1 1 2 3 CHARTER 4 5 NATIONAL HUMAN RESEARCH PROTECTIONS 6 ADVISORY COMMITTEE 7 8 Wednesday, December 20, 2000 9 10 11 12 13 14 15 16 17 18 19 20 21 22 2 1 ATTENDEES 2 MARY FAITH MARSHALL, Ph.D., Chairperson, Director 3 of Program in Bioethics, University of Kansas 4 Medical Center 5 6 GREG KOSKI, Executive Secretary, Ph.D., M.D., 7 Director, Office of Human Research Protections, 8 Office of Public Health and Science, OS 9 10 MARK BARNES, J.D., LL.M., Partner, Proskauer Rose, LLP 11 12 SANFORD CHODOSH, M.D. 13 ELLIOT N. DORFF, Ph.D., Rector, Distinguished 14 Professor of Philosophy 15 16 JENNIE R. JOE, Ph.D., M.P.H., R.N., Professor, 17 Family and Community Medicine, University of Arizona 18 ROBERT LEVINE, M.D., Professor of Medicine, Yale 19 University School of Medicine 20 ABBEY S. MEYERS, President, National Organization 21 for Rare Disorders 3 1 ATTENDEES (Continued) 2 MARY Z. PELIAS, Ph.D., J.D., Professor, Department 3 of Genetics, Louisiana State University Health 4 Sciences Center 5 6 ROBERT R. RICH, M.D., Executive Associate Dean of 7 Research, Emory University School of Medicine 8 9 ADIL E. SHAMOO, Ph.D., Professor, Department of 10 Biochemistry and Molecular Biology, University of 11 Maryland School of Medicine 12 13 JUDITH L. SIEGEL, Ph.D., Vice President, Head U.S. 14 Clinical Operations, Hoffman-La Roche, Inc. 15 DENYSE THORNLEY-BROWN, M.D., Assistant Professor, 16 Division of Nephrology, University of Alabama at Birmingham 17 KATE-LOUISE GOTTFRIED, J.D., M.S.P.H., Executive 18 Director, National Human Research Protections 19 Advisory Committee 20 21 22 4 1 ATTENDEES (Continued) 2 3 JACKIE COLEMAN, Personnel Specialist, Program 4 Support Center 5 6 DONNA E. SHALALA, Secretary of Health and Human Services 7 EDWARD M. KENNEDY, Senator from Massachusetts 8 9 FELICE J. LEVINE, Ph.D., Executive Officer, 10 American Sociological Association 11 12 STUART L. NIGHTINGALE, M.D., Senior Medical Advisor 13 to the Assistant Secretary for Planning and Evaluation 14 15 DAVID SATCHER, M.D., Ph.D., Assistant Secretary for 16 Health and Surgeon General 17 18 DIXIE E. SNIDER, M.D., M.P.H., Associate Director 19 of Science, Centers for Disease Control and Prevention 20 21 22 5 1 ATTENDEES (Continued) 2 ALAN FLEISHMAN, M.D., Senior Vice President, New 3 York Academy of Medicine, Clinical Professor of 4 Pediatrics and Clinic Professor of Epidemiology & 5 Social Medicine, Albert Einstein College, New York 6 7 ROBERT COOKE DEAGAN, National Institute of Medicine 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 6 1 P R O C E E D I N G S 2 [Time noted: 9:05 a.m.] 3 DR. KOSKI: We will begin our session. 4 I'm Greg Koski. I'm the Director of the 5 Office for Human Research Protection and the 6 Executive Secretary for this advisory committee. 7 On behalf of Secretary Shalala of the 8 Department of Health and Human Services, as well as 9 the Human Research Subcommittee of the Committee on 10 Science, the National Science and Technology 11 Council, I'm delighted to welcome all of you to 12 this inaugural session of the National Human 13 Research Protections Advisory Committee. 14 To all of the members, the private members 15 of the committee who constitute the voting members 16 of this panel, as well as to all of the government 17 representatives, our ex officio members, we 18 represent not only all of the operating divisions 19 and agencies within -- that are involved in human 20 research within the Department of Health and Human 21 Services, but also all of those Federal departments 22 and agencies that are engaged, are funding human 7 1 research under the common rule. I want to give you 2 a very, very hearty welcome. We're delighted that 3 you're here and look forward to your active 4 participation. 5 I'd also like to take this opportunity to 6 give a very, very special thanks to the members of 7 the general public who have made the effort to be 8 here, despite the weather, as well as to members of 9 the press who have joined us, who I believe play a 10 very important role in conveying the messages that 11 will come from this committee. 12 The impaneling of this federal advisory 13 committee is a very important first step in the 14 overall process of remodeling our national system 15 for the protection of human subjects. The 16 formation of this advisory committee, though, is 17 only one part of that effort. 18 To put this all in perspective, I think 19 it's fair to say that, as humans, we are often 20 limited in our perceptions and our behaviors by the 21 paradigm in which we find ourselves, our belief 22 about the world and the systems, how we interact 8 1 with them. 2 For a long time, people believed that the 3 earth was the center of the universe, and it wasn't 4 until that paradigm was broadened that we actually 5 began to have a fuller conception of the universe. 6 Our desire in the overall efforts that are 7 going forward is to move beyond the current 8 paradigm for the actual conduct, as well as 9 oversight of human research, one that has too often 10 been characterized as being too confrontational in 11 many instances, and perhaps so focused on 12 compliance, per se, as a goal, that it may have 13 actually detracted from our primary purpose, which 14 is, of course, the protection of human subjects in 15 the research that we undertake. 16 So our desire is to move toward a new 17 paradigm, one that's based upon the recognition of 18 the shared goals and responsibilities, and focuses 19 on the center of our universe becoming the well- 20 being, the interest of the research subjects on 21 whom we are critically dependent for all of our 22 human research activities. 9 1 Now, the position that we find ourselves 2 in today is one that has, at least in part, evolved 3 from disclosures of deficiencies and abuses in the 4 conduct of research, and certainly over the last 5 couple of years, we have had not only similar 6 disclosures, but real tragedies that have certainly 7 been the basis for elevated concern. 8 A very natural reaction in an instance 9 like this is to simply adopt a more stringent 10 regulatory structure to clamp down, okay, that can 11 further restrict our ability to do meaningful 12 science. In doing so, we could inadvertently 13 deprive all of us, all of our society, from the 14 very real and legitimate benefits that we all look 15 to science for, and that would be a tragedy in 16 itself. 17 So, while there's clearly a need to both 18 expand and enhance our oversight activities, we 19 also have an opportunity now to take a more 20 proactive approach, one that is positive, one 21 that's aimed at actually achieving a greater 22 simplicity and uniformity, efficiency, and above 10 1 all, effectiveness in our system for responsible 2 conduct of human research, and I hope that that's 3 the direction in which we can move. 4 But I think it's important to recognize at 5 the outset that the only way we are going to be 6 able to do this is by moving forward together. 7 Over the last couple of years, the 8 divisions among all of us, okay, have widened to 9 the point that debate has often been too heated, 10 perhaps not fully informed, but certainly not as 11 constructive as it could be. 12 And in pulling together this advisory 13 committee, we are looking for a new opportunity to 14 begin to seek the common ground, to have the 15 important dialogue that must go forward, and 16 actually, to identify and stand on that common 17 ground, which must be the high ground. So that as 18 we proceed with our research, we will do so in a 19 manner that continues to build public trust and 20 hope in what we do, and also allows us to be 21 rightfully proud of the accomplishments of our 22 endeavor. 11 1 So, it's in this spirit that the advisory 2 committee has been formed. It's in this spirit 3 that I encourage you to go forward. 4 The challenges that are before you are 5 enormous, as are the responsibilities. There are 6 many who will be looking to you for clarity and 7 balance and your advice that we hope will become 8 the basis for rational and effective policies and 9 procedures. 10 So, with that, again, I would like to 11 welcome all of you, and I would like to introduce, 12 for additional remarks, our Chair, Mary Faith 13 Marshall. 14 CHAIRPERSON MARSHALL: Thank you, Greg. 15 And, again, I would also like to extend a 16 heartfelt welcome to all of you, to our guests, to 17 our ad hoc committee members and committee members. 18 I want to thank Kate Gottfried and Greg 19 Koski for yeomanship work in the last few weeks for 20 pulling this meeting together. They have truly 21 done an outstanding and stellar job, and have set 22 the tone, I think, for our work. 12 1 Our guiding principle that was articulated 2 by Secretary Shalala in her sounding board article 3 in the New England Journal of Medicine of September 4 14th of this year gave a very simple message. She 5 said, "No priority in research is more important 6 than the protection of human subjects." 7 Our system of protection must be 8 exemplary. This sentiment and the resulting charge 9 to this committee has been occasioned by a 10 confluence of events resulting in the public and 11 the political will and the professional will for 12 substantial reform of the system of human research 13 protections. 14 This is an extraordinary opportunity for 15 our committee, for the Office of Human Research 16 Protections, for the research community as a whole, 17 for the public. 18 Victor Hugo said, "An invasion of armies 19 can be resisted, but not an idea whose time has 20 come." 21 Our time has come. We face significant 22 and important challenges, and our response must be 13 1 exemplary. 2 To that end, we must be ever mindful of 3 the social contract between the scientific 4 enterprise and the public. Exceptional outcomes 5 depend on the integrity of our process as a 6 committee. 7 So I would propose for our work the 8 following bywords: Integrity, fairness that we 9 must ensure that all who should be at the table are 10 at the table, and that their voices are heard; that 11 we are creative, that we are flexible, that we 12 think outside of the box; respect for our guests, 13 for our fellow committee members. 14 Collegiality among committee members 15 should be the byword, and as Chair of the 16 committee, I will take the prerogative of having a 17 heavy hand to ensure civility among our 18 deliberations, if that is needed. 19 Critical thinking. The essence of 20 critical thinking is the ability to suspend 21 judgment. Each of you, as committee members, was 22 chosen for your exceptional individual abilities 14 1 and for the constituencies that you represent. 2 We should be mindful, however, that in 3 meeting our charge that we aim for consensus, when 4 possible, for clarity; that we focus on our task, 5 that we entertain perhaps radical and innovative 6 ideas, that we are open-minded and flexible; that 7 we have respect for our staff; that we are not 8 reticent in raising controversial or sensitive 9 issues, and that we do not ignore the hippopotamus 10 in the middle of the room. 11 And, finally, I would hope that each of us 12 will feel ownership to the committee and its 13 charge, and that we will take pride in our work. 14 We have a daunting agenda over today and 15 tomorrow. Over the next two days, I would 16 anticipate that we will discuss, refine, and focus 17 on our tasks; discuss what is realistically 18 achievable, identify our needs for data, establish, 19 if need be, working groups, agree to a schedule and 20 a work plan. 21 And I would remind you that these are 22 public meetings, and, thus, we should be 15 1 consistent. We should be open. We should be 2 receptive, and we should be fair. 3 Simplicity, uniformity, efficiency and 4 effectiveness are Greg Koski's bywords. Many of 5 you have heard them already, and we should bear 6 them in mind over the coming months and the coming 7 years. 8 So, my fellow carpenters, let us raise the 9 roof beam high. And I will introduce to you Kate 10 Gottfried. 11 MS. GOTTFRIED: Thanks, Mary Faith. 12 Well, I, too wish to welcome all of you 13 here today and convey what an extraordinary 14 opportunity this is for me to work with such a 15 thoughtful, accomplished, and dedicated committee 16 members. 17 For the federal government, I think as a 18 whole, and DHHS, in particular, to approach 19 proactively such complex and thorny issues involved 20 in human subject research, and an opportunity for 21 us to engage in a dialogue with the public on 22 matters of such critical importance. 16 1 And, finally, for me personally to be 2 involved in an area that I've had a longstanding 3 and abiding interest in. 4 I'm thrilled that everyone made it here, 5 despite the weather, and recognize that the 6 turnaround time from the actual appointment of the 7 committee to this meeting has been rather short and 8 kind of a whirlwind of activities. 9 In the future, we'll have a greater lead 10 time, and I think things will be even more 11 prepared. 12 But I do want you all to know that I know 13 what a challenging task we have ahead of us now and 14 over the next several years, and I want you to know 15 that I'm here to make things happen as easily as 16 possible, and to make things run smoothly and to 17 facilitate your process. So you needn't at all 18 hesitate to contact me with any concerns, 19 questions, et cetera. 20 Thank you. 21 CHAIRPERSON MARSHALL: Jackie Coleman. We 22 -- is she -- is Jackie here? We need to be sworn 17 1 in. Then let us be flexible. 2 [Laughter.] 3 CHAIRPERSON MARSHALL: And I would ask our 4 ex officio members to introduce themselves to the 5 committee. And you are? You'll have to speak -- 6 PARTICIPANT: I'm -- 7 CHAIRPERSON MARSHALL: Thank you. 8 PARTICIPANT: -- at the Environmental 9 Protection Agency. 10 DR. RAKER: I'm Dr. John Raker with the 11 Veteran's Administration. 12 DR. KOSKI: If you could stand -- 13 CHAIRPERSON MARSHALL: Stand, please. 14 DR. KOSKI: -- so that people could see 15 you, please. 16 CHAIRPERSON MARSHALL: Thank you. 17 PARTICIPANT: I'm Bernard Schwetz, FDA. 18 PARTICIPANT: Mal Tanner with the National 19 Institutes of Health. 20 MR. GRAVE: Gilman Grave from the Child 21 Health Institute. 22 MS. LEVINSON: Rachel Levison, the 18 1 Assistant Director of -- Office of Science and 2 Technology. 3 MR. SHELTON: Jim Shelton, USAID. 4 MR. FORCINO: Doug Forcino, Department of 5 Defense. 6 CHAIRPERSON MARSHALL: Thank you very 7 much. 8 What we might do then, since we do still 9 have some time ahead of us, I would like to make an 10 announcement. There is sort of an addition to the 11 agenda. It is a wonderful addition that after 12 Secretary Shalala gives us our charge, we will also 13 have a visit from Senator Kennedy. 14 So, in light of that, and the fact that 15 our agenda may be pushed back, it might be well for 16 us to begin with our committee members. 17 I would ask each of you to introduce 18 yourself. Tell us a little bit about yourself and 19 your background, and also, it would be helpful, I 20 think, not only for our task today and tomorrow, 21 but for the future and in thinking of establishing 22 future agenda items, that you would articulate 19 1 areas that are of special concern or interest to 2 you, that you think we might want to entertain and 3 examine in the future. 4 Shall we start with Mark Barnes? 5 And let me just take, perhaps, the 6 prerogative of saying that, for committee purposes, 7 if you are agreeable, could we be informal and use 8 first names? 9 Thank you. 10 MR. BARNES: Thank you, Mary Faith. 11 I guess the first thing I want to say is, 12 I want to thank the three of you and your staffs 13 for organizing this, especially in what is, by 14 anyone's estimation, a turbulent period in 15 Washington with the changeover of administration. 16 What I think is significant about that is 17 that academic medicine, which is part of my 18 representation on the committee, because I'm a 19 practicing attorney and represent many academic 20 medical centers throughout the country in all sorts 21 of compliance issues, including research 22 compliance, but academic medicine is really quite 20 1 wedded to the idea that conflict of interest rules 2 and conflict of interest policies, for example, 3 among other kinds of research protections have to 4 be looked at. 5 So, regardless of political affiliation or 6 what administration is in charge, whether Bill 7 Roper or Tommy Thompson or anybody else is HHS 8 Secretary, or Donna Shalala, I think that you're 9 right, Mary Faith. This is an idea whose time has 10 come, regardless of the political winds. It's a 11 deeper current than simply one administration or 12 another. 13 I am a partner at a large law firm in New 14 York called Proskauer Rose, and I represent many 15 academic medical centers in all sorts of issues, as 16 I said. My background is as a legal academic, as a 17 patient rights advocate, particularly for patients 18 living with HIV-AIDS, and also as a public health 19 official. 20 I was the Associate Commissioner of Health 21 in New York City during the last couple of years of 22 the David Dinkins' administration and the first few 21 1 months of the Guiliani administration, and I was 2 intimately involved there with the crafting of 3 policies to combat tuberculosis, particularly the 4 crafting of a regulatory scheme to compel 5 tuberculosis patients to take their medication, and 6 if they didn't, to civilly detain them until they 7 could be stabilized and were able to take their 8 medication. In addition, a whole regime of 9 directly observed therapy for tuberculosis. 10 I also served, in 1995, as the Executive 11 Director of the AIDS Action Council in Washington, 12 which is a national lobbying group on behalf of 13 people living with HIV-AIDS. 14 And, before that, I worked at the New York 15 State Health Department as the Director of AIDS 16 Policy from 1989 to '91. 17 So I come to this from a background in, as 18 I said, representing academic medical centers, now 19 as a practicing attorney, as a public health 20 official in the past, as a legal academic. I 21 taught at Columbia Law School for four years and 22 still teach at a number of law schools in the New 22 1 York area. 2 And, also, as a patients' rights advocate. 3 Right now, my kind of particular interest in this 4 committee is that I have seen, both from my work as 5 a patient advocate, and also from my work 6 representing academic medical centers, there are 7 really great and massive achievements of medical 8 research in the area of cardiovascular disease, 9 orthopedic medicine, and particularly, the really 10 lifesaving way in which both the private and public 11 sectors have stepped up to the plate in regard to 12 HIV-AIDS. 13 The achievements in the treatment of that 14 disease are absolutely stellar and, you know, 15 despite the fact that it continues to rage as a 16 real epidemic, not only here, but in Africa and in 17 Southeast Asia. 18 The achievements really cannot be 19 underestimated. They have been phenomenal by 20 anyone's imagination. 21 What I'm interested in here is to see that 22 academic medicine is, and the research enterprise 23 1 are protected in ways that are as little 2 bureaucratic as possible, as least bureaucratic as 3 possible, and as most effective as possible. 4 The idea here, from my -- at least from my 5 perspective is not to saddle either physicians or 6 scientific researchers or academic medical 7 institutions with massive amounts of compliance 8 work. But, instead, to make sure that the end 9 product is that human subjects are protected in the 10 most efficient, least intrusive, but most 11 protective ways possible. 12 CHAIRPERSON MARSHALL: Thank you, Mark. 13 Sandy? 14 DR. CHODOSH: I'm Sandy Chodosh. I'm the 15 President of PRIMAR, which is Public Responsibility 16 in Medicine and Research. It's an organization 17 which, for the last 26 years, has been devoted to 18 teaching people about the ethical and practical 19 methods that need to be employed in doing both 20 human and animal research. It's been a long-term 21 process, one which is never-ending. 22 When we started this organization back in 24 1 1974, I thought that within ten years, we have 2 taught everyone everything they needed to know 3 about this, and we could move on to some other 4 things. The truth of the matter is that, 5 obviously, it continues to be a changing scene 6 requiring more and more work. 7 Why am I in this business at all? It's 8 not a business; we're non-profit. But it's based 9 on the fact I spent 40 years as a clinical 10 investigator. I'm a pulmonologist. I have been 11 treating patients and doing clinical research for 12 all those years. I've had 28 years, actually, in 13 PRIMAR business. 14 I spent 14 years as an IRB Chair, and, 15 actually, probably the toughest one is that I've 16 spent 72 years trying to be an ethical human being. 17 I have a lot of concerns about all this or 18 else I still wouldn't be doing it. A lot of it has 19 to do with the fact that IRB's, although they try 20 very hard to do their job properly, often don't 21 know what the job is, and that this requires 22 constant rethinking, reteaching, reaching out to 25 1 more and more people to try and get this 2 understood. 3 The main reason for that is that I've 4 always been most concerned about the protection of 5 human subjects, and it's not just because I'm an 6 M.D., but because I think that it's essential to 7 our whole process. 8 Way back when, when I guess the 1970's, 9 when they were reformulating some of the 10 regulations, and I asked Charlie McCarthy at that 11 time, "Why is it that we are -- the government does 12 not come out and say that all human beings, in the 13 United States, at least, who are going to be 14 subject to research be protected, rather than just 15 those who are federally funded?" 16 And he said, "We have to take one step at 17 a time." I hope we're ready for the next step. 18 I have concerns, as you do, about conflict 19 of interest. I think that it goes up and down the 20 line, and we'll hear more about it today, and I 21 hope that we can come up with some solutions for 22 this. 26 1 I think that, very often, when we look at 2 risk benefit, most IRB's are really not competent 3 often to determine the benefit side because they 4 don't understand the science adequately. This is 5 something we can correct by just teaching IRB 6 administrators. This has to be a change of how we 7 do business. 8 And I think one of my biggest concerns, 9 which has been something that's bothered me more 10 and more as the years go by, is there is an awful 11 lot of research that is done involving a lot of 12 human beings in which -- which does not advance 13 science, information which never gets into the 14 public domain because it's proprietary or because 15 it was negative results, et cetera, or it wasn't 16 going to look good on the CV. 17 This is sort of why I've been working with 18 PRIMAR and why I'm still here, and I think that all 19 these issues need to be addressed, and we keep 20 trying to address them, but we keep looking for new 21 solutions. So that's why I'm here, looking for 22 solutions. 27 1 CHAIRPERSON MARSHALL: Thank you. Thank 2 you, Sandy. 3 And because we have some leeway in terms 4 of time, I'd like to ask you a question, if that's 5 fair at the outset. 6 We have had already some feedback 7 regarding the composition of the committee and its 8 charge, and the question I have for you is, in your 9 experience with PRIMAR, how would you articulate 10 concerns of research administrators? 11 We have IRB Chairs here in full 12 representation, but I think there is a bit of a 13 concern that perhaps administrators don't have an 14 active voice at the table, and I wonder whether you 15 could speak to that for us. 16 MR. BARNES: Well, I think that there are 17 some IRB administrators who have had a very broad 18 experience of beyond just running an IRB and have 19 had to deal -- they're part of the whole process of 20 the human protection program; and as an integral 21 part, in some ways, and not being represented 22 probably is not a great idea. They probably -- I 28 1 think -- now, whether the input can come from 2 people like myself who, when I started out to be an 3 IRB Chair, I was also the administrator. There 4 wasn't such an office in those days. 5 I suspect Bob Levine here has had a 6 similar experience, that if we go back far enough, 7 we've had some of these experiences, but we're not 8 up to date on the current problems which beset 9 them, and I think that there are certainly real 10 problems. 11 Of course, I could think of probably five 12 other kinds of people who should be at the table, 13 also. 14 CHAIRPERSON MARSHALL: Right. Exactly. 15 And this might be a paradigm example and an 16 opportunity to say that we are a public committee 17 and that we will explore every avenue to make sure 18 that we communicate bi-directionally with the 19 public. 20 And so I guess I would like to say, on the 21 record, that any group that represents a particular 22 interest or a profession that doesn't feel as 29 1 though it has had a voice at the table, we would 2 like to hear from, and we're open and desperately 3 seeking input from all because we do -- fairness is 4 critical. 5 And, as I said earlier, having everyone at 6 the table and hearing those voices is critical to 7 the integrity of our process and our outcome. 8 Thank you, Sandy. 9 Elliot? 10 DR. DORFF: I'm Elliot Dorff. I have a 11 Doctorate in moral theory from Columbia, and have 12 done a lot of work in bioethics, as well as in 13 other areas of social ethics during the course of 14 my academic career. 15 I'm a professor at the University of 16 Judaism in Los Angeles, and I teach a course on 17 Jewish law at the Law School at UCLA. 18 I'm also a conservative rabbi. Despite 19 the name, conservative is the middle movement in 20 Judaism. 21 [Laughter.] 22 DR. DORFF: It's misleading. Never mind. 30 1 I wrote an article about 20 years ago 2 saying we should change our name because it's 3 misleading, and, of course, was ignored, but what 4 can I tell you? 5 My interests are, in terms of this 6 committee, really are, in part, philosophical, in 7 part, well, if I may say so, religious; 8 philosophically because -- well, it's the old 9 Contian principle that if you cannot do something, 10 then you never have to ask the question whether you 11 should. But, as soon as you can do something, 12 then, indeed, you have to ask the question about 13 whether you should. 14 And the fact that we now can do much, much 15 more in medicine and in social science, actually, 16 than what we have been able to do in the past is a 17 great boon to us, but it comes with much more moral 18 responsibility, and also with much more -- with 19 many more moral questions. 20 The issues that are now raised in terms of 21 privacy on the front page of this morning's paper 22 and issues of genetic engineering and genetic 31 1 screening that are going to be -- that are present 2 with us already today, it seems to me are major 3 issues in terms of protecting peoples' rights, and 4 at the same time, we want to be able to advance 5 scientific research as much as we possibly can in 6 order to be able to carry out -- and here is the 7 religious part -- I think our sacred duty, 8 actually, to try to improve this world and to 9 improve the human condition in it. 10 And so the real question then becomes, how 11 do you balance that sacred duty with a sense that 12 we want -- with another sacred duty of protecting 13 human subjects who are part of that research, and 14 those are my interests. 15 CHAIRPERSON MARSHALL: Thank you very 16 much. 17 Bob? 18 DR. LEVINE: I understand how to turn this 19 on. I don't know how to turn it off. There's a 20 green light on the left, though. 21 I was hoping to be sworn in before saying 22 anything. 32 1 [Laughter.] 2 DR. LEVINE: I've had a long collegial 3 relationship with our Chairperson and with Greg, 4 and I'm very optimistic after my first few 5 conversations with Kate Gottfried. So I think we 6 have wonderful leadership and staff for this group, 7 and if we don't do good things, it won't be because 8 of that. 9 I've been very interested in research 10 involving human subjects for a long time. In the 11 late sixties, when IRBs were just getting going, 12 all of my colleagues in clinical pharmacology were 13 appointed Chairs of IRBs across the country. There 14 weren't enough clinical pharmacologists to go 15 around, so some of them did more than one 16 assignment. 17 I got more specifically into the field of 18 research ethics in the mid-1970's when I was -- I 19 joined the National Commission for the Protection 20 of Human Research Subjects -- that's an abbreviated 21 definition -- as what they called the "Special 22 Consultant," and their assignment to me was to 33 1 write what they called their background theoretical 2 essays; things with such pompous titles as, "The 3 Nature and Definition of Informed Consent," and, 4 "The Boundaries Between Research and the Practice 5 of Medicine," and things of that sort. 6 Before that time, as I mentioned, I had 7 been chief of the section of Clinical Pharmacology 8 at Yale, and did a lot of work at the bench, and 9 also research involving living human subjects. 10 As I was thinking about what to say in my 11 allotted time, I noticed that they snipped off the 12 bottom of my paragraph. Some people have found a 13 way to cut me off. 14 [Laughter.] 15 Dr. LEVINE: And at the bottom of this, 16 there was a reflection of some of my major recent 17 interests, particularly in international research 18 ethics. 19 In the last few years, I was the 20 consultant responsible for drafting the U.N. AIDS' 21 guidance document on multi-national trials of HIV 22 preventive vaccines. 34 1 I was chair of the World Medical 2 Association, what they call their, "Electronic 3 Working Group," to propose a revision for the 4 Declaration of Helsinki Process, which just ended 5 about two months -- one and a half months ago. 6 I was co-chair of the Steering Committee 7 for CIOMS to write their international ethical 8 guidelines in 1993, and currently I'm chair of the 9 committee to revise those guidelines. So I have 10 had a longstanding interest in international 11 research. 12 As I look over our agenda, I can say that 13 my interest in research ethics pretty much covers 14 the whole topic of research ethics, but some of my 15 specific recent activities really are a match for 16 the current agenda. 17 I've been chair of the external working 18 group advisory to CDC on its human subjects 19 protection program, and in that role, have had 20 occasion to think, once again, about research 21 topics that are very closely related to social 22 science; in particular, much of the work done in 35 1 public health is a blend between some activities of 2 social scientists and just tending to the public 3 health in public health practices. 4 Also related to social science is the -- I 5 think a major current problem in how do we 6 evaluate, review, and approve health policy 7 research. This is a topic that's dealt with in the 8 current regulation simply by exempting it so that 9 there is no -- there need not be any review or 10 approval of this. 11 And the day before I got my agenda book, I 12 volunteered my opinion on the McWerb Internet chat 13 group that I thought social science was not 14 adequately covered by the current regulatory 15 system, and that this lack of adequate coverage was 16 not because they had not been represented by the 17 national commission, and it was a different 18 phenomenon. 19 Pediatrics is on our agenda. I finished, 20 two days ago rewriting my chapter for the third 21 edition of Mel Lewis' textbook on pediatric and 22 adolescent psychiatry. 36 1 I'm very interested in the field of 2 placebo controls and circumstances under which 3 they're justified, and part of this interplays with 4 my interest in the Declaration of Helsinki and its 5 recent revision. 6 And the final activity I want to mention 7 is I'm interested very much in data monitoring, in 8 data and safety monitoring boards, and in using 9 them intelligently to take off a tremendous amount 10 of the burden now borne by the Institutional Review 11 Board. 12 There's been a lot of criticism of 13 institutional review boards lately as being overly 14 burdened, and they are overly burdened. But the 15 majority of this burden, I believe, is in doing 16 work that either doesn't need to be done at all, or 17 that can be done much more effectively by other 18 groups and individuals. 19 I look forward to working with you, Mary 20 Faith, and with all of our colleagues in this 21 group. 22 CHAIRPERSON MARSHALL: Bob, thank you very 37 1 much. You not only bring a wealth of knowledge and 2 experience, but I think also within the field of 3 research ethics, an institutional memory that 4 perhaps the rest of us don't have, and that really 5 will be vitally important. Thank you. 6 Abbey? 7 MS. MEYERS: Yes, thank you. 8 I'm Abbey Meyers, President of the 9 National Organization for Rare Disorders, which is 10 known as NORD, and we're the patient advocacy group 11 that work for enactment of the Orphan Drug Act in 12 the area where there is no commercial interest or 13 little commercial interest in development of any 14 kind of treatment because the disease is rare. 15 And the Orphan Drug Act, of course, has 16 been very successful, but I got involved in this 17 area because I'm the parent of three children with 18 a genetic disease, and they have participated in 19 research for more than 20 years. 20 They are adults now. Some of them have 21 children of their own, but my youngest daughter 22 still participates in research. Any time Yale 38 1 calls her up and says, "Come on down. We need an 2 MRI," and she still goes down there. 3 So I've seen it from both ends. I've seen 4 it from being a parent. I've read those informed 5 consent forms, and I had no idea what was going on 6 beyond my own family's involvement until I got 7 involved with other committees and I served on the 8 RAC, the Recombinant DNA Advisory Committee for 9 many years. I think it was something like six 10 years on that and about four years on the Gene 11 Therapy Subcommittee before it was merged into the 12 RAC. 13 And my experience on the RAC was very 14 telling in that in reviewing dozens and dozens and 15 dozens of informed consent documents, I saw how bad 16 they could be. And every time we asked for it to 17 be changed, to be understandable, to be written in 18 a language that laymen could understand, we were 19 told that the institution has, or the investigator 20 and the sponsor have absolutely no authority to 21 change the RAC, that only the IRB has authority to 22 change an informed consent document. 39 1 Some of them were so bad, they said in 2 this Phase I study, "We hope that this gene therapy 3 will cure you," and there was no way we could 4 delete that sentence or amend that sentence. And 5 so I participated in the committee to revise the 6 RAC's standards for informed consent. 7 I think that when I served on the RAC and 8 we reviewed the OTC protocol in which Jesse 9 Gelsinger died, that it was an extraordinary 10 experience to see what happened in that case. And 11 that case involved nonconformance with existing 12 rules, but it certainly pointed out why these 13 things should be -- why the rules should be 14 expanded for everybody. 15 My particular areas of interest are why 16 the rules cover only federally funded research and 17 privately funded research is falling through the 18 cracks. And, as a matter of fact, we don't even 19 know how many thousands of people are falling 20 through those cracks. 21 I'd like to see the federal regulations 22 extended to all research, and in view of the 40 1 Washington Post series that's going on now, we 2 certainly need those rules to extend to overseas 3 research that's funded by American companies. 4 My particular interest right now, also, is 5 to assure that the current -- it's not just the 6 Tuskeegee experiment. We're still seeing Tuskeegee 7 experiments go on, and the latest one is this issue 8 on the west coast of the people who are getting a 9 thousand dollars to drink polluted water in order 10 to prove that polluted water has no health effects. 11 Something should be done to stop that, and it 12 appears from the brief overview that the federal 13 government is going to have no authority to step in 14 there. 15 So in seeing this from the patient's point 16 of view and knowing how much research has to be 17 done, we need to do everything we can to encourage 18 research and not to overly burden investigators. 19 But we need private industry to step up to the 20 plate and act with moral authority. 21 Thank you. 22 DR. KOSKI: Ms. Meyers, thank you very 41 1 much. 2 This is going to be a very brief 3 introduction, but simply the reason we're here is 4 because of Secretary Shalala. Secretary Shalala 5 has been just an absolute stalwart leader in this 6 entire effort. 7 We are here to fulfill the mission that 8 she has started, and without further discussion of 9 that, it gives me great pleasure and a real honor 10 to introduce Secretary Donna Shalala. 11 SECRETARY SHALALA: Thanks very much, 12 Greg. Thank you. 13 I'm very happy to be here with all of you. 14 Let me -- I don't know whether Ruth Kirchstein or 15 Jane Haney have gotten here yet, but they'll be 16 here eventually. I know their brains are here 17 because I see all their senior people. 18 [Laughter.] 19 SECRETARY SHALALA: My brain is here, too. 20 You know, some of us have made our careers 21 simply hiring people that are smarter than we are 22 and making sure they have the resources and the 42 1 strategy to get their work done. 2 Let me acknowledge Senator Edward Kennedy 3 of Massachusetts, who will be speaking to you right 4 after I finish, the acknowledged leader on health 5 care in the Senate, one of the great legislators, 6 one of the great advocates for scientific research 7 and public health in this country, a very good 8 friend of both the Department and the National 9 Institutes of Health, all of the science and health 10 agencies in this government, and every kid who ever 11 set foot in this world. 12 As you know, I'm actually in my final 13 weeks of an eight-year run as the Secretary of 14 Health and Human Services, and about to go back to 15 the Academy to take on these issues -- 16 Ruth Kirchstein just came in. 17 -- directly, myself. So let me start by 18 simply congratulating and thanking all the members 19 of the National Human Research Protections Advisory 20 Committee. In particular, let me thank our 21 Executive Director and Mary Faith Marshall, who's 22 going to chair this committee for us. 43 1 Professor Marshall, it's nice to see you. 2 This is really important. When we first 3 transferred the office to the Office of the 4 Secretary, we were under withering criticism from 5 the Hill who thought, you know, the fox is going to 6 protect the chicken coop, and this is not going to 7 work; that you just -- you're transferring too much 8 authority, and most importantly, asking academic 9 institutions to do some of this may be the wrong 10 way to go. 11 I did not believe that, in part, because I 12 come from the Academy, but in part, because I 13 didn't see the option to us strengthening what we 14 had. 15 But this is really important: As of the 16 last budget, we've increased the funding for NIH 17 alone by 50 percent. 18 This country's steady commitment to basic 19 science, to clinical research is now firm, firmly 20 non-partisan. Not even bi-partisan; non-partisan. 21 And we understand the relationship between those 22 investments and not only the quality of health care 44 1 around the world, but also the dynamic that exists 2 between the scientific community and the economic 3 health of our own country, as well as countries 4 around the world. 5 Everything that we said we needed, for 6 those of us that came from the Academy, steady 7 increases, investments, in training have now been 8 put in place, but -- which means -- and that 9 reflects public confidence. It's not just elected 10 officials. It's not just leaders of the Department 11 that were committed to scientific research or a 12 president that was committed before we came here. 13 It's more important than that. 14 We have public confidence in scientists. 15 Scientists are heroes these days in this country. 16 That can easily be undermined. If our 17 scientific institutions and if the leaders in 18 science -- if the leaders of the institutions that 19 are responsible for the great infrastructure, 20 scientific infrastructure that we have in this 21 country aren't careful in how that research is 22 conducted. 45 1 And if you want to see what happens in 2 this world when you don't have institutions that 3 are trusted, then look at Europe as they try to 4 handle some very complex scientific issues that 5 involve human health and animal health without both 6 the scientific institutions and the leaders in 7 science that their countries have not invested in 8 the way we have invested in. 9 So what you do here is really important, 10 but how your colleagues throughout this country and 11 throughout the world behave is important. 12 We have put in place everything that 13 everybody told us we needed to put in place. We've 14 put the office in place. We've recruited a first- 15 class leader for that office. 16 I personally recruited Greg Koski. I 17 promised him lots of things, most of which I will 18 have delivered on before I left. 19 I also personally recruited Harold Varmas, 20 Jane Haney, and all the other scientific leaders, 21 Jeff Copeland, who head the other scientific 22 institutions, and I transferred to them the great 46 1 complaint about NIH and all these agencies is they 2 never had the authority for personnel, never had 3 the resources to make the decisions. 4 We have done all of that. They have the 5 authority to make decisions. They have the 6 resources that they need. But the oversight in how 7 we conduct this research, and in particular, how we 8 protect human subjects, is not something, as Greg 9 has carefully taught me, that we can sort of fix. 10 It's putting in place a change in culture and a 11 system and a respect for human subjects, but also 12 for the American people that have invested in this 13 kind of research. 14 It is the most fundamental ethical issues 15 that we struggle with because we want to conduct 16 the research, but simultaneously, we want to make 17 sure it's conducted in the most ethical manner as 18 possible. 19 And if it's not, then those people that 20 don't want to do it the right way ought to get out 21 of the business, and we're going to be as tough 22 minded as we have been on the other parts of the 47 1 Department. And you can see this department and 2 our scientific institutions getting tougher and 3 tougher because we know what's at stake. 4 Fundamentally, human health, but also the 5 confidence that our people have in this research. 6 And we have been in and we have entered 7 this golden age of biomedical research, and to 8 undermine it now would be a human tragedy of 9 unbelievable dimensions. I get it, obviously. 10 And everything, every power that I have 11 had, I have put in place with outstanding leaders 12 and made the investments, and now, it's up to you. 13 I want you to be tough-minded, I want you to hold 14 our feet to the fire; I want you, in particular, to 15 hold our feet to the fire in transitions because 16 things fall between the cracks in transitions. And 17 you can't guarantee that every leader you're going 18 to get comes from a major research university and 19 sort of understands this business that we're in. 20 So it's up to us to put an infrastructure 21 in place that really makes a difference. And I 22 want us to have zero tolerance for the 48 1 mismanagement, whether it's an individual scientist 2 or the heads of the institutions. And more and 3 more, we need to hold the heads of institutions. 4 As I have said to college presidents in 5 this country, they pay more attention to the NCAA 6 rules and to violations in that area than they do 7 to their infrastructure on oversight of scientific 8 research. 9 The leaders of America's research 10 universities are far more knowledgeable about NCAA 11 violations than they are about IRBs and what kind 12 of investments they're making, and whether to 13 overload it or whether to not overload it. 14 You have a lot of responsibilities, and 15 they've written me some very nice talking points to 16 go through them. But your charge is to be as 17 tough-minded as you possibly can be and understand 18 what's at stake here. 19 And it's not just the individual 20 reputations of scientists. It's science itself and 21 the quality of science and the quality of health 22 care. 49 1 So consider yourself fully charged, and I 2 will make sure before I leave that Greg has 3 everything that he needs. He's a first-class 4 leader, the right man at the right time. 5 And basically, I've asked Greg to come 6 here for enough years to get this all set up and 7 then to recruit his successor. I well know that. 8 But, again, it's changing the culture. 9 And let me assure you, it is not just the 10 research institutions. Our own institutions within 11 the government are not holding themselves to high 12 enough standards. And Ruth and Jane and Jeff have 13 absolutely assured me that they have a long way to 14 go in their own institutions, so no one gets off 15 the hook here. 16 So I thank you for your service, 17 particularly at the beginning as we get this going, 18 and I will do everything I can between now and 19 January 20th and afterwards to make sure that all 20 of you have all of the support you could possibly 21 have. And Greg has a very thick skin, but he's 22 also very responsive, and he's going to have 50 1 regular meetings with me. No one gets regular 2 meetings with me between now and January 20th 3 except for Greg Koski, which gives you some sense 4 of what a high priority I've put on all of this. 5 So thank you very much. Thank you. 6 [Applause.] 7 SECRETARY SHALALA: I have to get going. 8 I finally got the President to come to the 9 Department to announce the privacy regulations. I 10 told him if he didn't come pretty soon, I was going 11 to begin to think that we were like Nebraska, you 12 know. 13 [Laughter.] 14 SECRETARY SHALALA: I don't know whether 15 any of you have any questions for me. 16 Professor Marshall? 17 CHAIRPERSON MARSHALL: I don't have a 18 question, but I do want to thank you. We are very 19 mindful of the fantastic opportunity that you have 20 given us, and we plan to be excellent stewards 21 relative to our charge, and to make, we hope, some 22 meaningful and wholesale reform. 51 1 SECRETARY SHALALA: Great. Surely. 2 CHAIRPERSON MARSHALL: So thank you so 3 much. 4 SECRETARY SHALALA: Thank you very much. 5 [Applause.] 6 DR. KOSKI: Okay. Let me tell you now 7 that Madam Secretary has left that it's nothing 8 short of remarkable that she was able to be here 9 with us today, given all that's going on downtown. 10 I think it truly is a mark of her real commitment 11 and dedication to this effort, and we're very 12 grateful to have her here. 13 Now, it gives me enormous pleasure also to 14 introduce to all of you, Senator Edward Kennedy. 15 As you know, Senator Kennedy has been in this game 16 since day one. It was shortly after the 17 revelations of the Tuskeegee study, when Senator 18 Kennedy was brand-new to the effort, that he 19 actually began with holding hearings that led to, 20 ultimately, the National Research Act, the entire 21 National Commission. 22 He has been a steadfast advocate for both 52 1 research and doing research right. It's truly an 2 honor, a very, very special honor to have the 3 Senator with us today. 4 Senator Kennedy? 5 SENATOR KENNEDY: Thank you. Thank you 6 very much, Greg. 7 As perhaps very few of you know, and 8 there's no reason that you should, Greg and I have 9 something in common. We both went to Harvard 10 College and we both played football at Harvard. I 11 played left end. Some people say that's where I 12 got my political philosophy. 13 [Laughter.] 14 SENATOR KENNEDY: I'll let Greg speak for 15 himself, but he was a great player. 16 I was listening to the Secretary, and I'm 17 grateful for her remarks and her overall assessment 18 is obviously right on target to what we're 19 certainly hoping for in the Congress. 20 Being with a group like this and talking 21 about the subject reminds me a little bit about the 22 person that survived the Johnstown flood, and there 53 1 was only survivor of the Johnstown flood. And 2 finally that survivor of the Johnstown flood went 3 to his eternal reward in heaven, and St. Peter at 4 the gate said, "You've been very good and you're 5 entitled to any wish that you want." 6 And he said, "I'd like you to get all the 7 angels and archangels together and let me tell 8 everyone how I survived the Johnstown flood." 9 "Fine," said St. Peter, and brought 10 everyone together and introduced this person. And 11 as St. Peter was walking back to the survivor, he 12 said, "I just want you to know that out in your 13 audience is Noah." 14 And I feel that way today, looking around 15 this room at many of those who have been good 16 enough to come on in and brief me over a period of 17 time on many of these issues that we have been 18 faced with and continue to be faced with. 19 Let me really pick up a little bit on the 20 themes that Secretary Shalala outlined. And I 21 think they really underline what I think are really 22 the most important challenge that all of you are 54 1 going to have, and that is how are we going to 2 ensure that science is going to control these 3 judgments and decisions and not the politics. 4 I was thinking in coming out here, the 5 hearings that we had -- we had 11 days of hearings 6 some 30 years ago and the first hearings on the 7 Tuskeegee syphilitic study. 8 And then we had the reviews of the 9 sterilization of the Ralph girls. 10 And then, of course, we read the Supreme 11 Court decisions about that, and that is an ominous 12 indicator as well. 13 And then we had the studies of Depo 14 Provera in Tennessee. And then we also had the 15 hearings -- difficult, very, very difficult 16 hearings into the CIA, where they gave various 17 drinks -- laced various drinks with hallucinogenic 18 drugs. And I don't think I'm certain to a moral 19 certainty that the tragic loss, that it was never 20 able to be definitely proved of a really 21 outstanding agent who became disoriented with the 22 consumption of the hallucinogenic drug and then 55 1 woke up the next day and thought somehow that they 2 had violated the secrecy, and went to New York and 3 threw himself off a hotel building and killed 4 himself. And there were virtually no guidelines at 5 that time. 6 And then I remember it was about this time 7 that my sister, Eunice, as a family that's been 8 enormously interested in the problems and the 9 challenges of ethics dealing with mental 10 retardation, and particularly a case that took 11 place over at Johns Hopkins where a child, a baby 12 was born with a correctable health hazard, which 13 about 95 percent success in being able to cure, to 14 fix this. But it did take a medical procedure, and 15 the parents refusing to have it because they were 16 not interested in having a mentally retarded child. 17 And so they left that child for about 23 days until 18 finally the child died. 19 And the various ethical challenges that 20 were there. The doctors had said, "Well, if we go 21 and do this in spite of the parents, we are part of 22 that 10 percent, then we put at risk the whole 56 1 hospital and its whole procedures." And the nurses 2 facing similar kinds of dilemma. 3 And this extraordinary ethical challenge 4 that we are there for all of those that we are 5 serving and caring, and parents who were enormously 6 troubled with a large family and a very small 7 income, and a country that still doesn't provide 8 health insurance. 9 So these were really the background where 10 we established the initial panel, and it was a very 11 significant group of men and women that served on 12 the panel. 13 And the interesting aspect for me, as a 14 legislator, is it had no powers whatsoever than the 15 recommendations that they made. They published 16 their recommendations in the Federal Register, and 17 every one of their recommendations that they made 18 were implemented. Not one was turned down, 19 although they had no authority and power other than 20 the fact of their consideration and their very 21 thoughtful consideration; the way they went about 22 trying to come to grips with the various kinds of 57 1 ethical issues, and then promulgating the rules and 2 regulations. 3 And it was really an extraordinary study 4 about how government can work and does work, and at 5 times when you really wonder when we saw that it 6 couldn't go ahead even with the routine kinds of 7 accountability that I think many of us feel, having 8 been around for a long time and seeing so many of 9 the nation's problems turned over to commissions 10 and the commission study for two years, and the 11 closets filled with these recommendations and 12 without being implemented. 13 And one that sees that the contrast to 14 that is, of course, the British system where the 15 Parliament has to act, and act within 90 days with 16 the recommendations, and the government has to give 17 clear explanations why they're not making the 18 recommendations, or otherwise, the government has 19 to embrace them. So you get accountability on many 20 of the challenges. 21 Well, that's along the edges of it. But I 22 was mindful of that, particularly coming through 58 1 the Vietnam War and civil rights challenges and all 2 the rest, and really wondering whether we had 3 really done something, but it had been done. 4 And then I saw the politicization, that 5 basically authorization, we were unable to get it 6 and we are already beginning to see the pressures 7 then we're coming in terms of politics of it. 8 And then we went through a long period of 9 time in the naming of the various panel. And we 10 could just see really the ends of what was 11 happening to a panel because the test was there was 12 whether they were pro life or pro choice, there 13 were going to be the recommendations that the first 14 thing that the panel was going to deal with was 15 going to be the abortion issue. 16 And, finally, compromises that were worked 17 out which Lo Wiker, very much involved in, was very 18 caring about to this whole issue, and actually, 19 Vice President Gore was interested and concerned 20 about this, as well, as a person that was involved 21 in it. 22 But, eventually, we get the completion of 59 1 it, but since it was so deadlocked at that period 2 of time and there was such a real exhaustion, or 3 really tiring and the Congress never appropriated 4 it, then it effectively dissolved. 5 And I have seen, as the Secretary has 6 mentioned, what happens when we have the politics 7 interfering with sound science. And in our great 8 challenge in the most recent times was on the whole 9 AIDS issue. And we were able to really move, I 10 think, for the first time sort of beyond it. 11 We had it for a while in terms of the 12 Americans With Disability Act, and anybody that 13 reads back on through that debate, even though it 14 was only one day in the United States Senate, look 15 in the late afternoon when Jesse Helms brought up 16 the Encyclopedia Cyclothropic -- is that the -- 17 Cyclothropic Encyclopedia -- and talks about mental 18 aberrations in sexual activity. And there's about 19 ten pages in there of things I never even heard of 20 or possibly even thought of or whatever. 21 And Jesse Helms offered an amendment, 22 tearing those pages out and saying that anything 60 1 like this will not be protected under the Americans 2 With Disability Act, and it was just going to stop 3 the whole legislation. Anybody that was going to 4 take that on was going to probably end up with the 5 five or ten votes on it. 6 And Dr. Roper, actually, was the one that 7 was actually representing the administration at 8 that time, went out and worked with Jesse Helms. 9 And he took and said, "Okay. We'll take a quarter 10 or a third." And a quarter and a third, they were 11 included in it. Absolutely no signs whatsoever. 12 Senator Helms has no idea what they were at the 13 time. No one else does, either, and I'm sure the 14 courts are confused what we intended to do at that 15 time. 16 [Laughter.] 17 SENATOR KENNEDY: But that was an 18 indication. We saw it in the AIDS debates for a 19 period of time until we really got beyond that 20 thing with the Brian White. And we tied that on 21 into the fact that it was hemophilia, which it was 22 with regards to the Brian White. But we were able 61 1 to make some progress in terms of the AIDS, and 2 then we moved forward on it. 3 But I am very, very hopeful that we are 4 going to, with this panel, be able to try and find 5 ways, we're going to be facing some enormously 6 complex challenges in the Congress. 7 We faced them in terms of the utilization 8 of fetal tissue, and we're around the corner on 9 stem cell research, which we're very, very familiar 10 with. 11 And as we move through with these 12 extraordinary potential breakthroughs in these wide 13 range of different areas, we're going to constantly 14 come back to the areas of science, ethics and 15 politics. 16 And to the extent that this panel can give 17 us the guidance because of the strength of their 18 credibility and the power of their concern and the 19 legitimacy of their presentations to keep us 20 focused on the real ethical issues on this in ways 21 which could commend the broadest range, and in this 22 sense, use positively the political landscape, 62 1 we're going to have made incredible, incredible 2 progress. And that would be something that I would 3 be very hopeful of as we look down the line towards 4 the future. 5 We have our job to do, obviously, as 6 legislators, to try and give support and help in 7 justifying it. But we want to, as the Secretary 8 mentioned, and I commend her for the establishment 9 of and the excellence of the panel, and I commend 10 her for her leadership over the period of time in 11 the HEW and the range of new -- the activities that 12 she has worked out recently in the coverage of 13 children, and the particular challenges that they 14 have just issued with Social Security, which is 15 extraordinary and going to be more inclusive, and 16 for the promulgation of these privacy 17 recommendations, which are just so important. 18 We were unable to get that in the Congress 19 in the last time, and the principal reason was the 20 medical records of teenage girls, whether they were 21 going to -- how protected were they going to be. 22 That was one of two items that basically halted us 63 1 from moving ahead in the very important area of 2 public policy. 3 And that is why we have to be so wary of 4 this. Hopefully, as a nation, we're going to 5 mature significantly. This won't be as much of a 6 challenge, but it certainly is today. 7 Finally, I was going to mention several of 8 the areas that the Secretary mentioned, a number of 9 the things that Greg has talked about in terms of 10 the overwork, the IRBs and the consolidation, using 11 these universities in ways which can eliminate some 12 of the duplication, the range of different 13 paperwork that are out there, things that we ought 14 to focus just generally. 15 I am concerned, as was mentioned in the 16 questions, about our drug companies and the actions 17 overseas. We went through a long debate a number 18 of years ago with the FDA whether we were going to 19 permit various products that were not going to be 20 consumed here in the United States to be actually 21 exported to be used overseas. That was a big issue 22 that we had. 64 1 And I happened -- I changed my position 2 from one that didn't think that they should be to 3 one that thinks that they ought to be able to be 4 used, and that ran into all kinds of ethical 5 questions, obviously, because if we're going to 6 have a breakthrough in terms of a lot of different 7 diseases that can make a difference in terms of 8 curing these matters overseas, we're not going to 9 be able to test them here in the United States. So 10 we're going to have to move them overseas, and we 11 can have a very positive impact in terms of the 12 health of people overseas. 13 So this is right on the deck, front and 14 center, whether we like it or not. I like it 15 because, I think, I've always felt that the United 16 States missed the opportunity, number one, in the 17 export of food overseas. We spent $35 billion last 18 year -- $35 billion to keep our farmers happy, and 19 we still don't send food overseas. 20 And one thing we know how to do is to grow 21 food, and the other thing we can do is deliver a 22 product any place in the United States overnight, 65 1 thank you, Federal Express. Well, we ought to be 2 able to -- well, that's a different issue at a 3 time. 4 But we're going to have with these 5 breakthroughs that are going to be out there real 6 opportunities. So what was mentioned here in terms 7 of overseas is right on our plate and we have to do 8 it. 9 And secondly is what was mentioned also in 10 the polluted water in California. We do know in 11 these areas that are related, not only in the FDA, 12 but also in the EPA, and what is happening in the 13 private, and the growth of those. We cannot avoid 14 those. We have to get focused because it's only a 15 matter of a year or two years we're going to be 16 faced with these extraordinary challenges, and 17 people are going to say, "What in the world did we 18 ever do about that, and what was that conference -- 19 what were thinking about out in Bethesda when they 20 had this conference and where we're going to do?" 21 And we're going to face some serious 22 challenges on that when we try to take the 66 1 administration to do something, working with Jane 2 Haney on safe food. 3 Because of the dramatic increase in foods, 4 we are looking to trying to get some examination 5 overseas of what kind of pesticides are being used 6 in the various foods. And the grocery 7 manufacturers came down hard on us, and we're 8 basically stalemated on that in spite, with all the 9 potential dangers that that has with a reduced 10 enforcement group, which we're seeing cutbacks, and 11 the dramatic increase in terms of the consumption 12 of food that's being produced overseas. It's just 13 inevitable we're going to face other kinds of 14 challenges. 15 So we need to try and focus what has been 16 presented by the Secretary. Many of us believe 17 that this is just a defining aspect, not only in 18 terms of science, but what our society is about, 19 and you're at really the cutting edge. 20 And not to do it right I think would be 21 something that isn't even something that any of us 22 can consider. To do it right is just an incredible 67 1 kind of a challenge, but it's one that I know that 2 those that are here on the panel and those that I 3 know that are out there and have thought about this 4 and are in different centers of learning that are 5 attempting to guide us, we need this. 6 Members of Congress and basically the 7 executives and the Congress, we're generalists. 8 I've been in the business for some period of time. 9 But we have some knowledge and understanding in 10 areas where we spend some time in education or in 11 health care, in other kinds, the civil rights 12 knocking down the walls and the other types, 13 poverty programs. 14 But this is an area that we are basically 15 generalists, and if we have powerful incentives 16 around that are -- which we used to have -- 17 remember where they had that -- I think it was 18 called the PS -- the NIH4. It was up in Cambridge. 19 And we had Al Balucci was out there and declared an 20 independent state in Cambridge, Massachusetts -- 21 [Laughter.] 22 SENATOR KENNEDY: -- and won the election 68 1 up there because he talked about the creepy 2 crawlies that were going to take place in terms of 3 DNA research and carried in Cambridge, 4 Massachusetts, which I just got the highest 5 percentage from in this last election. 6 [Laughter.] 7 SENATOR KENNEDY: So we all have to be 8 alert and we all have to be on our guard. 9 But we thank you so much for all the time 10 and the consideration. I'm grateful for the chance 11 to come out, and I want you to know you have a real 12 ally. We want to work very closely with you. I 13 know I speak for our committee, Republican and 14 Democrats, our committee. Our Human Resource 15 Committee is incredibly interested in this. We 16 want to take your recommendations. We want to be 17 constructive and we want to be positive, and we 18 want to be helpful. And I'm thankful to Greg for 19 letting me come by and say, "Hello." 20 Thank you very much. 21 [Applause.] 22 CHAIRPERSON MARSHALL: I am going to ask 69 1 one question of the Senator, and that is this: 2 First, I want to thank you for establishing the 3 legacy that has led to the genesis of what we are 4 all about. And we do plan to take issues, head on. 5 We are ethicists, and our job is -- we are 6 not all ethicists, but our job is ethical in 7 nature, and we will look things right in the eye. 8 Can you give us some advice that is not of 9 a partisan nature, but that might help us in terms 10 of being as effective as we can during a change of 11 administration? 12 SENATOR KENNEDY: Well, I think it's not 13 -- one thing I might suggest is, as soon as we have 14 the new Secretary for HEW, we ought to try and you 15 ought to, to the extent maybe get some kind of 16 meeting on it. We will let them know we are going 17 to ask a lot of questions about it, and you can be 18 helpful for us in terms of developing the questions 19 and be helpful to them. 20 I don't look at confirmations as a game to 21 try and capture people, but to try and develop 22 their own thinking where they get committed on 70 1 policy. Then we hold them accountable. 2 And I think there may be an area in there 3 where those, where Senator Frist or Senator 4 Jeffords and myself can lay the groundwork through 5 questions so that we get an administration on the 6 record, and also indicate, whoever that person is, 7 that these are questions going to be asked. They 8 can come to you and ask for the answers. 9 And this may sound rather rudimentary, but 10 it helps. You get them thinking about these 11 things. Whoever is going to get it is going to 12 start thinking about this and understand that 13 people are serious about it. 14 And I'd be more than glad to work in a 15 constructive way with you, and I'll mention this to 16 Senator Jeffords. And I'd be glad to sit down with 17 either Greg or with the group here, prior to the 18 time of those hearings, and get to your 19 recommendations and questions to ask. 20 And I'd be glad when the nominee comes by 21 in the courtesy call to indicate that this is 22 something that you'd like to meet with them on 71 1 prior to time. Then I'll come by and say, Hello, 2 and I'll mention that if you decide that you'd like 3 to proceed in that way. 4 I think that that could get us started in 5 an important way. It's an excellent question you 6 asked, and maybe there are other things that we 7 could think of. But I think that could be a useful 8 start. 9 CHAIRPERSON MARSHALL: Thank you. Thank 10 you. 11 SENATOR KENNEDY: Good. Thank you all. 12 Thanks a lot. 13 [Applause.] 14 DR. KOSKI: Well, obviously, in trying to 15 coordinate these kinds of events on a busy day, 16 flexibility is an asset, and I appreciate the 17 flexibility that you all have shown. 18 I'm sorry that Dr. Kirchstein from NIH, 19 unfortunately, had to leave early. I was hoping to 20 introduce her and if she wished to make a remark, 21 we would have benefitted from that, no doubt. But 22 she has been an absolute, again, stalwart 72 1 companion, as have all the colleagues in NIH, in 2 working through this, as well as at the other 3 agencies, you know, with Bern Schwetz and David 4 Lepay from FDA, and for the whole crew. 5 You know, we've done a lot here in the 6 last few months. There's still a lot to do, but, 7 you know, we'll keep pushing on that. 8 I think what we would do at this point, if 9 it's acceptable to the Chair, would be to sort of 10 backtrack a tiny bit in our agenda to do the 11 business portion of actually swearing in the 12 committee so that we can do work, which is required 13 under the federal regulations. 14 So, Madam Chairman, if you wish to do 15 that, we can proceed. 16 CHAIRPERSON MARSHALL: Thank you. I 17 certainly do. 18 Yes. Thank you. Jackie Coleman is here. 19 MS. COLEMAN: Hi. 20 DR. KOSKI: It actually takes about two 21 and a half days to complete the forms, so -- 22 MS. COLEMAN: Good morning. My name is 73 1 Jackie Coleman, and I work for the Department of 2 Health and Human Services, Personnel Office in our 3 downtown office. 4 This morning, I will be administering the 5 oath of office. I would like for everyone to stand 6 at this time. We will read Section A, starting 7 with the line above it. 8 When I say, "I," I want you to say your 9 name. If there is anyone here that does not swear, 10 you may say, "affirm," okay? 11 Raise your right hand. I -- 12 [Chorus of members.] 13 MS. COLEMAN: -- do solemnly swear or 14 affirm that -- 15 [Chorus of members.] 16 MS. COLEMAN: -- I will support and defend 17 the Constitution of the United States against all 18 enemies -- 19 [Chorus of members.] 20 MS. COLEMAN: -- foreign and domestic -- 21 [Chorus of members.] 22 MS. COLEMAN: -- that I will bear true 74 1 faith and allegiance to the same -- 2 [Chorus of members.] 3 MS. COLEMAN: -- that I take this 4 obligation freely -- 5 [Chorus of members.] 6 MS. COLEMAN: -- without any mental 7 reservation or purpose of evasion -- 8 [Chorus of members.] 9 MS. COLEMAN: -- and that I will well and 10 faithfully discharge the duties of the office on 11 which I am about to enter -- 12 [Chorus of members.] 13 MS. COLEMAN: -- so help me God. 14 [Chorus of members.] 15 MS. COLEMAN: Okay. You may be seated. 16 There's one that didn't sign that I have 17 to sign for. 18 CHAIRPERSON MARSHALL: -- to do now that 19 we have finished being charged and important 20 housekeeping duties is to continue with the 21 introductions of the members of the committee, and 22 we're doing well on time. 75 1 If we have a few extra minutes prior to 2 our break, which I assure you we will have in a 3 timely fashion, I would like to ask Robert Cooke 4 Deagan of the Institute of Medicine to tell us 5 about a project that the OHRP has charged the 6 Institute of Medicine with that may have some 7 bearing or relationship to the work of the 8 committee so that the members will understand the 9 nature of that charge. So we will do that, if we 10 have time. 11 And, Bob, thank you so much for being 12 willing to do that with no notice. 13 Abbey, I don't know whether you were cut 14 short, but I just wanted to say, if there was 15 anything else that you had wanted to share with us, 16 at this point, I'll give you the opportunity to do 17 so. 18 All right. Thank you very much. And I 19 did pay particular attention to -- I heard what you 20 said about having federal regulations that apply in 21 a somewhat universal manner. So -- and I think 22 that's vitally important, and it's obviously 76 1 something that the committee will need to take a 2 long, hard look at. 3 Mary? 4 DR. PELIAS: My name is Mary K. Pelias. 5 With regard to first names, I do go by Mary Kay, 6 and you might imagine, I take a good deal of flack 7 for that. 8 CHAIRPERSON MARSHALL: Well, I'm a Mary 9 Faith, and I can relate wholeheartedly to that. 10 DR. PELIAS: I grew up in the deep south 11 in the forties and fifties at a time when 12 photographs and reports of lynchings appeared on 13 the front page of the newspaper. 14 In the early sixties, I was a student in 15 Germany and worked in an anatomy department where 16 collections of specimens came from very dubious 17 origins. 18 After that, I trained in graduate school 19 in genetics, and finally, became specialized in 20 medical genetics. And I've been on the faculty at 21 the LSU Medical School for the last 25 years. 22 My professional interests in this area, in 77 1 these areas began in the early 1980's with the Baby 2 Doe cases that Senator Kennedy alluded to, Baby Doe 3 cases that raised questions of autonomy and who 4 should make decisions for these unfortunate infants 5 who are born with severe defects. 6 In the 1980's, I also was intrigued by the 7 litigation that arose in wrongful birth and 8 wrongful life, and the questions of duty to 9 disclose information to people who might have 10 children with severe birth defects, and who should 11 make these decisions and value judgments. 12 I then went back to law school for 13 interests in constitutional law and tort law and 14 medical malpractice and family law. 15 I'm here because I have a serious interest 16 in the new genetics and in possible regulations 17 that we might want to include in the Code of 18 Federal Regulations. 19 Particular questions in the new genetics 20 these days have to do with family histories and 21 privacy. These have come up in the last couple of 22 years, with questions of access to tissue 78 1 collections that researchers would like to get 2 into, but for which they have no consent from the 3 donors of the samples. 4 Questions about historical collections, 5 how we should treat them, as opposed to how we 6 should allow access to new collections and obtain 7 consent for the use of new collections as opposed 8 to old collections. 9 In particular, I've spent a lot of time on 10 questions of using newborn screening sample 11 collections for future genetic studies, and if and 12 how we should get consent for future use of newborn 13 screening samples in genetics research. 14 We have issues of gene therapy that have 15 already been mentioned by Abbey Meyers, and I think 16 an underlying problem that we should address at 17 this time is defining what we mean by "genetic 18 information," exactly what constitutes genetic 19 information, and how our IRBs should address 20 questions about future use of samples and any use 21 of samples from which genetic information can be 22 generated. 79 1 Thank you. 2 CHAIRPERSON MARSHALL: Thank you, Mary 3 Kay. 4 Robert? 5 DR. RICH: I'm Bob Rich. I'm Executive 6 Associate Dean for Research at the Emory University 7 School of Medicine, where I've been for the past, 8 just over two years. 9 Prior to that, I spent 25 years at Baylor 10 College of Medicine. 11 I'm a physician with specialty training in 12 internal medicine and a subspecialty in immunology 13 at Baylor. I was an investigator at the Howard 14 Hughes Medical Institute, so I had a substantial 15 research program. 16 Also, during that time, I had a ten-year 17 Omni IRB and served for a period as Program 18 Director of the General Clinical Research Center. 19 Among other things that I have done 20 relative to the interests of this committee I 21 think, or that I have chaired the National Research 22 Committees of both the Arthritis Foundation and the 80 1 National Multiple Sclerosis Society. 2 For the past ten years, I've been a member 3 of the advisory panel on research of the 4 Association of American Medical Colleges. 5 Recently, I was appointed to the Regulatory Burdens 6 Working Group of the National Institutes of Health. 7 I'm Vice President elect of the American 8 Academy of Allergy, Asthma and Immunology, and 9 President elect of the Federation of American 10 Society for Experimental Biology, or FASEB. 11 In terms of things that are on my mind, I 12 guess I'd like to begin my comments with simply 13 stating the obvious, which is that I feel 14 passionately that clinical research is a societal 15 good, and that what this committee must keep in 16 mind all the time during its deliberations is that 17 we're dealing with things that are basically good 18 for society and good for individual patients; that 19 although we are cognizant of problems in the 20 system, the idea of demonization of either 21 individual investigators or demonization of 22 institutions is not in, I think, anyone's interest. 81 1 And, in fact, I think there is a general 2 recognition that we are in a situation where we are 3 facing a dearth of clinical investigators. And I'm 4 hoping that the work of this committee will 5 encourage people to go into ethical clinical 6 investigation and not discourage what I regard as a 7 heroic thing that individuals can contribute. 8 I think part of our problems are that we 9 are really doing now 21st Century clinical 10 research, as Mary Kay has suggested, but I would 11 submit with largely a 1970's infrastructure. And I 12 think that many of our problems relate to that 13 disconnect between an infrastructure that would 14 develop 30 years ago and have not substantially 15 changed. 16 I find both our investigators and our 17 institutions to now be truly beleaguered as they 18 attempt to confront the issues that this committee 19 will be addressing. 20 We have enormous difficulties at present, 21 and I'm saying this now as a research 22 administrator, as well as an investigator, in 82 1 simply recruiting qualified IRB members, 2 particularly recruiting real clinical 3 investigators. Physicians are unwilling to spend 4 the time and give the effort to serve on IRBs too 5 often because of the lack of systemic rewards that 6 we put into the system for that amazingly valuable 7 service. 8 I'm concerned that too often over the past 9 decade, we've seen regulations promulgated from the 10 federal government with little or any attention to 11 the cost of those regulations, and it's something 12 that I've been rather outspoken about over the last 13 couple of years. 14 Or the provision of resources. I would 15 say that the system that we're talking about really 16 can't be fixed without first addressing the true 17 partnership between the government and the 18 universities. 19 One of the real problems, if you'll bear 20 with me just for a one-sentence diversion into the 21 arcana of research administration, is that the 26 22 percent tap on administrative costs on research 83 1 grants which basically all universities now are 2 faced with -- research-intensive universities are 3 faced with -- means that every new regulation 4 promulgated by the federal government is borne 5 entirely by the university. And I think that 6 that's inappropriate and that's something that this 7 committee needs to weigh in on and we need to see 8 changed. 9 We need to basically redress the idea of 10 the regulatory enterprise as being something that 11 is not simply the government regulating and the 12 university paying. We have to come together and do 13 those things together. 14 I'm concerned about the issues of 15 conflicts of interest that have been very much in 16 the news. I think this is a major area that needs 17 to be addressed in all elements of the research 18 enterprise. 19 I'm very much in sympathy with the notion 20 that not only federally funded research needs to be 21 the attention of this committee, but, in fact, I 22 think that many of the conflicts of interest or 84 1 most of the conflicts of interest, the serious 2 ones, are outside of federal funding. 3 And I would also particularly call to 4 attention my interest in seeing that we have a 5 level playing field from those of us who are 6 regulated between the universities, on the one 7 hand, and the private contract research 8 organizations, for example, on the other. The 9 private agent, the entirely nonaffiliated 10 physicians who are also carrying out now the 11 majority of clinical investigation, who seem to be 12 working with a different set of rules, and I don't 13 think that's appropriate. 14 I think there are a number of simple 15 things that we can do, and these might be seen as 16 small nits to attack. 17 One of the things that I find problematic 18 with our current approaches to informed consent is 19 simply consent forms. I think very few patients 20 who are really gaining informed consent have the 21 patience or willingness to sit and read through an 22 eight-page consent form that is filled with 85 1 legalese, and is basically only readable by a 2 lawyer. 3 And I think one of the things that needs 4 to be addressed is, really, what do we mean by 5 "informed consent," and how can we address the 6 issues of patients to really not simply communicate 7 a huge body of information with the signature of 8 the patient at the bottom of it, but truly informed 9 consent that speaks from one mind, the mind of the 10 investigator to the mind of the patient? 11 I'd like to see us look at enhancements in 12 our logistical capacities for review of protocols. 13 For example, electronic interactions, protocol 14 review, pre-review, preparation, and a professional 15 staff and professional support to help implement 16 those things, because I think, again, we're dealing 17 with a creaky, old system, developed 30 years ago. 18 There are lots of ways that we can 19 simplify things and really protect human subjects 20 more effectively and efficiently, and probably at 21 lower cost if we do it well. 22 Finally, I like the idea of enhancing the 86 1 education programs that have gotten a lot of 2 attention in the past year, both of IRB members and 3 of investigators. The new approaches to the 4 accreditations of IRBs I think is a healthy thing. 5 I hope that it will remain a non-government 6 program, and I would strongly urge that we develop 7 and support the development of mechanisms where 8 non-governmental, voluntary approaches can work 9 with the government to ensure the maximum 10 protection of human subjects in research. 11 Thank you. 12 CHAIRPERSON MARSHALL: Thank you very 13 much, and I just want to say that I couldn't agree 14 more with many of the things that you have said. 15 And it brings to mind a point that I would 16 like to make that I think is sort of overarching in 17 terms of our charge, and that is that we need to 18 think about systems of the protection of human 19 subjects of research. And there has been, I think, 20 too much focus, narrow focus, on IRBs and, perhaps, 21 finger pointing and so forth. 22 And so I would encourage us in our 87 1 thinking, in our deliberation, to think about not 2 only the systems that currently exist, but how we 3 might redefine those systems in the future to be 4 much broader and much more inclusive in terms of 5 those who should be responsible for the protection 6 of human subjects. And that would include the 7 public and having a public that has sort of a 8 higher level of literacy and understanding about 9 the research process, in general, and the 10 protection of human subjects of research. 11 So thank you very much. 12 Adil? 13 DR. SHAMOO: Thank you. 14 I'll start by making a few corrections to 15 the biosketch which is in the program, and, 16 hopefully, it will be corrected later. 17 I'm a professor and former Chairman of the 18 Department of Biochemistry and Molecular Biology, 19 and the word, "former," was missing, and I'm a co- 20 founder of the Journal of Accountability and 21 Research in 1988, not in 1998. That's a ten-year 22 difference. 88 1 And I also am a co-founder of a human 2 right organization called, CRCA, Citizens for 3 Responsible Research, four years old. 4 Let me give you my background which will 5 sort of inform you where I'm coming from. And I'm 6 originally from Baghdad, Iraq. A U.S. citizen now, 7 long time ago. 8 It was a thrill to me to speak a few words 9 of Arabic with Secretary Shalala. I have followed 10 her career since I was a graduate student at City 11 University of New York, and she was one of the 12 member -- she was the President of Hunter College, 13 which is a member of our institution. 14 A lot of you don't know she's an ex-nun, 15 and I know a lot of people don't know that. So 16 I've followed her career. 17 And that explain to you why I have passion 18 and deep love and appreciation to issues of 19 freedom, liberty and democracy. It also explain to 20 you why I strongly react to those who wants to 21 silence those of us who brought these ethical 22 issues and research to the forefront in the past 15 89 1 years. 2 In mid-eighties, I became interested in 3 issues of research integrity, and that's when I 4 started the Journal on Health, eight national, 5 international conferences, several of them in 6 Europe and the remainder here, on issues of 7 research ethics, and the last, specifically on 8 human subject. Some people in this audience have 9 attended some of these meetings. 10 It was in 1991 that I became interested in 11 issues of human subject, and especially the 12 vulnerable subject, that is, the mentally ill. 13 When the National Alliance for the 14 Mentally Ill, what I was serving in the Science 15 Review Committee of that organization, and later, I 16 became a board member of the National Alliance, 17 they referred to me the well-known case now, the 18 UCLA, the Aller case, which is still, by the way, 19 under litigation as I'm speaking now. 20 At the outset, let me say that I do 21 support research. I think research is important 22 because it would be counterproductive, slowing 90 1 and/or terminating research because desperate 2 patients will go and seek unproven medication, and 3 that would be contrary to all what we want to do. 4 But conduct of ethical research is not 5 mutually exclusive from conducting research. We 6 could do both very, very well. 7 Most researchers and research institutions 8 are noble people. They want to serve the public 9 good, and, of course, within our system of 10 government, they want to serve private good, that 11 is, making profit. That's agreeable. 12 However, the incidence of aberrant 13 behavior, at least its discovery, is becoming more 14 and more of it in the past three, four years. 15 I don't know what the percentage is. Is 16 it .1 percent, one percent or ten percent? I 17 really don't know. And, however, the cases we have 18 seen are very disturbing, and some of that research 19 is really shameful, and I'll give you a few 20 examples. 21 The washout experiment, taking psychiatric 22 patients on an out-patient basis and removing them 91 1 from all medication -- these are schizophrenic 2 patients, for example, and leave them in the 3 community for up to a year sometimes with psychosis 4 and delusions, in order to do research. 5 The other one is, while they're washed 6 out, they introduce chemicals into their body to 7 induce psychosis and delusion and study it 8 afterwards. And I thought those experiments should 9 only be done with rats. 10 Furthermore, we discovered that six to 12 11 year old children, they were given fenfluramine, 12 the active component of phen-fen. These children, 13 they were neither sick nor obese. They were simply 14 testing a hypothesis, whether the serotonin rise 15 was going to be very large, and therefore, they're 16 genetically or environmentally prone to violence. 17 University researchers and IRBs all 18 approved this, including NIH, these kind of 19 research. University researchers got involved, for 20 example, in breaking confidential court records to 21 find out who the siblings are so they could recruit 22 them. They were given Toys-R-Us gift certificates. 92 1 But, so far, what has served us really 2 well is really our First Amendment, that is, the 3 media, who brought some of these incidents to our 4 attention. And then were the Congressional 5 hearings through our Congress. And, to some 6 extent, to be very honest, is the OPRR and OHRP, 7 when they took actions that focused attention of 8 all of us to these issues. 9 In short, basically our democratic 10 institutions has really worked. It takes time, in 11 a democracy, to make changes. 12 Most specifically, my immediate concerns 13 are what everybody has mentioned and I have written 14 about, the lack of oversight on non-publicly funded 15 research and non-FDA bound; that is, no longer end 16 up as an MDA. 17 Second is the structure and flawed IRB. 18 They are constructed with a built-in conflict of 19 interest. They are simply employee of the research 20 institution. 21 Third is the aberrant experiments I 22 mentioned to you, and I think they should not 93 1 continue. 2 Fourth, the rapid rise in the use of 3 children in research, and I really look forward to 4 this committee to work and come into consensus to 5 reform the system. 6 I thank you. 7 CHAIRPERSON MARSHALL: Thank you very 8 much. 9 Judith? 10 DR. SIEGEL: I'd like to thank the 11 committee for actually asking for a representative 12 from the pharmaceutical industry, which is where I 13 reside. My experience is that I have a Ph.D. in 14 psycho-biology pre-clinical work. I worked with 15 animals for many years, looking at brains, 16 pharmacology and behavior. 17 I have, for the past 21 years, been 18 involved, in one form or another, of clinical 19 research in the pharmaceutical industry. My first 20 six years was involved in clinical pharmacology. 21 This is early phase testing. And the past 15 22 years, involved in various aspects of clinical 94 1 research. 2 For many years, I was the head, 3 domestically and globally, for CNS research. 4 That's both drugs for psychiatry, neurology and 5 anesthesiology. And for the past six years, I have 6 been responsible in the United States for all 7 clinical research that my company conducts. 8 For two of those six years, I was also 9 responsible for not on the United States, but also 10 the research that we conducted in Latin America, 11 both Central and South America. 12 I feel passionately that clinical research 13 does contribute to the public good. I've spent my 14 career doing it. The way I've decided to do it in 15 my career is through providing pharmaceutical 16 products. 17 I'm also an ethical person, and so part of 18 my contribution, I hope, to the companies that I 19 have worked for is to keep the focus -- I think 20 Greg said it very well -- not on the regulation, 21 but on why the regulations are there. 22 And so, for the past six years at the 95 1 company I'm presently at, what I have been involved 2 with is a revamping and a refocusing on what the 3 ICH guidelines, what good clinical practice, and 4 what all the other regulations that we do our 5 research with, not what the words say, but why they 6 say it, because I think -- and I think many people 7 have said it here also today -- what we're doing 8 is, we're checking off boxes that we've done this, 9 we've done this, and I think we've really lost 10 sight of the "why". 11 I think the "why" is becoming more 12 difficult as the environment is changing in the 13 pharmaceutical industry. Certainly, in the past 15 14 years, I don't think we could have predicted the 15 new challenges that we all have faced. 16 Patient advocacy groups really becoming a 17 major influence on what we do, how we do it, how 18 fast we do it, the types of pharmaceutical products 19 that we're now looking at, not just the old type of 20 molecules, but new types of molecules, and now, 21 genomics, which has totally put us in a place that 22 we have never been before, both ethically and 96 1 research based. 2 And where that's going, I think many 3 people within the industry are trying to sort out, 4 but I don't think any of us really know. And so, 5 to chart a course to someplace you don't know is 6 particularly difficult. 7 I think, also, the business aspects of how 8 we conduct our work have changed in the past years. 9 There are many, many, many new players, 10 biotechnology being, again, a huge piece that, I 11 think 15 years ago, we never could have predicted. 12 With that comes the pressure to put drugs 13 out there more quickly. There are more drugs that 14 are in the pipelines to be developed, and, 15 therefore, there is the press for patients to 16 actually contribute to those trials. 17 And I think clearly the issues that we are 18 facing now about American companies, or global 19 companies, for that matter -- I happen to be with a 20 company that does research. We're an international 21 company. We do research all over the world, in 22 many cases, where the patients exist. 97 1 And the questions are, how do we do that 2 research and still maintain the high moral and 3 ethical ground? 4 In countries where the fact of the matter 5 is, it's not like doing research in the United 6 States, where there is a huge amount of medical 7 support, medical availability -- in countries that 8 we are doing research, there is no such 9 infrastructure. 10 And so the question is, are we unduly 11 pressuring patients to come into trials just 12 because there is no option? I think we worry about 13 that a lot. 14 So I think my particular issues for this 15 committee, for myself, and probably for the 16 industry at large would be really how to facilitate 17 the ability to do clinical research, both in the 18 United States and worldwide, protect the patients 19 without whom we could not be effective, we couldn't 20 do this. 21 How not to introduce so much bureaucracy 22 that it becomes difficult, if not impossible, to 98 1 actually get the work done, while always 2 remembering not what the law says and what the 3 regulations say, but why we're doing what we're 4 doing? 5 Thank you. 6 CHAIRPERSON MARSHALL: Thank you. 7 Denyse? 8 DR. THORNLEY-BROWN: Thank you. With a 9 last name towards the end of the alphabet, I'm 10 always the last to speak. 11 But my name is Denyse Thornley-Brown, and 12 I'm an Assistant Professor of mythology, University 13 of Alabama at Birmingham. So I'm a lot earlier in 14 my career than many of the members of the panel. 15 I was born and raised in Canada and did my 16 medical training in this country. 17 As an academic nephrologist, I do several 18 things. I'm involved in clinical research. I 19 direct the local county renal clinic. That's a 20 clinic that deals with patients who are 21 economically disadvantaged, and I'm also involved 22 in taking care of a lot of patients on dialysis and 99 1 other patients with kidney disease. 2 As a junior faculty member and a clinical 3 investigator, I have several concerns: One of the 4 things in an academic setting, you see, is that 5 there is a lot of pressure for advancement. Good 6 things happen to those who recruit, who find 7 significant findings and who publish. Not only 8 financial rewards, but, also, tenure, grants and 9 reputation. 10 And so, often when we talk about 11 "conflicts of interest," we talk about financial 12 conflicts of interest, but there are also non- 13 monetary conflicts of interest that we see 14 sometimes. 15 I think that I echo the sentiments of 16 everyone on this panel that clinical research is 17 important, it's imperative, and we have all 18 benefitted from clinical research. 19 I guess my two main concerns are how do 20 you make oversight as effective and as unobtrusive 21 as possible? 22 Dealing with IRBs frequently involves the 100 1 letter of the law, as opposed to the spirit of the 2 law, the changing of the wording on the consent 3 form, very subtle changes, but missing the big 4 picture of the project and what is being done. 5 And, certainly, clinical research in a 6 place like Alabama, with the legacy of the 7 Tuskeegee syphilis experiments, we have to deal 8 with many people who don't even remember the 9 specifics of the experiments, but there's a 10 residual atmosphere of mistrust. And how can we 11 regain this trust? 12 How can we protect this trust, and how can 13 we protect the patients? 14 And then my second concern, one that was 15 echoed by many members of the panel is informed 16 consent. 17 While informed consent is hard enough to 18 get from someone who is very educated and 19 sophisticated, how do you honestly get informed 20 consent, truly informed consent, in groups who are 21 educationally and medically unsophisticated, and 22 how can we go about improving this? 101 1 Again, the informed consent document has a 2 lot of information, and all of the required things 3 are there. But are we truly getting informed 4 consent? 5 I'm looking forward to working with this 6 committee, and I think that we're at a very 7 exciting time, and there are a lot of things that 8 we can do as this committee, and I'm excited to be 9 here. 10 CHAIRPERSON MARSHALL: Thank you very 11 much, and I can echo your sentiments about the 12 Tuskeegee legacy, having just moved from the 13 Medical University of South Carolina. 14 A third of the citizens of South Carolina 15 are African-American, and that legacy is alive and 16 well, not only there, but throughout the United 17 States. 18 Thank you very much and thank all of you 19 committee members. We have a wealth of knowledge 20 and experience. 21 I would like to ask Robert Cooke Deagan if 22 he could, within the next eight minutes or so, 102 1 describe for us the charge that has been given to 2 the Institute of Medicine on evaluating the systems 3 for protection of human research subjects. 4 Our committee, the OHRP, has charged the 5 institute. They have accepted this responsibility, 6 and we will be hearing from them in the future. 7 But I would like for the committee members to know 8 the specifics of this project so that we are not 9 being inefficient, at least in the short term, and 10 also, so that we will have the comfort of knowing 11 that we will have a report that is well done and 12 stellar in the future. 13 So thank you so much, Bob. 14 MR. DEAGAN: Thank you, Mary Faith. 15 I'll spare you my bio because it's pretty 16 much irrelevant. It's irrelevant for two reasons: 17 One is, I'm not the Study director. The Study 18 Director is Laura Rodriguez, who just started work 19 two days ago, and also because of the nature of our 20 task. 21 We, at NIOM, as staff people, are really 22 just there to articulate the deliberations of a 103 1 committee, and it's actually the committee that 2 does the authorship. So my background is largely 3 irrelevant, with one exception: It was nice to 4 hear Senator Kennedy allude to the history of the 5 bioethics commissions. 6 I had the distinct honor of being the 7 Acting Executive Director of the Biomedical Ethics 8 Board Advisory Committee. This is the one that he 9 talked about that died in the abortion cross-fire a 10 decade ago. 11 So with that kind of spectacular success 12 on my resume, let me talk about two things: 13 Number one, what is the task that we've 14 been asked to do? 15 Two, I'll talk just a second about our 16 schedule, and number three, about what the content 17 is apt to be. 18 The task, we are doing a project that has 19 just started and will be completed some time in the 20 fall of 2002. Our contract goes through September, 21 2002. 22 We're doing two things: We're going to 104 1 produce two reports, the first of which will be 2 available in April of next year that will focus on 3 the accreditation process and the accreditation 4 standards that are part of that process. 5 We are relying heavily in that task on the 6 work that's already been done by public 7 responsibility in medicine and research that has 8 been working for several years on this. So that is 9 going to be the focus of our first report. 10 The second report is going to look at the 11 overall framework for human research review 12 programs, and so we're going to be looking at -- 13 there's a lot of overlap with the National 14 Bioethics Advisory Commission report that's already 15 underway for that second task. That report will be 16 out some time in the late summer or fall of 2002. 17 So that's the schedule and the task. Now, 18 what's the content? 19 The committee just met for the first time 20 yesterday and the day before, so we are just at the 21 beginning of our process. 22 The discussion was very rich and 105 1 insightful and wonderful, and that's a code word 2 for saying I don't have a clue what they're going 3 to say at the end of the process. 4 And for those of you who have followed the 5 IOM process, basically, we are going to have a -- 6 there's a -- there are open elements and closed 7 elements to our process. Our distinct value added 8 often comes from the fact that we can get people in 9 a room outside of the usual FACA constraints and 10 Federal Advisory Commission Act, and get an intense 11 discussion among our committee members that would 12 produce findings and recommendations. So those 13 will surface in our April report, and there's only 14 so much we can say about findings and 15 recommendations up to that point. 16 Aside from that, though, we're trying to 17 be as public as we can be, and part of that is we 18 will be holding a public forum in January. 19 Now I wish -- I didn't write down -- we 20 made a decision about what our next meeting is 21 going to be after our meeting yesterday, and it's 22 either going to be the 21st or the 22nd of January, 106 1 but I wish I remembered, and it's out in the car, 2 so I didn't get that. 3 But there will be a public forum the third 4 week of January. It will be either the 22nd or the 5 21st. 6 After that meeting, the committee will 7 hunker down. There will be another meeting in 8 February, and we will then go into our report 9 writing and review process and produce a report in 10 April. 11 As part of our process, though, we are 12 going to make available the PRIMAR draft standards 13 that actually already exist. We're trying to set 14 up a web site. In fact, we've set one up, but we 15 don't have a simple URL yet. It's going to take us 16 about a week, it sounds like, to get that. 17 So we're going to make the PRIMAR draft 18 guidelines available as soon as we can, probably 19 within the next week, and the committee composition 20 and our process and our schedule and all that will 21 also be out on that web site, including the members 22 of the committee. So stay tuned. 107 1 CHAIRPERSON MARSHALL: Thank you. And we 2 do have two minutes and then we will take a 15- 3 minute break. 4 Let me ask committee members: Do you have 5 any questions at the moment? Bob? 6 DR. ROBERT LEVINE: Thank you. 7 It's going to happen from time to time 8 that members of our committee will make statements 9 about stories that are widely known about research 10 and it's conduct and its ethics. And if we respond 11 to each one of these as they come up, we probably 12 won't get our job done. 13 But for the benefit of members of the 14 public, I want to say that we've already had some 15 examples of simplified statements about past 16 research activities, where there are many other 17 versions of the same events out there. 18 I particularly want to disassociate myself 19 from anything that's been so far about 20 fenfluramine, but we can't be responding to each 21 one of these as they come up. 22 I think we have some real experts among 108 1 our ex-officio members here, and from time to time, 2 if one seems particularly vexatious, I wonder if we 3 could call upon one of them. 4 CHAIRPERSON MARSHALL: I think we 5 certainly can. I mean one of the things that we 6 need to be particularly attuned to is our data 7 gathering, and so I agree with you. Yes. 8 DR. ROBERT LEVINE: But I wouldn't want, 9 for example, the statements on fenfluramine or the 10 placebo washout to be represented in the press as 11 something that this group has agreed to. Thank 12 you. 13 CHAIRPERSON MARSHALL: I hear you. 14 Mark, quick question. We will adjourn in 15 two minutes. 16 MR. BARNES: Yeah. I'd just like some 17 clarification, if you could, Mary Faith or Kate or 18 if Dr. Koski were here, he could do it, between the 19 charge of this committee as opposed to the National 20 Bioethics Advisory Committee, as opposed to the 21 IOM, and how you think. You know, where do we fit 22 in and what can we most -- you know, how can we 109 1 most profitably use our time? 2 CHAIRPERSON MARSHALL: I will speak first, 3 and then, Kate, please weigh in and keep me honest 4 and accurate. 5 My sense of the charge of our committee is 6 that we are concerned with the protection of human 7 subjects, that issues that arise that we are asked 8 to give advice on, whether it's taken or not, but 9 that will certainly be on the record will be the 10 sources of those questions will arise from the 11 Secretary, from the Office of Human Research 12 Protections, from the other federal agencies that 13 are associated with us, and that also do human 14 subjects research with academic institutions, with 15 non-academic institutions in a broad sense and from 16 the public. 17 So I think that we have a much broader 18 array of responsibilities in terms of those, who 19 can ask us for advice. 20 And we don't have a particular charge in 21 terms of our agenda. It's something that we can 22 set ourselves. 110 1 MS. GOTTFIELD: I think Mary Faith really 2 has summarized it. In terms of the scope, it is 3 broad, but I think that, as you see from the 4 agenda, that we have identified issues for this 5 meeting, and we will go and ask for input, both 6 from the public and from the members of the 7 committee, for what areas you all think we ought to 8 be focusing on, and be clear, also, and we'll do 9 this throughout the day, in terms of where we're 10 going to go with respect to products, whether they 11 be public hearings, papers, et cetera. So that 12 needs to be fleshed out. 13 CHAIRPERSON MARSHALL: So I think our 14 process, in terms of outcome, is vitally important 15 and that we have the freedom and the responsibility 16 to have a good process. 17 So, thank you, Bob, and let us adjourn for 18 15 minutes, and then, for the rest of the day, we 19 will keep to our schedule as it is written. 20 [Brief recess taken.] 21 CHAIRPERSON MARSHALL: While we're getting 22 settled, I wanted to let you know that Jennie Joe 111 1 is not able to be with us here today, but she will 2 be with us tomorrow, and that Dr. Koski has gone 3 downtown briefly to Health and Human Services, but 4 will return this afternoon. 5 So let us move on with our agenda so that 6 we can stay on time. 7 The first substantive item on the agenda 8 is institutional review and oversight of non- 9 biomedical research under the common rule. Felice 10 Levine from the American Sociological Association 11 is going to give us a presentation. 12 And I want to say that the fact that this 13 is the first item of substance on our agenda speaks 14 for itself in terms of how we view the importance 15 of social science research and the concerns that 16 have been raised by members of that community about 17 the review process, and the problems that they 18 perceive relative to their research. 19 So thank you so much, Felice. 20 DR. FELICE LEVINE: I think I'll press my 21 button, but I'm delighted to be here and to have 22 the opportunity to talk about some of the issues 112 1 and challenges for the social and behavioral 2 sciences under the current system for the 3 protection of human subjects. 4 And I missed the swearing in, inclement 5 weather here, but I really want to congratulate all 6 of you, both for your longstanding commitments to 7 these issues, and for your willingness to serve on 8 the advisory committee and underscore what Mary 9 just said, that I think both Greg and Kate, in 10 putting this -- I won't say center stage, but at 11 least putting it as a major substantive issue on 12 the agenda with your first meeting is, I think, 13 valued by all of us in the social and behavioral 14 science community, and I'd like to think all of us 15 in the science community. 16 I thought I might say a few things about 17 who I am. I missed the round robin, but at least 18 it will put me in a little bit of a context. 19 I am a social psychologist with a Ph.D. in 20 psychology. My early training was in sociology, 21 and actually had an interest in receiving 22 experimental social psychological training at the 113 1 University of Chicago, having been an undergraduate 2 there, switched over to the psych part of the soc- 3 psych program and so that my range of research 4 interests and skills really span from the field to 5 the laboratory. 6 My area of expertise is law and human 7 behavior. Actually, much of my early work focused 8 on the development of justice judgments and moral 9 and legal reasoning in children and youth. And my 10 interest in research ethics and the protection of 11 human participants in research sort of dates back 12 to the seventies, and that sort of interest in law 13 and human behavior and the role of law in 14 facilitating, or sometimes impeding various kinds 15 of actions and interactions. 16 I spent 12 years at the National Science 17 Foundation where I was one of the designated 18 program officers at the National Science 19 Foundation, addressing issues of human subjects 20 protection in the social sciences, and I became 21 Executive Officer of the American Sociological 22 Association in 1991. 114 1 And since that time, I've been deeply 2 involved in issues of human subjects protection, 3 research ethics, research integrity. It seems to 4 -- sometimes I wonder what the Executive Officer 5 does. This could be a full-time job, in and of 6 itself. 7 And one of the things that I think, as in 8 other fields of science, the social and behavioral 9 sciences have been long involved in the development 10 of ethical codes and standards, and over this past 11 decade, starting in the early nineties, we actually 12 revised our ethics code. That's not to say we 13 developed new standards of ethics. 14 But I think one of the things that we took 15 very seriously is fleshing out and providing better 16 guidance, especially in the areas of human subjects 17 protection. And, like much of the language that 18 informs the mission statements of and the 19 authorization documents of many of these panels and 20 committees, we really put a very heavy emphasis as 21 much as on education and on prevention as on our 22 regulatory and enforcement role, at least as it 115 1 reaches to members of the American Sociological 2 Association. 3 I really brought copies of this for your 4 advisory group, not because I think it's any better 5 than others, but as I think a exemplar of the 6 seriousness I think with which scientific societies 7 and the scientific community take these issues in 8 the social and behavioral sciences. And, indeed, 9 one of the sites at the end is an appreciation of 10 the American Psychological Association's code 11 because, in undertaking our revision over several 12 years, we used that document in fleshing out some 13 of our own principles and standards. 14 I mention this background for several 15 reasons: One, I think we share -- I, and the rest 16 of the social and behavioral science community 17 share rather strongly an affinity with the 18 biomedical community in a commitment to promoting 19 sound sciences, as requiring ethical practices, 20 especially with respect to the participants and 21 research. 22 I guess I will also say, as a true 116 1 believer and educator in this area, I sometimes 2 feel what we in social psychology have been saying 3 for decades is a dissonance between the growing 4 front lines in the system, despite my encouragement 5 that it needs to be used and embraced by the social 6 and behavioral sciences. 7 And one of the things you will see in the 8 code is that in areas where IRBs are the common 9 rule, and IRBs are not required, for example, non- 10 federally funded research, as we know, although 11 institutions have increasingly had IRBs consider 12 all forms of research involving human subjects 13 protection. 14 Our code explicitly uses the language, 15 "institutional review board or their equivalent," 16 and, indeed, are encouraging researchers to seek 17 out that kind of expertise, recognizing that you do 18 need feedback in making sometimes very difficult 19 decisions at choice points. 20 And so my concern is that as we are 21 promoting what are the right principles and 22 policies, that -- and this is not an uncommon thing 117 1 for a sociologist of law to reflect on -- that 2 there is a gap. I don't know if it's a growing 3 gap, but it certainly is a gap between the law and 4 the policy on the books and law and action. And I 5 guess that's why there's been a proliferation of 6 committees and high-profile attention to the issue, 7 and the very movement of the office to DHHS and in 8 the office of the Secretary. 9 I think, also, as a social scientist, sort 10 of watching and being engaged in all of what's 11 going on and, you know, printing a 250 page and 12 back report in the middle of the night last night 13 and thinking, "Well, it looks like that's done, and 14 what else can I add," not having much chance to 15 read it. 16 I think we need to be cautious. I'm an 17 action oriented person, but I think we need to be 18 cautious and move deliberatively, and we call this 19 a system of human subjects protection. Unlike the 20 biological system, you can't start altering too 21 many things simultaneously and know where those 22 causal hours are leading. 118 1 So I find myself sympathetic to a lot of 2 what one can read about or hear about in the back 3 reports or the kinds of commitments we have, both 4 to better training and education, both to 5 certification, both to accreditation. 6 But I do think we need to both, A, proceed 7 with reforms using something of a model of 8 evaluation and study, and we need to be thinking 9 not -- I'll say rush to judgment about putting too 10 many different changes in place simultaneously in a 11 way that may not always give us enough 12 understanding of what is moving us closer to our 13 aspirations. 14 That said, I'm not critiquing anyone, but 15 I do think this is a social system and it is a 16 social system that is a dynamic process and a 17 changeable process. We should not be reluctant to 18 change, but we should be thinking through these 19 changes as interventions in and of themselves. 20 Most importantly, for those of you who 21 carried the earliest agenda, and what is what 22 brought me here today, and received the phone call 119 1 from Kate late afternoon on Monday is that I'm not 2 Jonathan Knight, but I'm going to seek to be his 3 stand in. 4 He is, as you may all know, and I think 5 you received the paper. You may not have read the 6 paper, and the task before me is to give you a 7 little bit of an overview of the paper and what led 8 us there, is that he's Associate Secretary of the 9 American Association of University Professors. 10 He's a political scientist, by training, 11 and he was our team leader, as we might think of 12 it, of an informal group of representatives from 13 the American Anthropological Association, the 14 American Historical Association, the American 15 Political Science Association, the American 16 Sociological Association. I was the rep. The Oral 17 History Association and the Organization of 18 American History. 19 We've been working together for a little 20 bit over a year, and our goal was to examine the 21 experiences of social scientists and humanists with 22 IRBs and the human subjects protection system. 120 1 And the report you have, I'll say, is a 2 preliminary report based on the best of where our 3 thinking is and was at the point at which we at 4 least consolidated the information we received over 5 the course of last year, and we've posted it on the 6 web site, and we hope that you all read it and 7 respond so that we can continue to have that kind 8 of interaction. 9 Jonathan's out of town, and so I'm sort of 10 the stand in, in the process. 11 CHAIRPERSON MARSHALL: I just wanted to -- 12 excuse me for interrupting, but I wanted to say 13 that sort of our goal is to make things 14 transparent. 15 We will be posting this paper on our web 16 site, as well, so for those of you from the public, 17 we apologize for not having it available to you 18 today. In the future, we'll have copies of all of 19 our papers available to members of the public, and 20 it will be on the web site. 21 Sorry to interrupt. 22 DR. FELICE LEVINE: No. That's fine. 121 1 Just a little bit by way of background, 2 recognizing that those beyond the hollow square 3 haven't yet seen it and may not have known of this 4 activity because, indeed, we have just posted it 5 recently, the American Sociological Association and 6 the other social science amenities associations 7 responded to the AUP invitation to look at the role 8 and scope of institutional review boards because, 9 over the years, IRBs have played an increasingly 10 prominent role in all institutional campus 11 research, colleges, universities, research 12 institutes involving human subjects, not just 13 federally-funded research, which, of course, they 14 are mandated to do, at least with respect to the 15 agencies that have signed on to the common rules. 16 In the humanities, much more than in the 17 social sciences, there's been far less of a history 18 of experience with IRB review and with general 19 guidelines for the protection of human subjects. 20 So you will read an opening footnote that says, 21 "Well, the humanities for this purpose should be 22 considered part of the social and behavioral 122 1 science affinity group," and we were an affinity 2 group working together. 3 But the three history societies working 4 with us had a range of concerns that flowed from 5 work grounded in the humanistic and the historical 6 traditions that had not typically reached to IRB 7 review or approval, as the National Endowment for 8 the Humanities, for example, is not under the scope 9 of the common rule and is not one of the agencies 10 that require IRB approval. 11 So there were questions about oral history 12 and how that would unfold, and as you will learn in 13 reading the report, in discussions with IRBs, there 14 was an increasing incorporation of some of the 15 guidelines for oral history and other of the 16 principles that inform historical research 17 involving human subjects. But that's a more recent 18 entry into the field. 19 As a consequence, many of the members of 20 the humanistic traditions have less awareness of 21 when and where they are governed by IRB review 22 than, I will say, more typically the case with the 123 1 rest of the social and behavioral science community 2 that has felt itself to be a part of the -- and 3 their research certainly, that funded by the 17 4 agencies that sign onto the common rule to be under 5 the system for as long as the rest of the sciences 6 and the biomedical sciences. 7 All of us agreed at the time that we 8 needed to learn much more about IRBs, how they 9 operated, the areas that might need improvement, 10 the presence of IRBs in academic and other research 11 organizations, as you know dates back to 1974. And 12 as I just said, it's reach was one that certainly 13 incorporated the social and behavioral sciences. 14 But we thought that this was an 15 appropriate time to learn more and less 16 anecdotally, although we refer in the report to the 17 fact that it was, we stressed, an informal effort 18 to reach out to our research community, including 19 students. 20 But we did want to do so because 21 increasingly, we were concerned about what I've 22 referred to as those "fault lines," the sense that 124 1 there was a operational departures between what are 2 the rules and principles and the ethical standards 3 embedded in the common rule, and how, in practice, 4 they were being used, certainly across 5 institutions, and sometimes, even at that very same 6 institution, at different points in time. 7 And we all know that, in terms of social 8 interactions and the functioning of social 9 institutions, that there's a larger, I'm going to 10 say, environment, policy environment and political 11 environment, with a little "P", that shape the 12 culture of an institution and how it's 13 organizational structure functions at different 14 points in time. 15 An, indeed, embedded in the original 16 process was to give the local site, the site that 17 was sensitive to the norms in the culture, some 18 delegated authority to interpret and use the rules 19 and guidelines as is appropriate to those 20 circumstances, of course, within the general 21 limits. 22 And I think some of that is the, you know, 125 1 kind of the dynamic that sometimes has created some 2 degree of fuzziness, as one might say, especially, 3 I think, with respect to the social and behavioral 4 sciences, operating in an environment that still 5 remains very heavily defined and identified with 6 the biomedical parts of science, even though both 7 the ethical standards are shared widely across all 8 fields of science -- the common rules certainly 9 applies across all fields of science -- and IRBs 10 have reached, at least with respect to federal 11 funding, to all of the social and behavioral 12 sciences funded by this very same agencies that 13 support biomedical research. 14 That led us to the notion of asking some 15 questions, of course. Social and behavioral 16 sciences can hardly control themselves from doing 17 that. And I will say -- I was sort of thinking in 18 the middle of the night, you know, I did not get 19 IRB approval for this, but we did it. We posted it 20 as -- we all supposedly were going to post it, and 21 we did, in our newsletters, and we didn't even see 22 it as a survey. You know, you could just give us 126 1 and send us in anonymous form your answers to some 2 questions. 3 Well, actually, I have another handout. 4 But this is sort of what we were trying to cover, 5 getting over the past three years, including from 6 students. How many research protocols were 7 submitted? How long did the review take? What 8 types of review did your research receive? 9 And we started to expedite it. We're 10 aware, as most people in this room are, that those 11 definitions are clear, and yet may be interpolated 12 and interpreted differently in both the different 13 forms in time and in different locations. 14 Do you think the members of the IRB were 15 familiar with the research standards and practices? 16 Were you asked to alter your research 17 projects in some way, et cetera. 18 I think that one of the things you'll see 19 in the report is that we say that roughly 20 20 percent of the protocols considered by IRBs go 21 through without further interaction and across 22 sciences. That's not unique to the social and 127 1 behavioral sciences. 2 What we don't know is that largely with 3 respect to the social and behavioral sciences, 4 these are all good research questions. 5 We didn't stop there, though. I just 6 wanted you to know that our interest in this is 7 really embedded in understanding the system. So we 8 really wanted to know from the social and 9 behavioral scientists who have served on IRBs what 10 the nature of their experience is, whether they 11 felt prepared, what the training was, how they 12 ended up getting there, how much did they have to 13 invest in essentially being the token, the educator 14 about the social and behavioral sciences to persons 15 who might be heavily oriented and experienced in 16 other fields of science. 17 So we asked questions about level of 18 agreement, and also what institutional dedication 19 of time is given to those who are really giving 20 mightily, as you all are here, and then having your 21 careers in that area; that it's no small amount of 22 time to serving your institution and your other 128 1 colleagues in a review of their scientific work. 2 I'm showing these questions because in 3 part, when you read the report, and you will see us 4 refer to it as an "informal survey" -- well, we 5 didn't draw large samples and we weren't seeking to 6 do a highly formal piece of research. But we were 7 systematic in our questioning, and at least two of 8 the associations -- I think the American 9 Sociological Association and the American Political 10 Science Association put this on our home page, and 11 it was designed in such a way that we've, of 12 course, assured anonymity to the respondents. 13 And it went out, "Levine," and it came 14 back, "Levine." Indeed, I had sort of forgotten, 15 after I got my first 20 Levines back, I was sort 16 of, who is this Levine that's writing, and isn't 17 that ironic since my name is Levine. Then I caught 18 the drift here that it was the way that we had set 19 it up to essentially seclude the respondent. 20 And it was quite informative. It was 21 both, as you will read in the text of the paper, 22 there was a lot of support and very positive things 129 1 to be said about both experiences being and serving 2 as members of IRB and the gratification that comes 3 with doing that and doing a good job, and also a 4 range of concerns. 5 And I must say, over the past year, as the 6 topic has ratcheted up in saliency, it seems as if, 7 even beyond our report, that the number of concerns 8 articulated by social and behavioral scientists 9 have increased. 10 There have been many high profile cases, 11 and as a consequence of that, the ways that consent 12 and written consent, and when, indeed, there could 13 be waivers of written consent, have been altered in 14 ways that are less appreciative of the dynamic and 15 the elements of doing ethically sensitive research 16 in the social and behavioral sciences. 17 The frequency of this, we don't know, but 18 it's not uncommon now that I will get several e- 19 mails a day about what happened in an IRB, and 20 concerns about what to do. 21 I've listed some things that may come out 22 less clearly in just reading the report that I 130 1 think are very current concerns. 2 The use of public secondary analysis of 3 public use files where the data are structured in 4 totally anonymous ways without identifiers and both 5 data from federal statistical data collections, and 6 also national data sets like the panel study of 7 income dynamics. 8 Now, this is an example of gap. We all 9 know that, and this comes right from OPRR -- we all 10 know that with identifiable private data obtained 11 for research in a form that is associated with 12 individuals, yes, it needs to be reviewed. But it 13 doesn't apply with respect to data that, where 14 there are no identifiers, and that are data that 15 are in public use files, or that have been 16 previously have vetted the creation of public use 17 files by IRBs in the initial research. 18 So that is an illustration of the kind of 19 thing that, certainly in terms of the allowability 20 under the common rule, have been allowed, but in 21 terms of the practice of the system, that's the 22 fault line. 131 1 Ethnographic research, unobtrusive 2 research in public places. 3 Student research in the class is 4 increasingly being challenged so that professors 5 are reporting that it could take the whole semester 6 to have a student research training program, unless 7 one is either using the extent data or working 8 under an ongoing project approved by an IRB. So 9 this is not atypical. 10 Here is one question that we left 11 unresolved, and this was in the context of an 12 institution. To graduate students and seminars, I 13 have to get IRB clearance for term projects that 14 use nonidentifiable record data from public 15 archives. 16 The official new answer is, underlying 17 "new," yes, but it's unlikely that you could do it 18 in time to complete a term project in one semester, 19 especially if part of the seminar is devoted to 20 finding and developing a project. 21 You can always say that the work is not 22 supposed to contribute to generalizable knowledge. 132 1 And then this respondent goes on to say, but as an 2 academic and as someone training someone in 3 research, I truly would not want to say that your 4 work is not and should not be motivated by an 5 interest in producing useful and useable knowledge. 6 So these are the kind of situations that 7 I'm terming the gap or the fault line that are 8 especially problematic in the social and behavioral 9 sciences. 10 Let me conclude by emphasizing why. 11 The system is one without however it 12 evolved over time and because of the seriousness 13 with which biomedical research created the impetus 14 for the development of the system. It is still 15 very dominated, both in person power and advisory 16 structure, this advisory structure and other 17 advisory structures, IRB structure by persons who 18 are primarily knowledgeable and expert in fields 19 outside of the social and behavioral sciences. 20 And one of the things that's very 21 important in the consideration of this is how we 22 integrate and develop a system that sensibly looks 133 1 at the research and the kinds of expertise 2 necessary to consider that research, irrespective 3 of disciplinary divide. 4 And I think that as we look at the 5 recommendations, we need to seriously give serious 6 consideration to the place and location of social 7 and behavioral sciences expertise at each point in 8 the decision-making process. 9 CHAIRPERSON MARSHALL: Felice, thank you 10 for articulating those points for discussion. 11 Board members, I know that you have had 12 the opportunity to read the paper and to think 13 about it. 14 I just want to establish a couple of 15 ground rules, not only for this session, but 16 henceforth, and that is I would ask you, board 17 members, to make your questions clear, to make them 18 concise. No show off questions will be allowed. 19 And I will take questions. Unless they're on 20 point, I will take them in the order that I see 21 hands go up and I will brook no interruptions. 22 So we have half an hour for discussion, 134 1 and then we have half an hour for recommendations. 2 So, Elliot? 3 DR. DORFF: Thank you for the paper. I 4 must say that I was really enlightened by it in 5 ways that I -- I'm on my field's philosophy, so I 6 don't do this kind of research, and I've been 7 involved a lot in bioethics, so I assumed that, you 8 know -- and I've been in IRBs and it's all been 9 biomedical. 10 I have two questions: One is, when I got 11 to the end of the paper, I thought it fizzled out 12 in its recommendations because if I were writing a 13 paper, I would say, first of all, if you had -- 14 forget about the history of IRBs. 15 If you had your druggers and you thought 16 that -- and you were creating a completely new 17 structure for protecting human subjects in your 18 fields, then what would it look like? 19 In other words, you know, if you could 20 reconstruct the whole system for, you know, 21 sociology or for history or whatever, then, you 22 know, and be completely apart -- I mean one of the 135 1 recommendations you make is that in, at least large 2 universities, maybe you'll have a completely 3 separate IRB for only people, for non-violent, you 4 know, with people on it that are not biomedical 5 researchers, but rather in sociology. 6 Is that how you would do it, or would you 7 do it in some other way? 8 And the second question that I have is a 9 more limited one. In the end, you say -- I'm on 10 page 36. "Lastly, IRB members could discuss with 11 academic departments the possibility of blanket 12 exemptions for certain types of research; for 13 example, survey research or oral history research. 14 And the IRBs are delegated to the department 15 responsibility for an initial review of research 16 that does not pose a threat of physical or mental 17 harm to human subjects." 18 My question there, again, is why did you 19 limit that recommendation to specific IRBs 20 considering it? 21 Maybe the regulation altogether should 22 change. Maybe the common rules should change to 136 1 effectively say these things in addition to the 2 sixth, I guess, that are already exempted from the 3 common rule. Maybe there are some other things 4 that should be exempted from the common rule 5 altogether. 6 DR. FELICE LEVINE: I think all your 7 observations raise good and important questions 8 that we need to give more consideration. I think 9 if -- I'll say the phase we were at was longer on 10 hearing -- learning than on sharpening our 11 recommendations, and in a way, that's why we put 12 them out as kind of a working draft, because I 13 think our own thinking is still in process on 14 especially I think the two key issues I think that 15 you raised. Let me respond to the two key issues 16 that you raise. 17 I think it's always nice to imagine how we 18 would all start, where we would be able to start 19 the novel, and one of the reasons why I referred to 20 ASA's own thinking in the evolution in the code of 21 ethics is that, and my own set of believer in the 22 system, is that I think that the system really is 137 1 designed, has a lot that's positive. 2 And when we're looking at its problems and 3 its fault lines, I'm rather keen on not throwing 4 out babies with bath waters here. 5 And in figuring out how in the 6 operationalizing of this and in the dynamic 7 environments in which it lives, in areas that 8 sometimes can be very troublesome and very high 9 profile, how do we make this effectively work? 10 And I think that's what NBAC is about, and 11 I take it from Mary's remarks earlier before the 12 break that very much is what you all will be about. 13 I think in the social and behavioral 14 sciences, what we have lacked collaboratively 15 across all fields of science, and perhaps this 16 reflects some of our own growth and evolution as 17 fields of science, is sufficient integration into 18 the system. 19 And that is that in the examples that are 20 used, in the education and training that goes on, 21 in the composition, as I said, not just of IRBs, 22 but of staff, of staff administering the system, of 138 1 organizational forms accrediting the system, of 2 training programs that the biomedical model 3 predominates in such a way that it produces two 4 outcomes. 5 One, a lack of appreciation of the ways in 6 which ethical research, consonant with shared 7 standards, I believe, can and should be 8 operationalized. And, on the other hand, perhaps a 9 capacity of some researchers to almost distance 10 themselves as, well, that's about that kind of 11 risk, without sufficient understanding of how some 12 of those same issues come into play in different 13 contexts. 14 And so I think that this is, in a sense, 15 it's kind of a shake hand notion. Maybe this comes 16 from my years both at NSF and disciplinary work. 17 What I think is good for science, I think is good 18 for the social and behavioral sciences. 19 And by having a very imbalanced 20 biomedically driven system, the social and 21 behavioral sciences have not been able to 22 adequately contribute to the biomedical thinking 139 1 about their science because you're there 2 essentially to work on your own science, in a way. 3 And, similarly, social and behavioral sciences have 4 not had the benefit of more informed biomedical 5 input. 6 And so what I would like to see is a 7 transformation where the two can come to the table, 8 frankly, with great apparency. One of my 9 transparencies, because it sort of blew me away, 10 you know. We all know what the 17 agencies are, 11 and I got the NBAC report, and I knew I was hardly 12 going to have a chance to even print it, but I did 13 print the 17 agencies under the common rule. 14 And when you think of the Department of 15 Justice, the Department of Education, Agriculture, 16 EPA, there is so much research that is done and 17 supported NSF that doesn't flow from the biomedical 18 or the clinical framework that needs to be 19 integrated, even if the literal number of protocols 20 and projects, given the, especially at this point 21 in time, the disproportionate amount of federal 22 funding that goes to the biomedical sciences versus 140 1 the other sciences. Clearly, the disproportionate 2 amount of research protocols will come from other 3 fields of science. But I think the ideal framework 4 would be one that is much more truly integrated. 5 That probably gets to the response, a 6 briefer one, to your second issue. 7 I personally think that there may be some 8 range of things that could be delegated at the 9 department level, especially -- or, of course, 10 units, shared units, and this may be true across 11 different fields of science, especially with 12 respect to perhaps the review of classroom 13 research. 14 I have tended toward thinking the science 15 community has more to gain by working in common. 16 So I would find myself disaggregating less and 17 emphasizing more shared education and understanding 18 about the methods, and not ethics, but ethical 19 operationalizing of considerations as they relate 20 to the methods of research. 21 I think something is aggregated as survey 22 would need a lot of clarification as to the form of 141 1 survey, if I just can use that as an example, 2 before one could have a exemption. 3 Clearly, there are certain forms of 4 surveys which had either expedited review 5 previously that now are not necessarily receiving 6 expedited review, that are mailed anonymous surveys 7 to adult populations about, you know, opinions 8 about culture or dress or something. 9 Now, obviously, surveys that are dealing 10 with more vulnerable populations, like children, 11 have a process and procedure for IRB review. 12 And the other thing I wanted to pass out 13 is that we very much in the social and behavioral 14 sciences and the health-related community -- this 15 is a piece, a historical document, just one each, 16 and it was very much pushed for at a point at which 17 there was Congressional legislation pending that 18 would have required that all research involving 19 children had to be written consent. 20 And the social and behavioral science 21 community, with the health-related and education 22 community really said, "We have a system in place 142 1 that values written consent, but recognizes that 2 this must be understood and operationalized under 3 different circumstances that different research 4 might require. 5 So if you're studying youth gangs or 6 you're studying runaway children, you can't get 7 written consent, but the current rules allow for 8 that. 9 And so that to exempt all surveys or all 10 classes based on a methodology could be 11 problematic, but to have expedited review for 12 certain forms that have met minimal risk, and for 13 the re-review of that same research seems to me 14 well within I think what the articulated 15 aspirations initially were, and what we now need to 16 do is be able to specify that in a way that is more 17 uniformly both interpreted and understood by IRBs, 18 which probably relates to their training and 19 expertise to do that. 20 DR. DORFF: It would seem to me that, for 21 this community, it would be helpful if you people, 22 right, who know what kind of research you do, could 143 1 come up with -- I mean there's clearly a range of 2 things that you do that imperil human subjects to 3 different degrees. 4 Oral histories probably don't. That's on 5 one end of the spectrum, right? Something having 6 to do with -- I mean you define for me the other 7 end of the spectrum, and then define for me things 8 that are in between, because then, we would have a 9 better sense of what kinds of things maybe ought to 10 be completely exempted, and some things that have 11 to go through full review, and some things that 12 would be recommended for expedited review. 13 DR. FELICE LEVINE: Right. 14 DR. DORFF: And, frankly, I would depend 15 upon you to give me that kind of a list -- 16 DR. FELICE LEVINE: Right. 17 DR. DORFF: -- because I don't do this 18 kind of research. 19 DR. FELICE LEVINE: And I think I gave -- 20 in my examples, those were some examples that, 21 indeed, could either go through expedited review. 22 I think the current list in the common rule has 144 1 others that clearly would be classified as such, 2 and I think that both can be provided. 3 And one of the reasons why I circulated 4 our code is that it becomes clear, not when it 5 could go through expedited review, but when consent 6 is necessary, when consent isn't. 7 Clearly, the current problem of requiring 8 re-review of analyzing public use files is one 9 that's quite boggling to the researcher. 10 CHAIRPERSON MARSHALL: Thank you. 11 Bob, and then Bob, and then Adil. 12 DR. ROBERT LEVINE: Thank you. I want to 13 respond to the proposition that we might consider 14 blanket exemptions or blanket categories for 15 expedited review. 16 We have a history in this regard, and it 17 hasn't served us well. The National Commission 18 recommended expedited review for certain 19 categories, but one of the primary elements was 20 that it had to be related to the experience of the 21 local IRB. 22 If they had done something over and over 145 1 again, there comes a time when there's not much 2 more new to say. So that they could have a 3 responsible form of expedited review which included 4 a recommendation by the expedited reviewer to bring 5 it before the whole committee. 6 What we got instead, and the National 7 Commission published a proposed list for expedited 8 review that was then current in the NIH clinical 9 center. And before anybody -- well, what happened 10 is that this proposed list from the clinical center 11 became the only expedited review permitted under 12 the regulations for many, many years. 13 As far as blanket exemptions go, it's 14 tempting to say why we ought to give an exemption 15 to a certain category, for example, oral history. 16 That doesn't present any risk. 17 I'm from an institution where an oral 18 history work was done by Robert J. Lifton, where he 19 went around South America and interviewed all the 20 Nazi war criminals that were still hiding out. 21 There was some risk. 22 Breach of confidentiality. There would 146 1 have been -- had remarkable consequences. 2 But we have this all the time. Survey 3 research. You know, I could give example after 4 example. 5 What I think we need is what you're asking 6 for, and that is to have the sophisticated 7 understanding of the various research methodologies 8 and the ethos of various research groups built into 9 the human subjects protection system. 10 We also have to have a system where the 11 members of the IRBs are not intimidated by the 12 possibility of applying some sophisticated judgment 13 for fear that they will be second guessed and find 14 their names in the paper or find their -- 15 PARTICIPANT: -- 16 DR. ROBERT LEVINE: So what we're finding 17 more and more now is that members of IRBs -- Bob 18 talked about the loss of motivation to serve on an 19 IRB, as more and more, they're beginning to be 20 perceived as probably incompetent because that's 21 what the newspapers and the politicians and the 22 governmental committees keep saying. 147 1 And even at that, anything they might do 2 might be second guessed by somebody who had the 3 authority to make life very difficult for them. 4 They're not using what little bit of discretionary 5 judgment they might. We have to look into this 6 very carefully. 7 Thank you. 8 DR. FELICE LEVINE: I think that I 9 couldn't have said it better if I was Robert 10 Levine. I think you captured what I was trying to 11 communicate. 12 I have worried, especially, I think the 13 recent rash of phone calls over the, let's say the 14 false cycle of having your proposals reviewed I 15 think is a reflection of the chilling effect IRBs 16 are feeling in being in a fishbowl and not knowing 17 which way to go with respect to things that they 18 didn't get right. And, you know, we all face that 19 when we're in a fishbowl. You sort of overreact in 20 a variety of ways. 21 And it's having difficult consequences for 22 the researcher, for absolutely sure, and it 148 1 certainly is widening that fault in the system. 2 And some of it is, you know, the adverse 3 consequence of, you know, of the very troubling 4 things that needed remedy, and the problem is you 5 can overreact. 6 And that's why I said the staging and 7 sequencing of altering the system I think requires 8 some statespersonship, too, because, you know, 9 quick fixes aren't going to get us very far. 10 They're just going to postpone the problem. 11 CHAIRPERSON MARSHALL: Thank you. 12 Robert? 13 DR. RICH: I'd be interested in your views 14 of, and where the association would view a survey 15 that -- I would posit a survey which you would 16 agree would put subjects potentially at risk by the 17 nature of the questions that we're asking, and that 18 the same survey could be used either for scholarly 19 purposes in a university department of sociology or 20 psychology, could be used not for scholarly 21 purposes in the same institution, but simply as a 22 teaching exercise in the classroom, could instead 149 1 be used as a mechanism of public survey by a 2 private organization like the Gallup organization 3 or the Roper organization, or something like that, 4 or, finally, be used by the media in an effort to 5 simply go out and, as we see all the time, media 6 surveys of public opinion which might, in fact be, 7 put subjects at severe risk because not only is 8 their opinion published, but their name and 9 demographics are often -- also show up in the 10 newspaper. 11 And I think it's a terribly worrisome 12 issue to me is, and really comes down to what do we 13 mean by human subjects research in a sense, because 14 the same instrument might be used for very, very 15 different purposes, with different consequences, 16 and we seem to focus simply on the scholarly 17 activities, where the risk to human subjects may be 18 actually much more for some of these more public 19 kind of things that don't have a scholarly purpose. 20 DR. FELICE LEVINE: Are you literally 21 talking about the same research instrument, or are 22 you -- 150 1 DR. RICH: Same. 2 DR. FELICE LEVINE: -- as opposed to the 3 same methodology? 4 Well, the -- yeah? 5 DR. RICH: I mean I'm just giving you the 6 same research instrument for simplification -- 7 DR. FELICE LEVINE: Uh-huh. 8 DR. RICH: -- of the question. 9 DR. FELICE LEVINE: Uh-huh. Uh-huh. 10 Well, I think that probably goes back to both what 11 Bob and I were -- Professor Levine, I should say, 12 and I were sort of postulating, and that is that 13 I'll say a one-size-fits-all language probably 14 would have very dysfunctional sort of consequences, 15 and that is that under some framework of review, 16 the question is are people being put at risk, and 17 if so, in what ways? 18 Now, the production of knowledge may be, 19 in some general sense, might, you know, insofar as 20 knowledge challenges, common assumptions in all 21 fields of science may produce some risk for some. 22 I think that would be an overreach, to define human 151 1 subjects in such a broad stroke because it could 2 really cripple an interest in producing knowledge. 3 But it seems, from your question, it's a 4 little bit hard to envision this same instrument 5 asking questions that would make some vulnerable in 6 some context and not in other context. 7 But, certainly in my career at a research 8 institute, I was a non-academically based research 9 institute. I was very much a promoter of having 10 and creating an institutional review structure, 11 which I'm pleased to say, exists today at that same 12 institution, including with community members for 13 assessing any risk and potential risks involved in 14 doing research, and whether human subjects are 15 adequately being protected. 16 And, clearly, the federal discussion, at 17 least by the National Commission, is looking much 18 more at the research than where it occurs and/or 19 who it's funded by. And I think that, in general, 20 would be a standard and one that probably needs to 21 be scrutinized with respect to any specific method. 22 DR. RICH: If I could follow up? 152 1 CHAIRPERSON MARSHALL: Briefly, because I 2 want to entertain a question from Adil, and then I 3 would like to see if there are any of our ex- 4 officio members might have questions. And if I 5 have time, then I would entertain questions from 6 the public. Okay, and Sandy is on the list. So, 7 brief, concise. 8 DR. RICH: Okay. My follow-up is 9 basically what you view -- what the professional 10 view is of things like investigative reporting 11 been, which clearly puts subjects at risk in a 12 substantial kind of way. 13 I don't think any -- where probably 14 everybody in this committee right now is following 15 with interest the emerging stories in the 16 Washington Post about international drug trials, 17 and as a general premise, I think we think that's 18 probably a good thing to be happening. 19 But I doubt that there's been an IRB 20 that's looked at the nature of the processes that 21 are being promulgated to get that story. 22 DR. FELICE LEVINE: Well, let me say that 153 1 there are non-scientific fields that might use 2 scientific methods in inquiry, and that may -- or 3 might use some version thereof which may be true of 4 investigative reporting. 5 As a scientist, and I'm now speaking as a 6 scientist as much as a social or behavioral 7 scientist, certainly I and our part of the 8 scientific community has not expressed a view with 9 respect to the role and functioning of non- 10 scientific parts of the labor force, whether it's 11 the functioning of lawyers and how they might go 12 about their work, or journalists. 13 And I might, as a lay citizen, have a 14 view, but I think I would be going well beyond my 15 role as a scientist and a representative of the 16 scientific society to comment about what might be 17 the appropriate norms and practices, let's say 18 investigative reporting or journalism, which under 19 our understanding, certainly we would not define as 20 social and behavioral science. Let me put that 21 right on the table. 22 However good and useful it may be as a 154 1 public good, and the public may have a legitimate 2 interest in, and I believe it does, as a citizen, 3 in a fair and open press, clearly, that profession 4 also needs to scrutinize how it does its work and 5 whether, in light of it implementing those 6 appropriate professional goals, whether they are 7 also producing some harm that may need some 8 reflection and self-regulation. 9 CHAIRPERSON MARSHALL: Thank you. 10 Adil? 11 DR. SHAMOO: I want to ask, on the other 12 side of this issue, do you know currently if there 13 are research and social and behavioral sciences 14 which is not currently under common rule or 15 regulation that needs to be, and how should we do 16 it? 17 DR. FELICE LEVINE: I think that leads to 18 my knowledge and impression that the social and 19 behavioral science research that involves forms of 20 primary data collection on human participants does 21 fall within both the ethics codes that govern our 22 sciences, as well as the system in place. 155 1 But for the caveat of recognizing that 2 there may be some institutions, because that only 3 reaches currently to agencies under the common 4 rule, and the federally-funded research 5 technically, there certainly remain institutions 6 and in all fields of science, including in the 7 social and behavioral sciences, that these 8 guidelines do not technically govern. 9 And one of the reasons why I started this 10 by tipping, at least as an example in sociology to 11 our code, is that when I and our committee examined 12 the old code, we talked about investigators 13 submitting through a process of review work that 14 falls under federal guidelines. 15 And we had a conversation that went on for 16 quite some time about why we were doing that. 17 Weren't there principles at stake that required 18 review of all work of that genre and the code thus 19 now says, or the equivalent, because if it doesn't 20 exist, find something. 21 If your institution doesn't have it, ask 22 another IRB at a neighboring institution, and 156 1 that's what my research institute did for a while, 2 the one that I career line at, and that is that it 3 sought the advise and asked for the participation 4 of the peer review process and IRB process, I 5 should say, at the University of Chicago, until it 6 put in place its own IRB. 7 And, thus, there clearly are things that I 8 would like to see operate according to the more 9 general principles that are not now required. But 10 I think, increasingly, that's reducing because I 11 think certainly within institutions that have 12 assurances of compliance, they are now looking at 13 both federally and non-federally funded work. 14 CHAIRPERSON MARSHALL: Sandy? 15 DR. CHODOSH: I have to be a little bit of 16 a devil's advocate. I'm sorry. 17 CHAIRPERSON MARSHALL: That's okay. 18 DR. CHODOSH: I'm not sure that our rules 19 that we serve under right now don't cover a lot of 20 your concerns. I think the problem is that they're 21 not being implemented. 22 And this gets down to the fact that when 157 1 an IRB, for any reason, does not have the capacity 2 or the knowledge to review a protocol, they are 3 supposed to have outside review. If they are not 4 doing it, it's usually because of their ignorance 5 or because it costs money to do so, or for various 6 reasons. 7 And I certain understand that the 8 psychosocial behavioral sciences have suffered a 9 great deal in this respect, but it's because -- not 10 because the rules aren't there, but because it's 11 not being implemented properly. 12 But this is also true of a lot of medical 13 research. Most IRBs are not capable of doing, at 14 least even the best ones are really not capable of 15 reviewing probably ten percent of their research. 16 If they're not bringing in consultants for 17 outside review, then they're not doing the job that 18 the rule says it's supposed to do. 19 So I'm not sure that the correction is 20 where you say. Let's not change rules too quickly. 21 Let's make sure that the ones that we have are 22 being implemented properly, and I don't think they 158 1 are. 2 DR. FELICE LEVINE: I believe what you 3 said to be devil's advocate for the moment is 4 actually closer to what I said. Indeed, I've said 5 as a proselytizer of what we have on the books. 6 When either the full line or the 7 operationalizing of rules departs too far, then we 8 need to ask ourselves what do need in place to 9 really either redefine them or elaborate them or 10 train for them, or change the composition of those 11 implementing them so you don't have what are -- I'm 12 going to put it in quotes, but essentially, 13 discriminatory processes in the system where the 14 haves come out ahead, and the have nots don't in a 15 way that puts a burden on, in this case, on the 16 scientific enterprise. 17 CHAIRPERSON MARSHALL: Thank you. 18 And now, I would like to entertain 19 questions from our ex-officio members, if they have 20 questions, and then please, for my sake and for the 21 sake of others, if you could introduce yourselves, 22 and again, give your affiliation. 159 1 MR. SHELTON: This is working? Yeah. Jim 2 Shelton, U.S. Agency for International Development. 3 I really wanted to sort of follow up on 4 Dr. Rich's, I think, very important point, and 5 maybe extend it, even. But just to make the point 6 that, given that the top is non-biomedical 7 research, the field of play is really much wider 8 than the sense I would have gotten listening to 9 this today. 10 Mostly what I've gotten so far is 11 "university" and "science." And I may be mistaken, 12 but I don't actually think the word, "science" is 13 in the common rule. 14 The word, "research," is, but research, as 15 it is defined, is so broad that not only would it 16 include investigative reporting, but, arguably, 17 Supreme Court proceedings, and a host of other 18 human endeavors which are really very difficult to 19 deal with. 20 And to suggest that the committee -- we 21 collectively need to have a way of addressing those 22 kind of things, but I would also say better 160 1 addressing the categories in between. And my own 2 view is we really need a lot more tailoring, and 3 also different -- you know, get outside of these 4 metal boxes that we're in of 1970's, I would say, 5 command and control regulation, and to sort of come 6 up with better categories of activities, and figure 7 other ways to approach them. 8 For example, maybe there is some risk to 9 oral history. Maybe there is somewhere in there. 10 But, you know, given the vast amount of human 11 misery we have in the world to deal with, we need 12 to prioritize it and we need to think of some other 13 way of dealing with that besides making sure that 14 our overburdened IRBs have to take on yet more and 15 more work, which is what almost inevitably comes 16 out of these kinds of discussions. 17 Thank you. 18 Sorry if that was grandstanding. 19 CHAIRPERSON MARSHALL: No. That was 20 extremely helpful and very well put. Thank you. 21 DR. FELICE LEVINE: Yeah. And I'd say 22 that is sort of a point in the report, and it's 161 1 also, I think, a point, as quickly as I could skim 2 it, as it was being printed in the NBAC report 3 that's out for a common period that there needs to 4 be some sort of distributional energy in the areas 5 of higher risk versus more, let's say, innocuous 6 or, perhaps, you know, you don't legislate or have 7 a regulation or a rule around rare events, or we 8 will be legalistic to a fault. 9 And that's the concern about maybe how 10 they have things now operationalized, and we may 11 becoming legalistic to a fault. 12 MR. MESA: I'm John Mesa with the VA, and 13 I head the Office of Research Compliance and 14 Assurance that came into being a year ago because 15 OHRP's predecessor shut down the first of its 16 activities, being the West L.A. VA Medical Center 17 in March of 1999, and we've been sort of growing by 18 leaps and bounds over the course of the year. 19 One of the fundamental questions that we 20 keep asking ourselves as this office gets underway 21 is what do we know about the effectiveness of human 22 subjects' programs, procedures and processes? I'm 162 1 going to get very precise here to my question in 2 just a moment, because it seems to me, in part, 3 that if we can understand a knowledge base, how we 4 pull it together, about all of these activities 5 designed to protect human subjects, we would be 6 well off with understanding and having a deep sense 7 of knowledge about what it is that works and 8 doesn't work. 9 My question is along the lines of how do 10 we, in fact, in your opinion, pull that information 11 together? 12 We can do descriptive studies, which I 13 find, basically, what you've done, which is very 14 helpful. 15 We need analytical studies. We need some 16 kind of synthesis kind of work, and possibly, even 17 some solid evaluative kind of studies. 18 My question is sort of like a two-part 19 question: Who's best able to really pull that off? 20 Is it more of the private, public academic 21 center, or is it sort of like the feds again or the 22 agencies again? 163 1 My analogy is to the Office of Research 2 Integrity that has recently promulgated both its 3 role in research scientific misconduct compliance 4 activities, but also has stimulated the awarding of 5 the grant program, because it is part of NIH. 6 In fact, a research agenda or opportunity 7 to engage in research in the area of research 8 misconduct. So you have a better knowledge about 9 motivations and so on and so forth. 10 So my question is if you accept for the 11 moment we need better knowledge, what is your sense 12 about the best ways of getting a better 13 understanding of what is effective in this whole 14 room of human subject protection? 15 DR. FELICE LEVINE: Yeah. I think I was 16 sort of referring to that briefly in my prior 17 remarks, and that is that -- now, I'll use the 18 "science" somewhat more judiciously. 19 But the whole area of research relating to 20 humans -- how's that -- and those engaged in that 21 area have not necessarily been terribly interested 22 or engaged in research on their own operations as a 164 1 scholarly pursuit. 2 Not unusual. The legal profession, 3 really, until the early seventies, really didn't 4 have very much research on the structure of the 5 legal profession, the medical profession, too. I 6 mean there was the Flexner report, but it's not a 7 major area of pursuit. It's really a literature 8 that one can almost manageably put in a little 9 corner of a room and, you know, read over a few 10 months. 11 ORI, Office of Research Integrity, has 12 really now been pushing and promoting. There's 13 been two research-oriented meetings. One was a 14 research conference in November. Another one was 15 held under the auspices of AAAS last June. 16 And, frankly, even though one could think 17 of research integrity as defined by the standard 18 language in that area, much of the discussion also 19 related to human subjects issues. 20 I think that this is an important area, if 21 I could use sociology with a little less, for work 22 in sociology of science to encourage and enhance, 165 1 use a small subfield within the social and 2 behavioral sciences and in other research 3 traditions that deal with human phenomena. 4 I think that clearly we want to do some, 5 as Don Campbell would have said, reforms as 6 experiments. As we introduce change, we don't want 7 to build in such a process of evaluation that we 8 can't function, but we want to put in a process of 9 evaluation so that we know what we're doing as we 10 modify and change the system. 11 But I do think that, hand in hand with 12 this educative function, is a more sustained 13 research tradition and the creation of a more 14 sustained cadre of researchers who value and are 15 valued for doing work in this area. And I think 16 it's a terrific area and one that really has been 17 under study. 18 CHAIRPERSON MARSHALL: And I think that 19 question was a perfect segue into what we, after 20 the next two questions, our look at 21 recommendations. And that question was actually 22 going to be on my list, so that was perfect. 166 1 So I'm going to ask the next two speakers 2 to make their questions succinct and brief so that 3 we can move on to our discussion of 4 recommendations. 5 MR. RUBEN: Philip Ruben, National Science 6 Foundation. 7 Very briefly, I'd like to second the 8 comment on a request that there be a sensitivity to 9 the balancing of risks and definition of risks. 10 And, second, I'd like to ask you a 11 question: Dynamic think that there's adequate 12 representation of behavioral and social scientists 13 in other categories, on IRBs, committees, boards 14 and other bodies that attempt to come up with 15 policy related to human subject protection -- I'm 16 sorry -- to human protections? 17 DR. FELICE LEVINE: Read my lips. I must 18 have not been clear enough the first time through. 19 I think that's one of the faults in the system, 20 faults with the fault line, f-a-u-l-t, and that is 21 that there isn't, I think -- I think that one of 22 the long-term and current problems is that there 167 1 isn't adequate integration in all parts of the 2 system of the social and behavioral science 3 community, and that then, when one is present, one 4 is functioning either as the expert in only that 5 area that I think has adverse consequences for all 6 of science. 7 And that's true on the advisory panels 8 that are now being created. It was true of NBAC, 9 you know, with all due respect to this body, which 10 you didn't create, but was created, and IOM and 11 others that there is not sufficient depth of social 12 and behavioral science knowledge and expertise. 13 And to be in a position where that is 14 brought in as expert is different from being at the 15 high table of deliberation. We know that in any 16 decision-making body. 17 MR. SNIDER: Hi. Dick C. Snider. I'm the 18 Associate Director for Science at CDC. And I 19 wanted to represent a public health perspective in 20 that I wanted to first point out that the conduct 21 of public health requires medicine, requires 22 epidemiologists, requires behavioral social 168 1 scientists, engineers, et cetera, et cetera, et 2 cetera. 3 And we do need a mechanism for 4 inclusiveness. And so this just reemphasizes 5 what's been said. 6 There's a second issue, though, that's 7 extremely important and that is it's not always 8 clear to us when we are engaged in research and 9 when we're not engaged in research. 10 When we go to, for example, for Yemen to 11 deal with Rif Valley Fever, are we engaged in the 12 clinical equivalent of public health activity of 13 clinical care? Are we engaged in a research 14 activity? 15 And this has caused quite a bit of 16 consternation, and I would just request of the 17 advisory committee that you consider trying to 18 elaborate on the situation with regard to when 19 we're engaged in a research mode and when we're 20 not. 21 We certainly need to protect human 22 subjects obviously in all situations, and it's not 169 1 an issue of informed consent or not informed 2 consent, necessarily. 3 But it's not at all clear what activities 4 require approval sometimes and what do not require 5 approval. 6 CHAIRPERSON MARSHALL: Thank you very 7 much. 8 Yes? 9 DR. FELICE LEVINE: Can I make -- 10 CHAIRPERSON MARSHALL: Yes. 11 DR. FELICE LEVINE: -- one quick statement 12 about that? 13 CHAIRPERSON MARSHALL: I'm sorry. 14 DR. FELICE LEVINE: No. I think that's an 15 extremely important point, and it was actually one 16 we took up because it -- in this ethics code. 17 It's not your typical circumstance, but 18 you wear sometimes multiple professional hats 19 consistent with your role. 20 I'm sure obviously that happens in the 21 biomedical community and in the social and 22 behavioral science and public health communities, 170 1 as well. 2 And one of the things we addressed in the 3 code is that if you find yourself in a place where, 4 in a different role as sociologist, in this case, 5 you have, essentially over time, observations or 6 ideas that might, indeed, make persons post hoc 7 subjects in a way. 8 Then you have an affirmative 9 responsibility not to assume they are, and thus, 10 this is research that you can undertake because, my 11 God, I've been, you know, talking with this group 12 of adoptive parents for two years, providing some 13 counseling, and now, I'm going to write this great 14 story or this great academic article and give 15 biographical anonymity. 16 But, indeed, it may be that you need to 17 say to people who thought of you in role A that 18 you're now wearing hat B. And, indeed, we try to 19 address that in the code and say that there is a 20 responsibility to not assume that this is research 21 data and a research subject, but to make clear that 22 you would like to do that. 171 1 And I assume that this is an issue that 2 both is important and one that is as good a fit in 3 the biomedical sciences as it is in the social and 4 behavioral and public health area. 5 CHAIRPERSON MARSHALL: Felice, thank you 6 so much. 7 DR. FELICE LEVINE: Sure. Thank you. 8 CHAIRPERSON MARSHALL: That was just 9 superb, and given the length of time that you had 10 to prepare for this meeting, just stellar. So, 11 thank you. 12 DR. FELICE LEVINE: You know what happens 13 if you have too much time. 14 CHAIRPERSON MARSHALL: But I would ask you 15 if you might be willing, we are going to talk about 16 recommendations, but there may be questions that 17 arise during this discussion of recommendations. 18 Would you mind just staying here -- 19 DR. FELICE LEVINE: Sure. 20 CHAIRPERSON MARSHALL: -- if there's some 21 more need for information, committee. 22 So it seems to me that within the next 15 172 1 minutes or so that we need to define the issues 2 relative to this topic that we need to make 3 decisions about the data that we need and how to go 4 about gathering that, whether it would be research 5 studies that we commission, be they from social 6 scientists or philosophers of science, whether we 7 want to commission papers, whether we want to 8 convene meetings or workshops. 9 And once we've done those tasks, then we 10 need to assign priority to them. And if I'm 11 leaving something out, then I'm sure that you will 12 let me know. 13 I did hear some themes that did emerge, 14 and they had to do I think primarily with 15 definitions and large-scale definitions. To begin 16 with, what is social science research? Does it 17 include the fourth estate or not? I think that's 18 something that we need to attend to. 19 Research risks, how those are defined, 20 whether there's a sliding scale, where things fall 21 along the spectrum of risk relative to behavioral 22 and social sciences research. 173 1 An appropriate framework for review, not 2 only relative to the system that currently exists 3 that may be broken, in part, but could be fixed, 4 and what might need to be done in an innovative 5 way, and I guess the overall theme being balance. 6 So the floor is open, committee members. 7 Abbey and Elliot and Mark and Bob. 8 MS. MEYERS: I'm just wondering whether we 9 should examine what the implications would be if we 10 broke the non-biomedical research away from the 11 medical research. 12 Should there be a separate IRB system for 13 non-medical research, and if there is, are the 14 universities going to be furious because of the 15 cost or disruption of their other activities? 16 So I think we really need to look at 17 examining what would happen if it was broken off. 18 CHAIRPERSON MARSHALL: Thank you. 19 DR. DORFF: Yes, and that's exactly what I 20 was going to say. And I think that it doesn't have 21 -- that your recommendation along these lines 22 doesn't have to be limited to large universities. 174 1 You could have regional bodies of, you know, 2 regional IRBs that deal with social science 3 specific research so that even people, students and 4 researchers in small universities could do this. 5 But I think one of the recommendations for 6 this committee would be basically to endorse the 7 recommendation that came out of your report, that 8 there be minimally more social scientific, you 9 know, scientists on IRBs, but better yet, a whole 10 separate regimen of IRBs to deal with this kind of 11 research. 12 The second thing is, I mean I would just 13 like to repeat that at least I would like to know, 14 you know, what this spectrum would look like. And 15 if I can respond to Brown's point, you can do it 16 from a legal point of view. You can talk about, 17 you know, burden of proof. 18 In other words, for something like oral 19 histories, the burden of proof would be on those 20 that want to say that you need to have an IRB 21 review. 22 For something on the other end of things 175 1 like maybe psychiatric drugs or something like 2 that, right, the burden of proof would be on one 3 who would say that you don't need to have a review. 4 And then you'd have, you know, you'd have 5 that kind of a scale, and if we knew exactly what 6 was going on, and to the extent that they imperil 7 human subjects, then I think we would be able to 8 come to some kind of recommendations that would 9 make sense for your field. 10 CHAIRPERSON MARSHALL: I'm going to take 11 the Chair's prerogative here, and I'm going to ask 12 just a brief question of Bob Cooke Deagan. 13 Bob, part of what we're talking about is a 14 question that the IOM Committee will be looking, 15 and that is, is the IRB system broken? 16 And let me just ask whether you see any 17 inefficiencies in terms of the questions that we're 18 asking and what we might be looking at in terms of 19 data gathering and so forth, and what your 20 committee -- not your committee, but the IOM 21 Committee will be doing, and what plans, if any, it 22 has to address the social sciences aspect of human 176 1 subjects' protections review systems? 2 MR. DEAGAN: As you know, this is on our 3 radar screen, but more for the second report than 4 for the first report. 5 There are 11 members of our committee. 6 Two of them are members of the social sciences. 7 That's their background. 8 So we know that it's going to come onto 9 our radar screen, but frankly, I don't think we're 10 probably going to do too much about it until some 11 time in, you know, after April. 12 At that point, I think it's going to be 13 one of the things we really have to wrestle with. 14 I think it's one of the friction points that has 15 emerged over the last year. 16 But that's really vague. I mean it's on 17 our radar screen. I don't think I can say much 18 more than that. 19 CHAIRPERSON MARSHALL: But the point is 20 that we can expect some expert advice at some point 21 in the spring -- 22 MR. DEAGAN: Right. 177 1 CHAIRPERSON MARSHALL: -- from the IOM 2 Committee, as well. 3 MR. DEAGAN: I think you need data 4 gathering and stuff like that that we would do. 5 We're going to try to keep that part of our process 6 as open as possible, and that would be shared along 7 the way. 8 But I'd guess there's going to be a lot of 9 other activity that would be inputs to our 10 committee. 11 CHAIRPERSON MARSHALL: Mark? 12 MR. BARNES: Yeah. I don't know exactly 13 how we would, you know, go about it because I think 14 our working methodology as a committee is still 15 obviously in formation. 16 But it seems to me that, you know, that as 17 -- and I echo what Dixie Snider said about the 18 paradigm of public health regulation. 19 When you talk about regulation, there 20 really are two things that you want to achieve, and 21 I think that -- or two things are balanced. 22 Number one, you're balancing fundamental 178 1 rights that may be infringed by regulation, and 2 that's why, for example, in the journalism example, 3 there are very compelling fundamental rights that 4 lead us not to regulate that activity, even if we 5 choose to regulate activity which is funded by 6 government like social science research funded by 7 government. 8 And the second thing you'd look at is 9 you'd look at the severity of the risk that you're 10 trying to abate through the regulation, and you 11 make decisions really based on those mother 12 variables, but primarily, those two variables. 13 And when we talk about social science 14 research and we think about the issues of academic 15 freedom being a part of at least a fundamental 16 rights calculus, but government funding being part 17 of the compelling interest, and you compare that to 18 the rationale, the historical background through 19 which government heavily regulates, and for many 20 other reasons, medicine, the practice of clinical 21 medicine and the practice of clinical medical 22 research, then I think that -- and you sort of look 179 1 at the continuum there of fundamental rights, then 2 it does seem to me, at least what I've -- 3 You know, what I take away from this 4 discussion is that there is a realm of social 5 science research which is not clinical medicine, 6 for which there are fundamental academic freedom 7 rights and free speech rights that do emerge as an 8 important consideration, which makes it distinct 9 from clinical medical research. 10 And it seems to me that there are, you 11 know, compelling -- and, also, the severity of the 12 risk is, although it can be great within the realm 13 of social science research, it is perhaps as, on 14 the average, much less than in the realm of 15 biomedical stuff. 16 And then you look further at the issue 17 that even within biomedical research, as I think 18 we'll explore over our next meetings, the trend has 19 been more and more towards specialization. 20 One size does not fit all in IRBs any 21 longer. Biosafety is one issue. Genetic therapy 22 is one issue. Cardiovascular stuff is one issue. 180 1 Orthopedic devices are another issue. AIDS 2 research is another issue. 3 Our biomedical IRBs are not even competent 4 to address their areas of expertise. 5 I think it leads us to, in terms of 6 fundamental recommendations, toward, you know, 7 really the necessity to look at breaking out social 8 science, number one, as opposed to clinical 9 medicine in terms of the research regulation and 10 oversight, and within social science, looking at 11 the continuum of risk within social science, and 12 not having one size fit all, even within the realm 13 of social science. 14 So the final thing, the second part of 15 what I have to say, which will be quite brief, is 16 that in your paper, there is also an issue that 17 emerges, which I think also will emerge in our 18 discussions which is the risk of legal liability in 19 the operation of IRBs. It's talked about in a few 20 paragraphs in your report. 21 And I would like us, not only in the issue 22 of social science research regulation, but also in 181 1 the area just of clinical medicine and clinical 2 research, to look very carefully at the issue of 3 whether there should be a bedrock recommendation of 4 this committee, that there should be a federal 5 statute that insulates IRB members and IRBs 6 themselves from liability to anyone absent actual 7 malice or recklessness in the way that they do 8 their jobs. 9 Take the law out of it, and take the law 10 and the questions of legal liability out of the 11 operation of IRBs before we get to the point that 12 Canada has apparently already reached at which 13 individual lawsuits have actually been filed 14 against IRB members for their misprision or alleged 15 misprision of responsibilities in their operation 16 of the IRBs. 17 And I bring that up only because it's 18 present as a consideration in your report. 19 CHAIRPERSON MARSHALL: Here's how I would 20 like to proceed. I have three more people on my 21 list for questions, and I would, if they could be 22 brief and sort of data gathering questions, then we 182 1 really need to move on to talking about our plan 2 and assigning priorities to how we're going to 3 proceed. 4 Bob? 5 DR. ROBERT LEVINE: Thank you. Since I 6 raised my hand, several points have come up that 7 are even more interesting than the reason I raised 8 my hand. 9 Briefly, I don't think you should try to 10 redefine research. Whenever people try to redefine 11 something to reach a regulatory objective, they 12 secede from the union formed by use of the English 13 language. 14 You know, if you stipulate definitions, 15 you got to have a footnote every time you use it, 16 or else people will think you really mean research. 17 The definition we use of "research" was 18 submitted to the National Commission. Stapled to 19 it was a photocopy of one page of Webster's 20 Dictionary, because it was intended to comply with 21 what the English language did. 22 What you can do is say there is some 183 1 categories of research we're not interested in 2 regulating. These can be found in the exemptions. 3 Sometimes the exemptions cut too broadly. 4 I've already mentioned some examples of that. 5 I think we have to do sometimes a cost 6 benefit analysis. We must find a way to resist the 7 irresistible rhetorical question: Could you 8 possibly save an individual from embarrassment by 9 requiring that all, you know, research be reviewed 10 by a certain type of committee? 11 The answer must be, yes, it is possible. 12 But as we look at the crummy 26 percent we get from 13 the federal government, there is so many things 14 that are higher on the priority than that 15 infinitesimally small probability of sparing 16 somebody some embarrassment. 17 I think that dividing social and 18 behavioral research from biomedical research is a 19 dream I relinquished about 25 years ago when the 20 National Commission asked me to write a paper 21 distinguishing the two for regulatory purposes, and 22 I demonstrated to their satisfaction there's a very 184 1 broad area of overlap. 2 The exemptions related to free speech, 3 yes. The reason we have exemptions is not the 4 National Commission. It's because a political 5 scientist named Epheda Solapul persuaded Congress 6 that this was an abridgement of his First Amendment 7 rights to submit to IRB review. And what we got is 8 a series of exemptions. Some of them very well 9 thought out, some of them not so well thought out. 10 I must say I can't agree that the IRBs are 11 incompetent to review biomedical research. You can 12 support that statement only if you believe that 13 it's the task of the IRB to evaluate the scientific 14 design of research. 15 The IRB was deliberately created to be 16 incompetent at that. That's not its task, and 17 that's why I'm so sympathetic with Mary Faith's 18 call for an evaluation of the overall system, 19 rather than to say the IRBs got to do absolutely 20 everything. 21 What we need is somebody who evaluates the 22 scientific design and then tells the IRB, "We think 185 1 it's good or good enough." 2 We can't have enough oncologists and 3 cardiologists and so on, on these committees. I 4 can go on and on about that. 5 In an average sized institution, you've 6 only got one or two people who are really expert 7 enough to evaluate the scientific design, and 8 they're usually the principal investigator and the 9 co-investigator, and you got to kick them out of 10 the room while you're discussing the protocol, 11 anyhow. 12 We've got to have a way to get systematic 13 scientific review with NIH funded research. We get 14 it from the IRG. And now that we've got the just- 15 in-time regulations, we actually had that at the 16 time we were looking at the protocol. 17 Enough. Thank you. 18 CHAIRPERSON MARSHALL: Thank you, and we 19 really are in a time bind here. It's almost a 20 quarter till, and that's when we're scheduled to 21 convene for lunch. 22 Adil? 186 1 DR. SHAMOO: I'll be very brief. 2 I don't think we should lose sight of some 3 of the social and behavioral research can cause 4 dignitary harm, and I think all the talk here has 5 been on physical harm, you know, biomedical 6 research. 7 And a quick example of a high school that 8 has surveyed how many students take drug, and let's 9 assume that leaks, even though they are no name, 10 identification, nothing, it leaks in the community. 11 You're stigmatizing a whole high school, especially 12 in a small community. 13 And I want to make a comment on Mark. I 14 think I'm surprised he is a lawyer, and he says we 15 should have no liability. That means there are no 16 lawsuits for him anymore. He must be not a lawsuit 17 lawyer. 18 But having said that to me really is 19 unacceptable to remove liability because today's 20 unveiling of the privacy, which to me, is lesser 21 important than harming patients directly, there is 22 criminal and financial liability. And I would 187 1 oppose removing any liability from those involved. 2 It's important to keep -- the reason we 3 don't have too much regulation is that because the 4 ultimate deterrent, we give a lot of freedom for 5 people. But the ultimate deterrent, we give a lot 6 of freedom for people, but the ultimate deterrent 7 is high price you pay. Otherwise, then you have to 8 regulate over and over again. 9 Thank you. 10 CHAIRPERSON MARSHALL: Thank you. 11 MR. MESA: Very quickly, a comment about 12 the issue of IRBs and their memberships versus 13 devoted IRBs to the social and behavioral sciences. 14 We have an opportunity with the 15 registration of the IRBs that's coming about under 16 OHRP's leadership. I would suggest that we collect 17 that data at that particular point in time if we 18 possibly can on the 4500 roughly IRBs that are 19 believed to exist in the country. 20 I know at least five in the VA who are 21 devoted to social behavioral review, and that's all 22 they do. They're not biomedical. They are social 188 1 behavioral. 2 One other comment, and Bob Levine, I don't 3 know if I've got this right or not, but I do think 4 it's worthy, given the discussion, that under the 5 definition of research in the common rule under 6 that 46102D, that people be reminded that in there, 7 there's a nasty little kicker which says, for 8 example, under this definition, "Some demonstration 9 service programs may include research activities." 10 The implication is there's a broader 11 context here than just the simple notion we're 12 designing a protocol to get new knowledge. 13 And that is, I think for a lot of us in 14 the agencies, very confusing right now. Flat out 15 evaluation research which does not get funded out 16 of, quote, "a research pot of money" you define as 17 maybe operations research. But it involves 18 collecting new data from human subjects to be 19 coalesced, synthesized and published. 20 Now, I'm just pointing it out as an 21 example because there are all kinds of it, services 22 research, survey research, repositors of data. 189 1 And I would urge this committee at least 2 to gauge with the issue. You may not be able to 3 find the solution, but somewhere in there, that 4 issue I think has to be engaged with, given the way 5 it is in the common rule right now. 6 CHAIRPERSON MARSHALL: Thank you. 7 DR. CHODOSH: Can I just add something to 8 what John said? 9 CHAIRPERSON MARSHALL: Very brief, yes. 10 DR. CHODOSH: Very briefly, and that is, 11 yes, if you collect that data on how many protocols 12 are handled by how many IRBs, you should also 13 collect how many social scientists are on those 14 IRBs. Then you'll have a good idea of whether the 15 representation is appropriate to the number of 16 protocols. 17 And then you can also ask how many times 18 they get outside consultation, and that would give 19 you even more information about whether those that 20 are undersubscribed as social scientists in fact 21 are using outside help. 22 CHAIRPERSON MARSHALL: The rubber hits the 190 1 road, committee members. How shall we proceed in 2 terms of issues, staying together and assigning 3 priority to them? What is your pleasure? 4 DR. SHAMOO: I'll be the guy who is not 5 embarrassed by saying I don't know, and I think 6 since this is our first meeting, we are not clear, 7 and when I saw the word, "recommendation," I 8 immediately asked her and I asked others, "Where 9 are these recommendations I'm supposed to have read 10 and thought about and came back with an opinion?" 11 And maybe for subsequent meeting -- I know 12 this is rushed -- that we have some draft from a 13 subcommittee, obviously, and then we have -- 14 CHAIRPERSON MARSHALL: Yeah. 15 DR. SHAMOO: -- something to chew on -- 16 CHAIRPERSON MARSHALL: Right. Yeah. 17 DR. SHAMOO: -- and a language already 18 prepared. 19 CHAIRPERSON MARSHALL: Right, and Adil, 20 let me speak to that. 21 There is no expectation today -- let me 22 reassure you that we are going to, you know, within 191 1 the next five minutes, solve all of these issues 2 and, you know, make pronouncements about 3 recommendations. 4 What I would like to ask is, from a 5 procedural perspective, how would you like to go 6 about getting at the issues in terms of defining 7 them, data gathering, and then assigning priority 8 to what we've talked about today? 9 Bob? 10 DR. ROBERT LEVINE: I have one proposal 11 and I am not at all sure it's the most important 12 things we should do, but I would find it very 13 illuminating. 14 The National or the President's 15 Commission, in the early 1980's, commissioned a 16 paper from one Jerry Mashaw which was a theoretical 17 analysis of decision-making structures. And he 18 applied it to the IRB and came out with very 19 important insights, but they were theoretical. You 20 know, he said decision-making groups can be wise 21 judges or paternalistic professions or micro- 22 political accommodators and things like that. And 192 1 then he defended, on theoretical grounds, his 2 vision of what the IRB ought to be. 3 I think, 20 years later, it would be very 4 interesting to have some sort of collaboration 5 between Jerry, who is still very active, and any 6 other people who are highly experienced in what 7 actually is going on to see what does it look like 8 now, and how could it make recommendations for 9 improvement. 10 Thank you. 11 CHAIRPERSON MARSHALL: Elliot? 12 DR. DORFF: Along those lines, the things 13 that Sandy just mentioned before I think would be 14 very interesting to find out, namely, the number of 15 people in the social sciences that are on IRBs 16 relative to the number of protocols that they 17 consider. 18 And I would like to get from, you know, 19 the Association of Sociologists and so on, all 20 right, what your recommendations would be so that 21 we could -- I mean you gave us some concrete 22 recommendations at the end, but I would really like 193 1 to know your wish list. In other words, if you 2 really thought that this was going to be done well, 3 how would you do it well? 4 DR. SHAMOO: We are making recommendations 5 now about the social sciences and how it should be 6 handled over the overall system. 7 My thinking is really we should discuss 8 the overall issues related to human subjects 9 protections and go down there where the social 10 science would be an important component of all our 11 thinking and study, rather than we're going to take 12 piecemeal now. 13 I think it's we may lose the overall 14 picture or whatever we recommend within a given 15 area may not fit the overall picture we have 16 designed. 17 And I really think we should -- at least 18 my thinking is that we should think of the whole 19 system, what the over side should be, what the 20 rights should be, et cetera. 21 CHAIRPERSON MARSHALL: I think that's an 22 excellent point and that's sort of what I was 194 1 trying to get at with my question to Bob Cooke 2 Deagan because there is a great amount of overlap 3 in terms of looking at the entire system, and then 4 these more specific topics that we're looking at. 5 So I guess my sense is this: There is 6 nothing that precludes us from making sort of 7 interim recommendations and from coming back, once 8 we have had the wisdom of the IOM Committee and its 9 guidance and revisiting issues. 10 We have redefined our agenda, and we do 11 not want anything to be done in a precipitous, 12 inadequate fashion. So I think that we should have 13 that understanding up front, that if we think that 14 something needs to be revisited, then we have the 15 prerogative to do so. 16 Yes, Judy? 17 DR. SIEGEL: My point, which Adil actually 18 started, and I'll go a little bit further is, 19 someone just brought up what should the IRB be, and 20 I think this is a piece of that which I also agree 21 may be one of the first questions or one of the big 22 questions is what should an IRB be? 195 1 This definitely has -- this piece of 2 social science has data gathering components around 3 it. I, for one, am not very versed in what the 4 issues are. But, certainly, I would imagine that 5 the rest of today and maybe the rest of the times 6 we meet, there will be other issues that bracket 7 under what should the IRB be. 8 CHAIRPERSON MARSHALL: Bob and Roger and 9 then I'm going to make some concluding remarks, and 10 we'll go to lunch. 11 DR. RICH: I'd just like to hope that we 12 come back to the issue; that is that I'm finding 13 particularly vexing in my role as an institutional 14 official, which has to do with how one really 15 separates social and behavioral research in an 16 educational setting. 17 And I think there is a great deal of 18 confusion about that. I read from 45 CSR: "As an 19 exemption, research conducted in established or 20 commonly accepted educational settings involving 21 normal educational practices." 22 And I think there is great confusion, 196 1 particularly in undergraduate courses in psychology 2 and things like this, as to whether or not that is 3 simply an educational activity or whether it is 4 really is human subjects research that ought to be 5 under the scrutiny of an IRB. 6 And I would just simply say it would be 7 very helpful, in my efforts at a major institution, 8 and I suspect the others who are wrestling with 9 this issue to have more clarity on where that line 10 blurs between education and research. 11 CHAIRPERSON MARSHALL: Thank you, and, 12 excuse me, Roger? 13 PARTICIPANT: I would suggest the two 14 problems that ought to be right at the top of your 15 list is education of IRBs and investigators and 16 money. And a lot of decisions can be made locally, 17 and they may not be made the same way in California 18 that they're made in Massachusetts, but I sort of 19 say, so what, as long as people are trying to 20 implement the common rule in good faith. 21 But there is a serious problem of 22 educating IRB members and money to run them. And I 197 1 think that ought to be at the top of anybody's 2 list. 3 CHAIRPERSON MARSHALL: Hear, hear, and I 4 know that that is at the top of the list for the 5 folks at the IOM. 6 Abbey, I'm going to cut you short for this 7 reason; that is, tomorrow afternoon, we will have 8 the opportunity to recap and to revisit what we 9 have done over the course of today and tomorrow. 10 My sense is this, is that it is that the 11 group is in consensus that we will commission some 12 papers, that we will gather some data, and that the 13 general areas have to do with the number of people 14 in social science research relative to the number 15 of IRBs and those sorts of reviews that are done. 16 A wish list. We have asked Felice to come 17 up with a wish list from the American Sociological 18 Association. 19 I would ask that we also perhaps can 20 consider looking, asking for some wisdom on risk 21 relative to research, in general, but especially 22 looking at social and behavioral sciences research, 198 1 and then, certainly, the suggestion that Bob made 2 about Jerry Mashaw, and having that revisiting his 3 earlier paper. 4 So why don't we leave things at that for 5 now and we will break for lunch and -- 6 DR. FELICE LEVINE: Can I just make sure I 7 heard correctly what I thought I was saying "yes" 8 to? 9 I thought it was going to include both 10 components in that. And I'll say with my general, 11 not just ASA hat on, but I think -- 12 CHAIRPERSON MARSHALL: Correct. That is 13 -- thank you for keeping me honest. 14 DR. FELICE LEVINE: Okay. 15 CHAIRPERSON MARSHALL: Yes. You are 16 correct. 17 And we are due to -- we're running behind, 18 but we are due to reconvene from lunch for our next 19 session at 1:45 p.m. Thank you very much. 20 [Whereupon, at 12:15 p.m., the meeting was 21 recessed to be reconvened this same day at 1:45 22 p.m.] 199 1 A F T E R N O O N S E S S I O N 2 [Time Noted: 2:00 p.m.] 3 CHAIRPERSON MARSHALL: In the interest of 4 time, let us begin. We do have a quorum, although 5 all of our committee members have made it back from 6 bolting their lunches, the poor things. I 7 apologize to all of you. We will try and be more 8 organized and timely in the future. 9 We will follow the same format this 10 afternoon that we did this morning. We will have a 11 paper presentation. Then I will invite, during the 12 discussion period, questions from committee 13 members, from our liaison members and ex-officio 14 members from the agencies, and then also from what 15 I will refer to as our "public members," since we 16 are a public enterprise. 17 [Discussion off the record.] 18 CHAIRPERSON MARSHALL: Yes. Thank you 19 very much, Kate. 20 Jennie Joe has joined us. 21 Jennie, before we begin, would you mind if 22 we gave you five minutes to introduce yourself, 200 1 tell us a little bit about you, and also what 2 issues you have a special interest in that you 3 might like this committee to consider in the 4 future? 5 DR. JOE: Thank you. Sorry to be late, 6 but I'm glad to be here. 7 I'm from the University of Arizona. I'm 8 in family and community medicine. I'm a social 9 scientist, a medical anthropologist. 10 I'm also a Native American, member of the 11 Navajo Nation from the Southwest. 12 I've been an active member of the Indition 13 Health Services Institutional Review Board for a 14 number of years. 15 I'm particularly interested -- I think the 16 impact of research on Indition as peoples, and the 17 consequences that means not only for themselves, 18 but I think what happens about what we write about 19 them. How stereotypes end up hurting people and 20 not helping them. 21 And I'm particularly interested in sharing 22 this kind of value, I think, with young scientists. 201 1 I like for them to inherit this kind of ethics that 2 are important. And so that's one of my, I think, 3 passion for becoming and agreeing to be a member 4 here. 5 And I'm also interested in children, and I 6 know that this is one of the topics that will be 7 covered because this is an area of interest of 8 mine. 9 But, in general, I'm very interested in 10 just the way we carry out research and what kind of 11 value we put on people's lives by taking 12 information from them and what we do with that 13 information. 14 Thank you. 15 CHAIRPERSON MARSHALL: We are delighted 16 that you're here and we did miss you this morning 17 during the discussion about social and behavioral 18 sciences research. 19 We will be revisiting it tomorrow 20 afternoon in a strategic way, so thank you, Jennie. 21 And I would like to introduce our guest, 22 Stuart Nightingale, who is Senior Medical Advisor 202 1 to the Assistant Secretary for Planning and 2 Evaluation. And he is going to present to us a 3 paper on financial relationships in human research. 4 And if you don't know, that paper is 5 available at the table outside of the meeting room. 6 Thank you, Stuart. 7 DR. NIGHTINGALE: Thank you very much. 8 It's a pleasure to be here, and I am going to set 9 the stage for this agenda item. 10 This -- I think I was selected for this by 11 Dr. Koski because I chaired the planning group for 12 the actual meeting that we held in August on this 13 topic. And as I will describe, this is sort of 14 part of the end process of that conference was the 15 document that you have in you briefing books and is 16 available now. 17 Basically, we kept the planning group that 18 planned for that conference alive and used them to 19 help and develop this draft interim guidance that 20 we now have available. So in a way, it's a part of 21 the continuum. 22 But the other thing that I'm going to 203 1 mention today is that this is kind of a short-term 2 issue. We have this document. We also have, 3 again, coming out of the conference itself, maybe 4 four or five questions that we think that this 5 committee might wish to get involved in. There are 6 things that need to be addressed, we feel. But 7 that's, you know, for you all to consider. 8 How do we get to where we are today in 9 terms of this particular guidance document? 10 Well, I mentioned some of that. The 11 Secretary did identify a financial conflict of 12 interest as one of her five initiatives that would 13 involved in strengthening human subject protection. 14 We planned this public process. It centered on a 15 conference that would serve various functions, but 16 primarily to allow us to get to the stage where we 17 are. And it was supposed to really address issues 18 involving institutions, clinical investigators and 19 IRBs in human subject protection and financial 20 conflict of interest. 21 To put this further into perspective, 22 maybe I can show, well, a few overheads. 204 1 Kate, thanks. 2 The first is this conference was held 3 August 15th and 16th. A number of you who are 4 actually on the committee participated, were 5 speakers at that meeting. 6 We actually had something close to 700 7 people in August. It's a real testimony to the 8 importance of this topic, and I would say that we 9 had participants representing all the stakeholders. 10 We had many more in certain categories than others. 11 But people did share their experiences and 12 we did have a series of -- oh, next, please. 13 The purpose of the conference is basically 14 to implement one of the Secretary's five 15 initiatives that I mentioned. 16 We want to remind the participants of the 17 complex regulations and guidances that are already 18 available, both from the public health service and 19 FDA, on the issue of either financial conflict of 20 interest or financial disclosure. 21 We also wanted to have the examples 22 presented, which we did have. We wanted to get 205 1 public comments on six framework questions that we 2 used, developed prior to the conference, and ask 3 for comments through a Federal Register notice, and 4 I'll show you those in a second. 5 And, finally, this was, as I said, to help 6 us get information we needed to develop some 7 guidance. 8 Next one. 9 These are the six conference questions in 10 an abbreviated format. Basically, the first was to 11 find out what kind of information actually is out 12 there, empirical information that might help us. 13 Sorry. The first one was to find out what 14 kind of financial ties and relationships actually 15 exist. Then is there any information about what's 16 actually going on in terms of any research data. 17 Then we wanted to find out if disclosure 18 were to occur to research subjects, basically how 19 should the information be disclosed. 20 And then we also wanted to know about when 21 that should happen and how it should happen. 22 Then we also wanted to know something 206 1 about the appropriate roles of the different 2 entities involved in this area, and that includes 3 IRBs, institutions, conflict of interest committees 4 and others, and maybe more than we even know about. 5 And then, finally, are there other 6 protections available in the private sector that 7 we're not aware of. 8 And we put these out in the Federal 9 Register, hoping to get information prior to the 10 conference that would help us, and then we did not 11 get many responses, but we got a number that were 12 very thoughtful and comprehensive and useful. 13 We also left the record open after the 14 meeting itself, up until the beginning of October, 15 and got a number of further comments that were 16 quite helpful. 17 And as I said, we did have our interagency 18 group meeting after the conference to develop that 19 draft interim guidance. 20 Now, let me just, before mentioning the 21 specifics, can I have the next overhead, please? 22 I'm sure there's a better way to do this. 207 1 As the financial -- yes, the financial 2 conflict of interest certainly is seen as a major 3 and growing concern. We also heard that some of 4 the professional organizations have already taken 5 positions on this. More are working on it. Most 6 seem to center on the clinical investigators as 7 sort of the major target for these positions or 8 policy statements. 9 We heard a wide spectrum of views about 10 management of financial conflicts of interest, 11 including the prohibition of certain kinds of 12 financial arrangements at the meeting. Most of the 13 people, I would say, supported management reduction 14 or elimination of this, rather than prohibition. 15 We also heard that the views of potential 16 research subjects should be told about financial 17 conflict of interest or financial interests that 18 are relevant, and the informed consent document 19 appeared to be the best vehicle for providing this 20 kind of information. 21 Next, we heard that IRBs should not be the 22 sole focus or arbiter of financial conflict of 208 1 interest issues. It's not appropriate for them to 2 do this sort of thing, and furthermore, they don't 3 have resources to do it. 4 And then, finally, there was a real desire 5 in the community that we heard from for guidance, 6 but not new federal regulations at this time. 7 Bob? 8 DR. ROBERT LEVINE: Can I just ask, 9 Stuart, what's the difference between elimination 10 and prohibition? 11 You said they didn't want prohibition -- 12 DR. NIGHTINGALE: Okay. 13 DR. ROBERT LEVINE: -- they wanted 14 elimination. 15 DR. NIGHTINGALE: Oh, sorry. Well, 16 prohibition, elimination. 17 Yeah. Basically, it's when we get into 18 some of this, but it's complicated and, yeah. 19 Okay. Let me go on. 20 The document that you have before you is a 21 draft only. It's been developed by our group, and 22 it is in a form that in a way that we would be 209 1 interested in distributing it to the community. In 2 other words, we thought rather than develop 3 something with ideas and thoughts, a reaction 4 document, per se, this is something that could be 5 sent out to people right away for comment and use, 6 essentially. 7 This is in no way a regulatory document or 8 a set of requirements. It is tied to the common 9 rule and the equivalent FDA, IRB and informed 10 consent regulations that focus on human subject 11 protection. It is not tied formally to either the 12 Public Health Service requirements for grantee 13 institutions or the FDA financial disclosure 14 regulations. 15 These are separate legal requirements and 16 have their own published guidance. In fact, 17 neither the PHS requirements nor the FDA 18 requirements deal specifically with this issue of 19 IRBs and what the individual research participants 20 should be told. 21 However, the guidance is meant to be 22 applicable to everybody. In other words, 210 1 institutions, investigators and IRBs, whether they 2 receive PHS funds, whether or not they're regulated 3 by the FDA, in addition. They're really meant -- 4 and independent IRBs, for example, would also be a 5 target for this. 6 Then you'll notice that our conference had 7 the term, "financial conflict of interest" in its 8 title. The agenda for this session does not have 9 it, nor does our actual document. And that gets 10 back to kind of what Bob was getting into a little 11 bit, too. 12 It's not clear what financial conflict of 13 interest is. It's clear that there are financial 14 arrangements and financial relationships that 15 exist, so our document is -- thus, an attempt to 16 define any of this. But it focuses on information 17 and communication about the facts of financial 18 arrangements in relationships. 19 It doesn't have thresholds in it. There 20 are thresholds for reporting in, I think, both the 21 PHS and the FDA requirements, but it does -- or 22 you've seen emphasizes sharing, communication, et 211 1 cetera. 2 And the target here is really how best to 3 inform the IRB about what's going on so it, in 4 turn, can then inform the research participant, as 5 appropriate, what that actually is. 6 The document is organized into five 7 sections. The first is the institution. The 8 second is clinical investigators. Third is the IRB 9 members and staff. Fourth are the IRB review of 10 protocols and approval of consent. And, then 11 finally, the consent document itself. 12 Some of this may be seen as artificial. 13 Some of this document may appear to be redundant, 14 and you could even order it in a different way. 15 But our group felt this was the very best way to 16 present the information for review. 17 And then I guess before going further, I 18 just want to say that to put the draft in 19 perspective, this is draft interim guidance that we 20 want to have comment on. 21 These sort of longer-term questions are 22 important questions that came up from the 212 1 conference and during our own inter-agency 2 discussions. 3 Obviously, the draft interim guidance is 4 what we know about now. Clearly, if this group, 5 after some deliberation over a period of months, 6 comes up with some really important things, this 7 could obviously change this draft guidance. 8 But we wouldn't want to hold the draft 9 guidance until a lot of questions are answered that 10 take a lot of deliberation because we feel that 11 wouldn't be fair to the field to withhold something 12 that might be very useful, if, indeed, you agree 13 that this would be a useful contribution. 14 So it would be in that spirit that I would 15 read you some of the longer-term questions, again, 16 coming out of the conference and discussion of our 17 group. 18 The first would be, what is the definition 19 of financial conflict of interest and financial 20 disclosure? 21 FDA does not use the term, "financial 22 conflict of interest," and PHS leaves the 213 1 determination of financial conflict of interest to 2 institutions. 3 Is it possible to harmonize definitions 4 across HHS? That's the first. 5 The second is can the Public Health 6 Service, FDA regulations that currently exist 7 requiring conflict of interest and financial 8 disclosure reporting and management be harmonized? 9 The next is are there certain financial 10 arrangements and relationships involving 11 institutions, investigators, IRBs, et cetera that 12 clearly are, by their very nature, conflicts of 13 interest that cannot be managed, and must be 14 eliminated or prohibited? 15 Four, what is or should be the nature, 16 purpose and process of financial disclosure? 17 We heard a lot of comments at the meeting 18 about, well, if you inform the research 19 participants in the informed consent, they're not 20 going to understand what it means. It has to be 21 put in perspective. 22 Well, you know, the viewers, we think that 214 1 can be done, but it still really is a good issue 2 that deserves some deliberation. 3 And then, finally, what are the 4 appropriate roles and responsibilities in respect 5 to financial relationships with sponsors of the 6 various parties involved in human subject 7 protection institutions, conflict of interest 8 committees, IRBs, funding and regulatory agencies? 9 How does this all fit together? 10 Earlier, you talked about the idea of a 11 system. Can this be a system? Should it be a 12 system? 13 So that is the spirit that we're 14 approaching this, and I would just, before getting 15 into the document, say that there's been a lot 16 going on recently. 17 Before the meeting, the IG had come out 18 with a report, or maybe it was around the same time 19 of recruitment of subjects. A lot of concern about 20 recruitment approaches and some advice and 21 thoughts. 22 In the past several months, there have 215 1 been a tremendous amount of literature in the New 2 England Journal and in the Journal of the American 3 Medical Association on these kinds of issues. And 4 just last week, I think the AMA House of Delegates 5 adopted a position that relates to this same issue. 6 And we know NBAC has out for comment a 7 revised version of a document that does deal very 8 specifically with this. 9 So there's a lot going on, but, again, we 10 weren't -- we think that we have something that 11 came out of a process that is worthy of getting out 12 to the community, and we really want your comments 13 and thoughts on that document. 14 CHAIRPERSON MARSHALL: Thank you very 15 much, Stuart, and I think that's true, and we 16 commend you on your work, and also on giving us 17 something concrete that we can sink our teeth into 18 to begin our discussion. 19 So let me open the floor for discussion 20 among committee members first. 21 Yes? 22 MS. MEYERS: Well, first of all, I was 216 1 amazed at that conference at the interest that the 2 audience was so big they had to have an overflow 3 room. It was huge. 4 And so that's heart warming to know that 5 there is interest. And most of the audience, 6 however, were people from IRBs. 7 And the issue that is most disturbing I 8 think to consumers is that FDA already has a 9 regulation that requires the investigator to say 10 that he may own stock -- he or she may own stock or 11 have a conflict of interest, but that information 12 under the regulations has to be given to the 13 sponsor of the trial. 14 So when a drug company is paying an 15 investigator, the investigator simply writes back 16 to the drug company saying, "Yes, I've been paid by 17 you." And once that information is there, it is 18 kept secret. It is not accessible to the public. 19 So there's use in FDA having that regulation if 20 there is no requirement that the information is not 21 put into an informed consent document. 22 And among the many issues that are so 217 1 disturbing about the conflict of interest is that, 2 in recent years, a lot of doctors are getting paid 3 $1000 each just for referring patients. And it's 4 not right that when your family doctor says, "Gee, 5 I think you might want to try this arthritis 6 medicine. There's a clinical trial down the 7 block," that the patient's not told that the doctor 8 is being paid $1,000 a head just for referring you 9 down there. 10 So this whole conflict of interest thing 11 has gotten out of hand. And it's really imperative 12 I think that the government does something to at 13 least open the window and give some transparency to 14 this whole question. 15 CHAIRPERSON MARSHALL: Thank you, Abbey, 16 and I think you've raised the point that there is a 17 panoply of types of conflict of interest out there 18 that we need to address, which is what Stuart said. 19 DR. NIGHTINGALE: Yeah. Can I just say 20 one thing? 21 CHAIRPERSON MARSHALL: Oh, please. 22 DR. NIGHTINGALE: Just in response to 218 1 that. We did try to deal with the issue in this 2 document on paragraph 1.2, saying that the 3 information that the investigator is submitting to 4 the sponsor could be given to the institution. In 5 other words, it's not -- you are perfectly correct 6 in terms of your description. There's a closed 7 system. It goes from the investigator to the 8 sponsor of the FDA. There was never any thought 9 given to doing anything at the level of an 10 institution or an IRB, as far as I know. 11 But what we're doing, instead of trying to 12 change FDA's regulations or anything like that, but 13 the idea here is since the investigators at the 14 institution, and that person is filing information 15 with the sponsor, why not have the institution get 16 that same information and pass it on, if 17 appropriate, to the conflict of interest committee 18 or the IRB? 19 MS. MEYERS: To the patient. I think 20 that's the most important thing. 21 I don't care about the IRB. It's the 22 patients who should be told, and let them digest 219 1 that information and make a decision for 2 themselves. 3 And it's very disturbing, and I would 4 suggest, for example, people like me don't sit 5 around the house reading the Federal Register. 6 Lawyers are reading the Federal Register. 7 And so the fact that you want comments on 8 this will not be known to the patient community, 9 has the biggest stake in this subject. 10 So you need to mail this out to patient 11 organizations that represent diseases. Otherwise, 12 the only comments you're going to get will be from 13 IRB members who are going to tell you that they're 14 already overregulated and they don't want to do 15 this. 16 CHAIRPERSON MARSHALL: Abbey, I see heads 17 shaking back there among our public and community 18 members, so maybe they will have some thoughts and 19 ideas later on. 20 I have Mark next, and then Adil. Then 21 Bob, then Elliot. 22 MR. BARNES: Thank you. We actually 220 1 discussed this issue, at least among about half of 2 us at lunch, and I think actually there's probably 3 going to be a great unanimity of opinion, at least 4 on some of these conflict of interest issues, if 5 not on other issues on this committee, but at least 6 based on the discussion at lunch. 7 Just a few points: I regularly counsel 8 academic medical centers and physicians about 9 issues related to conflicts of interest, FDA 10 regulations, National Science Foundation, NIH. So 11 I do this -- I deal with these regulations with 12 both the legalities and the ethics of them, sort of 13 on a day-to-day basis, working with research 14 administrators. And just a few brief thoughts. 15 One is that the big question that's 16 hanging out there is whether the conflict of 17 interest disclosure requirements that apply under 18 the PHS to CC, NIH and other funding should be 19 essentially extended by federal regulation to cover 20 private research, privately-sponsored research. 21 I can tell you that I am telling my 22 clients that for ethical reasons, if not for legal 221 1 reasons, that that's exactly what they should be 2 doing. 3 And my -- I think that, you know, we, as a 4 committee, need to look carefully at that question, 5 you know, and think about the implications of that. 6 But that certainly is something that I think we 7 should weigh in on. 8 Another thing that Abbey referred to is, 9 given the understandable pressure for 10 pharmaceutical companies, medical device 11 manufacturers, genetic therapy companies to make 12 profits -- and I don't begrudge them that. It's 13 good that they do that -- there's a rush to get FDA 14 approval, and the rush to get FDA approval means 15 that there are what I call "cram payments" made to 16 doctors, to principal investigators, to co-PI's, 17 and sometimes even to hospitals for rapid 18 enrollment of patients into studies. And these 19 cram payments far exceed what the reasonable or 20 fair market value would be of their rendering those 21 research services. 22 That is a problem. It is a problem in 222 1 terms of informed consent. It's a problem in terms 2 of medical ethics, and I think it's a problem in 3 terms of the Federal Anti-Kickback Law and fee- 4 splitting issues, as well. But we'll leave that 5 aside. 6 That is certainly something, though, that 7 merits, you know, attention on, you know, not only 8 from this group, but I think also in terms of your 9 direct recommendations. 10 Another issue that I think merits our 11 attention, which I don't think is in the draft 12 guidance, although I know it was discussed at the 13 conference -- and, by the way, Dr. Knight, that was 14 a very fine conference that you guys put on. I 15 know that you were one of the primary organizers of 16 it and it really was a very fine conference, albeit 17 in Maryland in the middle of August. 18 One of the issues, though, that I find in 19 research contracts oftentimes that doctors are not 20 aware that they have even signed and hospitals 21 aren't aware they've signed is there are gag 22 clauses and severe -- I think excessively severe 223 1 pre-publication review causes that the medical 2 device manufacturers and the other private sponsors 3 reserve to themselves. 4 I understand the rationale for that, but 5 there are countervailing public health rationales 6 that need to be examined. 7 I'm not sure that those clauses would even 8 stand up to scrutiny by state medical boards, by 9 state boards of medicine, if that physicians signed 10 those clauses were brought to their attention, 11 because there are some real tensions there in 12 regard to medical ethics and patient care. 13 Finally, I think we need to look -- I mean 14 I see that sort of a tip of an iceberg, as probably 15 many of us see here, but the fact is that there are 16 the majority of research these days, the majority 17 of research dollars is flowing toward community- 18 based research, not in academic medical centers. 19 And that's why I think that one of the, 20 you know, the primary emphases of your 21 recommendations, and also, what this committee 22 should look at, is not just the academic medical 224 1 centers, but all of the research that is going on 2 in the way the flow of money is. 3 And that is not to say, by the way, that 4 we should cut off the flow of money or that we 5 should excessively regulate this area. 6 It is that the vitality of the research 7 enterprise itself is going to be protected by good, 8 effective regulation in this area. We will -- 9 If we enure, if we largely will adopt 10 standards that we can enforce and that are 11 realistic and do protect patients, then that will 12 only help in the end the research enterprise rather 13 than undermine it. 14 Finally, there is a whole separate thing 15 that I think this committee ought to look at in 16 this area which is that Medicare has recently put 17 out a national coverage determination, or an NCD, 18 regarding the coverage by Medicare, and therefore, 19 private insurers, because private insurers most 20 often follow the Medicare rules, will pay for 21 patients' participation in clinical trials, not for 22 the clinical trial intervention itself, but for all 225 1 the medical services and pharmaceuticals associated 2 with the clinical trial. 3 There is a big question that Medicare, 4 that HCVA has not yet answered about what qualifies 5 as a qualifying trial for those purposes. That's 6 out for public debate. It's out for discussion. 7 It's not going to be resolved in this 8 administration. It's going to be resolved in the 9 next one. 10 And that definition of what is a 11 qualifying trial for that national coverage 12 determination is very determinative of a number of 13 other decisions that go on in clinical trials, 14 especially about the flow of money and what kind of 15 money is going to be paid by the private insurers 16 as opposed to the research sponsors. 17 I think that we, as a committee, need to 18 weigh in on that issue as well and make sure that 19 we think that our voices have been heard on that 20 because there are many -- although it's a financial 21 issue, there are many, many ethical implications of 22 the decisions that are made about what is a 226 1 qualifying clinical trial and what is not. 2 CHAIRPERSON MARSHALL: Thank you, Mark. 3 That was wonderful. 4 Adil? 5 DR. SHAMOO: Thank you. I raise my finger 6 when Abbey hasn't told him that, "Back to the 7 patient. The information goes to the patient." 8 And she said, "In the meantime." 9 However, Stuart, your conference was 10 excellent. I think you've done a great job 11 including everybody in the discussion and coming up 12 with a consensus document. I congratulate you and 13 your staff. 14 The issue, Abbey said, is $1,000. You're 15 way behind. This money goes 3,000, 5,000, 10,000 16 and up to 20,000. So your local -- some of these 17 physicians make more money referring people than 18 taking care of you with 50 buck bill. So there is 19 an incredible incentive to shovel a lot of patients 20 to the research protocols. 21 I want to address that disclosure alone -- 22 I know this is, you know, sunshine, sunshine, 227 1 sunshine will disinfect everybody. 2 Disclosure alone, I don't think it's the 3 only solution. There has to be some prohibition, 4 elimination of conflict of interest. 5 And the one really has bugged me for years 6 is the institutions owning equity in biotech 7 companies where they themselves are doing the 8 clinical trials. 9 That's so corrosive, not for that 10 particular, corrosive to the faculty at large, 11 seeing their own institutional research environment 12 being bought and the institution, and especially 13 the academic institution, to me, they're the last 14 vestige remaining where through disinterested group 15 of people in our society who are seeking truth, as 16 they know it at the time. 17 Every other sector is basically controlled 18 by somebody else, and the universities are losing 19 really their soul when they are owning equity in 20 research endeavors. 21 And I would recommend Norman Bowie's book, 22 now he goes through the history of the Wisconsin 228 1 Alumni Foundation, how discovery made for public 2 good, how vitamin D, how slowly, but surely, 3 through 20, 30, 40 years, how it corrupted the 4 essence of what they wanted to do at the beginning 5 because of the influence of money and litigation, 6 et cetera, et cetera. 7 Thank you. 8 DR. NIGHTINGALE: Well, let me just say, I 9 think we put a lot of things into the document that 10 will draw this out and force discussion at the 11 level of the IRB. And, by the way, you're never 12 going to get to the patient unless you go through 13 the IRB. 14 So the fact that we were talking about the 15 IRB before, it didn't -- we don't mean it to stop 16 with the IRB. We mean that as a conduit to getting 17 to the consent process, et cetera. So I mean 18 that's it out there. 19 Otherwise, I mean the issues that are 20 raised by group just didn't decide to go further 21 based on what we heard at the conference, as I 22 said, to deal with specific prohibitions or other 229 1 things in this particular document this time. But, 2 obviously, the group -- our interagency group is 3 very concerned about some of the same things, and 4 we did have multiple drafts in our interagency 5 committee, and sometimes things that were in one 6 weren't in the other. 7 So I would just say this certainly did 8 come up. 9 CHAIRPERSON MARSHALL: Thank you. 10 Thank you, Adil. 11 Bob? 12 DR. RICH: I'd just like to suggest that I 13 think the most egregious conflicts of interest are 14 the ones that, in a sense, have been referred to 15 around this table that are not addressed in the 16 document, which since the document talks about 17 institutions, clinical investigators and IRBs, it 18 basically is leaving aside the majority of FDA- 19 regulated clinical trials that are done outside the 20 CDC, these huge fees and things being paid for 21 enrollments of patients under some sort of 22 accelerated payment schedule and things like that. 230 1 So I really would like to see a document 2 that at least gives attention to the fact that 3 there are serious conflict of interests issues that 4 attend when drug sponsors or clinical research 5 organizations pay these very large fees to private 6 physicians for patient enrollment. I think it's a 7 significant problem. 8 Relating to the issue of -- the one other 9 thing I want to talk about just very briefly is the 10 nature of institutional conflicts of interest, 11 which Adil just alluded to. 12 I think that there really is at least one 13 important way in which that conflict is 14 ameliorated, and that is simply by having a clear- 15 cut and arms length relationship between 16 institutional administration and IRBs. 17 I think that deans and institutional 18 administrators have no business basically inserting 19 themselves into the judgments of IRBs with regard 20 to the ethical aspects of an investigation. And I 21 think that so long as institutions assiduously 22 avoid being part of the IRB review process, I think 231 1 the IRBs themselves are largely insulated from 2 that, except as individual members when they 3 obviously have a responsibility to recuse 4 themselves. 5 CHAIRPERSON MARSHALL: Thank you, Bob. I 6 think there might be some discussion about that 7 later. 8 I have next -- I'm sorry, Stuart. Did you 9 have a response to that? 10 DR. NIGHTINGALE: Yes. Just one comment. 11 This document is supposed to apply to 12 privately-funded research, FDA-regulated research 13 every bit as much as it is to the FDA-regulated as 14 much as well as PHS funded. 15 And there is a reference. I mean 16 certainly independent IRBs would be a good example. 17 Obviously, you're not going to have an institution, 18 in certain cases, when you have privately-funded 19 research, but you're always going to have clinical 20 investigators and IRBs and informed consent. 21 So the majority of these things should 22 definitely be relevant, but we try to be all 232 1 inclusive and to cover institutions that aren't 2 part of the -- that don't have assurances because 3 they're not part of the PHS funding system, but 4 should look at the things that institutions should 5 look at. 6 But we certainly meant to include just 7 taking away the institution any investigator who is 8 doing the work that they may have their protocol be 9 reviewed by say an independent IRB or any other 10 IRB. 11 DR. RICH: I would just suggest then that 12 a clinical research organization is, in every 13 instance, an institution. And I think that one 14 should specifically note that when you speak of 15 institutions, you don't just mean PHS grantee 16 institutions. You basically mean any kind of 17 research sponsor, and that would include for-profit 18 institutions like a CRO. 19 CHAIRPERSON MARSHALL: Thank you. 20 Elliot? 21 DR. DORFF: I have three small points. 22 One is, on 1.8 in the document, you have the chair 233 1 and staff of the IRB. It's along the same lines 2 that Bob was just talking about and that Adil was 3 just talking about. 4 By the way, is that how you pronounce your 5 name? 6 DR. SHAMOO: Adil. 7 DR. DORFF: Adil. Thank you. 8 DR. SHAMOO: But I've been called 9 everything. 10 DR. DORFF: Okay. But I might as well get 11 it right. Adil. Okay. 12 The question -- I mean another possibility 13 other than the one that Bob mentioned is that you 14 have an IRB that's completely outside the 15 institution, because even if you have non- 16 administrators on the IRB, they are ultimately 17 faculty members of the institution whose promotion 18 and all kinds of other things are in the hands of 19 administrators. 20 Of course, the problem with doing that is 21 that if you get an IRB from a competing 22 institution, you know, then they would be a 234 1 conflict of interest in the opposite direction. So 2 I mean I don't know that you would get objectivity, 3 no matter what you do, but you can move towards 4 that. In other words, you can move towards some 5 kind of situation where the conflict gets 6 minimized. 7 On 2.2, I think that the document needs to 8 go further where you say if a potential conflict 9 cannot be eliminated, the committee's determination 10 of how the potential conflict is to be managed or 11 reduced should be shared with the IRB for 12 consideration during the discussion of the 13 protocol. 14 I think it would be very helpful in this 15 document if you gave some guidelines about how to 16 do this. In other words, how do you minimize, or 17 at least diminish, you know, the amount of conflict 18 of interest? What kind of steps can you take in 19 order to do that? 20 That would be considered to be, in other 21 words, now, but it wouldn't be this particular IRB 22 that accepts it, but that in the more national 235 1 basis are seen as being clearly good steps to take 2 in order to minimize conflict of interest. 3 And, then, finally, 3.3, where the IRB 4 policy and procedures manual should contain 5 institutional IRB conflict of interest and 6 financial relationship policies, it's under Section 7 3 and IRB members and staff. 8 But, clearly, those policies should be not 9 only for the IRB itself, but for institutions and 10 specific researchers. 11 And I think, you know, that you need to 12 indicate that those policies cover those people as 13 well as the IRB itself. 14 DR. NIGHTINGALE: Maybe this is the right 15 time to say that I'm here representing our inter- 16 agency group that includes the NIH, CDC and FDA. 17 The members of our working group, most of them I 18 think are here in the audience. So if any of them 19 want to step in at any point in terms of some of 20 these things, that would certainly be -- I think 21 would be appropriate, as far as I'm concerned. 22 And the management and guidelines for 236 1 management of some of these things are areas that 2 we really did not get involved in this particular 3 document partly because it's very complicated, 4 partly because there's a lot going on out there at 5 the institutional level of which we're not really 6 aware. There are all kinds of things that go on at 7 the institutions managing these. 8 And I know NIH, for example, has been very 9 much involved at looking at some of the practices. 10 But we don't know best practices right now. We 11 don't have guidelines right now for some of these 12 things. 13 So I think we would agree with the spirit 14 of what you're saying, but we didn't feel, at this 15 point, that we could put that sort of thing in here 16 or maybe, you know, even this is not the best place 17 for it. Maybe there is some other place. 18 CHAIRPERSON MARSHALL: I have Elliot, Bob 19 and then Sandy. Oh, I'm sorry. Elliot just spoke, 20 and then Judy. 21 Bob. 22 DR. ROBERT LEVINE: Thank you. I have a 237 1 couple of brief comments. 2 First, I want to say "congratulations" for 3 recognizing that federal grants can create similar 4 pressures to money contributed by industrial or 5 other sponsorship in the private sector. In fact, 6 when you consider the amounts of money involved, 7 the pressures can often be much greater. So, 8 congratulations on that. 9 Secondly, I have no doubt that it's 10 necessary to have important policies and oversight 11 in the area of conflict of interest, but what, the 12 IRB? 13 The IRB, I mean every agency that's 14 commented on the IRB lately has pointed to the fact 15 that it's overly burdened. I look at your list of 16 things that the IRB should consider on page eight, 17 and just consideration of the items in that list, 18 which is not exhaustive, would take longer than the 19 average time spent reviewing each protocol. 20 Why wouldn't you assign this to what -- I 21 don't know. They're called different things at 22 different institutions, but the organization at my 238 1 institution that looks at such matters is the 2 Office for Collaborative Research, and let them 3 review it, and then send a note to the IRB saying 4 we have identified this problem area or we have 5 identified no problem areas, but, somehow, not to 6 just continually add to the burden of the IRB. 7 I also have to say that, Adil, $20,000 for 8 a referral fee? 9 DR. SHAMOO: Yes. 10 DR. ROBERT LEVINE: Do you have 11 documentation -- 12 DR. SHAMOO: Yes. 13 DR. ROBERT LEVINE: -- of that? 14 DR. SHAMOO: Yes. 15 DR. ROBERT LEVINE: I'd like to see that. 16 DR. SHAMOO: Yes. The two people who did 17 it are in jail. You know which I'm talking about. 18 DR. ROBERT LEVINE: The Borson-Diamond 19 case. 20 DR. SHAMOO: Dr. Marshall, I wanted you to 21 comment, remember, on the issue of whether when I 22 speak, I speak on my behalf and I'm responsible for 239 1 what I speak. But no, I don't speak on behalf of 2 the committee. You speak on behalf of the 3 committee. And if we charge someone to speak on 4 behalf of the committee, you will give that charge 5 and you will give them what to say. It's a hearing 6 like any other commission I have known about. 7 And -- 8 CHAIRPERSON MARSHALL: Adil, just let 9 me -- 10 DR. SHAMOO: Dr. Levine -- 11 CHAIRPERSON MARSHALL: Yeah. 12 DR. SHAMOO: -- should not be inquisitive, 13 one on one, with a member of the committee. 14 CHAIRPERSON MARSHALL: Yeah. 15 DR. ROBERT LEVINE: I would like to -- if 16 I hear something said that seems contrary to my 17 experience, I would like to be able to ask if 18 there's documentation of it. 19 CHAIRPERSON MARSHALL: Let me just inject 20 here and say that if we have need for data 21 acquisition to further our mission, then we can 22 certainly state those sort of remarks or those 240 1 requests, and that they might actually come later 2 on in our discussion when -- you know, we sort of 3 organize the format for how we will proceed during 4 the discussion, so that that would probably be the 5 appropriate time to bring those sorts of things up. 6 So, well said, Adil. Thank you. 7 DR. SHAMOO: Thank you. 8 CHAIRPERSON MARSHALL: And I'm distracted. 9 Did you have a response that you wanted to make. 10 DR. NIGHTINGALE: Just I would say the 11 philosophy of the document is we are trying to get 12 the conflict of interest committees to really do 13 the work and give information as appropriate to the 14 IRBs. So now we've done that in different ways in 15 different parts of the document. 16 So we're cognizant of that and we try to 17 sort of get that tone into it. 18 CHAIRPERSON MARSHALL: And Bob is sort of, 19 again, this theme is emerging of a system, an 20 overarching or a larger system, and that there 21 needs to be another component of it. So thank you 22 very much. 241 1 I have Sandy and then Judy. 2 DR. CHODOSH: Yeah. I just wanted to 3 comment on what you said, Bob, about the concept of 4 organization. 5 As we've been writing these performance 6 standards, once of the major considerations is 7 looking at the whole human subjects protection 8 program. Now, that's going to be very different 9 out in the private sector where there are 10 independent review boards, where there are the 11 companies that are running the research. 12 But it needs to be identified for all 13 those instances because someone's got to be 14 responsible. So we've tried very hard to use the 15 word, "organization," not "institution," which I 16 agree with. 17 Now that leads to my real question, and 18 that is it seems to me the most difficult thing is 19 where in the institution -- and this agrees with 20 you, Elliot -- do you place the conflict of 21 interest committee? 22 If the institution, quote, itself at its 242 1 highest levels has potential conflict of interest, 2 then I think one of the potential possibilities is 3 in the board of trustees, if that board of trustees 4 is, indeed, made up of a lot of outside members 5 whose chief concerns are how the organization 6 operates, et cetera. 7 I'm not even sure that will work in all I 8 instances, but placing it at the, quote, just a 9 chief official in the institution doesn't really 10 solve the problem of looking at conflict of 11 interest. 12 It does need to be out of the IRB. I 13 couldn't agree more, but it's no different than 14 going to the radioisotope committee, if that's a 15 problem in the protocol. You get that information 16 and then the IRB can make a judgment. 17 How much of this is going to affect the 18 risk and the benefit, and if it is, then it needs 19 to be stated. 20 And it doesn't always have to be stated, 21 if they feel that this really is not a risk. 22 CHAIRPERSON MARSHALL: Thank you, Sandy. 243 1 Judy and then, also, Denyse, you spoke 2 earlier. I would like to put you perhaps on the 3 spot after Judy. 4 You did mention sort of the interests and 5 the challenges to junior faculty, and I know that 6 we're talking about financial arrangements here, 7 but I wonder if you have any thoughts that you 8 might be able to contribute to the group relative 9 to young physicians, investigators, faculty and so 10 forth, within the context of financial 11 arrangements. 12 So if you could just think about that, and 13 if you don't have anything, that's fine. 14 But, Judy? 15 DR. SIEGEL: Yeah. I'd like to go back to 16 the issue of developing a definition of "conflict 17 of interest." And the context that I will put that 18 in is in the context of the FDA regulations. 19 When these FDA regulations came out, there 20 were touch points that were actually defined above 21 which, you needed to potentially report, and below 22 which, you didn't. 244 1 And, you know, trying to implement out 2 there in the real world, the issue comes up why 3 that amount? Why not some other amount? Why not 4 lower, in some cases. 5 And so from the perspective from having to 6 implement those kind of rules, clearly, we struggle 7 with the whys. Where did they come from? 8 And then from the perspective and feedback 9 we've gotten, as we've gone out to all of our 10 investigators -- and I would also add from the FDA 11 regulations, this is not just investigators in the 12 United States where money and these kind of things 13 are things we talk about a lot, but outside the 14 United States where money and personal knowledge is 15 something that isn't really shared a lot. 16 So there are global implications of this. 17 But what we've come back with is what are you going 18 to do with this? And the issue we've asked FDA is, 19 "What are we going to do with this?" 20 And there has been no guidance, as you 21 said. We collect a lot, but there is nothing to 22 say that if you have someone out there who has an 245 1 interest of $50,000 or more in a study that has 2 five or 10,000 patients and they are contributing a 3 small piece, there is no guidance to say that that 4 person should not be included in the trial. 5 There is no guidance to say that if a 6 person refuses to give that information back to you 7 that they can't be in the trial. 8 You collect all of this information only, 9 and I agree, only if you submit an NDA is that 10 information ever transmitted to FDA. If not, it 11 sits with the sponsor. 12 And so from, you know, the perspective of 13 how do you actually implement this and what do we 14 do with it, I think the whole definition of -- and 15 I'm not talking about the other issues of conflict 16 of interest, which I think are also valid. 17 But from this particular one on the 18 investigator, have we really thought through why 19 we're asking investigators to do this, and what is 20 the touch point that we, as a society, not this IRB 21 or that conflict of interest committee, but sort of 22 in general, what is the touch point that we would 246 1 all get concerned, and I don't think we have that 2 definition. 3 And so I would encourage some discussion 4 of it, even no definition comes out of this. 5 CHAIRPERSON MARSHALL: Thank you so much 6 for reminding us that we need to be attuned to 7 international issues. That needs to be on our 8 screen, and it wasn't so far for this topic. 9 Stuart, any thoughts? 10 DR. NIGHTINGALE: Well, I guess that was 11 one of the reasons we wanted to tap into the 12 information, short circuiting what is required in 13 the regulations to allow the institutions, and then 14 the IRBs, to have some of that information, if 15 they're not getting it some other way. That long 16 list of items was another way to try to capture 17 some of that. 18 I can't really speak for FDA on this, and 19 David Lepay I think is here. But I think I would 20 just say briefly that FDA does make use of that 21 when they're doing their review of the application. 22 As you said, it comes in with the NDA. So it does 247 1 have a purpose there, you know, why the thresholds 2 are what they are, et cetera, et cetera. I'm not 3 sure. 4 But there is a guidance document which I 5 think is being revised, which is, hopefully, will 6 address more of your questions. 7 Does David want to say anything? 8 DR. SIEGEL: Actually, if I could just 9 respond. 10 I mean if the issue of conflict of 11 interest is an issue that is not a long-term issue, 12 but is an issue at the moment, waiting until an NDA 13 is filed, or in most cases, not, those information 14 will go nowhere and will not be evaluated, I don't 15 think, anywhere, except by the company. 16 CHAIRPERSON MARSHALL: Dr. Lepay? 17 DR. LEPAY: Yes. Is this on? 18 Just to answer to your comments, I think 19 they are very legitimate comments, certainly, and I 20 think we have to go back to the history of the 21 development of this regulation. 22 The regulation was not specifically 248 1 developed to deal with conflict of interest as we 2 are talking about it here. It had a much more 3 narrow focus at the time it was originally 4 conceived, and that was, in fact, in the review of 5 applications to determine whether there may be 6 considerations of a financial nature that could, in 7 fact, pose a bias to the data, and from a 8 standpoint of FDA review, would need to be taken 9 into consideration as we start to look at 10 individual sites, as we start to look at the 11 possible impact that these kind of issues could 12 have in our own interpretation, our review 13 interpretation, ultimately in our decision making 14 on the approvability of a product. 15 I'd say these are very fair comments right 16 now because, in fact, in approaching the whole 17 issue of guidance, as we are proposing to the 18 committee today, we want to look, we want to 19 consider beyond the original scope, if you will, of 20 what this regulation was put in place to do. 21 It had, in fact, a very specific series of 22 steps and specific parties that would be involved, 249 1 obviously from the standpoint of application. 2 Since the consideration was to look at biases in 3 application, we felt that it was most appropriate 4 that the sponsor should be the collector of this 5 information. The flow should be going from 6 investigator to sponsor to us. 7 We did not conceive, as I say, at that 8 time that this would be a conflict of interest 9 control more broadly, as we're discussing here 10 today, and consequently, there was no consideration 11 at that time to broadening this to distribution to 12 subjects, to distribution to the IRB. 13 We hope, in fact, that in this process of 14 discussion as we start to go forward in particular 15 with the guidance document that's in front of you 16 right now, we can start to think about areas in 17 which, in fact, the information that is collected 18 could be made more useful. Perhaps the 19 distribution could be made more useful. 20 You've asked the question of why these 21 particular thresholds. I'll say, from FDA's 22 perspective, there was no set reason. We didn't 250 1 have the kind of metrics that perhaps could form a 2 basis for why we wouldn't do $25,000 here and 3 $50,000 there. 4 They were figures that, in fact, were 5 rather arbitrarily decided upon. And as we talk 6 about the issue of pharmatization across agencies, 7 certainly this is something that should also be 8 considered by the committee. 9 So we're hoping today of bringing this 10 forward in the way that Stuart has presented. 11 We're going to get more information, one, about 12 areas in which perhaps FDA's regulations, up until 13 now, the financial disclosure regulation, has not 14 addressed certain aspects of conflict of interest, 15 given what its original scope was, whether there 16 are areas we should now be considering from the 17 standpoint of guidance to broaden the availability 18 of that information. Ultimately, how we might be 19 able to use the information that we are collecting 20 in a way that would be more useful broadly. 21 And I hope that provides at least some 22 perspective as we're starting to talk about why 251 1 historically it was collected this way and where we 2 are today. 3 CHAIRPERSON MARSHALL: Thank you so much. 4 Adil, and then I'm going to open the 5 floor. 6 Oh, I'm sorry. Oh, I apologize. Denyse 7 and then Adil. 8 DR. THORNLEY-BROWN: You said -- 9 CHAIRPERSON MARSHALL: I certainly did. 10 DR. THORNLEY-BROWN: You said you were 11 going to put me on the spot, and I think that some 12 of these issues are a little bit still vague in my 13 mind about -- 14 But the fundamental issue is what 15 motivates researchers. What motivates researchers 16 in their choice of research. What motivates 17 researchers in their procedures, and then the 18 outcomes of the research. 19 And, certainly, when we talk about 20 financial conflicts of interest, we talk about 21 making a lot of money. We talk about voluntary 22 things. 252 1 There are more subtle things, too, that 2 influence people's choice of projects and influence 3 data acquisition, things like the junior faculty, 4 oftentimes they're required to bring in their 5 salary. So we're not talking about a lot of money, 6 but we're talking about getting grants that are 7 going to pay for their salary and help facilitate 8 people getting tenure. 9 And sometimes the conflicts in those areas 10 could be very difficult. How you ferret out where 11 there truly is a conflict, where it truly 12 influences the choice of someone's project, and 13 whether there is compromise, that's a more 14 difficult issue. 15 But I think it's financial and large 16 amounts of money are one thing. But there are also 17 probably some more subtle conflicts of interest 18 that are more difficult to quantify. 19 CHAIRPERSON MARSHALL: And probably sort 20 of the hidden curriculum plays into that in terms 21 of what they see and the behavior of their mentors, 22 and what the institutional culture is and so forth. 253 1 Thank you. 2 Adil, and then we shall move on. 3 DR. SHAMOO: Judy mentioned that if it 4 doesn't go into NDA, this information is lost, and 5 this brings the point that if you do research on 6 animals, since 1966, regardless of the source of 7 funding is federally regulated. 8 Unfortunately, that is not true in human 9 subjects. Only if it is publicly funded, or I call 10 it "FDA bound," that is, going to go to FDA, then 11 it's federally regulated. And that's why that 12 issue -- if we're going to address eventually the 13 issue of overall oversight, that won't be resolved. 14 And since the discussion has moved to how 15 IRBs, I have thought of that and written about how 16 the IRB. And that's why in my preliminary remarks 17 I said, "structured and flawed IRBs." 18 That is, they are employee of the research 19 institution and the conflict of interest that I 20 just mentioned is really intertwined with the 21 institution. It's going to be very difficult. 22 And we have made two suggestions are 254 1 integral with my colleagues on that, and that is 2 either -- this is the extreme position -- all IRBs 3 should be outside the institution. And I'm really 4 quoting you from the Greg Koski one. He said, 5 "Remove the I from IRB. Remove the institution 6 from the IRB." That's one radical suggestion. 7 The other one is, at a minimum, 51 percent 8 of the membership should be from the community 9 where the subjects are coming from, and those 51 10 percent should not be appointed by the research 11 institution. And I think that could resolve -- I 12 don't claim any simple solution is going to resolve 13 everything. But that could resolve some of this 14 intertwining of IRB conflict of interest with their 15 own institution. 16 CHAIRPERSON MARSHALL: Hear, hear, and I 17 see Bob Deagan's ears are just perking up back 18 there concerning what you have said. 19 DR. ROBERT LEVINE: One very brief comment 20 in response to Denyse. 21 It's not just junior faculty that have to 22 bring in their salaries. You may not want tenure 255 1 as much as you think you do. 2 CHAIRPERSON MARSHALL: Okay. Jennie, I'm 3 going to allow a question for you and then I'm 4 opening the floor up to our ex-officio members and 5 our agency liaisons, and then after that, to our 6 public members. So one last question from the 7 committee, and there will be time during our 8 further deliberations. 9 DR. JOE: Actually, this is really a 10 simple request. You've made a comment about 11 empirical evidence, and I wondered if we could see 12 some of that, maybe in the proceedings or something 13 from this conference since I couldn't attend, but 14 I'm interested in what was said? Thank you. 15 DR. NIGHTINGALE: Well, the problem was 16 that we didn't get any. I mean there really is not 17 much on this topic, basically. And rather than 18 say, "Well, since there is no good information, 19 well, our hands are tied. There's nothing to be 20 done," we approach it based on all the other issues 21 at hand. 22 DR. DORFF: Could we make a recommendation 256 1 that such empirical information be done? 2 CHAIRPERSON MARSHALL: We could do that 3 later on during the recommendation period of our 4 deliberations. 5 I would like to point out, though, correct 6 me if I'm wrong, Stuart, but I do believe that the 7 agenda for your meeting and so forth is posted on 8 the web or it was posted on the web. 9 DR. NIGHTINGALE: Oh, yes. 10 CHAIRPERSON MARSHALL: So that may be 11 helpful, if you wanted to contact individual 12 presenters -- 13 DR. NIGHTINGALE: Yes. 14 CHAIRPERSON MARSHALL: -- and those sorts 15 of things. 16 DR. NIGHTINGALE: Right, and some of the 17 recent articles in the medical literature do talk 18 about the percentage of institutions whose IRBs do 19 get into this area. Generally pretty small, but, 20 well, the IG had told us 25 percent are actually 21 doing it. 22 So there is more data available now than 257 1 there was. And, yes, thank you for that wonderful 2 plug. 3 The conference web site is there with the 4 transcript tied to the agenda, and it has all the 5 PHS, FDA background documents, and it's an 6 excellent resource for those who want to look into 7 this area more. 8 There were some really interesting 9 presentations including lots of information from 10 those who are actually doing these things and what 11 they do, how they handle the issue, for example, of 12 when there are some institutional involvement, say 13 with patents and things. 14 CHAIRPERSON MARSHALL: And I might ask 15 you, Stuart, if, before you leave, you have that 16 information, if you might want to just put it on 17 our board back here where we also have the IOM web 18 site. 19 DR. NIGHTINGALE: Yeah. I think it's the 20 handout, isn't it? 21 CHAIRPERSON MARSHALL: It's in the 22 handout. Thank you. 258 1 DR. NIGHTINGALE: It is. Yeah. 2 CHAIRPERSON MARSHALL: Thank you. 3 DR. NIGHTINGALE: It's actually OHRP's web 4 site. It moved from where it was originally -- 5 CHAIRPERSON MARSHALL: Right. Okay. 6 DR. NIGHTINGALE: -- into the mainstream, 7 so it's now -- 8 CHAIRPERSON MARSHALL: All right. Thank 9 you very much. 10 So let me ask, what I'd like to do within 11 the next half an hour, we have half an hour before 12 we begin our discussion about recommendations is I 13 would like to give 15 minutes to our ex-officio 14 members and agency liaisons if they would like to 15 join the discussion, and then another 15 minutes to 16 our public members. 17 And just if you would please introduce 18 yourselves and your agency affiliation. And if you 19 are a public member, if you would introduce 20 yourself and your interest in being here. 21 MR. MESA: John Mesa from the VA ex- 22 officio. It was a great conference and I think the 259 1 part at this point in time that is going to be 2 valuable to the other agencies are the signatories 3 other the common rule. 4 You spoke about, you know, your inter- 5 agency group, which was actually an intra- 6 departmental group that was doing its thing, and 7 that's great. 8 I think from the standpoint of VA, it's 9 crucial our understandings about these financial 10 conflicts of interest because we have at least two 11 other mechanisms which put us in a jeopardy 12 situation; that is, any research in the VA can 13 simply be five-eights and they can enjoy a three- 14 eights appointment at his academic affiliate, which 15 can have salaries which are greater than the five- 16 eights, and they have other monies that flow. So 17 that's one aspect. 18 The other aspect is, in the VA, we have 19 these non-profit research foundations through which 20 a lot of money can flow through the pharmaceuticals 21 and ends up being sort of not quite salary 22 augmentations, but they're in that sort of frame of 260 1 reference. 2 So I would urge you that when you go out 3 that you specifically send at least to this 4 signatory to the common rule called the VA, and 5 send it to the Secretary and ask specifically for 6 our comments on it. 7 And then maybe that we'll speak from other 8 co-signatories of the common rule, but they might 9 like to feel the same way, as well, like Susan 10 Roses here from DO and so forth. 11 I think you might need to get that 12 specific set of comments because you're the big 13 gorilla, I mean DHHS. And, yes, you know, you have 14 FDA and you have NIH. But there's a few other 15 people like NSF and others over here that have 16 flows of money that we have to be seriously 17 concerned, as well. 18 I'd like to put a different systems piece 19 on this, and that is the ethical construct here is 20 limited to financial conflict of interest. 21 I would ask you to think about some other 22 words like, "vested interest," "enlightened self- 261 1 interest," and other words that I would put in the 2 general context of a governance structure that is 3 linked to and often has a nexus to the money that 4 flows. 5 We had here the comment about a junior 6 faculty and then a senior faculty person saying, 7 "Yeah, I got sort of a squeeze on me maybe from the 8 Dean to augment or at least replace my salary from 9 other sources of money." 10 I think the whole issue of when you, in a 11 narrow sense, sit on an IRB and make decisions and 12 you don't absent yourself from the room, that's a 13 ethical construct. And I think I would ask, you 14 know, you to think about in this committee. Not 15 just think of it in terms of financial conflict of 16 interest, but I'll put it the word on a governance 17 conflict of interest, which can be just as 18 pervasive and just as undermining. It's just 19 simply the money. 20 CHAIRPERSON MARSHALL: Thank you very 21 much. 22 Others? 262 1 [No response.] 2 CHAIRPERSON MARSHALL: Public members? 3 MR. WOLF: I'm very excited that this 4 division of HHS is started and that this is the 5 first meeting of the advisory committee, and it 6 looks like the advisory committee has a very good, 7 broad range of representation, which is more than 8 some other advisory committees I'm familiar with 9 having. 10 CHAIRPERSON MARSHALL: Please don't forget 11 to tell us who you are. 12 MR. WOLF: I'm Sid Wolf. I'm from Public 13 Citizens Health Research Group, formerly from the 14 NIH, but not for a long time. 15 I just want to talk about a couple of 16 things. First of all, unlike the National Advisory 17 Commission, which is a Presidential commission, 18 this committee is literally an advisory committee 19 to a regulatory agency. 20 The agency which Dr. Koski is now heading 21 up has regulatory authority. It has done, in its 22 previous incarnation, some investigations. It has 263 1 more staff, probably nowhere near as many as it 2 should. 3 But I think that when one moves beyond 4 just guidances and saying, "Maybe you should think 5 about this," whatever, which is where Stuart has, I 6 think, chosen to start, and I think it's a good 7 start, into regulations. And Mark Barnes talked 8 about standards and enforcement. 9 These are legal concepts and I think that 10 as you deliberate, not just today, but generally, 11 Dr. Koski and his colleagues are looking for some 12 basis to suggest regulations. 13 Yes, we have -- FDA has certain regulatory 14 authority, and NIH does, but the intention from the 15 way you wrote this document, Stuart, is that it 16 should apply to all of them. 17 So it's a policing function, and the 18 reason I use the word, "policing," is really to 19 distinguish between self-regulation. 20 I think that this industry, whether it is 21 the academic industry or the so-called "for-profit 22 industry," which fuses, to some extent these days 264 1 with the academic industry, it's been mainly self- 2 regulation and it's been things like disclosure. 3 And I think that part of a regulatory or 4 policing kind of atmosphere includes moving beyond 5 just education and disclosure. 6 It was pointed out by someone or other in 7 the conference in August that crawling on the back 8 of a patient, often sick or at least not fully, the 9 disclosure that their doctor or their institution 10 has a financial conflict of interest. I'm not sure 11 where that goes. They're not necessarily in a 12 position to say, "Oh, I would participate in this 13 but for the fact of this conflict of interest." 14 So I think that one of the things that 15 Marsha, Angel and I and I think a couple of other 16 people mentioned at the conference in August is 17 there needs to be really prohibitions. And I think 18 that the committee needs to start delineating what 19 things are just over the edge. And I'll just 20 mention a couple that I mentioned then and just 21 reflect on something that was said here today. 22 First of all, the referral fees or finder 265 1 fees or kickbacks -- we have a nationwide network 2 of about 250 physicians who are practicing medicine 3 part-time or full-time, and they send us examples 4 of attempts to get them to refer patients for drug 5 trials or to actually become clinical 6 investigators. This is very widespread, whether 7 the amount is a thousand, or in I guess the Georgia 8 case that Adil was talking about, the $20,000, it's 9 horrendous and it amounts to a kickback. 10 And either a clarification, or if 11 necessary, a modification of the Medicare or 12 Medicaid anti-fraud and abuse or kickback statute, 13 so that it is very clear that this kind of thing is 14 just as bad in terms of patient welfare as 15 accepting frequent flyer bonus miles or cash for 16 prescribing a certain drug. 17 Other things have to do with payment 18 beyond the actual cost of doing studies. Of 19 course, researchers in institutions should be paid 20 for doing studies. But why should they be allowed 21 to have any kind of significant, defined in some 22 way or other, equity interests? Why should they 266 1 be, in addition to being paid for doing the 2 studies, getting lucrative speaking fees for being 3 on the A-list of the drug company or other kinds of 4 things? 5 And I think that the same applies 6 generally to the institution in terms of its own 7 equity interests in a company for whom it may be 8 considered as a research participant. 9 I think that it's really an impossible and 10 irrevocable conflict between an institution that 11 owns stock or is a co-worker of a biotech or drug 12 company and one that obviously is going to have an 13 asymmetrical set of designing, carrying out and 14 interpreting studies when they can make a lot of 15 money if it comes out this way and not so much if 16 it comes out the other way. 17 A number of people have discussed the need 18 to come up with some definition of conflict of 19 interest. I'm sure that mine is just one of many, 20 but I heard at the conference in August a somewhat 21 narrower definition of conflict of interest that 22 says something like, "Anything that would -- any 267 1 financial interest that would interfere with the 2 outcome of the study." 3 I think it needs to be carried way back 4 further. The Inspector General's report of earlier 5 this year on recruitment practices really I think 6 speaks to the issue that financial conflict of 7 interest has to do with anything that would affect 8 the recruitment of subjects for trials, the process 9 of informed consent, the conduct of the trials, the 10 interpretation of them, or the process of seeking 11 approval of them. And I think there are all sorts 12 of examples of conflict of interest in all these 13 areas. 14 So these are just my thoughts, generally. 15 I'm pleased to be able to speak for two or three 16 minutes here, and I certainly pledge myself and my 17 colleagues to be of whatever help we can in getting 18 your part of HHS going, getting more funding for 19 it, because I think that, right off the bat, most 20 people who realize the enormity of your job realize 21 it will take more funding. 22 Bob Levine and I don't agree on all 268 1 things, but we fully agree on this whole issue of 2 all the dumping that is going on to the IRBs. 3 And if we had the right kind of system set 4 up for eliminating, when appropriate, or really 5 managing in those instances where it isn't 6 appropriate, and I think that there are fewer of 7 those than some people think, these issues would 8 never get to the IRB. 9 The IRB is a pathway that needs to be 10 there in an institution, but it should not be 11 additionally loaded with deciding things that are 12 really predecisional. The institution should have 13 its own policies that stop right at the first day 14 the process of doing certain kinds of research or 15 having certain kinds of conflict of interest. 16 And I think the IRB needs to become aware 17 of them, but I don't think it needs to be the 18 manager of them or the decider that they're going 19 to be forbidden. 20 The forbidden part is a policy of the 21 institution, generally. The board of trustees, at 22 least again, should be aware of it. 269 1 So those are a few of my thoughts. If you 2 have any questions of me, I'd be glad to try and 3 answer them, and I again pledge our help with 4 making your organization and committee do as good a 5 job at this very important function as it can. 6 CHAIRPERSON MARSHALL: Don't sit down, and 7 thank you so much for being here and for your 8 remarks. And I do have a question of you. 9 There has been discussion, even in Donna 10 Shalala's New England Journal of Medicine, sounding 11 board piece. She referred to the conflicts of 12 interest relative to the Gelsinger case as 13 "perceived conflicts of interest." 14 And do you have any thoughts on actual 15 versus perceived or that spectrum and the public 16 trust and public interest? 17 MR. WOLF: I don't like the phrase, 18 "perceived" or "apparent" or whatever conflict of 19 interest. There either is a conflict of interest 20 or there is not. 21 There may be a difference between conflict 22 of interest and a smoking gun, as in you have shown 270 1 that as a result of the conflict of interest, 2 someone has died or has been injured. The 3 Gelsinger case certainly is a conflict of interest 4 and a smoking gun. 5 But I think the idea is to prevent the gun 6 from smoking. To do the kinds of things, including 7 prohibitions and restrictions on certain kinds of 8 conflicts, so that it never turns into a smoking 9 gun. 10 I think that unless one puts aside the 11 hundreds or tens of thousands of years, depending 12 on your religious persuasion, of people and money, 13 it goes without saying that there are too many 14 instances of money influencing people's judgment. 15 Physicians are no more resistant to that 16 than anyone else, nor are other people involved in 17 biomedical research. 18 So I just don't like the perceived 19 conflict of interest. It's either conflict of 20 interest or not, and in ways that we need to start 21 delineating, it needs to be eliminated or 22 effectively managed, as opposed to just sort of 271 1 disclosing it to people who may not understand it. 2 Or as someone pointed out, if you know 3 your doctor has stock in a company, you may be even 4 more inclined to participate in the experiment 5 because you would say, "My doctor must really 6 believe in this because they actually own stock in 7 the company." 8 That just doesn't work too well. 9 CHAIRPERSON MARSHALL: Bob? 10 DR. ROBERT LEVINE: Sid, you made 11 reference, once again, to the Georgia case, Medical 12 College of Georgia case -- 13 MR. WOLF: Right. 14 DR. ROBERT LEVINE: -- and I thought I had 15 read that pretty carefully. 16 Was there, in fact, a finder's fee of 17 $20,000 in that case? And by that I mean a fee for 18 the referral of a patient? 19 MR. WOLF: That may not be one patient. 20 It may have been for the series of patients. I 21 mean I saw those documents about three years ago, 22 one of them. Actually, someone from the faculty 272 1 brought this whole thing to my attention. I turned 2 some of these things over. It was a huge amount of 3 money. It may have been more than one patient. 4 But it was a finder's fee enough to clearly 5 influence the judgment of people down there and to 6 get them criminally prosecuted. 7 DR. ROBERT LEVINE: Yeah. There was -- 8 well, the ones that were criminally prosecuted were 9 not the finders. They were the -- 10 MR. WOLF: The researchers. 11 DR. ROBERT LEVINE: They were the -- 12 MR. WOLF: Right. 13 DR. ROBERT LEVINE: Well, they weren't 14 researchers. They just said they were, and that's 15 what they really -- 16 MR. WOLF: That was part of the criminal 17 prosecution, saying -- 18 DR. ROBERT LEVINE: Right. 19 MR. WOLF: -- they were researchers when 20 they weren't, but -- 21 DR. ROBERT LEVINE: Right, but when I said 22 I found it startling that there would be a $20,000 273 1 fee for referral of a patient, I did read those 2 documents, and there were fees for doing services 3 to recruit large numbers of patients. 4 MR. WOLF: Then maybe that's what it was. 5 DR. ROBERT LEVINE: Twenty thousand might 6 not be an entirely unreasonable amount. 7 Anyway, thank you for the clarification. 8 MR. WOLF: Well, I think the idea of 9 finder's fees, as I said, when I introduced, I said 10 whether it's 1,000 or whatever, it's an amount of 11 money that's a kickback and really violates the 12 doctor-patient relationship. 13 DR. ROBERT LEVINE: Yeah. Okay. 14 CHAIRPERSON MARSHALL: And I'm just going 15 to interject here and say that we all know the old 16 joke that we don't want to get into the Federal 17 Register about amounts of money and definitions and 18 so forth. So perhaps we could let this dead horse 19 lie and are there others who have questions of Sid? 20 MS. MEYERS: Would you agree that a 21 financial conflict of interest is more or less a 22 perception that bias might occur and that just the 274 1 risk of this bias or the risk of endangering the 2 patient which is motivated by somebody's financial 3 desires is really where the problem is? 4 In other words, the harm doesn't have to 5 occur to the patient. It's the perception that 6 harm may occur or that a patient's welfare might be 7 put at risk? 8 MR. WOLF: Well, that, again, has to do 9 with the difference between actual financial 10 conflict of interest, something's that's 11 quantifiable, measurable, and what someone thinks 12 about it. 13 I mean different people, depending on 14 whether they are investigators or patients or 15 potential patients, may have a different view of 16 what the possible impact is, but what we're talking 17 about is something that is measurable, as Ruth 18 Kirchstein I think said at the beginning of the 19 conference, is that the collision between profit 20 and outcome is what makes us very worried about the 21 existence of financial conflict of interest, 22 particularly when it gets of the size that it gets, 275 1 not just the finder's fees, but just the amount of 2 equity, interest and other things that could 3 certainly sway the outcome. 4 Just to elaborate a little bit on that, 5 back in the early nineties, I got a call once from 6 the Commissioner's office when Dr. Kessler was 7 Commissioner, and he said, "I want to have a little 8 meeting. It's an informal meeting involving some 9 drug industry officials and some academicians, and 10 I'd like you to attend," and there were a couple of 11 people, "to talk about what can be done about 12 conflict of interest." 13 And the agenda included disclosure, but it 14 also included the possibility of disqualification. 15 I think I was the only person at the 16 meeting that thought that there should be 17 disqualification, not just disclosure, not 18 disqualification for anything, but some level 19 beyond which you just couldn't hold interest. 20 That never happened. What evolved, as 21 Judy discussed and other people discussed here, was 22 a policy on just disclosure with the sort of 276 1 tortured past of who discloses what to whom and 2 whatever else and what do you do with it. 3 I think that this is a good example. Now, 4 at least from the origin, seven years old -- the 5 reg came out I guess in '98 -- of the silliness of 6 trying to manage something that has that kind of 7 impact by just simply disclosing it, particularly 8 when it's disclosed in a largely, as I'll be 9 pointing out, secret kind of mechanism. 10 So I think that the perception of the 11 problem, as opposed to the actuality of conflict of 12 interest, gets even worse when people can't even 13 find out about it. 14 CHAIRPERSON MARSHALL: Elliot, did you 15 have a question for Sid? 16 DR. DORFF: Yes, I did. 17 First of all, on your last comment, this 18 is what reinforced the things that I was trying to 19 say to you before, that even if we don't have a 20 complete, you know, philosophically neat way of 21 defining what is ways that people can manage 22 conflicts of interest, it would be good to have at 277 1 least five or six examples of how IRBs have, 2 indeed, managed conflicts of interest that your 3 committee thinks are appropriate. 4 As a way of beginning to get toward a 5 definition, we're sort of at the beginning of 6 Plato's Republic, right, where you want to know 7 what justice is, so you get some examples first, 8 and then you try to move toward a definition from 9 those examples. 10 MR. WOLF: And stay out of the case. 11 DR. DORFF: And stay out of the case. 12 That's right. Only the sun's shining, right? 13 The question that I have for you is the 14 example that you gave in terms of lucrative 15 speaking fees, I do understand what you're after. 16 But it occurs to me that that's going to be 17 somewhat hard to distinguish between, you know, 18 from -- let me give you the opposite end of that 19 spectrum -- where people do the research in the 20 most above-board way possible, and then having come 21 through that research, come to some very important 22 finding, and then are asked, in fact, to go on the 278 1 lecture circuit based upon that. 2 Now that seems to me perfectly 3 appropriate. And so then the question is how do 4 you make sure that that kind of an outcome doesn't 5 influence the research in the first place. That I 6 do understand. That's the problem. 7 MR. WOLF: Well, they could go on the 8 lecture circuit without getting paid beyond their 9 actual expenses. I mean I'm not saying that anyone 10 who has ever done research shouldn't be allowed to 11 be published about it or teach about it or whatever 12 else. 13 It's just that, in addition to the 14 reimbursement that the person in their institution 15 gets for doing the research, it can be a sizeable 16 addition to their income in this country. In other 17 countries, it's even more sizeable. 18 Someone could be making ten, 20, 50, 19 80,000 or more a year just from a bunch of 20 carefully pieced together speaking fees, and that's 21 sort of an understanding that's there maybe almost 22 at the front end as sort of the reward beyond 279 1 actually doing experimentation. 2 So I think that some line needs to be 3 drawn, not on whether they can speak or not, but 4 how much money they get for it. 5 DR. DORFF: But lines that are different 6 from somebody who has written a book and goes on a 7 lecture series about the book. 8 MR. WOLF: Well, because if they've 9 written a book, I mean the topic here is protection 10 of human research -- 11 DR. DORFF: Right. 12 MR. WOLF: -- subjects. 13 DR. DORFF: Right. 14 MR. WOLF: And we're trying to think of 15 ways in which there may be an impairment of the 16 protection of human research subjects because of 17 financial arrangements. 18 DR. DORFF: Yeah. Yeah. I do. 19 MR. WOLF: That's the difference. 20 DR. DORFF: I do very much appreciate what 21 you're talking about. I'm just saying that on that 22 particular outcome, we've got to do a lot of 280 1 thinking about differentiating what is a 2 legitimate, you know, speaking engagement for a 3 fee, as opposed to that which is going to influence 4 the research. 5 MR. WOLF: Yeah, and the same true of 6 consultantships. They can be extraordinarily -- 7 DR. DORFF: Right. 8 MR. WOLF: -- and make major contributions 9 to someone's income. 10 DR. DORFF: Right. 11 MR. WOLF: It's the same sort of -- 12 CHAIRPERSON MARSHALL: Thank you very 13 much. 14 MR. WOLF: Thank you very much. 15 MS. BLEVINS: Hello. My name is Sue 16 Blevins, and I'm here first as a human being, and 17 second, as a representative of the Institute for 18 Health Freedom, a patient's rights group. 19 And, Abbey, I would first like to thank 20 you for your comments, and I think clearly 21 reflecting the needs of consumers. And I have an 22 appeal to make. 281 1 First, I want to say that I highly respect 2 research. I'm a nurse by training, and I've worked 3 at Johns Hopkins in Canada at NIH, and I admire 4 research and want to see the scientific technology 5 evolve in this country like it has over the last 6 century. 7 But having said that, just because we have 8 new technology, new genetic therapies, we have had 9 wonderful advances with informed consent that just 10 because we have new technologies, there's no reason 11 to get rid of informed consent. That's an appeal 12 to make. 13 And the second thing is, I'd like to 14 suggest that perhaps you could create a web site 15 for patients, Abbey, as you said, patients don't 16 have time to read the Federal Register. Presidents 17 of non-profits don't have time to read the Federal 18 Register. And we are a small organization. We 19 don't have money to pay lawyers to read the Federal 20 Register for us. 21 So I would highly recommend that you could 22 create a patient's rights web site that could 282 1 describe what are your rights as a patient involved 2 in a clinical trial. 3 We get people calling us with all kinds of 4 situations, and, quite frankly, I've worked at NIH. 5 NIH has an information office in every institute, 6 but try calling some time. It's very, very 7 complicated, and I think that could be very helpful 8 to the public. 9 And thank you for your work and being so 10 open. 11 CHAIRPERSON MARSHALL: Thank you very 12 much, and we hope to hear from you again. 13 And, yes, there are folks here from the 14 OHRP who deal exclusively in education, and I hope 15 that they're taking copious notes as well. 16 MR. SNIDER: Dixie Snider, Associate 17 Director for Science at CDC. 18 I just wanted to raise an issue that is 19 relevant here, I think particularly in light of Dr. 20 Wolf's comments that hasn't been brought up, and 21 that is the issue of technology transfer and 22 patenting and so forth. 283 1 As everybody is aware, I'm sure, there 2 were some laws passed back in the eighties that 3 encouraged academia and then subsequently, federal 4 laboratories to invent things and to patent things 5 and to get them into commercial production. 6 And what I'm saying is that we have some 7 competing societal goals here, and that we're 8 encouraging scientists, on the one hand, to be 9 innovative and to patent their products and get the 10 financial rewards that go with that. And, at the 11 same time, wondering at what point -- certainly as 12 a member of the work group, I hope everybody 13 understands I'm for full disclosure. So that's not 14 the issue. 15 The issue is, when do we prohibit people 16 from participating? And I think it's an important 17 issue for you to grapple with. 18 I don't have the answer to that question, 19 but I can tell you that on the work group, we 20 struggle with that. 21 Suppose, for example, we have the surgeon 22 that's developed a particular device and that 284 1 surgeon has practiced on all kinds of animals and 2 is the most competent person to install that device 3 on the first human being, and yet that person holds 4 the patent and maybe even owns the company that he 5 or she created? 6 That presents a real dilemma for us as a 7 society in terms of we want that product. 8 Presumably, it has some value to us. 9 At the same time, we don't want that 10 individual to be swayed by those financial 11 considerations and the other considerations into 12 doing something to us or one of our loved ones, or 13 anybody else, for that matter, that would be 14 unethical and that would be influenced by those 15 financial considerations. 16 So I just bring that to your attention 17 because I think it's really a very important aspect 18 to this whole issue. 19 CHAIRPERSON MARSHALL: It most certainly 20 is. 21 Bob, did you have a response to Dixie's 22 comments? Let's do that. Yes? 285 1 DR. ROBERT LEVINE: I'd like to endorse 2 what Dixie said because I think it's very important 3 that we don't lose sight of the important job that 4 universities have in technology transfer and in 5 bringing products to the marketplace. 6 And, also, the importance of inventors in 7 the initial processes of prosecution of inventions. 8 It's very difficult to make it work any way other 9 than that. 10 I think it's a quite different issue once 11 one has gone beyond initial proof of principle, or 12 in FDA jargon, beyond Phase I kind of trials, to 13 then say, "Should somebody who has an equity 14 position be engaged in Phase III trials or be 15 engaged in doing things which really bring a 16 product to the marketplace?" 17 But at the very outset of discovery, and 18 including the outset of discovery, inhuman 19 subjects, I think there really remains a role of 20 the inventor and because of the way our laws are 21 set up, the inventor often will have a financial 22 role in the successful prosecution of that 286 1 invention. That should be disclosed, but I don't 2 think it should be forbidden. 3 CHAIRPERSON MARSHALL: Thank you, and I 4 know in terms of our materials that we have and 5 discussions that have taken place earlier that that 6 level of transparency is very important, and that 7 there are organizational safeguards that can be put 8 in place to mediate those conflicts. Thank you. 9 MS. DELANEY: My name is Patty Delaney, 10 and I am actually an FDA employee, and I work in 11 the cancer program, but I'm here today as a member 12 of the public and as a patient advocate. 13 I think that much of what you talk about 14 today is so largely misunderstood by the public, 15 not understood at all, actually, so that when the 16 rank and file person enters the trial, it is 17 overwhelming. 18 I bring the experience of my own 19 participation in a clinical trial at the National 20 Cancer Institute to the position I hold at the FDA 21 and to my volunteer work as a patient advocate. 22 The conflict of interest, financial 287 1 conflict of interest, is only, of course, growing 2 and adding pressure, but there is also the conflict 3 of interest of scientific zeal that presents a 4 terrific problem for patients. 5 And I think as a practical matter, it's 6 very important that patients have, once they have 7 entered a trial, have an unbiased place to turn for 8 advice while they are in the trial. 9 I would like to say it was only my 10 anecdotal experience, but, of course, it isn't. 11 I've spoken and advised hundreds, if not thousands 12 of patients since 1987. And the problem is that 13 the advice I received on the ethical conflicts in 14 my trial were from what I call "people on the 15 payroll." You've all alluded to that this morning. 16 And it required, at the National Cancer 17 Institute, many of them coming to me, quote, "off 18 the record," sneaking into my room, telling me to 19 leave the trial, doing things like that. 20 I can only say that I would like to 21 believe that my experience is anecdotal, but, 22 again, I know it is not. So to the extent that 288 1 this committee can think really about the 2 individual experience of a much less sophisticated 3 person coming to the circumstance and how they 4 would proceed through the entire circumstance, they 5 must have advice from unbiased sources while they 6 are in the trial, and it cannot be from people on 7 the payroll. 8 If that's a funding issue, then it's an 9 advocacy issue that we all have to deal with. 10 CHAIRPERSON MARSHALL: Thank you, and I 11 hope a question for you, Patty. 12 One of the things that I have thought 13 about in the past -- this relates back to my 14 background as a critical care nurse and as a 15 clinical ethicist -- is whether or not there is an 16 analog from the model of an ethics consultation 17 service of an ethics committee to the same sort of 18 problem solving mechanism within the clinical 19 research enterprise? 20 But the question I have for you is, my 21 bias is that most well-trained ethics consultation 22 services or consultants do a good job, and that 289 1 they don't represent the interests of the 2 institution. They are there to help resolve an 3 issue. 4 Would you see the same sort of mechanism 5 as having an inherent conflict of interest because 6 they might be paid by the institution? 7 MS. DELANEY: Well, I think you'd have to 8 look at it on a case by case basis. I mean 9 patients, first of all, the people they believe the 10 most at this point are other patients. Not their 11 doctors, other patients. However, the organized 12 patient advocacy community is increasingly getting 13 conflicted by pharmaceutical funding. And so that 14 becomes a question. 15 It all becomes a question of exactly what 16 the circumstances of that trial and that ethics 17 committee. 18 I just remember -- I did not know anything 19 about clinical research when I joined my trial. I 20 just remember thinking to myself, all of these 21 physicians here have so much angst, and they're all 22 wringing their hands, and they're going to the 290 1 terminal board, and they're trying to figure out 2 what to do about me. But where am I supposed to 3 turn to figure out what to do about me. 4 And I did suspect harm, and I was then, in 5 fact, told that there was the potential of harm. 6 So, I mean when you're very ill with a 7 life-threatening disease, which many trials are 8 treating people who are very ill, they need to have 9 someone -- they don't have -- it shouldn't be a 10 matter of them having to ask, either. It should be 11 unsolicited where they are checked in with 12 periodically by this unbiased source. 13 CHAIRPERSON MARSHALL: Thank you very 14 much. 15 MS. FISHER: I'm sorry. 16 CHAIRPERSON MARSHALL: Go ahead, please. 17 MS. FISHER: My name is Barbara Lowe 18 Fisher, and I'm the President of the National 19 Vaccine Information Center. 20 Dr. Dorff, if there is a societal duty to 21 improve the human condition, and, Dr. Rich, if 22 clinical research is a societal good, of course, 291 1 the ultimate question is, who is going to define 2 "societal good" and decide which individuals will 3 be used by science to improve the human condition? 4 And from a health consumer perspective, I 5 think it's fair to say that most Americans do not 6 want to be used by science or by scientists, no 7 matter how much the research will benefit society, 8 without their voluntary informed consent. 9 And I think that this extends in the 10 future -- should extend to research that's going to 11 be conducted where government or industry will give 12 financial incentives to HMO's, particularly, and 13 doctors will have financial incentives to enroll 14 patients in clinical trials, particularly children 15 in clinical trials. 16 And then when HIPA is enacted, the Health 17 Insurance Portability and Accountability Act, is 18 enacted in 2002, third parties will be allowed to 19 go in and mine the medical records of these 20 patients without the patients' informed consent. 21 CHAIRPERSON MARSHALL: Any committee 22 members? Any -- 292 1 DR. SHAMOO: Can I -- 2 CHAIRPERSON MARSHALL: Yes. Yes, please, 3 Adil. 4 DR. SHAMOO: I just want to comment on the 5 previous speaker who asked a question, and I come, 6 again, from my experience with decision impaired. 7 This is why we came up with the suggestion that 8 because the same psychiatrist researcher was the 9 investigator. And so there's almost a double 10 jeopardy for decision impaired when the same 11 researcher is the same doctor who is treating the 12 patient. There alone, cancer patients who is not 13 decision impaired. 14 And at the time, we suggested very 15 strongly that they should be a disinterred 16 physician, just like we have a private physician, 17 who will advise us, on a continuing basis, whether 18 we should enter into the trial, we should continue 19 the trial, and when we should get off of the trial. 20 That could resolve some of those problems. 21 CHAIRPERSON MARSHALL: Elliot, and then I 22 want to begin -- I want to get Greg, and then I 293 1 want to begin our discussion of recommendations. 2 DR. DORFF: I just wanted to endorse 3 completely what -- what's your name, again? 4 MS. FISHER: Ms. Fisher. 5 DR. DORFF: -- what Ms. Fisher just said. 6 As a matter of fact, it goes very much to the 7 essence of what America is, which is a strong sense 8 of individual rights, as against communal good. 9 And so that when we think about the 10 communal good, that doesn't mean that individual 11 rights always trump the communal good, but it does 12 mean that whenever we're talking about the communal 13 good, such as, in our case, furthering research, we 14 have to take into consideration with very, very 15 strong protections of human rights. I think that's 16 why this committee was formed in the first place. 17 CHAIRPERSON MARSHALL: Well said. 18 Dr. Koski is back from glad handing the 19 President. Welcome group. 20 DR. KOSKI: Thank you. Nice to be back. 21 I'm sorry that I had to run out and miss part of 22 this. I understand you've had a very productive 294 1 day so far. 2 I just wanted to comment on the fact that 3 many institutions have already adopted programs, 4 either as specific patient advocate programs for 5 research or separate sort of components within the 6 human research office that is disconnected from the 7 IRB process, per se, and other parts, to do 8 specifically the kinds of things that are being 9 suggested to be a resource available to patients so 10 that there may be some examples of best practices 11 that are already available out there that might be 12 worth trying to identify more clearly and tap into. 13 CHAIRPERSON MARSHALL: Thank you, Greg. 14 So let me just remind the committee that 15 we have half an hour in which to deliberate about 16 our recommendations and that we can proceed in the 17 same way that we did this morning, that we need to 18 refine and focus on the issues; that we need to 19 identify any need for further data, and agree to a 20 work plan and a schedule. 21 And I really would like to thank you, 22 Stuart, for providing us with this list of five 295 1 questions. That is something that we can use as 2 food for thought, but I want to open the discussion 3 up then to committee members and perhaps we could 4 start with defining issues. 5 We have certainly talked -- there are some 6 general themes have had to do with how one defines 7 conflict of interest, and certainly the sense among 8 the group, as a whole, all of the folks in the room 9 is that it is very broad, and whether we need 10 prohibitions against certain types of conflicts of 11 interest or how others might be managed, whether 12 disclosure is adequate in some circumstances, 13 certainly not in all circumstances, issues that 14 have to do with technology transfer and 15 intellectual property and inventions. 16 And then other things that we might not 17 necessarily think of that fall under conflicts of 18 interest that have to do with faculty arrangements 19 and professional advancement and so forth. 20 So let me open the floor to members of the 21 committee. 22 Mark? 296 1 MR. BARNES: Thank you. 2 This is somewhat of a different situation 3 that we, the committee, are presented with and the 4 issue that we discussed this morning was really 5 quite undefined in terms of process and concrete 6 steps. 7 On the other hand, what we have here in 8 this case is we have a recent conference that was 9 convened by NIH, a very fine conference in which 10 many of these issues were discussed. We have 11 multiple articles in many different journals, 12 including JAMA and the New England Journal, about 13 the issue of conflict of interest, and we have a 14 proposed document on the table, a proposed guidance 15 on the table from HHS. 16 So it seems to me that, you know, one 17 action step that, you know, I would propose, at 18 least for discussion would be that we actually have 19 some kind of subcommittee of this group to simply 20 write a response to the draft guidance that's been 21 put out by HHS and that the subcommittee meet in 22 the interim between now and the next full meeting 297 1 or the next meeting of this full committee, and 2 that we have a report, you know, ready to present 3 back to the committee, hopefully, for its adoption, 4 and then our forwarding on to HHS. 5 I don't think that the timing would be a 6 problem here because I doubt that anything is going 7 to get passed until the next HHS Secretary gets 8 through the confirmation process and is fully 9 briefed on the whole thing of this -- the whole, 10 you know, meetings -- the whole process of all of 11 these issues. So I don't think that we're going to 12 lose valuable time by adopting some kind of process 13 to do that. 14 CHAIRPERSON MARSHALL: You read my mind, 15 and I really didn't slip in five dollars under the 16 table for that. 17 Let me ask first some response from the 18 rest of the group about that idea before we move 19 on. 20 Adil? 21 DR. SHAMOO: I agree. 22 DR. KOSKI: Just I don't know if this was 298 1 explained earlier. This is a technical sort of 2 clarification, if you will, with respect to the use 3 of certain terms that I have had to come to grips 4 with in government, and that is the difference 5 between guidance, between points to consider, 6 between rules and regulations. Each of those take 7 on specific meaning within government, so that we 8 need to keep that in context. 9 When we're talking about regulations, 10 we're talking about those new laws that are 11 actually passed by the Congress, and we're talking 12 about rules. Okay, they are basically the rules 13 that lay out how, in fact, specific regulations are 14 to be carried out within the government, and those 15 generally are promulgated through the rules-making 16 process. 17 And if my longer-term government 18 colleagues will help me here, if I get into water 19 that's deeper than I can stand it, so that that's 20 the other process. 21 And then, of course, with respect to 22 either points to consider, which was a specific 299 1 sort of designation that has been used in work 2 products from either NIH or HHS, or particularly, 3 FDA, then it comes in a certain thing. But it's 4 closer to guidance, which is something that can be 5 offered without going either through the rules- 6 making process or through the passage of new 7 regulations or amendments. 8 So that in terms of doing things quickly, 9 clearly, you'd want to do it with quality. But 10 it's possible to do things relatively quickly as an 11 interim step, which is, in fact, why this 12 particular document that's before the committee was 13 suggested as an interim guidance document because, 14 clearly, there's more work that would have to be 15 done and a decision would have to be made whether 16 or not it was desirable to actually promulgate 17 specific rules and so on, and if regulations are 18 required. Those are things that we clearly would 19 depend upon the guidance of this committee for. 20 So did I get it right, more or less, 21 Linda? Is that -- yes? Okay. Good. Thank you. 22 CHAIRPERSON MARSHALL: Bob? 300 1 DR. ROBERT LEVINE: I thought regulations 2 and rules were the same thing, and that Congress 3 passes their statutes and the regulations are 4 what's published in the Federal Register to 5 interpret the statutes? 6 DR. KOSKI: I see nodding heads, so we're 7 close. 8 CHAIRPERSON MARSHALL: Right. 9 DR. KOSKI: But that's -- okay. 10 CHAIRPERSON MARSHALL: And let me just 11 say, Greg, that Stuart sort of, in his introduction 12 to his remarks, made that very clear what the paper 13 was, and its interim status. 14 DR. KOSKI: Sorry. 15 CHAIRPERSON MARSHALL: No. No. No, and 16 so forth. But we rewrote the Federal Code while 17 you were gone. 18 No, so -- 19 DR. KOSKI: That's progress. 20 CHAIRPERSON MARSHALL: -- I would like, 21 while this is on the table, to say that I think 22 this is a wonderful action step. I would also ask 301 1 Mark whether you'd be willing to chair this small 2 group? 3 MR. BARNES: I guess I can't say, "no," 4 since I proposed it. 5 If you would like me to, I would. Yes. 6 CHAIRPERSON MARSHALL: It needs to be a 7 small group. 8 Do we have other volunteers? Adil? 9 Elliot? And I think that will suffice. Rob. And 10 I think that's large enough for a working group. 11 Yes? 12 DR. SHAMOO: May I ask a question? 13 CHAIRPERSON MARSHALL: Oh, of course. 14 DR. SHAMOO: Thank you. 15 I know NBAC's subcommittees meet also in 16 the public. They have the same rules governing 17 them as the full committee. 18 And my question to you big shots, to tell 19 us how the subcommittee should conduct itself, 20 before we get into hot water, if we make mistakes? 21 DR. KOSKI: I think what we should do, if 22 that requires specific legal clarification, we'll 302 1 get it from the FACA experts and legal counsel. 2 But we want to make sure of it. 3 There is, I believe, within our charter a 4 provision for putting together working groups in 5 order to come out with work product. 6 Clearly, the work product is ultimately 7 put up in the Federal Register and all, so that it 8 probably would be considered a working group rather 9 than a subcommittee, in which case, it can work in 10 private. Yes. 11 CHAIRPERSON MARSHALL: Right. Thank you. 12 Elliot? 13 DR. DORFF: That would be especially 14 helpful because it might be that this group could 15 meet by phone, rather than -- 16 CHAIRPERSON MARSHALL: Certainly. 17 DR. DORFF: -- in person. 18 CHAIRPERSON MARSHALL: Right. Right, and 19 I think that would be the expectation that this 20 working group would meet via e-mail and by 21 telephone and so forth. 22 But that as the process moves along, as I 303 1 will state over and over again, our work will be 2 available and transparent, and that we want to have 3 feedback from all of those who are concerned. So 4 you have that promise from us as a committee. 5 DR. CHODOSH: Could I just -- 6 CHAIRPERSON MARSHALL: Yes, Sandy? 7 DR. CHODOSH: -- make a small plea? 8 In the document, as it exists right now, 9 on page eight, you have a lovely list, which we've 10 already discussed really doesn't appropriately go 11 to the IRB, but maybe through the IRB. 12 But, you know, it's not really clear what 13 the answer should be, what's right and what's 14 wrong. And I think somewhere in the document, it 15 might talk about that a little bit, you know. 16 Who's the sponsor is not a bad term. I mean it's 17 not -- but there are some of them that are sort of 18 questionable about what am I supposed to answer? 19 You know, what is the right answer to get me off 20 the hook? 21 And I think that it would be worth 22 defining a little bit about what's implied. 304 1 CHAIRPERSON MARSHALL: Yes, Mary? 2 DR. PELIAS: I would like to request a 3 little bit more information about what patient 4 advocacy offices already exist and how they work in 5 terms of being close to or separated from 6 institutional review board. I'm very much 7 interested in patient advocacy and getting 8 information that we've talking to in this session 9 back to patients. 10 CHAIRPERSON MARSHALL: Mary, can you 11 explicate that just a little bit for me? I'm not 12 sure I've exactly wrapped my mind around what 13 you're getting at. 14 DR. PELIAS: Well, we mentioned just at 15 the end of our discussion about how to structure a 16 patient advocacy office as an unbiased source of 17 information for patients about research that they 18 might be participating in. 19 And in my own institution, I don't know of 20 a patient advocacy office. I would like very much 21 to know more about them and how patients can get 22 unbiased information, separate and apart from the 305 1 whole IRB process and signing consent forms. 2 CHAIRPERSON MARSHALL: Abbey? 3 MS. MEYERS: I don't think they exist -- 4 CHAIRPERSON MARSHALL: Abbey says they 5 don't exist. 6 MS. MEYERS: I never heard of that. 7 CHAIRPERSON MARSHALL: All right. Yeah. 8 Okay. 9 MS. MEYERS: Never. 10 CHAIRPERSON MARSHALL: Okay. All right. 11 MS. MEYERS: No. An ethics committee is 12 not a patient advocacy. 13 CHAIRPERSON MARSHALL: Right, and I'm 14 going to take the prerogative of the chair and that 15 we will go in order. 16 Elliot and then Greg, and I have a 17 comment. So if you would like to make a comment, 18 then you need to be acknowledged. 19 DR. DORFF: UCLA has an ombudsman for 20 patients. 21 CHAIRPERSON MARSHALL: Is that ombudsman 22 for a person that's being treated there or a person 306 1 who is in a clinical trial? 2 DR. DORFF: I honestly don't know how it's 3 defined. I know it is definitely for patients and 4 it may also be for people in clinical trials. I 5 don't know. 6 But, I mean specifically an office in the 7 hospital for patients to have their concerns aired 8 and dealt with. 9 CHAIRPERSON MARSHALL: I have Greg and 10 then I have Adil, and then I have myself. 11 DR. KOSKI: Actually, at PRIMAR this past 12 -- it's been a couple of months ago, whenever it 13 was. Time flies when you're having fun -- there 14 were presentations from several institutions where 15 they described, as one example, a separate office 16 that was set up at a cancer institute where they 17 were actively involved in clinical research. And 18 this office was totally independent and autonomous. 19 And at the time, people were approached 20 to, you know, ask them whether or not they were 21 interested in research, whether or not they wanted 22 to participate in it. 307 1 This office was made available to them. 2 In fact, they were actively introduced to one of 3 the individuals from this office whose sole 4 responsibility was to be there as a resource for 5 the patients who are involved in the research 6 activities. 7 And once the relationship is established 8 at that level, as the study progresses, there is an 9 ongoing visitation, active, you know, proactive 10 approach to the individual participants in the 11 trials to see, number one, how's it going? You 12 still want to do this? You got new problems, 13 questions, so on, but in an active kind of support 14 mode. 15 And, in fact, the institution has made an 16 attempt to assess this and they found that it's 17 been just enormously appreciated by the people who 18 are participating in the trials, and they believe 19 that it's been an important factor in promoting 20 both the quality of what they're doing, as well as 21 the satisfaction that the participants have had. 22 So that's one model. 308 1 At other institutions, it actually 2 established sort of separate offices so that there 3 may be a separate human research office that is the 4 staffing for the institutional review board and 5 much of that process, but a separate office that's 6 established as a resource to the patients where it 7 may be less active, but some of them have taken a 8 form of passing out a brochure to each patient who 9 is asked to participate or invited to participate 10 in a trial. 11 That explains what research is, explains 12 sort of the process that they would go through, how 13 it's reviewed and approved, what their rights, 14 expectations are, and actually it says, "Look, if 15 you have any concerns and questions, comments, you 16 know, call this office. There will be somebody 17 there to help you and that's available on a 24-hour 18 basis so that it can react to complaints, whether 19 they come from individual patients, from families, 20 whoever, and those are often coupled to quality 21 assurance, quality improvement efforts and so on. 22 So it's kind of they're the watch dog 309 1 within the watch dog sort of system, but a 2 separation of powers to make it very clear that 3 there is at least one place where a research 4 participant can go in order to get information 5 that's either not depending upon the IRB, nor upon 6 the investigators and the sponsors and so on. 7 And those are just two models. They both 8 exist currently, and my sense from the PRIMAR 9 meeting was that they're in recognition of the need 10 to improve what happens from the time the IRB says, 11 "Okay," to the time that they actually complete the 12 study and, you know, wrap up the data set. 13 That's where we need to put so much more 14 effort. That's where we need to put support. And 15 it emphasizes the fact that informed consent is -- 16 it's not signing the name. It's a process that 17 continues throughout the conduct of the activity. 18 So those are real life examples of what's 19 currently going on in some places. 20 CHAIRPERSON MARSHALL: Adil and then -- 21 MS. MEYERS: Can I ask Greg something? 22 CHAIRPERSON MARSHALL: Yes. 310 1 MS. MEYERS: You know, this is wonderful. 2 I wish every research institution should have it. 3 But if we write into the rules that every 4 hospital should have it, they're going to say, 5 "Who's going to pay for it," and what would be the 6 answer to that? 7 CHAIRPERSON MARSHALL: I want to interject 8 here, as the Chair, and this is, Mary, you have 9 raised a wonderful issue that is near and dear to 10 my own heart. 11 And I think that these sorts of mechanisms 12 to which one can appeal for help and assistance are 13 important not just for research subjects or 14 participants, but for those who do the research 15 themselves. And I'm thinking not on the 16 investigators if a problem arises, but research 17 nurses or others who may feel that their integrity 18 is compromised during the research process. 19 I think that this is something that when 20 the IOM committee gets to the second phase of its 21 charge and is looking at systems of protections of 22 human subjects, it will address. And I think that 311 1 we can certainly ask them to address this specific 2 issue. 3 There are excellent models out there that 4 could be adapted and some creative thinking might 5 even bring us forward in terms of new things. 6 So thank you very much. 7 Other things that we might want to put on 8 the table in terms of -- now, remember here, we are 9 trying to identify issues and a work plan for the 10 future. So that's the discussion that I would like 11 to hear within the next eight minutes. 12 Elliot? 13 DR. DORFF: It occurs to me that this is 14 not restricted to this particular field of 15 endeavor. Conflicts of interest occur in all kinds 16 of other fields. 17 And it would be interesting to just get a 18 kind of background paper on how lawyers deal with 19 conflict of interest and how social workers -- in 20 other words, those kind of things in order to get 21 ways -- to get this list that Mark just handed to 22 me, a list that he created, or some possible ways 312 1 of dealing with conflicts of interest in this 2 particular instance. 3 And I think whatever number of concrete 4 ways can be suggested, either in this field 5 specifically, as Mark's list deals with, or from 6 other fields, that that would be really helpful in 7 terms of diminishing the conflicts of interest that 8 exist. 9 CHAIRPERSON MARSHALL: Let me ask you, 10 Elliot. If we were to commission a paper of that 11 sort, would it be helpful then, if such a person 12 exists, to have something that is a survey paper? 13 DR. DORFF: Right. 14 CHAIRPERSON MARSHALL: What is the 15 pleasure of the committee? 16 MS. MEYERS: It sounds good. 17 CHAIRPERSON MARSHALL: And let me ask our 18 -- pardon me? Let me ask our staff folks, do you 19 see any objections to that in terms of resources, 20 et cetera? 21 PARTICIPANT: Not at this point. 22 CHAIRPERSON MARSHALL: We shall do that. 313 1 Thank you. 2 Adil? I'm sorry. 3 PARTICIPANT: Potential conflict of 4 interest or -- 5 CHAIRPERSON MARSHALL: No. 6 PARTICIPANT: -- is it any promotion to 7 tenure -- 8 CHAIRPERSON MARSHALL: Okay. 9 PARTICIPANT: -- conflict that you are 10 asking for? 11 CHAIRPERSON MARSHALL: It should be 12 everything. And let me ask, if you're going to ask 13 a question if you'd please come to the microphone. 14 But I think we would like for this to be 15 broadly based in terms of definitions and 16 approaches. 17 Greg and then Bob? 18 DR. SHAMOO: What happened to me? 19 CHAIRPERSON MARSHALL: Oh, I'm sorry. 20 Adil. Adil, Greg, Bob. 21 DR. SHAMOO: There is quite a bit of 22 literature on conflict of interest and financial 314 1 conflict of interest in the financial institutions. 2 I have actually looked at that in the mid-eighties, 3 so there is literature there, and it's really quite 4 extensive. And, as a matter of fact, that's why 5 you have strict rules in the financial, the 6 Securities and Exchange Commission, the Glass- 7 Stiegel Act of 1936, as Mark is shaking his head, 8 and I'm quite familiar with it. 9 And that's how I started my career in 10 terms of research integrity issues and how it 11 should be resolved, and they resolve it really 12 rather very well. They compartmentalize and they 13 prohibit, et cetera, et cetera. 14 So I think before we jump into this, there 15 are literature on the subject. Maybe we should 16 make some of them available. That's one. 17 The second thing is, Mark's committee or 18 Mark's working group -- I apologize. I learn 19 slowly -- with Stuart's permission, could we use 20 Stuart for the working group, his help, since he 21 has put a lot of thought in it, and we could tap 22 him whenever we need him? 315 1 CHAIRPERSON MARSHALL: I had the same 2 thought of asking Stuart if he could serve as a 3 consultant. And I also wanted to add a committee 4 member, and I wanted to ask Judy if you would be 5 willing to assist us in this endeavor, as well? 6 Thank you. 7 So does that suffice for a working plan? 8 And I think, you know, tomorrow afternoon, when we 9 wrap up and after we have had all of our 10 discussions, we can outline time frame and so forth 11 for all of these because what we're going to need 12 to do then is assign priority. 13 And, Greg? 14 DR. KOSKI: Thank you. This comment was 15 probably made earlier before I returned, but I 16 think one of the notions that came out of the 17 conference in August was that we needed to be 18 broader in our thinking, rather than just looking 19 at financial arrangements to recognize that other 20 types of issues pose real conflicts that should be 21 considered in this broad framework. So I would 22 just endorse that we would go in that direction. 316 1 CHAIRPERSON MARSHALL: I have Bob and then 2 Judy. 3 DR. ROBERT LEVINE: Thank you. My 4 comments follow directly on Greg's that the -- a 5 lot of what's written about conflict of interest, 6 conflict of commitment and the reward system really 7 does not pay good attention to what's really seen 8 as the coins of the academic realm. Its promotion 9 is very big. Being perceived as a good citizen of 10 the academic community is very big. 11 Even more so, these days, as we begin to 12 refer to our community of colleagues as a national 13 or international community, rather than the local 14 community, it's the recognition you get for the 15 quality of your work. 16 All too often, I see people saying, "Well, 17 we could fix the IRB problem. We'll give him more 18 money." Well, that's not what makes these people 19 move, and that's not what makes clinical 20 investigators move, for the most part, either. 21 They would much rather have their name attached to 22 some important discovery, or they say we could give 317 1 them released time from teaching. 2 That may work in the French Department, 3 but that's not what teaching in a medical school is 4 all about. Nobody can keep track of when they're 5 teaching and when they're not. There's always 6 teaching going on, no matter what you do. 7 The other problem I want to raise is the 8 idea of having people inside the institution to 9 serve as patient advocates or ombudsmen. Many of 10 these people really don't know enough about what a 11 clinical trial, for example, about what treatment 12 is all about to serve as effective advisors to the 13 patients. 14 The question came up about how are you 15 going to pay these people. What you have to 16 consider is that if you want to have truly 17 effective advisors to patients, they're going to 18 have to be people who have a substantial amount of 19 professional education themselves, and these people 20 are expensive. 21 I think it's very important to have people 22 available to serve as advisors. One device that 318 1 the IRBs have used is particularly and very 2 difficult decisions, particularly in areas where 3 you're dealing with patients that have a really 4 grave outcome, whether or not they get treated is 5 rather than attempt to write a script for a 6 conversation between an investigator and a 7 prospective research subject. 8 They say, "Take this protocol. Take this 9 consent form and show it to your own doctor. And 10 what you should do is ask your doctor to look at it 11 and discuss with you whether it would be a good 12 idea for you to consider getting involved in this." 13 We tried to think of other ways to 14 accomplish the same goal and really couldn't come 15 up with it. You simply can't get people who are 16 utterly disconnected to come in and offer that sort 17 of advice to individual research subjects as 18 they're going through their thinking process. 19 I have no way of knowing whether our 20 approach is effective. We have occasional 21 anecdotal evidence that it either is or is not. 22 CHAIRPERSON MARSHALL: Abbey? 319 1 MS. MEYERS: I'm just thinking that, along 2 those lines, maybe there ought to be a mandatory, 3 24-hour or 48-hour waiting period from the time the 4 informed consent is presented to the person until 5 they sign it and agree to go in to a trial. And 6 maybe this independent person, this advocate or 7 ombudsman, should be present during the informed 8 consent process. 9 CHAIRPERSON MARSHALL: Let me just say 10 from a process perspective that I think that 11 perhaps we're getting to a level of detail that is 12 something that we have commission the IOM to do, 13 and that perhaps the best use of our time would 14 then be to react to the advice that we're given by 15 them. I think we're bordering on micromanagement 16 at the moment. 17 I had Judy and then Sandy. And, pardon 18 me. I want to interrupt just for a moment because 19 I see that some folks are heading out the door, and 20 I wanted to let you know that, at 4:30, there is 21 going to be a reception to which we would like to 22 invite everyone in the room. It will be hosted by 320 1 the Surgeon General's office, and Deputy Surgeon 2 General Nicky Lorry will be here to host that 3 reception. So we hope that all of you will stay 4 for another half an hour and then will join us. 5 So, Judy? 6 DR. SIEGEL: Yeah. I'd just like to get 7 back to discussions of types of potential conflicts 8 of interest and where they arise. And I've heard 9 many things come up which we and the pharmaceutical 10 sponsor and I know are dealing with. 11 And I think what I'd like to get into a 12 public discussion somewhere is clinical trial 13 methodology in the 21st century and what the issues 14 are relating to doing clinical trials in the 21st 15 century. 16 Where, for instance, does the referral of 17 patients into clinical trials fit? How did that 18 come about? Why is it done? 19 What is the obligation of actually the 20 investigator relative to patients who are referred 21 to him from other investigators? 22 Because I actually think that it's a whole 321 1 research climate now that's very different from ten 2 years ago, and as we now start to think of it in 3 ways we've never thought of it before, which is 4 does this actually induce conflict of interest in 5 some way, I think actually a public discussion of 6 the whys may actually help to figure out how to 7 manage it better, because I don't think that we 8 actually manage it very well from the broader 9 conflict of interest financially. 10 And so I would like to get several of the 11 issues. Bonuses for rapid enrollment, where does 12 that come from? 13 I know in my own company, that is 14 discussed every time we do a clinical trial. And I 15 know there are major advocates within my company 16 that say this is not ethical. 17 And so I think within the industry, there 18 are probably those discussions already going on, 19 and I think maybe it would be valuable to actually 20 have a public discussion. 21 CHAIRPERSON MARSHALL: Thank you. 22 Sandy was next, and then Mark. 322 1 DR. CHODOSH: As I was waiting, you just 2 raised an issue which I found to exist, and that is 3 that patients have conflict of interest, 4 particularly the professional patient, okay. And 5 these people read the ads. They go to the 6 textbook. They find out what symptoms they're 7 supposed to have and they have them. 8 And one has to be very careful because 9 this is clear -- they're doing it purely, when 10 there is money involved, and, of course, that could 11 alter the results of the study much more than some 12 of the other things that we worry about. 13 So that's another aspect of conflict of 14 interest which I think belongs there. 15 And along the same line, we talk about the 16 advocacy business. We had to be very careful. All 17 of a sudden someone who's an advocate job depends 18 on research continuing in that institution to 19 justify their existence so that it's everywhere. 20 That doesn't mean it's not controllable, 21 but it's everywhere, and I think it has to be taken 22 into consideration at all levels. 323 1 CHAIRPERSON MARSHALL: Mark? 2 MR. BARNES: Just a couple of brief 3 points. One is that on the issue of other 4 professions and what kind of laws there are in 5 conflict of interest, I do just want to point out 6 to the committee that Bill Sage, who's a law 7 professor at Columbia, just completed last week, I 8 think it was, printed a report by the Millbank 9 Memorial Fund on Securities and Exchange Commission 10 laws, disclosure obligations, and what the medical 11 profession can learn from the SEC. 12 It's a thick report. I just got a copy a 13 couple of days ago, and I'd be happy to share that 14 with Kate, and it could be distributed to the 15 committee. I'm sure the Millbank Fund wouldn't 16 mind. 17 The second things is that we often talk -- 18 just a couple of brief comments -- we often talk in 19 terms of pharmaceutical companies as though they're 20 the only private sponsors out there. 21 But I just want to point out to the 22 committee's attention for future deliberations that 324 1 that's only one piece of it. There are medical 2 device manufacturers and biotechnology companies 3 that are equal players in this and in which there 4 are conflict of interest issues that arise that are 5 just as serious as anything that arises in terms of 6 the private pharmaceutical companies. And that's 7 just important to keep in mind, even though, to my 8 knowledge, there's not -- you know, there's nobody 9 that represents the medical device manufacturers at 10 the table or the biotech companies, for that 11 matter. 12 And, finally, just to put some of this 13 into context a little bit, I think it's important 14 to -- it's sort of economics 101 that when you have 15 any kind of a sector of the economy that is 16 essentially controlled, then money flows out of 17 that sector and flows into that part of the sector 18 that is uncontrolled. 19 And it's very important to understand that 20 it doesn't excuse the conflicts of interest. But I 21 think it's extremely important to understand that 22 we are under incredible cost compression in all of 325 1 medicine. 2 Real physicians' salaries have declined. 3 Academic medical centers and other hospitals and 4 nursing homes are in dire financial straits. In 5 many of our states, they're actually operating 6 every year at one and two percent losses, which 7 cannot be sustained forever. That's due to 8 Medicare cost compression and the Balanced Budget 9 Act. 10 And so when that occurs in the largest 11 part of the fiscal restraint or climate in which 12 these medical entities work, then one has to expect 13 that where the money is where the attention will 14 go. 15 And so although, again, it doesn't excuse 16 everything, I think it's important for all of us to 17 remember in our deliberations that all of our 18 deliberations are against a backdrop of incredible 19 cost compression in medicine which has put 20 imperatives in front of -- or incentives, I should 21 say, in front of physicians and hospitals that they 22 might not have responded to in a different set of 326 1 circumstances. 2 CHAIRPERSON MARSHALL: Thank you, and 3 Greg? 4 DR. KOSKI: I was just actually following 5 up on a suggestion. 6 There are several of the ex-officio 7 members here representing agencies who have not 8 participated in the HHS working group that had 9 developed the draft interim guidance. If any of 10 the other agencies, the ex officios, have comments, 11 it would be useful at this stage to try and 12 incorporate that, so I would encourage them to do 13 so, not at this moment, but in writing to the 14 working group. Thank you. 15 CHAIRPERSON MARSHALL: John? 16 MR. MESA: Greg, I'd just repeat what I 17 said earlier before you got back from your soiree 18 with the President. I mentioned the point that I 19 think it would be useful, certainly for the VA, for 20 it to formally come to our agency, the package, so 21 that we can at least engage, you know, the right 22 levels of the organization, which may not even 327 1 involve myself. 2 And the hint was that maybe the other 3 secretaries to the common rule might be similarly 4 interested in receiving such formal letters. I 5 mean we can do it through the back door. We would 6 do that, anyway. 7 But I think the notion that you put it on 8 the table, coming from DHHS, this is important to 9 us, and now Energy, Education, CIA, VA, would you 10 please seriously look at this. I think that would 11 be an important thing to do. 12 MR. RUBEN: The NSF agrees with that last 13 comment. Philip Ruben, National Science 14 Foundation. Same thing. We'd like to see that. 15 Thank you. 16 CHAIRPERSON MARSHALL: Thank you, Philip. 17 That will be done. 18 We have time now, 20 minutes or so, for 19 general discussion and a recap of the day. 20 I'm going to ask Kate to do this, not 21 today, but perhaps for tomorrow morning, where, 22 thinking ahead to the agenda, we are going to have 328 1 a -- I will -- a brief recap of today's discussion. 2 And then other issues that occurred outside of the 3 meeting, and thus, all the more reason for those of 4 you in the room to attend the reception this 5 evening because we will be receiving ideas, and you 6 will be helping to set the agenda. So please do 7 come. 8 What I would like Kate to do, if she's 9 amenable, is maybe to make a list for committee 10 members and that we could make available to our ex- 11 officio members, our agency liaisons, and our 12 community members of the action plans that we have 13 delineated today so that we can be thinking about 14 them through the course of the day tomorrow. 15 Obviously, we'll be adding onto those and 16 then we'll have sort of just a working draft that 17 we can use for the end of the day tomorrow relative 18 to our discussion. 19 I would, in the last few minutes that we 20 have, like to open the floor to general discussion 21 from anyone about process and procedure. 22 We are a new committee. There is sort of, 329 1 aside from federal guidelines relative to the sort 2 of committee that we are and under which we need to 3 operate, we would like to hear from you. I 4 certainly would like to hear from you suggestions 5 for how this committee could best serve you 6 relative to how the meetings are run and so forth. 7 So this is an opportunity for you to 8 educate us, if you would be willing to do so. 9 Yes? 10 MS. LEE: Bonnie Lee, and I'm from the 11 Food and Drug Administration, but I've also worked 12 in the past as staff on the Tuskeegee syphilis 13 study ad hoc advisory panel, and also on the staff 14 of the National Commission, and so I have always 15 been very critical of how advisory committees work. 16 The Tuskeegee syphilis advisory panel was 17 the first group to ever work under the Federal 18 Advisory Committee Act, and it was quite a shock. 19 When we were formed, the assumption was that things 20 would be done behind closed doors, and, of course, 21 they were not. It was a very sensitive topic. It 22 was very difficult for people to speak candidly. 330 1 By the time that the National Commission, 2 I think that everyone knew they needed to act in 3 public. And so I'm going to react to your first 4 day of your first meeting -- 5 CHAIRPERSON MARSHALL: Thank you. 6 MS. LEE: -- to give you at least my 7 impression. 8 You're really phenomenal as a group. I 9 want to commend you. I want to commend you as a 10 Chair for your interest in involving not only the 11 members at the table and the federal ex-officio 12 members, but also the community and other people 13 attending the meeting. 14 I think that your discussions, generally, 15 have really been very forthright and candid and not 16 particularly influenced by the fact that you know 17 or you don't know who's listening to you here in 18 the public. And that's certainly to be commended. 19 My only suggestions, and you've done some 20 of it well, and hopefully, you'll do more, as I 21 think you've indicated, is if you can have the 22 handouts. You all have notebooks here. Some of 331 1 the materials may not be relative to those of us 2 sitting out here, but to those where you will be 3 discussing them, if they could be out on the table 4 ahead of time, that would be very helpful. 5 And other than that, I think you're on the 6 right track, so I want to thank you. 7 CHAIRPERSON MARSHALL: Thank you very 8 much, and my mother thanks you, as well. 9 And the concern about the handouts has 10 been raised by others, and I think had time 11 permitted, that would have been the case. We 12 promise that in the future, and I think Greg wants 13 to speak to that, also. 14 DR. KOSKI: Thank you, Mary Faith, and 15 thank you very much, Bonnie. 16 I think I just need to get out, you know, 17 this particular message for everyone right now. I 18 want to simply say, right here in public, that what 19 Kate Gottfried has done in pulling this meeting 20 together in the short time frame that we had to 21 work on is absolutely nothing short of miraculous, 22 and I really want to applaud you, Kate, for 332 1 everything that you've done. 2 [Applause.] 3 DR. KOSKI: Clearly, there were certain 4 aspects of organizing, or the logistics of this 5 first meeting that were not optimal, and I can take 6 full blame for all of those because I notice that, 7 you know, poor Kate, who dropped me off at my 8 apartment last night at around 10:30, called me at 9 11:30 to say that the Secretary's advance people 10 had changed their requests. 11 And when I got here this morning, I 12 actually was presented with a completely rework 13 agenda that included the presentation by Senator 14 Kennedy that wasn't even there the night before, 15 and that doesn't happen by little elves that come 16 in the middle of the night. It comes from terribly 17 committed people who just take their 18 responsibilities very seriously. 19 So, Kate, I want to thank you once again. 20 And in the future, we will try to make sure that 21 not only is the announcement in the Federal 22 Register in there, you know, fully in advance of 333 1 the meeting, but that there will be agenda items 2 there. 3 We will try to make sure that there are 4 references to appropriate resources, web sites and 5 all, where information, background information, 6 will be available. 7 As our Chairperson has said, we clearly 8 want to have all of this done in a very 9 transparent, open and productive manner. So, 10 again, thank you. 11 CHAIRPERSON MARSHALL: And I guess, 12 finally, I would like to say, in that spirit, we 13 are all accessible, and, obviously, we're on the 14 web site. 15 But I would ask you if you're not able to 16 be here tomorrow to please, if you have questions 17 or issues or concerns or constructive feedback, 18 don't hesitate to contact anyone on the committee, 19 and, also to give us your suggestions in terms of 20 how we can communicate best with people who don't 21 read the Federal Register or who otherwise aren't 22 plugged in, in a systematic way to normal venues of 334 1 communication. 2 So we do hope to hear from you, and we 3 will take what you have to say very seriously. And 4 I need to, for those of you who can't stay, and I 5 hope all of you can, just to let you know if you're 6 attending the session tomorrow, we will be in a 7 different room. We will be in the Maryland Suite, 8 and that is back around by the hotel entrance and 9 down the corridor. 10 So we have perhaps ten minutes to take a 11 little break before we head down to the reception 12 which is -- oh, it's here? Oh, well. 13 DR. KOSKI: They need to set up. 14 CHAIRPERSON MARSHALL: But they do need to 15 set up, and Greg wants to have -- 16 DR. KOSKI: I'm sorry. 17 CHAIRPERSON MARSHALL: We'll give the 18 final word to Greg. I'm sorry. 19 DR. KOSKI: One final word. With respect 20 to getting information out, I'd like to point out 21 that the Office for Human Research Protections has 22 recently instituted a list serve to which everyone 335 1 can subscribe. You don't need to be an IRB member 2 or something to be on this. 3 We, in fact, wanted to be a source for 4 dissemination of information to the broadest 5 possible audience. 6 We will tomorrow bring information as to 7 exactly how one can subscribe to that. It's a one- 8 way sort of service where we send information out 9 to people. 10 We have mechanisms for getting information 11 in, also, but right now, it may be very 12 advantageous for us to use as a tool for any of you 13 who are interested to get on board with that. 14 So we're going to take a little break and 15 then come back here for a little reception. Dr. 16 Lorry will be hosting that. 17 Mary Faith, are you done? 18 That's it. We'll see you at the 19 reception. We can relax. Thank you. 20 [Whereupon, at 4:15 p.m., the meeting was 21 adjourned to reconvene on Thursday, December 21, 22 2000, at 8:30 a.m.] 336 1 CERTIFICATE OF OFFICIAL REPORTER 2 This is to certify that the attached 3 proceedings before the NATIONAL HUMAN RESEARCH 4 PROTECTIONS ADVISORY COMMITTEE held Wednesday, 5 December 20, 2000, were held as herein appears, and 6 that this is the original verbatim transcript 7 thereof, and is a full correct transcription of the 8 proceedings. 9 10 11 Gerald T. Brooks, Sr. 12 Official Reporter 13 14 15 16 17 18 19 20 21 22