[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:]
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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:]
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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:]
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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:]
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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:]
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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:]
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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:]
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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.]
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