CT
       
       
       
       
       
       
       
       
       
                  Department of Health and Human Services
       
       
                               Meeting of the
                    NATIONAL HUMAN RESEARCH PROTECTIONS
                        ADVISORY COMMITTEE (NHRPAC)
       
                          Monday, January 28, 2002
       
       
       
                                  VOLUME I
       
       
       
       
       
                      The Hyatt Regency Bethesda Hotel
                           Cabinet-Judiciary Room
                           7400 Wisconsin Avenue
                          Bethesda, Maryland 20814
       
       
       
       
                                       A G E N D A
       
       
       Monday, January 28, 2002
       
       AM Session
       
                 8:30-9:00 Welcome--Overview of Meeting and
                 Updates
                                          Mary Faith Marshall, Ph.D.
                           Chairperson, NHRPAC
       
       9:00-9:30      John Marburger, Ph.D.
                                               Director, Office of Science and
                           Technology Policy, Advisor to the
                           President
       
                      9:30-10:30     Update, Discussion & Closure:  Third
                      Parties:  Research Subjects?
                           Mary Faith Marshall, Ph.D.
       
       10:30-10:45    Break
       
                      10:45-12:30    Update and Discussion:  Social and
                      Behavioral Science
                      Risk and Harm
                      Confidentiality
                           Felice Levine, Ph.D.
                           Co-Chair Working Group
                           Executive Officer
                                               American Sociological Association
                           Jeffrey Cohen, Ph.D.
                                               Co-Chair, Working Group
                           Director, Education, OHRP/DHHS
       
       PM Session
       
       12:30-2:00     Lunch
       
                 2:00-3:15 Consequences of Civil Actions in Human
                 Subjects Research -- Panel Presentation
                 and Discussion
                           Alan Milstein, Esq.
                                               Sherman, Silverstein, Kohl, Rose
                           Podolsky
                                    AGENDA (Continued)
       
       2:00-3:15 (Cont'd.)
       
                           Respondents:
                           Karen Rothenberg, J.D., M.P.A.
                                               Dean, University of Maryland,
                           School of Law
                           Paul Lombardo, Ph.D., J.D.
                                               Associate Professor of Law and
                           Director, Program in Law and
                           Medicine, Center for Biomedical
                           Ethics
                           University of Virginia
       
       3:15-3:30 Break
       
       3:30-5:30 NHRPAC Work Group Meetings
                                               Social and Behavioral Sciences
                                               Third Party/Genetics
                                               Informed Consent and the
                           Decisionally Impaired
                                               Informed Consent
       
       5:30      Adjourn                             ROSTER OF MEMBERS
       
       MARY FAITH MARSHALL, Ph.D., Chairperson, Director of
       Program in Bioethics, University of Kansas Medical
       Center
       
       GREG KOSKI, Executive Secretary, Ph.D., M.D.,
       Director, Office of Human Research Protections,
       Office of Public Health and Science, OS
       
       MARK BARNES, J.D., LL.M., Partner, Ropes & Gray
       
       MS. MARGARET BORWHAT, President, Women's Cancer
       Advocacy Network
       
       SANFORD CHODOSH, M.D.
       
       ELLIOT N. DORFF, Ph.D., Rector and Distinguished
       Professor of Philosophy, University of Judaism
       
       ALAN R. FLEISCHMAN, M.D., Senior Vice President, The
       New York Academy of Medicine
       
       JENNIE R. JOE, Ph.D., M.P.H., R.N.
       Professor, Family and Community Medicine
       Director, Native American Research and Training
       Center, University of Arizona
       
       SUSAN Z. KORNETSKY, M.P.H., C.I.P., Director,
       Clinical Research Compliance, Department of Clinical
       Investigation
       
       FELICE J. LEVINE, Ph.D., Executive Officer, American
       Sociological Association
       
       ROBERT LEVINE, M.D., Professor of Medicine, Yale
       University School of Medicine 
       
       ABBEY S. MEYERS, President, National Organization
       for Rare Disorders
       
       JONATHAN D. MORENO, Ph.D., Emily Davie and Joseph S.
       Kornfeld Professor of Biomedical Ethics, Director,
       Center for Biomedical Ethics, University of Virginia
       Health System
       
       MARY KAY PELIAS, Ph.D., J.D., Professor, Department
       of Genetics, Louisiana State University Health
       Sciences Center       Roster of Members (Continued)
       
       ROBERT R. RICH, M.D., Executive Associate Dean of
       Research, Emory University School of Medicine
       
       ADIL E. SHAMOO, Ph.D., Professor, Department of
       Biochemistry and Molecular Biology, University of
       Maryland School of Medicine
       
       JUDITH L. SIEGEL, Ph.D., Vice President, Head US
       Clinical Operations, Hoffmann-La Roche, Inc.
       
       KATE-LOUISE GOTTFRIED, J.D., M.S.P.H., Office of
       Human Research Protections, Office of Public Health
       and Science, OS
       
       EX-OFFICIO MEMBERS
       
       Dr. James Shelton, USAID
       Maryann Danello, Ph.D., CPSC
       Dr. Joseph Spence, USDA
       Ms. Linda Beth Schilling, DOC
       Mr. Tryn Stimart, NIST
       Ms. Patty Boll, DOD
       Ms. Blanca Rosa Rodriguez, ED
       Dr. Susan L. Rose, DOE
       Dr. Dixie Snider, CDCP, DHHS
       Dr. David A. Lepay, FDA, DHHS
       Dr. Belinda Seto, NIH
       Alan Sandler, D.D.S., NIH
       Dr. Francis D. Chelsey, Jr., AHRQ
       Dr. Paul Gatons, HUD
       Dr. Donald Prosnitz, DOJ
       Mr. Thomas G. Raslear, DOT
       E. Donald Sussman, DOT
       John H. Mather, M.D., DVA, VHA
       Joan Porter, D.P.A., M.P.H., DVA, VHA
       Mr. Robert S. Cortesi, EPA
       Richard S. Williams, M.D., F.A.C.S, NASA
       Dr. Philip Rubin, NSF
       Mr. Howard L. Bradley, SSA                           P R O C E E D I N G S
                                            [Time noted:  8:40 a.m.]
                 CHAIRPERSON MARSHALL:  We are going to
       begin in just a couple of minutes.  There are still
       lots of folks outside and we would just like for
       them to get settled, so bear with us for two more
       minutes.
                 Welcome to NHRPAC.  Committee members, it's
       good to see all of you.  We've all been working very
       hard in the interim since our last meeting.  Some of
       us have been working extremely, extremely hard; and
       we have a lot of business to do over the course of
       the next two days, bringing some of our projects to
       closure and fruition and working hard on others.
                 I would like to open the meeting by talking
       a little bit in the next 15 minutes or so that we
       have about public bioethics and then opening the
       floor up for discussion.  We have talked in the past
       among this group about process and the importance of
       it.
                 I would like to read you just a couple of
       excerpts from a paper that was written by John
       Fletcher and Franklin Miller.  John Fletcher was the
       first Chief of Bioethics at the Clinical Center at
       the National Institutes of Health.
                 Franklin Miller works now at the NIH with
       several of their IRBs and their Human Subjects
       Protection Program.
                 So they have written a paper that's several
       years old on the "Promise and Perils of Public
       Bioethics," and this might just help open our
       discussion.
                 They say that:  "the main promise of public
       bioethics is that it will contribute to the
       development of sound public policy by timely,
       well-reasoned analyses of ethical controversies in
       the sphere of biomedical research, health care and
       public health.  Public bioethics contributes to the
       formulation of public policy by first clarifying the
       ethical considerations relevant to an issue of
       policy; second, articulating consensus of ethical
       standards for the guidance of policy; and, third,
       recommending specific safeguards to contain or
       prevent abuses that have occurred or that could
       occur when policy is implemented.
                 "A secondary promise of public bioethics is
       that the ethical analysis and recommendations issued
       in reports will provide valuable guidance to local
       institutional ethics committees and review boards
       which focus on protection of human subjects in
       research, ethical issues in patient care, use of
       animals, and so forth.
                 "Public bioethics is subject to four main
       perils:  Political coaptation, bioethics orthodoxy,
       neglect, and poor performance."
                 "Coaptation" distorts ethical reflection by
       imposing partisan demands or constraints on the
       work.
                 The peril of "bioethics orthodoxy" arises
       to the extent that a narrow ethical perspective
       controls the inquiry and the recommendations of the
       advisory committee.
                 "Neglect of public bioethics" occurs when
       the government sets public policy or intervenes in
       ethical controversies without being informed by the
       deliberations of public bioethics commissions.
                 "We argue..." Fletcher and Miller "...in
       favor of two functions of government in public
       bioethics, which have been only partially and
       inconsistently developed in the past.  The first
       function is to be a wise and consistent advocate of
       public bioethics in each political season in the
       interests of the public.  The second function for
       government is to be a wise user of public
       bioethics."
                 Many of the ideas that John and Frank
       Miller have put forward are things that we have
       talked about before here and I think have guided our
       work.  We have discussed the importance of bringing
       everyone to the table who should be at the table and
       ensuring that all who need to or would like to have
       a voice in our process.
                 For those of you who have not been to a
       NHRPAC meeting in the past, our process of working
       through the day is that we allot the same amount of
       time for discussion among the committee, among our
       representatives from the federal agencies, and among
       those whom we call our public members.
                 So I would encourage those of you who are
       here either as return visitors or first-time
       visitors to certainly feel free to engage in the
       dialogue as we go along.  That is really part and
       parcel of what we are about.
                 Someone asked me, just as we were chatting
       earlier this morning over coffee, whether the
       workgroups would be open to those who might be
       interested in sitting in on them.  We have divided
       our schedule for the next couple of days in a manner
       that allows us to work very hard and get some work
       done, and take advantage of the fact that we are all
       here and at the same place at the same time, and
       that many of our workgroup members are also here and
       those who aren't physically here will join us by
       conference call.
                 I think that that is a wonderful idea with
       the caveat that our workgroups have appointed
       members.  Our workgroups have to be given approval
       by this committee.  So the workgroups as they stand
       have been signed off on and the membership approved
       of by the members of NHRPAC.  So we would invite you
       not necessarily to be a member of the committee but
       certainly of the workgroup to sit in if you would
       like to observe.  And I think I would leave it up to
       the workgroup chairs to call on members of the
       public if they feel as though they would like to do
       so if there is time.
                 So let me ask if there are other thoughts
       about our procedure, about doing public bioethics,
       and I just would like to perhaps open the floor up
       for discussion among the committee first if anyone
       has thoughts.
                 Yes, Bob?
                 DR. R. LEVINE:  I have a couple of comments
       and one question.  I think many of the members of
       the committee were recruited to join the committee
       because this committee would have as its chief
       assignment providing oversight activity for the
       Office for Human Research Protection.  Certainly
       that was one of my main motivations for joining this
       committee.
                 There can be no doubt that there is intense
       controversy out there around the country over some
       of the activities of this office and I would just
       like to issue a plea, a request that we get to that
       part of the agenda.  There can be no doubt that the
       agenda we are looking at is important but it is also
       assigned to quite a number of other -- much of it is
       assigned to quite a number of other groups.  I do
       not know of any other group, though, that has been
       recruited to provide oversight to OHRP.
                 The other comment I have is that it is good
       to be a member of the workgroups but it is a problem
       when you are a member of two that meet
       simultaneously and I would look to the Chair for
       guidance on that.
                 CHAIRPERSON MARSHALL:  I hope you are not
       asking for solomnic wisdom.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Well, you know, we
       really cannot engage in cloning.  That might be the
       more modern solution to that problem but I will
       think on it over the course of the day.
                 Let me just respond, and I know Greg has
       something that he would like to say.
                 Welcome, Paul.  Paul Gelsinger has just
       joined us.
                 In terms of oversight activity, if we think
       back to the advisory committee that was chaired by
       Nancy Dubler -- and I am sorry I am blocking,
       co-chaired by Nancy Dubler and someone else --
       certainly the idea of providing oversight or
       feedback about how the federal government configures
       its regulatory affairs relative to human subjects
       concerns was part of their report and part of their
       thinking.
                 I do know that the committee of the
       Institute of Medicine that is taking a very broad
       look at protections of human subjects and the
       systems that are in place nationwide, both federal
       and other, and whether they are working, and
       mechanisms that might be brought into place to
       further the agenda in terms of providing safety to
       human subjects research and integrity of scientific
       research are looking and will be in their report, I
       think, speaking to a certain degree to the issue of
       oversight.
                 So that is one body that is looking at that
       but their report will not be out until September.
                 So, Greg, I know that you have something
       that you would like to say.
                 DR. KOSKI:  Bob, I don't know if there has
       been a misunderstanding but the purpose of this
       committee is not oversight of the Office for Human
       Research Protections.  The purpose for this
       committee, as stated in the charter, is to provide
       the Department, the Assistant Secretary for Health
       and the Director of OHRP with advice on a number of
       the complex issues that this office has to deal
       with.  So that I think maybe I just want to be very
       explicit about that.
                 The purpose of this committee is not
       oversight of our office.  And when there are issues
       about the operations of our office that we need
       advice on or the Department needs advice on then
       certainly that would be something that we would want
       to come to this committee and seek its advice on;
       but this is not intended as an oversight committee. 
       This is an advisory committee.
                 DR. R. LEVINE:  I think the current state
       of intense concern and controversy about the
       activities of OHRP can properly be viewed as a
       complex issue.  And, I do not know if our charter
       was written in such a way as to exclude us from
       commenting on that.
                 I was certainly told when I was called to
       join this committee that oversight was going to be a
       major part of the agenda.  Maybe the rest of the
       group here was not told such a thing.
                 Thank you.
                 CHAIRPERSON MARSHALL:  Committee members,
       any other thoughts on either this point or other
       points?
                 Bob?
                 DR. RICH:  I do not recall the language,
       specifically, that was in the DHHS appropriations
       report language that at least indirectly had some
       role in creation of this committee, but I did think
       that there was an intent from the Congress, at
       least, that there would be an element of oversight.
                 I actually had that impression, too, so if
       it is a mistaken impression, I do think there was
       Congressional interest in that as I understood the
       genesis of the process.
                 DR. KOSKI:  Again, this committee was not
       established through any action of Congress.  This
       was a committee that was put together by the
       Department of Health and Human Services on the
       initiative of the Secretary, and clearly the stated
       goal here was to obtain, have a forum for obtaining,
       you know, advice with public discussion, you know,
       on these issues.
                 Now, certainly there may be issues, you
       know, that the office would seek advice on with
       respect to operations.  There has been a real,
       though, need to focus on some of these, you know,
       again the challenging issues of children and all
       where basically the Department has been directed to
       look at those activities and offer new guidance,
       potentially new regulations and so on. 
                 So I think that, you know, certainly our
       office is working in every way that we reasonably
       can to take advantage of the enormous resource that
       this committee provides.
                 I think in all fairness there is certainly
       plenty of issues to discuss and they all have to be
       appropriately prioritized and worked through so we
       are doing that.  Indeed, a number of things.  We are
       anxious to have this committee complete its advice
       to us.
                 I don't know how to, you know, further
       explain that, though, except, you know, clearly our
       office and the Department are subject to oversight,
       oversight by Congress and all, and certainly there
       are a number of groups out there.
                 Particularly we have, as you know, asked
       the Institute of Medicine's Committee, as part of
       its ongoing project with us that we are funding, to
       actually look at this entire system.  So I think we
       want to make sure that we use our resources in the
       most effective way and I hope that clarifies the
       situation.
                 CHAIRPERSON MARSHALL:  Sandy?
                 DR. CHODOSH:  I just wanted to voice my
       opinion on this because it's not an opinion.  The
       charter is sitting right in our book.  It is very
       clear.  It's advice and recommendations.  Nothing
       about oversight and I don't know how anyone could
       misunderstand that.
                 CHAIRPERSON MARSHALL:  It's behind Tab 2,
       page --
                 DR. CHODOSH:  The one after page 6.
                 DR. KOSKI:  Let me just add one little
       comment.  I think one of the concerns that led to
       the creation of this committee was the fact -- the
       concern that, you know, perhaps too often guidance
       was developed or issued without, perhaps, the full
       public discussion that is warranted if one is going
       to try to produce the most useful guidance to help
       the investigators, institutions and IRBs do what
       they need to do.
                 So clearly this provides the opportunity to
       have that forum to seek that kind of advice and
       that's certainly what our office has been doing.
                 CHAIRPERSON MARSHALL:  I see Bob has his
       hand up and he's looking at the charter.  He has an
       alternate interpretation I think.
                 DR. R. LEVINE:  The charter says the
       function under the subtitle "Function" that "the
       committee shall advise the Secretary..." et cetera
       "...pertaining to the continuance and improvement of
       human subjects protection functions."
                 It goes on to say that "it will provide
       advice on the development and management of
       collaborations..." et cetera, et cetera, and then
       among the groups it specifies are "biomedical,
       academic and research communities and
       nongovernmental entities."
                 Finally, "the committee will provide
       counsel on opportunities to improve the public
       awareness of the function and importance."
                 I see nothing in there that's inconsistent
       with the request made to me by the people who
       appointed me to this committee.
                 I think that the communications between
       OHRP and the biomedical, academic and research
       communities are very much influenced by the -- not
       the policies but the practices of OHRP.
                 I see nothing here that excludes this topic
       from our agenda, and I would like to ask if this
       committee can set its own agenda; and, if it can,
       then I am going to make a motion at some appropriate
       time that we put oversight on our agenda.
                 CHAIRPERSON MARSHALL:  Go ahead, Adil, and
       then I'll speak to that.
                 DR. SHAMOO:  At least if I understand
       politics, since I live near Washington I hope I have
       some understanding by osmosis, the word "oversight"
       is used by Congress and officials of the federal
       government very precisely.  And since they did not
       use the word "oversight" I don't believe this
       committee has the authority to oversight OHRP.  It's
       really advice and counsel.  That's my understanding.
                 DR. R. LEVINE:  Let me then withdraw the
       word "oversight" and replace it with "advice and
       counsel on the practices of OHRP."
                 CHAIRPERSON MARSHALL:  I think that the
       operative word is "advice and counsel."  I know of
       nothing in the FACA rules that disallow us as a
       committee from looking at issues that we feel are
       important relative to human subjects protection. 
       So, I think certainly not oversight, but, perhaps
       advice and counsel.
                 The charter really speaks to, I think, how
       the various entities within the government
       collaborate and communicate not only among
       themselves but with the public at large.
                 Felice?
                 DR. F. LEVINE:  I think we are converging
       on the right balance but I think that there's an
       important element of the charter and that is that
       the advice and counsel is to the Secretary.
                 I am, as many of you know, on a similar
       committee and that is for the Census, which was
       appointed by the Department of Commerce Secretary,
       and the advice is to the Secretary on issues that
       the committee wishes to give it advice on, rather
       analogous to NHRPAC.
                 And what I was hearing was Greg saying what
       OHRP would like advice on and Bob saying what NHRPAC
       would like to give advice on, and I believe NHRPAC
       can determine what it wishes to give advice on and,
       indeed, can advise the Secretary on issues
       pertaining to the human subjects protection system
       and all of its aspects.  I think that is the right
       balance.
                 CHAIRPERSON MARSHALL:  One thought that I
       have -- and then, Greg, I'll turn -- is that Bob is
       making the case that there is timeliness in terms of
       this subject.  I would think that at the point also
       in the future when the Institute of Medicine report
       comes out that there would be elements there that
       the federal government may ask us about in terms of
       advice relative to implementing some of those
       recommendations.
                 Greg?
                 DR. KOSKI:  Just to --
                 CHAIRPERSON MARSHALL:  And then Jonathan?
                 DR. KOSKI:  Just to clarify Felice's
       remark.  This committee actually under its charter
       advises at three levels, the Secretary, the
       Assistant Secretary for Health, as well as the
       Director of OHRP.  So it covers that whole thing.
                 Certainly OHRP is not averse to, you know,
       hearing thoughtful advice, you know, from this
       committee or anyone else so that's not part of the
       issue.  But, as I think has been pointed out, I'm
       trying to be very clear that the purpose of this
       committee is not an oversight role.
                 CHAIRPERSON MARSHALL:  Jonathan?
                 DR. MORENO:  I think that the documentary
       history of the reports that led to the creation of
       this advisory committee, and this I think perhaps
       extends and sharpens Greg's point a bit, not only
       had to do with the need or perceived need for a more
       public discussion about the way that OPRR, now OHRP,
       does its work, but also to bring expertise from the
       academic and other related communities to help OHRP. 
       It was thought that OPRR could have been benefitted
       by drawing on some of these sectors and gets free
       labor this way. 
                 So, as I always like to point out, free to
       us.  Free, I guess in a way, and not free to you, I
       guess, Greg.  So I think it's a little sharper than
       only giving advice when it's asked.
                 And I think that one way of perhaps
       reinterpreting Bob's point is if people who bring
       their particular experience sitting around this
       table ask OHRP a question about its policies or
       operations that we feel we need in order to share
       our experience and expertise and OHRP says, "Sorry,
       you know, we don't want to get into that," then we
       can say, "Well, you've cut out the feet from under
       us and we can say it publicly, we can't give you the
       benefit of our expertise because we don't have any
       data to work with on this issue."
                 So, I guess, I'd say we have a little bit
       of persuasive power with respect to getting into the
       interstices of the operations of the agency even if
       we don't have a legal authority to subpoena how OHRP
       is doing its work.
                 CHAIRPERSON MARSHALL:  Let me open the
       floor up to any of those who have joined us today. 
       The microphones are there and are on so if you have
       a thought or a comment we certainly would welcome
       it.
                 [No response.]
                 CHAIRPERSON MARSHALL:  Elliot?
                 DR. DORFF:  What occurs to me is what
       happens with advice in normal inter-human, you know,
       relationships, people who don't ask for advice and
       get it are not usually too happy with the advice.
                 [Laughter.]
                 DR. DORFF:  So, I mean, I think that, you
       know, if there are very specific issues that have
       arisen, Bob, in the kinds of discussions that you've
       been having and that others have been having around
       the table about the operations, then I think maybe
       we should pinpoint those and ask Greg whether advice
       would be welcome on it or at least discussion would
       be welcome on those kinds of things.
                 The other issue that occurs to me is that,
       I mean, we had a conference -- the workshop on
       informed consent had a conference call and came up
       with ten different things that we have to talk
       about, which will take us 50 years to do.  And, I
       mean, it's not as if we're lacking for important --
       you know, for work that -- other important work that
       we're doing.
                 I'm not saying that the ongoing operations
       are unimportant.  I'm just saying that if we're
       going to deal with that at all, (a) we should make
       sure that the people that are going to hear our
       advice are going to welcome it; and, second, that it
       be very pinpointed because otherwise we just won't
       accomplish anything.
                 DR. KOSKI:  Bob, I think as you know and,
       in fact, many people here know, I personally have
       had great concerns not just about OHRP but about the
       operations of the entire federal process for
       protection of human subjects and we have been
       working for almost a year now to get together what
       has come to be known as the SUEE Task Force, which
       will focus on finding ways to achieve
       simplification, uniformity, efficiency and
       effectiveness.  It's a process in which all of the
       federal agencies have engaged through the Human
       Subjects Research Subcommittee that focuses
       specifically on the kinds of operational issues
       that, I think, you are referring to.
                 You know, I want you and everyone else to
       understand there's no resistance here to looking at
       those things.  Indeed, I think everyone benefits
       from having a close look at those things.  But I
       think in terms of the focus that is something that
       is clearly going forward as expeditiously as we've
       been able to do within the government and moving a
       process like that forward and encourage, you know,
       people to participate in that directly.
                 Again it's sometimes a question of trying
       to prioritize and using resources most effectively.
                 I think the particular constitution of this
       group is one that makes it well-suited for advising
       us on the issues of children as research subjects. 
       What is minimal risk, what is having a condition, on
       conflicts of interest, on the other kinds of
       important policy sort of issues that our office
       needs advice on as we struggle to produce clear and
       valuable guidance to help the research community.
                 So that, you know, again it's a question of
       just trying to do the many things that we have to do
       in the best fashion.  And I am very hopeful that the
       SUEE Task Force, which we hope will come together
       probably, you know, this spring or early summer will
       be an important step down that road.
                 And, of course, I'd be delighted to sit
       down with you or any other members of the committee
       personally and see if there are specific issues that
       ought to be brought forth before this committee,
       then we could do that.  So, you know, I hope that
       just clears up any misunderstanding.
                 CHAIRPERSON MARSHALL:  I have Alan.
                 DR. FLEISCHMAN:  I just wanted to remind
       the committee that I greatly benefitted from a whole
       panel explaining the work of OHRP with Greg's
       explanations as to the strategies and then the
       specific leaders from that group.  And we might
       consider over the course of our meetings having one
       of those folks come back and explain how they've
       been doing in terms of their goals and objectives
       which they clearly set out and to teach us how
       things are going.  You know, I certainly would
       appreciate that kind of interaction and I think we'd
       benefit from it.
                 I have one other question and that is:  now
       that we've carefully scrutinized the charter, there
       is this little thing called "termination" and I was
       wondering if we have any insight into that.
                 CHAIRPERSON MARSHALL:  Thank you.
                 John, let me just ask Kate to respond to
       where we are in terms of our charter renewal process
       and then the floor is yours.
                 DR. MATHER:  Thank you.
                 MS. GOTTFRIED:  The charter has been
       revised to be slightly more specific and it is
       wending its way through the administrative system
       for review by the Secretary and it is to be renewed
       every two years so it's up for renewal June of this
       year and we anticipate that it will be renewed; but
       we have no specific information one way or the
       other.
                 CHAIRPERSON MARSHALL:  Thank you, Kate.
                 John?
                 DR. MATHER:  I'm John Mather and I'm the ex
       officio representative from the Veterans
       Administration.  I just want to align myself and
       maybe other ex officio members would want to say the
       same thing that Greg has pointed out that there is a
       very active human subjects research subcommittee
       that constantly brings these issues of policies and
       how to better operationalize what is needed in this
       area of human subjects protection.
                 There's a lot of work that goes on in that
       particular committee and they're all signatures to
       the Common Rule who regularly attend these meetings
       on a monthly basis.  Greg has got us working so hard
       that we sometimes meet twice a month.  So you can
       see the level of expertise that comes to the table
       to try and address these issues.
                 Personally, I would very much welcome, Bob
       -- and I know, I think, the other members of HSRS
       would maybe through Greg's office -- any items that
       you would like to identify that are of an
       operational concern.  We understand policies
       translate into procedures, translate into immutable
       guidelines, translate into this is the way you shall
       do it.  And this issue of flexibility, I think,
       raises its head very, very quickly.  And each of us
       in the 16 agencies signatory to the Common Rule are
       very interested in ensuring that there's
       harmonization across the agencies.
                 Most recently we have particularly looked
       at the issue that raised its "ugly head" about when
       are continuing reviews needing to be done.  What is
       the anniversary of a continuing review?  What is it
       that represents an appropriately convened meeting of
       an IRB to approve a project?  What does approved
       with contingencies mean, and so on and so forth?
                 So it gets and drills down to that nitty
       gritty level and I think we probably come on this
       one issue to some consensus amongst the 16 agencies
       notwithstanding some dissent.  There is consensus
       and I think those kinds of things at the operational
       level are very, very helpful when we can do that.
                 So, Bob, I would welcome and I think any on
       the HSRS would welcome identified areas where you
       think there is ambiguity or undue rigidity or some
       need for flexibility.
                 CHAIRPERSON MARSHALL:  Thank you very much.
                 Abbey?
                 MS. MEYERS:  Since FDA is not a signatory
       to the Common Rule do they attend?  Are they part of
       the task force?
                 DR. KOSKI:  Yes.
                 MS. MEYERS:  They are?
                 DR. LEPAY:  Yes, we are.  Actually we do
       follow the Common Rule for FDA funded research.  FDA
       has its own variant of the Common Rule that's very
       closely related to the Common Rule based on our
       statutory authority which derives from the Food,
       Drug and Cosmetic Act but it is essentially
       equivalent in the terms of the protections provided.
                 We are part of the Human Subjects Research
       Subcommittee.  We work very closely also within the
       Department of Health and Human Services and with
       OHRP to coordinate activities between certainly 
       with our agency and OHRP, as well as with our agency
       and across the Department of Health and Human
       Services and with the members of the Human Subjects
       Research Subcommittee.
                 MS. MEYERS:  How much is FDA funded
       research?  Do you know?
                 DR. LEPAY:  FDA funded is a very small
       proportion of research.  Most of our research is
       regulated research and, of course, we are primarily
       a regulatory agency.  And that is part of the basis
       by which our regulations have developed off the
       Food, Drug and Cosmetic Act, because, again, we have
       to assure broad public protection based on our
       approval decisions and the labeling that goes with
       those products, as well as regulations that support
       applications to FDA in addition to assuring as a
       subset of our broad public protection mission the
       protection of human subjects who participate and/or
       human research participants in FDA regulated
       research.
                 MS. MEYERS:  But a commercially sponsored
       research that doesn't involve federal funds is not
       regulated under the same rules as the Common Rule?
                 DR. LEPAY:  It is regulated under our 21
       C.F.R. Part 5056 for IRBs and informed consent.  And
       actually I will challenge anyone here who has done a
       comparison of these two in terms of the areas of
       human subject protection that they represent and the
       operations of informed consent and IRBs they are
       essentially identical.
                 There are obviously, as I say, some changes
       in wording that are more appropriate to the statute
       under which we operate and that's why we have our
       own encoding in 21 C.F.R. but again I do not think
       that anyone here who has reviewed the two would say
       there are fundamental differences in the process of
       IRB review constitution or informed consent.
                 MS. MEYERS:  But there is in that -- for 
       years, as you know, I served on the Recombinant DNA
       Advisory Committee, and every time I would look at
       an informed consent, and say, "This is bad, this is
       misleading, this is inaccurate," the FDA would say
       -- and there was always FDA representatives in the
       room -- and they would say, "We do not have the
       authority to force a company to change its informed
       consent document."
                 DR. LEPAY:  Well, we have to make sure that
       the informed consent follows the elements that are
       part of FDA regulations.  The specifics of the
       informed consent document if they follow the
       regulatory standards that are contained within the
       elements of informed consent, certainly if they are
       misrepresenting the product or the study that is
       within the purview as long as there are no
       regulatory violations.
                 MS. MEYERS:  What I'd like --
                 DR. LEPAY:  The regulations that would
       govern those, though, would be identical to the
       regulations that would govern the same informed
       consent document if it were under review under 45
       C.F.R. Part 46.
                 CHAIRPERSON MARSHALL:  Abbey, let me --
                 MS. MEYERS:  Yes.
                 CHAIRPERSON MARSHALL:  -- I don't know
       whether we're sort of straying off of the subject at
       hand but I would say that the Informed Consent
       Working Group, you know, if this is a concern, and
       later on in our agenda we do have time, tomorrow
       afternoon, for members of each standing working
       group and members of the committee to interact with
       the co-chairs of the Informed Consent Working Group
       saying these are the issues that we see that should
       be put on your table and this is the priority in
       which we think they should be addressed.  So that
       might be a more direct route to having this issue
       discussed.
                 Thank you, David.
                 A couple of things.  Anyone else?  Have I
       missed a hand here?  Anyone in the audience?
                 [No response.]
                 CHAIRPERSON MARSHALL:  I guess sort of my
       thinking on bringing this particular topic to
       closure is this:  That I'm glad we're doing exactly
       what bioethics councils or advisory groups or
       committees should do, and that is looking directly
       at hard issues and not ignoring the hippopotamus in
       the middle of the room, which is quite often the
       behavior that leads us to need bioethics advice in
       the second place.
                 So I think that we must look at these hard
       issues.  And my thinking, having had the privilege
       to work on the Institute of Medicine's Committee on
       Assessing the System for Protecting Human Research
       Participants, I know that not only will there be
       advice about the federal government's regulation and
       oversight of human subjects protections but also all
       of the entities that currently exist or perhaps
       should exist in the future, including NHRPAC as an
       advisory committee.  The IOM will be looking at
       those and addressing those.
                 And so I think that probably the
       appropriate point in time for us is to wait until a
       report comes out and it has been presented to the
       folks who brought it into being and seeing if there
       are things, and if there are agencies, et cetera,
       Health and Human Services would like for us to
       implement or evaluate or provide advice on the
       implementation of certain recommendations, that
       would be the appropriate time to do so.
                 So I guess that's sort of my thinking.
                 So, Bob, I don't think that we're ducking
       your issue.  I think we've had a good discussion and
       that we can put some of your things on the table.
                 A couple of announcements that I would like
       to make.  One is that we have flexibility in our
       schedule today.  A little bit of wiggle room and I
       know that we are moving a little slowly but John
       Marburger is on his way so I am sorry that he is
       late but we do have some wiggle room in our
       schedule.
                 The second thing that we do have some
       business to do here during the first half hour and
       that is signing off as a committee on the memorandum
       to the Secretary and the Assistant Secretary for
       Health on public use data files.
                 Each of you should have a handout.  This is
       something that we have been working on relatively
       hard and I think that the committee through its
       discussions via the e-mail, et cetera, has arrived
       at a document that my understanding is we all agree
       on.
                 So let me ask, Felice, do you have any
       thoughts that you would like to share with the
       committee before we move forward on approving this?
                 DR. F. LEVINE:  Just quickly in the way
       that I still think technology seems to have some
       creep in terms of what happens between progress and
       transmission, the word "settings" got missed.  And I
       kept on sending updated drafts every time I got a
       word in but everyone probably picked it up.  On the
       background section it should include "are collected
       in academic" and it says "settings by research
       teams" at the moment.  The word "settings" got
       deleted.  I haven't rechecked my hard drive but
       somehow we had some creep in the loss of a word.  So
       I just want that in the final draft and I'll provide
       that later today.
                 Just to reiterate for the full group where
       we were in October was to delegate this to -- the
       final language to Susan and Elliot and I, and that's
       what we sort of saw ourselves as your eyes and ears
       in crafting this and we forwarded it to Mary Faith
       based on the understanding that we achieved what we
       had wanted to achieve so we hope we did.
                 CHAIRPERSON MARSHALL:  Thank you.  So let
       me ask, committee, you have that document in front
       of you, you've seen it on the e-mail, do we need any
       discussion before we move on approving it?
                 Adil?
                 DR. SHAMOO:  I just want to make sure what
       we are approving.  There is a cover page.  There is
       guidance on public use data files.  There is
       responsibility of users and it ends in Bureau of
       Labor.  Are we approving the background attachments? 
       Because the background attachments, and there is 10,
       15 pages, there is problems in certain areas.  I
       would not like to be associated with it.
                 I mean, they're okay if they are just there
       for information but if it ends by just the
       recommendations then I have no objection.
                 DR. F. LEVINE:  It looks like something
       additional got stapled on your copy.  It is the
       guidance and the recommendations as background so
       that we're forwarding the input of the working
       group.
                 CHAIRPERSON MARSHALL:  Phil?  Phil Rubin? 
       Well, we'll continue this discussion.
                 [Laughter.]
                 DR. MARBURGER:  It sounded like it was
       important.
                 CHAIRPERSON MARSHALL:  We have a long day
       ahead of us, so they won't be able to duck this.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  They may try.
                 Welcome.
                 DR. MARBURGER:  Thank you.
                 CHAIRPERSON MARSHALL:  Let me introduce to
       all of you, it is just a great pleasure and I'm so
       thankful that John Marburger is here.  I'm sure that
       all of you know who he is.
                 He is the Director of the Office of Science
       and Technology Policy and advisor to President Bush
       on issues of science and technology policy.
                 A little background:  Dr. Marburger has a
       Ph.D. in applied physics from Stanford University, a
       B.A. in physics from Princeton University.  He was
       president of the State University of New York at
       Sunybrook, also served as the Chairman of the
       University's Research Association, which runs the
       Fermilab, from 1988 to 1994.
                 And a little story telling here:  The
       Brookhaven National Laboratories, which he also
       directed, was very much in the news when Dr.
       Marburger became its director so he doesn't shy from
       controversy.  A tritium leak in the high flux beam
       reactor had attracted a large degree of attention in
       the media resulting in a call to close the reactor
       by local groups, a senator and a representative. 
       And at a late 1997 press conference, as the incoming
       director, Dr. Marburger remarked that the laboratory
       had failed to communicate adequately with the local
       community.
                 The reactor was closed in 1999 and Dr.
       Marburger has been roundly praised for the way in
       which he reestablished communication with the lab's
       neighbors.
                 Let me read you his personal statement
       which was on the Brookhaven National Laboratory's
       web site.
                 "As society holds us to ever higher
       standards of accountability for the impact of our
       work on health and environment we need to learn new
       ways of working and we need to learn new ways of
       describing our increasingly complex mission to the
       public that is skeptical and concerned about the
       undesirable side effects of technology."
                 And I think part of the reason that we
       exist as a committee is to serve as a liaison
       between the government and the community.  And in
       terms of doing public bioethics which, Dr.
       Marburger, we have spent the last half hour talking
       about, we can tell you that we are committed to
       engaging the public and to making sure that all of
       those who should be at the table are there and also
       have a voice.
                 So thank you very much for being here. 
       We're just delighted.
                 [Applause.]
                 DR. MARBURGER:  Well, thank you very much
       for inviting me and permitting me to say a few words
       at this very important occasion.  I'm here for at
       least three reasons that I want to speak briefly to.
                 The first one is the fact that this
       administration takes its ethical responsibilities
       very, very seriously in all aspects of its
       operations; and I think everyone has been impressed
       with the strong moral positions that President Bush
       has taken since beginning his administration and I
       feel very privileged to work with him and with the
       administration on these issues.
                 He understands quite clearly that science
       does not tell us what we should do, it tells us what
       we can do. and that, in addition to expert
       scientific input on policy decisions, the President
       welcomes expert -- as expert as any of us can be --
       input on the ethical and moral dimensions of the
       decisions that he has to make and expects us all to
       be conscious of the ethical and moral impact of our
       work and the fact that decisions need to be made
       explicit just as we make explicit decisions to fund
       this or that or to do this or that kind of work we
       need to be very clear about the fact that there are
       ethical inputs to guide us as well.
                 And the President is grateful to those who
       are willing to come forward and discuss these issues
       in a public and rational way, especially on issues
       that are controversial and could expose people who
       engage in these discussions to public scrutiny and
       perhaps criticism so I am grateful to you for being
       here and being willing to undertake these
       discussions and to provide guidance to Health and
       Human Services as it goes about exercising its
       responsibility.
                 The second reason that I'm here is that
       science continues to evolve in a strong and rapid
       way and it's giving us increasing insight into the
       processes of life and their relation to the very
       molecular structures that comprise all living
       things.  And not only how we metabolize and
       reproduce and how information is transmitted from
       one part to another in a cell or in an organism but
       also aspects of human behavior, psychiatry and
       behavioral issues that were formerly not easy even
       to conceive how they might be related to molecular
       structure are beginning to come under the purview of
       molecular biology and our understanding of the
       processes of life at even the atomic level.
                 And, consequently, a wider and wider range
       of human activities, not only health but also human
       behavior in many aspects, are coming within the
       realm of laboratory work and this movement is
       driving science.  This progress is driving science
       at an ever more rapid pace.  The availability of
       instrumentation to view the structures of life on
       the atomic and molecular levels and the ability of
       information science and computer simulation and so
       forth to advise us on how one might alter the
       molecules of life to alter the behavior of the
       organisms which are constructed from these elements.
                 These capabilities have created tremendous
       opportunities for science and offer a promise to
       address concerns not only with respect to human
       issues but also with respect to environmental,
       energy and other issues that face society that are
       very complex.
                 And, consequently, there's a real concern
       here that we maintain our options for getting and
       extracting the greatest benefit from this new
       knowledge while at the same time being responsible
       and keeping in mind the ethical and moral
       implications of what we are doing.
                 So the third point is this, and it derives
       from the others, that the range of activities that
       science undertakes that affect or involve human
       participation is increasing at a very remarkable
       rate.  Since 1991 when the first Common Rule was
       promulgated by the office that inherited -- the
       Office of Science and Technology Policy on the
       Protection of Human Participants in Research --
       since 1991 there's been a decade of evolution and
       expansion of these frontiers.  And during that
       period there's been an enormous increase in the
       range of activities that might fall under the
       purview of these issues, issues of ethics and
       morality and fairness and risks associated with
       human participation in experimentation.
                 So the challenge here is to achieve some
       uniformity and some effectiveness in protection of
       human subjects across this entire range without
       inhibiting the research unnecessarily and
       acknowledging the wide range.
                 Now, each agency that sponsors work of this
       sort, or that falls within this wide range of
       activities of human participation, is responsible
       for establishing its criteria consistent with
       various guidelines and legislation that governs it. 
       But each agency needs to be aware of the needs of
       the other agencies as well as it promulgates its
       guidelines, and it is important for us to try to
       educate ourselves about the entire spectrum of
       issues so that we do not inadvertently impose
       regulations that might inhibit the work and not give
       us commensurate gains in protection of human
       subjects.
                 The issue here is one of, I suppose,
       risk-based thinking.  In general, I favor risk-based
       approaches to regulation where you try to match the
       protections against the risks and so that the less
       the risk the fewer, the less intrusive and demanding
       the regulations should be.  And so it's clearly
       important for us to understand what the risks are of
       the different kinds of activities that are being
       undertaken and not just take the most stringent
       regulations and apply them to everything.
                 I am concerned about this because the
       original model and the original set of concerns that
       drove the movement to protect human subjects were
       associated with clinical trials where you have
       people who are at risk whether they participate or
       not in the trials.  They have some affliction,
       disease or condition that may or may not respond to
       drug or therapy that's being investigated.  This is
       sort of the most extreme situation that we have
       where we are actually conducting experiments to let
       us know whether or not a mode of therapy is
       effective.
                 But, increasingly, there is a large amount
       of work that's being done where participants in the
       work are healthy, where the modalities of
       investigation pose relatively little risk, and yet
       the work is quite important to society.
                 So it's important, I believe, to be able to
       be flexible to be able to craft regulations that are
       responsible at both extremes, both in terms of
       protecting the people who are most at risk and
       vulnerable to exploitation on the one hand, to
       protecting the ability of society to conduct
       constructive research with healthy patients who are
       at relatively little risk on the other.
                 The risks, of course, are different.  Risks
       of disclosure of confidential information, for
       example, are significant even when we're doing
       surveys that are related to social or psychological
       issues.
                 So it's not a simple task that you have to
       advise your agency on the issues here and to develop
       guidelines for the future but I do want to leave you
       with this message based on this set of issues that
       I've described here, and that is that bioethics is a
       broad area now and increasingly complex,
       increasingly engaged in activities that we never
       would have thought of decades ago as being covered
       by the types of regulations that we see.  And that
       it's going to be necessary for us to educate
       ourselves not only about the existing, but also
       about the potential future domains of application
       for our guidelines.
                 So my office continues to be very
       interested in this process.  We continue to work
       with all the agencies, and there are many of them
       that have responsibilities for the human beings as
       well as the other living things that participate in
       their experimentation, and we hope to learn from
       your deliberations as well as from those of others
       and have the best possible guidelines for the
       future.
                 So thanks very much.  I'll be glad to
       answer questions to the extent that I can as I'm
       somewhat of a nonexpert in this business and I wish
       you well in your deliberations.
                 CHAIRPERSON MARSHALL:  Thank you very much.
                 [Applause.]
                 CHAIRPERSON MARSHALL:  I would like to say,
       Dr. Marburger, I do hail from Kansas but I also
       believe in evolution.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  I believe strongly
       in it and when I give talks about research ethics I
       make the point that our ethics need to evolve along
       with our science and that they need to be, in a
       sense, ever changing and growing.
                 Our colleague in the bioethics world, Carol
       Levine, observed years ago that the ethics of
       research were born in scandal and reared in
       protectionism and I think that that is true.  You
       could say that the ethics of human subjects research
       almost evolved in a pattern of crisis and response. 
       But I think that we also have moved to a new level,
       and I think that's a good thing, of not only
       protecting but promoting research and that is
       something that we're very much interested in, is the
       integrity of the science, and that it moves forward.
                 I think your commitment to not just the
       clinical sciences but to the social and behavioral
       sciences is wonderful and the folks who are here,
       Felice Levine and others in the room who represent
       the social and behavioral scientists, I'm sure were
       listening attentively to every word.  And I want to
       tell you that we are spending the entire morning
       looking at ethical issues that inhere in the social
       and behavioral sciences.
                 Let me do open the floor up.  I'll tell you
       we do value input from our public members so I'll
       open it briefly for questions from the committee
       first, then our ex officios and then members of the
       public.  Committee folks, would you have questions
       of Dr. Marburger?
                 Abbey?
                 MS. MEYERS:  The Washington Post did a
       series of stories this winter or last winter about
       clinical trials that are being done overseas and the
       data is being used here to get new drugs approved,
       et cetera, in some of cases.  Has that caused any
       international problems?
                 DR. MARBURGER:  As far as I know it hasn't
       caused any problems in countries outside the U.S. 
       There certainly have been concerns raised within the
       U.S. regarding work done outside the U.S. and some
       of these concerns are commercial and I'm not
       completely conversant with all of them, but as far
       as I know in the broadest sense there's not an
       international concern.  This has not arisen as far
       as I know as a major issue.
                 Pharmaceutical companies in the U.S. are
       concerned that very strict regulations may drive
       business, as it were, to other countries and there's
       a kind of concern associated with that.  And there
       are organizations, of course, that always have
       concerns about the extent to which other nations may
       be as careful in their protection of human subjects
       as we are.  So these are issues that are meat for
       this commission, of course, committee and I would
       welcome your input on them.
                 CHAIRPERSON MARSHALL:  Bob?
                 DR. R. LEVINE:  Thank you very much for
       your comments.  I'd like to comment on the last
       topic.
                 I'm chair of the Committee for the Council
       of International Organizations of Medical Sciences
       to write or to revise what's known as the
       International Ethical Guidelines for Biomedical
       Research Involving Human Subjects.  The stories that
       came out in the newspapers looked terrible.  I think
       many of us know that sometimes the newspapers don't
       get it exactly right.
                 So without having personally looked into
       those stories I will jump ahead to say that if what
       was reported in the newspapers is correct that was
       in violation of international standards that have
       existed since 1993.  And right now the CIOMS,
       Council of International Organizations of Medical
       Sciences Guidelines are being firmed up to make
       behaviors of the sort that were in the newspapers
       even less acceptable.
                 The key point is that certain types of
       research carried out by sponsors and investigators
       from the wealthy countries can be done in the --
       what they now like to be called -- the low resource
       countries following exactly the same rules that
       exist in the wealthy countries unless they are
       focusing on a problem that's specific to the low
       resource country that they're working in.  Focused
       in such a way that bringing the data back to a
       wealthy country for purposes of marketing in the
       wealthy country would essentially be out of the
       question.  It's focused on development of products
       that have no market in the wealthy countries.
                 Thank you.
                 CHAIRPERSON MARSHALL:  Thank you, Bob.
                 Kathleen Rand Reed?  And those of you who
       do step up to the microphone, please tell us who you
       are.
                 DR. RAND REED:  Thank you, Dr. Marburger. 
       I'm an applied biocultural anthropologist and for
       many years have sort of gone between, you know,
       communities and rooms that look like this and so I
       wanted to -- you brought up several points and I
       wanted to take the opportunity to address a couple
       of the issues that you did bring up.
                 Around the issues of behavior and the move
       afoot to begin to look at molecular issues around
       behavior, I would say that there are many people at
       a grassroots level that when you start talking about
       social capital and exchange in networks and norms of
       reciprocity and these kinds of things that your door
       be very, very open for not just experts to come
       about behavior, but to provide the opportunity for
       people in the communities to give their version of
       behavioral issues.  Because often times what happens
       is that what is a behavior that may be "deviant
       behavior" in one group may very well be situational
       and "survivalist behavior" in another.
                 So when we start making these decisions
       about how people live their lives and how they
       experience their lives it would probably do you well
       to be able to have that broad view from lots of
       different corners so that when these decisions are
       made they truly represent all of the issues.
                 The second thing --
                 CHAIRPERSON MARSHALL:  The second brief
       thing.
                 DR. RAND REED:  The second very brief thing
       is the -- very brief -- is you mentioned about
       risk-based thinking and an approach to research.  I
       would also ask that you carve out some space and
       time in your office that those with the highest risk
       should also be very, very present at that table so
       that they get the opportunity to have the voice to
       offer their version of what that risk may be.
                 I thank you.
                 DR. MARBURGER:  Thank you.  Just briefly in
       response, the guidelines for membership on the
       Institutional Review Boards, that have been
       established under legislation, specifically require
       diversity of the sort that you've been describing. 
       We welcome and, indeed, insist on outside/outsider
       representation on these boards and I think that has
       been a strength of the guidelines from the beginning
       and it should continue to inform how we operate.  I
       completely agree.
                 CHAIRPERSON MARSHALL:  I have Elliot and
       then Alan and then Paul Gelsinger for brief
       questions.  I'm not sure how long Dr. Marburger has
       but I know he doesn't have all morning so brief
       questions.
                 DR. DORFF:  Just two comments and we don't
       know each other so my guess is that you know this
       already, okay, but you're a physicist and I'm an
       ethicist.  My doctorate is in ethical theory.  And I
       just wanted to make two brief points to make sure
       they're clear.
                 One is that although it is the case that
       more and more of human behavior is now being
       investigated on its molecular level.  One of the
       things that we're going to be talking about today
       actually are some of the necessary steps in research
       that are very different in social sciences from
       those in the physical sciences.  And I think that's
       an important thing to bear in mind.
                 The other thing that I wanted to talk about
       is that scientists are used to -- my father was a
       civil engineer so I'm used to this mentality --
       scientists are used to things being very black and
       white.  I mean it either shows up or doesn't in
       experimentations.
                 The world of ethics is excruciatingly
       imprecise and, in part, it's because what is really
       important in the world of ethics is the lens through
       which you're looking at the world in the first
       place.
                 And the reason why there are major ethical
       differences -- sometimes they are moral differences
       even within one particular system of ethics. 
       Different judgments of -- in other words, even if
       you assume one particular lens of -- these lenses
       tell us who we are and who we ought to be.  The
       various religions of the world give us very
       different pictures of that.  The various secular
       philosophies of the world give us very different
       pictures of who we are and who we ought to be, and
       the moral norms are rooted in those large pictures.
                 Now, it happens that on this particular
       issue, namely the issue of protecting human
       subjects, there's a lot of agreement across lenses
       in the world that that ought to happen.  Although I
       must say not universal agreement.  There are
       societies in which that is understood to be a much
       lesser value than some other value like political
       stability or something like that but at least in
       America this is sort of a given.
                 But as you do your work you should -- I
       mean, I think it's important to understand that when
       you come to other kinds, of things other than human
       subjects, other -- you talked about living beings, I
       mean stem cells and things on that order -- part of
       the real issue here is, as you say, not what is the
       case but how do you perceive what is the case from a
       variety of different lenses.
                 DR. MARBURGER:  I don't think I'll have any
       comment on that.
                 [Laughter.]
                 DR. MARBURGER:  But even the physical
       sciences are less black and white than they used to
       be.
                 CHAIRPERSON MARSHALL:  Alan, and then Paul?
                 DR. FLEISCHMAN:  My question will be much
       less philosophical and more pragmatic.  From the
       very beginning there's been controversy as to
       whether institutional review boards ought to have a
       local flavor or be more nationally focused and I was
       wondering if you have an opinion as to that.
                 DR. MARBURGER:  I do and I'm speaking
       personally.  You asked me for my opinion.  My
       opinion is that they should be more locally oriented
       but that pains should be taken to have training or
       presence of information and insights that reflect
       the broader national thing.
                 You can't just let every IRB be its own
       thing.  There have to be standards and they have to
       operate in a national context.  But, in general, you
       need to have -- in my opinion -- you need to have
       strong local flavor to understand the nature of the
       research and also to have some insights into the
       people and the culture in which the research is
       being done.
                 There are many different research cultures
       in different types of institutions, different
       regions in the nation that flavor the work.  And I
       think that the local culture of research, local
       sociology of research needs to be well understood in
       order to apply the national standards.
                 CHAIRPERSON MARSHALL:  Thank you.  Paul
       Gelsinger, for those of you who don't know who Paul
       is, he is the father of a young man, Jesse
       Gelsinger, who died in a gene transfer experiment a
       year or so ago.
                 Paul?
                 MR. GELSINGER:  Dr. Marburger, in your
       opening comments you indicated that technology was
       the driving force to our understanding of life even
       at the tiniest levels, the atomic level.
                 My perspective is a little different than
       that.  I see technology as only the door opening. 
       The driving force that I've uncovered is the
       financial end.  It's the thing that's pushing that
       door open maybe too fast.  I think that's where our
       ethical can of worms is and I'm wondering how the
       administration is dealing with the conflicts that
       arise out of that.
                 DR. MARBURGER:  To the extent that finances
       drive things one has to be very, very careful, I
       believe, that this administration is very clear on
       fundamental human values and the need for a
       principled approach to ethical and moral questions,
       seeks advice, tries to act on a very high moral
       plane.
                 I think the President's very public
       analysis of his decision regarding stem cells gives
       you some insight into how he thinks.  And I've found
       no trace of flexibility on this issue that ethics
       and moral principles are essential ingredients to
       policy decisions.  The President takes them
       seriously and requires that we all do.
                 I feel that only well-thought-out processes
       to advise and to guide the research at a local level
       that make their principles clear are going to
       prevent exploitation of people at risk for financial
       ends and no one in this administration wants to see
       that happen.
                 CHAIRPERSON MARSHALL:  Adil?
                 DR. SHAMOO:  I'm really taking advantage of
       the fact that you are here, I may as well put
       something in your mind.  I sympathize with you.  I'm
       originally also a physicist who 15 years ago had to
       learn human research protection issues.  However, I
       believe physicists can learn any subject.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  It is the mother of
       all science.
                 [Laughter.]
                 DR. SHAMOO:  My question is really rather
       informational and that is, animals, regardless of
       the source of funding, there's a federal regulation
       that you cannot do research with animals unless it
       is federally regulated.  I know this may come as a
       surprise to you, human beings, regardless of the
       source of funding, whether it's federal, private,
       industry or private foundation or state or out of my
       own pocket, that is not the case.  That umbrella of
       federal regulations, there are big holes in it.
                 That is, literally, if I am wealthy, just
       to give you an extreme example, I could do research
       with human subjects of any kind I want as long as I
       do it within one state so that I'm not crossing
       state lines and I'm supporting it with my own
       building, my own money, et cetera.  And there are
       big holes in it and what we have advocated and
       written about is that we would like to see a
       national human research protection act.
                 DR. MARBURGER:  Thank you.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Adil, someone said a
       while ago that I think physics envy is the curse of
       biology.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Let us give the last
       word to Dr. Marburger.
                 DR. MARBURGER:  Well, there is no last word
       on this issue.  And once again I'm grateful to you
       for giving your time and your attention to this
       issue.  It is complicated.  Remember that you're not
       the only group advisory panel dealing with this
       subject but you're a very important one and I know
       that whatever you do will have a big impact on what
       everyone else does.
                 Thank you.
                 CHAIRPERSON MARSHALL:  Thank you very much
       for being here.
                 [Applause.]
                 CHAIRPERSON MARSHALL:  We are going to have
       a short break.  We're bringing more chairs in, I
       hope.
                 Let me ask each of you who is here in the
       room who has not signed up please to do so.  Our
       meeting is a matter of public record so we would
       like to record the fact that you were good enough to
       be here.
                 So let us take -- we do have a half hour of
       flexibility in our schedule.  Let us take 15 minutes
       to break.
                 Thank you.
                 [Brief recess taken at 10:55 a.m.]
                 CHAIRPERSON MARSHALL:  Can people move
       towards their seats so that we may resume?
                 Welcome back, everyone.  Committee members,
       we're in the midst of discussing public use data
       files and coming to closure on that.
                 Adil, did you have the floor?
                 DR. SHAMOO:  No.
                 CHAIRPERSON MARSHALL:  Anyone else have
       comments on public use data files before we vote on
       the document as a committee?
                 MS. MEYERS:  I see this was on our desk
       when we come back, which looks like a run down of
       federal laws having to do with confidentiality.
                 CHAIRPERSON MARSHALL:  That's the next
       issue not on the table right now.
                 MS. MEYERS:  Oh, okay.
                 CHAIRPERSON MARSHALL:  That's later.
                 MS. MEYERS:  All right.
                 CHAIRPERSON MARSHALL:  So then, committee,
       can we -- I would like to then call a vote of the
       committee to get our final endorsement of this
       document.  So let me ask those of you who are in
       favor of approving the public use data file document
       as written and to moving it forward as a committee,
       please give us a show of hands. 
                 [Showing of hands.]
                 CHAIRPERSON MARSHALL:  Thank you.  We have
       achieved consensus this morning already.  Thank you,
       committee.
                 Can you all hear out there?
                 [Chorus of no.]
                 CHAIRPERSON MARSHALL:  We're not getting
       the microphone component of what's going on here.
                 Does this work?
                 [Chorus of yes.]
                 CHAIRPERSON MARSHALL:  Okay.  Great.  Good.
                 Then let us move forward and we will, in
       the next hour or so, achieve consensus on yet
       another document.
                 Yes.  Oh, I'm sorry.  Greg wanted to make a
       point.
                 DR. KOSKI:  I just, on behalf of OHRP,
       would like to thank the committee for its work on
       this.  Clearly it has been one of those things that
       provides an opportunity and all for the research
       community as well as for the IRBs and everything to
       have clarity here and we appreciate this.  Thank
       you.
                 CHAIRPERSON MARSHALL:  Thank you.  We've
       been working hard.  Let that go on the record, Dr.
       Koski.
                 Sandy?
                 DR. CHODOSH:  I think that the work that
       has been done by the working group is fantastic. 
       What's still going to be lacking and which we as an
       advisory group cannot do is how it's going to be
       implemented and we talk about qualified IRBs who can
       do -- establish public files -- 
                 PARTICIPANT:  We cannot hear.
                 DR. CHODOSH:  You can't hear.  Can you hear
       now?
                 [Chorus of no.]
                 DR. CHODOSH:  Can you hear now?  
                 CHAIRPERSON MARSHALL:  I will go ask
       Keisha.  There's music coming through.
                 DR. CHODOSH:  I don't know what it is.
                 CHAIRPERSON MARSHALL:  Someone is coming. 
       Thank you.
                 DR. CHODOSH:  Okay.  I'll try to speak up
       but essentially unless there is implementation of
       what we mean by qualified IRBs, training of
       investigators to understand what it is that has to
       be done, all of this is in here and it should be in
       here but, you know, we've had trouble doing this
       with other things that are sitting around for a
       longer time with IRBs in terms of training and
       whether we're talking about certification or what
       have you there needs to be some kind of control of
       who is qualified.
                 DR. KOSKI:  I'll just say, Sandy, thank
       you.  Certainly we recognize that and it's OHRP's
       intention to take this advice and put it together
       with that from the working group that the Human
       Research Subjects Subcommittee has, which I believe
       are largely consistent, and to move forward as
       quickly as we can.
                 In all honesty, as I've said at past
       meetings, the usefulness of this committee to us
       depends upon its ability to produce coherent
       guidance in a timely manner.  That's what public
       bioethics is all about.  So we're anxiously sitting
       on the receiving end and happy to get this.  Thank
       you.
                 CHAIRPERSON MARSHALL:  Thank you, Greg.
                 We do have someone coming to fix this
       problem.
                 Hello, Alan.  Welcome.
                 Elliot?
                 DR. DORFF:  We just approved the guidance. 
       There were some background.
                 There was a background attachment with
       recommendations that Adil wanted to --
                 CHAIRPERSON MARSHALL:  Separate.
                 DR. DORFF:  That's separate.
                 MS. GOTTFRIED:  Let me just make one
       logistical comment here that -- it's not just
       logistical -- the word "guidance" remember is really
       inaccurate.  These are advice and recommendations
       from NHRPAC to -- and I realize it's not that it
       says so in the document but it is officially advice
       and recommendations.
                 CHAIRPERSON MARSHALL:  Yes.  We don't --
       NHRPAC does not offer guidance documents.  We hope
       to bring guidance documents into being.  We midwife
       them, I think.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Then let us move
       forward with the agenda.  Felice and Jeff and their
       working group has been working inordinately hard
       over the last several months both prior to our last
       meeting and between our last meeting and this
       meeting.
                 The issue of third parties as research
       subjects I think may be perhaps the most difficult
       thing that we have worked on as a committee in terms
       of different perspectives and the possibility of
       coming to consensus, complete consensus on that.
                 I hope there won't be blood on the floor
       after the next hour is over but I can say that --
                 [Applause.]
                 CHAIRPERSON MARSHALL:  -- we have come to
       consensus once already this morning.  Let's do it
       again twice if we can.  The ideal would be that we
       achieve consensus but the de minimis would be that
       we agree to disagree.
                 So you have in front of you four documents. 
       One of which is what we are calling the "breakfast
       statement."  The iteration of the breakfast
       statement that Bob Levine moved us forward with. 
       The Mary Kay breakfast statement, the Mary Faith
       breakfast statement revision, and the NIH document.
                 It seems to me, just to boil all of this
       down to its essence -- 
                 MS. GOTTFRIED:  It says "Dear NHRPAC
       members" at the top.
                 CHAIRPERSON MARSHALL:  Does everyone have a
       copy?  It says, "Dear NHRPAC."  Everyone on the
       committee has a copy.  All right.
                 It seems to me that really the nut of what
       we're trying to get at in terms of agreement as a
       committee is the issue of when referenced by.  So we
       need to come to agreement if we can on whether a
       third party -- whether someone who is -- about whom
       information is provided by a person is a third party
       or whether we -- whether information that may be
       part of a medical record, genetic information and so
       forth also constitutes it because it is private
       information about an identifiable person, whether
       that also constitutes legitimacy in terms of human
       subject.
                 So I'll open the floor for some discussion
       but I would ask that as we're doing this that we try
       and narrow and focus our discussion about the topic
       at hand because my sense is that the rest of the
       document is something that for the most part we're
       agreed on and if there are disagreements about the
       rest of the document we can come to that but let's
       begin the discussion with "when referenced by" and I
       have Mary Kay.  I have Greg.
                 Mary Kay?  Oh, Bob?
                 DR. R. LEVINE:  Which document are we
       looking at?
                 MS. GOTTFRIED:  It's the document that
       says, "Dear NHRPAC members" on the top.
                 CHAIRPERSON MARSHALL:  Okay.  Let us begin
       -- all right.
                 MS. GOTTFRIED:  The last one is your's.
                 CHAIRPERSON MARSHALL:  The last one is
       mine.
                 DR. R. LEVINE:  They're stapled together.
                 MS. GOTTFRIED:  They're all stapled
       together.
                 CHAIRPERSON MARSHALL:  They're all stapled
       together.
                 DR. R. LEVINE:  But are we going to focus
       our discussion on one or more of these separate
       documents?
                 CHAIRPERSON MARSHALL:  You need to use your
       microphone, Bob.
                 DR. R. LEVINE:  I didn't plan to say
       anything worth hearing.
                 [Laughter.]
                 DR. R. LEVINE:  We have, yes, one document
       stapled and on the back of it there are about four
       separate statements of the proposed policy.  What
       I'm asking about is are we focusing this discussion
       on any one of those or is it just a general?
                 CHAIRPERSON MARSHALL:  Let's begin -- let
       us start in the back with the document that I sort
       of compiled from others.
                 Felice?
                 DR. R. LEVINE:  This last one?
                 CHAIRPERSON MARSHALL:  The last page.  The
       final page.  Status of third parties in biomedical
       and behavioral research.  Something -- I've got a
       list of people so unless this is procedural -- 
                 DR. F. LEVINE:  It's procedural.
                 CHAIRPERSON MARSHALL:  Okay.
                 DR. F. LEVINE:  Or at least I want to
       reflect on what I think are these documents.  The
       first document was the one that we -- that the
       breakfast consensus group presented in October.
                 CHAIRPERSON MARSHALL:  Correct.
                 DR. F. LEVINE:  The second was --
                 CHAIRPERSON MARSHALL:  Is your microphone
       on?
                 DR. F. LEVINE:  Sorry.  The second was the
       Mary Kay posting as you say.
                 The third, however, isn't the final posting
       of what we thought was the one circulating amongst
       us, which is a November 27th.  It's an earlier
       version because as the Levine team here we were
       taking everyone's, and on the 27th transmitted to
       you a final version.  It's very, very close but it's
       not identical.  I have the 27th version on a floppy.
                 CHAIRPERSON MARSHALL:  You're saying the
       Levine breakfast statement is not the final version?
                 DR. F. LEVINE:  Right.  Which was taking
       everybody's comments.
                 CHAIRPERSON MARSHALL:  All right.  Let's
       ask -- we will ask Keisha to copy that for us but
       let's -- for the -- okay.  So for purposes of
       discussion let's begin with the Mary Faith document
       if that's all right.  I mean, we can start with any
       one of these  We'll get at the same issue.
                 Sandy, I've got you on the list unless it's
       procedural.
                 DR. R. LEVINE:  This is procedural also and
       that is that in that case there are numbers of
       e-mail that went back and forth that are also not
       here and I think that we should stick with what we
       have in front of us and discuss it from that point
       on.  I mean, there were lots of other opinions that
       went around.
                 CHAIRPERSON MARSHALL:  Okay.
                 DR. R. LEVINE:  And those opinions --
                 CHAIRPERSON MARSHALL:  I just want to move
       forward with the discussion.  Let's start with
       "status of third parties in biomedical and
       behavioral research," the last page in your
       document.  And I have Abbey first.  I mean, I'm
       sorry, I have Mary Kay first.
                 DR. PELIAS:  I'm very happy that we're
       starting with this third document that Mary Faith
       put together because we did go around for a couple
       of months.  Mostly, I think, not disagreeing on
       content and substance but having differences having
       to do with writing style and how many words we
       wanted to use.  And I, for one, was very relieved
       when Mary Faith said she would take the two versions
       that were circulating.  Mine was a little bit
       shorter and Felice's was a little bit longer.
                 Mary Faith very carefully put together the
       substance of the two earlier -- the two earlier
       kinds of documents shall we say since there were
       several versions of them.  And it's my opinion that
       Mary Faith's synthesis of the earlier documents has
       all of the ideas in it that we were all trying to
       get to and is put together in the lesson that I
       learned long ago about trying to write one pagers so
       that people will actually read from the top to the
       bottom and perhaps absorb everything that's on the
       one page.
                 I would also like to say that when we
       received the document that NIH had put together I
       went through that line by line and I would like to
       say that I find the NIH document extremely workable
       and when it is read in concert with Mary Faith's
       document, the synthesis of the two earlier versions,
       when we read Mary Faith's synthesis together with
       the NIH document, I think we have something that is
       imminently workable and that's my bottom line on the
       whole issue.
                 CHAIRPERSON MARSHALL:  Thank you, Mary Kay.
                 Dr. Moreno, I will point out there is
       coffee available in case you're getting the
       withdrawal syndrome.
                 DR. MORENO:  Thank you for noting my
       addiction.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  It's in the record
       now.
                 Let's see.  I had Mary Kay.  Who did --
       Greg and then Felice?  I'm sorry, Greg.  Felice? 
                 Did I miss someone?  
                 DR. F. LEVINE:  The issue that I think is
       lost in the third document, and I actually think
       that the MK document and the Levine documents, B.
       Levine, were -- had the same intent.
                 I think that the last version that we began
       looking at in December had the same aspiration as
       well but in losing clarifying what the situation of
       third parties being persons referenced by human
       subjects and the relationship between those two and
       falling back into the general language of all
       situations in which a person may be a human subject
       where there is not direct interaction or
       intervention we lose the sharpness of the focus on
       what was the essential element of the topic and that
       is when human subjects make reference to others. 
       Those are the third parties and that's what the
       earlier document did. 
                 And when those third parties were or were
       not human subjects and how IRBs would go about that
       determination, and that's what I felt in my postings
       was lost in the last document.
                 CHAIRPERSON MARSHALL:  Thank you.  You are
       exactly right.  You hit the nail on the head.  So
       the major difference is -- if you look at the
       Levine/Levine document under number three it said,
       "Third parties about whom researchers obtain
       information..." here is the operative phrase
       "...from human subjects but who themselves have no
       interaction with research investigators or their
       agents."  So that versus on -- this would be my "B"
       on the last page, "Third parties about whom
       researchers obtain information but who themselves
       have no interaction with investigators or their
       agents."
                 So the real point is what is the source of
       the information about third parties?  
                 Sandy and then Bob?
                 DR. CHODOSH:  I do not think it is any
       secret to you that I have had a somewhat different
       approach and it goes back to actually in my first
       course in philosophy where we were taught logic, you
       know, and I unfortunately was at the University of
       Virginia in a rather illogical time but nevertheless
       there were simple things and number one was like you
       make definitions and then you try to see how they
       work through.
                 I think it's clear that what we're talking
       about here is anything that has to do with humans
       and the real question is when do they become a
       "subject?"  And if, in fact, one says that the
       research involves information about that human and
       the context is such that it is being used in the
       research that they are human research subjects. 
       Whether they are at risk or not I think is a whole
       other matter and I think that that's where we keep
       getting into trouble.
                 So that I -- wherever this information
       comes from, and I'm now getting back to addressing
       what we're talking about, is unimportant as to the
       issue.  The issue is that the information was
       obtained in some way but indirectly and not from
       that individual.  So that I would choose to avoid
       the use of "from human subjects" as the clarifying
       issue.
                 CHAIRPERSON MARSHALL:  Thank you very much.
                 Bob, this is perfect timing because Bob
       does have a different concept definitionally in
       terms of who a human subject is.
                 DR. R. LEVINE:  Thank you.  Actually, what
       I'm going to say is an attempt to be responsive to
       why we created a group to look at the problem in the
       first place.  Since 1981 there has been no doubt,
       and nobody has quibbled over it, that when you look
       at somebody's medical records with the aim of doing
       research that the individual whose records they are
       is a research subject.
                 There is no need now -- no one has raised
       the question as to whether or not they are a
       research subject.  They are adequately described in
       exemptions and in expedited review procedures and
       all we do by making our definition broader is to
       confound the issue.
                 We were convened for purposes of deciding
       what is the status of a third party.  In particular,
       when a researcher asks a known subject about another
       individual under what circumstances does that other
       individual -- under what circumstances is that
       individual to be regarded as a human subject with
       all of the associated rules, regulations, ethics and
       so on?
                 And it's for that reason that I greatly
       prefer in two places if we're looking at Mary
       Faith's document as our reference point, I would
       call for clarification and focusing in parts 1(b)
       and also in Part 3, the first sentence.  Just so
       that we would be responsive to the concern that
       brought us together.
                 Thank you.
                 PARTICIPANT:  How would you do it?
                 DR. R. LEVINE:  I've been asked how would I
       do it.  I would do it by excerpting -- either
       excerpting the relevant language from the
       Levine/Levine document or by putting this document
       aside and using the Levine/Levine document.  It can
       be accomplished either of those two ways.
                 CHAIRPERSON MARSHALL:  So that you would
       under, for example, 1(b) -- we would just insert the
       language "Who are referenced by human subjects."  Is
       that correct, Bob?
                 DR. R. LEVINE:  I think that the finished
       product that Felice has noted did not get circulated
       to this group had somewhat more felicitous language
       but that's the idea.
                 CHAIRPERSON MARSHALL:  Okay.  Thank you. 
       We'll get the most current and felicitous language
       possible.  Second, of course, to mine.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Just kidding.
                 DR. F. LEVINE:  I think it was an attempt
       to make a pun on my first name but the one that is
       circulating is quite close.  It's just that the one
       that's called "Levine" was an effort to take
       everyone's comments and the November 27th had
       everyone's last comments.  Whatever I got I put in.
                 CHAIRPERSON MARSHALL:  Thank you, Felice.  
                 Kate is standing right behind you.
                 Susan?
                 MS. KORNETSKY:  Bob and Felice, I would
       just like to ask you -- I know that we can come to
       a different opinion than the NIH did and both groups
       will give advice to OHRP but do you find what -- and
       I haven't seen the final document or haven't looked
       at it in a while, do you find that consistent or
       inconsistent with the NIH document that we have in
       front of us because I read it and I see some
       differences but I want to understand how you find
       it.
                 DR. F. LEVINE:  I'm going to call it the
       November 27th version for the moment.  I think it is
       consistent where it's addressing third parties and
       human subjects, which I think was the strength of
       what we were doing and turns out to be a squashier
       part of what they are doing.  And one of the things
       that I think we very directly addressed was also the
       protection to the human subject, meaning when an
       investigator is in interaction with that human
       subject what are the obligations to that human
       subject when that human subject is making reference
       to others?  
                 And that's a very vital part of what we're
       committed to and what was lost in losing the focus
       on the reference to others and the human subject.  I
       thought the breakfast version and the
       transformations through November 27th kept that
       attention, which was the issue that sort of led us
       to focus on that and not that broader question which
       we didn't think was really problematic.
                 CHAIRPERSON MARSHALL:  Alan, then Sandy?
                 DR. FLEISCHMAN:  I have a question really
       to follow up on Susan's concerns about the NIH
       December 7 document.  My concern with rule of thumb
       number one -- and here's where I'm trying to figure
       out whether we're in agreement with this or not. 
       Rule of thumb number one, I'm quite taken by things
       that have boxes around them and italicized because
       that's probably what people will read.
                 The second sentence says, "Therefore, a
       third party does not become a human subject unless
       and until the investigator obtains information..."
       da, da, da "...when this occurs the Common Rule
       pertains."
                 Now, you know, I'm just a country doc. 
       IRBs don't function that way.  They review protocols
       prospectively and I guess my concern is if it is
       predictable that the protocol will obtain
       information about a third party that is both private
       and individually identifiable, do we believe we
       ought to say that and we ought to make some process
       at the IRB level for dealing with that?  I think our
       documents say that.  I think the NIH document
       doesn't say that but I don't know whether it says
       it.  I just think it doesn't say it.
                 So I would hesitate to kind of bless this
       document because I don't think our's agrees with it. 
       I think our's is more clear.  It gives the IRB a
       stronger -- it demands that the IRB consider this
       prospectively and it sets out the standards for it.
                 Am I correct in that?
                 CHAIRPERSON MARSHALL:  Well, it looks as
       though we've just put that issue to rest.  Thank
       you, Alan.
                 So let's move back then to our document. 
       Well, since we -- the Mary Faith document just for
       purposes of having something in front of us to look
       at.
                 Others we haven't heard from?  Let's see. 
       Sandy, you're next on the list.
                 DR. F. LEVINE:  A comment on the
       Levine/Levine criticisms.  Number one, I've always
       had trouble, Felice, I must say, with the idea that
       "the human subject requires special attention."  To
       me any information that is private and confidential,
       et cetera, whether -- no matter how it's obtained --
       requires special attention and that the protection
       of those individuals is -- should be uniform.  There
       should not be a special category.
                 Now then we get into the informed consent
       which I'm sure Felice is going to mention.  Well,
       medical records there's no informed consent.
                 And I think, Bob, I interpret it a little
       bit differently.  The information that's obtained in
       a medical record and other ways like tissue samples,
       et cetera, are obtained not with the intent of doing
       research, the individual who gave the information
       did not give it with the intent of it being used in
       research, and certainly did not intend that anyone
       else that he mentioned in the medical record would
       be subject to be being used in medical research.
                 CHAIRPERSON MARSHALL:  Thank you, Sandy.
                 Bob, I've got you.  I just am going to
       interject here.
                 Kate and I were at a meeting in New York
       this past weekend and one of the presenters
       described to us the fact that st his institution all
       patients who are admitted sign a general consent
       document and included in that document is consent
       for the use of information in their medical record
       for research in the future, which is a scary idea. 
       I mean obviously they are not in compliance but I
       promise I won't tell who it was.
                 Bob? 
                 DR. R. LEVINE:  Sandy, whether or not there
       is informed consent to the use of information in the
       medical records or to the use of tissue specimens
       removed at surgery is entirely up to the IRB.  It's
       not correct to say there is always consent or always
       not consent.  You said that medical record
       information is used without consent.
                 Mary Faith, the scary idea you're talking
       about was recommended by the National Commission in
       1978 and we don't usually get people to sign
       documents but in most institutions there are
       statements in the patient information brochure that
       each patient gets on admission that says, "You are
       in an institution which has among its missions
       research and education.  It is customary in this
       institution to use medical records and various other
       things for research purposes."  
                 And it goes on to give a very minor
       description but then usually what happens is that
       all applications to do research involving medical
       records must pass through the IRB and the IRB then
       decides whether there's anything special about this
       proposition.  I don't know what more to say about
       that.
                 Sandy, if I hear your argument correctly I
       don't see why you don't include subjects in
       randomized clinical trials if your intention is to
       make sure that everybody in this situation is
       considered a research subject.
                 CHAIRPERSON MARSHALL:  I've got -- okay.  I
       have Susan and then Abbey.
                 Let me respond, Bob, just to your point.  I
       guess I'm not sure what purpose prospective consent
       of that nature means or how it is meaningful given
       the fact that, as you said, ideally we hope that
       investigators know that their proposals need to go
       before the IRB for review or for waiver if they
       involve human subjects.
                 DR. R. LEVINE:  Mary Faith, this is not
       prospective consent.  This is not consent of any
       type.  This is something that the National
       Commission said was a circumstance in which
       individual consent is ordinarily not necessary and
       what it called it instead was a response to a right
       of notification.
                 MS. MEYERS:  What happens if somebody
       doesn't want to sign it?  They say, "No, I won't
       sign it."  Do they say, "Okay, go to another
       hospital for your surgery?"  
                 CHAIRPERSON MARSHALL:  Probably not.  My
       guess would be that most people don't attend to it
       very well.
                 Okay.  If this is on point, Adil, and then
       I want to move to Susan.  
                 Adil?
                 DR. SHAMOO:  On the same point as Abbey. 
       This is the most coercive circumstances.  You're in
       an emergency room circumstances and you're going to
       sign this.  You sign any document then.  You are in
       pain.  This is horrible to have a blanket futuristic
       informed consent signed, wherever private
       information, any researcher can use it and maybe
       divulge that information.
                 And just because the National Commission
       said it's okay, Bob, I thought we are here to review
       those things and try to make advice and counsel on
       new issues regardless of whether the National
       Commission -- it's not the Bible yet.
                 CHAIRPERSON MARSHALL:  All right.  Susan?
                 MS. KORNETSKY:  I'll just make one comment. 
       I mean, I agree with Bob.  I think this is a very
       common practice.  I think more practically what IRBs
       are doing, there may be certain statements like that
       but as the medical record requests are coming
       through what they're doing is then thinking about
       the criteria for exemptions of waiver of informed
       consent on an individual basis.  So the overall
       consent may say something but I think IRBs are
       moving towards looking at each one individually.
                 CHAIRPERSON MARSHALL:  Okay.  We are
       getting off of target here really.  We need to be
       talking about "when referenced by" getting back to
       our subject.
                 Others on the committee because I would
       like to open the discussion up to the floor?  Ex
       officios?  
                 Margaret?  Oh, I'm sorry, Margaret.  I
       didn't see you.
                 MS. BORWHAT:  Well, I think one of the
       problems that came up from the case that brought
       this to our attention to begin with was the idea
       that research was somewhat of a fishing expedition
       and there was a lot of questions asked about third
       parties.  It really wasn't relevant to the research
       at all and would be kind of involved in a post hoc
       analysis.  And so I'm wondering if this document
       addresses any of that?  I know that we discussed it
       on the conference calls and the e-mails and I'm not
       sure that I see it specifically in this document.
                 DR. R. LEVINE:  I want to say that one
       thing we're seeing now is an artifact of focusing on
       one sentence in one version of a document.  To Adil
       I have to say what several people, including I, have
       said before is that the person who comes into the
       hospital and has a medical record created, when a
       researcher wants to look at that medical record that
       person is already considered a research subject. 
       It's not as if everybody has carte blanch to do
       whatever they like.
                 The individual who wants to use that
       medical record for research purposes then must go to
       an IRB unless we are working in an exempt category. 
       Must go to the IRB and the IRB will then say yes or
       no, you may proceed without consent.  In some
       circumstances they will call for consent and in some
       they won't.  All right.
                 So it really doesn't help anything to talk
       about all of the horrendous abuses that can come out
       of looking at one part of one sentence because
       there's so much other stuff written on this topic
       that establishes fairly secure safeguards.
                 CHAIRPERSON MARSHALL:  Judy?
                 DR. SIEGEL:  I'm trying to organize this in
       my brain and I'm getting a little lost.  What I'm
       hearing now, and maybe this is something I didn't
       really understand before, is that what we're talking
       about now is a clarification of more recently
       occurring events and that maybe what this document
       needs, although not dealing with previously covered
       events, is a reference to previously covered events
       of the type that Bob is talking about.
                 If there are situations that are already
       covered within the purview of the IRB to review and
       make decisions maybe it should be stated up front
       that that's not what this document is referring to. 
       Would that help sort this out a bit? 
                 DR. R. LEVINE:  Sure.
                 CHAIRPERSON MARSHALL:  Yes.  Yes.  Thank
       you, Judy.
                 DR. KOSKI:  It's going to fall to OHRP to
       take the advice that comes to it and develop
       guidance for the research community on this topic
       and clearly I think they would want to do that by
       providing the kind of contextual information that
       would give it meaning and place it in the overall
       spectrum so that whether or not the committee does
       that I can assure you that that's likely to happen
       anyway.  Okay.
                 CHAIRPERSON MARSHALL:  Yes, Judy?
                 DR. SIEGEL:  I guess what I was trying to
       get at, is that actually a sticking point around the
       table here?  Would that get us off this point and
       maybe on to something else?
                 CHAIRPERSON MARSHALL:  Right.  Well, let me
       ask you to do this maybe, I'd like to open the floor
       up, could you craft us a sentence?  Not that it
       would be the exact language we would use but to
       convey your idea.  Thank you.
                 Any one of our ex officio folks who are out
       there who would like to say something?  Anyone in
       the audience at all?  Our public members?  Yes, here
       comes someone.
                 MS. HILLSMAN:  Thank you.  I'm Sally
       Hillsman.  I'm the Director of the Office of
       Research and Evaluation at the National Institute of
       Justice, U.S. Department of Justice.
                 Just a quick comment.  This is -- the issue
       of third parties is a very important one to the
       kinds of research that are done by agency -- by
       researchers who do work in the justice system on
       criminality, on a variety of important social
       matters.
                 As I listen to this discussion, I came here
       hoping to get clarification on behalf of those
       researchers on the issue of what I thought the third
       parties were, which is that is information about
       individuals coming from a designated human subject
       where those other individuals are not human
       subjects.  It seems to me that most of the
       discussion this morning has not addressed those
       issues.  It has gone off on the question of people
       who are human subjects in their own right or may or
       may not be.  Hence the term "third party" has no
       meaning in this context.
                 I think the field, certainly the field of
       researchers that I deal with need guidance on the
       third party issue and this discussion is not getting
       us there.  I think the Levine/Levine document very
       much does that because it focuses exclusively on the
       issue of third parties and it raises questions about
       making a determination about their status by an IRB
       that involves questions about how the researcher is
       going to deal with his or her obligations to the
       primary research subject.
                 I think both of those questions are very
       important and are dealt with in that document giving
       the IRBs a fair amount of useful guidance in terms
       of thinking through those issues but if you add the
       question about folks who are research subjects in
       their own right then it seems to me it confuses the
       issue.  I'd like to see the two things separated.
                 This is not to imply in any way that that
       question about whether or not individuals who are
       research subjects because of their status in --
       because you're going directly to records and not
       having an immediate interaction with them is not an
       important question.  It's a very important question
       but it is in my judgment a different question and
       the question I'm concerned about, which is third
       parties, doesn't seem to be getting addressed
       adequately.
                 CHAIRPERSON MARSHALL:  Thank you.
                 Adil, before I call on you, Felice, I'm
       looking at the document that was just handed out.
                 DR. F. LEVINE:  And you're wondering what
       the difference is.
                 CHAIRPERSON MARSHALL:  Can you elucidate
       those for us, please?
                 DR. F. LEVINE:  Yes.  I mean, the one -- as
       opposed to the one in the packet?
                 CHAIRPERSON MARSHALL:  Yes.  Thank you. 
       Page 3 in your handout versus the page that was just
       handed out.
                 DR. F. LEVINE:  Well, you have to look very
       closely because what I was functioning as was -- in
       trying to build that consensus document was the -- I
       took all little comments so if you look at, for
       example, number 2 on the recommendations below, we
       received some language of clarification that made it
       clearer.  It's not one of substance but it is the
       most refined document based on the input I received
       from every member of NHRPAC who offered specific
       suggestions.
                 I mean, we had a number of other side
       e-mails but that -- so it was the final edition that
       I then passed along and it's not one that's
       substantially different than November 20th but it
       represents seven more days of -- in those last few
       days we did get a number of word changes that people
       believed were important and that made it a more
       readable document as Susan and I worked on public
       use, you know, made it a more readable document and
       captured in language what we were intending to do
       when we left our meeting on October 31.
                 CHAIRPERSON MARSHALL:  All right.  Thank
       you.  It seemed to me that "research investigator"
       is redundant and that's why I sort of --
                 DR. F. LEVINE:  Say that again.
                 CHAIRPERSON MARSHALL:  "Research
       investigator" seems redundant to me.  That's why I
       tried to clean that language up.
                 DR. F. LEVINE:  That is out.
                 CHAIRPERSON MARSHALL:  That's out.
                 DR. F. LEVINE:  Out of the 27th.
                 CHAIRPERSON MARSHALL:  Okay.  I'm looking
       at the old one.  All right.  Thank you.
                 DR. F. LEVINE:  All of those things that 
       we --
                 CHAIRPERSON MARSHALL:  That's the
       difference.
                 DR. F. LEVINE:  Yes, right.
                 CHAIRPERSON MARSHALL:  That's the main --
                 DR. F. LEVINE:  Well, there are --
                 CHAIRPERSON MARSHALL:  -- and others in 
       the --
                 DR. F. LEVINE:  -- clarifications of -- 
                 CHAIRPERSON MARSHALL:  Right.
                 DR. F. LEVINE:  Go ahead, Bob.
                 DR. R. LEVINE:  Most of it is matters of
       style and expression.  The one thing that's
       substantive that was not absent from the earlier
       document but is firmed up in the current, the
       November 27th document, which we're calling the
       brunch document, is that it's at the bottom of the
       page, item (2), to talk about the -- what an IRB has
       to take into account to the extent that they call
       for certain types of procedural safeguards for third
       parties.
                 They have to keep in mind that they might
       be compromised in the autonomy, welfare or safety of
       the actual human subject who is right in front of
       you.  So they should not -- to take an easy case,
       and there are more subtle ones -- they cannot, for
       example, insist that an individual can't give a
       family history without her mother's permission.
                 CHAIRPERSON MARSHALL:  I've got you.  Thank
       you very much.
                 Brief on point?
                 DR. F. LEVINE:  Yes, just on point.  Just
       everyone keep in mind that the bolding was just so
       that everyone internally would know what changes I
       was making and I was not intending that any ultimate
       document would be permanently bolded.
                 CHAIRPERSON MARSHALL:  Thank you, Felice.
                 I have Adil and then Alan, and then Mary
       Kay.  Am I missing anyone else?  No.
                 Adil?
                 DR. SHAMOO:  I think Bob clarified it to my
       dismay and that is the thrust of this Levine/Levine
       document of 11/27 is that if members of the IRB read
       it, it means you better watch it, you IRBs, not to
       call a third party a human subject because it keeps
       emphasizing it is a rare case in which third parties
       would become research subjects.  It continuously
       gives that impression.
                 If third parties are deemed to be human
       subjects investigators may request, an IRB may grant
       waivers of consent as set forth.  The whole document
       thrust is don't call them human subjects and I don't
       think that's what we want to do.  At least that's
       not what I want to do.
                 CHAIRPERSON MARSHALL:  Thank you, Adil.
                 Alan?
                 DR. FLEISCHMAN:  Looking at the November 27
       document I want to comment on three parts.
                 One is the rare case.  I agree with Adil
       that I don't think that sentence is necessary nor
       helpful in this document and I would recommend we
       strike it.
                 The second, the admonition to IRBs that
       there is the potential for granting waivers of
       consent I think is an important thing to be in the
       document.  It wasn't in the Mary Faith document and
       I think that would be helpful to remind IRBs that
       even if you do deem someone to be a human subject
       you may waive the need for consent and that should
       be clarified.
                 The third is the point that Bob Levine just
       spoke about, that is his number 2, and I think if
       we're going to remind IRBs that the primary -- let's
       call them the primary human subject -- may be
       compromised by creating a third party human subject,
       this language does, and I agree with Adil, suggest
       that IRBs not create third party human subjects.
                 I think we need to clarify if we wish to do
       this and I could be persuaded that we should do this
       but what this does is basically says that you
       shouldn't classify someone as a third party because
       you may compromise the autonomy of the primary
       person and I think that's not what we ought to say.
                 We ought to inform the IRBs that you might
       create a problem here that you will need to deal
       with in some way.  You may still have to deem
       someone a third party and then you've created
       additional problems in the informed consent process
       of the primary human subject but you need to deal
       with this problem, not just not deem them a human
       subject.
                 CHAIRPERSON MARSHALL:  Thanks, Alan.
                 I have Mary Kay and then Sandy.
                 DR. PELIAS:  I have three comments in
       comparing the Mary Faith document with the November
       27th document.  The first comment has to do with the
       question about who are third parties.  And I respect
       and acknowledge that the November 27th document,
       number 3 on defining third parties, is a wiser
       wording of what we're trying to get to.
                 My second comment has to do with the
       sentence somewhat further down the page having to do
       with the rare case that Alan just mentioned.  One of
       the e-mails that I sent back and forth had to do
       with the rare case and I emphasized in trying to
       define what a rare case is that in the world of
       genetics research third parties are not rare cases.
                 Third parties are every day occurrences
       because when we start a genetic study and we have to
       collect a family history we have to talk about all
       the other folks in the family so these are third
       parties out there with whom we have no contact
       whatsoever unless we get permission either from the
       subject or from a professional individual to find
       out whether that third party would like to be
       contacted for our study.
                 The idea here, bottom line is that in
       genetics studies third parties are not rare
       occurrences.  They are very common occurrences and I
       think this language should be deleted all together.
                 And my third comment has to do -- pardon
       me?
                 MS. MEYERS:  Which, the sentence about a
       rare case?
                 DR. PELIAS:  Yes, that's the sentence about
       a rare case.  In genetics rare cases are -- we don't
       have rare cases in this context.
                 I have one more comment, please.
                 And my last comment is the idea at the
       bottom of the November 27th document, the idea about
       protecting the autonomy and the confidentiality of
       the subject who gives information about other people
       is something that I think perhaps in your context
       are more important than in what I'm seeing in the
       world of genetics where I talk to everybody about
       all their family members all the time and keep it
       all quiet and confidential.  So I think this is an
       important idea in the number 2 at the bottom of the
       page that we do incorporate it into our final
       version, whatever that's going to be.
                 Thank you.
                 CHAIRPERSON MARSHALL:  Thank you, Mary Kay.
                 Let's let Bob and Felice respond.
                 Bob, the floor is your's.
                 And then I have Sandy.
                 DR. R. LEVINE:  The reason that I'm waiving
       so frantically is that I want to save you all some
       trouble about criticizing things that are on "do not
       resuscitate status" to begin with.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  We thought they were
       brain dead, Bob.
                 DR. R. LEVINE:  First, the rare case.  I
       wish the man who sponsored the word "rare" were here
       to defend it but there are no defenders of it in
       this room and I would be happy -- 
                 [Laughter.]
                 DR. R. LEVINE:  I would be happy to see
       "rarity" --
                 DR. SHAMOO:  Become even rarer.
                 [Laughter.]
                 DR. F. LEVINE:  It wasn't in the 20th
       version.
                 DR. R. LEVINE:  I want to see it yield in
       the interest of having a document that's well done.
                 CHAIRPERSON MARSHALL:  It's out of the gene
       pool.
                 DR. R. LEVINE:  At the bottom of the page I
       think that Adil and Alan come up with a very
       important point about item (2) at the bottom that
       without in any way compromising does suggest raising
       the interest of the subject who is standing right in
       front of you to such a high level that it would be
       impossible to overcome.  I don't think we have
       language to replace it but I think we want to go the
       route that Alan, I think, came closest to wording
       and that is to say, "You've got to keep this stuff
       in mind and deal with it."  All right?
                 Now the rest of the document is still open
       to criticism.
                 CHAIRPERSON MARSHALL:  Felice?
                 DR. F. LEVINE:  I share as the sort of
       synthesizer of comments had that comment arrived
       before the 27th it would have been -- 2 would have
       been appropriately distinguished to make that point. 
       I think that can be done readily.
                 CHAIRPERSON MARSHALL:  Okay.  It's deleted. 
       Can we all -- 
                 DR. F. LEVINE:  Oh, no --
                 CHAIRPERSON MARSHALL:  Oh, I'm sorry, a
       different point.  I'm sorry.
                 DR. F. LEVINE:  I think we can rewrite it
       to clarify the --
                 CHAIRPERSON MARSHALL:  Revise number 2.
                 DR. F. LEVINE:  -- distinction that Adil
       and Alan were making.
                 And I want to -- and I think the "rare"
       sentence should be deleted.  I want to emphasize,
       though, from a matter of substance that I think the
       social and behavioral sciences and the genetics view
       on this is more similar than different.  The meaning
       of rare was when the third party became a subject,
       not whether it was rare to have third parties, which
       was an element of both reports.
                 CHAIRPERSON MARSHALL:  Okay.  Thank you.
                 DR. F. LEVINE:  But I think it's best out.
                 CHAIRPERSON MARSHALL:  All right.  I would
       like to ask Judy to please read her language.
                 DR. SIEGEL:  I don't write government so
       this is what you got.
                 [Laughter.]
                 DR. SIEGEL:  This is relative to the
       clarification of what this document will deal with.
                 "This recommendation is meant to clarify
       issues specifically dealing with the information
       given by a human subject about someone else (e.g.,
       third party).  It is not meant to readdress
       situations where information about someone is
       gathered through indirect means (e.g., chart review)
       as these situations have already been covered in
       existing..." whatever the word is that takes care of
       that.
                 CHAIRPERSON MARSHALL:  Do we have agreement
       there?
                 All right.  Adil?
                 DR. SHAMOO:  Could we put "i.e."?
                 DR. SIEGEL:  Yes, I don't write English
       well either.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Read it one more
       time, Judy, please.
                 DR. SIEGEL:  Okay.  "This recommendation is
       meant to clarify issues specifically dealing with
       information given by a human subject about someone
       else (i.e., third party).  It is not meant to
       readdress situations where information about someone
       is gathered through indirect means (e.g., chart
       review) as these situations have already been
       covered in existing..." and whatever the appropriate
       wording is.
                 CHAIRPERSON MARSHALL:  All right.  I want
       to bring us to closure here.  We're out of time.
                 Elliot, if it's very brief.
                 DR. DORFF:  Yes.  Fixing the next to the
       last sentence, I think, is easy.  What you want to
       do is "whether classification of third parties as
       human subjects can be done without significantly
       compromising the autonomy, welfare..." and so on.
                 [Chorus of no.]
                 DR. DORFF:  No.
                 DR. SHAMOO:  Too easy.
                 DR. DORFF:  That's too easy?
                 DR. F. LEVINE:  But we can do it.
                 DR. DORFF:  What's --
                 DR. FLEISCHMAN:  Better, necessary but not
       sufficient.
                 DR. DORFF:  Okay.  Well --
                 CHAIRPERSON MARSHALL:  Here is what I'm
       going to propose:  Here's where I think we are and
       we're going to come to closure in the next couple of
       minutes here:  We are going to replace the first
       sentence that begins "this guidance is provided
       for..."  We're going to incorporate Judy's language.
                 Okay.  Then the paragraph that begins
       "simply because reference..." we are going to delete
       the sentence about the "rare case."
                 We are going to get some language on number
       two at the bottom.  We're just going to revise and
       clarify that language to reflect Alan's point.
                 And so let's go back to 1, 2, 3 at the top. 
       Let's go back to 3.  What is the committee's
       pleasure?  Do we leave it as it stands or do we
       delete "from human subjects who themselves..."?
                 Elliot?
                 DR. DORFF:  Can I ask why you wanted to
       delete "from human subjects" in your view?
                 CHAIRPERSON MARSHALL:  Well, because it
       seemed to me that we had a tension.  We sort of had
       two camps.  Okay.  One was you've got to have a
       narrow context in which the information is provided
       by the research subject.  The broader context was
       information that exists in medical records, genetic
       tissues that have been banked and so forth so I was
       allowing for that broader context.
                 MS. GOTTFRIED:  I think based on what Judy
       has now crafted that the committee is in consensus. 
       Is that right, Sandy?
                 CHAIRPERSON MARSHALL:  I think we are
       there.  I think we are there.  Does anyone else --
       Adil?
                 DR. SHAMOO:  I have one more thing.
                 CHAIRPERSON MARSHALL:  Wait.  Well,  let's
       -- I want to finish this one.
                 Sandy?
                 DR. CHODOSH:  The Justice Department spoke
       up, which I think is very interesting, and I just
       wondered how, in fact, a researcher who is using
       police records to talk about criminals who have not
       given informed consent, how that would be managed
       within this setting?  Whether that -- that's not
       obtained from a human subject and yet it is very
       critical kinds of information.  And I think that if
       we had people thinking around here about different
       ways in which this can occur that I think that
       specifying only for human subjects somehow restricts
       the coverage that I think that we should be
       providing.
                 CHAIRPERSON MARSHALL:  Thank you, Sandy.
                 Adil and Alan?
                 DR. SHAMOO:  I agree with Sandy but I have
       a new point like I mentioned.  When the IRB has
       decided that third parties are human subjects then
       they could go and comply with 45 C.F.R. 46.
                 CHAIRPERSON MARSHALL:  If they know what's
       good for them, yes.
                 DR. SHAMOO:  Which they have the right to
       waive consent, right?  Now when then do we keep
       emphasizing in bold letters at least in this
       document "if third parties are deemed to be human
       subjects investigators may request an IRB may grant
       waivers of consent."?  That's redundant and almost
       inviting the IRB to waive consent.  That sentence
       shouldn't be there.  It is redundant and it's an
       invitation to waive consent.  It's not necessary and
       we don't need it there.
                 CHAIRPERSON MARSHALL:  Take it out.  Take
       it out.  I mean it does seem to be understood.  All
       right.  It's gone, Adil.
                 So, Alan?
                 DR. FLEISCHMAN:  I just want to go on
       record as saying I think it should stay but if it's
       gone it's gone.
                 My -- you know, you put me next to him.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Let me just say
       this, Alan, before we move on, okay.  What if we
       said "when third parties are determined to be..."
       does that help?  If and when?  Okay.  Let's move on.
                 DR. FLEISCHMAN:  I have some suggested
       language.
                 CHAIRPERSON MARSHALL:  Okay.  Thank you.
                 DR. FLEISCHMAN:  To try to resolve this
       issue.  By the way, my feeling is that the Mary
       Faith (a), (b), (c), (d) is better than the 11/27 1,
       2, 3 on the bottom and I would urge us to do (a),
       (b), (c), (d) and make this (e).
                 And (e) is the possibility that
       classification of a third party as a human subject
       may impact on the welfare of the originally
       designated human subject and requires that the IRB
       deal with this issue to protect the interests of
       both subjects.
                 CHAIRPERSON MARSHALL:  One more time.  It
       was so good, Alan, one more time.
                 DR. FLEISCHMAN:  I know.  I'm looking at
       Elliot.
                 [Laughter.]
                 DR. FLEISCHMAN:  All right.  I'm not sure
       of the grammar here but Elliot will help me.
                 "The possibility that classification of a
       third party as a human subject may impact on the
       welfare of the originally designated human subject
       and requires the IRB to deal with this issue to
       protect the interests of both subjects."  
                 CHAIRPERSON MARSHALL:  Jonathan?
                 DR. MORENO:  Alan, the Mary Faith (c) talks
       about this problem with respect to the third party. 
       Why can't we simply add "might cause harm to the
       third party or the original research subject?" 
       You're worried about a blow back effect basically,
       right, and that could be a problem for either the
       third party or the designated subject.
                 DR. FLEISCHMAN:  I think, Jonathan, just to
       speak in favor of putting that in before Bob jumps
       over the table here that I was quite taken by that
       explication that was put in there.  I mean, I didn't
       understand this potential impact so I think we need
       a little more there.  That's why I think it needs a
       little bit more.
                 CHAIRPERSON MARSHALL:  Thank you very much,
       Alan.
                 Bob?
                 DR. R. LEVINE:  I think at this point we're
       well along the way to creating a camel.  We're
       jumping from one piece of paper to the other and
       revising some words in the Mary Faith and revising
       some words in the November 27th and we will
       inevitably lose track of what we revised where.
                 CHAIRPERSON MARSHALL:  No, we won't.
                 DR. R. LEVINE:  What I propose -- well,
       when you move from November 27th to -- back to Mary
       Faith you're leaving out -- I don't know if you know
       that you're leaving out some wording of the November
       27th document in item (1).
                 CHAIRPERSON MARSHALL:  Bob, the proposal
       that's on the floor is to take (a), (b), (c) and (d)
       from Mary Faith.
                 DR. R. LEVINE:  Yes, in that case let me
       preface my remarks by saying --
                 CHAIRPERSON MARSHALL:  But that doesn't --
                 DR. R. LEVINE:  -- I'm speaking against
       that.  What you're leaving behind in item (1) is
       that it's not merely the quantity of the information
       but it's the quantity or nature of the information
       and then it goes on to suggest that the third party
       is an actual subject of the research.
                 So it's not as if you can just say (1)
       corresponds to (a), et cetera.  I think that the
       best solution for this would be to assign those
       people who have been most vocal in this morning's
       discussion to come up with a substitute for the last
       passage and present it in writing to this group so
       that we all know what's on the agenda.
                 CHAIRPERSON MARSHALL:  Okay.  Here's what
       we're going to do.  Thank you, Bob.  We've got, I
       think, very accurate notes.  We've got it on tape
       exactly what the discussion was and what should go
       where so we have agreed that we are -- that
       beginning at the top of the document on the brunch
       document the sentence beginning "this guidance" will
       be replaced by Judy's sentence.  We are leaving (1),
       (2), (3) as they stand.
                 We are deleting in the paragraph beginning
       "simply because" -- we are deleting two sentences. 
       One is "it is the rare case."  The second is "if
       third parties are deemed to be..."  Those are
       deleted and we will take Alan's language and
       incorporate it into (1), (2), (3) and clean up the
       language.
                 So that's the proposal I'm putting on the
       floor and I would like for us to have a vote.
                 DR. R. LEVINE:  I have a point of
       clarification.
                 CHAIRPERSON MARSHALL:  Okay.
                 DR. R. LEVINE:  Does Alan's language
       include all the rest of item (1) that is not in item
       (a)?
                 CHAIRPERSON MARSHALL:  Item (1) stands. 
       We're simply adding something to the bottom.  Is
       that correct?
                 DR. R. LEVINE:  Item (1) being --
                 CHAIRPERSON MARSHALL:  Item (1) stands as
       it is.  (1) and (3) stand as they are.  I'm sorry,
       Alan.  I thought -- okay.  Go back.
                 DR. FLEISCHMAN:  I think (a) and (b)
       together deals with item (1).  I think it's clear. 
       I think the language is better.  Bob disagrees but I
       would take (a), (b), (c), (d) instead of (1), (2),
       (3) and add that additional piece.
                 CHAIRPERSON MARSHALL:  And add (e).  Okay.
                 Felice and Bob, can you live with that?
                 DR. F. LEVINE:  The inclination is to say
       yes but the problem in the long term is that on
       topics that are vulnerable, let's say like spouses
       of, where someone may be giving a lot of quantity
       and a lot of quality about another human being, that
       doesn't necessarily migrate solely on the basis of
       quantity and quality and that's why number (1) is
       written in the way it is.  There has to be an IRB
       --
                 CHAIRPERSON MARSHALL:  Felice --
                 DR. F. LEVINE:  -- it requires an IRB to
       determine.
                 CHAIRPERSON MARSHALL:  -- I know but it
       seems to me it's redundant if you read the last
       sentence in the paragraph -- the preceding
       paragraph.  It says exactly that.
                 "In cases in which a research subjects
       design -- project's design collects a significant
       amount of private information the investigator and
       IRBs should consider whether these third parties
       should be regarded as research subjects themselves." 
       And you're restating that in question number 1.  I
       mean that seems redundant to me.  And rather we just
       say "when making that determination here's what the
       IRB should consider."
                 DR. FLEISCHMAN:  You know, as a simple IRB
       chair if you look at (a), (b) and (c) you have the
       quantity, the nature and the sensitivity.  I mean
       that's exactly what you're arguing but this language
       is straight forward and the language that's -- you
       know, with all due respect, the November 27th
       document confuses me.
                 CHAIRPERSON MARSHALL:  All right.  So I'm
       putting on the table then the things that I said
       leading up to the final paragraph.  We will replace
       (1), (2) and (3) with (a), (b), (c), (d) and Alan's
       new (e).  That is on the table.  I would like to
       bring this issue to a vote.  All of those in favor
       please raise your hands so that Kate can see them.
                 [A show of hands was seen.]
                 CHAIRPERSON MARSHALL:  All right.  Bob
       raised his hand.  We have achieved consensus.
                 DR. FLEISCHMAN:  I assume we cede to the
       Chair the final judgment on what will be now --
                 DR. R. LEVINE:  It comes back to us.
                 DR. FLEISCHMAN:  -- transferred.
                 CHAIRPERSON MARSHALL:  Thank you.
                 DR. FLEISCHMAN:  Not for our comments but
       for our reading and awe in its clarity.
                 [Laughter.]
                 DR. DORFF:  And wisdom.
                 CHAIRPERSON MARSHALL:  Thank you, Alan.
                 We've come to consensus.  We did it yet
       again.  Thank you very much, committee members. 
       Thank you.
                 I want to say a special thanks to Felice
       and Jeff and I'm sure there are moments in the last
       six weeks or so when Felice would have liked to have
       had her hands around my neck and I'm glad we were
       four states removed from one another.
                 Felice, you have just done a fabulous job
       in a very difficult area so thank you and your
       workgroup.
                 Jeff, thank you.
                 Committee, thank you all for coming to
       closure.  That's just great.
                 So we need to move forward.  We have other
       work to do.
                 And, Felice, yet again the floor.
                 And, Jeff, would you like to come up?  
                 Risk and harm, confidentiality, update and
       discussion on the social and behavioral sciences.
                 I see some folks who have joined us. 
       Welcome, Dr. Lombardo, Alan Milstein and Vera.
                 DR. COHEN:  I will just sort of hold it. 
       I'm flexible.  I'm more flexible than the
       microphone.
                 I, hopefully, don't need a lot of time to
       spend on the -- I got the wrong one.
                 CHAIRPERSON MARSHALL:  I think that we --
       you know, if we need to, we will go to 1:00 o'clock
       because we have until 2:00 to come back.  The
       afternoon begins at 2:00 o'clock.  So we'll either
       go to 12:30 or if we need more time we can go to
       1:00 and that will give us an hour for lunch.
                 DR. F. LEVINE:  And interaction.
                 CHAIRPERSON MARSHALL:  And interaction. 
       Thank you, Felice.
                 DR. COHEN:  Okay.  I think we're in
       business.  Sorry for that.
                 The Social and Behavioral Sciences Working
       Group spent a considerable amount of time working on
       this, which is probably one of the key or crucial
       topics with regard to the oversight of social and
       behavioral sciences and what constitutes risks and
       harm in the social and behavioral sciences.
                 This report has been presented twice to
       NHRPAC at both the July and the October meeting but
       due to other more pressing issues never got fully
       discussed at either meeting so again we, hopefully,
       will bring this to some kind of resolution today.
                 The committee has with the materials on
       social risk and harm a table prepared by Joan Sieber
       which highlights or summarizes the potential for
       risk in social and behavioral sciences.  Actually
       risks in all research but particularly the risks in
       social and behavioral sciences.  And this was raised
       in our initial presentations of this topic as a
       concern because many biomedical researchers and
       people coming from biomedical orientation do not
       have a clear concept of what the potential harms
       might be in social and behavioral research.
                 So the purpose of creating this table was
       to indicate what those potential harms might be and
       to relate them to levels of risk and, in addition,
       the possibility of ameliorating those harms and so
       this table, we hope, will inform the committee.  I'm
       not going to spend time going through the table.  I
       don't think that's necessary at this point unless
       committee members have any specific questions about
       that.
                 First of all, there are two key issues in
       our presentation.  Two key recommendations that we
       would like the NHRPAC to make.  First focuses on the
       question of minimal risk and in order to establish
       the degree of risk in any kind of research.  We work
       from the regulations.  The only place where risk is
       defined in the regulations or at least in subpart
       (a) of the regulations is in the definition of
       "minimal risk."
                 One of the major problems with that
       definition is that it conflates two aspects of the
       possible outcomes of research into one concept of
       risk and that is the probability and magnitude of
       harm.  And one of our key recommendations is that
       those two are separate dimensions and must be
       considered together to determine risk but are two
       separate dimensions.
                 So for any possible outcome of research you
       have the magnitude of the harm that could come to
       subjects so that could range from no harm to minimal
       harm to significant harm.  And then you have the
       likelihood of that harm occurring, which could be
       very low probability or no probability.  It's not
       going to occur, a minor probability, a very low
       probability or a significant probability.
                 And in addition when you're looking at
       probability you have the probability for an
       individual subject, which whatever happens is always
       100 percent, or the probability for the class of
       subjects that are intended in the research.
                 So one of the most key elements that we
       want to make, key recommendations, is guidance for
       IRBs in separating these two dimensions.  
                 So, for example, if you have a survey which
       does a survey in very sensitive -- obtains very
       sensitive information about a subject, things to do
       with criminal activity or sexual conduct or
       substance abuse, the magnitude of harm of that
       information if it were inappropriately divulged is
       very significant.  And we'll get into this in the
       next topic when we talk about confidentiality.
                 The magnitude of harm is very significant
       but if the procedures to protect confidentiality are
       sufficient the likelihood of that information being
       inappropriately divulged could be minimal.  Thus
       when you take the magnitude and the probability
       together you can result in declaring this research
       minimal risk research.
                 And I think it's -- one of the problems
       that we've picked up in our feedback from the field
       is that IRBs as soon as they see sensitive
       information being obtained automatically assume the
       study involves risk and requires full IRB review. 
       So what we're saying is IRBs have to be more
       sensitive to separating these two dimensions.
                 The second part of minimal risk is the
       daily life standard and we make recommendations that
       IRBs pay more attention and that OHRP provide more
       guidance on what this daily life standard refers to. 
       There are transitory harms that occur to everyone
       all of the time but they occur, they are very
       transitory, a few moments later.  A day later it's
       as if they never happened.  That is all part of
       daily life and IRBs need much more guidance as to
       what that means.
                 The final recommendation is with regard to
       expedited review and that is that there's a great
       variability amongst IRBs in how they apply the
       categories of research that are eligible for
       expedited review.  And what we're urging is more
       clarification on the categories of research that are
       eligible for expedited review.  And going back to
       the example I gave before where you could have a
       very sensitive survey that has adequate protection
       on confidentiality, that could be a minimal risk
       study which would now be eligible for expedited
       review.
                 And finally we would like OHRP to look at
       the list of categories eligible for expedited review
       for possible refinement, perhaps expansion.  Right
       now a great -- almost -- most social and behavioral
       science research is lumped into one of the
       categories and it's again a conflated category,
       which includes everything but the kitchen sink and
       that doesn't provide much guidance at all to IRBs. 
       They don't know how to apply that category to
       different types of research and so either through
       guidance or actually changing the categories of
       research that that would be valuable.
                 That's basically our report.  The slide
       show goes on to detail the recommendations.
                 DR. R. LEVINE:  There is another component
       of the definition of minimal risk in the regulations
       and that's the relationship to the amount of risk
       one encounters in a routine physical, psychological,
       et cetera, examination.  And are you suggesting that
       that should not be taken into account?
                 DR. COHEN:  No, I, just in the interest of
       time sort of buzzed by that but that -- again our
       main recommendation is that the minimal risk
       definition be examined and additional clarification
       on all of those points be included.
                 DR. R. LEVINE:  When you buzzed by it one
       important concept is that in a routine medical
       examination one gets asked about one's habits and
       behaviors and so on.  One gets asked about drug
       abuse, abortions, all sorts of stuff.  And if we can
       count minimal risk as something that presents no
       more risk then that part of a routine medical
       examination changes the picture somewhat.
                 DR. COHEN:  As I said, that examination of
       that standard is part of our recommendation.
                 DR. F. LEVINE:  Which happens to be the
       recommendation that is up, Bob.  That sentence is
       literally there in the recommendation so the
       recommendation didn't change.  Jeff and I were
       trying to be a little bit more expeditious this time
       around to make sure we had good interaction both
       within NHRPAC and our attendees but all the
       recommendations are intact in the way that you saw
       them.
                 DR. COHEN:  I don't know who is chairing
       this.  Do I call on speakers or does our chair? 
                 CHAIRPERSON MARSHALL:  You and Felice are
       running this.
                 DR. COHEN:  Felice, you can see the group
       better.  Why don't you call on people?
                 CHAIRPERSON MARSHALL:  If we could follow
       our same pattern, committee, ex officios, public
       members.
                 DR. F. LEVINE:  Okay.  Alan?
                 DR. FLEISCHMAN:  At Wednesday's meeting of
       the Children's Workgroup the work product that Susan
       Kornetsky has been honcho-ing for the workgroup will
       be discussed concerning the definition of minimal
       risk.
                 An additional work product concerning minor
       increment over minimal risk and trying to bring
       those two very complex concepts into some kind of
       coherent examination will be done.  Sadly and
       unfortunately, we were not able to complete that
       work prior to today but we'll complete it on
       Wednesday or, hopefully, complete it or at least
       continue it on Wednesday.  I think it is important
       that we try to harmonize some of the work that is
       very good work that's being done here with the work
       that's being done in the child group.
                 There are two, I think, extraordinary
       things that Susan's committee brings forward and she
       can speak to it better than I but I just want to
       notice them publicly.  One is the concept of
       socially acceptable risks of daily life.  That is to
       say we all place ourselves or, as parents, we place
       our children at socially acceptable levels of risk
       by getting out of bed in the morning and going and
       doing our daily lives.  I think that concept is a
       good one.
                 And then, I think, in a just stunningly
       important concept the term that's used in Susan's
       document -- it's not comparability.  It's
       equivalence.  Equivalence of risk.  Speaking to what
       Bob has just commented on, when we think about the
       concepts of physical exams and going to school and
       going out to play or going out to work in the
       morning there are equivalent kinds of risks that we
       place ourselves at that also should be deemed
       minimal, and that's part of the process of
       examination here as we define these things.
                 Now one other comment and then I will
       cease.  One of the concerns that I think many of us
       are reading in these documents is concerns that
       individual investigators have in their own local
       environments and I'm not sure we're going to be able
       to do away with those concerns.  We're going to be
       able to clarify for IRBs.  We're going to be able to
       perhaps even allow investigators to grieve the IRBs
       but the fact of the matter is that we are in social
       constructs called universities or hospitals or
       medical schools and have group processes that will
       determine how much of this is interpreted.
                 And I'm very sympathetic when people say,
       you know, "There are no social scientists on the
       IRBs and those bad IRBs are doing bad things." 
       Well, there must be a way to infiltrate that social
       structure.  Certainly on the IRBs that I've served
       on those groups have been quite effective at being
       parts of those structures or even seeding to other
       groups and coming back, you know, and forth with
       those structures.
                 So I think we're not going to be able to
       fix all the problems with clarification that
       individual investigators are complaining about.  I
       would urge that the organizations responsible for
       social and behavioral research do some group
       dynamics and leadership training about infiltration
       of communities that one has every right to be part
       of.
                 DR. COHEN:  Let me just make a quick
       comment on that.  Two comments.  One I think it's
       very important that we do make the -- since both
       groups are working on the issue of minimal risk that
       we put those together and make sure they're
       consistent and I think we have the same goals in
       mind.
                 The issue about infiltration is a very good
       one.  As we've been telling the NHRPAC, one of the
       things that our working group is doing has been
       reaching out to professional societies and one of
       the messages I know I've been promoting and I think
       the others from the working group have each time we
       do this is stop complaining and get on the IRB. 
       And, you know, we've been promoting that and the
       professional societies have been very responsive to
       that and they're now reaching out to their
       membership with that message.  So I think that's
       being accomplished.
                 MS. KORNETSKY:  Jeff, I just want to say
       that Alan made the comments about what we're working
       on and I don't see -- I see these comments.  I don't
       know what will happen at the workgroup but there's
       nothing that is inconsistent and in areas that you
       said need further guidance from OHRP I think we're
       starting to delve into that a little bit and I'll be
       happy to share it with you.
                 DR. F. LEVINE:  Philosophically let me just
       add that as a working group -- and I'm on two other
       working groups -- it's that balance between taking
       all the things that are wrong and then trying to
       ratchet up to what usefully can be done generally so
       we're constantly trying to not try to fix everything
       and that has been my impression as a participant in
       the genetics and children's working group as well.
                 Okay.  Well, where can NHRPAC offer some
       generic advice that's more cross cutting if you have
       enough troubled situations that bubble up and then
       obviously there needs to be responsible conduct by
       other organizations and entities.
                 First Jonathan and then Bob and Greg third.
                 DR. MORENO:  I hope that whenever NHRPAC
       produces a document about risk that we be careful
       not to reproduce the same category mistake and using
       the terms "risk and harm" in the same logical
       breath.  I'm starting to sound like Elliot Dorff but
       risks are defined in terms of harm and, in
       particular, those two dimensional harm that you
       pointed out.
                 And so I just want to suggest that we not
       again aggravate a confused situation.  If I was king
       of the world the first thing I would do is change
       the term "risk benefit analysis" to "harm benefit
       analysis" along the same lines.
                 My second suggestion is that you insert a
       very simple two dimensional diagram where the X axis
       is magnitude and the Y axis is probability and point
       out that where they meet is no risk and then you get
       up to region A that's minimal, region B is a minor
       increase over minimal and region C is a significant
       increase over minimal.  It's very simple but it'll
       just help to conceptualize, to show a philosophy.
                 That is not hard and you already thought
       about doing that so great minds think alike.  
                 You have it where?  I didn't see that.
                 DR. F. LEVINE:  We had it at the November
       meeting.
                 DR. MORENO:  Oh, okay.
                 DR. F. LEVINE:  Without as much content in
       it.
                 DR. MORENO:  Well, okay, that's fine.
                 DR. F. LEVINE:  The goal of this table was
       to try to show that, of course, it's a dynamic
       process and steps that you take can ameliorate risk
       or harm.  They're not constant so it was almost
       three dimensional space which is, of course, hard to
       visualize.
                 DR. MORENO:  Right.  Actually I'm going to
       introduce -- I don't know -- an N dimensional space
       now.  I just came back from a meeting abroad which
       was largely attended by people from the nuclear
       engineering field and they made -- acquainted me
       with an extensive literature on risk, on risk
       governance, risk management that introduces the
       dimension of uncertainty.
                 And I hope that not only with respect to
       social behavioral but in general NHRPAC may well
       want to move to the next dimension, which I think is
       the real problem that IRBs have, which is even
       harder than this, which is how do you interpolate
       uncertainty into this kind of assessment.
                 DR. F. LEVINE:  Bob?
                 DR. RICH:  Coming from far outside the
       social sciences to this discussion I find your
       distinction between probability and magnitude of
       harm to be particularly useful in this setting.
                 I'm a little concerned, however, with the 
       -- what I thought I understood you to suggest, which
       was if the magnitude of harm was determined to be
       potentially great but the probability to be
       potentially very small that that would qualify a
       protocol for expedited review when I would think
       that as a social scientist one might believe that
       looking carefully at the quality of the processes
       that were to assure a low probability of harm might
       be the most important thing that the social
       scientist would do.
                 So that may be where the real task of the
       IRB in a social science protocol might be actually
       the in-depth assessment of the probability and the
       quality of those protections.
                 DR. F. LEVINE:  Greg, then Bob.
                 DR. KOSKI:  Just a quick expansion of
       Alan's thinking talking about children's -- the
       concepts of risk in children being, you know, sort
       of in a more global framework.  The current
       regulations address risk benefit in the principle
       subpart, Subpart (a), but then go on in additional
       subparts where there are special protections
       afforded populations deemed to be deserving of
       special protections by virtue of their age or
       situations and so on.
                 I would urge the committee in their
       thinking about this since another topic on the table
       we'll be discussing tomorrow are those who are
       decisional impaired, for instance, that we strive
       for the kind of framework that would provide a large
       enough umbrella, okay, to be sensitive to the
       various, you know, categories as well so that we can
       get something that basically gets to the point of
       kind of being common sense that you can apply across
       the board.
                 We'll all benefit from that rather than
       having in the final analysis something where minor
       increase over minimal risk is different for children
       than it is for another population so I urge you down
       that road, please.
                 DR. F. LEVINE:  Bob?
                 DR. R. LEVINE:  Thank you.  At one of our
       early meetings this group voted to establish an
       absolute standard for minimal risk which meant that
       it was not context related.  I think what you're
       recommending now is that we abandon the notion of an
       absolute standard.  I think also when it's
       relativised to either the risks of medical
       examinations or the risks of daily life we have big
       problems.
                 I not too long ago saw a new dimension of
       the problem when I spent some time at a game
       preserve in South Africa where a few of the nights
       were on a free range, which means that there are
       leopards and lions walking around the houses and it
       occurred to me that it had special meaning when you
       said to the kids, "Now go out and play."  
                 [Laughter.]
                 DR. R. LEVINE:  Now this in that part of
       the world is socially acceptable risk.  Thank you.
                 DR. F. LEVINE:  Sandy?
                 DR. CHODOSH:  Along those lines, you know,
       this is something that has always concerned me and
       I'm not sure we're going to resolve it now and that
       is that whenever I question what is a normal daily
       life occurrence and for whom, and that I know that
       many IRBs interpret that to mean that for the
       condition of the study, like say leukemia, that the
       daily -- I know that you're shaking your head and
       you're right -- the regs don't cover that but the
       truth of the matter is that I think that we're over
       emphasizing sometimes what is a risk for someone
       like that, what is the minimal risk for someone like
       that as opposed to not to.
                 Now I think IRBs get very confused about
       it.  I'm not coming down on one side or the other,
       Bob, but I think that IRBs are frequently confused
       by this and that investigators have a tendency to
       make that argument that this is not an increased
       risk for this kind of subject and somewhere we
       should clarify what is meant by that.
                 DR. F. LEVINE:  Susan, and then Bob, and
       then I'd like to open it up for our ex officios.
                 MS. KORNETSKY:  Sandy, again it's
       unfortunate that our group had -- that we're just
       meeting on Wednesday afterwards but again I don't
       know what the workgroup will decide but we are
       taking a stab at trying to come down on one side or
       the other on that and this group will obviously have
       a chance to talk about that.
                 DR. F. LEVINE:  Mary?
                 MS. KORNETSKY:  We did a lot of research
       and went back and looked at National Commission and
       did some stuff so we'll take a stab at that.
                 DR. R. LEVINE:  The regulations do take
       into account the context in which a child or perhaps
       some other vulnerable individual can be recruited as
       a research subject.  In the children's regulations
       it's especially well expressed that having made a
       determination that interventions or procedures that
       don't hold out the prospect of direct benefit for
       the individual child present more than minimal risk.
                 There are three further criteria that must
       be satisfied.
                 The one that's on the point right now is
       that the procedure itself must be commensurate with
       what the individual child has encountered or is
       likely to encounter given his or her relevant
       condition.
                 So, for example, if the child is being
       treated for leukemia and somebody wants to do a bone
       marrow aspiration for research purposes the
       requirement of the regulations would be that the
       bone marrow examination itself would be commensurate
       with what that child has experienced or would be
       likely to experience.
                 It's not the purpose of this to say, well,
       the kid is going to have ten bone marrows anyway
       then there's no problem with another.  The purpose
       of this is so that the child who is able to assent
       can give assent or refuse assent from a position of
       familiarity with what you're asking him or her to
       do.
                 Thanks.
                 DR. F. LEVINE:  Let me open it up for
       comments from our NHRPAC ex officio members.
                 [No response.]
                 DR. F. LEVINE:  General public?
                 DR. RAND-REED:  Hi.  I just wanted to add
       to the aspect of concept of daily risk.  It has been
       my experience that often times, and I'm sure I'm
       preaching to the choir here, that when you start
       making the assumptions that many times these
       assumptions don't take into account lifestyle
       analysis in terms of various and sundry variation in
       population exposures.
                 Let me give you an example and why I say
       that the ethno-cultural is going to become a much
       more important part especially vis-a-vis the
       behavioral and social science aspect of it.
                 If you have let's say an epidemiologist
       that's looking at a particular population in Chicago
       and they're looking at a group of children in terms
       of a particular time of exposure and growth spurt,
       if you don't know that that kid is leaving Chicago
       each summer to go down south to visit grandma in
       Yazoo in Holmes County, Mississippi, you've got a
       problem.
                 And the reason you have a problem is
       because 25 percent, three months of that child's
       life, over 13 years usually until they're about 13
       or 14, is spent in a totally different environment
       with totally different exposures with totally
       different risks but if you don't know to bring that
       into your epidemiological study then you've missed
       the whole ball game but it's hidden by culture.
                 So one of the things that many of the IRBs
       -- by the time it gets to the IRB it's almost a fait
       accompli.  The researchers are the ones that have to
       be trained to better understand and know their
       customer and know their population so that by the
       time they get it to the IRB both the IRB and the PI
       are operating on the same page for that level of
       understanding of the population.
                 So I want to throw that in.  I'll keep my
       comments short but I throw that in because when you
       talk about daily risk the issue about emic or etec
       as we would say is a choice, which is usually middle
       class Western, or is it superimposition, which is
       usually something like environmental justice.  These
       are the kinds of issues that when you're talking
       about human research populations need to be added in
       and part of the equation, otherwise we just, you
       know, are playing games with one another.
                 Thank you.
                 DR. F. LEVINE:  Vera, would you state your
       name just so we have it on the record?
                 MS. SHARAV:  Yes.  Vera Sharav.  I am
       president of the Alliance for Human Research
       Protection and, please, I'd like to correct the
       record.  I notice that I was referred to as doctor. 
       I'm not a doctor so please correct.
                 I'd like to remind NHRPAC about the
       Radiation Commission's report, the 1994 report,
       particularly on children.  The Radiation Commission
       evaluated 31 nontherapeutic radiation experiments
       that were conducted on about 800 children.  They
       were conducted between 1944 and '74.  Needless to
       say, by the standards today as far as radiation risk
       knowledge, you know, most would -- most people, I
       think, in America would consider them horrific as
       they would have at the time as well.
                 However, the commission made a very
       interesting statement, which was precisely in
       relation to this, which was that at the time the
       evaluation of those experiments was -- followed
       ethical standards of the day.
                 Now the additional protections that
       children now have in the existing regulations,
       Subpart (d), were adopted in '83, after all those
       radiation experiments.  I would caution that if the
       existing regulations were weakened and
       nontherapeutic experiments involving -- some of us
       would call it -- high risk, within the IRB community
       one wiggles and that's another issue.  How do you
       define "minimal risk?"  Is it with actual evaluation
       of data and harm done or is it just how do you
       measure the probability and the amount of harm that
       could be done?  This is very vague right now and it
       remains vague.
                 DR. F. LEVINE:  I think there is no doubt
       in this whole arena there is often an absence of
       systematic empirical inquiry on this subject and on
       others that we have addressed and it's a challenge,
       I think, to the research community to focus more of
       their attention on studies of that genre.
                 Any other comments?  Abbey?
                 MS. MEYERS:  I don't think that there's an
       average way that you can measure risk because if
       each IRB is allowed to interpret it the way they
       want there will be those who say just getting up and
       getting out of bed and crossing the street in the
       morning puts you at risk of getting hit by a car. 
       And I think we saw this translation of -- in the
       Kennedy Greiger Institute's study of lead poisoning
       in children because the way the university has
       defended itself, even though the court found them
       very guilty and compared it to the Tuskegee
       experiment, the institution has said, you know,
       "These children are poor minorities and in single
       family houses in downtown Baltimore and they would
       have been living in lead paint covered apartments
       anyway."  So I think the university hasn't felt that
       they have done anything wrong in improving that
       experiment.
                 So I think we really need to have very,
       very strong interpretations of minimal risk so that
       federally no university would be able to decide to
       interpret it in a more lenient way.
                 DR. F. LEVINE:  Sandy?
                 DR. CHODOSH:  I would like to get to
       recommendation number 4 and into the rationale.  It
       says here that "investigators who collect survey
       data on sensitive topics need instruction on how to
       properly safeguard raw data in computerized files. 
       My question about that is how do we do that?  Again
       are we talking now about certifying that they have
       received the proper education?  How will an
       institution know that they're certified?  Will the
       institution require that they have that training?  
                 Just putting -- you know, putting mandates
       in, and they're good ones, don't get me wrong but
       we're doing it as if it's going to happen because we
       say so and I really think that we have to look
       towards how it's going to be implemented and how
       we're going to be sure about it.
                 The other issue is just a general one and
       it's the last sentence about "under such
       circumstances of people at risk because of what they
       are; procedures for ensuring privacy, that is no
       signed consent form or recording of identifiers will
       be necessary."  Okay.  Or should be avoided
       actually.  But there's no consideration that there's
       another aspect of the informed consent process. 
       One's consent; the other is information.
                 And somewhere I think we should address
       that individuals like this must be supplied with
       information.  Somehow we're missing that.  You know,
       as I -- if you do away with informed consent, does
       that mean you've done away with the informed part of
       it?  I would say that that would be a mistake.
                 DR. F. LEVINE:  I think that wasn't the
       intent.
                 DR. CHODOSH:  I know but that's the way it
       reads.
                 DR. F. LEVINE:  Why don't you pick up that
       part and I'll refer to the other part?
                 DR. COHEN:  I believe -- I'm not so sure
       which exact sentence you're referring to but at
       least the intent of the working group was not to say
       informed consent shouldn't be obtained.  It was
       documentation of consent where the documentation
       could harm the subject.  That leaves informed
       consent if the document -- those are -- you know, I
       don't think of as our intent to not do the
       information.
                 DR. F. LEVINE:  No, I would just emphasize,
       though, that how do we know that the investigator,
       in fact, gave information?  There's no
       documentation.  I mean there needs to be some
       thought given to can that be managed in some way in
       which we're assured that investigators have, in
       fact, provided the information, particularly to this
       kind of a population and without putting them at
       risk.
                 DR. COHEN:  I think the working group would
       agree with that that there are other methods of
       documenting that this was -- information was
       provided other than a signed consent form.
                 DR. F. LEVINE:  I think in large part Jeff
       and I prepared the kind of overview memo and
       overview slides to sort of try to focus NHRPAC on
       where some key recommendations might issue because
       without in any way critiquing this document it was
       the July set of recommendations, and that's not to
       say they still don't obtain, they do but the text of
       some of the recommendations really has a little bit
       more of narrative appended.
                 So Recommendation 4 really ends before the
       "what investigators have to learn how to do."  Not
       that that's not important but it's really what OHRP
       -- how OHRP needs to inform IRBs in terms of what
       they need to be looking toward.  And so I think that
       has sometimes gotten a little bit mixed in.
                 We're getting better at crafting the
       recommendation to avoid having the commentary, I
       think, in the recommendation but I will say that
       awareness is what led us as a working group to put
       such a high priority on the issue of confidentiality
       and the protection of confidentiality, which then
       was spun off as a subject in and of itself and is
       the second subject we'll take up today.
                 DR. COHEN:  Let me reiterate what Greg said
       earlier and that is these recommendations will come
       to OHRP.  It is our responsibility to then implement
       them and to come up with guidance and, you know,
       requirements or whatever that would actually
       implement them.  If the NHRPAC wants to provide
       suggestions on that that's fine but we will receive
       them and then determine how best to implement them.
                 DR. F. LEVINE:  I think Greg is going to
       speak.
                 DR. KOSKI:  Thank you, Jeff, that's exactly
       right.  I just want to point out that when
       recommendations come from this committee a
       recommendation to us to say we should better define
       minimal risk and minor increase over minimal risk
       won't help us.  We know that.  Okay.  That's why we
       asked you to help us define minimal risk and a minor
       increase over minimal risk.  So I hope that that's
       clear.  Thank you.
                 DR. F. LEVINE:  Yes, Alan?
                 DR. FLEISCHMAN:  In response to Greg; yes,
       sir.  But I must comment, although it may spend a
       moment on Abbey's comment about, I think,
       inappropriately putting in the comment about the
       social and behavioral scientists at Hopkins who were
       doing work that was reviewed by the IRB as work
       intended to directly benefit the subjects. 
                 It was not reviewed as minimal risk or
       minor increase over minimal risk research and those
       social and behavioral scientists were doing public
       health intervention research which they considered
       as potentially therapeutic or of benefit to the
       subjects so that it really is not relevant to the
       conversation we're having right now to raise that
       particular research project.
                 DR. F. LEVINE:  Bob?
                 DR. R. LEVINE:  The mistake they made is
       the same mistake that everybody who uses the concept
       of therapeutic research makes.  That is they view a
       whole project as either be therapeutic or not where
       the regulations, which they apparently didn't read
       carefully, say you're supposed to evaluate each
       component of the protocol and those procedures that
       are done with the expectation and reasonable
       probability of a direct benefit for the individual
       are evaluated one way and those that are -- had no
       such probability or intent are evaluated another
       way.
                 If you're looking at therapeutic or
       beneficial procedures the definition of "minimal
       risk" doesn't even apply.  You only evaluate the
       procedures that are not expected or intended to
       benefit along the lines of whether they're
       beneficial.  This is a fairly common error.  It
       would be helpful if we clarified this matter once
       again.
                 DR. FLEISCHMAN:  On point.
                 DR. F. LEVINE:  Go ahead, Alan.
                 DR. FLEISCHMAN:  Reasonable people can
       disagree.  I don't disagree that it's a fairly
       common error.  The only thing that I would disagree
       on from my reading of what happened -- I am not
       involved in that IRB nor in that research project
       but have read a bit about it -- I don't believe they
       made that error.
                 DR. R. LEVINE:  I'm sorry, Alan.  I thought
       I heard you say that they evaluated this as
       therapeutic research.  I must have misunderstood.
                 DR. FLEISCHMAN:  My understanding is they
       evaluated it as the potential for direct benefit to
       the subjects of the research and that there were no
       subjects put at risk without the potential for
       direct benefit.
                 DR. R. LEVINE:  And in what relevant sense
       does the potential for direct benefit differ from
       the concept in the regulations of beneficial?  They
       were evaluating.  They thought that everything that
       was done to each child could be justified under the
       banner of therapeutic or beneficial.
                 DR. FLEISCHMAN:  There were control groups
       in that experiment who were not placed at any harm
       nor risk and the subjects who were in those control
       groups were -- the things that were done to them met
       the criteria for minimal risk but the subjects who
       were in the intervention groups with the potential
       for direct benefit were not being evaluated based on
       a minimal risk criteria nor minor increment over
       minimal risk as best I can tell in reading it.
                 DR. F. LEVINE:  I'm going to table that
       exchange and ask Elliot to --
                 DR. R. LEVINE:  I want to say I understand
       what Alan is talking about and I agree.  I think I
       misunderstood what you said earlier and I apologize
       for that.
                 DR. F. LEVINE: Elliot, and then I'd like to
       go through these recommendations so that we can get
       to the confidentiality.
                 DR. DORFF:  That's exactly what I was going
       to suggest.  Namely that apparently from what Greg
       just said, Recommendation 1, "OHRP should issue
       guidance to IRBs, to others associated with it..."
       and so on is not helpful to OHRP.  And the -- and
       so that maybe what effectively Greg has been saying
       to your group, Felice, is that actually they would
       like some help in doing that and that's the --
       that's exactly the point of the exchange that we had
       before about the child's -- the working group in
       regard to children and your group that maybe the two
       of you -- once you have your Wednesday meeting --
       maybe by e-mails and the like before our next
       meeting you could begin to work on that kind of a
       thing.
                 So I take it that we now want to go to
       Recommendation 2, right, and discuss that.  And
       there "OHRP should clarify that much of the research
       in the social and behavioral sciences involves
       minimal risk."  However we define that, right?  At
       the moment we're simply going to understand that
       there's going to be a much clearer definition of
       that but however we define that the recommendation
       is that much of the research in the social and
       behavioral sciences involves minimal risk.
                 The question that I have is the one that
       has been recurring throughout our discussion of
       this.  Well, what about people who are -- you know,
       a study of criminals or a study of people who are
       engaged in licentious sex or, you know, something on
       that order?  Right?  
                 In other words, where the -- it's not just
       the third party that's involved.  That we talked
       about before but the actual human subjects
       themselves are not really at minimal risk as a
       result of the study.
                 I mean, they may be indicted as a result of
       it.  You know, they may be -- they may lose their
       marriage as a result of it.  
                 You know, all of those kinds of things I
       think are not -- so that's why I'm really hesitant
       about much of the research in social and behavior.
                 I mean, I think maybe the recommendation
       ought to read something like, you know, that social
       and behavioral sciences involve sometimes different
       kinds of risks and that IRBs have to be aware of
       that but I'm just worried about much of what you had
       -- first of all, I should ask you what did you have
       in mind by "much of the research in social and
       behavioral sciences involve minimal risk"?  Maybe I
       should ask that question first.
                 DR. F. LEVINE:  I hear your problem because
       we can all think about the challenging kinds of work
       on vulnerable issues and/or at risk populations so
       what does one mean by much and many but the
       empirical reality is that many IRBs are looking at
       what is just a political attitude survey given to an
       adult population that is just, you know, your normal
       -- when someone -- how many cups of coffee people
       drink when they're completing boring questionnaires
       to see the relationship between sort of frustration
       level and, you know, preoccupation and it is just --
       I am not implying that that is trivial.
                 It is asking very important questions. 
       It's just noninvasive.  Noninvasive, I don't mean
       just biologically noninvasive, just noninvasive into
       the -- kind of the psychological and interpersonal
       aspects of people's lives, and that's why it's the
       second half of that recommendation, you know, in a
       way that's to the meat that if we could get a better
       description of expedited, and that's in a way that
       motivated the cover memo, but if we can -- which so
       much of the expedited examples, the listing are so
       embedded not in social and behavioral science
       examples.
                 And only one clause is that an IRB that
       doesn't have much foundation of experience in
       looking at this takes these every day kinds of
       research on adult populations and, indeed, gives it
       in a way the same kind of scrutiny, which isn't a
       really good allocation of their time.
                 And I understand your notion of, well, how
       many is many when there are all kinds of research we
       can cite, and I do all the time to you, that are,
       you know, challenging studies.
                 Let me do this if I can.  We have an ex
       officio member who I think we should -- and who is a
       member of the working group.  Susan and Greg, and
       then let's try to move to the next recommendation.
                 DR. RUBIN:  Philip Rubin, National Science
       Foundation.  I think we moved too rapidly by
       Recommendation 1 and dismissed it too easily.  Let
       me say that obviously the working group didn't solve
       all the problems of how you evaluate risk and harm
       but they should be commended for making two concrete
       steps that are a great advance beyond what has
       previously been done, first of all, to differentiate
       the probability and magnitude.  That issue is
       crucial to come up with a metric if one wants to.
                 And, secondly, the stunning advance of a
       chart that attempts to define kinds of harm and
       behavioral and social research and methods for
       ameliorating that --I'm not saying whether or not I
       agree with that chart or the details in it but those
       are the exact kind of concrete steps that you need
       to take to provide the kind of definition that OHRP
       wants.
                 Thank you.
                 MS. KORNETSKY:  I just want to pick up a
       little bit on Elliot's comment.  I also have a
       concern about number 2.  I mean, I understand what
       you're saying, Felice, but I come also from an
       academic medical institution that also does social
       and behavioral science research very different and
       I'm not so sure I would say the majority of social
       and behavioral research that we do at an academic
       medical institution is minimal risk.
                 So it's also -- it's within the context.  I
       understand that IRBs may overact but I think making
       broad statements like that to the IRB community
       interpreted, you know, throughout the country is not
       in the best interest.
                 DR. F. LEVINE:  I am wondering as I
       wondered about three months ago with public use
       whether we aren't at the point where some of us here
       could massage the recommendations that the working
       group has given us to better clarify what we want to
       say because, indeed, one of the advantages we saw
       that operationalize very well with public use, I
       think, and with third parties is that we have
       different professionals with different sets of
       experience, and certainly that is true when I think
       of a large quadrant of social and behavioral work
       that's done on crime related issues or health
       related issues that those are more sensitive.
                 And I think the point is more to get the
       emphasis on expedition with that but I'm not sure we
       need to go through each of those if we can accept
       them in spirit and then work through the detail, and
       I'm wondering whether we can get some consensus
       around that.
                 Elliot?
                 DR. DORFF:  First of all, in response to
       Phil, point noted and absolutely right.  I certainly
       did not mean to in any way, shape or firm minimize
       the work that the working group had done.  And quite
       the contrary, I think the two pieces that you
       mentioned are, indeed, very much steps forward and
       that now, hopefully, your working group and that
       working with the children's will now be able to take
       advantage of in crafting a sense of minimal risk. 
       Absolutely.
                 In terms of Recommendation 2, what we are
       looking for is some kind of language in which we say
       that, you know, while medical experiments commonly
       involve risks, the social and behavioral science
       studies do not necessarily involve them or something
       because I mean, we want some --
                 MS. KORNETSKY:  No.
                 DR. DORFF:  No, all right.
                 MS. KORNETSKY:  No, I think you
       misunderstood me.
                 DR. DORFF:  Okay.
                 MS. KORNETSKY:  Not at all.  No, it depends
       on the context in which you're working.  I mean a
       lot of the behavioral research that would be done at
       an academic medical community may not be minimal
       risk.  It's contextual within how you're evaluating
       it versus a lot of the research that, you know,
       Felice may have more experience, done outside of the
       medical community.
                 DR. DORFF:  So do you have language that
       you would see there?
                 MS. KORNETSKY:  Not right now, I don't have
       language but I can think about it.
                 DR. F. LEVINE:  And Susan will.
                 Greg?
                 DR. KOSKI:  Thank you.  I just want to
       again add a little bit of context here and perhaps
       go back to something that Dr. Marburger said this
       morning, which echoes something that we've been
       saying for better than a year, and that is we need
       to find the ways to make sure that this whole
       process for protection of human subjects ensures
       protections that are appropriate to the risks. 
       Okay.
                 And one of the problems that I see as I go
       around the country and look at IRBs and talk to
       investigators and all, in both the medical and the
       social and behavioral sciences, and recently the
       humanities is that in many instances our IRBs are
       struggling with a syndrome that I've referred to as
       reactive hyperprotectionism.
                 And that their uncertainty about their
       ability to faithfully exercise their
       responsibilities under the regulations leads many of
       them to sort of blindly shoot at anything that moves
       and looks like the research bird and bring it down
       sometimes inappropriately.
                 So that looking specifically at the area of
       social and behavioral sciences I think we would all
       agree, yes, there are whole groups of research
       projects that could legitimately be classified as
       either exempt or expeditable and yet those projects
       are being subject to full board reviews
       inappropriately further draining or at least wasting
       the precious resources that they already have
       available to them to do a monumental task.  That's
       self-defeating.
                 So that I think one of the things that we
       have to do here is to provide the kind of guidance
       to these investigators and IRBs and all to help them
       have a higher degree of confidence in how they're
       exercising their responsibilities.
                 And, of course, that's why the kinds of
       guidance and all that can be produced has to be
       coupled with ongoing efforts to evaluate and
       strengthen the actual program so that there is
       actually a system here that is being built so that
       ultimately the committees truly need to have the
       expertise and the confidence to be able to exercise
       their responsibilities in an appropriate and
       meaningful way.
                 So this -- what this committee is doing now
       in looking at issues of social and behavioral
       sciences and tomorrow or later today, I'm not sure
       when it is of actually looking at activities in
       other areas such as journalism and history and all,
       where do we or how can we appropriately, you know,
       guide the activities to make sure that we're using
       our resources in the most effective way.
                 So it's my hope that that's what these
       reports from this committee and all can help us get
       to and why I have pushed so hard over the last year
       to make sure that these issues stay on the agenda
       and very much in the lime light of these
       discussions.
                 DR. F. LEVINE:  Susan?
                 MS. KORNETSKY:  Greg, boy, do I want to
       believe you with the flexibility that you're giving,
       you know, to IRBs.  I know that you've been in the
       office a year-and-a-half and have inherited a
       history that you're working very hard to work
       against but you're right.  IRBs are scared.  They
       are taking a very conservative approach and I'm not
       so sure we're there yet after still reading on the
       listserve the noncompliance letters and the types of
       things that are being cited that those two concepts
       are merging.
                 So I'm being very frank about it but from
       the IRB community that's what we feel and that's the
       pressure we're getting and we're not going to take a
       chance.  So I urge the office to start, you know,
       your office -- what you're preaching and whatever
       and I don't mean it that way but I mean what I want
       to believe and I -- that we begin to see that
       flexibility allowed.
                 DR. KOSKI:  Just a quick response.  I think
       everyone as they again see the roll out of the
       efforts in quality improvement that dovetail with
       the developing private sector initiatives in
       accreditation, as well as coupled with the ongoing
       efforts in outreach and education, we'll begin to
       see it.  These aren't things that simply change
       overnight.
                 This is a major shift in the cultural
       paradigm that we operate in, in this research
       community, and it takes time to build but I think as
       the quality improvement initiative is rolled out to
       its full capacity where there are ongoing
       interactions on a daily basis.
                 I've had at least three people come up to
       me, for instance, today, who commented to me how for
       the first time their IRB or someone actually called
       and interacted with people in the office and how
       pleased they were with the approach and the support,
       the help that they got.  It takes time but again
       everybody has to share in that responsibility. 
       It'll get there.
                 DR. F. LEVINE:  I'm going to call on Judy
       and then I'd like to propose a strategy as to how we
       might proceed and see if we can get a consensus
       around that so that we can also move on to
       confidentiality.  We've been working very hard on
       that and the working group would like to have some
       feedback on those recommendations or advance them to
       you.
                 DR. SIEGEL:  I'd like to suggest for
       Recommendation 2 that instead of making assumptions
       about social and behavioral science, which you've
       done here, that if you use -- I'm going to give you
       some wording but it's very messy.  To really talk
       about what I think we're talking about, which is
       that there is a range within this subcategory that
       may be broader than the range in maybe medical
       research and I've written a sentence which I think
       maybe conveys it.
                 I'm not sure but you want to give
       recommendations and that's what Susan is saying. 
       People need to hear recommendations.  "Because the
       range of types of experiments in social and
       behavioral science is broad it is incumbent upon the
       IRB to consider..." and then whatever a body of
       recommendations could be "...and then based on that
       assessment proceed according to the assessed need."
                 Because again I think what this whole
       recommendation is trying to do is say you have to
       look at what you're given, given the range that you
       could possibly get, and I don't think you can just
       say because it's social and behavioral science you
       should look less.
                 DR. F. LEVINE:  I think that's an extremely
       helpful way of turning the emphasis and then that
       also then leads to the expansion of the expedited to
       better operationalize what's under minimal since
       that is not sufficiently understood.
                 Jonathan?
                 DR. MORENO:  I think what I find bothersome
       about the language and the use of the word "much"
       and so forth is that there's an implicit comparison
       with biomedical research here and I find that
       bothersome.
                 I'm not persuaded that the range is any
       different and so forth.  I think what you're trying
       to do, and I understand why and I understand Greg's
       point, you're trying to do is compensate for the
       fact that there is an expertise very often on IRBs
       with respect to social and behavioral research and
       I'm not sure this is the way to get at that problem.
                 The way to get at that problem is to do
       what the regulations already require that people
       with expertise in the relevant subject matter of the
       protocol be either on or consultants to the IRB and
       I think we all agree at least ethically if not in a
       regulatory sense the relevant communities be
       represented.  I think that's what you -- so I think
       we're sort of laboring here with language that isn't
       going to change anything.  It could be very
       misleading to IRBs.
                 OHRP says not to worry because much of this
       stuff is minimal risk anyway and I just think what
       we need to do is get to the system.  The system
       requires more social and behavioral science or
       presentation and more folks in the communities that
       are affected.
                 DR. F. LEVINE:  I think we're in heated
       agreement that Recommendation 2 can be reworded to
       either make an empirical statement about the range
       of different types of research in the social and
       behavioral sciences or an implicit comparison to how
       that diverges from other fields, I think, and I
       think Judy was moving us in that direction.  I think
       that was the intent.
                 Let me suggest the following to see if we
       can do this operationally:  I'd like to think that
       the spirit of what the working group was seeking to
       convey is being appreciated and valued by NHRPAC and
       that we can then take these, use the strengths of
       what the working group has, as Phil underscored,
       contributed to Recommendation 1 and to work on that
       with the Children's Working Group to offer the
       NHRPAC something that is a real value added building
       upon this contribution.  That the kinds of things
       that we're now talking about, the Recommendation 2,
       the Recommendation 3, and the abbreviation of
       Recommendation 4, I think, could be worked on as a
       modified document within NHRPAC that we can then
       bring back in March and I'd like it to reside here
       because I think there's a different way of reading
       within this group that helps bring it to closure in
       a way that a more homogeneous group is less likely
       to do.
                 Elliot?
                 DR. DORFF:  Just to -- I want to try to
       capture Greg's concern that, you know, IRBs are
       being over zealous in some of these kinds of things
       and maybe the way to do that is to use Judy's
       language and then use (a) through (e) for Mary
       Faith's language that we talked about this morning. 
       In other words, just remind IRBs that what you're
       looking at is things like the quantity.
                 I'm just adapting here but the quantity of
       information, the nature of information, the
       sensitivity of the information, right, because I
       mean if they're reminded of things like that and
       then look at a study of the senses or something like
       that they may decide that none of that really is
       relevant to this particular study and we're
       finished, right.
                 So, in other words, if they have some very
       clear issues or some very clear criteria for
       evaluating the risk of harm to human subjects, if
       they have those very clear bullet points then it
       may, in fact, lead them not to be over zealous when
       they shouldn't be.
                 DR. F. LEVINE:  Abbey, Sandy, and then we
       need to come to closure on our recommendation.
                 MS. MEYERS:  The last three pages of this,
       I'm very bothered by this.  "Categories of research
       that may be reviewed by the Institutional Review
       Board through expedited review procedure."
                 DR. F. LEVINE:  That's not our proposal.
                 MS. MEYERS:  Where did this come from?
                 DR. F. LEVINE:  That's the current regs. 
       We're saying that that needs to --
                 MS. MEYERS:  This is the current regs?
                 DR. F. LEVINE:  Yes.  We're saying that
       that needs to be reworked or rethought.
                 MS. MEYERS:  Okay.
                 DR. F. LEVINE:  Sandy, Jonathan and then
       I'd like to --
                 DR. CHODOSH:  Okay.  I just think that we
       have to remember there's a part of Recommendation 1
       that goes into Recommendation 2 and it's really, I
       think, key to how things actually operate.  We talk
       about a designated IRB person should have knowledge
       of what they're doing and this, I think, is the key
       is that there are three people.
                 It's the administrator of the IRB, the
       chair of the IRB and the designated persons who are
       doing expedited review.  Those people must be the
       most knowledgeable and that it seems to me could
       solve a great deal of the problem without
       encumbering the whole IRB group.  And if we don't
       stress that that is where the education clearly must
       be, the expertise must be there, just like you bring
       in an expert to review the protocol, an expedited
       review should require the same thing if they don't
       have the expertise.
                 DR. F. LEVINE:  The chair?
                 CHAIRPERSON MARSHALL:  So I would propose
       then that we accept Felice's suggestion that I would
       be happy to take a couple of names now for those who
       would be interested on the committee in fine tuning
       this document to bring back to the committee.
                 Sandy, Susan, Felice and I've got my eye on
       Abbey.  She's avoiding eye contact over there.
                 [Laughter.]
                 MS. MEYERS:  I think I'm on three
       subcommittees.
                 CHAIRPERSON MARSHALL:  You're on three.
                 MS. MEYERS:  I'll do it if you want me to
       but by e-mail.
                 CHAIRPERSON MARSHALL:  Okay.  By e-mail. 
       So you'll maybe give us sort of -- once we are close
       to penultimate to bring it back to the committee you
       would take a look at it.
                 Judy, Jenny.  All right.
                 Confidentiality?
                 DR. F. LEVINE:  Of course, no doubt, each
       of you have committed the report to memory by now so
       we're just going to give a little bit of an overview
       and then open it up for questions.
                 One of --
                 CHAIRPERSON MARSHALL:  I'm sorry.  I was
       just going to say procedurally, folks, we're going
       to break for lunch at 1:00 o'clock and resume at
       2:00.
                 DR. F. LEVINE:  So we're hoping to move
       things along.  As, I think, has been part of the
       texture of much of our discussion about research
       involving human subjects across fields and certainly
       centrally true in the social and behavioral sciences
       that a biggie is protecting the confidentiality of
       the data.
                 And in the social and behavioral sciences,
       this is not a more or less than any other science,
       but a key arena of risk as was clear from many of
       our discussions relates to issues of confidentiality
       and the question  And you can reduce that risk or
       ameliorate it by ensuring exceptional data
       protection plans.
                 So we spun off intensive attention to this
       issue with Sally Hillsman, a member of our working
       group, taking the lead and David Gleckman, who is on
       the Interagency Committee and also, I think, an ex
       officio member but, if not an ex officio member,
       certainly a presence at all the NHRPAC meetings from
       the National Institute of Justice helping us take a
       lead in our working group on these issues.
                 And essentially we have five areas where we
       have focused our recommendations and that is the
       first that I've just mentioned, reducing risk
       through confidentiality protections and then how we
       can go about the process of enhancing
       confidentiality protections, being wise and candid
       and often that would reach to, of course, consent
       about the limits of confidentiality.
                 And then something that we call, which may
       be vague in its title, building institutional
       support but by that we mean the home institution
       support for the investigator and the IRB, and the
       process that has been established in approving
       research.
                 And then the last issue is when and we're
       not taking up the issue of whether but when access,
       limited access has been approved on a limited basis
       for nonpublic use data that all obligations with
       respect to data protection plans and confidentiality
       by other users must still obtain.  And obviously
       there are other issues with respect to limited
       access.
                 We're not addressing those in the
       confidentiality part but we wanted to underscore
       that no matter who uses it or when they've been
       authorized to use it and with what approvals by IRBs
       that they must adhere to the same confidentiality
       standards.  We really worked on quite a high bar.
                 Recommendation 1:  "Reducing risk through
       confidentiality protections."  We feel, you know,
       life is a dynamic process.  It's clear from a lot of
       the issues we address and that the Recommendation 1
       is that "OHRP should issue guidance to IRBs
       indicating that the degree of confidentiality
       protection required in research protocols be
       commensurate with the degree of risks associated
       with the type of data collected."  And obviously in
       more than minimal risk there really needs to be real
       attention to the data and, if the issue is
       confidentiality, substantial attention to the nature
       of that data protection plan.
                 "OHRP should emphasize to IRBs that a good
       data collection plan can reduce or ameliorate the
       degree of risk if that is the core area of risk." 
       This is not to take up the other issues of risk. 
       Let me go through them.
                 "Enhancing confidentiality protections." 
       And you can see in the document and in the
       recommendations that there is attention to the issue
       of certificates of confidentiality, of which there's
       quite a -- we include a table to illustrate that
       there's quite a degree of variation that
       investigators need to be alert to and IRBs as well.
                 So we have as recommendation 2 "OHRP should
       clarify specifically what certifications are
       available to protect data, including how the
       certifications work, which agencies have the
       authority to grant them, when certifications may be
       sought, what certification protects."  For example,
       in some it's only the identifiers or whether it's
       the identifiers in all of the data.  There's great
       variation.
                 And (e) where confidentiality gaps in
       certification exist that need to be shored up so
       this is kind of a collective effort to identify
       those areas where NHRPAC and OHRP could usefully
       provide an important service in enhancing the
       strength of the confidentiality provisions.
                 "OHRP should lead an effort to ensure the
       adequacy and alignment of certificates of
       confidentiality issued by federal agencies."  We
       were not sure where it could ultimately reside but
       we thought OHRP could play a very important
       leadership role in getting something going so that
       this kind of process was put in place.
                 Recommendation 3 is that "OHRP should lead
       a federal review of existing legal authorities,
       including statutes and regulations which provide
       research confidentiality protections.  This review
       should identify with the various laws protect, how
       the protections are obtained, who administers them,
       and where potential gaps in the protections exist. 
       Where outstanding issues or gaps are identified a
       proposal to address these gaps in research
       confidentiality should be developed through some
       kind of advisory consensus process."  And we have a
       table that aligns with that.  As you can see there's
       again a great deal of ambiguity as to what exists.
                 We also think in this period, obviously it
       takes a while to improve the process, the mere
       posting of these materials or final versions of them
       would be a tremendous service to IRBs and to
       research investigators and could be a useful
       document in final form posted on the OHRP web site.
                 And, I think, that's the spirit of that
       clearing house function, an electronic clearing
       house linking information on all federal and state
       research confidentiality protections as they get
       better all to the good but even in its present form
       it certainly is instructive.
                 Recommendation 5 is one on "identifying the
       limits in confidentiality protections."
                 Four, I think, I just overviewed or at
       least tried to.
                 PARTICIPANT:  I wasn't listening.
                 DR. F. LEVINE:  You weren't listening.  You
       know the recommendations too well.
                 [Laughter.]
                 DR. F. LEVINE:  Five is "guidance should be
       developed for accurately and effectively describing
       the confidentiality protections in the consent
       process.  Special care should be given to describing
       when and under what circumstances confidentiality
       will or will not be maintained, along with any
       reasonable and anticipated risks associated with the
       disclosure of the information." 
                 For example, as we know in a number of
       ethics codes if a subject in the course of providing
       information says, "I'm considering killing my
       mother," then there is a limit to confidentiality. 
       There are competing principles and there needs to be
       thought about better informing researchers and IRBs
       about the interactions of those, however rare those
       cases may be.
                 Recommendation 6:  And Recommendation 6
       really flows from taking up the issue of the
       research institution's obligations with work that
       has been reviewed and approved by an IRB and the
       data collection plan has been approved and the
       guarantees have been provided, and investigators
       have committed themselves as researchers to these
       obligations, IRBs have also sought to have that same
       high bar, and that we thought that it was important
       that all parties, meaning the research institutions
       be singing from the same page.
                 So "host research institutions..." this is
       a very important issue and hopefully the text
       explain why "...should be cognizant of their
       obligations to actively support the investigator in
       protecting all confidential information from
       compelled disclosure or as otherwise agreed to in
       the data protection plan.
                 OHRP should consider explicitly requiring
       this as a term and condition of the assurance and
       any future accrediting bodies should consider
       requirements in this area."  And that is to really
       give more teeth to what investigators have sought to
       provide and create and to what IRBs have sought to
       ensure and that's an important -- we thought a very
       important new element in the range of issues that
       could really improve the operations of the system.
                 The seventh one I won't repeat because I
       started with that as an example and that is that
       even in circumstances where secondary users have
       access to nonpublic use data, data under some kinds
       of restrictions, that if they receive that data or
       have access to use it that there's a
       transportability of the data protection plan, that
       they have the same high bar as other users with
       restricted access to maintain that same degree of
       commitment to the confidentiality plan that was
       originally established, and that's the overview.
                 Elliot and then Sandy.
                 DR. DORFF:  I think this is all very good. 
       I would only in Recommendation 5, I would only add
       where you have "special care should be given to
       describing when and under what circumstances
       confidentiality will or will not be maintained..." I
       would say "and why" because in the paragraph that
       you have above you list several different reasons
       why not.  I mean, some of them are legal as in the
       mandatory reporting laws or the Tarasoft [ph]
       decision in regard to "I'm going to kill my mother,"
       right.
                 Some of them come from professional ethics
       codes as to why you would not do it, you know,
       maintain confidentiality.  And there may be other
       practical reasons or something like that so that I
       think it would be important to spell out when there
       are limitations and there definitely are.  When
       there are limitations to confidentiality what the
       grounds of those limitations are.
                 DR. F. LEVINE:  Let me say the motivation,
       the philosophical motivation is to strengthen
       confidentiality by acknowledging the limitations of
       confidentiality.
                 Sandy?  
                 Susan, was your hand up?  
                 Then Adil and then Greg.
                 DR. CHODOSH:  Felice, I want to
       congratulate the group.  I think it is an excellent
       piece of work.  Just one point that I would like to
       make and that is that I wouldn't want there to be an
       implication that when risk is extremely minimal that
       there is no need for confidentiality, that there
       needs to be a lower bar which you cannot go below,
       and that may be.  I'm not sure but I didn't quite
       get that in here.  I just don't want that
       implication to creep in.
                 DR. F. LEVINE:  Friendly amendment.  That
       was the intent and we'll fix it up.
                 Susan?
                 MS. KORNETSKY:  I think there is very
       little to argue with in here.  So much so that I
       almost see this as applicable.  I'm not sure why if
       we make this recommendation that it's just for
       social and behavioral science research because this
       type of protection applies throughout.  So I
       wouldn't just think that it's for that.
                 DR. F. LEVINE:  In a way nor did we but
       because that is a frequent dimension of risk that's
       why we took on sort of the charge of addressing it
       but we do see it as quite generic and I tried to
       introduce it in that way.
                 Adil?
                 DR. SHAMOO:  Thank you.  I concur with the
       previous comments.  I have a question and then a
       comment.  Your Recommendation 1, are you addressing
       the IRB or the investigator?  
                 DR. F. LEVINE:  Both.
                 DR. SHAMOO:  Well, by the time the research
       protocol comes and the informed consent comes to the
       IRB it's almost too late for "OHRP should emphasize
       to IRB that a good protection plan can reduce or
       ameliorate the degree of risk."  What you want is
       the investigator to spend time designing the
       protections and then the IRB review it and I don't
       think this is clear to me where that will come from.
                 DR. F. LEVINE:  Let me say that's why I
       said both because as this is more pervasively
       understood, investigators will be doing a better
       front end job in thinking this through in advance
       but it clearly is something that would inform how an
       IRB looks at a protocol.
                 DR. SHAMOO:  Why shouldn't we just clarify
       it?
                 DR. COHEN:  Yes.  You're absolutely right,
       Adil, but in the real world if the IRB isn't
       requiring it then most investigators aren't going to
       do it and so the idea here was that where the OHRP
       has its authority is primarily over the IRB.  So by
       making and reiterating to the IRB that they need to
       enforce this they need to look at the data
       protection plans and they need to require data
       protection plans from investigators then we
       accomplish the other end.  We could add, and perhaps
       maybe we should as we did in the other -- in our
       previous set of recommendations -- encouraging OHRP
       to expect training for investigators in this
       important area.
                 DR. SHAMOO:  But we do have places even in
       the 45 C.F.R. 46 where we give principles or
       elements of what ought to be and we could put that
       there so the investigators ahead of time rather than
       be a surprise, especially new investigators.
                 DR. F. LEVINE:  Jonathan, Greg, and then
       we're going to open it up for comments from our
       audience.  Brief comments so we can reach closure on
       what seems like seven minutes left the Chair said.
                 Jonathan?
                 DR. MORENO:  I've been covered by a
       previous comment.
                 DR. F. LEVINE:  Greg?
                 DR. KOSKI:  The Common Rule calls for
       appropriate protections for privacy and
       confidentiality so that I would anticipate that
       these would be issued in the form of guidance rather
       than changes to the Common Rule.
                 And while the recommendations here are
       appropriately directed toward OHRP as is the charge
       of this advisory committee, the issues here seem to
       be of the nature that all of the federal agencies
       that operate and deal with these kinds of issues
       would be interested in attacking that so that again
       I would anticipate that this is an item that these
       recommendations be taken up by the Human Subjects
       Research Subcommittee, of whom, you know, our ex
       officio members are here representing.  So I would
       think that this would be an appropriate area to go.
                 DR. F. LEVINE:  Comments from the floor?
                 DR. PETERSON:  My name is Dr. Joseph
       Peterson.  I'm a clinician and we are doing a lot of
       research now in behavioral, specifically HIV and
       AIDS.  I think when you are talking about IRB I
       think there was a lot more time given for the ones
       that are in an institution like Johns Hopkins or
       other places.  There are also other IRBs that are
       very minimum.
                 One, I think, is the one in Columbia that
       are not very much aware and they're very much scared
       actually taking some tasks that actually what the
       community is doing.  Some of the research that's
       going to be done in the future that will get applied
       for a couple of them are in the community like in
       the churches to see any kind of behavioral changes
       so how can we be able to address these IRBs that are
       independent that they're not going to be afraid of
       taking this kind of task, which really has a lot of
       confidentiality as far as I'm concerned because it
       doesn't have any names on it.
                 So is there anything that the committee
       could do to support them or if they have any problem
       of not understanding what the task is, is there any
       support on the confidentiality part?  I don't know
       if it's a question or a comment.
                 DR. COHEN:  Both the Common Rule and the
       FDA regulations apply to all.  You know, it doesn't
       matter where the IRB is.  Independent IRBs have to
       comply with the Common Rule and for FDA regulated
       research with FDA regulations.  Any guidance that's
       issued out of OHRP or FDA will apply to all IRBs
       regardless of whether they're independent or
       institutional.
                 DR. FANNING:  I'm John Fanning from the
       Department of Health and Human Services.  Your
       Recommendation 5 uses the term "confidentiality". 
       It is often not a very useful word because it
       doesn't convey a lot about what will really happen. 
       What people need to know is not the circumstances
       under which confidentiality will or will not be
       maintained but actually how their information will
       be maintained.
                 For example, they may answer questions and
       think that only the person to whom they're giving
       the answers will ever see them.  In fact, other
       people in the research term may see them and so on. 
       So I think confidentiality may be a useful catch all
       word but it's not very useful when you're explaining
       things to people and has the risk of suggesting more
       protection than actually exists.
                 I also have a few editorial comments about
       the use of the term "certification" in Item 2 which
       I can give you later.
                 DR. F. LEVINE:  Thank you.  And I think
       some of those issues will be returned to under the
       discussion of consent.  I'm going to turn this back. 
       Being in the awkward position of presiding over the
       preparation of this document, I think I should not
       chair the final acts on it.
                 CHAIRPERSON MARSHALL:  So let me see what
       the pleasure of the committee is.  It seems as
       though we are in a fair degree of consensus about
       the document.  Are we far enough along that we can
       move that we forward the advice to the Department of
       Health and Human Services?  Jonathan?
                 DR. MORENO:  Well, I move that we adopt the
       document in principle subject to further editorial
       clarification and improvement.
                 CHAIRPERSON MARSHALL:  Exactly.  Turn your
       mic on, Sandy?
                 DR. CHODOSH:  I presume that we will be
       able to do that by e-mail and that the whole group
       will be involved.
                 CHAIRPERSON MARSHALL:  Right.  Or at the
       level of the committee we would fine tune it, send
       it out via e-mail and so forth.  So let me ask for
       a show of hands for those who are in support of this
       document in principle and in fine tuning it and it
       bringing it back to the committee for its final
       approval?
                 MS. KORNETSKY:  Does that include making it
       broader or leaving it?
                 CHAIRPERSON MARSHALL:  That includes making
       it broader, the suggestions that we've talked about
       here.
                 [A show of hands.]
                 CHAIRPERSON MARSHALL:  All right.
                 PARTICIPANT:  A point of information.
                 CHAIRPERSON MARSHALL:  Yes.
                 PARTICIPANT:  When you say committee
       members does that include the ex officios?
                 CHAIRPERSON MARSHALL:  No, we're at the
       level of the committee now.
                 PARTICIPANT:  Okay.  Thank you.
                 CHAIRPERSON MARSHALL:  Those opposed? 
       Anyone opposed?
                 [No response.]
                 CHAIRPERSON MARSHALL:  It would be posted. 
       Let me clarify.  It would then be posted on our web
       site for general input.  All right.
                 Any further business?  We need to come to a
       close.  Well, thank you all for a very productive
       morning and we look forward to seeing all of you
       back here at 2:00 when we will hear from our guest,
       Alan Milstein.
                 [Whereupon, at 12:55 p.m., a luncheon
       recess was taken.]
                                   - - -                     A F T E R N O O N  S E S S I O N 
                                                                   [Time Noted:  2:07 p.m.]
                 CHAIRPERSON MARSHALL:  Everyone, be seated. 
       Find yourselves a space.  We are blessed with the
       problem of having perhaps more persons than chairs
       but I think that we can and hope that we can rectify
       that soon.
                 Welcome back.  I think we're going to have
       a very busy and interesting afternoon.  As the Chair
       of the NHRPAC I wear many hats or I guess just being
       here today I wear the hat of being the Chair but I
       also am a bioethicist at the University of Kansas
       Medical Center and I also am a daughter, and I just
       wanted to say hello to my mom and dad who are
       sitting back there.
                 [Applause.]
                 CHAIRPERSON MARSHALL:  Hi, mom and dad.
                 PARTICIPANT:  NHRPAC is a family.
                 CHAIRPERSON MARSHALL:  NHRPAC is a family. 
       There we go.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Those of you who
       have been reading the academic literature and
       actually the lay press, The Washington Post, know
       that the issue of informed consent is something that
       is pertinent these days not only to folks like us
       who are immersed in the ethics of human subjects
       research but also to others in government and to the
       public at large.
                 Anyone who has read the Chronicle of Higher
       Education recently may have seen the headline
       "Crusader for the Rights of Research Volunteers Sues
       Everyone in Sight."
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  Not a subtle
       headline.  I actually wanted to entitle this session
       "Who's Afraid of Alan Milstein" but Kate wouldn't
       let me do it so to continue our literary tradition
       but it is my distinct pleasure to introduce to you
       Alan Milstein.
                 Alan is an attorney for a private law firm
       and, as you know, I think he entered the arena of
       human subjects research and the adequacy or
       inadequacy of protection of human subjects by
       representing the Gelsinger family in their law suit
       against the University of Pennsylvania and he has
       since become active in other -- in the legal arena
       in other cases as well.
                 Alan also, aside from being a practicing
       attorney, Alan has his master's degree in American
       studies from the place where I work, which is the
       University of Kansas.  And aside from that, he also
       is a fan of Bob Dillon and other important musicians
       so that let's us know he's a great guy from the
       beginning.
                 I am also happy to introduce panel members. 
       We would like to present a balanced perspective here
       looking at the issue of the effect of civil
       litigation on the protection of human subjects
       research and I am delighted to introduce to you two
       panelists, Karen Rothenberg, who is the founding
       director of the Law and Health Care Program and also
       dean of the law school at the University of
       Maryland.  And Professor Rothenberg has done a lot
       of work in the area of health care, health care law,
       the inclusion of women in research as research
       subjects, genetics research.  She is well grounded
       in the area of human subjects research and things
       that attend to that.  So we are really delighted
       that she could be with us.
                 Thank you so much for coming today.
                 And Paul Lombardo, my colleague at the end
       of the -- close to the end of the table.  Paul is
       an attorney and a historian from the University of
       Virginia where he directs the Program in Law and
       Medicine.  What I can tell you about Paul aside from
       his professional title is that his dissertation was
       on the Buck versus Bell case, which those of you who
       don't know, this is a very important case.
                 It's the case that sort of established the
       legal precedent for involuntary sterilization in the
       United States.  Carrie Buck and her mother and her
       daughter were all inmates, I think, is maybe the
       most apt term at the Lynchburg Colony.  Their crime
       being that they were socially perhaps disadvantaged
       and gave birth, at least one or two of them, out of
       wedlock.
                 Paul did the defining research, the
       definitive research that showed that neither Carrie
       nor her mother nor her daughter had any mental
       disabilities at all.  Unfortunately Buck versus Bell
       still stands.  It went all the way to the Supreme
       Court.
                 My mother, who is sitting in the audience,
       actually grew up on the same street that Carrie Buck
       did.  It's visible from the University of Virginia
       hospital.  And Paul is an enophile [ph].  If you
       need any advice on fine wine he'd be happy to
       provide that as well.
                 [Laughter.]
                 CHAIRPERSON MARSHALL:  So I'm going to turn
       the session over to our own very capable Mark
       Barnes, who you all know is not only a practicing
       attorney but has worked in the area of advocacy for
       persons who have AIDS and are HIV positive; is, I
       think, the primary author of our report on financial
       relationships and conflicts of interest in research
       and always has the mojosed [sic].
                 So we are turning things over to you, Mark,
       and we look forward to a very interesting afternoon.
                 MR. BARNES:  Thank you, Mary Faith.
                 Welcome to our panelists.
                 The way that we're going to do this, this
       afternoon is the following:  We invited Alan to give
       a formal presentation and then have Karen and Paul
       really as respondents to Alan's presentation.  Alan
       and I spoke on a panel together, I guess it was over
       the summer, before the American Association of
       Medical Colleges, and I'm sure that he will be
       provocative and that there will be much to say in
       response.  Perhaps some in agreement and some in
       disagreement so I'm just going to go first and take
       about 15 or 20 minutes to do a presentation.
                 Is that fair?
                 CHAIRPERSON MARSHALL:  Yes.
                 MR. BARNES:  Okay.  And then both Karen and
       Paul will respond.
                 MR. MILSTEIN:  As somebody said once, I
       think they invited me so you could all see whether
       I'm as big a son of a bitch as you heard I was.
                 [Laughter.]
                 MR. MILSTEIN:  What I thought we would do
       is just go through some of the hot topics in the
       litigation that I've been involved with and I have
       chosen the topics that really, I think, I'm in
       disagreement with this group on.
                 The first has to do with the distinction
       between nontherapeutic and therapeutic research.  As
       I'm sure you know, a lot of bioethicists can't stand
       that distinction.  And the reason they give is a
       good one really and that is that the term
       "therapeutic research" from a lawyer's point of view
       is a misrepresentation.  It implies that the
       research is therapy when it's research.
                 Now whatever you guys decide to call this
       distinction, and you can call it pure volunteers
       versus patient subjects, there will always be a
       distinction.  Juries and judges will see the
       difference.  When you solicit an employee like Ellen
       Roche or Nurse Hardin-Able, when you pay $50 to a
       student like Nicole Wan, when you induce a
       volunteer, a sympathetic volunteer afflicted with a
       disease that's under study like Jesse Gelsinger, the
       risk must be extremely low.  I'm not going to get
       into that catch word whether it's minimal risk or
       minimal risk plus.  I'm telling you that if
       something goes wrong you've got a problem.
                 Let's talk about the sources of the ethical
       requirements.  Again most of the individuals here
       look to Helsinki and Belmont and the Common Rule. 
       As a lawyer, I look to the Nuremburg Code and what I
       call the right to be treated with essential human
       dignity, which I've argued is a fundamental right
       guaranteed by the United States Constitution.
                 There's a difference between the documents
       you look to, which are either recommendations or
       regulations written, in most part, by committees
       like yourselves, and the Nuremburg Code, which is,
       in essence, the judgment of a court and a court's
       opinion and, hopefully, there'll be some further
       opinions down the road that establish that the right
       to be treated with essential human dignity, that is
       the right not to be in a research study that
       violates the Nuremburg Code as an essential and
       fundamental human right.
                 Now I take out of these principles that for
       research to be ethical for one it must be valid,
       that is it's got to be based on good science,
       generally accepted scientific principles.  The
       animal studies must be completed.  But here is one
       key question for all of you that I think would be
       interesting to discuss, and this is a question
       that's come up both in the Gelsinger case and in the
       case I have against the Fred Hutchinson Center, and
       it has to do with how much preclinical research is
       required.
                 In a number of these cases what the
       researchers end up saying is, "We can only go so far
       to determine what we see as the universe of harm. 
       Unless we begin testing on human subjects we cannot
       learn of what that universe is."  In the Hutch they
       said, "We need to do human research in order to
       determine whether or not it is too risky."
                 So the question for you is how do you solve
       that problem?  Suppose you say to yourself, "We've
       done all the preclinical work on animals.  We know
       what we think is the best we can know based on that
       preclinical research but there are a lot of things
       we don't know.  We don't know how risky it is for
       humans."  Can you then without doing that final step
       begin to conduct research on human beings?  
                 As you know in the Gelsinger case it was
       after Jesse died that the group learned in animal
       studies and other studies what the cause of that
       death was but it was very apparent from the way they
       conducted the trial and the kinds of physicians that
       they had present when they injected Jesse with the
       adenovirus that they did not anticipate the reaction
       and you may have heard the comments of the
       researchers saying, "What happened to Jesse
       Gelsinger was totally unforeseeable.  We had no
       reason to believe this could happen."  
                 Well, as a lawyer, there's two kinds of
       unforeseeable.  There's unforeseeable because you
       haven't done all of the preclinical work and so it's
       unforeseeable because you didn't take the time to
       make sure you could see the universe of harm.  Now
       if it's that kind of unforeseeable it's
       unacceptable.
                 In addition to being valid one of the
       points of Nuremburg that hasn't received much
       attention is that the research be valuable.  In
       Nuremburg they talk about "it must yield fruitful
       results for the good of society, that it can't be
       obtained with conducting human research."  I think
       what it also means is that the research not be
       trivial.
                 There is such an over abundance of research
       studies going on today.  Now there's been various
       numbers coming up.  People have come up with maybe 2
       or 300,000.  And the biggest boom in such research
       is drug companies doing work or drugs coming off
       patent so perhaps if they can find another
       indication they can extend the patent.  Or drug
       companies tinkering with a drug so that they can
       create another marketable drug that's no better than
       the ones out there but it's just different, can be
       marketable, can be marketed.  Now this kind of what
       I would call trivial research wastes human
       resources.
                 Let's talk about conflicts of interest. 
       Here again my views differ with your views or at
       least the views of the committee.  I know that you
       all have concluded that conflicts can be managed and
       they can be managed if you inform the patient
       subject of the conflict.  That's my view that
       conflicts can't be managed, that neither researchers
       nor institutions should have any financial stake in
       the research that's being conducted.
                 You know, when you are talking about
       informing the subject of the conflict, in legal
       terms what you're really talking about is asking the
       subject to waive the conflict.  You don't waive a
       conflict merely by putting a two or three line
       sentence at the bottom of an informed consent
       document.  If you are going to waive a conflict
       you'd have something like this:  "I understand that
       the researcher has interests that may conflict with
       my health and protection, namely 100,000 shares in
       New Drug, Inc., which she got for a dollar and if
       this trial is successful will make her and her
       family financially secure for life."  
                 [Laughter.]
                 MR. MILSTEIN:  How many people do you think
       will sign that one?  
                 [Laughter.]
                 MR. MILSTEIN:  Let's talk about bounties
       for a second.  It is indefensible in my view that
       researchers are paid $100, $500, $1,000, $2,500. 
       When I say researchers we're talking about more
       often than not physicians, that they are paid to
       recruit subjects for clinical trials.  A researcher
       should have no financial stake in whether or not the
       subject agrees to participate.  And in these
       informed consent documents how many times do you see
       what that bounty was for the subject?  
                 Now you all spent a great deal of time
       talking about informed consent, requirements that it
       must contain the purpose, the procedure, the risks,
       the benefits, the selection criteria, the
       alternatives, and whatever financial interests.
                 I've talked about the myth of informed
       consent or what I call misinformed consent.
                 One of the problems with informed consent
       is just that phrase "informed consent" because it's
       the same phrase that all of us are familiar with
       when you go to a doctor to get a shot or to get an
       operation or to get any kind of procedure.  He
       sticks a form in front of your face, he says, "This
       is informed consent, I need you to sign this so that
       what I'm about to do is not considered a battery,"
       and you sign it.
                 Well, it's got the same name in the context
       of research but it's a totally different entity. 
       For one, the document itself in the context of
       research is simply evidence of this informed consent
       process that was supposed to have taken place.  It's
       not a mortgage.  It's not an insurance policy.  It's
       not buyer beware, if you don't read it you're stuck.
                 How many times -- and I assume we have a
       lot of IRB members in here.  How many times in your
       informed consent documents do you use the word
       "experiment?"  Do you describe the research that
       you're conducting as a human experiment?  I have
       deposed  various researchers in the cases that I've
       brought and the answer is "Frequently the same but
       we never use the word 'experiment' because that word
       carries too much baggage."  
                 Well, that's precisely why you should use
       it so that the subject understands that he or she is
       a subject; so the subject understands that the
       researcher is a researcher, not his physician; that
       the subject understands that what he's undergoing is
       not therapy but he's participating in an experiment.
                 Now this idea of the "therapeutic
       misconception" is something that has appeared in
       virtually every case that I've been involved with on
       the therapeutic side and in each case every single
       subject says, "I thought the doctors had my best
       interest at heart."  None of them say that they were
       participating in the research for the altruistic
       reason of benefitting science and medicine.  The
       reason cancer patients by and large participate in
       clinical trials is to get better.  The reason that
       parents enroll their children in clinical trials is
       to get them better.
                 Now if you look at some of the statistics,
       and the statistics are hard to come by with respect
       to Phase I and Phase II trials, the numbers that
       I've seen show that less than five percent of the
       subjects in the Phase I or Phase II trial see any
       benefit whatsoever.  Now if that's the case why
       would anyone enroll in such a study if not for
       altruistic reasons?  
                 The statistics that I've seen show that the
       percentage of Phase I trials that make it to Phase
       II trials, of Phase II trials that make it to Phase
       III trials is extremely low.  Whenever I give this
       talk and I get attacked as I'm sure you all will
       enjoy doing when I'm finished.
                 I mean the assumption is always from the
       audience that every study we do is important for
       medicine and research, that we need to test these
       drugs, in essence, because they work and they get
       patients well, when the facts are that particularly
       in Phase I and Phase II studies you're talking about
       very small percentages of drugs that ultimately make
       it through Phase III and Phase IV.  So again the
       only reason to participate in a Phase I or Phase II
       study is altruism and yet you see very few altruists
       on the cancer wards of the hospitals in this
       country.
                 Finally another hot topic, as I'm sure
       you're all aware of, is this issue of parents and
       their children.
                 Of course the bioethicists screamed bloody
       murder when the court in Maryland said that parents
       cannot give informed consent for their children in
       the research context.  Of course parents can give
       informed consent for their children in therapy. 
       Why?  Because the parents are going to have the best
       interests of the child at heart.  You need someone
       to okay what the physician is doing but to agree to
       participate in research is a moral choice and
       parents can't give consent for their children to
       make that moral choice.  That's one reason.
                 The other reason again has to do with all
       the other things I've been talking about.  Even if
       parents did give the okay of their children to
       participate in research we all know that the only
       reason they enrolled their child in the research was
       to get them well.  They weren't donating the child
       for the benefit of medicine and science, for the
       benefit of their neighbor's child, or the next
       generation's children.  They want to get the child
       well.
                 So there's a small sampling of hot issues. 
       I await your response.
                 [Applause.]
                 MR. BARNES:  Karen, would you like to go
       first?
                 MS. ROTHENBERG:  Let me first say thank
       you.  It's very nice to be here this afternoon and
       first of all to just look around the panel and see
       what a wonderful group of people have agreed to be
       part of this committee.  And, also, to thank Alan
       for, I think, whether you agree with him or not he
       has really stimulated and a lot of people thinking
       about these issues who in the past might not have
       thought about them.  Okay.
                 Now once I said that --
                 [Laughter.]
                 MS. ROTHENBERG:  -- I think in terms of
       full disclosure it's also important to know that I
       have been a law professor for close to 20 years and
       one of the courses I taught for many years was
       torts.  Torts is the study of a lot of what Alan
       does on a day to day basis but in terms of sort of
       understanding what it is behind the tort law system,
       which is compensating people for injuries in the
       civil law setting.
                 So what I thought I might do is -- and I
       didn't really know what Alan was going to say ahead
       of time -- I have two talks here so I'm going to try
       to separate them for a total of 15 minutes.  First
       I'm going to respond to just a few points that Alan
       made but I think more importantly than disagreeing
       with the details so much is that it would be more
       helpful, I think, for the committee to put what he's
       talking about in a broader perspective and that is
       what the public policy implications are for you as a
       committee in what your task is to us as a society.
                 So let me first talk, if I might just for a
       few minutes, maybe food for thought for your next
       talk, first of all the reason I think there may be a
       distinction between nontherapeutic and therapeutic
       from the perspective of a medical malpractice
       attorney is because of the way you go about proving
       a case when you're going to bring a case under tort
       law.  You need to ask yourself how are you going to
       prove causation for the negligent behavior and it is
       much easier to prove that case when a "normal
       subject" went into a research experiment and was
       injured than for a "sick person" who had no hope
       that went into an experiment and had to prove that,
       in fact, they were injured.  They were already
       desperate or many of them were, and a big challenge
       for a tort lawyer is to try to prove causation, to
       try to prove that the relationship between the
       negligent behavior and the ultimate injury was
       caused by that negligent act so that's why it's
       particularly important to draw those distinctions.
                 That's why Johns Hopkins from day one had a
       loser.  She was a normal healthy woman and, worse
       yet, she worked in the institution.  So, you know,
       from that perspective that was a difficult case for
       Johns Hopkins to be able to defend.
                 With respect to Gelsinger, I -- just for
       full disclosure -- I was on the Recombinant DNA
       Advisory Committee, I think, along with Abbey that
       approved that protocol.  What happened with respect
       to that plaintiff from the best I can tell from what
       has been made public was nothing that we approved
       because there was human behavior and human beings
       that made decisions with respect to what they were
       going to allow and what they weren't going to allow. 
       We certainly did not approve somebody like that
       individual to be part of that protocol and so the
       message there is there is always human behavior even
       under the best circumstances.
                 Next the Nuremburg Code.  My quick response
       to that is there are more people around here that
       are experts.  I think it's very important that we
       need to look at context.  The Nuremburg trials were
       following the war.  They were war crimes.  That is
       not to say that I am not sympathetic to concerns
       about the rights of human dignity.  I do think there
       would be a challenge constitutionally for that
       argument to be made.  I think it could keep us legal
       scholars busy for a long time.  In fact, I might
       want to have an academic meeting about this but I do
       think that it's very important to keep this in
       context.  I think there are many researchers in good
       faith trying to do well.  Sometimes people steer
       wrong for all the wrong reasons but it is not the
       holocaust and the war crimes following.  I think
       that's important.
                 Third, ethical principles.  I would agree
       that the most important ethical question for an
       institutional review board to make and the one that
       the University of Maryland always makes is this a
       worthwhile, is this a scientifically valid
       experiment to be doing, why are we asking the
       question and how are we going to go about proving
       it?  Unfortunately, too often, institutional review
       boards, perhaps ironically, spend most of their time
       worrying about the form, the informed consent form
       and not really worrying enough about is it good
       science.
                 Now what is or what is not unforeseeable, I
       think, I might disagree a little bit about us having
       a reality check because I think in science some of
       the best experiments, some of the best things we've
       done in science were serendipitous.  We might have
       been studying looking for one thing and something
       else came out.  That is not a total defense to there
       are trivial trials that are going on but I would
       think that that would be the exception rather than
       the rule if we ask that very first basic question
       why are we doing the study and what is our
       hypothesis and really to question that.  That makes
       ethical science.
                 Conflicts of interest --
                 MR. BARNES:  Karen, can I make one
       observation?
                 MS. ROTHENBERG:  Yes.
                 MR. BARNES:  I just wanted to say that for
       purposes of the discussion, this is not about
       anything that you've said, but I do want to observe
       that Jesse Gelsinger's parents are actually in the
       audience and I would just ask that -- not that
       you've said --
                 MS. ROTHENBERG:  Oh, I'm sorry.
                 MR. BARNES:  -- no one has said anything
       that would be inappropriate at all but I just wanted
       in advance to just note that not only for the
       speakers but for those who have questions as well.
                 MS. ROTHENBERG:  Okay.  Thank you.  I hope
       I didn't do anything in that way but I would be glad
       to meet them, in fact.
                 Okay.  I lost my train of thought.
                 Oh, conflict of interest.  Conflicts of
       interest.
                 PARTICIPANT:  Paul just slipped me a note
       and told me to name you in the next law suit.
                 [Laughter.]
                 MS. ROTHENBERG:  Okay.  I'm only wishing
       you were one of my alums so I could ask you for a
       nice donation for the building.
                 [Laughter.]
                 MS. ROTHENBERG:  Okay.  Lucky temple I
       should say.  Okay.
                 Now with respect to conflicts of interest,
       I think that Alan makes a very good point and that
       in a number of organizations that many people
       sitting around this room and the audience have been
       involved in we are often told to have to disclose
       information and then there are waivers that are
       associated with that but again I think it goes back
       to the very first point about what it means to be a
       human being and there are conflicts of interest that
       are much more significant for some of us than money. 
       I mean the tension and the pressure in the
       scientific community not only of how things get
       funded but how people get promoted and the graying
       of what used to be the good and bad guys between
       academics and the commercial market is very gray. 
       When I started in this field we thought we knew who
       the good guys and the bad guys are.  And it works
       both ways.  I mean, there can be good guys all over
       the place and there can be bad guys when you didn't
       think they were the bad guys.  
                 So I think that's a complicated issue and I
       think Alan has made some good points about it with
       respect to that.
                 Okay.  Informed consent.  I'm going to make
       a correction here.  I have a different perspective
       than informed consent.  My perspective on informed
       consent is that it is not a waiver for battery. 
       Battery is an intentional tort under torts. 
       Informed consent has evolved except for one state
       and, in fact, the only state left to -- I think the
       last time I looked was Pennsylvania, interestingly
       enough.  But informed consent is a negligent
       standard, not a battery standard and, in fact, I
       would say just the opposite in my perspective.
                 I think we are careless about the use of
       informed consent in the clinical setting, which is
       much more relevant to those of us on a day to day
       basis.  And, if anything, we go overboard perhaps
       with the wrong focus when it comes to experiments
       with respect to human experimentation so I think
       that's an area where there needs to be a lot more
       focus.  But in the State of Maryland at least it
       isn't the form, either in the clinical setting or
       the research setting.  It's just evidence that there
       has been a conversation.  It is not per se not
       negligence if, in fact, you have filed a form.  So
       that's very state by state specific.
                 But I think drawing these analogies between
       informed consent in the clinical context and the
       research context is very complicated because in the
       research context it's very much associated with the
       regulatory scheme at the federal level much more
       than at the state level so anyway that's a caution,
       I think, with respect to those analogies.
                 I would agree about the importance of
       language.  Again being on the Recombinant DNA
       Advisory Committee it was called gene therapy.  This
       was an issue that Abbey and I were constantly
       raising with them.  It wasn't therapy.  Now many,
       many of the patients who were desperately wanting to
       be in gene therapy trials, in all due respect for
       the scientists and for us, they were pressuring us
       and the motivation is why were they pressuring us. 
       Should they, which I didn't hear, should they have a
       right to say we're willing to, we know or maybe we
       don't know, maybe it's a perception but does an
       individual have a right to say I want in and what
       should be the role of a regulatory agency or
       researcher to say you can't get in, we have decided
       that this is not in your best interest, and how do
       we balance all those relative rights?  
                 Okay.
                 Another really good point about the
       conflict between your doctor and your doctor who
       happens to be doing the research.  And I think this
       is a very good point that I'm sure the committee has
       been grappling with is can the person that cares for
       you, that you think cares for you, also be the same
       person that does research on you?  And I think
       institutional review boards and this committee needs
       to further grapple with that.
                 Now why do people go into studies?  I don't
       think it's helpful to make generalizations and I
       think that this is an area that could use a lot more
       empirical work, and I'm going to give you a whole
       series of empirical studies that I think the
       committee might want to do but it's not only to be
       altruistic, it's not only to be because you think
       you're going to get better.  It's also because there
       may be a value to hope, whether or not you think
       you're going to get better.  Who is the one that
       should be depriving the individual of that and what
       kinds of shenanigans do we go through in order to
       make hope a reality?  I don't really have the answer
       to that.  I mean, that's an existential question.
                 Okay.  How much time do I have left?
                 MR. BARNES:  You have a couple of minutes.
                 MS. ROTHENBERG:  Okay.  Now I'm going to
       give you what I thought about before I knew what
       Alan was going to say, although I had some hint of
       it.  Okay.
                 First of all, you need to ask your question
       of where is the appropriate role for a private
       medical malpractice case or a tort case in the
       context of trying to get at our ultimate goal?  And
       I think the ultimate goal that we all share is that
       we do better research and we do research in a way
       that we feel good about the benefits and relative
       benefits and risks of the research study.
                 Now the role of tort law is twofold.  One
       it is a deterrent role and that is, I think, what
       Alan is focusing on here or in part here, is that if
       we punish people through their pocketbook they're
       going to be more careful the next time.  That's not
       unique to this.  That's been the debate that's gone
       on in the medical malpractice field.  That's been
       the debate that's gone on with tobacco.  That's been
       the debate that's gone on with asbestos.  Pick the
       issue.  All right.  It's always a question about
       what is the appropriate role for the civil law for a
       tort case in which after the person is injured you
       bring the lawsuit.  How much value will it have to
       fixing things for the future?  That's an empirical
       question.
                 And the second thing that the tort law
       does, which is very important in this context, it
       compensates people who get hurt and this is a
       significant social and public policy issue for you
       all to raise that has been debated and debated and
       debated.  How do we compensate individuals who
       volunteer to participate in studies, Phase I
       studies, Phase II studies, Phase III studies?  What
       is our communitarian ethic if at all?  
                 Or is this just the luck of the draw that
       if you happen to be in an institution where there
       has been some oversight or some study or a series
       from the newspaper like in Seattle or in some other
       way where this information gets public and then some
       lawyer takes it from there and develops it into a
       private case or a class action, so be it, but you
       need to put tort law into a larger context.  For
       example, what about the role of our current
       regulatory scheme?  Are we willing to give up on it? 
       Or how could we fix it?  
                 What about the role of the disciplinary
       laws at a state by state level?  All these
       researchers who are physicians can be disciplined. 
       In our state we have a disciplinary rule for people
       that don't do informed consent prior to breast
       cancer surgery.  All right.  Now that's pretty
       specific but there is the way of using a
       disciplinary law.  So what are the other ways
       besides the private tort system that might be
       effective?  And ironically this is an empirical
       question for you to ask:  What will happen to
       oversight if we have more cases?  
                 And here's an interesting analogy for you
       to think about:  A  number of years ago we decided
       on a state by state level to give immunity to peer
       review committees that evaluated mistakes that went
       on in health care institutions, not mistakes, things
       that might or might not be negligent.  And in our
       state and a number of other states this was a public
       policy decision.  It didn't give immunity to the
       institution.  It didn't give immunity to the
       researcher but it said the peer review committee or,
       by analogy here, perhaps the institutional review
       committee if they can do their job right, if they
       can do oversight, if they can ask hard questions, if
       they can develop a record, they're not going to do
       it if they're afraid that then they are also going
       to be sued.  So this is a public policy decision for
       us to make.  Do we want to give them any sort of
       immunity?  Is that a good thing or a bad thing? 
                 Now in our state, for example, ethics
       committees have immunity because we as a matter of
       public policy wanted to encourage that.  The records
       from peer review, the records from peer review have
       immunity because we wanted to encourage there to be
       more, not less peer review.  So that's an
       interesting question, I think, to ask.
                 What is the relatively role of all the
       players?  Now this is something I read, not
       something you said, but it's something I might teach
       if I were a plaintiff's torts lawyer and that's you
       sue everybody up and down the line initially because
       you need to do discovery to find out who was or who
       was not at fault so that has implications.  You're
       going to sue the bioethicist.  You're going to sue
       the committee.  You're going to sue the researchers. 
       You're going to sue the institutions.  Is that good
       public policy?  Who is really at fault or what
       combination of people are at fault or what
       combination of a regulatory scheme, a disciplinary
       scheme, a tort law scheme, a liability scheme,
       state, federal, constitutional do you want to have?
                 So here are some of the empirical questions
       I might leave you with:  First of all, what is --
       this is maybe not empirical.  This is an existential
       question.  What's research?  All right.  This is not
       a new question.  You've all thought about it but
       there's a real irony in the way our current federal
       regulations are written.  If you do bad research,
       meaning you don't have a hypothesis, you haven't
       even figured out what you're really doing as
       research, you have no review, nothing.  You don't go
       to an institutional review board, nobody asked you a
       series of question, there's no informed consent form
       that gets raised or any of this.  It just happens. 
       And believe me, the government once in a while has
       to decide if they can yank money from an institution
       when they're not really quite sure whether it was
       ever really research because they didn't even go
       through this process.  So the very first question is
       that it seems to me.
                 And, of course, the existential question of
       is any of this research that we're talking about. 
       What does it mean to have clinical interventions or
       clinical innovations or clinical therapies?  Again
       there are some semantics.
                 Second, what impact is this going to have
       on the future of research?  Now everybody makes
       hyperboles about this both ways.  It's going to
       paralyze the institutional review board.  It's going
       to paralyze researchers.  We're going to have less
       research.  The research that really needs to get
       done isn't going to get done.  I think it would be
       worth trying to study this question if we could. 
       Perhaps even in the institutions that have already
       had some liability.
                 Now when I first started to study the
       inclusion of women in clinical research I couldn't
       find on one hand lawsuits against researchers.  In
       part, because it goes to my very first point about
       how difficult it is under tort law to have brought
       these suits and there was not a lot of attention in
       the context of the normal subject.  There were a few
       cases.  Most of them had to do with informed consent
       but I do think -- and I give total credit to this to
       Dr. Levine.
                 We have had a paradigm shift in this
       country from protecting subjects to including
       subjects in which they're banging down the doors
       saying we have a right to get some treatment that
       started with AIDS, then it went into women's health,
       in which the pendulum is now starting to swing back
       because there is a real fear.
                 And my concern is this conversation about,
       well, altruism and communitarism and, you know, what
       we owe to each other as members of a society, as
       members of a community has gotten partly a little
       clouded because of all the financial interests.  So
       we have asked people to be altruistic and we have
       asked them to be supportive of science but we're
       talking out of both sides of our mouths because
       they're also filling out consent forms that say they
       can't have any financial interest in the result. 
       And so we can't have it all ways and I think we
       really have to be attentive to what the financial
       connection in research is to altruism if we really
       want people to be altruistic.  So that might be an
       interesting empirical question to ask too.
                 The next one -- I'm almost done -- do we
       have too many trials or do we have too few trials or
       do we have the wrong focus on the trials?  Now Alan
       has said we have a lot of trivial stuff going on and
       I'll give him that.  Maybe that's right.  Maybe
       that's not right but how much that needs to get done
       isn't currently getting done and who is to decide
       that?  And I think that raises some interesting
       questions about children, about the decisionally
       impaired.  There are experts around the table on
       that but the tougher we are in some of those areas
       may just mean that we're going to wipe out a large
       proportion of the community.
                 And I'll sort of end on -- before I get to
       children I'll come back to in a second, I want to
       just say something about the compensation scheme. 
       Now under traditional tort law somebody that brings
       these cases, and Lord knows he may be earning it,
       gets one-third.  All right.  Now you could have a --
                 MR. MILSTEIN:  You don't want to change
       that, do you?
                 MS. ROTHENBERG:  Not if you give me a nice
       donation, right?
                 [Laughter.]
                 MS. ROTHENBERG:  In some places they get
       more than that.  And if he loses he gets nothing and
       if he wins he gets a third.  Now there are some
       other options.
                 So one option would be a no fault
       compensation scheme.  Now what are the pros and what
       are the cons of that?  We've seen in the -- we've
       had some experience with that.  It has been proposed
       in a number of other commissions.  It doesn't go
       anywhere.  The answer is there are limits to what
       you can get under those schemes.  Is that a better
       thing than if there are millions and millions of
       people in these studies, there's only one guy here
       and a few others that can bring all these class
       actions so there may be a whole lot of other people
       that never get a penny.  So anyway that's -- what's
       the advantage of that?  What's the disadvantage of
       that?  I certainly think if somebody gets injured
       and altruistically participates in research for the
       good of our society we have to think hard about what
       we owe them in return.
                 And, finally, I just wanted to make a plug
       if I might about the research on children and what
       happened in Maryland against Kennedy-Kreiger.  The
       lawsuit is still going on.  I think it's a very
       complicated case.  Just to clarify, the decision was
       clarified so that minimal risk is something that
       parents can consent to on behalf of their children. 
       It's still a big question mark and on May 3rd the
       University of Maryland's Law and Health Care Program
       in collaboration with NICHD and the American Society
       of Law and Medical Ethics will have a meeting on
       this.  So this might be something you all would like
       to continue to participate in but I just wanted to
       say on behalf of the academy I think what you're
       doing is just bringing out a lot of interesting
       questions that need to be discussed, clarified and
       evaluated.
                 Thank you.
                 [Applause.]
                 MR. BARNES:  Paul?
                 MR. LOMBARDO:  Yes, this is the second time
       in ten days that I've followed a torts professor.  I
       said the last time it was like that line from W. C.
       Fields about not following children's acts or dogs
       or tort professors.  You get upstaged too often.
                 [Laughter.]
                 MR. LOMBARDO:  There is very little I could
       add to what Karen had to say about tort law but I do
       want to touch on a few points.
                 This is a peculiar situation to be in which
       is three lawyers who are supposedly bringing
       different perspectives to a problem which is very
       real and it reminds me of a line that my grandfather
       used to use.  He used to tell me when I was quite
       young, "Stay out of hospitals and stay out of
       courthouses because nothing good happens in either
       of those places."
                 [Laughter.]
                 MR. LOMBARDO:  And he probably -- he went
       to his greater reward before I took a job where I
       was a lawyer who was sitting in a hospital.
                 [Laughter.]
                 MR. LOMBARDO:  I think that the perspective
       of most people getting involved in litigation is the
       same as his was, which is it's something that
       happens to you once in your life and you never get
       over it.  And so I'm not -- never surprised when
       people react as negatively to people who litigate
       for a living but I think the perspective that
       probably those of us who teach in this area try to
       bring is that you need to think about litigation the
       same way you think about surgery.  Sometimes fairly
       precise technique, a fairly predictable outcome. 
       Other times a fairly rough process in which you're
       really not sure what's going to happen.
                 If you're the surgeon you're comfortable
       with that because it's what you do for a living.  If
       you're a litigator you're comfortable with that and
       so the three of us as lawyers are kind of
       comfortable with the notion that lawsuits are
       something that happen pretty regularly and they have
       a social place as Karen has spelled out for us.
                 I just want to tick off a few of things
       which I think Alan has said either here or in print
       or other places, which I agree with.  One is that
       obviously there's too much work for IRBs.  These are
       all things you've heard before.  There's not enough
       training.  There's not enough attention to what it
       means to face risks or what those risks are or
       whether, as Jonathan suggested earlier, they should
       be described as harms rather than risks.
                 I think that the conflict of interest
       discussion is one of the more interesting ones
       that's going on now in terms of research and the
       reason for that is because we have lawyers talking
       about conflict of interest and we think about this
       very differently than people in the medical world
       do.  To say this -- I discovered this the wrong way
       which was to actually do it.  I asked someone about
       a conflict of interest, one of my physician
       colleagues, and I thought he was going to punch me. 
       And that's because the term, the phrase is freighted
       with all kinds of baggage suggesting some kind of
       immoral position you put yourself in that you should
       know better.
                 And I think that this discussion about
       conflict of interest is going to force the medical
       profession and researchers particularly to look at
       what they think about conflicts, whether or not
       their relationship to patients/subjects is the kind
       of fiduciary relationship that other professions
       claim to have and we've never had that conversation
       quite that way so I think that's a good part.
                 I think the other good thing that Alan is
       doing is focusing public attention on some
       tremendous shortcomings in the system and when I
       talk about the system I have to take into account
       it's an enormous system and it's an enormously
       varied one.  As all of you know, you've got some
       institutions that have extraordinary resources and
       use them to good purpose in monitoring the kinds of
       research that goes on.  You have a great many
       programs in the middle and then you have some that
       don't even know that there's such a thing as a
       federal rule.
                 When I say that I say that not making that
       up as an example but rather because of the kinds of
       phone calls I get in consultation as a person who
       has been sitting on an IRB for about a dozen years
       and consults with other ones.  
                 Happily I don't get that call from my own
       institution but I do get it from others.
                 People are at varying stages of
       understanding about what kind of regulations exist
       and what the obligations they might have as
       researchers.  I think that is part of the tension
       we're seeing particularly this morning in
       discussions of behavioral science and other kinds of
       research, which people have not thought of in the
       same way before as being covered by the Common Rule.
                 So I think all that stuff is good but I
       come back to a question that a colleague and former
       teacher of mine, and I guess of your's, too, Karen,
       Jeff O'Connell, one of the fathers of no fault
       insurance, always raises and raised in a book years
       ago called The Lawsuit Lottery, and that is when we
       work with a system of tort law in which litigation
       happens on the behest of individual plaintiffs, some
       people may make a significant amount of money and
       that may very well have a deterrent effect on other
       people who might behave similarly, and most people
       get nothing.
                 And so systematically as a matter of
       policy, as Karen has pointed out, we have to look at
       that and see whether or not in the long term whether
       or not we want to craft a system in which the people
       who actually are harmed in research that we think is
       necessary to do actually get some compensation.  I
       mean that's probably the only take home point that I
       would want to make is that we don't have a system
       for compensating people that will get the most to
       the people who may need it but let me remind you we
       don't have a system like that in all of medicine, in
       all of science.  We don't have that in this country
       and we argue at various times about people like Alan
       who by their behavior professionally really push the
       boundaries of the system that we do have.
                 And that takes me to the semicolon.  One of
       my friends said, "You've got to watch out on the
       introductions when they get to the semicolon.  That
       first part is all the nice stuff and then they say,
       "However."  However, I think that the law is a blunt
       object.  It's a cliche to say that but it's true.  I
       don't have any idea whether or not Alan's theories
       of using the Nuremburg code will be successful in
       the context of litigation.  Perhaps they will be
       sometimes.  Perhaps they won't be.
                 I guess listening to the news last night I
       didn't get you as many points as I did last week and
       that's because I was listening to people discuss how
       international law might be applied to a real
       situation.  Like whether those people down in
       Guantanamo now are prisoners of war or something
       else.  So it's very hard to apply international law
       to much of anything.
                 On the other hand, coming back to the good
       side, I don't think you can avoid talking about
       Nuremburg.  I don't think you can avoid talking
       about the precedent that was set there.  Everyone in
       this room and many of you know a great deal better
       than I do the history of the development of the
       regulations that you're arguing about and those
       certainly gave more than a side ways glance to what
       happened during the holocaust.  So Karen is right. 
       You can't make too much of this.  We need to take it
       in context but we also can't ignore it.  
                 And so from that point of view you're on to
       something now and I guess it'll be the courts to
       tell us how much of what you're on to.
                 A couple of points just to conclude.  Mary
       Faith, you know, opened the door so I can say
       something historical.
                 [Laughter.]
                 MR. LOMBARDO:  I think that the history of
       American law is in some ways a tableau where scandal
       marks the threshold of legal change.  Certainly
       that's the case in terms of regulation of research. 
       There's a wonderful book by James Moore called
       Doctors and the Law in which he talks about the 19th
       Century and he says that the reason -- his theory is
       the reason that malpractice suits began to be
       generated late in the 19th Century had to do with
       developments in technology coupled with scandal and
       that the developments in technology had to do with
       understanding the germ theory and asepsis and also
       developing a technique for anesthetizing people.  So
       that once you got your leg sawed off you didn't die. 
       You actually lived and when you lived if you
       happened to have the good fortune of being able to
       ask to have your leg sawed off you had expectations
       that you might not have understood or your
       practitioner might not have understood.
                 The hope that came out of progress in
       medicine led people to expect more from it and as a
       consequence when they didn't get all that they
       expected they were disappointed, they went to court.
                 It also pointed up, as Moore says in his
       book, the fact that there was some over selling
       going on.  There was over selling going on by the
       medical profession of how exciting and how new and
       how valuable therapies might be and, particularly at
       a time then when medicine wasn't regulated, it was
       possible for all kinds of people to make promises
       that were too big for them to keep.
                 So I think keeping in mind that our
       perspective -- this is not all new.  We've been to
       some of these places before.  I would just end up by
       saying that I think a compensation system of some
       kind for research subjects would be a great thing
       for people to look at.  If you're concerned about
       people like our friend, the litigator, here then you
       really, really ought to think of ways of making him
       obsolete.  He won't be obsolete.  There'll be other
       things to do.  We certainly are not going to try to
       put him out of business but in this area it would be
       possible.
                 My concern is that rather than having a
       compensation system so that people who are actually
       harmed get compensated that what we will end up with
       is the kind of perverse legislation that is only
       protected.  That is it's legislation that says,
       "Well, if you're not on an IRB we just won't let
       them see you.  We'll just immunize you."  My own
       historical research focuses on that kind of
       legislation.  What happens when we just say, "Go
       ahead and do it, we don't want people to sue you." 
       Bad things happen.
                 So there is a benefit to the tort system
       working, both because it pushes things out in the
       open, as has already been suggested, but also
       because the kind of headline liability as compared
       to the financial liability makes all of us think
       more carefully about the job we're doing on an IRB
       and makes us realize that it may become something
       that is not private and secret but actually
       something that's very public.
                 The last comment I'm going to make, I just
       reminded myself of what happened this morning when
       you talked about confidentiality, it does seem to me
       that one of the things that these lawsuits are going
       to do is to force people to think more seriously
       about what happens when litigation intrudes on to
       research.  One of the things that happens is
       somebody ends up learning what the rules really are
       about disclosure and really has to look at that form
       and say, "Oh, don't worry about it.  We're going to
       protect you as far as the law permits."  It's a bad
       time for us to start telling people that the law
       permits a good deal.
                 [Applause.]
                 MR. BARNES:  We have Bob Levine and Adil
       Shamoo.
                 I want to make maybe one observation and
       that is that -- I'm not sure, it sort of relates to
       all three of your's but one of the things -- I
       attend several IRBs for clients and one of the
       things that has struck me over the past several
       months as I've sat through IRB meetings and you look
       at the sections of the informed consent forms, which
       really are only replicas or only replicate the
       underlying research contract with sponsors, is that
       the provisions about compensation for injury in
       research studies are all over the map.  It varies
       from sponsor to sponsor, from pharmaceutical company
       to medical device manufacturer, to biotech company,
       to venture capital start up biotech company, to
       investigator sponsored or institution sponsored
       studies.
                 And not only is there no rhyme or reason it
       appears to me in most of those compensation
       provisions in the underlying research plan, contract
       and also the informed consent form but also there is
       in most cases not really adequate attention that has
       even been paid to that part of it.  And people sort
       of think that the whole thing is going to take care
       of itself.  Not only it's not just -- I don't think
       that's either for or against anything that anyone
       here has said.  It's simply an observation about
       what I see as what's really happening out there.
                 Bob, and then Adil, and then Greg Koski.
                 DR. R. LEVINE:  Thank you very much.  I
       have extensive notes on what I want to comment on
       and I think you'll be relieved to hear that I'm not
       going to comment on all these notes.
                 [Laughter.]
                 DR. R. LEVINE:  Karen told us there are two
       purposes of tort law.  The first to serve as a
       deterrent is well understood.  However, recent
       experience indicates that it's a much broader
       deterrent than we really want.  It's turning people
       off service on IRBs.  It's turning people off
       service as research subjects.  It's making a lot of
       people do things or not do things that we think
       would be for the benefit of themselves and the
       public.
                 The second one is it creates a way to
       provide payment to people who are injured.  And I
       have to agree with Paul that we do much better if we
       look at no fault compensation.  We have had since
       1975 a large number of prestigious deliberative
       agencies starting with the Secretary's Task Force on
       Compensation for Injured Research Subjects and the
       National Commission and the President's.  They all
       have said unanimously we need no fault insurance.
                 I am not talking about payment for medical
       expenses.  I'm talking about compensation for death
       or disability.  And Paul is right that that's
       nowhere.  It gets nowhere because everybody says,
       "Oh, my God, we don't -- we can't tolerate that
       level of exposure."  But we do have models.  We have
       places where they've set up such programs and the
       University of Washington in Seattle, for example, it
       cost them, I think, $7,500 to pay off all the claims
       they got in eight years.  That shows what the level
       of risk is as well.
                 I also want to offer a comment on several
       of the points that Mr. Milstein made.  Some of them
       were just factually incorrect.
                 For example, the Nuremburg Code is not a
       court opinion.  The people -- the Nuremburg Tribunal
       tried the so-called doctors under what is called the
       Nuremburg Principles, which is international law. 
       The Nuremburg Code is something they wrote while
       they happened to be there trying to make sure that
       they would take certain principles and make them
       particularly relevant to research.  But you can't
       write the rules for trial of people, I have to tell
       this to a lawyer, after they've violated them.
                 It's our custom in the United States to
       write laws only after they've been broken but you
       can only enforce them after they've been written. 
       So the Nuremburg Code is not a court opinion.  It's
       the opinion of several American jurists who were
       advised.
                 The other thing is it has nothing whatever
       to do with what you're calling therapeutic research
       and they said themselves that their focus was only
       on competent adults who had no disease.
                 The other point I want to make is that when
       you say five percent of subjects in Phase I trials
       receive no benefit -- less than five percent receive
       any benefit, actually the percentage is vastly
       smaller and the reason for that is that in almost
       all clinical trials, except in the field of
       oncology, the subjects are normal volunteers.  That
       means that -- 
                 MR. MILSTEIN:  Cancer trials.
                 DR. R. LEVINE:  You didn't say cancer
       trials.  If you said cancer trials then I would tell
       you that less than five percent is almost in the
       right ball park for children, it's a bit lower for
       adults.  And then you extend it from Phase I to
       Phase II where your statement is wrong no matter who
       you're talking about because in Phase II the only
       subjects are patients with the target disease. 
       There are several other such examples but I'll let
       it go at that.
                 MR. MILSTEIN:  Thank you.
                 MR. BARNES:  Adil?
                 DR. SHAMOO:  Thank you, Mark.
                 There are three movements in the past forty
       years in our country that has gone through similar
       trials and tribulations.  The civil rights movement,
       the environmental and women's movement.  And the
       reason those movements used the tools that were
       given to them by what they can use is that they're
       all scandals, abuses and abuse of human rights,
       whether it's in the environment, whether it's the
       woman movement or civil right movement.
                 These movements, therefore, they used the
       media, that is they sought the help to publicize
       through public communication discussion of the
       issues.  They used legislation and they used the
       courts.
                 The only reason this committee is in
       existence and/or we're talking about it because in
       the past ten years and especially in the past seven
       years there has been horrendous abuses of human
       subjects.  No one wanted to talk about them then. 
       Those of us who talked about them then yelling and
       screaming, nobody paid attention to them.  Only
       after the formation of the National Bioethics
       Advisory Commission, only when the media started
       carrying abhorrent stories all across the country
       and the scandals, and now we have some good lawyers
       who are willing to take it to the next step. 
       Remember I said there's media, legislation and
       courts.
                 My attitude is this movement yet has not
       reached the same level of the environmental or civil
       rights or the women's movement where we have reached
       steady state that we want to make people like Alan
       Milstein obsolete.  I believe they have another ten
       years to go on further and, hopefully, there will be
       more of them to be as a deterrent and further
       publicize this cause in front of the American people
       because I truly and firmly believe, and I have
       talked to thousands of normal average human beings
       who have never heard of this issue, when they hear
       it they cannot believe the extent of how many abuses
       we have done to human subjects.  Children being
       healthy used in experimental protocols, Nazis only
       used, using them as truly guinea pigs, that is not
       the country we want all to live in and these must
       stop through all means, including the courts.
                 [Applause.]
                 MR. BARNES:  So in regard to Professor
       Rothenberg's or Dean Rothenberg's two tort
       principles, Dr. Levine endorses compensation and Dr.
       Shamoo endorses deterrence.  And with that, Dr.
       Koski?
                 DR. SHAMOO:  No, I really said all means
       has to be used, including the courts.  Not just the
       courts.
                 DR. KOSKI:  Well, thank you, Mark.
                 It seems to me that all reasonable people
       could agree that in the long run it's far better to
       prevent harm to people in the conduct of research
       rather than to either punish institutions, punish
       investigators.  You know, I think, in fact, the
       whole focus of the movement that is under way, and I
       feel comfortable calling it a movement, is to move
       from a system that has focused on issues of
       regulatory compliance to assist and that truly
       focuses on prevention.  And if we're able to succeed
       in implementing a system that truly looks in a
       prospective way at ways that we can actually prevent
       harm then there will be no need for, you know, more
       likely than not individuals to have to go and file
       suit except for those instances where there will be
       individuals who, as Karen pointed out, clearly are
       going to behave in ways that our society finds to be
       unacceptable.  And for those, I think, the
       punishment should be stern.  They deserve what they
       get.  So it's a question of trying to find that
       appropriate balance.
                 Adil, if your suggestion that we should
       continue our present forum basically for another ten
       years, I know what you meant, we cannot afford to
       allow the situation that has plagued us for 20 years
       already to continue for another ten years.  As Dr.
       Levine has pointed out already, the first
       recommendations for implementing a system of private
       voluntary accreditation, Human Research Protection
       Program, was actually made in the 1982 report from
       the President's Advisory Committee on Ethical
       Problems in Research.  We've had citations of other
       recommendations, okay, that have been there and, as
       I've said in my public presentations too many times
       over the last year the whole pathway of human
       subjects research is just strewn with these relics
       of recommendations from one committee, one
       commission after another, where very thoughtful
       recommendations have been discarded because of
       either the reluctance or the inability of private
       parties in government to stand up and take
       responsibility to do what needs to be done, and it's
       time that that change.  And, in fact, I think if you
       look at what has happened even in the last year
       things are changing.  They are changing in important
       ways.  After 20 years of waiting we not only have
       one program for accreditation of IRBs and human
       research program protection programs, we have two. 
       We have private voluntary certification programs for
       people at every single component of the research
       process already.
                 We see movement occurring in government as
       well.  We've talked about the role that financial
       conflicts and financial interests have played in
       undermining confidence.  Well, within the last year
       we've seen two of our major academic and research
       organizations actually step up to the plate.  We've
       seen the AAMC begin with saying that we have a --
       what's the word?  A rebuttable presumption that in
       human research financial relationships that pose any
       kind of a conflict of interest will not be
       permitted, that finders fees, bounties will not be
       permitted.  Okay.  We've seen the AAU step up.  And
       basically I will say with a little help from their
       friends in government have moved more aggressively
       than they otherwise would have to exercise their
       responsibility.  Similarly we've seen the American
       Academy of Pharmaceutical Physicians, those horrible
       docs who do clinical trials on human guinea pigs,
       adopt a code of ethics that puts as its very first
       principle the well-being, protecting the well-being
       and the interest of human research subjects as their
       single most important goal.  Okay.  This is a
       dramatic change and I think that we clearly want to
       see that continue.
                 I will say, as both Mary Faith and Kate
       know, that in planning for the upcoming meetings of
       this committee the issues of perhaps limitations on
       liability for IRBs and an appropriate compensation
       program for individuals who are harmed in research
       are already on the agenda.  And, indeed, today's
       discussion sort of provides some foreshadowing for
       the direction that we're going to be moving in the
       weeks ahead.
                 But I think we again need to every once in
       a while step back and say, look, there is a lot of
       thoughtful work that's going into this and we have
       to continue that momentum and recognize that we may
       need to rely upon some energizing of that process
       from a variety of different perspectives in order to
       keep them moving forward.
                 So thank you.
                 MR. BARNES:  Thank you very much, Greg.
                 We have Jonathan Moreno, and then Abbey,
       and then I'm going to open it to the floor.
                 DR. MORENO:  I just have a question rather
       than a statement and this is for anybody or
       everybody on the panel.  The discussion about
       conflict of interest was confined so far mainly to
       financial conflicts of interest but my experience as
       a lot item on the scientists has been that what
       motivates those people really isn't -- I mean
       there's always exceptions but it is not money.  They
       want to get the Nobel Prize.  They want to get a
       footnote in the textbook that medical students will
       read 100 years from now.  They want to have a
       disease named after them.  I don't think there are
       any body parts left to name after people but there
       are plenty of diseases and syndromes.  Are there
       some left?  Maybe I'll get -- give me one, would
       you? 
                 [Laughter.]
                 DR. MORENO:  Renaming some body parts.  I
       don't want to go there.
                 [Laughter.]
                 DR. MORENO:  How from the point of view of
       a lawyer are these less tangible conflicts
       understood?  The desire to be promoted?  That
       perhaps has some financial implications in itself
       but peer recognition.  How do you guys understand
       that in law?
                 MR. MILSTEIN:  Those other conflicts are
       just as sexy to us plaintiff's lawyers as the money. 
       In the Gelsinger case you may have seen the quote
       from the principal investigator when asked about his
       financial stake in the company he said, "How dare
       you say I'm motivated by money.  I want the Nobel
       Prize."  So those are certainly things but I think
       there's something else that needs to be said also. 
       It's not simply, that is the absence of
       self-interest does not mean the absence of conflicts
       of interest.  If you look at the history of research
       abuses, many of those abuses such as Tuskegee
       occurred where the researcher's aims were for the
       greater good.  It's any interest that places the
       interests of the research above the interest of the
       well-being of the subject that becomes a conflict of
       interest.  And I think is -- should be unlawful.
                 DR. MORENO:  Can I have a follow-up then? 
       I guess then the question is can there be research
       from this point of view that does not -- is not
       intended to or could not theoretically provide a
       benefit to the subject, a direct benefit?  Could
       that, would that be permissible in this
       interpretation of the law to the subject?  If there
       were -- could research that did not provide a
       benefit to the subject be permitted if that person
       were sick?  
                 MS. ROTHENBERG:  Well, I'll play a devil's
       advocate here.  First of all, I don't think it's per
       se unethical for people to be motivated for their
       own -- for winning a Nobel Prize.  In fact, some of
       the most wonderful things that have happened in our
       society are because people have interests in their
       own self-esteem and their own value as a member of
       society.  And I think we would be fooling ourselves. 
       I mean that's part of the human psyche and I would
       also think that that is pretty condescending to
       think that individuals who are gaining research
       don't realize that, in fact, wow.  In fact, they
       would share in the joy of that if, in fact, somebody
       that had treated them -- I'm sorry, somebody that
       had had them involved in some human experiment had
       won a Nobel Prize.  I mean, the opposite is sort of
       a selfish view about us being individual autonomous
       -- I'm sort of communitarian in this view.
                 On the other hand, I think that that's no
       different than when somebody goes into a tertiary
       care institution and has a medical student trying to
       draw their blood.  I mean, you know, there are
       contexts in which things go on like that every day
       and I would certainly err on the side of telling
       people more rather than less about that but I don't
       think that's necessarily an inherent conflict of
       interest.
                 On the other hand, I do agree, and I think
       I said this, that sometimes that is a greater
       motivator than money because really if people were
       motivated by money I'm not sure they would be going
       after NIH grants on a routine basis.  They would be
       going to work in other settings and so I don't --
       nor -- and also have to get through all the
       institutional review board stuff, you know, so there
       are easier ways to make a buck but I would agree
       with you but I don't think that necessarily says
       it's unethical.  That's my understanding.
                 MR. BARNES:  Abbey, you'll forgive me but
       we've only got like only a couple of minutes and I
       wanted to hear from the audience.  Is it -- can you
       make it very brief?
                 MS. MEYERS:  We do have the no fault system
       with childhood vaccines and the government fund
       that's put aside for childhood vaccines is huge. 
       Hardly anybody has collected on that money so it can
       be done.
                 MR. BARNES:  An interesting point.
                 Are there one or two questions from the
       audience?  If you would stand up at the microphone
       but we only have time for two brief comments and,
       please, make it brief because people are chomping at
       the bit to get in.
                 MS. SHARAV:  Okay.  First of all, I just
       wanted to mention the two law cases mentioned the
       Nuremburg Code, both T.D. versus New York State
       Office of Mental Health and Higgins versus
       Kennedy-Kreiger.  In both cases also I might say the
       justices strongly indicated that parents have a
       right to make martyrs of themselves but they do not
       have a right to make martyrs of their children.  In
       other words, in nontherapeutic research.
                 MR. BARNES:  Vera, I'm sorry.  Can you
       please ask a question?
                 MS. SHARAV:  Yes.  I would like to know how
       under the -- for the greater good of research one
       can justify conducting lumbar puncture in 45
       children for nontherapeutic purposes?  
                 MR. BARNES:  Well, I'm not sure that you're
       going to get an answer to that question because it's
       a -- well, it's rhetorical.  It certainly assumes
       something.
                 Are there other questions?  There's a
       gentleman in the front and a gentleman in the back. 
       Let's take these.  If you could just make it brief
       and to the point we would appreciate it.
                 MR. HANDY:  Just real quickly.  I've spent
       the last 24 years in the military and I've been
       looking at the forced experimentation some of our
       military members have undergone in the last four
       years with some vaccine policies and one quick
       question on -- 
                 MR. BARNES:  Could you identify yourself?
                 MR. HANDY:  Yes.  My name is Redmond Handy. 
       I have a nonprofit organization called No Abuse and
       I want to applaud Mr. Milstein in looking at some of
       things that we've been concerned about.  Just one
       quick comment on Nuremburg and then I'll ask the
       question.  The Nuremburg Code, the DOD actually
       submitted agreement to that code in 1953, according
       to a Washington Post article in the early 1990s and
       yet they've been probably the least likely to abide
       by that, and we really got in problems in World War
       II with Unit 731 in accepting Japanese experimental
       data in lieu of prosecuting them like we did in
       Nuremburg.
                 But my question is on didn't -- isn't it
       true that this argument about research, this
       definition of what is research is a very fine
       technical kind of thing but it centers around the
       problem that the FDA had during the Gulf War, which
       the DOD was trying to say, "Well, you know, we're
       not experimenting with bromide tablets, with
       botulism toxoid or anthrax vaccine because this is
       therapy."  And the FDA -- 
                 MR. BARNES:  Please get to the question.
                 MR. HANDY:  The question is isn't this the
       kind -- the same kind of issue that the FDA faced
       during the Gulf War?  The DOD is claiming it's
       therapy.  The FDA is saying, "Well, it's research." 
       And so we got ourselves into a lot of problems with
       Gulf War illness.
                 MR. BARNES:  Karen?
                 MS. ROTHENBERG:  I think it's an
       interesting point but let me just turn it on its
       head a little bit.  I think that if we look about
       what went on over the last few months when the
       public was scared to death about anthrax, maybe way
       out of proportion, it was the military, if I recall,
       that said, "This has not been used or tried -- we
       can't give it to the civilian population because
       there hasn't been sufficient amount of study on it." 
       And I raise this because there's always contextual
       questions that get raised when, when has the
       research been good enough before we start to give it
       to members of our society?  And it creates, I think,
       interesting tensions about what is research and what
       is therapy.  And we just saw that happening over the
       last few months with the supply of the vaccine.
                 MR. BARNES:  One final question from the
       gentleman in the red shirt.
                 PARTICIPANT:  Just a very brief comment and
       a question.  I think, you know, the highest
       biological level that we have, our feelings,
       thoughts, consent, really to our dignity, and good
       science would be respecting those highest levels. 
       And so it may not be good business always but good
       science should.
                 But the heart of my question is -- and
       we've talked a lot about language today -- is why
       not the use of common language when people go into
       studies to really know of the risk.  We don't use
       the word "experiment," we don't use the word "we
       induce a disease or cause an illness."  Just simple
       language to let people know.  It seems like a
       solution to some of this would be to have a neutral
       party given ordinary language, what is the real
       risk, and let the experimenter take the risk of his
       studies not being done.  We ask the subjects to take
       all the risk when maybe the experimenters need to
       have that risk too.  So what about just some
       phrasing in the law that says use common language,
       have some neutral noninterested party, you know, ask
       it.
                 MR. BARNES:  Alan, do you want to briefly
       answer that?
                 MR. MILSTEIN:  Yes.   I mean, Mr. Gelsinger
       and I have also advocated the use of a subject
       advocate but I would caution against what I would
       call dummying up the document, which is what some
       IRBs are trying to do, that is let's reduce the
       complexity of the document down the lowest common
       level because when you do that you eliminate a lot
       of the material information that the patient needs. 
       I think the better alternative is to have a subject
       advocate who has as much knowledge as the researcher
       who can understand the informed consent document and
       then can explain it to the subject and talk with the
       subject about what his or her choices are and
       whether or not it's in his or her best interest to
       participate in the research.
                 MR. BARNES:  Penultimate word to Karen.  I
       get the last.
                 MS. ROTHENBERG:  Thank you.  I just have to
       say, again let me emphasize, it isn't necessarily
       what's written in the form.  It's in its
       implementation.  And you can have it spelled out
       very clearly but if the researchers and the
       institution don't then abide by what was agreed to
       that I think is where there may be real concerns and
       where the liability system may be correct.  But you
       could call it whatever you want but you've got to be
       careful of the oversight and in its implementation.
                 MR. BARNES:  Well, this is certainly not
       the last word on these issues because this
       controversy will spin itself out and resolve itself
       in one way or another, whether it's with success or
       failure in the courts or legislation or, as Greg
       Koski said, whether most of this can be prevented. 
       As a lawyer who hates lawsuits, I will tell you it's
       much better for everyone if lawsuits get prevented
       and not filed.
                 Just a couple of things.  Mary Faith, I
       think, wants to talk about the committee meetings
       and I wanted to say briefly that we do have a draft
       HIPPA letter regarding suggested reforms to the
       HIPPA confidentiality regulations, which we're going
       to distribute.  You all can look at it tonight and I
       think we'll have time to talk about it at breakfast
       in the morning and then perhaps briefly in the
       morning.
                 Mary Faith, do you want to give the last
       word?
                 CHAIRPERSON MARSHALL:  First, let me thank
       Mark.  Let me thank you for moderating this fabulous
       panel.
                 Panel members, thank you so much for being
       willing to come, some of you on very short notice. 
       Just superb presentations.
                 [Applause.] 
                 CHAIRPERSON MARSHALL:  We have workgroups
       breaking out and just a few minutes of direction.
                 I do not feel the need for closing comments
       today from 5:15 to 5:30 so the workgroups can go
       until 5:30.  We're asking you to break out.  Your
       job this evening or this afternoon, workgroup and
       workgroup chairs, is to come up with your goals for
       the workgroup and to assign priority to those goals
       and to develop a time line.
                 And the workgroup chairs, the first thing
       in the morning, during the opening remarks at 8:30
       in the morning, I will give each workgroup chair
       five minutes total without discussion to present to
       the rest of the committee your goals in order of
       priority and the time line in which we can expect
       them to be accomplished.
                 So I thank all of you.  Those of you who
       might wish to sit in and observe a workgroup
       session, I think that you would be welcome to do so
       as observers.
                 Let me ask Kate and Keisha who are going to
       tell those of you on workgroups where to go.
                 MS. JOHNSON:  Yes.  Please everyone listen. 
       If you are a member of the Third Party Genetic
       Workgroup or Social and Behavioral Sciences
       Workgroup you will meet in this room.  If you are a
       member of the Informed Consent Workgroup or the
       Workgroup on Decisional Impairment you will meet
       upstairs in the lobby in Felini's restaurant.
                 [Laughter.]
                 MS. JOHNSON:  No, it's no food or anything. 
       It's just a room.
                 CHAIRPERSON MARSHALL:  Children's Workgroup
       is not meeting today.  The chair is not here.  It
       meets all day on Wednesday.
                 Committee members, we will meet.  Those of
       you who are going to dinner, we will meet in the
       lobby at 6:30.  We're going just right around the
       corner for dinner.  It's a block away so those of
       you who would like to join us in the lobby at 6:30.
                 [Whereupon, at 3:38 p.m., the proceedings
       were adjourned, to be resumed at 8:30 a.m., on
       Tuesday, January 29, 2002.]
                                   - - -
                        CERTIFICATE OF OFFICIAL REPORTER
       
                 This is to certify that the foregoing
       proceedings before the National Human Research
       Protections Advisory Committee held Monday, January
       28, 2002, was held as herein appears, and that this
       is the original verbatim transcript thereof, and is
       a full correct transcription of the proceedings.
       
       
       
                                                           
                                     Cynthia D. Thomas
                                     Official Reporter