CONSUMER PERSPECTIVES ON CURRENT ISSUES (Slide.) MS. BARR: It is easy for me to speak strongly about this topic because I have been working on it for a long time. I am an attorney. I come from Vermont. I am the chair of the Ethics Subcommittee of the National Action Plan on Biological Resources and I have been for the last six years a very active member on the National Breast Cancer Coalition. The Coalition in '93 had a campaign in which we called for a national partnership, public and private, to look at key issues in breast cancer and it was out of that petition campaign, which collected 2.6 million signatures that we developed the National Action Plan in Breast Cancer, and then I was lucky enough to be appointed to do some work with that group. (Slide.) Now we dealt with clinical samples, samples taken in clinical practice, and we dealt with some of the practical issues. So the approach that I am going to be presenting compliments to some extent the approach that you just heard earlier. Let me talk about what we decided to do because of the quagmire that we found ourselves in when we took on this issue. One, we limited ourselves to prospective collection because retrospective collection we felt as a starting point was going to be a very difficult starting point. We were most concerned with samples taken in routine clinical practice because many samples that are available for research are those samples held by individual pathologists who may or may not be affiliated with a research institution and we -- this program motivated by patients and advocates -- were very interested in ensuring that the role of the tissue donor was seen as an active role and a role of a partner. We wanted to develop user friendly -- a user friendly consent process, not just a document, that was going to be meaningful to both patients and researchers and we were looking to standardization because we believe standardization will facilitate research and our goal was to facilitate research. (Slide.) I want to talk about what we produced because you have -- and you have it. It was distributed in your meeting materials. We produced a consent form and it was initially a layered consent form. We produced an informational brochure because we felt that the form itself would not -- was not explanatory enough and we knew in clinical practice things were going to have to be somewhat telescoped in. We have a model for "banking" operations that I think addresses some of the concerns that I have heard raised before this morning and we provided principles for use in tissue collection and dissemination. We take a very strong position that we would like to distinguish between IRB's. There are IRB's that review research protocols. The researcher wants tissue and his or her institutional IRB is going to review that protocol. We believe there should be an IRB affiliated with every tissue resource. So if a pathologist, indeed, has collected samples and that pathologist is willing to distribute those samples that pathologist is a tissue resource and, therefore, certain principles should be in place for the operation of the distribution of the resource and there should be an IRB that is ensuring that those particular principles are followed. Now I should say at this point that it was always understood that though we were funded by the National Action Plan on Breast Cancer our work was to be a model and, therefore, we do not see this work at this point as only pertaining to breast cancer samples but see it as a model for any tissue banking that is done and tissue resource distribution, and that the language in the form is easily modified and, in fact, the PRIMER working group that took us on from us has done a lot of that modification. (Slide.) What are the challenges even to perspective collection that must be addressed? The independence and variability of expertise found in IRB's. The limited resources of IRB's. The IRB community responded to what we had presented saying how can this be paid for, how are we going to do it, and the informatics and processing difficulties in giving donor's choice. When you are not in the research setting, when you are in the clinical setting and an individual donor is given the choice of this can be used for cancer research only, this can be used for all research, this can be used for all research except behavioral research, I only want this used in this way or that way, you get a very difficult storage problem. You get a very difficult coding problem. You get a very difficult transfer problem. So as much as we wanted in the clinical setting to layer the consent form and as much as we wanted to give choice to the participant donor we opted because of the practicalities for two choices, "I will participate and my tissue may be used for cancer research, my tissue may be used for other research." And even with that the pathology community is very concerned. NCI is working with them now on costs and management of the process. So there are costs to pathologists that is real time and money in clinical practice. There are costs to the surgeons in real time and money in adding anything to the standard consents that they now use which we deemed totally inadequate for the purpose. And then we have come to learn that in clinical practice pathologists will routinely throw samples away. If what we are truly concerned with is the value of archived tissue as a national resource then, in fact, we have a problem about not only keeping the codes right but keeping the tissue properly stored for use. (Slide.) We are working on solutions or we have handed this over to other people to work on solutions. We wanted to summarize and stop doing this. Let me say by way of background that before I began doing this work I certainly was an advocate, I am an attorney, I did not particularly do ethics work, and I came to this with a kind of naivete and impatience because of my status that have proven to be very useful because people who are naive and people who are impatient tell other people, "Well, we can get this done," and they keep pushing and it gets done, and the group that worked on this was very multifaceted. There were pathologists. There were ethicists. There were other consumers. There were population studies people, public health people. There were surgeons. So there was a wide variety of mix. There were academicians and there were clinical practitioners in this group that worked on all these. So where are we? We handed our model documents to PRIMER or PRIMAR and they have put them together very beautifully with a summary of the joint meeting we had with their concerns and have distributed them at their plenary session at an annual meeting just last month with feedback information. Now some of that concerns me. When we took this material and we were looking at OPRR and said, "You know, we need to move to guidelines for IRB's because if we let them all flounder with their various levels of expertise we are not going to facilitate research and every researcher who wants to use tissue is going to be up against five different standards if he is going to five sites for a multisite program, ten different standards if it is ten sites for a multisite program. So there needs to be some standardization and what we were told is, "Well, NBAC will do this." So I feel greatly honored to be here before NBAC in great hopes that, in fact, you will do some of this and that will provide guidance to the IRB's who are concerned about their ongoing role in this area. One of the things that we -- that was most controversial and what we suggested that I think is very important is that there should be a panel associated with every tissue banking enterprise that will review protocols that come into it so the protocol may be reviewed by the researcher's institution that wants to support a researcher doing certain work but tissue is a limited resource. It is becoming very limited in breast cancer because of the size of tumor when the tissue is taken but I am sure that this is an issue in many other areas. If you have a limited resource then you have to prioritize how it is used and there has to be conversation with communities of interest about how it is going to be used. The concept we were talking about earlier which is community collaboration or community consultation. Someone has got to do that and there have to be standards for how it will be done. It seems the likely place for that to happen is with the tissue because they get an overview of what is being requested, the timeliness of it and the amount of it. So we have suggested that an IRB affiliated with a tissue banking institution have -- appoint a panel that will do that kind of review. IRB's do not want to be responsible for that panel. When we asked them, "Well, if not you, who?" There was no answer. So I will say to you, "If not them, who?" But clearly that is a very important function in all this. It is a vital function in all this. What needs to be done? Just clear OPRR or NBAC guidelines. Just what I have talked about. Some standardization of documents so researchers do not get approval in one place, then go to the next place and have to change it and then go back to the first place because they need consistency in their trial. If they know they are using tissue and we can simplify what has to be done so that they can use the tissue we will have facilitated research. That was our goal. And finally because we are looking at testing in a clinical setting we are doing some pilot testing with NCI of using this consent in the clinical setting. And what we have done with is it is an add on to the general surgical consent and we are doing some pilot testing and presenting it at different times, sometimes in the doctor's office and sometimes unfortunately the night before because that is when it really happens, and trying to get feedback. You should also know that we focused group the documents and as a result of that working with different ethnic communities we got a lot of very good feedback on how to change the documents and it was from that process that we did the informational brochure. (Slide.) A few more solutions. NCI is actually working with professional groups now regarding costs and storage guidelines. That is going to be a long process. NCI and DOD are talking about a national storage system. That is very preliminary. And then we are in a world where there is ongoing attention to informatics, questions of encoding and safety. Now what we did about the flow of information is that we said tissue needs to be used and no one can know today what the uses will be in five years or ten but that we can predict today that the valuable tissue will be linked and it will be linked to clinical information and that the need of the researcher will be for the clinical information with the tissue. And, therefore, we needed to come up with a model that could satisfy protecting the individual but allow the research to proceed. The model that we came up with was a fiduciary standing at the tissue standing with the bank. They devise a system for collecting the tissue and they send the tissue out with the appropriate clinical information but without the identifiers. Coded information is what we have used that we think is essential. Now I believe we can apply some of this to the archive samples that exist but we for political reasons, very good political reasons, look forward rather than back but I know you care about back so I decided to be brave and talk a little bit about backwards. (Slide.) The existing resources are vital. It will take us a very long time to get consents today and then prospectively deal with the longitudinal data that we want. The consents that are in those surgical practices are totally adequate so there is no way we are going to fix that. And it is not practical to reconsent. The cost is just too great to reconsent in a clinical setting. Research setting is different. In clinical setting it is not possible. So either we throw that stuff out, which I think would be a tragedy, or we come up with something that is going to help and make it possible to use it. When I first got into this field what was interesting to me was there was a profound conflict about ownership of the tissue. Pathologists thought they owned the tissue. Patients thought they owned the tissue. Now what I have learned to do, and I used to do a lot of mediation, is decide that the best thing to do is not talk about ownership. So I put it up here as a problem but it is a problem we can skip. We can jump around. We can dance around. What we talk about now is fiduciary responsibilities which is pretty comfortable for everyone to talk about and the pathologists agree they have a fiduciary responsibility here. If we are going to proceed to use archived samples we must have public confidence and if we do not have it we are going to lose our ability to do prospective research as well and that public confidence must be earned. It is not going to happen. It must be earned. (Slide.) So what are the considerations? We are going to have to establish standards for population studies using archival tissue. We are going to have to protect individuals the best way we can and we are going to have to address the interests of communities when we do population studies. We must provide adequate compensation for those who manage the collections and we have to standardize the management of the collections. I think those things are just essential. (Slide.) I want to talk a little bit about the pathologists because I know they talk a lot so I will talk a little bit about them. They have a fiduciary responsibility with respect to the patient. They acknowledge it and they talk a lot about it, and that is to ensure that what is there is preserved for care, patient care. They have a fiduciary responsibility also to the resource itself and this is where we are breaking new ground where we begin to think of these resources not as belonging to the pathologist but belonging to the research enterprise and that the pathologist is the fiduciary of that research enterprise. They become -- in a national system they are not the arbiter of who gets to use the tissue they hold. Now today they are the arbiters of who gets to use the tissue they hold. So I am presenting a radically different approach. But they do deserve adequate compensation for the work they do in serving as fiduciary responsibility to the research enterprise as a whole. I think that the model that we put in place of a neutral third party, the IRB and the tissue bank, is applicable to archival collections as well as perspective collections but the standards for what must be done in a population study or other study when we are using archival tissue is obviously going to be somewhat different than what it might be in a perspective situation. (Slide.) I am going to talk just briefly about standardization and then I think I am done, almost done anyway. Standardization impacts donor participation and I came to this enterprise because people wanted to help the research process. Now that is a limited population. There are populations that are much more skeptical than the population I came from and there are portions of the population that I speak for that are more skeptical than other parts of that population. But there is an interest in doing good and there is an interest in doing good particularly when you are faced with fearful circumstances. It is a way of gaining control and experiencing some sense of control. I would not underestimate that as a benefit to those who donate tissue for research but we have got to make it simple for those people because as you have talked about they are under a tremendous amount of stress. It has to be a system that is easy enough to explain and there is some discussion of it in the world out there. It is not a secret of researchers and academic institutions. You have to give these donors access to this system so it should not be dependent on, "Well, I have a doctor who is willing." There is some presumption that there is a way to access that system. Lack of standardization hampers research. It makes locating research is very difficult for researchers and the hoops they have to jump through because every site or every IRB is quirky are unreasonable. They are just unreasonable and time is lost and we cannot do the kind of multisite studies we want to do. (Slide.) So how do we deal with anonymity? I think that you have been struggling with it. I suggest that we separate the researcher from the linkage using a third party trustee. We insist on community participation and resource use review and we strictly limit reporting of individual results. My subcommittee said we just do not do it. Done. Easy. No. The IRB said don't be so limited. There may be a very important situation like a misdiagnosis that is discovered where you want to be able to get back to the patient. So we have strictly very rare -- and we put in some adjectives removed -- removed from that. But those are some of those factors that have to go into continued use. (Slide.) And the practical realities are we have got to come up with something relatively simple if we are going to do in clinical practice. We have to frame the solutions for the real reality out there. There is a lot of tissue out there without adequate consent. Every problem can be solved and many of the economic solutions and the solutions will be found in partnership. I think that is true of the Action Plan's experience that there has been a lot of betting, there has been a lot of concern, but in the end we moved forward in a very constructive way and we have been able to gain a lot of support for our work. DR. MURRAY: Thank you. Time for questions. Alex, Bernie and Zeke? Try to hold this microphone very close and be heard. MR. CAPRON: I will try. The presentation I have found was very informative and I want to thank you for the obvious work that has gone into it. I hope your expectations that NBAC will solve everything for you are not exaggerated. There are times when I wish that a couple of the major figures in the history of human experimentation and the analysis of it were with us. One of them, Jay Katz, could be; another, Hans Jonas, cannot. But the three thoughts I want to introduce along the lines of what Rhetaugh was doing in saying let's stay with fundamentals are the framework for a lot of what goes on in the field thinking practically is one in which researchers, physician researchers, begin from a sense of basic beneficence that they want to do good and that that sense of wanting to do good has at least in the past, not to speak to any present or future physician researchers, has led to a lot of paternalism. I am sure that in the breast cancer community that has been an issue to which a great deal of thought and writing has occurred but it is something to keep in mind here and it came through in your comments also about the pathologists. The sense that I have a resource, I want to do good, I want to determine what happens with it. The second is a phrase that you used about the tragedy of not doing research and it is here that I want to invoke Jonas' ghost because I still am convinced by his view that the greatest tragedy is doing things which end up harming or wronging people in the name of the greater good of progress and that progress in his phrase is an optional good and it is a good which ought not to be bought at certain other costs which can occur even in well intentioned circumstances. Now obviously he was not -- his was not an argument for doing nothing but it is a question of what presumption we go into things with and in that line I would like to put four points to you and ask you to elaborate on them because they were so intriguing as you went along. The first one was the notion that with some of this research, particularly I guess on retrospective research but maybe it went to both, public confidence was essential and you said public confidence had to be earned. I want to know have you given in your reports you think some attention to how it would be earned? Would it be a matter of a researcher being very public that I am going to be going to X, Y, Z source to get the tissues there and the research I am going to be doing is this and here is the protections that I have erected, and because I am not going to the individual women from whom the samples came I am going to the community. So, I mean, there is a public notice, as it were. If this bothers anyone who thinks that her tissues are there let me hear from her. Or is it a matter not of that kind of confidence that you actually would be able to have some say at a later time but something else? The second question is to ask you to tell us why this phrase "fiduciary responsibilities" was used. I understood one way in which it was being used. If I am a pathologist and I hold tissue I have a responsibility that the tissue continue to be usable for the clinical benefit of the women from whom it came. So that means I should not expend it all or I should not lose it or mislabel it and so forth. But part of the other notion of fiduciary is usually a fiduciary should not use the property or other things that are those of the beneficiary, the ward, or whoever, the client, in a way which benefits the fiduciary and does not benefit the ward. I mean, that is sort of -- and yet it does seem to me as though what you are talking about here are situations in which that on the surface would be -- I mean, if you see the person holding the goods as in some way related to the research project and as furthering research if it is done without the consent -- I just want you to say why that term really applies because fiduciary is a very -- to me is a very high standard and it invokes a lot of connotations which are different than paternalism and beneficence. There are some fairly strict ideas. You may have other ideas and, if so, I would favor another term. The third point is you talked about the burdens of allowing patients to define their role as subject and you explain that that led you just to make the two divisions that you made. We heard from the presentation that Susan made that many more divisions and a more refined consent process were being thought about. What it seemed to me you were saying was it would simply cost too much. Now research would also be easy to do if we could commandeer laboratory space, and pipettes, and beakers, and solutions, and so forth but we do not. We regard those as things on which money has to be spent. I want to understand if what we are talking about here is simply a trade off. It would be more expensive. Are you saying it would be logistically impossible to have a code attached to each sample because we are only talking here prospectively obviously, a code attached to each sample and so if someone says I want to have the available breast cancer -- the samples that meet the following definitions that you would run the computer and it would say, "Well, these women said you can study it only for breast cancer and you are doing another study so they are out and then these people said, 'I wanted to be recontacted before you did a study,' so we will have to contact them and if we are not willing to do that they are out, and so forth." Is it logistically impossible or is it simply a matter that that would be an expense where someone would have to pay the pathologist or the tissue bank or whatever to do? The third one is this thing that you came to toward the end which was a reason for breaking the barrier and you have cited one which would be an example of clinical benefit. My God, that was a misdiagnosis and we ought to tell the person now that our lab has run a different study that they were misdiagnosed and that something went wrong. You suggested that you had worked out a statement of when the barrier could be breached back. You did not work it out. I thought you said you had some criteria. DR. BARR: We compromised with the IRB's who felt that -- we compromised with the IRB community in working on these documents in saying that there needed to be room for IRB's to make decisions about when there could be a breach. MR. CAPRON: Okay. MS. BARR: Our committee felt very strongly that that would -- that was not appropriate, that you just do not go back because it is research, it is not clinical practice. MR. CAPRON: I mean I have a sense that your earlier intuition, which is IRB's need a lot of very firm guidance on this, is right and whenever we say, "Gee, there is too much disagreement, we cannot figure it out, we are going to leave it to the IRB --" MS. BARR: You are in trouble. MR. CAPRON: -- that we are in trouble and the variation you are going to get among IRB's from those that really have thought about this very well and really go through a very careful process to those for whom the issues just do not emerge and so they easily approve it or disapprove it is going to be extreme. I am very worried and I hope that -- this is to my fellow commissioners -- I hope that we in looking at it will think about what kinds of guidance that would be because that breaching the barrier and going back for "what are good reasons" is an essential issue on this anonymizable or identifiable, or whatever the phrase that we end up using, encrypted information. But I have those other three points if you could -- I think you took notes on them. MS. BARR: I did. Let me try and go backwards. On paying for the code, I basically come from a world that says you usually do not get the whole pie and that is because I come from a very political world. That was my prior activist sort of training. And so what I have learned is that you set -- sometimes move in incremental steps. And faced with a very large problem and a desire to move the process forward what our group did was locate two areas of grave concern in terms of facilitating research with research. One was lack of standardization and guidance for IRB's and the other was the consent process. And so we did the work we did to address those problems. In doing that work we wanted to give the donor as much freedom to code as possible but it seemed that at the state of technology and the world we were entering where they did not even give consent it would be a very good step forward to insist on consent and then at least offer choice. As a community gets used to simple choices then perhaps we can add more complex choices as our informatics become more sophisticated. In an ideal world would I be standing arguing for really sophisticated coding? Absolutely. But in a world in which there was going to be significant resistance from clinicians who are not researchers and who had a resource that researchers were going to want to use we made a judgment. Now if this group believes that the research community itself can get enough tissue for research purposes specifically designated for research purposes without going to the clinicians in the world, that is an interesting point. It does mean that participants like me, who may have her biopsy in a local hospital, never get to participate in the enterprise. So am I willing to trade off a lot of choices for some participation? My view is yes. Others might not and they can say no. MR. CAPRON: And how do they say no? MS. BARR: They say no by not agreeing to research or not agreeing to other research in the consent but at least that gets out to the public, which has a number of benefits. It allows individuals to participate. It raises our confidence in the research enterprise because a lot of people are participating and there is some exposure. Now the issue of fiduciary -- MR. CAPRON: May I ask you -- DR. MURRAY: Alex, I am going to have to -- MR. CAPRON: Well, let me -- DR. MURRAY: In the interest of time, we have about 30 minutes left for all of this morning's conversation, unless it is really urgent I am going to ask just to let Pat finish. MS. BARR: Okay. On the issue of fiduciary you have identified the traditional notion of what a fiduciary is and I am perfectly willing to change the word but it seems to me that what we are talking about here is that the pathologist has to stand apart from his or her world as researcher and that they have no higher right to use the tissue that they hold than anybody else. DR. MURRAY: Thank you. MR. CAPRON: And public confidence? MS. BARR: And the public confidence issue is exposure -- public exposure of this kind of debate. IRB's, local IRB's having a duty to inform their communities of what they do in some way through local hospital newsletters or whatever, guidelines for that sort of thing. Ensuring that communities of interest have a role in design of research and advisors to research panels, and advisors to consortiums. That would be a -- those three things would move us forward again incrementally but significantly. DR. MURRAY: I have noted Bernie, Zeke, Carol and David expressing an interest to say something. If anybody else does or I have missed them please let me know. Bernie? DR. LO: I want to thank you for your presentation and also the material you gave us. I have several questions all in the theme of trying to understand better the point of view of patients living with conditions for which these research might be done. First, you said -- I think your message came through very clearly about the urgent need to do research and how having the option to participate in research gives a sense of control and be beneficial. Could you also talk a little bit about what are the concerns that women with breast cancer have about these sorts of archival projects? The second question has to do with the consent process. To amplify some themes that Alex raised, are there barriers to a layered consent process from the point of view of the woman at different stages of breast cancer so that we had heard some anecdotal information that, you know, you have so much on your mind at the time of diagnosis, definitive treatment, that really is not the optimal time from the woman's point of view to enter into the kind of nuance layered discussion that Dr. Old was talking about. So again most of the barriers you were talking about were barriers from the clinician side or from the cost side. Are there also barriers to a layered approach to consent from a woman's point of view? Finally, if you could -- MS. BARR: Okay. DR. LO: We all try and get three questions under the guise of one. So part 2B or part 3 is could you address the issue of being recontacted? MS. BARR: Yes. DR. LO: You said that your group was very much against having recontact to provide research information back to women and yet other advocacy groups have said, "Give us the information and let us decide, do not tell us it is still experimental, it is our body, let us decide." Apparently you wanted an exception when there was clinical information that would make a difference to the woman, like a misdiagnosis, in either direction, more serious or less serious. How about being recontacted to be invited to participate in a research study in which it would be an identifiable link study? Is there -- is that a benefit? Is it a harm? It obviously is going to be different for different women but what should the policy be? MS. BARR: Let me tell you about the policy and the evolving policy. The policy of the Action Plan Working Group was that recontact for additional research was enough of an invasion that an individual should, indeed, agree to it at the time they donate tissue. I am going in for clinical work and one of the decisions I have to make is do I want to be part of this ongoing or not. The IRB community said that to promise that you would not be recontacted unless you gave your permission, which is what it is to ask that question, is misleading because there is information in registries. There is information in other documents. So researchers might contact you anyway for information and, therefore, a particular tissue banking enterprise to make the assumed promise that you would not be contacted. Although they could promise they would not contact you, it would be confusing and irritating. So we have another practical dilemma. My personal view is that, particularly if you are dealing with genetics, recontact about a study of genetics when you did not know your tissue was being used in a genetic study is an incredible invasion. I do not know how we put in place the appropriate protection. What I am telling you is my view, not a study view, and I think one of the things that is clear is that the whole area of study of what a response is and what is important is a study that is something that has to evolve and we need to be putting more resources into that. I do not think any representative patient group can really talk about what their constituency wants because you are generally listening to the most educated, the most -- you know, the strongest advocate speak and so we need other ways to do community consultation to get other points of view. What are the concerns of those active? They are about discrimination. They are about being given information you did not want. The right to not know as well as the right to know. And we are very concerned that the community understand the difference between research and clinical practice and that there be an understanding that significant amounts of research must occur before things get to clinical practice. Now that is not a desperate position. There are people who are suffering from disease who feel a great deal of desperation and I am sure that if they were sitting in this room or if I were in their shoes I would have a different view about where the line is between information I should have access to versus not. So I do not want to pretend that my view is more appropriate. I just want to explain where it comes from. DR. LO: Could you just comment on barriers to a layered consent process from a woman's point of view? MS. BARR: I think if we have a consent process that is not the night before and if we have a consent process that will occur in the doctor's office either with a trained nurse or someone that the patient at this point is trusting, and I think trust is what is important, then I think patients will be able to handle layered informed consents. I do not think it is a complex -- I do not think it is any more complex than we would like to use your tissue for research to say are there certain things that matter to you about how we use your tissue. I think that the compromise here was a practical one from the medical community's point of view and again it was our belief that we wanted to give patients an opportunity to participate. They do not have it now in a knowing way. So this was step one to give them a way of knowingly participating. DR. MURRAY: Thanks, Pat. Zeke? DR. EMANUEL: Like my fellow commissioners I want to thank you for an excellent and spirited discussion. I would like to identify -- I found many areas in which your approach is very consonant with the subcommittee's approach. I think overall there is very little disagreement and actually a lot of agreement, including the issue of standardization of rules for IRB's trying to create a framework that is uniform to minimize exceptions so that people know what the rules are while recognizing that in some cases there may be extraordinary reason. This issue of ownership is one you did not hear all morning because we also, I thought, agreed that ownership was a bad way of looking at it and at least in our mini-hearings found that most people did not have a sense of ownership. That is not to say no one does but to say by and large it is actually not the view that seems to be dominant. There has been spirited discussion and some disagreement about not going back. Some of us believing not going back is the right policy. Others worrying about occasional exceptions. The one thing I would like to raise, and I think this follows up on Bernie's comments, is it is not just a problem of informatics here, this layered consent. One of the advantages, I think, the Breast Cancer Coalition had, the same way that Heart, Lung and Blood Institute had, is they are dealing with specific diseases going in. The problem of writing a general consent not for a specific disease is much more difficult I will submit to you having tried it and I have encouraged all my fellow commissioners to try it because it is not so easy if you are going to take out -- if I go in for a breast biopsy, first of all what happens if it comes out benign is the disease that is similar cancer or is it benign breast diseases. You are already making certain assumptions. MS. BARR: We made the assumption it was cancer generally. That was what our language was. DR. EMANUEL: But if I turn out to have a negative biopsy, you know, what I have consented to then if you say can be used for similar diseases. Is it cancer or not or is it just benign breast diseases? You have already made certain assumptions that someone who goes in for a breast biopsy you are going to put them in the cancer classification even though if it is negative for them they might have gone far away from the cancer classification and they are now normal. Similarly for many other conditions. I think again the issue is not purely an informatics and money issue. The issue also is we may feel in our ideal notions of what informed consent does that the more we delineate the bigger that piece of paper is the better the consent. My suggestion is the more layers you have we, as ethicists, may feel more comfortable but, in fact, the process may be inhibited. What we need to concentrate on is not have we given 12 boxes as opposed to two boxes but do the people out there have a reasonable sense even if we have not included all the specifics and that is why I -- my own view is not because of the informatics necessarily and the complication and cost of the pathologist but for the comprehension and the consistency of the people out there and making sure that once it is implemented without draining all 600,000 doctors and X million nurses, we can be reasonably assured that people are going to know what is out there. So my -- I first was against your form, then very for your form, then having tried to do a general form coming to the view that a layered consent is a good idea but probably two layers is the limit you are going to get. MS. BARR: Yes. You know, I think that I probably agree with you about all of that and I think also that we struggled in an earlier edition of a genetics question specifically. DR. EMANUEL: Right. MS. BARR: And took it out. It is not clear to me that if you are going to work on a general consent and you might want to break down into genetic -- germ line genetic research versus other research as the right -- as a way of breaking this down with the two choices and that we might want to beef up the informational brochure about just what that is and what its implications are. We talk about it in a pretty simple way in our informed consent and in the brochure and that was as a result of focus groups which in this -- for this particular exercise were very useful. DR. MURRAY: Thanks. Carol and then David? DR. GREIDER: I just wanted to reiterate what Zeke said and I felt listening to your presentation that in the broad brush strokes that where you were coming from was very similar -- like I said -- in the broad areas of where the subcommittee at least was going. Some of the details may be different but I think that in general we are on the same page. One thing that you pointed out was different is that you were suggesting an IRB for tissue resource and the question then becomes what is a tissue resource. Ms. Elisa Eisman put together for us a very nice summary of all of the different kinds of tissues that are collected and it is not clear that you can define -- some you can define -- as a tissue resource and it is there to be a tissue resource and some of the NCI resources but others are just a researcher that decides that they want to get together with a surgeon and do a study. So how can you have an IRB when you do not necessarily have a defined group? MS. BARR: I think that by carefully delineating the principles and I think our's are pretty good but that is not to say they should not be changed or refined in some way, and then by saying anyone who collects and then distributes for purposes of research has to abide by those principles. So if I am a local hospital and I have got a doc in my local hospital who is doing this then my IRB in that local hospital has to take on that additional role of being sure it is done the best way to do it. Now it is not cost efficient, I mean, what we are again dealing with. But where do we want to put our money in making sure this works? I think we want to put it in the fiduciary role of those who oversee distribution of tissue and I think we want to put it in that panel that reviews uses of tissue. That is where I think we are better -- we are better protecting people rather than trying to reconsent everybody who is in those archived collections of individual pathologists. It is a judgment call and maybe it is worth it. I think the way I am suggesting allows us to continue to use those archived tissues where reconsent probably will not. So it is a compromise position. DR. MURRAY: Thanks. David? DR. COX: Very rapidly, I really think that where your statements are in process very different from what NBAC is doing, and I applaud your process, is to first have a goal that you are striving towards and that goal is not just how you deal with tissue samples but it is how you do research with tissue samples. I would just like to note that because I think that is the problem you are dealing with. Not tissue samples in isolation. Secondly, is that by having a set of principles that you want to have guide what that product is going to be it helps then for you to define a process and that process of putting things in place for the whole endeavor is what you have done which is what NBAC has not done yet. So I really applaud this as a process. I think that it would be a really good foundation for us to not only pay attention to what the scope of the problem you are looking at but the process that you use and the kinds of things that we would like to come out with. So it was really extremely helpful. DR. MURRAY: Jim Childress would like to ask something. DR. SHAPIRO: Got to be a rock star, Jim. DR. CHILDRESS: The comment I am going to make actually connects with Zeke's discussion earlier this morning and the presentation. I think it is true that it is -- well, I think it is useful to get away from the language of ownership as long as we do not forget that quite often in the legal context ownership simply refers to a bundle of rights and the real question here we are raising is who has what rights over what. The reason for raising the point this way now is to now move to a consideration of whether we think in relation to Zeke's discussion presumed consent with the possibility of opting out really is something that captures all that we want. The reason I raise it -- if we think in the context of organ and tissue transplantation generally there is a lot of dispute about whether presumed donation, for example of corneas in states with certain medical examiner's laws, whether that really is justifiable presumption if people are not aware that their corneas can be taken. So this is actually now picking up the ownership point moving to Zeke. I would like to know a lot more about what we can expect people to understand so that we can interpret their silence or their failure to consent is actually consent because that seems to me to be critical for how the recommendations work out. DR. EMANUEL: Let me, I think, clarify. I think it is a good question. First, presumed consent with opt out was something that had been suggested to us by Bartha Knopfers and I believe, and I do not want to -- if I mangled her name -- I believe I do not want to speak for the full subcommittee but we actually stepped back from that at our last meeting to a general consent. Okay. I know it is on that -- DR. CHILDRESS: At least it still appears on the materials handed out today on -- DR. EMANUEL: That is because what I have included for you is a comprehensive -- not comprehensive, but a thorough list of a kind of history rather than the absolute latest. And let me -- in part because it is in flux. You know, let's just be frank about it. This is in flux. The recommendations are not written in stone and different people have different views of where they want to be. But if you look at the second to last page. DR. CHILDRESS: And that is the one where you said there was an error that needed to be corrected, is that right? Because I still have presumed with opt out. DR. EMANUEL: What I have here is alternative proposed policy. This sheet. The back of it says "key distinctions." DR. CHILDRESS: Okay. DR. EMANUEL: Second to last page. DR. CHILDRESS: Sorry, I was not up -- DR. EMANUEL: No, no, this is confusing. Part of the reason is I was trying to get -- or had e-mailed to Henrietta a lot of the permutations that we had gone through and debated and discussed so people have a better sense. So if you look here at what we have -- and I may not be completely accurate -- migrated to is a general consent and not presumed consent with an opt out. If you would like me to defend the idea of a presumed consent with an opt out I would offer you -- DR. CHILDRESS: No, I was not interested in defending it but rather challenging it. DR. EMANUEL: Right. No, I actually think it is a reasonable position but -- DR. MURRAY: But we are not adopting it. DR. EMANUEL: But I am a minority and am willing to give in. DR. CHILDRESS: That takes care of it. I am sorry. I was on the wrong iteration of this. DR. MURRAY: Harold? DR. SHAPIRO: I have what I think is a very small question, small aspect of what you are doing, but you have focused on clinical samples as I understand it in your work. Do I understand your group to be saying that if a pathologist and a clinician, a surgeon of some type, decides to collect a sample for use in some way they want that neither of them has any privileged status in the use of that material but even if they want to use it for their own project that they have to go through the same thing the third party would have to go through or have I misunderstood that rather small part of this issue? MS. BARR: I think you misunderstood. DR. SHAPIRO: Okay. MS. BARR: If I, as a surgeon, go to a pathologist and say, "I have a protocol to do this particular research and it is within an institution and we have gone through the IRB and they have approved it and we are going to consent every individual before we do the research specifically to that research." DR. SHAPIRO: Then they are fine. MS. BARR: They are fine. But if I, as a pathologist, have a collection of the last 15 years of patients who had been through my hospital and I am dishing this out, no, you cannot do that anymore. DR. SHAPIRO: Yes. Thank you. DR. MURRAY: I actually have myself on the list mainly to praise you and the work of your group, Pat. I want to pick up on Jim's first point about how to understand property. Indeed, as I understand it historically, it is a bundle of both rights and duties. I think your group has stressed the duty aspect. Courtney Campbell, who wrote a background paper for us about some religious views about the human body and how they might be interpreted for the kind of problem that is facing us came up with, I thought, a very nice variant of the whole notion of the human body as gift and he talks about in this kind of context it is like a contribution that you make. It is not a gift to a specified individual but it is a contribution to a larger kind of effort and socially desirable goal worthy of our support. I think that is probably a good way to think about it in which the case the people who are then holders of that contribution have duties, not merely rights but duties, to handle it in certain respectful ways in keeping with the intent of the donor and the like. That to me -- and I have to confess that makes a great deal of sense to me. So that is the first item of praise. The second thing I would like to do is Rhetaugh asked a question earlier, which I think really -- it is an important one. It deserves as full an answer as we can give it and we do not have a lot of time left before we must begin to close the morning session but if I may try to repose the question. Why don't we go back and why don't we simply have a rule that says for samples collected prior to our report that none of them may be used without explicit consent? I think that -- Rhetaugh? DR. DUMAS: After hearing the presentation I -- DR. MURRAY: You need to use the mike. DR. SHAPIRO: You have got to get close to the mike. DR. DUMAS: After hearing this presentation I have had some second thoughts about that. I think, first of all, I would continue to feel that our overriding principles should be informed consent. If you have got a number of samples that you have had for a number of years and it is literally impossible to gain that consent then my next question would be what is the next best principle to use and I like the idea of the IRB's and the definition of the role of the pathologist. That softens the issue somewhat for me. DR. MURRAY: Pat, did you want to add anything? MS. BARR: I think I really tried to address it. I think it is problematic but I believe that this is a resource -- that our standards about ethics change over time and that is a good thing. We continue to improve and become more thoughtful and more careful but that does not mean that what we do today should bar us from doing important things tomorrow. So what we did ten years ago or what our standards were ten years ago I think we would all agree are wrong but we should not then throw that resource out. We should find a way to use it if we can. DR. DUMAS: And I also think that we should not eliminate the principle wholeheartedly, that we should maintain the principle that wherever it is possible and feasible we should have informed consent and that we should define as best we can the conditions under which we would operate when it is not possible or feasible in the case of accumulation of samples over a long period of time -- DR. MURRAY: Right. DR. DUMAS: -- where there was no consent to begin with. DR. MURRAY: And for me part of my own response to this question of how to think about samples that have been collected historically is in the considerations that Rhetaugh has really just described and Pat had described earlier but also in what we have gotten in the way of public feedback both in testimony in the kind of meetings that I have been reading the notes of that Pat -- many of which Pat has participated in but also in our mini-hearings where we found -- I thought quite surprising -- support of doing scientific research and a concern about having the information if it were ever linked back to the person come back and hurt them and that, you know, the insurance companies are the villains of the piece by and large. That is what people mentioned spontaneously. But generally a sense that it is very much in keeping with Pat's conception and Courtney's notion of this as a contribution. You should use it. If it is there and it might help people, by God, you should use it and that was key. So put all those together and I think it certainly influences my conclusions about how to treat those samples which we already have. DR. DUMAS: They have to have principles. DR. MURRAY: Pardon? DR. DUMAS: Not you should use them but not without principles and some protections. DR. MURRAY: Right. And now that we have been alerted to the significance, the potential significance of the tissue, we should not just -- we should not find past practices acceptable for the future. DR. DUMAS: Right. DR. MURRAY: And we should have a much more -- a much more serious consent process about potential use and I think we very much bear that in mind. It is 12:15. We have -- DR. SHAPIRO: No, no. DR. MURRAY: It is 11:45. I misread my watch yesterday. Excuse me. It is 11:45 by which I mean it is 15 minutes before 12:00 and I had promised Harold Shapiro that we would try to wrap things up about now so that he and I could say a little bit about next steps for this part of the report. Jim, I know, wants to make a comment in general about the report and we may have -- do we have any public testimony? DR. SHAPIRO: Yes, we have one person. DR. MURRAY: One person. So we will need five minutes for that. But can we start with Jim and then I will speak and then Harold?