1

          1

          2

          3                               CHARTER

          4

          5                 NATIONAL HUMAN RESEARCH PROTECTIONS

          6                         ADVISORY COMMITTEE

          7

          8                    Wednesday, December 20, 2000

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                                                                   2

          1                              ATTENDEES

          2    MARY FAITH MARSHALL, Ph.D., Chairperson, Director

          3    of Program in Bioethics, University of Kansas

          4    Medical Center 

          5

          6    GREG KOSKI, Executive Secretary, Ph.D., M.D.,

          7    Director, Office of Human Research Protections,

          8    Office of Public Health and Science, OS

          9

         10    MARK BARNES, J.D., LL.M., Partner, Proskauer Rose, LLP

         11

         12    SANFORD CHODOSH, M.D.

         13    ELLIOT N. DORFF, Ph.D., Rector, Distinguished

         14    Professor of Philosophy

         15

         16    JENNIE R. JOE, Ph.D., M.P.H., R.N., Professor,

         17    Family and Community Medicine, University of Arizona

         18    ROBERT LEVINE, M.D., Professor of Medicine, Yale

         19    University School of Medicine 

         20    ABBEY S. MEYERS, President, National Organization

         21    for Rare Disorders


                                                                   3

          1                        ATTENDEES (Continued)

          2    MARY Z. PELIAS, Ph.D., J.D., Professor, Department

          3    of Genetics, Louisiana State University Health

          4    Sciences Center 

          5

          6    ROBERT R. RICH, M.D., Executive Associate Dean of

          7    Research, Emory University School of Medicine

          8

          9    ADIL E. SHAMOO, Ph.D., Professor, Department of

         10    Biochemistry and Molecular Biology, University of

         11    Maryland School of Medicine 

         12

         13    JUDITH L. SIEGEL, Ph.D., Vice President, Head U.S.

         14    Clinical Operations, Hoffman-La Roche, Inc.

         15    DENYSE THORNLEY-BROWN, M.D., Assistant Professor,

         16    Division of Nephrology, University of Alabama at Birmingham

         17    KATE-LOUISE GOTTFRIED, J.D., M.S.P.H., Executive

         18    Director, National Human Research Protections

         19    Advisory Committee

         20

         21

         22


                                                                   4

          1                        ATTENDEES (Continued)

          2

          3    JACKIE COLEMAN, Personnel Specialist, Program

          4    Support Center

          5

          6    DONNA E. SHALALA, Secretary of Health and Human Services

          7    EDWARD M. KENNEDY, Senator from Massachusetts

          8

          9    FELICE J. LEVINE, Ph.D., Executive Officer,

         10    American Sociological Association

         11

         12    STUART L. NIGHTINGALE, M.D., Senior Medical Advisor

         13    to the Assistant Secretary for Planning and Evaluation 

         14

         15    DAVID SATCHER, M.D., Ph.D., Assistant Secretary for

         16    Health and Surgeon General 

         17

         18    DIXIE E. SNIDER, M.D., M.P.H., Associate Director

         19    of Science, Centers for Disease Control and Prevention

         20

         21

         22


                                                                   5

          1                        ATTENDEES (Continued)

          2    ALAN FLEISHMAN, M.D., Senior Vice President, New

          3    York Academy of Medicine, Clinical Professor of

          4    Pediatrics and Clinic Professor of Epidemiology &

          5    Social Medicine, Albert Einstein College, New York 

          6

          7    ROBERT COOKE DEAGAN, National Institute of Medicine

          8

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         22


                                                                   6

          1                        P R O C E E D I N G S

          2                                  [Time noted:  9:05 a.m.]

          3              DR. KOSKI:  We will begin our session.

          4              I'm Greg Koski.  I'm the Director of the

          5    Office for Human Research Protection and the

          6    Executive Secretary for this advisory committee.

          7              On behalf of Secretary Shalala of the

          8    Department of Health and Human Services, as well as

          9    the Human Research Subcommittee of the Committee on

         10    Science, the National Science and Technology

         11    Council, I'm delighted to welcome all of you to

         12    this inaugural session of the National Human

         13    Research Protections Advisory Committee.

         14              To all of the members, the private members

         15    of the committee who constitute the voting members

         16    of this panel, as well as to all of the government

         17    representatives, our ex officio members, we

         18    represent not only all of the operating divisions

         19    and agencies within -- that are involved in human

         20    research within the Department of Health and Human

         21    Services, but also all of those Federal departments

         22    and agencies that are engaged, are funding human


                                                                   7

          1    research under the common rule.  I want to give you

          2    a very, very hearty welcome.  We're delighted that

          3    you're here and look forward to your active

          4    participation. 

          5              I'd also like to take this opportunity to

          6    give a very, very special thanks to the members of

          7    the general public who have made the effort to be

          8    here, despite the weather, as well as to members of

          9    the press who have joined us, who I believe play a

         10    very important role in conveying the messages that

         11    will come from this committee.

         12              The impaneling of this federal advisory

         13    committee is a very important first step in the

         14    overall process of remodeling our national system

         15    for the protection of human subjects.  The

         16    formation of this advisory committee, though, is

         17    only one part of that effort.

         18              To put this all in perspective, I think

         19    it's fair to say that, as humans, we are often

         20    limited in our perceptions and our behaviors by the

         21    paradigm in which we find ourselves, our belief

         22    about the world and the systems, how we interact


                                                                   8

          1    with them.

          2              For a long time, people believed that the

          3    earth was the center of the universe, and it wasn't

          4    until that paradigm was broadened that we actually

          5    began to have a fuller conception of the universe.

          6              Our desire in the overall efforts that are

          7    going forward is to move beyond the current

          8    paradigm for the actual conduct, as well as

          9    oversight of human research, one that has too often

         10    been characterized as being too confrontational in

         11    many instances, and perhaps so focused on

         12    compliance, per se, as a goal, that it may have

         13    actually detracted from our primary purpose, which

         14    is, of course, the protection of human subjects in

         15    the research that we undertake.

         16              So our desire is to move toward a new

         17    paradigm, one that's based upon the recognition of

         18    the shared goals and responsibilities, and focuses

         19    on the center of our universe becoming the well-

         20    being, the interest of the research subjects on

         21    whom we are critically dependent for all of our

         22    human research activities.


                                                                   9

          1              Now, the position that we find ourselves

          2    in today is one that has, at least in part, evolved

          3    from disclosures of deficiencies and abuses in the

          4    conduct of research, and certainly over the last

          5    couple of years, we have had not only similar

          6    disclosures, but real tragedies that have certainly

          7    been the basis for elevated concern.

          8              A very natural reaction in an instance

          9    like this is to simply adopt a more stringent

         10    regulatory structure to clamp down, okay, that can

         11    further restrict our ability to do meaningful

         12    science.  In doing so, we could inadvertently

         13    deprive all of us, all of our society, from the

         14    very real and legitimate benefits that we all look

         15    to science for, and that would be a tragedy in

         16    itself.

         17              So, while there's clearly a need to both

         18    expand and enhance our oversight activities, we

         19    also have an opportunity now to take a more

         20    proactive approach, one that is positive, one

         21    that's aimed at actually achieving a greater

         22    simplicity and uniformity, efficiency, and above


                                                                  10

          1    all, effectiveness in our system for responsible

          2    conduct of human research, and I hope that that's

          3    the direction in which we can move.

          4              But I think it's important to recognize at

          5    the outset that the only way we are going to be

          6    able to do this is by moving forward together.

          7              Over the last couple of years, the

          8    divisions among all of us, okay, have widened to

          9    the point that debate has often been too heated,

         10    perhaps not fully informed, but certainly not as

         11    constructive as it could be.

         12              And in pulling together this advisory

         13    committee, we are looking for a new opportunity to

         14    begin to seek the common ground, to have the

         15    important dialogue that must go forward, and

         16    actually, to identify and stand on that common

         17    ground, which must be the high ground.  So that as

         18    we proceed with our research, we will do so in a

         19    manner that continues to build public trust and

         20    hope in what we do, and also allows us to be

         21    rightfully proud of the accomplishments of our

         22    endeavor.


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          1              So, it's in this spirit that the advisory

          2    committee has been formed.  It's in this spirit

          3    that I encourage you to go forward.

          4              The challenges that are before you are

          5    enormous, as are the responsibilities.  There are

          6    many who will be looking to you for clarity and

          7    balance and your advice that we hope will become

          8    the basis for rational and effective policies and

          9    procedures.

         10              So, with that, again, I would like to

         11    welcome all of you, and I would like to introduce,

         12    for additional remarks, our Chair, Mary Faith

         13    Marshall.

         14              CHAIRPERSON MARSHALL:  Thank you, Greg.

         15              And, again, I would also like to extend a

         16    heartfelt welcome to all of you, to our guests, to

         17    our ad hoc committee members and committee members.

         18              I want to thank Kate Gottfried and Greg

         19    Koski for yeomanship work in the last few weeks for

         20    pulling this meeting together.  They have truly

         21    done an outstanding and stellar job, and have set

         22    the tone, I think, for our work.


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          1              Our guiding principle that was articulated

          2    by Secretary Shalala in her sounding board article

          3    in the New England Journal of Medicine of September

          4    14th of this year gave a very simple message.  She

          5    said, "No priority in research is more important

          6    than the protection of human subjects."

          7              Our system of protection must be

          8    exemplary.  This sentiment and the resulting charge

          9    to this committee has been occasioned by a

         10    confluence of events resulting in the public and

         11    the political will and the professional will for

         12    substantial reform of the system of human research

         13    protections.

         14              This is an extraordinary opportunity for

         15    our committee, for the Office of Human Research

         16    Protections, for the research community as a whole,

         17    for the public.

         18              Victor Hugo said, "An invasion of armies

         19    can be resisted, but not an idea whose time has

         20    come."

         21              Our time has come.  We face significant

         22    and important challenges, and our response must be


                                                                  13

          1    exemplary.

          2              To that end, we must be ever mindful of

          3    the social contract between the scientific

          4    enterprise and the public.  Exceptional outcomes

          5    depend on the integrity of our process as a

          6    committee.

          7              So I would propose for our work the

          8    following bywords:  Integrity, fairness that we

          9    must ensure that all who should be at the table are

         10    at the table, and that their voices are heard; that

         11    we are creative, that we are flexible, that we

         12    think outside of the box; respect for our guests,

         13    for our fellow committee members.

         14              Collegiality among committee members

         15    should be the byword, and as Chair of the

         16    committee, I will take the prerogative of having a

         17    heavy hand to ensure civility among our

         18    deliberations, if that is needed.

         19              Critical thinking.  The essence of

         20    critical thinking is the ability to suspend

         21    judgment.  Each of you, as committee members, was

         22    chosen for your exceptional individual abilities


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          1    and for the constituencies that you represent.

          2              We should be mindful, however, that in

          3    meeting our charge that we aim for consensus, when

          4    possible, for clarity; that we focus on our task,

          5    that we entertain perhaps radical and innovative

          6    ideas, that we are open-minded and flexible; that

          7    we have respect for our staff; that we are not

          8    reticent in raising controversial or sensitive

          9    issues, and that we do not ignore the hippopotamus

         10    in the middle of the room.

         11              And, finally, I would hope that each of us

         12    will feel ownership to the committee and its

         13    charge, and that we will take pride in our work.

         14              We have a daunting agenda over today and

         15    tomorrow.  Over the next two days, I would

         16    anticipate that we will discuss, refine, and focus

         17    on our tasks; discuss what is realistically

         18    achievable, identify our needs for data, establish,

         19    if need be, working groups, agree to a schedule and

         20    a work plan.

         21              And I would remind you that these are

         22    public meetings, and, thus, we should be


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          1    consistent.  We should be open.  We should be

          2    receptive, and we should be fair.

          3              Simplicity, uniformity, efficiency and

          4    effectiveness are Greg Koski's bywords.  Many of

          5    you have heard them already, and we should bear

          6    them in mind over the coming months and the coming

          7    years.

          8              So, my fellow carpenters, let us raise the

          9    roof beam high.  And I will introduce to you Kate

         10    Gottfried.

         11              MS. GOTTFRIED:  Thanks, Mary Faith.

         12              Well, I, too wish to welcome all of you

         13    here today and convey what an extraordinary

         14    opportunity this is for me to work with such a

         15    thoughtful, accomplished, and dedicated committee

         16    members.

         17              For the federal government, I think as a

         18    whole, and DHHS, in particular, to approach

         19    proactively such complex and thorny issues involved

         20    in human subject research, and an opportunity for

         21    us to engage in a dialogue with the public on

         22    matters of such critical importance.


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          1              And, finally, for me personally to be

          2    involved in an area that I've had a longstanding

          3    and abiding interest in.

          4              I'm thrilled that everyone made it here,

          5    despite the weather, and recognize that the

          6    turnaround time from the actual appointment of the

          7    committee to this meeting has been rather short and

          8    kind of a whirlwind of activities.

          9              In the future, we'll have a greater lead

         10    time, and I think things will be even more

         11    prepared.

         12              But I do want you all to know that I know

         13    what a challenging task we have ahead of us now and

         14    over the next several years, and I want you to know

         15    that I'm here to make things happen as easily as

         16    possible, and to make things run smoothly and to

         17    facilitate your process.  So you needn't at all

         18    hesitate to contact me with any concerns,

         19    questions, et cetera.

         20              Thank you. 

         21              CHAIRPERSON MARSHALL:  Jackie Coleman.  We

         22    -- is she -- is Jackie here?  We need to be sworn


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          1    in.  Then let us be flexible. 

          2              [Laughter.]

          3              CHAIRPERSON MARSHALL:  And I would ask our

          4    ex officio members to introduce themselves to the

          5    committee.  And you are?  You'll have to speak -- 

          6              PARTICIPANT:  I'm -- 

          7              CHAIRPERSON MARSHALL:  Thank you. 

          8              PARTICIPANT:  -- at the Environmental

          9    Protection Agency. 

         10              DR. RAKER:  I'm Dr. John Raker with the

         11    Veteran's Administration. 

         12              DR. KOSKI:  If you could stand --

         13              CHAIRPERSON MARSHALL:  Stand, please. 

         14              DR. KOSKI:  -- so that people could see

         15    you, please.

         16              CHAIRPERSON MARSHALL:  Thank you. 

         17              PARTICIPANT:  I'm Bernard Schwetz, FDA.

         18              PARTICIPANT:  Mal Tanner with the National

         19    Institutes of Health. 

         20              MR. GRAVE:  Gilman Grave from the Child

         21    Health Institute. 

         22              MS. LEVINSON:  Rachel Levison, the


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          1    Assistant Director of -- Office of Science and

          2    Technology. 

          3              MR. SHELTON:  Jim Shelton, USAID.

          4              MR. FORCINO:  Doug Forcino, Department of

          5    Defense. 

          6              CHAIRPERSON MARSHALL:  Thank you very

          7    much.

          8              What we might do then, since we do still

          9    have some time ahead of us, I would like to make an

         10    announcement.  There is sort of an addition to the

         11    agenda.  It is a wonderful addition that after

         12    Secretary Shalala gives us our charge, we will also

         13    have a visit from Senator Kennedy.

         14              So, in light of that, and the fact that

         15    our agenda may be pushed back, it might be well for

         16    us to begin with our committee members.

         17              I would ask each of you to introduce

         18    yourself.  Tell us a little bit about yourself and

         19    your background, and also, it would be helpful, I

         20    think, not only for our task today and tomorrow,

         21    but for the future and in thinking of establishing

         22    future agenda items, that you would articulate


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          1    areas that are of special concern or interest to

          2    you, that you think we might want to entertain and

          3    examine in the future.

          4              Shall we start with Mark Barnes?

          5              And let me just take, perhaps, the

          6    prerogative of saying that, for committee purposes,

          7    if you are agreeable, could we be informal and use

          8    first names? 

          9              Thank you. 

         10              MR. BARNES:  Thank you, Mary Faith.

         11              I guess the first thing I want to say is,

         12    I want to thank the three of you and your staffs

         13    for organizing this, especially in what is, by

         14    anyone's estimation, a turbulent period in

         15    Washington with the changeover of administration.

         16              What I think is significant about that is

         17    that academic medicine, which is part of my

         18    representation on the committee, because I'm a

         19    practicing attorney and represent many academic

         20    medical centers throughout the country in all sorts

         21    of compliance issues, including research

         22    compliance, but academic medicine is really quite


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          1    wedded to the idea that conflict of interest rules

          2    and conflict of interest policies, for example,

          3    among other kinds of research protections have to

          4    be looked at.

          5              So, regardless of political affiliation or

          6    what administration is in charge, whether Bill

          7    Roper or Tommy Thompson or anybody else is HHS

          8    Secretary, or Donna Shalala, I think that you're

          9    right, Mary Faith.  This is an idea whose time has

         10    come, regardless of the political winds.  It's a

         11    deeper current than simply one administration or

         12    another.

         13              I am a partner at a large law firm in New

         14    York called Proskauer Rose, and I represent many

         15    academic medical centers in all sorts of issues, as

         16    I said.  My background is as a legal academic, as a

         17    patient rights advocate, particularly for patients

         18    living with HIV-AIDS, and also as a public health

         19    official.

         20              I was the Associate Commissioner of Health

         21    in New York City during the last couple of years of

         22    the David Dinkins' administration and the first few


                                                                  21

          1    months of the Guiliani administration, and I was

          2    intimately involved there with the crafting of

          3    policies to combat tuberculosis, particularly the

          4    crafting of a regulatory scheme to compel

          5    tuberculosis patients to take their medication, and

          6    if they didn't, to civilly detain them until they

          7    could be stabilized and were able to take their

          8    medication.  In addition, a whole regime of

          9    directly observed therapy for tuberculosis.

         10              I also served, in 1995, as the Executive

         11    Director of the AIDS Action Council in Washington,

         12    which is a national lobbying group on behalf of

         13    people living with HIV-AIDS.

         14              And, before that, I worked at the New York

         15    State Health Department as the Director of AIDS

         16    Policy from 1989 to '91.

         17              So I come to this from a background in, as

         18    I said, representing academic medical centers, now

         19    as a practicing attorney, as a public health

         20    official in the past, as a legal academic.  I

         21    taught at Columbia Law School for four years and

         22    still teach at a number of law schools in the New


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          1    York area.

          2              And, also, as a patients' rights advocate. 

          3    Right now, my kind of particular interest in this

          4    committee is that I have seen, both from my work as

          5    a patient advocate, and also from my work

          6    representing academic medical centers, there are

          7    really great and massive achievements of medical

          8    research in the area of cardiovascular disease,

          9    orthopedic medicine, and particularly, the really

         10    lifesaving way in which both the private and public

         11    sectors have stepped up to the plate in regard to

         12    HIV-AIDS.

         13              The achievements in the treatment of that

         14    disease are absolutely stellar and, you know,

         15    despite the fact that it continues to rage as a

         16    real epidemic, not only here, but in Africa and in

         17    Southeast Asia.

         18              The achievements really cannot be

         19    underestimated.  They have been phenomenal by

         20    anyone's imagination.

         21              What I'm interested in here is to see that

         22    academic medicine is, and the research enterprise


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          1    are protected in ways that are as little

          2    bureaucratic as possible, as least bureaucratic as

          3    possible, and as most effective as possible.

          4              The idea here, from my -- at least from my

          5    perspective is not to saddle either physicians or

          6    scientific researchers or academic medical

          7    institutions with massive amounts of compliance

          8    work.  But, instead, to make sure that the end

          9    product is that human subjects are protected in the

         10    most efficient, least intrusive, but most

         11    protective ways possible.

         12              CHAIRPERSON MARSHALL:  Thank you, Mark.

         13              Sandy?

         14              DR. CHODOSH:  I'm Sandy Chodosh.  I'm the

         15    President of PRIMAR, which is Public Responsibility

         16    in Medicine and Research.  It's an organization

         17    which, for the last 26 years, has been devoted to

         18    teaching people about the ethical and practical

         19    methods that need to be employed in doing both

         20    human and animal research.  It's been a long-term

         21    process, one which is never-ending.

         22              When we started this organization back in


                                                                  24

          1    1974, I thought that within ten years, we have

          2    taught everyone everything they needed to know

          3    about this, and we could move on to some other

          4    things.  The truth of the matter is that,

          5    obviously, it continues to be a changing scene

          6    requiring more and more work.

          7              Why am I in this business at all?  It's

          8    not a business; we're non-profit.  But it's based

          9    on the fact I spent 40 years as a clinical

         10    investigator.  I'm a pulmonologist.  I have been

         11    treating patients and doing clinical research for

         12    all those years.  I've had 28 years, actually, in

         13    PRIMAR business.

         14              I spent 14 years as an IRB Chair, and,

         15    actually, probably the toughest one is that I've

         16    spent 72 years trying to be an ethical human being.

         17              I have a lot of concerns about all this or

         18    else I still wouldn't be doing it.  A lot of it has

         19    to do with the fact that IRB's, although they try

         20    very hard to do their job properly, often don't

         21    know what the job is, and that this requires

         22    constant rethinking, reteaching, reaching out to


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          1    more and more people to try and get this

          2    understood.

          3              The main reason for that is that I've

          4    always been most concerned about the protection of

          5    human subjects, and it's not just because I'm an

          6    M.D., but because I think that it's essential to

          7    our whole process.

          8              Way back when, when I guess the 1970's,

          9    when they were reformulating some of the

         10    regulations, and I asked Charlie McCarthy at that

         11    time, "Why is it that we are -- the government does

         12    not come out and say that all human beings, in the

         13    United States, at least, who are going to be

         14    subject to research be protected, rather than just

         15    those who are federally funded?"

         16              And he said, "We have to take one step at

         17    a time."  I hope we're ready for the next step.

         18              I have concerns, as you do, about conflict

         19    of interest.  I think that it goes up and down the

         20    line, and we'll hear more about it today, and I

         21    hope that we can come up with some solutions for

         22    this.


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          1              I think that, very often, when we look at

          2    risk benefit, most IRB's are really not competent

          3    often to determine the benefit side because they

          4    don't understand the science adequately.  This is

          5    something we can correct by just teaching IRB

          6    administrators.  This has to be a change of how we

          7    do business.

          8              And I think one of my biggest concerns,

          9    which has been something that's bothered me more

         10    and more as the years go by, is there is an awful

         11    lot of research that is done involving a lot of

         12    human beings in which -- which does not advance

         13    science, information which never gets into the

         14    public domain because it's proprietary or because

         15    it was negative results, et cetera, or it wasn't

         16    going to look good on the CV.

         17              This is sort of why I've been working with

         18    PRIMAR and why I'm still here, and I think that all

         19    these issues need to be addressed, and we keep

         20    trying to address them, but we keep looking for new

         21    solutions.  So that's why I'm here, looking for

         22    solutions. 


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          1              CHAIRPERSON MARSHALL:  Thank you.  Thank

          2    you, Sandy.

          3              And because we have some leeway in terms

          4    of time, I'd like to ask you a question, if that's

          5    fair at the outset.

          6              We have had already some feedback

          7    regarding the composition of the committee and its

          8    charge, and the question I have for you is, in your

          9    experience with PRIMAR, how would you articulate

         10    concerns of research administrators?

         11              We have IRB Chairs here in full

         12    representation, but I think there is a bit of a

         13    concern that perhaps administrators don't have an

         14    active voice at the table, and I wonder whether you

         15    could speak to that for us.

         16              MR. BARNES:  Well, I think that there are

         17    some IRB administrators who have had a very broad

         18    experience of beyond just running an IRB and have

         19    had to deal -- they're part of the whole process of

         20    the human protection program; and as an integral

         21    part, in some ways, and not being represented

         22    probably is not a great idea.  They probably -- I


                                                                  28

          1    think -- now, whether the input can come from

          2    people like myself who, when I started out to be an

          3    IRB Chair, I was also the administrator.  There

          4    wasn't such an office in those days.

          5              I suspect Bob Levine here has had a

          6    similar experience, that if we go back far enough,

          7    we've had some of these experiences, but we're not

          8    up to date on the current problems which beset

          9    them, and I think that there are certainly real

         10    problems.

         11              Of course, I could think of probably five

         12    other kinds of people who should be at the table,

         13    also. 

         14              CHAIRPERSON MARSHALL:  Right.  Exactly. 

         15    And this might be a paradigm example and an

         16    opportunity to say that we are a public committee

         17    and that we will explore every avenue to make sure

         18    that we communicate bi-directionally with the

         19    public.

         20              And so I guess I would like to say, on the

         21    record, that any group that represents a particular

         22    interest or a profession that doesn't feel as


                                                                  29

          1    though it has had a voice at the table, we would

          2    like to hear from, and we're open and desperately

          3    seeking input from all because we do -- fairness is

          4    critical.

          5              And, as I said earlier, having everyone at

          6    the table and hearing those voices is critical to

          7    the integrity of our process and our outcome.

          8              Thank you, Sandy. 

          9              Elliot? 

         10              DR. DORFF:  I'm Elliot Dorff.  I have a

         11    Doctorate in moral theory from Columbia, and have

         12    done a lot of work in bioethics, as well as in

         13    other areas of social ethics during the course of

         14    my academic career.

         15              I'm a professor at the University of

         16    Judaism in Los Angeles, and I teach a course on

         17    Jewish law at the Law School at UCLA.

         18              I'm also a conservative rabbi.  Despite

         19    the name, conservative is the middle movement in

         20    Judaism.

         21              [Laughter.]

         22              DR. DORFF:  It's misleading.  Never mind.


                                                                  30

          1              I wrote an article about 20 years ago

          2    saying we should change our name because it's

          3    misleading, and, of course, was ignored, but what

          4    can I tell you?

          5              My interests are, in terms of this

          6    committee, really are, in part, philosophical, in

          7    part, well, if I may say so, religious;

          8    philosophically because -- well, it's the old

          9    Contian principle that if you cannot do something,

         10    then you never have to ask the question whether you

         11    should.  But, as soon as you can do something,

         12    then, indeed, you have to ask the question about

         13    whether you should.

         14              And the fact that we now can do much, much

         15    more in medicine and in social science, actually,

         16    than what we have been able to do in the past is a

         17    great boon to us, but it comes with much more moral

         18    responsibility, and also with much more -- with

         19    many more moral questions.

         20              The issues that are now raised in terms of

         21    privacy on the front page of this morning's paper

         22    and issues of genetic engineering and genetic


                                                                  31

          1    screening that are going to be -- that are present

          2    with us already today, it seems to me are major

          3    issues in terms of protecting peoples' rights, and

          4    at the same time, we want to be able to advance

          5    scientific research as much as we possibly can in

          6    order to be able to carry out -- and here is the

          7    religious part -- I think our sacred duty,

          8    actually, to try to improve this world and to

          9    improve the human condition in it.

         10              And so the real question then becomes, how

         11    do you balance that sacred duty with a sense that

         12    we want -- with another sacred duty of protecting

         13    human subjects who are part of that research, and

         14    those are my interests.

         15              CHAIRPERSON MARSHALL:  Thank you very

         16    much.

         17              Bob?

         18              DR. LEVINE:  I understand how to turn this

         19    on.  I don't know how to turn it off.  There's a

         20    green light on the left, though. 

         21              I was hoping to be sworn in before saying

         22    anything.


                                                                  32

          1              [Laughter.] 

          2              DR. LEVINE:  I've had a long collegial

          3    relationship with our Chairperson and with Greg,

          4    and I'm very optimistic after my first few

          5    conversations with Kate Gottfried.  So I think we

          6    have wonderful leadership and staff for this group,

          7    and if we don't do good things, it won't be because

          8    of that.

          9              I've been very interested in research

         10    involving human subjects for a long time.  In the

         11    late sixties, when IRBs were just getting going,

         12    all of my colleagues in clinical pharmacology were

         13    appointed Chairs of IRBs across the country.  There

         14    weren't enough clinical pharmacologists to go

         15    around, so some of them did more than one

         16    assignment.

         17              I got more specifically into the field of

         18    research ethics in the mid-1970's when I was -- I

         19    joined the National Commission for the Protection

         20    of Human Research Subjects -- that's an abbreviated

         21    definition -- as what they called the "Special

         22    Consultant," and their assignment to me was to


                                                                  33

          1    write what they called their background theoretical

          2    essays; things with such pompous titles as, "The

          3    Nature and Definition of Informed Consent," and,

          4    "The Boundaries Between Research and the Practice

          5    of Medicine," and things of that sort.

          6              Before that time, as I mentioned, I had

          7    been chief of the section of Clinical Pharmacology

          8    at Yale, and did a lot of work at the bench, and

          9    also research involving living human subjects.

         10              As I was thinking about what to say in my

         11    allotted time, I noticed that they snipped off the

         12    bottom of my paragraph.  Some people have found a

         13    way to cut me off. 

         14              [Laughter.]

         15              Dr. LEVINE:  And at the bottom of this,

         16    there was a reflection of some of my major recent

         17    interests, particularly in international research

         18    ethics.

         19              In the last few years, I was the

         20    consultant responsible for drafting the U.N. AIDS'

         21    guidance document on multi-national trials of HIV

         22    preventive vaccines. 


                                                                  34

          1              I was chair of the World Medical

          2    Association, what they call their, "Electronic

          3    Working Group," to propose a revision for the

          4    Declaration of Helsinki Process, which just ended

          5    about two months -- one and a half months ago.

          6              I was co-chair of the Steering Committee

          7    for CIOMS to write their international ethical

          8    guidelines in 1993, and currently I'm chair of the

          9    committee to revise those guidelines.  So I have

         10    had a longstanding interest in international

         11    research.

         12              As I look over our agenda, I can say that

         13    my interest in research ethics pretty much covers

         14    the whole topic of research ethics, but some of my

         15    specific recent activities really are a match for

         16    the current agenda.

         17              I've been chair of the external working

         18    group advisory to CDC on its human subjects

         19    protection program, and in that role, have had

         20    occasion to think, once again, about research

         21    topics that are very closely related to social

         22    science; in particular, much of the work done in


                                                                  35

          1    public health is a blend between some activities of

          2    social scientists and just tending to the public

          3    health in public health practices.

          4              Also related to social science is the -- I

          5    think a major current problem in how do we

          6    evaluate, review, and approve health policy

          7    research.  This is a topic that's dealt with in the

          8    current regulation simply by exempting it so that

          9    there is no -- there need not be any review or

         10    approval of this.

         11              And the day before I got my agenda book, I

         12    volunteered my opinion on the McWerb Internet chat

         13    group that I thought social science was not

         14    adequately covered by the current regulatory

         15    system, and that this lack of adequate coverage was

         16    not because they had not been represented by the

         17    national commission, and it was a different

         18    phenomenon.

         19              Pediatrics is on our agenda.  I finished,

         20    two days ago rewriting my chapter for the third

         21    edition of Mel Lewis' textbook on pediatric and

         22    adolescent psychiatry.


                                                                  36

          1              I'm very interested in the field of

          2    placebo controls and circumstances under which

          3    they're justified, and part of this interplays with

          4    my interest in the Declaration of Helsinki and its

          5    recent revision.

          6              And the final activity I want to mention

          7    is I'm interested very much in data monitoring, in

          8    data and safety monitoring boards, and in using

          9    them intelligently to take off a tremendous amount

         10    of the burden now borne by the Institutional Review

         11    Board.

         12              There's been a lot of criticism of

         13    institutional review boards lately as being overly

         14    burdened, and they are overly burdened.  But the

         15    majority of this burden, I believe, is in doing

         16    work that either doesn't need to be done at all, or

         17    that can be done much more effectively by other

         18    groups and individuals.

         19              I look forward to working with you, Mary

         20    Faith, and with all of our colleagues in this

         21    group.

         22              CHAIRPERSON MARSHALL:  Bob, thank you very


                                                                  37

          1    much.  You not only bring a wealth of knowledge and

          2    experience, but I think also within the field of

          3    research ethics, an institutional memory that

          4    perhaps the rest of us don't have, and that really

          5    will be vitally important.  Thank you.

          6              Abbey?

          7              MS. MEYERS:  Yes, thank you.

          8              I'm Abbey Meyers, President of the

          9    National Organization for Rare Disorders, which is

         10    known as NORD, and we're the patient advocacy group

         11    that work for enactment of the Orphan Drug Act in

         12    the area where there is no commercial interest or

         13    little commercial interest in development of any

         14    kind of treatment because the disease is rare.

         15              And the Orphan Drug Act, of course, has

         16    been very successful, but I got involved in this

         17    area because I'm the parent of three children with

         18    a genetic disease, and they have participated in

         19    research for more than 20 years.

         20              They are adults now.  Some of them have

         21    children of their own, but my youngest daughter

         22    still participates in research.  Any time Yale


                                                                  38

          1    calls her up and says, "Come on down.  We need an

          2    MRI," and she still goes down there.

          3              So I've seen it from both ends.  I've seen

          4    it from being a parent.  I've read those informed

          5    consent forms, and I had no idea what was going on

          6    beyond my own family's involvement until I got

          7    involved with other committees and I served on the

          8    RAC, the Recombinant DNA Advisory Committee for

          9    many years.  I think it was something like six

         10    years on that and about four years on the Gene

         11    Therapy Subcommittee before it was merged into the

         12    RAC.

         13              And my experience on the RAC was very

         14    telling in that in reviewing dozens and dozens and

         15    dozens of informed consent documents, I saw how bad

         16    they could be.  And every time we asked for it to

         17    be changed, to be understandable, to be written in

         18    a language that laymen could understand, we were

         19    told that the institution has, or the investigator

         20    and the sponsor have absolutely no authority to

         21    change the RAC, that only the IRB has authority to

         22    change an informed consent document.


                                                                  39

          1              Some of them were so bad, they said in

          2    this Phase I study, "We hope that this gene therapy

          3    will cure you," and there was no way we could

          4    delete that sentence or amend that sentence.  And

          5    so I participated in the committee to revise the

          6    RAC's standards for informed consent.

          7              I think that when I served on the RAC and

          8    we reviewed the OTC protocol in which Jesse

          9    Gelsinger died, that it was an extraordinary

         10    experience to see what happened in that case.  And

         11    that case involved nonconformance with existing

         12    rules, but it certainly pointed out why these

         13    things should be -- why the rules should be

         14    expanded for everybody.

         15              My particular areas of interest are why

         16    the rules cover only federally funded research and

         17    privately funded research is falling through the

         18    cracks.  And, as a matter of fact, we don't even

         19    know how many thousands of people are falling

         20    through those cracks.

         21              I'd like to see the federal regulations

         22    extended to all research, and in view of the


                                                                  40

          1    Washington Post series that's going on now, we

          2    certainly need those rules to extend to overseas

          3    research that's funded by American companies.

          4              My particular interest right now, also, is

          5    to assure that the current -- it's not just the

          6    Tuskeegee experiment.  We're still seeing Tuskeegee

          7    experiments go on, and the latest one is this issue

          8    on the west coast of the people who are getting a

          9    thousand dollars to drink polluted water in order

         10    to prove that polluted water has no health effects. 

         11    Something should be done to stop that, and it

         12    appears from the brief overview that the federal

         13    government is going to have no authority to step in

         14    there.

         15              So in seeing this from the patient's point

         16    of view and knowing how much research has to be

         17    done, we need to do everything we can to encourage

         18    research and not to overly burden investigators. 

         19    But we need private industry to step up to the

         20    plate and act with moral authority.

         21              Thank you.

         22              DR. KOSKI:  Ms. Meyers, thank you very


                                                                  41

          1    much.

          2              This is going to be a very brief

          3    introduction, but simply the reason we're here is

          4    because of Secretary Shalala.  Secretary Shalala

          5    has been just an absolute stalwart leader in this

          6    entire effort.

          7              We are here to fulfill the mission that

          8    she has started, and without further discussion of

          9    that, it gives me great pleasure and a real honor

         10    to introduce Secretary Donna Shalala. 

         11              SECRETARY SHALALA:  Thanks very much,

         12    Greg.  Thank you.

         13              I'm very happy to be here with all of you. 

         14    Let me -- I don't know whether Ruth Kirchstein or

         15    Jane Haney have gotten here yet, but they'll be

         16    here eventually.  I know their brains are here

         17    because I see all their senior people. 

         18              [Laughter.] 

         19              SECRETARY SHALALA:  My brain is here, too.

         20              You know, some of us have made our careers

         21    simply hiring people that are smarter than we are

         22    and making sure they have the resources and the


                                                                  42

          1    strategy to get their work done.

          2              Let me acknowledge Senator Edward Kennedy

          3    of Massachusetts, who will be speaking to you right

          4    after I finish, the acknowledged leader on health

          5    care in the Senate, one of the great legislators,

          6    one of the great advocates for scientific research

          7    and public health in this country, a very good

          8    friend of both the Department and the National

          9    Institutes of Health, all of the science and health

         10    agencies in this government, and every kid who ever

         11    set foot in this world.

         12              As you know, I'm actually in my final

         13    weeks of an eight-year run as the Secretary of

         14    Health and Human Services, and about to go back to

         15    the Academy to take on these issues --

         16              Ruth Kirchstein just came in. 

         17              -- directly, myself.  So let me start by

         18    simply congratulating and thanking all the members

         19    of the National Human Research Protections Advisory

         20    Committee.  In particular, let me thank our

         21    Executive Director and Mary Faith Marshall, who's

         22    going to chair this committee for us. 


                                                                  43

          1              Professor Marshall, it's nice to see you.

          2              This is really important.  When we first

          3    transferred the office to the Office of the

          4    Secretary, we were under withering criticism from

          5    the Hill who thought, you know, the fox is going to

          6    protect the chicken coop, and this is not going to

          7    work; that you just -- you're transferring too much

          8    authority, and most importantly, asking academic

          9    institutions to do some of this may be the wrong

         10    way to go.

         11              I did not believe that, in part, because I

         12    come from the Academy, but in part, because I

         13    didn't see the option to us strengthening what we

         14    had.

         15              But this is really important:  As of the

         16    last budget, we've increased the funding for NIH

         17    alone by 50 percent. 

         18              This country's steady commitment to basic

         19    science, to clinical research is now firm, firmly

         20    non-partisan.  Not even bi-partisan; non-partisan. 

         21    And we understand the relationship between those

         22    investments and not only the quality of health care


                                                                  44

          1    around the world, but also the dynamic that exists

          2    between the scientific community and the economic

          3    health of our own country, as well as countries

          4    around the world.

          5              Everything that we said we needed, for

          6    those of us that came from the Academy, steady

          7    increases, investments, in training have now been

          8    put in place, but -- which means -- and that

          9    reflects public confidence.  It's not just elected

         10    officials.  It's not just leaders of the Department

         11    that were committed to scientific research or a

         12    president that was committed before we came here. 

         13    It's more important than that.

         14              We have public confidence in scientists. 

         15    Scientists are heroes these days in this country.

         16              That can easily be undermined.  If our

         17    scientific institutions and if the leaders in

         18    science -- if the leaders of the institutions that

         19    are responsible for the great infrastructure,

         20    scientific infrastructure that we have in this

         21    country aren't careful in how that research is

         22    conducted.


                                                                  45

          1              And if you want to see what happens in

          2    this world when you don't have institutions that

          3    are trusted, then look at Europe as they try to

          4    handle some very complex scientific issues that

          5    involve human health and animal health without both

          6    the scientific institutions and the leaders in

          7    science that their countries have not invested in

          8    the way we have invested in.

          9              So what you do here is really important,

         10    but how your colleagues throughout this country and

         11    throughout the world behave is important.

         12              We have put in place everything that

         13    everybody told us we needed to put in place.  We've

         14    put the office in place.  We've recruited a first-

         15    class leader for that office.

         16              I personally recruited Greg Koski.  I

         17    promised him lots of things, most of which I will

         18    have delivered on before I left.

         19              I also personally recruited Harold Varmas,

         20    Jane Haney, and all the other scientific leaders,

         21    Jeff Copeland, who head the other scientific

         22    institutions, and I transferred to them the great


                                                                  46

          1    complaint about NIH and all these agencies is they

          2    never had the authority for personnel, never had

          3    the resources to make the decisions.

          4              We have done all of that.  They have the

          5    authority to make decisions.  They have the

          6    resources that they need.  But the oversight in how

          7    we conduct this research, and in particular, how we

          8    protect human subjects, is not something, as Greg

          9    has carefully taught me, that we can sort of fix. 

         10    It's putting in place a change in culture and a

         11    system and a respect for human subjects, but also

         12    for the American people that have invested in this

         13    kind of research.

         14              It is the most fundamental ethical issues

         15    that we struggle with because we want to conduct

         16    the research, but simultaneously, we want to make

         17    sure it's conducted in the most ethical manner as

         18    possible.

         19              And if it's not, then those people that

         20    don't want to do it the right way ought to get out

         21    of the business, and we're going to be as tough

         22    minded as we have been on the other parts of the


                                                                  47

          1    Department.  And you can see this department and

          2    our scientific institutions getting tougher and

          3    tougher because we know what's at stake. 

          4    Fundamentally, human health, but also the

          5    confidence that our people have in this research.

          6              And we have been in and we have entered

          7    this golden age of biomedical research, and to

          8    undermine it now would be a human tragedy of

          9    unbelievable dimensions.  I get it, obviously.

         10              And everything, every power that I have

         11    had, I have put in place with outstanding leaders

         12    and made the investments, and now, it's up to you. 

         13    I want you to be tough-minded, I want you to hold

         14    our feet to the fire; I want you, in particular, to

         15    hold our feet to the fire in transitions because

         16    things fall between the cracks in transitions.  And

         17    you can't guarantee that every leader you're going

         18    to get comes from a major research university and

         19    sort of understands this business that we're in.

         20              So it's up to us to put an infrastructure

         21    in place that really makes a difference.  And I

         22    want us to have zero tolerance for the


                                                                  48

          1    mismanagement, whether it's an individual scientist

          2    or the heads of the institutions.  And more and

          3    more, we need to hold the heads of institutions.

          4              As I have said to college presidents in

          5    this country, they pay more attention to the NCAA

          6    rules and to violations in that area than they do

          7    to their infrastructure on oversight of scientific

          8    research.

          9              The leaders of America's research

         10    universities are far more knowledgeable about NCAA

         11    violations than they are about IRBs and what kind

         12    of investments they're making, and whether to

         13    overload it or whether to not overload it.

         14              You have a lot of responsibilities, and

         15    they've written me some very nice talking points to

         16    go through them.  But your charge is to be as

         17    tough-minded as you possibly can be and understand

         18    what's at stake here.

         19              And it's not just the individual

         20    reputations of scientists.  It's science itself and

         21    the quality of science and the quality of health

         22    care.


                                                                  49

          1              So consider yourself fully charged, and I

          2    will make sure before I leave that Greg has

          3    everything that he needs.  He's a first-class

          4    leader, the right man at the right time.

          5              And basically, I've asked Greg to come

          6    here for enough years to get this all set up and

          7    then to recruit his successor.  I well know that. 

          8    But, again, it's changing the culture.

          9              And let me assure you, it is not just the

         10    research institutions.  Our own institutions within

         11    the government are not holding themselves to high

         12    enough standards.  And Ruth and Jane and Jeff have

         13    absolutely assured me that they have a long way to

         14    go in their own institutions, so no one gets off

         15    the hook here.

         16              So I thank you for your service,

         17    particularly at the beginning as we get this going,

         18    and I will do everything I can between now and

         19    January 20th and afterwards to make sure that all

         20    of you have all of the support you could possibly

         21    have.  And Greg has a very thick skin, but he's

         22    also very responsive, and he's going to have


                                                                  50

          1    regular meetings with me.  No one gets regular

          2    meetings with me between now and January 20th

          3    except for Greg Koski, which gives you some sense

          4    of what a high priority I've put on all of this.

          5              So thank you very much.  Thank you. 

          6              [Applause.] 

          7              SECRETARY SHALALA:  I have to get going. 

          8    I finally got the President to come to the

          9    Department to announce the privacy regulations.  I

         10    told him if he didn't come pretty soon, I was going

         11    to begin to think that we were like Nebraska, you

         12    know.  

         13              [Laughter.]

         14              SECRETARY SHALALA:  I don't know whether

         15    any of you have any questions for me. 

         16              Professor Marshall?

         17              CHAIRPERSON MARSHALL:  I don't have a

         18    question, but I do want to thank you.  We are very

         19    mindful of the fantastic opportunity that you have

         20    given us, and we plan to be excellent stewards

         21    relative to our charge, and to make, we hope, some

         22    meaningful and wholesale reform.


                                                                  51

          1              SECRETARY SHALALA:  Great.  Surely.

          2              CHAIRPERSON MARSHALL:  So thank you so

          3    much. 

          4              SECRETARY SHALALA:  Thank you very much.

          5              [Applause.] 

          6              DR. KOSKI:  Okay.  Let me tell you now

          7    that Madam Secretary has left that it's nothing

          8    short of remarkable that she was able to be here

          9    with us today, given all that's going on downtown. 

         10    I think it truly is a mark of her real commitment

         11    and dedication to this effort, and we're very

         12    grateful to have her here.

         13              Now, it gives me enormous pleasure also to

         14    introduce to all of you, Senator Edward Kennedy. 

         15    As you know, Senator Kennedy has been in this game

         16    since day one.  It was shortly after the

         17    revelations of the Tuskeegee study, when Senator

         18    Kennedy was brand-new to the effort, that he

         19    actually began with holding hearings that led to,

         20    ultimately, the National Research Act, the entire

         21    National Commission.

         22              He has been a steadfast advocate for both


                                                                  52

          1    research and doing research right.  It's truly an

          2    honor, a very, very special honor to have the

          3    Senator with us today.

          4              Senator Kennedy? 

          5              SENATOR KENNEDY:  Thank you.  Thank you

          6    very much, Greg.

          7              As perhaps very few of you know, and

          8    there's no reason that you should, Greg and I have

          9    something in common.  We both went to Harvard

         10    College and we both played football at Harvard.  I

         11    played left end.  Some people say that's where I

         12    got my political philosophy.  

         13              [Laughter.] 

         14              SENATOR KENNEDY:  I'll let Greg speak for

         15    himself, but he was a great player.

         16              I was listening to the Secretary, and I'm

         17    grateful for her remarks and her overall assessment

         18    is obviously right on target to what we're

         19    certainly hoping for in the Congress.

         20              Being with a group like this and talking

         21    about the subject reminds me a little bit about the

         22    person that survived the Johnstown flood, and there


                                                                  53

          1    was only survivor of the Johnstown flood.  And

          2    finally that survivor of the Johnstown flood went

          3    to his eternal reward in heaven, and St. Peter at

          4    the gate said, "You've been very good and you're

          5    entitled to any wish that you want."

          6              And he said, "I'd like you to get all the

          7    angels and archangels together and let me tell

          8    everyone how I survived the Johnstown flood."

          9              "Fine," said St. Peter, and brought

         10    everyone together and introduced this person.  And

         11    as St. Peter was walking back to the survivor, he

         12    said, "I just want you to know that out in your

         13    audience is Noah."

         14              And I feel that way today, looking around

         15    this room at many of those who have been good

         16    enough to come on in and brief me over a period of

         17    time on many of these issues that we have been

         18    faced with and continue to be faced with.

         19              Let me really pick up a little bit on the

         20    themes that Secretary Shalala outlined.  And I

         21    think they really underline what I think are really

         22    the most important challenge that all of you are


                                                                  54

          1    going to have, and that is how are we going to

          2    ensure that science is going to control these

          3    judgments and decisions and not the politics.

          4              I was thinking in coming out here, the

          5    hearings that we had -- we had 11 days of hearings

          6    some 30 years ago and the first hearings on the

          7    Tuskeegee syphilitic study.

          8              And then we had the reviews of the

          9    sterilization of the Ralph girls.

         10              And then, of course, we read the Supreme

         11    Court decisions about that, and that is an ominous

         12    indicator as well.

         13              And then we had the studies of Depo

         14    Provera in Tennessee.  And then we also had the

         15    hearings -- difficult, very, very difficult

         16    hearings into the CIA, where they gave various

         17    drinks -- laced various drinks with hallucinogenic

         18    drugs.  And I don't think I'm certain to a moral

         19    certainty that the tragic loss, that it was never

         20    able to be definitely proved of a really

         21    outstanding agent who became disoriented with the

         22    consumption of the hallucinogenic drug and then


                                                                  55

          1    woke up the next day and thought somehow that they

          2    had violated the secrecy, and went to New York and

          3    threw himself off a hotel building and killed

          4    himself.  And there were virtually no guidelines at

          5    that time.

          6              And then I remember it was about this time

          7    that my sister, Eunice, as a family that's been

          8    enormously interested in the problems and the

          9    challenges of ethics dealing with mental

         10    retardation, and particularly a case that took

         11    place over at Johns Hopkins where a child, a baby

         12    was born with a correctable health hazard, which

         13    about 95 percent success in being able to cure, to

         14    fix this.  But it did take a medical procedure, and

         15    the parents refusing to have it because they were

         16    not interested in having a mentally retarded child. 

         17    And so they left that child for about 23 days until

         18    finally the child died.

         19              And the various ethical challenges that

         20    were there.  The doctors had said, "Well, if we go

         21    and do this in spite of the parents, we are part of

         22    that 10 percent, then we put at risk the whole


                                                                  56

          1    hospital and its whole procedures."  And the nurses

          2    facing similar kinds of dilemma.

          3              And this extraordinary ethical challenge

          4    that we are there for all of those that we are

          5    serving and caring, and parents who were enormously

          6    troubled with a large family and a very small

          7    income, and a country that still doesn't provide

          8    health insurance.

          9              So these were really the background where

         10    we established the initial panel, and it was a very

         11    significant group of men and women that served on

         12    the panel.

         13              And the interesting aspect for me, as a

         14    legislator, is it had no powers whatsoever than the

         15    recommendations that they made.  They published

         16    their recommendations in the Federal Register, and

         17    every one of their recommendations that they made

         18    were implemented.  Not one was turned down,

         19    although they had no authority and power other than

         20    the fact of their consideration and their very

         21    thoughtful consideration; the way they went about

         22    trying to come to grips with the various kinds of


                                                                  57

          1    ethical issues, and then promulgating the rules and

          2    regulations.

          3              And it was really an extraordinary study

          4    about how government can work and does work, and at

          5    times when you really wonder when we saw that it

          6    couldn't go ahead even with the routine kinds of

          7    accountability that I think many of us feel, having

          8    been around for a long time and seeing so many of

          9    the nation's problems turned over to commissions

         10    and the commission study for two years, and the

         11    closets filled with these recommendations and

         12    without being implemented.

         13              And one that sees that the contrast to

         14    that is, of course, the British system where the

         15    Parliament has to act, and act within 90 days with

         16    the recommendations, and the government has to give

         17    clear explanations why they're not making the

         18    recommendations, or otherwise, the government has

         19    to embrace them.  So you get accountability on many

         20    of the challenges.

         21              Well, that's along the edges of it.  But I

         22    was mindful of that, particularly coming through


                                                                  58

          1    the Vietnam War and civil rights challenges and all

          2    the rest, and really wondering whether we had

          3    really done something, but it had been done.

          4              And then I saw the politicization, that

          5    basically authorization, we were unable to get it

          6    and we are already beginning to see the pressures

          7    then we're coming in terms of politics of it.

          8              And then we went through a long period of

          9    time in the naming of the various panel.  And we

         10    could just see really the ends of what was

         11    happening to a panel because the test was there was

         12    whether they were pro life or pro choice, there

         13    were going to be the recommendations that the first

         14    thing that the panel was going to deal with was

         15    going to be the abortion issue.

         16              And, finally, compromises that were worked

         17    out which Lo Wiker, very much involved in, was very

         18    caring about to this whole issue, and actually,

         19    Vice President Gore was interested and concerned

         20    about this, as well, as a person that was involved

         21    in it.

         22              But, eventually, we get the completion of


                                                                  59

          1    it, but since it was so deadlocked at that period

          2    of time and there was such a real exhaustion, or

          3    really tiring and the Congress never appropriated

          4    it, then it effectively dissolved.

          5              And I have seen, as the Secretary has

          6    mentioned, what happens when we have the politics

          7    interfering with sound science.  And in our great

          8    challenge in the most recent times was on the whole

          9    AIDS issue.  And we were able to really move, I

         10    think, for the first time sort of beyond it.

         11              We had it for a while in terms of the

         12    Americans With Disability Act, and anybody that

         13    reads back on through that debate, even though it

         14    was only one day in the United States Senate, look

         15    in the late afternoon when Jesse Helms brought up

         16    the Encyclopedia Cyclothropic -- is that the --

         17    Cyclothropic Encyclopedia -- and talks about mental

         18    aberrations in sexual activity.  And there's about

         19    ten pages in there of things I never even heard of

         20    or possibly even thought of or whatever.

         21              And Jesse Helms offered an amendment,

         22    tearing those pages out and saying that anything


                                                                  60

          1    like this will not be protected under the Americans

          2    With Disability Act, and it was just going to stop

          3    the whole legislation.  Anybody that was going to

          4    take that on was going to probably end up with the

          5    five or ten votes on it.

          6              And Dr. Roper, actually, was the one that

          7    was actually representing the administration at

          8    that time, went out and worked with Jesse Helms. 

          9    And he took and said, "Okay.  We'll take a quarter

         10    or a third."  And a quarter and a third, they were

         11    included in it.  Absolutely no signs whatsoever. 

         12    Senator Helms has no idea what they were at the

         13    time.  No one else does, either, and I'm sure the

         14    courts are confused what we intended to do at that

         15    time.  

         16              [Laughter.] 

         17              SENATOR KENNEDY:  But that was an

         18    indication.  We saw it in the AIDS debates for a

         19    period of time until we really got beyond that

         20    thing with the Brian White.  And we tied that on

         21    into the fact that it was hemophilia, which it was

         22    with regards to the Brian White.  But we were able


                                                                  61

          1    to make some progress in terms of the AIDS, and

          2    then we moved forward on it.

          3              But I am very, very hopeful that we are

          4    going to, with this panel, be able to try and find

          5    ways, we're going to be facing some enormously

          6    complex challenges in the Congress.

          7              We faced them in terms of the utilization

          8    of fetal tissue, and we're around the corner on

          9    stem cell research, which we're very, very familiar

         10    with.

         11              And as we move through with these

         12    extraordinary potential breakthroughs in these wide

         13    range of different areas, we're going to constantly

         14    come back to the areas of science, ethics and

         15    politics.

         16              And to the extent that this panel can give

         17    us the guidance because of the strength of their

         18    credibility and the power of their concern and the

         19    legitimacy of their presentations to keep us

         20    focused on the real ethical issues on this in ways

         21    which could commend the broadest range, and in this

         22    sense, use positively the political landscape,


                                                                  62

          1    we're going to have made incredible, incredible

          2    progress.  And that would be something that I would

          3    be very hopeful of as we look down the line towards

          4    the future.

          5              We have our job to do, obviously, as

          6    legislators, to try and give support and help in

          7    justifying it.  But we want to, as the Secretary

          8    mentioned, and I commend her for the establishment

          9    of and the excellence of the panel, and I commend

         10    her for her leadership over the period of time in

         11    the HEW and the range of new -- the activities that

         12    she has worked out recently in the coverage of

         13    children, and the particular challenges that they

         14    have just issued with Social Security, which is

         15    extraordinary and going to be more inclusive, and

         16    for the promulgation of these privacy

         17    recommendations, which are just so important.

         18              We were unable to get that in the Congress

         19    in the last time, and the principal reason was the

         20    medical records of teenage girls, whether they were

         21    going to -- how protected were they going to be. 

         22    That was one of two items that basically halted us


                                                                  63

          1    from moving ahead in the very important area of

          2    public policy.

          3              And that is why we have to be so wary of

          4    this.  Hopefully, as a nation, we're going to

          5    mature significantly.  This won't be as much of a

          6    challenge, but it certainly is today.

          7              Finally, I was going to mention several of

          8    the areas that the Secretary mentioned, a number of

          9    the things that Greg has talked about in terms of

         10    the overwork, the IRBs and the consolidation, using

         11    these universities in ways which can eliminate some

         12    of the duplication, the range of different

         13    paperwork that are out there, things that we ought

         14    to focus just generally.

         15              I am concerned, as was mentioned in the

         16    questions, about our drug companies and the actions

         17    overseas.  We went through a long debate a number

         18    of years ago with the FDA whether we were going to

         19    permit various products that were not going to be

         20    consumed here in the United States to be actually

         21    exported to be used overseas.  That was a big issue

         22    that we had.


                                                                  64

          1              And I happened -- I changed my position

          2    from one that didn't think that they should be to

          3    one that thinks that they ought to be able to be

          4    used, and that ran into all kinds of ethical

          5    questions, obviously, because if we're going to

          6    have a breakthrough in terms of a lot of different

          7    diseases that can make a difference in terms of

          8    curing these matters overseas, we're not going to

          9    be able to test them here in the United States.  So

         10    we're going to have to move them overseas, and we

         11    can have a very positive impact in terms of the

         12    health of people overseas. 

         13              So this is right on the deck, front and

         14    center, whether we like it or not.  I like it

         15    because, I think, I've always felt that the United

         16    States missed the opportunity, number one, in the

         17    export of food overseas.  We spent $35 billion last

         18    year -- $35 billion to keep our farmers happy, and

         19    we still don't send food overseas.

         20              And one thing we know how to do is to grow

         21    food, and the other thing we can do is deliver a

         22    product any place in the United States overnight,


                                                                  65

          1    thank you, Federal Express.  Well, we ought to be

          2    able to -- well, that's a different issue at a

          3    time.

          4              But we're going to have with these

          5    breakthroughs that are going to be out there real

          6    opportunities.  So what was mentioned here in terms

          7    of overseas is right on our plate and we have to do

          8    it.

          9              And secondly is what was mentioned also in

         10    the polluted water in California.  We do know in

         11    these areas that are related, not only in the FDA,

         12    but also in the EPA, and what is happening in the

         13    private, and the growth of those.  We cannot avoid

         14    those.  We have to get focused because it's only a

         15    matter of a year or two years we're going to be

         16    faced with these extraordinary challenges, and

         17    people are going to say, "What in the world did we

         18    ever do about that, and what was that conference --

         19    what were thinking about out in Bethesda when they

         20    had this conference and where we're going to do?"

         21              And we're going to face some serious

         22    challenges on that when we try to take the


                                                                  66

          1    administration to do something, working with Jane

          2    Haney on safe food.

          3              Because of the dramatic increase in foods,

          4    we are looking to trying to get some examination

          5    overseas of what kind of pesticides are being used

          6    in the various foods.  And the grocery

          7    manufacturers came down hard on us, and we're

          8    basically stalemated on that in spite, with all the

          9    potential dangers that that has with a reduced

         10    enforcement group, which we're seeing cutbacks, and

         11    the dramatic increase in terms of the consumption

         12    of food that's being produced overseas.  It's just

         13    inevitable we're going to face other kinds of

         14    challenges.

         15              So we need to try and focus what has been

         16    presented by the Secretary.  Many of us believe

         17    that this is just a defining aspect, not only in

         18    terms of science, but what our society is about,

         19    and you're at really the cutting edge.

         20              And not to do it right I think would be

         21    something that isn't even something that any of us

         22    can consider.  To do it right is just an incredible


                                                                  67

          1    kind of a challenge, but it's one that I know that

          2    those that are here on the panel and those that I

          3    know that are out there and have thought about this

          4    and are in different centers of learning that are

          5    attempting to guide us, we need this.

          6              Members of Congress and basically the

          7    executives and the Congress, we're generalists. 

          8    I've been in the business for some period of time. 

          9    But we have some knowledge and understanding in

         10    areas where we spend some time in education or in

         11    health care, in other kinds, the civil rights

         12    knocking down the walls and the other types,

         13    poverty programs.

         14              But this is an area that we are basically

         15    generalists, and if we have powerful incentives

         16    around that are -- which we used to have --

         17    remember where they had that -- I think it was

         18    called the PS -- the NIH4.  It was up in Cambridge. 

         19    And we had Al Balucci was out there and declared an

         20    independent state in Cambridge, Massachusetts -- 

         21              [Laughter.] 

         22              SENATOR KENNEDY:  -- and won the election


                                                                  68

          1    up there because he talked about the creepy

          2    crawlies that were going to take place in terms of

          3    DNA research and carried in Cambridge,

          4    Massachusetts, which I just got the highest

          5    percentage from in this last election. 

          6              [Laughter.]

          7              SENATOR KENNEDY:  So we all have to be

          8    alert and we all have to be on our guard.

          9              But we thank you so much for all the time

         10    and the consideration.  I'm grateful for the chance

         11    to come out, and I want you to know you have a real

         12    ally.  We want to work very closely with you.  I

         13    know I speak for our committee, Republican and

         14    Democrats, our committee.  Our Human Resource

         15    Committee is incredibly interested in this.  We

         16    want to take your recommendations.  We want to be

         17    constructive and we want to be positive, and we

         18    want to be helpful.  And I'm thankful to Greg for

         19    letting me come by and say, "Hello."

         20              Thank you very much. 

         21              [Applause.]

         22              CHAIRPERSON MARSHALL:  I am going to ask


                                                                  69

          1    one question of the Senator, and that is this: 

          2    First, I want to thank you for establishing the

          3    legacy that has led to the genesis of what we are

          4    all about.  And we do plan to take issues, head on.

          5              We are ethicists, and our job is -- we are

          6    not all ethicists, but our job is ethical in

          7    nature, and we will look things right in the eye.

          8              Can you give us some advice that is not of

          9    a partisan nature, but that might help us in terms

         10    of being as effective as we can during a change of

         11    administration? 

         12              SENATOR KENNEDY:  Well, I think it's not

         13    -- one thing I might suggest is, as soon as we have

         14    the new Secretary for HEW, we ought to try and you

         15    ought to, to the extent maybe get some kind of

         16    meeting on it.  We will let them know we are going

         17    to ask a lot of questions about it, and you can be

         18    helpful for us in terms of developing the questions

         19    and be helpful to them.

         20              I don't look at confirmations as a game to

         21    try and capture people, but to try and develop

         22    their own thinking where they get committed on


                                                                  70

          1    policy.  Then we hold them accountable.

          2              And I think there may be an area in there

          3    where those, where Senator Frist or Senator

          4    Jeffords and myself can lay the groundwork through

          5    questions so that we get an administration on the

          6    record, and also indicate, whoever that person is,

          7    that these are questions going to be asked.  They

          8    can come to you and ask for the answers.

          9              And this may sound rather rudimentary, but

         10    it helps.  You get them thinking about these

         11    things.  Whoever is going to get it is going to

         12    start thinking about this and understand that

         13    people are serious about it.

         14              And I'd be more than glad to work in a

         15    constructive way with you, and I'll mention this to

         16    Senator Jeffords.  And I'd be glad to sit down with

         17    either Greg or with the group here, prior to the

         18    time of those hearings, and get to your

         19    recommendations and questions to ask.

         20              And I'd be glad when the nominee comes by

         21    in the courtesy call to indicate that this is

         22    something that you'd like to meet with them on


                                                                  71

          1    prior to time.  Then I'll come by and say, Hello,

          2    and I'll mention that if you decide that you'd like

          3    to proceed in that way.

          4              I think that that could get us started in

          5    an important way.  It's an excellent question you

          6    asked, and maybe there are other things that we

          7    could think of.  But I think that could be a useful

          8    start.

          9              CHAIRPERSON MARSHALL:  Thank you.  Thank

         10    you. 

         11              SENATOR KENNEDY:  Good.  Thank you all. 

         12    Thanks a lot. 

         13              [Applause.] 

         14              DR. KOSKI:  Well, obviously, in trying to

         15    coordinate these kinds of events on a busy day,

         16    flexibility is an asset, and I appreciate the

         17    flexibility that you all have shown.

         18              I'm sorry that Dr. Kirchstein from NIH,

         19    unfortunately, had to leave early.  I was hoping to

         20    introduce her and if she wished to make a remark,

         21    we would have benefitted from that, no doubt.  But

         22    she has been an absolute, again, stalwart


                                                                  72

          1    companion, as have all the colleagues in NIH, in

          2    working through this, as well as at the other

          3    agencies, you know, with Bern Schwetz and David

          4    Lepay from FDA, and for the whole crew. 

          5              You know, we've done a lot here in the

          6    last few months.  There's still a lot to do, but,

          7    you know, we'll keep pushing on that.

          8              I think what we would do at this point, if

          9    it's acceptable to the Chair, would be to sort of

         10    backtrack a tiny bit in our agenda to do the

         11    business portion of actually swearing in the

         12    committee so that we can do work, which is required

         13    under the federal regulations.

         14              So, Madam Chairman, if you wish to do

         15    that, we can proceed.

         16              CHAIRPERSON MARSHALL:  Thank you.  I

         17    certainly do.

         18              Yes.  Thank you.  Jackie Coleman is here. 

         19              MS. COLEMAN:  Hi.

         20              DR. KOSKI:  It actually takes about two

         21    and a half days to complete the forms, so --

         22              MS. COLEMAN:  Good morning.  My name is


                                                                  73

          1    Jackie Coleman, and I work for the Department of

          2    Health and Human Services, Personnel Office in our

          3    downtown office.

          4              This morning, I will be administering the

          5    oath of office.  I would like for everyone to stand

          6    at this time.  We will read Section A, starting

          7    with the line above it.

          8              When I say, "I," I want you to say your

          9    name.  If there is anyone here that does not swear,

         10    you may say, "affirm," okay?

         11              Raise your right hand.  I -- 

         12              [Chorus of members.] 

         13              MS. COLEMAN:  -- do solemnly swear or

         14    affirm that -- 

         15              [Chorus of members.] 

         16              MS. COLEMAN:  -- I will support and defend

         17    the Constitution of the United States against all

         18    enemies --

         19              [Chorus of members.] 

         20              MS. COLEMAN:  -- foreign and domestic --

         21              [Chorus of members.] 

         22              MS. COLEMAN:  -- that I will bear true


                                                                  74

          1    faith and allegiance to the same --

          2              [Chorus of members.] 

          3              MS. COLEMAN:  -- that I take this

          4    obligation freely --

          5              [Chorus of members.]

          6              MS. COLEMAN:  -- without any mental

          7    reservation or purpose of evasion --

          8              [Chorus of members.] 

          9              MS. COLEMAN:  -- and that I will well and

         10    faithfully discharge the duties of the office on

         11    which I am about to enter --

         12              [Chorus of members.] 

         13              MS. COLEMAN:  -- so help me God.

         14              [Chorus of members.] 

         15              MS. COLEMAN:  Okay.  You may be seated.

         16              There's one that didn't sign that I have

         17    to sign for.

         18              CHAIRPERSON MARSHALL:  -- to do now that

         19    we have finished being charged and important

         20    housekeeping duties is to continue with the

         21    introductions of the members of the committee, and

         22    we're doing well on time.


                                                                  75

          1              If we have a few extra minutes prior to

          2    our break, which I assure you we will have in a

          3    timely fashion, I would like to ask Robert Cooke

          4    Deagan of the Institute of Medicine to tell us

          5    about a project that the OHRP has charged the

          6    Institute of Medicine with that may have some

          7    bearing or relationship to the work of the

          8    committee so that the members will understand the

          9    nature of that charge.  So we will do that, if we

         10    have time.

         11              And, Bob, thank you so much for being

         12    willing to do that with no notice. 

         13              Abbey, I don't know whether you were cut

         14    short, but I just wanted to say, if there was

         15    anything else that you had wanted to share with us,

         16    at this point, I'll give you the opportunity to do

         17    so.

         18              All right.  Thank you very much.  And I

         19    did pay particular attention to -- I heard what you

         20    said about having federal regulations that apply in

         21    a somewhat universal manner.  So -- and I think

         22    that's vitally important, and it's obviously


                                                                  76

          1    something that the committee will need to take a

          2    long, hard look at.

          3              Mary? 

          4              DR. PELIAS:  My name is Mary K. Pelias. 

          5    With regard to first names, I do go by Mary Kay,

          6    and you might imagine, I take a good deal of flack

          7    for that. 

          8              CHAIRPERSON MARSHALL:  Well, I'm a Mary

          9    Faith, and I can relate wholeheartedly to that.

         10              DR. PELIAS:  I grew up in the deep south

         11    in the forties and fifties at a time when

         12    photographs and reports of lynchings appeared on

         13    the front page of the newspaper.

         14              In the early sixties, I was a student in

         15    Germany and worked in an anatomy department where

         16    collections of specimens came from very dubious

         17    origins.

         18              After that, I trained in graduate school

         19    in genetics, and finally, became specialized in

         20    medical genetics.  And I've been on the faculty at

         21    the LSU Medical School for the last 25 years.

         22              My professional interests in this area, in


                                                                  77

          1    these areas began in the early 1980's with the Baby

          2    Doe cases that Senator Kennedy alluded to, Baby Doe

          3    cases that raised questions of autonomy and who

          4    should make decisions for these unfortunate infants

          5    who are born with severe defects.

          6              In the 1980's, I also was intrigued by the

          7    litigation that arose in wrongful birth and

          8    wrongful life, and the questions of duty to

          9    disclose information to people who might have

         10    children with severe birth defects, and who should

         11    make these decisions and value judgments.

         12              I then went back to law school for

         13    interests in constitutional law and tort law and

         14    medical malpractice and family law.

         15              I'm here because I have a serious interest

         16    in the new genetics and in possible regulations

         17    that we might want to include in the Code of

         18    Federal Regulations.

         19              Particular questions in the new genetics

         20    these days have to do with family histories and

         21    privacy.  These have come up in the last couple of

         22    years, with questions of access to tissue


                                                                  78

          1    collections that researchers would like to get

          2    into, but for which they have no consent from the

          3    donors of the samples.

          4              Questions about historical collections,

          5    how we should treat them, as opposed to how we

          6    should allow access to new collections and obtain

          7    consent for the use of new collections as opposed

          8    to old collections.

          9              In particular, I've spent a lot of time on

         10    questions of using newborn screening sample

         11    collections for future genetic studies, and if and

         12    how we should get consent for future use of newborn

         13    screening samples in genetics research.

         14              We have issues of gene therapy that have

         15    already been mentioned by Abbey Meyers, and I think

         16    an underlying problem that we should address at

         17    this time is defining what we mean by "genetic

         18    information," exactly what constitutes genetic

         19    information, and how our IRBs should address

         20    questions about future use of samples and any use

         21    of samples from which genetic information can be

         22    generated.


                                                                  79

          1              Thank you. 

          2              CHAIRPERSON MARSHALL:  Thank you, Mary

          3    Kay.

          4              Robert?

          5              DR. RICH:  I'm Bob Rich.  I'm Executive

          6    Associate Dean for Research at the Emory University

          7    School of Medicine, where I've been for the past,

          8    just over two years.

          9              Prior to that, I spent 25 years at Baylor

         10    College of Medicine.

         11              I'm a physician with specialty training in

         12    internal medicine and a subspecialty in immunology

         13    at Baylor.  I was an investigator at the Howard

         14    Hughes Medical Institute, so I had a substantial

         15    research program.

         16              Also, during that time, I had a ten-year

         17    Omni IRB and served for a period as Program

         18    Director of the General Clinical Research Center.

         19              Among other things that I have done

         20    relative to the interests of this committee I

         21    think, or that I have chaired the National Research

         22    Committees of both the Arthritis Foundation and the


                                                                  80

          1    National Multiple Sclerosis Society.

          2              For the past ten years, I've been a member

          3    of the advisory panel on research of the

          4    Association of American Medical Colleges. 

          5    Recently, I was appointed to the Regulatory Burdens

          6    Working Group of the National Institutes of Health.

          7              I'm Vice President elect of the American

          8    Academy of Allergy, Asthma and Immunology, and

          9    President elect of the Federation of American

         10    Society for Experimental Biology, or FASEB.

         11              In terms of things that are on my mind, I

         12    guess I'd like to begin my comments with simply

         13    stating the obvious, which is that I feel

         14    passionately that clinical research is a societal

         15    good, and that what this committee must keep in

         16    mind all the time during its deliberations is that

         17    we're dealing with things that are basically good

         18    for society and good for individual patients; that

         19    although we are cognizant of problems in the

         20    system, the idea of demonization of either

         21    individual investigators or demonization of

         22    institutions is not in, I think, anyone's interest.


                                                                  81

          1              And, in fact, I think there is a general

          2    recognition that we are in a situation where we are

          3    facing a dearth of clinical investigators.  And I'm

          4    hoping that the work of this committee will

          5    encourage people to go into ethical clinical

          6    investigation and not discourage what I regard as a

          7    heroic thing that individuals can contribute.

          8              I think part of our problems are that we

          9    are really doing now 21st Century clinical

         10    research, as Mary Kay has suggested, but I would

         11    submit with largely a 1970's infrastructure.  And I

         12    think that many of our problems relate to that

         13    disconnect between an infrastructure that would

         14    develop 30 years ago and have not substantially

         15    changed.

         16              I find both our investigators and our

         17    institutions to now be truly beleaguered as they

         18    attempt to confront the issues that this committee

         19    will be addressing.

         20              We have enormous difficulties at present,

         21    and I'm saying this now as a research

         22    administrator, as well as an investigator, in


                                                                  82

          1    simply recruiting qualified IRB members,

          2    particularly recruiting real clinical

          3    investigators.  Physicians are unwilling to spend

          4    the time and give the effort to serve on IRBs too

          5    often because of the lack of systemic rewards that

          6    we put into the system for that amazingly valuable

          7    service.

          8              I'm concerned that too often over the past

          9    decade, we've seen regulations promulgated from the

         10    federal government with little or any attention to

         11    the cost of those regulations, and it's something

         12    that I've been rather outspoken about over the last

         13    couple of years.

         14              Or the provision of resources.  I would

         15    say that the system that we're talking about really

         16    can't be fixed without first addressing the true

         17    partnership between the government and the

         18    universities.

         19              One of the real problems, if you'll bear

         20    with me just for a one-sentence diversion into the

         21    arcana of research administration, is that the 26

         22    percent tap on administrative costs on research


                                                                  83

          1    grants which basically all universities now are

          2    faced with -- research-intensive universities are

          3    faced with -- means that every new regulation

          4    promulgated by the federal government is borne

          5    entirely by the university.  And I think that

          6    that's inappropriate and that's something that this

          7    committee needs to weigh in on and we need to see

          8    changed.

          9              We need to basically redress the idea of

         10    the regulatory enterprise as being something that

         11    is not simply the government regulating and the

         12    university paying.  We have to come together and do

         13    those things together. 

         14              I'm concerned about the issues of

         15    conflicts of interest that have been very much in

         16    the news.  I think this is a major area that needs

         17    to be addressed in all elements of the research

         18    enterprise.

         19              I'm very much in sympathy with the notion

         20    that not only federally funded research needs to be

         21    the attention of this committee, but, in fact, I

         22    think that many of the conflicts of interest or


                                                                  84

          1    most of the conflicts of interest, the serious

          2    ones, are outside of federal funding.

          3              And I would also particularly call to

          4    attention my interest in seeing that we have a

          5    level playing field from those of us who are

          6    regulated between the universities, on the one

          7    hand, and the private contract research

          8    organizations, for example, on the other.  The

          9    private agent, the entirely nonaffiliated

         10    physicians who are also carrying out now the

         11    majority of clinical investigation, who seem to be

         12    working with a different set of rules, and I don't

         13    think that's appropriate.

         14              I think there are a number of simple

         15    things that we can do, and these might be seen as

         16    small nits to attack.

         17              One of the things that I find problematic

         18    with our current approaches to informed consent is

         19    simply consent forms.  I think very few patients

         20    who are really gaining informed consent have the

         21    patience or willingness to sit and read through an

         22    eight-page consent form that is filled with


                                                                  85

          1    legalese, and is basically only readable by a

          2    lawyer.

          3              And I think one of the things that needs

          4    to be addressed is, really, what do we mean by

          5    "informed consent," and how can we address the

          6    issues of patients to really not simply communicate

          7    a huge body of information with the signature of

          8    the patient at the bottom of it, but truly informed

          9    consent that speaks from one mind, the mind of the

         10    investigator to the mind of the patient?

         11              I'd like to see us look at enhancements in

         12    our logistical capacities for review of protocols. 

         13    For example, electronic interactions, protocol

         14    review, pre-review, preparation, and a professional

         15    staff and professional support to help implement

         16    those things, because I think, again, we're dealing

         17    with a creaky, old system, developed 30 years ago.

         18              There are lots of ways that we can

         19    simplify things and really protect human subjects

         20    more effectively and efficiently, and probably at

         21    lower cost if we do it well.

         22              Finally, I like the idea of enhancing the


                                                                  86

          1    education programs that have gotten a lot of

          2    attention in the past year, both of IRB members and

          3    of investigators.  The new approaches to the

          4    accreditations of IRBs I think is a healthy thing. 

          5    I hope that it will remain a non-government

          6    program, and I would strongly urge that we develop

          7    and support the development of mechanisms where

          8    non-governmental, voluntary approaches can work

          9    with the government to ensure the maximum

         10    protection of human subjects in research.

         11              Thank you. 

         12              CHAIRPERSON MARSHALL:  Thank you very

         13    much, and I just want to say that I couldn't agree

         14    more with many of the things that you have said.

         15              And it brings to mind a point that I would

         16    like to make that I think is sort of overarching in

         17    terms of our charge, and that is that we need to

         18    think about systems of the protection of human

         19    subjects of research.  And there has been, I think,

         20    too much focus, narrow focus, on IRBs and, perhaps,

         21    finger pointing and so forth.

         22              And so I would encourage us in our


                                                                  87

          1    thinking, in our deliberation, to think about not

          2    only the systems that currently exist, but how we

          3    might redefine those systems in the future to be

          4    much broader and much more inclusive in terms of

          5    those who should be responsible for the protection

          6    of human subjects.  And that would include the

          7    public and having a public that has sort of a

          8    higher level of literacy and understanding about

          9    the research process, in general, and the

         10    protection of human subjects of research.

         11              So thank you very much.

         12              Adil? 

         13              DR. SHAMOO:  Thank you.

         14              I'll start by making a few corrections to

         15    the biosketch which is in the program, and,

         16    hopefully, it will be corrected later.

         17              I'm a professor and former Chairman of the

         18    Department of Biochemistry and Molecular Biology,

         19    and the word, "former," was missing, and I'm a co-

         20    founder of the Journal of Accountability and

         21    Research in 1988, not in 1998.  That's a ten-year

         22    difference.


                                                                  88

          1              And I also am a co-founder of a human

          2    right organization called, CRCA, Citizens for

          3    Responsible Research, four years old.

          4              Let me give you my background which will

          5    sort of inform you where I'm coming from.  And I'm

          6    originally from Baghdad, Iraq.  A U.S. citizen now,

          7    long time ago.

          8              It was a thrill to me to speak a few words

          9    of Arabic with Secretary Shalala.  I have followed

         10    her career since I was a graduate student at City

         11    University of New York, and she was one of the

         12    member -- she was the President of Hunter College,

         13    which is a member of our institution.

         14              A lot of you don't know she's an ex-nun,

         15    and I know a lot of people don't know that.  So

         16    I've followed her career.

         17              And that explain to you why I have passion

         18    and deep love and appreciation to issues of

         19    freedom, liberty and democracy.  It also explain to

         20    you why I strongly react to those who wants to

         21    silence those of us who brought these ethical

         22    issues and research to the forefront in the past 15


                                                                  89

          1    years.

          2              In mid-eighties, I became interested in

          3    issues of research integrity, and that's when I

          4    started the Journal on Health, eight national,

          5    international conferences, several of them in

          6    Europe and the remainder here, on issues of

          7    research ethics, and the last, specifically on

          8    human subject.  Some people in this audience have

          9    attended some of these meetings. 

         10              It was in 1991 that I became interested in

         11    issues of human subject, and especially the

         12    vulnerable subject, that is, the mentally ill.

         13              When the National Alliance for the

         14    Mentally Ill, what I was serving in the Science

         15    Review Committee of that organization, and later, I

         16    became a board member of the National Alliance,

         17    they referred to me the well-known case now, the

         18    UCLA, the Aller case, which is still, by the way,

         19    under litigation as I'm speaking now.

         20              At the outset, let me say that I do

         21    support research.  I think research is important

         22    because it would be counterproductive, slowing


                                                                  90

          1    and/or terminating research because desperate

          2    patients will go and seek unproven medication, and

          3    that would be contrary to all what we want to do.

          4              But conduct of ethical research is not

          5    mutually exclusive from conducting research.  We

          6    could do both very, very well.

          7              Most researchers and research institutions

          8    are noble people.  They want to serve the public

          9    good, and, of course, within our system of

         10    government, they want to serve private good, that

         11    is, making profit.  That's agreeable.

         12              However, the incidence of aberrant

         13    behavior, at least its discovery, is becoming more

         14    and more of it in the past three, four years.

         15              I don't know what the percentage is.  Is

         16    it .1 percent, one percent or ten percent?  I

         17    really don't know.  And, however, the cases we have

         18    seen are very disturbing, and some of that research

         19    is really shameful, and I'll give you a few

         20    examples.

         21              The washout experiment, taking psychiatric

         22    patients on an out-patient basis and removing them


                                                                  91

          1    from all medication -- these are schizophrenic

          2    patients, for example, and leave them in the

          3    community for up to a year sometimes with psychosis

          4    and delusions, in order to do research.

          5              The other one is, while they're washed

          6    out, they introduce chemicals into their body to

          7    induce psychosis and delusion and study it

          8    afterwards.  And I thought those experiments should

          9    only be done with rats.

         10              Furthermore, we discovered that six to 12

         11    year old children, they were given fenfluramine,

         12    the active component of phen-fen.  These children,

         13    they were neither sick nor obese.  They were simply

         14    testing a hypothesis, whether the serotonin rise

         15    was going to be very large, and therefore, they're

         16    genetically or environmentally prone to violence.

         17              University researchers and IRBs all

         18    approved this, including NIH, these kind of

         19    research.  University researchers got involved, for

         20    example, in breaking confidential court records to

         21    find out who the siblings are so they could recruit

         22    them.  They were given Toys-R-Us gift certificates.


                                                                  92

          1              But, so far, what has served us really

          2    well is really our First Amendment, that is, the

          3    media, who brought some of these incidents to our

          4    attention.  And then were the Congressional

          5    hearings through our Congress.  And, to some

          6    extent, to be very honest, is the OPRR and OHRP,

          7    when they took actions that focused attention of

          8    all of us to these issues.

          9              In short, basically our democratic

         10    institutions has really worked.  It takes time, in

         11    a democracy, to make changes.

         12              Most specifically, my immediate concerns

         13    are what everybody has mentioned and I have written

         14    about, the lack of oversight on non-publicly funded

         15    research and non-FDA bound; that is, no longer end

         16    up as an MDA.

         17              Second is the structure and flawed IRB. 

         18    They are constructed with a built-in conflict of

         19    interest.  They are simply employee of the research

         20    institution.

         21              Third is the aberrant experiments I

         22    mentioned to you, and I think they should not


                                                                  93

          1    continue.

          2              Fourth, the rapid rise in the use of

          3    children in research, and I really look forward to

          4    this committee to work and come into consensus to

          5    reform the system.

          6              I thank you. 

          7              CHAIRPERSON MARSHALL:  Thank you very

          8    much.

          9              Judith? 

         10              DR. SIEGEL:  I'd like to thank the

         11    committee for actually asking for a representative

         12    from the pharmaceutical industry, which is where I

         13    reside.  My experience is that I have a Ph.D. in

         14    psycho-biology pre-clinical work.  I worked with

         15    animals for many years, looking at brains,

         16    pharmacology and behavior.

         17              I have, for the past 21 years, been

         18    involved, in one form or another, of clinical

         19    research in the pharmaceutical industry.  My first

         20    six years was involved in clinical pharmacology. 

         21    This is early phase testing.  And the past 15

         22    years, involved in various aspects of clinical


                                                                  94

          1    research.

          2              For many years, I was the head,

          3    domestically and globally, for CNS research. 

          4    That's both drugs for psychiatry, neurology and

          5    anesthesiology.  And for the past six years, I have

          6    been responsible in the United States for all

          7    clinical research that my company conducts.

          8              For two of those six years, I was also

          9    responsible for not on the United States, but also

         10    the research that we conducted in Latin America,

         11    both Central and South America.

         12              I feel passionately that clinical research

         13    does contribute to the public good.  I've spent my

         14    career doing it.  The way I've decided to do it in

         15    my career is through providing pharmaceutical

         16    products. 

         17              I'm also an ethical person, and so part of

         18    my contribution, I hope, to the companies that I

         19    have worked for is to keep the focus -- I think

         20    Greg said it very well -- not on the regulation,

         21    but on why the regulations are there.

         22              And so, for the past six years at the


                                                                  95

          1    company I'm presently at, what I have been involved

          2    with is a revamping and a refocusing on what the

          3    ICH guidelines, what good clinical practice, and

          4    what all the other regulations that we do our

          5    research with, not what the words say, but why they

          6    say it, because I think -- and I think many people

          7    have said it here also today -- what we're doing

          8    is, we're checking off boxes that we've done this,

          9    we've done this, and I think we've really lost

         10    sight of the "why".

         11              I think the "why" is becoming more

         12    difficult as the environment is changing in the

         13    pharmaceutical industry.  Certainly, in the past 15

         14    years, I don't think we could have predicted the

         15    new challenges that we all have faced.

         16              Patient advocacy groups really becoming a

         17    major influence on what we do, how we do it, how

         18    fast we do it, the types of pharmaceutical products

         19    that we're now looking at, not just the old type of

         20    molecules, but new types of molecules, and now,

         21    genomics, which has totally put us in a place that

         22    we have never been before, both ethically and


                                                                  96

          1    research based.

          2              And where that's going, I think many

          3    people within the industry are trying to sort out,

          4    but I don't think any of us really know.  And so,

          5    to chart a course to someplace you don't know is

          6    particularly difficult.

          7              I think, also, the business aspects of how

          8    we conduct our work have changed in the past years. 

          9    There are many, many, many new players,

         10    biotechnology being, again, a huge piece that, I

         11    think 15 years ago, we never could have predicted.

         12              With that comes the pressure to put drugs

         13    out there more quickly.  There are more drugs that

         14    are in the pipelines to be developed, and,

         15    therefore, there is the press for patients to

         16    actually contribute to those trials.

         17              And I think clearly the issues that we are

         18    facing now about American companies, or global

         19    companies, for that matter -- I happen to be with a

         20    company that does research.  We're an international

         21    company.  We do research all over the world, in

         22    many cases, where the patients exist.


                                                                  97

          1              And the questions are, how do we do that

          2    research and still maintain the high moral and

          3    ethical ground?

          4              In countries where the fact of the matter

          5    is, it's not like doing research in the United

          6    States, where there is a huge amount of medical

          7    support, medical availability -- in countries that

          8    we are doing research, there is no such

          9    infrastructure.

         10              And so the question is, are we unduly

         11    pressuring patients to come into trials just

         12    because there is no option?  I think we worry about

         13    that a lot.

         14              So I think my particular issues for this

         15    committee, for myself, and probably for the

         16    industry at large would be really how to facilitate

         17    the ability to do clinical research, both in the

         18    United States and worldwide, protect the patients

         19    without whom we could not be effective, we couldn't

         20    do this.

         21              How not to introduce so much bureaucracy

         22    that it becomes difficult, if not impossible, to


                                                                  98

          1    actually get the work done, while always

          2    remembering not what the law says and what the

          3    regulations say, but why we're doing what we're

          4    doing?

          5              Thank you. 

          6              CHAIRPERSON MARSHALL:  Thank you.

          7              Denyse? 

          8              DR. THORNLEY-BROWN:  Thank you.  With a

          9    last name towards the end of the alphabet, I'm

         10    always the last to speak. 

         11              But my name is Denyse Thornley-Brown, and

         12    I'm an Assistant Professor of mythology, University

         13    of Alabama at Birmingham.  So I'm a lot earlier in

         14    my career than many of the members of the panel.

         15              I was born and raised in Canada and did my

         16    medical training in this country.

         17              As an academic nephrologist, I do several

         18    things.  I'm involved in clinical research.  I

         19    direct the local county renal clinic.  That's a

         20    clinic that deals with patients who are

         21    economically disadvantaged, and I'm also involved

         22    in taking care of a lot of patients on dialysis and


                                                                  99

          1    other patients with kidney disease.

          2              As a junior faculty member and a clinical

          3    investigator, I have several concerns:  One of the

          4    things in an academic setting, you see, is that

          5    there is a lot of pressure for advancement.  Good

          6    things happen to those who recruit, who find

          7    significant findings and who publish.  Not only

          8    financial rewards, but, also, tenure, grants and

          9    reputation.

         10              And so, often when we talk about

         11    "conflicts of interest," we talk about financial

         12    conflicts of interest, but there are also non-

         13    monetary conflicts of interest that we see

         14    sometimes.

         15              I think that I echo the sentiments of

         16    everyone on this panel that clinical research is

         17    important, it's imperative, and we have all

         18    benefitted from clinical research.

         19              I guess my two main concerns are how do

         20    you make oversight as effective and as unobtrusive

         21    as possible?

         22              Dealing with IRBs frequently involves the


                                                                 100

          1    letter of the law, as opposed to the spirit of the

          2    law, the changing of the wording on the consent

          3    form, very subtle changes, but missing the big

          4    picture of the project and what is being done.

          5              And, certainly, clinical research in a

          6    place like Alabama, with the legacy of the

          7    Tuskeegee syphilis experiments, we have to deal

          8    with many people who don't even remember the

          9    specifics of the experiments, but there's a

         10    residual atmosphere of mistrust.  And how can we

         11    regain this trust?  

         12              How can we protect this trust, and how can

         13    we protect the patients?

         14              And then my second concern, one that was

         15    echoed by many members of the panel is informed

         16    consent.

         17              While informed consent is hard enough to

         18    get from someone who is very educated and

         19    sophisticated, how do you honestly get informed

         20    consent, truly informed consent, in groups who are

         21    educationally and medically unsophisticated, and

         22    how can we go about improving this?


                                                                 101

          1              Again, the informed consent document has a

          2    lot of information, and all of the required things

          3    are there.  But are we truly getting informed

          4    consent?

          5              I'm looking forward to working with this

          6    committee, and I think that we're at a very

          7    exciting time, and there are a lot of things that

          8    we can do as this committee, and I'm excited to be

          9    here. 

         10              CHAIRPERSON MARSHALL:  Thank you very

         11    much, and I can echo your sentiments about the

         12    Tuskeegee legacy, having just moved from the

         13    Medical University of South Carolina.

         14              A third of the citizens of South Carolina

         15    are African-American, and that legacy is alive and

         16    well, not only there, but throughout the United

         17    States.

         18              Thank you very much and thank all of you

         19    committee members.  We have a wealth of knowledge

         20    and experience. 

         21              I would like to ask Robert Cooke Deagan if

         22    he could, within the next eight minutes or so,


                                                                 102

          1    describe for us the charge that has been given to

          2    the Institute of Medicine on evaluating the systems

          3    for protection of human research subjects.

          4              Our committee, the OHRP, has charged the

          5    institute.  They have accepted this responsibility,

          6    and we will be hearing from them in the future. 

          7    But I would like for the committee members to know

          8    the specifics of this project so that we are not

          9    being inefficient, at least in the short term, and

         10    also, so that we will have the comfort of knowing

         11    that we will have a report that is well done and

         12    stellar in the future.

         13              So thank you so much, Bob. 

         14              MR. DEAGAN:  Thank you, Mary Faith.

         15              I'll spare you my bio because it's pretty

         16    much irrelevant.  It's irrelevant for two reasons: 

         17    One is, I'm not the Study director.  The Study

         18    Director is Laura Rodriguez, who just started work

         19    two days ago, and also because of the nature of our

         20    task.

         21              We, at NIOM, as staff people, are really

         22    just there to articulate the deliberations of a


                                                                 103

          1    committee, and it's actually the committee that

          2    does the authorship.  So my background is largely

          3    irrelevant, with one exception:  It was nice to

          4    hear Senator Kennedy allude to the history of the

          5    bioethics commissions.

          6              I had the distinct honor of being the

          7    Acting Executive Director of the Biomedical Ethics

          8    Board Advisory Committee.  This is the one that he

          9    talked about that died in the abortion cross-fire a

         10    decade ago.

         11              So with that kind of spectacular success

         12    on my resume, let me talk about two things:

         13              Number one, what is the task that we've

         14    been asked to do?

         15              Two, I'll talk just a second about our

         16    schedule, and number three, about what the content

         17    is apt to be.

         18              The task, we are doing a project that has

         19    just started and will be completed some time in the

         20    fall of 2002.  Our contract goes through September,

         21    2002.

         22              We're doing two things:  We're going to


                                                                 104

          1    produce two reports, the first of which will be

          2    available in April of next year that will focus on

          3    the accreditation process and the accreditation

          4    standards that are part of that process.

          5              We are relying heavily in that task on the

          6    work that's already been done by public

          7    responsibility in medicine and research that has

          8    been working for several years on this.  So that is

          9    going to be the focus of our first report.

         10              The second report is going to look at the

         11    overall framework for human research review

         12    programs, and so we're going to be looking at --

         13    there's a lot of overlap with the National

         14    Bioethics Advisory Commission report that's already

         15    underway for that second task.  That report will be

         16    out some time in the late summer or fall of 2002. 

         17              So that's the schedule and the task.  Now,

         18    what's the content?

         19              The committee just met for the first time

         20    yesterday and the day before, so we are just at the

         21    beginning of our process.

         22              The discussion was very rich and


                                                                 105

          1    insightful and wonderful, and that's a code word

          2    for saying I don't have a clue what they're going

          3    to say at the end of the process.

          4              And for those of you who have followed the

          5    IOM process, basically, we are going to have a --

          6    there's a -- there are open elements and closed

          7    elements to our process.  Our distinct value added

          8    often comes from the fact that we can get people in

          9    a room outside of the usual FACA constraints and

         10    Federal Advisory Commission Act, and get an intense

         11    discussion among our committee members that would

         12    produce findings and recommendations.  So those

         13    will surface in our April report, and there's only

         14    so much we can say about findings and

         15    recommendations up to that point.

         16              Aside from that, though, we're trying to

         17    be as public as we can be, and part of that is we

         18    will be holding a public forum in January.

         19              Now I wish -- I didn't write down -- we

         20    made a decision about what our next meeting is

         21    going to be after our meeting yesterday, and it's

         22    either going to be the 21st or the 22nd of January,


                                                                 106

          1    but I wish I remembered, and it's out in the car,

          2    so I didn't get that.

          3              But there will be a public forum the third

          4    week of January.  It will be either the 22nd or the

          5    21st.

          6              After that meeting, the committee will

          7    hunker down.  There will be another meeting in

          8    February, and we will then go into our report

          9    writing and review process and produce a report in

         10    April.

         11              As part of our process, though, we are

         12    going to make available the PRIMAR draft standards

         13    that actually already exist.  We're trying to set

         14    up a web site.  In fact, we've set one up, but we

         15    don't have a simple URL yet.  It's going to take us

         16    about a week, it sounds like, to get that.

         17              So we're going to make the PRIMAR draft

         18    guidelines available as soon as we can, probably

         19    within the next week, and the committee composition

         20    and our process and our schedule and all that will

         21    also be out on that web site, including the members

         22    of the committee.  So stay tuned. 


                                                                 107

          1              CHAIRPERSON MARSHALL:  Thank you.  And we

          2    do have two minutes and then we will take a 15-

          3    minute break.

          4              Let me ask committee members:  Do you have

          5    any questions at the moment?  Bob? 

          6              DR. ROBERT LEVINE:  Thank you.

          7              It's going to happen from time to time

          8    that members of our committee will make statements

          9    about stories that are widely known about research

         10    and it's conduct and its ethics.  And if we respond

         11    to each one of these as they come up, we probably

         12    won't get our job done.

         13              But for the benefit of members of the

         14    public, I want to say that we've already had some

         15    examples of simplified statements about past

         16    research activities, where there are many other

         17    versions of the same events out there.

         18              I particularly want to disassociate myself

         19    from anything that's been so far about

         20    fenfluramine, but we can't be responding to each

         21    one of these as they come up.

         22              I think we have some real experts among


                                                                 108

          1    our ex-officio members here, and from time to time,

          2    if one seems particularly vexatious, I wonder if we

          3    could call upon one of them. 

          4              CHAIRPERSON MARSHALL:  I think we

          5    certainly can.  I mean one of the things that we

          6    need to be particularly attuned to is our data

          7    gathering, and so I agree with you.  Yes. 

          8              DR. ROBERT LEVINE:  But I wouldn't want,

          9    for example, the statements on fenfluramine or the

         10    placebo washout to be represented in the press as

         11    something that this group has agreed to.  Thank

         12    you. 

         13              CHAIRPERSON MARSHALL:  I hear you.

         14              Mark, quick question.  We will adjourn in

         15    two minutes. 

         16              MR. BARNES:  Yeah.  I'd just like some

         17    clarification, if you could, Mary Faith or Kate or

         18    if Dr. Koski were here, he could do it, between the

         19    charge of this committee as opposed to the National

         20    Bioethics Advisory Committee, as opposed to the

         21    IOM, and how you think.  You know, where do we fit

         22    in and what can we most -- you know, how can we


                                                                 109

          1    most profitably use our time? 

          2              CHAIRPERSON MARSHALL:  I will speak first,

          3    and then, Kate, please weigh in and keep me honest

          4    and accurate.

          5              My sense of the charge of our committee is

          6    that we are concerned with the protection of human

          7    subjects, that issues that arise that we are asked

          8    to give advice on, whether it's taken or not, but

          9    that will certainly be on the record will be the

         10    sources of those questions will arise from the

         11    Secretary, from the Office of Human Research

         12    Protections, from the other federal agencies that

         13    are associated with us, and that also do human

         14    subjects research with academic institutions, with

         15    non-academic institutions in a broad sense and from

         16    the public. 

         17              So I think that we have a much broader

         18    array of responsibilities in terms of those, who

         19    can ask us for advice.

         20              And we don't have a particular charge in

         21    terms of our agenda.  It's something that we can

         22    set ourselves. 


                                                                 110

          1              MS. GOTTFIELD:  I think Mary Faith really

          2    has summarized it.  In terms of the scope, it is

          3    broad, but I think that, as you see from the

          4    agenda, that we have identified issues for this

          5    meeting, and we will go and ask for input, both

          6    from the public and from the members of the

          7    committee, for what areas you all think we ought to

          8    be focusing on, and be clear, also, and we'll do

          9    this throughout the day, in terms of where we're

         10    going to go with respect to products, whether they

         11    be public hearings, papers, et cetera.  So that

         12    needs to be fleshed out. 

         13              CHAIRPERSON MARSHALL:  So I think our

         14    process, in terms of outcome, is vitally important

         15    and that we have the freedom and the responsibility

         16    to have a good process.

         17              So, thank you, Bob, and let us adjourn for

         18    15 minutes, and then, for the rest of the day, we

         19    will keep to our schedule as it is written. 

         20              [Brief recess taken.]

         21              CHAIRPERSON MARSHALL:  While we're getting

         22    settled, I wanted to let you know that Jennie Joe


                                                                 111

          1    is not able to be with us here today, but she will

          2    be with us tomorrow, and that Dr. Koski has gone

          3    downtown briefly to Health and Human Services, but

          4    will return this afternoon. 

          5              So let us move on with our agenda so that

          6    we can stay on time.

          7              The first substantive item on the agenda

          8    is institutional review and oversight of non-

          9    biomedical research under the common rule.  Felice

         10    Levine from the American Sociological Association

         11    is going to give us a presentation.

         12              And I want to say that the fact that this

         13    is the first item of substance on our agenda speaks

         14    for itself in terms of how we view the importance

         15    of social science research and the concerns that

         16    have been raised by members of that community about

         17    the review process, and the problems that they

         18    perceive relative to their research.

         19              So thank you so much, Felice. 

         20              DR. FELICE LEVINE:  I think I'll press my

         21    button, but I'm delighted to be here and to have

         22    the opportunity to talk about some of the issues


                                                                 112

          1    and challenges for the social and behavioral

          2    sciences under the current system for the

          3    protection of human subjects.

          4              And I missed the swearing in, inclement

          5    weather here, but I really want to congratulate all

          6    of you, both for your longstanding commitments to

          7    these issues, and for your willingness to serve on

          8    the advisory committee and underscore what Mary

          9    just said, that I think both Greg and Kate, in

         10    putting this -- I won't say center stage, but at

         11    least putting it as a major substantive issue on

         12    the agenda with your first meeting is, I think,

         13    valued by all of us in the social and behavioral

         14    science community, and I'd like to think all of us

         15    in the science community.

         16              I thought I might say a few things about

         17    who I am.  I missed the round robin, but at least

         18    it will put me in a little bit of a context. 

         19              I am a social psychologist with a Ph.D. in

         20    psychology.  My early training was in sociology,

         21    and actually had an interest in receiving

         22    experimental social psychological training at the


                                                                 113

          1    University of Chicago, having been an undergraduate

          2    there, switched over to the psych part of the soc-

          3    psych program and so that my range of research

          4    interests and skills really span from the field to

          5    the laboratory.

          6              My area of expertise is law and human

          7    behavior.  Actually, much of my early work focused

          8    on the development of justice judgments and moral

          9    and legal reasoning in children and youth.  And my

         10    interest in research ethics and the protection of

         11    human participants in research sort of dates back

         12    to the seventies, and that sort of interest in law

         13    and human behavior and the role of law in

         14    facilitating, or sometimes impeding various kinds

         15    of actions and interactions.

         16              I spent 12 years at the National Science

         17    Foundation where I was one of the designated

         18    program officers at the National Science

         19    Foundation, addressing issues of human subjects

         20    protection in the social sciences, and I became

         21    Executive Officer of the American Sociological

         22    Association in 1991.


                                                                 114

          1              And since that time, I've been deeply

          2    involved in issues of human subjects protection,

          3    research ethics, research integrity.  It seems to

          4    -- sometimes I wonder what the Executive Officer

          5    does.  This could be a full-time job, in and of

          6    itself.

          7              And one of the things that I think, as in

          8    other fields of science, the social and behavioral

          9    sciences have been long involved in the development

         10    of ethical codes and standards, and over this past

         11    decade, starting in the early nineties, we actually

         12    revised our ethics code.  That's not to say we

         13    developed new standards of ethics.

         14              But I think one of the things that we took

         15    very seriously is fleshing out and providing better

         16    guidance, especially in the areas of human subjects

         17    protection.  And, like much of the language that

         18    informs the mission statements of and the

         19    authorization documents of many of these panels and

         20    committees, we really put a very heavy emphasis as

         21    much as on education and on prevention as on our

         22    regulatory and enforcement role, at least as it


                                                                 115

          1    reaches to members of the American Sociological

          2    Association.

          3              I really brought copies of this for your

          4    advisory group, not because I think it's any better

          5    than others, but as I think a exemplar of the

          6    seriousness I think with which scientific societies

          7    and the scientific community take these issues in

          8    the social and behavioral sciences.  And, indeed,

          9    one of the sites at the end is an appreciation of

         10    the American Psychological Association's code

         11    because, in undertaking our revision over several

         12    years, we used that document in fleshing out some

         13    of our own principles and standards.

         14              I mention this background for several

         15    reasons:  One, I think we share -- I, and the rest

         16    of the social and behavioral science community

         17    share rather strongly an affinity with the

         18    biomedical community in a commitment to promoting

         19    sound sciences, as requiring ethical practices,

         20    especially with respect to the participants and

         21    research. 

         22              I guess I will also say, as a true


                                                                 116

          1    believer and educator in this area, I sometimes

          2    feel what we in social psychology have been saying

          3    for decades is a dissonance between the growing

          4    front lines in the system, despite my encouragement

          5    that it needs to be used and embraced by the social

          6    and behavioral sciences.

          7              And one of the things you will see in the

          8    code is that in areas where IRBs are the common

          9    rule, and IRBs are not required, for example, non-

         10    federally funded research, as we know, although

         11    institutions have increasingly had IRBs consider

         12    all forms of research involving human subjects

         13    protection. 

         14              Our code explicitly uses the language,

         15    "institutional review board or their equivalent,"

         16    and, indeed, are encouraging researchers to seek

         17    out that kind of expertise, recognizing that you do

         18    need feedback in making sometimes very difficult

         19    decisions at choice points.

         20              And so my concern is that as we are

         21    promoting what are the right principles and

         22    policies, that -- and this is not an uncommon thing


                                                                 117

          1    for a sociologist of law to reflect on -- that

          2    there is a gap.  I don't know if it's a growing

          3    gap, but it certainly is a gap between the law and

          4    the policy on the books and law and action.  And I

          5    guess that's why there's been a proliferation of

          6    committees and high-profile attention to the issue,

          7    and the very movement of the office to DHHS and in

          8    the office of the Secretary.

          9              I think, also, as a social scientist, sort

         10    of watching and being engaged in all of what's

         11    going on and, you know, printing a 250 page and

         12    back report in the middle of the night last night

         13    and thinking, "Well, it looks like that's done, and

         14    what else can I add," not having much chance to

         15    read it.

         16              I think we need to be cautious.  I'm an

         17    action oriented person, but I think we need to be

         18    cautious and move deliberatively, and we call this

         19    a system of human subjects protection.  Unlike the

         20    biological system, you can't start altering too

         21    many things simultaneously and know where those

         22    causal hours are leading.


                                                                 118

          1              So I find myself sympathetic to a lot of

          2    what one can read about or hear about in the back

          3    reports or the kinds of commitments we have, both

          4    to better training and education, both to

          5    certification, both to accreditation.

          6              But I do think we need to both, A, proceed

          7    with reforms using something of a model of

          8    evaluation and study, and we need to be thinking

          9    not -- I'll say rush to judgment about putting too

         10    many different changes in place simultaneously in a

         11    way that may not always give us enough

         12    understanding of what is moving us closer to our

         13    aspirations. 

         14              That said, I'm not critiquing anyone, but

         15    I do think this is a social system and it is a

         16    social system that is a dynamic process and a

         17    changeable process.  We should not be reluctant to

         18    change, but we should be thinking through these

         19    changes as interventions in and of themselves.

         20              Most importantly, for those of you who

         21    carried the earliest agenda, and what is what

         22    brought me here today, and received the phone call


                                                                 119

          1    from Kate late afternoon on Monday is that I'm not

          2    Jonathan Knight, but I'm going to seek to be his

          3    stand in.

          4              He is, as you may all know, and I think

          5    you received the paper.  You may not have read the

          6    paper, and the task before me is to give you a

          7    little bit of an overview of the paper and what led

          8    us there, is that he's Associate Secretary of the

          9    American Association of University Professors.

         10              He's a political scientist, by training,

         11    and he was our team leader, as we might think of

         12    it, of an informal group of representatives from

         13    the American Anthropological Association, the

         14    American Historical Association, the American

         15    Political Science Association, the American

         16    Sociological Association.  I was the rep.  The Oral

         17    History Association and the Organization of

         18    American History.

         19              We've been working together for a little

         20    bit over a year, and our goal was to examine the

         21    experiences of social scientists and humanists with

         22    IRBs and the human subjects protection system.


                                                                 120

          1              And the report you have, I'll say, is a

          2    preliminary report based on the best of where our

          3    thinking is and was at the point at which we at

          4    least consolidated the information we received over

          5    the course of last year, and we've posted it on the

          6    web site, and we hope that you all read it and

          7    respond so that we can continue to have that kind

          8    of interaction.

          9              Jonathan's out of town, and so I'm sort of

         10    the stand in, in the process. 

         11              CHAIRPERSON MARSHALL:  I just wanted to --

         12    excuse me for interrupting, but I wanted to say

         13    that sort of our goal is to make things

         14    transparent.

         15              We will be posting this paper on our web

         16    site, as well, so for those of you from the public,

         17    we apologize for not having it available to you

         18    today.  In the future, we'll have copies of all of

         19    our papers available to members of the public, and

         20    it will be on the web site.

         21              Sorry to interrupt. 

         22              DR. FELICE LEVINE:  No.  That's fine.


                                                                 121

          1              Just a little bit by way of background,

          2    recognizing that those beyond the hollow square

          3    haven't yet seen it and may not have known of this

          4    activity because, indeed, we have just posted it

          5    recently, the American Sociological Association and

          6    the other social science amenities associations

          7    responded to the AUP invitation to look at the role

          8    and scope of institutional review boards because,

          9    over the years, IRBs have played an increasingly

         10    prominent role in all institutional campus

         11    research, colleges, universities, research

         12    institutes involving human subjects, not just

         13    federally-funded research, which, of course, they

         14    are mandated to do, at least with respect to the

         15    agencies that have signed on to the common rules.

         16              In the humanities, much more than in the

         17    social sciences, there's been far less of a history

         18    of experience with IRB review and with general

         19    guidelines for the protection of human subjects. 

         20    So you will read an opening footnote that says,

         21    "Well, the humanities for this purpose should be

         22    considered part of the social and behavioral


                                                                 122

          1    science affinity group," and we were an affinity

          2    group working together.

          3              But the three history societies working

          4    with us had a range of concerns that flowed from

          5    work grounded in the humanistic and the historical

          6    traditions that had not typically reached to IRB

          7    review or approval, as the National Endowment for

          8    the Humanities, for example, is not under the scope

          9    of the common rule and is not one of the agencies

         10    that require IRB approval.

         11              So there were questions about oral history

         12    and how that would unfold, and as you will learn in

         13    reading the report, in discussions with IRBs, there

         14    was an increasing incorporation of some of the

         15    guidelines for oral history and other of the

         16    principles that inform historical research

         17    involving human subjects.  But that's a more recent

         18    entry into the field.

         19              As a consequence, many of the members of

         20    the humanistic traditions have less awareness of

         21    when and where they are governed by IRB review

         22    than, I will say, more typically the case with the


                                                                 123

          1    rest of the social and behavioral science community

          2    that has felt itself to be a part of the -- and

          3    their research certainly, that funded by the 17

          4    agencies that sign onto the common rule to be under

          5    the system for as long as the rest of the sciences

          6    and the biomedical sciences. 

          7              All of us agreed at the time that we

          8    needed to learn much more about IRBs, how they

          9    operated, the areas that might need improvement,

         10    the presence of IRBs in academic and other research

         11    organizations, as you know dates back to 1974.  And

         12    as I just said, it's reach was one that certainly

         13    incorporated the social and behavioral sciences.

         14              But we thought that this was an

         15    appropriate time to learn more and less

         16    anecdotally, although we refer in the report to the

         17    fact that it was, we stressed, an informal effort

         18    to reach out to our research community, including

         19    students.

         20              But we did want to do so because

         21    increasingly, we were concerned about what I've

         22    referred to as those "fault lines," the sense that


                                                                 124

          1    there was a operational departures between what are

          2    the rules and principles and the ethical standards

          3    embedded in the common rule, and how, in practice,

          4    they were being used, certainly across

          5    institutions, and sometimes, even at that very same

          6    institution, at different points in time.

          7              And we all know that, in terms of social

          8    interactions and the functioning of social

          9    institutions, that there's a larger, I'm going to

         10    say, environment, policy environment and political

         11    environment, with a little "P", that shape the

         12    culture of an institution and how it's

         13    organizational structure functions at different

         14    points in time.

         15              An, indeed, embedded in the original

         16    process was to give the local site, the site that

         17    was sensitive to the norms in the culture, some

         18    delegated authority to interpret and use the rules

         19    and guidelines as is appropriate to those

         20    circumstances, of course, within the general

         21    limits.

         22              And I think some of that is the, you know,


                                                                 125

          1    kind of the dynamic that sometimes has created some

          2    degree of fuzziness, as one might say, especially,

          3    I think, with respect to the social and behavioral

          4    sciences, operating in an environment that still

          5    remains very heavily defined and identified with

          6    the biomedical parts of science, even though both

          7    the ethical standards are shared widely across all

          8    fields of science -- the common rules certainly

          9    applies across all fields of science -- and IRBs

         10    have reached, at least with respect to federal

         11    funding, to all of the social and behavioral

         12    sciences funded by this very same agencies that

         13    support biomedical research. 

         14              That led us to the notion of asking some

         15    questions, of course.  Social and behavioral

         16    sciences can hardly control themselves from doing

         17    that.  And I will say -- I was sort of thinking in

         18    the middle of the night, you know, I did not get

         19    IRB approval for this, but we did it.  We posted it

         20    as -- we all supposedly were going to post it, and

         21    we did, in our newsletters, and we didn't even see

         22    it as a survey.  You know, you could just give us


                                                                 126

          1    and send us in anonymous form your answers to some

          2    questions. 

          3              Well, actually, I have another handout. 

          4    But this is sort of what we were trying to cover,

          5    getting over the past three years, including from

          6    students.  How many research protocols were

          7    submitted?  How long did the review take?  What

          8    types of review did your research receive? 

          9              And we started to expedite it.  We're

         10    aware, as most people in this room are, that those

         11    definitions are clear, and yet may be interpolated

         12    and interpreted differently in both the different

         13    forms in time and in different locations. 

         14              Do you think the members of the IRB were

         15    familiar with the research standards and practices?

         16              Were you asked to alter your research

         17    projects in some way, et cetera.

         18              I think that one of the things you'll see

         19    in the report is that we say that roughly 20

         20    percent of the protocols considered by IRBs go

         21    through without further interaction and across

         22    sciences.  That's not unique to the social and


                                                                 127

          1    behavioral sciences.

          2              What we don't know is that largely with

          3    respect to the social and behavioral sciences,

          4    these are all good research questions.

          5              We didn't stop there, though.  I just

          6    wanted you to know that our interest in this is

          7    really embedded in understanding the system.  So we

          8    really wanted to know from the social and

          9    behavioral scientists who have served on IRBs what

         10    the nature of their experience is, whether they

         11    felt prepared, what the training was, how they

         12    ended up getting there, how much did they have to

         13    invest in essentially being the token, the educator

         14    about the social and behavioral sciences to persons

         15    who might be heavily oriented and experienced in

         16    other fields of science.

         17              So we asked questions about level of

         18    agreement, and also what institutional dedication

         19    of time is given to those who are really giving

         20    mightily, as you all are here, and then having your

         21    careers in that area; that it's no small amount of

         22    time to serving your institution and your other


                                                                 128

          1    colleagues in a review of their scientific work. 

          2              I'm showing these questions because in

          3    part, when you read the report, and you will see us

          4    refer to it as an "informal survey" -- well, we

          5    didn't draw large samples and we weren't seeking to

          6    do a highly formal piece of research.  But we were

          7    systematic in our questioning, and at least two of

          8    the associations -- I think the American

          9    Sociological Association and the American Political

         10    Science Association put this on our home page, and

         11    it was designed in such a way that we've, of

         12    course, assured anonymity to the respondents.

         13              And it went out, "Levine," and it came

         14    back, "Levine."  Indeed, I had sort of forgotten,

         15    after I got my first 20 Levines back, I was sort

         16    of, who is this Levine that's writing, and isn't

         17    that ironic since my name is Levine.  Then I caught

         18    the drift here that it was the way that we had set

         19    it up to essentially seclude the respondent.

         20              And it was quite informative.  It was

         21    both, as you will read in the text of the paper,

         22    there was a lot of support and very positive things


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          1    to be said about both experiences being and serving

          2    as members of IRB and the gratification that comes

          3    with doing that and doing a good job, and also a

          4    range of concerns.

          5              And I must say, over the past year, as the

          6    topic has ratcheted up in saliency, it seems as if,

          7    even beyond our report, that the number of concerns

          8    articulated by social and behavioral scientists

          9    have increased.

         10              There have been many high profile cases,

         11    and as a consequence of that, the ways that consent

         12    and written consent, and when, indeed, there could

         13    be waivers of written consent, have been altered in

         14    ways that are less appreciative of the dynamic and

         15    the elements of doing ethically sensitive research

         16    in the social and behavioral sciences.

         17              The frequency of this, we don't know, but

         18    it's not uncommon now that I will get several e-

         19    mails a day about what happened in an IRB, and

         20    concerns about what to do.

         21              I've listed some things that may come out

         22    less clearly in just reading the report that I


                                                                 130

          1    think are very current concerns.

          2              The use of public secondary analysis of

          3    public use files where the data are structured in

          4    totally anonymous ways without identifiers and both

          5    data from federal statistical data collections, and

          6    also national data sets like the panel study of

          7    income dynamics.

          8              Now, this is an example of gap.  We all

          9    know that, and this comes right from OPRR -- we all

         10    know that with identifiable private data obtained

         11    for research in a form that is associated with

         12    individuals, yes, it needs to be reviewed.  But it

         13    doesn't apply with respect to data that, where

         14    there are no identifiers, and that are data that

         15    are in public use files, or that have been

         16    previously have vetted the creation of public use

         17    files by IRBs in the initial research.

         18              So that is an illustration of the kind of

         19    thing that, certainly in terms of the allowability

         20    under the common rule, have been allowed, but in

         21    terms of the practice of the system, that's the

         22    fault line.


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          1              Ethnographic research, unobtrusive

          2    research in public places. 

          3              Student research in the class is

          4    increasingly being challenged so that professors

          5    are reporting that it could take the whole semester

          6    to have a student research training program, unless

          7    one is either using the extent data or working

          8    under an ongoing project approved by an IRB.  So

          9    this is not atypical.

         10              Here is one question that we left

         11    unresolved, and this was in the context of an

         12    institution.  To graduate students and seminars, I

         13    have to get IRB clearance for term projects that

         14    use nonidentifiable record data from public

         15    archives.

         16              The official new answer is, underlying

         17    "new," yes, but it's unlikely that you could do it

         18    in time to complete a term project in one semester,

         19    especially if part of the seminar is devoted to

         20    finding and developing a project.

         21              You can always say that the work is not

         22    supposed to contribute to generalizable knowledge. 


                                                                 132

          1    And then this respondent goes on to say, but as an

          2    academic and as someone training someone in

          3    research, I truly would not want to say that your

          4    work is not and should not be motivated by an

          5    interest in producing useful and useable knowledge.

          6              So these are the kind of situations that

          7    I'm terming the gap or the fault line that are

          8    especially problematic in the social and behavioral

          9    sciences.

         10              Let me conclude by emphasizing why.

         11              The system is one without however it

         12    evolved over time and because of the seriousness

         13    with which biomedical research created the impetus

         14    for the development of the system.  It is still

         15    very dominated, both in person power and advisory

         16    structure, this advisory structure and other

         17    advisory structures, IRB structure by persons who

         18    are primarily knowledgeable and expert in fields

         19    outside of the social and behavioral sciences.

         20              And one of the things that's very

         21    important in the consideration of this is how we

         22    integrate and develop a system that sensibly looks


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          1    at the research and the kinds of expertise

          2    necessary to consider that research, irrespective

          3    of disciplinary divide.

          4              And I think that as we look at the

          5    recommendations, we need to seriously give serious

          6    consideration to the place and location of social

          7    and behavioral sciences expertise at each point in

          8    the decision-making process. 

          9              CHAIRPERSON MARSHALL:  Felice, thank you

         10    for articulating those points for discussion.

         11              Board members, I know that you have had

         12    the opportunity to read the paper and to think

         13    about it.

         14              I just want to establish a couple of

         15    ground rules, not only for this session, but

         16    henceforth, and that is I would ask you, board

         17    members, to make your questions clear, to make them

         18    concise.  No show off questions will be allowed. 

         19    And I will take questions.  Unless they're on

         20    point, I will take them in the order that I see

         21    hands go up and I will brook no interruptions.

         22              So we have half an hour for discussion,


                                                                 134

          1    and then we have half an hour for recommendations. 

          2    So, Elliot? 

          3              DR. DORFF:  Thank you for the paper.  I

          4    must say that I was really enlightened by it in

          5    ways that I -- I'm on my field's philosophy, so I

          6    don't do this kind of research, and I've been

          7    involved a lot in bioethics, so I assumed that, you

          8    know -- and I've been in IRBs and it's all been

          9    biomedical.

         10              I have two questions:  One is, when I got

         11    to the end of the paper, I thought it fizzled out

         12    in its recommendations because if I were writing a

         13    paper, I would say, first of all, if you had --

         14    forget about the history of IRBs.

         15              If you had your druggers and you thought

         16    that -- and you were creating a completely new

         17    structure for protecting human subjects in your

         18    fields, then what would it look like? 

         19              In other words, you know, if you could

         20    reconstruct the whole system for, you know,

         21    sociology or for history or whatever, then, you

         22    know, and be completely apart -- I mean one of the


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          1    recommendations you make is that in, at least large

          2    universities, maybe you'll have a completely

          3    separate IRB for only people, for non-violent, you

          4    know, with people on it that are not biomedical

          5    researchers, but rather in sociology.

          6              Is that how you would do it, or would you

          7    do it in some other way?

          8              And the second question that I have is a

          9    more limited one.  In the end, you say -- I'm on

         10    page 36.  "Lastly, IRB members could discuss with

         11    academic departments the possibility of blanket

         12    exemptions for certain types of research; for

         13    example, survey research or oral history research. 

         14    And the IRBs are delegated to the department

         15    responsibility for an initial review of research

         16    that does not pose a threat of physical or mental

         17    harm to human subjects."

         18              My question there, again, is why did you

         19    limit that recommendation to specific IRBs

         20    considering it?

         21              Maybe the regulation altogether should

         22    change.  Maybe the common rules should change to


                                                                 136

          1    effectively say these things in addition to the

          2    sixth, I guess, that are already exempted from the

          3    common rule.  Maybe there are some other things

          4    that should be exempted from the common rule

          5    altogether. 

          6              DR. FELICE LEVINE:  I think all your

          7    observations raise good and important questions

          8    that we need to give more consideration.  I think

          9    if -- I'll say the phase we were at was longer on

         10    hearing -- learning than on sharpening our

         11    recommendations, and in a way, that's why we put

         12    them out as kind of a working draft, because I

         13    think our own thinking is still in process on

         14    especially I think the two key issues I think that

         15    you raised.  Let me respond to the two key issues

         16    that you raise.

         17              I think it's always nice to imagine how we

         18    would all start, where we would be able to start

         19    the novel, and one of the reasons why I referred to

         20    ASA's own thinking in the evolution in the code of

         21    ethics is that, and my own set of believer in the

         22    system, is that I think that the system really is


                                                                 137

          1    designed, has a lot that's positive.

          2              And when we're looking at its problems and

          3    its fault lines, I'm rather keen on not throwing

          4    out babies with bath waters here.

          5              And in figuring out how in the

          6    operationalizing of this and in the dynamic

          7    environments in which it lives, in areas that

          8    sometimes can be very troublesome and very high

          9    profile, how do we make this effectively work?

         10              And I think that's what NBAC is about, and

         11    I take it from Mary's remarks earlier before the

         12    break that very much is what you all will be about.

         13              I think in the social and behavioral

         14    sciences, what we have lacked collaboratively

         15    across all fields of science, and perhaps this

         16    reflects some of our own growth and evolution as

         17    fields of science, is sufficient integration into

         18    the system.

         19              And that is that in the examples that are

         20    used, in the education and training that goes on,

         21    in the composition, as I said, not just of IRBs,

         22    but of staff, of staff administering the system, of


                                                                 138

          1    organizational forms accrediting the system, of

          2    training programs that the biomedical model

          3    predominates in such a way that it produces two

          4    outcomes.

          5              One, a lack of appreciation of the ways in

          6    which ethical research, consonant with shared

          7    standards, I believe, can and should be

          8    operationalized.  And, on the other hand, perhaps a

          9    capacity of some researchers to almost distance

         10    themselves as, well, that's about that kind of

         11    risk, without sufficient understanding of how some

         12    of those same issues come into play in different

         13    contexts.

         14              And so I think that this is, in a sense,

         15    it's kind of a shake hand notion.  Maybe this comes

         16    from my years both at NSF and disciplinary work. 

         17    What I think is good for science, I think is good

         18    for the social and behavioral sciences.

         19              And by having a very imbalanced

         20    biomedically driven system, the social and

         21    behavioral sciences have not been able to

         22    adequately contribute to the biomedical thinking


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          1    about their science because you're there

          2    essentially to work on your own science, in a way. 

          3    And, similarly, social and behavioral sciences have

          4    not had the benefit of more informed biomedical

          5    input.

          6              And so what I would like to see is a

          7    transformation where the two can come to the table,

          8    frankly, with great apparency.  One of my

          9    transparencies, because it sort of blew me away,

         10    you know.  We all know what the 17 agencies are,

         11    and I got the NBAC report, and I knew I was hardly

         12    going to have a chance to even print it, but I did

         13    print the 17 agencies under the common rule.

         14              And when you think of the Department of

         15    Justice, the Department of Education, Agriculture,

         16    EPA, there is so much research that is done and

         17    supported NSF that doesn't flow from the biomedical

         18    or the clinical framework that needs to be

         19    integrated, even if the literal number of protocols

         20    and projects, given the, especially at this point

         21    in time, the disproportionate amount of federal

         22    funding that goes to the biomedical sciences versus


                                                                 140

          1    the other sciences.  Clearly, the disproportionate

          2    amount of research protocols will come from other

          3    fields of science.  But I think the ideal framework

          4    would be one that is much more truly integrated. 

          5              That probably gets to the response, a

          6    briefer one, to your second issue.

          7              I personally think that there may be some

          8    range of things that could be delegated at the

          9    department level, especially -- or, of course,

         10    units, shared units, and this may be true across

         11    different fields of science, especially with

         12    respect to perhaps the review of classroom

         13    research.

         14              I have tended toward thinking the science

         15    community has more to gain by working in common. 

         16    So I would find myself disaggregating less and

         17    emphasizing more shared education and understanding

         18    about the methods, and not ethics, but ethical

         19    operationalizing of considerations as they relate

         20    to the methods of research.

         21              I think something is aggregated as survey

         22    would need a lot of clarification as to the form of


                                                                 141

          1    survey, if I just can use that as an example,

          2    before one could have a exemption.

          3              Clearly, there are certain forms of

          4    surveys which had either expedited review

          5    previously that now are not necessarily receiving

          6    expedited review, that are mailed anonymous surveys

          7    to adult populations about, you know, opinions

          8    about culture or dress or something.

          9              Now, obviously, surveys that are dealing

         10    with more vulnerable populations, like children,

         11    have a process and procedure for IRB review.

         12              And the other thing I wanted to pass out

         13    is that we very much in the social and behavioral

         14    sciences and the health-related community -- this

         15    is a piece, a historical document, just one each,

         16    and it was very much pushed for at a point at which

         17    there was Congressional legislation pending that

         18    would have required that all research involving

         19    children had to be written consent.

         20              And the social and behavioral science

         21    community, with the health-related and education

         22    community really said, "We have a system in place


                                                                 142

          1    that values written consent, but recognizes that

          2    this must be understood and operationalized under

          3    different circumstances that different research

          4    might require.

          5              So if you're studying youth gangs or

          6    you're studying runaway children, you can't get

          7    written consent, but the current rules allow for

          8    that.

          9              And so that to exempt all surveys or all

         10    classes based on a methodology could be

         11    problematic, but to have expedited review for

         12    certain forms that have met minimal risk, and for

         13    the re-review of that same research seems to me

         14    well within I think what the articulated

         15    aspirations initially were, and what we now need to

         16    do is be able to specify that in a way that is more

         17    uniformly both interpreted and understood by IRBs,

         18    which probably relates to their training and

         19    expertise to do that.

         20              DR. DORFF:  It would seem to me that, for

         21    this community, it would be helpful if you people,

         22    right, who know what kind of research you do, could


                                                                 143

          1    come up with -- I mean there's clearly a range of

          2    things that you do that imperil human subjects to

          3    different degrees.

          4              Oral histories probably don't.  That's on

          5    one end of the spectrum, right?  Something having

          6    to do with -- I mean you define for me the other

          7    end of the spectrum, and then define for me things

          8    that are in between, because then, we would have a

          9    better sense of what kinds of things maybe ought to

         10    be completely exempted, and some things that have

         11    to go through full review, and some things that

         12    would be recommended for expedited review. 

         13              DR. FELICE LEVINE:  Right. 

         14              DR. DORFF:  And, frankly, I would depend

         15    upon you to give me that kind of a list --

         16              DR. FELICE LEVINE:  Right. 

         17              DR. DORFF:  -- because I don't do this

         18    kind of research. 

         19              DR. FELICE LEVINE:  And I think I gave --

         20    in my examples, those were some examples that,

         21    indeed, could either go through expedited review. 

         22    I think the current list in the common rule has


                                                                 144

          1    others that clearly would be classified as such,

          2    and I think that both can be provided.

          3              And one of the reasons why I circulated

          4    our code is that it becomes clear, not when it

          5    could go through expedited review, but when consent

          6    is necessary, when consent isn't.

          7              Clearly, the current problem of requiring

          8    re-review of analyzing public use files is one

          9    that's quite boggling to the researcher. 

         10              CHAIRPERSON MARSHALL:  Thank you.

         11              Bob, and then Bob, and then Adil. 

         12              DR. ROBERT LEVINE:  Thank you.  I want to

         13    respond to the proposition that we might consider

         14    blanket exemptions or blanket categories for

         15    expedited review.

         16              We have a history in this regard, and it

         17    hasn't served us well.  The National Commission

         18    recommended expedited review for certain

         19    categories, but one of the primary elements was

         20    that it had to be related to the experience of the

         21    local IRB.

         22              If they had done something over and over


                                                                 145

          1    again, there comes a time when there's not much

          2    more new to say.  So that they could have a

          3    responsible form of expedited review which included

          4    a recommendation by the expedited reviewer to bring

          5    it before the whole committee.

          6              What we got instead, and the National

          7    Commission published a proposed list for expedited

          8    review that was then current in the NIH clinical

          9    center.  And before anybody -- well, what happened

         10    is that this proposed list from the clinical center

         11    became the only expedited review permitted under

         12    the regulations for many, many years.

         13              As far as blanket exemptions go, it's

         14    tempting to say why we ought to give an exemption

         15    to a certain category, for example, oral history. 

         16    That doesn't present any risk.

         17              I'm from an institution where an oral

         18    history work was done by Robert J. Lifton, where he

         19    went around South America and interviewed all the

         20    Nazi war criminals that were still hiding out. 

         21    There was some risk.

         22              Breach of confidentiality.  There would


                                                                 146

          1    have been -- had remarkable consequences.

          2              But we have this all the time.  Survey

          3    research.  You know, I could give example after

          4    example.

          5              What I think we need is what you're asking

          6    for, and that is to have the sophisticated

          7    understanding of the various research methodologies

          8    and the ethos of various research groups built into

          9    the human subjects protection system. 

         10              We also have to have a system where the

         11    members of the IRBs are not intimidated by the

         12    possibility of applying some sophisticated judgment

         13    for fear that they will be second guessed and find

         14    their names in the paper or find their -- 

         15              PARTICIPANT:  --

         16              DR. ROBERT LEVINE:  So what we're finding

         17    more and more now is that members of IRBs -- Bob

         18    talked about the loss of motivation to serve on an

         19    IRB, as more and more, they're beginning to be

         20    perceived as probably incompetent because that's

         21    what the newspapers and the politicians and the

         22    governmental committees keep saying.


                                                                 147

          1              And even at that, anything they might do

          2    might be second guessed by somebody who had the

          3    authority to make life very difficult for them. 

          4    They're not using what little bit of discretionary

          5    judgment they might.  We have to look into this

          6    very carefully.

          7              Thank you. 

          8              DR. FELICE LEVINE:  I think that I

          9    couldn't have said it better if I was Robert

         10    Levine.  I think you captured what I was trying to

         11    communicate.

         12              I have worried, especially, I think the

         13    recent rash of phone calls over the, let's say the

         14    false cycle of having your proposals reviewed I

         15    think is a reflection of the chilling effect IRBs

         16    are feeling in being in a fishbowl and not knowing

         17    which way to go with respect to things that they

         18    didn't get right.  And, you know, we all face that

         19    when we're in a fishbowl.  You sort of overreact in

         20    a variety of ways.

         21              And it's having difficult consequences for

         22    the researcher, for absolutely sure, and it


                                                                 148

          1    certainly is widening that fault in the system. 

          2    And some of it is, you know, the adverse

          3    consequence of, you know, of the very troubling

          4    things that needed remedy, and the problem is you

          5    can overreact.

          6              And that's why I said the staging and

          7    sequencing of altering the system I think requires

          8    some statespersonship, too, because, you know,

          9    quick fixes aren't going to get us very far. 

         10    They're just going to postpone the problem. 

         11              CHAIRPERSON MARSHALL:  Thank you.

         12              Robert? 

         13              DR. RICH:  I'd be interested in your views

         14    of, and where the association would view a survey

         15    that -- I would posit a survey which you would

         16    agree would put subjects potentially at risk by the

         17    nature of the questions that we're asking, and that

         18    the same survey could be used either for scholarly

         19    purposes in a university department of sociology or

         20    psychology, could be used not for scholarly

         21    purposes in the same institution, but simply as a

         22    teaching exercise in the classroom, could instead


                                                                 149

          1    be used as a mechanism of public survey by a

          2    private organization like the Gallup organization

          3    or the Roper organization, or something like that,

          4    or, finally, be used by the media in an effort to

          5    simply go out and, as we see all the time, media

          6    surveys of public opinion which might, in fact be,

          7    put subjects at severe risk because not only is

          8    their opinion published, but their name and

          9    demographics are often -- also show up in the

         10    newspaper.

         11              And I think it's a terribly worrisome

         12    issue to me is, and really comes down to what do we

         13    mean by human subjects research in a sense, because

         14    the same instrument might be used for very, very

         15    different purposes, with different consequences,

         16    and we seem to focus simply on the scholarly

         17    activities, where the risk to human subjects may be

         18    actually much more for some of these more public

         19    kind of things that don't have a scholarly purpose.

         20              DR. FELICE LEVINE:  Are you literally

         21    talking about the same research instrument, or are

         22    you -- 


                                                                 150

          1              DR. RICH:  Same. 

          2              DR. FELICE LEVINE:  -- as opposed to the

          3    same methodology? 

          4              Well, the -- yeah? 

          5              DR. RICH:  I mean I'm just giving you the

          6    same research instrument for simplification --

          7              DR. FELICE LEVINE:  Uh-huh.

          8              DR. RICH:  -- of the question. 

          9              DR. FELICE LEVINE:  Uh-huh.  Uh-huh. 

         10    Well, I think that probably goes back to both what

         11    Bob and I were -- Professor Levine, I should say,

         12    and I were sort of postulating, and that is that

         13    I'll say a one-size-fits-all language probably

         14    would have very dysfunctional sort of consequences,

         15    and that is that under some framework of review,

         16    the question is are people being put at risk, and

         17    if so, in what ways?

         18              Now, the production of knowledge may be,

         19    in some general sense, might, you know, insofar as

         20    knowledge challenges, common assumptions in all

         21    fields of science may produce some risk for some. 

         22    I think that would be an overreach, to define human


                                                                 151

          1    subjects in such a broad stroke because it could

          2    really cripple an interest in producing knowledge.

          3              But it seems, from your question, it's a

          4    little bit hard to envision this same instrument

          5    asking questions that would make some vulnerable in

          6    some context and not in other context.

          7              But, certainly in my career at a research

          8    institute, I was a non-academically based research

          9    institute.  I was very much a promoter of having

         10    and creating an institutional review structure,

         11    which I'm pleased to say, exists today at that same

         12    institution, including with community members for

         13    assessing any risk and potential risks involved in

         14    doing research, and whether human subjects are

         15    adequately being protected.

         16              And, clearly, the federal discussion, at

         17    least by the National Commission, is looking much

         18    more at the research than where it occurs and/or

         19    who it's funded by.  And I think that, in general,

         20    would be a standard and one that probably needs to

         21    be scrutinized with respect to any specific method.

         22              DR. RICH:  If I could follow up? 


                                                                 152

          1              CHAIRPERSON MARSHALL:  Briefly, because I

          2    want to entertain a question from Adil, and then I

          3    would like to see if there are any of our ex-

          4    officio members might have questions.  And if I

          5    have time, then I would entertain questions from

          6    the public.  Okay, and Sandy is on the list.  So,

          7    brief, concise.

          8              DR. RICH:  Okay.  My follow-up is

          9    basically what you view -- what the professional

         10    view is of things like investigative reporting

         11    been, which clearly puts subjects at risk in a

         12    substantial kind of way.

         13              I don't think any -- where probably

         14    everybody in this committee right now is following

         15    with interest the emerging stories in the

         16    Washington Post about international drug trials,

         17    and as a general premise, I think we think that's

         18    probably a good thing to be happening.

         19              But I doubt that there's been an IRB

         20    that's looked at the nature of the processes that

         21    are being promulgated to get that story. 

         22              DR. FELICE LEVINE:  Well, let me say that


                                                                 153

          1    there are non-scientific fields that might use

          2    scientific methods in inquiry, and that may -- or

          3    might use some version thereof which may be true of

          4    investigative reporting.

          5              As a scientist, and I'm now speaking as a

          6    scientist as much as a social or behavioral

          7    scientist, certainly I and our part of the

          8    scientific community has not expressed a view with

          9    respect to the role and functioning of non-

         10    scientific parts of the labor force, whether it's

         11    the functioning of lawyers and how they might go

         12    about their work, or journalists.

         13              And I might, as a lay citizen, have a

         14    view, but I think I would be going well beyond my

         15    role as a scientist and a representative of the

         16    scientific society to comment about what might be

         17    the appropriate norms and practices, let's say

         18    investigative reporting or journalism, which under

         19    our understanding, certainly we would not define as

         20    social and behavioral science.  Let me put that

         21    right on the table.

         22              However good and useful it may be as a


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          1    public good, and the public may have a legitimate

          2    interest in, and I believe it does, as a citizen,

          3    in a fair and open press, clearly, that profession

          4    also needs to scrutinize how it does its work and

          5    whether, in light of it implementing those

          6    appropriate professional goals, whether they are

          7    also producing some harm that may need some

          8    reflection and self-regulation. 

          9              CHAIRPERSON MARSHALL:  Thank you.

         10              Adil? 

         11              DR. SHAMOO:  I want to ask, on the other

         12    side of this issue, do you know currently if there

         13    are research and social and behavioral sciences

         14    which is not currently under common rule or

         15    regulation that needs to be, and how should we do

         16    it? 

         17              DR. FELICE LEVINE:  I think that leads to

         18    my knowledge and impression that the social and

         19    behavioral science research that involves forms of

         20    primary data collection on human participants does

         21    fall within both the ethics codes that govern our

         22    sciences, as well as the system in place. 


                                                                 155

          1              But for the caveat of recognizing that

          2    there may be some institutions, because that only

          3    reaches currently to agencies under the common

          4    rule, and the federally-funded research

          5    technically, there certainly remain institutions

          6    and in all fields of science, including in the

          7    social and behavioral sciences, that these

          8    guidelines do not technically govern.

          9              And one of the reasons why I started this

         10    by tipping, at least as an example in sociology to

         11    our code, is that when I and our committee examined

         12    the old code, we talked about investigators

         13    submitting through a process of review work that

         14    falls under federal guidelines.

         15              And we had a conversation that went on for

         16    quite some time about why we were doing that. 

         17    Weren't there principles at stake that required

         18    review of all work of that genre and the code thus

         19    now says, or the equivalent, because if it doesn't

         20    exist, find something.

         21              If your institution doesn't have it, ask

         22    another IRB at a neighboring institution, and


                                                                 156

          1    that's what my research institute did for a while,

          2    the one that I career line at, and that is that it

          3    sought the advise and asked for the participation

          4    of the peer review process and IRB process, I

          5    should say, at the University of Chicago, until it

          6    put in place its own IRB.

          7              And, thus, there clearly are things that I

          8    would like to see operate according to the more

          9    general principles that are not now required.  But

         10    I think, increasingly, that's reducing because I

         11    think certainly within institutions that have

         12    assurances of compliance, they are now looking at

         13    both federally and non-federally funded work. 

         14              CHAIRPERSON MARSHALL:  Sandy? 

         15              DR. CHODOSH:  I have to be a little bit of

         16    a devil's advocate.  I'm sorry.

         17              CHAIRPERSON MARSHALL:  That's okay. 

         18              DR. CHODOSH:  I'm not sure that our rules

         19    that we serve under right now don't cover a lot of

         20    your concerns.  I think the problem is that they're

         21    not being implemented. 

         22              And this gets down to the fact that when


                                                                 157

          1    an IRB, for any reason, does not have the capacity

          2    or the knowledge to review a protocol, they are

          3    supposed to have outside review.  If they are not

          4    doing it, it's usually because of their ignorance

          5    or because it costs money to do so, or for various

          6    reasons.

          7              And I certain understand that the

          8    psychosocial behavioral sciences have suffered a

          9    great deal in this respect, but it's because -- not

         10    because the rules aren't there, but because it's

         11    not being implemented properly.

         12              But this is also true of a lot of medical

         13    research.  Most IRBs are not capable of doing, at

         14    least even the best ones are really not capable of

         15    reviewing probably ten percent of their research.

         16              If they're not bringing in consultants for

         17    outside review, then they're not doing the job that

         18    the rule says it's supposed to do.

         19              So I'm not sure that the correction is

         20    where you say.  Let's not change rules too quickly. 

         21    Let's make sure that the ones that we have are

         22    being implemented properly, and I don't think they


                                                                 158

          1    are. 

          2              DR. FELICE LEVINE:  I believe what you

          3    said to be devil's advocate for the moment is

          4    actually closer to what I said.  Indeed, I've said

          5    as a proselytizer of what we have on the books.

          6              When either the full line or the

          7    operationalizing of rules departs too far, then we

          8    need to ask ourselves what do need in place to

          9    really either redefine them or elaborate them or

         10    train for them, or change the composition of those

         11    implementing them so you don't have what are -- I'm

         12    going to put it in quotes, but essentially,

         13    discriminatory processes in the system where the

         14    haves come out ahead, and the have nots don't in a

         15    way that puts a burden on, in this case, on the

         16    scientific enterprise. 

         17              CHAIRPERSON MARSHALL:  Thank you.

         18              And now, I would like to entertain

         19    questions from our ex-officio members, if they have

         20    questions, and then please, for my sake and for the

         21    sake of others, if you could introduce yourselves,

         22    and again, give your affiliation. 


                                                                 159

          1              MR. SHELTON:  This is working?  Yeah.  Jim

          2    Shelton, U.S. Agency for International Development.

          3              I really wanted to sort of follow up on

          4    Dr. Rich's, I think, very important point, and

          5    maybe extend it, even.  But just to make the point

          6    that, given that the top is non-biomedical

          7    research, the field of play is really much wider

          8    than the sense I would have gotten listening to

          9    this today.

         10              Mostly what I've gotten so far is

         11    "university" and "science."  And I may be mistaken,

         12    but I don't actually think the word, "science" is

         13    in the common rule.

         14              The word, "research," is, but research, as

         15    it is defined, is so broad that not only would it

         16    include investigative reporting, but, arguably,

         17    Supreme Court proceedings, and a host of other

         18    human endeavors which are really very difficult to

         19    deal with.

         20              And to suggest that the committee -- we

         21    collectively need to have a way of addressing those

         22    kind of things, but I would also say better


                                                                 160

          1    addressing the categories in between.  And my own

          2    view is we really need a lot more tailoring, and

          3    also different -- you know, get outside of these

          4    metal boxes that we're in of 1970's, I would say,

          5    command and control regulation, and to sort of come

          6    up with better categories of activities, and figure

          7    other ways to approach them. 

          8              For example, maybe there is some risk to

          9    oral history.  Maybe there is somewhere in there. 

         10    But, you know, given the vast amount of human

         11    misery we have in the world to deal with, we need

         12    to prioritize it and we need to think of some other

         13    way of dealing with that besides making sure that

         14    our overburdened IRBs have to take on yet more and

         15    more work, which is what almost inevitably comes

         16    out of these kinds of discussions. 

         17              Thank you. 

         18              Sorry if that was grandstanding. 

         19              CHAIRPERSON MARSHALL:  No.  That was

         20    extremely helpful and very well put.  Thank you.

         21              DR. FELICE LEVINE:  Yeah.  And I'd say

         22    that is sort of a point in the report, and it's


                                                                 161

          1    also, I think, a point, as quickly as I could skim

          2    it, as it was being printed in the NBAC report

          3    that's out for a common period that there needs to

          4    be some sort of distributional energy in the areas

          5    of higher risk versus more, let's say, innocuous

          6    or, perhaps, you know, you don't legislate or have

          7    a regulation or a rule around rare events, or we

          8    will be legalistic to a fault. 

          9              And that's the concern about maybe how

         10    they have things now operationalized, and we may

         11    becoming legalistic to a fault. 

         12              MR. MESA:  I'm John Mesa with the VA, and

         13    I head the Office of Research Compliance and

         14    Assurance that came into being a year ago because

         15    OHRP's predecessor shut down the first of its

         16    activities, being the West L.A. VA Medical Center

         17    in March of 1999, and we've been sort of growing by

         18    leaps and bounds over the course of the year.

         19              One of the fundamental questions that we

         20    keep asking ourselves as this office gets underway

         21    is what do we know about the effectiveness of human

         22    subjects' programs, procedures and processes?  I'm


                                                                 162

          1    going to get very precise here to my question in

          2    just a moment, because it seems to me, in part,

          3    that if we can understand a knowledge base, how we

          4    pull it together, about all of these activities

          5    designed to protect human subjects, we would be

          6    well off with understanding and having a deep sense

          7    of knowledge about what it is that works and

          8    doesn't work.

          9              My question is along the lines of how do

         10    we, in fact, in your opinion, pull that information

         11    together?

         12              We can do descriptive studies, which I

         13    find, basically, what you've done, which is very

         14    helpful.

         15              We need analytical studies.  We need some

         16    kind of synthesis kind of work, and possibly, even

         17    some solid evaluative kind of studies.

         18              My question is sort of like a two-part

         19    question:  Who's best able to really pull that off?

         20              Is it more of the private, public academic

         21    center, or is it sort of like the feds again or the

         22    agencies again?


                                                                 163

          1              My analogy is to the Office of Research

          2    Integrity that has recently promulgated both its

          3    role in research scientific misconduct compliance

          4    activities, but also has stimulated the awarding of

          5    the grant program, because it is part of NIH.

          6              In fact, a research agenda or opportunity

          7    to engage in research in the area of research

          8    misconduct.  So you have a better knowledge about

          9    motivations and so on and so forth.

         10              So my question is if you accept for the

         11    moment we need better knowledge, what is your sense

         12    about the best ways of getting a better

         13    understanding of what is effective in this whole

         14    room of human subject protection? 

         15              DR. FELICE LEVINE:  Yeah.  I think I was

         16    sort of referring to that briefly in my prior

         17    remarks, and that is that -- now, I'll use the

         18    "science" somewhat more judiciously.

         19              But the whole area of research relating to

         20    humans -- how's that -- and those engaged in that

         21    area have not necessarily been terribly interested

         22    or engaged in research on their own operations as a


                                                                 164

          1    scholarly pursuit. 

          2              Not unusual.  The legal profession,

          3    really, until the early seventies, really didn't

          4    have very much research on the structure of the

          5    legal profession, the medical profession, too.  I

          6    mean there was the Flexner report, but it's not a

          7    major area of pursuit.  It's really a literature

          8    that one can almost manageably put in a little

          9    corner of a room and, you know, read over a few

         10    months.

         11              ORI, Office of Research Integrity, has

         12    really now been pushing and promoting.  There's

         13    been two research-oriented meetings.  One was a

         14    research conference in November.  Another one was

         15    held under the auspices of AAAS last June.

         16              And, frankly, even though one could think

         17    of research integrity as defined by the standard

         18    language in that area, much of the discussion also

         19    related to human subjects issues.

         20              I think that this is an important area, if

         21    I could use sociology with a little less, for work

         22    in sociology of science to encourage and enhance,


                                                                 165

          1    use a small subfield within the social and

          2    behavioral sciences and in other research

          3    traditions that deal with human phenomena.

          4              I think that clearly we want to do some,

          5    as Don Campbell would have said, reforms as

          6    experiments.  As we introduce change, we don't want

          7    to build in such a process of evaluation that we

          8    can't function, but we want to put in a process of

          9    evaluation so that we know what we're doing as we

         10    modify and change the system.

         11              But I do think that, hand in hand with

         12    this educative function, is a more sustained

         13    research tradition and the creation of a more

         14    sustained cadre of researchers who value and are

         15    valued for doing work in this area.  And I think

         16    it's a terrific area and one that really has been

         17    under study. 

         18              CHAIRPERSON MARSHALL:  And I think that

         19    question was a perfect segue into what we, after

         20    the next two questions, our look at

         21    recommendations.  And that question was actually

         22    going to be on my list, so that was perfect.


                                                                 166

          1              So I'm going to ask the next two speakers

          2    to make their questions succinct and brief so that

          3    we can move on to our discussion of

          4    recommendations.

          5              MR. RUBEN:  Philip Ruben, National Science

          6    Foundation.

          7              Very briefly, I'd like to second the

          8    comment on a request that there be a sensitivity to

          9    the balancing of risks and definition of risks.

         10              And, second, I'd like to ask you a

         11    question:  Dynamic think that there's adequate

         12    representation of behavioral and social scientists

         13    in other categories, on IRBs, committees, boards

         14    and other bodies that attempt to come up with

         15    policy related to human subject protection -- I'm

         16    sorry -- to human protections? 

         17              DR. FELICE LEVINE:  Read my lips.  I must

         18    have not been clear enough the first time through. 

         19    I think that's one of the faults in the system,

         20    faults with the fault line, f-a-u-l-t, and that is

         21    that there isn't, I think -- I think that one of

         22    the long-term and current problems is that there


                                                                 167

          1    isn't adequate integration in all parts of the

          2    system of the social and behavioral science

          3    community, and that then, when one is present, one

          4    is functioning either as the expert in only that

          5    area that I think has adverse consequences for all

          6    of science.

          7              And that's true on the advisory panels

          8    that are now being created.  It was true of NBAC,

          9    you know, with all due respect to this body, which

         10    you didn't create, but was created, and IOM and

         11    others that there is not sufficient depth of social

         12    and behavioral science knowledge and expertise.

         13              And to be in a position where that is

         14    brought in as expert is different from being at the

         15    high table of deliberation.  We know that in any

         16    decision-making body. 

         17              MR. SNIDER:  Hi.  Dick C. Snider.  I'm the

         18    Associate Director for Science at CDC.  And I

         19    wanted to represent a public health perspective in

         20    that I wanted to first point out that the conduct

         21    of public health requires medicine, requires

         22    epidemiologists, requires behavioral social


                                                                 168

          1    scientists, engineers, et cetera, et cetera, et

          2    cetera.

          3              And we do need a mechanism for

          4    inclusiveness.  And so this just reemphasizes

          5    what's been said.

          6              There's a second issue, though, that's

          7    extremely important and that is it's not always

          8    clear to us when we are engaged in research and

          9    when we're not engaged in research.

         10              When we go to, for example, for Yemen to

         11    deal with Rif Valley Fever, are we engaged in the

         12    clinical equivalent of public health activity of

         13    clinical care?  Are we engaged in a research

         14    activity?

         15              And this has caused quite a bit of

         16    consternation, and I would just request of the

         17    advisory committee that you consider trying to

         18    elaborate on the situation with regard to when

         19    we're engaged in a research mode and when we're

         20    not.

         21              We certainly need to protect human

         22    subjects obviously in all situations, and it's not


                                                                 169

          1    an issue of informed consent or not informed

          2    consent, necessarily.

          3              But it's not at all clear what activities

          4    require approval sometimes and what do not require

          5    approval. 

          6              CHAIRPERSON MARSHALL:  Thank you very

          7    much.

          8              Yes?  

          9              DR. FELICE LEVINE:  Can I make --

         10              CHAIRPERSON MARSHALL:  Yes. 

         11              DR. FELICE LEVINE:  -- one quick statement

         12    about that? 

         13              CHAIRPERSON MARSHALL:  I'm sorry.

         14              DR. FELICE LEVINE:  No. I think that's an

         15    extremely important point, and it was actually one

         16    we took up because it -- in this ethics code.

         17              It's not your typical circumstance, but

         18    you wear sometimes multiple professional hats

         19    consistent with your role. 

         20              I'm sure obviously that happens in the

         21    biomedical community and in the social and

         22    behavioral science and public health communities,


                                                                 170

          1    as well.

          2              And one of the things we addressed in the

          3    code is that if you find yourself in a place where,

          4    in a different role as sociologist, in this case,

          5    you have, essentially over time, observations or

          6    ideas that might, indeed, make persons post hoc

          7    subjects in a way. 

          8              Then you have an affirmative

          9    responsibility not to assume they are, and thus,

         10    this is research that you can undertake because, my

         11    God, I've been, you know, talking with this group

         12    of adoptive parents for two years, providing some

         13    counseling, and now, I'm going to write this great

         14    story or this great academic article and give

         15    biographical anonymity.

         16              But, indeed, it may be that you need to

         17    say to people who thought of you in role A that

         18    you're now wearing hat B.  And, indeed, we try to

         19    address that in the code and say that there is a

         20    responsibility to not assume that this is research

         21    data and a research subject, but to make clear that

         22    you would like to do that.


                                                                 171

          1              And I assume that this is an issue that

          2    both is important and one that is as good a fit in

          3    the biomedical sciences as it is in the social and

          4    behavioral and public health area. 

          5              CHAIRPERSON MARSHALL:  Felice, thank you

          6    so much. 

          7              DR. FELICE LEVINE:  Sure.  Thank you. 

          8              CHAIRPERSON MARSHALL:  That was just

          9    superb, and given the length of time that you had

         10    to prepare for this meeting, just stellar.  So,

         11    thank you. 

         12              DR. FELICE LEVINE:  You know what happens

         13    if you have too much time. 

         14              CHAIRPERSON MARSHALL:  But I would ask you

         15    if you might be willing, we are going to talk about

         16    recommendations, but there may be questions that

         17    arise during this discussion of recommendations.

         18              Would you mind just staying here -- 

         19              DR. FELICE LEVINE:  Sure.

         20              CHAIRPERSON MARSHALL:  -- if there's some

         21    more need for information, committee.

         22              So it seems to me that within the next 15


                                                                 172

          1    minutes or so that we need to define the issues

          2    relative to this topic that we need to make

          3    decisions about the data that we need and how to go

          4    about gathering that, whether it would be research

          5    studies that we commission, be they from social

          6    scientists or philosophers of science, whether we

          7    want to commission papers, whether we want to

          8    convene meetings or workshops.

          9              And once we've done those tasks, then we

         10    need to assign priority to them.  And if I'm

         11    leaving something out, then I'm sure that you will

         12    let me know.

         13              I did hear some themes that did emerge,

         14    and they had to do I think primarily with

         15    definitions and large-scale definitions.  To begin

         16    with, what is social science research?  Does it

         17    include the fourth estate or not?  I think that's

         18    something that we need to attend to. 

         19              Research risks, how those are defined,

         20    whether there's a sliding scale, where things fall

         21    along the spectrum of risk relative to behavioral

         22    and social sciences research.


                                                                 173

          1              An appropriate framework for review, not

          2    only relative to the system that currently exists

          3    that may be broken, in part, but could be fixed,

          4    and what might need to be done in an innovative

          5    way, and I guess the overall theme being balance.

          6              So the floor is open, committee members.

          7              Abbey and Elliot and Mark and Bob. 

          8              MS. MEYERS:  I'm just wondering whether we

          9    should examine what the implications would be if we

         10    broke the non-biomedical research away from the

         11    medical research.

         12              Should there be a separate IRB system for

         13    non-medical research, and if there is, are the

         14    universities going to be furious because of the

         15    cost or disruption of their other activities?

         16              So I think we really need to look at

         17    examining what would happen if it was broken off. 

         18              CHAIRPERSON MARSHALL:  Thank you. 

         19              DR. DORFF:  Yes, and that's exactly what I

         20    was going to say.  And I think that it doesn't have

         21    -- that your recommendation along these lines

         22    doesn't have to be limited to large universities. 


                                                                 174

          1    You could have regional bodies of, you know,

          2    regional IRBs that deal with social science

          3    specific research so that even people, students and

          4    researchers in small universities could do this.

          5              But I think one of the recommendations for

          6    this committee would be basically to endorse the

          7    recommendation that came out of your report, that

          8    there be minimally more social scientific, you

          9    know, scientists on IRBs, but better yet, a whole

         10    separate regimen of IRBs to deal with this kind of

         11    research.

         12              The second thing is, I mean I would just

         13    like to repeat that at least I would like to know,

         14    you know, what this spectrum would look like.  And

         15    if I can respond to Brown's point, you can do it

         16    from a legal point of view.  You can talk about,

         17    you know, burden of proof.

         18              In other words, for something like oral

         19    histories, the burden of proof would be on those

         20    that want to say that you need to have an IRB

         21    review.

         22              For something on the other end of things


                                                                 175

          1    like maybe psychiatric drugs or something like

          2    that, right, the burden of proof would be on one

          3    who would say that you don't need to have a review.

          4              And then you'd have, you know, you'd have

          5    that kind of a scale, and if we knew exactly what

          6    was going on, and to the extent that they imperil

          7    human subjects, then I think we would be able to

          8    come to some kind of recommendations that would

          9    make sense for your field. 

         10              CHAIRPERSON MARSHALL:  I'm going to take

         11    the Chair's prerogative here, and I'm going to ask

         12    just a brief question of Bob Cooke Deagan. 

         13              Bob, part of what we're talking about is a

         14    question that the IOM Committee will be looking,

         15    and that is, is the IRB system broken?  

         16              And let me just ask whether you see any

         17    inefficiencies in terms of the questions that we're

         18    asking and what we might be looking at in terms of

         19    data gathering and so forth, and what your

         20    committee -- not your committee, but the IOM

         21    Committee will be doing, and what plans, if any, it

         22    has to address the social sciences aspect of human


                                                                 176

          1    subjects' protections review systems? 

          2              MR. DEAGAN:  As you know, this is on our

          3    radar screen, but more for the second report than

          4    for the first report.

          5              There are 11 members of our committee. 

          6    Two of them are members of the social sciences. 

          7    That's their background.

          8              So we know that it's going to come onto

          9    our radar screen, but frankly, I don't think we're

         10    probably going to do too much about it until some

         11    time in, you know, after April.

         12              At that point, I think it's going to be

         13    one of the things we really have to wrestle with. 

         14    I think it's one of the friction points that has

         15    emerged over the last year.

         16              But that's really vague.  I mean it's on

         17    our radar screen.  I don't think I can say much

         18    more than that. 

         19              CHAIRPERSON MARSHALL:  But the point is

         20    that we can expect some expert advice at some point

         21    in the spring -- 

         22              MR. DEAGAN:  Right. 


                                                                 177

          1              CHAIRPERSON MARSHALL:  -- from the IOM

          2    Committee, as well. 

          3              MR. DEAGAN:  I think you need data

          4    gathering and stuff like that that we would do. 

          5    We're going to try to keep that part of our process

          6    as open as possible, and that would be shared along

          7    the way.

          8              But I'd guess there's going to be a lot of

          9    other activity that would be inputs to our

         10    committee. 

         11              CHAIRPERSON MARSHALL:  Mark? 

         12              MR. BARNES:  Yeah.  I don't know exactly

         13    how we would, you know, go about it because I think

         14    our working methodology as a committee is still

         15    obviously in formation.

         16              But it seems to me that, you know, that as

         17    -- and I echo what Dixie Snider said about the

         18    paradigm of public health regulation.

         19              When you talk about regulation, there

         20    really are two things that you want to achieve, and

         21    I think that -- or two things are balanced.

         22              Number one, you're balancing fundamental


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          1    rights that may be infringed by regulation, and

          2    that's why, for example, in the journalism example,

          3    there are very compelling fundamental rights that

          4    lead us not to regulate that activity, even if we

          5    choose to regulate activity which is funded by

          6    government like social science research funded by

          7    government.

          8              And the second thing you'd look at is

          9    you'd look at the severity of the risk that you're

         10    trying to abate through the regulation, and you

         11    make decisions really based on those mother

         12    variables, but primarily, those two variables.

         13              And when we talk about social science

         14    research and we think about the issues of academic

         15    freedom being a part of at least a fundamental

         16    rights calculus, but government funding being part

         17    of the compelling interest, and you compare that to

         18    the rationale, the historical background through

         19    which government heavily regulates, and for many

         20    other reasons, medicine, the practice of clinical

         21    medicine and the practice of clinical medical

         22    research, then I think that -- and you sort of look


                                                                 179

          1    at the continuum there of fundamental rights, then

          2    it does seem to me, at least what I've -- 

          3              You know, what I take away from this

          4    discussion is that there is a realm of social

          5    science research which is not clinical medicine,

          6    for which there are fundamental academic freedom

          7    rights and free speech rights that do emerge as an

          8    important consideration, which makes it distinct

          9    from clinical medical research.

         10              And it seems to me that there are, you

         11    know, compelling -- and, also, the severity of the

         12    risk is, although it can be great within the realm

         13    of social science research, it is perhaps as, on

         14    the average, much less than in the realm of

         15    biomedical stuff.

         16              And then you look further at the issue

         17    that even within biomedical research, as I think

         18    we'll explore over our next meetings, the trend has

         19    been more and more towards specialization.

         20              One size does not fit all in IRBs any

         21    longer.  Biosafety is one issue.  Genetic therapy

         22    is one issue.  Cardiovascular stuff is one issue. 


                                                                 180

          1    Orthopedic devices are another issue.  AIDS

          2    research is another issue.

          3              Our biomedical IRBs are not even competent

          4    to address their areas of expertise.

          5              I think it leads us to, in terms of

          6    fundamental recommendations, toward, you know,

          7    really the necessity to look at breaking out social

          8    science, number one, as opposed to clinical

          9    medicine in terms of the research regulation and

         10    oversight, and within social science, looking at

         11    the continuum of risk within social science, and

         12    not having one size fit all, even within the realm

         13    of social science.

         14              So the final thing, the second part of

         15    what I have to say, which will be quite brief, is

         16    that in your paper, there is also an issue that

         17    emerges, which I think also will emerge in our

         18    discussions which is the risk of legal liability in

         19    the operation of IRBs.  It's talked about in a few

         20    paragraphs in your report.

         21              And I would like us, not only in the issue

         22    of social science research regulation, but also in


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          1    the area just of clinical medicine and clinical

          2    research, to look very carefully at the issue of

          3    whether there should be a bedrock recommendation of

          4    this committee, that there should be a federal

          5    statute that insulates IRB members and IRBs

          6    themselves from liability to anyone absent actual

          7    malice or recklessness in the way that they do

          8    their jobs.

          9              Take the law out of it, and take the law

         10    and the questions of legal liability out of the

         11    operation of IRBs before we get to the point that

         12    Canada has apparently already reached at which

         13    individual lawsuits have actually been filed

         14    against IRB members for their misprision or alleged

         15    misprision of responsibilities in their operation

         16    of the IRBs.

         17              And I bring that up only because it's

         18    present as a consideration in your report. 

         19              CHAIRPERSON MARSHALL:  Here's how I would

         20    like to proceed.  I have three more people on my

         21    list for questions, and I would, if they could be

         22    brief and sort of data gathering questions, then we


                                                                 182

          1    really need to move on to talking about our plan

          2    and assigning priorities to how we're going to

          3    proceed.

          4              Bob? 

          5              DR. ROBERT LEVINE:  Thank you.  Since I

          6    raised my hand, several points have come up that

          7    are even more interesting than the reason I raised

          8    my hand.

          9              Briefly, I don't think you should try to

         10    redefine research.  Whenever people try to redefine

         11    something to reach a regulatory objective, they

         12    secede from the union formed by use of the English

         13    language.

         14              You know, if you stipulate definitions,

         15    you got to have a footnote every time you use it,

         16    or else people will think you really mean research.

         17              The definition we use of "research" was

         18    submitted to the National Commission.  Stapled to

         19    it was a photocopy of one page of Webster's

         20    Dictionary, because it was intended to comply with

         21    what the English language did.

         22              What you can do is say there is some


                                                                 183

          1    categories of research we're not interested in

          2    regulating.  These can be found in the exemptions.

          3              Sometimes the exemptions cut too broadly. 

          4    I've already mentioned some examples of that.

          5              I think we have to do sometimes a cost

          6    benefit analysis.  We must find a way to resist the

          7    irresistible rhetorical question:  Could you

          8    possibly save an individual from embarrassment by

          9    requiring that all, you know, research be reviewed

         10    by a certain type of committee?

         11              The answer must be, yes, it is possible. 

         12    But as we look at the crummy 26 percent we get from

         13    the federal government, there is so many things

         14    that are higher on the priority than that

         15    infinitesimally small probability of sparing

         16    somebody some embarrassment. 

         17              I think that dividing social and

         18    behavioral research from biomedical research is a

         19    dream I relinquished about 25 years ago when the

         20    National Commission asked me to write a paper

         21    distinguishing the two for regulatory purposes, and

         22    I demonstrated to their satisfaction there's a very


                                                                 184

          1    broad area of overlap.

          2              The exemptions related to free speech,

          3    yes.  The reason we have exemptions is not the

          4    National Commission.  It's because a political

          5    scientist named Epheda Solapul persuaded Congress

          6    that this was an abridgement of his First Amendment

          7    rights to submit to IRB review.  And what we got is

          8    a series of exemptions.  Some of them very well

          9    thought out, some of them not so well thought out.

         10              I must say I can't agree that the IRBs are

         11    incompetent to review biomedical research.  You can

         12    support that statement only if you believe that

         13    it's the task of the IRB to evaluate the scientific

         14    design of research.

         15              The IRB was deliberately created to be

         16    incompetent at that.  That's not its task, and

         17    that's why I'm so sympathetic with Mary Faith's

         18    call for an evaluation of the overall system,

         19    rather than to say the IRBs got to do absolutely

         20    everything.

         21              What we need is somebody who evaluates the

         22    scientific design and then tells the IRB, "We think


                                                                 185

          1    it's good or good enough."

          2              We can't have enough oncologists and

          3    cardiologists and so on, on these committees.  I

          4    can go on and on about that.

          5              In an average sized institution, you've

          6    only got one or two people who are really expert

          7    enough to evaluate the scientific design, and

          8    they're usually the principal investigator and the

          9    co-investigator, and you got to kick them out of

         10    the room while you're discussing the protocol,

         11    anyhow.

         12              We've got to have a way to get systematic

         13    scientific review with NIH funded research.  We get

         14    it from the IRG.  And now that we've got the just-

         15    in-time regulations, we actually had that at the

         16    time we were looking at the protocol.

         17              Enough.  Thank you. 

         18              CHAIRPERSON MARSHALL:  Thank you, and we

         19    really are in a time bind here.  It's almost a

         20    quarter till, and that's when we're scheduled to

         21    convene for lunch. 

         22              Adil? 


                                                                 186

          1              DR. SHAMOO:  I'll be very brief.

          2              I don't think we should lose sight of some

          3    of the social and behavioral research can cause

          4    dignitary harm, and I think all the talk here has

          5    been on physical harm, you know, biomedical

          6    research.

          7              And a quick example of a high school that

          8    has surveyed how many students take drug, and let's

          9    assume that leaks, even though they are no name,

         10    identification, nothing, it leaks in the community. 

         11    You're stigmatizing a whole high school, especially

         12    in a small community.

         13              And I want to make a comment on Mark.  I

         14    think I'm surprised he is a lawyer, and he says we

         15    should have no liability.  That means there are no

         16    lawsuits for him anymore.  He must be not a lawsuit

         17    lawyer.

         18              But having said that to me really is

         19    unacceptable to remove liability because today's

         20    unveiling of the privacy, which to me, is lesser

         21    important than harming patients directly, there is

         22    criminal and financial liability.  And I would


                                                                 187

          1    oppose removing any liability from those involved.

          2              It's important to keep -- the reason we

          3    don't have too much regulation is that because the

          4    ultimate deterrent, we give a lot of freedom for

          5    people.  But the ultimate deterrent, we give a lot

          6    of freedom for people, but the ultimate deterrent

          7    is high price you pay.  Otherwise, then you have to

          8    regulate over and over again.

          9              Thank you. 

         10              CHAIRPERSON MARSHALL:  Thank you. 

         11              MR. MESA:  Very quickly, a comment about

         12    the issue of IRBs and their memberships versus

         13    devoted IRBs to the social and behavioral sciences.

         14              We have an opportunity with the

         15    registration of the IRBs that's coming about under

         16    OHRP's leadership.  I would suggest that we collect

         17    that data at that particular point in time if we

         18    possibly can on the 4500 roughly IRBs that are

         19    believed to exist in the country.

         20              I know at least five in the VA who are

         21    devoted to social behavioral review, and that's all

         22    they do.  They're not biomedical.  They are social


                                                                 188

          1    behavioral.

          2              One other comment, and Bob Levine, I don't

          3    know if I've got this right or not, but I do think

          4    it's worthy, given the discussion, that under the

          5    definition of research in the common rule under

          6    that 46102D, that people be reminded that in there,

          7    there's a nasty little kicker which says, for

          8    example, under this definition, "Some demonstration

          9    service programs may include research activities."

         10              The implication is there's a broader

         11    context here than just the simple notion we're

         12    designing a protocol to get new knowledge.

         13              And that is, I think for a lot of us in

         14    the agencies, very confusing right now.  Flat out

         15    evaluation research which does not get funded out

         16    of, quote, "a research pot of money" you define as

         17    maybe operations research.  But it involves

         18    collecting new data from human subjects to be

         19    coalesced, synthesized and published. 

         20              Now, I'm just pointing it out as an

         21    example because there are all kinds of it, services

         22    research, survey research, repositors of data.


                                                                 189

          1              And I would urge this committee at least

          2    to gauge with the issue.  You may not be able to

          3    find the solution, but somewhere in there, that

          4    issue I think has to be engaged with, given the way

          5    it is in the common rule right now. 

          6              CHAIRPERSON MARSHALL:  Thank you. 

          7              DR. CHODOSH:  Can I just add something to

          8    what John said? 

          9              CHAIRPERSON MARSHALL:  Very brief, yes. 

         10              DR. CHODOSH:  Very briefly, and that is,

         11    yes, if you collect that data on how many protocols

         12    are handled by how many IRBs, you should also

         13    collect how many social scientists are on those

         14    IRBs.  Then you'll have a good idea of whether the

         15    representation is appropriate to the number of

         16    protocols.

         17              And then you can also ask how many times

         18    they get outside consultation, and that would give

         19    you even more information about whether those that

         20    are undersubscribed as social scientists in fact

         21    are using outside help. 

         22              CHAIRPERSON MARSHALL:  The rubber hits the


                                                                 190

          1    road, committee members.  How shall we proceed in

          2    terms of issues, staying together and assigning

          3    priority to them?  What is your pleasure? 

          4              DR. SHAMOO:  I'll be the guy who is not

          5    embarrassed by saying I don't know, and I think

          6    since this is our first meeting, we are not clear,

          7    and when I saw the word, "recommendation," I

          8    immediately asked her and I asked others, "Where

          9    are these recommendations I'm supposed to have read

         10    and thought about and came back with an opinion?"

         11              And maybe for subsequent meeting -- I know

         12    this is rushed -- that we have some draft from a

         13    subcommittee, obviously, and then we have --

         14              CHAIRPERSON MARSHALL:  Yeah.

         15              DR. SHAMOO:  -- something to chew on --

         16              CHAIRPERSON MARSHALL:  Right.  Yeah.

         17              DR. SHAMOO:  -- and a language already

         18    prepared. 

         19              CHAIRPERSON MARSHALL:  Right, and Adil,

         20    let me speak to that.

         21              There is no expectation today -- let me

         22    reassure you that we are going to, you know, within


                                                                 191

          1    the next five minutes, solve all of these issues

          2    and, you know, make pronouncements about

          3    recommendations.

          4              What I would like to ask is, from a

          5    procedural perspective, how would you like to go

          6    about getting at the issues in terms of defining

          7    them, data gathering, and then assigning priority

          8    to what we've talked about today? 

          9              Bob? 

         10              DR. ROBERT LEVINE:  I have one proposal

         11    and I am not at all sure it's the most important

         12    things we should do, but I would find it very

         13    illuminating.

         14              The National or the President's

         15    Commission, in the early 1980's, commissioned a

         16    paper from one Jerry Mashaw which was a theoretical

         17    analysis of decision-making structures.  And he

         18    applied it to the IRB and came out with very

         19    important insights, but they were theoretical.  You

         20    know, he said decision-making groups can be wise

         21    judges or paternalistic professions or micro-

         22    political accommodators and things like that.  And


                                                                 192

          1    then he defended, on theoretical grounds, his

          2    vision of what the IRB ought to be.

          3              I think, 20 years later, it would be very

          4    interesting to have some sort of collaboration

          5    between Jerry, who is still very active, and any

          6    other people who are highly experienced in what

          7    actually is going on to see what does it look like

          8    now, and how could it make recommendations for

          9    improvement.

         10              Thank you. 

         11              CHAIRPERSON MARSHALL:  Elliot? 

         12              DR. DORFF:  Along those lines, the things

         13    that Sandy just mentioned before I think would be

         14    very interesting to find out, namely, the number of

         15    people in the social sciences that are on IRBs

         16    relative to the number of protocols that they

         17    consider.

         18              And I would like to get from, you know,

         19    the Association of Sociologists and so on, all

         20    right, what your recommendations would be so that

         21    we could -- I mean you gave us some concrete

         22    recommendations at the end, but I would really like


                                                                 193

          1    to know your wish list.  In other words, if you

          2    really thought that this was going to be done well,

          3    how would you do it well? 

          4              DR. SHAMOO:  We are making recommendations

          5    now about the social sciences and how it should be

          6    handled over the overall system.

          7              My thinking is really we should discuss

          8    the overall issues related to human subjects

          9    protections and go down there where the social

         10    science would be an important component of all our

         11    thinking and study, rather than we're going to take

         12    piecemeal now.

         13              I think it's we may lose the overall

         14    picture or whatever we recommend within a given

         15    area may not fit the overall picture we have

         16    designed.

         17              And I really think we should -- at least

         18    my thinking is that we should think of the whole

         19    system, what the over side should be, what the

         20    rights should be, et cetera. 

         21              CHAIRPERSON MARSHALL:  I think that's an

         22    excellent point and that's sort of what I was


                                                                 194

          1    trying to get at with my question to Bob Cooke

          2    Deagan because there is a great amount of overlap

          3    in terms of looking at the entire system, and then

          4    these more specific topics that we're looking at.

          5              So I guess my sense is this:  There is

          6    nothing that precludes us from making sort of

          7    interim recommendations and from coming back, once

          8    we have had the wisdom of the IOM Committee and its

          9    guidance and revisiting issues. 

         10              We have redefined our agenda, and we do

         11    not want anything to be done in a precipitous,

         12    inadequate fashion.  So I think that we should have

         13    that understanding up front, that if we think that

         14    something needs to be revisited, then we have the

         15    prerogative to do so.

         16              Yes, Judy? 

         17              DR. SIEGEL:  My point, which Adil actually

         18    started, and I'll go a little bit further is,

         19    someone just brought up what should the IRB be, and

         20    I think this is a piece of that which I also agree

         21    may be one of the first questions or one of the big

         22    questions is what should an IRB be?


                                                                 195

          1              This definitely has -- this piece of

          2    social science has data gathering components around

          3    it.  I, for one, am not very versed in what the

          4    issues are.  But, certainly, I would imagine that

          5    the rest of today and maybe the rest of the times

          6    we meet, there will be other issues that bracket

          7    under what should the IRB be. 

          8              CHAIRPERSON MARSHALL:  Bob and Roger and

          9    then I'm going to make some concluding remarks, and

         10    we'll go to lunch. 

         11              DR. RICH:  I'd just like to hope that we

         12    come back to the issue; that is that I'm finding

         13    particularly vexing in my role as an institutional

         14    official, which has to do with how one really

         15    separates social and behavioral research in an

         16    educational setting.

         17              And I think there is a great deal of

         18    confusion about that.  I read from 45 CSR:  "As an

         19    exemption, research conducted in established or

         20    commonly accepted educational settings involving

         21    normal educational practices."

         22              And I think there is great confusion,


                                                                 196

          1    particularly in undergraduate courses in psychology

          2    and things like this, as to whether or not that is

          3    simply an educational activity or whether it is

          4    really is human subjects research that ought to be

          5    under the scrutiny of an IRB.

          6              And I would just simply say it would be

          7    very helpful, in my efforts at a major institution,

          8    and I suspect the others who are wrestling with

          9    this issue to have more clarity on where that line

         10    blurs between education and research. 

         11              CHAIRPERSON MARSHALL:  Thank you, and,

         12    excuse me, Roger? 

         13              PARTICIPANT:  I would suggest the two

         14    problems that ought to be right at the top of your

         15    list is education of IRBs and investigators and

         16    money.  And a lot of decisions can be made locally,

         17    and they may not be made the same way in California

         18    that they're made in Massachusetts, but I sort of

         19    say, so what, as long as people are trying to

         20    implement the common rule in good faith.

         21              But there is a serious problem of

         22    educating IRB members and money to run them.  And I


                                                                 197

          1    think that ought to be at the top of anybody's

          2    list. 

          3              CHAIRPERSON MARSHALL:  Hear, hear, and I

          4    know that that is at the top of the list for the

          5    folks at the IOM. 

          6              Abbey, I'm going to cut you short for this

          7    reason; that is, tomorrow afternoon, we will have

          8    the opportunity to recap and to revisit what we

          9    have done over the course of today and tomorrow.

         10              My sense is this, is that it is that the

         11    group is in consensus that we will commission some

         12    papers, that we will gather some data, and that the

         13    general areas have to do with the number of people

         14    in social science research relative to the number

         15    of IRBs and those sorts of reviews that are done.

         16              A wish list.  We have asked Felice to come

         17    up with a wish list from the American Sociological

         18    Association.

         19              I would ask that we also perhaps can

         20    consider looking, asking for some wisdom on risk

         21    relative to research, in general, but especially

         22    looking at social and behavioral sciences research,


                                                                 198

          1    and then, certainly, the suggestion that Bob made

          2    about Jerry Mashaw, and having that revisiting his

          3    earlier paper.

          4              So why don't we leave things at that for

          5    now and we will break for lunch and -- 

          6              DR. FELICE LEVINE:  Can I just make sure I

          7    heard correctly what I thought I was saying "yes"

          8    to?

          9              I thought it was going to include both

         10    components in that.  And I'll say with my general,

         11    not just ASA hat on, but I think --

         12              CHAIRPERSON MARSHALL:  Correct.  That is

         13    -- thank you for keeping me honest. 

         14              DR. FELICE LEVINE:  Okay.

         15              CHAIRPERSON MARSHALL:  Yes.  You are

         16    correct.

         17              And we are due to -- we're running behind,

         18    but we are due to reconvene from lunch for our next

         19    session at 1:45 p.m.  Thank you very much.

         20              [Whereupon, at 12:15 p.m., the meeting was

         21    recessed to be reconvened this same day at 1:45

         22    p.m.] 


                                                                 199

          1                 A F T E R N O O N   S E S S I O N 

          2                                        [Time Noted:  2:00 p.m.]

          3              CHAIRPERSON MARSHALL:  In the interest of

          4    time, let us begin.  We do have a quorum, although

          5    all of our committee members have made it back from

          6    bolting their lunches, the poor things.  I

          7    apologize to all of you.  We will try and be more

          8    organized and timely in the future.

          9              We will follow the same format this

         10    afternoon that we did this morning.  We will have a

         11    paper presentation.  Then I will invite, during the

         12    discussion period, questions from committee

         13    members, from our liaison members and ex-officio

         14    members from the agencies, and then also from what

         15    I will refer to as our "public members," since we

         16    are a public enterprise. 

         17              [Discussion off the record.] 

         18              CHAIRPERSON MARSHALL:  Yes.  Thank you

         19    very much, Kate.

         20              Jennie Joe has joined us.

         21              Jennie, before we begin, would you mind if

         22    we gave you five minutes to introduce yourself,


                                                                 200

          1    tell us a little bit about you, and also what

          2    issues you have a special interest in that you

          3    might like this committee to consider in the

          4    future?

          5              DR. JOE:  Thank you.  Sorry to be late,

          6    but I'm glad to be here.

          7              I'm from the University of Arizona.  I'm

          8    in family and community medicine.  I'm a social

          9    scientist, a medical anthropologist.

         10              I'm also a Native American, member of the

         11    Navajo Nation from the Southwest.

         12              I've been an active member of the Indition

         13    Health Services Institutional Review Board for a

         14    number of years.

         15              I'm particularly interested -- I think the

         16    impact of research on Indition as peoples, and the

         17    consequences that means not only for themselves,

         18    but I think what happens about what we write about

         19    them.  How stereotypes end up hurting people and

         20    not helping them.

         21              And I'm particularly interested in sharing

         22    this kind of value, I think, with young scientists. 


                                                                 201

          1    I like for them to inherit this kind of ethics that

          2    are important.  And so that's one of my, I think,

          3    passion for becoming and agreeing to be a member

          4    here.

          5              And I'm also interested in children, and I

          6    know that this is one of the topics that will be

          7    covered because this is an area of interest of

          8    mine.

          9              But, in general, I'm very interested in

         10    just the way we carry out research and what kind of

         11    value we put on people's lives by taking

         12    information from them and what we do with that

         13    information.

         14              Thank you. 

         15              CHAIRPERSON MARSHALL:  We are delighted

         16    that you're here and we did miss you this morning

         17    during the discussion about social and behavioral

         18    sciences research.

         19              We will be revisiting it tomorrow

         20    afternoon in a strategic way, so thank you, Jennie.

         21              And I would like to introduce our guest,

         22    Stuart Nightingale, who is Senior Medical Advisor


                                                                 202

          1    to the Assistant Secretary for Planning and

          2    Evaluation.  And he is going to present to us a

          3    paper on financial relationships in human research.

          4              And if you don't know, that paper is

          5    available at the table outside of the meeting room.

          6              Thank you, Stuart. 

          7              DR. NIGHTINGALE:  Thank you very much. 

          8    It's a pleasure to be here, and I am going to set

          9    the stage for this agenda item.

         10              This -- I think I was selected for this by

         11    Dr. Koski because I chaired the planning group for

         12    the actual meeting that we held in August on this

         13    topic.  And as I will describe, this is sort of

         14    part of the end process of that conference was the

         15    document that you have in you briefing books and is

         16    available now.

         17              Basically, we kept the planning group that

         18    planned for that conference alive and used them to

         19    help and develop this draft interim guidance that

         20    we now have available.  So in a way, it's a part of

         21    the continuum.

         22              But the other thing that I'm going to


                                                                 203

          1    mention today is that this is kind of a short-term

          2    issue.  We have this document.  We also have,

          3    again, coming out of the conference itself, maybe

          4    four or five questions that we think that this

          5    committee might wish to get involved in.  There are

          6    things that need to be addressed, we feel.  But

          7    that's, you know, for you all to consider.

          8              How do we get to where we are today in

          9    terms of this particular guidance document?

         10              Well, I mentioned some of that.  The

         11    Secretary did identify a financial conflict of

         12    interest as one of her five initiatives that would

         13    involved in strengthening human subject protection. 

         14    We planned this public process.  It centered on a

         15    conference that would serve various functions, but

         16    primarily to allow us to get to the stage where we

         17    are.  And it was supposed to really address issues

         18    involving institutions, clinical investigators and

         19    IRBs in human subject protection and financial

         20    conflict of interest.

         21              To put this further into perspective,

         22    maybe I can show, well, a few overheads.


                                                                 204

          1              Kate, thanks.

          2              The first is this conference was held

          3    August 15th and 16th.  A number of you who are

          4    actually on the committee participated, were

          5    speakers at that meeting. 

          6              We actually had something close to 700

          7    people in August.  It's a real testimony to the

          8    importance of this topic, and I would say that we

          9    had participants representing all the stakeholders. 

         10    We had many more in certain categories than others.

         11              But people did share their experiences and

         12    we did have a series of -- oh, next, please.

         13              The purpose of the conference is basically

         14    to implement one of the Secretary's five

         15    initiatives that I mentioned.

         16              We want to remind the participants of the

         17    complex regulations and guidances that are already

         18    available, both from the public health service and

         19    FDA, on the issue of either financial conflict of

         20    interest or financial disclosure. 

         21              We also wanted to have the examples

         22    presented, which we did have.  We wanted to get


                                                                 205

          1    public comments on six framework questions that we

          2    used, developed prior to the conference, and ask

          3    for comments through a Federal Register notice, and

          4    I'll show you those in a second. 

          5              And, finally, this was, as I said, to help

          6    us get information we needed to develop some

          7    guidance.

          8              Next one.

          9              These are the six conference questions in

         10    an abbreviated format.  Basically, the first was to

         11    find out what kind of information actually is out

         12    there, empirical information that might help us.

         13              Sorry.  The first one was to find out what

         14    kind of financial ties and relationships actually

         15    exist.  Then is there any information about what's

         16    actually going on in terms of any research data.

         17              Then we wanted to find out if disclosure

         18    were to occur to research subjects, basically how

         19    should the information be disclosed.

         20              And then we also wanted to know about when

         21    that should happen and how it should happen.

         22              Then we also wanted to know something


                                                                 206

          1    about the appropriate roles of the different

          2    entities involved in this area, and that includes

          3    IRBs, institutions, conflict of interest committees

          4    and others, and maybe more than we even know about.

          5              And then, finally, are there other

          6    protections available in the private sector that

          7    we're not aware of.

          8              And we put these out in the Federal

          9    Register, hoping to get information prior to the

         10    conference that would help us, and then we did not

         11    get many responses, but we got a number that were

         12    very thoughtful and comprehensive and useful.

         13              We also left the record open after the

         14    meeting itself, up until the beginning of October,

         15    and got a number of further comments that were

         16    quite helpful.

         17              And as I said, we did have our interagency

         18    group meeting after the conference to develop that

         19    draft interim guidance.

         20              Now, let me just, before mentioning the

         21    specifics, can I have the next overhead, please? 

         22    I'm sure there's a better way to do this.


                                                                 207

          1              As the financial -- yes, the financial

          2    conflict of interest certainly is seen as a major

          3    and growing concern.  We also heard that some of

          4    the professional organizations have already taken

          5    positions on this.  More are working on it.  Most

          6    seem to center on the clinical investigators as

          7    sort of the major target for these positions or

          8    policy statements.

          9              We heard a wide spectrum of views about

         10    management of financial conflicts of interest,

         11    including the prohibition of certain kinds of

         12    financial arrangements at the meeting.  Most of the

         13    people, I would say, supported management reduction

         14    or elimination of this, rather than prohibition.

         15              We also heard that the views of potential

         16    research subjects should be told about financial

         17    conflict of interest or financial interests that

         18    are relevant, and the informed consent document

         19    appeared to be the best vehicle for providing this

         20    kind of information.

         21              Next, we heard that IRBs should not be the

         22    sole focus or arbiter of financial conflict of


                                                                 208

          1    interest issues.  It's not appropriate for them to

          2    do this sort of thing, and furthermore, they don't

          3    have resources to do it.

          4              And then, finally, there was a real desire

          5    in the community that we heard from for guidance,

          6    but not new federal regulations at this time. 

          7              Bob?

          8              DR. ROBERT LEVINE:  Can I just ask,

          9    Stuart, what's the difference between elimination

         10    and prohibition? 

         11              You said they didn't want prohibition -- 

         12              DR. NIGHTINGALE:  Okay.

         13              DR. ROBERT LEVINE:  -- they wanted

         14    elimination. 

         15              DR. NIGHTINGALE:  Oh, sorry.  Well,

         16    prohibition, elimination.

         17              Yeah.  Basically, it's when we get into

         18    some of this, but it's complicated and, yeah. 

         19              Okay.  Let me go on.

         20              The document that you have before you is a

         21    draft only.  It's been developed by our group, and

         22    it is in a form that in a way that we would be


                                                                 209

          1    interested in distributing it to the community.  In

          2    other words, we thought rather than develop

          3    something with ideas and thoughts, a reaction

          4    document, per se, this is something that could be

          5    sent out to people right away for comment and use,

          6    essentially.

          7              This is in no way a regulatory document or

          8    a set of requirements.  It is tied to the common

          9    rule and the equivalent FDA, IRB and informed

         10    consent regulations that focus on human subject

         11    protection.  It is not tied formally to either the

         12    Public Health Service requirements for grantee

         13    institutions or the FDA financial disclosure

         14    regulations.

         15              These are separate legal requirements and

         16    have their own published guidance.  In fact,

         17    neither the PHS requirements nor the FDA

         18    requirements deal specifically with this issue of

         19    IRBs and what the individual research participants

         20    should be told.

         21              However, the guidance is meant to be

         22    applicable to everybody.  In other words,


                                                                 210

          1    institutions, investigators and IRBs, whether they

          2    receive PHS funds, whether or not they're regulated

          3    by the FDA, in addition.  They're really meant --

          4    and independent IRBs, for example, would also be a

          5    target for this.

          6              Then you'll notice that our conference had

          7    the term, "financial conflict of interest" in its

          8    title.  The agenda for this session does not have

          9    it, nor does our actual document.  And that gets

         10    back to kind of what Bob was getting into a little

         11    bit, too.

         12              It's not clear what financial conflict of

         13    interest is.  It's clear that there are financial

         14    arrangements and financial relationships that

         15    exist, so our document is -- thus, an attempt to

         16    define any of this.  But it focuses on information

         17    and communication about the facts of financial

         18    arrangements in relationships.

         19              It doesn't have thresholds in it.  There

         20    are thresholds for reporting in, I think, both the

         21    PHS and the FDA requirements, but it does -- or

         22    you've seen emphasizes sharing, communication, et


                                                                 211

          1    cetera.

          2              And the target here is really how best to

          3    inform the IRB about what's going on so it, in

          4    turn, can then inform the research participant, as

          5    appropriate, what that actually is.

          6              The document is organized into five

          7    sections.  The first is the institution.  The

          8    second is clinical investigators.  Third is the IRB

          9    members and staff.  Fourth are the IRB review of

         10    protocols and approval of consent.  And, then

         11    finally, the consent document itself.

         12              Some of this may be seen as artificial. 

         13    Some of this document may appear to be redundant,

         14    and you could even order it in a different way. 

         15    But our group felt this was the very best way to

         16    present the information for review.

         17              And then I guess before going further, I

         18    just want to say that to put the draft in

         19    perspective, this is draft interim guidance that we

         20    want to have comment on.

         21              These sort of longer-term questions are

         22    important questions that came up from the


                                                                 212

          1    conference and during our own inter-agency

          2    discussions. 

          3              Obviously, the draft interim guidance is

          4    what we know about now.  Clearly, if this group,

          5    after some deliberation over a period of months,

          6    comes up with some really important things, this

          7    could obviously change this draft guidance.

          8              But we wouldn't want to hold the draft

          9    guidance until a lot of questions are answered that

         10    take a lot of deliberation because we feel that

         11    wouldn't be fair to the field to withhold something

         12    that might be very useful, if, indeed, you agree

         13    that this would be a useful contribution.

         14              So it would be in that spirit that I would

         15    read you some of the longer-term questions, again,

         16    coming out of the conference and discussion of our

         17    group.

         18              The first would be, what is the definition

         19    of financial conflict of interest and financial

         20    disclosure?

         21              FDA does not use the term, "financial

         22    conflict of interest," and PHS leaves the


                                                                 213

          1    determination of financial conflict of interest to

          2    institutions.

          3              Is it possible to harmonize definitions

          4    across HHS?  That's the first.

          5              The second is can the Public Health

          6    Service, FDA regulations that currently exist

          7    requiring conflict of interest and financial

          8    disclosure reporting and management be harmonized?

          9              The next is are there certain financial

         10    arrangements and relationships involving

         11    institutions, investigators, IRBs, et cetera that

         12    clearly are, by their very nature, conflicts of

         13    interest that cannot be managed, and must be

         14    eliminated or prohibited?

         15              Four, what is or should be the nature,

         16    purpose and process of financial disclosure?

         17              We heard a lot of comments at the meeting

         18    about, well, if you inform the research

         19    participants in the informed consent, they're not

         20    going to understand what it means.  It has to be

         21    put in perspective.

         22              Well, you know, the viewers, we think that


                                                                 214

          1    can be done, but it still really is a good issue

          2    that deserves some deliberation.

          3              And then, finally, what are the

          4    appropriate roles and responsibilities in respect

          5    to financial relationships with sponsors of the

          6    various parties involved in human subject

          7    protection institutions, conflict of interest

          8    committees, IRBs, funding and regulatory agencies? 

          9    How does this all fit together? 

         10              Earlier, you talked about the idea of a

         11    system.  Can this be a system?  Should it be a

         12    system?

         13              So that is the spirit that we're

         14    approaching this, and I would just, before getting

         15    into the document, say that there's been a lot

         16    going on recently.

         17              Before the meeting, the IG had come out

         18    with a report, or maybe it was around the same time

         19    of recruitment of subjects.  A lot of concern about

         20    recruitment approaches and some advice and

         21    thoughts.

         22              In the past several months, there have


                                                                 215

          1    been a tremendous amount of literature in the New

          2    England Journal and in the Journal of the American

          3    Medical Association on these kinds of issues.  And

          4    just last week, I think the AMA House of Delegates

          5    adopted a position that relates to this same issue.

          6              And we know NBAC has out for comment a

          7    revised version of a document that does deal very

          8    specifically with this.

          9              So there's a lot going on, but, again, we

         10    weren't -- we think that we have something that

         11    came out of a process that is worthy of getting out

         12    to the community, and we really want your comments

         13    and thoughts on that document. 

         14              CHAIRPERSON MARSHALL:  Thank you very

         15    much, Stuart, and I think that's true, and we

         16    commend you on your work, and also on giving us

         17    something concrete that we can sink our teeth into

         18    to begin our discussion.

         19              So let me open the floor for discussion

         20    among committee members first.

         21              Yes? 

         22              MS. MEYERS:  Well, first of all, I was


                                                                 216

          1    amazed at that conference at the interest that the

          2    audience was so big they had to have an overflow

          3    room.  It was huge.

          4              And so that's heart warming to know that

          5    there is interest.  And most of the audience,

          6    however, were people from IRBs.

          7              And the issue that is most disturbing I

          8    think to consumers is that FDA already has a

          9    regulation that requires the investigator to say

         10    that he may own stock -- he or she may own stock or

         11    have a conflict of interest, but that information

         12    under the regulations has to be given to the

         13    sponsor of the trial.

         14              So when a drug company is paying an

         15    investigator, the investigator simply writes back

         16    to the drug company saying, "Yes, I've been paid by

         17    you."  And once that information is there, it is

         18    kept secret.  It is not accessible to the public. 

         19    So there's use in FDA having that regulation if

         20    there is no requirement that the information is not

         21    put into an informed consent document.

         22              And among the many issues that are so


                                                                 217

          1    disturbing about the conflict of interest is that,

          2    in recent years, a lot of doctors are getting paid

          3    $1000 each just for referring patients.  And it's

          4    not right that when your family doctor says, "Gee,

          5    I think you might want to try this arthritis

          6    medicine.  There's a clinical trial down the

          7    block," that the patient's not told that the doctor

          8    is being paid $1,000 a head just for referring you

          9    down there. 

         10              So this whole conflict of interest thing

         11    has gotten out of hand.  And it's really imperative

         12    I think that the government does something to at

         13    least open the window and give some transparency to

         14    this whole question.

         15              CHAIRPERSON MARSHALL:  Thank you, Abbey,

         16    and I think you've raised the point that there is a

         17    panoply of types of conflict of interest out there

         18    that we need to address, which is what Stuart said.

         19              DR. NIGHTINGALE:  Yeah.  Can I just say

         20    one thing? 

         21              CHAIRPERSON MARSHALL:  Oh, please. 

         22              DR. NIGHTINGALE:  Just in response to


                                                                 218

          1    that.  We did try to deal with the issue in this

          2    document on paragraph 1.2, saying that the

          3    information that the investigator is submitting to

          4    the sponsor could be given to the institution.  In

          5    other words, it's not -- you are perfectly correct

          6    in terms of your description.  There's a closed

          7    system.  It goes from the investigator to the

          8    sponsor of the FDA.  There was never any thought

          9    given to doing anything at the level of an

         10    institution or an IRB, as far as I know.

         11              But what we're doing, instead of trying to

         12    change FDA's regulations or anything like that, but

         13    the idea here is since the investigators at the

         14    institution, and that person is filing information

         15    with the sponsor, why not have the institution get

         16    that same information and pass it on, if

         17    appropriate, to the conflict of interest committee

         18    or the IRB? 

         19              MS. MEYERS:  To the patient.  I think

         20    that's the most important thing.

         21              I don't care about the IRB.  It's the

         22    patients who should be told, and let them digest


                                                                 219

          1    that information and make a decision for

          2    themselves.

          3              And it's very disturbing, and I would

          4    suggest, for example, people like me don't sit

          5    around the house reading the Federal Register. 

          6    Lawyers are reading the Federal Register.

          7              And so the fact that you want comments on

          8    this will not be known to the patient community,

          9    has the biggest stake in this subject.

         10              So you need to mail this out to patient

         11    organizations that represent diseases.  Otherwise,

         12    the only comments you're going to get will be from

         13    IRB members who are going to tell you that they're

         14    already overregulated and they don't want to do

         15    this. 

         16              CHAIRPERSON MARSHALL:  Abbey, I see heads

         17    shaking back there among our public and community

         18    members, so maybe they will have some thoughts and

         19    ideas later on.

         20              I have Mark next, and then Adil.  Then

         21    Bob, then Elliot. 

         22              MR. BARNES:  Thank you.  We actually


                                                                 220

          1    discussed this issue, at least among about half of

          2    us at lunch, and I think actually there's probably

          3    going to be a great unanimity of opinion, at least

          4    on some of these conflict of interest issues, if

          5    not on other issues on this committee, but at least

          6    based on the discussion at lunch.

          7              Just a few points:  I regularly counsel

          8    academic medical centers and physicians about

          9    issues related to conflicts of interest, FDA

         10    regulations, National Science Foundation, NIH.  So

         11    I do this -- I deal with these regulations with

         12    both the legalities and the ethics of them, sort of

         13    on a day-to-day basis, working with research

         14    administrators.  And just a few brief thoughts.

         15              One is that the big question that's

         16    hanging out there is whether the conflict of

         17    interest disclosure requirements that apply under

         18    the PHS to CC, NIH and other funding should be

         19    essentially extended by federal regulation to cover

         20    private research, privately-sponsored research.

         21              I can tell you that I am telling my

         22    clients that for ethical reasons, if not for legal


                                                                 221

          1    reasons, that that's exactly what they should be

          2    doing.

          3              And my -- I think that, you know, we, as a

          4    committee, need to look carefully at that question,

          5    you know, and think about the implications of that. 

          6    But that certainly is something that I think we

          7    should weigh in on.

          8              Another thing that Abbey referred to is,

          9    given the understandable pressure for

         10    pharmaceutical companies, medical device

         11    manufacturers, genetic therapy companies to make

         12    profits -- and I don't begrudge them that.  It's

         13    good that they do that -- there's a rush to get FDA

         14    approval, and the rush to get FDA approval means

         15    that there are what I call "cram payments" made to

         16    doctors, to principal investigators, to co-PI's,

         17    and sometimes even to hospitals for rapid

         18    enrollment of patients into studies.  And these

         19    cram payments far exceed what the reasonable or

         20    fair market value would be of their rendering those

         21    research services.

         22              That is a problem.  It is a problem in


                                                                 222

          1    terms of informed consent.  It's a problem in terms

          2    of medical ethics, and I think it's a problem in

          3    terms of the Federal Anti-Kickback Law and fee-

          4    splitting issues, as well.  But we'll leave that

          5    aside.

          6              That is certainly something, though, that

          7    merits, you know, attention on, you know, not only

          8    from this group, but I think also in terms of your

          9    direct recommendations.

         10              Another issue that I think merits our

         11    attention, which I don't think is in the draft

         12    guidance, although I know it was discussed at the

         13    conference -- and, by the way, Dr. Knight, that was

         14    a very fine conference that you guys put on.  I

         15    know that you were one of the primary organizers of

         16    it and it really was a very fine conference, albeit

         17    in Maryland in the middle of August.

         18              One of the issues, though, that I find in

         19    research contracts oftentimes that doctors are not

         20    aware that they have even signed and hospitals

         21    aren't aware they've signed is there are gag

         22    clauses and severe -- I think excessively severe


                                                                 223

          1    pre-publication review causes that the medical

          2    device manufacturers and the other private sponsors

          3    reserve to themselves.

          4              I understand the rationale for that, but

          5    there are countervailing public health rationales

          6    that need to be examined.

          7              I'm not sure that those clauses would even

          8    stand up to scrutiny by state medical boards, by

          9    state boards of medicine, if that physicians signed

         10    those clauses were brought to their attention,

         11    because there are some real tensions there in

         12    regard to medical ethics and patient care.

         13              Finally, I think we need to look -- I mean

         14    I see that sort of a tip of an iceberg, as probably

         15    many of us see here, but the fact is that there are

         16    the majority of research these days, the majority

         17    of research dollars is flowing toward community-

         18    based research, not in academic medical centers.

         19              And that's why I think that one of the,

         20    you know, the primary emphases of your

         21    recommendations, and also, what this committee

         22    should look at, is not just the academic medical


                                                                 224

          1    centers, but all of the research that is going on

          2    in the way the flow of money is. 

          3              And that is not to say, by the way, that

          4    we should cut off the flow of money or that we

          5    should excessively regulate this area. 

          6              It is that the vitality of the research

          7    enterprise itself is going to be protected by good,

          8    effective regulation in this area.  We will -- 

          9              If we enure, if we largely will adopt

         10    standards that we can enforce and that are

         11    realistic and do protect patients, then that will

         12    only help in the end the research enterprise rather

         13    than undermine it.

         14              Finally, there is a whole separate thing

         15    that I think this committee ought to look at in

         16    this area which is that Medicare has recently put

         17    out a national coverage determination, or an NCD,

         18    regarding the coverage by Medicare, and therefore,

         19    private insurers, because private insurers most

         20    often follow the Medicare rules, will pay for

         21    patients' participation in clinical trials, not for

         22    the clinical trial intervention itself, but for all


                                                                 225

          1    the medical services and pharmaceuticals associated

          2    with the clinical trial.

          3              There is a big question that Medicare,

          4    that HCVA has not yet answered about what qualifies

          5    as a qualifying trial for those purposes.  That's

          6    out for public debate.  It's out for discussion. 

          7    It's not going to be resolved in this

          8    administration.  It's going to be resolved in the

          9    next one.

         10              And that definition of what is a

         11    qualifying trial for that national coverage

         12    determination is very determinative of a number of

         13    other decisions that go on in clinical trials,

         14    especially about the flow of money and what kind of

         15    money is going to be paid by the private insurers

         16    as opposed to the research sponsors.

         17              I think that we, as a committee, need to

         18    weigh in on that issue as well and make sure that

         19    we think that our voices have been heard on that

         20    because there are many -- although it's a financial

         21    issue, there are many, many ethical implications of

         22    the decisions that are made about what is a


                                                                 226

          1    qualifying clinical trial and what is not. 

          2              CHAIRPERSON MARSHALL:  Thank you, Mark. 

          3    That was wonderful. 

          4              Adil?

          5              DR. SHAMOO:  Thank you.  I raise my finger

          6    when Abbey hasn't told him that, "Back to the

          7    patient.  The information goes to the patient."

          8              And she said, "In the meantime."

          9              However, Stuart, your conference was

         10    excellent.  I think you've done a great job

         11    including everybody in the discussion and coming up

         12    with a consensus document.  I congratulate you and

         13    your staff.

         14              The issue, Abbey said, is $1,000.  You're

         15    way behind.  This money goes 3,000, 5,000, 10,000

         16    and up to 20,000.  So your local -- some of these

         17    physicians make more money referring people than

         18    taking care of you with 50 buck bill.  So there is

         19    an incredible incentive to shovel a lot of patients

         20    to the research protocols. 

         21              I want to address that disclosure alone --

         22    I know this is, you know, sunshine, sunshine,


                                                                 227

          1    sunshine will disinfect everybody.

          2              Disclosure alone, I don't think it's the

          3    only solution.  There has to be some prohibition,

          4    elimination of conflict of interest.

          5              And the one really has bugged me for years

          6    is the institutions owning equity in biotech

          7    companies where they themselves are doing the

          8    clinical trials.

          9              That's so corrosive, not for that

         10    particular, corrosive to the faculty at large,

         11    seeing their own institutional research environment

         12    being bought and the institution, and especially

         13    the academic institution, to me, they're the last

         14    vestige remaining where through disinterested group

         15    of people in our society who are seeking truth, as

         16    they know it at the time.

         17              Every other sector is basically controlled

         18    by somebody else, and the universities are losing

         19    really their soul when they are owning equity in

         20    research endeavors.

         21              And I would recommend Norman Bowie's book,

         22    now he goes through the history of the Wisconsin


                                                                 228

          1    Alumni Foundation, how discovery made for public

          2    good, how vitamin D, how slowly, but surely,

          3    through 20, 30, 40 years, how it corrupted the

          4    essence of what they wanted to do at the beginning

          5    because of the influence of money and litigation,

          6    et cetera, et cetera.

          7              Thank you. 

          8              DR. NIGHTINGALE:  Well, let me just say, I

          9    think we put a lot of things into the document that

         10    will draw this out and force discussion at the

         11    level of the IRB.  And, by the way, you're never

         12    going to get to the patient unless you go through

         13    the IRB.

         14              So the fact that we were talking about the

         15    IRB before, it didn't -- we don't mean it to stop

         16    with the IRB.  We mean that as a conduit to getting

         17    to the consent process, et cetera.  So I mean

         18    that's it out there.

         19              Otherwise, I mean the issues that are

         20    raised by group just didn't decide to go further

         21    based on what we heard at the conference, as I

         22    said, to deal with specific prohibitions or other


                                                                 229

          1    things in this particular document this time.  But,

          2    obviously, the group -- our interagency group is

          3    very concerned about some of the same things, and

          4    we did have multiple drafts in our interagency

          5    committee, and sometimes things that were in one

          6    weren't in the other.

          7              So I would just say this certainly did

          8    come up. 

          9              CHAIRPERSON MARSHALL:  Thank you.

         10              Thank you, Adil.

         11              Bob? 

         12              DR. RICH:  I'd just like to suggest that I

         13    think the most egregious conflicts of interest are

         14    the ones that, in a sense, have been referred to

         15    around this table that are not addressed in the

         16    document, which since the document talks about

         17    institutions, clinical investigators and IRBs, it

         18    basically is leaving aside the majority of FDA-

         19    regulated clinical trials that are done outside the

         20    CDC, these huge fees and things being paid for

         21    enrollments of patients under some sort of

         22    accelerated payment schedule and things like that.


                                                                 230

          1              So I really would like to see a document

          2    that at least gives attention to the fact that

          3    there are serious conflict of interests issues that

          4    attend when drug sponsors or clinical research

          5    organizations pay these very large fees to private

          6    physicians for patient enrollment.  I think it's a

          7    significant problem.

          8              Relating to the issue of -- the one other

          9    thing I want to talk about just very briefly is the

         10    nature of institutional conflicts of interest,

         11    which Adil just alluded to.

         12              I think that there really is at least one

         13    important way in which that conflict is

         14    ameliorated, and that is simply by having a clear-

         15    cut and arms length relationship between

         16    institutional administration and IRBs.

         17              I think that deans and institutional

         18    administrators have no business basically inserting

         19    themselves into the judgments of IRBs with regard

         20    to the ethical aspects of an investigation.  And I

         21    think that so long as institutions assiduously

         22    avoid being part of the IRB review process, I think


                                                                 231

          1    the IRBs themselves are largely insulated from

          2    that, except as individual members when they

          3    obviously have a responsibility to recuse

          4    themselves. 

          5              CHAIRPERSON MARSHALL:  Thank you, Bob.  I

          6    think there might be some discussion about that

          7    later. 

          8              I have next -- I'm sorry, Stuart.  Did you

          9    have a response to that? 

         10              DR. NIGHTINGALE:  Yes.  Just one comment.

         11              This document is supposed to apply to

         12    privately-funded research, FDA-regulated research

         13    every bit as much as it is to the FDA-regulated as

         14    much as well as PHS funded.

         15              And there is a reference.  I mean

         16    certainly independent IRBs would be a good example. 

         17    Obviously, you're not going to have an institution,

         18    in certain cases, when you have privately-funded

         19    research, but you're always going to have clinical

         20    investigators and IRBs and informed consent.

         21              So the majority of these things should

         22    definitely be relevant, but we try to be all


                                                                 232

          1    inclusive and to cover institutions that aren't

          2    part of the -- that don't have assurances because

          3    they're not part of the PHS funding system, but

          4    should look at the things that institutions should

          5    look at.

          6              But we certainly meant to include just

          7    taking away the institution any investigator who is

          8    doing the work that they may have their protocol be

          9    reviewed by say an independent IRB or any other

         10    IRB.

         11              DR. RICH:  I would just suggest then that

         12    a clinical research organization is, in every

         13    instance, an institution.  And I think that one

         14    should specifically note that when you speak of

         15    institutions, you don't just mean PHS grantee

         16    institutions.  You basically mean any kind of

         17    research sponsor, and that would include for-profit

         18    institutions like a CRO. 

         19              CHAIRPERSON MARSHALL:  Thank you.

         20              Elliot? 

         21              DR. DORFF:  I have three small points. 

         22    One is, on 1.8 in the document, you have the chair


                                                                 233

          1    and staff of the IRB.  It's along the same lines

          2    that Bob was just talking about and that Adil was

          3    just talking about.

          4              By the way, is that how you pronounce your

          5    name? 

          6              DR. SHAMOO:  Adil. 

          7              DR. DORFF:  Adil.  Thank you.

          8              DR. SHAMOO:  But I've been called

          9    everything.

         10              DR. DORFF:  Okay.  But I might as well get

         11    it right.  Adil.  Okay.

         12              The question -- I mean another possibility

         13    other than the one that Bob mentioned is that you

         14    have an IRB that's completely outside the

         15    institution, because even if you have non-

         16    administrators on the IRB, they are ultimately

         17    faculty members of the institution whose promotion

         18    and all kinds of other things are in the hands of

         19    administrators.

         20              Of course, the problem with doing that is

         21    that if you get an IRB from a competing

         22    institution, you know, then they would be a


                                                                 234

          1    conflict of interest in the opposite direction.  So

          2    I mean I don't know that you would get objectivity,

          3    no matter what you do, but you can move towards

          4    that.  In other words, you can move towards some

          5    kind of situation where the conflict gets

          6    minimized.

          7              On 2.2, I think that the document needs to

          8    go further where you say if a potential conflict

          9    cannot be eliminated, the committee's determination

         10    of how the potential conflict is to be managed or

         11    reduced should be shared with the IRB for

         12    consideration during the discussion of the

         13    protocol.

         14              I think it would be very helpful in this

         15    document if you gave some guidelines about how to

         16    do this.  In other words, how do you minimize, or

         17    at least diminish, you know, the amount of conflict

         18    of interest?  What kind of steps can you take in

         19    order to do that? 

         20              That would be considered to be, in other

         21    words, now, but it wouldn't be this particular IRB

         22    that accepts it, but that in the more national


                                                                 235

          1    basis are seen as being clearly good steps to take

          2    in order to minimize conflict of interest.

          3              And, then, finally, 3.3, where the IRB

          4    policy and procedures manual should contain

          5    institutional IRB conflict of interest and

          6    financial relationship policies, it's under Section

          7    3 and IRB members and staff.

          8              But, clearly, those policies should be not

          9    only for the IRB itself, but for institutions and

         10    specific researchers.

         11              And I think, you know, that you need to

         12    indicate that those policies cover those people as

         13    well as the IRB itself. 

         14              DR. NIGHTINGALE:  Maybe this is the right

         15    time to say that I'm here representing our inter-

         16    agency group that includes the NIH, CDC and FDA. 

         17    The members of our working group, most of them I

         18    think are here in the audience.  So if any of them

         19    want to step in at any point in terms of some of

         20    these things, that would certainly be -- I think

         21    would be appropriate, as far as I'm concerned.

         22              And the management and guidelines for


                                                                 236

          1    management of some of these things are areas that

          2    we really did not get involved in this particular

          3    document partly because it's very complicated,

          4    partly because there's a lot going on out there at

          5    the institutional level of which we're not really

          6    aware.  There are all kinds of things that go on at

          7    the institutions managing these.

          8              And I know NIH, for example, has been very

          9    much involved at looking at some of the practices. 

         10    But we don't know best practices right now.  We

         11    don't have guidelines right now for some of these

         12    things.

         13              So I think we would agree with the spirit

         14    of what you're saying, but we didn't feel, at this

         15    point, that we could put that sort of thing in here

         16    or maybe, you know, even this is not the best place

         17    for it.  Maybe there is some other place. 

         18              CHAIRPERSON MARSHALL:  I have Elliot, Bob

         19    and then Sandy.  Oh, I'm sorry.  Elliot just spoke,

         20    and then Judy. 

         21              Bob. 

         22              DR. ROBERT LEVINE:  Thank you.  I have a


                                                                 237

          1    couple of brief comments.

          2              First, I want to say "congratulations" for

          3    recognizing that federal grants can create similar

          4    pressures to money contributed by industrial or

          5    other sponsorship in the private sector.  In fact,

          6    when you consider the amounts of money involved,

          7    the pressures can often be much greater.  So,

          8    congratulations on that.

          9              Secondly, I have no doubt that it's

         10    necessary to have important policies and oversight

         11    in the area of conflict of interest, but what, the

         12    IRB?

         13              The IRB, I mean every agency that's

         14    commented on the IRB lately has pointed to the fact

         15    that it's overly burdened.  I look at your list of

         16    things that the IRB should consider on page eight,

         17    and just consideration of the items in that list,

         18    which is not exhaustive, would take longer than the

         19    average time spent reviewing each protocol.

         20              Why wouldn't you assign this to what -- I

         21    don't know.  They're called different things at

         22    different institutions, but the organization at my


                                                                 238

          1    institution that looks at such matters is the

          2    Office for Collaborative Research, and let them

          3    review it, and then send a note to the IRB saying

          4    we have identified this problem area or we have

          5    identified no problem areas, but, somehow, not to

          6    just continually add to the burden of the IRB.

          7              I also have to say that, Adil, $20,000 for

          8    a referral fee? 

          9              DR. SHAMOO:  Yes. 

         10              DR. ROBERT LEVINE:  Do you have

         11    documentation --

         12              DR. SHAMOO:  Yes. 

         13              DR. ROBERT LEVINE:  -- of that? 

         14              DR. SHAMOO:  Yes. 

         15              DR. ROBERT LEVINE:  I'd like to see that.

         16              DR. SHAMOO:  Yes.  The two people who did

         17    it are in jail.  You know which I'm talking about.

         18              DR. ROBERT LEVINE:  The Borson-Diamond

         19    case. 

         20              DR. SHAMOO:  Dr. Marshall, I wanted you to

         21    comment, remember, on the issue of whether when I

         22    speak, I speak on my behalf and I'm responsible for


                                                                 239

          1    what I speak.  But no, I don't speak on behalf of

          2    the committee.  You speak on behalf of the

          3    committee.  And if we charge someone to speak on

          4    behalf of the committee, you will give that charge

          5    and you will give them what to say.  It's a hearing

          6    like any other commission I have known about.

          7    And --

          8              CHAIRPERSON MARSHALL:  Adil, just let 

          9    me --

         10              DR. SHAMOO:  Dr. Levine -- 

         11              CHAIRPERSON MARSHALL:  Yeah.

         12              DR. SHAMOO:  -- should not be inquisitive,

         13    one on one, with a member of the committee. 

         14              CHAIRPERSON MARSHALL:  Yeah.

         15              DR. ROBERT LEVINE:  I would like to -- if

         16    I hear something said that seems contrary to my

         17    experience, I would like to be able to ask if

         18    there's documentation of it. 

         19              CHAIRPERSON MARSHALL:  Let me just inject

         20    here and say that if we have need for data

         21    acquisition to further our mission, then we can

         22    certainly state those sort of remarks or those


                                                                 240

          1    requests, and that they might actually come later

          2    on in our discussion when -- you know, we sort of

          3    organize the format for how we will proceed during

          4    the discussion, so that that would probably be the

          5    appropriate time to bring those sorts of things up.

          6              So, well said, Adil.  Thank you.

          7              DR. SHAMOO:  Thank you. 

          8              CHAIRPERSON MARSHALL:  And I'm distracted. 

          9    Did you have a response that you wanted to make. 

         10              DR. NIGHTINGALE:  Just I would say the

         11    philosophy of the document is we are trying to get

         12    the conflict of interest committees to really do

         13    the work and give information as appropriate to the

         14    IRBs.  So now we've done that in different ways in

         15    different parts of the document.

         16              So we're cognizant of that and we try to

         17    sort of get that tone into it.

         18              CHAIRPERSON MARSHALL:  And Bob is sort of,

         19    again, this theme is emerging of a system, an

         20    overarching or a larger system, and that there

         21    needs to be another component of it.  So thank you

         22    very much.


                                                                 241

          1              I have Sandy and then Judy. 

          2              DR. CHODOSH:  Yeah.  I just wanted to

          3    comment on what you said, Bob, about the concept of

          4    organization.

          5              As we've been writing these performance

          6    standards, once of the major considerations is

          7    looking at the whole human subjects protection

          8    program.  Now, that's going to be very different

          9    out in the private sector where there are

         10    independent review boards, where there are the

         11    companies that are running the research.

         12              But it needs to be identified for all

         13    those instances because someone's got to be

         14    responsible.  So we've tried very hard to use the

         15    word, "organization," not "institution," which I

         16    agree with.

         17              Now that leads to my real question, and

         18    that is it seems to me the most difficult thing is

         19    where in the institution -- and this agrees with

         20    you, Elliot -- do you place the conflict of

         21    interest committee?

         22              If the institution, quote, itself at its


                                                                 242

          1    highest levels has potential conflict of interest,

          2    then I think one of the potential possibilities is

          3    in the board of trustees, if that board of trustees

          4    is, indeed, made up of a lot of outside members

          5    whose chief concerns are how the organization

          6    operates, et cetera.

          7              I'm not even sure that will work in all I

          8    instances, but placing it at the, quote, just a

          9    chief official in the institution doesn't really

         10    solve the problem of looking at conflict of

         11    interest.

         12              It does need to be out of the IRB.  I

         13    couldn't agree more, but it's no different than

         14    going to the radioisotope committee, if that's a

         15    problem in the protocol.  You get that information

         16    and then the IRB can make a judgment.

         17              How much of this is going to affect the

         18    risk and the benefit, and if it is, then it needs

         19    to be stated.

         20              And it doesn't always have to be stated,

         21    if they feel that this really is not a risk. 

         22              CHAIRPERSON MARSHALL:  Thank you, Sandy.


                                                                 243

          1              Judy and then, also, Denyse, you spoke

          2    earlier.  I would like to put you perhaps on the

          3    spot after Judy.

          4              You did mention sort of the interests and

          5    the challenges to junior faculty, and I know that

          6    we're talking about financial arrangements here,

          7    but I wonder if you have any thoughts that you

          8    might be able to contribute to the group relative

          9    to young physicians, investigators, faculty and so

         10    forth, within the context of financial

         11    arrangements.

         12              So if you could just think about that, and

         13    if you don't have anything, that's fine.

         14              But, Judy? 

         15              DR. SIEGEL:  Yeah.  I'd like to go back to

         16    the issue of developing a definition of "conflict

         17    of interest."  And the context that I will put that

         18    in is in the context of the FDA regulations.

         19              When these FDA regulations came out, there

         20    were touch points that were actually defined above

         21    which, you needed to potentially report, and below

         22    which, you didn't.


                                                                 244

          1              And, you know, trying to implement out

          2    there in the real world, the issue comes up why

          3    that amount?  Why not some other amount?  Why not

          4    lower, in some cases.

          5              And so from the perspective from having to

          6    implement those kind of rules, clearly, we struggle

          7    with the whys.  Where did they come from?

          8              And then from the perspective and feedback

          9    we've gotten, as we've gone out to all of our

         10    investigators -- and I would also add from the FDA

         11    regulations, this is not just investigators in the

         12    United States where money and these kind of things

         13    are things we talk about a lot, but outside the

         14    United States where money and personal knowledge is

         15    something that isn't really shared a lot.

         16              So there are global implications of this. 

         17    But what we've come back with is what are you going

         18    to do with this?  And the issue we've asked FDA is,

         19    "What are we going to do with this?"

         20              And there has been no guidance, as you

         21    said.  We collect a lot, but there is nothing to

         22    say that if you have someone out there who has an


                                                                 245

          1    interest of $50,000 or more in a study that has

          2    five or 10,000 patients and they are contributing a

          3    small piece, there is no guidance to say that that

          4    person should not be included in the trial.

          5              There is no guidance to say that if a

          6    person refuses to give that information back to you

          7    that they can't be in the trial.

          8              You collect all of this information only,

          9    and I agree, only if you submit an NDA is that

         10    information ever transmitted to FDA.  If not, it

         11    sits with the sponsor.

         12              And so from, you know, the perspective of

         13    how do you actually implement this and what do we

         14    do with it, I think the whole definition of -- and

         15    I'm not talking about the other issues of conflict

         16    of interest, which I think are also valid.

         17              But from this particular one on the

         18    investigator, have we really thought through why

         19    we're asking investigators to do this, and what is

         20    the touch point that we, as a society, not this IRB

         21    or that conflict of interest committee, but sort of

         22    in general, what is the touch point that we would


                                                                 246

          1    all get concerned, and I don't think we have that

          2    definition.

          3              And so I would encourage some discussion

          4    of it, even no definition comes out of this.

          5              CHAIRPERSON MARSHALL:  Thank you so much

          6    for reminding us that we need to be attuned to

          7    international issues.  That needs to be on our

          8    screen, and it wasn't so far for this topic.

          9              Stuart, any thoughts? 

         10              DR. NIGHTINGALE:  Well, I guess that was

         11    one of the reasons we wanted to tap into the

         12    information, short circuiting what is required in

         13    the regulations to allow the institutions, and then

         14    the IRBs, to have some of that information, if

         15    they're not getting it some other way.  That long

         16    list of items was another way to try to capture

         17    some of that.

         18              I can't really speak for FDA on this, and

         19    David Lepay I think is here.  But I think I would

         20    just say briefly that FDA does make use of that

         21    when they're doing their review of the application. 

         22    As you said, it comes in with the NDA.  So it does


                                                                 247

          1    have a purpose there, you know, why the thresholds

          2    are what they are, et cetera, et cetera.  I'm not

          3    sure.

          4              But there is a guidance document which I

          5    think is being revised, which is, hopefully, will

          6    address more of your questions.

          7              Does David want to say anything? 

          8              DR. SIEGEL:  Actually, if I could just

          9    respond. 

         10              I mean if the issue of conflict of

         11    interest is an issue that is not a long-term issue,

         12    but is an issue at the moment, waiting until an NDA

         13    is filed, or in most cases, not, those information

         14    will go nowhere and will not be evaluated, I don't

         15    think, anywhere, except by the company. 

         16              CHAIRPERSON MARSHALL:  Dr. Lepay? 

         17              DR. LEPAY:  Yes.  Is this on?

         18              Just to answer to your comments, I think

         19    they are very legitimate comments, certainly, and I

         20    think we have to go back to the history of the

         21    development of this regulation.

         22              The regulation was not specifically


                                                                 248

          1    developed to deal with conflict of interest as we

          2    are talking about it here.  It had a much more

          3    narrow focus at the time it was originally

          4    conceived, and that was, in fact, in the review of

          5    applications to determine whether there may be

          6    considerations of a financial nature that could, in

          7    fact, pose a bias to the data, and from a

          8    standpoint of FDA review, would need to be taken

          9    into consideration as we start to look at

         10    individual sites, as we start to look at the

         11    possible impact that these kind of issues could

         12    have in our own interpretation, our review

         13    interpretation, ultimately in our decision making

         14    on the approvability of a product.

         15              I'd say these are very fair comments right

         16    now because, in fact, in approaching the whole

         17    issue of guidance, as we are proposing to the

         18    committee today, we want to look, we want to

         19    consider beyond the original scope, if you will, of

         20    what this regulation was put in place to do.

         21              It had, in fact, a very specific series of

         22    steps and specific parties that would be involved,


                                                                 249

          1    obviously from the standpoint of application. 

          2    Since the consideration was to look at biases in

          3    application, we felt that it was most appropriate

          4    that the sponsor should be the collector of this

          5    information.  The flow should be going from

          6    investigator to sponsor to us.

          7              We did not conceive, as I say, at that

          8    time that this would be a conflict of interest

          9    control more broadly, as we're discussing here

         10    today, and consequently, there was no consideration

         11    at that time to broadening this to distribution to

         12    subjects, to distribution to the IRB.

         13              We hope, in fact, that in this process of

         14    discussion as we start to go forward in particular

         15    with the guidance document that's in front of you

         16    right now, we can start to think about areas in

         17    which, in fact, the information that is collected

         18    could be made more useful.  Perhaps the

         19    distribution could be made more useful.

         20              You've asked the question of why these

         21    particular thresholds.  I'll say, from FDA's

         22    perspective, there was no set reason.  We didn't


                                                                 250

          1    have the kind of metrics that perhaps could form a

          2    basis for why we wouldn't do $25,000 here and

          3    $50,000 there.

          4              They were figures that, in fact, were

          5    rather arbitrarily decided upon.  And as we talk

          6    about the issue of pharmatization across agencies,

          7    certainly this is something that should also be

          8    considered by the committee.

          9              So we're hoping today of bringing this

         10    forward in the way that Stuart has presented. 

         11    We're going to get more information, one, about

         12    areas in which perhaps FDA's regulations, up until

         13    now, the financial disclosure regulation, has not

         14    addressed certain aspects of conflict of interest,

         15    given what its original scope was, whether there

         16    are areas we should now be considering from the

         17    standpoint of guidance to broaden the availability

         18    of that information.  Ultimately, how we might be

         19    able to use the information that we are collecting

         20    in a way that would be more useful broadly.

         21              And I hope that provides at least some

         22    perspective as we're starting to talk about why


                                                                 251

          1    historically it was collected this way and where we

          2    are today. 

          3              CHAIRPERSON MARSHALL:  Thank you so much.

          4              Adil, and then I'm going to open the

          5    floor.

          6              Oh, I'm sorry.  Oh, I apologize.  Denyse

          7    and then Adil. 

          8              DR. THORNLEY-BROWN:  You said -- 

          9              CHAIRPERSON MARSHALL:  I certainly did. 

         10              DR. THORNLEY-BROWN:  You said you were

         11    going to put me on the spot, and I think that some

         12    of these issues are a little bit still vague in my

         13    mind about --

         14              But the fundamental issue is what

         15    motivates researchers.  What motivates researchers

         16    in their choice of research.  What motivates

         17    researchers in their procedures, and then the

         18    outcomes of the research.

         19              And, certainly, when we talk about

         20    financial conflicts of interest, we talk about

         21    making a lot of money.  We talk about voluntary

         22    things.


                                                                 252

          1              There are more subtle things, too, that

          2    influence people's choice of projects and influence

          3    data acquisition, things like the junior faculty,

          4    oftentimes they're required to bring in their

          5    salary.  So we're not talking about a lot of money,

          6    but we're talking about getting grants that are

          7    going to pay for their salary and help facilitate

          8    people getting tenure.

          9              And sometimes the conflicts in those areas

         10    could be very difficult.  How you ferret out where

         11    there truly is a conflict, where it truly

         12    influences the choice of someone's project, and

         13    whether there is compromise, that's a more

         14    difficult issue.

         15              But I think it's financial and large

         16    amounts of money are one thing.  But there are also

         17    probably some more subtle conflicts of interest

         18    that are more difficult to quantify. 

         19              CHAIRPERSON MARSHALL:  And probably sort

         20    of the hidden curriculum plays into that in terms

         21    of what they see and the behavior of their mentors,

         22    and what the institutional culture is and so forth.


                                                                 253

          1              Thank you. 

          2              Adil, and then we shall move on. 

          3              DR. SHAMOO:  Judy mentioned that if it

          4    doesn't go into NDA, this information is lost, and

          5    this brings the point that if you do research on

          6    animals, since 1966, regardless of the source of

          7    funding is federally regulated.

          8              Unfortunately, that is not true in human

          9    subjects.  Only if it is publicly funded, or I call

         10    it "FDA bound," that is, going to go to FDA, then

         11    it's federally regulated.  And that's why that

         12    issue -- if we're going to address eventually the

         13    issue of overall oversight, that won't be resolved.

         14              And since the discussion has moved to how

         15    IRBs, I have thought of that and written about how

         16    the IRB.  And that's why in my preliminary remarks

         17    I said, "structured and flawed IRBs."  

         18              That is, they are employee of the research

         19    institution and the conflict of interest that I

         20    just mentioned is really intertwined with the

         21    institution.  It's going to be very difficult.

         22              And we have made two suggestions are


                                                                 254

          1    integral with my colleagues on that, and that is

          2    either -- this is the extreme position -- all IRBs

          3    should be outside the institution.  And I'm really

          4    quoting you from the Greg Koski one.  He said,

          5    "Remove the I from IRB.  Remove the institution

          6    from the IRB."  That's one radical suggestion.

          7              The other one is, at a minimum, 51 percent

          8    of the membership should be from the community

          9    where the subjects are coming from, and those 51

         10    percent should not be appointed by the research

         11    institution.  And I think that could resolve -- I

         12    don't claim any simple solution is going to resolve

         13    everything.  But that could resolve some of this

         14    intertwining of IRB conflict of interest with their

         15    own institution. 

         16              CHAIRPERSON MARSHALL:  Hear, hear, and I

         17    see Bob Deagan's ears are just perking up back

         18    there concerning what you have said. 

         19              DR. ROBERT LEVINE:  One very brief comment

         20    in response to Denyse. 

         21              It's not just junior faculty that have to

         22    bring in their salaries.  You may not want tenure


                                                                 255

          1    as much as you think you do. 

          2              CHAIRPERSON MARSHALL:  Okay.  Jennie, I'm

          3    going to allow a question for you and then I'm

          4    opening the floor up to our ex-officio members and

          5    our agency liaisons, and then after that, to our

          6    public members.  So one last question from the

          7    committee, and there will be time during our

          8    further deliberations. 

          9              DR. JOE:  Actually, this is really a

         10    simple request.  You've made a comment about

         11    empirical evidence, and I wondered if we could see

         12    some of that, maybe in the proceedings or something

         13    from this conference since I couldn't attend, but

         14    I'm interested in what was said?  Thank you.

         15              DR. NIGHTINGALE:  Well, the problem was

         16    that we didn't get any.  I mean there really is not

         17    much on this topic, basically.  And rather than

         18    say, "Well, since there is no good information,

         19    well, our hands are tied.  There's nothing to be

         20    done," we approach it based on all the other issues

         21    at hand. 

         22              DR. DORFF:  Could we make a recommendation


                                                                 256

          1    that such empirical information be done? 

          2              CHAIRPERSON MARSHALL:  We could do that

          3    later on during the recommendation period of our

          4    deliberations.

          5              I would like to point out, though, correct

          6    me if I'm wrong, Stuart, but I do believe that the

          7    agenda for your meeting and so forth is posted on

          8    the web or it was posted on the web. 

          9              DR. NIGHTINGALE:  Oh, yes. 

         10              CHAIRPERSON MARSHALL:  So that may be

         11    helpful, if you wanted to contact individual

         12    presenters -- 

         13              DR. NIGHTINGALE:  Yes. 

         14              CHAIRPERSON MARSHALL:  -- and those sorts

         15    of things. 

         16              DR. NIGHTINGALE:  Right, and some of the

         17    recent articles in the medical literature do talk

         18    about the percentage of institutions whose IRBs do

         19    get into this area.  Generally pretty small, but,

         20    well, the IG had told us 25 percent are actually

         21    doing it.

         22              So there is more data available now than


                                                                 257

          1    there was.  And, yes, thank you for that wonderful

          2    plug.

          3              The conference web site is there with the

          4    transcript tied to the agenda, and it has all the

          5    PHS, FDA background documents, and it's an

          6    excellent resource for those who want to look into

          7    this area more.

          8              There were some really interesting

          9    presentations including lots of information from

         10    those who are actually doing these things and what

         11    they do, how they handle the issue, for example, of

         12    when there are some institutional involvement, say

         13    with patents and things. 

         14              CHAIRPERSON MARSHALL:  And I might ask

         15    you, Stuart, if, before you leave, you have that

         16    information, if you might want to just put it on

         17    our board back here where we also have the IOM web

         18    site.

         19              DR. NIGHTINGALE:  Yeah.  I think it's the

         20    handout, isn't it? 

         21              CHAIRPERSON MARSHALL:  It's in the

         22    handout.  Thank you. 


                                                                 258

          1              DR. NIGHTINGALE:  It is.  Yeah.

          2              CHAIRPERSON MARSHALL:  Thank you. 

          3              DR. NIGHTINGALE:  It's actually OHRP's web

          4    site.  It moved from where it was originally --

          5              CHAIRPERSON MARSHALL:  Right.  Okay.

          6              DR. NIGHTINGALE:  -- into the mainstream,

          7    so it's now -- 

          8              CHAIRPERSON MARSHALL:  All right.  Thank

          9    you very much. 

         10              So let me ask, what I'd like to do within

         11    the next half an hour, we have half an hour before

         12    we begin our discussion about recommendations is I

         13    would like to give 15 minutes to our ex-officio

         14    members and agency liaisons if they would like to

         15    join the discussion, and then another 15 minutes to

         16    our public members.

         17              And just if you would please introduce

         18    yourselves and your agency affiliation.  And if you

         19    are a public member, if you would introduce

         20    yourself and your interest in being here. 

         21              MR. MESA:  John Mesa from the VA ex-

         22    officio.  It was a great conference and I think the


                                                                 259

          1    part at this point in time that is going to be

          2    valuable to the other agencies are the signatories

          3    other the common rule.

          4              You spoke about, you know, your inter-

          5    agency group, which was actually an intra-

          6    departmental group that was doing its thing, and

          7    that's great.

          8              I think from the standpoint of VA, it's

          9    crucial our understandings about these financial

         10    conflicts of interest because we have at least two

         11    other mechanisms which put us in a jeopardy

         12    situation; that is, any research in the VA can

         13    simply be five-eights and they can enjoy a three-

         14    eights appointment at his academic affiliate, which

         15    can have salaries which are greater than the five-

         16    eights, and they have other monies that flow.  So

         17    that's one aspect.

         18              The other aspect is, in the VA, we have

         19    these non-profit research foundations through which

         20    a lot of money can flow through the pharmaceuticals

         21    and ends up being sort of not quite salary

         22    augmentations, but they're in that sort of frame of


                                                                 260

          1    reference.

          2              So I would urge you that when you go out

          3    that you specifically send at least to this

          4    signatory to the common rule called the VA, and

          5    send it to the Secretary and ask specifically for

          6    our comments on it.

          7              And then maybe that we'll speak from other

          8    co-signatories of the common rule, but they might

          9    like to feel the same way, as well, like Susan

         10    Roses here from DO and so forth.

         11              I think you might need to get that

         12    specific set of comments because you're the big

         13    gorilla, I mean DHHS.  And, yes, you know, you have

         14    FDA and you have NIH.  But there's a few other

         15    people like NSF and others over here that have

         16    flows of money that we have to be seriously

         17    concerned, as well.

         18              I'd like to put a different systems piece

         19    on this, and that is the ethical construct here is

         20    limited to financial conflict of interest.

         21              I would ask you to think about some other

         22    words like, "vested interest," "enlightened self-


                                                                 261

          1    interest," and other words that I would put in the

          2    general context of a governance structure that is

          3    linked to and often has a nexus to the money that

          4    flows.

          5              We had here the comment about a junior

          6    faculty and then a senior faculty person saying,

          7    "Yeah, I got sort of a squeeze on me maybe from the

          8    Dean to augment or at least replace my salary from

          9    other sources of money."

         10              I think the whole issue of when you, in a

         11    narrow sense, sit on an IRB and make decisions and

         12    you don't absent yourself from the room, that's a

         13    ethical construct.  And I think I would ask, you

         14    know, you to think about in this committee.  Not

         15    just think of it in terms of financial conflict of

         16    interest, but I'll put it the word on a governance

         17    conflict of interest, which can be just as

         18    pervasive and just as undermining.  It's just

         19    simply the money.

         20              CHAIRPERSON MARSHALL:  Thank you very

         21    much. 

         22              Others? 


                                                                 262

          1              [No response.] 

          2              CHAIRPERSON MARSHALL:  Public members? 

          3              MR. WOLF:  I'm very excited that this

          4    division of HHS is started and that this is the

          5    first meeting of the advisory committee, and it

          6    looks like the advisory committee has a very good,

          7    broad range of representation, which is more than

          8    some other advisory committees I'm familiar with

          9    having. 

         10              CHAIRPERSON MARSHALL:  Please don't forget

         11    to tell us who you are. 

         12              MR. WOLF:  I'm Sid Wolf.  I'm from Public

         13    Citizens Health Research Group, formerly from the

         14    NIH, but not for a long time. 

         15              I just want to talk about a couple of

         16    things.  First of all, unlike the National Advisory

         17    Commission, which is a Presidential commission,

         18    this committee is literally an advisory committee

         19    to a regulatory agency.

         20              The agency which Dr. Koski is now heading

         21    up has regulatory authority.  It has done, in its

         22    previous incarnation, some investigations.  It has


                                                                 263

          1    more staff, probably nowhere near as many as it

          2    should.

          3              But I think that when one moves beyond

          4    just guidances and saying, "Maybe you should think

          5    about this," whatever, which is where Stuart has, I

          6    think, chosen to start, and I think it's a good

          7    start, into regulations.  And Mark Barnes talked

          8    about standards and enforcement.

          9              These are legal concepts and I think that

         10    as you deliberate, not just today, but generally,

         11    Dr. Koski and his colleagues are looking for some

         12    basis to suggest regulations.

         13              Yes, we have -- FDA has certain regulatory

         14    authority, and NIH does, but the intention from the

         15    way you wrote this document, Stuart, is that it

         16    should apply to all of them.

         17              So it's a policing function, and the

         18    reason I use the word, "policing," is really to

         19    distinguish between self-regulation. 

         20              I think that this industry, whether it is

         21    the academic industry or the so-called "for-profit

         22    industry," which fuses, to some extent these days


                                                                 264

          1    with the academic industry, it's been mainly self-

          2    regulation and it's been things like disclosure.

          3              And I think that part of a regulatory or

          4    policing kind of atmosphere includes moving beyond

          5    just education and disclosure.

          6              It was pointed out by someone or other in

          7    the conference in August that crawling on the back

          8    of a patient, often sick or at least not fully, the

          9    disclosure that their doctor or their institution

         10    has a financial conflict of interest.  I'm not sure

         11    where that goes.  They're not necessarily in a

         12    position to say, "Oh, I would participate in this

         13    but for the fact of this conflict of interest."

         14              So I think that one of the things that

         15    Marsha, Angel and I and I think a couple of other

         16    people mentioned at the conference in August is

         17    there needs to be really prohibitions.  And I think

         18    that the committee needs to start delineating what

         19    things are just over the edge.  And I'll just

         20    mention a couple that I mentioned then and just

         21    reflect on something that was said here today.

         22              First of all, the referral fees or finder


                                                                 265

          1    fees or kickbacks -- we have a nationwide network

          2    of about 250 physicians who are practicing medicine

          3    part-time or full-time, and they send us examples

          4    of attempts to get them to refer patients for drug

          5    trials or to actually become clinical

          6    investigators.  This is very widespread, whether

          7    the amount is a thousand, or in I guess the Georgia

          8    case that Adil was talking about, the $20,000, it's

          9    horrendous and it amounts to a kickback.

         10              And either a clarification, or if

         11    necessary, a modification of the Medicare or

         12    Medicaid anti-fraud and abuse or kickback statute,

         13    so that it is very clear that this kind of thing is

         14    just as bad in terms of patient welfare as

         15    accepting frequent flyer bonus miles or cash for

         16    prescribing a certain drug.

         17              Other things have to do with payment

         18    beyond the actual cost of doing studies.  Of

         19    course, researchers in institutions should be paid

         20    for doing studies.  But why should they be allowed

         21    to have any kind of significant, defined in some

         22    way or other, equity interests?  Why should they


                                                                 266

          1    be, in addition to being paid for doing the

          2    studies, getting lucrative speaking fees for being

          3    on the A-list of the drug company or other kinds of

          4    things?

          5              And I think that the same applies

          6    generally to the institution in terms of its own

          7    equity interests in a company for whom it may be

          8    considered as a research participant.

          9              I think that it's really an impossible and

         10    irrevocable conflict between an institution that

         11    owns stock or is a co-worker of a biotech or drug

         12    company and one that obviously is going to have an

         13    asymmetrical set of designing, carrying out and

         14    interpreting studies when they can make a lot of

         15    money if it comes out this way and not so much if

         16    it comes out the other way.

         17              A number of people have discussed the need

         18    to come up with some definition of conflict of

         19    interest.  I'm sure that mine is just one of many,

         20    but I heard at the conference in August a somewhat

         21    narrower definition of conflict of interest that

         22    says something like, "Anything that would -- any


                                                                 267

          1    financial interest that would interfere with the

          2    outcome of the study."

          3              I think it needs to be carried way back

          4    further.  The Inspector General's report of earlier

          5    this year on recruitment practices really I think

          6    speaks to the issue that financial conflict of

          7    interest has to do with anything that would affect

          8    the recruitment of subjects for trials, the process

          9    of informed consent, the conduct of the trials, the

         10    interpretation of them, or the process of seeking

         11    approval of them.  And I think there are all sorts

         12    of examples of conflict of interest in all these

         13    areas.

         14              So these are just my thoughts, generally. 

         15    I'm pleased to be able to speak for two or three

         16    minutes here, and I certainly pledge myself and my

         17    colleagues to be of whatever help we can in getting

         18    your part of HHS going, getting more funding for

         19    it, because I think that, right off the bat, most

         20    people who realize the enormity of your job realize

         21    it will take more funding.

         22              Bob Levine and I don't agree on all


                                                                 268

          1    things, but we fully agree on this whole issue of

          2    all the dumping that is going on to the IRBs.

          3              And if we had the right kind of system set

          4    up for eliminating, when appropriate, or really

          5    managing in those instances where it isn't

          6    appropriate, and I think that there are fewer of

          7    those than some people think, these issues would

          8    never get to the IRB.

          9              The IRB is a pathway that needs to be

         10    there in an institution, but it should not be

         11    additionally loaded with deciding things that are

         12    really predecisional.  The institution should have

         13    its own policies that stop right at the first day

         14    the process of doing certain kinds of research or

         15    having certain kinds of conflict of interest.

         16              And I think the IRB needs to become aware

         17    of them, but I don't think it needs to be the

         18    manager of them or the decider that they're going

         19    to be forbidden.

         20              The forbidden part is a policy of the

         21    institution, generally.  The board of trustees, at

         22    least again, should be aware of it.


                                                                 269

          1              So those are a few of my thoughts.  If you

          2    have any questions of me, I'd be glad to try and

          3    answer them, and I again pledge our help with

          4    making your organization and committee do as good a

          5    job at this very important function as it can. 

          6              CHAIRPERSON MARSHALL:  Don't sit down, and

          7    thank you so much for being here and for your

          8    remarks.  And I do have a question of you.

          9              There has been discussion, even in Donna

         10    Shalala's New England Journal of Medicine, sounding

         11    board piece.  She referred to the conflicts of

         12    interest relative to the Gelsinger case as

         13    "perceived conflicts of interest."  

         14              And do you have any thoughts on actual

         15    versus perceived or that spectrum and the public

         16    trust and public interest? 

         17              MR. WOLF:  I don't like the phrase,

         18    "perceived" or "apparent" or whatever conflict of

         19    interest.  There either is a conflict of interest

         20    or there is not. 

         21              There may be a difference between conflict

         22    of interest and a smoking gun, as in you have shown


                                                                 270

          1    that as a result of the conflict of interest,

          2    someone has died or has been injured.  The

          3    Gelsinger case certainly is a conflict of interest

          4    and a smoking gun.

          5              But I think the idea is to prevent the gun

          6    from smoking.  To do the kinds of things, including

          7    prohibitions and restrictions on certain kinds of

          8    conflicts, so that it never turns into a smoking

          9    gun.

         10              I think that unless one puts aside the

         11    hundreds or tens of thousands of years, depending

         12    on your religious persuasion, of people and money,

         13    it goes without saying that there are too many

         14    instances of money influencing people's judgment.

         15              Physicians are no more resistant to that

         16    than anyone else, nor are other people involved in

         17    biomedical research. 

         18              So I just don't like the perceived

         19    conflict of interest.  It's either conflict of

         20    interest or not, and in ways that we need to start

         21    delineating, it needs to be eliminated or

         22    effectively managed, as opposed to just sort of


                                                                 271

          1    disclosing it to people who may not understand it.

          2              Or as someone pointed out, if you know

          3    your doctor has stock in a company, you may be even

          4    more inclined to participate in the experiment

          5    because you would say, "My doctor must really

          6    believe in this because they actually own stock in

          7    the company."

          8              That just doesn't work too well. 

          9              CHAIRPERSON MARSHALL:  Bob? 

         10              DR. ROBERT LEVINE:  Sid, you made

         11    reference, once again, to the Georgia case, Medical

         12    College of Georgia case -- 

         13              MR. WOLF:  Right. 

         14              DR. ROBERT LEVINE:  -- and I thought I had

         15    read that pretty carefully.

         16              Was there, in fact, a finder's fee of

         17    $20,000 in that case?  And by that I mean a fee for

         18    the referral of a patient? 

         19              MR. WOLF:  That may not be one patient. 

         20    It may have been for the series of patients.  I

         21    mean I saw those documents about three years ago,

         22    one of them.  Actually, someone from the faculty


                                                                 272

          1    brought this whole thing to my attention.  I turned

          2    some of these things over.  It was a huge amount of

          3    money.  It may have been more than one patient. 

          4    But it was a finder's fee enough to clearly

          5    influence the judgment of people down there and to

          6    get them criminally prosecuted. 

          7              DR. ROBERT LEVINE:  Yeah.  There was --

          8    well, the ones that were criminally prosecuted were

          9    not the finders.  They were the --

         10              MR. WOLF:  The researchers. 

         11              DR. ROBERT LEVINE:  They were the --

         12              MR. WOLF:  Right. 

         13              DR. ROBERT LEVINE:  Well, they weren't

         14    researchers.  They just said they were, and that's

         15    what they really -- 

         16              MR. WOLF:  That was part of the criminal

         17    prosecution, saying -- 

         18              DR. ROBERT LEVINE:  Right. 

         19              MR. WOLF:  -- they were researchers when

         20    they weren't, but -- 

         21              DR. ROBERT LEVINE:  Right, but when I said

         22    I found it startling that there would be a $20,000


                                                                 273

          1    fee for referral of a patient, I did read those

          2    documents, and there were fees for doing services

          3    to recruit large numbers of patients. 

          4              MR. WOLF:  Then maybe that's what it was.

          5              DR. ROBERT LEVINE:  Twenty thousand might

          6    not be an entirely unreasonable amount.

          7              Anyway, thank you for the clarification.

          8              MR. WOLF:  Well, I think the idea of

          9    finder's fees, as I said, when I introduced, I said

         10    whether it's 1,000 or whatever, it's an amount of

         11    money that's a kickback and really violates the

         12    doctor-patient relationship.

         13              DR. ROBERT LEVINE:  Yeah.  Okay.

         14              CHAIRPERSON MARSHALL:  And I'm just going

         15    to interject here and say that we all know the old

         16    joke that we don't want to get into the Federal

         17    Register about amounts of money and definitions and

         18    so forth.  So perhaps we could let this dead horse

         19    lie and are there others who have questions of Sid?

         20              MS. MEYERS:  Would you agree that a

         21    financial conflict of interest is more or less a

         22    perception that bias might occur and that just the


                                                                 274

          1    risk of this bias or the risk of endangering the

          2    patient which is motivated by somebody's financial

          3    desires is really where the problem is?

          4              In other words, the harm doesn't have to

          5    occur to the patient.  It's the perception that

          6    harm may occur or that a patient's welfare might be

          7    put at risk? 

          8              MR. WOLF:  Well, that, again, has to do

          9    with the difference between actual financial

         10    conflict of interest, something's that's

         11    quantifiable, measurable, and what someone thinks

         12    about it.

         13              I mean different people, depending on

         14    whether they are investigators or patients or

         15    potential patients, may have a different view of

         16    what the possible impact is, but what we're talking

         17    about is something that is measurable, as Ruth

         18    Kirchstein I think said at the beginning of the

         19    conference, is that the collision between profit

         20    and outcome is what makes us very worried about the

         21    existence of financial conflict of interest,

         22    particularly when it gets of the size that it gets,


                                                                 275

          1    not just the finder's fees, but just the amount of

          2    equity, interest and other things that could

          3    certainly sway the outcome. 

          4              Just to elaborate a little bit on that,

          5    back in the early nineties, I got a call once from

          6    the Commissioner's office when Dr. Kessler was

          7    Commissioner, and he said, "I want to have a little

          8    meeting.  It's an informal meeting involving some

          9    drug industry officials and some academicians, and

         10    I'd like you to attend," and there were a couple of

         11    people, "to talk about what can be done about

         12    conflict of interest."

         13              And the agenda included disclosure, but it

         14    also included the possibility of disqualification.

         15              I think I was the only person at the

         16    meeting that thought that there should be

         17    disqualification, not just disclosure, not

         18    disqualification for anything, but some level

         19    beyond which you just couldn't hold interest.

         20              That never happened.  What evolved, as

         21    Judy discussed and other people discussed here, was

         22    a policy on just disclosure with the sort of


                                                                 276

          1    tortured past of who discloses what to whom and

          2    whatever else and what do you do with it.

          3              I think that this is a good example.  Now,

          4    at least from the origin, seven years old -- the

          5    reg came out I guess in '98 -- of the silliness of

          6    trying to manage something that has that kind of

          7    impact by just simply disclosing it, particularly

          8    when it's disclosed in a largely, as I'll be

          9    pointing out, secret kind of mechanism.

         10              So I think that the perception of the

         11    problem, as opposed to the actuality of conflict of

         12    interest, gets even worse when people can't even

         13    find out about it. 

         14              CHAIRPERSON MARSHALL:  Elliot, did you

         15    have a question for Sid? 

         16              DR. DORFF:  Yes, I did. 

         17              First of all, on your last comment, this

         18    is what reinforced the things that I was trying to

         19    say to you before, that even if we don't have a

         20    complete, you know, philosophically neat way of

         21    defining what is ways that people can manage

         22    conflicts of interest, it would be good to have at


                                                                 277

          1    least five or six examples of how IRBs have,

          2    indeed, managed conflicts of interest that your

          3    committee thinks are appropriate.

          4              As a way of beginning to get toward a

          5    definition, we're sort of at the beginning of

          6    Plato's Republic, right, where you want to know

          7    what justice is, so you get some examples first,

          8    and then you try to move toward a definition from

          9    those examples. 

         10              MR. WOLF:  And stay out of the case.

         11              DR. DORFF:  And stay out of the case. 

         12    That's right.  Only the sun's shining, right?

         13              The question that I have for you is the

         14    example that you gave in terms of lucrative

         15    speaking fees, I do understand what you're after. 

         16    But it occurs to me that that's going to be

         17    somewhat hard to distinguish between, you know,

         18    from -- let me give you the opposite end of that

         19    spectrum -- where people do the research in the

         20    most above-board way possible, and then having come

         21    through that research, come to some very important

         22    finding, and then are asked, in fact, to go on the


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          1    lecture circuit based upon that.

          2              Now that seems to me perfectly

          3    appropriate.  And so then the question is how do

          4    you make sure that that kind of an outcome doesn't

          5    influence the research in the first place.  That I

          6    do understand.  That's the problem. 

          7              MR. WOLF:  Well, they could go on the

          8    lecture circuit without getting paid beyond their

          9    actual expenses.  I mean I'm not saying that anyone

         10    who has ever done research shouldn't be allowed to

         11    be published about it or teach about it or whatever

         12    else.

         13              It's just that, in addition to the

         14    reimbursement that the person in their institution

         15    gets for doing the research, it can be a sizeable

         16    addition to their income in this country.  In other

         17    countries, it's even more sizeable.

         18              Someone could be making ten, 20, 50,

         19    80,000 or more a year just from a bunch of

         20    carefully pieced together speaking fees, and that's

         21    sort of an understanding that's there maybe almost

         22    at the front end as sort of the reward beyond


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          1    actually doing experimentation. 

          2              So I think that some line needs to be

          3    drawn, not on whether they can speak or not, but

          4    how much money they get for it. 

          5              DR. DORFF:  But lines that are different

          6    from somebody who has written a book and goes on a

          7    lecture series about the book. 

          8              MR. WOLF:  Well, because if they've

          9    written a book, I mean the topic here is protection

         10    of human research -- 

         11              DR. DORFF:  Right. 

         12              MR. WOLF:  -- subjects. 

         13              DR. DORFF:  Right. 

         14              MR. WOLF:  And we're trying to think of

         15    ways in which there may be an impairment of the

         16    protection of human research subjects because of

         17    financial arrangements. 

         18              DR. DORFF:  Yeah.  Yeah.  I do.

         19              MR. WOLF:  That's the difference. 

         20              DR. DORFF:  I do very much appreciate what

         21    you're talking about.  I'm just saying that on that

         22    particular outcome, we've got to do a lot of


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          1    thinking about differentiating what is a

          2    legitimate, you know, speaking engagement for a

          3    fee, as opposed to that which is going to influence

          4    the research. 

          5              MR. WOLF:  Yeah, and the same true of

          6    consultantships.  They can be extraordinarily --

          7              DR. DORFF:  Right. 

          8              MR. WOLF:  -- and make major contributions

          9    to someone's income. 

         10              DR. DORFF:  Right. 

         11              MR. WOLF:  It's the same sort of -- 

         12              CHAIRPERSON MARSHALL:  Thank you very

         13    much. 

         14              MR. WOLF:  Thank you very much. 

         15              MS. BLEVINS:  Hello.  My name is Sue

         16    Blevins, and I'm here first as a human being, and

         17    second, as a representative of the Institute for

         18    Health Freedom, a patient's rights group.

         19              And, Abbey, I would first like to thank

         20    you for your comments, and I think clearly

         21    reflecting the needs of consumers.  And I have an

         22    appeal to make.


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          1              First, I want to say that I highly respect

          2    research.  I'm a nurse by training, and I've worked

          3    at Johns Hopkins in Canada at NIH, and I admire

          4    research and want to see the scientific technology

          5    evolve in this country like it has over the last

          6    century.

          7              But having said that, just because we have

          8    new technology, new genetic therapies, we have had

          9    wonderful advances with informed consent that just

         10    because we have new technologies, there's no reason

         11    to get rid of informed consent.  That's an appeal

         12    to make.

         13              And the second thing is, I'd like to

         14    suggest that perhaps you could create a web site

         15    for patients, Abbey, as you said, patients don't

         16    have time to read the Federal Register.  Presidents

         17    of non-profits don't have time to read the Federal

         18    Register.  And we are a small organization.  We

         19    don't have money to pay lawyers to read the Federal

         20    Register for us.

         21              So I would highly recommend that you could

         22    create a patient's rights web site that could


                                                                 282

          1    describe what are your rights as a patient involved

          2    in a clinical trial.

          3              We get people calling us with all kinds of

          4    situations, and, quite frankly, I've worked at NIH. 

          5    NIH has an information office in every institute,

          6    but try calling some time.  It's very, very

          7    complicated, and I think that could be very helpful

          8    to the public.

          9              And thank you for your work and being so

         10    open. 

         11              CHAIRPERSON MARSHALL:  Thank you very

         12    much, and we hope to hear from you again. 

         13              And, yes, there are folks here from the

         14    OHRP who deal exclusively in education, and I hope

         15    that they're taking copious notes as well. 

         16              MR. SNIDER:  Dixie Snider, Associate

         17    Director for Science at CDC.

         18              I just wanted to raise an issue that is

         19    relevant here, I think particularly in light of Dr.

         20    Wolf's comments that hasn't been brought up, and

         21    that is the issue of technology transfer and

         22    patenting and so forth.


                                                                 283

          1              As everybody is aware, I'm sure, there

          2    were some laws passed back in the eighties that

          3    encouraged academia and then subsequently, federal

          4    laboratories to invent things and to patent things

          5    and to get them into commercial production.

          6              And what I'm saying is that we have some

          7    competing societal goals here, and that we're

          8    encouraging scientists, on the one hand, to be

          9    innovative and to patent their products and get the

         10    financial rewards that go with that.  And, at the

         11    same time, wondering at what point -- certainly as

         12    a member of the work group, I hope everybody

         13    understands I'm for full disclosure.  So that's not

         14    the issue. 

         15              The issue is, when do we prohibit people

         16    from participating?  And I think it's an important

         17    issue for you to grapple with.

         18              I don't have the answer to that question,

         19    but I can tell you that on the work group, we

         20    struggle with that.

         21              Suppose, for example, we have the surgeon

         22    that's developed a particular device and that


                                                                 284

          1    surgeon has practiced on all kinds of animals and

          2    is the most competent person to install that device

          3    on the first human being, and yet that person holds

          4    the patent and maybe even owns the company that he

          5    or she created?

          6              That presents a real dilemma for us as a

          7    society in terms of we want that product. 

          8    Presumably, it has some value to us. 

          9              At the same time, we don't want that

         10    individual to be swayed by those financial

         11    considerations and the other considerations into

         12    doing something to us or one of our loved ones, or

         13    anybody else, for that matter, that would be

         14    unethical and that would be influenced by those

         15    financial considerations.

         16              So I just bring that to your attention

         17    because I think it's really a very important aspect

         18    to this whole issue. 

         19              CHAIRPERSON MARSHALL:  It most certainly

         20    is.

         21              Bob, did you have a response to Dixie's

         22    comments?  Let's do that.  Yes? 


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          1              DR. ROBERT LEVINE:  I'd like to endorse

          2    what Dixie said because I think it's very important

          3    that we don't lose sight of the important job that

          4    universities have in technology transfer and in

          5    bringing products to the marketplace. 

          6              And, also, the importance of inventors in

          7    the initial processes of prosecution of inventions. 

          8    It's very difficult to make it work any way other

          9    than that.

         10              I think it's a quite different issue once

         11    one has gone beyond initial proof of principle, or

         12    in FDA jargon, beyond Phase I kind of trials, to

         13    then say, "Should somebody who has an equity

         14    position be engaged in Phase III trials or be

         15    engaged in doing things which really bring a

         16    product to the marketplace?"

         17              But at the very outset of discovery, and

         18    including the outset of discovery, inhuman

         19    subjects, I think there really remains a role of

         20    the inventor and because of the way our laws are

         21    set up, the inventor often will have a financial

         22    role in the successful prosecution of that


                                                                 286

          1    invention.  That should be disclosed, but I don't

          2    think it should be forbidden. 

          3              CHAIRPERSON MARSHALL:  Thank you, and I

          4    know in terms of our materials that we have and

          5    discussions that have taken place earlier that that

          6    level of transparency is very important, and that

          7    there are organizational safeguards that can be put

          8    in place to mediate those conflicts.  Thank you.

          9              MS. DELANEY:  My name is Patty Delaney,

         10    and I am actually an FDA employee, and I work in

         11    the cancer program, but I'm here today as a member

         12    of the public and as a patient advocate.

         13              I think that much of what you talk about

         14    today is so largely misunderstood by the public,

         15    not understood at all, actually, so that when the

         16    rank and file person enters the trial, it is

         17    overwhelming.

         18              I bring the experience of my own

         19    participation in a clinical trial at the National

         20    Cancer Institute to the position I hold at the FDA

         21    and to my volunteer work as a patient advocate. 

         22              The conflict of interest, financial


                                                                 287

          1    conflict of interest, is only, of course, growing

          2    and adding pressure, but there is also the conflict

          3    of interest of scientific zeal that presents a

          4    terrific problem for patients.

          5              And I think as a practical matter, it's

          6    very important that patients have, once they have

          7    entered a trial, have an unbiased place to turn for

          8    advice while they are in the trial.

          9              I would like to say it was only my

         10    anecdotal experience, but, of course, it isn't. 

         11    I've spoken and advised hundreds, if not thousands

         12    of patients since 1987.  And the problem is that

         13    the advice I received on the ethical conflicts in

         14    my trial were from what I call "people on the

         15    payroll."  You've all alluded to that this morning.

         16              And it required, at the National Cancer

         17    Institute, many of them coming to me, quote, "off

         18    the record," sneaking into my room, telling me to

         19    leave the trial, doing things like that.

         20              I can only say that I would like to

         21    believe that my experience is anecdotal, but,

         22    again, I know it is not.  So to the extent that


                                                                 288

          1    this committee can think really about the

          2    individual experience of a much less sophisticated

          3    person coming to the circumstance and how they

          4    would proceed through the entire circumstance, they

          5    must have advice from unbiased sources while they

          6    are in the trial, and it cannot be from people on

          7    the payroll.

          8              If that's a funding issue, then it's an

          9    advocacy issue that we all have to deal with. 

         10              CHAIRPERSON MARSHALL:  Thank you, and I

         11    hope a question for you, Patty.

         12              One of the things that I have thought

         13    about in the past -- this relates back to my

         14    background as a critical care nurse and as a

         15    clinical ethicist -- is whether or not there is an

         16    analog from the model of an ethics consultation

         17    service of an ethics committee to the same sort of

         18    problem solving mechanism within the clinical

         19    research enterprise?

         20              But the question I have for you is, my

         21    bias is that most well-trained ethics consultation

         22    services or consultants do a good job, and that


                                                                 289

          1    they don't represent the interests of the

          2    institution.  They are there to help resolve an

          3    issue.

          4              Would you see the same sort of mechanism

          5    as having an inherent conflict of interest because

          6    they might be paid by the institution? 

          7              MS. DELANEY:  Well, I think you'd have to

          8    look at it on a case by case basis.  I mean

          9    patients, first of all, the people they believe the

         10    most at this point are other patients.  Not their

         11    doctors, other patients.  However, the organized

         12    patient advocacy community is increasingly getting

         13    conflicted by pharmaceutical funding.  And so that

         14    becomes a question.

         15              It all becomes a question of exactly what

         16    the circumstances of that trial and that ethics

         17    committee.

         18              I just remember -- I did not know anything

         19    about clinical research when I joined my trial.  I

         20    just remember thinking to myself, all of these

         21    physicians here have so much angst, and they're all

         22    wringing their hands, and they're going to the


                                                                 290

          1    terminal board, and they're trying to figure out

          2    what to do about me.  But where am I supposed to

          3    turn to figure out what to do about me.

          4              And I did suspect harm, and I was then, in

          5    fact, told that there was the potential of harm.

          6              So, I mean when you're very ill with a

          7    life-threatening disease, which many trials are

          8    treating people who are very ill, they need to have

          9    someone -- they don't have -- it shouldn't be a

         10    matter of them having to ask, either.  It should be

         11    unsolicited where they are checked in with

         12    periodically by this unbiased source. 

         13              CHAIRPERSON MARSHALL:  Thank you very

         14    much. 

         15              MS. FISHER:  I'm sorry.

         16              CHAIRPERSON MARSHALL:  Go ahead, please. 

         17              MS. FISHER:  My name is Barbara Lowe

         18    Fisher, and I'm the President of the National

         19    Vaccine Information Center.

         20              Dr. Dorff, if there is a societal duty to

         21    improve the human condition, and, Dr. Rich, if

         22    clinical research is a societal good, of course,


                                                                 291

          1    the ultimate question is, who is going to define

          2    "societal good" and decide which individuals will

          3    be used by science to improve the human condition?

          4              And from a health consumer perspective, I

          5    think it's fair to say that most Americans do not

          6    want to be used by science or by scientists, no

          7    matter how much the research will benefit society,

          8    without their voluntary informed consent.

          9              And I think that this extends in the

         10    future -- should extend to research that's going to

         11    be conducted where government or industry will give

         12    financial incentives to HMO's, particularly, and

         13    doctors will have financial incentives to enroll

         14    patients in clinical trials, particularly children

         15    in clinical trials.

         16              And then when HIPA is enacted, the Health

         17    Insurance Portability and Accountability Act, is

         18    enacted in 2002, third parties will be allowed to

         19    go in and mine the medical records of these

         20    patients without the patients' informed consent. 

         21              CHAIRPERSON MARSHALL:  Any committee

         22    members?  Any -- 


                                                                 292

          1              DR. SHAMOO:  Can I --

          2              CHAIRPERSON MARSHALL:  Yes.  Yes, please,

          3    Adil. 

          4              DR. SHAMOO:  I just want to comment on the

          5    previous speaker who asked a question, and I come,

          6    again, from my experience with decision impaired. 

          7    This is why we came up with the suggestion that

          8    because the same psychiatrist researcher was the

          9    investigator.  And so there's almost a double

         10    jeopardy for decision impaired when the same

         11    researcher is the same doctor who is treating the

         12    patient.  There alone, cancer patients who is not

         13    decision impaired.

         14              And at the time, we suggested very

         15    strongly that they should be a disinterred

         16    physician, just like we have a private physician,

         17    who will advise us, on a continuing basis, whether

         18    we should enter into the trial, we should continue

         19    the trial, and when we should get off of the trial. 

         20    That could resolve some of those problems. 

         21              CHAIRPERSON MARSHALL:  Elliot, and then I

         22    want to begin -- I want to get Greg, and then I


                                                                 293

          1    want to begin our discussion of recommendations.

          2              DR. DORFF:  I just wanted to endorse

          3    completely what -- what's your name, again? 

          4              MS. FISHER:  Ms. Fisher. 

          5              DR. DORFF:  -- what Ms. Fisher just said. 

          6    As a matter of fact, it goes very much to the

          7    essence of what America is, which is a strong sense

          8    of individual rights, as against communal good.

          9              And so that when we think about the

         10    communal good, that doesn't mean that individual

         11    rights always trump the communal good, but it does

         12    mean that whenever we're talking about the communal

         13    good, such as, in our case, furthering research, we

         14    have to take into consideration with very, very

         15    strong protections of human rights.  I think that's

         16    why this committee was formed in the first place. 

         17              CHAIRPERSON MARSHALL:  Well said. 

         18              Dr. Koski is back from glad handing the

         19    President.  Welcome group. 

         20              DR. KOSKI:  Thank you.  Nice to be back. 

         21    I'm sorry that I had to run out and miss part of

         22    this.  I understand you've had a very productive


                                                                 294

          1    day so far.

          2              I just wanted to comment on the fact that

          3    many institutions have already adopted programs,

          4    either as specific patient advocate programs for

          5    research or separate sort of components within the

          6    human research office that is disconnected from the

          7    IRB process, per se, and other parts, to do

          8    specifically the kinds of things that are being

          9    suggested to be a resource available to patients so

         10    that there may be some examples of best practices

         11    that are already available out there that might be

         12    worth trying to identify more clearly and tap into.

         13              CHAIRPERSON MARSHALL:  Thank you, Greg.

         14              So let me just remind the committee that

         15    we have half an hour in which to deliberate about

         16    our recommendations and that we can proceed in the

         17    same way that we did this morning, that we need to

         18    refine and focus on the issues; that we need to

         19    identify any need for further data, and agree to a

         20    work plan and a schedule.

         21              And I really would like to thank you,

         22    Stuart, for providing us with this list of five


                                                                 295

          1    questions.  That is something that we can use as

          2    food for thought, but I want to open the discussion

          3    up then to committee members and perhaps we could

          4    start with defining issues.

          5              We have certainly talked -- there are some

          6    general themes have had to do with how one defines

          7    conflict of interest, and certainly the sense among

          8    the group, as a whole, all of the folks in the room

          9    is that it is very broad, and whether we need

         10    prohibitions against certain types of conflicts of

         11    interest or how others might be managed, whether

         12    disclosure is adequate in some circumstances,

         13    certainly not in all circumstances, issues that

         14    have to do with technology transfer and

         15    intellectual property and inventions.

         16              And then other things that we might not

         17    necessarily think of that fall under conflicts of

         18    interest that have to do with faculty arrangements

         19    and professional advancement and so forth.

         20              So let me open the floor to members of the

         21    committee. 

         22              Mark? 


                                                                 296

          1              MR. BARNES:  Thank you.

          2              This is somewhat of a different situation

          3    that we, the committee, are presented with and the

          4    issue that we discussed this morning was really

          5    quite undefined in terms of process and concrete

          6    steps.

          7              On the other hand, what we have here in

          8    this case is we have a recent conference that was

          9    convened by NIH, a very fine conference in which

         10    many of these issues were discussed.  We have

         11    multiple articles in many different journals,

         12    including JAMA and the New England Journal, about

         13    the issue of conflict of interest, and we have a

         14    proposed document on the table, a proposed guidance

         15    on the table from HHS.

         16              So it seems to me that, you know, one

         17    action step that, you know, I would propose, at

         18    least for discussion would be that we actually have

         19    some kind of subcommittee of this group to simply

         20    write a response to the draft guidance that's been

         21    put out by HHS and that the subcommittee meet in

         22    the interim between now and the next full meeting


                                                                 297

          1    or the next meeting of this full committee, and

          2    that we have a report, you know, ready to present

          3    back to the committee, hopefully, for its adoption,

          4    and then our forwarding on to HHS.

          5              I don't think that the timing would be a

          6    problem here because I doubt that anything is going

          7    to get passed until the next HHS Secretary gets

          8    through the confirmation process and is fully

          9    briefed on the whole thing of this -- the whole,

         10    you know, meetings -- the whole process of all of

         11    these issues.  So I don't think that we're going to

         12    lose valuable time by adopting some kind of process

         13    to do that. 

         14              CHAIRPERSON MARSHALL:  You read my mind,

         15    and I really didn't slip in five dollars under the

         16    table for that. 

         17              Let me ask first some response from the

         18    rest of the group about that idea before we move

         19    on.

         20              Adil? 

         21              DR. SHAMOO:  I agree. 

         22              DR. KOSKI:  Just I don't know if this was


                                                                 298

          1    explained earlier.  This is a technical sort of

          2    clarification, if you will, with respect to the use

          3    of certain terms that I have had to come to grips

          4    with in government, and that is the difference

          5    between guidance, between points to consider,

          6    between rules and regulations.  Each of those take

          7    on specific meaning within government, so that we

          8    need to keep that in context.

          9              When we're talking about regulations,

         10    we're talking about those new laws that are

         11    actually passed by the Congress, and we're talking

         12    about rules.  Okay, they are basically the rules

         13    that lay out how, in fact, specific regulations are

         14    to be carried out within the government, and those

         15    generally are promulgated through the rules-making

         16    process.

         17              And if my longer-term government

         18    colleagues will help me here, if I get into water

         19    that's deeper than I can stand it, so that that's

         20    the other process.

         21              And then, of course, with respect to

         22    either points to consider, which was a specific


                                                                 299

          1    sort of designation that has been used in work

          2    products from either NIH or HHS, or particularly,

          3    FDA, then it comes in a certain thing.  But it's

          4    closer to guidance, which is something that can be

          5    offered without going either through the rules-

          6    making process or through the passage of new

          7    regulations or amendments.

          8              So that in terms of doing things quickly,

          9    clearly, you'd want to do it with quality.  But

         10    it's possible to do things relatively quickly as an

         11    interim step, which is, in fact, why this

         12    particular document that's before the committee was

         13    suggested as an interim guidance document because,

         14    clearly, there's more work that would have to be

         15    done and a decision would have to be made whether

         16    or not it was desirable to actually promulgate

         17    specific rules and so on, and if regulations are

         18    required.  Those are things that we clearly would

         19    depend upon the guidance of this committee for.

         20              So did I get it right, more or less,

         21    Linda?  Is that -- yes?  Okay.  Good.  Thank you.

         22              CHAIRPERSON MARSHALL:  Bob? 


                                                                 300

          1              DR. ROBERT LEVINE:  I thought regulations

          2    and rules were the same thing, and that Congress

          3    passes their statutes and the regulations are

          4    what's published in the Federal Register to

          5    interpret the statutes? 

          6              DR. KOSKI:  I see nodding heads, so we're

          7    close. 

          8              CHAIRPERSON MARSHALL:  Right. 

          9              DR. KOSKI:  But that's -- okay. 

         10              CHAIRPERSON MARSHALL:  And let me just

         11    say, Greg, that Stuart sort of, in his introduction

         12    to his remarks, made that very clear what the paper

         13    was, and its interim status. 

         14              DR. KOSKI:  Sorry. 

         15              CHAIRPERSON MARSHALL:  No.  No.  No, and

         16    so forth.  But we rewrote the Federal Code while

         17    you were gone. 

         18              No, so -- 

         19              DR. KOSKI:  That's progress. 

         20              CHAIRPERSON MARSHALL:  -- I would like,

         21    while this is on the table, to say that I think

         22    this is a wonderful action step.  I would also ask


                                                                 301

          1    Mark whether you'd be willing to chair this small

          2    group? 

          3              MR. BARNES:  I guess I can't say, "no,"

          4    since I proposed it. 

          5              If you would like me to, I would.  Yes. 

          6              CHAIRPERSON MARSHALL:  It needs to be a

          7    small group.

          8              Do we have other volunteers?  Adil? 

          9    Elliot?  And I think that will suffice.  Rob.  And

         10    I think that's large enough for a working group.

         11              Yes? 

         12              DR. SHAMOO:  May I ask a question? 

         13              CHAIRPERSON MARSHALL:  Oh, of course. 

         14              DR. SHAMOO:  Thank you.

         15              I know NBAC's subcommittees meet also in

         16    the public.  They have the same rules governing

         17    them as the full committee.

         18              And my question to you big shots, to tell

         19    us how the subcommittee should conduct itself,

         20    before we get into hot water, if we make mistakes?

         21              DR. KOSKI:  I think what we should do, if

         22    that requires specific legal clarification, we'll


                                                                 302

          1    get it from the FACA experts and legal counsel. 

          2    But we want to make sure of it.

          3              There is, I believe, within our charter a

          4    provision for putting together working groups in

          5    order to come out with work product.

          6              Clearly, the work product is ultimately

          7    put up in the Federal Register and all, so that it

          8    probably would be considered a working group rather

          9    than a subcommittee, in which case, it can work in

         10    private.  Yes. 

         11              CHAIRPERSON MARSHALL:  Right.  Thank you. 

         12              Elliot? 

         13              DR. DORFF:  That would be especially

         14    helpful because it might be that this group could

         15    meet by phone, rather than -- 

         16              CHAIRPERSON MARSHALL:  Certainly. 

         17              DR. DORFF:  -- in person. 

         18              CHAIRPERSON MARSHALL:  Right.  Right, and

         19    I think that would be the expectation that this

         20    working group would meet via e-mail and by

         21    telephone and so forth. 

         22              But that as the process moves along, as I


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          1    will state over and over again, our work will be

          2    available and transparent, and that we want to have

          3    feedback from all of those who are concerned.  So

          4    you have that promise from us as a committee. 

          5              DR. CHODOSH:  Could I just -- 

          6              CHAIRPERSON MARSHALL:  Yes, Sandy? 

          7              DR. CHODOSH:  -- make a small plea?

          8              In the document, as it exists right now,

          9    on page eight, you have a lovely list, which we've

         10    already discussed really doesn't appropriately go

         11    to the IRB, but maybe through the IRB.

         12              But, you know, it's not really clear what

         13    the answer should be, what's right and what's

         14    wrong.  And I think somewhere in the document, it

         15    might talk about that a little bit, you know. 

         16    Who's the sponsor is not a bad term.  I mean it's

         17    not -- but there are some of them that are sort of

         18    questionable about what am I supposed to answer? 

         19    You know, what is the right answer to get me off

         20    the hook?

         21              And I think that it would be worth

         22    defining a little bit about what's implied. 


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          1              CHAIRPERSON MARSHALL:  Yes, Mary? 

          2              DR. PELIAS:  I would like to request a

          3    little bit more information about what patient

          4    advocacy offices already exist and how they work in

          5    terms of being close to or separated from

          6    institutional review board.  I'm very much

          7    interested in patient advocacy and getting

          8    information that we've talking to in this session

          9    back to patients. 

         10              CHAIRPERSON MARSHALL:  Mary, can you

         11    explicate that just a little bit for me?  I'm not

         12    sure I've exactly wrapped my mind around what

         13    you're getting at. 

         14              DR. PELIAS:  Well, we mentioned just at

         15    the end of our discussion about how to structure a

         16    patient advocacy office as an unbiased source of

         17    information for patients about research that they

         18    might be participating in.

         19              And in my own institution, I don't know of

         20    a patient advocacy office.  I would like very much

         21    to know more about them and how patients can get

         22    unbiased information, separate and apart from the


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          1    whole IRB process and signing consent forms. 

          2              CHAIRPERSON MARSHALL:  Abbey? 

          3              MS. MEYERS:  I don't think they exist --

          4              CHAIRPERSON MARSHALL:  Abbey says they

          5    don't exist. 

          6              MS. MEYERS:  I never heard of that. 

          7              CHAIRPERSON MARSHALL:  All right.  Yeah. 

          8    Okay.

          9              MS. MEYERS:  Never. 

         10              CHAIRPERSON MARSHALL:  Okay.  All right. 

         11              MS. MEYERS:  No.  An ethics committee is

         12    not a patient advocacy. 

         13              CHAIRPERSON MARSHALL:  Right, and I'm

         14    going to take the prerogative of the chair and that

         15    we will go in order.

         16              Elliot and then Greg, and I have a

         17    comment.  So if you would like to make a comment,

         18    then you need to be acknowledged. 

         19              DR. DORFF:  UCLA has an ombudsman for

         20    patients. 

         21              CHAIRPERSON MARSHALL:  Is that ombudsman

         22    for a person that's being treated there or a person


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          1    who is in a clinical trial? 

          2              DR. DORFF:  I honestly don't know how it's

          3    defined.  I know it is definitely for patients and

          4    it may also be for people in clinical trials.  I

          5    don't know.

          6              But, I mean specifically an office in the

          7    hospital for patients to have their concerns aired

          8    and dealt with. 

          9              CHAIRPERSON MARSHALL:  I have Greg and

         10    then I have Adil, and then I have myself. 

         11              DR. KOSKI:  Actually, at PRIMAR this past

         12    -- it's been a couple of months ago, whenever it

         13    was.  Time flies when you're having fun -- there

         14    were presentations from several institutions where

         15    they described, as one example, a separate office

         16    that was set up at a cancer institute where they

         17    were actively involved in clinical research.  And

         18    this office was totally independent and autonomous.

         19              And at the time, people were approached

         20    to, you know, ask them whether or not they were

         21    interested in research, whether or not they wanted

         22    to participate in it.


                                                                 307

          1              This office was made available to them. 

          2    In fact, they were actively introduced to one of

          3    the individuals from this office whose sole

          4    responsibility was to be there as a resource for

          5    the patients who are involved in the research

          6    activities.

          7              And once the relationship is established

          8    at that level, as the study progresses, there is an

          9    ongoing visitation, active, you know, proactive

         10    approach to the individual participants in the

         11    trials to see, number one, how's it going?  You

         12    still want to do this?  You got new problems,

         13    questions, so on, but in an active kind of support

         14    mode.

         15              And, in fact, the institution has made an

         16    attempt to assess this and they found that it's

         17    been just enormously appreciated by the people who

         18    are participating in the trials, and they believe

         19    that it's been an important factor in promoting

         20    both the quality of what they're doing, as well as

         21    the satisfaction that the participants have had. 

         22    So that's one model.


                                                                 308

          1              At other institutions, it actually

          2    established sort of separate offices so that there

          3    may be a separate human research office that is the

          4    staffing for the institutional review board and

          5    much of that process, but a separate office that's

          6    established as a resource to the patients where it

          7    may be less active, but some of them have taken a

          8    form of passing out a brochure to each patient who

          9    is asked to participate or invited to participate

         10    in a trial.

         11              That explains what research is, explains

         12    sort of the process that they would go through, how

         13    it's reviewed and approved, what their rights,

         14    expectations are, and actually it says, "Look, if

         15    you have any concerns and questions, comments, you

         16    know, call this office.  There will be somebody

         17    there to help you and that's available on a 24-hour

         18    basis so that it can react to complaints, whether

         19    they come from individual patients, from families,

         20    whoever, and those are often coupled to quality

         21    assurance, quality improvement efforts and so on.

         22              So it's kind of they're the watch dog


                                                                 309

          1    within the watch dog sort of system, but a

          2    separation of powers to make it very clear that

          3    there is at least one place where a research

          4    participant can go in order to get information

          5    that's either not depending upon the IRB, nor upon

          6    the investigators and the sponsors and so on. 

          7              And those are just two models.  They both

          8    exist currently, and my sense from the PRIMAR

          9    meeting was that they're in recognition of the need

         10    to improve what happens from the time the IRB says,

         11    "Okay," to the time that they actually complete the

         12    study and, you know, wrap up the data set.

         13              That's where we need to put so much more

         14    effort.  That's where we need to put support.  And

         15    it emphasizes the fact that informed consent is --

         16    it's not signing the name.  It's a process that

         17    continues throughout the conduct of the activity.

         18              So those are real life examples of what's

         19    currently going on in some places. 

         20              CHAIRPERSON MARSHALL:  Adil and then -- 

         21              MS. MEYERS:  Can I ask Greg something? 

         22              CHAIRPERSON MARSHALL:  Yes. 


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          1              MS. MEYERS:  You know, this is wonderful. 

          2    I wish every research institution should have it.

          3              But if we write into the rules that every

          4    hospital should have it, they're going to say,

          5    "Who's going to pay for it," and what would be the

          6    answer to that?

          7              CHAIRPERSON MARSHALL:  I want to interject

          8    here, as the Chair, and this is, Mary, you have

          9    raised a wonderful issue that is near and dear to

         10    my own heart.

         11              And I think that these sorts of mechanisms

         12    to which one can appeal for help and assistance are

         13    important not just for research subjects or

         14    participants, but for those who do the research

         15    themselves.  And I'm thinking not on the

         16    investigators if a problem arises, but research

         17    nurses or others who may feel that their integrity

         18    is compromised during the research process.

         19              I think that this is something that when

         20    the IOM committee gets to the second phase of its

         21    charge and is looking at systems of protections of

         22    human subjects, it will address.  And I think that


                                                                 311

          1    we can certainly ask them to address this specific

          2    issue.

          3              There are excellent models out there that

          4    could be adapted and some creative thinking might

          5    even bring us forward in terms of new things.

          6              So thank you very much. 

          7              Other things that we might want to put on

          8    the table in terms of -- now, remember here, we are

          9    trying to identify issues and a work plan for the

         10    future.  So that's the discussion that I would like

         11    to hear within the next eight minutes. 

         12              Elliot? 

         13              DR. DORFF:  It occurs to me that this is

         14    not restricted to this particular field of

         15    endeavor.  Conflicts of interest occur in all kinds

         16    of other fields. 

         17              And it would be interesting to just get a

         18    kind of background paper on how lawyers deal with

         19    conflict of interest and how social workers -- in

         20    other words, those kind of things in order to get

         21    ways -- to get this list that Mark just handed to

         22    me, a list that he created, or some possible ways


                                                                 312

          1    of dealing with conflicts of interest in this

          2    particular instance.

          3              And I think whatever number of concrete

          4    ways can be suggested, either in this field

          5    specifically, as Mark's list deals with, or from

          6    other fields, that that would be really helpful in

          7    terms of diminishing the conflicts of interest that

          8    exist. 

          9              CHAIRPERSON MARSHALL:  Let me ask you,

         10    Elliot.  If we were to commission a paper of that

         11    sort, would it be helpful then, if such a person

         12    exists, to have something that is a survey paper?

         13              DR. DORFF:  Right.

         14              CHAIRPERSON MARSHALL:  What is the

         15    pleasure of the committee? 

         16              MS. MEYERS:  It sounds good. 

         17              CHAIRPERSON MARSHALL:  And let me ask our

         18    -- pardon me?  Let me ask our staff folks, do you

         19    see any objections to that in terms of resources,

         20    et cetera? 

         21              PARTICIPANT:  Not at this point. 

         22              CHAIRPERSON MARSHALL:  We shall do that. 


                                                                 313

          1    Thank you.

          2              Adil?  I'm sorry.

          3              PARTICIPANT:  Potential conflict of

          4    interest or --

          5              CHAIRPERSON MARSHALL:  No. 

          6              PARTICIPANT:  -- is it any promotion to

          7    tenure -- 

          8              CHAIRPERSON MARSHALL:  Okay.

          9              PARTICIPANT:  -- conflict that you are

         10    asking for? 

         11              CHAIRPERSON MARSHALL:  It should be

         12    everything.  And let me ask, if you're going to ask

         13    a question if you'd please come to the microphone.

         14              But I think we would like for this to be

         15    broadly based in terms of definitions and

         16    approaches.

         17              Greg and then Bob? 

         18              DR. SHAMOO:  What happened to me? 

         19              CHAIRPERSON MARSHALL:  Oh, I'm sorry. 

         20    Adil.  Adil, Greg, Bob. 

         21              DR. SHAMOO:  There is quite a bit of

         22    literature on conflict of interest and financial


                                                                 314

          1    conflict of interest in the financial institutions. 

          2    I have actually looked at that in the mid-eighties,

          3    so there is literature there, and it's really quite

          4    extensive.  And, as a matter of fact, that's why

          5    you have strict rules in the financial, the

          6    Securities and Exchange Commission, the Glass-

          7    Stiegel Act of 1936, as Mark is shaking his head,

          8    and I'm quite familiar with it.

          9              And that's how I started my career in

         10    terms of research integrity issues and how it

         11    should be resolved, and they resolve it really

         12    rather very well.  They compartmentalize and they

         13    prohibit, et cetera, et cetera.

         14              So I think before we jump into this, there

         15    are literature on the subject.  Maybe we should

         16    make some of them available.  That's one.

         17              The second thing is, Mark's committee or

         18    Mark's working group -- I apologize.  I learn

         19    slowly -- with Stuart's permission, could we use

         20    Stuart for the working group, his help, since he

         21    has put a lot of thought in it, and we could tap

         22    him whenever we need him? 


                                                                 315

          1              CHAIRPERSON MARSHALL:  I had the same

          2    thought of asking Stuart if he could serve as a

          3    consultant.  And I also wanted to add a committee

          4    member, and I wanted to ask Judy if you would be

          5    willing to assist us in this endeavor, as well? 

          6    Thank you. 

          7              So does that suffice for a working plan? 

          8    And I think, you know, tomorrow afternoon, when we

          9    wrap up and after we have had all of our

         10    discussions, we can outline time frame and so forth

         11    for all of these because what we're going to need

         12    to do then is assign priority. 

         13              And, Greg? 

         14              DR. KOSKI:  Thank you.  This comment was

         15    probably made earlier before I returned, but I

         16    think one of the notions that came out of the

         17    conference in August was that we needed to be

         18    broader in our thinking, rather than just looking

         19    at financial arrangements to recognize that other

         20    types of issues pose real conflicts that should be

         21    considered in this broad framework.  So I would

         22    just endorse that we would go in that direction. 


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          1              CHAIRPERSON MARSHALL:  I have Bob and then

          2    Judy. 

          3              DR. ROBERT LEVINE:  Thank you.  My

          4    comments follow directly on Greg's that the -- a

          5    lot of what's written about conflict of interest,

          6    conflict of commitment and the reward system really

          7    does not pay good attention to what's really seen

          8    as the coins of the academic realm.  Its promotion

          9    is very big.  Being perceived as a good citizen of

         10    the academic community is very big. 

         11              Even more so, these days, as we begin to

         12    refer to our community of colleagues as a national

         13    or international community, rather than the local

         14    community, it's the recognition you get for the

         15    quality of your work. 

         16              All too often, I see people saying, "Well,

         17    we could fix the IRB problem.  We'll give him more

         18    money."  Well, that's not what makes these people

         19    move, and that's not what makes clinical

         20    investigators move, for the most part, either. 

         21    They would much rather have their name attached to

         22    some important discovery, or they say we could give


                                                                 317

          1    them released time from teaching.

          2              That may work in the French Department,

          3    but that's not what teaching in a medical school is

          4    all about.  Nobody can keep track of when they're

          5    teaching and when they're not.  There's always

          6    teaching going on, no matter what you do.

          7              The other problem I want to raise is the

          8    idea of having people inside the institution to

          9    serve as patient advocates or ombudsmen.  Many of

         10    these people really don't know enough about what a

         11    clinical trial, for example, about what treatment

         12    is all about to serve as effective advisors to the

         13    patients. 

         14              The question came up about how are you

         15    going to pay these people.  What you have to

         16    consider is that if you want to have truly

         17    effective advisors to patients, they're going to

         18    have to be people who have a substantial amount of

         19    professional education themselves, and these people

         20    are expensive. 

         21              I think it's very important to have people

         22    available to serve as advisors.  One device that


                                                                 318

          1    the IRBs have used is particularly and very

          2    difficult decisions, particularly in areas where

          3    you're dealing with patients that have a really

          4    grave outcome, whether or not they get treated is

          5    rather than attempt to write a script for a

          6    conversation between an investigator and a

          7    prospective research subject.

          8              They say, "Take this protocol.  Take this

          9    consent form and show it to your own doctor.  And

         10    what you should do is ask your doctor to look at it

         11    and discuss with you whether it would be a good

         12    idea for you to consider getting involved in this."

         13              We tried to think of other ways to

         14    accomplish the same goal and really couldn't come

         15    up with it.  You simply can't get people who are

         16    utterly disconnected to come in and offer that sort

         17    of advice to individual research subjects as

         18    they're going through their thinking process.

         19              I have no way of knowing whether our

         20    approach is effective.  We have occasional

         21    anecdotal evidence that it either is or is not. 

         22              CHAIRPERSON MARSHALL:  Abbey? 


                                                                 319

          1              MS. MEYERS:  I'm just thinking that, along

          2    those lines, maybe there ought to be a mandatory,

          3    24-hour or 48-hour waiting period from the time the

          4    informed consent is presented to the person until

          5    they sign it and agree to go in to a trial.  And

          6    maybe this independent person, this advocate or

          7    ombudsman, should be present during the informed

          8    consent process. 

          9              CHAIRPERSON MARSHALL:  Let me just say

         10    from a process perspective that I think that

         11    perhaps we're getting to a level of detail that is

         12    something that we have commission the IOM to do,

         13    and that perhaps the best use of our time would

         14    then be to react to the advice that we're given by

         15    them.  I think we're bordering on micromanagement

         16    at the moment. 

         17              I had Judy and then Sandy.  And, pardon

         18    me.  I want to interrupt just for a moment because

         19    I see that some folks are heading out the door, and

         20    I wanted to let you know that, at 4:30, there is

         21    going to be a reception to which we would like to

         22    invite everyone in the room.  It will be hosted by


                                                                 320

          1    the Surgeon General's office, and Deputy Surgeon

          2    General Nicky Lorry will be here to host that

          3    reception.  So we hope that all of you will stay

          4    for another half an hour and then will join us. 

          5              So, Judy? 

          6              DR. SIEGEL:  Yeah.  I'd just like to get

          7    back to discussions of types of potential conflicts

          8    of interest and where they arise.  And I've heard

          9    many things come up which we and the pharmaceutical

         10    sponsor and I know are dealing with.

         11              And I think what I'd like to get into a

         12    public discussion somewhere is clinical trial

         13    methodology in the 21st century and what the issues

         14    are relating to doing clinical trials in the 21st

         15    century.

         16              Where, for instance, does the referral of

         17    patients into clinical trials fit?  How did that

         18    come about?  Why is it done?

         19              What is the obligation of actually the

         20    investigator relative to patients who are referred

         21    to him from other investigators?

         22              Because I actually think that it's a whole


                                                                 321

          1    research climate now that's very different from ten

          2    years ago, and as we now start to think of it in

          3    ways we've never thought of it before, which is

          4    does this actually induce conflict of interest in

          5    some way, I think actually a public discussion of

          6    the whys may actually help to figure out how to

          7    manage it better, because I don't think that we

          8    actually manage it very well from the broader

          9    conflict of interest financially.

         10              And so I would like to get several of the

         11    issues.  Bonuses for rapid enrollment, where does

         12    that come from? 

         13              I know in my own company, that is

         14    discussed every time we do a clinical trial.  And I

         15    know there are major advocates within my company

         16    that say this is not ethical.

         17              And so I think within the industry, there

         18    are probably those discussions already going on,

         19    and I think maybe it would be valuable to actually

         20    have a public discussion. 

         21              CHAIRPERSON MARSHALL:  Thank you. 

         22              Sandy was next, and then Mark. 


                                                                 322

          1              DR. CHODOSH:  As I was waiting, you just

          2    raised an issue which I found to exist, and that is

          3    that patients have conflict of interest,

          4    particularly the professional patient, okay.  And

          5    these people read the ads.  They go to the

          6    textbook.  They find out what symptoms they're

          7    supposed to have and they have them.

          8              And one has to be very careful because

          9    this is clear -- they're doing it purely, when

         10    there is money involved, and, of course, that could

         11    alter the results of the study much more than some

         12    of the other things that we worry about.

         13              So that's another aspect of conflict of

         14    interest which I think belongs there.

         15              And along the same line, we talk about the

         16    advocacy business.  We had to be very careful.  All

         17    of a sudden someone who's an advocate job depends

         18    on research continuing in that institution to

         19    justify their existence so that it's everywhere.

         20              That doesn't mean it's not controllable,

         21    but it's everywhere, and I think it has to be taken

         22    into consideration at all levels. 


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          1              CHAIRPERSON MARSHALL:  Mark? 

          2              MR. BARNES:  Just a couple of brief

          3    points.  One is that on the issue of other

          4    professions and what kind of laws there are in

          5    conflict of interest, I do just want to point out

          6    to the committee that Bill Sage, who's a law

          7    professor at Columbia, just completed last week, I

          8    think it was, printed a report by the Millbank

          9    Memorial Fund on Securities and Exchange Commission

         10    laws, disclosure obligations, and what the medical

         11    profession can learn from the SEC.

         12              It's a thick report.  I just got a copy a

         13    couple of days ago, and I'd be happy to share that

         14    with Kate, and it could be distributed to the

         15    committee.  I'm sure the Millbank Fund wouldn't

         16    mind.

         17              The second things is that we often talk --

         18    just a couple of brief comments -- we often talk in

         19    terms of pharmaceutical companies as though they're

         20    the only private sponsors out there.

         21              But I just want to point out to the

         22    committee's attention for future deliberations that


                                                                 324

          1    that's only one piece of it.  There are medical

          2    device manufacturers and biotechnology companies

          3    that are equal players in this and in which there

          4    are conflict of interest issues that arise that are

          5    just as serious as anything that arises in terms of

          6    the private pharmaceutical companies.  And that's

          7    just important to keep in mind, even though, to my

          8    knowledge, there's not -- you know, there's nobody

          9    that represents the medical device manufacturers at

         10    the table or the biotech companies, for that

         11    matter.

         12              And, finally, just to put some of this

         13    into context a little bit, I think it's important

         14    to -- it's sort of economics 101 that when you have

         15    any kind of a sector of the economy that is

         16    essentially controlled, then money flows out of

         17    that sector and flows into that part of the sector

         18    that is uncontrolled.

         19              And it's very important to understand that

         20    it doesn't excuse the conflicts of interest.  But I

         21    think it's extremely important to understand that

         22    we are under incredible cost compression in all of


                                                                 325

          1    medicine.

          2              Real physicians' salaries have declined. 

          3    Academic medical centers and other hospitals and

          4    nursing homes are in dire financial straits.  In

          5    many of our states, they're actually operating

          6    every year at one and two percent losses, which

          7    cannot be sustained forever.  That's due to

          8    Medicare cost compression and the Balanced Budget

          9    Act.

         10              And so when that occurs in the largest

         11    part of the fiscal restraint or climate in which

         12    these medical entities work, then one has to expect 

         13    that where the money is where the attention will

         14    go. 

         15              And so although, again, it doesn't excuse

         16    everything, I think it's important for all of us to

         17    remember in our deliberations that all of our

         18    deliberations are against a backdrop of incredible

         19    cost compression in medicine which has put

         20    imperatives in front of -- or incentives, I should

         21    say, in front of physicians and hospitals that they

         22    might not have responded to in a different set of


                                                                 326

          1    circumstances. 

          2              CHAIRPERSON MARSHALL:  Thank you, and

          3    Greg? 

          4              DR. KOSKI:  I was just actually following

          5    up on a suggestion.

          6              There are several of the ex-officio

          7    members here representing agencies who have not

          8    participated in the HHS working group that had

          9    developed the draft interim guidance.  If any of

         10    the other agencies, the ex officios, have comments,

         11    it would be useful at this stage to try and

         12    incorporate that, so I would encourage them to do

         13    so, not at this moment, but in writing to the

         14    working group.  Thank you. 

         15              CHAIRPERSON MARSHALL:  John? 

         16              MR. MESA:  Greg, I'd just repeat what I

         17    said earlier before you got back from your soiree

         18    with the President.  I mentioned the point that I

         19    think it would be useful, certainly for the VA, for

         20    it to formally come to our agency, the package, so

         21    that we can at least engage, you know, the right

         22    levels of the organization, which may not even


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          1    involve myself.

          2              And the hint was that maybe the other

          3    secretaries to the common rule might be similarly

          4    interested in receiving such formal letters.  I

          5    mean we can do it through the back door.  We would

          6    do that, anyway.

          7              But I think the notion that you put it on

          8    the table, coming from DHHS, this is important to

          9    us, and now Energy, Education, CIA, VA, would you

         10    please seriously look at this.  I think that would

         11    be an important thing to do. 

         12              MR. RUBEN:  The NSF agrees with that last

         13    comment.  Philip Ruben, National Science

         14    Foundation.  Same thing.  We'd like to see that. 

         15              Thank you.

         16              CHAIRPERSON MARSHALL:  Thank you, Philip. 

         17    That will be done.

         18              We have time now, 20 minutes or so, for

         19    general discussion and a recap of the day.

         20              I'm going to ask Kate to do this, not

         21    today, but perhaps for tomorrow morning, where,

         22    thinking ahead to the agenda, we are going to have


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          1    a -- I will -- a brief recap of today's discussion. 

          2    And then other issues that occurred outside of the

          3    meeting, and thus, all the more reason for those of

          4    you in the room to attend the reception this

          5    evening because we will be receiving ideas, and you

          6    will be helping to set the agenda.  So please do

          7    come. 

          8              What I would like Kate to do, if she's

          9    amenable, is maybe to make a list for committee

         10    members and that we could make available to our ex-

         11    officio members, our agency liaisons, and our

         12    community members of the action plans that we have

         13    delineated today so that we can be thinking about

         14    them through the course of the day tomorrow.

         15              Obviously, we'll be adding onto those and

         16    then we'll have sort of just a working draft that

         17    we can use for the end of the day tomorrow relative

         18    to our discussion.

         19              I would, in the last few minutes that we

         20    have, like to open the floor to general discussion

         21    from anyone about process and procedure.

         22              We are a new committee.  There is sort of,


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          1    aside from federal guidelines relative to the sort

          2    of committee that we are and under which we need to

          3    operate, we would like to hear from you.  I

          4    certainly would like to hear from you suggestions

          5    for how this committee could best serve you

          6    relative to how the meetings are run and so forth.

          7              So this is an opportunity for you to

          8    educate us, if you would be willing to do so. 

          9              Yes? 

         10              MS. LEE:  Bonnie Lee, and I'm from the

         11    Food and Drug Administration, but I've also worked

         12    in the past as staff on the Tuskeegee syphilis

         13    study ad hoc advisory panel, and also on the staff

         14    of the National Commission, and so I have always

         15    been very critical of how advisory committees work.

         16              The Tuskeegee syphilis advisory panel was

         17    the first group to ever work under the Federal

         18    Advisory Committee Act, and it was quite a shock. 

         19    When we were formed, the assumption was that things

         20    would be done behind closed doors, and, of course,

         21    they were not.  It was a very sensitive topic.  It

         22    was very difficult for people to speak candidly.


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          1              By the time that the National Commission,

          2    I think that everyone knew they needed to act in

          3    public.  And so I'm going to react to your first

          4    day of your first meeting -- 

          5              CHAIRPERSON MARSHALL:  Thank you. 

          6              MS. LEE:  -- to give you at least my

          7    impression.

          8              You're really phenomenal as a group.  I

          9    want to commend you.  I want to commend you as a

         10    Chair for your interest in involving not only the

         11    members at the table and the federal ex-officio

         12    members, but also the community and other people

         13    attending the meeting.

         14              I think that your discussions, generally,

         15    have really been very forthright and candid and not

         16    particularly influenced by the fact that you know

         17    or you don't know who's listening to you here in

         18    the public.  And that's certainly to be commended.

         19              My only suggestions, and you've done some

         20    of it well, and hopefully, you'll do more, as I

         21    think you've indicated, is if you can have the

         22    handouts.  You all have notebooks here.  Some of


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          1    the materials may not be relative to those of us

          2    sitting out here, but to those where you will be

          3    discussing them, if they could be out on the table

          4    ahead of time, that would be very helpful.

          5              And other than that, I think you're on the

          6    right track, so I want to thank you. 

          7              CHAIRPERSON MARSHALL:  Thank you very

          8    much, and my mother thanks you, as well.

          9              And the concern about the handouts has

         10    been raised by others, and I think had time

         11    permitted, that would have been the case.  We

         12    promise that in the future, and I think Greg wants

         13    to speak to that, also. 

         14              DR. KOSKI:  Thank you, Mary Faith, and

         15    thank you very much, Bonnie.

         16              I think I just need to get out, you know,

         17    this particular message for everyone right now.  I

         18    want to simply say, right here in public, that what

         19    Kate Gottfried has done in pulling this meeting

         20    together in the short time frame that we had to

         21    work on is absolutely nothing short of miraculous,

         22    and I really want to applaud you, Kate, for


                                                                 332

          1    everything that you've done. 

          2              [Applause.] 

          3              DR. KOSKI:  Clearly, there were certain

          4    aspects of organizing, or the logistics of this

          5    first meeting that were not optimal, and I can take

          6    full blame for all of those because I notice that,

          7    you know, poor Kate, who dropped me off at my

          8    apartment last night at around 10:30, called me at

          9    11:30 to say that the Secretary's advance people

         10    had changed their requests.

         11              And when I got here this morning, I

         12    actually was presented with a completely rework

         13    agenda that included the presentation by Senator

         14    Kennedy that wasn't even there the night before,

         15    and that doesn't happen by little elves that come

         16    in the middle of the night.  It comes from terribly

         17    committed people who just take their

         18    responsibilities very seriously.

         19              So, Kate, I want to thank you once again. 

         20    And in the future, we will try to make sure that

         21    not only is the announcement in the Federal

         22    Register in there, you know, fully in advance of


                                                                 333

          1    the meeting, but that there will be agenda items

          2    there.

          3              We will try to make sure that there are

          4    references to appropriate resources, web sites and

          5    all, where information, background information,

          6    will be available.

          7              As our Chairperson has said, we clearly

          8    want to have all of this done in a very

          9    transparent, open and productive manner.  So,

         10    again, thank you. 

         11              CHAIRPERSON MARSHALL:  And I guess,

         12    finally, I would like to say, in that spirit, we

         13    are all accessible, and, obviously, we're on the

         14    web site. 

         15              But I would ask you if you're not able to

         16    be here tomorrow to please, if you have questions

         17    or issues or concerns or constructive feedback,

         18    don't hesitate to contact anyone on the committee,

         19    and, also to give us your suggestions in terms of

         20    how we can communicate best with people who don't

         21    read the Federal Register or who otherwise aren't

         22    plugged in, in a systematic way to normal venues of


                                                                 334

          1    communication. 

          2              So we do hope to hear from you, and we

          3    will take what you have to say very seriously.  And

          4    I need to, for those of you who can't stay, and I

          5    hope all of you can, just to let you know if you're

          6    attending the session tomorrow, we will be in a

          7    different room.  We will be in the Maryland Suite,

          8    and that is back around by the hotel entrance and

          9    down the corridor. 

         10              So we have perhaps ten minutes to take a

         11    little break before we head down to the reception

         12    which is -- oh, it's here?  Oh, well. 

         13              DR. KOSKI:  They need to set up. 

         14              CHAIRPERSON MARSHALL:  But they do need to

         15    set up, and Greg wants to have -- 

         16              DR. KOSKI:  I'm sorry.

         17              CHAIRPERSON MARSHALL:  We'll give the

         18    final word to Greg.  I'm sorry.

         19              DR. KOSKI:  One final word.  With respect

         20    to getting information out, I'd like to point out

         21    that the Office for Human Research Protections has

         22    recently instituted a list serve to which everyone


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          1    can subscribe.  You don't need to be an IRB member

          2    or something to be on this.

          3              We, in fact, wanted to be a source for

          4    dissemination of information to the broadest

          5    possible audience.

          6              We will tomorrow bring information as to

          7    exactly how one can subscribe to that.  It's a one-

          8    way sort of service where we send information out

          9    to people.

         10              We have mechanisms for getting information

         11    in, also, but right now, it may be very

         12    advantageous for us to use as a tool for any of you

         13    who are interested to get on board with that.

         14              So we're going to take a little break and

         15    then come back here for a little reception.  Dr.

         16    Lorry will be hosting that. 

         17              Mary Faith, are you done?

         18              That's it.  We'll see you at the

         19    reception.  We can relax.  Thank you. 

         20              [Whereupon, at 4:15 p.m., the meeting was

         21    adjourned to reconvene on Thursday, December 21,

         22    2000, at 8:30 a.m.]


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          1                  CERTIFICATE OF OFFICIAL REPORTER

          2              This is to certify that the attached

          3    proceedings before the NATIONAL HUMAN RESEARCH

          4    PROTECTIONS ADVISORY COMMITTEE held Wednesday,

          5    December 20, 2000, were held as herein appears, and

          6    that this is the original verbatim transcript

          7    thereof, and is a full correct transcription of the

          8    proceedings.

          9

         10                                                        

         11                                  Gerald T. Brooks, Sr.

         12                                  Official Reporter

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