```

[House Hearing, 106 Congress]
[From the U.S. Government Publishing Office]

     DO CURRENT FEDERAL REGULATIONS ADEQUATELY PROTECT PEOPLE WHO 
                    PARTICIPATE IN MEDICAL RESEARCH?

=======================================================================

                                HEARING

                               before the

                   SUBCOMMITTEE ON CRIMINAL JUSTICE,
                    DRUG POLICY, AND HUMAN RESOURCES

                                 of the

                              COMMITTEE ON
                           GOVERNMENT REFORM

                        HOUSE OF REPRESENTATIVES

                       ONE HUNDRED SIXTH CONGRESS

                             FIRST SESSION

                               __________

                            DECEMBER 9, 1999

                               __________

                           Serial No. 106-145

                               __________

       Printed for the use of the Committee on Government Reform

  Available via the World Wide Web: http://www.gpo.gov/congress/house
                      http://www.house.gov/reform

                               __________

                    U.S. GOVERNMENT PRINTING OFFICE
66-523                     WASHINGTON : 2000

                                 ______

                     COMMITTEE ON GOVERNMENT REFORM

                     DAN BURTON, Indiana, Chairman
BENJAMIN A. GILMAN, New York         HENRY A. WAXMAN, California
CONSTANCE A. MORELLA, Maryland       TOM LANTOS, California
CHRISTOPHER SHAYS, Connecticut       ROBERT E. WISE, Jr., West Virginia
ILEANA ROS-LEHTINEN, Florida         MAJOR R. OWENS, New York
JOHN M. McHUGH, New York             EDOLPHUS TOWNS, New York
STEPHEN HORN, California             PAUL E. KANJORSKI, Pennsylvania
JOHN L. MICA, Florida                PATSY T. MINK, Hawaii
THOMAS M. DAVIS, Virginia            CAROLYN B. MALONEY, New York
DAVID M. McINTOSH, Indiana           ELEANOR HOLMES NORTON, Washington, 
MARK E. SOUDER, Indiana                  DC
JOE SCARBOROUGH, Florida             CHAKA FATTAH, Pennsylvania
STEVEN C. LaTOURETTE, Ohio           ELIJAH E. CUMMINGS, Maryland
MARSHALL ``MARK'' SANFORD, South     DENNIS J. KUCINICH, Ohio
    Carolina                         ROD R. BLAGOJEVICH, Illinois
BOB BARR, Georgia                    DANNY K. DAVIS, Illinois
DAN MILLER, Florida                  JOHN F. TIERNEY, Massachusetts
ASA HUTCHINSON, Arkansas             JIM TURNER, Texas
LEE TERRY, Nebraska                  THOMAS H. ALLEN, Maine
JUDY BIGGERT, Illinois               HAROLD E. FORD, Jr., Tennessee
GREG WALDEN, Oregon                  JANICE D. SCHAKOWSKY, Illinois
DOUG OSE, California                             ------
PAUL RYAN, Wisconsin                 BERNARD SANDERS, Vermont 
HELEN CHENOWETH-HAGE, Idaho              (Independent)
DAVID VITTER, Louisiana

                      Kevin Binger, Staff Director
                 Daniel R. Moll, Deputy Staff Director
           David A. Kass, Deputy Counsel and Parliamentarian
                    Lisa Smith Arafune, Chief Clerk
                 Phil Schiliro, Minority Staff Director
                                 ------                                

   Subcommittee on Criminal Justice, Drug Policy, and Human Resources

                    JOHN L. MICA, Florida, Chairman
BOB BARR, Georgia                    PATSY T. MINK, Hawaii
BENJAMIN A. GILMAN, New York         EDOLPHUS TOWNS, New York
CHRISTOPHER SHAYS, Connecticut       ELIJAH E. CUMMINGS, Maryland
ILEANA ROS-LEHTINEN, Florida         DENNIS J. KUCINICH, Ohio
MARK E. SOUDER, Indiana              ROD R. BLAGOJEVICH, Illinois
STEVEN C. LaTOURETTE, Ohio           JOHN F. TIERNEY, Massachusetts
ASA HUTCHINSON, Arkansas             JIM TURNER, Texas
DOUG OSE, California                 JANICE D. SCHAKOWSKY, Illinois
DAVID VITTER, Louisiana

                               Ex Officio

DAN BURTON, Indiana                  HENRY A. WAXMAN, California
           Sharon Pinkerton, Staff Director and Chief Counsel
                   Steve Dillingham, Special Counsel
                          Lisa Wandler, Clerk
                    Cherri Branson, Minority Counsel

                            C O N T E N T S

                              ----------                              
                                                                   Page
Hearing held on December 9, 1999.................................     1
Statement of:
    Lawrence, Arthur J., Ph.D., Deputy Assistant Secretary for 
      Health, Office of Public Health and Science, U.S. 
      Department of Health and Human Services, accompanied by 
      Gary Ellis, Director, Office of Protection from Research 
      Risks, National Institutes of Health; Mark Yessian, 
      Regional Inspector General for Evaluations and Inspections, 
      Office of Inspector General, U.S. Department of Health and 
      Human Services, accompanied by Laura McBride, Policy 
      Analyst; Eric Cassell, M.D., Commissioner, National 
      Bioethics Advisory Commission, accompanied by Eric Maslin, 
      executive director, National Biology Commission; and John 
      Oldham, M.D., director, New York State Psychiatric 
      Institute, accompanied by Timothy Walsh, M.D., former 
      director of the IRB at the New York Institute..............     8
    Zucker, Cliff, executive director, Disability Advocates, 
      Inc., Albany, NY; Adil Shamoo, Citizens for Responsible 
      Care in Psychiatry and Research, New York, NY; Charisse 
      Johnson, Brooklyn, NY; and Sherry Grenz, National Alliance 
      of Mentally Ill............................................    88
Letters, statements, et cetera, submitted for the record by:
    Cassell, Eric, M.D., Commissioner, National Bioethics 
      Advisory Commission, prepared statement of.................    44
    Grenz, Sherry, National Alliance of Mentally Ill, prepared 
      statement of...............................................   120
    Lawrence, Arthur J., Ph.D., Deputy Assistant Secretary for 
      Health, Office of Public Health and Science, U.S. 
      Department of Health and Human Services, prepared statement 
      of.........................................................    12
    Oldham, John, M.D., director, New York State Psychiatric 
      Institute, prepared statement of...........................    52
    Shamoo, Adil, Citizens for Responsible Care in Psychiatry and 
      Research, New York, NY, prepared statement of..............   106
    Yessian, Mark, Regional Inspector General for Evaluations and 
      Inspections, Office of Inspector General, U.S. Department 
      of Health and Human Services, prepared statement of........    24
    Zucker, Cliff, executive director, Disability Advocates, 
      Inc., Albany, NY, prepared statement of....................    92

 
     DO CURRENT FEDERAL REGULATIONS ADEQUATELY PROTECT PEOPLE WHO 
                    PARTICIPATE IN MEDICAL RESEARCH?

                              ----------                              

                       THURSDAY, DECEMBER 9, 1999

                  House of Representatives,
Subcommittee on Criminal Justice, Drug Policy, and 
                                   Human Resources,
                            Committee on Government Reform,
                                                      New York, NY.
    The subcommittee met, pursuant to notice, at 10:38 a.m., in 
the Auditorium of the New York County Lawyers Association, 14 
Vessey Street, New York, New York, Hon. John L. Mica (chairman 
of the subcommittee) presiding.
    Present: Representatives Mica and Towns.
    Staff present: Sharon Pinkerton, staff director and chief 
counsel; Steve Dillingham, special counsel; and Lisa Wandler, 
clerk.
    Mr. Mica. Good morning, I'd like to call to order the 
Subcommittee on Criminal Justice, Drug Policy, and Human 
Resources of the U.S. House of Representatives. We're pleased 
to be in New York City this morning for this field hearing, and 
I want to first extend my appreciation to our subcommittee 
member, Mr. Towns, who I've had the honor of working with in 
Congress since I came in 1993, and the previous chair of one of 
the subcommittees. We've worked together over the last four 
terms on issues of usual concern and I appreciate your 
persistence in the issues before us today and also the 
leadership that he has provided us both on this issue and on 
other matters we've worked together with in the Congress.
    I thank you for hosting us today, and we will proceed. I 
will proceed in this fashion. I will start with an opening 
statement. I'll recognize Mr. Towns. Then we will proceed to 
our panels, and there are two panels today, of witnesses.
    Today's hearing before the Subcommittee on Criminal 
Justice, Drug Policy, and Human Resources, will examine an 
issue of great importance and tremendous complexity. The issue 
before us today is whether Federal regulations offer adequate 
protection to participants in medical research, a topic that 
probably couldn't be more timely.
    In recent weeks, considerable national attention has been 
devoted to the tragic death of 18 year old Jessie Gelsinger of 
Tucson, AZ. He died in September as a result of a gene therapy 
experiment. Jessie died 4 days after being injected with a 
modified cold virus, and engineered genes into an artery 
leading to his liver. Researchers were shocked by his death and 
have not determined exactly why he died.
    The case has stirred a national debate on gene therapy 
experiments and the reporting of its adverse affects. It also 
prompted the National Institutes of Health to issue a 
solicitation to the medical community requesting related help.
    I noticed today in reading this morning's edition of the 
New York Times, Mr. Towns and others, FDA officials, I guess 
yesterday have come up with some disclosures on what took place 
with this case, and it said, let me just cite for the record,

    Officials of the Food and Drug Administration said today 
Jessie Gelsinger, an 18 year old Arizona man who lost his life 
in a gene therapy experiment in September was ineligible for 
the clinical trial and should not have been treated because his 
liver was not functioning well enough before doctors infused 
him with a dose of corrective genes. In announcing the 
preliminary results of their inquiry of Mr. Gelsinger's death, 
officials also said the University of Pennsylvania scientists 
running this has violated FDA requirements by failing to report 
immediately information about two patients long before the 
death who had experienced serious side effects and had said the 
informed consent form the investigators gave patients deviated 
from the one the agency had approved.

    I thought that was interesting and timely, given the 
subject before us today. NIH is now calling on researchers to 
report ill effects from experiments of this type. It appears, 
as this article points out, the previous deaths have occurred 
from experimental research that had not been reported to NIH. 
Accordingly, Federal regulatory changes have been proposed.
    The example of gene research illustrates a question before 
us today. What further Federal regulations are needed to reduce 
unnecessary health and safety risks to human subjects? I will 
keep an open mind throughout this hearing, but I do think there 
is a growing concern that current Federal regulations do not 
offer the full range of protections that many would like to 
see. This is true despite the fact that many Members of 
Congress, including myself, are often very skeptical of 
increasing government regulations, particularly Federal 
regulations imposed on business and private activities.
    I'd also add, one of the things that we do not want to do 
is to hamper legitimate research in any way, or deter 
legitimate research and basic fundamental human research, which 
is so important.
    Our focus today, however, is on research and institutions 
that receive Federal money. Our subcommittee has oversight 
responsibility to insure that such research is conducted both 
properly and safely. A key topic in this discussion is the 
critical roles played by institutional review boards, commonly 
referred to as IRBs. These IRBs oversee human subject research. 
IRBs are required to protect human subjects participating in 
federally funded research projects.
    IRBs are governed by common Federal regulations adopted by 
17 agencies that are engaged in human subject research. IRBs 
typically review and approve research plans before research is 
carried out. This review includes research protocol, the 
informed consent document to be signed by the subjects, and 
advertisements to be used in recruiting subjects.
    In carrying out this review, the IRBs seem to insure that 
potential risks are warranted and reasonable in relation to 
potential benefits. IRBs insure that informed consent documents 
clearly identify known risks and the true nature of the 
research being conducted. This includes guarding against 
advertisements that might be misleading and selection 
procedures that might be biased or unfair.
    The responsibilities of IRBs do not stop once the research 
has begun. They're required to exercise continued oversight of 
research studies involving human subjects. Such oversight 
includes examining reports of adverse incidents involving 
research subjects and also requests for changes in the research 
methodology.
    The Federal department that has the greatest role in 
overseeing human subject research is the Department of Health 
and Human Services. Within HHS, the Food and Drug 
Administration [FDA], and the Office of Protection from 
Research Risk [OPRR], are the two agencies with primary 
responsibilities for overseeing activities and also for 
implementing human research subject regulations and 
protections.
    In studies involving biomedical research, the FDA monitors 
the safety of human subjects through its Center for Drug 
Evaluation and Research, also known by the CDER designation.
    The Office of Protection from Research Risk [OPRR], has the 
critical responsibility of implementing basic HHS policy for 
protecting human research subjects in HHS research and also 
overseeing the IRBs.
    HHS annually invests approximately $5 billion of its 
research dollars in approximately 16,000 research projects that 
involve human subjects. To provide oversight for these research 
projects, OPRR has agreements with more than 4,000 federally 
funded institutions to insure and protect the human subjects 
that are involved. Each institution that receives funding must 
establish an IRB. IRBs are typically made up of scientists, 
doctors and patient representatives to monitor and enforce 
ethical research standards. Federal regulations require that a 
non-scientist and an individual not affiliated with the 
institution be included in each of the IRB panels.
    Under OPRR guidelines, all potential research subjects must 
be fully briefed on the purpose, duration and procedures of a 
research project before agreeing to participate. OPRR has the 
authority to investigate and require corrective action or 
suspend funding to an institution until problems are resolved.
    For example, there was much publicity this year when OPRR 
temporarily suspended Duke University research funds because of 
Federal compliance concerns. Obviously, with so many 
departments and agencies involved, so many research protocols 
to enforce, so many projects to monitor, so many dollars 
invested, and so many human subjects at potential risk, the 
complicated task of insuring an adequate level of protection 
from avoidable risk, or even abuse, can become somewhat 
overwhelming.
    As we will hear today, there is significant concern that 
OPRR has been overwhelmed in the past and that reforms may be 
needed. This was the conclusion of the HHS Office of Inspector 
General in a report that they issued.
    Today we'll hear that some changes are underway in response 
to these concerns. For example, Secretary Shalala recently 
announced the relocation of OPRR from NIH. OPRR will now report 
to her office and leave the regulation of animal research 
within NIH.
    But are these minor changes enough? If not, what additional 
changes are needed? Furthermore, shouldn't we have a clear 
accounting of the 3,000 to 5,000 estimated IRBs that are bound 
and required to implement Federal standards? If we aren't sure 
of the number of IRBs, and how to contact them, how can an 
OPRR, FDA or anyone else adequately monitor their activities 
and their capabilities?
    In considering reforms, there are a number of specific 
concerns that I feel merit our closest attention. Foremost 
among these is the need to protect against conflicts of 
interest that might result in increased risk of research 
participants and others who may be impacted from the research. 
I read recent accounts, situations even here in New York, where 
IRB members may have received money and funds from 
pharmaceutical companies with a financial interest in research 
projects that they oversee. Pharmaceutical research, of course, 
can have enormous financial consequences.
    Doesn't this present a serious potential conflict that can 
influence research decisions and judgments? Is the mere 
disclosure of financial interest enough to assure scientific 
and medical objectivity? I'm concerned that while this 
subcommittee and HHS, Office of Inspector General have 
previously identified some of these problems, and have put 
forth some valuable solutions and recommendations, it appears 
that none of these solutions have been implemented to date.
    Why not? We'll also review today if legislative action or 
administrative additional action is necessary.
    Human subject research is an issue that is national in 
scope and deserves attention at all levels of government. 
Today's hearing hopefully will increase our understanding of 
what additional improvements and protections may be needed. 
We'll have with us today a number of distinguished government 
officials, medical researchers, and others who are 
knowledgeable and experienced with research involving human 
subjects. We appreciate their willingness to appear before the 
subcommittee to share both their knowledge and experience with 
us. We look forward to their insight, to their recommendations 
and also for their update on the progress that's being made 
with the recommendations that have been made in the past.
    I'm pleased at this time to yield to Mr. Towns, a member of 
our subcommittee, and as I said, Mr. Towns has pursued this 
matter for some time. I believe this is the third Federal 
congressional hearing on this matter, and his persistence has 
brought both attention and some reform that is needed, and we 
anticipate this hearing will result in some additional changes 
in procedures, but I thank him for his participation and for 
his leadership on this issue, I'm pleased at this time now to 
yield to the gentleman from New York, Mr. Towns.
    Mr. Towns. Thank you very much, Mr. Chairman. Let me also 
add that I really appreciate you taking the time from your busy 
schedule to come to New York to have this hearing. Also, it's 
been a pleasure to work with you on this issue and also other 
issues over the past 8 or 9 years, so I want to let you know I 
appreciate that as well.
    I want to take this opportunity to thank all of you for 
coming, especially those from Washington, DC, Albany, NY, and 
places near and far, to attend this hearing, and I want to 
thank the New York County Lawyers for providing space for us to 
have this hearing.
    Mr. Chairman, medical research on human subjects knowingly 
subjects some individuals to potential harm to seek benefits 
for a greater number of people. Federal regulations are 
intended to provide guidelines that protect the individual 
without reasonably hampering research goals. Under Federal 
regulations, research could only proceed if the research 
subject provides a valid, informed consent, has a capacity to 
understand the information, the ability to weigh the advantages 
and disadvantages of pursuing the research and access the 
benefit and risk of the drug or procedure. Yet numerous cases 
have been in the press lately, where this has not been the 
case, so it's so important for us to consider that and take a 
look at where we are today.
    In light of the risk and dangers posed by these types of 
experiments, we must seriously consider legislation that will 
make the IRBs fully independent of research institutions; that 
will assure that research methods meets customary standards of 
scientific excellence that will assure that children and 
parents are fully informed about the real purpose and intent of 
the research; that will permit them to decline or refuse to 
participate without fear of retaliation, and that will subject 
research programs that confer no benefits on the subject or 
that result in stigmatization of racial groups.
    Mr. Chairman, again, I want to thank you for taking the 
time out, and I say to you that we've had some success already, 
but we hope to be able to have some more, because I am also 
concerned about the fact that these independent review boards, 
IRBs, we don't even know how many are out there. We don't even 
know whether there are qualifications for them, we don't know 
that. The point is that it also has potential for all kinds of 
conflict, and if you don't know how many are out there, how can 
you regulate them? I think that's also a real concern, but 
also, I can't help but think about those experiments that took 
place in the time of the Tuskegee experiment, I can't help but 
think about that, and many, many others. Of course you referred 
to one in the Washington Post, so a lot of things are going on, 
and I think we can no longer close our eyes. We have to come to 
grips with this and begin to deal with it because we're talking 
about human beings. I think that's very, very important.
    And the last thing, Mr. Chairman, that, you know, I'm 
getting reports coming from various sources that people are 
being encouraged to participate in research groups and reported 
that many times they're given, like, toys, or being paid a few 
dollars to be in it, and they don't even know the danger or the 
risk that's involved, and that really bothers me as well, so 
I'm hoping that we can sort of come up with some guidelines and 
have some legislation, of course, that I think that will 
correct that, but my point is I think that through this hearing 
process maybe we can get a better handle on this. Because to 
have these review boards out there, and we don't even know how 
many that exist, there's no qualifications in terms of people 
on them, so you pick your friends, your buddies, that just to 
me should not be in the United States of America.
    So Mr. Chairman, here again, I thank you so much for coming 
to New York and having this hearing.
    Also, we've had some success, as I indicated early on. We 
have a letter from the Office of Surgeon General David Satcher 
and we have a note, I think I'll just read this paragraph, Mr. 
Chairman, before we go forward.
    It says,

    Moreover, we believe that no federally supported research 
should be compromised by any selection of human subjects that 
is not supportable by clear and advised scientific 
explanations. To this end, I will convene a group comprised of 
knowledgeable individuals who have not been associated with the 
investigation to examine the process and the context of the 
regulations, make recommendations, and to provide me with a 
summary report. I will contact you with the results upon 
completion.

    Then it goes on to say he will get back.

    The Department has not previously issued guidelines on 
these terms and the context of regulations and I agree that the 
terms need clarification. An essential element in the 
Secretary's decision to relocate human subject protection 
component of OPRR is the formation of an independent advisory 
body organized under the Federal Advisory Committee Act to 
provide guidance, assist in setting standards, review the 
operations of the new office and address human subjects' 
protection in general. This advisory committee will be known as 
National Advisory Council on Human Research and Protection, 
NACHRP.
    I believe the best approach to the development of a 
clarification of the term is for the question to be addressed 
by the council. In this way, multiple interests and views can 
be considered and methodology examined, thus providing a 
solution for acceptable regulatory clarification that protects 
both human subjects and does not necessarily impinge on the 
advancement of science. I will bring this issue to the council 
for their attention as one of the first matters of priority 
business.

    Mr. Chairman, I think that's a step in the right direction. 
I wish I could say it's a giant step. It's not a giant step, 
but it's a step in the right direction. So thank you so much 
for having this hearing today. Let me say this of note. It 
says--well, actually let me now yield.
    Mr. Mica. Mr. Towns, if you want that part of the record?
    Mr. Towns. Also, Mr. Chairman, may I add, that I'd like to 
put my entire statement in the record.
    Mr. Mica. Without objection, the entire statement, letter 
from the Surgeon General Satcher will be made part of the 
record.
    Mr. Towns, if it's appropriate, we will leave the record of 
this hearing open for 3 weeks for statements of Members who 
haven't been able to attend, and also the hearing may generate 
additional questions of these and other witnesses.
    Without objection, so ordered.
    We'll proceed now, and let me say at the outset that this 
is an investigations and oversight subcommittee of Congress. We 
have a broad range of authority and responsibility. We do swear 
in our witnesses, which I'll do in just a minute.
    I will introduce the first panel, and we have two panels 
today. The first panel consists of Dr. Arthur J. Lawrence, who 
is the Deputy Assistant Secretary for Health, Office of Public 
Health and Science in the U.S. Department of Health and Human 
Services. Some of you have accompanying witnesses. Dr. 
Lawrence, do you have anyone with you?
    Dr. Lawrence. Yes, sir, Dr. Ellis.
    Mr. Mica. Could you identify that individual for the 
record, please? Will he be testifying?
    Dr. Lawrence. I will be referring technical questions to 
him as needed, sir.
    Mr. Mica. Maybe he could pull up a chair. Could you again 
identify him for the record, and his title?
    Dr. Lawrence. Certainly. Accompanying me is Dr. Gary Ellis, 
who is the Director of the Office for Protection from Research 
Risks, National Institutes of Health.
    Mr. Mica. Thank you.
    We also have Dr. Mark Yessian, Regional Inspector General 
for Evaluations and Inspections, the Office of Inspector 
General, the U.S. Department of Health and Human Services. Dr. 
Yessian, do you have anyone accompanying you who will be 
testifying?
    Mr. Yessian. Yes, I do, Mr. Chairman.
    Mr. Mica. Could you identify that individual for the record 
and his title?
    Mr. Yessian. With me is Laura McBride, she's a policy 
analyst in our Boston office and was a major contributor to our 
work on IRBs.
    Mr. Mica. Thank you.
    We also have Dr. Eric Cassell, Commissioner of the National 
Bioethics Advisory Commission. Dr. Cassell, are you by yourself 
today?
    Dr. Cassell. No, I also have somebody with me.
    Mr. Mica. Could you identify that individual and also give 
us his title?
    Dr. Cassell. Yes, Dr. Eric Maslin, is who is the Executive 
Director of the National Biology Commission and who is right 
here.
    Mr. Mica. Welcome. Pull up a chair, please.
    Finally, is it Dr. John Oldham?
    Dr. Oldham. Right.
    Mr. Mica. Director of the New York State Psychiatric 
Institute. Do you have someone accompanying you, Doctor?
    Dr. Oldham. Yes, I do.
    Mr. Mica. Could you identify that individual and their 
title, for the record?
    Dr. Oldham. With me is Dr. Timothy Walsh who was former 
chair of the IRB at the New York State Psychiatric Institute.
    Mr. Mica. Thank you. I guess this will be our largest 
panel, Mr. Towns, in history. But we welcome each of you. We 
appreciate your participation in the hearing today, and helping 
us to find out how we can do a better job, and again, 
protecting people who participate in medical research and also 
making certain that we fulfill our legislative oversight 
responsibilities.
    With that, what we will do is begin, first I'll swear in 
all the witnesses that are here, and we will limit the 
principal witnesses to 5 minutes, approximately, of oral 
presentation. Then we'll proceed to questions after we've heard 
from all of the witnesses, and get their responses.
    However, I might say that upon request of the subcommittee, 
we will be glad to enter into the record, and it will be a full 
record of your statement, such as this house record. Any 
additional supporting information or documents, upon request, 
will be made part of the record. So again, I welcome you.
    If you will please all stand. Raise your right hands.
    [Witnesses sworn.]
    Mr. Mica. The witnesses answered in the affirmative.
    Thank you and welcome each of you. We will start with Dr. 
Arthur J. Lawrence, who is the Deputy Assistant Secretary for 
Health in the Office of Public Health and Science. Welcome, 
sir, and you are recognized.

   STATEMENTS OF ARTHUR J. LAWRENCE, Ph.D., DEPUTY ASSISTANT 
SECRETARY FOR HEALTH, OFFICE OF PUBLIC HEALTH AND SCIENCE, U.S. 
 DEPARTMENT OF HEALTH AND HUMAN SERVICES, ACCOMPANIED BY GARY 
  ELLIS, DIRECTOR, OFFICE OF PROTECTION FROM RESEARCH RISKS, 
NATIONAL INSTITUTES OF HEALTH; MARK YESSIAN, REGIONAL INSPECTOR 
 GENERAL FOR EVALUATIONS AND INSPECTIONS, OFFICE OF INSPECTOR 
    GENERAL, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, 
  ACCOMPANIED BY LAURA McBRIDE, POLICY ANALYST; ERIC CASSELL, 
  M.D., COMMISSIONER, NATIONAL BIOETHICS ADVISORY COMMISSION, 
   ACCOMPANIED BY ERIC MASLIN, EXECUTIVE DIRECTOR, NATIONAL 
 BIOLOGY COMMISSION; AND JOHN OLDHAM, M.D., DIRECTOR, NEW YORK 
  STATE PSYCHIATRIC INSTITUTE, ACCOMPANIED BY TIMOTHY WALSH, 
   M.D., FORMER DIRECTOR OF THE IRB AT THE NEW YORK INSTITUTE

    Dr. Lawrence. Thank you, Mr. Mica.
    Mr. Mica. You might have to pull that mic up closer.
    Dr. Lawrence. Thank you very much, Mr. Mica, Mr. Chairman 
and members of the subcommittee, good morning. As Mr. Mica as 
pointed out, my name is Art Lawrence, I am Assistant Surgeon 
General and Deputy Assistant Secretary for Health Operations in 
the Office of Public Health and Science within the Office of 
the Secretary of the Department of Health and Human Services. I 
am accompanied this morning by Dr. Gary Ellis, Director of the 
Office for Protection from Research Risks which is currently 
within the National Institutes of Health. Dr. Ellis also chairs 
the interagency agency committee on protecting research 
subjects, in which 17 Federal departments and agencies 
participate.
    We are pleased to appear before the subcommittee to 
describe our well developed, yet ever evolving system of 
protection for research subjects. I've submitted the 
Department's written testimony for the record. I ask that I be 
permitted to briefly summarize a few highlights from that 
testimony, and that my written testimony be entered into the 
record in full.
    Mr. Mica. Without objection, the entire statement will be 
made part of the record.
    Dr. Lawrence. Thank you sir. Together with Dr. Ellis I'll 
then be happy to entertain any questions the committee members 
might have concerning the importance of this subject meeting.
    First, Dr. Satcher has asked that I extend his best regards 
and his personal regrets for not being able to be here with you 
today. He has also asked me to extend his personal gratitude to 
you, Mr. Towns, for the leadership that you have taken in 
promoting high energy efforts to eliminate racial and ethnic 
disparities in health status in the United States. He looks 
forward to continuing to work with you on this and other 
matters of importance to the public's health.
    He also asked me to relate to you that he shares your 
concerns about research that is conducted on populations that 
lack diversity. And in particular, about research that is 
conducted entirely in minority populations, unless there is a 
clear and compelling need to do so. As the letter submitted 
today to Congressman Towns states, ``The Department has 
recognized the need to increase diversity of participants in 
clinical trials and has taken many steps to accomplish that in 
federally funded research.'' A good example of this is seen in 
the diversity of the Women's Health Initiative studies. The 
Department is committed to continue these efforts until our 
goals are met. In addition, we have made a commitment to 
involve communities in the design and conduct of research and 
are moving forward with plans to be sure that research 
addresses the needs of communities and is responsive, 
considerate of community concerns.
    This year has marked a quarter century of the formal 
promulgation of the Department's regulations for the protection 
of human subjects in research. This enduring and vigorous 
system of protections is designed to prevent physical injury, 
psychological injury, and harm to the dignity to the research 
subjects as biomedical and behavioral scientists pursue new 
knowledge for the common good. We are always interested in 
improving the system to make research as safe as possible.
    My written submission, gentlemen, outlines in some detail 
the multiple layers of protection for human subjects. These 
feature at least half dozen levels of protection. They include 
the system of institutional review boards or IRBs, the keystone 
of the system. These are boards of scientists and nonscientists 
who independently review research involving human subjects. By 
regulation, the Department and 16 other Federal agencies cannot 
provide funds for human subject research unless an IRB approves 
the protocols for such studies. Once such research is underway, 
the IRB must conduct continual review of the research at 
intervals that are appropriate to the degree of risk, at least 
once a year.
    Exerting oversight over the whole process are OPRR and when 
investigational drugs, devices or biologics are involved, the 
Food and Drug Administration as well. An additional layer of 
review which may be employed especially in large studies is an 
independent data and safety monitoring board or DSMB. These 
bodies are appointed to oversee and evaluate the research 
investigation. DSMB reviews accumulated study data and makes 
recommendations on continuation or modification of research or 
clinical studies involving human subjects. It is OPRR's role to 
make certain that the IRB process works at institutions within 
its jurisdiction.
    OPRR has taken a number of actions to bolster effective 
oversight of individual IRBs on a variety of fronts. We believe 
that with this system of IRBs that the risks are minimized by 
using research consistent with sound research design and which 
do not unnecessarily expose subjects to risks. It helps insure 
that the risks are reasonable to anticipated benefits, that the 
selection of subjects is equitable, that there are proper 
informed consents and that the rights and welfare of subjects 
are maintained in other ways as well. IRBs watch out especially 
for research involving children, prisoners, pregnant women, and 
individuals with mental disabilities. They also guard the 
rights and safety of other vulnerable populations, including 
the economically disadvantaged, and individuals who are also 
educationally disadvantaged.
    It is the IRB's responsibility to assure that additional 
safeguards are included in studies involving any of these 
responsibilities.
    OPRR oversees implementations of the regulations in all 
department facilities as well as domestic or foreign 
institutions or sites receiving Federal and Health and Human 
Services funds. OPRR requires all departmental agencies and 
extramural research institutions that conduct research 
involving human subjects to set forth the procedures it will 
use to protect human subjects in a policy statement formally 
called an assurance of compliance. This is a written commitment 
to ethical principles, and institutional procedures that are 
adequate to safeguard the rights and welfare of human subjects. 
The assurance statement becomes a specific instrument that OPRR 
uses to gauge an institution's compliance with human subject 
protections if there is a problem.
    This description, of course, gentlemen, is a brief outline 
of the human subjects research protection system. Additional 
details involving informed consent regulations and research 
education training methods are included in my written 
submission.
    I wanted to take a final moment here to convey a few facts 
about what the Department is doing to strengthen and expand the 
significant human research subjects protection apparatus. What 
I've outlined mandates a strong and effective OPRR operation. 
Responding to other concerns in May of this year, an expert 
panel transmitted a report to the Director of the National 
Institutes of Health where OPRR is now located. That report 
recommended that OPRR be relocated from NIH to the Office of 
the Secretary. It also suggested that the OPRR Director be at 
the Senior Executive Service or SES level following that 
transfer.
    Third, it was recommended to the Secretary that an 
independent advisory committee be created, this is the 
committee which Mr. Towns has just referred to, to provide 
guidance and to assist in standard setting and review the 
operation of the OPRR.
    Finally, the report suggested that resources currently 
available to the OPRR may be inadequate for fulfilling its 
mission. In turn, the Director of NIH transmitted its report to 
the Secretary indicating agreement with the panel in 
recommending that the Secretary accept and act on its findings.
    In August the Secretary took action on the central 
recommendations and findings and asked Dr. Satcher to undertake 
review processes to determine whether to relocate OPRR as a 
unit or rather to move only the human subjects protections 
component. A work group was formed to address organizational 
structure and management consultant has been engaged to examine 
the question of resources. In October the Secretary accepted 
the recommendation that the newly relocated office focus solely 
on human subjects protection with animal welfare functions 
remaining at NIH. The management study has not been completed 
yet and a target date has been set for completion of activities 
of March 2000.
    Finally, the Department has currently put out for comment a 
notice of proposed rulemaking or an NPRM on privacy. It shows a 
commitment to reviewing the human subjects protections 
regulations with an eye toward enhancing the privacy 
protections of research subjects. This is yet another example 
of the Department's commitment to another important area of 
strengthening protections for human research subjects.
    We believe we have a system in place which to the greatest 
degree possible minimizes the potential for harm, enables and 
protects individuals' autonomous choice and promotes the 
pursuit of new knowledge.
    Thank you, Mr. Chairman, and members for the opportunity to 
address you this morning on this critical topic. Dr. Ellis and 
I will be pleased to answer any questions you may have.
    Mr. Mica. Thank you.
    [The prepared statement of Dr. Lawrence follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.001
    
    [GRAPHIC] [TIFF OMITTED] T6523.002
    
    [GRAPHIC] [TIFF OMITTED] T6523.003
    
    [GRAPHIC] [TIFF OMITTED] T6523.004
    
    [GRAPHIC] [TIFF OMITTED] T6523.005
    
    [GRAPHIC] [TIFF OMITTED] T6523.006
    
    [GRAPHIC] [TIFF OMITTED] T6523.007
    
    [GRAPHIC] [TIFF OMITTED] T6523.008
    
    [GRAPHIC] [TIFF OMITTED] T6523.009
    
    Mr. Mica. We'll hear now from our second witness, Mark 
Yessian. Dr. Mark Yessian is Regional Inspector General for 
Evaluations and Inspections for the U.S. Department of Health 
and Human Services. Welcome. The chair will recognize him.
    Mr. Yessian. Mr. Chairman, Congressman Towns, the current 
system of protecting human subjects who participate in medical 
research is in need of major reform. This is a conclusion we 
emphasized in a June 1998 report; it's one that we reiterate 
here today.
    Our June 1998 report was based on a year-long inquiry into 
the work of the institutional review boards. That inquiry led 
us to sound a warning signal that the effectiveness of the 
boards is in jeopardy.
    Here's what we based that on: IRBs review too much, too 
quickly with too little expertise. They conduct minimal 
continuing review of approved research. They face conflicts 
that threaten their independence. They provide little training 
for investigators and board members. And, not least of all, 
they must cope with major changes that are fundamentally 
transforming the research environment from what it was a 
quarter of a century ago when the current Federal protections 
were put in place. In our report we made numerous 
recommendations to the National Institutes of Health and to the 
Food and Drug Administration. At the core of them was a search 
for ways to give IRBs more flexibility so they could do their 
job better, but to hold them much more clearly accountable for 
results.
    Let me provide an update, if I could, on what's happened in 
the year and a half or so since we issued our report. First, 
I'd say there are some encouraging developments. At the Federal 
level, the most notable action has been an increased 
enforcement effort by the Office of Protection from Research 
Risks [OPRR]. In the year prior to our report, OPRR had made 
only one site visit to investigate the adequacy of an IRB's 
efforts. Since that time, it has made numerous site visits, 
some very high profile and some resulting in the actual 
suspension of federally funded research at major medical 
centers.
    At the local level, a number of institutions have put more 
resources into their IRBs and a number of IRBs have undertaken 
training and other educational kinds of initiatives intended to 
sensitize principal investigators and IRB board members to 
issues involving human subject protection. Then also at the 
professional level it's important to note there's some stirring 
there, too. There's a movement toward certifying IRB 
administrators and one toward private accreditation of IRBs. 
Both of these movements have some significance.
    But as important as these developments are, the system of 
protections provided by IRBs remains in jeopardy. From the 
ground up, if you look at IRBs, you see the same danger signs. 
Expanded work loads, quick reviews, threats to their 
independence, inadequate information, insufficient training, 
minimal outside representation. Moreover, and this is the basic 
point, the underlying pressures on IRBs continue to build and 
to make it difficult for them to do their job adequately.
    Let me touch on three of those pressures. The most 
important one is the increased commercialization of the 
research environment. Industry sponsors, anxious to bring new 
products to market and to contain their development costs, seek 
to expedite the clinical trials process and to conduct their 
trials in the quickest, most efficient settings. For IRBs, this 
means doing more quicker and better. It also means that it can 
be quite difficult to slow down the research process by raising 
nettlesome questions for instance, about the adequacy of the 
informed consent process.
    A second pressure is the continuing and escalating pressure 
on the IRB members themselves. Most of the time these are 
volunteers that serve on these boards. They find it difficult 
to spend the time it takes to review proposals that are 
increasing both in numbers and complexity.
    Finally, I'll note there's an intensified quest for human 
subjects. If you look at this as a supply-demand situation, we 
have a substantial unmet demand for human subjects. This 
heightens recruitment pressures for research sponsors and 
investigators and leaves IRBs with many difficult questions to 
face. For instance, should they be concerned about recruitment 
bonuses that sponsors give to investigators for subjects? 
Should they be concerned about the mining of patient data bases 
to find potential human subjects? What about the payment of 
fees to physicians referring their patients as potential 
subjects? What are the standards or guidelines to answer such 
questions? Where are they?
    We end up as we did in 1998 calling for a much stronger 
Federal presence here, and I'll just touch four of the issues 
that we highlight. There are others, but certainly one would be 
more extensive onsite performance based reviews of IRBs. The 
OPRR has started this. It's a good start, but only a start. We 
recommend this kind of effort intensify and that it conduct 
both unannounced and announced site visits.
    We should also not forget the Food and Drug Administration 
here. They are actually onsite more often than the OPRR, and 
have a substantial responsibility here. As we said before, we 
think it's essential that they broaden their reviews to go 
beyond simple compliance matters and focus more on performance.
    My second point is that we need a strengthened commitment 
to educational outreach and mandates. Everybody says the answer 
is always more education, but I think it's really crucial to go 
beyond the talk and have some action. Action at the Federal 
level where we provide more in the way of web based tutorials 
and the like. But also mandates that investigators and board 
members participate in educational programs concerning human 
subject protections.
    The third direction we're emphasizing is much more 
extensive representation of non-scientific and non-
institutional members on IRBs community members, if you will. 
It just simply doesn't seem adequate to have situations, as you 
often do, where there may be 14 or 15 IRB members and one, 
maybe two from outside the institution. This noninstitutional 
member can provide a vital counterbalance to the kind of 
pressures IRBs face. It's a way of sharpening the focus on 
subjects and what is in their best interest.
    And last, as Congressman Towns has already referred to, we 
simply need a mandate to register IRBs with the Federal 
Government. This need not be a major burden on anybody, but how 
can we provide effective oversight and guidance if we don't 
even know who the IRBs are and where they're at. So some kind 
of registration requirement with minimally descriptive 
information would seem to be important.
    In closing, I'd like to emphasize that notwithstanding what 
may sound like a rather harsh critique, we recognize the major 
contributions that investigators, sponsors, IRB members and 
staff are making in this area. There are a lot of committed, 
dedicated people here, but they work in a system that needs to 
be reformed. That's the basic point. Such reform is essential 
to provide necessary protections for human subjects. It's also 
essential to sustain the progress we are making in clinical 
research.
    Thanks for the opportunity to testify, we are certainly 
open to questions.
    Mr. Mica. Thank you.
    [The prepared statement of Mr. Yessian follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.010
    
    [GRAPHIC] [TIFF OMITTED] T6523.011
    
    [GRAPHIC] [TIFF OMITTED] T6523.012
    
    [GRAPHIC] [TIFF OMITTED] T6523.013
    
    [GRAPHIC] [TIFF OMITTED] T6523.014
    
    [GRAPHIC] [TIFF OMITTED] T6523.015
    
    [GRAPHIC] [TIFF OMITTED] T6523.016
    
    [GRAPHIC] [TIFF OMITTED] T6523.017
    
    [GRAPHIC] [TIFF OMITTED] T6523.018
    
    [GRAPHIC] [TIFF OMITTED] T6523.019
    
    [GRAPHIC] [TIFF OMITTED] T6523.020
    
    [GRAPHIC] [TIFF OMITTED] T6523.021
    
    [GRAPHIC] [TIFF OMITTED] T6523.022
    
    [GRAPHIC] [TIFF OMITTED] T6523.023
    
    [GRAPHIC] [TIFF OMITTED] T6523.024
    
    [GRAPHIC] [TIFF OMITTED] T6523.025
    
    [GRAPHIC] [TIFF OMITTED] T6523.026
    
    [GRAPHIC] [TIFF OMITTED] T6523.027
    
    Mr. Mica. We'll now hear from Dr. Eric Cassell, who is the 
Commissioner of the National Bioethics Advisory Commission. 
Welcome, sir. You're recognized.
    Dr. Cassell. Thank you. I would like to thank the chair and 
members of the subcommittee for the opportunity to appear. I am 
Eric Cassell, Commissioner of the National Bioethics Advisory 
Commission. I would appreciate it if the entire statement could 
be included in the record.
    Mr. Mica. Without objection, so ordered.
    Dr. Cassell. I think it would be appropriate if the 
National Bioethics Commission report and its recommendations be 
included in the record.
    Mr. Mica. Without objection, so ordered.
    Dr. Cassell. Interest in this subject goes back to its very 
beginnings. It's a society's primary obligation to provide 
improved ways of protection of subjects in research. But in 
this instance, there are special problems. During its 18 months 
of study, NBAC held hearings, heard witnesses from community 
members to psychiatrists, from OPRR and other experts, and have 
confirmed the problem of lack of protection or inadequate 
protection for persons with mental disorders who are subjects 
of research.
    These persons have need for special protection, primarily 
arising from several things. First of all, persons with mental 
disorders have a really important need to find adequate 
treatment, which is often not available outside of the research 
setting, or at the very least, the most modern treatment is now 
in the research setting so that they are often forced to go 
into research protocol to get what they need. They are often 
stigmatized, and so they don't have the protection of the 
community that is normally present and often invisible, but is 
always there, people who know their rights and so forth.
    They have varying capacity to consent. Their illness may 
make it impossible for them to recognize what their needs are, 
what they should consent to, what they shouldn't consent to at 
some times, while at other times, they have the same capacity 
as persons without disorders.
    There also are problems that arise from the enthusiasm of 
investigators, and but most of all I'd like to echo what's just 
been said, from a lack of education of investigators about 
ethical issues in research. When you're hot on the trail of 
something exciting, and when that's your life's work, sometimes 
enthusiasm overcomes other objectives and people enter into 
research that otherwise might not, and the subject is a willing 
participant for the same reasons I noted before. Now, after 
reviewing all the problems that came before, in fact, we made a 
number of recommendations. The recommendations which are 
primarily what this, our large report is about, are 21 in 
nature. They are currently under review by Federal agencies 
that are subject to the common rule, and under review by the 
White House, and we are very hopeful that the role of this 
committee will in part be to move forward a review of those 
recommendations, and make them appear in regulations in the 
future.
    There are six categories of recommendations: The first has 
to do with the nature of IRB's and the importance of having 
membership in the IRB of persons from the community, of persons 
with mental disorders so that they are adequately represented. 
Also, there are questions that may come before IRBs which are 
beyond their competence and which should be reviewed by a 
special panel in the office of HHS that can bring before it 
problems of a more general nature that should be seen.
    Next, the research design for persons with mental disorders 
have to be more carefully gone over. For one thing, wherever 
possible, other subjects should be used who do not have mental 
disorders. There should be great concern about the use of 
placebo controls in people who have mental disorders because on 
occasion they may heal again by going back to a placebo state. 
Certain others, special projects like what happens when 
somebody has a washout period, that means their medication is 
removed, they're given time for their illness to appear, which 
is one thing with diabetes but a different thing with 
schizophrenia.
    Next thing, we were very concerned about the nature of 
informed consent. It is crucial whether it is clearly known 
whether a person has the capacity to consent, and in this we 
requested that there be assessment of individuals with mental 
disorders by a qualified, independent professional, something 
that is not used in other areas of research.
    Next, there are categories of research relating to levels 
of risk and the prospective benefit which must be clearly 
spelled out so people are not subjected to research where 
there's no benefit possible, but risk is present.
    We also recommended that it be possible for there to be 
certain decisionmakers who are members of the patient's family 
or are friends and who can represent them when they do not have 
the capacity to represent themselves.
    And finally, we, like everybody else, emphasize the 
importance of education. But I cannot state too strongly that 
we have to educate people in IRBs or we have to educate 
investigators; but then it just sort of trails off. It's not 
adequate. It requires resources to educate people and requires 
putting in place those resources and the people to do it, and 
I'm hoping very strongly that the subcommittee sees the 
importance of education and sees the importance of adding extra 
resources.
    We used to say that people who had a huge budget but didn't 
do research, that that was faulty. We should now say that where 
there's money for research, there should always be money for 
education of investigators and IRBs about ethical issues in 
research.
    I'd like to conclude by pointing out that NBAC's special 
mission is to look at the whole system of protection of human 
subject from research risk. That's our primary obligation, and 
we are now starting a long and detailed investigation of that 
issue and we expect to issue a report with detailed 
recommendations about changes in the IRB system and in the 
general system to protect human subjects of research. I 
appreciate very much the opportunity to testify.
    Mr. Mica. Thank you.
    [Note.--The report entitled, ``Research Involving Persons 
with Mental Disorders That May Affect Decisionmaking 
Capacity,'' may be found in subcommittee files.]
    [The prepared statement of Dr. Cassell follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.028
    
    [GRAPHIC] [TIFF OMITTED] T6523.029
    
    [GRAPHIC] [TIFF OMITTED] T6523.030
    
    [GRAPHIC] [TIFF OMITTED] T6523.031
    
    [GRAPHIC] [TIFF OMITTED] T6523.032
    
    Mr. Mica. I can now recognize Dr. John Oldham, director of 
the New York State Psychiatric Institute. You're recognized, 
sir.
    Dr. Oldham. Thank you, Chairman Mica, Congressman Towns. 
I'd like to thank you for the opportunity to testify today on 
this important topic. Joining me today is Dr. Timothy Walsh, a 
research scientist at the New York State Psychiatric Institute 
and former chair of the Institute's IRB. Also I'd like to 
request that our entire testimony be entered into the record.
    Mr. Mica. Without objection so ordered.
    Dr. Oldham. It's been approximately 25 years that 
institutional review boards have been formally carrying out 
their function and it's appropriate to review the Federal 
regulations and the IRBs that are at their center. Currently 
institutions, such as New York Psychiatric Institute, which 
I'll refer to as NYPI, are required to enter into a multiple 
project assurance or MPA with OPRR, an agreement which governs 
research at that facility. Under an MPA, reporting mechanisms 
that are established for unanticipated problems that involve 
research risks and for suspension or termination of IRB 
approval for specific research protocols. OPRR provides 
oversight of research programs conducted under an MPA and it 
also conducts investigation of allegations of violations of 
human subject regulations.
    NYPI has chosen to apply the Federal regulations to all of 
its research, including that which is not federally funded. 
Elsewhere in the country, however, some non-federally funded 
research falls outside the scope of Federal regulations. One 
issue to consider in protection of research participants would 
be to mandate universal application of the Federal regulations.
    The IRB serves an important and useful role in the system 
of protecting human subject research. NYPI has a highly 
committed and responsible IRB. As this committee is aware, NYPI 
was the subject of allegations filed with OPRR regarding a 
portion of a particular study carried out in 1995. And Dr. 
Walsh and I testified before the Subcommittee on Human 
Resources in June 1998.
    OPRR conducted a lengthy and thorough investigation to 
determine whether NYPI complied with the detailed Federal 
regulations that applied to the research. They were provided 
with extensive documentation of the study and its IRB review 
and oversight. They made multiple requests for additional 
information and received lengthy responses to detailed 
questions. In March 1999 a team of six OPRR staff and three 
outside consultants questioned NYPI investigators, IRB chairs 
and members and institutional representatives at length and 
reviewed their decisions and actions in light of Federal 
regulations.
    After 16 months of investigation, OPRR concluded that not 
only were there no deficiencies in the IRB's review of the 
research and human subject protections provided, it also 
commended the psychiatric institute's IRB: for its ``detailed 
understanding of the specific requirements of the Federal human 
subject regulations,'' and for its members who are, 
``enthusiastic and dedicated to the protection of human 
subjects and have the diversity, including consideration of 
race, gender and cultural backgrounds, and sensitivity to such 
issues as community attitudes, to promote respect for its 
advice and counsel in safeguarding the rights and welfare of 
human subjects as required under Federal regulations.''
    The study in question was one component of a larger study 
which sought to identify factors that contribute to the 
development of antisocial and violent behavior in young boys, a 
concern of pressing importance in our country today. It has 
been scientifically established in adults that violent behavior 
is correlated with low levels of a brain chemical called 
serotonin. Serotonin can be indirectly measured by blood tests 
after the administration of a drug called fenfluramine, a test 
for serotonin much like a glucose tolerance test, is a test for 
diabetes, and a cardiac stress test is a test for heart 
irregularities.
    For many years prior to the study at NYPI, fenfluramine 
studies were a well-established mechanism for measuring 
serotonin. Researchers outside of NYPI had described 
experiences with more than 2000 research subjects, including 
over 200 children and adolescents who had participated in 
fenfluramine studies. Even after concerns about the long term, 
large dose safety of the drug led to its withdrawal from 
approved use for obesity, which did not occur until almost 2 
years after the NYPI study was concluded, the FDA still allowed 
it to be used in small, single dose research studies, since 
this had always been judged to be entirely safe and indeed, the 
FDA continues to permit this use today.
    The study at NYPI involved the administration of 
fenfluramine to younger brothers of already adjudicated 
delinquents. It has been scientifically well-established that 
these younger brothers are at high risk to develop behavioral 
problems. In fact, the majority of the boys in the study were 
described by their teachers and/or family as showing evidence 
of significant behavioral problems. The process for selecting 
participants in the overall study was approved by the IRB and 
did not exclude anyone on the basis of race. The investigators 
recognized that the study they proposed ultimately needed to be 
broad-based with a geographically and ethnically diverse 
sample, but as is generally the case in an initial phase of the 
investigation, funding and methodological issues dictated 
beginning with a smaller sample drawn from the surrounding 
community.
    For this reason, investigators obtained information on 
eligible families from records of the family courts of 
Manhattan and Bronx. The IRB specifically required that there 
be no ethnic or racial exclusions as a condition for approving 
the protocol. The consent process occurred over several visits 
and children participated only if both parents and children 
agreed to the procedures at all times. Families were 
specifically told that participation would not influence any 
court or correctional decisions. At the time of the selection, 
all of the older siblings had already been adjudicated.
    In the fenfluramine study, a small dose of fenfluramine was 
given in the form of a single, oral tablet, an amount that has 
always been judged safe. Although the IRB determined that the 
study provided no direct benefit to the individual 
participants, it was anticipated that the children would 
receive a number of indirect benefits, and they did. The 
children received expert neuropsychological, general medical 
and mental health evaluations. Findings from these evaluations 
led to referrals for visual, dental, pediatric and mental 
health care, and in the case of children with educational 
problems, were used to expedite appropriate educational 
assistance.
    The study helped provide a foundation for a new approach to 
help parents raise children who are at risk for behavioral 
problems. Studies to examine the utility of these interventions 
are now underway with Federal support, including a recent grant 
from the Department of Education. This is the goal of research, 
to lead to the development of effective services and 
treatments.
    Again, we appreciate the opportunity to testify at this 
hearing. We would be happy to respond to your inquiries.
    [The prepared statement of Dr. Oldham follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.033
    
    [GRAPHIC] [TIFF OMITTED] T6523.034
    
    [GRAPHIC] [TIFF OMITTED] T6523.035
    
    [GRAPHIC] [TIFF OMITTED] T6523.036
    
    [GRAPHIC] [TIFF OMITTED] T6523.037
    
    [GRAPHIC] [TIFF OMITTED] T6523.038
    
    [GRAPHIC] [TIFF OMITTED] T6523.039
    
    [GRAPHIC] [TIFF OMITTED] T6523.040
    
    [GRAPHIC] [TIFF OMITTED] T6523.041
    
    [GRAPHIC] [TIFF OMITTED] T6523.042
    
    [GRAPHIC] [TIFF OMITTED] T6523.043
    
    [GRAPHIC] [TIFF OMITTED] T6523.044
    
    [GRAPHIC] [TIFF OMITTED] T6523.045
    
    [GRAPHIC] [TIFF OMITTED] T6523.046
    
    [GRAPHIC] [TIFF OMITTED] T6523.047
    
    [GRAPHIC] [TIFF OMITTED] T6523.048
    
    [GRAPHIC] [TIFF OMITTED] T6523.049
    
    Mr. Mica. Thank you, and I thank each of our witnesses and 
our first panel, and what I'd like to do now is begin a series 
of questions and I'll yield to ranking member this morning, Mr. 
Towns.
    Obviously, there's an incredible explosion of research, 
probably beyond anything we could have imagined even a decade 
ago. And it's important that we move that research forward and 
human beings benefit by that process. As we heard from our 
witnesses, we have a system to deal with this in regulations to 
protect people that were developed some two and a half decades 
ago. There's a system somewhat convoluted in its structure, and 
antiquated, but progressing with the rapid advances we're 
making today and the sheer scope of research that's being 
conducted. The purpose of this hearing is to try to sort 
through the maze and there are many, many questions and aspects 
for all of us.
    I'd like to start today by asking the Inspector General, I 
read through all the testimony of the past hearing, and there 
was another hearing before this. You came today and said the 
system is badly in need of reform. There are many aspects of 
that reform. Let me deal first with structural aspects.
    The Secretary has moved OPRR from NIH to the Secretary's 
office. Is that sufficient structural change to deal, again, 
with the administration, the oversight, and the management of 
this whole order, or do we need other structural changes that 
have not been put in place? Let's deal with the structure 
first.
    Mr. Yessian. Mr. Chairman, we haven't focused on 
organizational structure. If the human subject protection 
function gains some independence and visibility that would seem 
to be desireable. But our position has been that that isn't an 
issue for us to address in any detail, and that there are basic 
issues that go much beyond structure.
    The basic reforms remain to be carried out. They have to do 
with the nature of oversight, the kind of educational mandates, 
if and how we change any of the regulations, what happens at 
the IRB level. There's still a full agenda there.
    Mr. Mica. The second question would be if you have 
identified any legislative changes that may be necessary to 
deal with the overall structure, and do you have any 
recommendations dealing with legislation that may be required 
either for structural changes or processes?
    Mr. Yessian. I think a number of our recommendations could 
be enhanced by legislative changes. It's possible in some cases 
they could be done administratively as well. But on call for a 
mandate that there be a registration of all IRBs would probably 
take legislation.
    Mr. Mica. That cannot be done by rule?
    Mr. Yessian. I defer to Dr. Ellis on that.
    Mr. Mica. Dr. Ellis, can that be done by rule?
    Mr. Ellis. The current regulations and statutes I think 
would permit registration of a large portion of the 
institutional review boards in the United States, but there are 
some that just simply fall outside of our current statutes.
    Mr. Mica. So you would need additional statutory authority 
to bring everyone into the fold, is that what you're saying?
    Mr. Ellis. For instance, currently OPRR has the name and 
address of every institutional review board within our 
authority. This registration not a problem for OPRR, I think 
it's an opening question for FDA, but even a combination of 
OPRR and FDA and their overlapping jurisdictions wouldn't reach 
a completely private institutional review board that doesn't 
engage in FDA regulated research, for example. Couldn't get 
every last one from where we stand right now.
    Mr. Mica. Back, if I may, to the Inspector General.
    The first hearing contained a substantial number of 
recommendations. Now, first of all, the Inspector General, your 
report had offered a number of recommendations. What percentage 
of your recommendations have been instituted; 10 percent; 8 
percent; 5 percent performed?
    Mr. Yessian. Probably 5 to 10 percent. The most significant 
response is the enhanced enforcement effort from the Office of 
Protection from Research Risks.
    Mr. Mica. And you did cite whether there were some 
instances of changes in procedures?
    Mr. Yessian. But much remains to be done. A few highly 
visible enforcement efforts, by the way, have a lot of 
reverberations. Some have said, some of those efforts are like 
the nuclear bomb of enforcement. Many have sort of said there 
but for the grace of God go I, after they went into Duke 
University, so there has been some positive reverberations 
there.
    Mr. Mica. But you're saying 5 to 10 percent actually----
    Mr. Yessian. I would say so.
    Mr. Mica. Dr. Lawrence, the Inspector General has made 
recommendations at this last hearing, the hearing that was 
conducted June 11, 1998, from some pretty substantial 
organizations; the Center For Biomedical Ethics offered 
recommendations. The American Association for Medical Ethics 
and the American Psychiatric Association offered 
recommendations. I read through some of these recommendations. 
Some of them are very similar to what the Inspector General has 
offered.
    These were recommended almost a year and a half ago. The 
National Bioethics Advisory Commission report was a year old. 
Why has there been such a delay in implementing the 
recommendations by the Department?
    Dr. Lawrence. Mr. Mica, I have no way of calculating 
percentages on this, I'll start by saying that.
    Mr. Mica. We can go over each of these one at a time. It 
appears that one or two minor changes or recommendations were 
instituted by the Department. Our responsibility in an 
oversight capacity is to find out, what's the holdup?
    Dr. Lawrence. Let me say this: The OPRR did move to 
increase its enforcement activities, and I think that the IG 
has underscored that. In response to the NBAC report that 
referred to human subjects with impaired capacities, while 
there is not a regulatory change, there are a set of NIH-issued 
guidelines that address many of the particular areas that the 
impact report pointed up.
    Third thing is that OPRR moved very, very aggressively in 
its educational forum to put more and more information on to 
the Internet so that those individuals who needed it most could 
be able to refer to, had it available, and also that patients 
had it available to take a look at to see what it is that they 
should be expecting.
    Now, let me add something about the structural change, for 
a moment, if I may. The structural change from NIH to OS, I 
think is very significant. Will the structural change itself 
make a difference? No. It's what the Secretary and what Dr. 
Satcher wishes to do with it. The structural change moves OPRR 
into a position where it will focus solely on human subjects 
protections. The office in OS will also have an increased 
capacity to have sway over the agencies within the Public 
Health Service that do fund services, making it much easier to 
communicate and it also makes it easier to communicate on a 
chief officer, as in Secretary to Secretary level with the 
other signatories to the common rule. So I think there are 
things that are currently moving.
    Now, let me give you a prognostication. OPRR is working 
assiduously on looking at the streamlining of assurances. We're 
almost there, I can't say that we are there. I would say that 
probably within the next 120 days OPRR will be in a position to 
directly respond by the simplification of the process without 
compromising patient safety.
    Mr. Mica. Let me ask you, Dr. Lawrence; I guess 
structurally and from an oversight standpoint, IRBs that 
receive Federal funds or projects that receive Federal funds 
that have IRBs, OK. It would be a given that we would want to 
make certain proper procedures and reforms are in place with 
that group, is that correct?
    Dr. Lawrence. Yes, sir.
    Mr. Mica. OK. Now, your colleague, Dr. Ellis, has said that 
there's a larger universe out there, and there are many 
research activities that don't receive Federal funds. Is it the 
Department's position that all of these should be covered?
    Dr. Lawrence. We believe very strongly that all 
participants in human subjects research should be afforded the 
maximal protections possible. We urge those groups that are not 
part of our funding, of course, to adopt our own approach to 
things. Where there is an MPA, a multiple project assurance, 
the institution signing that MPA actually pledges its entire 
research portfolio, as I recall----
    Mr. Ellis. Essentially, 98 percent----
    Mr. Mica. Dr. Ellis.
    Mr. Ellis. Thank you. Essentially 98 percent of the major 
biomedical research institutions that have a multiple project 
assurance, that's an umbrella agreement with our office, 
voluntarily pledged all their activities irrespective of 
funding to our rules. So that's one way we've been able by 
jawboning, I guess, to extend the coverage as far as we 
possibly can.
    Mr. Mica. Dr. Lawrence, so it is the intent of the 
Department to include all of those participating in human 
research projects, experimental projects, to come under an 
umbrella?
    Dr. Lawrence. We are currently operating a work group that 
takes a look at both FDA and OPRR human subjects protections 
activities to see where the overlaps are, where the gaps are.
    Mr. Mica. Now, Dr. Ellis testified that he did not believe 
that you had statutory authority to really include this other 
group that does not receive Federal funds and regulate them, 
and it would require, I don't want to take anything out of 
context, but it might require legislative change.
    Dr. Lawrence. Yes, sir.
    Mr. Mica. Is the Department preparing anything for Congress 
for legislative change or to expand that authority?
    Dr. Lawrence. The President has asked the National 
Bioethics Advisory Committee to take a very, very broad based 
look at this.
    Mr. Mica. Now, we've heard Dr. Cassell say that well, 
they've produced this document, but he said that in the 
research area, I believe he said it was going to be 6 more 
months before they complete their study and recommendations. 
Dr. Cassell, is that correct?
    Dr. Cassell. Yes. That's the goal. The goal is that 
comprehensive recommendations about the protection of human 
subjects, and it will be probably 6 or more months before those 
are finished. However, what is presently in the report that you 
have in your hands, if those recommendations were implemented, 
we would have already gone a large step forward.
    Mr. Mica. Now, how many of the recommendations contained in 
this December 1998 report have been instituted?
    Dr. Cassell. I think zero is probably an accurate number.
    Mr. Mica. So we're 5 to 10 percent with the IG and we're 
zero in this, and you're telling the subcommittee this morning 
that because there has not been action on your report, that 
has, in fact, delayed the next step in your process, is that 
correct?
    Dr. Cassell. Oh, yes, and I agree with the Inspector 
General, what they recommended would move the whole process 
forward. There's considerable inertia in making things happen.
    Mr. Mica. So let's go back to the Department. How does the 
Department respond to not taking action on 90 to 95 percent of 
IG's recommendations, and zero percent of these 
recommendations, and delaying the process to where we do not 
have any of these protocols, procedures, regulatory assurances 
in place? Dr. Lawrence.
    Dr. Lawrence. As I said, Mr. Mica, subject to that report, 
OPRR did take a very, very careful look, especially at the 
impaired participants section and they did take action. The 
second thing is that I think that we are in a position where 
structurally, and inside the Department, we want to be as 
careful as we can. We have to keep in mind when we take these 
steps, that there is also a potential for doing things wrong. 
We prefer to take very thoughtful, deliberative steps.
    I do take exception to the characterization that so little 
was done by the Department. I have outlined for the committee 
those things that were done as the result of the IG's report. 
Is it 100 percent? No, sir.
    I also think that the substantive steps that NIH took to 
produce guidance, specific guidance in response to NBAC to 
protect those individuals who are impaired were substantial. 
Have we done 100 percent? No, sir, and that's why the secretary 
has decided to move forward and to reorganize OPRR into OS, to 
give it a higher level of visibility, to give it a higher level 
of flexibility and also to start working on the actual 
activities to protect human subjects.
    Mr. Mica. My next area of concern would be individuals who 
are in a situation where they're not able to really make a 
decision, whether they be mentally ill, retarded, or children, 
and you're telling me that some changes in procedures have been 
made, then today's paper cites the case of this young man, who 
just turned 18, Jessie Gelsinger, and I guess your Department 
has said he should have been eligible for this, and then found 
out that the informed consent form that investigators gave 
patients deviated from the one the agency had approved.
    So I have concerns that while some of these procedures to 
protect children, to protect others who may not be able to make 
informed decisions, you're saying changes have been made and 
today's newspaper cites, maybe it's just one case but it 
appears that some of the protections, in any event, and changes 
have not been instituted.
    How would you respond?
    Dr. Lawrence. As to your reading the article, Mr. Mica, as 
it turns out, I was kind of ticking off some things here in 
taking notes. First off, let me say that the death of anyone or 
the injury of anyone is truly a regrettable event. And that's 
what we're all trying to protect.
    Now, in this case, I think if we reread the article again, 
what we would find is that had that investigator followed the 
existing requirements, that there would have been informed 
consent. So it seems to me that if this article was true, and I 
have no specific knowledge, that if there is an issue here, 
OPRR's regulations and guidance cover all of these areas. 
That's my answer, sir.
    Mr. Mica. Well, what concerned me when I read this report 
is one of the matters in which some of these IRBs proceed in 
and I can't find the passage, I thought I had it marked here. 
It said the way the IRB proceeded was if the patient, if some 
of the patients hadn't died, then they would proceed, and that, 
they tried it on a few, and if some didn't die, that would be 
the criteria for proceeding.
    I was a little bit concerned that some of the 
recommendations that had been made by almost every group 
relating to educational assistance of the IRB people who served 
has not been put into place. I was concerned a little bit about 
the representation on the Board, nothing in that area has been 
put into place that I know of, a requirement there. What also 
concerns me are the reports that some people who serve on these 
Boards, and they may be federally funded, may be receiving 
payments or some type of funds from pharmaceutical companies 
that have an interest in that particular research or the 
product that's being applicated by them. Where are we with 
those matters?
    Dr. Lawrence. I will answer part of that and ask Dr. Ellis 
to address part of the question about financial disclosures.
    Let me say a couple of things about education. Education is 
very important. NBAC has said it, everyone has said it. As we 
move forward in the restructuring of OPRR, we are going to be 
looking very carefully at how the current resources are being 
distributed. I think the strategy, Mr. Mica, that we're going 
to be using as we move forward with advancing OPRR and its 
ability to protect human subjects, to use the current phrase, 
is to pick the low hanging fruit. There are some things that we 
can do right now, there are things that we can do very, very 
quickly, not the least of which is to have an oversight and 
advisory board that is totally independent, where we can ask 
this kind of question, where we can go to this board and say 
what are the priorities.
    I think one of the important things in seeking to improve 
human subjects protections is we have to keep asking questions, 
because the target, quite frankly, sir, keeps moving.
    So I think that many of the recommendations that are in 
each of these reports, if not having been addressed in 
specifics, they're going to be addressed through the process of 
conversation with that advisory committee.
    Mr. Mica. Let me ask you this: Some of these things----
    Dr. Lawrence. Would you like to have----
    Mr. Mica. We'll get to Dr. Ellis on the disclosure and 
conflict of interest.
    Dr. Lawrence. Sure.
    Mr. Mica. But I come from a pretty conservative side of the 
spectrum. I don't like additional government regulations and 
red tape and bureaucracies. Has the Secretary or OPRR or any of 
these agencies sent out an advisory memo to--Dr. Ellis, didn't 
you tell me we could identify the IRBs that are getting Federal 
money?
    Mr. Ellis. That's correct.
    Mr. Mica. We can identify them. Have we sent out a simple 
advisory statement or recommended procedure asking them to 
address peer education, broader representation disclosure, or 
conflict of interest? Has any of the overseeing agencies 
involved sent out anything on this since the last hearing?
    Mr. Ellis. Well, the answer is emphatically yes.
    Mr. Mica. Can you produce copies of those for the record 
and the subcommittee, please?
    Mr. Ellis. Certainly.
    Mr. Mica. OK. In all of the areas or some of the areas?
    Mr. Ellis. Probably the single best integrated advice went 
to the 240,000 subscribers of the Journal of the American 
Medical Association November 24, 1999 where I wrote an 
editorial titled ``Keeping Research Subjects Out of Harm's 
Way.'' The main point of that was education, education, and 
education. I'll be glad to supply that and others.
    Mr. Mica. Has the Department sent an advisory notice or 
specific guidelines or recommendation to the IRBs outlining 
maybe what was in your probably excellent editorial comment?
    Mr. Ellis. You're too kind. We have addressed institutions 
and their IRBs directly by first class mail through the years 
with a 1993 edition of an IRB guidebook.
    Mr. Mica. My question dealt with since the last hearing, 
can you produce for the committee your advisory notices in any 
or all of these areas?
    Mr. Ellis. Sure. Let me submit for the record everything 
we've produced since June 11, 1998. I'll be glad to do it.
    Mr. Mica. Great, that would be excellent.
    Now, Dr. Ellis, if you could tell us about our addressing 
the problem of disclosure and conflict of interest, then I'll 
go to Mr. Towns. I have more questions, Mr. Towns, but I'll----
    Mr. Towns. Go right ahead.
    Mr. Mica. Since we've gotten into this, I appreciate your 
patience. Go ahead, Dr. Ellis.
    Mr. Ellis. Mr. Chairman, this issue of the flow of money 
through human research is 1 of the 10 most frequently asked 
questions, 1 of the 10 most frequently discussed topics and 
there are two issues. One is payment to research subjects, but 
I think you're most interested now in payment to investigators, 
or a variant of that--conflicting financial interests of IRB 
members as they review research.
    The Department's human subject regulations get at this only 
peripherally. There's one very direct clause that says no 
voting IRB member may have a conflicting interest in the 
research put before that Board, and we see the widespread 
practice of recusal when a voting IRB member sees something 
that could be a conflict. A conflict many times is intellectual 
or academic, a collaborator's proposal, but it can be 
financial.
    Now, that's the strongest hold that the regulations have on 
this, and it is admittedly weak. The only other portion of the 
regulations that I can see that pertains to this is instruction 
that informed consent from a subject shall only be sought under 
circumstances that minimize the possibility of undue influence 
or coercion. My reading of that means that if the investigator 
is somehow reaping financial benefit, that the IRB has full 
entree to ask about all those circumstances, because the IRB 
has the absolute mandate to minimize the possibility of 
coercion or undue influence on the subject that the 
investigator is recruiting. Those are the two places I see it 
in the human subject regulations.
    This is something that's going to have to be addressed at 
the national level, and my guess is will eventuate in some 
additional detailed guidance, if not regulation, because it's a 
very important topic and a current topic.
    Mr. Mica. I see that the Inspector General wanted to 
respond. I would be interested--again, we want to insure that 
protections are there, particularly in this conflict area with 
IRB members. We don't want to dissuade people from serving and 
getting into all kinds of complicated disclosure mechanisms. 
That can be a deterrent to having people who are highly 
qualified participate. If you would.
    Mr. Yessian. Yes, Mr. Chairman. I wanted to comment on 
this, because since the last hearing, most of our work in this 
area has been on the issue of recruitment and industry 
sponsored trials and I have to say conflicts are just inherent 
in this process. They apply where there's a government grant as 
well as in industry trials, but it's important to emphasize how 
at the IRB level, at the ground up, how the environment is 
really turning into much more of a marketplace environment, and 
some major research institutions, one of the IRBs I just talked 
to, one of the best teaching centers in the United States has 
half of their proposals now come from industry sponsored 
research.
    This raises all kinds of questions and there's very little 
guidance that the IRBs have and they don't often know where to 
turn when it comes to OK, what's appropriate here, Dr. Ellis 
touched it. Are there circumstances in which informed consent 
is being provided, being tarnished in some way in is there 
coercion here, maybe unintentional. Is it really voluntary? Is 
confidentiality being broached if somebody is being called 
about participating in a project because of, without their, 
without their knowledge that their records are being accessed?
    These issues are really stirring up at the IRB and 
institutional level, and it's for this kind of reason in a way, 
notwithstanding the fact that some progress has been made, at 
the Federal level in addressing some of these issues, at the 
ground level in a way, the problems are extenuating even faster 
than our progress is, because it's not static there, it's a 
rapidly changing marketplace.
    Mr. Mica. Thank you, I'll probably go a second round. Mr. 
Towns, you're recognized.
    Mr. Towns. Thank you very much, Mr. Chairman. I want to 
point out this is a very important area to discuss, because 
we're talking about protecting people and I think based on that 
would be the New York Times article today, and of course the 
Washington Post yesterday, you know, we have some very serious 
problems.
    Let me begin by saying first, Dr. Lawrence, when will the 
move of the OPRR be complete?
    Dr. Lawrence. We are targeting March 2000.
    Mr. Towns. And how will this move improve the protection of 
human beings who are subject to biomedical research?
    Dr. Lawrence. Well, first off, Mr. Towns, I think it's 
important to have an office that focuses solely on human 
subjects. This is not to say that animal welfare protection is 
not important, they are, but to have a staff that focuses very, 
very specifically on the issue, I think is of great value.
    The second thing is having the cachet of having the office 
located in the Office of the Secretary, and the ability of the 
secretary to speak out on these issues, supported by her own 
staff, which is very, very important.
    The third thing is that I believe we will find 
communications inside the Department and intra departmentally 
improve significantly with the office on that level. How this 
translates exactly to human subjects protections, I cannot give 
you a number or a value. However, I do believe that it is a 
major step forward in what needs to be a sequence of events, 
including the appointment of the advisory committee that will 
then be able to identify the very, very specific solid steps 
that need to be taken to move forward.
    Mr. Towns. Have you consulted the Office of Personnel 
Management about the necessity to change Director of OPRR or to 
the position with the Senior Executive Service?
    Dr. Lawrence. Our administrative division, which is 
Assistant Secretary for Management and Budget now has all that 
paperwork and they are responsible for the interface with other 
agencies. I have no specific knowledge of exactly where it sits 
at the moment, sir.
    Mr. Towns. Right. So actually I can assume from that 
statement, no. That was a no, wasn't it?
    Dr. Lawrence. I have no knowledge of exactly where it is, 
so I can't say yes or no.
    Mr. Towns. So, then, I think we could say no. Maybe you 
don't have yes or no, I think we could be on the safe side and 
say no, OK? I don't want to--I think we can do that, no.
    Dr. Lawrence. Yes.
    Mr. Towns. I think when we move forward we don't forget 
about the fact that the Inspector General noted that last year 
OPRR has moved, improved and of course had been much more 
aggressive in conducting site visits and elevating the 
importance of protecting human subjects. I think that's 
important. So while I support the plan to move the office over 
to NIH, and some people, you know, feel that based on the fact 
that some folks have been very aggressive in doing things, they 
will not be rewarded, but they will be penalized, and I'm 
hoping that we don't see that in this particular instance. I'm 
talking about Dr. Ellis, who has done research in terms of, and 
written in terms of articles about harm's way, so I just want 
to pass that along, because there's rumors floating everywhere, 
which has nothing to do with anything, I'm sure, but I just 
sort of wanted to make that comment on the chance we had to 
have this exchange.
    Dr. Lawrence. Thank you, sir.
    Mr. Towns. Let me move forward. First of all, I want to ask 
the general question to any of you, how many IRBs do we have 
out there? Anybody know? How many IRBs are there?
    Mr. Shamoo. Around 5,000.
    Mr. Towns. I wish I could accept your answer, I wish it was 
true and all that, but anybody at the table here, if you could 
tell me how many we have. Yes, Dr. Ellis.
    Mr. Ellis. We have estimated there's some 3,500 to 5,000 
IRBs in the United States. It's not really possible to give a 
more precise estimate.
    Mr. Towns. 3,500 to 5,000. Anyone else want to give me a 
number? Or you don't know? That's my problem. Even the person 
that knows is saying 3,500 to 5,000, there's 1,500 in there 
we're not certain about, and I think that's the real issue here 
today. I think that we need to some way or another come up with 
a way to know what's out there. I think that's the first thing, 
so--let me just move to one of the things that sort of keeps me 
involved in this in a very serious way. I want to let you know 
that I'm not going to go away on this one, I'm going to stick 
with it. I'm going to be here, you need to know this, I make it 
clear, it's not somebody who will come in, say something and 
then move on.
    Let me begin by asking you, Dr. Cassell, the fenfluramine 
study was that a central, valid piece of research based on your 
many years of professional work?
    Dr. Cassell. Well, I tell you, it's not for me to decide 
that. It's not within my competence, but I'll tell you what is 
important, that we heard testimony about that research in July 
1997. It is research like that, whether valid or not, that 
raised issues of the protection of human subjects, and my own 
belief is, if we were talking 5 years from now, it would have 
more difficulty getting passed an IRB than it had now. I don't 
question for a moment the expertise of the people that did that 
research, it's their line of work, they're good people. I don't 
question the validity of the hypotheses that went into it, 
that's their work, and I believe they're correct, that isn't 
really the issue.
    There are a lot of good studies that people would like to 
do that will move science forward and so forth, but that's not 
the only value present. Progress isn't the only value. The 
protection of human subjects, the care of people who cannot 
take care or protect themselves, ranks as high or higher than 
scientific progress and that's really what we're talking about.
    Mr. Towns. Thank you very much. I couldn't agree with you 
more.
    Let me just go to you, Dr. Walsh. In your testimony, it was 
June 1998, before the committee, subcommittee, you said that 
all of the participants in the New York Psychiatric Institute 
fenfluramine research involving children were not members of 
minority groups.
    Dr. Walsh. If that's in the testimony, sir, that's an 
error. All of the members of the fenfluramine challenge study 
were members of minority groups.
    Mr. Towns. It's in the record. In fact, I want to be honest 
with you, I read it four times.
    Dr. Walsh. It is then my error, for which I apologize, if I 
failed to correct the record. Certainly there was no attempt to 
say that, in the fenfluramine study, the children were not 
African American.
    Mr. Towns. Let me give it to you, to correct the record, I 
think we should. What was the breakdown?
    Dr. Walsh. I'd have to look at the paper, sir. If you want 
accurate information, I'll have to look through my papers.
    Mr. Towns. Also in Dr. Oldham's testimony, he said that 
race was not an issue here. You mean to say by happenstance or 
coincidence, it just happened that everybody was minority?
    Dr. Walsh. Yes, sir.
    Mr. Towns. That's a strange coincidence.
    Dr. Walsh. Let me explain. Here's how the recruitment 
occurred. These investigators were interested in finding out 
ways to help families, help parents raise their kids in a 
difficult environment. They focused on the development of 
antisocial behavior and proposed in their research to identify 
families who were involved in the family court systems of 
Manhattan and the Bronx, because they were in close 
geographical proximity to where our institution is. They were 
proposing to do was to conduct home visits and follow these 
families for 4 years.
    It turns out that the overwhelming majority of families in 
these court systems are African American and Hispanic. In the 
study that was conducted, the overall study, I think the 
proportion of Caucasians are 2 or 3 percent, there are a few, 
but it's a very small number. But my understanding from the 
investigators is this is not different from the makeup of the 
Manhattan and Bronx family court systems.
    Mr. Towns. Dr. Walsh, you're a dancer. I want you to know 
I'm not your partner, either. You're a dancer. You mean to say 
you could not find one white kid?
    Dr. Walsh. No, sir, there were two or three Caucasians in 
the overall sample of 126 children.
    Mr. Towns. But they ended up being blacks and Hispanics.
    Dr. Walsh. Let's be careful to be clear. There was a broad 
study to look at factors that were related to the development 
of antisocial behavior among youth. It's well-established 
scientifically that one of the risk factors, one of the ways to 
identify kids at risk is to find kids with an older brother who 
has had some trouble, and that's the procedure that the 
researchers proposed. They chose to get them, as was described, 
from the Bronx and Manhattan court systems.
    People were recruited, families were recruited from that 
court system without regard for race or ethnicity. The 
investigators initially proposed to have an ethnic exclusion. 
The IRB did not permit it. We absolutely told them you cannot 
have ethnic exclusions in this research. Nonetheless, their 
final sample composition of 126 kids involved 3 Caucasians, and 
I am told, that that is a reasonable statistical reflection of 
the makeup of the families in the Bronx and Manhattan court 
systems.
    Mr. Towns. Dr. Walsh, really, we've been down this road 
before, and of course, and I don't want you to have to correct 
the record again when we talk. I want you to know that this is 
a little different from what was said the last time, which 
would be how you arrived at getting them. So I don't know how 
you change, I mean, you're going to have to correct the record 
again evidently. Yes, Dr. Oldham.
    Dr. Oldham. Congressman, let me clarify one thing I do not 
think is clear. Dr. Walsh described this as an initial overall 
sample of about 125 young boys. Of that 125, which did include 
a few nonminorities, there was a substudy of about 36. Those 36 
boys were the 36 boys that participated in the fenfluramine 
study. Those 36 were entirely African American or Hispanic.
    That was a completely random result of the volunteers who 
participated in the substudy, in other words, those 36 who 
agreed to participate in the substudy by coincidence did not 
include the very few who were in the entire sample, but when a 
statement is made that the sample did not exclude any subjects 
on the basis of race or ethnicity, that is correct.
    Mr. Towns. Let me put it this way: Why don't we include 
Staten Island or Queens?
    Dr. Oldham. This is actually the first----
    Mr. Towns. It's part of the city, I figured you would look 
at the city.
    Dr. Oldham. I think Dr. Walsh addressed part of that. We 
had a multi-phase design. This was step one of a multi- phase 
study and the second phase of the study was to move to other 
regions which would include other parts of the surrounding 
area, that would have included some other boroughs of New York 
as well as some other counties outside of New York City, which 
would have been a very different ethnic and racial 
distribution. This was actually submitted and approved by NIH 
as a followup study.
    So we began actually where we had contacts already with the 
court systems that were adjacent to our exact location, which 
were the court systems of Manhattan and the Bronx, as a pilot 
to start the study. We didn't know until we received the 
information from those courts what the specific racial profiles 
would be of these groups.
    Mr. Towns. I just want to ask you, before we move on, 
that's a strange coincidence that you had nobody, just black or 
Hispanic. That's a strange coincidence. Let me move on. I don't 
want to belabor that.
    In your testimony, you note that the children involved in 
the study had behavior problems, yet you do not state that 
these so-called behavior problems were the result of mental 
disorders. Was there ever a finding that all the children in 
this study had a specific mental disorder?
    Dr. Oldham. Let me ask Dr. Walsh to comment on that. There 
were a number of types of problems that were identified.
    Dr. Walsh. The majority of the children had symptoms of or 
met diagnostic criteria for mental disorders. At 1 year, in the 
overall sample, the number was I think about two-thirds. In the 
fenfluramine study to which you may be referring, it was about 
the same proportion, between two-thirds and three quarters of 
the subjects had behavioral problems, diagnosable behavioral 
problems.
    Mr. Towns. Let me ask you about the study itself, 
fenfluramine. Some of these children were under 12.
    Dr. Walsh. Yes, sir.
    Mr. Towns. I think all of them were all under 12. Now, even 
in the research, the pharmaceutical company didn't have anybody 
under 12 involved in the research of the trials initially.
    Now, they didn't have anybody, then you bring the 
youngsters in, and you use a drug on them that was not even 
tested in the trials with someone under 12. I mean, didn't that 
bother you?
    Dr. Walsh. It's actually a common problem in pediatrics. 
Many drugs that are widely used for children, have not been 
specifically tested and approved by the FDA for use in 
children. I think that's recently been addressed or there's a 
change in the FDA approval procedure, but----
    Mr. Towns. Let me interrupt you here. That's a drug that's 
going to benefit the kid, but in this situation it does not 
benefit them in any way.
    Dr. Walsh. Yes, sir.
    Mr. Towns. That's a difference.
    Dr. Walsh. There was substantial data at the time in the 
literature about the use of fenfluramine in these very types of 
challenge tests in both children and adults prior to the 
initiation of the study at the Psychiatric Institute. There 
were thousands of adults and hundreds of children who prior to 
our approving this study, had participated in this kind of 
study without any significant risk or harm. And we determined 
that. We accessed that information, consulted with colleagues 
to try to determine that before the study was approved.
    Mr. Towns. Even though they were not involved in the 
research initially, you still felt that somebody else had done 
it, now you can do it. I mean, is that your rationale?
    Dr. Walsh. No----
    Mr. Towns. I just want the record to reflect.
    Dr. Walsh. I think this reflects what the job of the IRB 
is. An investigator has a proposal, a proposal that certainly 
involves unknowns. Questions that have not been answered to 
which there are no firm answers available. It's the job of the 
IRB to use its best judgment to evaluate what the risks of 
those procedures are.
    I still believe we did a very conscientious job of doing 
so. We consulted with other people who did this kind of work, 
we looked at the literature, and we concluded, and it's a 
conclusion which I believe has not been seriously challenged: 
Fenfluramine used in the way it was used in this study, even in 
youngsters, poses no significant harm.
    Mr. Towns. Let me just say, I'm trying to move on. You 
stated in your testimony, Dr. Oldham, these children were at 
risk because they had a sibling who was in trouble with the 
law. Should everyone who has a sibling that's in trouble with 
the law be a candidate for biomedical research? If not, then 
what made these children candidates?
    Dr. Oldham. Well, certainly that would be too broad a 
generalization to make, but there is a very good body of 
scientific evidence that younger brothers, not any children, 
not any siblings, but younger brothers of males who have been 
already identified as delinquents with antisocial behavior that 
is clear enough so that there has actually been an adjudication 
and a guilty finding and a decision by the court system, that 
children of these families, if there are younger brothers, are 
at increased risk to develop this kind of behavior, we feel 
this is an important, enormously critical problem, that needs 
to be studied. We do not at all feel that this is something 
that should be done without careful, careful thought, and 
studies like this need to be very, very seriously considered, 
both because of their importance, but because one has to guard 
against inappropriate research with inappropriate individuals.
    However, if we feel that these younger brothers were in a 
category of high risk to develop similar problems and be on a 
course that would lead them to a very disturbed and difficult 
life course, if we could identify a way to intervene and to 
prevent some of this unfortunate outcome, we feel that this is 
very important.
    I mentioned in my testimony the fact that there had been 
federally funded studies based on the methodology and the 
initial preliminary findings of these studies that are 
underway, funded both by NIH and by the Department of Education 
to try to involve prevention and avoidance of this unfortunate 
path by the youngsters.
    Mr. Towns. Did you develop any treatment strategies?
    Dr. Oldham. There were intervention and prevention 
strategies, that's what it would be at this point for these 
individuals, and they were referred for treatment in every case 
where there was a willingness on the part of the family to 
accept treatment and treatment was indicated because of 
diagnosed conditions that needed treatment.
    Mr. Towns. Let me say that, you know, I'm trying to move 
on, but you know, I'm not sure that some of this is not 
society, poverty and all these kinds of things rather than 
being biological. I sort of raise that issue with you as well. 
Yes, Dr. Walsh?
    Dr. Walsh. I agree with you, sir, very much, and that in 
fact was the point of the research. I want to underline, I 
appreciate your concern, sir, and I am very interested in your 
opinions and concerns about how we can better help people in 
our community. And I think we're an institution well known to 
be located in a minority community and I think we have an 
obligation to try to help the people who come to our hospital 
and live around us.
    The problem is we have a lot of ignorance about what to do 
that would be helpful. A lot of the causes of some of the 
problems are social, environmental, economic, there's no doubt. 
But we're doctors and we try to find out ways that the medical 
and psychological professions can help these people, and the 
only way that we can help break through the ignorance is 
through research. So we have to do research with these people--
not on them, not to them, but with them, so we can get a better 
idea of what we might be able to do to help them, so that we 
can help them. And, sir, I strongly believe that that is what 
this study did.
    The broad study identified things that parents were doing 
with their children that helped children avoid problems. And 
yes, it explicitly led to treatment studies that are now 
ongoing in the same community, in northern Manhattan, with, 
what I understand to be, the strong support of the local 
community, to help families living under difficult 
circumstances, help raise their kids the way we all want our 
kids to grow up.
    So, sir, I understand your concerns. I deeply respect them, 
but I feel that we must continue to work with the community in 
which we live so we can help the people who come to us. I think 
it is our moral obligation.
    Mr. Towns. Let me just go back to the IRBs. How should we 
structure them? Because we're hearing all kinds of things about 
conflicts, we've heard even corruption, lack of training, lack 
of qualifications, and I think that these are the things that 
we have to be concerned about, and the other part, you know, 
I'm not hearing any kind of real sanctions, that if anybody is 
guilty of all of this or any of it, what happens? Are there any 
sanctions of any sort that would sort of discourage someone 
from being involved in a negative kind of way?
    I think, Dr. Ellis, let's start with you and then come 
around the room and let everybody comment on it.
    Mr. Ellis. Congressman Towns, the ultimate sanctions, I'm 
saying the extreme, under our Department human subject rules is 
denial to an institution of further research funds for human 
subject research.
    Mr. Towns. I'm sorry, repeat it?
    Mr. Ellis. The ultimate sanction under our Department human 
subject protection rules is denial of the opportunity for 
further research funds from this point forward, let's say, to 
do human subject research.
    Mr. Towns. Right, but if some of the things I'm hearing, 
you know, the point of that is if I'm hearing some of them 
might even have arrangements with the pharmaceutical companies, 
so all they need is one shot, and then after that, they can 
move on, so the point is that's my concern. For instance, all 
of a sudden you find out that there's conflict or corruption, 
whatever else, collusion, whatever you want to refer to it as, 
and then you say, well, from this point on, we're not going to 
deal with you, but the point is if a person has arrangements 
with a pharmaceutical company, then they're prepared to move 
on. So I think it has to be really thought out in a major kind 
of way where something happens that will further discourage 
people from being involved in that kind of way.
    Anybody have further comments on that? I think this is a 
real issue here. We have all these IRBs out there, and of 
course nobody seems to know the number, what they're doing and 
how they're doing. Dr. Cassell.
    Dr. Cassell. I think the points you raise are important, 
but the future for IRBs will not be improved simply by being 
able to slap, no matter how hard, the wrist of a misperforming 
one as it will be improved by adequate staff and adequate 
training and adequate connection to a larger structure of IRBs 
in the country. They labor under, really, inadequate resources. 
They were set up for something much easier than where they are 
now, but there wouldn't be adequate resources by just saying, 
there wouldn't be adequate resources, unless there is a 
legislative intent behind it, at least legislative intent 
behind it that provides enough people to run an IRB and enough 
money to do it properly and enough education so the people who 
are sitting on that IRB knows something, are not just good 
hearted or kind, and they know enough not to take money, we all 
know that there are bad people everywhere, that's hard to 
argue, but there are less bad people where a structure is set 
up that encourages goodness than where a structure isn't even 
in place.
    Mr. Towns. Any other comments on that? Yes.
    Mr. Yessian. Congressman Towns, I have one point, and Laura 
McBride has one. On your point of structure, we talked about 
OPRR's location in the Office of the Secretary, well there's a 
very concrete issue there you could apply with academic health 
centers where there are IRBs, and I would say there you should 
assure there's adequate independence of the IRB. You don't have 
that, it seems to me, where you have an IRB that's part of a 
grants office as is sometimes the case, with the very office 
that's responsible for bringing in grants and contracts, 
typically from the pharmaceutical industry is the office that 
would oversee the IRB, in some cases representatives of that 
office are on the IRB itself, so I would say that's a conflict 
that we ought to watch out for.
    Furthermore, investigators in these institutions are going 
to have industry money for their own projects. I don't think 
there's any getting around that or that there is anything wrong 
with that. But certainly, should recuse themselves for any 
project for any review that involves any project they're 
associated with, I think most probably do, but we should 
certainly make sure that happens.
    Did you want to add something?
    Ms. McBride. Along those same lines I'll reiterate a point 
we made before, the need for greater representation of 
independent members on the IRBs. As Dr. Lawrence said before, 
there could be 1 out of 20 or 50 IRB members, and independent 
voices can play a good role in balancing institutional voices, 
other members' conflicts, but also representing the interests 
and the perspectives of the community outside the institution.
    Mr. Yessian. We've seen places where independent members 
have played that role and have raised questions that have made 
a difference.
    Mr. Towns. Thank you very much. I yield, Mr. Chair.
    Mr. Mica. Thank you, Mr. Towns. Dr. Ellis, in the hearing 
June 11, 1998, I think you testified, we have to date eight 
separate complaints about a body of research in New York City 
under the auspices of four institutions, and at that time you 
said you had not concluded your investigation. Have all of 
those investigations been complete?
    Mr. Ellis. Yes, all four are complete.
    Mr. Mica. Could you provide us, for the record, with a 
summary of your resolution of those investigations?
    Mr. Ellis. Yes.
    Mr. Mica. Dr. Ellis, you testified also at that hearing the 
last time your office suspended an assurance for human subjects 
research, I believe it was in 1991. From the hearing last June, 
what's the status of suspended human research subjects?
    Mr. Ellis. Mr. Chairman, I'll just have to go back to the 
hearing record to see exactly which institution I would have 
been referring to. I can't tell from your reading.
    Mr. Mica. You said there was one suspension. Suspended an 
assurance for human subject research in 1991. Have there been 
any since the last?
    Mr. Ellis. Oh, I'm sorry, I misunderstood. Yes, OPRR 
suspended Rush Presbyterian St. Lukes Medical Center in October 
1998. OPRR restricted the West Los Angeles VA Medical Center's 
assurance in March 1999, which caused the Department of 
Veterans Affairs to simultaneously suspend all research, human, 
animal and otherwise at its West Los Angeles VA facility.
    Then in May 1999 OPRR suspended the assurance at Duke 
University Medical Center. I think that captures all the 
actions of the type you inquired on.
    Mr. Mica. The IRBs that received Federal funds, is there in 
place a Federal registration requirement?
    Mr. Ellis. Yes, for any institution that receives research 
funds for human research from the Department of Health and 
Human Services, OPRR follows the money assiduously and receives 
a formal written agreement, we call it an assurance, from the 
institution. One component of that formal written assurance is 
the IRB roster or rosters, so I can say unequivocally for human 
subject research that falls within OPRR's purview, that we have 
the name and address of every IRB member.
    Mr. Mica. But they're not required to register, it would be 
through that document, is that right?
    Mr. Ellis. That's right. For us it's a de facto 
registration.
    Mr. Mica. And those who do not receive Federal funding are 
not required to register?
    Mr. Ellis. I shouldn't speak for FDA, but I understand that 
FDA has several data bases that include names and addresses of 
IRBs, but no comprehensive system of registration.
    Mr. Mica. And the Inspector General had recommended that 
there be a registration, I believe, for all of these groups, is 
that correct?
    Mr. Ellis. That is a principal recommendation of the June 
1998 report.
    Mr. Mica. The other thing that concerns me is many of the 
recommendations that were presented by many of these groups 
could be instituted by at least for those who receive Federal 
funds to the IRBs, by an advisory memo from the Secretary or 
from the agency. Dr. Lawrence, do you think that might be 
possible?
    Dr. Lawrence. OPRR communicates with its IRBs and through 
the granting systems frequently, and we can go back----
    Mr. Mica. We're going to get a copy of all of those 
communications.
    Dr. Lawrence. We can go back and take a look at the 
recommendations and see how we can educate our IRBs about what 
those recommendations are, and see if there are other actions 
that we need to take. I don't have a list of each and every, 
so----
    Mr. Mica. Well, again, it seems like common sense. I come 
from the business sector, and it seems that some things can be 
done as advisory, and certainly these folks that are getting 
Federal money it can be made a condition of. I just can't 
understand why the Secretary or the agency cannot, at minimum, 
request some of these changes that have been recommended by the 
Inspector General, national medical college groups, American 
Psychiatric Association, by the President's Advisory 
Commission.
    Dr. Lawrence. I understand your question, and I appreciate 
it as well. I'll restate that some of these things already have 
happened, especially with the issuance of the guidance. 
However, we can go back, sir, and we can go through----
    Mr. Mica. I just throw that out as a suggestion. Then when 
we do the next hearings, which I'm sure Mr. Towns will be 
requesting----
    Mr. Towns. Right.
    Mr. Mica. You can't come in and say hey, we've done even 
this minute step in the right direction.
    A final question here. Dr. Cassell, some of the things that 
you recommended, they require the expenditure of some funds. 
Should it be a requirement in the case of Federal funds going 
for research that those who receive that money contribute out 
of those funds sufficient resources to make certain that the 
recommendations you have are in place?
    Dr. Cassell. Yes.
    Mr. Mica. Thank you. That's the best, most succinct answer 
we've had today.
    Well, there are many additional questions that I would like 
to ask, and we will, with the permission of our ranking 
memoranda submit them to you for submission to the panel. I'll 
yield at this time for any final questions to Mr. Towns.
    Mr. Towns. Thank you. I just have one final question. In 
this very vulnerable population that we're dealing with in some 
instances in research, the mentally ill and of course in some 
instances, I just sort of feel that maybe the structure should 
be different in research with that population. If the physician 
is involved in the research, it is my feeling that that 
physician is so involved that some of the other kinds of 
symptoms that they might not be watching them closely enough, 
so the structure should be in the case like that, that there 
should be a doctor that's not a part of the research really 
responsible for the medical well-being of his particular 
patient, because I think that they're very vulnerable, and 
you're so involved in research you just ignore everything else.
    So I think that the structure should be different when you 
have a vulnerable population. I just need some quick comments 
on that. Yes, sir, Dr. Cassell.
    Dr. Cassell. That is a specific recommendation that NBAC 
made as part of its report. A specific and wise recommendation 
that somebody besides the investigator have responsibility for 
the well-being of those patients.
    Mr. Towns. Yes?
    Dr. Walsh. I too think there's a lot of wisdom to that 
philosophy. IRB worried, when I was on it, and I hope still 
worries about it, because we still deal with a psychiatric 
population. So I think in many ways it's a solid recommendation 
that should be carried out. We in many instances have done it. 
We have, for example, a clinical team taking care of the 
patient and a research team who is not part of the clinical 
team.
    The issue that is a tough call is where to draw the line, 
where does this level of vulnerability start. And frankly from 
trying to work our way through assorted research protocols, it 
never became a crystal clear line, where you could say I'm not 
comfortable, for example, saying all psychiatric patients must 
participate in the way that's just been described. Because many 
psychiatric patients are not particularly vulnerable, but some 
are very vulnerable, and where, how that gets decided I think 
is a very important question, which at the moment is wrestled 
with by IRBs.
    Mr. Towns. Yes, Dr. Oldham.
    Dr. Oldham. Mr. Towns, if I may add one point, I think 
that's a very important suggestion and a very important 
concern.
    I would just want to add that I think there are many 
categories of vulnerable populations, and to focus on the 
mentally ill is one category and as Dr. Walsh said and I agree 
with this, some of these patients are particularly vulnerable, 
other of them may not be any different than the capable 
population.
    There are others who are also potentially vulnerable who 
may not have mental illness, for example people with stroke, 
people with other kinds of incapacity and other with life-
threatening terminal diseases which put them in a very 
vulnerable state, so I think all of these need to be looked at 
very carefully with the same level of concern.
    Mr. Towns. I agree. Dr. Cassell.
    Dr. Cassell. There's no question what Dr. Oldham said is 
true, but that should not take away from the fact that the 
protection of persons with certain mental disorders require 
special attention if for no other reason than they have not 
received the attention up until this time whereas the other 
categories he mentioned are already, do already come under 
regulation and custom that is not present here.
    Mr. Towns. Any other comments before we close out? Yes?
    Mr. Yessian. I would just agree. Many have commented that 
the most vulnerable subjects are those that are already 
patients of the investigator. That's one of the reasons why I 
think it's especially important to look at informed consent, 
not just in the context of what's in that document, but how is 
it explained to a potential subject and who does it, and in 
certain kinds of trials, it may be especially important that 
that be a quite independent party that the potential subject 
can communicate with without getting in the way of the doctor 
patient relationship.
    Mr. Towns. All right. Thank you very, very much. Thank you, 
Mr. Chairman. I yield back.
    Mr. Mica. Just one question to Dr. Cassell. The Bioethic 
Commission that you're on, was formulated by Executive order, 
is that correct? It's still under Presidential Executive order?
    Dr. Cassell. That's correct.
    Mr. Mica. What's your feeling toward codifying that?
    Dr. Cassell. I think that's important.
    Mr. Mica. You would recommend it?
    Dr. Cassell. Yes.
    Mr. Mica. Thank you.
    We have additional questions which we will submit to the 
panel, and we are keeping the record open by unanimous consent 
for at least 3 weeks. At this time I'd like to thank each of 
our witnesses for being with us this morning into this 
afternoon, and for your cooperation. We have an important task 
before us. We need everyone's cooperation to make certain that 
we put in place proper safeguards and regulations and 
protections for people who participate in medical research and 
that's our intent, to see that that's done wisely, that we as 
Members of Congress see that the laws are changed and the 
administration of the laws and regulations is proper to protect 
the public and also public funds.
    I thank you and I'll excuse the panelists at this time and 
call our second panel.
    Our second panel today consists of Mr. Cliff Zucker, 
executive director of the Disability Advocates, Inc., of 
Albany, NY.
    Our second witness is Dr. Adil Shamoo, and Dr. Shamoo is 
with Citizens for Responsible Care in Psychiatry and Research 
in New York City.
    Our third panelist is Miss Charisse Johnson, and she is 
from Brooklyn, NY.
    Our fourth panelist is Ms. Sherry Grenz, and she is with 
the National Alliance of Mentally Ill.
    These four panelists make up our second panel. If they 
could all come forward, please.
    As I explained to our first panelists and witnesses, this 
is an investigations and oversight subcommittee of the U.S. 
House of Representatives. We do swear in our witnesses. We also 
allow approximately 5 minutes to present your oral testimony 
before the subcommittee. Any additional records or lengthy 
statements will be made part of the record upon request. We're 
going to try to hold the panelists to those constraints today, 
particularly since the first panel ran us a little bit behind 
schedule.
    I would like to welcome each and every one of you, and if 
you could please stand and be sworn.
    [Witnesses sworn.]
    Mr. Mica. The witnesses have answered in the affirmative.
    I would like to welcome you this afternoon to our 
subcommittee hearing, and I will first recognize the statement, 
and we will go through all of the statements, then go to 
questioning.
    I'll recognize Mr. Cliff Zucker, executive director of 
Disability Advocates of Albany, New York. Welcome, sir, and 
you're recognized.

  STATEMENTS OF CLIFF ZUCKER, EXECUTIVE DIRECTOR, DISABILITY 
    ADVOCATES, INC., ALBANY, NY; ADIL SHAMOO, CITIZENS FOR 
  RESPONSIBLE CARE IN PSYCHIATRY AND RESEARCH, NEW YORK, NY; 
  CHARISSE JOHNSON, BROOKLYN, NY; AND SHERRY GRENZ, NATIONAL 
                    ALLIANCE OF MENTALLY ILL

    Mr. Zucker. Thank you, Chairman Mica.
    I appreciate very much the opportunity to testify before 
the committee today. I am executive director of Disability 
Advocates, which is a not for profit public interest law office 
in Albany, NY and for the last almost 10 years we have 
attempted to advocate for the rights of human subjects of 
medical experiments who have medical disabilities.
    The first thing I think that we have to remember is that 
if, to answer the question the committee poses, are Federal 
protections adequate, we need information, and that so long as 
IRB deliberations are cloaked in secrecy, that we can never 
really know what is going on there. A number of witnesses 
earlier made the point, but it really goes far beyond 
registration of IRBs and knowing how many IRBs there are. We 
also don't know what sort of experiments they approve, who the 
subjects are, what their characteristics are, whether they have 
mental disabilities, what the nature of the risks they are 
subjected to is, what the premises that are being studied are, 
and whether those are important premises.
    It's been said that sunlight is the best disinfectant. I 
think we will go a long way toward protecting subjects if you 
enact legislation that would require the, both the registration 
of IRBs and annual reports of all experiments that are approved 
by IRBs and additional characteristics of human subjects and of 
the experiments which are detailed in my written testimony, 
which I request be made part of the record.
    Mr. Mica. Without objection, so ordered.
    Mr. Zucker. What I'm proposing is somewhat similar to a 
bill that Congressman Towns drafted and introduced I believe a 
year or two ago, which has a similar purpose.
    The second thing that I'd like to call the committee's 
attention to is an experiment which was until very recently 
ongoing at Bellevue Hospital in New York City conducted there 
by New York University School of Medicine and funded by the 
Novartis Pharmaceutical Corp. The experiment was conducted 
using the experimental drug Iloperidone on homeless mentally 
ill individuals who were approached to be part of the research 
very shortly after admission to the hospital, within hours or 
days of being admitted to the hospital in a florid psychotic 
state.
    One thing I want to highlight before I get into the details 
of that experiment is that my office filed a complaint with the 
Office of Protection for Research Risks concerning problems 
which I am going to outline. The Office of Protection from 
Research Risks declined jurisdiction, said that they did not 
have any jurisdiction to review the experiment of what the IRB 
had done here. These are major research institutions in New 
York City and they get a lot of Federal money and they conduct 
a lot of Federal research. They have an insurance, which is 
this contract with the Office of Protection from Research 
Risks, which in most instances requires them to provide Federal 
protections to all of their research, even drug company funded 
research. However, NYU and Bellevue have exempted themselves 
from that and OPRR let them do it.
    So we're in the remarkable situation where very serious 
complaints are raised about research of homeless, psychotic 
individuals that is allegedly conducted on their consent and 
OPRR says we can't touch it. That's a problem, I think it needs 
to be addressed by legislation.
    Each of these subjects in this protocol arrived in the 
emergency room in a florid psychotic crisis. There were 14 
subjects, we examined the records of all of them. Most of them 
are homeless. Within hours or days, they were approached to 
give informed consent to be patients in this experimental drug 
study and 14 of them did give that consent.
    In every instance, the very same day or the day before or 
the day after, there are concurrent notes from clinicians 
describing these patients as floridly psychotic, as disordered 
thinking, as having no insight or judgment into their mental 
illness, as responding to voices, and yet in every instance 
sandwiched in between those comments about their florid 
psychosis, we have a note that says ``we asked the patient to 
participate. We answered all his questions, we explained all 
the risks and benefits, and after that discussion he gave 
informed consent.''
    It's an interesting thing. There are 14 patients. The notes 
describing the informed consent process are word-for-word 
identical, hand written, word-for-word identical notes for 
every patient and they're not all entered by the same person, 
either. So it's a boilerplate purported description of an 
informed consent process, which is very apparent when you read 
these records that these patients were floridly psychotic and 
at this particular time they certainly were not capable of 
giving informed consent.
    My written testimony contains, does not name the patient, 
uses a pseudonym, but it contains quotes from the record so you 
can judge for yourselves whether it's conceivable that these 
patients had a momentary, a moment of lucidity in which they 
could comprehend a multi page, complex informed consent 
document that I submit not too many college graduates could 
read and understand.
    It's also significant that none of these subjects were 
tried on nonexperimental drugs and had failed on it before they 
were put into the experimental drug protocol. These were people 
who very likely would have responded well to conventional 
medications, including some of the more newly developed 
antipsychotic medications, but those are expensive, and there's 
a financial conflict of interest here for Bellevue Hospital, if 
they offered respiradol, that's an expensive drug they had to 
pay for, if they instead offered the experimental drug 
iloperidone they're paid to do it by the drug companies, so 
there's a conflict of interest there.
    Every one of the patients did poorly on the study, they 
either withdrew themselves or were withdrawn by the 
experimenters, got much more psychotic. They were taken off the 
drugs, put on a placebo washout, then some of them were put on 
the drug, some put on placebo, they became so ill none of them 
could finish. When they were taken out of the program they were 
put on drugs, lo and behold they got better, and discharged 
into the community or other facilities.
    In my view it's unconscionable, when people are brought to 
the hospital in crisis, these are people dangerous to 
themselves or others, this is a life-threatening situation, 
some of them had dangerous histories of injuring themselves, 
threatening people, animals, that instead of given treatment, 
they're taken off treatment, given placebos and put on an 
experimental drug that wasn't proven to be effective and in 
every instance proven ineffective. The hospital has a desire to 
enroll patients, the institution has an impetus to enroll 
people and not pay for expensive drugs, who is looking out for 
the patient's interests? Supposedly it's the IRB. But it's 
interesting. The minutes of the IRB, the IRB considered this 
protocol on September 28th. On that day, the IRB considered 110 
projects. The minutes, we were provided with the minutes of the 
September 28th IRB meeting. One page contains the minutes of 
five protocols. The minutes consist of at most three words per 
protocol, if you don't count the name of the protocol, the 
heading, if you count the substantive discussion of what 
happens, three words and the number voted for and against.
    What it demonstrates is, without knowing more, I think we 
all know, you can't consider 110 protocols on 1 day. The kind 
of consideration that should have happened, that's required by 
the Federal regulations isn't happening.
    Among other things, I think that you need to consider 
whether Federal law should limit the number of protocols that 
are considered by an IRB, should set actual limits for the 
workload, and should require that certain resources be devoted 
to this process, because right now these volunteer IRBs just 
can't possibly do the job. I might add again, echoing some of 
the things said earlier, that independent consent monitors 
would be very, very important, independent of the facility 
which has a lot to gain financially from enrolling subjects in 
these protocols.
    Furthermore, I think we need to consider legislation that 
would make it unlawful to place acutely psychotic individuals 
who come to the hospital seeking care in experiments without 
first determining that they won't benefit from nonexperimental 
treatment, I think we have an ethical duty to first offer 
people what we know might work and to then only experiment if 
those things are unsatisfactory to them.
    I want to also touch on the fenfluramine experiments.
    Mr. Mica. Could you begin to conclude?
    Mr. Zucker. OK, I'm going to refer you to my written 
testimony which contains very specific recommendations 
concerning changes in Federal law and statutory language that I 
think is worthy of your consideration. I think we need to make 
it clear that neither poverty, nor race, nor family 
relationship to a person who is accused of crime, nor being the 
parent, excuse me, being the child of parents who are allegedly 
poor parents is the kind of condition that permits children to 
be experimented on in a way that is impermissible with so-
called normal, middle class children. What OPRR did in the 
fenfluramine case, if you look at what they did to Mt. Sinai, 
they condemned them for doing this challenge on middle class 
control children, but when they were poor children over here at 
Columbia University, it was OK.
    It's just inconceivable to me that you can, that because 
you're poor, because you have older brothers in trouble, that 
such experiments can be conducted if they're impermissible to 
other children. You don't get special rights because you're 
poor. Thank you very much.
    Mr. Mica. Thank you.
    [The prepared statement of Mr. Zucker follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.050
    
    [GRAPHIC] [TIFF OMITTED] T6523.051
    
    [GRAPHIC] [TIFF OMITTED] T6523.052
    
    [GRAPHIC] [TIFF OMITTED] T6523.053
    
    [GRAPHIC] [TIFF OMITTED] T6523.054
    
    [GRAPHIC] [TIFF OMITTED] T6523.055
    
    [GRAPHIC] [TIFF OMITTED] T6523.056
    
    [GRAPHIC] [TIFF OMITTED] T6523.057
    
    [GRAPHIC] [TIFF OMITTED] T6523.058
    
    [GRAPHIC] [TIFF OMITTED] T6523.059
    
    [GRAPHIC] [TIFF OMITTED] T6523.060
    
    Mr. Mica. I'll now recognize Dr. Shamoo who is with the 
Citizens for Responsible Care in Psychiatry and Research. Dr. 
Shamoo, you are welcome and recognized, sir.
    Mr. Shamoo. Thank you, sir. I'm Adil Shamoo from Columbia, 
MD. I am here to speak today on behalf of thousands of families 
who are not able or willing to speak for themselves. I'm here 
to speak on behalf of Citizens for Responsible Care in 
Research. Just for identification, I am a professor at the 
University of Maryland School of Medicine, former chairman, I 
have been addressing questions on issues of research, have 
written extensively for several years, I'm editor in chief of a 
journal called Accountability in Research where I study and the 
papers submitted to our journal study the issues of integrity 
in research and how it is conducted ethically.
    I also have chaired seven international conferences on 
issues of ethics on research.
    I would like to thank you, Mr. Chairman. I also would like 
to ask that my entire statement be entered into record.
    Mr. Mica. Without objection, so ordered.
    Mr. Shamoo. I will give simply highlights of my testimony, 
since the first panel covered a lot of ground.
    I would like to thank you, Mr. Chairman, and members of the 
subcommittee to give me this opportunity to inform you of my 
personal and organization's grave concerns regarding current 
ongoing and ethical research practices. Vulnerable human 
beings, such as children, veterans, and mentally disabled 
individuals are being used as human subjects in high risk 
experiments with no potential medical benefit which cause them 
harm. It was our organization that brought the public attention 
to the fact that fenfluramine was given experimentally to 
minority children.
    The voluntary, comprehending, informed consent is 
universally recognized as a fundamental human right. It must be 
applied to all human beings, be they privileged or 
disadvantaged. Our national public policy was formulated to 
provide safeguards aimed at preventing unethical human 
experimentation, such as the notorious New York Willowbrook 
hepatitis experiments conducted on mentally retarded children 
in the 1950's and 1960's and the Tuskegee syphilis study 
conducted on African American men in the 1940's to 1970's. But 
current Federal safeguards are inadequate, especially for 
mentally disabled persons and disadvantaged children. These 
groups are incapable of protecting themselves from unwanted, 
coercive even harmful experimentation.
    It is the government's obligation to strengthen protection 
because the current regulation have proved to be inadequate, 
leaving researchers to circumvent them.
    The rights of the powerless and disadvantaged individuals 
must not be compromised for the benefit of the powerful and the 
politically influential biomedical research establishment. To 
claim that individual rights must be sacrificed for the good of 
society is a self-serving motive which is not an ethical 
justification for overriding the rights of some incapacitated 
individuals. The universally adopted Declaration of Helsinki 
unequivocally affirms that, ``the interest of science and 
society must never take precedent over consideration related to 
the well-being of the subject.''
    The violations and experimental procedures that greatly 
concern us are, and one is the abrupt washout experiment which 
you heard of and I will not give you more detail.
    Second is the chemical challenge, the studies conducted on 
various human beings and third, the wholesale violations of 
informed consent.
    The principle of informed consent is intrinsic to a 
democracy and can rarely if ever be violated. Perhaps in the 
event of national emergency, or for compelling public safety 
reasons. There are no compelling reasons to justifying 
experimenting on disabled human beings without gaining their 
informed consent. Involuntary research on disabled and the 
disenfranchised individuals does not serve the good of society. 
To the contrary, such research threatens its fundamental moral 
underpinnings.
    Drug washout and chemical challenge experiments designed to 
produce rather than prevent a psychotic relapse in order to 
study its effect and conduct-photo imaging brain scans. They 
have routinely been approved by IRBs, thereby demonstrating 
that IRBs do not protect the interests of a subject and let me 
digress. Those fenfluramine experiments were approved by four 
different IRBs, four different grant proposals to four 
different study sections within the NIH and they were funded 
and carried over by four different sites within our research 
institutions.
    I will give you some of our recommendations. These are 
concrete recommendations.
    One; a moratorium on abrupt drug washouts and chemical 
provocation experiments that are likely to exacerbate severe 
incapacitating illnesses and expose vulnerable persons to 
addictive drugs, which may with repeated exposure lead to 
addiction or cause toxic brain damage.
    The enactment of National Human Subject Welfare Act to 
cover all human subjects enrolled in research, whether 
supported by Federal or private sources of funding. This act, 
and I want everybody to pay attention to this, this act brings 
protections to human beings at least to a comparable level to 
the protections available since 1966 for animals through the 
National Animal Welfare Act. That means if we just take the 
National Animal Welfare Act and substitute ``human beings,'' 
human beings will have greater protection because in this 
country you cannot conduct an experiment on animals, regardless 
of the source of funding, regardless of the site of research 
conducted without going through, applying the requirement of 
the Federal regulations. That is not, ladies and gentlemen, the 
case with human beings.
    There is a lot of research, tens of thousands of patients 
in research experiments are not regulated, and he just gave you 
one of thousands of examples.
    Three; a prohibition of conducting above minimal risk 
experiments on those incapable of evaluating the risks or 
appreciating the consequence to themselves unless they can be 
demonstrated to be in their interests. Mental capacity should 
be assessed by an independent physician and informed consent 
procedures should be monitored by independent observers. I'm 
very pleased to see NBAC and Dr. Oldham himself say that's an 
appropriate way of evaluating that. When I stated that in 1993, 
that was considered a heresy.
    Four; establish an independent, community based, that's 
important, review board to provide oversight for research 
involving vulnerable human beings. Protected classes must be 
represented whenever such individuals are being considered as 
subjects, and investigators must be held accountable for the 
conduct of the research and the well-being of human subjects.
    Let me tell you something about IRBs. IRBs are employees of 
the research institution. They get their paycheck monthly from 
that research institution which is trying to get millions of 
dollars from the pharmaceutical company and Federal Government. 
There is an inherent conflict of interest in that design.
    Five, require no fault liability insurance for every human 
subject of research to cover, this should satisfy Congressman 
Mica this is not a Federal bureaucracy, require the human 
subject research to cover, that is no fault liability insurance 
to cover the duration of the research and 1 year following 
completion of the research. We believe such insurance, in the 
amount of about $250,000 per subject, would be an incentive to 
reduce unnecessary risks and would compensate individual 
families for undue harm. It would also reduce the taxpayers' 
burden for uninsured persons who may require costly aftercare 
as a result of experimental adverse consequences.
    In closing, Mr. Chairman, the current state of protection 
for the vulnerable among us is very poor and it requires 
Federal regulations to strengthen, close the loopholes and 
mandate accountability for the harm done to our citizens and I 
thank you, Mr. Chairman.
    Mr. Mica. Thank you.
    [The prepared statement of Dr. Shamoo follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.061
    
    [GRAPHIC] [TIFF OMITTED] T6523.062
    
    [GRAPHIC] [TIFF OMITTED] T6523.063
    
    [GRAPHIC] [TIFF OMITTED] T6523.064
    
    [GRAPHIC] [TIFF OMITTED] T6523.065
    
    [GRAPHIC] [TIFF OMITTED] T6523.066
    
    [GRAPHIC] [TIFF OMITTED] T6523.067
    
    [GRAPHIC] [TIFF OMITTED] T6523.068
    
    [GRAPHIC] [TIFF OMITTED] T6523.069
    
    [GRAPHIC] [TIFF OMITTED] T6523.070
    
    [GRAPHIC] [TIFF OMITTED] T6523.071
    
    Mr. Mica. I would now like to recognize Ms. Sherry Grenz. 
She's with National Alliance of Mentally Ill. You are 
recognized.
    Ms. Grenz. Thank you. I'd also like this to become part of 
the official record.
    Mr. Mica. Your entire statement will be made part of the 
official record without objection.
    Ms. Grenz. I apologize for leaving out the names of the 
dignitaries. I just heard about these hearings about 2 days ago 
on the Internet, so once again, I apologize if I left anybody's 
name out.
    My father recently died from a stroke and he developed 
depression during these last painful years of his life. My 
mother has Alzheimer's type disease. My uncle is mentally 
retarded, and my brother suffers from schizophrenia. I am a 
primary caregiver for all. So given my family background, you 
can certainly see why research is so very important to me.
    I am the first vice president of the National Alliance for 
the Mentally Ill of New York State, the largest family consumer 
organization in the country. We have tens of thousands of 
members nationally, more than 8,000 in New York State alone. I 
am president of the Albany chapter, and I was also the only 
citizen advocate to serve on the New York State Department of 
Health's work group charged with developing research 
recommendations for protected classes. The months I spent as a 
member of this prestigious DOH task force gave me the 
opportunity to learn in detail about ethical issues of research 
with persons too incapacitated to give consent themselves. It 
also sensitized me to the enormous variety of ways in which 
ethical issues present themselves in research studies.
    I was particularly interested to learn that many of our 
mentally ill loved ones feel quite strongly about participating 
in research studies, so future generations don't have to suffer 
as they have. You know just because someone is mentally ill 
doesn't mean they are incapacitated all the time and incapable 
of being altruistic like many others of us in the population. 
So I come here not only with a deep commitment to helping those 
who are mentally incapacitated, but with a solid background of 
knowledge in trying to deal with these complicated issues as 
well.
    I want to emphasize that I am not a professional and I am 
not speaking on behalf of any group or person other than 
myself. Now, let me just briefly share with you a story about 
my brother. I call him Steven in the testimony but that's not 
his real name. I assume that's acceptable, right? Yes, he did. 
Well, Steven was a handsome, outgoing young man who was so 
smart that he skipped 2 years in school. He was on the school 
football team and liked by his teachers and peers alike. His 
future looked bright and promising.
    However, while Steven was still attending college we 
noticed a startling change in his personality. He insisted that 
people were staring at him and making derogatory remarks behind 
his back. Well, things quickly started to unravel after that. 
Many months and many doctors later we were told that Steven 
suffered from one of the most serious mental illnesses known to 
man, paranoid schizophrenia. Our hearts were broken. His life 
was destroyed. For the next 25 years, Steven was in and out of 
hospitals, lived on the streets of New York City where he was 
often beaten and robbed, and lived a life that was controlled 
by the terror and the demons in his head. His future looked 
bleak. Then about 7 years ago I received a call from my parents 
who were living in Queens at that time telling me that Steven 
said he could not take it anymore and would be willing to go to 
a hospital if I could find a place that would treat him with 
dignity and give him a chance at a better life. He had heard 
that there was some promising medications out here, ones with 
less unpleasant side effects. He was desperate and so were we.
    Through my years in NAMI, I gained a wealth of people to 
network with, and as I called around and found out more 
information, it was suggested that I call this facility that 
had a wonderful reputation with NAMI folks, the New York State 
Psychiatric Institute, PI. Many NAMI people told me of their 
positive experiences with this institute, but I decided to find 
out for myself to be sure. Well, after days of filling out 
endless forms and participating in many interviews, Steven was 
hospitalized in the schizophrenia research unit at PI and 
enrolled in a research protocol. For the first time in years we 
dared to hope again.
    Steven received a thorough mental health workup as well as 
an outstanding physical workup. Sadly, families have found out 
that once our relatives are diagnosed with a mental illness and 
get into the system, their general health care is often 
neglected, leading to a significantly shorter life expectancy 
and this fact has been substantiated by those having done 
research on this matter. What this extensive health workup 
turned up was something we never dreamed of. Steven had a tumor 
on his kidney and it was cancerous. We were shocked. 
Specialists were called in and informed us that there was no 
choice but to operate, but Steven refused. In a psychotic 
state, he proclaimed he would only agree to surgery when he 
felt the pain of the advancing cancer. The oncologists and 
psychiatrists explained to him that by the time he felt this 
pain it would be too late, the cancer would have spread to his 
spine, but Steven still refused to cooperate.
    Out of desperation I came up with the idea that perhaps if 
we gave Steven something as innocuous as Epicac, the stuff that 
you gave to kids to make them throw up, he would be convinced 
that he was sick enough and agree to the surgery. Well, PI 
adamantly refused to allow such a plan to take place, of 
course, but they continued to spend endless hours with Steven 
patiently explaining to him the seriousness of his situation. 
They also spent many hours with me and with my parents, 
compassionately offering us the support and information we 
needed.
    Then 1 day miraculously Steven agreed to the surgery. The 
surgeon found that the cancer on his kidney was totally 
encapsulated and removed the kidney. Chemotherapy was not 
needed. The point I was making is that the thorough work of the 
physicians at PI literally saved Steven's life and that none of 
the many doctors that Steven had seen on a regular basis over 
the years even picked up on this problem.
    Sometime after that, Steven was readmitted to PI, tried on 
Clozapine, a new type of medication that was discovered through 
research only a few short years ago and joined the world of the 
living once again. All is thanks to the wonders of research and 
the dedication and medical excellence of those at PI.
    You know, I would like to quickly add something else to the 
testimony at this time that I think is very important. In light 
of the outstanding treatment my brother received at PI, I was 
really shocked to see the horrendous story that appeared in the 
New York Post. What the Post reported was really in total 
contrast to what my family and many other NAMI families 
experienced and believe me, I would never, ever support any 
person or research institute that conducted research in an 
unethical, dangerous, or cruel manner. What compassionate 
person would? I even tried calling the Post on several 
occasions to give them my perspective and share several NAMI 
families' experiences with them, but curiously my calls were 
never returned.
    As a member of the DOH task force on protected classes I 
received a report from OPRR which they addressed here saying 
that these New York Post allegations were unfounded and untrue. 
As I understand it, and it's been confirmed they even went on 
to say that the research being done at PI is to be of the 
highest caliber, so I'm still struggling to find out what this 
is really all about.
    Well, to wrap it up, the story of my brother's positive 
experience participating in a research program of PI is of 
course my own personal story, but I don't think it's unique.
    Of course we must always strive for the highest of 
standards, particularly when it comes to vulnerable populations 
and we advocates have to be ever vigilant to be sure that all 
research studies are done in the safest way possible with the 
least risk possible and the truth is that in any profession, be 
it judges, lawyers, doctors, even legislators, there is an 
occasional negative experience or bad apple that surfaces, but 
it's not reasonable to paint every one in every given 
profession with the same brush. Mistakes should not and must 
not be ignored, but let's not throw out the baby with the 
bathwater.
    Where would we be without the benefit of research; all 
research, cancer, diabetes, heart disease et cetera. After all, 
who of us has not had a beloved family member or friend who has 
been stricken with one of these devastating illnesses? Please 
remember, research is our hope for the future. Thank you.
    Mr. Mica. Thank you for your testimony.
    [The prepared statement of Ms. Grenz follows:]

    [GRAPHIC] [TIFF OMITTED] T6523.072
    
    [GRAPHIC] [TIFF OMITTED] T6523.073
    
    [GRAPHIC] [TIFF OMITTED] T6523.074
    
    [GRAPHIC] [TIFF OMITTED] T6523.075
    
    [GRAPHIC] [TIFF OMITTED] T6523.076
    
    [GRAPHIC] [TIFF OMITTED] T6523.077
    
    [GRAPHIC] [TIFF OMITTED] T6523.078
    
    Mr. Mica. We'll now hear from Ms. Charisse Johnson of 
Brooklyn, NY. Welcome, and you're recognized.
    Ms. Johnson. Thank you, Mr. Chairman, and committee members 
who extended this invitation to me to testify at this public 
hearing----
    Mr. Mica. If you could pull that mic up as close as 
possible.
    Ms. Johnson [continuing]. ``Do Current Federal Regulations 
Adequately Protect People who Participate in Medical 
Research?''
    If my family's experience is taken into consideration, then 
there are really no protections for people like my family from 
the outrageous behavior for some researchers who are supposed 
to be regulated by State and Federal laws. How else can you 
explain the use of children as young as 6 years old by 
researchers? How did they decide that he and 33 other healthy 
African-American and Hispanic boys were perfect subjects for 
the experimentation for the dangerous drug fenfluramine?
    As you're aware, fenfluramine is the dangerous half of fen-
phen, a diet drug taken off the market because it causes heart 
valve damage in adults. I later learned that these researchers 
specifically set out to experiment with African-American and 
Hispanic children while excluding white children.
    My involvement with this nightmare experience started in 
1992 when my 16 year old son became a first time juvenile 
offender. I did not know how the juvenile justice system worked 
or exactly what to expect. A few months after my 16 year old 
son was sentenced to juvenile detention I was contacted by 
experimenters. They requested my involvement in a study being 
conducted at the New York Psychiatric Institute Columbia 
University by Danny Pines and Gail Wasserman and other 
experimenters.
    At first I did not understand how and from what source they 
obtained my name and knew I had a 6-year old son. I later came 
to the conclusion that this information came to them because of 
my 16 year old son's involvement with the juvenile justice 
system. Needless to say, I decided to cooperate with the 
experimenters. I felt at the time that if they could find me 
and knew I had a 6-year old son they had enough power to affect 
the well being of my 16 year old son who was being held in a 
detention facility.
    This started a series of visits by my 6 year old son and 
myself to the campus of Columbia University, where we were 
subject to a series of intimate, degrading questions, tests and 
interviews. The experimenters also took advantage of my fear 
for the well-being of my 16 year old son to intrude on my 
privacy of my home.
    Sometime in 1994 the experimenters Pine and Wasserman and 
the team decided it was time to take off the kid gloves and 
give the drug fenfluramine to my son, who was a normal healthy 
happy go lucky child until that day. Since being given 
fenfluramine by experimenters, my son and my family have 
suffered tremendously and continue to suffer.
    About 2 weeks after he was given the drug he started having 
sharp painful headaches. Then as the headaches became more 
unbearable, he started having anxiety attacks and 
hyperventilating. He would start gasping for breath as if he 
couldn't breathe, as with someone who was having an asthma 
attack.
    I then imagined that maybe he had asthma and took him to 
the doctor. The doctor after completing tests on him concluded 
that he did not have asthma. Nonetheless, the headaches, the 
anxiety attacks and the hyperventilating continued. Later his 
condition would only get worse. He started having horrible 
nightmares. He would wake up in the night screaming, thinking 
that someone was in his room. To this day my son continues to 
suffer the severe consequences of the reckless disregard for 
him as a human being by these experimenters. To them he was 
just another guinea pig.
    It may be asked by some why would you participate? I would 
answer the question by posing a question of my own. If you were 
in my position, had a son who was a first time offender in the 
juvenile system and out of nowhere people started writing you 
for information about your family, maybe you think that they 
had enough power to affect the well-being of your son who was 
locked up in the juvenile facility, what would you have done? 
If they did not give you a true explanation of the drug 
fenfluramine, if you had never heard of such a drug, if they 
also presented themselves as doctors who you have been thought 
to think only act in the best interests of you and your family, 
if they are operating out of the well known institution of 
Columbia University, I suspect that a lot of parents would be 
likely to cooperate with these seeming good doctors not knowing 
that they may be dealing with Dr. Jekyl and Mr. Hyde.
    At the end of these experiments, they did not have the 
human decency to admit that my son was used as a guinea pig for 
their selfish purposes. Requests by my attorneys for my sons 
records were met with refusals for 9 months. It was only after 
the involvement of the dedicated staff membership from the 
congressional committee office that the records of my son's 
experiments were finally realized. The records confirm that the 
nightmare experience was indeed a nightmare. Thank you.
    Mr. Mica. Thank you for your testimony.
    I'd like to thank all of our witnesses on this panel. A 
couple of quick questions.
    Mr. Zucker, you have reviewed the recommendations of the 
Bioethics Advisory Commission for protecting human subject 
research involving mentally ill patients. Do you have any 
additional recommendations other than what you provided us 
with?
    Mr. Zucker. We may be able to provide you with some 
additional recommendations. And I can, if I could take the 
liberty of submitting an additional statement.
    Mr. Mica. Would you recommend that these be instituted by 
statute or by regulation?
    Mr. Zucker. I think that it is important that the Congress 
act and enact statutes. First recommendations were imposed by 
the Belmont commission, they were proposed and they were 
defeated; there were special protections for other vulnerable 
groups. I am afraid in 20 years from now if the Legislature 
does not act, then we will be looking back at the impact of the 
Board in an unfavorable light.
    I think there are some key principles that the Congress 
could enact and I've made some proposals in my written 
testimony along those lines.
    Mr. Mica. Thank you. Dr. Shamoo, one of the members, I read 
the entire testimony but one of the Members' remarked sort of 
echoed yours in this June hearing over a year ago, that 
rodents, he said, had more protections than human beings, and 
you sort of echoed that in your testimony.
    You also said that some of the protections that are in law 
for an animal you could substitute human being. Would that in 
fact be adequate or would you certainly have to massage other 
language?
    Mr. Shamoo. Absolutely. I was sincere in that comparison. 
It was the first time I gave written testimony to 1995, I 
mentioned those facts. For example, in animal research, there 
is monitoring, there is audit at this time, there is inspection 
of the facilities. None of that exists for human beings, and 
the most important difference, that no matter what site of 
research is, who the source of funding, anywhere in the United 
States, you must comply with the Federal regulations. That is 
not the case, and I don't know what the percentage is, but I 
will guesstimate somewhere around 30 to 40 percent of all human 
subject experiments are not subject to any regulations in this 
country.
    Mr. Mica. Dr. Zucker, you said I think the Bellevue case, 
where you had sought to file a complaint with OPRR and that 
they said they had no jurisdiction. There's no other source for 
you to appeal to? Or can you file a complaint?
    Mr. Zucker. They referred the matter to the Food and Drug 
Administration.
    Mr. Mica. They did.
    Mr. Zucker. They did. It's unclear to me what has happened 
to the complaint in the Food and Drug Administration because 
it's my impression this is not the sort of investigation they 
normally conduct. We are also pursuing a complaint with the New 
York State Department of Health.
    Mr. Mica. So at the Federal level, you feel there's 
inadequate overall jurisdiction, and that should be specified 
by law?
    Mr. Zucker. I think so. OPRR does have, I think it is the 
agency within the Federal Government with the most expertise in 
overseeing the operation of institutional review boards, and it 
seems ridiculous to expect FDA to replicate that expertise 
within the FDA.
    Mr. Mica. It seems to be it would be better to have the 
most expert agency review complaints of this nature.
    And I would imagine both of you, dealing with either 
children or mentally ill individuals, would want to have some 
extra protections instituted or legal procedures that would be 
closer to follow, is that correct?
    Mr. Zucker. That is correct. In my written testimony I 
propose some statutory language and I'd be happy to work with 
your staff to fine tune that or to develop that.
    Mr. Mica. I thank you both. I yield now, if I may, to Mr. 
Towns.
    Mr. Towns. Thank you very much, Mr. Chairman. Let me thank 
all of the witnesses for their testimony. It was very 
enlightening. Let me ask you too, Mr. Zucker, in your 
testimony, you noted that the definition of the word 
``condition'' was a pivotal concern in OPRR's failure to 
discipline New York State Psychiatric Institute. Could you 
elaborate on why the redefinition of the word ``condition'' as 
used in this decision would serve as a dangerous precedent in 
the future?
    Mr. Zucker. I think so. I mean, to really understand this, 
I think you have to contrast what OPRR said and did with the 
research that was occurring at Mt. Sinai and the results that 
were reached at PI, which are very hard to reconcile. Mt. Sinai 
was sharply criticized for putting so-called normal control 
children in a fenfluramine challenge, because it was said these 
children did not have a condition, and therefore, it was wrong 
to subject these children to the risks of a fenfluramine 
challenge.
    OPRR then turned around and said that it was OK to subject 
the children--the young minority boys at the Psychiatric 
Institute to the very same risks, because they were not normal 
controls, they were poor children who had an older brother who 
was a juvenile delinquent and some people thought maybe their 
parents weren't such great parents.
    That was the criteria. In a city like New York, I mean, 
they said it themselves. 90 percent, 98 percent I believe PI 
says of the children in the juvenile delinquent system in New 
York City are apparently minority children, so that if the law 
can be interpreted the way OPRR is now interpreting it, it 
means that minority children in New York don't have the same 
protections as middle class children who don't, presumably will 
not be labeled as coming from an adverse child rearing 
environment, and I don't think we want to create a two-tiered, 
class-based system that has a disparity impact on race in the 
major cities that after all where is this research primarily 
occurring, it's occurring in New York, Chicago, Los Angeles, in 
cities which large minority populations and where there's going 
to be a disproportionate number of minority kids found in the 
juvenile justice system.
    So I think Congress has to say that as a matter of public 
policy, this is not an acceptable interpretation of Federal 
law, that if you can't do this to middle class kids who may be 
largely white in a lot of communities, then you can't do it to 
poor children who are going to be predominantly minority 
children in the major cities where the research occurs.
    Mr. Towns. Thank you very much.
    Ms. Johnson, let me ask you, let me begin by first, wanting 
to express my sympathy for the ordeals that you and your son 
went through, and also to commend you on coming forward to 
testify, because I think as a result of your testimony, I think 
you're going to save a lot of folks some pain and agony as a 
result of your stepping forward and to share that which 
happened to you.
    As to the side effects that your son has experienced since 
his participation in the experiment, has your son been offered 
any treatment or assistance by the researchers? Talking about 
the New York State Psychiatric Institute or anyone affiliated 
with the organization.
    Ms. Johnson. No.
    Mr. Towns. I was concerned about the way in which you and 
your son were recruited as well. I thought that the juvenile 
court records were supposed to be confidential records.
    Ms. Johnson. Right.
    Mr. Towns. That was my impression.
    Ms. Johnson. Mine, too.
    Mr. Towns. Purely by releasing the names of you and your 
son to researchers, the confidential nature of those records, I 
think was breached. Were you ever told by the researchers, by 
the juvenile court or family court or any of the authorities 
that if you refused to participate, that refusal would in no 
way affect the case of your older son who was in the juvenile 
detention facility, were you ever told?
    Ms. Johnson. No.
    Mr. Towns. They never told you that?
    Ms. Johnson. No.
    Mr. Towns. So you probably just sort of felt it was 
important to cooperate, because you wouldn't do anything to 
further bring about harm to your older son.
    Ms. Johnson. Sure.
    Mr. Towns. Were you afraid that by coming forward you would 
place your older son in jeopardy, that you felt if by not 
coming forward, that would be a problem?
    Ms. Johnson. That's what I felt.
    Mr. Towns. So that's like a little form of intimidation.
    Representatives of the New York Psychiatric Institute have 
testified that the overwhelming majority of children in the 
study had behavioral problems. Did your son have any kind of 
behavior problems before he participated in the study?
    Ms. Johnson. None whatsoever, no.
    Mr. Towns. Were you told at any point in time that your 
son, who was 6 years old at the time, that the drug they were 
going to put him on had never been tested with anyone under the 
age of 12, never been tried on them at that time, were you told 
that?
    Ms. Johnson. No.
    Mr. Towns. Well, let me just say, Mr. Chairman, I think 
this further points out that we have to act in Congress in 
order to make certain that people are protected, and that I 
think the only way we could do that is by legislation, I think 
if we leave it out there loosely, I don't think the protection 
that's needed will come about.
    So I want to thank you very much for sharing and also to 
say also to Ms. Grenz that I really appreciate your coming 
forward and sharing as well, because here you have several 
situations wherein you feel yourself responsible for and I 
think that people might not be able to make the decision as to 
whether or not they should be involved in a research kind of 
setting, and you would be called upon, and I think being called 
upon to make those kinds of decisions without having all the 
information is not fair.
    So whether it's in your case, I think that you point out to 
us that you need to have information in order to be able to 
move forward, and I got that from your testimony, that it's 
important to have this data so you could make the decision as 
to what should happen from that point on.
    I guess the last one I sort of wanted to throw out there, 
Mr. Chairman, I guess that this is for Mr. Zucker. In your 
testimony you discuss washout. Do you believe that washout 
should be banned?
    Mr. Zucker. I think that would go too far, but I do think 
that washouts and placebos involve significant risks that are 
not therapeutic risks, and again, to bring it back to the 
situation at the Bellevue New York University School of 
Medicine study, there I think it was inappropriate there, 
because you had people who were coming into the hospital, 
histories of suicidal and other violent behavior, who either 
came to the hospital or were brought to the hospital because 
they were really in a psychiatric crisis and potentially 
dangerous, that to take those people and then put them on a 
placebo or just to wash them out of any medication and not to 
offer them care during that period, I think is unethical, 
because patients who come to the psychiatric hospital in crisis 
reasonably expect care.
    I think that they will have a very hard time understanding 
that it is a delusion, kind of a therapeutic delusion that when 
the doctor says would you like to participate in this 
experiment, that he's offering them something which is not in 
their best interests, which may allow them to suffer for weeks.
    There was a potential here. Everyone got a 1-week washout, 
and then some people were put on a placebo, and so continued to 
receive no medication and others did receive the experimental 
drug or another drug.
    Under those particular facts, I believe it is unethical to 
offer a washout and a placebo before you determine that you 
can't help this person using nonexperimental treatments that 
are readily available.
    Mr. Towns. Thank you. Thank you very much, Mr. Chairman. I 
really appreciate your coming to New York and having this 
hearing. I think it means a lot to a lot of people, because I 
think there's more going on, Mr. Chairman, than we really 
realize. I think that we feel the situation here, we read about 
an incident that occurred maybe in the newspaper, but I think 
that there's a lot more going on. I think that we have to sort 
of make certain that we put legislation into a new form, 
legislation that's going to help people, and I think there's a 
definite need to do that.
    When you think of a youngster 6 years old being put on a 
drug that not even the pharmaceutical company tested to find 
out whether or not it would do harm to anyone under 12, I mean, 
that to me is just something that should not happen in the 
United States of America, and Mr. Chairman, I think we have an 
obligation and responsibility to so provide.
    Mr. Mica. I thank the gentleman from New York for his 
persistence on this issue, and his leadership in Congress on 
this and many other issues, and I'm pleased to state that I've 
had the opportunity to work with him for many years, and we, 
when our side was in the minority, I've often cited Mr. Towns' 
respect for the minority and working with me as a Member at 
that time, in fact, I came in as a junior in Congress, and the 
respect with which he treated me, I thank him for that publicly 
and personally. And also for again his leadership on this 
issue.
    It is important that we fulfill our congressional 
responsibilities and oversight, as I said, and also 
legislatively to see that we have in place the adequate 
protections both under statute and regulation. We'll work with 
the administration to see the kinds of things that can be put 
into place and are put into place and don't have foot dragging 
on an area that's so important and where the public needs to be 
protected, not only the public at large, but particularly 
children, mentally ill and others who society must protect, so 
hopefully we can use this as a constructive basis to proceed 
and I know that knowing Mr. Towns very well, we will have 
additional followup to this inquiry that's taken place in New 
York today.
    There being no further business to come before this 
subcommittee, this meeting of this Subcommittee on Criminal 
Justice, Drug Policy, and Human Resources is adjourned.
    [Whereupon, at 2 p.m., the subcommittee was adjourned.]
    [Additional information submitted for the hearing record 
follows:]

[GRAPHIC] [TIFF OMITTED] T6523.079

[GRAPHIC] [TIFF OMITTED] T6523.080

[GRAPHIC] [TIFF OMITTED] T6523.081

[GRAPHIC] [TIFF OMITTED] T6523.082

[GRAPHIC] [TIFF OMITTED] T6523.083

[GRAPHIC] [TIFF OMITTED] T6523.084

[GRAPHIC] [TIFF OMITTED] T6523.085

[GRAPHIC] [TIFF OMITTED] T6523.086

[GRAPHIC] [TIFF OMITTED] T6523.087

[GRAPHIC] [TIFF OMITTED] T6523.088

[GRAPHIC] [TIFF OMITTED] T6523.089


```