GB

	Department of Health and Human Services

	Meeting of the
	NATIONAL HUMAN RESEARCH PROTECTIONS
	ADVISORY COMMITTEE (NHRPAC)

	Wednesday, October 31, 2001

	The DoubleTree Hotel
	1750 Rockville Pike
	Rockville, Maryland 20852

	A G E N D A

Wednesday, October 31, 2001

8:30-9:00	Protection of Human Subjects; Managing Financial Conflicts of Interest in Clinical Research
		Jordan Cohen, M.D.
		President
		American Association of Medical Colleges (AAMC)

9:00-9:30	Updates:  NHRPAC's Financial Relationships Document; NHRPAC's Letters to the FDA & OHRP Respectively on Exceptions for Children's Informed Consent and 45 CFR Part 46 Subpart B
		Mary Faith Marshall, Ph.D.
		Chairperson, NHRPAC

9:30-10:00	Brief Discussion about Indianapolis Conference:  Accountability in Clinical Research:  Balancing Risk and Benefit, April 24-26
		Kate-Louise Gottfried, J.D., MSPH
		Executive Director, NHRPAC

10:00-10:30	Informed Consent - Generally
		Tom Beauchamp, Ph.D.
		Professor of Philosophy, Georgetown Unv
		Senior Research Scholar, Kennedy Institute of Ethics

10:30-10:45	BREAK

10:45-12:30	Informed Consent and the Decisionally Impaired:  Discussion of the Department's Report in Response to NBAC's Report 

AGENDA (Continued)

		  NBAC Report - "Research Involving
		  Persons with Mental Disorders that
		  May Affect Decision-making Capacity"
			Eric Cassell, M.D.,
			Former NBAC Commissioner
			Clinical Professor of Public Health Cornell Medical Center

		  HHS Response to NBAC Report
			Lily Engstrom, M.S.
			Office of Science Policy, OASPE, DHSS, Senior Science Policy Analyst

		OHRP's Reponse to HHS's Report
			Greg Koski, M.D., Ph.D.
			Director, OHRP, DHHS
			Jonathan Moreno, Ph.D.
			Director, Center for Biomedical Ethics University of Virginia Health System
			Adil Shamoo, Ph.D.
			Professor, Department of Biochemistry and Molecular Biology
			University of Maryland School of Medicine

12:30-1:30	LUNCH

1:00-3:00	NHRPAC WORKGROUP MEETINGS
		o  Social & Behavioral Sciences
		o  Third Parties
		o  Informed Consent & the 
		     Decisionally Impaired

5:00-5:30	RECAP of Meeting and Action Items
		Mary Faith Marshall

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, 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

Roster of Members (Continued)

MARY K. PELIAS, Ph.D., J.D., Professor, Department of Genetics, Louisiana State University Health Sciences Center

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, Hoffman-La Roche, Inc.

DENYSE THORNLEY-BROWN, M.D., Assistant Professor, Division of Nephrology, University of Alabama at Birmingham

KATE GOTTFRIED, J.D., M.S.P.H., Office of Human Research Protections, Office of Public Health and Science, OS

EX-OFFICIO MEMBERS

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., Healthcare Research
Dr. Paul Gatons, DHUD
Dr. Donald Prosnitz, DOJ

	P R O C E E D I N G S

	[Time noted:  8:30 a.m.]
	CHAIRPERSON MARSHALL:  Good morning and Happy Halloween everyone.  It does feel like herding cats up here, on occasion, not all the time.
	Well, we had a very productive day yesterday, half of the committee has been working since 7:30 this morning, putting words on paper, doing the hardest kind of work -- thinking and writing.
	But, we have a whole day ahead of us as well and we're going to try and stay strictly to schedule so that we can make the most of our day.  I am delighted to introduce to you although I don't think he probably needs an introduction, Jordan Cohen, who is the president of the Association of American Medical Colleges.
	You all may remember that one of the first projects we embarked on was looking at financial relationships and potential conflicts of interest both at the institutional level and at the level of the investigator.  And I think we probably got more e-mail in response to our draft documents along the way from the folks at the AAMC and others who were, I guess, sort of colleagues and perhaps taking the same tack as the AAMC.  I do recall a few words like perhaps "overreaching" or "burdensome." 
	[Laughter.] 
	CHAIRPERSON MARSHALL:  But we'd like to invite everyone to the table who should be at the table and to make sure that they have a voice.  And the AAMC has embarked on a very important project of their own.  They have a large task force that is investigating financial relationships and conflicts of interest.  And 20-some people on that task force many of our colleagues, very broad representation, and we're looking forward to hearing about their work and the good work of the AAMC.
	I also would also like to observe that the AAMC in terms of position papers and endorsing the ethics of research with human subjects and the importance of informed consent has been right out there in the front and been a leader and a proponent for good research ethics.  And so thank you very much for joining us.  We are glad to have you here. 
Protection of Human Subjects:  Managing
Financial Conflicts of Interest in Clinical Research
	DR. COHEN:  Thank you very much, Mary Faith.   This is a really wonderful opportunity for me to sort of bring you all up-to-date about one of the activities that the association is involved with, as Mary Faith just mentioned, the task force only financial conflicts of interest and clinical research.  I'm sure you all are also aware of that we had a very broad interest in protection of human research subjects and another major initiative that I am very proud of is AAHRPP, the Association for Accreditation of Human Research Protection Programs,  which is now actually officially launched and has an Executive Director, Marjorie Spears, and is really well on the way to getting that activity actually I think a meaningful contribution to our staff.
	What I wanted to do today was just to bring you up-to-date.  It's really a progress report, it's not a final report.  The task force that has been in existence now for several months is just now in the process of finalizing its initial report and that's what I'm going to be talking about here today.  But let me just -- the copy edit at the beginning is that what I am going to say today is still in draft.  So it's subject to some change, although I think in fact it's pretty close to finished.
	I don't need to dwell on the context or why we're getting involved here, you know all of this well or better than I do; there's just, I think, a great deal of concern, appropriate concern, about the financial entanglements that many investigators have with commercial enterprises and at least the perception of the possible bias that that might introduce and other problems related to that.  And our task force was constructed to have a very broad representation of stakeholders, and I'll show you the membership in a moment.  Its goal was to try to create a model for an effective, incredible institutional self-regulation.  That's our whole idea is to rely upon the academic community to endorse and enforce a set of principles that will meet the test of accountability to the public on these issues.
	Our philosophy is that we want to preserve the advances that diagnoses and treatment that I think assume we all agree are really the fundamental purpose of trying to get rapid translation of basic science information into useful clinical services and products.  And that one sort of extreme way to handle financial conflicts of interest is to just say you can't have any.  And that, we believe, would in fact not be in the public's interest because it would, we believe, stifle the kind of incentives and motivations and commercialization of these products that is really important.
	Having said that though we do need to find a balance that adequately safeguards the integrity of the research but obviously more importantly even the welfare of the human subjects involved.
	So striking that balance is where I think the difficult work is, and I think where some of the judgments need to be made.
	Well, here is the committee it's chaired by Bill Danforth, you all know is the Chancellor Emeritus of Washington University.  And Bill, I'm just so delighted he's taking a really serious interest in this issue and has lead the group exceptionally well and very thoughtfully.  It has a number of leaders from academic, medicines are listed here, it has researchers, involved people who themselves in some instances have important financial backing by commercial enterprises.
	It has three -- what's the word I want -- attorneys -- 
	[Laughter.] 
	CHAIRPERSON MARSHALL:  It's a little difficult getting that one out, isn't it. 
	[Laughter.]
	DR. COHEN:  Sue Eringhouse from North Carolina, Joan Leonard here from Howard Hughes and Dorothy Robinson form Yale.  A couple of ethicists, I think you know both of these names.  We felt it important to involve people from industry, we have folks from the pharmaceutical industry as well as the device industry and a number of people representing the public in terms of journalists and media who have be very, very important contributors to the work of the group.
	And then public representatives that you see here and the staff David and Jennifer Kulnich in liaison with Richard Sherman who is in the office from AAU as you know has its own task group looking at similar issues.
	The charge for the group was to review what we call the "Harvard Principles."  As you may know I guess over a year ago now, Joe Martin, Dean at Harvard convened a group to begin to noodle about some of the basic principles and that was designed to be and was very helpful as a point of departure for this task force.
	We also wanted to review the monograph that we had put together, the AAMC had put together in 1990, Alan Shift who is in the audience was the major author of that document that was released in 1990, that has served, I think, usefully to inform our community over the decade of the 90s but we felt it was time to update that and develop guidelines now for managing individual conflicts of interest of faculty and others as the first stage.  Then when we are finished with that we are planning to move and will move into managing institutional conflicts of interest and also to coordinate these efforts again with the AAU's task force.
	Well, the guidelines that have been drafted for individual financial interests in human subjects research, as I say, we hope will be released in a month or so.  There is no outright prohibitions as I mention.  We thought that was not the way to go but that tougher standards both for reporting and for disclosing financial and obviously for monitoring and managing those conflicts is what we thought was the right thing to do.
	The overarching framework which is quite compatible with the AAU's approach to this is the so-called "rebuttable presumption" that we begin with the sort of philosophical notion that financial conflicts of interest should be disallowed unless there is a compelling reason to allow them and that needs to be documented, demonstrated, agreed to by a conflict of interest committee.
	It sets a very high standard for the prior review of this conflict of interest committee so that things that could potentially be problematic are reviewed in an open way about the committee.  It's, like I say, not an absolute prohibition and the compelling circumstances are that the research could not otherwise be conducted as safely or as effectively without the involvement of the individual who is conflicted financially.  And the judgment needs to be made both on the magnitude of the financial interest, on its relatedness to the project, that as something that is quite tangential might be more allowable than something right cored to the actual performance of the research.
	And also, again, recognizing the key public policy issues here, namely the Bayh-Dole mandates and expectations of the institutions, that has to be a part of the considerations of how important the work is to get into the public domain.
	A successful rebuttal that is an instance where the individual who is conflicted can adequately or successfully rebut.  The presumption triggers a disinterested oversight, some kind of mechanism for watching the conduct of the research from a disinterested perspective to ensure that it needs all of the criteria that the committee, the conflict of interest committee, determines what that appropriate monitoring is, and that sets a floor.  At least our view is that that then would be communicated to the IRB after the committee documents its findings and the IRB could set a higher standard of monitoring in they felt the circumstances warranted.  But this would constitute a minimum level of monitoring and, as I say, the committee would document its findings and disclosure would be required, full disclosure to the IRB.  I'll mention in a moment some of the other aspects of the disclosure and reporting.
	The standing, we call advising the standing COI committee, although I think institutions might elect to have other kinds of mechanisms.  But I think the functionality of some kind of institutional group that would constitute this body which would review all of the significant financial interests, again not just the government sponsorship but we're calling for all sponsorship to be looked at in this way and the context of all human subjects research.  That they would forward their recommendations to the IRB prior to protocol approval, and that the committee also would review any proposed agreements for technology transfer and licensing during the process of negotiations simply to be sure that those are the negotiating agreements would know whether or not the COI committee would judge the financial conflict to be such a nature that the individual couldn't conducted the research.
	So we felt it was important for that judgment to be made before the agreements were signed by the institutions so as not to be caught in that vine.  Not that this group would approve the agreements but would simply make a preliminary determination as to whether the individual or individuals involved would be problematic in terms of conducting the research that was proposed.
	The communication needs to the effectivem, obviously, at least among the COI committee, IRB, and the Office of Technology and Licensing.  The documentation we are advising that there be electronic reporting mechanisms, so as to ease the administrative burden of maintaining this kind of robust reporting mechanisms.
	The scope of reporting we think should be very large.  By "reporting" we are talking about within the institution, what is reported within the institution.  That any significant financial interest with any commercial entity whose interest might reasonably appear to be effective, words that you're familiar with, by the research.  Not all reported interests will obviously be problematic, we went to set a low threshold for what is to be reported so that in case.  The committee assesses the issue on a case-by-case basis and the reports of the COI creed are confidential, disclosed only when the COI committee permits the researcher to conduct human subjects research.  That if a judgment is made that it's not going to go forward then that information is not any, not subject to further release.
	All individuals who conduct human subjects research must report to the institution, all significant national interest, those quotations I now will define.  By conducting research, anything, designing, conducting, serving as a PI, enrolling subjects, determining eligibility, analyzing reporting research data, submitting publications, these are all functions that would be subsumed under the concept of "conducting."  And in terms of significant financial interest, first of all the individual conducting the research and his or her spouse and dependent children and any foundation or indenty that's controlled directly by the individual or their spouse are trying to get a handle on any connection that might serve as a potentially biasing influence.
	These I'm going to go through quickly these sort of litany of things that the committee thought should be subsumed under "significant financial interest" and you will see some of these things will go further than currently exists in most of the -- at least as far as we know -- the guidelines that currently exist.  Consulting fees, honorary gifts, any other emoluments or in-kind compensation from a financially interested company or an entitlement to any of that in the future, another issue.  Whether for consulting, lecturing, traveling, service on any advisory board or any purpose not directly related to the reasonable costs of conducting the research.
	We recognize that in research agreements there is obviously the cost of the research are legitimately recoverable by the sponsor and those should not be regarded, we believe, as part of the individual's conflicted financial arrangements.
	Again, the current guidelines that exist and what's not listed here is that we want to include a statement that if these should be changed in the future, they would become the controlling, sort of threshold.  If the public health service should decide that $5,000 is right or $50,000, we want to build in the expectation that that guidance would now control the way this set of guidance would be viewed.
	Equity interest including stock options of any amount in a nonpublicly traded financially interested company or any entitlement, future entitlement to those so that a nonpublicly traded company we don't believe there should be, what should be reported should be any financial interest however seemingly small at the time; obviously the reason being that in the future those small stock options or stock or whatever could escalate dramatically.  In a publicly traded company or entitlement to the same as long as any interest that exceeds a de minimus exception as I'll come to any moment.
	Royalty income, the right to receive future royalties under a patent license, the research related to the licensed technology including any royalties that might flow through the institution to the individual would be reportable.  Any nonroyalty payments in connection with the research that are not, again, directly related at a reasonable cost to the research.
	Services and even if they are not payed for, services as an officer, director, or any other fiduciary role for a financially interested company whether or not it's remunerated.
	Now, the exceptions are that significant financial interests that do not need to be reported are the following:  that any interest of any amount in a publicly traded diversified mutual fund, we think that such totally diluted interests would not reach a threshold of potentially biasing influences.  Any stock or stock options in a publicly traded company, if it's valued at $10,000 or less, or if not more than 5 percent ownership, so that's at least what is regarded as the de minimus exception for the publicly traded company; and any, again, payments to the institution that are directly related to the reasonable cost of the research.
	Disclosure guidelines in terms of what needs to be not reported to the COI committee but after this is done and if the committee accepts the rebuttable presumption then the question is what's disclosed and to whom is it disclosed?  How is that information made available?  Well, as far as to research subjects, we think that the IRB should determine the form of the disclosure and in some cases that might be no more than to say that it exists, but that the consent form should indicate that any detail that all the detailed information is available to the subjects upon request so that it is not hidden someplace beyond availability.
	The presence of the financial conflicts of interest should also be disclosed.  Like I said, to any federal or state agencies in compliance with the requirements,, journal editors, audiences at presentations of the research work and the public upon request.  Again, we had a lengthy discussion about this issue and felt that if the press wanted to know about a financial conflict of interest, and, again, a study that had been approved in the presumption rebutted all the details ought to be openly available to anybody who asked.
	Additional policy guidelines that there is no payment for the results or referrals.  It is not uncommon practice for companies to put bounty payments on recruitment for clinical trials and the like, that is not to be allowed.  Reasonable costs must be specified in the research agreement, again to tie into this issue of what's accepted from these guidelines.  Bonuses or recruitment bonuses, as I mentioned, are an affirmation that institutional policies on intellectual property an publication rights, that we wanted to be sure that the institution was standing behind the view that this kind of control or attempt at controlling the publication or the rights of the individual should not be allowed.
	Protection of students and trainees in the course of conducting research again an issue that has been raised by many.  Education, compliance, monitoring should be spelled out in the institutional guidelines.  Sanctions up to and including dismissal from the institution, we think needs to be spelled out and the of appeals mechanisms well-established.  Adequate resources need to be made available by the institution in order to support this kind of activity and that we think that an assessment of the conflict of interest oversight mechanisms within the institution should be an element of the accreditation of the human subject protections.  As an example this will be part of what AHRP will be looking at in the context of a whole raft of things, but financial conflicts of interest and how they are managed should be a part of that issue.
	So that's where we are in the course of the task force recommendations.  As I mentioned these are now still being sort, it's a very interesting process.  I don't know how many of you have been involved in electronic sort of drafting and re-drafting of things but our e-mail traffic has been quite interesting.
	I must say, at some point in the archives we may want to publish the traffic because it will be an interesting thing to look at.  But in any event it has been a very lively task force.  The people have really been very, very engaged.  And I just can't tell you how valuable, invaluable it's been to have people outside of academia participate and provide their perspective, it really has been nice.
	And it's also very interesting that some of the contentious issues have not broken down in terms of academia versus nonacademia.  It's cut across both of the communities so that is has really been fascinating to sort of see the kind of commonality of interest really when you get down to the core of the matters here that surfaces in this kind of discussion.
	So I have been enormously pleased with the seriousness, with the thoughtfulness with which this process has gone forward and I hope we can come to closure on it within the next several weeks and get it out to the public.  So what that I'm right on time.  And do we have remaining time for questions?
	CHAIRPERSON MARSHALL:  I think we do.  And thank you very much.  I saw a lot of head nodding around the table.  And I do, before I forget this, I want to mention that the AAMC is having it's annual meeting beginning this weekend, here in Washington and on Monday afternoon from 1 to 4, there will be a session on financial relationships and conflicts of interest that is sponsored by the American Society for Bioethics and Humanities. 
	DR. COHEN:  Who is chairing that?
	CHAIRPERSON MARSHALL:  I am.
	[Laughter.] 
	CHAIRPERSON MARSHALL:  It will be in the Washington Hilton in the Map Room and I can tell you who will be on that panel, our very own Mark Barnes, who chaired our working group on financial relationships and conflicts of interest.  Jennifer Coolidge from the AAMC who is Director of the Division of Biomedical and Health Sciences Research.  Richard Turman who is here in the audience today, Director of Federal Relations at the Association of American Universities and the primary, I think author of their report.  Allen Milstein, attorney who has been involved in some lawsuits and complaints involving human subjects recently.  Ann Develor who is senior policy analyst at the GAO, will be there.  Their report is not public yet unfortunately so she won't be able to speak necessarily to the particulars of it, but she will be there in the audience and I think can contribute to the discussion.  So, that's Monday November 5th, from 1 to 4.
	Yes.  So let me, Bob Rich had his hand up first.  We are going to try to stick to time, so I'm only going to allow a few questions here, sorry.  And I also want to report that we will put Jordan Cohen's slides that you just saw on our web site, so that they will be available.  We will send them to the committee members, but they will be on the web site available to anyone who would like them, if that's all right with you. 
	DR. COHEN:  I just want to be sure that you know they are in draft, I'm a little -- about their being publicly available -- 
	CHAIRPERSON MARSHALL:  Well we won't put them on our web site but we'll send them to committee members, is that all right? 
	DR. COHEN:  That will be fine.
	CHAIRPERSON MARSHALL:  Draft.  Okay.  Thank you.
	Robert I had you first.
	DR. RICH:  Jordan, I very much appreciated that update of what you're doing and appropriately both AAMC and AAU have had their focus on issues as they impact academic research.  However, as you mentioned, you also have thought it important to involve both academic and nonacademic participants in the review process.  I am very much hopeful that you'll take the same view when you prepare your report; which is, as you very well know, the majority of the pharmaceutical company sponsored research is conducted outside of academia.  And I think that it will be imperative if this report is to have the impact that it needs to have for the issue of noninstitutionally supported clinical research to also have the same kind of careful scrutiny.  I don't know whether one might call, for example, for the creation of proprietary conflict of interest committees like we have proprietary IRBs, or some other kind of mechanism, but I really do believe that it's critically important that we don't focus just on the problems in academia but see the whole thing.
	Same thing with regard to when you get to institutional conflicts of interest the institutional conflicts of interest are not only our medical schools but also include, for example, professional societies who get substantial support from pharmaceutical companies. 
	DR. COHEN:  Just to comment, you're absolutely right, of course, Bob.  I guess the question is, what is a AAMC do to influence that other than to say please pay attention to these guidelines because they should apply to you as well.  We have no enforcement ability even within our own community let alone outside. 
	DR. RICH:  I agree with that, but I also believe that this document if it is to have the impact that I think we all hope it should have needs to speak forcibly to the issue and then I think it will have, it could have enormous positive benefit by virtue of it's moral suasive powers. 
	DR. COHEN:  Right.  I hope so.
	CHAIRPERSON MARSHALL:  So I am going to ask committee members, I'm going to impose sort of time constraints here, you may ask one question no response and don't try and smuggle anything in.
	[Laughter.] 
	CHAIRPERSON MARSHALL:  Margaret.
	MS. BORWHAT:  The public has been very concerned about this issue especially in light of all the different media articles et cetera.  How have you planned to disseminate this information to the public?  Do you have any media campaign planned?  And will you be updating the representatives of the media on an ongoing basis to reassure that this does get disseminated to the public and that it builds confidence? 
	DR. COHEN:  Yes, we do.  I wouldn't say that our communication plan is fully developed yet, but clearly the intent is to get it as broadly publicized as we can.  Again, in connection with Bob's comments as well, to be sure that everybody is aware of this, and we do have a pretty robust communication apparatus at the Association to get the press and other involved.  So, yes, we will disseminate it very widely and it will be on our web site.
	CHAIRPERSON MARSHALL:  Abbey.
	MS. MYERS:  The disclosure, you're going to require disclosure, but who is the disclosure to?  Is it just disclosure to the conflict of interest committee or disclosure to the patient who is going into the trial? 
	DR. COHEN:  Well, as I mentioned, we sort of made what may sound like an artificial distinction or semantic distinction between "reporting" and "disclosure."  "Reporting" we will use that word.  It means internal to the institution so that all of these potential conflicts are reported to the COI committee and then determination is made about whether the research can go forward.
	If the determination is made, then the question is, to whom is the conflict disclosed?  And I mentioned it's disclosed to the patient through the IRB mechanism and the consent form needs to include that information to the extent that the IRB thinks it's appropriate; and whatever it thinks is appropriate, the statement should be there that detailed information is available upon request.
	So if the individual or the family is not satisfied with what they're learning from the consent from, that information is available on record in the COI committee.  It is also disclosed to journal editors.  Whenever a presentation is made the oral presentation needs to indicate that it's, that the conflict of interest existed as well as to the public on demand.  So wide disclosure.
	CHAIRPERSON MARSHALL:  Adil.
	DR. SHAMOO:  If this comes to existence and compliance by your members I think you should be commended.  This is a very, very positive and an excellent step for those of us who have criticized severely in the past few years.
	However, one of the aspects of a medical center which is part of the university community is acquisition of new knowledge, not purely making money for the sake of money.  We are not, and I'm part of a medical center, we are not a CRO, contract research organization.  Could AAMC discourage medical centers which are part of the university community acquisition of new knowledge from becoming like the CRO and doing all of these what I call them, they are purely for bringing money and salary to the faculty like phase 3 and phase 4, that's where the big money is and that basically fosters conflict of interest. 
	DR. COHEN:  Well, we have not taken a position as an association on whether or not institutions ought to engage in that late stage develop of clinical trials kind of work.  I think the marketplace is doing a pretty good job of diverting that activity more and more to the private sector.
	There are, however, some examples, I'm sure you are aware, of very large CROs within our academic institutions that are attempting, I believe, quite legitimately to retain a major presence of academia in this activity and do it in a way that is consistent with all of the ethical guidelines that we're trying to impose. 
	And I think, you know, it's hard for me to make myself in the head of people who are making the leadership decisions, I don't think it is done solely for the purpose of making money.  I do believe that there is a view and I subscribe to it, that there is a legitimate role for the academic community in these late stage trials because I think a lot of them do require the kind of sophisticated judgments and expertise that tends to reside within academic institutions.
	So I wouldn't personally be in favor of a sort of dichotomous view of the world that those kind of trials should be excluded from academia.  I think when they are conducted the clearly need to comply with proper guidance.
	CHAIRPERSON MARSHALL:  Susan.
	DR. KORNETSKY:  I have a question.  One of the things that we have thought about as far as conflict of interest, I don't know if you've given any thought to that is that, there is a lot of emphasis placed on when you're negotiating, asking for fair and reasonable costs associated with doing trials so that you're not sort of padding budgets; is there any discussion about money that remains at the end of the trial; and whether there are any, I mean, that's something that we've been thinking about our own institution about maybe it's an institutional sort of policy, but investigators sometimes have very clever ways of not using all of their funds. 
	DR. COHEN:  That's correct.  And not just from commercial sources, I think.  But in any event, yes, we have talked a bit about that.  I think that will come up clearly in the institutional conflict of interest discussions.  But I think one of the reasons for emphasizing the cost reasonably related or reasonable cost related to the research however that word is used was attempting to try to indicate that those agreements really have to be negotiated legitimately for what is reasonable costs.  If there is money left over then we will need to figure out how to deal with that.  But clearly, it can't be redounded to the individual or to the lab.
	CHAIRPERSON MARSHALL:  Jonathan.
	DR. MORENO:  Bob actually already anticipated one of my questions, and I'm not as happy as Adil about losing these good colleagues to private industry for these late phase studies.  I think I'd rather keep them in the tent where we can keep an eye on them.  But in any case, we can talk about that.  I think that your committee's thorough process have captured the following state of affairs.  But I want to make sure that I understand it that the focus is not just on a specific project and the conflicts that might adhere in that, but in the individual's relationship to the company, for example, or to the source; is that right? 
	DR. COHEN:  That is exactly correct.
	DR. MORENO:  I have in mind to CSX Michigan situation that I know OHRP is very involved in right now where professors previously got money from a company, later on do some work for it, they claim sort of pro bono on the university time and they say, oh, well, we didn't have any conflict because we weren't doing this project for the company even though they paid us for something else in the past.  It looks to me as though based on one of your slides that you have captured that situation. 
	DR. COHEN:  We certainly have attempted to.  And, again, that's what was in the concept of how related is the financial interest to this project?  Bit the fact that it exists needs to be reported irrespective of whether it is related or not.
	CHAIRPERSON MARSHALL:  Elliot and Greg and then I'm going to take the last word.
	DR. DORFF:  I also was very much impressed by the whole procedure and by what looks to be a really wonderful document.  I was just, the more that you were talking, the more that it sounded like our own procedure and our own document.  So I was wondering where you found us overreaching? 
	[Laughter.]
	CHAIRPERSON MARSHALL:  Let me be accurate.  I think that it was the guidance that we were responding to. 
	DR. COHEN:  Right.  I think so too.
	CHAIRPERSON MARSHALL:  Those where the comments.  That was very early on before we, I believe, had even began.  Am I accurate, Mark?  I'm not sure that the comments were necessarily directed at us, the overreaching burdensome -- I don't -- go ahead. 
	MR. BARNES:  Are you -- what Elliot is saying in terms of the overreaching by the alleged -- I thought the allegation was that HHS was overreaching, not that we were overreaching in our detail commentary on the HHS -- 
	[Laughter.] 
	DR. KOSKI:  If I could weigh in on this.  I don't think that the word was "overreaching," I think there was as expression of concern that for some of the issues it might be premature because there was a need for further discussion within a stakeholder community, and that to the extent that any guidance might be construed as regulation, there would clearly be a need to make sure that it went through appropriate process.
	I think in fact that the question of prematurity has clearly been answered in that now the professional organizations -- maybe I should just go ahead with a full comment that I was going to make.  But, you know, after more than a year of having issued a challenge to the academic community and the research community to step up to the plate and show initiative, to take responsibility for this on their own, I want to publicly applaud the efforts of both AAU and AAMC for doing exactly that.  And I think it's a demonstration of the fact that in fact there is responsibility there.  I think it's a wonderful accomplishment.  I think everyone here applauds you for those efforts.
	The one concern -- maybe not concern, but an issue of relevance to me.  As you may know I run a federal regulatory agency and -- 
	[Laughter.]  
	DR. COHEN:  No kidding.  You mean those rumors are true? 
	[Laughter.]
	DR. KOSKI:  You have indicated in your slides the need for, the desire for the stakeholders to endorse and enforce these guidelines to develop an effective, incredible system for self-regulation.  Jerry Kasera [ph] wrote an article in JAMA not so long called "Pseudo Accountability" which raises the issue that the medical profession, in particular, has not always done a good job of bringing to there efforts at self-regulation appropriate accountability.
	Now, to the extent that these guidelines will clearly be enormously valuable, in fact the way that they are written in drafts that I have seen, there are a lot of words like "should" and so on that -- and even a couple of "must"s.  That's right.
	I was thinking about writing a little letter to you to ask you to withdraw these because they were overly prescriptive and sounded like regulations. 
	[Laughter.] 
	DR. KOSKI:  But here's the real concern.  To the extent that these policies are in fact followed, they clearly are going to serve the entire human research community well.  To the extent that they are not is going to pose a burden.  What is the appropriate relationship from your view between these private organizations and what we on the government side would have to do with respect to real enforcement should the guidelines and the initiatives that we are seeing among the stakeholder communities not be adequate for their task?  In other words, what would you advise me to do with respect to either pursuing additional regulations or guidance itself? 
	DR. COHEN:  Well, I guess I'd make a couple of comments, Greg, and thank you for your previous remarks.
	First of all, I absolutely subscribe to Jerry Cacirro's views, I think there has been an enormous amount of pseudo accountability and I think we really have to address that issue forthrightly.
	Secondly, I think, as I indicated, one of the things that I think is going to be new in the future that never existed in the past is an accreditation process for human subjects protection programs and that's why I wanted to be sure you understood that we are planning to think these guidelines with the accreditation mechanism so at least there will be an opportunity for a periodic and intensive review of the degree to which institutions have in fact adopted and enforced these guidelines in the course of their activities.  And I hope that is going to elevate or increase the degree of compliance with the standards that we think the community ought to establish for itself.
	Having said that, I have no doubt that there will be some failures to comply and some opportunities for improvement clearly that the accreditation process itself is going to try to foster, but may very well need the additional scrutiny and involvement of the federal government to ensure that these guidelines -- or if it agrees that these are the guidelines that all appropriate.
	One of the things that would be helpful with these sorts of -- and, again, maybe I'm not using the words properly because I don't know the government-ese well enough, but some kind of deemed status for the accreditation mechanism, for example, that would allow them to be viewed as working in the same context as your office and others would be interested in.
	But I do think there has to be some kind of linkage with public policy here and public scrutiny of the activity.  I just think that the standards need to be those that we believe within the community all appropriate and I hope everybody agrees that these are tough standards.
	CHAIRPERSON MARSHALL:  I think we would and I'm going to take the chair's prerogative and note that our report and at least the draft of your report have many similarities and we're wondering how our work might have informed your work?  Or, was it serendipity? 
	DR. COHEN:  Well, I think probably both.  I mean, it's hard for me to believe that when thoughtful people sit down and start thinking about these things they don't come up with pretty much the same kind of general comments.  But I think there's been enough dialogue back and forth that I certainly don't take any pride and authorship here.  I think this has been a community effort, and I think what you all have done has been very important in contributing to it.
	CHAIRPERSON MARSHALL:  That was our hope was that people didn't see it as sort of the final word, but that really because as David Korn has pointed out, this is relatively new in terms of being an issue and the response is an evolving process.
	So I commend you.  Your draft report looks just wonderful and thank you so much.  And I would like to take advantage of your presence just for a moment and perhaps also Richard Termins to say that we spent some time as a committee yesterday discussing possible research ethics that may be or have been occasioned by the events of September 11th, concerns about overburdening particular research populations in New York or Washington and so forth, and that we will be perhaps working as a committee on looking at the ethics of research relative to the events of September 11th, but that also it would be important for organizations such as the AAMC and the AAU to be thinking along those lines and providing guidance as well to their own research communities.
	Thank you very much, Jordan, appreciate it so much. 
	[Applause.]
	CHAIRPERSON MARSHALL:  So, we do need to move along.  Im going to pass out to all of you a letter, a very nice letter, that we have received from Art Lawrence, thanking us for our comments on the Department's draft interim guidance on financial relationships in clinical research.  The letter was written to me, but I think really it belongs to all of us and I'm going to ask Kate, she will do this in about two minutes, to move us into the next agenda item which is really updating you on the progress of our report so far.
	MS. GOTTFRIED:  Well, just in the spirit of follow-up, I wanted to update the Committee or where we are with the various documents and reports we've drafted thus far or finalized as well.  Just so you all know on our web site, we had a new section that says one the homepage, "NHRPAC," and then it's "reports/documents."  And so if you click on that link it will take you to everything that we've done to date in chronological order.
	So Mary-Faith has distributed the letter from Art, which acknowledges our final recommendations and advise on financial relationships to the department noting that that's NHRPAC's recommendation.
	The other two thing that we drafted were letters; one to the FDA and one to the HHS that were submitted within timelines that were required by the various closing of comment period.  So the FDA is working and these have to do with 45 CFR 46 Subpart D, specifically related to 408C, that was the that the FDA had proposed a rule that virtually adopted Subpart D, with the exception of that provision 408C , which had to do for parental permission or guardian permission and whether or not it was reasonable to require it in certain instances.  And so we, from the children's workgroup, initiated it, but the Committee as a whole forwarded this to the FDA.
	And I just wanted to tell you that the FDA is working on its response to those comments that they received.  And they received about 19 comments; five from pharmaceutical companies, five from health-care professionals, four from national member organizations, three from the federal government sources, one from a state legislator and one from a private citizen.  And they are hoping to have the rule cleared within the FDA by the end of the year.
	DR. FLEISCHMAN:  What are we?
	MS. GOTTFRIED:  I assume we are a governmental source.
	The other letter that was drafted and sent on behalf of the Committee was the one in response to the interim rule on Subpart B that was issued by the department and those comments have been received and are under review and evaluation, and the process, as everyone knows, is governed by the APA the Administrative Procedures Act, for formal rule making.  And the Department also expects to publish a final rule by November 14th, or as soon thereafter as possible, but really their target date is the 14th.
	And I see Irene and Susan Sherman, just wanted to give either of you an opportunity if you wanted to say anything further with respect to that because these are our two pinpoint people in the department dealing with this.  Anything?
	AUDIENCE PARTICIPANT:  No, that's it.
	MS. GOTTFRIED:  Great.  Thank you.
	Alan?
	DR. FLEISCHMAN:  I had the opportunity to chat with Irene yesterday and shared with her an observation that surprised me, that I think NHRPAC should hear about.  In terms of Subpart B, those of you may remember that there was some concern about the definition of neonate and the potential to preclude important research in neonates based on a conflict in regulation between Subpart B and Subpart D.
	I don't want to get into all of the specifics of the language, but we tried to sort that out and our letter.
	I learned over the course of the last two weeks that some very fine institutions with very fine IRB administrators have read the proposed regulations of Subpart B be as if they were final regulations and have precluded some research already and have stopped research in process in neonates.  So it does speak to, (a) the importance of the risk averse concerns of IRB administrators and, (b) the way that this will be read if in fact Subpart B is passed as proposed.
	Irene assures me that she can tell us little until November 14th about what the final rules will be, but I just would argue that we could predict what will happen if those rules are not dramatically altered.
	CHAIRPERSON MARSHALL:  Thank you, Alan.
	We will give Kate the floor again.
	MS. GOTTFRIED:  This is just a quick sort of informational we were going to have time, or leave time for discussion but I think in the interest of moving on to the social science revisit to the third party issue I will just briefly tell you about this conference that's coming up in April.  There are a number of sponsors involved in this; OHRP is one of them.
	Bill Hendy [ph] who is a former colleague of mine on another project actually initiated this out of the University of Wisconsin -- no, I am sorry the Medical College of Wisconsin, Milwaukee.  It's a topic that is near and dear to everybody's heart, accountability and clinical research balancing risk and benefit.  And you'll see in your briefing books that there is a draft agenda there which he allowed me to share with you.  It starts on a Wednesday evening and it's basically the full day on Thursday and then part of the day on Friday.
	Bob Levine, who we all know, is opening that meeting as the keynote.  And I should say actually Greg Koski is opening it in the evening prior and Bob Levine is following the day after. Both billed as keynotes.  But as you see the issues that are going to be covered are ones that we are all familiar with.  But I think it will be a very strong meeting and the interest is really to look at the issues and figure out how in fact to balance risks and benefits so that we don't have a chilling effect on research and that we can encourage people to volunteer and at the same time ensure that they are protected properly.  So, unless anyone has any input.  Alan?
	DR. FLEISCHMAN:  I don't want to speak for Dr. Rich, but the issues that he raised with Jordy Cohen and the issue that I think it becoming more and more obvious and that is the role of private practicing physicians and nonacademic research needs to be accounted for and balanced as well and I don't quite see that in this agenda.  So just as a suggestion, since I think you ask for those, that is an area of import; it is hard to get one's hand around, but it is one that we're going to have to think about.
	MS. GOTTFRIED:  No, I greatly appreciate that and indeed that was the purpose of this segment was to in fact have a brief discussion with the Committee to invite input on what areas you think might be further proposed to their organizing sponsors.  So if anyone has additional comments now I love to hear them and if not please feel free to communicate with me by via e-mail or phone on this.
	AUDIENCE PARTICIPANT:  Where and when?
	MS. GOTTFRIED:  Sorry, April the 24th to 26.  I mentioned the dates, I didn't mention the location.  It's in Indiana, Indianapolis, a city we all love.  I've never been there so I'm assuming I'm going to love it and I don't have the particulars.
	No, you see, you have to have an open perspective wherever you go.  I don't know the exact location yet and so as we get more I'm sure they will have a huge dissemination.  As a matter-of-fact we've offered, I think, to put it on our web site and give them our list serve.  So many of you will have that information and if you don't get it for some reason and you want the information just contact our office.
	CHAIRPERSON MARSHALL:  I think Greg wanted to make a comment.
	DR. KOSKI:  Just to respond to a point that Bob and Alan had raised.  The American Academy of Pharmaceutical Physicians which represents many of those private practice physicians who are engaged in clinical trials, at their annual meeting just a week or so ago, actually adopted a code of ethical behavior for conduct of clinical trials which is a milestone event in my mind, and historic, really, in its importance a wonderful thing.  It seems to me that there may also be an opportunity, Mary-Faith and I were talking about this, about using a venue like that for encouraging them to also adopt, for instance, something very similar to, if not identical to, what AAU or AAMC have put together with respect to conflicts of interest.  It would fit right into this overall notion and seeing the pharmaceutical industry and the device and trials step up to the plate as well.  So I think there's some enormous progress being made and would like to see that go forward.  But this professional society may be another that could join the ranks.
	CHAIRPERSON MARSHALL:  So we have 15 minutes now we need to move along.
	AUDIENCE PARTICIPANT:  Greg is that posted?
	DR. KOSKI:  I believe it was adopted by their executive committee.  At the meeting they gave me a copy of it.  I suspect that you will find it on the web site for the American Academy of Pharmaceutical Physicians, yes.
	CHAIRPERSON MARSHALL:  We can get that for all of the committee members.  So let's move along and I would like to turn the floor over to Mary Kay.  We have somewhere around 15 minutes.  We are starting with Tom Beauchamp at 9:45, so you guys have been working hard this morning.
	DR. PELIAS:  Yes we have, and we were even awake when we were doing it, I think.  I'd like to report to you where the working group on third parties is and if Felice if you don't mind could we send out this statement now around the table, please.
	We started out a few months ago our first discussions had to do with the possibility of change in the language, the definitions and the CFR.  And after we went over and over this for a while I think the general consensus was that to change the language in the Code of Federal Regulations is such a formidable task that what we would do would be to try to work within the language as it exists now and provide guidelines for contemporary applications of the content, of the definitions as they are now to situations that have come up since the regulations were promulgated a couple of decades ago, I think.
	We have been thinking these questions over for six months.  We spent a good deal of time and three conference calls and I think that the conference calls and the summaries that we prepared and distributed over the course of the last six months have been pulled together in the materials that have been provided for you at this meeting.  At the end of the materials that we provided for you, we have a draft of some guidelines.  This has become the famous pages 9 and 10, all right.
	One of the things that we've done with this draft is to prepare three parts.  The first part was parties to research projects.  The second part deals with confidentiality issues and the third part is called the "Role and Responsibility of IRBs."
	Our attention yesterday and today has been directed to the issue of parties in research projects and I am happy to report that as of breakfast this morning we seem to have a consensus on the issue of third parties.  This consensus is represented in the handout that has just been passed out.  It was prepared at breakfast by Felice Levine and Mark Barnes.  And if I can find it -- I know I have been here somewhere -- this is called "the breakfast statement." 
	[Laughter.] 
	DR. PELIAS:  And it will -- 
	MS. GOTTFRIED:  Not to be confused with the breakfast club. 
	[Laughter.] 
	DR. PELIAS:  Not to be confused.  So this page which has just been distributed to you was put together by Felice and Mark and it covers the first area that was contained in the handout material about who should be regarded as parties in research.  Including the investigators or their agents, human subjects who interact personally with research investigators, and third parties about whom researchers obtain information but who have no interaction with the research.
	The next sentence is significant.  It has to do with the determination of who is and is not a research subject and the fact this determination rests with the IRB.  So essentially what we have agreed on is this:  not all third parties are automatically human subjects.  And this is an issue that should be left for the consideration of the Institutional Review Board.  There is some explication in the rest of this statement.  I would like to just wind this up by saying, I think we are in a agreement on principles.   The principles are in tact and I would say -- and this is partly my own -- from my own orientation, I would say that the language in this statement is subject to modifications and that's largely because I have a healthy suspicion of adverbs and adjectives and dependent clauses. 
	[Laughter.] 
	DR. PELIAS:  So we will work this over.  The principles and the ideas are going to remain in tact.  The language may change but you can anticipate a slight modification of the prose before the end of January.
	With regard to the other two parts of our proposed guidelines on confidentiality and on the role and responsibility of the IRB we haven't gotten to that yet, but we will eventually.  And that's where we are right now.  We hope to have some good guidelines by the end of January.
	CHAIRPERSON MARSHALL:  Thank you very much.  Let me ask that we open the floor for a discussion from committee members.  Yes, Susan?
	DR. KORNETSKY:  As one of the people who is concerned, I just want to commend the people who wrote this.  This is beautifully written and I think very useful and will be very helpful for the IRB community.
	DR. PELIAS:  Thank you. 
	CHAIRPERSON MARSHALL:  Alan.
	DR. FLEISCHMAN:  I share Susan's view.  And I merely suggest that we would remind people about the potential to waive informed consent somewhere in that process that even though you are a human subject you can deem such consent as optional.
	DR. THORNLEY-BROWN:  I just wanted to echo Susan's view too; I think it's very good and much clearer than yesterday.
	CHAIRPERSON MARSHALL:  May I ask, Mary Kay, for the benefit of our ex officio and public members, could you read the document?  So that they have some sense of what we're talking about.  And Sandy, I've got you.
	DR. PELIAS:  I think this should go into the record.  The title of this new paper is "Clarification of Third Parties in Research.
	In regard to considering third parties in research, the parties whose roles and interests must be considered include:  (1) research investigators or their agents.  (2) Human subjects who interact personally with research investigators.  (3) Third parties about whom researchers obtain information but who have no interaction with the research.
	    The determination of who is and is not a research subject rests with the IRB.  In most instances the identity of human subjects of research is clear.  Whether through interaction, intervention, or identifiable private information, persons are human subjects when they are providing personal or contextual information about their own lives, circumstances, perceptions, or histories, even when they make reference to others.
	     Simply because a third party is contemplated in research design or a third party's information is recorded in research results does not necessarily suggest that a third party must be regarded as a research subject.
	     Investigators in designing and proposing research projects and IRBs in considering and reviewing research projects and in conducting continuing review should consider how the research design might focus not only on the identified subjects, but on other persons as well.
	     In cases in which a research project's design collects a significant amount of information in identified form on third parties, the investigator and IRB should consider whether any of these third parties should be regarded and treated as research subjects themselves.
	     In making this determination the following factors should be considered among others.  (1) The quantity of information collected on the third party; (2) the nature of information collected; (3) the sensitivity of the information collected and the possibility that information may be turned to possible harm to the third party; and (4) the possibility of recording information on third parties in such a way as to protect the identity of those parties.
	 And that's it.
	CHAIRPERSON MARSHALL:  Thank you.  I have Alan.  No.  You went.  Oh, I'm sorry.  Sandy.
	DR. CHODOSH:  You wanted something about including something about waiver.  I think what we are trying to do is to leave open to the IRB all of their avenues of approaching this problem.  And to just mention waiver against sort of like focuses and bound to that as the possibility as the alternative, when in fact there are other alternatives.
	Once we start that then I think we have to start putting down all the possibilities which may vary and may change and certainly will change from protocol to protocol.
	DR. FLEISCHMAN:  I just wanted to respond that again in a kind of risk averse fashion, IRB administrators may assume that NHRPAC is saying once you are deemed a human subject therefore you must have a formal consent document and process.
	And I just a wanted to be clear that in our document that we lay out all the options that once, just to remind IRBs that we took that into account and once you are deemed a research subject, by the IRB, it means several things are possible in terms of potential actions.  That was my point.  I didn't mean to say that was the only direction they could go. 
	CHAIRPERSON MARSHALL:  I have Felice and then Phil.
	DR. F. LEVINE:  In response I think we could conceivably add a sentence to the effect of:  the issue of consent or the waiver of consent pertains only to those deemed to be human subjects.  I think that's -- this all is about who is a human subject and when a third party becomes a human subject.  So that would account for the possibility of waiver.
	PARTICIPANT:   [Off mic.]
	DR. F. LEVINE:  No.  I think what we are trying to avoid is a situation where third parties who are not deemed to be human subjects have some kind of the consensual waiver.  So that's why it wasn't in, because all of the other issues with respect to human subjects are there.
	I have a -- I don't know whether I should -- 
	CHAIRPERSON MARSHALL:  The floor is yours.
	DR. F. LEVINE:  Okay.  I find this meeting what I think MK and FJ thought originally was the shared agreement that we both had when we discussed the issues substantively.  The area where I feel it trails off and where I would be less comfortable, at this point, is from -- in making this determination.  Because I think how to make the determination raises some flags that I think we should defer.  So I would prefer ending after IRB should consider whether any of these third parties should be regarded and treated as research subjects themselves, and have the part from "in making" deferred until we take up those processes.
	In part I am saying that because there are a lot of instances with respect to one, two, three, or four where what an IRB would see to be the subject might have a different interest with respect to a third party who is the acknowledged third party.  And I can give three ready instances of that.
	CHAIRPERSON MARSHALL:  Let me ask, Felice, then maybe we will need to explicate that a bit.  But Committee members is this a compromise in terms of leaving the last sentence and sort of the specification at deferring for the future or not?
	DR. BARNES:  Well, I know that Felice does not like it, but I thought that what we had worked out in this statement was largely a compromise among many people.  Some who wanted more and some who wanted less, and I -- this is just my personal opinion, but I prefer not to defer it.  I think that it may need more wordsmithing.
	I think that ultimately Mary Kay has got to go back and take this entire document and make it internally consistent so that the rhetoric and the terms used et cetera are all consistent with the overall ideas that has been expressed both in this document and also in the discussion.
	But I think that my opinion was, based on the conversation both yesterday and today, that there was a sense that the IRBs needed some guidance as to what criteria they need to consider in the same way that in the, although it's not exactly analogous but in some way in determining whether to waive informed consent, they are given a series of four criteria and then they are told that they have to discuss it and may have to address, and it should be reflected in their minutes but the determination is really left up to them.
	CHAIRPERSON MARSHALL:  Felice.  And I want to keep us to our time table, so I think I am going to call the discussion after this.
	DR. F. LEVINE:  Let me just say that I think the entire document up through points one through four reflect a lot of compromise.  So in that sense there was compromise in the three sentences above, of which I share that view.
	My concern about one, two, three, and four at this point is that I think a lot more thought needs to go into how can give IRBs that guidance and I don't think we had yet reached a meeting of the minds.  So I am happy to ultimately give that guidance.  I am concerned about this specific guidance because it could conflict with our responsibility to the identified human subject.  And that's why I am inhibited about the last sentence and one, two, three and four at this point.
	DR. KORNETSKY:  As everyone refers to the IRB administrator who is going to have to help their IRB make this decision, I have to say this:  these last four lines are probably the most useful part of the document.
	Now, I do understand that there may need to be information behind this, but I think that without this there's a real void.  I think IRBs are used to sort of thinking about certain things and I think without this it is a naked document.
	DR. F. LEVINE:  If I can just clarify one more moment.  I'm not suggesting that they are not be a one, two, three, or four.  I am only suggesting we give more thought to what that one two, three, or four, or five, or six are between now and January, because I think some of these may be problematic.  That's the only thing I'm saying, not that they should be absent, I just have a concern about these at this point.
	DR. KORNETSKY:  I think these are general, and I think that certainly that a lot of the things that we discussed can certainly fit in to any of these.  I don't see anything that is really missing from here, but I think certainly expanding on these things and including all of the things that you're concerned about within this would be appropriate.
	CHAIRPERSON MARSHALL:  Kate informs me that we can take two or three more minutes.  Elliot, then Mary Kay.
	DR. DORFF:  If you remember our very first meeting, we were presented with a document from I think it was the American Sociological Association, complaining about the intervention of IRBs in a kind of unsophisticated way into social science research.  And I think I personally was very much moved by the document, and I think that we need to be very sensitive to the problems that social scientists have had with overzealous IRBs or with IRBs that don't really know how to judge social science research in comparison to medical research.
	So, therefore, I would be very much interested in hearing the three cases that Felice has in mind, and would be very much interested in having -- I also share Susan's view that I think these four are very clear and in that way they are very neat.  But if these things that in practice are going to interfere with social science research in significant ways, then I would go with Felice on this to be very honest, to make sure that we think out these four very carefully so as not to impede the kind of social science research that is really important.
	CHAIRPERSON MARSHALL:  Mary Kay.
	DR. PELIAS:  I think that we have to be very careful about any kind of specific guidance that we put down in terms of the language of one, two, three and four, and any others that we might want to be, because we might want to write down, because I think that we have to be careful about not introducing inflexibility into this document.  We need it to continue to be flexible.
	CHAIRPERSON MARSHALL:  Thank you.  Phil.
	MR. REUBEN:  Phil Reuben, National Science Foundation, I want to commend the compromise and the hard work.  I think as the document presently stands it will impede social science research.  I think it's getting closer and I would second Elliot's concerns and Alan's concerns on this particular one.
	It looks good but it's a matter of perspective, I think it's getting very close and could use a bit more fine tuning.  I'd be happy to contribute some additional stuff, but I think that you're moving in the right direction.  But I think Elliot's point is a subtle one, and is matter of perspective.  I can almost guarantee you as it is worded it will impede social science research.
	MS. WATERMAN:  Paula Waterman, Department of Veterans Affairs.  I just wondered why you removed sponsors from participants in research?
	DR. BARNES:  We did not remove them.  The point is, because there are many interested parties in research.  The point here is what parties were particularly important to this particular analysis, which was the investigator, the research subject and the third party.  It's not to say that sponsors aren't important but if you start listing all the interested parties in research, you can have three pages of interested parties in the research, that's all.
	CHAIRPERSON MARSHALL:  So here is what I propose, Committee, is that we agree in principle as a Committee with this document; that we acknowledge that there is fine tuning of sort of specifying the guidance in the latter part of the document to IRBs; that I would ask Felice, Mary Kay, Elliot, Phil and any others on the Committee who are interested in working on that language to do so in short order and that we then get that draft document out to the Committee as a whole for consensus so that we can post it on the web so that we can have something that is final by January.  Alan?
	DR. FLEISCHMAN:  Could we please take one extra minute to have Felice tell us the examples.  Because -- 
	CHAIRPERSON MARSHALL:  Let's do.
	DR. FLEISCHMAN:  You know we're right at that moment in time and my head would be much better served, in terms of thinking about this.
	CHAIRPERSON MARSHALL:  Let's do.
	DR. F. LEVINE:  My concern and my three quick examples are really no different than others I've offered on this, really relate to how the primary commitment to the human subject even in the face of certain forms of information, in particular, sensitive information about others.  So three examples:  a study of drug addiction which are real and live; a study of drug addiction among hookers, focusing on the roles of pimps.  Now, that may be considered sensitive information about pimps.  It may be considered  -- so of course we're all talking about protecting privacy and confidentiality of that information, but an IRB could begin focusing on whether that party, when the study is about a hooker, becomes a human subject because of it being sensitive information.  That's a recurrent theme here in many of these examples.
	A study -- and this one actually an IRB recently told a person to remove these questions -- a study of adult male violent offenders who were providing history about their own experiences with their own fathers.  A very -- forget it as social and behavioral science, that's biomedical as well and health.  I mean these aren't, what I'm saying is not idiosyncratic to the social and behavioral science.  It's just our work is very oriented to social relations and interactions.
	The one I've given before, health risks to migrant farm workers and working conditions and the expectations of employers.  So if you asked, that could be something that the employers would not love.  It could be highly sensitive information.  So I'm worried about when it's a real third party. Meaning, it meets the criteria of the paragraph in most instances and it meets the paragraph all the way up to and making these determinations that we want to be very clear when you're focusing on the sensitive information about a third party, it doesn't migrate them too quickly to becoming a subject.  And that's why I'm concerned specifically about -- 
	CHAIRPERSON MARSHALL:  I'm going to break.  Thank you Felice, I am going to break in and I guess I'm confused because it seems to me that we are very explicit that ultimately this responsibility lies with the IRB.  That it involves a judgment, and that the sensitivity of the information collected, and the risks of harm to the third party are there explicitly.  So it seems to me we've taken care of your concern.  None of those three examples seems to me is excluded in the process that has been delineated here.  We really need to move on.  Greg?
	DR. KOSKI:  I'll just make a final comment here.  As I pointed out to many members of the Committee and the Chair yesterday the effectiveness of this committee is really determined by its ability to deliver coherent, well-reasoned, and substantive advice on these very complex dilemmas that we face, and I think that you're making real progress there.
	I want to caution you, remember that your job, however, is not to write guidance.  Okay.  Your job is to advise the department.  The guidance will be written by our office on behalf of the department with input not only from your Committee but also from such groups as the NIH trans institute bioethics committee and so on, there are a number of stakeholders.
	I think one of the key issues here will be to have sufficient information available to the IRBs in this guidance to really give them something they can put their teeth into.  So that specific examples of the types of research that you're talking about and how they can be appropriately addressed under the regulations and the guidance will be a key to addressing the kinds of concerns that you raise, Felice; and clearly what comes out of the Department must take into consideration not only be biomedical model but social and behavioral science as well.  Otherwise it's not going to be effective.  So it will, it has to is the bottom line.
	But, again, remember in your drafting that what you need to do is to give us your advice and substantiate that advice, don't get into the game of writing guidance we have people that do that.
	CHAIRPERSON MARSHALL:  Thank you, Greg.  So I'm going to move to ask that the Committee endorse the document as it is written so that we can move forward.  We are not finished with the product.  It will be posted, there will be opportunities for further discussion and fine tuning, but we need to move on.
	DR. DORFF:  Could we include her examples along the lines that Greg just mentioned? 
	CHAIRPERSON MARSHALL:  No, I don't see the necessity for doing that.
	DR. SHAMOO:  So moved.
	CHAIRPERSON MARSHALL:  Can I have a vote of the committee?  Okay, those for posting. 
	[No response.] 
	CHAIRPERSON MARSHALL:  Those opposed to posting. 
	[Showing of hands.] 
	CHAIRPERSON MARSHALL:  We are in consensus.  Thank you very much.
	We have voted on posting the document as it stands on the web site.  It is still open to revision, to comment and revision.  So thank you all very much.  I appreciate it.
	And let us invite Tom Beauchamp to the table.  I've asked Tom to come and talk to us because I think in terms of discussing informed consent he has more moral authority than most to lead a discussion and to educate us as a committee.  We've begun that education.  But I asked Tom to come and talk about informed consent generally and apprised him of the fact that in our work so far in every working group, financial relationships, children, looking at social and behavioral sciences, that certainly a common theme has been informed consent.
	We are about to embark on investigating problems associated with research with the decisionally impaired, so I think that we need to -- and perhaps I think form a working group on inform consent itself, because it is so pervasive.  And I would say that we do not want to constrain ourselves by closing our minds ahead of time to the idea of changing the regulations or moving in any direction.
	Tom, we are delighted to have you here to help us, to educate us, and to help us perhaps arrive at a frame work for thinking about informed consent.  Welcome.
	DR. BEAUCHAMP:  Thank you.  To have more moral authority than most may not be to have very much more moral authority.  I was very glad that Mary Faith put it in terms of informed consent generally because I felt free to talk about anything that I wanted to talk about.
	The other speakers seem constrained by these more minute topics and, Eric, perhaps you are happy to be constrained by a more minute topic.  But I am just going talk about things that interest me about informed consent and then you can turn it, I suppose, in the direction of things that interest you.
	Yesterday afternoon I was engaged in a conference call about whether a research protocol could pass muster with a funding agency.  This protocol had been submitted by a young psychologist, a very young psychologist, to an East Coast University IRB which approved the protocol, though I do not believe that there were any psychologists or behavioral scientists on the IRB who were particularly familiar with the nuances of this kind of research.
	The IRB deliberated largely on the basis of an IRB written form filled out by the investigator.  That is to say, the IRB had prewritten this form, it had blanks in it, filled with blanks.  The form was clearly written for biomedical not behavioral research.  For example, the form requested that the investigator provide a statement of, "appropriate alternative procedures or courses of treatment that might be advantageous to the subject."  Something that was totally irrelevant to this type of research which is questionnaire research.
	The IRB approved the investigator's proposal for obtaining informed consent and here is where things get interesting.  In the protocol, under the heading of "work proposed methods of procedure" there is the one and only statement about informed consent.  The statement there is that a potential subject has given an informed consent to the study once the subject has read a brief introduction to the research.
	I'll say that again, the statement there is that a potential subject has given an informed consent to the study once the subject has read a brief introduction to the research.
	Now, you will think perhaps the I am exaggerating, that I have left something out here.  Here is the exact statement from the protocol and the only statement about informed consent in that protocol and the only thing that went before the IRB when it approved it.  I quote, "I will provide a brief letter of introduction of the researcher an the study, the reading of which constitutes the giving of informed consent."
	Now, this would be laughable were it not so common for reasons that I will get to in a moment that is to say why it is so common.  But first there is another reason why such a ludicrous proposal is really far from laughable.  A careful reading of this protocol shows that this study is actually potentially dangerous and at multiple levels.  It is quite possible that some of the information proposed to be collected could fall into the hands of the employer of those being studied.  It's quite possible in this circumstance.  And if this were to happen it could have devastating consequences.
	If I were in an employer and I had the kind of information this study is collecting and I knew certain things about the employees I would fire them; right?  And that's a quite possible outcome here.  I don't say it's a likely outcome but it is a quite possible one.
	Further it's proposed that if certain facts about the attitudes and feelings of the subjects were revealed by the research, clinical interventions would be proposed to the subjects including psychological counseling and even psychiatric evaluation.  Other mentioned possible recommendations are for antidepressant medication.  It is not said who would make these recommendations.
	Pretty soon the risks of research accumulate, but as far as this investigator and this IRB are concerned, as far as we were able to study, that is to say external evaluators looking at this protocol and the whole situation which is the reason for the conference call, as far as we can see both the investigator and the IRB thought this is risk-free research.  None of this is mentioned to potential subjects, as you can see by the one and only one statement about informed consent.
	Now, the view reflected in this protocol and many others that I've seen over the years is that once the subject has read a disclosure the subject has given an informed consent.  Again, it seems like something is left out and undoubtedly something is left out, but, to read the protocol you would never know that.  This curious idea is deeply at odds with prevailing view in the literature of biomedical ethics and I believe the ethics of the behavioral sciences as well since the mid-1970s.  The primary justification for requirements of informed consent is the protection of autonomous choice.
	I believe that this is the right justification and I believe it is the only justification for the imposition of duties on biomedical and behavioral scientists to obtain the informed consent of patients and subjects.  And so in a way that's the overall theme that I've got this simple theme that I hope I will play it out in a somewhat more subtle fashion.
	Strangely in the imperative to protect autonomy or self-determination has itself often been viewed as merely a letter of making adequate disclosures.  This outlandish notion is gained so much currency in the literature of clinical and research ethics that many people equate good disclosure with good informed consent.  They have thought it a great moral advance, if you monitor the quality of the disclosure on a consent form.
	In some reason presentations that I have seen, such as the presentation I'm now making before you on the Committee, some people seem to think that this is really what informed consent is all about, making good disclosures and monitoring those disclosures.  This idea has been nurtured from the birth of the notion of informed consent by the fact that informed consent was delivered to us in the wrappings of a legal doctrine that was imposed first on medicine.
	The legal doctrine of informed consent of the United States has been primarily a requirement of disclosure based on a physician's general obligation to exercise reasonable care by giving information.  This focus results from the legal systems need for a serviceable mechanism to assess injury and responsibility.
	However, from the moral viewpoint, informed consent has literally nothing to do with the legal liability of professionals, vectors of disclosure and has entirely to do with the autonomous choices of patients and subjects.  Both health care professionals and patients need to ask and answer questions and this process is less a matter of disclosing information than of discovering what the relevant information is.
	The real meaning of disclosure in the consent process is informational exchange that moves toward a meaningful and informed decision by the patient or subject.
	Some polls especially one memorable poll that I'm sure many of you have seen conducted by Lou Harris for the President's Commission indicate that physicians and investigators themselves regard adequate disclosure as more or less synonymous with informed consent.  This shallow idea has been brilliantly criticized, in my view, for a quarter of a century in the writings of Jay Katz.  He and others who have followed him, including the President's Commission, have used the idea of autonomy to reconstruct the idea of informed consent as "shared decision-making" to use their language.  That is to say, shared decision-making between doctor and patient or extended to research context investigator and subject to participant, whatever your favorite language is.
	Their thesis is not that informed consent has this meaning in ordinary language or law.  It's really a reforming proposal.  Their view is that its should have this meaning.   And, of course, that doctors and investigators should create an environment of mutual decision-making whenever they are required to obtain an informed consent.
	This proposal is plausible when consent involves ongoing exchanges of information.  And we owe Katz a great for his contribution to our understanding of informed consent.  Scarcely anyone I think could be said to have contributed more.  However, I believe it is a conceptual and a moral mistake to reduce informed consent to shared decision-making.  Indeed shared decision-making is a misleading model because it fails to capture what in the end informed consent is all about.
	Informed consent is an individual's autonomous authorization of a medical intervention or for participation and research.  Contrary to what is said over and over in the literature of biomedical ethics, informed consent has nothing to do with mutuality, with disclosure by health professionals, or with anything having to do with more than one party.  It is of course true that a person will generally be expressing agreement with or complying with an offer or proposal proffered by a professional.   But an informed consent is neither more nor less then authorizing through an individual's act of informed involuntary consent.  That's what is and it is not anything else.
	An informed consent occurs if and only if a patient or subject with substantial understanding and an absence of substantial control by others intentionally authorizes a professional to do something.  I do not mean to imply, by all of this, that disclosure is not a pivotal topic for discussion of informed consent.  Without information many subjects will have an inadequate basis for decision-making.  The professionals' knowledge, perspective, opinions and even recommendations are often essential.  Professionals are, of course, morally obligated to disclose a core set of information.  They may also be morally obligated to make recommendations.  But this is only one aspect of informed consent and it is often not the most important one.  Nor, as I have argued, does it lie at all at the heart of the meaning of informed consent.
	Our medical ethics has moved in recent years, and I think behavioral research ethics as well, from a narrow focus on a researcher's obligation to disclose information to the quality of the patient or subject's understanding of information and right to authorize or refuse some kind of intervention or procedure.  This has been a solitary shift of emphasis at least in the literature of the field.
	We can look in and beyond that literature to ask, how we are actually doing at the present time and how we've done in the past for that matter, in communicating risks, uncertainties, the nature of procedures, reasonable expectations and the like.  How then are we doing at getting people to understand and to consent with understanding?
	The answer, I think, seems to be something like, well not as well as we might hope, and not as well as we are often told that we are.  What we are often told, I think, builds on the idea that informed consent is disclosure and so what we are often told has the character of being misleading.
	For many years now studies have been published on problems in communicating information in the informed consent context.  Let me mention just a few of the studies and their conclusions within the context of what I am saying.  Has Jeremy Sugarman talked to you before about some of the studies?
	CHAIRPERSON MARSHALL:  He did at our last meeting.
	DR. BEAUCHAMP:  Right.  So some of this that you may have heard, but I'm obviously trying to craft it in the context of what I'm saying.
	I have it from an informed source that you learned a few things yesterday about ACHRE and of course I had the wisdom of Jonathan Moreno to back up or challenge anything that I might say before you, but I wanted to start since I know you do something about ACHRE and I am sure Jeremy would have mentioned something about it as well.
	I want to mention one study done by ACHRE. In that study, which is supported by ACHRE, they examined informed consent forms that had been given to an approved by IRBs and I thought this would be a study worth mentioning for this reason.  The study found that informed consent documents raised serious ethical concerns in about 14 percent of the protocols.  Moreover, reviewers determined whether their research proposals as described in the documents involved minimal risk or greater than minimal risk of harm to subjects.
	All of the studies that raised serious ethical concerns, let's say those falling in a 14 percent were considered greater than minimal risk.  Every one of the studies raised ethical and communication questions regarding inadequate information on the consent forms as well as issues and understanding the information that was provided on those forms.  In the most worrisome studies -- I'm giving you my own view here -- the disclosure made on the forms overestimated and overemphasized the possibility of benefits and underestimated and underemphasized the magnitude and probability of risks in the research.
	The committee was particularly troubled by consent forms that when compared with the information provided in the grant proposal, or other research documents, appeared to overstate the therapeutic potential of the research.
	It was found that the more troublesome the consent form the more likely are the benefits to be exaggerated.  One consent form, for example, stated and I quote, "it is possible that the treatment will cause the tumor to shrink or disappear, or eliminate any symptoms and thus increase life expectancy."  Although this statement conveys a promise of possible benefit to the patient subject, the protocol clearly indicates that any benefits would be fortuitous since they were neither an aspect of the research objective nor supported by evidence thus far accumulated.
	This is in effect a deceptive practice in the guise of a disclosure.  One consent form for a project that was designed solely to establish the maximum tolerated dose of an intensive care chemotherapy schedule stated, and I quote, "it is not possible to predict whether or not any personal benefit will result from the use of the treatment program.  A possible benefit could be the treatment achievement of a remission."
	There was, however, no therapeutic intent whatever in this proposal.  Physician investigators were interested only in learning if it could be used safely in a subsequent randomized clinical trial.  The subjects, however, could easily be led to believe that there was probable therapeutic benefit.
	Such overstatement of benefits is particularly worrisome because patient subjects so desperately long for these benefits in some studies.
	I could wax on about the Gailsinger case and it's analogy and how it's analogous, but I'm sure you've heard ad nauseam about the Gailsinger case and I am not going to do that, but I do think it fits this kind of description fairly well also. 
	The issue is of particular concern when the subjects being recruited our patients with poor prognoses.  For example, one study which was presented as primarily a toxicity study in the accompanying research documents was cast very differently in the informed consent form that was presented to the subjects.  Quote:  "One objective from that form, one objective is to find out how well patients respond to treatment.  If treatment works in your case, it may shrink your tumor or cause it to temporarily disappear and/or prolong your life and/or improve the quality of your life.
	Another objective of the study is to find out what kind of side effects this treatment causes and how often they occur."
	Again I think you have little more than deception at work in such a statement.  Several studies provide evidence that patients who become research subjects often have an unreasonable vision of what life will be like to them and of their therapeutic prospects.  They are muddled about the differences between research and therapy, and many think they are receiving treatment designed by a physician with their best interests in mind when in fact the work is driven by the demands of a research protocol.
	In a well-known study and analysis published way back in 1982, Applebaum, Roth and Litz, introduced the now well-appreciated language of therapeutic misconception to treat this problem.  They focused attention on the prevalence of a defective understanding, a scientific methodology.  The nature of the risks involved and misconceptions about therapeutic promise.  They cited as one example a study by my friend and former colleague back in the days when I was doing the kind of work that you're doing on this group.  This was back in the mid-1970s, this is my colleague, Brad Gray.  His study was of patient subjects in a double-blind clinical trial in which he found that 69 percent of the subjects could attach no meaning whatever to the idea of double-blind and almost none understood the methodology a randomization virtually zero.
	Instead patient subjects substituted their own idea that they were individually the focus of the investigation.  In their own study Applebaum, Roth, and Litz used interviews with psychiatric patients again involving a randomized trial.  They underwent an exhaustive process of disclosure by the own accounting, what they called "a nearly ideal consent process."  That's a direct quote from their study.  During it subjects were informed about the nature and goals of the study.  They were then asked what they understood about randomization and what they believed about how they had been assigned to a particular arm of the study.
	Only eight of 18 understood that assignment would be at random.  Six of the 18 believed that assignment to a group was strictly for therapeutic purposes.
	Some others had an even poorer understanding of both methodology and therapeutic intent.  Many thought the doctors would decide which medication they should receive by talking to them.  Around one-third of the patient subjects believed that they had been assigned to a protocol arm based exclusively on their therapeutic needs and that the doctor would decide which drug they received based on those needs and those needs only.
	The hung tenaciously to this view even when the methodology was again explained to them by the investigators.  Applebaum, et al., argued in their conclusion that patients, and I quote, "will invent logical but incorrect methodological details to support the beliefs about therapy that they originally held when they entered the trial."  In other words, a therapeutic misconception from start to finish.
	This well-known result was from 1982 but it has several times been replicated in more recent studies.  The typical problem is that despite very meaningful disclosures patient subjects continue to be motivated to participation by their hope for a therapeutic benefit and their belief that this is why they have been offered participation in the first place.
	Some studies have found that it is no accident that patients have this belief because their physicians have this belief as well.  That is, they too have somewhat unrealistic expectations of therapeutic benefits for the patients.
	In one recent study this is by Dougherty, et al, investigators found that 85 percent of patients decided to participate in a phase 1 trial for a cancer drug exclusively for reasons of possible therapeutic benefits.  The other 15 percent enrolled on grounds of either a physician or family advice to do so.  None enrolled primarily for altruistic reasons, not one.  Although 6 percent mentioned some altruistic reason as a secondary consideration. 
	Of these patient subjects only 33 percent were able to state the purpose of the trial and fewer than 50 percent understood that the purpose of the trial had to do with determining a proper dose of the drug.  Fifty-two percent of the patience said that the purpose was either to determine the response of their tumor to the drug or to determine the therapeutic effect of the drug for them.
	Moreover, even the oncologists who recommended the trial to their patients tended to have very different view of its possible benefits and toxicities.  Researchers also discovered that many patients believe that their physicians had not discussed other options of therapy, including the alternative of no therapy, just supportive care.  Yet this option was clearly stated on the written informed consent form giving to every subject.
	Let me conclude.  I think we should all recognize the difficulties facing physicians and investigators in communicating to patients or subjects a complex set of procedures, side effects, long-term risk, tradeoffs relative to alternatives, and whatever relevant information pertains to this particular investigation.  This task, however, is not impossible.  Documents from many complex research proposals were reviewed in many of the studies that I mentioned that had excellent consent forms and excellent subject comprehension.
	It is far more a question of spending time and getting the language right and ensuring that communication occurs, not a problem, I think, of some impossible goal presented by the requirement to obtain an informed consent.  It is a myth that informed consent is a myth.  Thank you. 
	[Applause.] 
	CHAIRPERSON MARSHALL:  Thank you, Tom.
	I'm glad that perhaps we don't have an impossible task ahead of us.  Let me ask that we do this procedurally.  What if we take a break and then come back and have our discussion, so that we have no interruptions and we have ample time.  How does that sound, we have not had a break this morning.
	DR. BEAUCHAMP:  Doesn't matter to me.  Whatever you guys prefer.
	CHAIRPERSON MARSHALL:  So why don't we take about 10 minutes or so and then reconvene.
	[Brief recess taken at 10:25 a.m.]
	CHAIRPERSON MARSHALL:  I really do feel a little wicked witch-like today, but -- 
	[Laughter.] 
	CHAIRPERSON MARSHALL:  Mark Barnes is not at the table, but he has said in the spirit of full disclosure, just in case there is anyone in the room who doesn't know the relationship Tom Beauchamp and Ruthie, we really don't have a mole on our committee although I'm not sure how we could have a mole, because we are by definition a public body and nothing we do is in secret.  Tom and Ruth wrote the book on informed consent and they are spouses.  So that's where the inside information comes from. 
	So I'd like to begin a general discussion about informed consent and for us to bear in mind and to consider over the next 45 minutes the notion of a working group on informed consent.  What it's charge and goals might be.  Should we do it?  How should we do it?  If we do it, what would this group's relationship to other working groups be?   How or should we inform the process of informed consent and improve the process of informed consent.
	So, lets just open the floor.   And, Tom, I just want to tell you what our procedure is.  We give the same amount of time to the Committee to our ex officio members, and we have in theory members of each the 18 federal agencies that abides by the common rule and are what we call our public members.  Those folks who are here because they are interested and want to be.  So we like to give everyone equal time and I see Jonathan's hand up.  Keep your hands up and I will write quickly, but Jonathan go ahead.
	DR. MORENO:  Tom, I have a question for you about the therapeutic misconceptions and then a question about normal volunteers in research, a topic that you didn't quite have the time to get into.  As you know, when the Radiation Advisory Committee did the subject interview study of 1,900 research subjects around the country, that was a paper survey, but they then did a small focus group, several focus groups, small group and the following interaction was not untypical I'm told.  	Do you understand that this particular study, imagine it was a phase one study, was not designed to help you?  And indeed most research is not.  And the person would say yes.  Well, why did you agree to the enroll in the study?  Because I hoped it would help me.
	Now, what if it turned out, and I thought about this and have no good answer for it.  What if it turned out that for psychological reasons that you and I are not competent to explicate, but perhaps others in the room are, that the therapeutic misconceptions for people who are ill particularly people who are very ill was not eliminable, no matter how cognitively you did this thing?  Would that undermine the moral justification for doing research?  And what implications would that have for the whole doctrine on informed consent that has been developed?
	And then my other question having to do with healthy volunteers and then I'll shut up.  At least one plaintiff's attorney that I've talked to reasonably believes that no risk is permissible for a normal healthy volunteer.  And I wondered if you would comment on whether any degree of risk is acceptable.  Again, partly depended on the nature of the informed consent process, granted, but given the limitations of the process.
	DR. BEAUCHAMP:  On the first question, can I reframe it this way and see if this is what we are dealing with.  If the therapeutic misconception is such that the patient consents without an adequate appreciation of their situation, does this invalidate the consent in the sense of meaning that it's not a valid consent or more common language of not an informed consent because it fails to satisfy one of the conditions of informed consent.
	I would think the answer to that would be, yes, there could be circumstances in which that would be precisely what's happening.  Whether that would be so in every circumstance I'd say nearly that you had a therapeutic misconception without knowing anything else about the information that was important to you on the basis of your consent or whatever would be something we would have to look into.  But, yes, I would think that it would do so and that if you therefore proceeded with the consent that was not an informed consent, it would do something to morally undermine the legitimacy of the research.  Was that the way in which you cast it?  Now, have I got that right?
	DR. BARNES:  Yes.  But what if it further turned out to be the case that the psychologist convinced us that you can't get rid of a degree of therapeutic misconception?
	DR. BEAUCHAMP:  A part of my answer here is, I think it depends on what the degree is and how the information affects the validity of the consent and so on.  But I would think that it wouldn't be very hard to construct a case in which you would say, yes, you can't proceed, they are consenting.
	Now, of course, that's going to be a hard one.  Given the Applebaum, Litz, et cetera study that I mentioned, you've got to be very cautious.  On the other hand, presumably once you're onto the problem of therapeutic misconception, you can take steps to overcome it and hopefully it's not as you framed.  Of course, we know about framing problems.  We know a lot about framing problems now, but hopefully it's not something that's an in liminal problem. 
	Now, the second question which surprises me a little bit, and as I would frame it, with healthy volunteers, you cannot, it's a moral imperative, that you cannot proceed even to offer the research or to send the research to an IRB or anything else, unless you can show that it is no-risk research.  Is that right?
	DR. BARNES:  That's what one attorney has asserted to me.
	DR. BEAUCHAMP:  Yeah, this reminds me, I don't want to do this to much today, but it reminds me of back in the days of our commission that I mentioned earlier in the mid-70s when the great Paul Ramsey, Eric and I used to hang out with and discuss these issues at the Hastings Center, the great Paul Ramsey was basically defending this view from a contient perspective, it was little bit different perspective, but that was the view that he was defending.  And I think basically the outcome was even with children he got no takers, nobody was really buying this line.  And you'd really had to sell it to me.  I mean, because what you're saying is here is a circumstance in which for any number of reasons people might want to be volunteers and to assume this level of risk and you're not even going to offer it to them.
	Moreover there's the problem of whether any research is really no risk research and how we set up the definitions of what no risk is a minimal risk and that which exceeds minimal risk and all those problems that have been around for many years.
	CHAIRPERSON MARSHALL:  Adil.
	DR. SHAMOO:  Thank you, Mary Faith.
	You emphasized autonomous decisions of the volunteer as the cornerstone for informed consent and I guess disclosure plays some role in that exercise of the autonomy.
	DR. BEAUCHAMP:  May.
	DR. SHAMOO:  May.  Okay.  And you gave us examples presumably this was normal volunteers and now we have an example from Jonathan for very ill patients and since we're going to discuss later the decisionally impaired, I want your take on how that problem of autonomous decision is confound by those who are mentally ill?  And I am talking about serious mental illness and what's your reaction to the past 10 years disclosure of cases of what some of us consider abuses of psychiatric patients?
	DR. BEAUCHAMP:  Are we, or are we not talking about mentally ill or otherwise impaired patients including decisionally impaired who can or cannot process information and reach a critical threshold such that it's reasonable to say that they've given a consent in which they understand the information that's of relevance and importance to them.  In other words, at some point you've got to draw a threshold just as you do with confidence.  You've got to draw a threshold and you're going to say, if you satisfy conditions above this, you're competent and if you don't then you're incompetent.  And so here we've got to have some kind of a threshold as to whether or not they have the capacity or whatever it is that we are looking for to give an informed consent.
	So what we talking about, above the threshold even if very minimally above the threshold or are we talking about below the threshold?
	DR. SHAMOO:  I'm talking about past experience where there was no threshold and their own psychiatrist gives them a piece of paper to sign as an informed consent and there was not a single case in 30 year surveys we've done that the case you talked about, either of LAR, legally authorized person, or that somebody was above the threshold or below the threshold.  They were all treated like we recruited 300 patients, blah, blah, blah, and they all voluntary signed the informed consent.  So I'm talking about past experiences and still the practice is still basically the same other than those who are frightened by the current atmosphere.
	DR. BEAUCHAMP:  You know, I don't think w are in a context here of something like a reasonable person standard.  I think we are in a context of something like a subjective standard, that is to say, I'd have to know in the case of each one of those patients what kind of capacities they had.  And as I understand it you're saying, they passed only this one piece, this is an informed consent form they passed only this one piece of paper before this one person.  There wasn't also a surrogate that signed off, but just this one person.  I just have to know in every case what the capacities of the individual are
	And in the case of some of these patients you would have to spend a great, great deal of time, I think, in asking them questions to see whether or not they have the proper understanding.
	DR.  SHAMOO:  So you would design a system where there is some capacity assessment for some of those who are seriously mentally ill if they are going to volunteer for research?
	DR. BEAUCHAMP:  Yes.  I think it's the only morally responsible thing to do.  I'll give you an analogy, I'll admit it's not a perfect analogy, but my mother is in a nursing home and most of the people in the nursing home are incompetent, there is no absolutely no question about that.  My mother happens to be competent, she happens to be very competent, but they don't pass any documents by her.  They send them to me, they want me to design them.  I think this is immoral and illegal, right.  But they won't hear anything about this.
	It's a great nursing home in terms of its services and I want her to have nursing, but I just don't think this is right.  I think she should be the person that they send the form to first and they should find out whether she and other people in that nursing home have the capacity to consent for themselves for a flu shot or whatever it is that they want the consent for.  I don't think it's easy, and in the case of some of them that are marginal people there, but I think that's the responsible thing to do.
	CHAIRPERSON MARSHALL:  Elliot.
	DR. DORFF:  I have two issues, Tom, one is a very theoretical issue.  You came out with a very strong statement that the primary justification of informed consent is the protection of autonomous choice and that is the right and only justification.  That's a very contient ethic.  And I'm so to wondering couldn't you on a communitarian ethic come up with a very different kind of justification for informed consent.  Namely that you have a communal duty to provide for, to use the constitution's phrase, "the communal welfare"; and that a part of the communal welfare is for the community to worry about the protection of human subjects.
	So, I think that you've privileged the contient ethic over all kinds of others, I'm just mentioning one.  And I think that informed consent could be justified in a series of other kinds of ethical systems and I'm just giving you one example.
	The other thing that I wanted to mention was, we need to, at some poor on another, deal with the responsibility of the patient and not just the responsibility of the researcher in this informed consent process.  I mean, I think we have, we clearly have the focus has been rightly on the requirements of the researcher to make sure that the patient at least should know what is involved, both in terms of risks and benefits and about the problems in that process.  And I think that focus is correct. 
	But at some point or another we have to, very much along the lines like Jonathan was suggesting, at some point or another we have to ask ourselves, when has the researcher done all that is necessary and the responsibility is on the patient who agrees to be a part of the research.
	In other words, at what point does one of those parties' responsibilities end and the other parties' responsibilities begin?
	When Jonathan raised the question about, you know, what happens if we're completely, his lawyer friend who says that no risk is acceptable for healthy patients.  Well, that means that I shouldn't walk out into the street, right?  Because the vast majority of accidents happens within, what is it, a mile of my house.  So I should never leave my house, because there's risk involved.  I think that at some point or another we have to figure out how to make that kind of balance.
	DR. BARNES:  I think that you can leave, but not if you're going to be a subject in a study.
	[Laughter.] 
	DR. BEAUCHAMP:  Big questions and important ones.  When I first got into biomedical ethics and started studying the history of the ethics of experimentations or whatever you want to call it, the pattern that I detected was that the original motivation including most of the motivation in the federal government of the United States was not to protect autonomous choice.  I'm reaching back into the 1960s and before, but rather something like what you referred to as a communal duty.  What you're arguing here I think could be argued not only on communitarian grounds but on utilitarian grounds just as well and many policies of the federal government on my reading today and for decades back have been utilitarian policies.  And you could certainly understand the supplying of information.
	In fact, I traced it back to even further.  If you look at some of the great enlightenment figures in the history of medical ethics like Benjamin Roche and John Gregory where the idea of actually supplying information to patients first start popping up.  I mean, it actually gets serious in the history of medicine about the obligation to provide information.  The main reason why you have that obligation was to make them healthier.
	Right.  It wasn't to make them more informed so that they could make autonomous choice, that wasn't the point.  And I think that history bears out that that has always been the primary concern.  And I think what we started to come to somewhere like the early 1970s some people would trace it back to say law cases in the late 1950s was that the primary premise in both morals and law was the premise of self-determination, not the premise to protect.  Because the premise to protect could be cut all sorts of ways.  In fact, we have lots of people in the history of medicine riding on this subject who argue for deception at certain stages, not disclosing information at certain stages, and so on in order to protect against harm.
	And it seemed that, and I still do believe that, the cleanest justification and I think in the end the only right justification, whether one seeks contient grounds for it or not is I think is another question.  I don't happen to care for contient ethics very much myself, but I would agree with you that you can devise a contient justification for this conclusion that the right conclusion is the protection of autonomy.
	The way which I would think of it, trying to frame both of these objectives in terms of duties and rights is the correlativity between rights and obligations.  I think that the subject has a right to the information and I think the investigator on the responsible party has the obligation to provide that information.  And I think the only way to make sense out of that right is as an autonomy right.  And, to me, that's the logic of the situation.  We could get into long discourses about whether that's contient or not and so on, but that's more or less the long and the short of.
	As to where responsibility ends and begins, I take it to be more or less axiomatically true that what I understood you to be arguing for is correct.  This is not one sided.  If you've got subject who will not read forms that you put before them, or will not discuss matters with you when you know there is misconception or whatever, then it seems that they are not living up to their responsibilities.
	On the other hand, I think what your probing for is much deeper than that, namely how far do we have to go.  We've got a subject who is just not getting it.  We're spending hours at this and the family doesn't get it either, so they can't be a medium of translating it.  What do you do?
This is probably going to depend heavily on the context.  I was very impressed a few years ago when I went to Japan.  There was one Japanese sociologist I talked to, he asked me, he said, "Do you have any ideas what the average number of patients is that a Japanese physician sees each day?"  These are Japanese physicians who see patients, they don't all, but for those who do see patients what the average number is.  I had no idea of course.  He said, "The average number is 64."
	Well, imagine what informed consent can mean in such a system if that is the medical   system.  And this is one of the more elite systems of the world in terms of the funding for health-care.  So the more variables you throw in, the more it is going to alter, I think, the extent to which you have to go.
	Now, this is probably not going to change one's view as to whether or not one obtains an informed consent, but it may change substantially one's view as to how far one has to go to get an informed consent and even where you draw the line and you say, look we have to proceed with this even though we don't have an informed consent, or we have a halfway informed consent or something like this.  And I think that bears a great deal of discussion in your Committee as to how you handle that one.
	CHAIRPERSON MARSHALL:  Procedurally, I have Susan and then Alan and I want to open the floor after that to the other folks who are here, and note that we have only 15 minutes left for this discussion.  So please be mindful of your time and generous to others.
	DR. KORNETSKY:  Thank you.   Well, I'm going to go from a very philosophical discussion to a very practical discussion.  I'm an IRB administrator at a pediatric institution, so I'll preface it by saying that.  The first question I have is, bioethicists spends a lot of time thinking about these things.  IRB's are beginning to spend more time thinking about these things and understanding the things.  The community that actually goes through or gets informed consent and the informed consent process is the investigator community, and I'm wondering if you have just some general ideas as to how best we can begin to improve or think about the informed consent process and with the investigator community and with the IRB community?
	My second question is that you ended your statement by saying the myth that informed consent is not a myth.  There's a second myth that assent in pediatrics is a myth, do you feel the same?  Is that a myth?
	DR. BEAUCHAMP:  How can we best improve the system?  I think that Katz, who I challenge both conceptionally and morally, but Katz has been onto something that's right for a long time.  In many of these settings it has to involve meaningful dialogue.  Meaningful dialogue of a certain sort and that is where the questions that -- it's not just receiving questions from the patient/subject it's also questions that are directed at the patient/subject that have a point.  And they are questions that test for the understanding in that patient/subject.
	I found over the years in talking to various groups a lot of skepticism about this and it puzzles me, I'm a teacher like I'm sure many of the rest of you in the room are teachers and for years the only way that I knew whether I'm really communicating in lectures with students or in seminars is to ask pointed questions to see if they've got it.  And if I got 65 students in the class that very, very difficult.  If I got 12 or fewer it becomes progressively easier, but I think I'm good enough at conversation with students, I may not be the greatest teacher in the world, but I'm good enough to figure out whether they've got it or not even with pretty complicated subjects.  And it baffles me as to why investigators or nurses or whoever it is who is involved in the consent process often, not always, but often seem to be so skeptical of the idea that there can be meaningful discourse in which you can actually check through questions as to whether or not they've got it.  I think it really is the best thing.
	Now, part and parcel with that, I had some negative things to say about what people have been saying recently about monitoring.  I heard one talk, I think Mary Faith was at this talk or maybe some of the rest of you in the room were at this talk, where a person made a great deal out of how industry, and I'm not a foe of industry, I'm actually a friend of industry for reasons that I won't go into here.  But this was an industry representative, how far industry is ahead of universities in this respect, because they monitor the informed consent process.  And what she meant under questioning was, we pass this paperwork all over the place.  We have people look at these forms  and check these forms and revised these -- it turned out that monitoring meant nothing but paperwork.
	If you want to revise the system in terms of monitoring, which I think is a really good idea, it's monitoring the process of consent.  The process of consent, not the forms that are placed under people's nose.  So if your asking for practical things to do those would be the things that would come first to my mind.
	Now, the second question that you asked was about was assent in children.  We studied this and in fact you might even be interested in going back and looking at some of our documents in the -- national commission.  We had several papers written by scholars on the subject.  This was 1970s research.  One was written by a woman at the University of Michigan, I remember I can remember her name now, and I am sorry to say, behavioral scientist, I believe, and it was a particularly good paper on the subject which she argued for, in the case of at least some children, not indiscriminately but at least some children it was meaningful as early in ages seven to obtain consent.
	Now, it depends a little bit on how old these children are that we are talking about.  I started with age seven because, at that time -- and I looked at several pieces of literature since then -- I don't think that there are very many people who think you can meaningfully start before the age of seven and then throw in a doctrine of assent and get a lot of sense out of it, but as you get progressively older, it makes more and more sense.  And I seen a number of cases over the years -- and I imagine you have too if you're in pediatrics -- where I thought a teenager maybe even a very young teenager understood their medical situation, what they needed what should be done, far better than the parents did, right, and yet, of course, they were minors and considered incompetent so on and all that, under the law, but to me it didn't make any sense.
	In fact, I saw one case many years ago, this was in 1976, but I think the case was in 1974 of an organ transplant where I thought that the teenager who was to receive the transplant -- a kidney transplant -- had an incredibly better understanding than the parents, such a good understanding that it was close to the understanding of the transplant surgeon in that case.  So again, just like what Adil and I were talking about earlier, I think that this is not something where I want to come from the reasonable person standard.  I wouldn't want to say something like well once they reach seven, assent is meaningful, you know, if they're reasonable or something like that.  I think it depends highly on the individual case.
	My son is 13 and, you know, I talk with him about these issues all the time.  He certainly could make a mistake of judgment, we all can make mistakes of judgment, he certainly can for reasons of things like immaturity and so on.  But he understands so much that I would put a great deal of stock both in assent and refusal on his case, in his case for a lot of medical procedures.
	CHAIRPERSON MARSHALL:  I have Alan and then I'd like to open the floor up.
	DR. FLEISCHMAN:  Tom, if I understood Ruth's comments yesterday, her interpretation of the ACHRE studies and her concerns about vulnerability of subjects, from many perspectives, I think particularly focused in the underserved in Baltimore or that population caused her to prioritize beneficence in IRB's work over respect for autonomy in the informed consent process.  And I wonder if you might comment on your thoughts about that, suggesting, I think, and I'm paraphrasing what she said that we shouldn't put any research out there that we wouldn't think quite reasonable in terms of someone consenting.
	DR. BEAUCHAMP:  Is that a reference to good research versus bad research or something like that? 
	DR. FLEISCHMAN:  No, I think it was concerning the IRB's responsibilities to be more beneficently inclined rather than to use respect for autonomy as the major principle, the cornerstone in informed consent.
	DR. BEAUCHAMP:  Are we interpreting beneficence here in the context of risks and benefits so that the IRB should pay a great deal of attention to risks and benefits and not approve research if it looked like the risk ratio just wasn't worth it for these subjects.  Is that -- so that you never even offer them the opportunity to -- 
	DR. FLEISCHMAN:  I think her concerns were also the levels of vulnerability of some of the subjects and the concern about this process that you so well described, the autonomous authorization, her concerns about the limitations of the capability of people who certainly have capacity, but that we have obligations to assure higher levels of protection.  You know, having been brought up with Bob Veech sitting in an IRB with me, his beliefs in the autonomous choices of perhaps healthy volunteers were such that he would allow whatever levels of risk for autonomous choicemakers. 
	DR. BEAUCHAMP:  Now he wants to abandon informed consent. 
	[Laughter.]  
	DR. FLEISCHMAN:  But he's come a long way.
	[Laughter.] 
	DR. BEAUCHAMP:  It's because of his contract doctrine, of course, which has the underlying autonomy theme.
	I don't know what Ruth said, so -- 
	[Laughter.] 
	DR. BEAUCHAMP:  I mean, I have it on good authority she was here yesterday.  That's about it.
	[Laughter.] 
	DR. BEAUCHAMP:  That's about all that I know.  The language that he used was priority or prioritize, I believe, and this is something that over the years I've become progressively reluctant to put it in that way because it sounds like something like "trumping" -- to use a term that came up through rights discourse -- that beneficence concerns trump autonomy concerns or autonomy concerns trump beneficence concerns or something like this.  I never found it to be that way.  I don't believe the moral ground or world works that way.  Because I think something that's important from the perspective of autonomy in one research protocol or one medical context may be very trivial in another research protocol or context.  A benefit or a risk that's quite minimal in one may become quite maximal in another.  So I've always felt that you have to get out of the mode of thinking about prioritizing.
	Now, however, you have to turn that around a little bit.  One of the things that I've been accused of for years, and I think a number of people in biomedical ethics have been accused of is to use the language that Carl Schneider [ph] uses in his recent book, "Autonomists."  He's against autonomists and autonomists are people, in effect, who have always got autonomy out there first in any given context.  So it gets priority or it get prioritized.  And I don't believe in that any more than I would believe in a priority of beneficence.
	I think that Schneider has actually misunderstood the role of autonomy in contemporary biomedical ethics and is making up something  of a myth of it.
	So the real answer to your question is, yes, you definitely ought not to say -- well, we'll just take a quick look at these risks and benefits, that's not really so important like the informed consent form is.  We'll spend all our time on the informed consent form or something like that would be a huge mistake for IRBs.
	On the other hand, to say that risk benefit considerations take precedence over autonomy considerations in even cases where you have vulnerable subjects and reasonably it's always hard to put this in communicate, but let's just say levels above minimal risk, some level above minimal risk.  To say that an IRB ought to turn that down is, I think, a great mistake.
	For example, some of that is research is very, very important to some groups.  I remember a research protocol that I saw 30 years ago that was turned down by an IRB.  This was back in the real primitive days of IRBs, right.  It was turned down by an IRB and it was a group of the -- I forget which group it was, but people who were interested in blindness.  And they actually lined up the subjects and the subjects really wanted to see this research go forward.  The group that was funding it, this particular group interested in blindness, everybody, but the IRB said no.  Risks were too great.  In this particular case it involved some kind of brain surgery, I don't recall remember exactly what kind it was.
	I would want to be really careful about making those kinds of judgments.  You easily get yourself into the situation of paternalism.  I'm not a person who believes that paternalism is always unjustified, but I do think the burden shifts on you in a circumstance of paternalism to show that you have good grounds for overriding what people are willing to consent to, to autonomously authorize, especially when they have good reason for wanting to see that research go forward.
	CHAIRPERSON MARSHALL:  Let me ask if there are ex officiis or public members who would like to ask Tom some questions.  Please do because we are going to move forward.  So if you would just come to the mikes and let us know who you are, please.
	MR. SUSSMAN:  Tom Sussman, not speaking for the Department, but commenting on what you said.   The research we do often does not accrue direct benefits to the subjects.  It does accrue benefits to general public safety.  Example would be testing of pilots and general aviation aircraft.  There is a significant risk every time you step into one of these airplanes.  These people who are pilots have already been tested on simulators, but they need to be tested in the airplane.  And we can't ever say, there's no risk.  And these people -- major pilots often don't understand the risk, we don't make them do anything unusual, and so sometimes risk is unavoidable and we have to make the judgment that the general benefit is there.
	Any comments on that.
	DR. BEAUCHAMP:  I think you and I are in complete agreement.  I think that kind of work has to go forward, right, and I think it's justified that it goes forward.  And the only thing that might be interesting is how -- it gets back to Elliot's earlier question, how high a level of risk are you willing to sign off on and does it float with the level of benefit for the public?  In other words, is it okay in such a circumstance to place an individual -- this would be a consenting individual, let us assume -- a consenting individual in a circumstance in which the risks are quite high for that person, the benefits are virtually nonexistent for that particular individual, but the benefits may be great for the public.
	This is a utilitarian calculus, of course, that has greatly concerned some people for years.  I've been interested in it not only in human research, but in animal research.  Animal research is a particularly graphic example because it will place animals at extremely high level of risk for no benefit at all to them in order to accrue benefits to us.  So when you take that kind of problem and you transplant it to the human context, I think you do get interesting issues.
	MR. SUSSMAN:  I would be glad to discuss this off line.  We do consider the risks very, very carefully, the animals that we can speak for. 
	[Laughter.] 
	MR. CHORE:  [Off mike.]  My name is David Chore, I'm from the National Institute of Mental Health, perhaps some of token psychiatrists to whom Dr. Moreno referred.  Just a couple comments.  As it was pointed out, the assessment of informed consent and the therapeutic misconception are absolutely essential issues.  And as you probably know, in 1998 NBAC recommended research on this.  As sometimes happens, some government agencies have already started doing that and we -- I think some of you are now aware of at least three studies that are ongoing to assess that, that is the ability to which people are capable of making these decisions and learning about research -- learning about what is therapeutic research and what is not.
	The final comment I would make is it was pointed out that consents often overvalue the benefits and part of my job at NIMH is to make sure that what we sponsor does not do that.  However, I would also point out that in many cases we overvalue therapeutic research and undervalue research on the underlying causes and prevention of disorders and that that, I think, can be just as harmful. 
	DR. BEAUCHAMP:  Helpful comment.  If I were to put one gloss on it that does not in any way reflect negatively on what you said, but it might be interesting to this committee, I'm always a little bit bothered when groups like NBAC, and you might consider yourself a group like NBAC and I realize that we were guilty of this to the a certain extent also back in the days of the National Commission, but when groups recommend studies, they don't take a position, the recommend that somebody else study it and then they go out of existence which is the situation you may find yourself in.
	[Laughter.] 
	DR. BEAUCHAMP:  The one that has bothered me for years is the issue of compensation for injures subjects because that's what we did back in the 1970s.  We got onto this issue and basically what happened was NIH lawyers came to our committee and said, boy, you need to really be careful this one because, you know, you could get yourself in a really nasty situation.  And we said, well, we better study this, right, and so, of course, we didn't really say anything of any substance about compensation for research subjects.
	Well, now, 25 years later the torch has been passed down over the generations of, well, you better study it; well, you better study it; you better study it and we still don't know anything about compensation for injured research subjects.
	So, if you guys get a chance to look at that, I hope you won't say, well, we've got to study that issue, you know. 
	CHAIRPERSON MARSHALL:  That will be on our agenda, Tom, I can -- it's one of my favorite issues.  So we will be looking at it.
	We're out of time, Sandy.  I'm sorry.  We're not really out of time.  We're going to continue the discussion.  Tom, I would like to thank you very much.  This has been a wonderful discussion.
	[Applause.] 
	CHAIRPERSON MARSHALL:  And I know that you have teaching obligations, but we certainly would invite you to stay if you would like to because we are going to move into informed consent and research with the decisionally impaired.
	Yes.
	AUDIENCE PARTICIPANT:  [Off mike.]
	CHAIRPERSON MARSHALL:  Thank you, Bob.  Tom did actually have words on paper.
	DR. BEAUCHAMP:  Yes, I do.  I'll get my secretary to clean it up a little.  It's a little messy.  I'll get her to clean it up and give you a copy.
	CHAIRPERSON MARSHALL:  And would we have your permission to post it on our web site, Tom? 
	DR. BEAUCHAMP:  Sure.  Why not.
	CHAIRPERSON MARSHALL:  All right.  Thank you very much.  And we hope to be seeing a great deal of you in the near future.
	[Laughter.] 
	DR. BEAUCHAMP:  Well, thank you.  We'll have to see about that.
	CHAIRPERSON MARSHALL:  Eric.
	We are going to move on and I think procedurally we have from now until 3:30 for this large discussion of informed consent and the decisionally impaired.  I think that probably what we will do is break for lunch at 12:30 as we are scheduled to.  So just to let you know, don't despair, lunch will happen.
	I first interfaced with Eric Cassell many years ago when I was a graduate student in bioethics.  And talked to him on the telephone somewhere around 7:00 in the evening.  I remember being very impressed that he had evening hours and was taking care of patients that late in the day, and thought that I had scooped the world because he very generously agreed to provide me with his working manuscript of the new draft of the "Nature of Suffering and the Goals of Medicine."  And he's just a wonderful man and so generous of his time and his thoughts with someone he had never heard of before in his life.  And he has been very generous in agreeing to come today representing NBAC.
	We are going to begin the discussion with talking about the NBAC report on Research involving persons with mental disorders that may affect their decision-making capacity because that and a response to that report is really going to provide, I think, the framework -- at least the initial framework -- for our move in that direction as a Committee.
	So, Eric, thank you so much for being here.  And you forgot your hat.
	DR. CASSELL:  I didn't forget it.  It's in my -- I'm not going to wear a hat. 
	[Laughter.]
	INFORMED CONSENT AND THE DECISIONALLY
	IMPAIRED:  DISCUSSION OF THE DEPARTMENT'S
	REPORT IN RESPONSE TO NBAC'S REPORT
	NBAC REPORT -- "RESEARCH INVOLVING PERSONS
	WITH MENTAL DISORDERS THAT MAY AFFECT
	DECISION-MAKING CAPACITY"
	DR. CASSELL:  I actually rather like this document except for one thing:  I think decision-making is two words.
	[Laughter.] 
	DR. CASSELL:  But -- and my spell checker keeps putting that little red thing under it.
	I'm going to really talk, I think, briefly.  But I would like to start off by doing a little history.
	You know, the research establishment, at least the way we know it, is not much more than 50 years old.  I mean, there was a lot of research earlier before the second World War, but it was small as were medical school faculties small, and they talked about things besides money.  But the idea of the control trial is a new idea.  It has taken a long time to graduate investigators really whetted to it.  It has taken a long time not to get subjects like they were objects and this has gradually happened over this period of time.  And if you forget that, you tend to think well, we are where we are now, and so the task is what we're going to do about research now instead of seeing that we are in a historical process in which everybody is changing, including what we are beginning to call "participants."
	The very idea of calling them "participants" suggests a change in their relationship to research.  People are much more interested in research than they were in the past.  They are much more willing in some ways or in some kinds of research to volunteer.  They are much more active participants, they know -- I mean, any doctor will tell you that people know a lot.  They actually think they know everything.  But they know a lot.  And that's a big change.
	So, as we look at this, we have to understand that.  However, there are some communities of research where the progress is variable, I would say.  I was also an IRB member before IRBs were required and we had a community of investigators that took a lot of training, the oncologists.  They took a lot of it.  Incidentally, I'll tell you that the reasons nails are put in coffins are to keep the oncologists out.
	[Laughter.] 
	DR. CASSELL:  In any case, our problem with them was that they were doing vitally important work.  They were looking for the cure for cancer and they were doing things that were often harmful but in a good cause.  They were good persons and true as they were glad to tell you at any time.  And the fact that their consent forms were unreadable and ununderstandable, and overly optimistic was only in the service of this work and that's -- I'm talking about the 1970s and so forth.
	Now, that's not the problem it was before.  It has changed in large measure.  The oncologists and the cardiologists and everybody else has come to understand this all much better as people have moved forward.
	However, when we are talking about this particular subject today, we are not quite where everybody else in relationship to consent forms, to consent in general, to the relationship of the investigator to the subject who is still the subject, and, in fact, to the relationship of the larger community to the group of people who make up the members of research subjects.
	No set of recommendations that was proposed by NBAC have provoked as much dispute by the members of the specific research community as have the ones in this document.  Rigorous objections by psychiatrists and psychiatric researchers to the Commission's proposals were offered during the proceedings, in testimonies by the psychiatrists before the Commission, during private mortgages with NBAC members and in published papers and continuing to the current time.
	The objections focused -- which were very heated.  I can tell you that some meetings were really very heated.
	The objections focused primarily on the fact that NBAC had selected this particular special population, persons with mental disorders that may affect the decision-making capacity, I must confess, that was my idea to call it that, because of the difficulty we all have in being more specific about what we're talking about.  What we meant by that, persons with mental illness, rather than all potential research subjects who might not have the capacity to consent.  We were talking about a particular group.
	Also, there was a great deal of distress at NBAC's recommendation number eight that required an independent, qualified professional to assess a potential subject's capacity to consent where more than minimal risk is involved in the research.
	And, in general, the focus on special regulations for a population of potential research subjects including recommendations that HHS convened a special standing panel to help IRBs with protocols that might not otherwise be approved or that might present special difficulties but also special promise.  Because all of this was apparently taken by the research community as imposing very difficult burdens on the continuation of research in mental illness.
	Now, there is a background to this particular report which is very important to realize.  In 1974, Tom's commission, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research -- which that's why it's called "The National Commission" -- 
	[Laughter.] 
	DR. CASSELL:  -- identified certain populations as potentially vulnerable to breaches of ethically imperative standards for their protection; children, pregnant women, prisoners, and persons with mental illness.
	The Neuremberg code prohibited research on persons who could not give consent because of the fundamental principal of research ethics was a freely given, fully informed, understood consent of the subjects and the Helsinki Declaration was only slightly less restrictive in 1964.
	Now, at that time, however, research in patients with mental illness was primitive compared to where it is today, absolutely primitive.
	There has been a great expansion in psychiatric research and the discovery of many effective treatments where virtually none existed before this.  But it remained the case, however, that consent was thought to be -- and actually, Tom said it before, consent was thought to be the equivalent of autonomy almost.  Self determination is what autonomy is.  But self determination is not what autonomy is.  It is a part of being autonomous is to make your own decisions, fully informed and entered into decisions.
	But also to be autonomous you have to be allowed to be the authentic person you are in the environment in which you exist, and you have to be protected from certain harms which you might not know about, but which somebody caring for you might know about.  And these aspects of autonomy in most populations we don't pay too much attention to because the patients are considered able to take care of themselves.  Whether that's true or not, and it actually often isn't.
	Now, in these populations of vulnerable people, registration were proposed by the National Commission for the protection of institutionalized mentally infirm patients that were very similar to the children regulations, but as you all know they were never adopted.  So here was a population of persons recognized 30 years or so ago, or 25 years ago as being vulnerable for whom special regulations should be promoted, but they never got adopted.
	And the present report presents NBAC's proposals to remedy that lack of special regulation. 
	Now, why current protections may be inadequate, well, for one thing, when the National Commission was deliberating, many persons with these disorders were institionalized.  As a matter of fact they were called, "the institutionalized mentally infirm" weren't they, at the time of the National Commission.  But since that time, of course, the institutionalization movement has happened and most patients with mental disorders are not in mental institutions.  They get their treatment primarily in outpatient settings, but there is something else about their treatment.  It's often very expensive and they often do not have insurance that's adequate to cover their treatment.
	So it's a group of patients who because of these problems can often only get their treatment if they are enrolled in protocols.  In other words, many, many, many persons with mental disorders who are subjects of research cannot get treatment outside of the research setting because of expense and also because of innovative research that's happening.  And, of course, this creates a coercive research environment that requires special attention.
	There are other problems.  The treating psychiatrist is often also the research person.  So the patients may feel that if they don't participate in the research they will be denied treatment or incur the disapproval of their doctor if they don't participate.  And they are much more at risk for the therapeutic misconception that we've been talking about, believing often that research offers benefits when in fact no such benefit is known or really actually promised in the protocol.
	Their level of decision-making capacity may vary over time, yet this fact may not influence the continuation of the research after the initial consent.  The initial consent is only one step in the research process, some of which some of this research goes on for a long period of time in a person with fluctuating capacity, and yet that does not take into account, is this person really still a proper research subject for this program.
	Caregivers for patients with mental disorders are frequently members of the person's family or are close friends who have borne the burden of the patient's care and interests, but are not recognized in the research setting.
	And the next final thing is, the Commission -- our Commission heard testimony about research involving manipulations that were inherently risky sometimes threatening the precipitation of further or more severe illness including placebo-controlled trials in sick persons, symptom provocation, washout procedures that might precipitate a return of illness, or challenged studies. 
	At the time of the Commission's deliberations and subsequently as you probably all know, there were a number of egregious examples of disregard for the safety of research subjects with mental illness.
	NBAC conducted a small study to find out -- to look at the protocols and consent forms of research that had been done that had greater than minimal risk and did not offer direct benefit to the subject.  We did this actually by looking in the literature and identifying such studies and then going and writing to the investigators and requesting the copy of the protocol and the consent form.  We did this -- the studies were the ones published after 1995.  We did this with 60 such studies.  We only got 13 responses.
	In those responses in that small sample revealed coercive recruitment practices, inadequate disclosure of risks, false characterization of risks as minimal, overemphasis on benefits, and the use of psychiatric patients as controls in studies not related to their disorders.
	These are problems that should not arise if investigators are following the common rule as it exists today.  In other words, the regulations to prevent that kind of thing is already out there.
	As I said earlier, for those of us who are familiar with the early days of human subject research and IRBs, these problems were very reminiscent of research on cancer.
	Now, why do investigators do this?  Why do investigators sometimes fail to protect their subjects in the manner described?  Why do they recruit coercively?  Why do they fail to provide full disclosure?  Why are they overly optimistic and minimize risks and promote therapeutic conception?  Well, it's very simple, they want to recruit subjects to their research and there is a longstanding belief that if you put it badly people won't sign up.  And that's not just in this kind of studies.  I've seen that kind of thing in studies that are so innocuous that there's no reason for somebody not to sign, yet the consent form is tilted to make it somewhat more optimistic or to conceal what little risk there may be.  Why?  Because the belief is, nobody will participate in my research.  Why would they do that?  And it's an unfortunate thing that happens.
	And because, and this is very important, the investigators are overly optimistic.  I mean, it's like the research equapoi situation, it's very hard to get people to really accept, do you really believe that these two therapies that you are studying are either of equal benefit or you don't know what the -- you know, that kind of thing.  It's very difficult to get investigators to do those things because they're human and they're trying to -- you know, they're trying to get their work done and they're going to be unkind toward the Nobel Prize and sometimes that isn't unkind, and they want to get their work done, and they want to get ahead in their work without venal intent.
	There is no venal intent in it.  And that's, of course the problem.  If it's really venal, people are doing bad things because they're bad people.  That's a very different problem.  But in this case subjects are being put at risk by good people.  And not only are they good people, but they believe that they have the best interests of their subjects at heart.  That they would want to take care of them, that they would not have any question about their devotion to their subjects.
	But, of course, what is forgotten here as almost everywhere an investigator who is both responsible for the care of the patient and the research in which the patient is involved must, without question, have a conflict of interest.  And this is true in any other research as it is in psychiatric research. 
	If there is a conflict between the welfare of the patient and the proper research procedures so that the protocol produces know, the protocol comes first.  And that's extremely difficult for people to accept often.  The research comes first.  If it doesn't, then we can't trust the knowledge that's coming out of the research that's being done.  The patient doesn't come first.  The research comes first.
	Now, because of that conflict of interest which most investigators don't see, they certainly wouldn't do anything to harm anybody, because of that, we have special problems answer we have special problems wherever there can be no other care giver besides the investigator.  If there's a conflict there, then there has to be some way of protecting those patients, monitoring or other people taking care of them.
	Now, whatever else I say, and as I go on, I don't have very much more, but one of the things you hear again and again is we really have to educate.  Education is the key to changing what happens in the research setting.  Not a little education, a lot of education.  We talk about it in NBAC, we put it in reports, we talk about it in NBAC and at the end of NBAC, that's what we say.  We believe education is a good thing.  I hope you all agree that it's a good thing too.
	Unfortunately it's also expensive, time consuming, requires institution resources that the institutions may not wish to use, and it's going to take a lot more than somebody saying, "education is a good thing."
	But, I mean, an educated consumer may be Sy Simms' best friend, but an educated investigator is a patient's best friend.  And I just can't say enough.  If major important educational programs for investigators and for subjects who are about to be participants are part of the proposals that come out of this organization, this agency, it will be a wonderful thing.
	Well, let me just finish up by saying, NBAC's recommendations were proposed to address these problems.  Protest against NBAC's recommendations, hot and heavy as it may be, that it will impede scientific progress is what everybody always says.  Scientific progress is not the most important value in human life.  It is something that can be weighed against the protection of human subjects, weighed against the protection of a community.  Scientific progress is only one value.  We are all into it.  But in point of fact, progress is slow, it can be put off, you can actually delay research without everybody dying of whatever it is you're supposed to die of when you don't do what you want to do.  These could be put off, further protections can be added, people can see how things work before they go back and change it.  Agencies can do that, try new ways of protecting patients and if it doesn't work, going on and doing something else.  All of that.
	Although Senator Moynihan once said to me, "Eric, we never change anything."  That wasn't too comforting.  Anyway, it is something that can't be used as a club against making human subject protection.  Every field has made the same claim over the years only to find that progress continued, human subject protection does not seem to impede good research.  These regulations have singled out one group of disorders in which the capacity for consent may be compromised.  Other disorders such as head trauma, coma from various causes, very sick patients, dementias and so forth, are not in these regulations.
	Much of the criticism is, why did we do that?  Why didn't we treat everybody who might lose capacity the same?  I think if you will look on that document, the working group document, on page 9, you will find that by making it extend to everybody, then by a reducu adicertum you shouldn't have any -- you shouldn't bring any criticism against one group.
	Why did we do that?  Very simple.  The other groups are protected by current regulations and this group of patients are not.  Next, they are a special group.  Is it not discriminatory to tell somebody who lacks the capacity to consent that they lack the capacity to consent.  Is that discriminatory or is it protective?  Is the ADA -- the Americans With Disabilities Act is that discriminatory? 
	I must say I'm so tongue-tied because I got up at 3:00 this morning and then I couldn't fall back to sleep again.
	It's not discriminatory to protect somebody from something that is really true.  It does not single them out.
	So, it remains confidential between the subject and the investigators or the assessor.  It protects the potential subject from harm.
	I think it is unfortunate that the lack of capacity to consent is not recognized in other sick people and I actually have a paper out in June in the Anals of Internal Medicine about impaired thinking in very sick patients which you might take a look at because it is a real problem.  But the problem would not exist if researchers in this era knowing the capacity might vary over time may not exist at all, or may require special conditions to elicit and to recognize and dealt with the issue over these years.
	Failure to include a category between -- one final thing.  Failure to include a category between minimal and more than minimal risk, we did not have it like they do in children, slightly more than minimal risk.  It's not that we never heard of that.  It's not that we didn't hear a lot of people talk to us about it, it's just that when we were all finished, we could not figure out a way that would really make a definition of slightly more than minimal risk that had any real meaning that would protect subjects and might not, in fact, keep research from being done that should be done.  For that reason we said, where there is a problem let there be a special panel to examine that problem and see if the research should go forward.
	There are reasons for research going forward as we just heard.
	Anyway, that's our report.  The protection of human subjects comes first.  It comes first.  It comes before anything else.  It isn't -- there isn't a doubt about it.  There really is, but there should not be a doubt about it.  After that the search for new knowledge is permissible, but only after that. 
	[Applause.]
	CHAIRPERSON MARSHALL:  Thank you, Eric.  The protection of human subjects coming first is our sentiment as well.
	I'm going to ask Lily Engstrom to come now because she does have a time constraint and I want to make sure that she has time for her presentation.  So what I would like to do is have Lily make her presentation and then given the amount of time that -- Eric, don't leave. 
	DR. CASSELL:  I'm not going anywhere.
	CHAIRPERSON MARSHALL:  Good.  Don't go anywhere.
	Then we'll open the floor for questions prior to lunch and come back and continue.
	So, Lily, thank you very much for being here.  And Lily is going to talk about the HHS Reponse to the NBAC's Report.
	HHS RESPONSE TO NBAC REPORT 
	MS. ENGSTROM:  Thank you.
	First of all, I want to start off by endorsing what Dr. Cassell just said, which is human subjects protections do come first and I don't think that there is anyone in this room who would dispute that.
	And I think that that would be, I think, the basic context and framework on which I'm going to make the remarks that I'm going to make in the next few minutes.
	I would also like to extend to you apologies of Dr. Robb, the chair of the HHS working group that developed the departmental response to the NBAC report.  He is unable to join you today because he is actually on annual leave and in England.  So he sent me.  I'm a poor substitute, but if you'll bear with me, I'll try not to make this too painful. 
	First of all, I really would like very much to commend NBAC for its report.  And I know that they worked long and hard on this report.  I attended a number of their working group meetings and I think that with respect to the kinds of protections that have in fact been proposed in that report we recognize that despite significant improvements in human subjects protection over the last several decades there are still very dificult issues that remain in the area of research involving individuals with impaired decision-making capacity.  And we feel that this report, the working group, we truly felt that this report represented a very thoughtful, a very insightful document that really constitutes a contribution to the field of research involving individuals who are decisionally impaired.
	When the report arrived at the Department, the Office of Science Policy, within the Office of the Assistant Secretary for Planning and Evaluation convened an interagency working group.  And this interagency working group included representatives from NIH, FDA, CDC, the Agency for Health Care Research and Quality, the Substance Abuse and Mental Health Service Administration, the Office of Public Health and Science, the Office of General Counsel, the Office of the Assistant Secretary for Legislation, and the Predecessor to OHRP, the Office of Protections and Research Risk.  And, as a matter of fact, there are several members of the working group in this room, one of which is seated at this table. 
	Kate Gottfried was one of the working group members and there are others here.  So, if after my presentation, any of the working group members would like very much to make some comments on the report, particularly on our working group's response, I would very much welcome that.
	In preparing the report, the working group developed a set of general comments and then developed individual responses to each of the recommendations that were made by NBAC.  In the section on general comments, the working group stated that, "Notwithstanding the title of the NBAC report which suggests that the scope of applicability is restricted to individuals with mental disorders whose decision-making capacity has been impaired, we believe a broader scope is warranted."  And Dr. Cassell referred to that a few times in his remarks.
	We arrive at this conclusion based on two factors.  Number one, the need for special protections for a broader population of person with decisional impairment; and, two, the potential for stigmatization either real or perceived if those protections are limited to individuals with mental disorders that may affect decision-making capacity.
	It is the view of the working group that not all mental disorders are associated with decisional impairment, nor is the decisional impairment associated only with individuals with mental disorders.
	The work group noted that some physical disorders or conditions may also result in decisional impairment and therefore to give the ability to give voluntary informed consent to research.
	We are not going to start the slides yet.
	Some believe that focusing on persons with mental disorders that impair decision-making improperly stigmatizes a category of people most of whom may be quite capable of making their own decisions.  The Surgeon General's mental health report in fact indicated one out of five Americans experience a mental health disorder during the course of a year.  Yet most of them are capable of making major life decisions.
	NBAC recognized this as a matter of fact, in the text of its report and encouraged use of the report as guidance for conducting research on other person whose decision-making capacity may be impaired.
	For these reasons the working group proposed that the Department consider the applicability of NBAC's recommendations in this report to research directed at persons with either mental or physical conditions associated with decisional impairment. 
	Could I have the first slide?
	Next one.  Next slide.  Thank you.
	Thus, the working group findings were that the scope of NBACs recommendations seems applicable to all persons with decisional impairment irrespective of diagnosis.  And that limiting the scope of protections may be perceived to be stigmatizing.  And that HHS should treat NBAC's recommendations as potentially applicable to all research subjects who decision-making capacity is impaired.
	Second slide, please.
	Therefore, the working group concluded that the scope of the report's recommendations seems appropriately applicable to all persons with decisional impairment irrespective of diagnosis.
	NBAC reports in this report a regulatory framework that would require IRBs to classify all proposed research involving persons with decisional impairment into three categories.  It would be minimal risk, greater than minimal risk, but offering the prospect of direct medical benefit.  Or, greater than minimal risk and offering no prospect of direct medical benefit. 
	Now, this means that an individual who lacks decision-making capacity could be enrolled in minimal risk research if either the IRB actually waives the informed consent requirements according to regulations, or the research is actually permitted by the subject's legally authorized representative.
	If the research offers a prospect of direct medical benefit, regardless of risk, a person with impaired decision-making capacity may still be enrolled in the research if his or her legally authorized representative has given their okay.
	However, if the proposed research is greater than minimal risk and offers no prospect of direct medical benefit, then, in fact, that subject cannot be enrolled in the research unless it meets one of two conditions that was laid out by NBAC.
	And these conditions, the first of which is, the subject must have executed in advance a directive note as a perspective authorization to participate in that type of research.  Or, the research must be reviewed by a special standing panel, an SSP, that's been convened by the Secretary of Health and Human Services.  And that panel must conclude that the prospective authorization or the protocol has been approved by the SSP.
	That same individual -- I'm sorry, I skipped a page.  My fault.
	Conclude that the NBAC report -- I'm sorry.
	Let me start over.
	The two conditions, one of which must be met in order for that research that's great or minimal risk that offers no prospect of direct medical benefit.  The subject either must have executed an advance -- of notice of prospective authorization for that type of research or the review must have been conducted by the special standing panel, the SSP.  And that SSP must have been convened by the Secretary of Health and Human Services and the panel must conclude that the research office -- the possibility of substantial benefit to the population under study, that its risk to subjects are reasonable in relation to this benefit, and that it could not be conducted without the proposed population.  And, finally, that all safeguards are in fact incorporated.
	The working group spent a fair amount of time discussing this proposed regulatory framework and concluded that since prospective authorizations are not likely to be widely used, the SSP, at least until it is developed and distributed guidance for IRBs, would be required to review all research involving even a slight increase over minimal risk that does not offer the prospect of direct medical benefit.
	This SSP review would apply to all arenas of research including clinical, epidemiology, social, behavioral, health services research, and the like.  Now this, we believe, could create a bottleneck that could significantly delay the review process and consequently the progress of important research protocols that pose reasonable, albeit greater than minimal risk.
	The working group felt that introduction of intermediate category of risk, which Dr. Cassell also referred to, akin to that provided in Subpart D, the children's protection regulations.  That along with ability to consider direct, non-medical benefits, would allow IRBs to determine when the risks are justifiable and whether the safeguards are appropriate.  This could obviate the need for a national level review body.
	The working group was also concerned about seeming discordance between NBACs recommendation and the children's regulations.  For example, the children's regulations permit a child's parents or guardians to enroll a chile in research that represents a minor increase over minimal risk and offers no direct benefit.
	Thus, if an IRB were to determine that protocol with no direct benefit and posing a minor increase over minimum risk was likely to yield generalizable knowledge that would be vitally important to understanding or treating autism.  A 17-year-old with autism could be enrolled in that research protocol by his parents or guardians.
	However, if you went with the framework that's been suggested by NBAC, unless there is a prospective authorization signed in advance, naturally, or the protocol has been reviewed and approved by that special standing panel, the same individual at 19 could not participate in the very same protocol that he or she could have at 17.
	Another anomaly created by the NBAC recommendation has to do with assessment of the benefit to the subject.  Children may be enrolled in greater than minimal risk research if the research holds out the prospect of a direct benefit for the child.  By contrast under NBAC's recommendation adults who lack decision-making capacity may be enrolled in greater than minimal risk research only if it offers the prospect of direct medical benefits.  This means that other possible benefits including psychological, social, educational would be excluded from consideration by the IRBs.
	The working group is not arguing for identical protections for adults with impaired decision-making capacity and for children, rather it does not believe that differences between these two groups justify limiting IRB authority for adults with impaired decision-making capacity more than for children in similar situations.  This could lead to confusion and perhaps uneven compliance by investigators and IRBs.
	Next slide.
	In summary, the regulatory framework envisioned by NBAC could result, we believe, in an unnecessarily lengthy review process speaking here about the standing review panel, and it could alter IRB authority in ways that could produce anomalous results.
	Next slide, please?
	So the framework which consists of essentially these four recommendations, number two, on establishment of the special standing panel, recommendation 10 through 12 which essentially categorizes the types of research that would involve persons with impaired decision-making capacity.
	For these, the working group proposed that OHRP working in consultation with FDA solicit additional public input.  We suggested that this solicitation be in the form of a Federal Register notice requesting comments on a variety of elements that have been spelled out in our working group's report.  And they include mechanisms for ensuring needed protections, appropriate regulatory frameworks for characterizing informed consent and IRB approval requirements as a function of differing levels of risks and acceptability of certain overarching principles.
	Now, rather than cover each of the remaining 17 NBAC recommendations individually, I would like to take the rest of my time to address these recommendations by groups.  As you will have noted, the executive summary of our report, the recommendations are clustered by type of proposed action that's been recommended by our working group.
	Now, eight of NBAC's recommendations are consistent with, but generally more specific than current existing regulations for two of these.
	Next slide, please.
	Namely recommendation number one on IRB membership, recommendation three on appropriate subject selection, please forgive me, I did not make an attempt to display entire text of each recommendation and therefore I developed a shorthand to cover them.  And, of course, if you're interested your committee meeting books have these full recommendations.  And for these two recommendations the working group proposes that OHRP, again in consultation with FDA develop and issue interpretive guidance that addresses the concerns identified both by NBAC in this report and by the working group in its response.
	Next slide, please.
	This slide is a little busy.  I usually don't make slides up like this because the rule in making overhead transparencies, I've been told, is limit the number and type of words you have on your slide.  But I really want to show you all six of them because they share something in common.  And what they share in common is the proposed action that is recommended by the working group.  So for recommendations four, five, seven, eight, nine, and 17, the working group proposes that OHRP in consultation with FDA develop and issue interpretive guidance that it deems necessary for implementation of these recommendations.
	Now, you may ask what the difference between this proposed action is, and the one before it and the distinction is the following:  The proposed action on the previous slide actually comes with specific instructions from the working group in terms of elements that should be considered by OHRP as it goes about developing its guidance.
	On the six recommendations shown on this slide, we are essentially saying review NBAC's report, review our response, and then use your judgment and just question in terms of developing what you believe is appropriate guidance for implementing these recommendations.
	Five recommendations shown on this slide as well as the one prior to this, I would like to share with you some of the working group's thinking that offers a slightly different take on the issues being addressed.
	On recommendation one which speaks to IRB membership, the working group agrees that IRB deliberations should include persons who are familiar with the conditions that may affect decision-making capacity and with the concerns for the population being studied.  However, the working group did not endorse the specific recommendations that IRBs be required to include two members who are knowledgeable of mental disorders and the concerns of the population to be studied.  It was felt that such a specific requirement might set a precedent that would be impractical to implement especially in consideration of other categories of vulnerable subjects.
	Nevertheless, the working group shares NBAC's concern and therefore this proposed action recommends that OHRP consider incorporating into its guidance the following elements:
	(1)  That a diagnosed mental disorder does   not necessarily imply decisional impairment relative to participation research.  And that certain physical disorders may well result in such impairment. 
	(2)  Where an IRB regularly reviews research directed at persons with conditions associated with decisional impairment, the IRB should include members who are familiar with this condition and with concerns of a population being studied.
	(3)  Where an IRB only occasionally reviews research directed to its persons with conditions associated with decisional impairment, the IRB should involve consultants who are familiar with these conditions and with the concerns for the populations being studied.
	And, finally, that every effort should be made to include among IRB members or consultants at least one person who has the background, experience, and willingness to serve as an advocate for the population being studied.
	Now, in recommendation four, some of the texts in the NBAC report suggests that protocols designed to provoke symptoms to withdraw subjects or therapies or to use placebo controls are inherently unethical.  The workgroup recognizes that these designs may sometimes expose subjects to heightened risks and therefore do warrant greater scrutiny by IRBs, rigorous justification by investigators and closer scrutiny, particularly in terms of attention to the subjects.  But they are not inherently unethical.
	In recommendation eight NBAC proposes that for research protocols with greater than minimal risks an IRB should require independent, qualified professional to assess the potential capacity of the patient to consent the subject.  Adopting this recommendation could create a strong presumption that IRBs should require former capacity assessments for greater -- for all greater than minimal risk research even though NBAC does note, and I would like to make sure that you're aware of this, that NBAC does note that IRBs may forego this requirement if there are good reasons for doing so.
	We realize, of course, that obtaining valid informed consent from the subject requires that the subject have capacity.  Determining that the subject has capacity and can give legally effective consent is primarily the task of the investigator.  The IRB, however, does share in this responsibility in that it must determine that the protocol satisfies both state and federal informed consent requirements.
	The workgroup believes that requiring a formal assessment may be problematic for a number of reasons.  NBAC itself recognizes most persons with mental disorders that may affect decision-making capacity are not decisionally impaired.  Thus, a recommendation for formal capacity assessment in all cases with greater than minimal risk will most likely cast a broad net that will draw individuals who in fact do have capacity.  Therefore, such a requirement would often be unnecessary and could contribute to the lingering stigmatization of persons with mental disorders.
	Requiring a formal capacity assessment may also be premature at this time because to our knowledge there are no known accurate and validated capacity assessment instruments for clinical care, much less or participation in research.  There is also no consensus regarding the professional qualifications of those who would perform the capacity assessments.
	Furthermore, determining whether the person performing the assessment is truly independent is tricky if he or she is paid by investigator or otherwise affiliated with a research institution.  Moreover, the standard for legal capacity consent must be determined under local laws and those are not uniform.
	In view of these uncertainties, the working group felt that it would be inappropriate for the Department to require formal capacity assessments.  Having said that, I do want to point out that the working group concluded that the IRB should continue to have the discretion to determine on a case-by-case basis whether or not capacity assessments or other safeguards are warranted.
	Recommendations nine speaks to notification of subjects regarding their incapacity to consent to research participation and the potential objection to such participation.  The working group agrees in principle with NBAC's recommendation, but places a slightly different emphasis on the issue.
	Respectful persons includes a potential subject's right to object to a determination that he or she lacks capacity.  To object to the proposed involvement of third parties and to object to any participation in research.  Consequently, whether or not the person had the capacity to give informed consent, he or she is entitled to object to participation or continuation in research without the involvement of third parties.
	Recommendation 17 addresses the maintenance of ongoing communications between the investigators and the subject's family and friends.
	Where protocols involve subjects with fluctuating or limited decision-making capacity or prospective incapacity, the working group agrees that participatory discussions with the subjects, their care givers, the investigators and/or other concerned parties could contribute materially to safeguarding the welfare of the individual, the subject, during the course or research.  The working group does not endorse the specific recommendation that IRB be required to ensure that investigators establish and maintain ongoing communications.
	Implementation.  This recommendation is inherently problematic because of the lack of consensus of who is an involved caregiver.  How to safeguard the subject's autonomy and medical confidentiality and additional burdens of time, effort, and costs that may be imposed on IRBs which we know are already hard pressed to discharge their current functions.
	And in the interest of not overstaying my welcome here I would like to quickly run through the remaining nine NBAC recommendations.  They are essentially very noncontroversial.
	Briefly they relate to legal matters that fall substantially within the authority of states.  The role of professional organizations and associations in terms of developing materials are research involving persons with mental disorders, in terms of research with respect to capacity assessments, and increased funding to support human subjects protections.
	With respect to legal matters that fall under the state's jurisdiction the working group proposes the Secretary of Health and Human Services make states aware of NBAC's recommendation and the working group proposed actions and encourage states to address them.
	And the working group also proposes the director of NIH determine and take whatever action is needed to implement the two recommendations with respect to research.  And that HHS continue its effort to increase the financial support available to IRBs.
	In concluding my remarks, I would be remiss if I left this room and left you with an impression that the working group found fault with a lot of the recommendations in NBAC's report.  My job here this morning was to share with you the thinking and deliberative process the working group went through in coming up with its response.  By and large, if you look at our report, we endorsed an heartily agreed with most of the recommendations in the NBAC report.  But on those where we either agreed only in principle or actually had some disagreement either in principle or philosophy or with the details, I wanted to share with you why we came to that particular position.
	So I wish to convey the working group's sentiments that NBAC's report on research involving the decisionally impaired is one of the many valuable contributions that NBAC has made that will indeed inform our national discourse for the protection of human subjects. 
	I applaud Dr. Cassell and the rest of NBAC for its long, hard, arduous, and thoughtful work on the many issues that it took on and if you followed their work you know they took on a lot of really, really challenging and difficult issues.  And for that I really applaud them.  And on behalf of Dr. Robb I would like to extend our thanks and our appreciation to NBAC. 
	[Applause.]
	CHAIRPERSON MARSHALL:  Thank you, Lily, very much.
	Let me ask, we have 15 minutes so that you direct questions to Lily that you may have of her and Eric are you with us until 3:30. 
	DR. CASSELL:  Oh, yes. 
	CHAIRPERSON MARSHALL:  Oh, wonderful.  Okay.  So Eric will be here for the remainder of the discussion after lunch.  So we might want to use this time to direct questions to Lily then.  She's got five minutes. 
	MS. ENGSTROM:  I have to be downtown for a 1:00 meeting and I apologize for that.  Because of the change of sequence of agenda items this morning, I find that there is now a conflict on my calendar which I had not anticipated.
	MS. MYERS:  If I could just ask why -- I certainly am very happy that you expanded this.  I was very concerned about populations of mentally retarded people would not have been included under the other category, but why are you assigning this to the FDA?  The FDA doesn't have any bioethicists on staff.  They have no resources, they can't put a user fee on this, how are they going to do this? 
	MS. ENGSTROM:  We're not assigning to FDA. We are saying that OHRP should take the lead.  But they need to consult with FDA because FDA has also its set of human subject protection regulations.  So we want to make sure the effort goes on in harmony so that in fact OHRP in developing guidance is not actually going down a path which might inadvertently run countercurrent to the kinds of regulations FDA must also enforce in the air of human subject protections. 
	MS. MYERS:  But NIH and CDC they all have human protection rules. 
	MS. ENGSTROM:  Yes.  And they all work within the human subjects regulations that area actually part of the oversight responsibilities and OHRP.
	MS. MYERS:  I see. 
	MS. ENGSTROM:  Yes.  The common rule.
	PROFESSOR NOBLE:  Yes, thank you very much for recognizing me. 
	CHAIRPERSON MARSHALL:  You need to tell us who you are.
	PROFESSOR NOBLE:  I am Professor John Noble from Catholic University and I am also a member of the National Alliance for Human Research Protection.
	I'm very interested by the analysis and the provisions of the HHS response to the NBAC report.  And as I listened, I'm thinking practically, you know, what it all means, and here is my major problem.  Given the cloak or veil of confidentiality involving the patient/client relationship, with the research/psychiatrist or physician, does this not effectively exclude the involvement of anybody else in determining whether the clients -- the client was willing and able to participate with fully informed consent.
	After the person dies, you can, through a lawsuit, penetrate that relationship and get access to the records by depositions.  Before the person dies, the parents or any relation does not have access to any information about what transpired between that psychiatrist -- treating psychiatrist and the patient.  So what good are all these provisions if you can't penetrate and discover what actually goes on?  I think -- 
	CHAIRPERSON MARSHALL:  I'm going to stop you there because we've got other people.  So, if that was your question, I'll ask Lily to respond. 
	MS. ENGSTROM:  I'm not sure I understood exactly the thrust of your question.  If you are talking about legal access, not being a lawyer, I'm very ill prepared to respond to your question.  If you are talking about a legally authorized representative who is able and been given obviously advance directive to make a decision on behalf of the individual on whether or not to participate in research, that is recognized in a number of states.  And therefore would be legally effective. 
	Now, I don't know what the requirements would be and imagine they would be probably different from state-to-state, and giving -- I'm now speculative on grounds, you will have to bear with me, but if in fact the issue covers only whether or not the individual has provided such an advance directive, I'm not sure that itself would penetrate the confidential nature of interactions between that particular physician and his or her client.
	CHAIRPERSON MARSHALL:  Elliot and then Adil and anyone else, please go to the microphone if you have a question.
	DR. DORFF:  This comes out of my ignorance about how the government works.  I take it that the working groups, decisions that have to do with their asking OHRP to do things are basically marching orders for Greg and company, right.  But my question then becomes, what about the things that you say belong to the states or professional organizations, how did they ever even get informed that this whole discussion is taking place? 
	MS. ENGSTROM:  Two of our recommendations in this arena essentially says that NBAC's report and our response should be disseminated to the states and we would encourage the state governors, obviously, to look at that very closely or their assigned staff to look at it closely and to address these issues.  But you are right, technically speaking we cannot make the states do anything.  And that's why, in fact, we recognize that and say that those particular recommendations are addressed to the states, just as the one that is addressed to professional association organizations, we have no jurisdiction over them.  We can only encourage them. 
	DR. DORFF:  -- other mechanisms and make them aware? 
	MS. ENGSTROM:  Yes.  We can certainly share the reports with them.
	CHAIRPERSON MARSHALL:  Adil and then Vera.
	DR. SHAMOO:  In 1998 NIH issued points to consider and they recommended that there should be an independent capacity assessment.  Also NBAC recommended that.  Now, I'm trying to understand the logic of the working group in saying there shouldn't be capacity assessment by an independent professional, or leave it to an IRB of some kind of an assessment.  If you have somebody -- some group of 100 patients, you don't know which one has the capacity, which one does not have the capacity, but that group as a whole is known medically that they will have decisional impairment, some percentage of them, maybe, 10 percent, 50 percent, 70 percent.  How in the world are you going to have them enrolled then in research without valid informed consent because they -- some of them, 30, 40 percent will not be able to sign an informed consent even though the researchers will have them sign an informed consent as far as I'm concerned is invalid.
	CHAIRPERSON MARSHALL:  Let's be terse with our questions, okay.  I mean, you all can phrase them, I'm sure, in a more concise manner. 
	MS. ENGSTROM:  I apologize, but this may be the last question I take before I leave.  What the working group was saying is that we don't think this should be required.  And we brought in several people to talk to the working group, individuals who we believed were experts in the area of capacity assessments.
	DR. SHAMOO:  [Off mic.] 
	MS. ENGSTROM:  Yes 
	DR. SHAMOO:  That's why. 
	[Laughter.] 
	MS. ENGSTROM:  I guess we screwed up.  And we were told that in fact there are no instruments out there that are truly accurate and validated and therefore making a recommendation that would constitute a requirement makes it very, very problematic.  And then, of course, there is the issue of if in fact using the example you provided of 100 individual subjects you want to enroll, if you went ahead and did a capacity assessment on each and every one of them, that is pretty stigmatizing in the sense that there are individuals out there who are perfectly capable of making a decision and -- 
	DR. SHAMOO:  [Off mic.]  Especially if you know that too.  Normal people -- but if you know that -- in this order there is a large capacity -- large percentage of decisional impairment and I don't think it is stigmatizing.  It is protective because they lack capacity. 
	DR. CASSELL:  Lily, if it can't be done, how do the investigators do it? 
	MS. ENGSTROM:  No, no, we are talking about formal capacity assessment by -- 
	DR. CASSELL:  Well, wait a minute, if capacity assessment can't be done, how do the investigators assess capacity? 
	MS. ENGSTROM:  We are not saying -- 
	DR. SHAMOO:  We do that all the time, by the way.  Psychiatrists do that for the courts.  The professional physicians do that on a continuing basis for the past 50 years.  We say, he has capacity and does not have capacity.  Psychiatric researchers are making excuses and they have convinced some people with you that those excuses are valid.  We have been doing that for 50 years in courts. 
	MS. ENGSTROM:  I think in this particular case we've been told, based on the individuals we had consulted with, that in fact there are no instruments right now that really are accurate.  And I agree with what you said because obviously if you followed any cases on the news you know that the capacity assessments are being made in the courts.  But we believe that making that a requirement, and I emphasize that, that making it a requirement in all cases above minimal risks is where the working group did not want the Department to endorse that kind of recommendation.
	Again, I apologize, my boss, Dr. Robb, as I said earlier, is out of the country.  I am acting in his place and there is a meeting that I do need to attend the his afternoon. 
	[Applause.]
	CHAIRPERSON MARSHALL:  I want to give the floor to Susan Kornetsky who has a couple of things that she would like to say.
	Lily, thank you very much.  I really appreciate you being here and sorry we had to change the schedule around 
	MS. ENGSTROM:  That's no problem. 
	DR. KORNETSKY:  These are unrelated things.  One Kate had asked me to announce and the other is a plea for involvement from the working group and the people out there.
	This morning it was mentioned that there was the new accreditation process that is being formed and going forward with AHRP and I just want to let people know that the standards that will be used in an interim basis, the draft standards, are out for public comment.  And if you go to the web site, www.AAHRPP.org, they are there and they are accepting comments until December 3rd.  I think it's very, very important that this group contribute.  Adil has constantly brought up the issue, how do we know IRBs are doing a good job?  Well, these are some of the ideas and tools that will be used to assess IRBs so your input is important.
	Second of all, Kate had asked me -- before Mark left Mark suggested that perhaps the working group or something be done to look at HIPAA regulations and the implementation on clinical research.  We also spoke a little bit with Julie and it's our understanding that sort of how research is being handled is still under some discussion.  So we still don't know exactly how that will turn out, however, there are some guidelines that are out there.
	Kate suggested that it may be helpful if Mark and I sort of took the lead in maybe at least sort of bringing up some of the issues, drafting a letter for the working group and I think there's a time commitment of trying to do this, I think, before January, before they make public any other different changes, just what some of the issues are about HIPAA and the impact on clinical research and things that are covered under the common rule.
	So, I have agreed to do that with Mark and to circulate it to the Committee, but I don't think we will be meeting before that.  So, I don't know if there is, you know, process issues or whatever, but to let the Committee know that we are willing to do that.  And that's it.
	So I would ask whether you agree with us to do that or there is going to be discussion.  I won't be here later this afternoon.  Mark won't either, but you can certainly, if there is time to discuss it, get back to us.
	CHAIRPERSON MARSHALL:  Thank you.  We will discuss it during our wrap-up.
	I want to acknowledge there is someone here from NCQA.  We would like to give you equal billing, please.
	MS. FRENCH:  Thank you.  My name is Jessica Brefer French, I'm here from the National Committee for Quality Assurance.  Some of you may be aware of the work that we're doing under contract with the Veterans Health Administration in which we are accrediting the human research protection programs at the 120 Veterans Affairs Medical Centers around the country.  We have been working at this for the past year now.  Our standards were publicly commented upon back in the spring.  We pilot tested the program and are now in full scale implementation.
	The program does address many of the issues that this group has been discussing today.  Excuse me.  We will be making efforts over the next several months to expand the program specifically to make it applicable for other types of research settings, beyond the VA medical centers. 
	You will notice, if you review ou standards, that there are some peculiarities that address VA policies specifically and there are some gaps in the standards where VA research is particularly limited.  But we will be making those revisions and we would welcome any input, comments, suggestions that you have in that regard.
	CHAIRPERSON MARSHALL:  Thank you very much. 
	And Vera will give you -- we are going to continue this discussion after lunch, I want to point out.  So brief remark and then we will adjourn for lunch.
	MS. SHEROV:  For the record Vera Sherov [ph] Alliance for Human Research Protection, AHRP.
	Dr. Cassell, I want to come and help a little bit in clarifying why NBAC in fact focused on -- and I will call them the "mentally ill" as -- the term that is used colloquially out there by the general public.  And one of -- I suggest that one of the reasons that you're getting these attacks as to why single out this one group?  What's so special and why are they different and why are you stigmatizing them?  I think a good deal of that would have not occurred had NBAC included in its report the evidence, the testimonies, in the details in which they were presented to you documented testimony.
	Now, I'm referring to particularly some 12 testimonies, September 18th, 1997.  Those testimonies not only led to three federal improvements to the Boston Globe series which was a prize-winning series, but it also led -- and this is most important, it led the director of the National Institute of Mental Health who is just now resigning, Dr. Steve Hyman, to evaluate the research at NIMH, the total package, 109 clinical trials at the time.  This was in '98.  And what he found was so bad that he shut down 29 clinical trials and an additional 50 were sent back to the investigators to justify the science.
	Now, if my arithmetic is right, that's at least 80 percent of the clinical trials at NIMH were found to be either ethically and/or scientifically unjustifiable.  That gives a picture of what kind of research is being done on these people outside of NIMH as well.  And I would assume at NIMH the standards are not less than the extramural.
	So, yes, this particular population is in fact being subjected to experiments that are not being done to any other group.  And when one talks about the so-called challenged studies, one needs to really provide a description such as you were given in testimony of what it actually does to the patient and what does it mean when a scientist writes in a consent form?  And this particular consent form was published in the New York Times where ketamine which is known to induce psychosis, the consent form told patients, ketamine is a medication for schizophrenia. 
	In other words, all the rules do not apply and I think that's why the strong recommendations that you came up with are justified and validated by the actual evidence in the field, but they're absent in the report. 
	CHAIRPERSON MARSHALL:  Would you like to respond? 
	MS. FRENCH:  And I suspect that it was sanitized in my opinion. 
	DR. CASSELL:  Well, thank you, Vera.  I mean, they are a special group.  This report came out of that kind of problem and came out of the long history that goes.  There is a kind of reducio that you can do by adding in everybody else, people with strokes and head trauma and all that, and then you add in everybody else and then you say, oh, it would be impractical to have special assessment.  And then you can dismiss the whole thing.  They shouldn't allow that kind of reductio.
	It's all through the working group's documents, enlarging the group to include all kinds of other patients who are not the same, and then dismissing it because it's impractical for all of those patients.  This is not about all of those patients.  I the's about a special group that were treated poorly and have not received the ethical attention that they should have received in the past.  And that's what this report is about.  It's not about anybody else.  If you want to do it for other people, that's fine.  But this report is about a special group.
	CHAIRPERSON MARSHALL:  Thank you, Eric.  And let us thank all of you.  Let us adjourn for lunch.  We will be back at 1:30 and begin with Greg Koski.
	[Whereupon, at 12:35 p.m., the meeting was adjourned to reconvene this same day at 1:30 p.m.]

	A F T E R N O O N   S E S S I O N
	[Time noted:  1:35 p.m.]
	CHAIRPERSON MARSHALL:  We will perhaps adjourn at 3:30 and if there are working groups who will be working, I know that many of you need to leave to get to your 6:00 flights.  So we'll just see what happens at 3:30.  But it's possible that the majority of folks may leave by then.
	So given the fact that we have slightly less than two hours, let's move on.
	Greg is next on the agenda and then Jonathan and Adil, and let's hope for fruitful discussion.
	OHRP's Response to HHS's Report
	DR. KOSKI:  Thank you very much, Mary Faith.  Welcome back from lunch everyone.  I will be extremely brief.
	The question that we actually would have been good to perhaps talk about before we broke for lunch, but the timing didn't permit it, was sort of a what next approach.  So I just wanted to give you a very brief sense of where we are thinking about or intending to go with the specific recommendations.
	Clearly NBAC has done a very thorough job, produced their report which then was sent to the Department.  The Department not only responded to it directly, but convened the working group, the report of which you heard described by Lily Engstrom earlier.  That was a Department-wide working group, she said.  It clearly was intended to assess what the implications of the NBAC report were for all of the operating divisions and agencies in the Department and I think that that working group has done a very thorough and thoughtful analysis and as a result of that, in their report have now appropriately transferred, if you will, to OHRP the responsibility for implementation of the recommendations from the departmental working group.  So we will be doing that.
	You've heard the recommendations.  Some of those are more concrete than others.  The ones that are immediately obvious no-brainers, we simply will go ahead with.  There are still some issues that will need to be resolved as to the most effective and appropriate form for implementing some of the recommendations.
	Clearly the call for broader public comment or more information on certain of the points is very clear and bringing those specific points to this committee for discussion, not the entire report.  We do not want this committee to repeat the work that has already been done by the HHS working group.  We appreciate your enthusiasm, but I would ask you to please confine your valuable efforts to those specific points upon which the Department seeks broader comment.
	And we are launching that process here, that's why it was put on the agenda at the same time we will be seeking comment from other sources as well as we begin to establish the best way to go forward. 
	I think it's clear to all, including NBAC, that some of the recommendations that they have made fit neatly into the framework that has been adopted under the HHS regulations, 45 CFR 46 in terms of the core, Subpart A, which is the basis that is the common rule, but also the additional Subparts B, C and D each of which in turn addresses special protections afforded to groups that for one reason or another are deemed to be in a position where special protections would be appropriate.
	I hesitate to use the term "vulnerable populations" because I know having been the father of three children that a pregnant woman is not necessarily vulnerable. 
	[Laughter.] 
	DR. KOSKI:  They may be vicious, but -- 
	[Laughter.] 
	DR. KOSKI:  I wouldn't say "vulnerable."  So like I say, the key point here is that we have within the Department deemed that there are special populations that are in positions where special protections are reasonable and appropriate.  One possibility, of course, would be to formulate a new subpart under the regulations, a Subpart E that would be directed towards special protections for another population that has been deemed worth of such special protections.
	So we need to explore that and we need to explore that within the scope of the recommendations from the working group.
	So, I think you can anticipate that we will go ahead in the most timely fashion possible within the limits of our resources to communicate this information to the states attorneys general as has been recommended.  Certainly there is some specific work that has been remanded to the director of NIH and we will not get in the way there.  That is NIH's job. 
	There, I think, again, is a continuing need and interest in finding appropriate mechanisms for providing resources.  That's not an immediately solvable problem and is somewhat broader than the specific issues that were raised from this particular working group.  But nevertheless it has to, in my opinion, be given a higher level of priority than what perhaps we have been giving it.  I think that it is essential that we push forward to try to get that done.
	So, basically I think that OHRP on behalf of the Department understands what its responsibilities are.  We work hand-in-hand with our colleagues at FDA on all of these things and will continue to do so as recommended in this particular working group report also.
	So I will stop at that point and if there is anyone that has any questions, you've got two minutes. 
	DR. CHODOSH:  Not really a question, but a comment.  And that is it seems to me that at some point we're going to have to address the whole business of informed consent, not just for this special category.  And I just hope that we don't keep going at this piece-by-piece.  I mean, I see that what has happened to informed consent has been beset by lawyers and that something has to change here to make the process correct.  So I just -- if we go forward with this special aspect, it would be nice if there was sort of like the tag on, let's really look at informed consent.
	CHAIRPERSON MARSHALL:  Sandy, we are planning on having, if it is the will of the Committee, a separate working group on informed consent. 
	DR. KOSKI:  I would just add to that, again, given the number of issues that we have to deal with, you know, clearly we need to sort of bite off pieces that we can chew on, and I think the issue of informed consent is clearly one that's critically important.  How we actually get to the stage of focusing on process instead of forms is a very, very important one.  There has been some very exciting work that's done that's actually gone beyond what was available at the time of the NBAC report as well in terms of even things utilizing web based, you know, tools to augment the consent process or other specific assessment tools that have been shown to be effective in patients with mental disorders and so on.
	I think we have already made some progress down that road, but pulling it all together is going to be a very, very important thing and that's why we -- we would ask that the issues be placed on the agenda.  In the broad context though for this Committee we do though have this one specific sort of more targeted issue to deal with and I think we can get that one out of the way.
	CHAIRPERSON MARSHALL:  Other questions for Greg?  I'm sorry, Vera, for the record you need to tell us who you are?
	MS. SHEROV:  Vera Sherov, AHRP.  In terms of informed consent, the only thing that I have not heard at all mentioned is enforcement, in other words, enforcement of the lack of process and the lack of disclosure on the part of researchers and IRBs.
	CHAIRPERSON MARSHALL:  So you're talking about sanctions for those who violate -- 
	MS. SHEROV:  Whatever.  I mean, there are committees working on what kind of sanctions, what constitutes a violation of informed consent.  In other words, I'm only hearing the one side addressed and not the other.  And some of us happen to think that that is the thing that would actually alter the table.
	CHAIRPERSON MARSHALL:  I agree with you.  And I think Ruth did mention sanctions yesterday and Tom briefly today.  But that is certainly something I agree wholeheartedly that we need to consider.  You can have all the policies in the world and if they don't have teeth, they don't mean anything.  Thank you.
	Susan?
	DR. KORNETSKY:  Greg, I understand you've asked us not to repeat the work of NBAC.  I don't think any of us are doing it.  I'm sort of looking at these lists of the different things.  Are there specific points here within that report that you are specifically looking for guidance on?  And is that clear to this group as we embark on that?
	DR. KOSKI:  Yes, Susan, it was made explicit in the request to NHRPAC to consider specifically those areas, points two, I believe it's nine, 10 and 11, or 10, 11, and 12, okay.  I learned how to count back in Ohio, what can I say.
	So that, yeah, we've made a very specific request to NHRPAC as part of the process recommended by the working group. 
	CHAIRPERSON MARSHALL:  Mary Kay.
	DR. PELIAS:  I have a question.  If we're going to become interested or start dealing with the idea of sanctions, what is our role there?  Do we just recommend that sanctions be imposed or be devised and imposed?  Or do we make specific recommendations about what kind of sanctions, civil fines, or criminal or whatever, I don't know where we should go with that. 
	CHAIRPERSON MARSHALL:  Well, I think that will probably be something perhaps that we discover when we get there.  But, again, bearing in mind the fact that we are advisory to different folks including the OHRP, the director of the OHRP.  So I think we would couch any of our advice or recommendations knowing that they would be implemented and perhaps further specified by those to whom we give advice assuming that they choose to take our advice.
	Well, if there are not other questions of Greg, then shall we move on then to Jonathan and to Adil, bearing in mind that we hope to have -- we will have time at the end to continue the discussion and that you can then ask questions also of Greg and of Eric.  Jonathan.
	DR. MORENO:  I've long been especially interested in this topic.  In fact, some of you have probably heard me talk about it.  I mentioned in the past that the first time I witnessed a clinical trial with psychiatric patients was when I was ten years old.  My father who was a psychiatrist did some LSD research with patients from Hudson River State Hospital in Hudson Valley.  And in those days, this is 1962, there were a lot of distinguished psychiatrists who were doing LSD research before Timothy Leery came along.  And ever since that weekend -- I didn't take it, by the way -- 
	[Laughter.] 
	DR. MORENO:  And neither did he. 
	I was interested -- an interest that only surfaced 20 years later consciously -- in the whole process of how you decide to do research and so forth.  And, of course, in those days there were not consent requirements and I'm not sure exactly what the process was, in fact, with that group of patients.  And I also had quite a bit to do with the drafting of this, as you've heard already that Eric mentioned this very controversial report, not all of which I agree with, even though I do agree with most of it, most of the recommendations certainly.  And it has been an interesting experience.  It was a very interesting experience to sort of have an autobiographical connection to the psychiatric research community at the same time to be trying to work through these issues.
	That having been said, I want to say a couple of things for the information of the advisory committee about the territory of this document -- of the NBAC document.  And as you might have gathered from this morning's conversation, an historic problem, Eric alluded to this, but I want to expand on it, an historic problem about dealing with this population with respect to clinical research standards has been what's the population?  How do we get our arms around what the relevant population is? 
	Now, if you think about the four groups that the National Commission recommended have special protections, they have something in common.  They have a couple things in common, actually two things, prisoners, pregnant women, and fetuses, children, and what was called at first the institutionalized mentally infirmed who came later to be called by the National Commission, those institutionalized as mentally infirmed.  The qualification is important because these were the institutionalization days and a lot of people who were institutionalized as mentally infirm were not mentally infirm.  Some of them were deaf and so forth.
	What did those four groups have in common?  These -- I think it's important to appreciate that the subparts of 45 CFR 46 were not pulled out of the air.  There were basically two reasons that they were focused upon by the National Commission and by B, C, and D.  First of all, because they were institutionalized, they were convenient, kids were convenient in vaccine trials because they were usually in asylums and in orphanages.  Pregnant women were lying in hospitals and were convenient, and prisoners, of course, particularly long-term prisoners were the most convenient of all.
	The mentally ill were also convenient because they too were, of course, in those days, institutionalized.  They were in asylums.
	So that's one reason that those -- we keep returning to those four groups as vulnerable, quote/unquote, because they have -- there is some history behind them.  And, secondly, there were also press reports, scandals, if you will, for 100 years about each of these groups being in experiments.
	In fact, in 1900, some of you know, there was a bill in Congress to prohibit experiments with pregnant women in the District of Columbia.  That was the Gallanger Bill which did not pass.
	There were similar bills offered in a number of states around that time along these lines.  So there is a long history to these populations.  It's no accident that we keep returning to them, and it's no accident that persons with mental disorders are part of this set of groups.
	But now that they're not institutionalized any more, it's harder to see who exactly we ought to be talking about.  And that, I think, has been a continuing problem, a continuing sort of stumbling block and explains partly why there has been division, as you heard this morning, among people who are of good will and concerned about these issues who feel that NBAC was too specific should not have focused only on persons diagnosed with a mental disorder on those who felt that the whole -- all of those who have some mental disorder that could impair their medical decision-making capacity should be in the hopper.
	So I think it's important for the members of the advisory committee to appreciate that there is a good reason for this disagreement.  This is a group that is hard to get ones arms around as it were.
	The other thing I want to say is with respect to the stigmatization argument that Lily mentioned, but to identify persons with mental disorders as perhaps incapable of giving capable consent and therefore requiring some further independent assessment used to stigmatize them.
	I find it a very peculiar argument.  It's an argument, by the way, that was made in the early '80s by the opponents of the National Commission's recommendations with respect to those institutionalized as mentally infirmed.  And, I guess, part of what I find puzzling, I find a number of things puzzling about it, but one of the things I find puzzling about it is that many of those, not all, but many of those who find that approach stigmatizing prefer that they be treated along the lines of the pediatric reg model.  And it seems to me that to say that we should treat these people as though they were children, is at least as stigmatizing as to call into question in another breath whether they should be presumed to have the ability to give consent.
	So I just don't know, I think the stigmatization argument frankly is a red herring.  I don't know what to make of it, and I don't find it persuasive.
	Now, that's enough on that.
	I do want to say that I think it's very encouraging that out of the 17 recommendations that NBAC made with respect to HHS that really 13 of them, we're very close on 13 of them.  I think that's really good.  There really has been progress, more progress in this area in the last four or five years than in the last 20-plus years.  So that's a good thing.  And I hope that we can move forward on those last four.  They are hard ones and they all, if you look at them, they all have to do with levels of risk and how we interpret them and what we make of those risk levels.
	Now, I want to add one other point that really does go to the states and not to us, but I think it's interesting and we should all, in our own institutions be aware of it, if we are not already, in our own jurisdictions, and this has to do with recommendation 15.  And I think probably Susan and other people who work closely in IRBs are aware of this problem.  The problem is that legally authorized representatives, health care agents, whatever you want to call them, do not have the legal authority to enter the persons in their charge into research.  And, yet, that's frequently done and a blind eye is cast to that.
	So this is a really critical issue for the states and it's puzzled me why it hasn't gotten more attention at that level.  Now, what some jurisdictions do, just again for the information of the advisory committee, is interpret potentially beneficial trials as therapy.  And depending on how the jurisdiction statute reads, they allow their legally-authorized representatives to enter, say a person with mental disorders who acts -- with Alzheimer's disease who now lacks capacity, they allow them to be entered into a trial under that rubric.  That is to say, it's potentially beneficial, it's considered as therapy, not research, for that purpose.
	But that's, you know, that's playing it a little fast and loose.  So, I think every effort should be made to encourage states to recognize that they have this issue and they need to have a public debate about whether they want to give their legally authorized representatives, whatever they called them in that state, the kind of authority that is being contemplated in this recommendation.  And I'll stop there.
	CHAIRPERSON MARSHALL:  Thank you, Jonathan.  Questions particular to Jonathan's remarks?
	DR. KOSKI:  On your last point, I think it's important we recognize that there is research in which, for instance, both arms of a trial are in fact therapy. 
	DR. MORENO:  Yes. 
	DR. KOSKI:  And we don't want to somehow misconstrue the fact that just because it happens to be conducted under the rubric of a research trial that in fact it's not therapy, this all adds into the thing, but there are those types of research in which there truly is therapy provide and the purpose of the research is simply to determine which of those therapies is safest and most effective.
	DR. MORENO:  Right.  They might be comparing a drug therapy and a psychotherapy or some combination thereof.  And they're in equipoise about which is preferable.  But unfortunately not all studies are like that.
	CHAIRPERSON MARSHALL:  Other questions for Jonathan?  Abbey.
	MS. MYERS:  I just want to clarify.  As you were talking about the past violations of rights in the mental illness community that the mental retardation community has been equally abused if not more so.  And so that, do you advocate this covering more than the mental illness community and all of the decisionally impaired?
	DR. MORENO:  The way that -- and Eric may want to speak to this too, but the way that the framework was constructed by NBAC was that this was a build up -- Jim Childress -- build up strategy.  Let's deal with this population so far as we can get our arms around it and then let's see how we can apply similar standards to relevantly similar populations.  And persons with mental retardation could well be the next population that's attended to.
	CHAIRPERSON MARSHALL:  Eric, did you want to make any remarks in response to that? 
	DR. CASSELL:  Yes.  And I think that that's correct.  Of course, if you are an advocate for the population not yet on line, coming on line, then that's a disappointing matter.  But on the other hand, if you deal with this population the way these recommendations go, you are going to find out those things that really do work well and are applicable and so rather than diluting the effort out and then at the end it gets to -- there are so many different kinds of people in there that you can't really see whether it is the thing that's the real problem so that there are good reasons, I believe, for dealing with this population. 
	First, you could turn around and say how about the mentally retarded first.  But the point is, by defining the population relatively strictly rather than including a very large group that then dilutes out the effort.
	MS. MYERS:  But HHS has told us not to do that.  They've told us that they want regulations for the whole population despite, you know, not diagnosis specific. 
	DR. CASSELL:  Well, I don't know, you know, I don't know whether it's like the victrola or not in relation to HHS and here.  Who is the master's voice?  Do you just take what HHS recommends and then move forward or do you have independent -- 
	DR. KOSKI:  I think, again, Lily laid it out pretty clearly that the Department working group felt strongly that the framework here is one that is broadly applicable to all with impaired decision-making capability.  And I don't see any need to delay the sort of broader -- for implementation of a broader framework that would provide special protections recognizing and being sensitive to the potential that Eric and others have already raised to allow this broadening to detract from the more specific goals.
	I think we just need to be very sensitive to that and as we move forward recognize that under a regulatory framework, if that's the form that it would take, that there is still the need for specific guidance and interpretation of how those regulations might be applied to again specific populations.  So that I don't see the two goals as being either incompatible or inconsistent with what the working group has recommended.
	But, again, it means we have to be sensitive to the potential, or if we allow this broadening, okay, to sort of, as Eric was saying, allow there to be claims made to say, now the problem is too big to deal with so that we can't.  Then we will have, I think, lost something along the way and so we don't want to see that happen.
	CHAIRPERSON MARSHALL:  I have Denyse and then Bob. 
	DR. THORNLEY-BROWN:  I have a question about prospective authorization.  Is that useful at all?  What percentage of patients with mental illness have done some kind of document like this and is it worth even discussing?
	DR. MORENO:  I'll get it started.  Our psychiatrists have said that maybe 10 percent of the patients they have historically seen might be enrolled in this fashion.  Now, if you're talking about kinds of disorders that people had in mind when this recommendation was developed, it's people who have disorders that involve waxing and waning capacity.  And so, while they're waning, they might want to be in the study, but not have the capacity to at that moment to enroll.  It's a small piece of the pie.
	DR. KOSKI:  I think though if we look at the broader experience from the medical community, okay, we know that if no effort is made to utilize preauthorizations for care, predeterminations, whatever you want to call them, then it doesn't happen.  But in institutions that make a very dedicated effort to try to make sure that every patient who comes in basically is given the opportunity with a full explanation of the pluses and the minuses are doing so to execute such an instrument from medical care that in some institutions there may be more than 80 percent of the patients that actually do that and it's often very valuable because they make very clear this is what I want.
	And if you end up in a situation where they can't make a decision for themselves, everybody knows exactly what they wanted.  So that until there is a framework that would basically, you know, raise this issue for people to consider and in fact encourage its use it's not likely to happen.  Once there is, you know, guidance or whatever that would say, this can be a valuable tool and this is how it has been used effectively sort of thing, that's not going to happen.  But I don't think we should use that as an excuse for not exploring it and where appropriate utilizing it to its full benefit.
	DR. DORFF:  Alzheimer's patients are a wonderful group for that.
	DR. MORENO:  I mean, even as one who is sympathetic to the idea, there is an interesting sort of philosophical reservation about it.  Why should we limit this only to people who have a diagnosed psychiatric or neurologic disorder.  Why not let everybody decide that if they ever lose decision-making capacity and/or are hospitalized that they should allow themselves to be enrolled in what could be a trial that is not necessarily beneficial to them.
	This is a potentially disconcerting arrangement, I think, and so we need to craft this concept very carefully.  Because basically what you would be doing then is allowing everybody to say, I want to devote my body to science -- dedicate my body to science while I'm still alive.  So this really has to be crafted very carefully, and I think limited very carefully which is why the recommendation is written as carefully as it is.
	DR. DORFF:  What is your objection to everybody doing that?
	DR. MORENO:  Well, you don't really know what you're getting into.  And so the question is, you know, okay, well, Dorff said 30 years ago that we could, you know, use his brain and body in science while he's still alive, but incapacitated.  You know, is that a license to open him up and see how he ticks?  As long as we're experimenting with him, it's okay. 
	DR. THORNLEY-BROWN:  It also creates a lot of distrust.  I mean, you come to the hospital and they say, well, if something were to happen to you, would you like to participate in research?  A lot of people would perceive that as -- you know, they're not really going to make every effort to keep me alive and to keep me doing well.  I mean, they need some research subjects.  Whoops, you know.
	[Laughter.] 
	DR. THORNLEY-BROWN:  I think a lot of people would look at it that way.  And a lot of educated people as well. 
	DR. MORENO:  A lot of care needs to go into this concept. 
	CHAIRPERSON MARSHALL:  Step up to the microphone, please, if you have questions.  Bob.
	DR. RICH:  I want to return just very briefly to a comment that Abbey and then Greg made about the scope of the decisionally impaired population that this refers to.  And I strongly support Abbey's point of view, and the Department's point of view too. 
	I think it would be a huge disservice to carve out one particular subpopulation of the decisionally impaired, and I would like to add one further argument to the point which is that most of what we've been hearing about is the role of psychiatrists in this population.  And, in fact, I think that it's important that we engage a much broader community than the psychiatric community as we discuss these issues.
	Many of the health care givers for the decisionally impaired, for example, for mentally retarded individuals, for individuals with brain injury, all kinds of things are far afield from the psychiatric community, and I think we very much need their input into these discussions as well.  Because whatever is decided by the Department is going to impact those communities down the line certainly. 
	CHAIRPERSON MARSHALL:  Thanks, Bob.  Please go ahead. 
	MR. CHORE:  Three quick comments.  David Chore, National Institute of Mental Health.  I agree with Dr. Cassell that there has been enormous progress in the treatment of the mentally ill and that many of the people that we work for have carried the diagnosis of mental disorder and would probably highly object to having themselves have to take a test to be able to participate in a paper and pencil questionnaire survey. 
	I would also point out that if you actually read the report as opposed to the executive summary and the recommendations, you would find numerous instances in which there are references far beyond mental disorders that there are dementias, that there are all sorts of metabolic disorders that can impair capacity.  And so while there was an insistence in putting into the title "people with mental disorders" that if you actually read the report you would find that it really already refers to other groups. 
	Now, I think maybe one or two more just brief comments.  This issue of "stigma" is very controversial.  A lot of people think that initially people in institutions were picked on whether they had autism or whether they were mentally retarded or had schizophrenia.  I believe Subpart A already contains the principle of distributive justice.  I believe that that is already outlawed and the idea that you need a separate subpart to protect people with mental disorders who are institutionalized is redundant given that distributive justice is already a principle.  You don't use people as subjects because they are convenient.  You use them because the research refers to their condition.  And I thought that was the whole principle of it.
	And, finally, I think the issue of surrogacy, I believe, Greg, that legally authorized representatives are already permitted for adults to consent to nontherapeutic research.  I think it's already in there. 
	DR. CASSELL:  I'm all for the principle of distributive justice.  I mean, me and my mother.  On the other hand, the population was picked because of injustices that were perpetuated overruled a long period of time and in part occasioned by a lack of regulation which -- excuse me -- excuse me.  I'm answering -- and that were promulgated -- not promulgated when they would have been originally.  So that this population came to attention for a reason.  You can't brush the reason off by saying, oh, it's not true, or something like that without producing contrary evidence.  I mean, it's that these are evidential matters that they don't have to be argued about.
	DR. KOSKI:  The issue of having a legally authorized representative -- a complex one.  Because all that wording that is used in federal regulation, it's not actually been fully detailed and explored in state regulations.  In fact, most state regulations that pertain to consent for medical procedures, for instance, are completely silent on the issue of research.  So this is an area that, again, needs to be addressed.  Because I think the prevailing practice is that we often rely upon individuals who we kind of designate as a proxy on behalf of a person -- they in fact have no legal -- true legal authority unless they have a durable power of attorney or some other instrument that gives them that status as the legally authorize representative. 
	So there is an area there for some work to be done.  And there are some pitfalls in that.  I think we could all imagine the situation where Uncle Joe, who has no one left now in the family to kind of take care of him with his Alzheimer's disease, is actually a drain on the family that's trying to care for him, a drain on the finances, and everything else where they might just as soon, you know, have Uncle Joe put in a box somewhere.  And so it's not necessarily true that a family member always has the very best interests of any individual research subject, you know, at heart.  And so we need to be careful and thoughtful about how we proceed with this.  But that is certainly an area that needs further exploration and development. 
	AUDIENCE PARTICIPANT:  [Off mic.]  As someone who also had a family member with Alzheimer's disease in a nursing home and who participated in a research protocol, I want to comment that the procedures for obtaining legal guardianship took four months and were 100 times more traumatic than the drawing of the tube of blood and looking at medical records involved in research. 
	CHAIRPERSON MARSHALL:  Anyone else? 
	[No response.] 
	CHAIRPERSON MARSHALL:  Adil, the floor is yours.
	DR. SHAMOO:  Thank you, Mary Faith.
	I want to echo what Jonathan said that the fact that we have around 13 recommendations, the working group is recommending that basically the OHRP in consultation with FDA issue some kind of guidance or clarifications or refer them to the state.  So that's a very good positive step.
	Having said that, since it's on the table, the broadening, I have never objected to broadening the definition of decisionally impaired to include other decisionally impaired other than mental illness.  However, that should not preclude some specificity to protecting those groups which recent history has shown that they were abused, like the mentally ill.  And we could do -- both those things are not mutually exclusive.
	Eric Cassell today did a great job of showing the history of protection of the mentally ill.  The two commissions, the National Commission and the President's Commission, wanted some kind of a subpart and/or legislation or some mentioning of protection of the mentally ill.  Those of you who are willing to go to the archive and you will see less than ten psychiatric researchers killed that process of getting a subpart because they had access to the DHEW then how to stop that getting subpart.
	Prisoners got it because they had advocacy group.  The National Alliance for the Mentally Ill didn't exist then.  Other Advocacy groups didn't exist in the '80s.  The prisoners, the pregnant women, all of them got the subpart, but not the mentally ill, which in my book they were the ones who should have been the first protected group, to be very honest.
	It is unfortunately the same access, and that's why I asked Lily who she consulted.  Again, it took few psychiatric researchers to go to the upper echelon of HHS to after all what NBAC and all of us in the advocacy group have tried for about ten years and NBAC for nearly three years of hearings, of deliberation, and somehow they are scuttlebutting the recommendations, these four recommendations.  And these are the heart and soul of NBAC's recommendation.  So I want to put that on record.
	The mentally ill, and I'm going to use the example, my favorite example, schizophrenia patients because they have the most severe mental illness, the most serious which is characterized by thought disorder, psychosis.  But there is one thing the psychiatric researchers somehow don't want you to know that one of the first characteristics and primary characteristics of schizophrenia patients lose the executive decision-making ability, volition.  The ability to say "no."
	Now, how in the world for 30 to 40 years, psychiatric researchers who know better than all of us that this group of 100 schizophrenic patients, there ought to be one or two or three at least, ten, who cannot sign informed consent.  They say they voluntarily signed informed consent with a straight look on their face.  But that is what they did.  So I really think we should not trust those who have abused psychiatric patients -- not all psychiatric researching community, those who have abused and allowed their institution to be our role model.  For example, in the booklets we got there are two articles, these were apologists for all these years for the common practice of the psychiatric researchers with those subjects.
	I checked every textbook that was taught in medical school since 1965 because I was planning to write paper on it.  What do they say about psychiatric patient?  All these textbooks which were required in their psychiatric teaching in the medical school, they say thought disorder -- large percentage -- they use those words, "large percentage," majority they have thought disorder, psychosis, delusion, and definitely lack of volition.  However, the same psychiatrists who have been trained in our great medical schools, they are the great luminaries of the field did research the way it's been done all the time.
	So, from these four, you know, items, recommendations, 2, 10, 11, and 12, we need really to stress the capacity assessment and is not stigmatization.  I agree fully with what you said, that's a red herring.  That's being disingenuous on their part, capacity assessment -- somehow -- Bonnie and I had a discussion -- it does not have to be that every schizophrenia patient or every mentally ill, we have 300 in the hospital -- well, you lack capacity to determine and we are going to give you a test.  That's what they say to us.  That's not the way you have to do it.
	You could have his own private psychiatrist who is not part of the research team to come in the informed consent process to look over what's going on and say, hey, guys, hey, you, PI, this guy really can't signed informed consent.  He is the one we should do some kind of capacity assessment.  You assume they have capacity to sign informed consent.  You assume everybody, that's their autonomous God-given rights.  Nobody is taking that away from him.  And definitely I don't want to take that right from my son or those whom I know with schizophrenia.  But, when I know darned well that they cannot sign informed consent, they shouldn't.  There should be a bell ringing in somebody's head.
	So this capacity assessment is very important and the most important I am going to the sort of core problem and that is high risk research.  That is recommendation number 12, high risk research with no medical benefits.  I think that has to be only under unique and compelling circumstances should be done.  Otherwise, what we are using, we are exploiting those poor patients for the benefit of others.  And I thank you. 
	CHAIRPERSON MARSHALL:  Thank you, Adil.
	Questions for Adil, or comments?  Denyse.
	DR. THORNLEY-BROWN:  I've got two questions about the capacity assessment.  I mean it is a term that we put around a lot.  Is there really a good way to assess people, to objectively assess their capacity?  I know we deal with this sometimes in the medical field.  How can you tell if someone is really competent to make decisions?
	And the second question is, how often would you do it?  Because clearly if this is a waxing and waning thing, get someone to sign on the dotted line but how often would you re-evaluate them?  What would your determination criterion be?
	DR. SHAMOO:  There is no formal way yet available to assess capacity.  However, like I said before, for 50 years we've been doing it.  The courts have all the time bought some professional independent of the prosecutor or the defending lawyer and says this person cannot -- you know, lacks capacity.  And the courts have accepted it and all of the subsequent decisions have been accepted.
	So there is a way to assess capacity.  I think any independent psychiatric psychiatrist who was not a psychiatric researcher will tell you I can tell you.  And he may be wrong with 10 percent of the time, but that's okay, error at the side of being safe.  Okay.  That's one.
	How often, again, if in my paper in 1994, the very first time I mentioned it, I said, usually you should get your own private psychiatrist who is treating him, who is not a part of the research team.  I made it very specific, that should be your advocate in during the informed consent process that's the person who knows you well, who has been treating you for six months, a year, two years, or three, sometimes 10, 15 years, and he will give an opinion to the PI rather than now what it is the PI is the same person as a psychiatric patient's health-care provider and there is a huge conflict of interest because he wants to get more subjects.
	CHAIRPERSON MARSHALL:  I think one thing we might want to consider for this working group is finding persons who are doing independent or have programs that require independent capacity assessments prior to enrolling certain types of research subjects.  I know, for example, that Don Rosenstein at the NIH and others are requiring independent capacity assessments for potential research subjects in Alzheimer trial and so forth.  So there are people who are doing it and we probably would benefit from their expertise and their experience in this area.
	I have Eric, Bob, Elliot and Greg. 
	DR. CASSELL:  I just want to read what the actual recommendation says so it doesn't get confused with, there is no decent instrument and so forth.  The recommendation does not refer to instruments for assessment.  It says: 
	for research protocols that present greater than minimal risk,"
so right away it narrows it down to a special group
	an IRB should require that an independent, qualified professional assess the potential subject's capacity to consent.
	The protocol should describe who will conduct the assessment and the nature of the assessment.
	An IRB should permit investigators to use less formal procedures to assess potential subject's capacity if there are good reasons for doing so."
	So it doesn't require it, and we know that people are assessing capacity all the time.  Of course they're going to be wrong sometimes.  But most of the time if they've been doing it for a while they're rather good at it.
	CHAIRPERSON MARSHALL:  Bob.
	DR. RICH:  I just think we need to be careful in our choice of adjectives to not over inflame this area.  And I want to particularly make sure that we understand that when Adil was talking about recommendation number 12 as dealing with high risk research in actual recommendation number 12 deals with greater then minimal risk research.  And I think that is one of the major problems that the working group actually had, was the capacity to distinguish risk anything other than minimal risk and I believe that really is an important point.
	Recommendation 12 is not directed explicitly to high risk research.
	CHAIRPERSON MARSHALL:  Thank you very much.  That is a very important distinction and we do need to be mindful of and accurate with our language.
	DR. SHAMOO:  My comment was for high risk that means a subcategory of that description.
	DR. RICH:  I would just say that there is nothing that says anything about high risk in recommendation 12.  All it refers to -- it regards everything as greater than minimal risk as being a single category; and I think that's a very problematic issue.
	CHAIRPERSON MARSHALL:  Greg has a comment that's on point.
	DR. KOSKI:  Right.  I think inherent in all of our efforts to protect subjects in research is the notion of making sure that the protections are always commensurate with an appropriate to the risks that I actually inherent in the research and if we approach all of this with that mindset then we will hopefully avoid requiring something under a regulation that would mean you'd have to go through it no matter what which would pose unnecessary burdens to research with no real benefits.
	That's the kind of thing I think we need to be very careful to avoid.  And I think in both of those comments I know you both agree with that.
	CHAIRPERSON MARSHALL:  Elliot.
	DR. DORFF:  When I read what we were given before our meeting, one of the things that there's no page number on this, but it's on the overview of the issues and it's just before the last section, additional issues in research with persons with mental disorders and it says here, "finally a basic difficulty essential to the deliberations and research involving those who may be decisionally impaired, our society has not decided what degree of impairment counts as a lack of decision-making capacity although there are certain clear cases of those who are fully capable and those who are wholly incapable, persons with fluctuating or limited capacity present serious challenges to assess.
	The first thing that came to my mind is that this is a really old story.  In the Talmud you have the same exact issue.  In that case it has to do with legal ability to write a divorce document or to authorize a divorce document and it talks about times -- there are times when a person is clear minded and a time when a person is insane and therefore incapable to execute that or even to authorize that kind of a document to be written.
	And they also talk in terms of some criteria that they tried to establish.  This is 1,500 years ago to determine legal liability.  Because there are very clear exceptions to legal liability in Jewish law for those who are insane.
	I would hope at any rate that the expertise in doing that has advanced over the years -- 
	[Laughter.] 
	CHAIRPERSON MARSHALL:  Lawyers are the same.
	DR. DORFF:  But I mean, I think -- and I am very much with Adil on this.  I think there has to be in fact even if the ability to do this is not as exact as some of the other things like knowing whether you have bronchitis or not nevertheless there is at least some expertise in the field at least I hope.  Okay.
	No, all kidding aside I really do believe that and so consequently what you need to do is, this goes back to Aristotle, you want to have a measure that is appropriate to the complexity of particular thing you are trying to measure.  And so if this is very difficult, and we don't really have very clear measurements yet, nevertheless, we have some measurements.  It's not no knowledge whatsoever.  And so consequently what we have to be careful about doing is, first of all applying what we know and recognizing in the process the complexity of it and sort of the ways in which we are not as certain as we are in other areas, and then take precautions for human subjects that are appropriate to our lack of -- to our ability to assess, and to our lack of ability to assess.
	CHAIRPERSON MARSHALL:  I have Jonathan and then Sandy.
	DR. MORENO:  I thought I was going to go back a long way in history, Elliot, but you always have a way of pulling the rug out from under me.  I was going to just mention that about 1,450 years after that writing, the new Neuremberg Courts expert Leo Alexander, who was a Boston neurologist, at the end of the doctor's trial gave the judges several recommendations, all of which became a part of the Neuremberg code except for one that had to do with special protections for the mentally ill.  And the judges said that they did -- essentially according to Leo Alexander his interpretation of their rejecting that recommendation was that they did not want to get into doctor/patient stuff.  They were talking about prisoners.
	So even in that important context there was an awareness of this issue.  Not quite as old a reference as yours but nevertheless a reference.
	Secondly, there are -- as some psychiatrists in the room will say, there are some capacity assessment scales that are in the process of being validated.  One of them is called the MACAT CT and now they are for clinical trials.  There's now a MACAT CR that's being developed, so there are some that are in various stages of validation.  And I think within the next couple of years two, three, four years we are going to have some quote/unquote more of objective standards.  Quite apart from the clinical intuitions that we obviously have to rely on.
	I want to get to Bob's point about the fact that there is a big -- there are two big categories here, minimal risk, and greater than minimal risk, and that struck a lot of people as problematic.  And NBAC worried about that as well.  Alan Fleischman is not here but he would want me to mention that on the New York task force that he was part of and I was a part of until I left New York, they recommended a tri-apartheid system framework along the lines of the pediatric regs so that there would be a minor increment of minimal risk.
	And while I was working for NBAC, I actually went through several documents and I'm thinking of this especially of the Canadian tri-council report and the report by the Alzheimer Disease Association.  They like the idea of a minor increment of minimal risk for this population.  And they actually gave examples one of them was lumbar puncture.
	And so the at one point, Eric, you probably remember, maybe you don't remember this, but while I was drafting the NBAC report I had a section in draft in which I said okay you can do given the consensus of these group a minor increment over minimal risk category and you can give some examples and the NBAC talked, as I recall, about that and decided that if they were to do that, given the history, I shouldn't put words in the mouth of Eric and the other commissioners, but for various reasons it was decided not to do that.
	So it's not as though NBAC did not contemplate another category, but there was concerned I guess, and you'll have to correct me, Eric, about whether that would be a sort of a category through which one could drive a truck, and whether that could really be contained.
	And there are those who thought that even though it might be containable, they didn't want to give examples, because then the IRBs would say, oh, your research isn't one of the NBAC, minor increment over minimal risk examples, therefore it doesn't apply.  So that's a real tough problem.
	CHAIRPERSON MARSHALL:  Thank you, Jonathan.  I have Sandy and then Susan.
	DR. CHODOSH:  I'm sitting here stewing about this difference between those who are decisionally impaired due to "mental disorders," as opposed to those who may have "organic disease."  The more we learn about "mental disorders" the more they are clearly related to organic causes, many of which -- some of which we can now treat and reverse, to a large extent and we also have other agents that in normal people make them decisionally impaired and so I'm having trouble in understanding why we are defining this down to just, in quotes, "mentally impaired."
	DR. SHAMOO:  We are not.
	DR. CHODOSH:  Well, it sounds like we are.
	DR. SHAMOO:  We are not.  I mean, I'm a biochemist, I'm not going to differentiate between one organic disorder and another.  I think even anything has an organic origin although even that far.  I mean -- so I think there was a misperception on both parts.
	DR. CHODOSH:  But we're being told that they don't want to deal with people like with Alzheimer's or with head trauma.
	DR. SHAMOO:  That was not my view and that was not the view of the working group.
	DR. CHODOSH:  -- mental retardation and that we should limit what this group does now in looking at this in terms of just those with mental disorders.  So I just question whether there is a good rationale that will hold up five years from now when we have even more evidence that there are all alike.
	DR. KOSKI:  Sandy, I will respond to that.  Hopefully the Chair does her gracious goodbyes and thank yous to Dr. Cassell.  I think the Department's working group has already stated very clearly their belief that there is a broader context for providing special protections for individuals with impaired decision-making capacities whether it's from mental disorder or dementia of some other organic cause, or even poisoning, or whatever it happens to be, so that the intention of the Department is to move forward with the assumption that this will be broadly applicable to the entire group of decisionally impaired. 
	[Simultaneous conversation.]
	CHAIRPERSON MARSHALL:  Order, order, order, I'm sorry people are starting to interrupt others and so forth.  Sandy?
	DR. CHODOSH:  Then I apologize because I must have misunderstood what was said earlier in that it was going to be limited to those with mental disorders as the first hunk -- the first chunk.
	DR. KOSKI:  As I said earlier, we would hope that you would confine your discussions to the four specific points on which we've asked for advice.  That's not one of them.  Thank you.
	DR. MORENO:  Just to clarify for Sandy, the NBAC did confine itself to persons with mental disorders and I think that a reason they decided to start there, but not to necessarily end there was that the cases that had been of great public interest had to do with people who were, by any definition, people who had mental disorders and particularly people with schizophrenia.
	CHAIRPERSON MARSHALL:  Susan. 
	DR. KORNETSKY:  As many of you probably can tell right now I'm one who believes in flexibility.  And one of the -- flexibility for IRBs -- one of the things that bothers me about sort of this determination of competence, you know, prior to enrollment in studies is there are other models that exist and I do know of institutions already without something like this, who in higher-risk psychiatric types of research have a system -- and it was mentioned this morning -- of speaking, having a consent advocate, speaking with individuals after they have consented, asking them questions as one of the suggestions this morning to make sure that they indeed do understand what the risks and the benefits are.
	So I think if we require certain things up front and I'm not particularly for that.  I think that obviously we need to make sure that people are competent and understand, but I would want to box ourselves in to other types of creative and probably effective ways of doing things.
	CHAIRPERSON MARSHALL:  Thank you.  Other hands? 
	AUDIENCE PARTICIPANT:  [Off mic.] -- Enterology Institute at NIH.  I would just like to make one comment and that has to go with the issue of coverage and what you will be considering.  And because the NBAC really did start out with and continue all the way through focused on mental illness and then really at the point -- and which Dr. Cassell acknowledged this morning -- recommending the title to sort of mask that, and there were things thrown in like Huntington's, and stroke, and brain trauma, that the input that was obtained really was focused on psychiatrists were invited and except for the Alzheimer's Association, really groups that dealt with the mentally ill were the ones that provided input and comment on that report.
	So I know you said this morning the recommendation of the HHS workgroup was to get broader comment and if you are considering a broader application to do decisional impairment to please make sure you do open it up and include the neurological community because they had absolutely no input on this process.
	CHAIRPERSON MARSHALL:  Yes.  And I would like to say something too.  Don't sit down yet.  I think we would welcome as we are looking and will be discussing shortly at setting up a working group and certainly our processes are open and documents as we move forward on them are open.  But if you can inform the process up front in terms of suggestions for persons or groups or categories of professionals, or lay persons, we should be -- including from the get-go, we need to hear those now and soon. 
	AUDIENCE PARTICIPANT:  [Off mic.]  I would be delighted. 
	CHAIRPERSON MARSHALL:  Thank you very much and that's a general comment.
	Jonathan.
	DR. MORENO:  I don't want anybody to be left with the impression that on behalf of the Commissioners who are not here that they attempted to exclude any group professional or otherwise.  Quite the contrary.  I think they received what -- at least 90 comments on the draft recommendations and as a FACA committee like this one, anybody could come and testify.
	I don't remember if anybody came from the neurologic societies, but they certainly had the opportunity to do so and there was plenty of opportunity to comment in writing on the report. 
	AUDIENCE PARTICIPANT:  [Off mic.]  Yes, but largely because in all the discussions and including even the press release where Dr. Shapiro announced the release of this report, he also referred to the mentally ill.  And partly for that reason there is a whole community out there -- for example, I can tell you the brain injured do not think of themselves as mentally ill.  But they certainly suffer from cognitive impairment so that there was a whole community that because of the discussion and the focus and the specific invitation sent out by NBAC which are listed in the back of the report were individuals involved with psychiatric disorders.
	So, yes, it's true that if you wanted to go in and open the web site for NBAC, you certainly were free to comment.  So it wasn't that you were being necessarily kept out.  But at the point at which people realized the breadth of this report, for example, autism groups that I know wrote to the NBAC, they were told, sorry, comment period closed.  Because it was very much near the end, but it was the point at which large groups of individuals involved with neurological disorders, not traditionally considered psychiatric, realized that this would impact them.
	CHAIRPERSON MARSHALL:  Thank you very much and I hope that -- I think we pride ourselves on being open to the community at large, both -- not only in terms of our meetings and the give and take, but in terms of the composition of our workgroups and so forth. 
	So, again, we welcome any and all suggestions.  I have Abbey then Kate.
	MS. MYERS:  I would just like to comment on that.  A lot of these organizations are very small organizations and they don't have the resources to get down here to Washington to talk to government committees.  Moreover -- and like my organization represents 6,000 rare diseases, and a lot of them, for example, Creutzfeldt-Jacob disease, they don't have support groups.  So they don't have these consumer advocates who speak on their behalf.
	And I think I feel, as Sandy said, I'm sitting her stewing just thinking that this should be something that should address only mental illness.  It has got to be much broader, decisional impairment can be caused by a lot of things.  And as long as you brain doesn't work right so that you can't make a decision, you've got to be included in this. 
	CHAIRPERSON MARSHALL:  I think we all agree.  I think we are all -- thank you, Abbey.  We are all in agreement with that and that's how we'll proceed. 
	Kate.
	MS. GOTTFRIED:  I just wanted to comment to the Committee and to the people who are here that the NBAC report, the most recent report, on human subjects has a section on vulnerability.  In that section they talk about -- and I can get you the cite or send it to you or whatever -- a whole discussion about approaches to different kinds of vulnerable populations, one of which is in fact the cognitively impaired.  And so I think that there are ways to think about handling and approaching these issues and we all should take a look at that.  It will inform us both for this discussion and for other discussions that we take up as a committee.
	CHAIRPERSON MARSHALL:  Any other general comments? 
	[No response.] 
	CHAIRPERSON MARSHALL:  I wonder if we might want to think about focusing now on the idea of two working groups, one on informed consent, the other on research with the decisionally impaired, and perhaps we should start with the decisionally impaired since that's what we're talking about at the moment.
	And I might ask Jonathan and Adil who have helped organize this section and brought this subject to bear to the Committee for some advise and thoughts about how to proceed.
	DR. MORENO:  I recommend we let Adil tell us first how to proceed. 
	[Laughter.] 
	DR. MORENO:  I'm limited if not impaired.
	DR. SHAMOO:  Well, Madam Chairwoman, you will do the same thing we have been doing with other working groups, and that is, you appoint a chair which I recommend Jonathan -- 
	[Laughter.]
	DR. SHAMOO:  -- since he had me to speak first.  And -- 
	DR. MORENO:  I take it back.
	DR. SHAMOO:  -- have a comprehensive group which represents all sides.  But we want to make absolutely sure is not only the psychiatric researchers in that group.  In that group we should have patients, patient advocates and -- 
	DR. MORENO:  Neurologists. 
	DR. SHAMOO:  Neurologists.  Brainologists.
	[Laughter.] 
	DR. SHAMOO:  Yeah, whatever you want.  But I think it should be comprehensive and we should hear all sides.  And I think there is enough documentation, enough work done by NBAC and by other groups for the past four or five years that I think the working group doesn't have to reinvent the wheel and the working group.  So we need to concentration on those four recommendations and move forward. 
	CHAIRPERSON MARSHALL:  Exactly.  And I think at least in terms of the decisionally impaired that our charge is pretty specific.  So that's helpful.
	Greg?
	DR. KOSKI:  I just second that.  From our perspective I would urge that that is more focused component be prioritized to address that first.  And it provides then a valuable sort of way to move into the broader discussion too.  But given the fact that the NBAC report was issued in 1998 and we are now several years beyond that, I think it's urgent that we move ahead with this in a timely fashion so that I think you've got the right framework here.
	CHAIRPERSON MARSHALL:  So if we are proceeding according to established method, then we will need to vet the composition of the working group through the Committee.  But I would ask that Committee members and other might want to make suggestions in terms of individuals or groups who have a particular interest and should be represented to Jonathan who it seems to me has just accepted the Chairmanship, if not the Co-Chairmanship of this working group. 
	[Applause.] 
	CHAIRPERSON MARSHALL:  Any final words procedurally along the lines of the decisionally impaired working group? 
	AUDIENCE PARTICIPANT:  [Off mic.] 
	CHAIRPERSON MARSHALL:  And to me.  Or send them to Kate and she will send them to us. 
	DR. SHAMOO:  I have made specific suggestions, as you know, three, four of them, and I think transfer them to Jonathan or -- thank you.
	CHAIRPERSON MARSHALL:  So let's talk now about an informed consent working group. 
	And that's a little bit more difficult in that it perhaps has a wider purview and a charge that isn't as clean cut.  But I would love to hear your thoughts about the nature of that group and what it is charge purview might be.
	MS. MYERS:  This is such a huge undertaking, is there a way to slice it into sections in a way?  I mean, it's too much for -- when I think about what I care about with informed consent is that it was written what, 30, 40 years ago, the whole concept is very old and yet we have all these new technologies that have been developed in the last few years that aren't even addressed in the whole informed consent thing.  And today we spoke about our new section.  There should be a requirement added about conflict of interest so that there is a paragraph in there.
	Is there a way to break it down into small pieces?
	CHAIRPERSON MARSHALL:  One thought that comes to mind and then I'll take these questions is that certainly we have talked about and I think acknowledged that at least one goal of this group should be looking at the process of informed consent in ways to improve that process.  So that's just a thought. 
	I have Kate, Jonathan, just put your hand up.
	MS. GOTTFRIED:  I certainly appreciate what you're saying Abbey, and I think when we first thought of this idea we had talked about the fact that we're not interested in the legalistic approach as to the extent of an informed consent form and whether it's properly drafted and passed muster by the attorneys.  But, again, the issue of the process, and I think Tom Beauchamp said it today, monitoring the process of informed consent.  And perhaps we should identify that as just a primary recommendation/suggestion, a primary goal monitoring the process of informed consent and use that as our foundation and focus on that initially and then go on from there as other issues may arise that we want to address.
	CHAIRPERSON MARSHALL:  I have Jonathan then Felice.
	DR. MORENO:  Another, I think, reasonable approach, perhaps complimentary to that one might be to recognize that it's, I think, 20 years since the President Commission's report on making health care decisions.  And it may be very useful and also wise to try to build on what our predecessors did.  Look at that report and see the extent to which it's underlying principals are still valid and perhaps how the -- to the extent that they will refer us to clinical research.  And see if -- how the environment has changed in such a way that some new considerations need to be introduced, including, perhaps, the consent monitoring concept.  Then there are other documents as well.  But, I mean, there are several documents that come to mind from which the group could work without sort of starting from ground zero which it should not.
	CHAIRPERSON MARSHALL:  Felice.
	DR. F. LEVINE:  Well, Abbey, I'm sort of sympathetic to the "chunk up" need and in a way, you know, the social and behavioral science working group from the broadest original outline we presented in April have begun chunking up pieces that we're working our way through and you're doing it with us.  But we are doing it for you.
	On the other hand, I would love to start, given the passage of time and the changing nature and understanding of what the consent process is, not reinventing the wheel, but using a lot of the good input that we've had, to at least develop a framework of what the map and the schema would be.  Because if we start too early chunking, we'll sort of lose, I think, studying that process dynamically including not just the process of informed consent, but even these arenas that may fall outside of the areas of consent.
	And because originally a lot of this was so heavily determined both by the laboratory, I won't say the biomedical, because I think it's the laboratory even in the social and behavioral sciences that there is just a range of issues that have changed dramatically also.  What used to be not require consent about observation in public places, now with recording raise questions about where consent is necessary and where it isn't.
	Our discussion yesterday about studying traumatic context and how you modify and address issues of consent and that, so I almost would like a group, perhaps, by January, to provide a sense of the landscape and the issues and what a reasonable map would look like for this committee to chunk into and then we might decide how to best chunk.
	CHAIRPERSON MARSHALL:  Greg -- strategic planning.
	Susan.
	DR. KORNETSKY:  Greg, I hate to put you on the spot here, but thinking about our role being advisory to OHRP and thinking about the issues that I know are on the minds of IRBs about informed consent, where do you think it would be helpful for us to begin as far as where are the problems that you're seeing with IRBs and evaluation and informed consent?  There are lots of very interesting academic issues to explore, but I think we need to sort of prioritize them and be most useful as well.
	DR. KOSKI:  Well, Susan, for more than -- I don't know -- a decade now, you know, we've heard this phrase, you know, it's not the form, it's the process thrown around.  And yet IRBs when they're dealing with informed consent spend 90 percent of their time trying to decide which words are appropriate in the form so that we really need to help IRBs get out of that box.
	Now, one of the problems is, of course, that most people end up doing those things that they're most comfortable with or that they find easiest, so it's easier to look at the words.
	Many IRBs are already beginning to adopt a notion of actually -- strange as it sounds -- incorporating the consent process as part of the research protocol.  I know that's a radical concept, but to actually consider as part of the protocol how we're going to identify, approach, interview, discuss with subjects these things, test their competence, the whole works, to the extent that that kind of broad advice would be useful to the research community and could be conveyed through guidance, you know, by our office, I think that would be a very laudable goal to get away from the technical aspects of development consent form legal aspects of the development consent forms, finding ways to improve those parts of the process.
	And there's no reason -- I mean, we do need to have consent forms that are written in appropriate, you know, lay language, and all, but is that what we should be doing at an IRB meeting?  Thinking in terms of the programmatic concept of protection of human subject.  You know, it may be that other parts of the program are in some respects better prepared to do the wordsmithing or better prepared to check and see that each element of the protocol is actually reflected in the consent form.  And I'm just brainstorming here.
	So those are things that would be very, very helpful.  The comment that I made on the side, to Mary Faith was -- and I think it addresses Felice's concern as well as Abbey's, is that maybe a place to start would be to just have a small group to initially strategize.  Say, well, how might we approach this.  Do that first and then align or construct working groups accordingly in an appropriate structure so that this takes a broad thing and makes it manageable into the chunks as Abbey has suggested.  So I would offer those as a very broad framework.
	And, again, don't lose site of the fact that we heard from Jeremy Sugarman and others that there are well over, you know, I think, 200 studies of informed consent that have already been done and published that are out there.  Most people will say, we don't know anything about the informed consent process.  I reject that.  We know a lot about it.
	Also, we have the whole series of new studies that have been done under the LC program where specific projects have been funded.  We don't yet have the results of those.  We ought to get those.  We ought to incorporate those in the process that we're working.  We ought to look at the technological aspects of all of this.  Because there is some very good work that's being done, some of it here at NIMH, we heard about Rosenstein stuff and others, are there tools that we can use to facilitate process.
	So I urge you to think a little out of the box, but, again, strategy so that it makes it manageable is going to be very important.
	DR. KORNETSKY:  I just want to say I'm glad you liked -- we are one of the institutions that not only require an informed consent form, but we have an informed consent process form and do ask for the who, what, why, when, how are you going to know, those types of things.  So I think that is the type of very concrete type of creative ideas and other things that can be -- that we can think about and maybe offer some advice. 
	MR. REUBEN:  Phil Reuben, NSF.  I want to support that too.  In terms of what we see and in terms of prioritizing, in traveling around the country and meeting with different -- both members of IRBs and with professional societies, and it's clear that we need to both educate -- disseminate information, and provide guidance to the IRBs to give them an indication of the flexibility that's either available to them or that they need to think about or develop on their own.  And they don't actually -- not all IRBs do understand that and they are, for various reasons, very technically driven at this point.  And there is a great role that we can play and that societies can play to provide information about that flexibility.
	CHAIRPERSON MARSHALL:  Thank you.
	Sandy.
	DR. CHODOSH:  I think that it is time for us to stop playing games with informed consent.  And what I am talking about is I think we need to really look at this and say, what is required?  And what is required to inform the subjects and what is required to protect the investigator and what is required to protect the institution and separate them out so that the poor subject isn't beleaguered, you know, with all the legalese terms that really, quotes, "are used to inform the subject that he really doesn't have rights here." 
	Well, I think that we really need to look at this from a very different point of view of what is it that a subject needs to know how we're going to deliver it, how we're going to get that information to them, and get rid of some of the -- if we want legal documents, a lot of institutions do and a lot of sponsors do, let's make it a legal document.  Separate.  Okay.  Sign a contract; fine.  But not when it comes to, this is what you're going to be expected to do, this is what is going to happen to you, this study, et cetera, et cetera.  That should be separate.  And if we could do that, I think we would make it a lot easier.  But I may be wrong.
	Right now I think that, what, 60 percent of informed consent form, what's in there, could -- much to do with that study.  If that much. 
	CHAIRPERSON MARSHALL:  Adil.  Thank you, Sandy.
	DR. SHAMOO:  I think we're supposed to learn from the speakers who we got today.  And Jim Childress said, the informed consent may or may not contribute to preserving autonomy.  And our primary concern should be preserving autonomy.  Just Sandy put it a different way.  And my attitude is, why concentrate on the informed consent as a piece of paper because we will talk about a piece of paper.  Why not protection of the subject's welfare or preserving patient's autonomy or something like that.  That will be our thematic committee deliberation.  And then because there is disclosure issue, there is benefit, analysis and there is, of course, monitoring the informed consent process.  So these are all subjects but overall we're trying to preserve autonomy for the subject. 
	CHAIRPERSON MARSHALL:  Thank you, Adil.
	Other thoughts. 
	[No response.] 
	CHAIRPERSON MARSHALL:  Then we will proceed to -- especially some of the most recent comments that you all have made in terms of ideas of:  (1) bringing this group together, but (2) letting the group sort of do some initial work and then come back and refocusing so that the Committee knows or has input into how the working group would proceed is, I think, good advice.  So then I will take it as having the agreement of committee members that we will move forward with both of these new working groups.  Any other discussion about that? 
	[No response.] 
	CHAIRPERSON MARSHALL:  Then let me move to perhaps just to recap what we've done in the last couple of days, action items that I understand to make sure that we're all of one mind and understanding on the work that we have to do.
	I will send for the Committee a letter to DHHS that reflects a couple of things.  One is, sort of, our availability as a committee to help the Department and others conceptualize the human research concerns that have arisen as a result of the events of September 11th and certainly incorporating in those sort of concrete things that Jonathan brought to bear that are legacies from former commissions or other groups that are especially pertinent here and to get an update as to the status of those and perhaps a nudge as to moving forward with those that are just hanging out there in space waiting to happen and be operationalized.
	The third-party document we will be posting on our web site for comment.  It will come back to us in a final form in January.  The public use document is going to Susan Kornetsky and a group of the Committee here for fine tuning as well.
	Susan and Mark are also going to -- Susan, you might want to speak to this.  Someone asked me a question, I didn't have the answer to it.  I know that we are under a time limit here in terms of providing input to DHHS regarding the portion of the HIPAA regs that has to do with research, but what is the time frame that we're talking about?
	DR. KORNETSKY:  Kate can answer that.  I sort of stepped out of the room for that final discussion. 
	MS. GOTTFRIED:  Both Mark and Susan have been talking about a working group with respect to HIPAA and in light of concern about HIPAA and research, and we were informed by Julie Kanashero that the Department is still working on that issue and they have not made any final decisions yet with respect to the research component.  And, therefore, there was an idea floated by Mark that -- similar to what we did with the children's letter on Subpart B that a letter be drafted that he and Susan would take time to work on that and circulate it among the committee for review and consideration.
	And assuming no one had any major principled disagreement -- we're not talking wordsmithing now -- but that would be forwarded to the appropriate individual within the Department sometime by the end of November, late as mid-December, just to give input from NRPAC on this issue.  With the understanding that come early next year the Department will likely issue another round of the reg looking for comments.  And that would probably be sometime, Julie thought, around January, February, hard to say, but sometime early next year.  Then we would convene a workgroup whenever that happens to review what the Department issues and provide -- again, a reasoned comment from NHRPAC. 
	DR. RICH:  If I could make a comment to that point which is, everybody who has seen HIPAA knows that it looks like a telephone book.  I mean, it is really an awesome document.  My understanding is the Department will be opening certain aspects of the document for additional public comment and the initial thinking was that research would not necessarily even be part of that -- of what was reopened for public comment. 
	I think it's important to weigh in advance of that to be sure that the research-specific part of it is appreciated at the Department level as something that needs additional public comment.
	MS. GOTTFRIED:  Yeah, that's great.  I think that was the notion that even -- we expected they probably will open that area, but even if they don't, that was the idea is to send some preliminary comments to the Department in advance of their issuing another iteration of certain provisions of the regulation. 
	CHAIRPERSON MARSHALL:  Thank you, Susan and Kate for clarifying that.  And that's good advice, Bob.
	Felice is this on point to this issue?
	Okay.  Well, let me just move forward then.  The social and behavioral sciences working group is still proceeding along in the risk and harm area and so that we would expect to have something by our January meeting that is sort of close to penultimate to come to our group for action.
	Felice, go ahead. 
	DR. F. LEVINE:  It may be that a mid-cross correction won't make much sense now, but I had an alternative to suggest for public use data files given our experience with third parties, where at least on the public use data files the basic element we started with shared agreement and so I started crafting -- last night -- trying to put it into the form that I thought was more of the form that would be appropriate for -- although I hadn't yet finished it and printed -- but I thought it was more appropriate for the form that you all -- we all were -- I have my NHRPAC hat on now -- thinking about with respect to the kinds of things that came up from Susan and Elliot and Mark.  And not that I think that we should necessarily post it sooner, but frankly, had the third-party discussion happened first, I could see how readily as part of that group we were able to come up with something that could be posted.
	And in that area there was really a great deal of unanimity both on the working group as well as in this group.  So I'm wondering whether we could maybe with dragooning Elliot whether the three of us could work in a way that may or may not, but conceivably could have something that could be made available sooner and accelerate that process on a topic where I think there was really shared concerns. 
	CHAIRPERSON MARSHALL:  I think that's a wonderful idea.  Let me ask Susan and Elliot what their druthers are. 
	DR. KORNETSKY:  I have no problem.  But now I have two things that have to be accelerated.  And, I mean, I'll work on them, but -- I mean, I would be happy to do that if you would take the lead, Felice.  It's just I have two things -- 
	DR. F. LEVINE:  [Off mic.]
	DR. KORNETSKY:  No problem.  No problem.
	CHAIRPERSON MARSHALL:  Greg, you look as though you have something you would like to say.
	DR. KOSKI:  I do.
	Felice mentioned posting documents on the web.  It's been brought to my attention a couple of times over yesterday and today about the need to be sure that when something is posted that's a NRHPAC working group document or something that it be very, very clearly distinguished in any posting so that it cannot possibly be misconstrued as an OHRP document or anything else.  I know Kate and all are sensitive to that.  But I think, again, it's very important that the public understand that when NHRPAC posts something there for comment that it's NHRPAC's operation and not what OHRP is doing.
	CHAIRPERSON MARSHALL:  I couldn't agree with you more and try and reiterate every chance I have that NHRPAC is not OHRP or OHRP's committee.  Thank you.
	DR. CHODOSH:  I would think at first we would get something out on the list serve to all the members. 
	PARTICIPANT:  Oh, of course.  Yes. 
	[Simultaneous conversation.] 
	MS. GOTTFRIED:  No, the Committee members are first and then absolutely.  But just a point, and Greg knows this in response to his comment, that as I said earlier today, the web site for NHRPAC has a new section and we are looking into -- somebody had mentioned they had difficulty accessing it and I think our system was kaflewie for a few days there.  But the new section is NHRPAC report/documents and when you link to that the chronology of the different documents that NHRPAC specifically has drafted and a qualifying comment that these are NHRPAC's recommendations, they are merely recommendations of NHRPAC provided to the Department, et cetera, et cetera.  So, it's on NHRPAC's web site, they're NHRPAC documents, and it states that they're NHRPAC recommendations.
	DR. F. LEVINE:  If I can add in that spirit.  When we as a working group are posting things it says very clearly, this is a work of a working group that will be providing ideas to NHRPAC.  Indeed, I think the segregation of this working group web site makes sense because so that there is no confusion between a working group seeking input and then what ultimately comes to NHRPAC. 
	CHAIRPERSON MARSHALL:  Thank you.  And I might just clarify.  This brings to mind a point that I wanted to raise sort of a housekeeping -- or a procedural detail, and that is, Felice has said a couple of times today, I wear my NHRPAC hat.  And each of us here on the table wears a NHRPAC hat.  I mean, you are here for a reason.  But you are not here as an organization.  Nor is anyone who is appointed to a workgroup here for an organization.  So that the interactions that occur between working group members and among working group members and the committee are among those individuals supplementally.  And the documents that we will work on and our work products, are not done to facilitate taking back to boards of individual societies, waiting for boards to look at them that is not appropriate, that's not why people are appointed to this group.  So I want to make that abundantly clear and hope never to receive that sort of e-mail coming my direction again.
	So enough bad witch stuff here.
	It is hard to believe, but we have been in existence for a year now.  And I would like to acknowledge all of you and your hard work.  And I think that we have done, as a committee, some very good work.  We've tried to be expeditious and focused in the work that we do.  I hope that the Department and those to whom we are charged will continue to bring us challenging assignments and to keep us foremost in their minds, especially when they're thinking of allocating important resources.
	[Laughter.] 
	CHAIRPERSON MARSHALL:  Which we need as a committee to do our good work.
	I would like to thank specifically Denyse Thornley-Brown because I do believe -- are you rotating off?  I think that that's the case.  So thank you very much, Denyse. 
	[Applause.] 
	CHAIRPERSON MARSHALL:  We have certainly benefitted from your being here.  Thank you and don't be a stranger to us.
	Anything else for the good of the order that I am forgetting -- being neglectful of?  
	[No response.] 
	CHAIRPERSON MARSHALL:  Kate, are folks outside?  I would like to thank the folks who have helped us be organized.
	Oh, yes.  Well, Gerald is the last.  We save the most handsome for the last.
	Mary Kay, yes. 
	DR. PELIAS:  At the risk of being a glutton for punishment I would like to be involved with the informed consent group when it gets going.  But I am not volunteering to chair anything until my current term -- I really would like to be involved with that. 
	CHAIRPERSON MARSHALL:  Thank you.  All you have to do is ask.  Any other Committee members as well.
	Yes, Adil?
	DR. SHAMOO:  The same as Mary Kay.
	CHAIRPERSON MARSHALL:  The same as Mary Kay.  All right.
	DR. SHAMOO:  I would like to be on that informed consent. 
	CHAIRPERSON MARSHALL:  Great.
	So most of the Committee knows Toni Goodwin because she is the one who gets us there on time and gets things to us and keeps our lives in order, Kate's life in order. 
	[Applause.] 
	CHAIRPERSON MARSHALL:  And for those of you who weren't here yesterday, Kisha Johnson is our new boss here.  And Kisha thank you so much.  We are so glad that you are on board. 
	[Applause.] 
	CHAIRPERSON MARSHALL:  And we will now adjourn.
	And now we will -- ten minutes early, I want this to go into the record -- adjourn our meeting.  And thanks all of you and we look forward to seeing you in January.
	[Whereupon, at 3:15 p.m., the meeting was adjourned.]

	CERTIFICATE OF OFFICIAL REPORTER
	This is to certify that the attached proceedings before the National Human Research Protections Advisory Committee held Wednesday, October 31, 2001, was held as herein appears, and that this is the original verbatim transcript thereof, and is a full correct transcription of the proceedings.

		                      
		Gerald T. Brooks, Sr.
		Official Reporter
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