Dr. VARMUS. No. 

Mr. SHAYS. OK. I would like to be clear on—just very quickly. 

Not a lot of time on this. But the nutrition conditions of an individual overseas, malnutrition, other issues that are cultural in 

terms of wealth, does that distort findings making them applicable 

to the United States? Just go down the line. 

Dr. SATCHER. It can definitely. I think there are instances in 

which the nutritional or status of the participants—and maybe 

even in the cases that we’ve been discussing—has impact. Those 

are the kinds of things that we want to understand better. But 

there are instances where we think that we can. One—if I could 

just get back for 1 second to the EZ studies? 

152

Mr. SHAYS. Yes, sir. 

Dr. SATCHER. There are many who believe that the differential 

mortality that was observed in the countries in Senegal and Haiti 

could well have been related to the nutritional status of the participant. Now, we haven’t had enough studies to know, but there are 

many who think so. 

Mr. SHAYS. Fair enough. OK. 

Dr. VARMUS. I would just comment that the hope of obtaining a 

useful and convincing result in studies carried out and in environments that, as you point out, may be affected by a number of other 

contributing factors like sanitation, can be most effectively pursued 

with a randomized control trial. 

Mr. SHAYS. Private sector—we haven’t even gotten into the issue 

of when the private sector conducts—we haven’t focused on it— their own studies, who oversees the ethical conduct of those studies? 

Ms. PENDERGAST. The Food and Drug Administration does, sir. 

Mr. SHAYS. So basically you’re the operative force in those areas? 

Ms. PENDERGAST. Yes. For products that the FDA regulates, we 

do. 

Mr. SHAYS. OK. CDC doesn’t get involved, Institutes of Health 

don’t get involved unless—— Dr. VARMUS. We do if there is a collaboration with an NIH supported institution. 

Mr. SHAYS. OK. 

Dr. SATCHER. Same with the CDC. 

Mr. SHAYS. HHS? Through FDA. 

Mr. RAUB. Through FDA or, as Dr. Varmus and Dr. Satcher indicated, when there is a collaborative arrangement with work funded 

by them. 

Mr. SHAYS. OK. Dr. Varmus, why don’t we let you get on your 

way so you have some time to get there at 1 p.m. 

Dr. VARMUS. I appreciate it. 

Mr. SHAYS. And we’re going to end in just a few minutes, but let 

me just pursue this. Ms. Pendergast, Dr. Satcher and Dr. Raub, if 

you could just participate in this last part. How does the process 

work in the private sector in terms of informed consent? Tell me 

how the process would work, the oversight process of FDA. 

Ms. PENDERGAST. The—— Mr. SHAYS. In other words, I’m looking for—you don’t have a 

board. Do you have a separate board that oversees the informed 

consent issue? Who deals with that issue? 

Ms. PENDERGAST. The system is very parallel to what governs 

Federal research. Before a study can be conducted in the United 

States, the company has to seek the FDA’s approval of the trial. 

The informed consent, and making sure that the trial is ethical, 

and that the risks are outweighed by the benefits is, again, handled by an institutional review board, which has to be a diverse 

group of people who will review this study. So you have overlapping responsibilities with the sponsor of the trial who has to make 

sure that the trial is properly designed and that the clinical investigators are competent. 

The clinical investigator is obliged to get informed consent. The 

institutional review board is obliged to oversee the study and the 

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consent. And then the FDA has a bioresearch monitoring program 

where we do inspections of all three: the sponsors, the clinical investigators, and the institutional review boards in an effort to 

make certain that they are living up to their commitments. 

Mr. SHAYS. OK. I’m not quite clear if this is an individual or a 

board that oversees this process. 

Ms. PENDERGAST. With respect to the FDA, we have employees 

in all of our different centers and across the United States that 

work on this. We did 1,000 inspections last year with respect to research integrity issues. So there are many people at the FDA involved in this. But every clinical trial has a specific institutional 

review board at the institution, whether it’s a hospital or academic 

center, that reviews the study before it goes forward as well as the 

FDA. 

Mr. SHAYS. Are there any questions that you wish we had asked 

that you were prepared to answer, that you would like to answer? 

Ask the question and answer it; something you feel we should have 

asked? 

Dr. SATCHER. I just want to say that, if we haven’t said it before, 

that I think this discussion is very important, and despite our defense of what we do we understand that these issues require a lot 

more discussion and debate continually. And I think that’s what’s 

going to get us where we want to be in terms of protecting the 

rights of people in this country and throughout the world. So we 

appreciate the discussion, and we plan to continue to participate in 

it, here and outside. 

Mr. SHAYS. Doctor, I thank you. This is something that this subcommittee—we have extraordinary oversight because we oversee 

five departments. And HHS is so gigantic as the Department has 

a larger budget than most gross domestic products of other countries. So how HHS puts everything together and is able to fulfill 

its mandate is quite something. We have always tried not to take 

pot shots at any of you in this business. 

We know that we have not always provided the resources for you 

to do the job, and there is so much that needs to be done. The one 

thing that we’ve always liked is candidness. And we’re not trying 

to dig people into holes and then have them climb out. I just want 

to know, Ms. Pendergast, if you have any comment you want to 

make, any question you wish we asked or any qualifying statement 

on anything that you said? 

Ms. PENDERGAST. Thank you. I think it’s important to recognize 

that we share your basic concern that the troops during the Persian Gulf conflict were not given the information that we had 

hoped they would get. Perhaps I was too bureaucratic in my response. We were disappointed. We let the Defense Department 

know that. And we will submit for the record the precise documents, where they made the promises and our responses back so 

that you can see what the agency did back then. But I think it’s 

fair to say that that experience taught us a lot. And we will not 

move forward with other kinds of waivers of informed consent in

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the military until there has been another round of public discussion, rulemaking, where we take into account the views of the veterans, take into account all that we learned as a result of this effort, and take into account the concerns raised by the Presidential 

Commission on the Gulf War. We learned a lot, and we will use 

that information as we go forward. 

[The information referred to follows:]

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Mr. SHAYS. I appreciate that comment. Let me just say it’s not 

meant to be an aggressive statement on my part, but words like 

‘‘hoped’’ and ‘‘disappointed’’—it’s not that we want the hope that 

they do it—and the mere fact that that word is still being used— and I’m not trying to nit-pick here. I just think that what we will 

probably, as a subcommittee, give you plenty of warning before we 

have a hearing just on the whole issue of what the military was 

supposed to do with the waiver, and how they responded and then 

how you responded. 

And I’m hopeful that maybe that hearing won’t be necessary. 

We’ll look at what you have given us. But I’m going to just suggest 

it. It may be what will be required to have it publicly understood 

how strongly you feel about it and how strongly Congress feels 

about it as well, so that it will be an added incentive for the people 

that take your place. Because, God help us, we won’t have this 

kind of need for many years in the future, if ever. Any other comments that others might want to make? Yes, sir. 

Mr. RAUB. Mr. Chairman, just the comment of thanks to you for 

focusing on these issues. In particular, the notion of having some 

continuing mechanism to address ethical issues has not always received a lot of attention, its significance not always understood. I 

believe your hearings have sharpened those questions and provided 

an important set of information. 

Mr. SHAYS. Well, I thank you. I have to say that as I talked 

about a permanent advisory board, I was thinking, there you go 

again. You say you want to reduce the size of Government, and you 

want something permanent. So I acknowledge that in this area I 

think that there needs to be something a bit more permanent. And 

maybe I’m wrong and maybe I’ll reconsider. But I will look forward 

to the dialog that we’ll have. It’s always been a constructive dialog 

with the FDA, the Institutes of Health, HHS, and CDC. We’ve really always appreciated the cooperation we’ve received and the staff 

has received. 

I thank you all, and I thank all those of you who were sworn in 

who never got to testify. I really frankly probably would have 

learned more from all of you. I just wish I knew that question that 

would have triggered you to come forward. Thank you, and we’ll 

hear the next panel. Thank you all. 

Ms. PENDERGAST. Thank you. 

Mr. SHAYS. This committee will call forward Arthur Caplan, professor of bioethics, University of Pennsylvania, Benjamin Wilfond, 

who is professor of pediatrics, University of Arizona; Dr. Peter 

Lurie, professor of medicine, University of California; and Laurie 

Flynn, executive director, National Alliance for the Mentally Ill. 

So we will proceed in the order of Dr. Caplan, Dr. Wilfond, Dr. 

Lurie, and then Ms. Flynn. Do we have all of the witnesses here? 

And I’m going to catch you before you sit down, Ms. Flynn, because 

we’re going to have everybody stand and I’ll swear you in. 

[Witnesses sworn.] 

Mr. SHAYS. Thank you. For the record, we had five who stood up 

and four witnesses who will actually testify. And all responded in 

the affirmative. I’m sorry. We have a vote. I’ve gotten you sworn 

in; that’s one task. We have a 15-minute vote and a 5-minute vote. 

So I will say that it’s unlikely that we will be back until 1:30 p.m. 

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And I’m sorry about that. I will say before we recess that I am very 

grateful to the four of you for coming to testify and listening to the 

first panel, and will welcome your response and observations of 

what you’ve heard from the first panel. So you can digress a bit 

from your statement to also include comments about that. And we 

will recess. And given the vote, we will probably not be here until 

1:30 p.m. 

[Recess.] 

Mr. SHAYS. This hearing is called to order. Do any of you have 

plans for this evening? I think, Dr. Caplan, we’re going to begin 

with you. And welcome. 

STATEMENTS OF ARTHUR CAPLAN, PROFESSOR OF BIOETHICS, UNIVERSITY OF PENNSYLVANIA; BENJAMIN 

WILFOND, PROFESSOR OF PEDIATRICS, UNIVERSITY OF ARIZONA; PETER LURIE, PROFESSOR OF MEDICINE, UNIVERSITY OF CALIFORNIA-SAN FRANCISCO; AND LAURIE FLYNN, 

DIRECTOR, NATIONAL ALLIANCE FOR THE MENTALLY ILL 

Mr. CAPLAN. Thank you, Mr. Chairman. I’m very pleased to have 

the chance to testify before you and the committee. The question 

of whether the time has come to consider changes in the way 

Americans are recruited to and participate in biomedical research 

is of obvious importance, as we’ve heard some of the issues discussed this morning. I think research is very crucial to the high 

level of care Americans receive and that is available to them. But 

it also does require the participation, the sacrifice and even the voluntary altruism of people who are going to be subjects. 

And so protecting their interests and their rights is crucial in 

order for continuing progress to be made in the quality of care we 

receive. It seems to me that this Nation has not always done what 

it ought to do to ensure the welfare and dignity of those who make 

themselves available as subjects. We’ve heard reference already 

this morning to incidents in our own past—the Tuskegee study and 

some of the exploitation of people in the military in the 1950’s and 

60’s involved in radiation experiments, mentally retarded children. 

So we know we have to do better. We have to be vigilant. And 

at the same time I think we’ve tried to institute a series of protections—informed consent and peer review by IRBs—that will keep 

us away from some of our most egregious failures in the past. Really what I want to do is talk just a bit. You have my written statement. So I’d like to just concentrate on a few areas where I think 

those two protections are in jeopardy. We’ve heard a lot today 

about one of the areas that I want to especially focus in on. 

That is the IRB system. I’ve been on IRBs for a long time. I have 

chaired a number of IRBs at different institutions. I think I have 

a very good understanding of what IRBs—institutional review 

boards—can do. And their charge, in part, is to make sure that people do get informed consent by looking at the informed consent 

forms, by weighing risk and benefit that is put before them. But 

Mr. Chairman, I think there are a number of factors in the research world as we now know it that are impairing the ability of 

the IRBs to do their jobs. 

We’ve had reference briefly to the phenomena of privatization of 

research funding. More and more of our research is now supported 

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by private sources, not the NIH and not Federal sources. We find 

ourselves in situations where private sources are beginning to put 

restrictions on information that is available to not only subjects but 

to IRBs. 

And in this area in particular I’d like to note for the Chair that 

we’ve had incidents where private companies have now stepped forward and said research cannot be published because it is held as 

a secret or that it has been contracted with an institution, that it 

will be done with condition that the company must sign off. A recent example of this was Boots, now the Knoll Pharmaceutical Co., 

with its drug Synthroid—is one such example of restriction of information. 

Mr. Chairman, if an IRB cannot get all the information that it 

needs to have about conflict of interest, financial sources of funding, if a firm is in a position to say that it will not publish legitimate findings about a particular drug or device, then the interest 

of subjects cannot be protected. So if we need to—and I feel we 

must—we have to ensure that IRBs have the information available 

to them so they can know when a researcher has a conflict of interest. We need to make sure that secrecy and provisions of restriction 

on findings of information are not part of what goes on in American 

institutions. In the end, to fail to publish findings—and I say this 

knowingly and deliberately—but to fail to publish findings that you 

have is a betrayal of what is owed to human subjects. If you don’t 

get results out, if you don’t put them in the peer reviewed literature, then you’ve asked people to carry burden, be involved in 

risk, face a sacrifice in coming to and from experimentation, for no 

purpose. 

And so for me, one of the most sad and unfortunate consequences 

of what we’re asking our IRBs to do is we’re asking them to work 

sometimes without the information, without the access that they 

need to have to do the job right. 

That makes me cite a secondary issue, which I think the chair 

should pay close attention to. I’m very impressed with the previous 

panel and its comments about the role of IRBs and making sure 

that informed consent forms are understandable and that people 

have information. 

But Mr. Chairman, I feel we have a system now that is spending 

too much time at the front end of research, looking at the written 

informed consent forms—that’s what IRBs do. And the ones that 

I’ve served on—I would estimate that 97 to 99 percent of the time 

is spent in a room looking at an informed consent form, trying to 

translate medical jargon back to English. Sometimes that works 

and sometimes it doesn’t. Sometimes subjects know more than you 

think because they’ve been involved with the disease process and 

have learned a lot about medical issues. So what looks difficult to 

understand to the outsider may be understandable to those subjects. 

But where the system is not doing its job is in monitoring and 

making sure that what is on that form is actually taking place in 

the research setting. Very rarely do IRBs spend any time talking 

to subjects. Very rarely do they debrief anybody. Very rarely, if 

ever, do they find themselves in contact with researchers, actually 

going out and saying, did you sign this form, did you understand 

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this form, is it capturing the things that turned out to have been 

of interest and concern to you as you were a subject in research? 

In other words, the feedback loop that ought to be there between 

actual subjects and actual research, and what goes on in practice, 

and what you see at the front end when someone says, here is 

what I propose to do, and here is what the form is to accompany 

it, is broken. It is simply broken. And we have to do something to 

restore that loop of information so that when an IRB is taking a 

look at a research protocol it can say, we’ve been out and talked 

to some of these subjects, we know that the researchers are doing 

what they told us they would do. 

We need more audit. We need more oversight. We need to get 

more time available for IRB members to spend talking with subjects. In this era—and I’m just going to make two more points and 

then I’ll stop in the interest of time—in the era of IRB and informed consent work, there’s something else that’s missing, Mr. 

Chairman. 

If you were to ask any of the officials who were with us in the 

previous panel, tell me; who is in research? What is the composition in America of who participates? What are the statistics about 

who is involved in the military? From the ranks of those with mental disability or mental illness? Minority people? Poor people? 

That can’t be answered. We have never insisted as a Nation that 

we collect basic statistics and demographics on who is involved. Are 

women over or underrepresented? Are the elderly over or underrepresented? Are Native Americans getting the access that they might 

have? We don’t know. There is no data collected. In fact, sadly, incredibly, we collect more standardized data on animal use than we 

do for people in this country. And it seems to me some of the questions of informed consent, the adequacy of how research proceeds, 

and fairness and equity and access to research and, how well people are treated, require basic information for answers. 

That leads me to the last point I’d like to make. In looking at 

research and informed consent it is clear to anyone who wants to 

look out here—and you’ve talked about some of this this morning 

already, and I have to confess given the tone of direction of some 

questions, I’m on that Presidential Advisory Committee for Gulf 

War Illnesses, and the interest of research in the military has been 

of special concern to me as a member of that committee. But, I 

have to tell you, Mr. Chairman, that for our vulnerable populations—people who are impaired or unable to consent on their own 

for reasons of age or mental disability or institutional settings like 

a prison or service in the Army or even being a student, a medical 

student dare I say—it is clear that informed consent has its limits, 

that there are just people out there who want to be in research, 

who want the opportunity to be in research, who, one way or other, 

are not going to be able to give a full informed consent to their participation in research. 

We have not yet, I think written the regulations and put the 

kind of oversight in that would help those people. I’m sorry to tell 

you, Mr. Chairman, I don’t think we have a policy today that is any 

different from what we had in 1990 prior to the Gulf war about research in the military. I think the issue could arise tomorrow as 

to what could or couldn’t be done with soldiers or sailors or people 

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in the armed forces with respect to research and who would approve that and how that would proceed. We are operating with an 

interim, temporary rule in that area right now. We have been for 

6 years. 

And it seems to me we ought to fix that. When we look at issues 

involving research with the mentally ill or people who are institutionalized with Alzheimer’s and see the number of problems and 

scandals and difficult cases that have arisen—at UCLA, the Medical College of Georgia—there are many, many settings where people have, I would say, been taken advantage of or not understood 

what is happening to them in terms of recruitment to research. The 

time has come, I think, to toughen those regulations and perhaps 

to add more than just IRB oversight. It may be time to say that 

we need to have some national or regional review of certain kinds 

of high risk groups involved in research and certain types of high 

risk research itself, that local IRB review may not be enough. 

So Mr. Chairman, in summary, I think that the system we’ve got 

is better than what we once had, but it hasn’t been much changed 

since 1981. That’s the last time the rules of informed consent and 

IRB review got a thorough going over. I think it’s overdue. I think 

there are some concrete steps that could be taken to toughen those 

regulations and afford better protection to those who make the gift 

of themselves to participate in research so that they and others 

may benefit. 

[The prepared statement of Mr. Caplan follows:]

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Mr. SHAYS. Thank you very much. And I guess we are going next 

to Dr. Wilfond. 

Dr. WILFOND. I thank you, Mr. Chairman. 

Mr. SHAYS. I didn’t say your name well, so when you heard me 

say it, you wondered who the heck is he talking about. Is it 

Wilfond? 

Dr. WILFOND. Wilfond. 

Mr. SHAYS. Thank you, Dr. Wilfond. 

Dr. WILFOND. I’d like to thank you for inviting me to participate 

in this meeting. Currently, I’m an assistant professor of pediatrics 

in the sections of pediatric pulmonology and medical and molecular 

genetics at the University of Arizona in Tucson. As a pulmonologist 

I care for children with cystic fibrosis and asthma as well as other 

lung disorders. I also teach bioethics, and I’m a member of the 

American Academy of Pediatrics Bioethics Committee. I’ve been a 

member of IRBs for the last 9 years, and I have a particular interest in research issues related to children. 

Informed consent has been a central tenet of research ethics 

since the Nuremberg trials 50 years ago. In fact, as a legacy of the 

trials, in the 1970’s there was great debate whether children ever 

should be able to participate in research, since they are unable to 

give their consent. This debate was considered in the Belmont Report and expressed in the Federal regulations by acknowledging 

that parents give permission and not consent for their children to 

participate in research. 

This distinction is important, although it’s subtle. But it provides 

a conceptual justification for IRBs having a greater role in terms 

of the review of projects on children. For those studies that involve 

greater minimal risk, the IRB is to make a normative judgment 

about whether or not the risks are balanced by the benefits before 

the parents are able to give the decision to allow their child to participate. I think this is a very good thing, although there still remains a lot of conceptual vagueness in exactly how this is carried 

out. There is room for a more conceptual work trying to understand 

even what counts as minimal or a minor increase over minimal 

risk as a regulation state or considering this review. 

Although the regulations tend to be more careful in how research 

is done on children, often the regulations are misinterpreted and 

are used as a justification for why research in children is not done 

on a more routine basis. In fact, as a pediatrician, often because 

of a lack of research, there are many circumstances in which clinical judgments must be made without the availability of sound clinical data. Additionally, many drugs that are used on children are 

off label. 

In fact, taking care of patients with asthma, there are very few 

drugs that have been approved by the FDA for the use in children. 

I don’t think, though, this problem is really because of the regulatory mechanisms for research. I actually think that it’s more related to the lack of incentives for conducting research on children. 

Once a new drug is approved, pharmaceutical companies have few 

incentives to conduct studies in children. And so that there need 

to be requirements to conduct studies in children concomitantly 

with those of adults. Because it’s better to expose children to the 

risks of research than to the risks of unscientific practices. 

176

What I’d like to do is talk about what I see as some of the problems with IRBs. What I’d like to do is mention five problems I see, 

but only will talk in detail about one of them. As was alluded to 

earlier, there needs to be a better mechanism for the oversight and 

monitoring of multicenter trials. This is a real challenge for IRBs 

when they review a study that’s being done at 10 different places. 

And if one IRB has problems there’s no opportunity for us to correct those problems at all centers. All we can do is choose whether 

or not we want to accept or reject the proposal. 

As was mentioned before, some research that’s done in the private sector does not fall under FDA or NIH purview. And so there 

can be some research that could be done without the involvement 

of either oversight institution or organization. But I think more importantly and related to that, there needs to be a single mechanism 

for oversight of IRBs that includes not only the FDA and NIH but 

for all research. But what I’d like to do is to talk with you about 

one particular problem. 

Mr. SHAYS. I just missed your point. And it’s a very important 

point. 

Dr. WILFOND. OK. 

Mr. SHAYS. You said there may not be review by either FDA 

or——

Dr. WILFOND. If—OK. Certainly any study that involves the use 

of drugs or investigational devices will come under FDA. Any study 

that is done with NIH funding will come under the review of NIH. 

Any study that is done at an institution that has a multiple project 

assurance from either of those organizations will come under their 

review. But if——

Mr. SHAYS. Come under their review? 

Dr. WILFOND. Come under the review of a local IRB. 

Mr. SHAYS. Of a local IRB? 

Dr. WILFOND. Right. 

Mr. SHAYS. But you’re basically telling me that the FDA—the 

question I had put to FDA was: Who oversees the private sector? 

And you’re suggesting that there’s some private sector that they 

don’t oversee. 

Dr. WILFOND. If there’s research that’s being conducted that does 

not involve an investigational drug or investigational device or 

even one that’s been approved for other purposes, then—for example, nutritional modifications or behavioral issues, that it’s being 

done by somebody——

Mr. SHAYS. Let me just clarify something. I’m making a leap 

here. My mind is thinking this way. 

Dr. WILFOND. Sure. 

Mr. SHAYS. If something is not going to the marketplace, are you 

suggesting that the FDA wouldn’t be involved? 

Dr. WILFOND. That is correct. 

Mr. SHAYS. There are a lot of circumstances where something 

isn’t coming to the marketplace. That isn’t being funded. Well, who 

the heck——

Mr. KUCINICH. Nobody. 

Ms. FLYNN. No one. 

Mr. CAPLAN. No one. 

177

Dr. WILFOND. But actually, even when it does come under FDA—

actually what I’d like to do is talk to you about a particular problem in more detail. 

Mr. SHAYS. Do you all have any other little secrets you want to 

tell me about? 

Dr. WILFOND. Well, actually, the next one is the one I want to 

tell you about in more detail——

Mr. SHAYS. OK. 

Dr. WILFOND [continuing]. Which has to do with researchers who 

are in private practice where they have greater incentives for recruiting patients—and this is a case where the IRB mechanism is 

very different, and essentially are for-profit IRBs. Let me try to explain what I mean by that. Recently at the University of Arizona, 

we reviewed a study for a new anti-inflammatory treatment for 

childhood asthma. 

Mr. SHAYS. Don’t feel you have to read so quickly. You can slow 

down a bit. 

Dr. WILFOND. OK. 

Mr. SHAYS. OK. 

Dr. WILFOND. We reviewed the study for a new treatment for 

asthma. The study involved putting patients either on this new 

anti-inflammatory treatment or a placebo. The problem is that 

there already are currently available good treatments—anti-inflammatory treatments for asthma. When our IRB looked at this proposal we said this is unethical to do because it denies half of the 

patients a known effective therapy. 

Even with the permission or consent of the parents we felt that 

this was unfair and unsafe to expose children to this risk. So this 

was a multicenter trial. All we could do is say, you can’t do it here. 

Two miles down the road there is a physician in private practice 

who also was doing the same study. What he did was, he had it 

reviewed by an IRB in another State, and he paid the IRB to review the study and they approved it. 

And so I think there are two problems here. One is the obvious 

problem of the investigator specifically paying an IRB to review 

their protocol. But more importantly, this review occurred in another State. And I think it completely subverts the whole notion of 

an institutional review board. In other words, this person was not 

from the community. And I think that becomes really a challenging 

thing. I’m not sure I would agree with this. The way IRBs really 

work is not only looking at the consent forms but trying to be careful that we understand that the investigators, when they present 

the information, hopefully will do it in a non-coercive way. 

Because we don’t really have a good way of monitoring exactly 

how well they do that. The best we can do is to know about the 

integrity of the investigators. And I want to give you an example 

of how this happened with this particular study. When it was submitted to the University of Arizona the patients were going to be 

paid $250 to participate in the study. Our policy is that if payment 

is going to be made for children two things must happen. First, it 

cannot be advertised in newspapers in terms of a dollar amount. 

Our concern is that parents will see a dollar amount. That may be 

an incentive for them if they’re a little short of cash that month 

178

to have their children enroll in studies. So we exclude dollar 

amounts. 

Second, although money may be paid, it’s usually paid in the 

form of a savings bond that is made out in the name of the child. 

The physicians in private practice usually will have advertisements 

with dollar amounts. But often the dollar amounts are much higher 

than we would have otherwise approved. So for example this one 

study that we looked at, the dollar amount at the university setting 

was $250, but at the private sector it was $750 that the parents 

would be paid. And this is being advertised in local newspapers. I 

see this as being a very big problem. 

You know, in the community setting there is greater financial 

benefit to the investigator to recruit patients. They have increased 

promotional activities. The studies themselves may be more risky 

and they’re getting less review. And I think this is really one of the 

biggest issues I think that needs to be addressed. Because I think 

more and more research will be happening outside of academic institutions. My recommendation would be that whenever feasible all 

research be reviewed within the same community and that the 

same IRB have a jurisdiction over all the particular investigator’s 

protocols. One of the problems that the investigator can mail his 

protocol to different IRBs. So if he gets turned down at one place 

he can go somewhere else. And I think there needs to be some way 

of having some control over that. 

Mr. SHAYS. Elaborate a little bit on that. 

Dr. WILFOND. OK. For example, if a person is in private practice, 

and he sends it to IRB A and IRB A turns it down, he could send 

it to IRB B and have them approve it. There’s not one designated 

IRB—whereas in the university setting, at the University of Arizona, if we don’t approve a protocol, that investigator essentially 

can’t do that study. 

Mr. SHAYS. If you’re not part of the university and you’re in the 

same town as the university, tell me where you would go? 

Dr. WILFOND. Wherever you want. Whoever gives you the lowest 

price. There are IRBs around the country that are essentially commercial IRBs that are set up, where they will receive protocols from 

investigators who mail in a check and mail in the protocol and they 

will review it. 

Mr. SHAYS. I wish this panel had gone first. 

Mr. CAPLAN. It’s called IRB shopping, by the way. 

Ms. FLYNN. Yes. IRB shopping. 

Mr. SHAYS. OK. Keep going. 

Dr. WILFOND. That’s really the main thing I wanted to say. I 

think this is the biggest issue. I agree with Art about the issue of 

monitoring in the future. But I think this is really a problem that 

needs careful evaluation. I think at this point I’ll stop and let the 

other people go. 

[The prepared statement of Dr. Wilfond follows:]

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Mr. SHAYS. I just don’t quite understand. Literally, you could live 

in Florida and you could—— Dr. WILFOND. Absolutely. 

Mr. SHAYS. Oh, yes? I didn’t finish my question. 

Mr. CAPLAN. No, he just meant you could live in Florida. 

Dr. WILFOND. I’m sorry. 

Mr. SHAYS. So absolutely means that if I made an application in 

St. Louis, I could? 

Dr. WILFOND. Yes. 

Mr. SHAYS. Or New York or Alaska or Hawaii? 

Dr. WILFOND. Mm-hmm. 

Dr. LURIE. Please don’t send it to Alaska. 

Mr. SHAYS. I hear you. 

Dr. WILFOND. I think the problem is, we do face very challenging—in terms of the IRB in Arizona—with our own investigators, they’re often very challenging decisions. Often we will have 

the investigators come before us and talk with us, try to hash 

things out, try to come to a compromise that seems to work. And 

we know who the investigators are. But when you mail to somewhere else in another State, it’s not as easily done. The thing I also 

want to point out as an example of this is that these studies are 

being done around the country. 

So it’s not just a problem only out of the community IRB, but 

what ideally would be the best would be some way of there being 

some sort of additional centralized mechanism of review of these 

multicentered trials. Because what happened is, as of the study, 

the investigator came to us and said, look, if we don’t do it they 

will do it somewhere else. Unfortunately, there was no way of us 

being able to communicate our concerns about the ethics of this 

study to someone else. It essentially was just up to us to say, it 

can’t happen in Tucson. But there was nobody just who was looking out for everybody else. 

Mr. CAPLAN. Just a quick comment on this point. 

Mr. SHAYS. Sure. And then we’ll get to you, Dr. Lurie. 

Mr. CAPLAN. There are many situations, Mr. Chairman, in which 

local IRBs feel threatened by a private researcher saying, well, if 

you don’t approve it, they will do it down the road, and we’ll be 

down the road in no time. And that can cast a pall over a local 

IRB’s willingness to get tough with a particular informed consent 

form or a particular protocol. Because it’s well understood that 

there are other places to go for the private researcher. 

Mr. SHAYS. Can I make an assumption that there are no conflicts 

on those who serve on those boards? 

Mr. CAPLAN. Well, the conflict—you’re right. You can’t. 

Mr. SHAYS. I cannot? 

Mr. CAPLAN. You cannot make that assumption. 

Mr. SHAYS. OK. We’ll come back to this. You’ve whetted my appetite. Dr. Lurie. 

Dr. LURIE. Good afternoon. 

Mr. SHAYS. Good afternoon. 

Dr. LURIE. I’m going to talk about three separate subjects today. 

I’m going to talk first about HIV vaccine trials. I’m going to second 

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ibbean, Thai mother to infant transmission studies that were discussed this morning. 

Mr. SHAYS. Can you do that in 10 minutes? 

Dr. LURIE. I would say so. 

Mr. SHAYS. Yes. OK. 

Dr. LURIE. There are several things that link these. One is the 

difficulty of obtaining informed consent in vulnerable populations. 

A second is the need to provide research subjects with state-of-theart medical care. And the third is the conflict of interest between 

the purported needs of researchers about which we heard much 

this morning and the clear needs of research subjects about which 

we sometimes heard less. 

Let me talk about the HIV vaccine trials first. We know that behavioral interventions such as safe sex counseling, the provision of 

condoms, the provision of sterile syringes have the ability to reduce 

the number of new HIV infections in any given group. And if you’re 

setting up an HIV vaccine trial it therefore becomes ethically necessary to provide state-of-the-art counseling and other interventions to the subjects. 

Now, the problem is that, to the extent that you are successful, 

there will be fewer HIV infections in your subjects. And that creates the ‘‘problem’’ over time of having more difficulty in establishing that, say, the vaccine is more effective than a placebo. This, 

I think, creates a real conflict of interest which I believe is best resolved with the following. Creating an independent group of people 

to provide counseling in these kinds of HIV vaccine trials separate 

from the investigators. Unfortunately, every time that this is raised 

as a proposal I always encounter resistance from people in Government and researchers. But I do think that that is a straight-forward answer to what is a real problem. 

A second issue in HIV vaccine research involves the so-called 

gp120 HIV preventive vaccines. Now, back in June 1994 the AIDS 

Research Advisory Council, otherwise known as ARAC, found that 

the data were insufficient to support Government-funded studies in 

this country. But what we have now is a San Francisco based company named Vaxgen which is planning, with logistical and statistical help from the Centers for Disease Control and Prevention, to 

conduct an efficacy trial of gp120 in Thailand even though the vaccine has been rejected for efficacy trials by another arm of HHS—

NIH—in this very country. 

It seems unethical. It seems exploitative. Particularly because 

there really is no guarantee that Thai citizens will ultimately have 

access to any vaccine that’s proven effective. 

Subject 2, subject of the needle exchange program in Anchorage, 

AK. Since 1991, there have now been seven—count them—seven 

federally funded studies looking at whether or not needle exchange 

programs reduce the number of new HIV infections and whether 

they increase drug use or not, and every one of them has concluded 

that, yes, they reduce HIV infection, and no, they do not increase 

drug use. Despite that there is a plan to do a randomized control 

trial of needle exchange in Anchorage, AK. This despite that fact 

that the seventh of the studies that I mentioned was an NIH Consensus Development Panel which reached the same conclusion as 

its six predecessors. 

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Now we have NIH with a $2.8 million study in which people are 

going to be randomized either to needle exchange or else to a socalled enhanced pharmacy intervention, which means that if you 

try to get—they were going to give you information about how to 

walk, how to talk, how to dress when you go into a pharmacy and 

try to purchase syringes. Now, we see three problems with this 

study. Problem one, if you’re not in the study you cannot go to the 

needle exchange. Problem two, if you’re in the study, you only 

stand a 50–50 chance of going to the needle exchange. Now, that 

seems a problem seeing as though the researchers themselves 

admit in their protocol that this ‘‘represents the withholding of a 

potentially life saving service,’’ the very thing that is precluded by 

the Nuremberg Code and practically every code thereafter. 

The third problem with the study involves hepatitis B. And here 

the problem confronted by the researchers is that fortunately there 

is relatively little HIV in the drug users of Anchorage. And so 

they’re using hepatitis B as a kind of a proxy marker because it’s 

more common than HIV is. The problem is that there happens to 

be a very effective vaccine for hepatitis B, and so the researcher 

has a conflict of interest again, much like the situation with the behavioral intervention in the vaccine trials, whereby, to the extent 

that people are vaccinated, there will be fewer clinical outcomes 

and therefore it will be more difficult to show a difference between 

the two study groups. 

Those are the problems that we raised in a series of letters to 

Dr. Varmus in the beginning of October 1996. And he immediately 

put the study on hold and convened a 10-person panel to review 

our concerns. The panel did not include anybody who was either a 

drug user or might be otherwise expected to represent their interests—like someone who runs a needle exchange. And it had a 

bunch of academics, many of whom were themselves recipients of 

grants from the National Institutes for Drug Abuse, in fact that 

very same division within the National Institutes of Drug Abuse 

and so, themselves, might have been reluctant to criticize the Institute. 

That committee said, no, actually there’s no problem with the 

study at all, it’s fine. They signed off on the study completely. Fortunately, to his credit, Dr. Varmus went beyond what they had 

done and said, you need to do more to provide hepatitis B vaccine 

to people, although in our view he still didn’t go far enough, because he should have required onsite vaccination of the subjects. 

And that didn’t happen. To summarize, this unethical research proposal passed six levels of review. No. 1: the IRB at the University 

of Alaska. No. 2: the OPRR. No. 3——

Mr. SHAYS. Slow down. What was the second? 

Dr. LURIE. The OPRR. The Office for Protection——

Mr. SHAYS. Yes. Right. 

Dr. LURIE. Right. The third: the NIH AIDS Review Committee. 

The fourth: the panel that Dr. Varmus pulled together to review 

our complaint. The fifth: Advisory Committee to Dr. Varmus. And 

then finally: Dr. Varmus himself. Yet, despite this—and as Dr. 

Caplan quite accurately pointed out—the meat and potatoes of Ethics Review Committee work is looking at informed consent forms. 

There was no mention of any inadequacies in the informed consent 

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form, despite the fact that the informed consent form failed to include such basic information as that the researcher believed— again, in their own words—that this was a potentially life saving 

service, that the researchers estimate that the drug users in the 

pharmacy group were at up to four times increased risk of getting 

hepatitis B. 

And importantly it didn’t explain that if you were a drug user 

assigned to the pharmacy and you showed up at the needle exchange, they’d ask you for your card, if your card showed that you 

were, in fact, somebody assigned to the pharmacy group, they’d 

send you packing with more information about how to walk and 

talk and a buildings map for Alaska so that you could find the 

pharmacies. And finally, it didn’t make any mention whatsoever of 

hepatitis B vaccine. 

The informed consent form had other problems. A readability 

analysis was done—and, again, this was alluded to earlier—and 

the degree of schooling that was needed for this was 15 years of 

schooling to be able to read the informed consent form, this despite 

the fact that Dr. Fisher, who had done readability analyses with 

the drug users of Anchorage had himself concluded that the drug 

users of Anchorage read with a ninth grade level. And the informed 

consent form, which all six of these reviews said was OK, finally, 

because of the attention that we drew to it, was reviewed and reviewed and reviewed and revised and revised and revised over and 

over again until instead of being two pages long, it is five pages 

long. 

Even so, it still contains a new fiction which had not been in the 

previous ones, which is that there is no other needle exchange program in Anchorage. And that is incorrect. Back in December 1996, 

a new needle exchange did open. And this was trumpeted on the 

front page of the Anchorage Daily News. The investigator acknowledged it in a national magazine. And it was on Anchorage television station as well. So this is a well known, blatant falsehood 

right there in the informed consent form. 

Mr. SHAYS. Let me do this. We have 15 minutes. I’d like Ms. 

Flynn to kind of get some on the record before we break. So if you 

want to—— Dr. LURIE. I just want to talk about the Africa stuff—— Ms. FLYNN. It’s all right. 

Mr. SHAYS. OK. I think what I want to do, Ms. Flynn, is have 

you go, and then we’ll come back to you. 

Dr. LURIE. OK. 

Mr. SHAYS. We’ll be able to get that on the record. 

[The prepared statement of Dr. Lurie follows:]

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Ms. FLYNN. All right. Thank you. Thank you, Chairman Shays. 

I appreciate very much the opportunity to appear before the subcommittee today. I am a member of the President’s National Bioethics Advisory Council. Within my day-to-day work for the past 

121⁄2 years, I’ve served as executive director of the National Alliance for the Mentally Ill, which is a large, grass roots, family and 

consumer organization concerned with issues that affect the lives 

of people with severe mental illnesses, including schizophrenia, bipolar disorder, major depression and other disabling mental illnesses. 

We are families. We are patients. We are the grass roots. We are 

the folks who rely on the kinds of protections of human subjects 

that have been addressed repeatedly today. From the beginning of 

our organization we have been very strong supporter and advocates 

for biomedical research on severe mental illnesses. Such research 

has yielded remarkable breakthroughs in the understanding and 

treatment of these disorders, which are among the most devastating known to mankind. 

We particularly look to the development of promising new medications for the treatment of schizophrenia and other debilitating 

brain disorders, which have occurred as a direct result of biomedical research. We’ve also had great advances in understanding 

the ideology of brain disorders, advances that we believe may ultimately lead to much better control of symptoms and even potentially cures. And it’s important, as has been noted several times 

today that none of these advances that have been so dramatic in 

treatment of mental disorders would have been possible without 

the participation of individuals who suffer from these disorders. 

And I think it’s important to note that they are not just subjects 

but indeed participants in the research, which I think is a stronger 

term and a more appropriate term. And at least in the view of 

NAMI members, they are really the heroes here in the research 

arena. It is, however, very important, as we confront these issues, 

to try to strike the balance so that we can maintain a healthy climate for research, which all of us view as the long-term hope for 

conquering these illnesses. 

And so it’s important that we look at the issues that surround 

many of the complex ethical questions that you have raised with 

this hearing. The use of human subjects in research presumes that 

individuals who participate are capable of comprehending the nature and scope of the research and, therefore, can participate in an 

informed way and consent to their participation. But as you know, 

the nature of severe mental illnesses often renders individuals with 

these disorders sometimes incapable of such consent. It is good to 

see the dialog we’ve had today. And it is good to note that scientists join bioethicists and advocates in being committed to balancing the importance of creating and maintaining a healthy climate for vital research with the equally important paramount concern of protecting vulnerable subjects who may lack the capacity to 

fully understand the nature, the risks and the benefits of the research they’re asked to participate in. 

Recently, there have been a number of issues which have received a great deal of attention, including revelation several years 

ago about specific research protocols at UCLA Neuropsychiatric ReVerDate 0ct 02 2002 09:43 Oct 05, 2002 Jkt 010199 PO 00000 Frm 00198 Fmt 6633 Sfmt 6602 W:\DISC\44389 44389
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search Institute, in which it has been alleged and, indeed confirmed, that there were flaws in the informed consent procedures. 

And there continue to be concerns about whether this research was 

conducted in the highest possible ethical manner. Members of 

NAMI obviously looked at this situation with great concern. 

And for the past several years we have brought our concerns 

about this study to the officials at the National Institute of Mental 

Health and the Office for Protection from Research Risks. The entire lay board of the National Alliance, after hearing from a great 

many experts, consultants, family members moved forward in February 1995 to adopt some very straightforward and, we think, very 

helpful concrete suggestions as policies that I would like to share 

with you at this hearing. 

Mr. SHAYS. Can you say the last statement you made? I got distracted. What was the last point? 

Ms. FLYNN. That in February 1995 the lay board of the National 

Alliance, again, made up of families and patients, adopted some 

specific policies that I would like to share with the subcommittee 

today, which we think will offer some of the concrete guidance that 

you are looking for and ways to strengthen the climate that we currently have. I guess I’m not certain, sir, whether you want me to 

try to deliver my entire—— Mr. SHAYS. No. You have about 3 or 4 more minutes, if you’d like 

to continue. 

Ms. FLYNN. OK. Well, let me try to move forward, then, and just 

try to capsulize. Because my written statement does go into greater 

detail. Let me just try to move forward and try to highlight what 

the specific policies are that we think need to be adopted. 

Mr. SHAYS. And we’ll be able to cover some of it in the questioning part as well. 

Ms. FLYNN. OK. Thank you. 

Mr. TOWNS. The entire statement will be included in the record. 

Mr. SHAYS. Yes. 

Ms. FLYNN. I appreciate that. We would like to see national 

standards developed to govern voluntary consent, comprehensive 

exchange of information and related protections of persons with 

cognitive impairments who become research subjects, and that the 

development of these national standards must include individuals 

who have these disorders, their family care givers, who are directly 

involved and directly affected. We note that there is not currently 

existing in Federal regulations specific protections for this vulnerable population, although they have been highlighted by several 

prior national ethical bodies as needing this kind of support. 

We believe that the National Institute of Mental Health, which 

funds the great bulk of research on severe mental illnesses, should 

take the lead in the development of such national standards. And 

we are pleased to see that Dr. Steven Hyman, the new NIMH director has moved forward to convene a group that will be looking 

at the development of not only standards, but potentially best practices and other guidance to the research community to strengthen 

the way in which informed consent and other psychiatric issues in 

research are handled. 

We think it’s important to note that informed consent as has 

been referenced is not just the gaining of a signature at the front 

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end of a research protocol. But particularly for vulnerable subjects 

who may be cognitively impaired, it needs to be seen as an ongoing 

process. Comprehensive information needs to be provided both orally and in writing, including information that makes clear not only 

the risks and benefits of research, the scope, scale and objectives 

of the research, but also other modes of treatment, other options 

than the research that may be available. 

This is important because of unique characteristics of most people in this country with serious mental illness, Mr. Chairman, who 

frequently do not have health care coverage except through the 

public mental health system. These folks are uniquely vulnerable 

to the potentially coercive effects of being able to access novel or 

experimental or potentially more valuable treatment through research settings. 

We believe that it is very, very important that the capacity of individuals to participate in research be assessed not only at the outset, should there be any question, but also be able to be assessed 

continuously through the research should there be any question of 

their continuing ability to consent, and that that should be conducted by someone not directly involved in the research, as I think 

has been noted previously. Should it be determined that the individual lacks decisional capacity, surrogate consent should be 

sought from family members, if they are willing and able. And here 

we are particularly concerned that family members are often not 

involved, not informed, and not able to then participate on behalf 

of a relative that may have fluctuating ability to consent and participate. 

Institutional review boards which review research on mental illness must include consumers and family members with direct personal experience with these severe and debilitating illnesses. It has 

been our experience that most IRBs do not get this kind of representation from the community, even when they do a regular review of psychiatric research protocols. This is something that can 

be addressed easily. This is something that our organization is in 

a position to be a resource on. And we think there should be strong 

guidance to IRBs, that they should include representatives of the 

community of individuals with psychiatric illness. 

We believe that investigators must ensure that individuals who 

participate in research as outpatients, where most of this research, 

including research on new medications is conducted, they need to 

be linked to appropriate care, treatment and supports for the entire 

duration of the research. 

Mr. SHAYS. I need you to finish up here because we have two 

votes. 

Ms. FLYNN. All right. One final point, then. Let me say that 

many people enter into research on new medications because they 

hope for great improvement in their treatment. We then find that 

when the research is over—9 weeks, 12 weeks—that the medication is no longer available to them. We find this unethical. We find 

this a procedure that truly can be very damaging. And we believe 

that when there are protocols approved that involved offering new

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medications to individuals who may have no other way to get them, 

that they must be guaranteed that they will be able to continue if 

the medication has been seen as safe and effective even beyond 

their tenure in the research program. 

[The prepared statement of Ms. Flynn follows:]

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Mr. SHAYS. Thank you, Ms. Flynn. I’m sorry we’ve been pushing 

you a bit. Dr. Lurie, we’ll be able to come back. And then you can 

tell us about Africa. And then we’ll start our questioning. We have 

two votes, and we’ll be back after that. 

[Recess.] 

Mr. SHAYS. The subcommittee will come to order. Dr. Lurie. 

Dr. LURIE. Yes. Thank you very much. I just want to talk briefly 

about the Africa, Asia, Caribbean vertical transmission studies. To 

start off by just making very clear—— Mr. SHAYS. Let me just—I’m sorry. First, some of you need to be 

on your way by when? 

Mr. CAPLAN. Twenty of. 

Mr. SHAYS. Twenty of? OK. 

Mr. CAPLAN. But I have a substitute behind me. 

Ms. FLYNN. I do, too. 

Mr. SHAYS. Well, you know what, I’m not going to have substitutes. We’ll just deal. You can stay later? 

Dr. LURIE. Excuse me? 

Mr. SHAYS. You can stay later? 

Dr. LURIE. I can. 

Mr. SHAYS. OK. Why don’t we just deal with the issue, then, that 

I’m finding absolutely fascinating. The local institutional review 

boards are licensed by whom? 

Dr. WILFOND. The institutional review boards usually will have 

to file what is called a multiple project assurance with the OPRR 

at universities or hospitals. 

Mr. SHAYS. What happens if the OPRR isn’t involved? 

Dr. WILFOND. Well, generally for any sort of large institution like 

a university it will be. 

Mr. SHAYS. No, no. You’ve already told me under two circumstances where there’s basically no review. 

Dr. WILFOND. Correct. 

Mr. SHAYS. Yes. 

Mr. CAPLAN. The OPRR is not always involved. 

Mr. SHAYS. They’re only involved if Federal dollars are involved. 

Mr. CAPLAN. Or IRBs if there is a new medical innovation that 

doesn’t involve a drug or device that—the FDA is triggered there. 

And it has to be, I might add, for interstate commerce. If it’s a new 

innovation in surgery, rehabilitation medicine, nursing, where 

there’s no drug or device, there is no necessity of IRB review or 

OPRR connection or any review at all unless there is some commercial purpose involved and unless this work is being done at an 

institution that is getting NIH money for other purposes. So if it’s 

privately funded within the State, no commercial purpose—a good 

example, by the way, Mr. Congressman, would be the Baby Fay baboon transplant. That looks pretty experimental—technically did 

not have to be reviewed by an IRB. It was privately funded, not 

done for a commercial purpose. 

Mr. SHAYS. Now, these IRBs are commercial or not commercial? 

I’m not clear on that issue. At bottom line first, they don’t have to 

be licensed? 

Mr. CAPLAN. No. 

Mr. SHAYS. Unless they might have to be reviewed if they are involved with the Institutes of Health. 

211

Mr. CAPLAN. Correct. And they have regulations pertaining to 

their composition from the Code of Federal Regulations that require, I think, a minimum of five people, one lay person to be involved—and that lay person represents the community, although 

the community—— Mr. SHAYS. Do they have to register with some national board? 

Mr. CAPLAN. The NIH, basically. 

Dr. WILFOND. Or the FDA. So for example, these for-profit IRBs 

are almost exclusively—— Mr. SHAYS. Do they register with one or the other or both? 

Dr. WILFOND. They could do both. 

Mr. SHAYS. Do we know how many there are out there? 

Mr. CAPLAN. No, we do not. 

Ms. FLYNN. No. 

Mr. SHAYS. This is getting a little silly. 

Mr. CAPLAN. No, we do not. 

Ms. FLYNN. It’s very unregulated. 

Mr. CAPLAN. And the definition of community member could be 

a community member in which the research is being conducted or 

10 States away. 

Mr. SHAYS. Dr. Lurie, do you want to comment on this? 

Dr. LURIE. No. I think just to make a point that the IRBs have 

too much ‘‘I’’ and not enough ‘‘R.’’ I mean, there’s too many people 

from the institutions themselves and reviews that are occurring, 

are occurring much too quickly. I mean, these people are spending 

1, 2 minutes on a proposal many times. But I think that, as pointed out, the financial incentives here are very powerful. And I do 

think there’s a role for some regulation of this. 

Mr. SHAYS. OK. Explain to me the whole concept of commercial 

IRBs. 

Dr. WILFOND. Maybe I could try this again a little more carefully. 

Mr. SHAYS. Yes. 

Dr. WILFOND. I think Peter is right, that even within institutions 

like universities, there may be some conflicts of interest. But the 

point is that if a person is in private practice, they don’t belong to 

any institution, the FDA still requires a review by an IRB. So 

where that IRB comes from is usually somebody who has set up 

their own IRB, files their own forms with the FDA, calls themselves an IRB, and then receives money from the investigators who 

want them to review their projects. 

Mr. SHAYS. Are those what are referred to as commercial IRBs? 

Dr. WILFOND. Yes. 

Mr. SHAYS. OK. What is a non-commercial IRB? 

Dr. WILFOND. A non-commercial IRB would be an IRB from an 

institution like a university or a hospital that would be reviewing 

all the projects within there. They would also have their own conflicts, but they won’t be as egregious potentially. 

Mr. CAPLAN. It’s important to point out, too, about the institutionally based, which is university and hospital 99 percent of the 

time, IRBs—that they don’t get paid and don’t receive any money. 

Ms. FLYNN. They’re volunteers. 

Mr. CAPLAN. They are volunteers who then work as overhead— that’s where those overhead fees that the NIH charges and puts 

onto its grant. So there’s no payment. And what you’ve got is some 

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very hard—I don’t want to just beat up on the IRB members—

you’ve got some very hardworking volunteers who are asked to 

carry a ball that in the commercial sector they would be paid fairly 

well for. 

Mr. SHAYS. Any questions? Again, Dr. Caplan, you need to leave 

in about 7 minutes. Dr. Wilfond, you need to leave when? 

Dr. WILFOND. I don’t leave until 5 o’clock. 

Ms. FLYNN. As soon as possible. 

Mr. SHAYS. As soon as possible? OK. 

Ms. FLYNN. Yes, sir. Thank you. 

Mr. SHAYS. Do you have any comment you want to make before, 

and I’ll just let you get on your way? 

Ms. FLYNN. Beyond the comments that I was making in my 

statement in the record, I just want to reinforce the concerns that 

are being expressed about the IRB procedures. I think the IRB is 

the crux of protecting human subjects. And it is enormously variable across the country. And I think we have been very slow to recognize the training needs at IRBs, to recognize the potential importance of looking at community participation as more than just fellow physicians in the same hospital or fellow members of the same 

research community. 

And that some of the issues we’re hearing about commercial 

IRBs are particularly important. Because to the degree that you 

can buy approval—or the appearance is there, that you can buy approval—to that degree is public trust in the IRB process tremendously diminished. So I appreciate the chairman’s raising these 

subjects and the time and attention that has been devoted to it is 

not beyond what is needed. And I think we’ve just begun a dialog 

that I hope will continue. 

Mr. SHAYS. I thank you. And I do recognize that we have kept 

this panel extraordinary late. I apologize. And we’ve had lots of 

interruptions. We would have been out hours ago without the interruptions. So I do apologize. Ms. Flynn wants to get on her way. 

Should we let her get on her way? 

Mr. TOWNS. You can put it in writing to me. 

Mr. SHAYS. Sure. 

Mr. TOWNS. You made a comment earlier that I’m very concerned 

about in terms of mental patients, in terms of the competency, in 

terms of privacy and all that. And I would like for you to sort of 

give us something in writing as to what you think we might be able 

to do to protect them. For instance, especially with the medication 

that they’re getting. If it’s helping them, and all of a sudden the 

medication disappears—and I guess sometimes it’s probably the 

cost factor as the reason why they are not able to get it. So I would 

like for you to give us some suggestions. Because I think some of 

these things are going to require legislation. 

Ms. FLYNN. I appreciate that, sir, and would be glad to provide 

you with some concrete and specific suggestions in writing. 

Mr. TOWNS. Right. Thank you. 

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Mr. SHAYS. And if the gentleman will yield. Dr. Caplan, we do 

need on the record one question and then you can have someone 

who was sworn in take your place. And we will honor that. The 

question I need to ask you is, in what ways do you feel that the 

FDA’s waiver of informed consent would permit DOD to use PB 

and botulism toxin vaccines on Gulf war troops was ill-advised or 

unethical? 

Mr. CAPLAN. I think the handling of the waiver with respect to 

the troops was unethical in three ways. First, I think they did not 

demand and insist upon followup, so that people who were exposed 

to these substances who were de facto, acting as subjects or even 

guinea pigs, would know whether or not there were harms or problems that arose, which may have happened now in terms of Gulf 

War Syndrome. I’m not sure that’s true. At least they failed in the 

obligation that was owed to followup. They failed in the obligation 

to disclose what was done to these troops. You were asking the 

FDA in the previous panel, were you satisfied that they were in 

compliance with what the agreement was? 

Well, I will say that I think they failed dismally and they have 

not—the Defense Department. Those military agencies did not do 

what they needed to do to, after the fact; inform people when they 

were exposed to innovative or experimental substances. 

The last area of failure is, there’s still been no formulation of a 

policy about what to do with respect to research on our troops. We 

don’t have it today. We didn’t have it 6 years ago. And I find it incredible that we have not had more than an interim rule to guide 

us with respect to research in the military. 

Mr. SHAYS. And clearly we’ve had enough time. 

Mr. CAPLAN. I would say we’ve had more than enough time. 

Dr. WILFOND. Can I just add something? 

Mr. SHAYS. Sure. 

Dr. WILFOND. I think it was not convinced this morning that 

they ever gave a clear reason why it was not feasible to have asked 

for consent in the first place. Presumably, if you asked the soldiers, 

you may be exposed to nerve gas, this medication may help you but 

we really don’t know, and we would like to do a project, would you 

like to participate, most would probably say yes. 

Mr. CAPLAN. We took a lot of testimony at the Presidential Advisory Committee on this matter. 

Mr. SHAYS. Yes. 

Mr. CAPLAN. And it was summed up fairly well by one of our people who came to testify to us who said, if someone is shooting very 

large bullets at you which may be filled with biological weapons, 

the likelihood of you refusing an antidote is zero. So that we could 

assume that most people would, in fact, have taken the opportunity 

to get the best protection possible. 

Mr. SHAYS. Yes. 

Mr. CAPLAN. I wouldn’t deny it. But the opportunity to ask was 

there. And even if it was difficult due to the quick mustering up 

of forces, after the fact notification is an absolute—it’s just something that has to be done. 

Mr. SHAYS. Yes. 

Dr. WILFOND. But my point is that there’s still no—it’s not clear 

that they couldn’t have done it ahead of time either. 

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Mr. SHAYS. Dr. Caplan, you’ve been terrific to wait so long. Did 

you want to ask him a question before he left? Yes. 

Mr. TOWNS. Yes. This whole thing about ethical standards, there 

seems to be some disagreement on the meaning of the term. Some 

people think it means having standard operating procedures to review proposals. And other people think it means that the contents 

of the proposal should be reviewed to determine whether they meet 

some kind of moral standards. Can you tell me what you believe 

the requirements are for ethical standards in reviewing research 

proposals? 

Mr. CAPLAN. Well, I’ll try to answer that simply, Congressman 

Towns, by saying this. I think the job of the IRB in terms of ethical 

standards is to make sure that comprehensible information is given 

to the person so they can use their values to decide how they want 

to deal with risk and benefit. So the real moral principle that has 

to guide what the IRB is doing with the informed consent forms 

and all the rest of it is, can we make it so that we empower the 

person to be able to make a choice. The problem is that we put a 

lot of weight right now in our review on the front end, what’s on 

paper, what happens at the start. 

And there’s very little in the middle and at the end whereby we 

go back and say, did you understand it, do you think we picked up 

the right issues, are we doing our job as committees, as people trying to empower you? But the moral principle, I would say is, empower the subject to make a choice. That’s really what the job is 

of these IRBs, public, private, whatever they are supposed to be. 

They are trying to let people make choices according to their best 

values. Not everybody will agree. 

There’s no right answer about when is it too risky, when is it too 

dangerous, is it worth the benefit for me? But you do need information and you do need time and you do need to make sure that the 

person giving you that information is giving you all your choices. 

That’s what those committees have to do. And I don’t think they’re 

doing it as well as they ought to. 

Mr. TOWNS. Dr. Wilfond, your comment? 

Mr. SHAYS. Thank you, Dr. Caplan. 

Dr. WILFOND. Well, actually, I would take it a little further—— Mr. SHAYS. And let me just—excuse me. We will be having join 

us Dr. Jonathan Moreno, who was sworn in, I believe. Is that correct? 

Mr. MORENO. I was. 

Mr. SHAYS. Yes. And welcome. 

Mr. MORENO. Thank you. 

Dr. WILFOND. Yes. I think at least for children the IRBs are expected to do much more than just make sure that people have information. They are supposed to make some sort of judgment about 

the balance of the benefits and the risks. And the regulations are 

very detailed in terms of the various categories of benefits and 

risks. I think one of the challenges is that for research that is identified of being no direct benefit can only be approved if it—and 

these are the exact words—‘‘if it is a minor increase over minimal 

risk.’’ The problem is, it’s not clear what counts as minor increase over 

minimal risk. And many medical journals or ethics journals are 

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spent discussing these issues, of what counts as a minor increase 

over minimal risk. So I think there is really a need to conceptual 

clarity to be improved to allow the IRBs to do this better. 

Mr. TOWNS. All right. Thank you. 

Dr. LURIE. Yes. Let me add to what Dr. Wilfond is saying. Obviously, adequately informing people is critical, but it’s at times not 

sufficient. So as bad as the informed consent form was in the Alaska study, it couldn’t have made the study ethical. So an unethical 

study is an unethical study. And the IRBs need to stop those from 

proceeding regardless of how good the informed consent form is. 

And the same thing, I believe, is true in the African studies, which 

we’ll get to later. There may indeed be problems with informed consent. We haven’t looked at all the informed consent forms yet. But 

there is no informed consent form that could satisfy me that these 

studies are ethical. The study is unethical by design. And you can’t 

informed consent your way out of that. 

Mr. TOWNS. Right. Let me just ask one more question, Mr. Chairman. May I? 

Mr. SHAYS. Yes. 

Mr. TOWNS. I’m concerned about when these studies go wrong, 

they seem to be conducted on poor people, minorities in particular, 

and in some instances their children. I wonder if one factor considered in the approval process is the economic status of the people 

to be studied. Wouldn’t the economic status have a bearing on nutrition, other factors that could influence the outcome of the study? 

Mr. MORENO. Perhaps I could address that. 

Mr. TOWNS. Sure. 

Mr. MORENO. Incidentally, I work at the Health Science Center 

at Brooklyn—— Mr. SHAYS. Yes. Would you—— Mr. MORENO. My name is Jonathan Moreno. I’m a professor of 

bioethics at the Health Science Center at Brooklyn State University of New York. 

Mr. SHAYS. OK. 

Mr. TOWNS. That’s a very important place, Mr. Shays. 

Mr. SHAYS. It is a very important place. Not the most important, 

but a very important place. 

Mr. TOWNS. Thank you. 

Mr. MORENO. It’s near Connecticut, at least. We deal with this 

issue all the time at an institution like ours. As you know, we have 

a large minority population and many subjects who don’t have economic means and are vulnerable. The one ethical principle that 

has, I think, been the most difficult to interpret and apply in our 

system that came from the National Commission in the late 1970’s 

is justice. And according to the National Commission, justice in the 

context of the use of human subjects in research means that you 

don’t overburden any population in the society with respect to research participation, and that you also, importantly, make sure 

that the fruits of research are available across the board, through 

the whole society. 

That’s really very hard to do, partly because when people don’t 

have economic means they may not have the ability to participate 

in research because they are, for example, taking care of older people or younger people, or they don’t have the money to come to the 

221

center to be part of a study, or because of the possibility that they 

could get sick from being on a drug, and to be taken off-line from 

work or taking care of those other people, could represent a serious 

practical obstacle to being in a study. 

So there are problems on both ends, I would say, Congressman. 

One problem is that, yes, it’s true that people who are in the position you’ve described may be more vulnerable. At the same time, 

we aren’t very good at recruiting them to research that could benefit them or could benefit other people in their circumstances. 

Mr. TOWNS. Yes. Would you like to add anything to that? 

Dr. WILFOND. It goes—he’s correct. It goes both ways. It’s a problem both on the side of recruiting appropriate subjects. And in fact, 

the NIH has really tried over the last few years to try to increase 

the enrollment of minorities and women in studies. I think there 

also is a problem of inappropriate recruitment. One problem that 

I see which I alluded to in my comments has to do with the issue 

of reimbursement for money. We were asked at one point to review 

a study on volunteers. Well, why didn’t they get 8 hours of general 

anesthesia for the cost—for which they would be paid $1,000. And 

we thought that this was potentially risky. And we thought that 

the only people who would be willing to do this would be people 

who really needed that money. 

And so we actually did not approve that study. But for precisely 

that reason, that, as Peter mentioned, it’s not just the risks but 

what will make people do it. And often it’s for the money. 

Dr. LURIE. I think you’re raising a very important point. And let 

me emphasize it by saying that I think your observation is accurate, that I think the anecdotes that are being brought up today 

illustrate your very point. I mean, I’ve talked about injection drug 

users. I’ve talked about poor people in developing countries. People 

talk about people with mental illness. People in the military whose 

ability to refuse participation is limited. I mean, I think it’s absolutely consistent with your point. 

Let me illustrate it perhaps by comparison. In the needle exchange study, there was no hepatitis B vaccine, at least in the initial phase, planned to be administered in any important way to the 

subjects. And so the idea was to watch people and see whether or 

not they got hepatitis B even though there was a vaccine. Now, 

let’s imagine a study of young infants in which the question was 

did they get tetanus or not, and the researchers just kind of 

watched to see if they did without providing them with tetanus 

vaccine. 

It’s inconceivable. Nobody would have done anything like that. 

But when it’s injection drug users I think somehow there’s an acceptance of the poor quality of medical care that often is afforded 

to these people. The same thing is true with regard to the degree 

of evidence that we now seem to require of needle exchange programs. There are no randomized controlled trials of whether or not 

condoms work to prevent the transmission of HIV. 

Yet suddenly, primarily for political reasons, people dredge up 

the idea that we need randomized control trials for needle exchange. No one dreams of a randomized control trial of condoms for 

gay men, for example, because as discriminated against as gay 

men, in fact, are in this country, they are still better organized 

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than drug users. So I think both of those points really emphasize 

what you say. And I think in many ways that’s what’s operating 

the African, Asian and Caribbean studies where there is in fact an 

incentive now. 

If we’re saying we only have to provide the standard of care that 

exists in these impoverished countries that can’t afford our overpriced drugs, what we’re saying is, there’s really an incentive for 

people to go overseas and find the place with the least medical 

care, and then we can get away with doing nothing. Provide getting 

a bunch of information that may or may not benefit them. And we 

may very well take the results back to our countries ourselves 

where our people will benefit. That is exactly—so I highly endorse 

the concern that you’re raising. 

Mr. TOWNS. Last question and then I’m going to—— Mr. SHAYS. No, that’s fine. We want to make sure that, Dr. 

Lurie, that you get to talk about Africa. 

Mr. TOWNS. Africa. Yes. Maybe this can lead him into it. I have 

this feeling—I’m not certain—but based on the information that 

I’ve received, and reading in terms of the way in many times these 

programs are structured, in terms of research programs are structured, that you have a physician in a foreign country doing research. And he’s so involved and wrapped up in his research, that 

he’s really not paying attention to some of the other symptoms of 

the patient that might give him signs that certain things are happening. But they just continue with their research, because, after 

all, that’s what I’m into, my research. 

As a result, in many instances, patients that are lost should not 

be lost. If this patient had a physician that was responsible for the 

medical care while the other person is responsible for the research, 

that it seemed to me that some of the things that occur might not 

occur. Now, am I right in my assumption that this is the structure, 

when I have my patients and I am involved in the research—and, 

of course, you do not have a physician that’s responsible for the 

day-to-day health. 

Dr. LURIE. Well, Dr. Jay Katz—that’s for you, Congressman 

Shays—a nice mention of Connecticut—— Mr. TOWNS. Right. Yes. 

Dr. LURIE [continuing]. Has the notion of a physician researcher, 

people who have, in fact, these dual responsibilities and should 

really take both of them into account when acting as researchers 

either in this country or in a foreign location. And I think that is 

the way that we need to be thinking about it. Unfortunately, 

there’s been a kind of a specialization of function in which people 

consider themselves to be one or the other, and say, well, that’s not 

my job, I’m doing the research here, somebody else is providing 

clinical care, that’s not my problem. 

So I think that is exactly right. The problem, in fact, becomes, 

as I indicated in my testimony, that sometimes there is, in fact, a 

conflict or an apparent conflict between what the researcher thinks 

that he or she needs and what it is that the people in the trial 

need. Those women who are HIV positive and pregnant and stand 

a 25 percent at least chance of delivering an HIV positive baby, 

they don’t need research. Those women need AZT. 

Mr. TOWNS. Yes. 

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Dr. LURIE. It works. Not 100 percent, but it works. It works better than most other things we have to prevent HIV in this country. 

It works. That’s what they need. They don’t need more research. 

Yet, somehow what we heard a lot of this morning was the idea 

that yes, it’s true that these women might be placed at risk, but 

there are going to be future benefits. 

And one of the clearest principles that came out of the Nazi experiments during World War II was the notion that you can’t place 

individuals at risk in the present for potential future benefits, that 

the people in the study have their own integrity, that they have to 

be protected in and of themselves, and that you can’t justify any 

old research simply by saying, well, we’re going to get good information from this and other women like this are going to benefit in 

the future. It may never happen, and it’s a slippery slope to some 

very, very dangerous places. 

Mr. MORENO. Clinical investigators are often called double 

agents in the bioethics literature. 

Mr. SHAYS. Say that again. 

Mr. MORENO. A double agent problem is the problem that Congressman Towns alluded to, namely that, ‘‘I’ve got a grant and I’m 

doing some research, and I’m also using some patients in the study 

who in a certain sense may assume that I’m primarily concerned 

with their individual care.’’ And while I may indeed be concerned 

with their well being, I also want to get some data. That’s a problem, though, not only on the side of the physician investigator—I 

worked for the President’s Advisory Committee on Human Radiation Experiments, and we did focus groups with hundreds of people who are in studies. 

We found that even through they were theoretically and 

documentedly informed that this was primarily research, that it 

was not intended to benefit them—and most research is not intended to benefit the subject—nevertheless, they had a hard time 

integrating that information. It’s very hard to face that when 

you’re sick and you’re looking for an answer. So this is not something perhaps too amenable to legislation. It’s human psychology. 

It’s often very difficult for people to accept that they’re making a 

big personal investment of both time and hope. And it may not 

help them. 

We did find that as people went on through the course of their 

disease, they were more willing to accept that their participation 

was not going to help them, but might well help somebody else. We 

also find—I want to point this out—from the point of view of the 

person who is sick and in a study—this work we did for the Advisory Committee on Human Radiation Experiments—we also found 

that a very important motivation for people to be in studies is that 

they trust the institutions that are sponsoring the studies. 

This is a guy in a white coat who has a lot of knowledge and a 

lot of power and a lot of authority. This is a great institution. Look 

at these buildings. Look at the labs. Look at all the nurses. This 

is an important place in my community—the State University of 

New York. Surely what they’re doing is going to be good for me. 

Trust is a very—what I’m saying is something that you already 

know: trust is a very delicate thing. 

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Mr. SHAYS. That’s very true, Doctor, and very important to point 

out. Dr. Lurie, how long do you think it will take you to—because 

I do have some follow questions, and we’re going to go to a vote 

soon. But I do want you to deal with Africa. But give me a sense 

of how long it will take you to describe the clinical research? 

Dr. LURIE. I’d say probably 3 minutes. 

Mr. SHAYS. Let’s do it. 

Dr. LURIE. Let me just emphasize from the beginning that there 

is nothing in the position that we have taken that states that we 

are opposed to randomized, controlled trials. And there’s nothing in 

our statement that says we are opposed to placebo controlled trials 

per se. We are in this particular situation. But not in general. 

We’re also not opposed to international research. What we are opposed to is double standards. And we don’t like a double standard 

where, for example—there are two American studies in which AZT 

is provided, or something similar to AZT is provided to the treatment groups, yet the minute people go overseas, it’s like they check 

their research ethics at the customs desk. Only 1 out of the 16 

studies that are being done in developing countries provides AZT 

to all treatment groups. That’s a double standard. 

And it is that particular one study that in many cases illustrates 

the inconsistency and lack of coordination that have plagued this 

particular set of studies. How can it be that the National Institutes 

of Health is funding a non-placebo controlled trial of these motherto-infant transmission prevention interventions in the very same 

country that the Centers for Disease Control is conducting a placebo controlled trial? 

How can that be? And I think that perhaps the most important 

thing that I heard, at least with regard to the African studies or 

Thai studies, was what Dr. Varmus said this morning, which was, 

when asked that very question by Mr. Kucinich, he responded that 

the placebo controlled trial was ‘‘not the only way to achieve results.’’ That’s exactly right. It is not the only way to achieve results. And the difference between the method that has been chosen 

by the CDC in Thailand and the NIH and the CDC in other places 

is not the only way to achieve results. 

Unfortunately, one result that it will achieve is that if you add 

together the American and the foreign-funded studies, there will be 

1,500 HIV positive babies in this world which need not happen. 

Even though we have a big research infrastructure that goes in, it 

doesn’t cost that much to provide AZT. In many cases you get it 

free form the drug company. And yet we’re effectively staring those 

women in the eye and saying, no, we need a placebo controlled 

trial. And consequently there are 1,500 HIV positive babies that 

will exist within a couple years from now when they need not. 

The final point I wanted to make was about the IRBs. And we 

heard a lot about how this all went through the IRB in these local 

countries. I think that Dr. Wilfond, Dr. Caplan and others spoke 

very well to the problems of IRBs in this country. 

Mr. SHAYS. I’m not clear. There are IRBs in other countries just 

like in the United States? 

Dr. LURIE. Well, whether it’s reasonable to call them per se an 

IRB, I’m not exactly sure. I’m sure they are not constituted necessarily with the kinds of regulations that we have in this country. 

225

Mr. SHAYS. So you’re basically talking about the health ministries of the country? 

Dr. LURIE. In many cases there is some kind of review committee 

that will review this. I mean, myself, I’ve conducted quite a bit of 

research—— Mr. SHAYS. Is that set up by international agreement, World 

Health—— Dr. LURIE. My understanding is that it’s understood that studies 

like this will be reviewed, but there is not the same kind of detailed information about who will sit on these things. I don’t believe that there is a requirement—— Mr. SHAYS. Let me just say something. I’m truly exposing my ignorance in this area. But it does blow my mind. I mean, the value 

that someone like I bring to this is, I know nothing. 

Dr. LURIE. Yes. That’s right. 

Mr. SHAYS. But I come with a clean slate. And there are things 

that just frankly have blown my mind about what I’ve learned 

today. Because I made assumptions. I made assumptions about a 

lot of things that are very different than what I’ve learned. And so 

there will definitely be followup at the urging of my ranking member, as well. This is an issue we’re going to get into with a lot more 

interest than we’ve shown in the past. Why don’t you finish your 

point. 

Dr. LURIE. Well, you know, I think you are exactly the right person to be making a judgment about these kinds of things. I mean, 

the scientists are themselves too close to the problem. And I think 

that’s a lot of what we heard this morning, that there are people 

standing up and basically defending either their government institution or otherwise their university. We’ve heard a lot of that. I 

think it’s the kind of distance that a sort of naive observer like 

yourself has to offer. 

And the common sense thing is no; 1,500 lives that could be 

saved. Why not do it? Why not do it if you can get data that are 

good enough to make decisions, which even Dr. Varmus himself 

says are good enough to make decisions. I think they’re too close. 

I think that’s part of the problem. Anne Marie Finley used the expression from a song recently: ‘‘blinded by science.’’ And I think 

that’s part of what the problem is. It’s too much on the science, not 

enough on the broad of social and ethical contexts of things. 

Mr. SHAYS. OK. 

Dr. LURIE. My final comment with regard to IRBs, then, is, can 

we trust the IRBs overseas? And as somebody, as I said, who has 

done quite a bit of research in Africa and Asia, I’ve used IRBs in 

those countries myself. I have no confidence in the fact that they 

say that my research is OK. It does nothing for me. At least the 

research I have done. I am sure that the research committees, the 

ethics committees established for these studies, are in fact better 

than the ones that I have run my research through. There’s nothing I can do about that. 

Of course, it runs through an ethics committee in our country, 

as well. But if you take, for example, some FDA inspections from 

the period of 1977 through 1995 published here in the Cleveland 

Plain Dealer, the United States—there were 32 percent of studies 

in these inspections which deviated from protocol. And their inspecVerDate 0ct 02 2002 09:43 Oct 05, 2002 Jkt 010199 PO 00000 Frm 00229 Fmt 6633 Sfmt 6602 W:\DISC\44389 44389
226

tions of foreign IRBs, there were 54 percent that so deviated. And 

with regard to the keeping of adequate or accurate records, there 

were 27 percent of American IRBs that had inadequate or inaccurate records. And in that same period, the percentage in foreign 

countries was 53 percent. 

So there is reason to believe that, for starters, the very same 

pressures so well described by Dr. Wilfond and Dr. Caplan that 

exist in this country exist over there. And seeing as though these 

committees are much newer, they don’t have the same research infrastructure, there are fewer people with formal training in ethics 

than exist in this country, I think it’s reasonable—and the data 

support the idea—that ethical review over there is likely to be poor. 

Mr. SHAYS. I just have about four more questions. And I can go 

through them fairly quickly. I don’t know if the answers will be 

quick. But it’s Dr. Moreno. 

Mr. MORENO. Moreno. 

Mr. SHAYS. Moreno. I’m sorry. Dr. Moreno. How is data collection 

and monitoring of animal subjects more extensive than required for 

human subjects? First, is it? And if so—— Mr. MORENO. I think it is. I sat on an animal care and use committee in my school a number of years ago. So my memory may not 

be fresh. But as I recall—and I hope other people will correct me 

if I’m wrong—there is annual auditing of animal care and use committees. And I believe that they are unannounced. There is at least 

regular auditing of animal care and use committee records. And I 

believe they are unannounced. In the case of human subject review 

committees, I believe that they can take place every several years 

and they are announced. 

Mr. SHAYS. Well, we will be looking into that. But the bottom 

line is—— Mr. MORENO. The bottom line is there is less regulation for 

human subjects than there is for animals, in that sense, in the 

sense of auditing by a Government body. 

Mr. SHAYS. OK. Dr. Wilfond, how would a functioning HHS ethics advisory board provide greater oversight of informed consent in 

the United States? One, should we allow that board to continue to 

just sit there or should we activate it? 

Dr. WILFOND. Well, I think it should be activated. I think there 

are two things that having a functioning board—a permanent 

board could do. One would be, as I alluded to, trying to help over 

time develop some more conceptual clarity about how to resolve 

ethical issues. But I think more importantly it could be a mechanism for having one singular mechanism of oversight of IRBs and 

make sure that all research goes through those IRBs, make sure 

that those IRBs are at a community level, and make sure that the 

IRBs do ongoing monitoring of the research. And the only way that 

can be done is by having one single agency who is responsible for 

doing all this stuff. 

Mr. SHAYS. Yes. 

Mr. MORENO. Can I just add to that, also? 

Mr. SHAYS. Sure. 

Mr. MORENO. There are big philosophical and policy issues 

emerging that local IRBs may not be comfortable in settling. For 

example, the use of AZT in pregnant women, which I dealt with in 

227

Brooklyn a few years ago. That also could be subject to an open 

public review that would take some of the moral pressure off the 

local institutions. 

Mr. SHAYS. Do you have anything to respond to those two questions? 

Dr. LURIE. No. 

Mr. SHAYS. We have a vote. I think what we’re going to do is call 

it quits here. You have definitely encouraged this subcommittee to 

move forward as this is an extraordinary issue. I’ve made assumptions about the local boards and their powers in oversight. I’ve 

made assumptions about what the FDA has done or hasn’t done. 

I’ve made assumptions about the Institutes of Health that are quite 

the same as I thought. And I know everybody is wrestling with this 

issue. But it strikes me that we’ll be able to focus in a little bit 

more. I’ll be able to do some homework in the meantime to make 

sure that we don’t let the first panel get away without asking some 

of them these questions. So with that—do you have anything to 

add, Mr. Towns? 

Mr. TOWNS. No. I think it was terrific in terms of information 

that they were able to share with us. I really appreciate it. Thank 

you very much. 

Mr. SHAYS. Yes. I’d just like to thank the staffs on both sides 

who worked close together and have provided very helpful information to prepare us and have gotten us some excellent witnesses. So 

thank you for coming. Do any of you just wish to say something 

before leaving? Is there any one last parting comment you want to 

make? 

Dr. WILFOND. Actually, I do have one. 

Mr. SHAYS. Yes? 

Dr. WILFOND. Since I haven’t really spoken to the issue of the 

studies of the AZT trials I think there’s two points I want to emphasize. 

Mr. SHAYS. Sure. 

Dr. WILFOND. One is that Peter is correct that these studies 

could be done using AZT as the control, but it would take more 

time and it would cost more money. So essentially, the ethical 

question is whether or not it’s appropriate to spend that time and 

money. And I think we need to understand that. The second thing 

was a comment that I heard earlier that the reason why those 

studies were justified is because the host countries thought it was 

appropriate. Well, the host country thought that Tuskegee was appropriate. So the fact that people agree in a country that a study 

should be done it doesn’t make it ethical or unethical itself. 

Mr. SHAYS. Right. That’s a very good point. 

Dr. WILFOND. And so, be careful about that. 

Mr. SHAYS. Very good point. 

Dr. LURIE. If I just may respond to that, about more time or 

money. You know, it is quite unclear that’s necessarily so. It depends to a certain degree where the short version of AZT falls out, 

whether it turns out to be closer in effectiveness to placebo or closer in effectiveness to the 076 regimen. So the answer is, it depends. 

And again, as we pointed out earlier, oddly enough, the placebo 

controlled trial that is being done with four arms involved 1,900 

subjects, whereas the only other four arm study which was not plaVerDate 0ct 02 2002 09:43 Oct 05, 2002 Jkt 010199 PO 00000 Frm 00231 Fmt 6633 Sfmt 6602 W:\DISC\44389 44389
228

cebo-controlled, oddly enough, required less. So I don’t think it’s 

necessarily true. But most importantly, whatever increment in additional money is necessary to make the studies ethical should be 

money that we’re willing to pay. if it costs double the money to do 

the study, as far as I’m concerned, that’s money we need to spend, 

and we cannot afford to be unethical. 

Mr. SHAYS. No, we can’t. We do have to be very up front with 

the point that everything is an opportunity cost. And I would say 

it’s unethical to spend money on research that may not optimize 

the results. Maybe it’s more ethical to spend money on something 

that will give better results and help more people. There are lots 

of ways to evaluate the concept of money. I want to be very clear. 

I’m not disputing that you should never, whenever money is spent, 

you shouldn’t spend it on research that isn’t ethical and done properly. But we make choices in how best to allocate a resource. 

Dr. LURIE. I think it’s a reasonable point. But let’s not forget that 

in this particular case, the choice involves not only money, not only 

time, but actually involves people’s lives, which in many cases in 

some of the other studies that we’ve talked about—as terrible as 

they may be—you could not predict the number of deaths that were 

likely to ensue as the case here. If it costs double the amount of 

money, and 1,500 more babies are alive to see their 7th or 10th 

birthday because we did our studies better, I’d be willing to pay 

that. 

Mr. SHAYS. I hear you. And I think most would. Any other comment, or should we call this hearing to a close. I guess it would be, 

again, appropriate to thank you all for your flexibility with all the 

votes we had today. And those of you who have attended and sat 

through this hearing, we thank you for your participation. I was 

thinking as we were going on that with the powers invested in me 

as a chairman some time, I’d like to just invite people from the audience sometimes after they’ve heard it, you know, at random to 

allow four or five, because I see nodding of head and shaking of 

head. And I’d love to know why you nodded your head or shook 

your head. 

With that, we’ll call this hearing to a close. 

[Whereupon, at 3:10 p.m., the subcommittee was adjourned.]

Æ