1 THE DEPARTMENT OF HEALTH AND HUMAN SERVICES + + + + + MEETING OF THE SECRETARY'S ADVISORY COMMITTEE ON HUMAN RESEARCH PROTECTIONS + + + + + Tuesday, August 1, 2006 + + + + + The meeting was held in Salon C of the Grand Ballroom, The North Bethesda, Bethesda, Maryland at 8:00 a.m., Dr. Ernest Prentice, Chairman, Presiding. PRESENT: JOHN AGWUNOBI, M.D., ASSISTANT SECRETARY FOR HEALTH ERNEST D. PRENTICE, Ph.D., CHAIRMAN BERNARD A. SCHWETZ, DVM, Ph.D., EXECUTIVE SECRETARY CATHERINE SLATINSHEK, MA, EXECUTIVE DIRECTOR KELLY BOOHER, PROGRAM ANALYST JEFFREY BOTKIN, M.D., MPH, MEMBER CELIA B. FISHER, Ph.D., MEMBER 2 PRESENT (Continued): MYRON GENEL, M.D., MEMBER NANCY L. JONES, Ph.D., MEMBER DANIEL K. NELSON, MS, CIP, MEMBER NEIL R. POWE, M.D., MPH, MBA, MEMBER JAMES H. POWELL, M.D., MEMBER FRANCINE C. ROMERO, Ph.D., MPH, MEMBER SAMUEL TILDEN, M.D., J.D., LLM, MEMBER SUSAN L. WEINER, Ph.D., MEMBER PATTY DECOT, EX OFFICIO MEMBER SANDRA SCHNEIDER, Ph.D., EX OFFICIO MEMBER ROGER CORTESI, ALTERNATE EX OFFICIO MEMBER SALLY FLANZER, Ph.D., ALTERNATE EX OFFICIO MEMBER SARAH CARR, ALTERNATE EX OFFICIO MEMBER LAURENCE UHTEG, M.D., Ph.D., ALTERNATE EX OFFICIO MEMBER ALSO PRESENT: MYRA CHRISTOPHER, PRACTICAL BIOETHICS LAURIE FLYNN, COLUMBIA UNIVERSITY DENISE GEOLOT, HRSA CHARLES MacKAY, Ph.D., STL, NIH 3 ALSO PRESENT (Continued): ANDREW POPE, NIH DAVID SHORE, M.D., NIMH DAVID STRAUSS, M.D., STATE PSYCHIATRIC INSTITUTE WENDY VISSCHER, Ph.D., ORPE 4 C O N T E N T S PAGE Introduction, Chairman Prentice . . . . . . . . . .5 Background of IOM Prisoner Report, Dr. Bernard A. Schwetz . . . . . . . . . . . . . . . . .6 Presentation of IOM Prisoner Report, Dr. Wendy Visscher . . . . . . . . . . . . . . . . . 10 Panel on Research Involving Individuals with Impaired Decision Making Capacity: Dr. David Strauss . . . . . . . . . . . . . 99 Dr. Charles MacKay . . . . . . . . . . . .116 Dr. David Shore . . . . . . . . . . . . . .127 Laurie Flynn . . . . . . . . . . . . . . .138 Myra Christopher . . . . . . . . . . . . .150 Public Comment: Sarah Putney . . . . . . . . . . . . . . .216 5 1 P-R-O-C-E-E-D-I-N-G-S 2 (8:09 a.m.) 3 CHAIRMAN PRENTICE: Good morning, 4 everybody. Why don't we get started? 5 I'm going to present an overview of the 6 agenda for today very briefly. As you can see, the 7 first item on our agenda is a presentation of the IOM 8 prisoner report, and we'll talk a little bit more 9 about that in a moment. 10 Then we're going to have a break after 11 that. We'll proceed to our panel on research 12 involving individuals with impaired decision making 13 capacity, where we've got David Strauss, Charles 14 MacKay, David Shore, Laurie Flynn and Myra Christopher 15 as our panelists. 16 We will proceed to a public comment period 17 at 12:30. If anybody would like to sign up for the 18 public comment period, please contact the SACHRP 19 staff. 20 At 12:45 to 1:15 we'll have our discussion 21 wrap-up, and then we will adjourn at that time. 22 Now, yesterday we had a problem with the 6 1 sound and the microphones. I would encourage everyone 2 to speak close to the microphone, which should help 3 with the sound problem. 4 I want to remind everybody that our next 5 SACHRP meeting will be November 2nd and November 3rd, 6 2006, and of course, information will be published in 7 the Federal Register and available on our Website. 8 Okay. Now I'm going to return back to my 9 seat at the table and introduce our panelists for the 10 next presentation. We're now going to have a 11 presentation on the IOM prisoner report and a 12 discussion of that report after that. 13 But before I introduce the individuals who 14 are going to present that report, I would like to ask 15 Bern Schwetz to give us a little bit of the history 16 behind this particular report. 17 Bern. 18 DR. SCHWETZ: Thanks, Ernie. 19 When SACHRP decided to look at Subpart C, 20 I was quite pleased because this is a topic over which 21 we within OHRP get a lot of questions, and as we 22 interact with the community about the issues that are 7 1 in front of the research community, whether it's the 2 investigators or IRB members or whomever. It was 3 fairly clear to us that there was a fair amount of 4 uncertainty and confusion about what the regulations 5 really meant and how they could be complied with. So 6 it was certainly a topic that I thought was 7 appropriate for the Advisory Committee. 8 And then the more we looked at it and the 9 more we talked about it, we realized that compared to 10 some of the other subpart discussions that we were 11 looking at, discussions about Subpart C were not about 12 to fix the significant problems that there were with 13 Subpart C in the same sense that you could pick a 14 piece of Subpart A and go after it and have a 15 discussion and make some recommendations. 16 So as you may recall, we made the decision 17 within SACHRP, made the decision that there were some 18 immediate things that they would look at. But in 19 addition, there were some long-term things that needed 20 to be reviewed in the context of fixing problems with 21 Subpart C, and it was my sense that it was not the 22 right thing to just start over and do a line-by-line 8 1 review and revision of Subpart C because the whole 2 issue of who was a prisoner and what is the prison 3 situation in the country today is quite different than 4 it was when Subpart C was written. 5 And it was my feeling that this area would 6 be best served if we went back and started at the 7 beginning and asked what are the ethical 8 considerations that surround the use and the 9 involvement of prisoners in research; that we would 10 start back at that place to look at the ethics of 11 doing research in prisoners, and then answer a bunch 12 of other questions about the prison community today. 13 So that led to the idea that, well, we 14 should have those long-term questions reviewed by 15 going to the IOM and asking them to pull a committee 16 of experts together to review the current situation 17 with prisons and also to review the ethics of doing 18 research in prisoners. So that's why we went to IOM, 19 and that's the nature of the report that we have. 20 So that's what we're going to be hearing 21 today, and at some point then we need to fold in the 22 rest of the recommendations from SACHRP with whatever 9 1 we're going to do regarding this report. 2 So, Ernie, that's kind of the background, 3 if that helps. 4 CHAIRMAN PRENTICE: Thanks, Bern. 5 I might add that I had the privilege of 6 attending almost all of the Subpart C subcommittee 7 meetings and, quite frankly, I found it to be an 8 absolutely fascinating experience, one of the more 9 challenging subcommittees that I've ever had the 10 privilege to interact with. 11 And as Bern indicated, the IOM report 12 arose out of the subcommittee deliberations. 13 Now, I would like to introduce the 14 individual who is going to present the report. It's 15 Windy Visscher. She is a Director of the RTI 16 International's Office of Research Protection and 17 Ethics. And RTI is an independent, nonprofit 18 organization that conducts research and development 19 projects for government and commercial clients 20 worldwide. 21 Dr. Visscher oversees the operation of 22 RTI's three IRBs and chairs one of the committees. 10 1 I won't read her entire bio, but I will 2 tell you that Wendy Fischer was on the IOM committee 3 who developed this particular report, and her 4 colleague, Dr. Andrew Pope, is with her and I'm sure 5 he will assist her in presenting the report or 6 responding to questions. And Dr. Pope is the Director 7 of the Board on Health Science Policy for the IOM. 8 So welcome, Wendy and Andrew. We 9 appreciate you taking the time to talk with us about 10 the IOM report. 11 DR. VISSCHER: Okay. Good morning. Can 12 everybody hear me? 13 Okay. Thanks for the introduction. I am 14 the IRB Director at RTI International. So I was one 15 of the members of the IOM committee that had a lot of 16 experience with IRB issues related to this topic, 17 although as Ernie said, it's a very large and 18 complicated topic. 19 I'm the spokesperson for the committee. 20 I'm certainly not the only member of the committee. 21 The committee was very large and very diverse and had 22 lots of experience. I was only one small part of the 11 1 committee. 2 But I was honored to be on the committee, 3 and I'm also honored to be able to speak to you today. 4 I'd like to acknowledge OHRP and Institute 5 of Medicine. This is Andy Pope who was our project 6 director for this particular project. 7 What I'm going to do today is give a 8 background of the report. We'll take it a little bit 9 further than Bern did and tell you what our charge was 10 as a committee, tell you a little bit more about the 11 committee membership and the methods we used to come 12 up with our recommendations and talk about five broad 13 areas of recommendation, and then within each of those 14 areas some very specific recommendations that we have. 15 Okay. So our committee's charge: to 16 examine whether the conclusions of the National 17 Commission back in 1976 were still appropriate, 18 considering the impacts of developments in 19 correctional systems and society's perception of the 20 balance between research burdens and the potential 21 benefits of research. 22 The Commission published the report called 12 1 "Report and Recommendations, Research Involving 2 Prisoners" in '76, and then in 1978, Subpart C was 3 developed. 4 So a lot has happened in the last 30 years 5 both in terms of who a prisoner is, what the 6 correctional system looks like, what types of research 7 people are interested in doing with this group. 8 So SACHRP had its own subcommittee on 9 subpart C, and they recommended to OHRP that the 10 Subpart C be revised, and as Bern said, they wanted to 11 step back a little bit and look at ethical 12 considerations before they did that. 13 So they commissioned this report. I 14 should say that we were not commissioned to rewrite 15 the recommendations ourselves, just to look at ethical 16 considerations, and in particular; consider whether 17 the ethical bases for research with prisoners is 18 different with non-prisoners; develop an ethical 19 framework for doing research with prisoners; and look 20 at what other types of safeguards or other 21 considerations we needed to look at when we do 22 research in this group; and finally, identify issues 13 1 and other needs for future study. 2 A quote from our Chair, Larry Gostin, was, 3 "Getting the balance right between scientifically 4 rigorous research and ethically appropriate treatment 5 of prisoners is vital to a decent, humane society, and 6 so I think that gives you an idea of what the 7 challenge we had ahead of us to be able to do 8 research, but to do it in an ethical fashion. 9 And we certainly recognized the abuses 10 that happened in prisons with prisoners doing research 11 in the '60s and before, and these abuses engendered 12 well justified distrust of research. And so the 13 committee was looking at whether we could move on from 14 that point. 15 The composition of the committee was, as 16 I said before very diverse. We had researchers, some 17 of whom were clinicians. We had ethicists, attorneys, 18 a former prison official, a former prisoner, some IRB 19 and regulatory people, including IRB members at the 20 various institutions, and then we had members who had 21 lots of experience in more than one of these areas. 22 So it was tremendous combined expertise, 14 1 and we were able to, I think, look at all sides of 2 this issue, and we definitely challenged each other 3 and learned from each other. And I was impressed with 4 how committed all of the members were to the interests 5 of prisoners as we did our work. 6 So here is the committee. As I said, 7 Larry Gostin was our chair, and the other people on 8 the list, I'm sure you recognize some of them or all 9 of them, and you can see, like I said, the 10 researchers, attorneys. 11 Okay. The project time line. The project 12 was started in January of last year. We didn't 13 meeting. We met for the first time in March of 2005. 14 So you can see in a little over a year we met several 15 times, had workshops and visits and released the 16 report in mid-July. It's a little over a year, and it 17 was quite an impressive process to see the report take 18 place over this time period. 19 The methods and data sources we used. We 20 had some commissioned papers to help us understand 21 some of the issues. We had open and closed sessions 22 with the committee. We have had workshops with 15 1 presentations, and some of the people that talked to 2 us were from OHRP, from different researchers around 3 the country that do research with prisoners. We had 4 prisoner advocate groups. We had human subjects 5 advocate groups. We had prison officials, ACLU, 6 attorneys. So we got a broad range of information and 7 perspectives from that group. 8 We also did telephone interviews and an E- 9 mail survey with State Department of Corrections to 10 try to find out what type of research is being done 11 and what type of protections and review these 12 different research studies have in the different 13 states. 14 We did a literature review. We did site 15 visits to correctional facilities. We visited San 16 Quentin and also the California medical facility in 17 Vacaville, California, and that was very interesting 18 for the committee and gave us a good feel for the 19 setting, and we were also able to interview prisoners 20 when we went on those site visits. 21 And finally we had a prisoner liaison 22 panel, and these are the members of that committee or 16 1 that panel, and that was made up of, again, 2 researchers, some former prisoners, attorneys, 3 community organizations that work with prisoners, and 4 this panel was very, very helpful to the committee 5 because they knew a lot about the history of research 6 with prisoners, and so they gave us a good feel for 7 these past abuses and also gave us a feel for the 8 current realities of what it means to be a prisoner. 9 So very, very helpful group. 10 So we recommended five paradigm shifts, 11 and they're on this slide. First, and I'll go over 12 each of them in more detail, but first we wanted to 13 expand the definition of a prisoner to fit the current 14 situation. As I said, a lot has changed in the last 15 30 years, and we felt it was time to redefine prisoner 16 to be more expansive. 17 We wanted to insure universal protections 18 for all prisoners. Right now the prisoners fall under 19 different types of protections, and we wanted to fix 20 what we call the patchwork of regulations that 21 currently exist for protecting prisoners in research. 22 The third is that we wanted to shift from 17 1 a category base to a risk-benefit approach to research 2 review. So from the category base Subpart C rubric to 3 the risk-benefit approach that we use in Subpart D. 4 We wanted to include collaborative 5 responsibility in our research with prisoners and what 6 that meant was to get a lot more people involved in 7 all parts of the research so that we could be more 8 transparent, more accountable so that people would 9 know exactly what we were doing and what our 10 objectives were. 11 And finally, enhance the systematic 12 oversight of research. We suggested giving OHRP some 13 slightly different responsibilities and a broader 14 range of responsibilities and oversight. 15 So under the first broad recommendation, 16 expanding the definition of prisoner, the specific 17 definition was to redefine prisoners to expand the 18 reach of human subjects protection, and as you know, 19 in Subpart C the definition of prisoner is somebody 20 that is involuntarily combined or detained in a penal 21 institution. So somebody behind bars, and we found 22 out as we were going through our work that really a 18 1 very small percentage of prisoners, prisoners being 2 people who have their liberty restrained in some way 3 by the criminal justice system, are in prisons and 4 jails. 5 Since 1976, the population of prisoners 6 has quadrupled and now we have about seven million 7 people that you would call prisoners in prison, jail, 8 parole and probation, and of these seven million, only 9 about two million are actually in prisons and jails. 10 So we felt like the same protections 11 needed to be afforded to the other five million people 12 who have their liberty constrained by the criminal 13 justice system. 14 And the other thing that we found out as 15 we were looking at who are prisoners today is that the 16 population of prisoners has changed quite a bit in 17 terms of not only its size, but there are more 18 minorities, more women, more people with chronic 19 diseases. The population is aging, and so we felt 20 like we had to take those considerations into account 21 as well. 22 One note on the definition of prisoner is 19 1 that we decided that our report was not going to cover 2 children unless they were treated as adults, the 3 people that are committed to mental institutions and 4 people covered by such things as the U.S. Patriot Act. 5 That didn't mean that we didn't think those people 6 didn't need extra protections. We felt like we 7 couldn't cover all of those groups in this committee. 8 So we want to redefine prisoners so that 9 we include people that are not only behind bars, 10 prisons and jails, but also people on probation, 11 parole, and in various alternative settings, community 12 settings and alternative correctional programs, work 13 release, community programs, et cetera. 14 So that was a big recommendation and very 15 different than what Subpart C says right now. 16 Our second broad recommendation was to 17 insure universal, consistent, ethical protection of 18 prisoners, and this has several smaller 19 recommendations associated with it. The first one is 20 to establish uniform guidelines for all human subjects 21 research involving prisoners, and we learned that most 22 of the research that is currently done with prisoners 20 1 falls outside the purview of OHRP, and that's because 2 not all research with prisoners is funded by DHHS, and 3 in addition, even agencies that have adopted the 4 common rule have not adopted Subpart C. In fact, only 5 two agencies, the Social Security Administration and 6 the CIA, have adopted Subpart C. 7 And then finally, institutions that do 8 research, of course, get federal-wide assurances, and 9 not all of them decide to adopt Subpart C in their 10 federal-wide assurance. In fact, we had an estimate 11 that only about 60 percent of institutions with FWAs 12 adopt Subpart C. So there's a lot of research going on 13 with prisoners that doesn't fall under the regulation 14 that we're most familiar with. 15 Department of Justice, Bureau of Prisons 16 have their own regulations. FDA tried to enact a 17 Subpart C back in 1978 and there was a lawsuit that 18 was brought by a group of prisoners that said that 19 they wanted to participate in medical research. So 20 that was pulled back. So FDA does not have a Subpart 21 C comparable to 45 CFR 46, and so we felt that it was 22 really unethical for prison research that's going on 21 1 in different settings funded by different groups 2 should fall under different regulations and have 3 different oversight. 4 So our first recommendation under the 5 universal ethical protection is to establish uniform 6 guidelines, and Congress, of course, would have to get 7 involved in order to mandate this. 8 So we felt like this patchwork of 9 different regulations, different research being 10 covered by different regulations, was not justified. 11 The second recommendation under the 12 universal ethical protection was to maintain a public 13 database of all research involving prisoners, and 14 really we should say maybe create a database. As we 15 were trying to figure out how much research is going 16 on with prisoners, we found out that there is no 17 repository where we would get a lot of information 18 about the percentage of social, behavioral, medical, 19 low risk, minimal risk, what types of research were 20 going on, how they are protecting the prisoners in the 21 studies, what type of review the studies are having. 22 So we felt like there needed to be a 22 1 public database for all research involving prisoners, 2 and we felt like the DHHS and Department of Justice 3 could collaborate on such a database, and we thought 4 a repository like this would have several different 5 advantages or serve a lot of different purposes. 6 One is, of course, define the universe of 7 studies that are being done with prisoners. 8 The second, help researchers network with 9 each other to identify best practices and find out 10 what types of protection different researcher are 11 putting in place for different studies and also 12 identify other researchers that are doing research on 13 topics that you're interested in. 14 Help the IRBs share these protective 15 practices so that we can get some consistency there. 16 And finally, enhance the application of 17 research findings to different populations. So it 18 would give us all a place to look for the types of 19 research that's going on and what the results are so 20 that we're able to, you know, use the best things from 21 different studies for future studies and continue to 22 build on those. 23 1 So we thought that would be very, very 2 helpful in this area. 3 The third sub-recommendation under 4 universal ethical protection was to insure 5 transparency and accountability in our research with 6 prisoners, and this has not been, you know, the norm, 7 I guess, in doing research with prisoners, but we felt 8 that researchers needed to be very open about what 9 they're doing inside the prison, and transparency and 10 accountability are just hallmarks of good research, 11 and we felt that there was no reason why these 12 wouldn't be applied also to research with prisoners. 13 So we wanted to make sure that everybody 14 knows what's going on in a study and involve them in 15 the process to the extent possible so that they can 16 help develop the mechanisms that will be used to 17 protect the prisoners. 18 Okay. Our third broad recommendation is 19 to shift from a category based to a risk-benefit 20 approach, and we wanted to apply the risk-benefit 21 framework to research review with prisoners. This is, 22 of course, similar to what's currently used in Subpart 24 1 D. 2 Subpart C has categories, and you have to 3 fit the research into a category before it can be 4 approved, and that approach grew from sort of an era 5 of protectionism. In other words, we were only going 6 to allow certain types of research, and so we had 7 these categories, and you had to fit it into a 8 category before you could approve it. 9 The committee thought that Subpart D 10 really was a more natural fit for research with 11 prisoners. It's also a very vulnerable group, as are 12 children, and it puts the IRBs back in the mode in 13 which they're most comfortable. They're used to 14 looking at risks and benefits and deciding if the 15 balance between risks and benefits is appropriate for 16 the given study. 17 So we felt like Subpart C was a much 18 better framework for IRBs to look at research with 19 prisoners. And in addition, it allows the IRB not 20 only to look at risk and benefits, but to identify 21 specific ethical issues that relate to a protocol and 22 decide what protections need to be put in place based 25 1 on those ethical issues instead of trying to see if it 2 fits into Category 1, 2, 3 or 4. 3 So this was a strong recommendation by the 4 committee to shift the focus of the research from 5 category based to risk-benefit. 6 The fourth broad recommendation was to 7 update the ethical framework to include collaborative 8 responsibility, and we wanted to use the collaborative 9 research approach, and this goes hand in hand with 10 what I was talking about earlier about being 11 transparent and accountable. 12 We want to be able to consult with prison 13 officials and prisoners as we design our studies and 14 as we decide whether a study can be done ethically in 15 a given setting, and so that means you have to know 16 something about that setting, and the best people to 17 find out about the setting would be the prison 18 officials and the prisoners themselves. 19 When we talked to prisoners in California, 20 they said they wanted to be in research or at least 21 they wanted to be given the opportunity to participate 22 in research, and they also thought they would be very 26 1 helpful in helping the researchers develop ways to do 2 the study in a way that made sense in their facility. 3 So things that you could ask these people 4 as you're trying to decide if you can do a study in 5 this setting and what protections to put in place were 6 whether you thought or whether they thought that 7 people could really give informed consent in that 8 setting, whether you could really assure privacy in 9 your interview, in an interview setting or in an exam 10 setting, and could you protect confidentiality of the 11 information. 12 And then finally could subjects, research 13 participants report problems to the IRB. You know, 14 they don't usually have ready access to phones or 15 other types of communication that other people might, 16 and so how would they report problems? How would they 17 ask questions of the IRB? 18 And so those would all be questions that 19 you could ask prison officials and the prisoners 20 themselves before you would start out doing research 21 in that setting. 22 Another recommendation related to 27 1 collaborative responsibility was to insure adequate 2 standards of care, and a lot of prisons don't have 3 ideal medical care situations. In fact, some of them 4 have quite poor medical care, and the committee 5 thought that it was really unethical to do a study in 6 a setting that doesn't even have adequate medical or 7 psychological care, particularly the medical studies, 8 but also interview studies where you might be asking 9 people some upsetting questions where you'd need some 10 resources to deal with that if there were adverse 11 reactions. 12 And so we said if the prison does not have 13 appropriate medical care, then it's not ethical to do 14 the study in that setting because if it's not 15 adequate, then there's some sort of inherent coercion 16 where a person might be influenced to participate in 17 the study because they can get access to other care, 18 in other words, the care associated with the research 19 protocol itself, and that is not -- so we want to 20 guard against this undue influence. 21 In addition, as I said, the facility that 22 doesn't have adequate care is not going to be equipped 28 1 to either follow the protocol if they're helping 2 implement the study or to respond to adverse events if 3 they happen. 4 So this was an important recommendation 5 and would be a requirement before you could conduct a 6 study in a setting. 7 Another recommendation about collaborative 8 responsibility was to support critical areas in 9 correctional research. We said that the or we found 10 the prisoner population was growing and becoming 11 different in many ways and also becoming more 12 vulnerable in many ways. And so we felt that research 13 would be very helpful in gaining information about how 14 to improve the correctional system and promote the 15 well-being of the people that we have in the criminal 16 justice system, improve the system and hopefully help 17 people successfully reenter into the society, reduce 18 recidivism and just improve the whole system 19 And it was interesting. We've had a 20 little bit of press on this study, and the press have 21 said that the committee is recommending opening up 22 research, and I think they may have gotten it from 29 1 this particular recommendation, but that's not really 2 what we're saying. We are not saying that we want to 3 go back and do Phase 1 and Phase 2 clinical trials 4 because we specifically said that those should still 5 be banned in the setting, but we do think that 6 research is helpful, and we were reinforced by this 7 when we talked to the prisoners who thought that, as 8 I said, they wanted to be given the opportunity to 9 participate in research, and they wanted to help 10 improve the system, and they knew that research could 11 help improve the system to gain the information we 12 needed to to improve the system. 13 And our other recommendation is to enhance 14 systematic oversight of the research. The first part 15 of that is that we thought we needed to strengthen the 16 monitoring of research with prisoners. We, of course, 17 would do initial IRB review, but we wanted to have 18 more monitoring going on between an initial review and 19 a continuing review with the researchers, and we came 20 up with this idea that for especially high risk 21 studies or studies in very closed settings, to use a 22 prison research subject advocate, and that person 30 1 would be independent from the research, and would be 2 sort of the eyes and the ears of the IRB. And they 3 would be able to talk to the IRB separately from the 4 researchers from the prison, and tell how the research 5 is being conducted, and also they would be an avenue 6 for the people to ask questions, for the participants 7 to ask questions and to express concerns to the IRB. 8 So we felt like more monitoring needed to 9 be done with research with prisoners. 10 The second way to enhance systematic 11 oversight was to modify review consideration, and we 12 needed to look more at what the different ethical 13 concerns were for a different protocol, and also look 14 at each specific correctional setting to make sure it 15 can be done in that setting. 16 And we said that proposals would no longer 17 need to go to OHRP for certification, and that's 18 consistent with our new Subpart D review 19 recommendation. Instead there would only be very few 20 proposals that would go to OHRP for federal level 21 review. So there would be no certification process 22 anymore. 31 1 And, again, it frees both the IRBs and 2 OHRP from thinking about these categories and thinking 3 more about risks and benefits than about specific 4 issues that are important. So the only protocols that 5 would go to OHRP then would be research not otherwise 6 approvable that offers opportunity to understand, 7 prevent, alleviate a serious problem, and it will be 8 a serious problem in prisoners rather than in children 9 as it is in Subpart D. 10 So we think this will be a better use of 11 time and really expertise for both the IRBs and OHRP. 12 The third recommendation under systematic 13 oversight would be to actually enhance OHRP's 14 responsibilities, and this is for studies it already 15 covers, and we talked about how it doesn't cover all 16 the research with prisoners at the current time, but 17 we would want them to maintain this registry, this 18 database of research with prisoners; make 19 determinations for these 407-like categories, the 20 research not otherwise approvable; enforce compliance 21 with the regulations; and then serve as a national 22 resource for IRBs in human research protection 32 1 programs to promote sort of consistent understanding 2 of the regulations and also application of the 3 regulations in settings and with different types of 4 prisoners. 5 So OHRP already does some of those tasks. 6 They already make determinations for the higher risk 7 studies. They already enforce compliance. They 8 already serve as a national resource. The new 9 responsibility would be to maintain the registry. 10 And one responsibility we take away is the 11 certification process, which we felt was not necessary 12 in our new system of the risk-benefit review. 13 The fourth sub-recommendation on the 14 systematic oversight is to establish systematic 15 oversight of all research involving prisoners, and 16 this would involve action by Congress to put all 17 research with prisoners under one set of regulations, 18 and we felt like it really was not justified to have 19 people covered by two different sets of regulations, 20 well, more than two sets; multiple sets of 21 regulations. 22 And of course, there is research that's 33 1 not covered by any federal regulations that is done in 2 prisons. So Congress would need to act to make this 3 happen. They could expand OHRP's authority or they 4 could use the sending clause to help people decide to 5 comply with OHRP's regulations. 6 But we felt this was a critical need and 7 that it was really unethical to have this patchwork of 8 regulations, that everybody needed to fall into the 9 same set of regulations. 10 Two more basic recommendations that we 11 have under this systematic oversight area. First, 12 insure voluntary informed consent. The committee felt 13 like the National Commission, that the two Belmont 14 principles of respect for person and justice were 15 paramount in research with prisoners, and respect for 16 persons requires that people are able to make 17 autonomous decisions about participating in a research 18 study, and this can be quite a difficult task in a 19 prison setting, but even if it's difficult, it's not 20 impossible and its up to the researchers and the IRBs 21 to figure out ways that people are able to give 22 informed consent. 34 1 And the prisoners we talked to in 2 California really told us that they thought they could 3 make their own decision, that they wouldn't be 4 influenced one way or the other by the prison 5 officials to participate or not participate in a 6 study, but the researchers and the IRBs have to be 7 convinced of that before they go ahead and do a study 8 in a particular setting. 9 Another sort of basic recommendation under 10 systematic oversight is that we need to protect the 11 privacy of the prisoners engaged in research, and 12 again, this is a difficult thing to achieve in the 13 prison setting, especially the prison settings that 14 are the behind bar prison settings. But this is 15 another key component of ethical research. 16 This, I think, would be helped by getting 17 the prison officials and the prisoners involved in the 18 planning for a study because they can tell us ways 19 where we could insure privacy when we do the study, 20 and there are different ways that you can do it. For 21 example, you can have different data collection 22 methodologies where you're using computerized data 35 1 collection, where the person types in their own 2 answers, and you can certainly have other study design 3 components that will help with privacy. 4 But, again, the IRB has to be convinced 5 that the proper protections are in place to protect 6 privacy before doing a study in a setting. 7 So, in conclusion we offered these 8 recommendations to encourage the development of a 9 uniform system for protecting all prisoners involved 10 in research, and we felt that ethical research has the 11 potential to help us understand and promote the 12 welfare of this large and growing segment of our 13 society. 14 And, again, our five recommendations are 15 expanding the definition of the prisoner because it 16 has changed considerably in the last 30 years; insure 17 universal protections for all prisoners; shift from a 18 categorical to a risk based approach, a risk-benefit 19 approach; include collaborative responsibility in our 20 planning and conduct of research with prisoners; and 21 enhance a systematic oversight of research with 22 prisoners. 36 1 So there is our Website, and Andy's E- 2 mail, and so you can ask him the questions, and the 3 book, I think, is going to be published maybe October, 4 November, but there's more information available on 5 the Website. 6 CHAIRMAN PRENTICE: Okay. Thank you very 7 much for an informative presentation. It's very clear 8 that the IOM committee did a tremendous amount of work 9 on this very important issue. 10 As usual, I will exert the Chairman's 11 prerogative to ask the first few questions, and I 12 apologize in advance if the answers are in the IOM 13 report itself, and I've not really looked at it in 14 great detail. 15 In looking at expansion of the definition 16 of prisoner, it's very clear that the penal system of 17 the United States has already forms of restraint and 18 incarceration, and you've recommended expanding the 19 definition of prisoner, and I assume that that would 20 include individuals who are on parole and individuals 21 who were on perhaps electronic monitoring. 22 Would that be a fair statement? 37 1 Okay. As I recall, the Subpart C 2 Subcommittee recommended also expanding the definition 3 of prisoner, but I don't recall them recommending that 4 an expanded definition of prisoner be included in an 5 amended Subpart C. I think that they said additional 6 protections would be appropriate for prisoners under 7 the provisions of 46-111(b). So I assume that you 8 must have discussed that and said, "You know, that's 9 not good enough. we want to have specific protections 10 for prisoners." 11 So perhaps you could comment on that. 12 DR. VISSCHER: Right. We did think that 13 a broader group of people needed to be covered by 14 Subpart C protections, and in particular, as you said, 15 the parolees and probationers, but also people that 16 are in community settings where they're not 17 necessarily able to make decisions without thinking 18 about what implications they might have for their 19 status in that setting. 20 One clarification, I guess, is that a 21 person who is in that type of situation, for example, 22 electronic monitoring, in the community, and they have 38 1 an opportunity to participate in a study that's 2 available to everybody in their community, they are 3 able to participate in that study without the study 4 having to come under Subpart C because their 5 participation has nothing to do with their status as 6 a prisoner. 7 What we were talking about is if you're 8 designing a study about parolees, probationers, people 9 with electronic monitoring or in some kind of 10 community setting, and you're enrolling them for that 11 reason, because you're trying to learn about that 12 group, then they would have to fall under Subpart C 13 protections. 14 CHAIRMAN PRENTICE: Okay. Thanks for the 15 clarification. 16 One of your, I think, really important and 17 perhaps more problematic recommendations is 18 establishing uniform guidelines for all human subjects 19 research involving prisoners, which obviously would 20 take congressional action. So you must have thought 21 about that a great deal. 22 Is there any sentiment in Congress to 39 1 support such a mandate? And if so or if not, have you 2 thought about how OHRP or other federal agencies might 3 try to initiate such a mandate? 4 DR. VISSCHER: We did talk a lot about the 5 fact that different research with prisoners falls 6 under different regulations, and I'm not an attorney. 7 So I can't talk about really how Congress would do 8 this, nor can I say whether there would be support in 9 Congress for making such a change. 10 Perhaps Dr. Schwetz could comment on 11 that. 12 DR. SCHWETZ: I'm not an attorney either, 13 but what I can say is that one of the things that we 14 need to do from the standpoint of OHRP, we have 15 briefed the Assistant Secretary for Health on the fact 16 that this report is now available and that there are 17 recommendations in there that are bigger than OHRP. 18 So we need to identify the components of this that 19 represent a larger than OHRP issue within HHS or in 20 other agencies and brief the ASH so that they can 21 decide within the department within their legislative 22 groups how they want to respond to these kinds of 40 1 issues that are now raised through this report. 2 So that would be our avenue. they know 3 the connections within Congress to deal with that, but 4 it's a decision that would need to be made in the 5 department first. 6 DR. VISSCHER: I mentioned that about 60 7 percent, I think, of FWAs, institutions say that they 8 will adopt Subpart C, and I suppose that OHRP could 9 recommend to more people that they adopt that subpart. 10 That would be one thing. 11 CHAIRMAN PRENTICE: I think one of the 12 reasons why institutions have opted out of adopting 13 Subpart C except for HHS funded research is that it's 14 restrictive and prohibitory, and it's a big of a 15 hassle to go through the process. 16 I think a lot of institutions have what 17 they view as equivalent protections, but they've 18 eliminated some of the requirements that they find 19 problematic, which is evidence that really Subpart C 20 needs to be amended in the first place. 21 You went to prisons. You interviewed 22 prisoners. You talked to prison authorities, and it's 41 1 hard to get a handle on how much research is actually 2 being conducted in prisons. Did you find that there 3 are prisons or prison systems that just arbitrarily 4 prohibit research involving prisoners, period? The 5 warden says or the state correctional system says, 6 "You know, you're not going to do research in this 7 prison or that prison? 8 DR. VISSCHER: I believe in our survey of 9 the State Departments of Corrections we had people 10 tell us that they would not do biomedical research at 11 all, and I don't remember if any of them said they 12 wouldn't do any research. 13 Mostly biomedical, but the interesting 14 thing about talking to the prison officials in the 15 different states were the different ways they go about 16 reviewing research. They have internal research 17 committees that look at research. Sometimes they 18 treat research that's done by internal investigators 19 differently from external investigators. So they 20 treat the way that they allow research very 21 differently in different settings. 22 CHAIRMAN PRENTICE: Okay. I have two more 42 1 questions, and then I will encourage our committee to 2 ask questions, and I won't ask the question that I 3 know Nancy Jones is dying to ask. 4 DR. JONES: (Speaking from an unmiked 5 location.) 6 CHAIRMAN PRENTICE: No, but I know what 7 you're going to ask. So I'm not going to ask it. 8 Okay? I'll get you it's one of your questions at 9 least. 10 The current Subpart C, of course, is 11 category based which is obviously a problem because if 12 the research doesn't fit into the category you can't 13 do it, and we all recognize that that's a limitation. 14 So you are recommending a risk-benefit based approach 15 similar to Subpart D. 16 You seem, in applying an analogous Subpart 17 D approach, you are differentiating a little bit 18 between biomedical research and behavioral social 19 science research. You say in your report, "Ethically 20 permissible research must offer potential benefits to 21 prisoners that outweigh the risks," not just balance 22 the risks; actually outweigh the risks, which is a 43 1 calculus that may be hard to accomplish because we all 2 know that there's no algebraic formula we can apply to 3 looking at a risk-benefit assessment. 4 But nonetheless, I think that's a laudable 5 goal in terms of a risk-benefit assessment, and you go 6 on to say that under this framework it's clear that 7 studies offering no potential benefit, the subjects 8 would be precluded, and you of course use testing of 9 cosmetic products, which that's understandable 10 considering what happened in Philadelphia. 11 And you go on to say that biomedical 12 research in correctional settings would be severely 13 limited, i.e., Phase 1 and Phase 2 studies would be 14 basically prohibited. Phase 3 studies might be 15 allowable. 16 And then I go on to page 10, and you 17 elaborate a little bit more about proposals involving 18 behavioral and social science and epidemiology that 19 carry very low risks for the prisoner subjects, but no 20 personal benefit for the subjects. Instead the 21 potential benefits may be for prisoners as a class. 22 So you say low risks. In Subpart D, the 44 1 risks are tied to the risk threshold of minimal risk. 2 Is your risk threshold tied to minimal risk when you 3 say low risks? 4 DR. VISSCHER: Right. 5 CHAIRMAN PRENTICE: It is? 6 DR. VISSCHER: Yeah, we were talking about 7 minimal risk, right. 8 CHAIRMAN PRENTICE: That's probably in 9 your report that I didn't read. 10 DR. VISSCHER: Okay. 11 CHAIRMAN PRENTICE: Okay, right. 12 DR. VISSCHER: Right. 13 CHAIRMAN PRENTICE: Okay. And then one 14 final question. You refer to adequate standards of 15 care, and I think we would all agree that prisoners, 16 in general, regardless of whether or not research is 17 conducted in a prison environment, ought to be 18 provided adequate standards of care, and you say that 19 human research participant protection programs 20 together with the prison administration and prison 21 health care professionals are responsible for insuring 22 that research with prisoners occurs in an environment 45 1 that is appropriate to the health and well-being of 2 the prisoners, i.e., adequate standards of health 3 care. 4 How would you suggest that an HRPP 5 determine whether or not a prison actually has 6 adequate standards of health care? 7 DR. VISSCHER: Right. We discussed that 8 quite a bit, and that is a hard thing to determine, 9 and felt like it was going to be the responsibility of 10 the researcher to determine what the level of care is 11 in that setting, and also another way for us to be 12 able to get information would be to talk to the 13 prisoners themselves. 14 But you're right. It's a very hard thing 15 to determine, but a very important thing for 16 especially these biomedical studies. 17 CHAIRMAN PRENTICE: So I could gather that 18 your recommendation would be that when an investigator 19 submits a protocol to the IRB, there ought to be some 20 kind of documentation as to how that determination was 21 made, right? 22 DR. VISSCHER: Right, exactly. 46 1 CHAIRMAN PRENTICE: Okay, great. All 2 right. Thank you very much. 3 James, I don't know how your name got 4 first on my list, but it is. 5 DR. VISSCHER: Can I just clarify 6 something on the risk-benefit? 7 CHAIRMAN PRENTICE: Yes. 8 DR. VISSCHER: We felt like the studies 9 needed to have benefit to either the prisoners or the 10 prisoners as a class, and for these epidemiologic 11 studies, the benefit would be to the prisoners as a 12 class as they are members of the population. So we 13 allowed ourselves some latitude in our definition of 14 benefit. 15 CHAIRMAN PRENTICE: Okay. Thanks. 16 James. 17 DR. POWELL: Yes. I believe my name got 18 on the list first because when you were speaking about 19 the committee discussion on Subpart C, the question 20 was regarding FDA and where it stood. I know that it 21 has not signed on to Subpart C, but the question was 22 was FDA a part of those discussions or is there any 47 1 effort at all. 2 CHAIRMAN PRENTICE: The answer to that is 3 -- and correct me if I'm wrong -- but the answer is 4 no. As Wendy indicated, FDA did propose to adopt 5 Subpart C back in the '70s, and they got sued by a 6 prisoner who said, "You're taking away my right to 7 participate in research by all of these restrictions," 8 and it got withdrawn and never to be seen again, and 9 FDA is not part of the common rule. 10 However, if the IOM recommendation would 11 go forth with congressional, you know, mandate for all 12 coverage, then that would solve that particular 13 problem. 14 DR. POWELL: Exactly. That was my thought 15 exactly. If this goes through, then of course FDA 16 would necessarily be a part of the regulation. The 17 question I have is one of the reasons the suit came 18 about was that prisoners said that they would not 19 necessarily be afforded the benefit of participating 20 in research, and one of the things you talk about is 21 protection of prisoners, but the question is in such 22 a regulation or if Congress takes an action, would 48 1 prisoners then be necessarily offered the opportunity 2 or benefit under such a regulation to participate in 3 research, biomedical research. 4 Am I being clear in my question? 5 DR. VISSCHER: Well, I think what the 6 committee was saying was that prisoners did need -- it 7 was appropriate to offer prisoners the opportunity to 8 participate in research that could be done in an 9 ethical fashion. In other words, the setting was 10 appropriate, and that the risk-benefit ratio was 11 appropriate, and that it was not, as you said, Phase 12 1 or Phase 2 testing of drugs. 13 DR. POWELL: I think my think about it is 14 that it's important because one of the issues that I 15 have is that the research, such as biomedical 16 research, might be important not only for the 17 prisoners, but if I take it a little further, for the 18 community to which they reenter. 19 DR. VISSCHER: Exactly. 20 DR. POWELL: And that I would want to have 21 appropriate research done in prisoners as a part of 22 understanding epidemiology of disease of reentry of 49 1 prisoners into the community. 2 DR. VISSCHER: Right. For example, if 3 you're doing a study on hepatitis, for example, a lot 4 of prisoners have hepatitis, and being able to have a 5 study that involves both prisoners and non-prisoners 6 with that disease would help us understand the 7 disease. 8 CHAIRMAN PRENTICE: Ed. 9 DR. POWE: I endorse everything you said 10 an found and so won't pick on any of that. I think it 11 addresses many of the problems that we experience 12 today. I have, I guess, a strawman proposal I'll 13 throw out for SACHRP to consider that's bigger than 14 both OHRP and certainly bigger than the IOM report or 15 Subpart C, and that is if we're thinking of going a 16 route or if anybody is thinking of going a route to 17 petition Congress to take action like this, why don't 18 we go for broke and extend the universal consistent 19 set of protections to all human research subjects 20 rather than just the isolated subset of prisoners? 21 As you know, this is a component of 22 legislative proposals already through Diana DeGette 50 1 and, I believe, Teddy Kennedy and others, and of 2 course, those have ebbed and waned over the last 3 couple of years, and I think probably the most 4 important things SACHRP could do during its tenure is 5 to reignite this discussion and get it back on the 6 agenda. So that's a proposal for batting around. 7 The question that I have, I guess, that is 8 directed at your report deals with, again, I think the 9 items that you have proposed to address, many of the 10 problems that we see today. We often bump into the 11 problem with what I'll call incidental prison research 12 or research that isn't intended to target prisoners or 13 the prison setting, but where you have either an 14 enrolled subject who happens to get incarcerated or 15 reverse. You have somebody who is sick and is to be 16 enrolled in a study with 1,000 people who aren't 17 prisoners, that they happen to be incarcerated. 18 Both of these situations trigger, I think, 19 unexpectedly or unwittingly for researchers Subpart C 20 regulations, and I was wondering if your committee 21 considered that. I think the holdup for implementing 22 that right now and what leads people to say, well, 51 1 then that person just needs to get out of the study 2 rather than keep them enrolled or put them on in the 3 first place; some of that may be ameliorated by 4 changing to getting rid of the categorical approach, 5 which is problematic and getting rid of the 6 certification, which is an additional step that brings 7 the whole study under that process. 8 I was just wondering if your committee 9 batted that around. 10 DR. VISSCHER: Right. We did talk about 11 the situation where a person becomes a prisoner after 12 the study starts, and we felt like it was appropriate 13 for them to continue in the study, especially if it's 14 some type of biomedical study that's offering benefit 15 to them as an individual. 16 We did think that the study did need to be 17 re-reviewed by the IRB under the Subpart C rubric, and 18 that could be done within I think we said 30 days of 19 the person becoming incarcerated. So that's the first 20 situation you offered. 21 The second one was that just one person? 22 DR. POWE: Just a variation of the same 52 1 theme, but you have somebody who happens to show up 2 with breast cancer and their treating physician 3 happens to suggest enrollment in a clinical trial, but 4 it hasn't been reviewed with the prison setting with 5 prisoners in mind, has nothing to do with prison 6 research per se. 7 DR. VISSCHER: Right, right. So that 8 would have to be -- that would be the same situation 9 where the IRB would have to review that person's 10 participation under the Subpart C, and one of the main 11 reasons would be to make sure there's adequate care 12 available to that person in the facility where they're 13 being housed. 14 CHAIRMAN PRENTICE: Mike. 15 DR. GENEL: If I could, I'd like to 16 explore some implications of the expanded definition 17 of prisoner with you because what I'm struggling with 18 is, one, how would the research advocate function 19 outside of the traditional correctional institutional 20 setting. I could see where a research advocate within 21 an institution could function, but I'm not quite sure 22 how well that individual could function outside of 53 1 that setting. 2 And I have a second part of that, but 3 perhaps you might want to comment on that. 4 DR. VISSCHER: The prison research subject 5 advocate is one of the protected mechanisms the 6 committee came up with, and we had a whole set of 7 design mechanisms that you could use for a given study 8 and a whole set of other types of like monitoring 9 provisions that you could have, including the subject 10 advocate. 11 And we said that the IRB would decide 12 which of these protected mechanisms to put in place 13 for a given study. So the research advocate might 14 only be used in the behind bars settings, or if it's 15 a very high risk study, then we would have to figure 16 out how to use them with parolees, probationers, or in 17 other settings. 18 So it's sort of a graduated approach. 19 DR. GENEL: Well, it's comparable in a way 20 to the discussion we had yesterday in terms of wards 21 of the state and children, that you could empower a 22 research subject advocate in the same sort of role if 54 1 you choose. 2 The second question really relates to -- 3 and maybe it's more a statement than a question -- is 4 I'm not sure I understand why one would preclude 5 enrollment in Phase 1 and Phase 2 trials for prisoners 6 who are outside of the correctional institution. 7 You're in the community. They obviously have 8 reporting requirements, but they are, in essence, part 9 of the community. If they can enroll in a therapeutic 10 study, as any other member of the community, why can't 11 they enroll if they choose in a Phase 1 or Phase 2 12 study? 13 DR. VISSCHER: Well, you can correct me if 14 I'm misstating something, but the Phase 1 and Phase 15 2 studies don't offer benefit to the individual, 16 right, and if we're choosing the people for those 17 studies because they're prisoners, whether they're in 18 prisons or jails or whether they're in some community 19 situation, parole, probation, work release, whatever, 20 if we're choosing them because they're in that 21 setting, the committee thought that we should not 22 allow Phase 1 and Phase 2. 55 1 Now, if they're choosing to be in a study 2 because they're a community member and we don't select 3 them based on their criteria or their status as a 4 prisoner, then they would be able to do that. 5 The other thing we said about biomedical 6 study or the Phase 3 biomedical studies is that we 7 thought you could have no more than 50 percent 8 prisoners in your population or in your study group. 9 DR. GENEL: Well, yeah. What I'm 10 struggling with is by expanding the definition of 11 prisoner, which I think is appropriate, one has to 12 perhaps calibrate the level of risk differently for 13 prisoners in that definition who are in different 14 settings. 15 DR. VISSCHER: Right. 16 DR. GENEL: But what I hear you saying is 17 that what you're proposing would not preclude somebody 18 who we define as a prisoner who is perhaps in a 19 community setting from enrolling in a Phase 1 study so 20 long as the recruitment was not directed solely at 21 prisoners. 22 DR. VISSCHER: Well, you couldn't -- like 56 1 you couldn't go into an alternative community setting 2 and try to select subjects from that group because 3 then obviously they are prisoners, right? And so they 4 would fall under the definition. 5 DR. GENEL: But that person could respond 6 to an advertisement that they sa on the bus or 7 something like that. 8 DR. VISSCHER: Well, I think that would be 9 only sort of people living in the community, not 10 living in settings. Isn't that what we said? 11 How do I turn that off? 12 MR. POPE: That's a pretty fine point I 13 think you're making, Mike, and I don't know that we 14 looked at it that way, frankly. You know, the whole 15 purpose was to insure that prisoners, defined more 16 broadly as we have here, are protected against any 17 undue influence as a function of their restricted 18 liberty. 19 And it's a good point. If they are in the 20 community, and even though they have this restricted 21 liberty situation, but on their own decide that they 22 want to participate in a Phase 1 or 2 trial, I guess 57 1 maybe it's a question for an IRB to answer. It's not 2 something that we took on directly. 3 Our, you know, principle was that there 4 should be a balance in favor of benefit to the 5 prisoner in order to protect them against undue 6 coercion. 7 DR. GENEL: No, I understand that, and 8 partly the question came to me because of Dr. Powell's 9 question. That is, I mean, if prisoners have a right 10 to enroll in studies, why deprive them of that right 11 in the community setting? 12 So I won'[t belabor the point. One other 13 thing. I know that you called for a registry because 14 you do not have a fixed number of the prisoners who 15 are involved. Do you have any estimates? Do we have 16 any estimates, any sort of ball park figures? How 17 many prisoners are we talking about in both settings? 18 Do we have any idea at all? 19 MR. POPE: I don't think we do. 20 DR. VISSCHER: We found that we didn't 21 know, is that we couldn't get a handle on exactly how 22 much was going on, how much research was going on. We 58 1 think most of it is social-behavioral that's going on. 2 Back to your question on the Phase 1-Phase 3 2, I think what the committee was trying to guard 4 against was using people in a convenient setting that 5 have different constraints on them as subjects for 6 these types of studies that have no benefit to them 7 because that brings us back to the abuses that 8 happened in the past. 9 MR. POPE: Now, the question, again, on 10 how many prisoners there are out there in this 11 expanded definition or even in the other more limited 12 definition is a very good one, and it's one that we 13 explored with great vigor and came up with basically 14 no good answers. 15 There's a fair description of what we went 16 through, I think, in the report. The really big 17 question is how much is being done in the private 18 sector, and there just absolutely are no good data on 19 that. 20 CHAIRMAN PRENTICE: Jeff. 21 DR. BOTKIN: Thank you. 22 Your recommendations certainly seem 59 1 imminently reasonable to me not being intimately 2 familiar with this domain. I have two rather broad 3 questions, and I'll go ahead and state both of them 4 first. 5 The first one relates to how we know the 6 scope and nature of the current problems in this 7 domain, and I think as you've just emphasized there's 8 not much data at all on the nature of research in this 9 arena, and so I guess the question is how do we know 10 that the recommendations you're providing are 11 addressing to nature of the problems that are actually 12 out there, and again, they seem imminently reasonable, 13 but do we have any concrete knowledge of abuses of 14 prisoners that's an ongoing part of the research 15 enterprise here or, secondly, do we have any evidence 16 that prisoners are being systematically denied the 17 benefits of research? 18 So I guess it's perhaps a question about 19 emphasis, and certainly as part of your major 20 recommendations said we need more oversight here, but 21 might it be more appropriate to say we need a more 22 comprehensive assessment of the nature of the problems 60 1 in this domain before we go too far down the road with 2 revising regulations and sort of fixing problems that 3 we suspect may be there, but actually don't know. 4 DR. VISSCHER: Right. You're absolutely 5 right. We don't know the scope. As we mentioned, we 6 tried to figure out what the scope of this issue is, 7 how much research is being done with prisoners and 8 what type and in what setting, and we're just not able 9 to find out the full scope. 10 And so your point was then how do you know 11 that there's a problem. And we think that because 12 there is no broad oversight, in other words one agency 13 or group that's overseeing all of the research that 14 goes on with prisoners and because we know that 15 research with prisoners is reviewed in all different 16 ways, it's reviewed by standard IRBs. It's reviewed 17 by internal research committees. Some of it is not 18 reviewed at all when it falls under the broad 19 classification of quality assurance or something else 20 that's going on in the prison, and so we felt like, 21 yes, we don't know the scope, but we feel like it 22 would be an advantage to be able to know, to put 61 1 people under the same regulations so that the same 2 protections could be put in place. 3 But in terms of what you do first, you 4 could certainly, you know, do a database first and 5 then decide what needs to be done for the protections 6 once you find out what's really out there. 7 DR. BOTKIN: So it really might be 8 reasonable to emphasize early on the need for 9 additional data collection and research on 10 characterizing the nature of the issues. 11 MR. POPE: We do offer some data in this 12 report about the prison population and the fact that 13 it has expanded tremendously in the past decade or so. 14 I think our figure is fourfold or four times, and 15 that's before you add this expanded definition. So 16 it's a much larger population than existed before, and 17 by virtue of that fact perhaps alone begs to insure 18 that there are good protections for them in 19 participating research. 20 DR. BOTKIN: A second questions if I 21 might. I didn't catch and I don't remember from the 22 executive summary which subgroups you had decided was 62 1 not reasonable to take on within your evaluation, but 2 I wanted to touch on that a little bit. It seems 3 prisons and prisoners sort of concentrate a lot of 4 different vulnerable populations together with 5 juveniles, folks with mental health problems, 6 substance abuse women, et cetera. 7 Do you have a sense that there are 8 significantly different issues that arise with some of 9 these subpopulations within the prison system? And if 10 so, would it be appropriate to try to expand the work 11 that your committee has done to try to address some of 12 those particular issues prior to a more comprehensive 13 attempt to revise regulations in this arena? 14 DR. VISSCHER: Right. I think the three 15 groups that we explicitly excluded from our report's 16 recommendation were the children, unless they're being 17 treated as adults in the prison system, the people 18 that are committed for mental illness and political 19 type prisoners, like under the Patriot Act. 20 And we did talk about how they would need 21 very similar protections to the prisoners, but we felt 22 like our committee didn't have the expertise to deal 63 1 with those groups at this time. But, yes, I think it 2 would be very, very similar. 3 CHAIRMAN PRENTICE: So it would be 4 reasonable perhaps to call for an extension of the 5 work that you've done to perhaps look at these 6 subgroups prior to an attempt to pull together 7 regulatory changes in this arena. Would that be fair? 8 DR. VISSCHER: Right, right. In fact, I 9 remember the committee wanted to include those groups, 10 but in the end felt that we just couldn't tackle all 11 of it at this time, but that would be a good idea. 12 CHAIRMAN PRENTICE: Same. 13 MR. POPE: I think the need for a 14 universal set of regulations stands separate from any 15 need to explore these individual vulnerable 16 populations individually. Certainly there is the 17 expertise to focus on the individual vulnerable 18 populations was not resident within our committee, 19 which is how they felt about it, but the need for some 20 uniform set of guidelines I think exists anyway. 21 CHAIRMAN PRENTICE: Sam. 22 DR. TILDEN: I want to congratulate the 64 1 committee on a job well done. I did happen to get 2 through the report, the whole report this morning 3 before the meeting. I had to revisit it about four or 4 five times, and the more I read it, it got better and 5 better. 6 A couple of comments I had is that -- and 7 I'm sure you all realize this -- but it seems to me 8 rather than couch this as an expansion of a definition 9 of prisoner, it gives me the sense, well, once a 10 prisoner always a prisoner. It might be in reality 11 what you're saying is that the protections that are 12 being applied to prisoners should be expanded to a 13 larger group, maybe those under the correctional 14 system. I think that the idea of expanding the 15 definition of a prisoner may be a little bit 16 pejorative in that sense. 17 The other thing about the report is that 18 there's sort of this when you make that, identify that 19 as an issue and a recommendation, the question is what 20 are the implications related to the substance behind 21 that. It seems very logical, but as was pointed out 22 here and in many contexts in terms of research 65 1 institutions, there are these research issues that go 2 on that are available to individuals in the community 3 that may be under the jurisdiction of the correctional 4 system,b ut still they want to make their own choices 5 in research that's not designed to test prisoner or 6 activities related to being a prisoner under the 7 correctional system itself, but rather designed for 8 individuals at large, and those research activities 9 would be available to that population. 10 So I think there is more overlap once you 11 expand those protections. It draws more research 12 activities that may be available. 13 The other question -- so anyway, I think 14 that needs to be explored a little bit more. It's not 15 really brought out in the report or addressed. 16 The other thing that the report misses as 17 I got into it is just the point you're making, is that 18 really what activities fall under the scope, okay, of 19 these protections and what don't. It is sort of 20 buried in there, and I think that it would have been 21 more worthwhile to bring that out, especially since 22 much research is done through academic institutions 66 1 to try to tease out what that separation is. I think 2 it would help IRBs more, and I think it's more buried 3 than brought to the forefront. 4 And I find it ironic that really what 5 we're saying is that we need more research to 6 understand what the problem is, not less. I think 7 your report sort of without stating that certainly 8 brings that issue. 9 CHAIRMAN PRENTICE: James. 10 DR. VISSCHER: Can I comment on those? 11 CHAIRMAN PRENTICE: Yes. 12 DR. VISSCHER: First, I think it's a very 13 good point. You could say that we're expanding our 14 protections to cover more people rather than 15 expanding the definition of prisoner, but when you 16 look at a regulation, you know, the first thing they 17 do is define what they're covering or who they're 18 covering, and so that's the reason that we approached 19 it from that standpoint. 20 But it's true that we are trying to expand 21 the protections to cover more people that are in this 22 vulnerable situation. 67 1 The second thing about community 2 participation, I think you're right. We could have 3 said more about this, but, again, if you're going into 4 a correctional setting in a community and you're 5 trying to get participants from that setting for any 6 type of study that's being done in the community, 7 those would be considered prisoners, and you would 8 have to put the Subpart c protections or apply the 9 Subpart C protections. 10 On the other hand, if a person goes out 11 and finds out about a study on their own and it has 12 nothing to do with the fact they're in that setting, 13 there's a possibility that they would be able to 14 participate in it, but again, it depends on what the 15 setting. It's a residential setting versus electronic 16 monitoring. Those are two very different types of 17 prisoners, and you'd have to think about, you know, 18 who you're involving. 19 The reality is that in a lot of community 20 studies you don't know the status of some of the 21 people that are participating because you don't 22 necessarily ask them, you know, as you're screening 68 1 people in a community. Do you happen to be a 2 probation or parolee? Do you happen to be using 3 electronic monitoring? 4 And so if that's totally irrelevant to 5 their participation in the study, then it would be 6 allowed under the regular Subpart A protections. 7 What activities fall under the scope? 8 That's an issue that we struggle with for all types of 9 research because people say, "Well, this isn't really 10 research. You're not adding to generalizable 11 knowledge. I'm just trying to evaluate a program or 12 look at the quality assurance issues in my facility." 13 And so there's a problem with defining 14 research regardless of whether you're in a prison 15 setting or non-prison setting. 16 And finally, I guess we were saying to do 17 more research or that it was okay to do more research. 18 I think we're getting away from this sort of 19 protectionist era and into an era where it's 20 appropriate to do research with prisoners if it's done 21 in the right way. 22 And as I said, the prisoners themselves 69 1 said that they wanted to have that opportunity, and 2 they wanted to help, you know the researchers 3 understand different issues. 4 CHAIRMAN PRENTICE: Thank you. 5 Let's see. On my list, Sarah. 6 MS. CARR. I have a question about the 7 recommendation related to the adequate level of care. 8 And I guess I'm not sure who would decide that. I 9 think you indicated the researchers would be 10 responsible for assessing the standard of care, the 11 level of care, and whether it's adequate in a 12 particular setting. 13 What if it's found not to be? 14 DR. VISSCHER: Well, we said that the 15 researchers had the responsibility to investigate what 16 the level of care was in a facility and to bring the 17 evidence to the IRB, suggesting that they thought it 18 was adequate for their particular study. If it's 19 found not to be adequate, then we said that the study 20 shouldn't go forward in that facility. 21 MS. CARR: And would the nature of the 22 research that's proposed to be done in that setting 70 1 make any difference? I mean if it were in some way 2 trying to improve the level of care in that setting or 3 had that potential outcome. Would it make a 4 difference? 5 DR. VISSCHER: Right. Well, we felt, 6 first of all, that the prisoner shouldn't be under 7 undue influence to participate. In other words, if 8 they participate they get better care than if they 9 don't participate. That was the first thing. So if 10 it's a medical study, obviously you have to have good 11 medical care in the facility. 12 Also, if you're expecting any type of 13 adverse event, either a medical adverse event or a 14 psychological event, you have to be sure that you have 15 adequate resources in house to deal with those. 16 If you're not expecting any type of 17 adverse event, then the level of care could be less. 18 I think that's what the committee was saying. 19 CHAIRMAN PRENTICE: Nancy. Is this 20 directly related to that question, James? Okay. 21 Nancy is next. 22 DR. JONES: And part of my question was to 71 1 follow up on this concept that you're adding this new 2 framework for collaborative research or collaborative 3 responsibility, and one of the things that Sarah did 4 point out it does seem like this one recommendation 5 for the adequate standards of care -- well, I mean, I 6 agree with the whole concept. 7 To me it does seem like you're asking the 8 research community to bear a larger part of the 9 responsibility that may fall in other places in that 10 in the end it does seem like this is more directed 11 towards biomedical research, you know, if you're going 12 to do biomedical research. 13 If this did stay as a recommendation or 14 was adopted, it would be important, too, though to 15 separate it. Like if a study was not related to the 16 medical care, it was a behavioral and social and maybe 17 you didn't have to have follow-up for an adverse event 18 or different things like that, then having this, it 19 has to be worded correctly so that you wouldn't 20 preclude, you know, doing other types of research in 21 a setting that could, in fact, inform practice. 22 Do you catch my drift here? 72 1 DR. VISSCHER: Yes. 2 DR. JONES: But it does seem like that 3 while I agree and I would say there's even parallels 4 when we start to look at international research. This 5 whole concept of is the infrastructure there in order 6 to do the research and are the care mechanisms there 7 to do the research and whose responsibility is that. 8 I guess my one hesitation in that is I 9 don't know if that's all of the research community's 10 responsibility and that if we preclude research 11 because care is inadequate in the prisons, then in a 12 sense you're protecting them from getting the benefits 13 of research as well as the risk. 14 I'll let you answer that, but I wanted -- 15 I may not have another chance -- so I wanted to follow 16 up on the collaborative responsibility, too, in this 17 collaborative approach. You know, this one follows 18 off of that. 19 And that is, you know, it does seem like 20 there's some movement in the field, you know, where 21 people are asking the researchers to consider what's 22 important to the community that they're researching, 73 1 and I would agree with that, but it is somewhat of a 2 paradigm shift, and I think the precedent that you set 3 in the prisoners could extend to other populations. 4 I mean it is already being done in some 5 ways like high risk or international where it becomes 6 more and more important to get the community involved 7 in asking the questions that are important to the 8 community that you're researching. 9 But, on the other hand, we put this cap to 10 say to the prisoner community, you know, you can do 11 important research that's important to you as long as 12 there's some benefit to you and only minimum risk. 13 So, you know, if we really were doing a collaborative 14 approach, could that community actually say under 15 certain circumstances, you know, we would as a 16 community say, you know, it was appropriate to do 17 research in the setting that may not -- you know, the 18 protectionist categories that we put down in the other 19 category. 20 So I guess I mean sort of comment on how 21 you see this collaborative research working and also 22 does this end up being a level of protectionism if we 74 1 can't achieve this that then the research can't be 2 done? 3 And like you were saying, a lot of the 4 things that happened before in a sense we've precluded 5 research because we couldn't -- you know, we had these 6 different categories, and I would say this one about 7 making assurances for what the state of the care is in 8 the prison may actually put a bar up so high again 9 that we would have the default mechanism of actually 10 precluding research that could be helpful. 11 DR. VISSCHER: Well, I think you make a 12 good point about the requirement for adequate care, 13 and that would need to, I think, vary between whether 14 you're talking about a biomedical study or a social 15 behavioral study because, as you both said, you could 16 have very important research that could actually help 17 improve the care in these settings. 18 In terms of whose responsibility it is, I 19 was saying that it's the responsibility of the 20 researcher to convince the IRB that the care is 21 available for that study in that setting, but in terms 22 of providing adequate care to prisoners, that's a much 75 1 broader responsibility. That takes in research 2 community. It takes in prisons. It takes in policy 3 makers, you know. It's huge, and it's a very big 4 problem because a lot of prisons don't have adequate 5 health care. 6 In terms of collaborative responsibility 7 and letting prisoners sort of get involved in what 8 types of research might be done in their group, I 9 think that's good and some of the researchers that 10 talked to us in our open sessions in our workshops 11 actually do that. They go out and have more like 12 focus groups in the prisons and talk to the prisoners 13 about what types of research they think is important 14 in their setting, and I think that would be very 15 useful. 16 In terms of what types of studies they can 17 and can't get involved with, what we said was that it 18 needed to have benefit either to the prisoner or to 19 the prisoner as a class or, and by extension, to the 20 group in the population to which they belong. And so 21 it's a very broad range of benefit that we were 22 including in our sort of definition of what a benefit 76 1 is in a prison study, and that's why we thought 2 epidemiologic studies would be allowable. 3 DR. JONES: And just for clarification, 4 did you also say for that the benefit had to outweigh 5 the risk, not just balance? 6 DR. VISSCHER: We said the benefits had to 7 outweigh the risk, yes. 8 MR. POPE: I want to add one comment if I 9 could on the collaborative responsibility concept. It 10 reminded me actually of a conversation and work that 11 we did with the AMA years ago where or AAMC, I guess, 12 where I think it was Brownie Anderson made the point 13 that I'm sure many of you have heard before, but if 14 you've seen one medical school, you've seen one 15 medical school. It's the same kind of a thing with 16 prisons as we were told. 17 Each prison has its own culture and they 18 are distinct and unique. Certainly many similarities 19 exist, but the idea here is to have some collaboration 20 in designing and conducting the research that's done 21 in each individual prison so that you have a sense of 22 that culture integrated into that research design. 77 1 That's not to equate medical schools with 2 prisons, of course. 3 (Laughter.) 4 CHAIRMAN PRENTICE: medical students might 5 think otherwise. 6 Susan. 7 DR. WEINER: A procedural question for Dr. 8 Pope. 9 Given that this report is likely to 10 stimulate interest in legislation, and I understand 11 that the role of the National Academies is advisory. 12 Is it your responsibility to be the liaison on this 13 study to any members of Congress or staff that would 14 be interested in pursuing this? 15 MR. POPE: The short answer is yes. We 16 would be happy to talk to anyone on the Hill about the 17 content and the recommendations in this report, and 18 we've had some conversations about trying to identify 19 who the right people might be to brief on this. 20 So, no, we're very happy to do that. 21 CHAIRMAN PRENTICE: Let's see. Neil. 22 DR. POWE: I just want to commend the 78 1 committee and the staff for taking on a tough issue, 2 the issue where there is little data, and to try to 3 dig and get that data and to try to make some big and 4 bold recommendations. 5 I do know that the report underwent a very 6 rigorous review that I'm sure you all are aware of, 7 but I guess one of the questions I have here, some of 8 the -- we have many recommendations. Some require 9 acts of Congress, I guess a couple at least. Some 10 have resource implications, tremendous resource 11 implications either for the federal government, for 12 researchers that have to provide more information 13 about the settings, maybe even for IRBs, although I'm 14 not sure I see much of that. 15 So my question is this, and as I said, I 16 really commend you for trying to make some bold 17 recommendations to free us from the constraints and 18 prior language and regulations that we have. 19 But for this committee what I'd like to 20 know: if there were one or two of these 21 recommendations that you would recommend happen, which 22 ones would they be? 79 1 DR. VISSCHER: I think for myself I would 2 recommend that all prison research fall under one set 3 of oversight, one set of regulations, one oversight 4 system. That would be the one I would pick. 5 How about you? 6 MR. POPE: I don't think I get a vote 7 really. It's sort of like picking a favorite child. 8 But certainly if there were to be an act of Congress 9 that established some uniform guidelines for 10 protecting human subjects, not just prisoners, that 11 would solve a lot, maybe, a lot of problems, although 12 on another level, I guess, you have to be careful what 13 you ask for. 14 DR. VISSCHER: Right, and when I say I 15 want everything to fall under one set of regulations, 16 I'd also want the regulations to be more in the line 17 of what we were talking about, especially in terms of 18 the risk-benefit approach that we were suggesting. 19 In terms of the process, it was really an 20 interesting process for me to sort of see the report 21 take shape. I know that Andy has been on a lot of 22 these projects and seen a lot of reports take shape. 80 1 this was the first one that I was on, and it was 2 really quite interesting with all of the discussion, 3 all of the input that we had from everybody, and then 4 in the end we came up with some recommendations that 5 we were all quite happy with. 6 In terms of resource implications, you're 7 right. It will involve more resource allocation, more 8 funding for OHRP to be able to do more of these tasks 9 that we talked about, and also more funding for grants 10 because the prison research subject advocate would 11 have to be funded through the grant itself. 12 CHAIRMAN PRENTICE: We have about ten 13 minutes left. I would like to reserve some time for 14 discussion as to what we would like to do with the 15 report. So I would ask you if you would hold your 16 questions until perhaps the break unless they are 17 absolutely compelling and necessary for our 18 deliberations. 19 No? James. You already had three times. 20 Can you hold off or do you want to make one last 21 statement? 22 DR. POWELL: It will hopefully be on my -- 81 1 CHAIRMAN PRENTICE: You're going to do 2 what? 3 DR. POWELL: I'm going to ask a question, 4 if you don't mind. 5 CHAIRMAN PRENTICE: Brief, brief. 6 DR. POWELL: Okay. 7 CHAIRMAN PRENTICE: Succinct. 8 DR. POWELL: The brief question is there 9 has been a lot written about clinical child diversity 10 with respect to ongoing clinical trials, lack of 11 minority participation, whereas minority has a 12 different meaning inside the prison system. 13 Unfortunately the majority of prisoners are people of 14 color. 15 The question I have is did the committee 16 consider cultural and racial diversity with respect to 17 the collaborative representation of people in the IRBs 18 that review these things. Throughout the process was 19 that a part of the discussion of your committee? 20 DR. VISSCHER: Well, we certainly did 21 discuss the distribution or the proportion of 22 minorities in the prisons in the way that you're 82 1 suggesting, which is really the majority in the prison 2 setting, and by extension then if we were going to 3 involve prisoners, we would be involving more people 4 in those groups in this decision or this collaborative 5 approach. 6 CHAIRMAN PRENTICE: Okay. Thank you. 7 All right. I would like to thank you very 8 much for all of your hard work and for spending your 9 time with us today. 10 MR. POPE: I want to thank you for the 11 opportunity to have worked on this study and to have 12 produced it for OHRP and for SACHRP. We stand at the 13 ready to respond in other circumstances if the need 14 should arise. 15 CHAIRMAN PRENTICE: Okay, good. Thank 16 you. 17 MR. POPE: Thank you very much. 18 CHAIRMAN PRENTICE: All right. I have a 19 suggestion for SACHRP's consideration. As you know, 20 there is a Subpart C subcommittee report that contains 21 recommendations that has been accepted by the 22 Secretary and handed down to OHRP for implementation 83 1 as appropriate, and obviously OHRP needed to wait for 2 any implementation of those recommendations until the 3 IOM report was issued. 4 The IOM report in some ways reflects many 5 of those recommendations. In other ways it's not 6 totally consistent with some of those recommendations. 7 If you look at the IOM report, there are 8 clearly recommendations that pertain to HHS and 9 Congress, and there are clearly recommendations that 10 pertain to specifically OHRP. 11 I would like to suggest for your 12 consideration that we write a letter to Secretary 13 Leavitt asking the Secretary to consider those 14 recommendations that pertain to HHS, and we also ask 15 in that letter that OHRP consider those 16 recommendations that directly pertain to OHRP, as well 17 as consideration of the Subpart C subcommittee's 18 report. 19 In addition, I would suggest for your 20 consideration that in light of the fact that the IOM 21 report has strongly recommended establishment of 22 uniform protection of all prisoners involved in 84 1 research, and that was indicated by both Wendy and 2 Andy as an extremely important recommendation, and in 3 light of my colleague Dan's strawman proposal, that 4 perhaps we should consider extending a recommendation 5 that pertains to universal protection of all human 6 subjects, which as you know has been the subject of a 7 number of congressional bills, never went anywhere. 8 Perhaps it would be appropriate to tie the two 9 together and say this is what the IOM report 10 recommended. We urge you to consider this, and while 11 you're doing that, you might as well look at universal 12 protection for all human subject. 13 Obviously the language would have to be 14 crafted very carefully in terms of that letter. So 15 I'm just off the top of my head just articulating some 16 of the thoughts. 17 I would also suggest that OHRP be asked to 18 report back to the committee at its November meeting 19 as to their analysis of the IOM report, as well as 20 their plans to implement what we've often referred to 21 as the short-term fix, in other words, those 22 recommendations of Subpart C that do not require an 85 1 amendment of Subpart C. 2 So I put that out on the table for your 3 consideration and discussion. Dan? 4 DR. SCHWETZ: Sounds good to me, Ernie. 5 Actually the question I just held back on is relevant 6 to this. So I'll ask it now. I was going to ask Bern 7 or others who might know this process for a reality 8 check of sorts. 9 What's the incremental -- the relative 10 degree of difficulty as we move from fixing the 11 current Subpart C in the ways that have been 12 described, shifting from categories to risk-benefit, 13 et cetera, but excepting that that doesn't apply to 14 any more than it applies right now, to the next step 15 up asking that it apply to all research involving 16 prisoners to the farthest reaches of asking that a 17 uniform set of regulations apply across the board. 18 What are we looking at in terms of 19 accomplishing anything in our lifetimes, I guess? 20 (Laughter.) 21 DR. SCHWETZ: Well, I'm not sure what 22 reference point we put against that, but I would just 86 1 remind you that now that the Subcommittee for Research 2 Involving Children is done and there's a large bulge 3 of work that will come out of that, at the same time 4 now that potentially a large bulge of work comes from 5 this report on research involving prisoners, that does 6 create an awful lot of work at one time. 7 So we have to figure out what are our 8 priorities, and, Dan, in terms of just the -- and I've 9 been thinking a little bit about that this morning, 10 about how the response to the prisoner work load for 11 us is perhaps similar or different from writing more 12 guidance for research involving children, I think the 13 issues around research involving children are ones 14 that are very specific to the regulations, and it 15 doesn't require an awful lot of additional research to 16 know what to do about those recommendations. They're 17 pretty specific, and they're ones that we are familiar 18 with and have dealt with all the time. 19 There are some relatively new pieces in 20 the recommendations regarding research involving 21 prisoners, for example, the development of a database. 22 My reference point was, you know, we've been involved 87 1 in a database regarding federal-wide assurances and 2 mandatory registration of IRBs. I don't know the 3 difficulty of now moving into a whole other type of 4 database where we don't have access to the 5 information. So it might well be easy to build a 6 database compared to going out to every prison site, 7 every community to gather information, or with this 8 IRB prospective, in which case it wouldn't be very 9 helpful for decades if it's just prospective. 10 So, Dan, in that context, I think there 11 are some new things. If we switch from the 12 certification system to something that is risk based, 13 that requires a significant change in how we do 14 business within OHRP, how we interact with the 15 community. So there is a little bit more uncertainty 16 in how we're going to deal with those issues compared 17 to you know. We ask the team that writes guidances 18 this is what you're going to work on next, and they're 19 working on these kinds of guidances all the time. 20 So in response to your expectation for 21 November, sure, we'll be happy to give you an update, 22 and I don't know if it will be an update or if it will 88 1 be a plan, but we'll give you as much as we can 2 because at this point we also need to dovetail. After 3 we have analyzed the prisoner report and look at the 4 SACHRP recommendations again to see where they are 5 complementary, where they are in conflict with each 6 other and how are we going to deal with this broader 7 package; after we look at that internally at OHRP, 8 then we have to begin to talk more to the department 9 and figure out from them what they think the plan 10 should be for the broader response to the 11 recommendations within the report on prisoners. 12 So I assure you that we'll be happy to 13 give you an update in November, and if that includes 14 part of the plan, fine. If it includes a broader plan 15 than what we're going to do about it, we'll give you 16 everything that we have. I just can't guarantee that 17 we'll have an answer to how we're going to provide 18 protection to everybody and some of the other broader 19 questions that go beyond OHRP. 20 CHAIRMAN PRENTICE: Okay. Any -- yes, 21 Nancy. 22 DR. JONES: I do think that there are 89 1 ramifications with what Dan said of these 2 recommendations that would impact how we think about 3 human subject research beyond just the prison 4 population. It would be nice if we could extend human 5 research protection to all research. 6 But in the recommendation or at least one 7 of the suggestions for expanding the oversight, I 8 might be misstating this, but they were talking about 9 one way that you could get authority is through the 10 money line. So if you have federal and state 11 supported prisons, you then can say you want federal 12 monies into your Department of Justice at either the 13 federal or the state level. then you have to play by 14 these rules. 15 So it's analogous to how we follow the 16 money for human research protection that OHRP 17 oversees. 18 So that's one strategy that may actually 19 be easier to mandate in Congress. There was a 20 considerable resistance to expanding all human 21 research protection and then you wouldn't necessarily 22 want to expand protection without re-looking at 90 1 Subpart C because from their recommendation, we didn't 2 want to have Subpart C because instead it may have the 3 unintended consequences in its current form of 4 shutting down. 5 CHAIRMAN PRENTICE: Yeah. 6 DR. JONES: I guess what I'm saying is 7 that before I wrote a letter to the Secretary, I would 8 like a little more time to digest, in other words, how 9 they fit together so that you would responsibly pass 10 on the recommendations or just -- 11 CHAIRMAN PRENTICE: Well, let me respond. 12 My impression of the IOM report is they're not talking 13 about expanding Subpart C in its unamended form to 14 cover all prisoners involved in research. That's not 15 what we're talking about here. We're talking about an 16 amended Subpart C. That's point number one. 17 Point number two, above and beyond that, 18 extending it to all research involving prisoners, I 19 don't think there's any reason to try to look at the 20 old Subpart C and say, "Okay. How can we go ahead and 21 expand that to cover all research involving 22 prisoners?" 91 1 That doesn't make any sense to try to do 2 that. It would be counterproductive. Okay? That's 3 point number one. 4 Point number two, relative to how you 5 achieve universal coverage of research involving 6 prisoners. That's not up to SACHRP or even OHRP. It 7 goes way beyond us. We can simply make the 8 recommendation that the Secretary strongly considered 9 this recommendation from the IOM, and while you're 10 doing that, why not also reconsider -- and the term 11 would be reconsider -- whether or not it would be 12 appropriate to cover all human subject research, and 13 that's not going to be an expanded, you know, 14 paragraph or statement. Simply it would be an 15 opportunity for SACHRP to tie that in as we're asking 16 for consideration. 17 So I would suggest that we don't really 18 need to try to flesh out the details of how this would 19 happen, not in our letter, anyway. Would that be 20 fair, Nancy? 21 DR. JONES: I understand all of the 22 points, and I would say that that would be the intent 92 1 of the IOM, too. But in reading the report, I don't 2 know if all of those -- you know, I'm trying to 3 understand what SACHRP's responsibility is or should 4 be. Is it just to say the IOM or their 5 recommendations are sound? Should we also see what 6 implications they're going to make? 7 I do think they have implications for all 8 of research so that if you passed them on, I do 9 think -- 10 CHAIRMAN PRENTICE: We're not passing them 11 on. 12 DR. JONES: Okay. 13 CHAIRMAN PRENTICE: I agree with you. We 14 have not had an opportunity to study this report. As 15 a matter of fact, I think to actually endorse all of 16 these recommendations, we probably have to have a week 17 to sit down here and debate them all. That's not the 18 intention. 19 The intention is to ask the Secretary to 20 look at these recommendations. That's all. The same 21 with OHRP, and have OHRP come back to us in November 22 and say, "Look. This is what we think," and obviously 93 1 OHRP will be in communication with HHS. So they can 2 probably provide us some information as to what HHS is 3 thinking. That's about all we can do with a report 4 like this. Okay? 5 All right. Any other discussion? 6 (No response.) 7 CHAIRMAN PRENTICE: If not, I'll entertain 8 a motion. 9 MR. POWE: So moved to accept your -- 10 CHAIRMAN PRENTICE: Whatever I said. 11 MR. POWE: -- proposal. 12 (Laughter.) 13 MR. POWE: Your proposal. 14 CHAIRMAN PRENTICE: Okay. Good. It's all 15 written down. Kathy will tell me what I said. 16 Okay. Is there a second? 17 MR. GENEL: Second. 18 CHAIRMAN PRENTICE: Yes, there's two 19 seconds. All right. Any further discussion? 20 (No response.) 21 CHAIRMAN PRENTICE: All those in favor? 22 DR. JONES: Wait. Could you please just 94 1 restate your motion? 2 CHAIRMAN PRENTICE: Oh, geez. 3 DR. JONES: Just for the record, please. 4 CHAIRMAN PRENTICE: I'll try. The Subpart 5 C subcommittee contained very specific recommendations 6 with regard to what we refer to as the short term fix. 7 In other words, guidance that could be implemented by 8 OHRP without amending Subpart C. 9 Okay. Those recommendations were accepted 10 by the Secretary, passed on down to OHRP to implement, 11 and I quote, as appropriate. OHRP obviously was not 12 going to implement any recommendations till the IOM 13 finished their report. 14 The IOM has completed their report. You 15 have it. Many of you have read it. Many of those 16 recommendations reflect the Subpart C subcommittee 17 recommendations. Some do not, but that's neither here 18 nor there. 19 What I am recommending to you is that 20 SACHRP write a letter to the Secretary asking the 21 Secretary to give consideration or study, if you like 22 -- we'll have to figure out the exact phraseology -- 95 1 of those recommendations that pertain to HHS. And 2 clearly if you look at these recommendations you can 3 say, you know, this is out of OHRP's ball park. They 4 can't do anything about it. It's at the level of HHS 5 and, indeed, even Congress. 6 Okay. so we carve out those 7 recommendations and say we would like you to consider 8 this. Relative to the universal coverage of research 9 involving prisoners, tying in the opportunity to say 10 while you're doing it, how about further consideration 11 be given to extending coverage to all human subject 12 research, and it's not something the Secretary is 13 going to be surprised about. They're obviously aware 14 of the Getville (phonetic) and Kennedy's position. 15 Then a second part of the letter would be 16 asking for OHRP to study the IOM report, consider the 17 Subpart C subcommittee's recommendations which have 18 been accepted by the Secretary, and then report back 19 to SACHRP at the November meeting as to their 20 progress. 21 And Bern already went through how he views 22 what they may or may not be able to do and the 96 1 constraining factors. That's the substance of my 2 motion. Is that clear? 3 CHAIRMAN PRENTICE: Okay. It's been 4 approved. It's been seconded. Any further 5 discussion? 6 (No response.) 7 CHAIRMAN PRENTICE: All those in favor. 8 (Show of hands.) 9 CHAIRMAN PRENTICE: Is there any opposed? 10 (No response.) 11 CHAIRMAN PRENTICE: Any abstentions? 12 (No response.) 13 CHAIRMAN PRENTICE: Okay. One more piece 14 of business before we take a break. If you have not 15 already made transportation arrangements to get to the 16 airport or wherever else you need to get to, please 17 contact Kelly, and Kelly will assist you in that 18 endeavor. Okay? 19 Now, we're about eight minutes over. So 20 I'd like to cut the break back a little bit. If you 21 don't mind, please reconvene at 10:20. 22 (Whereupon, the fo