National Bioethics Advisory Commission
19th Meeting

February 5, 1998
1:43 p.m.
Los Angeles, CA



1:30 p.m.

Welcome, Overview of Agenda
Harold T. Shapiro, Ph.D.
1:35 p.m.
Executive Directorís Report
1:45 p.m.
Future Commission Research Activities
Eric J. Cassell, M.D., and Commissioners
2:15 p.m.
Capacity Assessment Instruments
Elyn Saks, J.D., University of Southern California, and Commissioners

2:45 p.m.
3:00 p.m.
Public Testimony
3:50 p.m.
Federal Oversight of Research Involving Human Subjects
R. Alta Charo, J.D., and Commissioners

4:15 p.m.
Tissue Samples Report: Analysis of Professional Society Requirements
4:50 p.m.
Next Steps
Harold T. Shapiro, Ph.D.

5:00 p.m.



DR. SHAPIRO: Good afternoon, colleagues on the right and the left. Think about that the way you want to. You like being on the right, Eric?

DR. MESLIN: He likes to think right, not necessarily on the right.

DR. SHAPIRO: Maybe I can change my position so you can be on the left, over there. All right, Iíd like to call the meeting to order, and let me spend a few moments just talking about our agenda over the next day and a half. There are some members of the Commission who will be arriving during the afternoon, depending on their flight arrangements and so on. But I think the agenda is long enough that we have to proceed.

If you look at the agenda for this afternoon, after a few words from Eric weíll deal with our future agenda. We all have a memo on that from Ericówhich is in our booksóand that discussion will proceed after hearing from Eric. And then Elyn Saks, who is sitting on my left over here, will be here to present to us on capacity assessment instruments. Thank you very much for being here; weíre very grateful for your taking the time. Weíll then take a relatively short break and weíll have public testimony. We have quite a few people who have signed up for public testimonyóquite a few meaning five, although some come in pairs, so it could be more than five people. Weíll try to start the public testimony no later than 3:00. Just out of deference for those whoíve come to give testimony. Weíll then pick up an item that we had scheduled at our last meeting in Washington but didnít quite get toóhaving to do with the process of changing regulationsóand Rachel will lead that discussion. Weíll then go on to continue our discussion that began last time, or the last two times, dealing with federal oversight of research involving human subjects. Alta will lead that discussion. Weíve had some material on that, weíve had some guests on that; the last couple of meetings had some experts report to us. We have a number of different propositions to consider and thatíll be an important discussion. The item thatís currently scheduled at 4:10óthe Staff Analysis of Published Researchóweíre going to take that off the agenda. We really donít have a discussion item there. Itíll come up tomorrow as appropriate when we deal with that general overall subject, but it doesnít seem to me that itís a necessary part of our business this afternoon. And then weíll go through some analysis of professional society positions on the tissue sampling area, and we all have that information put together by staff and weíll see if we understand that. Thatíll be quite important as background for our more general discussion tomorrow on that issue. And I really want to thank the staff for putting that material together. I found it really very helpful. And weíll conclude the afternoon with whatever miscellaneous issues seem to be appropriate to comment on at that time.

So to begin, let me turn to Eric.

DR. MESLIN: Just very briefly, welcome everyone, to Los Angeles and to the Omni. I want to make a couple of brief housekeeping remarks from the staffís perspective. Weíre in the process now of transitioning to a logistics contractor who will help us not only in our travel arrangements but also in putting together meeting agendas and the like. The briefing book you received is sort of a first effort to try to make what is often an awful lot of information more simple and accessible to you. Comments that you have about the books would be greatly appreciated. I want to thank Pat Norris for working so hard to put together this briefing book. Youíll find that it has a number of tabs that correspond to the items, and we hope that those tabs are at least reasonably accessible to you. Obviously there are items underneath the tabs and weíll try to direct you to them in the event that theyíre hard to find.

I want to identify one item in particular under Tab B, which is the Annual Report for the Commission. This is a report in which Kathi Hanna had a major role in providing some draft guidance. Staff has continued this effort and we now have what we hope is a final Annual Report for 1996Ė97. Weíre hoping that you will find this to be a noncontroversial document. It really says only what our accomplishments are, and in that spirit we would greatly appreciate your giving us any comments you can within the next week, seven days from today. We would then like to begin publishing it and making it widely available. In that same spirit of "widely available," I know that many of the Commissioners are aware, but for the public citizens attending, on the 28th of January we were able to launch the revised and updated NBAC website, located at

DR. SHAPIRO: I might add, sir, it has very attractive pictures of the Commissioners on that website.

DR. MESLIN: I feel like Iím in court here. Rob Tanner, one of our staff members, has handed me the absolute, up-to-the-minute number of visits to the website: As of the 28th of January, weíve had 1,732 visits to that website with approximately 65 dedicated comments. There is a comment section at the website, which NBAC staff will answer. Many people send their requests for publications there, so please tell your friends about that website. It is constantly being updated and revised. It is our hope that all of the transcripts for all of the meetings will be available on that website; that all of our reports will be available on that website; and that contents of the briefing books that are relevantóagendas, tabular forms and the likeówill also be available. We made the decision to put the website up sooner so that it would be useful; and please bear with us if youíre hoping to get the transcript from many meetings ago and itís not quite available. Weíre doing our best to get that done. The only other item from the staff is to mention that we are starting to wrap up our staff complement, and we are pleased that Melissa Goldstein who, although she isnít here with us today, has joined the NBAC staff as a consultant. She is a Yale-trained lawyer who is currently a Greenwald Fellow at Johns Hopkins University. And you will note Melissaís imprint on some of the documents in the briefing book. There will be some other announcements of "staffing up" at the appropriate time. We are also pleased that we have attracted a contract paper from a Professor Alan Buchanan, currently of the University of Wisconsin and soon of the University of Arizona. More on that later, but many of you are aware that Professor Buchanan has an extensive history and involvement in bioethics activities in this country. He is providing a very useful paper for the stored tissue report.

And I suppose the last item in this five-minute overview is to thank the Commissioners who were following the last Commission meeting, who were very generous in their time in being able to respond to numerous press requests from both the print and visual media in response to stories about cloning. We are able toóI thinkómeet all of the press requests and many of you around the table were very generous in your time and very eloquent in your presentations, and I think you helped the public understand what the Commission said when it issued its report last year.

Those are the only items, Mr. Chair, except for the pleasure to tell you that we are set for our next five meetings, and I think you will all join me in breathing a great sigh of relief that the meetings have been finalized and the dates are in your briefing books. We will be meeting March in Washington, DC; May in Cleveland; July in Portland; September in the Washington, DC area; and November in Miami. For those who are interested in those dates, they are available outside at the registration desk.

DR. SHAPIRO: If I could just say one other word about the awakened interest in cloning ever since the State of the Union speech. Many scientific societies and other groups from Washington are rushing ahead to try to get positions established on this issue. Many of them not necessarily take off from but at least build around our own set of recommendations. The astonishing thing is they may normally send me copies of what theyíre proposing. And I would say that 50 percent of the cases have had to call back up and correct just the way they read the document, let alone whether they thought their position was right or wrong. But there is a lot of interest, and I would say that the Congressóvarious senators and so onóis receiving at the other end of these memos that people are drafting on this issue. So Iím sure weíll hear more about that as time goes on.

All right, letís go on to our ... any questions for Eric? On the meeting or any other aspects? Letís go on to the Future Commission Research Activities. There is a memo from the staff, Eric, outlining some of the discussions that have taken place, and this is staffís view of the summary of those discussions we had last time. So let me turn to Eric to see if he feels theyíve captured the kind of main issues that he and his colleagues had wanted to advance regarding our future agendas. Eric?

DR. CASSELL: We indeed do have a revved-up staff, and in numbers and energy. And this discussion about our proposed future projects takes advantage of that. Eric Meslin and I had conversations about this during the past couple of weeks. One of the things I should say is that as we go through this, this is an action discussion. We should be able to nearly finalize what it is we want to do. However, we should also realize that staff can be asked to prepare detailed plans about how we would accomplish things, in what order, what we have to do, and what our timing would be and so forth. So we ought to come out of this with some idea of what we actually are going to do and then get feedback on that. Youíre seeing what you saw the last time we discussed this, in essence. There are some things that seemed more immediate than others. The ethical and legal issues in research supported and conducted in other countries is really quite pressing. I donít know about the rest of you but I got a letter from the Journal of Black Higher Education asking for some discussion about it, and I told them it would be a great idea if they attended the meetings where it was discussed. And I think we ought to come up early with that one. The same thing is true of Institutional Review Boards. Weíve committed ourselves already to a discussion of them and in the Moreno Report, which I think is excellent, we talk about them constantly; itís now time to come down to what we think they ought to do and what changes ought to be made. The issue of genetic discrimination and privacy is part of our mandate, and thatís there.

Now, the ownership of the body, if Alta could say a word about it, it was her proposal and Iím not sure we have captured what you meant by that. Could you...

MS. CHARO: In the course of the discussions about the use of tissues, it occurred to me that there really is not a well-developed and coherent set of rules in law. And I couldnít speak to ethics but I suspect in ethics about how it is that we regard personal control in every aspect of oneís own body, both the tissues while theyíre still incorporated into your body, and particularly once excised. There are very different and conflicting rules about the ownership of tissues once excised. Sometimes theyíre treated as if it were your regular, ordinary, toaster-oven kind of property; other times itís treated as a nonproperty item that doesnít have any kind of property rules attached to it; other times itís considered to be your essential self because of the information it contains. And when one takes a close look at itóit happens that I supervised a masterís law thesis on this topicóone finds that the absence of a coherent, legal regime is part of what leads to confusion about who gets to do what with which. Itís part of a deeper set of issues about personal control and personal autonomy that reach into things as varied as self-mutilation, suicide, the disposition of corpses, archaeological and ethicological work on the long-dead, and community ownership in particular among people like Native Americans. And in the more immediate sense, the legal background has so far been undiscussed of the stored tissue problem, and whether or not there is any degree of residual control that belongs to the people who were the sources for that tissue. Since it comes up in so many different contexts, it occurred to me that it might be worth taking a look at it as a topic on its own.

DR. CASSELL: And, Eric, I think this would be one in which sort of sketching out just exactly how would we go about this would be a very good idea. Thereís a lot of background. We would need a lot of background input from other people and papers about the issue of relationship to the bodyónot just ownership, but relationship to the body.

DR. SHAPIRO: Could I ask a question? It may have come up as your student and you did work in this area. I understand exactly the issues youíre raising regarding ownership and you had some e-mail on that subject also. In that literatureóreview and/or analyses that were doneóare there laws that consider this "gift" as opposed to "property"? That is, a gift of property as opposed to just your property you sort of hang on to?

MS. CHARO: You mean your tissue?

DR. SHAPIRO: Yes, thatís right.

MS. CHARO: It depends on the context. There are times when the tissue of your bodyóletís focus just on excised tissueóonce separated from the rest of your bodyóis sometimes considered your personal property that youíve now abandoned, which would be typical of things like excretia. Other times it is considered a gift, and thatís a classic formulation of the notion of what happens in blood, although we backed away from that when we needed to call blood-giving a service rather than delivery of a gift for product liability purposes, lest the blood banks wind up strictly liable for transmission of HIV. This is a good example, by the way, of the kind of ridiculous levels of complication we get into. Other times, itís considered neither a gift nor personal nor abandoned property. An example would be corpses, in which your continued control over disposition through indications is in your will but your kinís control leaves it with no particular statusówhich is exactly why we donít understand what to do with the burial remains. So the usual lawyerís answer, Harold, is "it depends."

DR. SHAPIRO: Okay, thank you. Eric.

DR. CASSELL: That also underscores what an interesting topic it is and how pervasive its reach is. We have next a Belmont Report revisited which, as laid out here, is really a scholarly effort to rethink the process. And I think weíre ... thatís Larry (teleconferencing in). Yes, okay, Larry, wonderful, wonderful. Iím not too sure how you make it louder so that Larry can hear. Anyway, I think we saw the Belmont Report revisited as a scholarly effort to rethink these older concepts that went into the first Commissionís report. And I think weíre committed to that, so that should go ahead. Eric Meslin and I talked about the issue of education. Bette Kramer is also very interested in the issue, and the question is, is it really a separate topic in which we have hearings and we go at what we mean by education and so forth? Or should we make it a part of every one of the other topics, such as when weíre talking about genetic discrimination and so forth, what is being done to educate people about the problem; and for Institutional Review Boards, what is being done to educate members of Institutional Review Boards? As Eric Meslin and I have left it now, we have made it a part of every other rather than a separate topic. And I think that may get our work accomplished and also save some meeting time.

Informed consent is another one. Itís really related to the topics we are discussing now. Itís certainly important enough to revisit, and it speaks for itself.

Compensation for research-related injuries is a topic that comes up again and again, and I think weíre just going to have to have some discussion about whether we want to pick that up or not.

Experimental medicine is an issue, particularly now. A great deal is done that does not come under the rubric of research and yet thereís inadequate protection of the people who participate. They see it as therapy; it may not be therapy, really; it may be somebody doing a piece of research. But I do not think that we would have to devote a lot of time to that.

And then we discussed the last couple of times the right to health care and reproductive technologies as both difficult topics and very time-consuming, so we had them listed this way because we think that at the present time they shouldnít occupy the center of our agenda, though all of you may vote that thatís exactly where the action is and thatís what we should do.

That leads us to the summary that Eric Meslin has here: ethical and legal issues in research in other countries, genetic discrimination, privacy and confidentiality, Institutional Review Boards, ownership of the body, the Belmont Report revisitedówith education specifically a part of every one of those topicsóand reports. We would prefer if you would just give us your input so we know just exactly what we are going to do.

DR. SHAPIRO: Okay. Jim, then Trish.

DR. CHILDRESS: Thanks very much, Eric and Committee, both Erics and the Committee. I think this is exceedingly helpful to have a good, clear sense of what we think to this point we are committed to and how we might revise this over time, revisiting it at each meeting. I very much agree with the topics in the order and let me just take the first three in that order. But let me say a word about Institutional Review Boards because weíve discussed this several times, agreeing that this is a central matter for us, and yet weíve also indicated that we need to have access to the reports that are under way: the report from the Office of the Inspector General and the McKay Report. Over the last few days I have talked to the parties involved in both of those, and it looks as though weíll have access to the material by March. So by March we should have the McKay material. Iíve seen a draft of some of the materials presented out of the data at the December meeting of Primer, and I think that the data will be very interesting and helpful to us. That should be available by March.

DR. MESLIN: Is that 1998?

DR. CHILDRESS: 1998, yes. Although now that youíve raised it, Iím not sure I was as clear in my conversation I should have been. Thank you.

DR. MESLIN: I learned a long time ago as a forecaster that you donít forecast an event and a date together. One or the other is your best bet.

DR. SHAPIRO: Good to know that.

DR. CHILDRESS: We have heard about that particular study several times. But the other one weíve not heard as much about recently and I was somewhat surprised, actually, to find that its scope has expanded considerably, and that now, instead of just one report there will actually be four, and theyíre available now in working draft from going to the FDA and NIH and OPRR. We should be able to get those in March as well.

Let me just mention what will be covered there. One will be the challenges in oversight for already-approved research protocols. Promising approaches emerging in the research oversight on the part of IRBs will be the second one. Third is an examination of independent IRBsóhow many there are, how theyíre functioning, and what their workload is; and then finally a wrap-up report with recommendations. I donít now have a sense of direction to each of those; this is just simply an indication of what theyíre covering. But again, we should have that material in March because the Office of the Inspector General would very much like to have him back in the loop and have this material be useful. So I think this is very encouraging for our own work on IRBs.

DR. SHAPIRO: Thank you. Patricia?

MS. BACKLAR: I donít know if everybody knows that the NIH has an RFA of a T-15 type on education, as Eric is nodding his head. But I think itís important that the Commissioners see that RFA and get some idea of the scope that would be involved. This would be educating researchers and IRBs; itís a little bit vague in the RFA, but it would be a big help to us if this was going to happen. And itís quite a large grant. I think itís between two and three hundred thousand a year for about three years, going out to various institutions throughout the country. Have I described it adequately, Eric, or do you want to add something?

DR. MESLIN: Yes. The only thing is that a T-15 refers to one of the NIH granting mechanisms, which is a training grant, and this is designed as an opportunity to develop short courses in research ethics.

MS. BACKLAR: But with some kind of method of evaluation, so it could be more than just short courses and using the electronic media as a way of getting this kind of education out to researchers and IRBs.


MR. HOLTZMAN: Regarding this subject on education, I was curious how you folks thought about this translating to the level of college courses and graduate courses. I was very impressed with the presentation in San Francisco a year and half ago by the Danish group talking about the development of tools used just for the common person, even for children, and to what extent you were thinking about that, to what extent LC monies, for example, are going into that, and is that something that we ought to be thinking about?

DR. CASSELL: Well, one of the reasons in my own view of it is that itís reasonable to put it as part of other subject is that clarifying just those points, what do we mean by it? Do we mean that the level of education about science and science-related mattersóof which ethics is oneóshould be at all levels of education in the United States, or do we mean more specifically that we want to see IRB be? That idea, what exactly do we mean by it, I think, is one of the things that ought to shake out as we go through these other subjects and talk about it as part of the other subjects. Myself, I also mean education stretching down to younger grades.

DR. SHAPIRO: It was a Danish group that discussed their material last June over a year ago.

DR. CHILDRESS: I need to be refreshed on the question of whether the Commissioners received last year, when we were beginning our work, a copy of the report on compensating for researcher injuries. Was that distributed to everyone?

DR. SHAPIRO: Yes, I think it was.

DR. CHILDRESS: Okay. Because itís not noted in the helpful write-up from the staff here on that topic, and certainly the notion that what we are doing is pushing through on a topic that has received prior study from at least three groups, including the Presidentís Commission, which laid out a very specific plan about how to go about finding out data and assessing the potential effect of having a system of compensation. Obviously an issue of having a system of compensation is that injuries may suddenly start arising that didnít exist before, something akin to the moral hazard problem. And one doesnít want to move in that direction and just create a problem that doesnít exist. But at the same time, as the staff memo notes, we really have no data on the extent of injuries. And it may be that the anecdotal sense that they are few in number is correct or it may simply be that theyíre below the radar. So it would probably be helpful in the future, if we are going to explore this topic, to have some way of refreshing ourselves on what that earlier reportówhich in turn summarized the two prior reportsósaid on the subject.

DR. SHAPIRO: Thank you. Other comments? Let me make a general comment. As I look ahead over the next year and a half or so, we really should think about this in the context of what we can get done in that time period as opposed to just listing topics, every one of which is very interesting and topical. Itís my own sense that it is a good time regarding new topics, topics weíre not yet engaged in. It is a good time to take up this issue described here as an ethical and legal issue: research done abroad supported by the U.S. Itís extremely topical, all of you have been reading about it, itís a very interesting issue on which, in my own view at least, adequate analysis is yet to be fully formed, so I think we could have a contribution to make to this analysis. And it seems to me that itís a well-defined problem. We donít know all the answers yet, obviously, but itís a well-defined problem. And somethingóin the timeframe that we have and with the resources we haveówe could incorporate into our overall ethics. But the staff did leave it listed here asóI donít know if itís superiority order or not, Ericóon the last summary and next steps. But I really would be interested specifically in whether other Commissioners agree that this is a topic that is useful for us. Itís a new topic, weíd have to mobilize ourselves, staff would of course have to create an agenda for us, and so on. We donít have that worked out. Jim?

DR. CHILDRESS: Iíd very much agree with the view that this should take first priority. In my comments I just concentrated on Institutional Review Boards in order to lay out the backgroundóthe foundationófor approaching that area. I think that this is a topic that is continuing to receive a lot of attention, obviously, growing out of the controversy about the AIDS trials, but also in regard to Dr. Satcherís nomination. And I think it would beóI guess I want to say it a little differentlyónot only do I think itís important and something that we could do and do very well in a reasonably short period of time, but I think in some ways it would be a failure of moral responsibility for us not to do it. That is to say, with this topic being discussed in this society as it is, for us not to attend to it as quickly as we can in a very responsible way would be a failure on our part.

DR. SHAPIRO: How do others feel? Does that seem like people agree? Because if soóand I sense agreement around the tableówe would ask the staff by our next meeting to have a proposed action plan for us including resources that we would have to access in order to reach our conclusions. All right, letís...Alta, did you want to add something to that?

MS. CHARO: No, never mind.

DR. MESLIN: In the spirit of collaboration and recognizing that we start our bimonthly meetings after the March meeting, meaning weíre going to be convening again within 30 days, staff would be grateful if you have suggestions of individuals who might be appropriate to come before the Commission and offer their input. I think everyone can come up with a very helpful listósome of you in the room would be helpful testifyingónot only of those who can appear before us but who might be appropriate for preparing commissioned papers. So please use the regular e-mail/telephone method for getting those suggestions to us. We will collect them, work with you, and come back with an action plan in March.

MR. CAPRON: If weíre thinking of getting started on that in March, or the possibility that we might even want to do it then, I think weíd be remiss if we didnít turn right away to Drs. Angel and Varmus to hear from them in person. We saw some of the correspondence and the commentary that came out of that. And right there in Washington, Larry Gosten at Georgetown served as a consultant when he was with the American Society of Law, Medicine, and Ethics to the Council of International Organizations of Medical Sciences for their work. And if we can go to your home countryóto a transplanted BritisheróBernard Dickens took the lead. Heís at University of Toronto Law School. All of these are people who could gear up extremely quickly and prepare consultantsí reports and also would be able to provide a verbal overview of what that report might deal with. And I do feel the pressure of time. And if the March agenda isnít firmly set, you may find that theyíre even available on that kind of notice, not waiting until May.

DR. SHAPIRO: Those are excellent suggestions. I also thought that it was a thoughtful article in Science that bloomed it, which I found to be very carefully thought out. He had his core structure in his head about how to work his way through this problem, which was helpful, and thatís another possibility. You donít have to ... canít accommodate everybody all at once. But if there are other suggestions, please let Eric know.

MS. CHARO: Rachel, perhaps, may be right person to ask this question of. To what extent does the State Department have an interest in this issue, since they do have a section that deals with international science cooperation. Do they have anybody there who actually focuses at all on this, or are we free to influence?

MS. LEVINSON: Iím not sure what to make of your last comment, whether or not youíre free of State Department influence.

DR. SHAPIRO: I declare myself independent of those things.

MS. LEVINSON: But itís primarily an HHS issue because theyíre the funding agency. So that would be the lead and then there are other aspects having to do with the State Department or ID, but I think you can focus first of all on HHS.

DR. CASSELL: Although there are aspects of this that have to do with anthropology and sociology and the issues of cultural imperialism and so forth that came up, particularly after the second World War and which has sort of died down now, the same arguments apply here and it would be interesting if we could find whoís still interested in that and who might talk to us. I think we could dig back in an older literature and get people for that.

DR. SHAPIRO: Okay, well Iíll take that as something that weíll turn our attention to right away. As with Alex, I feel some pressure of time on this one myself, and I think itís a timely issue so we should really get started.

MR. CAPRON: Could I ask for clarification on one point, Mr. Chairman? I donít understand quite where we stand in responding to this staff memo. The staff has recommended the five reports that are set forth under B as the priority. My own sense of priority would include a slightly different ranking. Are we going to collectively come to a consensus on this at this or some other meeting?

DR. SHAPIRO: I think the answer to that is yes. Itís not the whole list, at least with those we think we want to address quickly. That was our purpose of my bringing up this latter topic. And so if you or anyone else has ideas about how you would rank these and/or insert other ones, nowís a perfectly appropriate time for that.

MR. CAPRON: Iím also not quite clear in my head what the eventualónot only direct staffing strength but ability to have for three or six months on staffófour part-time consultants, so I donít really know what person-power is going to be available for this. Thereís the additional question of whether we would begin any studies that we do not anticipate could be finished by October of 1999. What is the possibility that either we or some other group would be able to continue the work? In other words, do we aim for having everything done by the Summer of 1999 and voted on it finally in October? Or do we say this is going to be rolling process, with reports in various conditions, and if weíre demonstrating our value we might expect that the Commission will be authorized beyond 1999? The President certainly anticipated last June a five-year lifetime for the Commission so that it would be available to respond to the Sunset Provisions in the cloning statute.

DR. SHAPIRO: My view of that is that we should take the latter strategyóthat this is a rolling effort. We donít need to aim for the completion of everything by some magic date in 1999 or any other date. And if weíre as lively as we ought to be, no matter what date we pick, weíre going to have unfinished business in front of us. So on the one hand, I think of it as a rolling process and weíll generate reports as we can. On the other hand, I do want to make sure that we have sufficient concentration to staff these orders and to get a certain number of reports out between now and thenóperhaps four or so that we might want to complete by then, given the work that we already have under way plus that that weíll take on. So it is a kind of rolling process with the presumption, however, that weíre going to focus enough to get some of these reports done and out in that period. Obviously, the ones that weíre discussing at tomorrowís meeting will be done. I hope we can take on this one. I think that could get done by that time, and the Institutional Review Boards strike me as an important issue that we can still discuss. That will be another option. But there are others that wonít get done and other efforts that wonít get done. Bette?

MS. KRAMER: Harold, do we...are we obliged to give a high priority to those issues that were specifically mentioned in the samples?

DR. SHAPIRO: Well I think we are, although thereís one of those issues that is so broad that we couldnít possibly sort of respond to it in any kind of complete way. The genetic information item in there is so broad and includes so many things that I wouldnít have any sense of completion just by doing some aspect of it. But I think we are obliged to take on important aspects of those.

MS. LEVINSON: I thought you were going to mention the first one, not genetic information, but the protection of human subjects. Because several of these reports relate to that. Itís an ongoing issue. But you might also want to think about these as not individual, self-contained studies. Think about ways to tie them together to address the adequacy of human subject protections.

DR. SHAPIRO: I think thatís a good point. I think one of the issues in front of usóand weíll probably have to pick up some of this discussion later because we have a guest and I donít want to keep her waiting longer than necessaryóis how we do package the various ongoing efforts, let alone those that weíll take up, in ways that are really effective. So weíre going to be discussing the OPRR issue later. In what kind of framework should that be packaged with other kinds of things that are very closely related to that? So thatís an issue we still have to address. I donít know, Eric, how you feel about that.

DR. MESLIN: I think it is entirely appropriate given that there is some ongoing research that the Commission is deliberating about: both the federal agency survey that is soon to be completed, and the IRB study that is being considered here based on what Jim Childress is discussing. Weíve been talking about the federal oversight of human subjects in this country, and it seems that there are a couple of very neat and logical ways of packaging those so that we can both fulfill the mandate of the Commission in being able to respond to the requests for commenting on the adequacy of the system, and also address what are some very pressing matters. One can easily see two or three of these things being linked in one report. The only other point to raise is that we specifically wrote the suggestion about genetics in an ambiguous way, and that was purposeful for at least one important reason. And that there has been an awful lot of work under way, both at NIH and HHS, on various aspects of genetics subjects. In your briefing books, you have seen materials released by the Vice President at the James Watson lecture he gave at the NAS a few weeks ago. And Iím aware, as Iím sure David Cox is, that the National Human-Genome Research Institute has a longstanding interest in many of these subjects. Bill Robb has indicated to us, although heís not here today, that in his capacity at chairing an interagency committee, which was constructed following the report of the Task Force on Genetic Testing, that there is a considerable amount of interest within HHS about many of these matters. So the suggestion that staff is raising is whether we ought not to consult very carefully with those who are already well ahead and to elicit from them what NBACís contribution to this discussion might be.

DR. CASSELL: On the genetic issue?

DR. MESLIN: On the genetic issue.

DR. SHAPIRO: Other comments right now? If not, we can return to this subject as time allows. Iíd like to turn to our guest, Eric.

DR. CASSELL: I myself would move the Institutional Review Board up under as the second topic, and that also will allow us to sort of shake out a little bit what we mean by the genetic issue.

DR. COX: Harold, I really second that. I think that for all the things that we talk about in essentially almost all of our reports, we schlep everything off onto Institutional Review Boards. In fact I think thatís not just our group but that has been the tendency for recommendations with respect to ethical issues. I, for one, think itís going to make it very difficult for people who are members of the Institutional Review Boards unless we revamp that soon, or at least consider it.

DR. SHAPIRO: Letís not end the discussion here, but weíll leave it for a moment. There are three issues on this list that Iíd like to spend some time with the staff working on before our next meeting, which is only weeks from now. One is the ethical/legal issues regarding research abroad; the Institutional Review Board that Dave and others and just talked about, and Eric; and the Belmont Report revisited, which is a different kind of thing. Itís not the same kind of activity. Weíll probably go about that in a different way. But I want to give some careful thought to how we might sponsor something that might really be a contribution to the world of scholarship in that particular area. Itís a good time to do it, and as someone mentioned we have the 20th anniversary coming up shortly. I donít know when, exactly.

DR. MESLIN: April 1999.

DR. COX: Harold, can I just make one point about that? I am also extremely keen on that Belmont Report revisited as I said at the last meeting, and I think that some of the words that the staff used in this really capture my own feeling quite wellóto think of it now in the context of access rather than just the context of protection.


MR. HOLTZMAN: And thatís exactly the context that Iím particularly interested in.

DR. CASSELL: Thatís an issue that just came up at our very first meeting. And I think maybe Eric raised it and that is obviously a very important issue very much on peopleís minds. Steve?

MR. HOLTZMAN: Again, this is about education and maybe reaching out to the public ... national policy is being decided today, or whenever, but not on the basis of scholarly position.

DR. SHAPIRO: There have been some times when ideas moved the world. This might be just one of them.

MR. HOLTZMAN: ... ideas to move the world is because the world has access to those ideas.

DR. SHAPIRO: Oh thatís not arguable. The issue of...I mean itís an important issue you raise, I donít know what we can or should do in that respect but weíll certainly give that some thought, whether I think in my own mind that it is an appropriate time and appropriate for us to sponsor something that is quite scholarly in this area. We donít need to put that aside as one for the other. And we ought to think through how we can mobilize ourselves. Itís the least of something that might have the effect of the topic. Well I am going to insist that we end; Alta, youíll have to hold your comments until later. I apologize for having to end, but I do want to turn to our guest, whom I didnít quite introduce, just mentioned before: Elyn Saks, whoís over here on my left, from the University of Southern California is here to talk to us on capacity assessment instruments. Welcome, and thank you for coming.

PROFESSOR SAKS: Oh, thank you very much. Iím very pleased that the Commission has invited me to talk about a topic thatís interested me for a long time. The one bit of it that Iím going to talk about todayónamely, assessing the sort of premier treatment competency from an available lotóis very much a work in progress.

The issue Iím going to discuss today, assessing the MacArthur Treatment Competency instruments, is very much a work in progress. I need to do more reading, more rereading, and more thinking but I wanted to tell you what Iím thinking about today. Itís a common place and itís block-letter law as well that decisions to undergo treatment or participate in research must be voluntary and formed in competence. And then the question becomes what do those terms mean. Iím going to talk about competency and the premier instruments devised to answer that question are MacArthurís Treatment Competency instruments, designed in particular by Drs. Tom Grisso and Paul Applebaum. Theyíre the foremost researchers. Their instruments measure four things. Their Understanding Treatment Disclosure (UTD) instrument measures whether the patient can understand general information about his treatmentóhis illness in the treatment. The Perception of Disorders (POD) instrument measures whether he appreciates what illness he has and treatment prognosis with and without treatment; in other words, as applied to general information about his particular situation. The Thinking Rationally about Treatment (TRAT) measure measures fundamental reasoning ability. And a submeasure of the TRAT measures whether a patient can evidence a choice. These instruments, the researchers say, measure capacity as opposed to legal competencyóin other words, capacities that are relevant to what we might define as legal competency. They also propose something called the MacCAT-T, which is a streamlined version of the research instruments that requires some clinical judgment and allows for a competency finding.

What Iím going to do today in my talk is talk about the normative dimensions that we need to think about when weíre talking about designing a competency instrument, and how MacArthur does on that count. Iím going to assess the different measures and talk about importing these treatment competency instruments to the research context, and then conclude.

The normative issues. As is usual in the case of bioethics, the key conflict is between autonomy and paternalism, and many people think we draw the line between autonomy and paternalism interests by saying that we allow competent, and only competent, people to decide. But that just pushes back the question because how we define competency is going to really itself draw the line. Obviously requiring much in the way of ability is going to favor paternalistic interests and vice versa. Itís also not widely appreciated, I think, and not by the MacArthur research designers, that the autonomy/paternalism question replicates itself when we ask how to define competency. And that freedom includes not only freedom to decide what to choose to doówhether to be treated or participate in researchóbut also within broad limits how to decide. So more specificity is saving the values at stake: we want to protect the vulnerable. And that translates into requiring needed abilities to make a decision, at least at a high level of generality. Second, we want to protect peopleís rights to be unconventional, and that translates allowing people some scope in the methods that they use to decide, and to decide on what to believe. And third, we want to take into account the widespread mild irrationality that psychiatrists, psychologists, and psychoanalysts have long discussed. This is important because we either must declare many more incompetent or we must not declare incompetent the floridly ill who are exhibiting these same mild deficiencies.

In practical terms, what does this all mean? It means weíve got to justify the ability to the chosen, we have to justify the skill level of the tasks prescribed and measured. For instance, on the UTD, whatís the reading level when information is disclosed? And then we must justify the level of performance required on each task. And all of those balances, all of those line-drawn problems are going to require balancing autonomy versus paternalism.

I think the MacArthur researchers fall down a little bit on the normative dimensions, and they acknowledge that. In fact, they say they are not answering the normative questions at all. In fact, they smuggle some normative judgments in. For instance, even by selecting instruments that they select and abilities that they measure, theyíre making the normative judgment that those abilities that measure up to and down from certain levels are important for treatment competency. You could also devise an instrument that measures facility at learning foreign languages, but nobody would propose that as an instrument that was relevant to treatment competency. So they are making normative judgments and theyíre not really justifying them.

And then there are other judgments that they explicitly leave open and need to be justified, such as where to draw the line. They suggest where impairment is on their capacity instruments but not what level of impairment should translate into incompetency. Any adequate competency standard must struggle with these issues, and the MacArthur instruments are at least an incomplete effort to respond to the need for instruments.

Now Iím going to look at the instruments themselvesófirst of all, to evaluate the classificatory scheme itself. I think the big problem is that four measures are incomplete. They incompletely cover the field in the sense that the Understanding Treatment Disclosure information I read as requiring comprehension but not necessarily belief of some general information, whereas the Perception of Disorders instrument requires belief of that information as applied to one specific situation.

What this means is that youíre not testing for forming adequate beliefs about the general information or understanding the specific information. The general specific distinction is beside the point; I think itís sort of a red herring. What you should really distinguish between is understanding and the sense of comprehension: you understand my view that itís 2:30 versus understanding of the sense of belief you understand that itís 2:30. So thatís kind of an incompleteness in their classificatory scheme.

Are the abilities that they describe necessary for treatment competency? I think they all are and maybe more are. To go through this quickly, comprehension seems important because you have to comprehend in order to assess evidence and form beliefs. Forming beliefs is important because decisions are made on the basis of desires and beliefs, so you must adequately capture the world and how youíre interests are going to be affected. Reasoning is important. You need to be able to put the information together. If you canít put it togetheróif someone is reasoning, "If I want to do P I must do Q, I want to do P therefore Iíll not Q," we would say that the personís decision to not Q is probably not competent. Evidencing a choice, you know that there we have a decision, whether itís a threshold issue that triggers a competency issue or is necessary for competency itself. It may not be necessary for competency itself. Someone who canít communicate may very well go through the reasoning processes that we would require for him or her to make a competent decision. But itís probably not important to decide that because you have to have someone evidencing a choice to decide whether to honor the choice.

Now letís look at the specific abilitiesóand maybe more abilities are required, by the way, than these four. Decisions, I said, are made on the basis of beliefs and desires. Maybe you need to be in touch with your true desires. Maybe you really have to be yourself so youíre making authentic choices. Maybe you need to not be subject to volitional impairment. There are other things that we need to require. I think there are probably problems with these ideas but they at least need to be thought about.

The specific instruments. The Understanding Treatment Disclosures instrument, or the UTD, appears to suffer from minor problems that could be easily corrected. First, it does not give the patient credit for reciting information about his illness and about the treatment, even if it may be correct, if it hasnít been given to him in the disclosure. One theory is that we want patients to understand what theyíve been told. Another theory is maybe they have better information about themselves than what theyíve been told, and they do understand that information. And maybe all we really require is information at a high level of generality; for example, that mental illness is an illness that affects mental symptoms and there are treatments for them and there are not horrendous risks, but there are some risks, rather than what the particular risks are. At the very least, the UTD, I think, does need to warn people being evaluated that when they give information thatís extra-disclosure information, theyíre only really being asked to tell what theyíve just been told. We donít want to mark people down for that.

Second, the UTD may measure things that arenít necessary to understanding. It measures being able to attend and process, which clearly are but also being able to retain for quite a bit of time, so that may be a problem. Conversely, it may measure only retention and not understanding. Presumably, a very clever parrot could repeat back information that it was given, or somebody who has a perfect auditory memory but has no comprehension of a language could repeat back information and not really understand it. So these are problems with the UTD but I think with some work the instrument could be quite a good instrument and it does measure something very important.

Letís go on to the Thinking Rationally about Treatment measure, the TRAT. This measure, I think, may require evidence of abilities that arenít at all necessary in a given case. It measures things like transitive reasoning ability and weighing consequences and measuring, comparing alternatives. But imagine a situation where a patient so disfavored one risk of a particular treatment that that was enough for him to decide that he wanted the other one. And he trusted that the doctor wasnít going to give him something that was really horrendously dangerous. That person may not need to evidence all those reasoning abilities.

Second, it may underestimate the existence of these reasoning operations by the way they are tested. Basically they give a vignette and then ask the patient how he decided. He may have met or done a lot of the measures, but just not say that he did them. So maybe he should be asked, "Did you think of other consequences?" although maybe thatís too leading and sort of leaves to psychometricians the task of revising the instrument in light of this concern.

Third, thereís a submeasure on the TRAT that measures expressing a choice, and I think it doesnít make sense to mark patients down if they only evidence a firm choice on a second inquiry. Canít people take a little bit of time to make up their minds? So I think thatís a problematic measure that could be revised easily as well. The Perceptions of Disorder instrument includes two subparts: the nonacknowledgment of disorder (NOD) subpart and the nonacknowledgment of treatment potential subpart. I think the POD is a deeply flawed instrument and needs to be really rethought. The POD measures patientsí beliefs about their condition and its treatment. But requiring certain beliefs is a tricky business because many beliefs are controversial and theyíre not obviously false. Requiring such beliefs, then, is not obviously necessary to competency; that is, it doesnít serve our "protecting the vulnerable" concerns. Indeed, the patient with such a belief, as against the majority view, who turns out to be right is in a sense super-competent. Also given that many beliefs are controversial, itís part of patientsí freedom within broad limits to decide whatís true no less than whatís good. Thatís our autonomy concern. And finally, many people suffer from mild distortions and that raises our concern about discriminating against the mentally ill.

In my view, itís a very hard question where you draw the line, but I think the POD draws it at the wrong place. The first subtest on the NOD requires a patient to believe the diagnosis his doctor gives him, making the doctor the final authority on truth. Why ever do we then get second opinions? His doctor, of course, may be wrong. What if the patient believes a former doctorís diagnosis? What if he admits heís ill but disagrees with the particular diagnosis?

The second test on the NOD requires patients to rate the severity of their illness as given on the brief psychiatric rating scale. But if the question is how severely ill patients feel, they may know that better than anyone else. And if the issue is their location on a common metric of severity, how are we to expect patients to know that common metric? Theyíre not in a position to make comparative judgments about their own illness compared to other patientsí illness. The NOD also requires patients to admit symptoms they have been displaying. To the extent that these are grossly demonstrable symptoms and donít require a good deal of interpretation, and to the extent that they donít just duplicate the illness question, I think this subtest makes sense. Itís a patent distortion of reality to deny that youíre evidencing grossly demonstrable symptoms like frenetically pacing or not sleeping. The NOD requires patients essentially to agree with their doctors about their prognosis with and without treatment in general and medication in particular. Once again, the general data may be fairly indisputable; for instance, the odds of doing a certain way with or without treatment. But itís perfectly plausible for patients, for instance, to expect to be in the bottom ten percent, say, that doesnít respond to the treatment. That may be pessimistic, but a lot of people are pessimistic and a lot of people are unduly optimistic, too. So I donít think thatís a gross distortion of reality. It will be clear that thereís a range in the kinds of beliefs you can require when youíre trying to judge competency. At one far end is the POD, which basically requires patients to believe whatever their doctors believe about them. At the other far end is a standard that would say that you had only not believed things that are impossible. I think that goes a little bit too far: you can believe things that are completely implausible given the evidence, but not impossible and maybe you should be incompetent then.

In the middle thereís a range of standards. You could require patients to believe what most doctors would believe about them, or what most people would believe. Or, since these are kind of majoritarian referrings-on, you could talk about skills themselves involved, like you canít believe beliefs that are based on no evidence or that are patently false or that are delusional. Anyway, these are some of the possibilities, but I think the POD makes the wrong choice.

I like a kind of patently false belief standard because I think it adequately protects autonomy concerns and meets other values at issue. And I think on such a standardóand this is controversialódenial of mental illness would rarely count as a sufficient distortion of reality to imagine your own competency. I hasten to add that I have no doubts whatsoever about the reality of mental illness and the severe suffering it causes. Thatís not the issue at all. I still think denial generally should not make one incompetent.

First, patients may simply be unwilling to admit something thatís very stigmatizing. They may be frankly dissimulating. Second, even if theyíre in denial, denial is common; itís fairly understandable, and itís often an adaptive defense. Third, there are no incontrovertible physical means of establishing a mental illness diagnosis except for some organic disorders. Itís as if we were living in the time of no EEGs when you couldnít really tell if someone suffered from epilepsy or hysterical seizures. Someone who looks as if they suffer from a psychotic disorder may really suffer from a factitious disorder or whatever. By the way, this is true of many physical illnesses too. Fourth, thereís widespread skepticism and misunderstanding about mental illness in society. Much of this is a failure to understandóitís unenlightenedóbut to the extent that itís common we run into problems again around discriminating against the mentally ill.

Fifth, patients, since in my view must believe they are suffering from obvious symptoms, arguably have enough reason to take medication that theyíre told is likely to ameliorate their symptoms, as if they admitted that they were ill. Perhaps we should require them to admit that they have a condition that looks like, say, X or Y mental illness and that with this condition they are believed by doctors to be as antecedentally likely to benefit from treatment as people who really have it and so forth. But to actually make them say they have the mental illness, Iím not sure thatís necessary. And it may be a difficult thing for them to do. So I think the POD should be revised.

At the very least, it should set a number of different levels of beliefs that should be required, and then let individual evaluators make their own normative judgments. Alternatively, if itís agreed that the line that they draw is the wrong line, then maybe some kind of intermediate standard should be adopted.

The MacCAT-T is the treatment instrument. It suffers from many similar problems as the other instruments. It allows clinical judgment to play a role; itís a more streamlined version; itís more tailored to the individual patient. But without going into details, Iím going to suggest that it suffers from a lot of the same problems as the other instruments.

Now Iíd like to talk about importing the instruments to the research context. In this context you may require that patients demonstrate additional abilities than the ones we discussed; in particular, the ability to withstand pressure to accede to their doctorís request. Transference is very powerful in all doctor/patient relationships, but in the ordinary doctor/patient relationship there is a coincidence of interest in what the doctor is recommending and what the patientís acceding to so we need to be less concerned, arguably. Second, you need to revise the instruments to accommodate the research situation. For instance, in the UTD, one needs to include the most important informationósuch as that the treatment is experimental or that it is a nontherapeutic experimental measure, and that the doctor has an interest in doing the research as wellóand make sure that patients understand that. Third, there are additional normative inquiries that are raised by this context.

First of all, there is a value of increasing scientific understanding that needs to be factored in when we decide how we measure competency. Second, the old question of whether we should have a variable competency standard reappears here. Itís arguable that since patients making decisions in the research context arenít making such obviously good choices as when they accede to their treaterís treatment choices, we should require a higher level of ability. There are arguments pro and con there and I think a kind of compromised solution makes sense, although I donít think thereís time to go into that.

So to conclude, there are questions around what the NBAC should recommend to IRBs, and I think thatís a really difficult issue because the best instrument around has quite a few flaws and it doesnít make a lot of the normative judgments that you need to make in order to use the instruments. I think thereís a real danger that people are simply going to say, "This is the level that they marked for impairments so thatís the level Iím going to use," without thinking about it. On the other hand, itís the best instrument we have around. Maybe clinical evaluation should be possible. I think that in the research context, particularly with vulnerable subjects, you should assess for competency if thereís any reason to think that itís not there. But how you should assess is a difficult question. An easy recommendation is that more research should be done. We need more research on how maybe some of the criticisms I and others have made of these instruments could be accommodated by revising the instruments. We need research into what level of belief should be required, and finally, we need much more research into the normative questions. Thank you.

DR. SHAPIRO: Thank you very much. You managed to give us a lot of information, and a lot to think about in a very short period of time.

PROFESSOR SAKS: I know, I talk fast.

DR. SHAPIRO: I appreciate it, and I thank you very much. It was helpful to me, and thank you very much for distributing the outline to help me get along as you were talking, so thank you very much. Let me turn to questions. Jim and Eric?

DR. CHILDRESS: Thank you very much. This was very helpful. A couple of things for clarification. Did I understand you to say you believe these are the best instruments available?

PROFESSOR SAKS: So far as I know, yes.

DR. CHILDRESS: And in your overall discussion, are you putting them in a larger context, that is, are you also looking at some of the invalued questions that are lurking behind the alternatives as youíre thinking about this in your larger context?

PROFESSOR SAKS: You mean in terms of looking at other ....

DR. CHILDRESS: Not necessarily in the same detail because youíve already ... one reason you focus on these is that you think they are the best, but are you doing a bit of ....

PROFESSOR SAKS: I had not really looked in detail at any of the other instruments. If indeed there really are some that have been studied and tested, so far as I know, there may be individual evaluators who have their own kind of instrument. But this is sort of...this is where the actionís at right now.



DR. CASSELL: One of the issues we have to face is that there isnít really a good instrument, but this is the only instrument that we recommend to IRBs, for example. But itís not really good. Itís the only boat we have. It happens to have a big hole in the bottom, but would you please just row faster? And I have a prejudice against that kind of a recommendation. I think weíre able to say that this is an issue that should be a high priority research issue; not just more research is necessary. Some research is necessary because I have sick people who can meet every one of these criteria but cannot decenter. And because they cannot decenter, they cannot make a consent....

DR. SHAPIRO: Excuse me, I didnít understand what you ...

DR. CASSELL: "Decenter" means to take the position of another. They can only see things from their own position. You can actually show that with a childís A-B-C-D block. You show them all four faces, all rotated around like that; then you go back to the A and you say "Whatís on the other side?" and they canít do it. And it isnít because they donít remember it, itís because they cannot take the position of somebody on the other side of the block. There are just issues about all of this that are very important because it may turn out, and in fact I think it does, that people cannot demonstrate capacity like this alone. These all presume an isolated, using your word, autonomous person out there making a decision and whether you judge it to be a capacitative decision or not. And that may be the basic problem. So I would like us not to come out for an inadequate instrument at all.

DR. SHAPIRO: Thank you. Alex, then Alta.

MR. CAPRON: Iím trying to think about what Professor Saks said in light of where we were in this process, and I want to know whether my sense is correct. We can obviously call, and probably will end up like every good Commission calling for more research on any number of different topics. But in the present context, we are stepping into a stream that has been flowing for many years and into which the National Commission for the Protection of Human Subjects placed a rock. And unlike the other rocks that it placed there, it did not become a stepping stone toward the adoption by HHS and eventually the whole federal government of standards for research in a particular area. Now their stepping stone was a little bit different. It was the mentally institutionalized, but itís many of the same issues. And one of the things we talked about last time, and we had to deal with in the report, is whether there are separate categories among those who have some incapacity, or who have...where thereís lack of clarity about the mental capacity if they are institutionalized. The question that we will have to address is whether when we put forward a report, our expectation is that out of that report, the federal regulators could draw a set of recommendations that would say, "In addition to the usual standards that apply for research on anyone else, here are special steps that have to be taken." And part of my expectation has been that where the treatment involves treatment for mental illness, one of those steps would be the assessment of the capacity for the person to make decisions for him or herself. I think Eric is quite right and heís reminded of this in other contexts, that it isnít only the mentally ill but it is anyone facing an illness for whom a research intervention is being offered as a possible means of addressing that illness in some fashionóconnected in some fashion to that illness, either with a so-called therapeutic intent or even without that, but in that context. We have to be worried about the ability of the person to do what the model bioethics said they should be doing, of making a judgment of whether this makes sense for them now.

Obviously, if we are going to give guidance to IRBs outside the scope of the regulations, part of that guidance could be what they should expect investigators to do. And I think Professor Saksí eventual paper for us could very useful as a document for IRBs to read in the interim between the timeóif there is any time, if it doesnít take forever for there to be regulations on the subjectóthe time that the regulations come into effect and the time that all the additional research which we would love to see being done on instruments like this, is completed enough to have revisions in the instruments. And I think weíre going to be faced, therefore, with a couple of choices. One choice would be whether we, after having the full paper and deliberating about it, want to say, "Actually, the instrument should only be used if," and then address qualifications that we would expect IRBs to insist upon. Or, whether we are going to say simply that the instruments should be used with the following thoughts in mind, but be very unspecific about that. In light of that, I would likeóand this is not a staged question, this is not like one of those questions on the floor of the HouseóElyn and I have not had a chance to talk about this questionóI would like to have your further reflection on a couple of the points that you raised. And I, actually I guess theyíre really one point, itís just something that you brought out about the point. The basic question, it seems to me, is whether this instrument, which was developed for use mostly in treatment settings ought to lead one to say whatever gradationsóand Iím like everybody else, not entirely clear about what kind of scoring this yields, and Trish Backlar has described the instrument to us before and we talked a little bit about it, but we probably need to know more before we say much more. But, whether, as you were suggesting at the end, one would expect it were a higher score, I guess, on this because the assumption that whateverís being done is being done for the benefit of the patient, cannot be made in the context that weíre most concerned about, which is nontherapeutic research that may involve more than minimal risk. Thatís the area that concerns us the most. And if so, how in particular a couple of the points that you raised play into this. You talked about the authenticity point, and you made a passing reference to questions about volition. And the authenticity point is obviously of great importance because when weíre dealing, as we are, at least with the original impetus for this, our subjects who at the present moment may or may not truly reflect their true selvesóand thatís in a way the underlying questionóare they able to do that now? And so it seems to me that if you think these instruments donít adequately attend to authenticity, then they are missing a dimension that seems centrally important here. And I donít quite know how to evaluate that because if a person has a mental illness which is not by any surgical or organic means fully curable, in a way that authentic person has a set of values that involves being a person with that illness. And this is something that other people in the disability community have reminded us very strongly of; that it would be wrong for us to look at this and say we understand the standards that ought to be used as if you didnít have paraplegia or something. I mean you doóthat is the authentic; you have to decide in terms of that. But I also think that the volition question is very much at the heart of what weíve been concerned about. So Iím bothered also by the sense that the measurement doesnít get into volition. So this is a very long-winded wind-up to the question: Could you tell us anything more about that now, and to the extent that you canít fully now, would you think that your eventual paper will delve into those particular points? Because I think that would be particularly helpful to us in addressing what are central issues. Thank you.

PROFESSOR SAKS: Well, Alex, I think you raised a lot of interesting questions. Unfortunately my paperís only supposed to be about 20 or 30 pages; Iím up to page 45 now so I donít know how much Iím going to be able to get into those things. But you raised a number of points. One, should you require a higher level in the research context in which you donít have the added protection of the doctor acting solely for the patientís benefit, and I think thatís arguable. Maybe not...maybe itís a sort of risk variable, not because you think you should vary the level of competency if a patientís making a possibly bad choice but because thereís a chance that the evaluator, sinceóIím not saying evaluators are malicious or anything, but they have unconscious reasons for wanting something to happenóevaluators may be likelier to find competency when itís not there. There may be those additional reasons that have a variable competency standard in this context.

As to the authenticity question, I think itís a fascinating question, and I think sort of noncognitive, both authenticity and volition are important things to think about in terms of competency. The authenticity question is really, really hard, right to the very reasons you bring up. You know you give the person the medication and afterwards sheís back to herself and says thank you. You know, you could reverse the experiment. You have a doctor who doesnít believe in medication, takes a manic patient off his medication and heís kind of reluctant to get off of it, then he gets off of it and he feels great and he thanks the doctor. So it canít be just the later self, and do we preferówe want to say we preferóhealthier selves, well I kind of do too. But maybe thatís just importing the value judgment. These instruments do not speak to authenticity or volition. And the volition problem is important too. I mean I think those are really difficult questions. I donít know that I could get to them in this paper; maybe in another paper. I donít know if other people have thoughts about them.

MR. CAPRON: Well I guess then what you would end up doing is flagging the fact.

PROFESSOR SAKS: I would flag them, yes.

MR. CAPRON: The instrument doesnít and then we would be faced with whether we have any means of suggesting. I mean we arenít engaged in an academic exercise here. In the end, we have got to take input from all the different sources weíre getting input and say either because of the total inadequacies of instruments and measurements and the history of abuses and so forth, the regulations should say, "Donít do research of this sort with these people." Or we should say that the research may go forward ...the regulations ought to embody the following additional protections. And it comes down to something fairly practical, but it has to be clear enough that an IRB that doesnít sit around and get to hear Elyn Saks give her paper, and may not even all of them ever go to our appendix and read the paper, can do a decent job just looking at the regulation, knowing whether or not theyíve added the suitable protections. And it would be lovely if you had come in here and said the MacCarthy instrument is so perfect and you just use it and just insist everybody use it. But youíre not saying that, so youíve complicated our lives.

DR. SHAPIRO: Weíll hold you responsible for that altered interest.

MS. CHARO: Thank you. I heard you making some criticisms that focused on seemingly extraneous information being collected by the instrument. And then in other points it appeared that there was an absence of information gathering that might be pertinent, this past discussion being one example. And it struck me, unless I missed it, that thereís also an absence of any measurement of emotionally-appropriate reactions to information, so that thereís some measure that people are appalled by things that they should be appalled by, and attracted to things they should be attracted to. It would be very helpful to understand from you exactly what the list is of gaps, because extraneous information seems to me to be less problematic than gaps.

PROFESSOR SAKS: Why is that?

MS. CHARO: Because if we unduly screen people out but not to the point that there are no human subjects available, weíve not hindered the research endeavor and a few people that might have been eligible just donít become research subjects, big deal. But if there are people who shouldnít be enrolled that do get enrolled, that is more of a matter of concern. And since we are potentially in a situation in which we say that anybody whose ability to make decisions is in question, and certain mental illnesses will be presumptive evidence that their decisionmaking ability is in question, weíre at the point of saying for people where thereís this question raised, it may be necessary to administer an instrument. Iíd like to understand from your presentation exactly how far away we are from being able to say that such an instrument exists. So what would be the list of gaps that need to be filled so that we know exactly how realistic it is to build this kind of requirement into a regulatory framework?

PROFESSOR SAKS: Well, I think what youíd need to do is ... if youíre not worried about the false positives, people being found incompetent who arenít incompetent...

MS. CHARO: Itís not great and it has a stigmatizing possibility that is of concern but itís of a different order of concern than inappropriate enrollment.

PROFESSOR SAKS: Right. What are the gaps, what needs to be done? Well, the central gap is addressing the normative question. As one example, in my third sort of normative issue I said that a lot of people are mildly irrational, and Dr. Cassell was saying that a lot of his patients, even if theyíre not psychiatric patients, canít decenter, arenít in a good position to decide. And people may be subject to transference or misweighing, misunderstanding probabilities, or whatever, overvaluing the vivid memory. One normative question that I havenít really stressed is do you want a standard that finds many, many more people, incompetent? Mildly irrationally people too, and that again depends on how you balance autonomy versus paternalism. So the value questions are important questions because I think you canít recommend that the MacArthur instruments be used without somebody, whether it be you or the individual researchers or the IRBs or the MacArthur researchers, deciding where the line should be drawn. The things that the instruments leave out are the kinds of things Alex talked about, capacities that arenít included, all the noncognitive capacities like knowing your true needs and values, being true to yourself, not being subject to irresistible impulses or other volitional impairments. Maybe not being overwhelmed by really profound emotions that disable you from choosingómaybe those would interfere with other abilities like ability to understand or ability to exercise your true preference. But all of those things are not measured at all by this instrument. And so I think those are sort of normative questions. Theyíre capacities that are not looked at. I think it is a problem, possibly a problemówe might be concerned about false positives here, too. Some people who might want to contribute to research think theyíll ultimately benefit.

MS. CHARO: So should my take-home message be that up until now there has never been a defensible way to assess competency?

PROFESSOR SAKS: No, not at all. People assess for diseases all the time without having reliable and valid instruments; they do the best they can and maybe we should have a clinical evaluation. Or maybe people should use the MacArthur instruments with some modifications and flag the level theyíre going to use and give a few sentences or a paragraph or a page about why they think the line should be drawn here. Or you all should do it. I donít think the answer is, since thereís not a great instrument around to say, "Well, letís just not assess."

MS. CHARO: No. Thatís exactly what Iím trying to get at, and Iím going to conclude with this, because I appreciate that an instrument can be incapable of handling the hard, borderline cases. I understand that there can be a definitional problem. You know what day is, you know what night is, but dusk poses a problem. What Iím trying to figure out is whether this is a question of whether the instrument can now sort dusk out into day and night or whether the problem is we canít tell day from night. Right? Because that to me is a crucial thing. Because if the only issue is that it doesnít handle the hard cases, you can then set a policy in which there is a presumption. In hard cases, if thereís any doubt at all, you do enroll, you donít enroll, and you can just make a pragmatic decision based upon your preferences about protecting access to research or protecting people from abuse. But if a problem is bigger than that and you really canít tell, it seems to me...

PROFESSOR SAKS: It depends on what you mean by hard cases. Do you mean the few cases who come up who are questionable and nobody really knows what the answer is, or do you mean some of the value questions that come up over and over and over again that are just not answered by this instrument, or may be answered the wrong way? Iím not sure what you mean by hard cases.

MS. CHARO: That would almost lead you to ... wouldnít part of the answer be we donít know day from night if we were really judging what day and night is? We donít know day from night with this instrument. It isnít just the borderline.

MR. CAPRON: Could I be permitted just a quick intervention?

DR. SHAPIRO: Yes, then Trish has been waiting patiently to speak. But just quickly.

MR. CAPRON: The quick one is, Alta, Iím not sure that the result of being found incompetent on this instrument would be you wouldnít be in research. The crucial question is...

MS. CHARO: But weíre on the verge of making recommendations where under some circumstances, if you canít decide for yourself, you canít be enrolled.

MR. CAPRON: For certain research. But for other research, it shifts over to families, and that is not an uncontroversial move. If a person feels that he ought to be making the choice and somebody runs an instrument on him and says you canít make the choice, X is going to make the choice for you because this is not highly risky research or whatever....

DR. SHAPIRO: Trish, I apologize for taking a long time to get back to you.

MS. BACKLAR: I really appreciate very much youíre coming, Professor Saks, and giving us such a detailed analysis, and I really look forward to reading your paper. There are two suggestions I want to make. When we get Professor Saksí paper, it might be very interesting to ask Dr. Grisso and Dr. Applebaum to write a small response because you are talking about things which I think will be of great interest to them, and Iím sure that they may have some agreement with you. One of my concerns about the MacArthur Competence Assessment tool is that it may be manipulating consent, which is really in a sense part of what you were talking about. The other issue, though, where I come out differently from you, is that I think that the easy cases are the clear cases of serious mental disorder. The difficult cases will be in that twilight zone where itís very difficult to tell if somebody actually does have capacity or if they donít. I think it would be exceedingly difficult to get this absolutely precisely answered as we wish it. And thatís why weíre building and developing protections and safeguards so that when we get that particular group of people weíre sure weíve got something in place. We know certain cases are clearly the way they represent themselves.

DR. SHAPIRO: Thank you. Weíll take two more questions right now, then ask Dr. Saks anything sheíd like to add, then weíre going to break. Eric?

DR. CASSELL: Well, my colleagues had a right to put this instrument out there; even as you say itís flawed according to rules, itís going to be used. Here is a recent paper in the New England Journal about tests for dementia. Four well-accepted standards for dementia vary by ten-fold. Ten-fold in the number of people classified as demented. And that would seem to be a much simpler thing, so we may have to come out and say there is no. In the absence of a test that has reliability, what then is to be done?

DR. SHAPIRO: Trish, special privileges.

MS. BACKLAR: I think one really has to look at this and understand the tests. The test was really very oriented towards people with schizophrenia. Then everything that you see here, and when you read Berg and Applebaumís paper on research issues, this all makes sense if youíre looking at people with schizophrenia. The rest of it, thatís where it goes into the shadows.

PROFESSOR SAKS: I mean I donít know that I agree with you about people with schizophrenia.

MS. BACKLAR: Another time.... You donít have to make another talk.

PROFESSOR SAKS: Itís voluntary. I would just add one bit of research that was done on the instruments, which was quite interesting. They compared schizophrenics and people with angina and people with depression to normal controls. They found that schizophrenics only scored in the impaired range on each of the tests 25 percent of the time, omitting the evidence in the choice test. If you combined them, it was 50 percent, and the three tests didnít track each other. The POD, which is the one I find most objectionable, was not really well correlated with the other two, and the other two were well correlated with each other, which may say something about it. They say since they all measure different things we should use all of them, but thatís one of those normative judgments.

MS. BACKLAR: They did an aggregate in which it came out half full or half empty.

PROFESSOR SAKS: Right. Which is sort of interesting that only 50 percent if you aggregate them are incompetent.... Iíd want to test them a few months later in the community. I think we suppose that people with mental illnesses are incompetent much more often than they are. Thank you very much for having me.

DR. SHAPIRO: Thank you very much, and thank you very much for your work. Itís very stimulating and we look forward to your paper. We had scheduled a break at 2:45. We are, of course, well beyond that and into a period where we had scheduled for public comment. Now I made a mistake before when I indicated the number of people that were making comments. Most of those who will be speaking to us will be here tomorrow as opposed to this afternoon. We do have someone here this afternoon, though, from the Patient Rights Network, Mr. Bob Aller, if Iíve pronounced the name correctly. And my proposal to the Commission would be that we allow Mr. Aller to address us right now and then weíd take a break subsequently so we donít have to keep him waiting. Mr. Aller, I very much appreciate your being here, and weíre ready. The normal rules of the Commission are five minutes. Thank you, and thank you very much for coming.

MR. ALLER: We just had a few questions for the Commission. Dr. Shure is here from NIMH, and a few years ago I wrote to him and said, "Could you send us a sample of an informed consent thatís proper for medication withdrawal study?" And the reply at that time wasóand the reply currently, of courseóis that NIMH doesnít keep informed consents. At that time I wasnít sufficiently sophisticated to say, "Well, what about your intramural research?" It was basically, "We donít have copies of the extramural research." But out of curiosity a couple of years ago, we did a Public Records Act request to one of the local hospitals that does a great deal of research, or they receive about $70 million a year. We asked for all of their consents across the spectrum, about 60 of them, and particularly everything in psychiatry was deficient. Now, of course, we wrote to OPRR and sent them on to OPRR. But the deficiencies were things like if anything happens itís your problemóexculpatory language. Failure to provide alternative treatments. They were rather material issues that had been somehow not properly conveyed. And so a lot of us who are looking at the problem have said, "Well, we kind of suspect that itís possible there is widespread noncompliance with the current regulations." Now the answer to all of these...there are a lot of academic issues and questions, and people are thoughtfully commenting on them, but is the Commission, and what is the extent of the Commissionís acquisition of current consents on either symptom-provoking, nontherapeutic research, or other kinds of research thatís conducted with those who are decisionally impaired? And we would like to know what the Commission is doing about it because itís easy to acquire all of the NIMH consentsóthatís a simple requestóbut it gets much more difficult when the individual institutions are addressed. And they have been often difficult in response to public records requests. They have kind of stalled and weíve had difficulties. But what is the Commissionís take on this matter?

DR. SHAPIRO: Let me turn to our staff to respond to that question. Eric?

DR. MESLIN: This issue has come up before and Iím pleased to tell you what the status of it is. Several Commission meetings ago it was put to us that that very problem is worth investigating. And staff, over the last month and a half, have been putting together a formal research report which will identify as broad a range of studies with respect to various designs, types of conditions, and various pharmacologic agents so that we can be better informed about what the published research is and therefore to find out what the actual protocols are in the consent documents that have been used. We had hoped that by this meeting we would have a sufficient analysis of that literature available for the Commissionís deliberations. As it turns out, itís taking us a bit longer to gather those data but we are hopeful that we will be able to present a full staff summary of both those types of research and an analysis of the protocols and consent forms by the next meeting.

MR. ALLER: So youíre acquiring protocols and consent forms after the papers are reviewed?


MR. ALLER: Is there a ... what kind of number?

DR. MESLIN: Weíve got a number of different search strategies and depending on which model one uses, there are anywhere from 60 to 350 different types of papers that we think fall under this general net. The good news about the way we proceeded is that we are trying to capture what the range of research is rather than identifying what we believe to be especially problematic alone and then zeroing in on particular papers. Weíd like to be able to see what the world looks like and this has allowed us to captureóand Iíve sort of got some staff notesóabout 330 papers at this point. And we hope that we can acquire as many of those protocols as possible. I would rather we donít...

MR. ALLER; And the informed consents...?

DR. MESLIN: And the consent documents. They go hand-in-hand because an analysis of the consent forms alone is incomplete. And analysis of the protocols alone is incomplete. And because itís a staged approach, one can only go through published papers, at least thatís the way we feel itís best and most appropriate. It will take us a little bit of time but weíre putting this as a very high priority.

DR. SHAPIRO: Well we think that will be a very enlightening question that can be answered, particularly because there are suspicions that there may be widespread noncompliance and perhaps there is a great deal of compliance. But we think answering those questions has a lot to do with formulations of new policies.

MR. ALLER: Thank you very much. Itís very much appreciated.

DR. SHAPIRO: Well, Dr. Aller, thank you very much for coming. We very much appreciate your taking the time to be here with us today. Letís try to take a break for about 10 minutes.

BREAK: 3:23 p.m.

DR. SHAPIRO: We have a couple of agenda items left this afternoon. And one has to do with the issue of changing regulations, the processes that are involved in changing regulations, as we might very well be in that situation. And Iím going to turn to Rachel Levinson in a moment to take up that subject, and then weíll get to the federal oversight of research. Rachel?

MS. LEVINSON: Okay, Iím going to try and get through this as quickly as we can. Can everybody hear? Iím going to tell you about the mechanics of the rulemaking process because thatís what weíre really talking about doing. Itís no different to change a rule than to make a new rule, even when youíre talking about changing the common rules. So Iíll talk about how federal agencies make rules, regulations. The rulemaking process is defined in the Administrative Procedure Act that was signed into law by President Truman in 1946. It has a purpose relating to rulemaking, which is to give the public advance notice of what the government is thinking about doing, and to gather some language and to run it by those people particularly who would be affected by such a rule.

The way this happens is that the agency that is effecting the rule will publish a notice of proposed rulemaking in the Federal Register for comment. That is not a document that people ordinarily read in everyday life. What the agency should do, and often does, is to take that publication and send it around to the affected parties, maybe the chemical industry if it has to do with regulating chemicals. Or sending it to professional societies or industry advocacy groups, whatever group might particularly be affected or interested in the rule. They have a minimum of a 30-day comment period. It can be extended and often is for a rule thatís particularly complex. We encourage up to at least 60 days, not 30 days, as long a period as possible, assuming that there isnít any particular reason to rush it. And all of the comments that are received in response to this publication become part of a public docket thatís available for review by anyone. You have to provide a reading room or some space where someone can come in and read those documents. The comments that are received must be considered and given weight in the development of the final rule, which will contain a discussion of the comments. So that if certain comments were taken, then thatís explained. If comments were not taken, that also must be explained as to why the agency decided that they should not incorporate those comments into the final document. Then there is a final rule that will be published and it should go into effect at least 30 days after publication, again to ensure that the public isnít blindsided by a rule. So this process is necessary in order to make sure that there is ample time for the public to comment and to give feedback to the agency thatís putting a rule into effect.

The rule itself may be done in order to interpret, implement, or define either a law thatís been passed that tells that agency what they should be doing, or a policy, a major policy change that the agency is going to put into effect. And it defines for the public, in advance, what they are going to do.

There are possibilities for an interim final rule that will go into effect even before the comment period, but that only happens in rare instancesóones that probably would not affect NBAC unless there is one that has to do with a public health emergency. And thatís probably the only instance that would affect NBAC.

The President issued an Executive Order that instructs executive agencies to the extent permitted by law to take regulatory action only if the potential benefits to society for the regulation outweigh the potential costs to society. So there is a general attitude that you donít regulate unnecessarily. And this is also part of the current reg reformóregulatory reformóeffort to cut back on regulations, to put them in plain English, to try and make them understandable, to try and make them sensible, and to make sure that we try and cut back on the regulatory burden to the extent possible. So where a rule might affect several different groups, we want to make sure that thereís only one rule and not several rules that are trying to accomplish the same feat that would be applied to the same community, thereby having a layered burden.

The common rule adds a level of complexity that Joan Porter described, I think, in great, if not excruciating, detail. And I would encourage you to go back and look at that. That didnít start out to be a rule; it started out to be a model policy, implementing the recommendation from the Presidentís Commission and Iíll read it one more time because I think itís very useful: "The President should, through appropriate action, require that all federal departments and agencies adopt as a common core the regulations governing research with human subjects issued by the Department of Health and Human Services, as periodically amended or revised, while permitting additions needed by any department or agency that are not inconsistent with these core provisions." So what that anticipated is that there would be a need for customization, if you will, by individual agencies depending on their statutory authorities or depending on the communities that they service, that would require that they have some form of individualization.

OMB didnít like that because they felt that there had to be uniformity across the government and that that is a central tenet in developing a common rule. And if it canít be done that way, then it doesnít...basically canít be a common rule. And they said there must be no departures. And that added to the complexity of trying to get the language worked out in every single individual section of the common rule. And it took a long time to iron that out.

When you tinker with a common rule, then, you have to understand that it canít be at such a great or fine level of detail that it would cross or conflict with existing policies in each of those agencies. So youíre almost forced to deal with the level of general principles. And that may or may not be satisfactory to accomplishing whatever youíre desired ends are.

OMB, the Office of Management and Budget, will be involved in reviewing all proposed rules and negotiating with the agency sponsors. And they are often the convening body in negotiating between agencies who have policies that are dealing with the same subject. And the National Science Foundation and the National Institutes of Health, for example, both wanted to put out policies dealing with scientific misconduct, and OMB had them sit down over and over again to try and make sure that they used exactly the same words. Because both agencies fund the same researchers, and there is great justification in having them use exactly the same policies so you donít have to have researchers who are funded by both agencies filling out two different sets of forms. So Iíll remind you again that it took ten years to adopt only Subpart A of the old HEW regulations.

There are several different options for initiating the process of revisiting the common rule. And the choice of the method should be based on the substance of the desired result. Thatís the take-home message. Donít start with what the rules are and what the process is for changing the rules. Start with what you want to accomplish and work backward and then weíll figure it out; weíve got plenty of people, administrative attorneys within the departments or outside, who will help you figure out the best way to get to where you want to go. But thatís really the place to start: what do you want to accomplish?

Informally, you could start with dealing directly with the agencies. They have a great deal of latitude within the common rule or within their statutory authorities to change their policies. You may not want to revisit the common rule; it may not be something thatís appropriate. You can talk to the Interagency Subcommittee on Human Subjects; thatís one way to get started, to get ideas, to think about sort of a reality check, how could you implement a change. But the membership of that group is limited to those agencies that are signatory to the common rule. Also, these people often have a low level of authority. Joan Porter pointed out that while these people may be the ones who are most committed within the agency to seeing these changes take place, they often have a difficult time in bumping it up to the appropriate level to get it done. But there are ways to help with that through, for example, the National Science and Technology Council process.

Number two. You have in your charter a forcing clause. We bled over getting that forcing clause in there, which turns out now to be standard language in a lot of charters. But at the time it was very difficult to get it included, and Iíll read it to you just so you have it in mind: "Reports by the National Bioethics Advisory Commission on specific issues shall be submitted to the National Science and Technology Council chaired by the President and then to the appropriate committees of Congress," etc., etc. "The Commission may specifically identify the federal department agency or other entity to which particular recommendations are directed, and request a response from the federal department agency or other entity within 180 days of publication of such recommendation." Then you put reports in the Federal Register and on the web, and these reports may specifically list the department agency or entity to which any recommendations are directed, and the date by which such responses are expected. This could be very powerful. You may or may not want to use that. Again, it depends on what it is that youíre trying to accomplish.

A third option is recommending executive action through the President, through an Executive Order or a Presidential Directive, or other ways. Just a statement, but that is available also. An example is the review of classified research, classified human subject research, that was carried per the recommendations of the Advisory Committee on Human Radiation Experiments. The President gave those agencies conducting human subject research a year to do a survey and to report back, and to change the common rule having to do with classified research involving human subjects. So they are told absolutely by the President to get this done. And theyíre going to get it done.

So thatís another option, and those are three at least obvious ones in a kind of range of formality. And Iím sure weíll come back to this when you have recommendations and you want to think about the best way to get them implemented. These are just sort of an introduction. I donít think you need to focus on the mechanics of the process at all, but just think about what you want to get done and weíll figure out with help the best way to get it accomplished.

DR. SHAPIRO: Thank you very much. This really is a very helpful outline of some of the possibilities, excuse me, for us. Are there any questions for Rachel?

DR. COX: What happens then to the process?

MS. LEVINSON: The law is the starting point from which the agencies then develop the rules that implement the law. The law doesnít have, or rarely has, any specifics that tell you how to do it. The agencies then have to work and develop a rule through this process.

DR. COX: Exactly. But if a law exists it means people have to do it, right?


DR. COX: Thank you.

DR. SHAPIRO: Any other questions? Okay, thank you very much. Letís go on to our next topic, which is Federal Oversight and Research Involving Human Subjects. Alta?

MS. CHARO: In many ways, this is kind of a holding pattern right now as we await further information from the Gonzales contract, from the McKay study, from the OIG study, etc. But itís a good opportunity to tie what Rachel was just saying and whatís been going on in the decisionally-impaired people to something which I hope you had a chance to read, as well as to listen to, a couple of months ago. And that is the way in which the structures that are used for the protection of human subjects in the United States affect what seem to be two intersecting goals that have been identified by this Commission. One of those goals is to ensure the appropriate protection of those who are currently covered by existing regulations and that is the purpose of the federal agency survey: looking at the effectiveness of the federal agencies at accomplishing just the tasks that they have taken on themselves up until now. And the second goal, which was expressed in the resolution that was passed last year, is the expansion of some minimum core protections to all peopleóregardless of the source of funding that is behind the research in which they are being enrolled. Now these two things are not the same. The expansion of protections to something that is universal throughout the United States might be the expansion of some minimum level of protection in which what you got as a guarantee might depend upon the source of funding. Just as the common rule now commits a variety of agencies to a core level of protection at the level of things like informed consent, but does not commit all agencies to certain special kinds of protections aimed at specific populations that are identified as being particularly vulnerable to exploitation. One can imagine a system in which you have universal protection to the extent of informed consent, but that particular kinds of implementation strategies, through IRBs for example, or special protections such as the ones weíre considering for people with decisional impairments wouldnít necessarily apply unless the funding source was from a particular place like a particular agency.

Now the recommendations that we got from Fletcher and McCarthy and that have been analyzed for us by Rob Tanner and the rest of the staff, along with the Glenn bill, focus on some of the problems that we can identify ahead of time in trying to translate these goals however we decide upon them into some kind of action. And just by way of a quick reminder for you, Fletcher and McCarthy in their presentations identified certain kinds of structural issues that will dog us. One is the location of the office thatís in charge of protection of human subjects. The suspicion has been that absent an office, that is, sufficiently high up in the government with some degree of authority over agencies and departments, itís going to be very difficult on a regular basis to ever have steady improvement in a quality protection of human subjects. Concrete example: When we get to the discussion of Marinoís paper and the recommendations, there are going to be recommendations for change that if we wanted to incorporate into regulation, would first require that there be some degree of departmental enthusiasm and sponsorship at HHS, which in turn requires that the heads of many, many different agencies that could be affected by these regulatory changes were equally enthusiastic about the Secretary pushing for such a change. We can anticipate at the pragmatic level but this would be difficult to accomplish.

Second, even if the Secretary of HHS were interested in this kind of improvement and had either overruled or persuaded or been supported by her various agency heads, she would not have had the authority under any kind of current structure to impose this kind of view upon other departments that might have the same issue, but instead were left with persuasion. So one of the key questions had been location. An independent kind of agency that sits outside any particular department in theory has that kind of jurisdictional power over all departments but suffers from being all by itself out thereónot necessarily with strong congressional sponsorsówithout a large portfolio that gives it leverage with various congressional oversight committees on appropriations committeesóand so, therefore, may be rather vulnerable.

It would be easier, structurally, to try and move human subjectsí protection at least higher up in HHS so that one could get around some of the difficulty of the negations among agency heads in order to get a common message going up to the Secretary, and begin to work right within the Office of the Secretary on a common policy within HHS. But of course that does leave us with the problem of HHS not having any authority over the departments.

In addition, there is the question of accountability and enforcement, and again youíve been given a review of the different ways that Fletcher and McCarthy proposed this might be handled and how the Glenn bill would handle it. There is an opportunity here for us to keep in mind, Iím not sure when the discussion would actually take place, the kind of intersection between accountability and enforcement and the current ways in which OPRR operates. For example, by way of reminder, OPRR now has an extremely voluminous kind of assurance document that it tends to negotiate with individual institutions, which goes into excruciating detail about how it is that they plan to regularly review and protect human subjects. And for institutions that donít regularly do this kind of work, itís quite typical that theyíre not going to have this complicated, negotiated, multiple project assurance but instead theyíll have single project assurances; and occasionally OPRR itself is in the business actually of reviewing protocols, something for which it doesnít actually have a lot of personnel.

The expansion of human subjects protection into non-federally-funded, non-multiple project assurance institutions, non-FDA investigational drug and device settings means that the question of administerability of any of these kinds of mechanisms for accountability and enforcement is crucial. And whether one wants to continue with the current assurance mechanisms or move to something more like the registration type of mechanisms that were being proposed with more streamlined kinds of guarantees and even some consideration about the acceptability of either regional governmental level or privatized IRBs offering up some opportunity for review for people at institutions that rarely do research are all part and parcel of this collection of items. Again, if you think about the kinds of recommendations that might emerge from the Marino paper in which there is the possibility of asking for competency assessments, consent monitors, standardization of the people who are presumed to be capable of acting as surrogates for those who are incapable of speaking for themselves temporarily, one has to keep in mind the workability of those recommendations against the backdrop of who exactly is going to be in charge of implementing these things, whoís in charge in Washington of making sure that these implementation plans are adequate and are followed through, and whoís in charge of cracking down if these things are not done properly according to new rules.

And so if this looked complicated before, itís even more complicated now. I hope that Iíve made it worse for you. Eric, Iím going to leave to you the description of what youíre hoping to get out of the discussion because I know that with very little time allocated today, the goal was not for everybody to decide here and now which set of structures they want to vote on.

DR. MESLIN: think thatís a fair summary. First, I want to just echo your gratitude to Rob Tanner, who is sitting at the back, who put in an awful lot of work on this analysis. This was requested by the Commission at its previous meeting, and we were able, with both Rob and Melissa Goldsteinís excellent help, to put together this side-by-side for you. It really is meant to be a permanent part of the Commissionís record of deliberations so that we do not need to continue reminding ourselves of whatís gone on before.

There are two points that I think are worth reminding the group. The first is that itís entirely appropriate, as Alta as indicated, that if the Commission decides that a somewhat more comprehensive report that encompasses the federal agencies survey, encompasses IRBs, and encompasses the appropriate administrative structure for federal oversight is the way that you want to go, then this is a first step to understanding what the basic facts are for any recommendations that you wish to carry forward.

The second point is that we still have an awful lot of information that can be brought in. We are anxiously awaiting, we believe it will be within the next ten days, the commissioned paper by C.K. Gonzales which is, if you will, the third leg of the three legs that weíve commissioned that will provide background on aspects of privately funded research. It was staffís suggestion in the accompanying memo that you might also want to consider commissioning a paper from an administrative law person or someone who has the kind of skills that Rachel was referring to in her description of the nuts and bolts and the details, because this is, as I think the Commission has agreed to describe it at its previous meeting, not a discussion simply about the location of the current Office for Protection from Research Risks, but consistent with the Commissionís mandate, a far more unique opportunity to talk about what is the appropriate structure, not just for now but for 15 to 20 years from now. So the reason for raising it is to keep it on the agenda. It will become a regular theme at future meetings, and we want the Commission to ask staff for further input and to recommend to us what else you would like to know in order to keep this item relevant and current for you.


DR. COX: Thereís something Iíd be really interested in knowing. In the history of the Congress of the United States, has there ever been a situation where the Congress felt strongly enough about an issue that they protected a free-standing agency with the kind of ability to go and look across different agencies, as we might be suggesting here?

MS. LEVINSON: One example they gave would be Office of Government Ethics, and that gives you the flavor of how it can be kind of faddish. They can be interested in something for a while and then it can go away. And thatís the problem with their free-standing office that I think both of the presenters intimated before, and one reason why having it within another existing structure is beneficial to a certain extent.

DR. COX: But there has ... but thanks, because I asked for one example and you gave it. But I mean thatís that kind of situation, right, where...

MS. LEVINSON: I can give you one more.

MR. CAPRON: I donít think itís possible to answer that question in a way thatís really useful for us in the abstract, and I think Alta hinted at one point. There are certainly a lot of, and have been more in the pastóseveral of them have been closed downófree-standing governmental agencies that at various time have stepped on important peopleís toes and have been under threat. When they are protected, itís often, as Alta suggested, because they have enough breadth in their work that there are congressmen who have ongoing interest in their survival for sometimes parochial reasons. An agency that mostly exists to protect human subjects might find one or more knights-in-shining-armor who share that concern. It might also find that to the extent that it is interfering with the headlong rush of scientific research at a major research institution in somebodyís state that that senator or representative hears volubly about what a nuisance it is to comply with regulations. I frankly am not at all convinced, however, that having it in a department provides that much additional insulation, for the simple reason that the people who often have broader interests are also themselves vulnerable to those broader interests of their department, not being dragged down by what they, themselves, may regard as a peripheral enterprise. And ironically, I would be most comfortable thinking of this agency, if it were to be lodged in the department, being put in the Treasury or some other place that doesnít conduct research. The whole problem here is that, I mean there are two problems that weíre trying to address. One is the ability of the present structure to actually operate well on a government-wide basis. And the other is that the lead agency is at two or three levels down from the top of the department which sponsors most of the research and the sense that it is, itself, not able to operate independently might be increased, might be helped, by putting it at the right hand of the head of the department instead of under the table of the person conducting or sponsoring most of the research, perhaps. But it might not. I mean itís not at all clear to me that we solve the central problem of conflicts of priority. I donít even say conflicts of interests, just conflicts of priorities, what comes first. And it is not to be critical of the department that is sponsoring the research, it is just that as we found with the Atomic Energy Commission, it had a dual agenda and I think we see a dual agenda here.

I would like to get a better sense than I now have because we had a discussion of this with Drs. Fletcher and McCarthy when they first reported. We had a discussion of this at the last meeting when I was asked to review it. Weíve had a discussion thatís begun by Alta now which sheís reviewed. We have the charts. My sense is that this is an integral part of our report on the federal agency response. Because while we are not finished with that, and I am very desirous of having more input and feedback from the federal agencies on their sense of how well; we have represented what theyíve done well and havenít done well; I think there will be no question that there are certain deficiencies that exist. Not the least of which is the absence of any database on how much research and how many subjects there are in the federally-sponsored side, to say nothing of the private site.

Knowing that, certainly one response to that set of problems will be the response of saying we really need to change the structure. And so it seems to me that itís logical that it should be an integral part of that report. And I just want to have some sense from the staff side or from my fellow Commissioners that these two things are proceeding so that they are likely to get done at the same time, that the part that Bill Freedman has been working on the federal agencies and so forthóweíve seen drafts of that and thatís moving along and we know where that is. This is still at a more conceptual level. I mean we see what the problems are. At what point are we going to go down this list and say these are the suggestions about locations, these are the suggestions about function, these are the suggestions about design and so forth. Weíre not adopting the McCarthy model or the Fletcher model or the Glenn model. Weíre making recommendations and to the extent we say this is similar to or this one draws from, fine. But weíre going to have to have our own answers to that. When are we going to do that? Thatís what Iím not clear about. Are we going to do some of that today? Are we going to set aside hours to do it at a future meeting? Because I think we have to do that for the staff to know what they should start writing about this. We have to give them directions as to ... in the end we have a certain amount of evidence and a certain amount of argumentation from different groups. What we need is our own version of those, of that evidence and argumentation, that will lead to the kinds of conclusions which we think are appropriate. We need to reach the conclusions and then fill in the evidence in terms of writing it out. And thatís going to take time.

One final point. I do agree with the staffís suggestion that it might be useful to have someone with administrative law background look at and think about any peculiar problems that would arise in one place or another in terms of the ability to promulgate and enforce regulations from different postures. I think that could be helpful.

DR. CASSELL: What youíre saying is that we have to come down and make a decision on what we believe this, what this form is, what itís meant to do, and where we believe it ought to be.

MR. CAPRON: Yes, exactly. Thank you for a briefer statement.

DR. SHAPIRO: I think thatís right, and our current intention is in fact to have those come out in the same report together, both the issues regarding OPRR, however you want to discuss the slide. That issue and the project weíve been involved in for a long time now which Bill Deemanís been working on. And also likely, although Iím not so sure, that the issue ...what we have to say for the IRBs in general might also be part of such a report because that would give us a kind of look at the structure of this whole thing. Weíll have to see how it goes along. And I think in terms of the actual discussion of when do we actually say we want it in Treasury or HHS or do we want it in an independent agency or whatever else weíre going to decide, I think thatís going to come up sometime in the next two meetings as we get a chance to put the material together for staff.

DR. MESLIN: Just a quick update for Professor Capron where some of these reports are, we expect the federal agency survey data to be completed by the end of March and written up at that point and be available. That would mean it would not be available at the March meeting, which is at the beginning of the month, but it would be at the May meeting. And that could be very advantageous. If the two reports that are currently under discussion and close to prime time are presented, and Iím just saying this hypothetically, presented for the Commissionís sign-off in its draft interim mode at the next meeting, then my sense is that you all would recognize what the major issues were that came out of those two reports that would inform the analysis of the Freeman data and would further inform any analysis of the federal oversight issue. If all goes according to what might be optimistically described as a unique plan, there could be a comprehensive report that deals with all three of these by the summer, a working draft of a report by the summer.

MR. CAPRON: I followed everything up to the last sentence or two.

DR. MESLIN: Not including the IRBs. Iím not even mentioning that.

MR. CAPRON: Well, that goes to an earlier point. Alta mentioned in passing something with which I agree, indeed we discussed it a little last time, which is that the ... we donít have to think of this as a report on OPRR. I mean we really ought to think of it as a report on a means of protection, and OPRR and its equivalents are very likely to be necessary in any sense in the departments as their local administrator of these issues. Then the question comes up about the IRB, and as you may recall, at the last meeting I tried to argue that the issues about adequacies and inadequacies of IRBs are actually relevant in indicating that thereís a problem there that needs to be addressed. What not to hold up and ought not to be directly handled in a report dealing with the location of the office, because whether itís OPRR and its equivalent agencies or a new office or some combination, those IRB issues are going to have to be addressed. And so it doesnít...the one doesnít turn on the other.

I also do not see any value, in fact I see ... if weíre talking about the same three reportsóthe tissue report, the impaired subjects report, and the federal agency reportóI donít see any value in putting the three of them together.

DR. MESLIN: No, no, no.

MR. CAPRON: So I misunderstood what you were saying.

DR. MESLIN: Yes, you misunderstood.

MR. CAPRON: Well, what were you saying then about linking the three of these in a report?

DR. MESLIN: Iím sorry you misunderstood. By having them completed, those reports would be on the table and serve as excellent case studies for the Commissionís deliberations about the broader issues of human subject protection. We wanted to wait for the Freeman data to be complete before we said anything about the location of OPRR. I didnít mean to lead you to believe that those would be linked. Those are reports, stand-alone reports, issued on their own and deliberated about on their own.

MR. CAPRON: Okay, I see.

DR. MESLIN: Iím sorry you misunderstood.

DR. SHAPIRO: Arturo?

DR. BRITO: I just had a brief question for Alta to see what her thoughts were and Alex touched on a little bit about possible conflict of interest or conflict of priorities. With placing this or having the location in the HHS, what do you there any way to actually avoid that and is there another location that youíve thought about thatís still doesnít make it an independent agency?

MS. CHARO: Yes. This has come up before in some ways by way of review. Alex has made the comparison to the old Atomic Energy Commission that was simultaneously charged with the promotion of research and deployment of nuclear technologies, and at the same time regulation of them for the purpose of insuring safety. And over time that proved to be unwieldy and eventually we had a separation of function into DOE and NRC. Similarly, the INS has been coming under very similar kinds of scrutiny right now in its role of being both the kind of intake and outtake agency with regard to foreign nationals. There is no way to completely overcome this kind of problem. If you locate an office, for example, at the level of the Secretary of HHS there will be a variety of agencies that are trying to promote research for whom many of the regulations, although recognized as valuable and essential to ethical research, nonetheless create paperwork barriers to quickly accomplishing some of their goals and this will bring pressure on the Secretary to balance those agenciesí goals for promotion of research against the commitment to a kind of uniform enforcement. And weíve seen some of the debates on this topic about research needs and human subjects protection in very recent days, such as the question about emergency settings. And both wanting very much to promote new ways to treat injuries like brain traumas at accident sites, and at the same time to protect people against having been made into experimental subjects in inappropriate ways.

Alexís suggestion of putting something at Treasury reminds me of a conversation I had actually with Gary Ellis, because one of my first instincts was we put it in Justice Department because it really is a matter of civil rights, that people not be exploited. And then the hint of possible problems with Justiceís own research agendas made it seem that that was not necessarily going to be the perfect solution, although at first blush it seemed like a great solution. Iíve also suggested in conversationóI suspect other people have as well, half facetiously and half seriouslyólooking at OMB because OMB already has its fingers all over the place. Itís too entrenched to be killed by Congress. Everybodyís scared of it. And so if you put enforcement research ethics and got their commitment to this, it could be a devilishly strong place. On the other hand, I donít think thereís anybody in government that trusts those people. I mean government people feel about OMB the way citizens feel about the IRS. I mean theyíre a necessary evil in our life. Rachel says no, but when I worked in government I never knew anybody that liked OMB. So we just have differing views on a cranky, terrible problem. Finally, there is a genuine question about jurisdiction here because to the extent that one wants to extendóthis is how Iím starting, by the wayóby saying do you want to extend human subject protections to everybody or do you want to strengthen for those who are currently protected? And you want to extend human subject protection to encompass those people in currently uncovered settings; for example, privately sponsored research that doesnít involve investigational drugs and devices. People at state psychiatric hospitals would be another example of an uncovered institution. Youíve got to question about the authority of any particular part of the federal government to exercise that kind of jurisdiction, right? If thereís no federal money flowing so that itís a condition of spending, if it is not pursuant to the FDAís own authorizing statute which sets out rules for investigational drugs, and if itís not because itís part of the federal agencyís own activity, the question is on what basis are you regulating. But that becomes a kind of uncomfortable fit for an office thatís located entirely within a single department whose mission is spelled out in its own enabling statutes and may not extend to gross levels of regulation of the private sector. So if your goal is to extend protection to all the people in the U.S., you do have the beginnings of some arguments in favor of a stand-alone agency whose enabling statutes really get to that kind of thing but leaves you with all the problems that have been identified already about political support for that agency over the long run.

DR. BRITO: The conflict of interest of the apparentóor what would appear sometimes to be a conflict of interestówith a lot of the agencies in Washington, since it is the same group of people or it appears to be the same group of people within and out.... So is there a place for, if we decide to recommend an independent agency as opposed to having it as part of HHS, is there a place to have a place outside of Washington and still be national? Is that too far-fetched to...?

MS. CHARO: Well you could put them at the missile sites that arenít being used anymore out West, but I donít know that geography is really going to be the key here. I think the key in the pressure to make ... in some ways it always comes down to the funding issue because youíve got agency directors that want to fund certain kinds of research. And if theyíre running into problems in getting their grants-making operations under way.

DR. SHAPIRO: It seems to me that as we begin to think seriously about this, our discussion here tends to focus on the location issue. Itís the easiest one to describe and problems with the existing location are pretty obvious. And then there are these other complications all of you have heard. And it seems to me that that may not be independent of the other, one of the other characteristics, that is the jurisdiction issue. Which I think is a burden of your comment, Alta, if I understood it correctly, that these things in fact may be related to each other. We ask ourselves, just a thought experiment, supposing we want to put aside for the moment extending the protection beyond the federal government tether. What decisions would we make? What would seem to us to be the most logical issue or the preferred way to deal with location and the other issues that are coming up? That might actually be a useful exercise.

MS. CHARO: One of the things that would be helpful in the clarification of goals, because I completely agree with Rachel, you start with what you want to come out with, and figure out if it is not going to be, for example, immediately extension of human subject protection, even within the federal government, is it an extension of the common rule to all federal agencies which doesnít yet exist, I mean? Is it to get the entire federal government to sign on, even though a lot of places donít do a lot of research just for the sake of consistency. Or is it to deepen the quality of the protections for the agency who are already members...adhering to the common rule or is to extend the subparts for those people who have only got Subpart A. It would be a good starting point to figuring out what level of office would be most appropriate, how many sign-offs youíd need, how many people would likely not sign off.

DR. SHAPIRO: You know I think itís important that we have this discussion before we start honing in on exactly where its location ought to be.

DR. CAPRON: If you think that the impediment to extending federal jurisdiction over privately-sponsored research are substantial, and independent of the question of the objections of particularly departments to having to be accountable to either another department or a new federal agency, you might still say if the evidence is eventually there, that you have a well-operating federal system that has avoided problems and the research, that kind of research is better than it once was because of this agency, and some indication that privately-sponsored research continues to have problems, at that point what would it be like to extend? And you could design in, you might adopt a method not because you intend to recommend today or believe that today you have enough evidence to say we have a crying national need to regulate privately-sponsored or state-sponsored research. But to say weíre not going to make two changes inside of a decade; youíre not going to move it to the Office of the Secretary of X, and five or ten years later set up a separate agency barring the most incredible crisis of the world, you might say weíre going to design it in a way that would allow the addition of another function at a future date when the evidence is strong enough to justify that.

DR. SHAPIRO: Thatís my own advice is to learn how we might approach it in a useful way. I think it makes the subject less complicated and Iíd like to solve an easier problem first. Itís as simple as that. And if thatís very easy to solve, we can then ask ourselves the question whether at this time we are prepared to go for more. Do we feel we know enough and have enough good ideas?

MS. CHARO: No. I would like not to see us back away from that but there is the question of how one gets there. You can suggest that it ought to be recognized that everybody should be protected, but leave to state common law, state legislation, individual institutions the way in which to do it, or you can also...or you could say weíre now in a position to start recommending federal legislation that will reach these people. They are separate questions.

MR. CAPRON: And we could also say that we recommend that we recognize that additional evidence may be needed. Part of it, if Congress were to do this, it would be based on findings. I mean part of the reason...this would certainly be challenged. If someone were doing totally privately-sponsored research at an institution that doesnít even get any other funds, you donít have the argument that came up around funding of colleges where they were getting money for one activity and the question was could you then control their discrimination on the basis of religion or sex, when funds werenít used for that fashion. And the basic answer of the court was couldnít, actually. But it would require finding that we have bad abuses and a reason for saying that having federal jurisdiction would prevent those abuses from occurring. My own sense would be, if we were...if we were called to testify before Congress right now, we donít have full evidence. We have anecdotal evidence, we have certain examples of the problems. But we also do not have the ability to say that there is in place a federal mechanism which, when faced with comparable problems in federal research, solves them and avoids them occurring. And so itís harder to make out either side of the argument, the need or the solution. It might, therefore, make sense for us to say we are in principle, we believe as a matter of protection of every person in the United States, that it shouldnít matter in that protection whether the research is sponsored by a private entity or the federal government. You should at least have informed consent and prior IRB review. We could say that, and we have said that already. But we might say that while we recommend that the agency be capable of taking that step, that we believe further evidence needs to be gathered on both of the two points that I just described in order to have the kind of legislation that would stand up to challenges that might be mounted against it. And I would just as soon see us address it in those terms. Now if between now and time we write the report that evidence is strong enough, maybe the fact that we donít have in place the perfect federal mechanism yet becomes a reason for thinking, well, the mechanism that weíre recommending we believe would solve the identified problems and would be a mechanism capable of supervising private research in a way that actually does avoid the kinds of problems that weíre now enumerating in our report, that are sufficient to justify either legislative findings or the act of Congress. When it is up for passage people in the private sector coming forward and saying we donít believe there are grounds for you to assert your jurisdiction. There arenít the kinds of problems that would justify federal intervention. And then post-passage, also, if it were passed, someone coming in and saying this legislation exceeds federal authority. Thereís not a sufficient nexus of federal concern. Now, under civil rights legislation there was, and I donít follow this well enough, maybe Alta does know, at one time the notion that a bottle of ketchup was being delivered to a motel in Atlanta was enough for the federal government to say you cannot discriminate against someone sitting at that lunch counter or checking into that motel. You know, that was enough. It was some interstate traffic and itís hard to believe that anybody conducts research without getting pipettes and reagents and books and so forth in interstate commerce. So if itís that kind of a challenge, but frankly that kind of a challenge is obviously harder to mount if you also say "and thereís a screaming need for this." When left to their own devices, the states have not regulated this adequately and private parties are exposing research subjects to unjustifiable risks. I mean the court is not unmoved by such arguments. It was obviously the fact of racial discrimination at an absolute level that led to the upholding of those civil rights statutesónot just a bottle of ketchup going through interstate commerce. And so I wouldnít want to see a statute recommended when we could not ourselves say to a committee of Congress here is the bill of particulars that would support your legislation. I think we need to have that, as well as some assurance that weíre recommending a mechanism that will work.


MS. CHARO: Iíd like to bring this back a little bit closer to something concrete for this group of people. As we go through the recommendations from the draft report on people with decisional impairments we have a opportunity to make recommendations about regulatory changes. Now, I think the value of that exercise for this discussion is going to be in having people realize how futile most of our work is going to be because of the extremely remote possibility that any regulatory changes that you might want could actually be implemented because of the current placement that those regulatory changes would be proposed and the number of sign-offs, coupled with the enormous number of people who wouldnít be affected by those regulator changes because they exist in uncovered institutions like state mental hospitals and are not being treated with experimental drugs. Theyíre being treated...theyíre in research protocols that involve previously uninvestigated uses of already approved drugs, very commonplace in this field. Or the withdrawal of approved drugs. I think itís important for us to keep that in mind, not because itís an exercise in getting depressed, I mean, we can do that on a regular basis anyway. Itís because I think that will help to concretize exactly what people want to focus on. Unlike Alex, Iíve tussled with him across the table a number of times and the issue would be evidence of abuse because there would be no way to cumulate that evidence absent a regulatory mechanism that forces an accounting. And if youíre going to require the evidence in order to create the regulatory mechanism to get the accounting to create the evidence, we have an impossible paradox here. But I do agree with him completely that any effort to go beyond a simple resolution that there ought to be universal, at least minimal, protections is going to be impossible to implement until we have some experience with a workable system in an area where itís easier to implement than that is where weíve already got jurisdiction, like the federally-sponsored research. On that score, I agree with him completely.

Until we solve the problem of how you get everybody to do what theyíre supposed to do already if theyíre already under an obligation to do it, which is the IRB report about the ability of a decentralized local IRB-based system thatís governed by multiple assurances and minimal oversight in education from OPRR, until you tackle that and tackle the question of uniformity of regulation among federal agencies and change regulation at the federal level, you donít have any kind of system to build on as you try to expand that into the private sector. It is worth, though, keeping in mind as we talk about these location issues the possibility that you might want to eventually extend it so that whatever youíre recommending in terms of structures within the federal government be done either with the eye toward having a new and different structure someday when youíre ready to tackle the private sector, or the creation of a structure today for the federal government thatís flexible enough to handle the private sector. Again, the jurisdiction under the commerce clause I donít think is really all that problematically investigated for the cloning report, but the enabling statutes of individual departments are problematic because they donít really have the reach of some of these and need some attention. So itís that kind of staging thatís really kind of part of the discussion here, is the order of events.

DR. SHAPIRO: I think the issue of staging is a critical strategic issue in all of these concerns, and I think that weíre more easily going to be able to develop useful ideas if we allow ourselves that freedom of saying, you know, approach this problem instead of stage it. And we can learn as we go. We donít have to know it all right now, we can learn as we go. At least speaking for myself, I find that extremely helpful. It came up in the cloning issue when we were trying to decide whether we wanted to recommend legislation right away or we wanted to try something else first and then go to legislation. Well we decided a certain way there, but even going through the discussion of staging as opposed to just trying to get to the final institutions, I think, can be very helpful and it can develop interesting and helpful strategies on which we can agree a good deal faster. Thatís my own sense of it.

MR. HOLTZMAN: ...think about an alternative view which has issues like this; sometimes bigger things are easier to accomplish than little things.

DR. SHAPIRO: Weíll remember that, too. As they say, you, too, have a point. Okay, letís go on to the final agenda topic we have for this afternoon, which is the material in Tab F of your book. It was an analysis of the various statements that have been made on the tissue samples issue. The staff has produced a comparison of this in a tabular form. Let me first turn to Eric to see what heíd like to say, and then Iíd like to turn to Tom and see what his reaction is.

DR. MESLIN: Thanks very much. In the voluminous Tab F, there are 11 items, three of which really relate to this afternoonís discussion. The first is a memo to me from one of our staff, Shawn Simon, who did a very thorough job of providing what was intended to be at the request of the Commission from last meeting a mirror put up to your face which allowed you to reflect on both where other professional associations...

DR. CASSELL: ...put up to your face to see if youíre still breathing.

DR. MESLIN: Iím trying to figure out what, if you hold the mirror up to my face whatís on the other side of that mirror. Itís that block problem ... two-sided mirror. Itís hard to come back after that. Following the memo is the side-by-side which both shows a number of organizational perspectives and NBACís positioning based on where we think you think you are. The purpose of presenting that to you is to confirm that thatís where you might be and to alert you to both some consistencies and some inconsistencies in the way that your views have been expressed so far.

A second item, or third item if you count those as two, follows about four items later and it is a memo to me from Melissa Goldstein. And Melissa has provided a very helpful summary, again based on your request, where the current federal regulations sit with respect to some of the proposals that you are currently debating. And thatís a five-part analysis. I donít think I need to say much more than that since it was merely a way to get us started in the discussion today which will obviously continue tomorrow, and maybe Tom Murray would like to either add some comments or lead the discussion a bit more fully.

DR. SHAPIRO: Well I think it is very hard to look at this topic without taking on the real issues that lie behind this, and whether we like the various categories that have been proposed and whether itís identifiable or not identifiable, all those various issues. So perhaps, and I donít want to do that today because we donít have enough time to give some thoughtful consideration of that, but maybe we could begin by asking whether there are any questions and information from members of the Commission. Is it clear whatís here, do you understand, do you donít understand it? Steve?

MR. HOLTZMAN: It may or may not be substantive. I wanted some clarification about Melissaís memo because Iím not sure I understood it or how it was consistent with Shawnís memo. And even trying to understand the conclusions that she says are the letter of the language, cohere with what she then says under B. Is anyone...did anyone else feel a tension?

DR. MESLIN: Part A and B?

MR. HOLTZMAN: Part A and B. I mean A seems...says basically draws a conclusion on what the statute says. Then B offers interim to alternative interpretation of what the statute says. Is that fair, Eric?

DR. MESLIN: Yes. Just to put this into context, the genesis for the memo was two-fold. One, there was a considerable amount of discussion at previous meetings about whether or not the proposed framework that Dr. Emanuel had been sharing with us did or did not fully include or was covered by the current regs. And at a previous meeting, I believe Zeke stood up and indicated certain numbers of his boxes were or were not covered by the regs. And Gary Ellis, who was present at the time, was concerned about whether that interpretation was correct. So in order to provide a bit of clarity, it was suggested to us by some of the Commissioners that an attempt to put that issue into some context would be of use. Melissa then produced a document which identified five items, which had been proposed in the boxes, existing versus proposed items of identifiable tissues, and you can see the rest of the memo. And it was her effort to provide an interpretation of the regs with respect to those five items that is before you.

MR. HOLTZMAN: Right. So under subsection A she draws and interpretation about what is meant by identified, letís put it that way. And then under B, which is the same issue, she offers an alternative interpretation.

MS. CHARO: I think when I read it, I got to tell you, I felt like she was a very well-trained, Yale-trained lawyer who was struggling to find any possible way to make what had been the current discussion at NBAC consistent with existing regs. And she came up with the best possible, stretched, taffy-thin interpretation that I personally would never want to rely upon as the basis for our recommendations because I think the struggle she goes through just shows what weíd have to go through if we were going to do this.

MR. HOLTZMAN: To me this is all very simple actually. In terms of whatís really at stake here is this sentence that if the information is recorded by the investigation in such a manner the subjects could not be identified directly or through identifiers linked to the subject. You either take that to mean that the "cannot" is a statement of logical possibility and therefore itís anonymous or itís not. And if itís not anonymous, then it fails. Or, we put the emphasis on with respect to the investigatorís epistemic state

MS. CHARO: And the facts break. The fact is it does not say that itís okay to use, da-da-da-da-da. If the investigator canít identify the source of the tissue, itís that itís the source of the tissue cannot be identified by anybody.

MR. HOLTZMAN: Iím sorry.

MS. CHARO: Thatís the bottom line.

MR. HOLTZMAN: Youíre saying thatís what it says.

MS. CHARO: Thatís right. If there are links, if there are links that exist...

MR. HOLTZMAN: Okay, no, actually, the ...

MS. CHARO: Then the person can be identified.

MR. HOLTZMAN: ... the question is which of those two things it says.

MS. CHARO: Right. What Iím suggesting is that as a fellow lawyer, when I read her memo and she attempted to somehow interpret these words so that they only apply from the subjective point of view from the investigator, I was impressed by the extreme creativity and the need to have gone to a school as good as Yale to come up with an argument that was even tolerable for that interpretation. I was ... I was quite persuaded by how hard it was for her to do this.

MR. HOLTZMAN: So in other words...

MS. CHARO: That we shouldnít try to do this ourselves.

MR. HOLTZMAN: ... but you found that what she did in section A was just the plain language interpretation of this, whereas in B she was doing a stretch.

MS. CHARO: Correct.


MR. CAPRON: That was my interpretation. I would like for the record to say that I believe a Columbia-trained lawyer would be able...

DR. SHAPIRO: To do even better, right?

MR. CAPRON: ... besides agreeing with Altaís sense when I read this, I want to suggest something about NBACís posture here. I would find it ironic for us to be working on the one hand on reports that aim to ensure protection of human subjects, and on the other to reach a conclusion which says that either a existing protection ought to be removed or ought to be read in this strange fashion. It seems to me it puts the omission in an extraordinarily uncomfortable posture if in one of our earlier reportsógiven the fact the cloning report is already out there, probably our second reportówe say well although past Commissions have said this and that and that has led the federal government to adopt a common rule which says this, that ought to be out the window when it comes to tissue samples. Or that can be read in such a way as it would still allow. The other thing is I wanted to know, although weíre not really discussing fully the substance of it, my impression, looking through the report, the very useful charting that is in the staff document, is that other than situations in which the particular group making the recommendations doesnít make the distinction at all, and just applied the same rules to all categories, almost all of them in some fashion treated differently the anonymous versus the encrypted or coded. And so it really does make very stark how, compared to the LC group and HHS thinks in terms of the existing regulations, we would look very, very different just in our way of describing the world by going with the standards that are here. Now I understand the argument was well you start off by saying that there are these "categories" but you say you donít want to apply different rules to them so you might as well treat them all as one category. But even that step of saying weíre going to end up describing them all as one category will look very different. It doesnít mean itís wrong, itís just that we should be very clear that we are departing from the way that almost everybody has looked at this.


MR. HOLTZMAN: I think itís very important for our terminology to be accessible and be explained against the backdrop. If we want to define certain categories in terms of the policies we use, we should make that very clear. Just for the record, and Zeke is unfortunately not here, some of us... Some of us who are neither Columbia nor Yale nor wherever-trained lawyers, okay, or lawyers at all, but feel we have some sense of plain-speaking language, actually read this entirely differently than you do without any twisting of logic whatsoever. Because I find important the phrase, "recorded by the investigator," okay. And maybe we...and therefore the notion, or what I wanted to say is that when I was first exposed to this subject, I found it a real twist of the logicóthe notion that it was based on the nature of the sample as opposed to how it was being used. Because it goes to the logic of what youíre trying to protect, which is the subject. And if in the nature of the study, you can...itís in the nature of the study that they cannot be identified, that they would be protected.

DR. SHAPIRO: Okay, Tom, then Alta, then David.

DR. MURRAY: Thereís a distinction, one distinction which I think is important that I would like...that I believe is a good one to make. And that is between whether or not the tissue is effectively anonymous in its use by the investigator versus whether the tissue in its original state, say, held in the collection somewhere, is anonymous. And weíve opted for the former and I think that is ...thatís the right thing to do and I will be happy to talk about that more tomorrow.

Now, that still leads to a series of distinctions about what makes tissue anonymous in its use in research. And there I think weíve got several different distinctions and I will also offer some of them. And I think I just donít want to confuse the first distinction with a series of other things having to do with whether or not thereís a coding scheme that will allow someone to reidentify the tissue, whether it comes with lots of additional demographic information versus no demographics. Those are other kinds of distinctions that we do need to focus on because I think there was merit in the criticism last time that we were not careful enough in making those distinctions. So I think we do need to make those. But I would...Iím going to propose tomorrow that the first one is a useful one for it.


MS. CHARO: Iíd like to make a suggestion about the vocabulary being used. The word anonymous is being used in different ways by different people. For example, in Melissaís memo she uses the word anonymous to mean unidentifiable by any possible means. She does not use the word anonymous to mean coded so that itís impossible for anybody without a code-breaker to know about whom the tissue is...from whom the tissue is brought. And yet in our the Subcommitteeís own work, the word anonymous seems to be used for coded samples in many situations. And so Iíd like to suggest an abandonment of the word anonymous because it is prone to so many differing and perfectly natural interpretations. Just for the sake of making sure we all know what weíre saying when we say it. And to suggest no matter what rules eventually emerge, and whether or not theyíre the same for any of these different categories, that we stick to "unidentifiable," meaning thereís no way anybody outside of an admission team could track back the tissue to the donor. Unidentifiable, period, end of story, no links at all, coded for those things that are linked, and identified for those that come with a name. Tom has already...Iím open to suggestions but something thatís truly clear so that at least when we continue to talk we all know what weíre saying.

DR. MURRAY: I actually like the idea of talking and saying nonidentifiable or unidentifiable rather than anonymous. I am perfectly happy with that. I think...maybe should I Iíll say it very quickly. Iím sure weíll talk more about it tomorrow. In Shawnís memo, he talks about the standards the Secretary offered, reasonable, a standard of reasonableness. They reasonablyóI donít have the precise language hereóbe regarded as nonidentifiable. I think, I donít think we want a standard of divine unidentifiability. I think we want a standard of reasonable unidentifiability.

MS. CHARO: But if you go back to the history of that, what weíre talking about there really is about the N in various of your boxes. I mean if youíve got certain kinds of demographic data, does it yield the ability to know who it came from right ... so it was not by implication. If youíve got it coded and youíve got a big enough firewall, it renders it unidentifiable. That was not the intent behind that notion. It was that demographic data does not render something identifiable. It can still be considered unidentifiable so long as the N is large enough that you donít know who itís from. And thatís very different from coded data.


DR. COX: Iíd like to step back for a second and ask a broader question. What are we really talking about? Whatís our goal? And I think Pat Barr at our last NBAC meeting did this quite eloquently. Because itís not really whether one should look at the definition of whatís anonymous or identifiable or any of that, but what is it...why are we considering this issue? And weíre considering it, in my view, to figure out how to in one hand use stored tissue samples to advance research, and on the other hand protecting subjectsí rights in the process of doing that. And so I think that one of the reasons why this discussion continues to focus on this statement about whatís identifiable or whatís not identifiable, is really sort of obfuscating what the real issue is, which is are things okay the way they are now or is it going to require a change in the way weíre doing business? I canít answer that question unless I step back and say, what is it weíre trying to achieve, whatís going to be the practical structure in which weíre going to achieve it? So talking about it in context of firewalls that donít exist is very difficult for me. Talking about it in the context of structures that may exist right now, that allow research to be ongoing and then say do they afford the appropriate human subjects protections, I find a much more useful endeavor. So thatís what Iím going to try and do tomorrow. And not really have a discussion about is there a way to sort of fit this into the present regs or not. I mean I donít find that useful. I see why itís one way of looking at the problem, but I donít find it nearly as useful as saying what is it weíre trying to accomplish and is things that we have in place right now sufficient to allow that to take place.

DR. SHAPIRO: David, Iíd like to ask a question which really came from an issue which you raised last time and as also, we donít have time to resolve today, but we can get back to it tomorrow. You may remember that you raisedóI believe it was you that raised the issueóthat you looked at all the interesting research thatís been going on, that it really required extensive access to the medical records in order to make some sense out of it, in order to carry the projects forward in most cases. And indeed if you look at Dr. Kornís paper, his examples have that characteristic. Many of these cases required detailed knowledge of the medical record of 70 or 80 subjects or whatever it was in order to carry forward. Now to the extent that thatís correct, you always need a lot of information but nameless, Social Security number aside, so itís not name and address, but itís substantial medical information or substantial information content. Iím trying to figure out in my own mind whether that per se will make this identifiable and whether one is really faced with that sort of irreducible problem. That you need enough information or you donít. Given what you think about...and itís really a question of what the scientific agenda looks like in this area.

DR. COX: So Harold, Iíll give you my answer to that. Thatís exactly where Iím coming from personally, because I think that if the scientific research is going to lead to something thatís useful, which to me is a therapy, then to think about that youíre just going to not need...not every single piece of research thatís being done is going to need the detailed medical records. But ultimately a structure that allows that to happen and focuses primarily on that end of it instead of what the traditional end has been which is that you just do it where you donít need the medical record. I think thatís whatís different here. And the... and so I donít believe that the structure that weíre looking at right now and that weíve used for the past hundred years is going to serve us well in the next hundred years.

MS. CHARO: Harold, a lot of the information you need really does not identify people, you know, 36-year old female with following condition and following history, right.

DR. SHAPIRO: Iím just asking a question. I donít have a view of it.

MS. CHARO: Right, but long as the cell slide is large enough that is doesnít reduce it to two people in the country, you know, on this particular Chippewah reservation in Wisconsin, youíre not going to have this problem. But the trick that exists is when what you want to do then is move forward and continue tracking, not the person but their medical records.

DR. SHAPIRO: Thatís what scientists want to do, you know.

MS. CHARO: Right. Thatís some ways this is a very temporary problem because for all the people that are already dead the entire medical record is accessible already. So you can get their entire life history with the disease. For the people whose tissues are just being collected now, you can in fact create a prospective consent process that allows for going back into the medical record and extracting information. So itís only for people whoíve got existing tissue or currently alive, part of their prior medical history...their medical history prior to the tissue collection is accessible and what you want is only their current and future medical status. Itís a transient problem in some ways that is creating all this enormous....

DR. COX: I think I really disagree with that, Alta. I donít think itís transient. And Harold, you said it in a very nice way in this other issue in terms of staging. Now maybe this is not a good analogy but thatís the way Iím using it, because I think that one of the ways that much of this research is done is first you go and you look at a very large sample of people, and then you would say I want to look at a subset of those people in more detail. And then you look at even a more subset of those people. Now certainly the conclusions that you come to ultimately youíd like to go out and apply it to a very broad-based number of people. But the process by which the research is done is that getting a sample and then learning more about that sample and learning even more about the subsample of that. The, I think that thatís the process. And given that being the process, to set it up so that everything is well, you donít really need to know that much about a particular group of people, in fact the process says just the opposite, that what you want to do is learn more and more and more. Now it depends on what the stage youíre at is, because if people always stay at one stage and theyíre just at that general stage, they never need to learn more. But what are we trying to accomplish? Weíre trying to accomplish more detailed information and more specific clinical trials to come up with therapies than I think that you do get more and more detailed information. So itís the staging where you have broad numbers of people and then more specific, and then you get more specific.

DR. SHAPIRO: In that environment I think Altaís right. A lot depends on whether the material you need as you go ahead in the process you describe is the prospectively collected or whether it requires going back to stored tissue. All right, we will get our chance to exercise a good deal of this tomorrow again. So...letís not...

MR. HOLTZMAN: Itís not a transient problem.

DR. SHAPIRO: Oh thatís not. I understand that.

MR. HOLTZMAN: Weíre going to continue to have the issue of people giving tissues in the surgical context simply or under generalized consent because you canít envision all of the future studies you will want to do and you will want to have a system to continue this epidemiological information, it can be more and more detailed but it wonít necessarily be sufficient to identify the individual.

MS. CHARO: Wisconsin is currently writing up a surgical consent form that will allow people to release for an enormous variety of currently unforeseeable uses. So I do think itís possible to have for prospective collection a solution for this problem.

MR. HOLTZMAN: And therefore those samples will have to be maintained in a fashion such that they are not unidentifiable, using nomenclature.

MS. CHARO: You mean, in other words, coded.


DR. SHAPIRO: The issue for me, Alta, there is Iím sure that those kinds of consent forms can be structured. Now I havenít looked at...

MS. CHARO: Whether or not theyíre legitimate.

DR. SHAPIRO: ... but whether they have..what the ethical content of that kind of thing is as exactly the issue that weíre going to have to struggle with.

MR. CAPRON: But isnít part of the issue here whether the consent should basically be a little bit clearer notification that such research is out there, do we have your permission to get back to you about this, or to use youróone choice, which is what the cancer people suggested we look atóor to use this tissue without your further consent provided that we do it only with coding so that we wonít have your name on the sample. I mean that choice could be put to somebody in a way...which in effect says before you really get involved in research, weíll come back to you with the specific project and weíll get your consent. But what weíre asking for now is whether you want to have this tissue thatís available for that, just be alerted that this is going on. And that would be a huge change because all the studies that weíve seen indicate that most people donít even know that their tissues are saved and used for research.

DR. COX: Yes. But, Alex, the process ... what you just described is the way the process of research is going to be done. And you said the bottom line: itís a huge change from what weíre doing right now in terms of how the people that are giving the samples are involved in the process.

MR. CAPRON: But weíre...I think what, frankly, what I sense the tension in this room is when I was talking about the Secretary of HHS. There is a conflict of priorities here. And we can derive any conclusions we want. Itís appropriate that we be a body that represents the spectrum of views but there is that conflict of priorities and weíre going to be pressed to come up with the most reasonable balance of those priorities.

DR. SHAPIRO: With that we are four minutes past our adjournment time. And itís the first time weíve allowed us to go past adjournment. So thank everyone very much. Eric, what time do we reassemble tomorrow morning?

DR. MESLIN: Tomorrow morning weíre at 8:00 a.m. And weíre in the Wilshire Room, which is just around the corner, same floor, just out the back of the doors here. Itís the entire Wilshire. You get three chairs a person. Weíll see you at 8:00 tomorrow morning. Thank you very much.

ADJOURNMENT, DAY 1: 5:34 p.m.