1 DEPARTMENT OF HEALTH AND HUMAN SERVICES + + + + + SECRETARY'S ADVISORY COMMITTEE ON HUMAN RESEARCH PROTECTION + + + + + MEETING + + + + + TUESDAY, APRIL 19, 2005 + + + + + The Advisory Committee met in the Jefferson Ballroom in the Radisson Hotel Old Town Alexandria, 901 North Fairfax Street, Alexandria, Virginia, at 8:30 a.m., Ernest Prentice, Ph.D., Chairman, presiding. PRESENT: ERNEST D. PRENTICE, Ph.D., Chairman BERNARD A. SCHWETZ, D.V.M., Ph.D., Executive Secretary CATHERINE SLATINSHEK, M.A., Executive Director THOMAS L. ADAMS, CAE, Member MARK BARNES, J.D., L.L.M, Member NANCY L. JONES, Ph.D., Member FELIX A. KHIN-MUANG-GYI, Pharm. D., Member SUSAN KORNETSKY, M.P.H., Member MARY LAKE POLAN, M.D., Ph.D., M.P.H., Member ADA SUE SELWITZ, M.A., Member SUSAN L. WEINER, Ph.D., Member 2 EX OFFICIO MEMBERS: PEG BARRATT, Ph.D., National Science Foundation KATHRYN LYNN CATES, M.D., U.S. Department of Veterans Affairs ROGER CORTESI, U.S. Environmental Protection Agency SUZANNE GAYNOR, DrPH, RN, MBA, U.S. Department of Housing and Urban Development DAVID LePAY, M.D., Ph.D., Food and Drug Administration VICTOR SCHNEIDER, M.D., National Aeronautics and Space Administration LAWRENCE UHTEG, U.S. Department of Commerce, NIST ALSO PRESENT: KELLEY BOOHER, Office of Human Research Protections MICHAEL CAROME, Office of Human Research Protections JULIA GOREY, Office of Human Research Protections JULIE KANESHIRO, Office of Human Research Protections LAURA ODWAZNY, Office of General Counsel IVOR PRITCHARD, Office of Human Research Protections KEVIN PROHASKA, Office of Human Research Protections IRENE STITH-COLEMAN, Office of Human Research Protections 3 A-G-E-N-D-A PAGE I. Welcome: Opening Remarks . . . . . . . . . .4 II. Perspectives on the Role of the Institutional Official -- Judith Brookshire. . . . . . . . . . . . .6 -- Richard Bianco . . . . . . . . . . . . . 21 -- Question/Answer Session. . . . . . . . . 35 III. HRPP Accreditation Standards for Investigator Education -- Jessica Briefer-French . . . . . . . . . 93 -- Marjorie Speers. . . . . . . . . . . . .111 -- Question/Answer Session. . . . . . . . .125 IV. Issues Involving Investigator Education -- David Korn . . . . . . . . . . . . . . .153 -- Charles Flexner. . . . . . . . . . . . .168 -- Paul Braunschweiger. . . . . . . . . . .183 -- Question/Answer Session. . . . . . . . .196 V. Public Comment. . . . . . . . . . . . . . .218 VI. Incentives and Disincentives for IRB Monitoring/Audit Programs -- Dennis Swanson . . . . . . . . . . . . .235 -- Ada Sue Selwitz. . . . . . . . . . . . .254 -- Question/Answer Session. . . . . . . . .271 VII. Wrapup and Adjourn. . . . . . . . . . . . .302 4 1 P-R-O-C-E-E-D-I-N-G-S 2 (8:38 a.m.) 3 CHAIRMAN PRENTICE: Let's start with the 4 agenda. We're going to have a whole series of panels 5 all day long. We're going to begin at -- in about 6 five minutes with perspectives on the role of the 7 institutional official, and then we will have a break. 8 Then, we will reconvene for the HRPP accreditation 9 standards for investigator education, and then we're 10 going to follow that after lunch with issues involving 11 investigator education. 12 So as you can see, there is a real focus 13 this morning on investigator education and 14 institutional culture. 15 At 1:00, again, issues involving 16 investigator education, then there's going to be a 17 public comment period. At 3:00, we'll have incentives 18 and disincentives for IRB monitoring and auditing 19 programs, and then we're going to wrap up our 20 discussion of committee business at 4:15 and, 21 hopefully, adjourn at 4:30. 22 I want to remind everybody that we've 5 1 already scheduled two more meetings for this calendar 2 year -- August 1st and August 2nd, 2005 and November 3 1st and November 2nd, also in 2005. 4 Okay. All right. Now, the first panel is 5 going to be on perspectives of the role of the 6 institutional official with Judith Brookshire and 7 Richard Bianco, and I will introduce both of them in 8 a moment. But the format for these panels is that we 9 would like each panelist to present for approximately 10 20 minutes, and then we will hold questions until the 11 very end of both presentations. 12 And I will introduce each individual as 13 they come up, and I will not go through an extensive 14 bio because we want to try to conserve time as much as 15 possible, but you all have the bios of our panelists 16 in your packets. 17 So with no further ado, Judith, would you 18 please come up? 19 Now, as Judy is getting set up, let me 20 provide the rationale for this particular panel. I 21 think everybody knows that the institutional official 22 is the representative from the institution who 6 1 provides the assurance of compliance with the federal 2 regulations. 3 Obviously, that position is key, 4 particularly in terms of the leadership role and the 5 cultural role. So we thought it would be extremely 6 important to get two perspectives on the role of an IO 7 -- one perspective from a very well-known IRB 8 administrator, that's Judy Brookshire, who is the 9 Director of the Office of Protection for Research 10 Subjects at the University of California, Los Angeles. 11 And the other perspective will come from Richard 12 Bianco, who I'll introduce in a moment, who is 13 actually an IO himself. 14 So, Judy, we're looking forward to your 15 comments, and we appreciate you taking the time and 16 coming to address us. 17 MS. BROOKSHIRE: Thank you. I'd like to 18 thank Drs. Schwetz and Prentice for inviting me here. 19 I really appreciate it, and this is a great 20 opportunity for me. 21 My perspective is actually as a director 22 for three separate academic institutions. And so it's 7 1 not just from my perspective of where I am at UCLA at 2 this point. And I've also, for the last 10 years, 3 been an OHRP site visitor, and also an AAHRPP site 4 visitor, as well as a consultant for other academic 5 institutions. 6 So what I'm going to give you now is my 7 perspective, having had that experience since 1986 8 basically. That's why I guess we didn't go through 9 the bios, because we were just too old. 10 (Laughter.) 11 Anyway, what I want to talk about is the 12 significance and the value of the institutional 13 official at academic institutions, and how this can 14 define the culture. I'm going to go over the 15 definition of the IO, role and responsibility, and how 16 the institutional official can make a difference and 17 be part of a foundation for a very successful IRB 18 program. 19 The regulations don't specify the 20 necessary qualifications of an institutional official, 21 and the person responsible for ensuring the 22 independence of the IRB, its support, and its standing 8 1 within the institution. 2 However, the guidelines in the OHRP 3 guidebook do say that the institutional officials 4 should have the legal authority to act and speak for 5 the institution and should be someone who can ensure 6 that the institution will effectively fulfill its 7 research oversight function. 8 And I have FOIA'd many compliance letters 9 for my own edification. And one written by Mike 10 Carome to an institution, an academic institution, 11 reminded that institution that the office strongly 12 recommended elevation of the IRB to a higher level 13 within the institutional hierarchy in order to 14 demonstrate a greater institutional commitment to 15 human subjects protections. 16 The IO is accountable for all research 17 involving human subjects performed under the auspices 18 of the institution. And the institutional official is 19 also responsible for creating a campus culture that 20 promotes and upholds the highest ethical and 21 scientific principles in the review of human subjects 22 research. 9 1 The IO is responsible for committing the 2 institution to compliance with HHS and FDA regulations 3 and local law for the protection of human subjects, 4 designing one or more IRB -- designating one or more 5 IRB to fulfill the requirements of the federal 6 regulations, and ensuring that the IRB is properly 7 constituted and functions in accordance with the 8 regulations. 9 The IO is also accountable for ensuring 10 the IRB receives appropriate institutional support and 11 adequate staffing to support the IRB review and 12 recordkeeping duties. This is very important, and 13 those of us who have been administrators for years 14 understand that the IRB is dependent on the 15 administrative staff for all the information that they 16 have to review. And without adequate staffing and 17 resources, the IRB doesn't have the information it 18 needs to be responsible and to perform their own 19 duties. 20 The IO is also responsible for ensuring 21 that investigators meet their obligations to the IRB 22 -- and I'll get into that in just a little bit -- and 10 1 ensuring that the IRB has the authority to approve, 2 require modifications, or disapprove all human 3 research activities, including proposed changes in 4 ongoing, previously-approved human subjects research. 5 More duties of the IO. The IO is 6 accountable for ensuring the IRB has the authority to 7 suspend or terminate the approval of ongoing, 8 previously-approved research, and that it is being 9 conducted in accordance with IRB approvals, and that 10 it has been associated with unexpected -- anything 11 that's been associated with unexpected serious harm to 12 subjects, that the IRB knows and follows its 13 responsibility and authority to terminate that 14 research. 15 And the IO is responsible for making sure 16 that there is sufficient communication, training, and 17 education of all stakeholders in an IRB program, 18 including the IRB and administrative staff. 19 In the year 2000, the Association of 20 American Universities formed a task force, and it was 21 on research accountability, and they wrote a report on 22 university protections of human beings who are the 11 1 subjects of research. In this report, they wanted to 2 assess the university research management challenges 3 related to the protection of human subjects, and they 4 endorsed institutional obligations articulated in the 5 Federal Regulations. 6 Of the recommendations -- and they had 7 many -- they recommended that the institution 8 strengthen training and support in the operations of 9 the IRB. And when I see that they said senior 10 university management, I'm thinking that that must -- 11 they must be referring to the institutional official 12 in this report. 13 And they said that that person should 14 state clearly to the entire campus community the 15 importance of conducting human subjects research in 16 accordance with the highest ethical standards. There 17 has to be a public voice saying, "This is the way this 18 institution wants to perform human subjects research 19 and ensure that the safeguards are there for 20 volunteers who choose to participate." 21 Institutions should maintain ongoing 22 communications between the institutional official and 12 1 the IRB, and that active institutional support is the 2 foundation for a successful, ethical, human subjects 3 research program. 4 And then we have another task force that 5 was in 2002, and they wrote a report, "Protecting 6 Subjects, Preserving Trust, Promoting Progress," and 7 they had formed a task force on financial conflicts of 8 interest in clinical research. 9 And the result of that -- one of the 10 points that they made is that an individual who is 11 directly involved and responsible for research funding 12 such as the Director of Research and Development or, 13 in some instances, the equivalent of a Vice Chancellor 14 or Vice President for Research, that that person may 15 not be sufficiently immunized against financial and 16 other pressures. 17 And that an Assistant Dean or Assistant 18 Vice Chancellor may not have sufficient authority to 19 avoid institutional conflicts and be able to ensure 20 that an IRB is given the necessary respect and 21 autonomy. 22 The institutional officials should be at 13 1 the highest -- this is my opinion, and it's from my 2 perspective, so -- I know that other institutions work 3 differently, and I'm not saying that this is the only 4 way to go. 5 But from my perspective, the institutional 6 officials should be at the highest level in the 7 institution, in order to have the authority to speak 8 for and make decisions on behalf of the institution, 9 and to garner the respect of the research community 10 and create an institutional culture in which ethics 11 are valued and the importance of IRB review is 12 honored; a culture that engages a collective 13 commitment of all parties to carry out their ethical 14 responsibilities and comply with the federal 15 regulations, and results in a culture of respect and 16 responsibility where all stakeholders participate and 17 contribute to the institutional accountability. 18 In an effective system of review, the 19 institutional official sets the highest ethical 20 standards for the research community and fosters 21 awareness and reinforces the importance of ethical and 22 legal conduct of human subjects research and insists 14 1 on an institutional culture that demonstrates this 2 support for the charge of the IRB. 3 In an article in JAMA, Charles Marwick 4 wrote that institutional officials should foster a 5 culture of conscience in the research enterprise. And 6 this goes beyond interpretation and application of the 7 regulations and internal policy. 8 Research programs and practices are 9 facilitated and supported by the IRB -- by the IO, I 10 made a mistake here -- by the institutional official 11 and conducted under ethical standards endorsed by the 12 institution. 13 When an IRB is able to function at a high 14 level and its decisions are supported by the 15 institutional official and respected by all 16 stakeholders, that's when I believe the institutional 17 official is most effective. And this encourages 18 investigators to participate in the process of 19 negotiation with the IRB rather than be resistant or 20 follow other paths that I'll get into in just a 21 minute. 22 Lack of private and public support from 15 1 the institutional official can undermine and devalue 2 the charge-in ability of the IRB and its 3 administrative staff to function, to carry out policy, 4 and to protect the rights and welfare of human 5 research subjects. 6 Without sufficient staff and 7 infrastructure, an IRB is essentially paralyzed and 8 cannot carry out its basic functions, which are 9 applications of the Belmont Principles and federal 10 regulations, appropriate assessment and review of 11 possible risks to subjects, education and training of 12 all stakeholders, appropriate letters of conditions to 13 investigators, necessary tracking and review of 14 adverse event reports, conducting appropriate new and 15 continuing review, addressing violations and/or 16 subject complaints, or receiving and providing 17 guidance regarding changing interpretations of the 18 regulations. 19 Lack of support can result in a culture 20 where investigators are given the message that 21 compliance is not important. They are -- this is a 22 message that they can petition the institutional 16 1 official to change IRB decisions when they are not 2 happy, when they feel that the conditions of approval 3 are not to their liking or they feel they're 4 ridiculous -- and I'm sure many of you have heard this 5 before. 6 This kind of a culture can support 7 investigators going directly to the IO and skirting 8 the IRB. This really encourages investigators to 9 ignore the process of IRB review and approval and 10 entirely. And I believe this can happen. 11 When IRB is not provided sufficient 12 resources to promote program accountability, the IRB 13 becomes isolated and faculty do not want to serve as 14 members. And this is a big problem because everyone 15 knows if you have the correct disciplines on the 16 committee, that negotiation process that goes on 17 between an investigator and the committee is a 18 positive one, one of respect and one of communication. 19 Lack of support and infrastructure -- what 20 happens in that case? Staff are blamed for decisions 21 that the IRB makes. They're blamed for delays in 22 turnaround time. And, basically, if there aren't 17 1 enough people to do the work and take responsibility 2 for the conditions that the IRB has made for approval, 3 then it's just going to be one problem after another. 4 In that situation, you're going to have a problem with 5 lack of retention of high-level educated staff. 6 And for those of you who are 7 administrators and chairs, you know that the learning 8 curve for administrative staff is very, very steep. 9 And in my office, we say -- and at every level of 10 administrative staff -- it takes from six months to a 11 year to really get on board. And I would say that's 12 true for most IRB members as well, because they come 13 in representing their disciplines and the standards of 14 their disciplines, but they're not chosen because of 15 their knowledge of the Federal Regulations for 16 protection of human subjects. 17 So it's a shared responsibility. And if 18 you don't have the support, again, lack of retention 19 is very, very problematic, and burnout is inevitable 20 when you have people working 60 hours a week or more 21 just trying to keep up with the work, and you're 22 having -- you're getting calls and blamed for the lack 18 1 of turnaround time. And investigators are going to 2 the IO saying that every other institution in the 3 world has approved this, what's wrong with you? 4 And in that kind of -- in that kind of 5 scenario, I would presume that intellectual capital is 6 lost, because people can't keep up with it, and they 7 burn out, and mistakes are made. And that's my 8 biggest fear, because when you don't do an adequate 9 review people are at risk, and, after all, we all have 10 to look at our responsibility for protection and 11 putting in those essential safeguards for those who 12 volunteer to be in research. And the institution is 13 at risk as well. 14 The foundation for a successful program, 15 I believe is -- indicates that active institutional 16 support is the foundation for a successful, ethical, 17 human research program, and that the institutional 18 official is responsible for upholding the assurance 19 and is accountable for the actions of the 20 investigators and the IRB, and for the culture that 21 supports that program. 22 Active institutional support promotes 19 1 accountability. It promotes accountability for the 2 investigators, for the IRB, and all of those 3 stakeholders who are responsible for the program. It 4 also promotes responsibility and responsible actions. 5 It also promotes trust and respect, and I 6 think that's very, very important, because we -- if we 7 go back to Belmont, the first ethical principle is 8 respect, and that should be applied to all parties. 9 All parties -- the administrative staff that support 10 the IRBs, the investigators that submit their 11 protocols. Again, it should be a collegial one of 12 negotiation and respect. 13 And trust in the integrity of the IRB 14 process in the research community is really the result 15 of active institutional support. 16 Academic institutions are responsible for 17 ensuring that the Federal Regulations, institutional 18 policies, and ethical standards that guide responsible 19 research practices are systematically communicated to 20 research faculty and staff, and also applied. 21 The institutional officials should endorse 22 the understanding that the responsibility for 20 1 assistive of human subject protections goes beyond 2 education of the IRB, IRB staff, and investigators. 3 It requires a culture where all stakeholders work 4 together in an environment of support, trust, and 5 respect. 6 This kind of culture acknowledges the 7 interrelationship and collective responsibility for 8 maintaining a system that honors and protects the 9 rights and welfare of research subjects. When 10 collective responsibility is attained, the research 11 program will gain public trust. 12 Thank you. 13 (Applause.) 14 CHAIRMAN PRENTICE: Thank you, Judy. 15 Our next speaker is Richard Bianco. 16 Richard is the Assistant Vice President for Research 17 at the University of Minnesota, and he is the IO for 18 both human subjects protection as well as the animal 19 care and use program. 20 As he will tell you, he is the "Go to Jail 21 Guy," so he is in double jeopardy being a twice IO for 22 two programs. 21 1 Dick, welcome. We appreciate you taking 2 the time to come here. 3 DR. BIANCO: Thank you. Good morning 4 everybody, and thanks for inviting me. I appreciate 5 it. It's one of the first -- the only times of the 6 year that the weather is identical to Minnesota, so 7 just -- it was an easy culture change. 8 I think that the order of speaking was 9 perfect. Judy really set the definitional stage of 10 the IO. And I don't really want to talk about the 11 definitions. I want to talk about -- I want to speak 12 about Minnesota and our model there, why I think it is 13 a good model, and certainly I am biased; I am the IO 14 there. 15 But I think that the first part of my 16 comments will be addressing why we are at -- why we 17 are where we are, the sentinel events that changed us 18 in the '90s, that put us in a position to achieve a 19 higher accreditation, put us in the position perhaps 20 to avoid institutional shutdowns or breakdowns in the 21 system. 22 So as Ernie mentioned, I am the "Go to 22 1 Jail Guy," and I -- I find this description -- I think 2 I first heard it through PRIM&R. I find it a bit 3 specious. I don't think it's very funny. But it 4 actually -- if you think about it, I don't think 5 there's any IOs in Leavenworth, to my knowledge, yet. 6 But if you think about it, it really puts 7 it in perspective -- that I do sign assurance to the 8 Federal Government on behalf of the regions of the 9 university that we are going to do certain things. 10 And I will be held accountable if we don't. 11 So if you think about it in those terms, 12 and it's not just a position, it's not a transient 13 position, you'd better know what you're doing, you'd 14 better know what you're signing. 15 So to cone it in on myself a little bit -- 16 and I mean this in a humble way -- I currently am the 17 IO for both animal and human subjects protection, but 18 I also have oversight for all other research 19 compliance activities, which is an important point, a 20 conflict of interest, both personal and institutional, 21 biosafety issues, and security of the research 22 programs, protecting the investment of the Federal 23 1 Government. 2 Now, there may not be any grant mechanism 3 to achieve security money. I mean, as we went through 4 animals rights pressures, as many of you did, we 5 needed to lock up our place. We have select agents, 6 we have HIPAA issues -- all of that requires security. 7 And I believe that we need -- as we invest millions of 8 dollars of security out of our own pockets, I think 9 that that's part of the issue here, where an IO must 10 have an integrated approach to all of the research 11 programs. 12 I've been on the IRB for I think it was at 13 least 12 years, and part of that was in a leadership 14 position, 15 years plus on the Animal Care Committee 15 as chair most of the time -- that time, 10 years 16 dealing with conflict management. Our institutional 17 policy and conflict of interest will be going to our 18 regions in May, but we've already implemented the 19 policy, basically. 20 And I also continue to do active research 21 with animal models, cardiac devices, primarily, and I 22 think that's an important point of what I'm going to 24 1 say about IO. 2 So in the early 1990s, we had a problem at 3 the University of Minnesota involving the drug ALG. 4 And it primarily devolved into financial issues, NIH 5 grant management, and we really didn't -- we didn't 6 get shut down, but we came very close. 7 Now, there were some conditions at 8 Minnesota that created this problem. We had a weak, 9 decentralized oversight system. It was a period of 10 dramatic advancements, particularly in transplant 11 surgery. We had a superstar that was beyond 12 oversight, frankly. It was a department head. We had 13 a weak dean in place, and our grant and clinical 14 income were at all-time highs. 15 Now, this was the institution that was 16 primarily involved in the fifties in inventing heart 17 surgery, cardiac valves, pacemakers. All of that came 18 out of our laboratories. 19 And then we had a whistleblower, and it 20 was discovered, after many audits and visits by the 21 Federal Government, that we have serious program and 22 institutional violations, and millions of dollars 25 1 worth of sanctions. And the sanctions had an impact, 2 and we were designated exceptional in the negative 3 sense of the word by the NIH. 4 And that had serious implications to all 5 researchers, whether you're using a rodent or you're 6 conducting clinical research on a Class III device. 7 Everybody was affected by this, because of the actions 8 of one individual. 9 But with -- like every disaster, there was 10 a silver lining in the situation. And I don't 11 recommend that this is the way to achieve success, but 12 at a large institution sometimes this is the only way 13 to achieve changes. Resources where none existed 14 appeared magically. 15 Education and training programs were set 16 up institutional-wide for all levels of investigator, 17 faculty, staff, and students. But most importantly, 18 I think we integrated our compliance program. We put 19 the IRB, the Animal Care Committee, biosafety, 20 conflict of interest, and post-approval monitoring 21 under one umbrella of regulatory affairs. 22 And there was a new institutional respect 26 1 for effective, functional research oversight, not to 2 say, of course, that there wasn't one before the '90s, 3 but it was refocused -- Moira, what was the check we 4 wrote to the Federal Government? $33 million? $33 5 million of more intense focus on oversight. 6 The faculty certainly knew or had a real 7 appreciation of their role in the process. They 8 mandated RCR training and a variety of other 9 certification steps before you could conduct research, 10 animals or humans. The message that research -- 11 conducting research at the institution was a 12 privilege, not a right, was a new concept in the issue 13 of academic freedom. It was not an academic freedom 14 issue. That had to be established over and over 15 again. 16 So we really -- we really did change the 17 culture. New faculty are coming in with this 18 appreciation of their role in the research process, 19 the role of the IRB in the research process. It is 20 becoming easier and easier to maintain the change of 21 culture. 22 The senior faculty -- I'm not going to say 27 1 they're beyond hope, and I'm close to being at that 2 level now, so I have to be careful what I say. The 3 senior faculty remain a problem. You have to 4 concentrate on that issue. 5 So "trust but verify" is an old cliche. 6 I've been using it for years, and it is actually quite 7 applicable here. Post-approval monitoring is the key 8 step in maintaining a compliant program, and an 9 institutional official is essential. 10 Integrated compliance, I believe, helps 11 prevent system breakdowns from occurring. It's not 12 going to eliminate them, because the primary risk 13 always remains at the individual PI level. 14 You heard a lot from Judy about resources. 15 I think that's -- at least three or four times a day 16 I heard that word relative to not enough, of course. 17 Nobody ever tells me we have plenty of resources, why 18 don't you take some and give some to somebody else. 19 But 90 percent of my job as IO is balancing resources 20 and making sure the money flows in the right 21 direction. 22 The compliance staff, IRBs, one of my 28 1 duties is to make sure everybody is adequately 2 trained. I can't emphasize more how important the 3 certification for IRB professionals is. It really 4 does standardize the level of training, 5 professionalizes your staff, and earns respect from 6 faculty. 7 And accreditation, same comments. We've 8 certainly been ALAC accredited for years and years and 9 years, but AAHRPP, I think, establishes the same level 10 of trust, both here in Washington, from your faculty, 11 and from the staff that have to administer it, and 12 certainly from your patients. 13 So moving to the IO model at the 14 university, now, I disagree quite wholeheartedly and 15 strongly about the IO should be positioned at the 16 highest level of the institution. I think that is 17 incorrect. I think that has -- that is the reason 18 that we have such an inconsistent level or 19 inconsistent behavior of IOs nationwide. 20 I think it should be lower than that. I 21 think -- in Minnesota, the President of the university 22 has no idea what IRB rules and regulations are. That 29 1 signature on an assurance would mean close to nothing. 2 Same goes for the VPR, the Vice President for 3 Research. 4 I'm on I think my fifth or six Vice 5 President for Research. With the exception of the one 6 that just joined us, we had a computer engineer, we 7 had a botanist, we had other academic specialties that 8 really had no links to the human subjects research 9 whatsoever. 10 More importantly, the VPR, in my view, 11 advocates for intellectual property transfer, 12 certainly the funding of research programs, and 13 certainly serves as a faculty advocate. Now, I think 14 that role -- those roles can be in conflict with the 15 roles of an IO, and I just throw that out there. I 16 think it's a serious issue, and I think until we 17 address that issue we're not going to make a lot of 18 progress in the quality of the IO. 19 So our model, is I'm an Assistant Vice 20 President, and I focus only on compliance, my non- 21 faculty role actually -- subject protection, animal 22 protection, occupational health and safety for our 30 1 research workers. And I think it helps me to avoid 2 raw confusion. I certainly can advocate for research 3 and at the same time advocate for compliance. 4 I certainly have an intimate knowledge of 5 day-to-day activities and global issues, as Moira 6 Keane will attest. She and I meet on a daily basis. 7 I can focus on compliance issues. And I believe I 8 have credibility with both faculty and the 9 administration as an active researcher and my long 10 service on the IRB. 11 I know both sides of the issues. I know 12 what my role is. And, frankly, there is no one person 13 that speaks for large institutions. Now, Minnesota, 14 we have five campuses spread out throughout the state. 15 Not even the President really speaks at all times on 16 behalf of the institution, so we have to put this into 17 reality in terms of a large public university. 18 So we, in the '90s, formed an Office of 19 Regulatory Affairs, for lack of a better word. It's 20 not usually a term used in academics. It's usually a 21 corporate-type office. And we'd certainly function 22 differently than a corporate regulatory affairs, but 31 1 we couldn't think of a better name for it. 2 But it really is where all of the -- the 3 intersection where all compliance activities come 4 together. So we can integrate and correlate. When we 5 have a problem with an animal program, we usually have 6 a problem in the clinical component of that program. 7 We can put all of these things together, including 8 financial information, conflict of interest, etcetera. 9 Post-approval monitoring. Post-approval 10 monitoring does not report to the IRB. Clinical 11 monitors monitor the clinical protocol, certainly, but 12 they also monitor the activities of the IRB relative 13 to any procedural issues or things like that. Those 14 reports come to me separately, so we can approve the 15 process -- improve the process of IRB, and we can 16 improve the quality of protocol compliance. 17 We have a comparable program in our 18 veterinary compliance programs with the same symmetric 19 reporting requirements, and similar to conflict of 20 interest. Since we're all integrated, we can cross- 21 correlate. We serve on each other's committees. IRB 22 administrators serve as ex officios on conflict, so we 32 1 can make sure that all programs are in compliance, not 2 just segments of them. 3 IBC we haven't completely moved over to 4 subjects protection, but that's in the process now 5 with the same integrated, systematic approach. And 6 all other oversight activities are also centered here, 7 such as use of controlled drugs or investigative drugs 8 and research, occupational health and safety, 9 etcetera. 10 So this is -- I'm not a fan of org charts, 11 but this sort of shows that it's not as complicated as 12 it looks. Veterinary compliance, clinical compliance, 13 and conflict of interest report up to -- to me in 14 Regulatory Affairs, and obviously I keep the Senior 15 Vice President of the Academic Health Center and the 16 Vice President for Research in the loop, and straight 17 up would be the President of the university. 18 So as IO, I report to the President of the 19 university. Now that's fairly highly positioned. 20 And subjects protection -- or Moira 21 Keane's organization -- fits in here. We have the IRB 22 and the animal care -- this is symmetry in its purest 33 1 form. Reports up to me, and we correlate all these 2 functions, then, up to the President. The 3 institutional veterinarians are down here, and they're 4 also linked into this. 5 Now, here is the -- I think these are the 6 instructions that you all are aware of, and I bolded 7 the part -- the part that I have a problem with, and 8 I think this has created a lot of issues. Generally, 9 the IO is someone at the level of the President, CEO, 10 or Vice President of the company, etcetera. 11 This is where I think the problem is 12 relative to large academic institutions. Those 13 individuals rarely have sufficient knowledge to serve 14 as an IO of a subjects protection program. 15 So in summary, our integrated approach, in 16 my opinion, my biased opinion, assures programmatic 17 compliance, not just project compliance, enhances 18 responsiveness by the institution to protect human 19 subjects, and it really does lead to more credible 20 assurance verification, and, hopefully, less risk to 21 go to jail. 22 The role of the IO should be based on 34 1 experience and position, both experience and position, 2 not just position. It must be hands-on and active, 3 and active research is preferable. It leads to 4 credibility, but it also leads to knowledge of day-to- 5 day activities and should have other compliance 6 responsibilities because they are all related. 7 They should obviously know the culture, 8 and that takes years at an institution, as you all 9 know. And the understanding that assuring compliance 10 protects the subjects and facilitates research. These 11 are not mutually exclusive. 12 And I believe we need some sort of a 13 national organization, maybe through PRIM&R, or 14 somewhere, where the IOs can get together and get 15 organized and discuss these issues. I think that's a 16 really important issue, and I don't sense any movement 17 in that direction, but I'd certainly like to start it. 18 Anybody who wants to help me, we can have the first 19 meeting in Minneapolis. 20 (Laughter.) 21 In January. 22 (Laughter.) 35 1 So everybody stays inside and pays 2 attention, right? 3 (Laughter.) 4 And if you need any more information on 5 our -- on regulatory affairs, it's certainly through 6 the University of Minnesota website. If you're 7 interested, I'd be happy to talk about it. 8 Thank you very much. 9 (Applause.) 10 CHAIRMAN PRENTICE: Thanks very much, 11 Dick. 12 As usual, I get the first 15 questions. 13 (Laughter.) 14 Actually, we have quite a bit of time, and 15 I am really enthusiastic about the amount of time that 16 we have to devote to this particular topic, because I 17 think it's very, very important. 18 Judy, you, as you indicated, have been on 19 a lot of OHRP compliance site visits. Indeed, you and 20 I have been on a number of them together, and I know 21 that you have gone on AAHRPP site visits for 22 accreditation purposes. You have also consulted 36 1 across the country. 2 I'm sure you have a perspective as to what 3 kind of IOs have you seen out there. I think Dick is 4 an exception, personally. I don't think that very 5 many IOs come from an IRB/IACUC compliance background. 6 Actually, Dick, that's why we chose you, because we 7 thought you were a model IO. 8 DR. BIANCO: Did you say exception or 9 exceptional? 10 (Laughter.) 11 And which sense of exceptional? 12 (Laughter.) 13 CHAIRMAN PRENTICE: So I personally don't 14 think there are too many Dick Biancos out there. So 15 I wonder what your perspective is. Do you think that 16 IOs are with it? Do you think they understand the 17 regulations? Do you think they are supportive of 18 compliance and the IRB and they provide resources, 19 generally, generally speaking? 20 MS. BROOKSHIRE: Generally speaking, I do 21 believe that the institution ¦- I'm a Luddite -- 22 institutional officials want to be responsive and 37 1 supportive, but oftentimes -- and I do agree with Dick 2 about a lot of the things that you said, because I 3 think the institutional official should be integrated. 4 And I think it all comes down to communication and 5 respecting all stakeholders, regardless of what that 6 position is. 7 I mean, I do have a prejudice as to where 8 that position should be, from my experience as a site 9 visitor as well as my experience as a director. 10 However, I think the most important quality of an 11 institutional official is one who will listen and be 12 integrated and understands the parameters and the 13 autonomy of an IRB. 14 CHAIRMAN PRENTICE: And do you think that 15 most IOs understand that role, in your experience? 16 MS. BROOKSHIRE: No. 17 CHAIRMAN PRENTICE: Or not? 18 MS. BROOKSHIRE: I do not. 19 CHAIRMAN PRENTICE: You do not. Okay. 20 MS. BROOKSHIRE: So you're an exception. 21 (Laughter.) 22 CHAIRMAN PRENTICE: I've been doing IRB 38 1 work for a long time, and initially my IO was the 2 Provost of the University of Nebraska, which was the 3 second in command of the entire system. That was when 4 we had one IRB for, at that time, three campuses. 5 Then, eventually, the IO position moved 6 down to the Office of the Chancellor of the Medical 7 Center, and we had an IO for two campuses at that 8 particular time. And he was, of course, the CEO of my 9 institution, and he was very, very supportive of the 10 IRB. But he had no concept of what we did, and 11 basically all of the authority for running the program 12 was delegated to me, but I had no resources, and I had 13 to go to him. 14 Now, fortunately, I was given all the 15 resources I needed. And then, over time, we felt it 16 was probably better to -- to adopt the Minnesota 17 model, and the IO's position was moved down to the 18 Vice Chancellor for Academic Affairs, who basically 19 had kind of the same attitude as the CEO. He was a 20 basic scientist, didn't know very much about the IRB, 21 but was very, very supportive. And, again, it was 22 relegated to me. 39 1 I'm still in the same position of running 2 the program but having no resources, being totally 3 dependent upon someone else to give me the resources, 4 which is usually the Chancellor. I have to go to the 5 Chancellor and say, "I want -- I want the money." 6 MS. BROOKSHIRE: Right. 7 CHAIRMAN PRENTICE: So I guess my question 8 to you, Dick, is as a -- in your position, do you 9 control the budget totally for compliance-related 10 activities? 11 DR. BIANCO: Well, I don't want to sound 12 like a former President, but define "control." I mean 13 -- 14 CHAIRMAN PRENTICE: Well, do you -- 15 DR. BIANCO: -- not even the President can 16 control the budget to a certain level. 17 CHAIRMAN PRENTICE: Well, I mean, are you 18 given -- are you given a definitive budget, and when 19 you need money you're able to get it -- 20 DR. BIANCO: Yes. 21 CHAIRMAN PRENTICE: -- rather easily? 22 DR. BIANCO: Yes. Well, not rather 40 1 easily. I am -- we must provide a case. And when we 2 -- like most states, we're in a period of shrinking 3 support of institutional, but we have a budget that I 4 think is -- is pretty good. 5 We recently added three people, and I can 6 advocate for resources directly to the President or 7 the VPR or the Academic Health Center, which is 8 actually a much more effective position. I have three 9 pots to go after rather than one. 10 CHAIRMAN PRENTICE: Now, you mentioned the 11 change in culture at Minnesota as a consequence of the 12 ALG problem, which actually the FBI investigated us as 13 well because we were buying your drugs. 14 DR. BIANCO: Oh, I didn't realize that. 15 CHAIRMAN PRENTICE: Yes. 16 DR. BIANCO: Okay. Have you paid the 17 bills? 18 (Laughter.) 19 CHAIRMAN PRENTICE: Fortunately for you, 20 we are very responsible in paying you. 21 DR. BIANCO: Very good. Thank you. 22 (Laughter.) 41 1 CHAIRMAN PRENTICE: That'll enable you to 2 pay that fine to the Federal Government. 3 DR. BIANCO: It's quite a fine. 4 (Laughter.) 5 CHAIRMAN PRENTICE: So back in the '90s, 6 you had some impetus that obviously changed your -- 7 your culture. And then, certainly -- and we indicated 8 this yesterday -- beginning in 1998, there were lots 9 of institutions that had the impetus that changed 10 their culture as a consequence of the shutdowns. 11 There is some worry that institutional 12 memory is beginning to fade. Do you think that that's 13 the case? We're kind of over the fear of the 14 shutdowns, so consequently, we're beginning to -- to 15 regress across the country where, yes, we have more 16 resources for IRBs, but we don't have the same 17 motivation that we had in the late 1990s and the early 18 part of this decade to really make changes. Do you 19 think that that's becoming a problem? And that would 20 be a question for both of you. 21 MS. BROOKSHIRE: Well, I have heard an 22 institutional official say that OHRP is not the last 42 1 word. Does that answer your question? 2 CHAIRMAN PRENTICE: Bern, would you care 3 to comment? 4 (Laughter.) 5 DR. BIANCO: That's interesting. I think 6 that we're all human. I mean, human nature comes into 7 play here. I mean, obviously, there is -- as 8 financial pressures get higher in the States. There 9 is a tendency to cut corners, I believe. And I think 10 this is a time that we must be vigilant. I do see a 11 little bit of a backslip in attitude. 12 Not to saying that shutdowns -- well, 13 shutdowns, as they occur, they occur, and that wakes 14 up everybody. And sentinel events are important, 15 because of human nature. It refocuses you, and you 16 feel sorry for the other guy, but you say, "I'm glad 17 it's not -- let's make sure it's not us next." 18 So I do -- to answer your question, yes, 19 there has -- I think there is some slippage, and a 20 little bit more of a relaxation out there. 21 CHAIRMAN PRENTICE: So given that, what do 22 you think we ought to do about that? That's a 43 1 question for both of you. 2 DR. BIANCO: Well, I think that one little 3 part of it is part of the message I was trying to give 4 this morning, is that the IO part of the human 5 subjects protection program is the weakest link we 6 have. I really do believe that. 7 We have professionally -- we have 8 accredited the programs, and I know that AAHRPP 9 visitors look at the integrated approach and make 10 comments on the organization -- and make comments on 11 the organizational structure that are very helpful. 12 But I don't think other institutions have gotten that 13 message. 14 I think that if we -- from my little part 15 of it, the IO part of it, we need to strengthen that, 16 and that will lead to culture -- the maintenance of 17 the culture of compliance, I believe. 18 CHAIRMAN PRENTICE: You mentioned a 19 recommendation to have a conference for IOs, and you 20 -- I think you offered to host it in January. 21 DR. BIANCO: Absolutely. And I will do 22 that. 44 1 (Laughter.) 2 We can move it to July, if you wish. 3 (Laughter.) 4 CHAIRMAN PRENTICE: Would you care to 5 comment further on that? 6 DR. BIANCO: Well, I think -- I mean, it 7 has the -- my counterpart at Iowa, who, as we all 8 know, they've been under attack by the animal rights 9 people recently, but he suggested a Big 10 IO 10 conference, and I said, "No, it's got to be a 11 national," because we've all been going to PRIM&R for 12 years, or many of us, and there's only -- when I first 13 started going to PRIM&R, I think I might have been the 14 only IO there. 15 There was no interest in this, and there's 16 no other conference in the country or annually that is 17 focused on the issues we should be focused on than 18 PRIM&R. There were no IOs. There's more now, but we 19 need to engage the IOs. We need to -- they need to 20 understand what their signature on the assurance 21 means. They need to be trained in subjects 22 protection, 2005 standards. 45 1 Perhaps it will lead to more applications 2 for accreditation if there's a knowledgeable IO. So 3 I just think that to share experiences, to share our 4 institutional foibles, and to get organized a little 5 bit, perhaps include the chairs of IRBs in this group, 6 and the directors of subject protection programs, to 7 make it a really -- a focused -- focused organization 8 on subjects protection that can be responsive to 9 changes -- relaxation in the culture, responsive to 10 changes out of Washington, and regulations out of 11 Washington. 12 That's just my personal view. I mean, I'm 13 not a fan of another organization or another meeting. 14 God knows, we go to enough of them. But I think that 15 this one is needed, because there isn't one. 16 CHAIRMAN PRENTICE: I guess one final 17 question that I have, and I'd like to open it up to 18 the members of SACHRP to ask more questions, if an 19 institution has a culture problem, and you have an IRB 20 administrator and an IRB chair who are -- who are 21 dedicated to human subject protection, what do you 22 think they can and should do to try to change the 46 1 culture? Is it possible to change the culture from 2 within at a lower level? 3 MS. BROOKSHIRE: I think it is certainly 4 possible in the process of the negotiation that goes 5 on between the IRB and investigators, and I think it's 6 -- you know, having that communion is really a way to 7 change a culture. And from my experience, some of the 8 most difficult investigators have really come on board 9 and understood their responsibilities, if they're 10 treated with respect by the IRB administrators as well 11 as the committee. 12 And one of the ways that we have achieved 13 that is by explaining to investigators why we have the 14 conditions that we do, and basically tell them what it 15 is we need to see in order to get approved. And so we 16 have established a very -- a very strong dialogue with 17 investigators just to help them through the process, 18 and that really does help in terms of that part of the 19 hierarchy and the culture. 20 CHAIRMAN PRENTICE: Okay. And I guess one 21 final comment, Dick. I've met your superstar. I went 22 to Minnesota on an LCME accreditation visit, and -- 47 1 and he came in to address the site visit team that 2 consisted of a whole lot of deans of medical schools. 3 And it was very clear -- he walked in, and he was 4 running it. He was running the meeting. So I'm sure 5 you had your hands full during those years. 6 DR. BIANCO: It was an interesting period 7 of my life. 8 (Laughter.) 9 CHAIRMAN PRENTICE: Okay. The format is, 10 of course, you need to be recognized. 11 Mark, you had your hand up first. 12 MR. BARNES: Thank you for, I think, very 13 enlightening presentations. Those were -- those were 14 thought provoking. 15 I want to sort of throw a fire bomb and 16 then get your reaction to it. Okay? I have a feeling 17 I know what your reaction will be. I think you will 18 probably agree with me. 19 You know, the -- and this I think I'm also 20 going to put on the table, since the whole day is 21 really -- or much of today is about investigator 22 education and training and compliance. What we talk 48 1 about in terms of research compliance is only one part 2 of sponsored research compliance. 3 There are other parts of sponsored 4 research compliance that are integrally connected to 5 human subjects protection, but they are also about the 6 wise use of money, the wise hiring of staff, 7 appropriate time and effort reporting of 8 investigators. And I will tell you that my personal 9 experience is where there's -- where an investigator 10 is lax and sloppy about one area, they are lax and 11 sloppy about other areas as well. 12 And so the fire bomb that I would like to 13 throw is to say this, and, of course, different 14 universities, you know -- the cultures of different 15 universities are different, and I myself come from an 16 academic family and am very -- therefore, very 17 sympathetic to the idea of these beleaguered doctors 18 and investigators being pummeled by regulations and 19 everything else. 20 With that said, here's the fire bomb, and 21 that is that -- that the NIH, CDC, HRSA, and the other 22 federal agencies, they do nobody any favors when they 49 1 deify the principal investigators of grants and allow 2 principal investigators to bypass institutional 3 officials, not only for IRB and human subjects 4 protection but also for grant terms and conditions and 5 financial compliance, when they allow those PIs to 6 bypass the institution, go directly to the NIH grant 7 official, or the CDC grant official, and that grant 8 official allows the institution itself and its 9 accountability and its responsibility and its 10 authority to be bypassed. 11 That's what I would like to put on the 12 table is that they do us no favors, they do science no 13 favors, they do human subjects protection no favors, 14 and they do financial accountability no favors by 15 deifying principal investigators. 16 MS. BROOKSHIRE: I agree. And it's 17 interesting because those investigators -- and I've 18 seen this at site visits -- and we -- you know, every 19 institution has their star, or stars as it may be, but 20 those are the people -- those -- it's interesting, 21 because those investigators who submit the poorest 22 documents and do not really apply the regulations to 50 1 their applications are the ones that are the -- who 2 complain and go, you know, to the different levels, 3 saying, you know, "I need special treatment." 4 And it's -- and I think that what you're 5 saying is exactly what I'm saying that happens at some 6 institutions. They want to bypass institutional 7 policy. They want to bypass institutional regulations 8 and policy and go and get special treatment. And it's 9 usually those people who have -- who really need more 10 help than others and are not submitting protocols on 11 the IRB level that can be approved. 12 DR. BIANCO: Well, as you probably know, 13 Mark, I would totally agree with that, and it is -- 14 for other entities to handcuff us, and me, in our 15 roles is incomprehensible to me, and especially 16 concerning the areas of biosafety, the shipment of 17 materials to our institution without us knowing about 18 that. This is directly contrary to the laws and 19 regulations. 20 We hold the faculty accountable to the 21 policies of the Regents of the University of 22 Minnesota, certainly the laws of the land, but also to 51 1 the policies. So if they are outside of those 2 policies, and even if the Federal Government says this 3 is wonderful, they are in default with our policies, 4 and there will be consequences. 5 MS. BROOKSHIRE: It seems to me that there 6 should be another session just on your point, because 7 it's really separate from the issues we have with 8 institutional officials are what we want to do in 9 terms of education and integration of institutional 10 officials. But I think what you're saying is very, 11 very important, and it should be looked into. 12 CHAIRMAN PRENTICE: Mary Lake? 13 DR. POLAN: I actually have two questions 14 that are really informational. The first one I'm 15 going to follow right up on this. I didn't know that 16 there were two-tiered or three-tiered levels of 17 compliance in this country. How frequently does this 18 occur, that you have superstars who walk in and are 19 able to waive or change regulations? Is this a common 20 occurrence? You know, is it one out of 100 PIs, or 21 one out of 1,000? 22 MS. BROOKSHIRE: I would say it's fairly 52 1 common, but I would -- I would codicil that with, it's 2 more -- it's a difficult thing to -- to assess, 3 because it's more pressure than going around the 4 regulations. It's pressure on the Institutional 5 Review Board to approve. It's complicated, but I 6 don't think it's going actually -- in the face of the 7 regulations, by putting pressure on the committee to 8 perhaps not do due diligence in the review and look at 9 safeguards to the level that they should. 10 DR. BIANCO: Do you know where that 11 pressure most often comes from is the office of a 12 Senator or a Congressman. 13 DR. POLAN: Oh, really. So it's not the 14 PI, or it's the PI working through some political 15 process. 16 DR. BIANCO: Exactly. Exactly. 17 DR. POLAN: Interesting. And what happens 18 in private institutions? 19 DR. BIANCO: What happens what? I'm 20 sorry? 21 DR. POLAN: What happens in private -- not 22 state-sponsored institutions? What happens in private 53 1 institutions? Do Senators -- 2 DR. BIANCO: I have no idea. I've never 3 been in a private institution. 4 DR. POLAN: Okay. Mark? 5 MR. BARNES: I'll tell you what my 6 experience is. Again, every institution is different. 7 So Boston University -- this is not true. Boston 8 University, in the tradition of John Silber, then 9 clearly the PIs answer to the Provost and the 10 administration. 11 But in many private universities, then, 12 the -- you know, and especially in the medical school 13 setting, there is -- you know, the sort of superstar 14 status is tied to patient admissions, it's tied to 15 financial clout, it's tied to specialty, with, of 16 course, surgeons being at the -- and transplant 17 surgeons being, for example, at the top, because they 18 attract so much funding, etcetera. Oncology as well. 19 But what's most important is -- in my 20 experience has been, what is the tradition of the 21 university? And if the tradition of the university is 22 that -- that individual tenured faculty most often are 54 1 allowed to cry academic freedom as the defense to any 2 oversight of their research practices, financial 3 practices, grant administration practices, personnel 4 practices within their labs, if that's the tradition, 5 then that's the tradition, and they're allowed to say 6 academic freedom and, thus, you know, really sort of 7 shorten or abbreviate or even completely frustrate any 8 kind of oversight, any kind of meaningful oversight by 9 the administration. 10 DR. POLAN: Well, that ties into my second 11 question, which was: how do you change -- prior 12 discussion. How do you change the culture of an 13 institution? 14 And as I listened to Dick talk, the 15 statement that you are involved in IRB -- not just IRB 16 processes but also in research, so you see it from 17 both sides, I think it's tremendously important when 18 you deal with people who are clinicians or basic 19 researchers who are trying to get animal protocols 20 through. 21 It is much nicer to talk to somebody who 22 actually understands why you are pushing and what the 55 1 issues are. So I -- I don't -- where I am, the people 2 who run the IRBs are physicians. Now, it's a very 3 difficult thing to get people to give time to that, 4 since it's not reimbursed by anybody, including the 5 university. 6 So how do you -- how do you get that sort 7 of buy-in by your faculties so that they participate? 8 Because one way to answer some superstar who screams 9 "academic freedom" is to say, "Wait a minute. I'm a 10 tenured faculty member," and that is just not so. 11 DR. BIANCO: That is the most effective 12 response. We -- the issue is not financial. We do 13 reimburse our chairs for service, or offsets. The 14 issue with academic progress, how do you reward your 15 physicians for service in terms of their academic 16 career, but also in the lost patient revenue? Those 17 are issues we're all wrestling with constantly. 18 I think it's more important to provide 19 some academic in the promotions and tenures process, 20 some academic credit for service. And we are working 21 towards that at Minnesota. 22 But I am lobbied constantly, every day, by 56 1 faculty, by subjects protection staff, by IRB members. 2 By knowing the issues, I can't be swayed -- I can be 3 swayed certainly, but I certainly know both sides, and 4 it helps me be more of an effective advocate for both 5 sides. And I think you can only do that if you're -- 6 if you're in both sides of the camp, really. 7 DR. POLAN: Well, you can be swayed, but 8 you can't be blind-sided, or have an argument -- 9 DR. BIANCO: Exactly. 10 DR. POLAN: -- that's got no validity at 11 all dumped on you. 12 DR. BIANCO: You can recognize nonsense 13 when you hear it. 14 DR. POLAN: Right. 15 (Laughter.) 16 CHAIRMAN PRENTICE: Felix, you're next. 17 After Felix, Ada Sue. 18 DR. GYI: I find this discussion to be 19 very enlightening, as well as informative, so thank 20 you very much for your time. And when you're ready to 21 pull that meeting together, I hope you'll call me, 22 because right now, when we talk about IOs, we tend to 57 1 look at it under a linear institutional model, which 2 is not where most of the research exists. 3 And I don't have data to support that 4 human subject protection has been compromised or that 5 there is lack of appropriate oversight in those 6 private research settings. But, clearly, if we're 7 going to harmonize and have one system, we should have 8 people who are held accountable in an appropriate way. 9 FDA looks towards the clinical 10 investigator, but doesn't have that institutional 11 empowerment, so you'll have to correct me, David, in 12 terms of how you view this whole model transferring 13 over. 14 But it seems to me that there needs to be 15 some level of institutional oversight and a go to jail 16 guy that exists everywhere, so that we can have that 17 permeation of that culture that exists. But even as 18 we talk now, and as we look at the education of 19 investigators, we still focus in on the academic 20 medical center model, where perhaps less and less 21 research is being done that's commercially sponsored. 22 And how do we hold those folks 58 1 accountable? And how do we incorporate them into this 2 model? There are certification programs for clinical 3 investigators, but I don't hear a lot of investigators 4 from the academic side rushing to get that type of 5 certification because I think that there's this 6 prevailing feeling that I'm in an academic medical 7 center, and, therefore, I'm afforded the patina of 8 working within the academic institution. And I think 9 that carves out a whole body of investigators away 10 from clinical research. 11 Sponsors are fighting with this particular 12 notion, because they are having less and less 13 qualified investigators to go to. If we take a look 14 at the 1572s, the majority of them have investigators 15 that have conducted research less than a year or many 16 investigators that conduct one research study and then 17 don't come back. 18 So I think that that hurts the human 19 subject protection program. So how do we integrate 20 the model that we have of having one go to jail guy, 21 institutional official, and impose that onto the other 22 side which is a non-academic medical model? 59 1 DR. BIANCO: By non-academic model you're 2 talking -- are you speaking of social research? Are 3 you speaking of private physicians with adjunct 4 appointments? 5 DR. GYI: Well, you know, let's not 6 complicate it. Let's talk about the non -- just this 7 biomedical model of clinical research, because I think 8 that when we start to talk about the social science 9 research, it takes on a complexity. But most of that 10 research still is being conducted under an academic 11 umbrella, even though we see a fair amount of that 12 shifting away from the academic side into the private, 13 non-academically affiliated investigator population. 14 MS. BROOKSHIRE: I would say that most 15 institutions, medical institutions, do require 16 certification and training for all of their 17 investigators. And I would say that that model should 18 be out in private -- you know, in private IRBs and for 19 all clinical research. And that's what you're talking 20 about? 21 DR. BIANCO: That is. 22 MS. BROOKSHIRE: That the requirement for 60 1 certification and training for all investigators, 2 regardless if they're institutional investigators or 3 out in the community. 4 DR. BIANCO: We have a centralized model 5 where we -- and we also are developing an affiliation 6 agreement. I think the problem is IRB-shopping in a 7 lot of respects, but we hold our faculty -- if they 8 have a faculty appointment at Minnesota, they are 9 required to use our IRB. Period. And they're held to 10 the same standard as a full-time tenured professor of 11 surgery. There is no difference to us. 12 But I think the most effective way that 13 you can get a handle on this is post-approval 14 monitoring of all clinical protocols. I mean, our 15 monitors go to all hospitals that we are affiliated 16 with to maintain -- to make sure that all protocols 17 have gone through the right approvals and are in 18 compliance. But the way you maintain the culture is 19 to have one culture. 20 MS. BROOKSHIRE: So, in that instance, 21 when they come back and they find that there are 22 deviations to the protocol, does it come back to the 61 1 IRB? 2 DR. BIANCO: It does. 3 MS. BROOKSHIRE: Okay. 4 DR. BIANCO: It does. And we have an 5 affiliated -- we have the Fairview system in 6 Minnesota, who owns our hospital, but they also have 7 non-affiliated hospitals. But Fairview has contracted 8 with us to do the post-approval monitoring for them. 9 So we try to have a consistent -- consistent rules and 10 apply them consistently. 11 CHAIRMAN PRENTICE: Felix, let me try to 12 get a clarification of where you're going. Roughly 13 70, 75 percent of clinical research is conducted out 14 in the private sector by private physicians who are 15 not necessarily affiliated with an academic medical 16 center, who have to utilize the review services of an 17 independent IRB. 18 There is no IO model for those 19 individuals. So is that -- is that where you're 20 going? And FDA has no requirement for, obviously, an 21 IO, and you can't really have an IO that would have 22 oversight authority over a couple of private docs, you 62 1 know, in an internal medicine clinic doing a clinical 2 trial. 3 It seems to me that the oversight almost 4 has to rest with the independent IRB, because you're 5 the ones that review the protocol. You're the ones 6 that review the site, the investigators, the 1572, and 7 you decide whether or not you're prepared to -- you 8 know, to approve the addition of that investigator. 9 So perhaps I'm going to throw this back at 10 you. What do you think you ought to do to solve this 11 problem? 12 DR. GYI: Because I am the IO, I am 13 concerned about the fact that I will be going to jail 14 because somebody else might not be in compliance with 15 what they're doing. 16 CHAIRMAN PRENTICE: Exactly. 17 DR. GYI: And so the concern, though, is 18 that to put the gatekeeping activity -- and Dr. 19 Schwetz will perhaps have a chance to talk about this 20 still -- gatekeeping activity back on the IRB, may not 21 be entirely appropriate in a decentralized model that 22 has -- that doesn't have a linear relationship. 63 1 But a shared responsibility may be more 2 appropriate. And I haven't thought this through, but 3 -- and the reason for asking the question is: how do 4 we disseminate information to those research sites 5 that they have to have some level of authority and IO 6 responsibility? Right now, the stick is through the 7 FDA's bioresearch monitoring program, and the clinical 8 research has responsibilities. But that's a little 9 bit different than the IO model that we've been 10 discussing here in terms of allocating resources. 11 I think it ties back in, but it is a 12 little bit different. My question to this group is: 13 how can we disseminate that and have one system of 14 oversight and protection that makes sense? And we may 15 not have an answer to that, and we may have to have, 16 you know, folks like Dr. Speers help us to provide 17 that stick appropriately through the accreditation 18 process, et cetera. 19 CHAIRMAN PRENTICE: That's a good idea. 20 I think AAHRPP ought to be the IO. 21 (Laughter.) 22 The "Go to Jail Gal." 64 1 (Laughter.) 2 All right. Ada? Ada Sue? 3 MS. SELWITZ: Again, I want to thank you. 4 You all did a wonderful job. It was provocative. It 5 was interesting. I want to make two comments. 6 First of all, Dick, I love your idea of 7 IO. I think PRIM&R would be very interested in co- 8 sponsoring, and I think that's a good idea. I think 9 the key is: how do you get the IOs to go to something 10 like that? And another option might be to co-sponsor 11 with PRIM&R and with an organization such as AAMC or 12 AAU where the IOs are going to the meetings anyway 13 with their other hats on as well as their research 14 compliance hat. But something along that line might 15 work well, but I think that's a great idea. 16 The question I have to you -- and I will 17 first explain it -- in my situation at Kentucky, I 18 really do have an ideal IO situation, because my IO is 19 educated, plus she controls the resources. I don't 20 have to go to somebody else. I don't have an in- 21 between person. Our IO controls the resources, at 22 least at this present time. 65 1 And it had bothered me when AAMC -- you 2 know, Judith, you had the slide up there -- AAMC came 3 out questioning whether even a vice president of 4 research could avoid conflicts of interest. And, you 5 know, there is a point at which I get very concerned, 6 because at least in my experiences -- and I have gone 7 through a number of vice presidents -- I have not 8 experienced conflict of interest. I mean, they have 9 understood compliance and been supportive, so I 10 haven't had the conflict of interest experience. 11 And I would like for you all to discuss 12 that if you could a little bit further. I mean, what 13 are your opinions on this whole concern that even a 14 vice president for research might have conflicts of 15 interest and wouldn't be appropriate as serving as the 16 IO? Because often it's the vice president that does 17 have adequate resources and access. 18 MS. BROOKSHIRE: If that's the same person 19 that's responsible for bringing in grants, and 20 bringing in money, and the only thing that's standing 21 behind -- between bringing in the money and -- is the 22 Institutional Review Board, there could be a conflict 66 1 there, and there could be pressure exerted upon that 2 person. 3 It's the same as an investigator who has 4 an interest in both their patient as well as the 5 research, and interest in the subject. I mean, I 6 think conflict of interest is -- can happen in the 7 instance where somebody is responsible for bringing -- 8 having a very large portfolio of research and is -- 9 and may or may not, because they're not educated or 10 integrated into the process, understand the importance 11 of the IRB review and look at it as a boondoggle. 12 MS. SELWITZ: Well, let me ask -- and then 13 we'll go to Dick -- one followup question on that. 14 But if we followup on what Felix said -- I mean, in 15 that situation, you have an investigator, and the 16 investigator or the investigator sponsor is paying the 17 IRB to do the review -- and, Felix, this is not -- I'm 18 just saying there are inherent conflicts of interest 19 there at will. 20 And so if you accept what Ernie said, 21 which is what I was sitting here thinking, I thought 22 -- in that situation, I really thought that the 67 1 independent IRB was also sort of the equivalent, not 2 completely, but along the lines of the IO. All right? 3 And I'm not sure that's accurate. That was just my 4 outside perception. 5 But there are inherent conflicts of 6 interest there, because there you've got the IRB who 7 is also sort of an IO. I know these private 8 physicians don't have -- and you have -- I mean, 9 you've really got two players as opposed to three. So 10 how does that sort out? So you're talking from an 11 academic standpoint, so what do you think in terms of 12 the private sector and the private physician? I mean, 13 isn't that also a potential conflict of interest? 14 MS. BROOKSHIRE: Well, actually, I think 15 it's very possible to put these safeguards in place 16 and policies that enable people to do this without a 17 conflict. And I think in terms of academic 18 institutions the -- to me, I don't think that academic 19 institutions are going to be able to continue to 20 support and provide an infrastructure sufficient to do 21 an adequate IRB review for clinical trials as we go 22 forward. 68 1 There just -- there's not the 2 institutional, you know, resources for that. And I 3 think it's very important -- your position and your 4 point is very important for everyone to iron out, so 5 that we don't have these conflicts, and that we follow 6 a pattern of -- and standard for all research 7 enterprise in IRBs, whether they're private or 8 institutional. 9 I think there are clearly ways to do it, 10 and, as you were saying earlier, it really depends on 11 the culture. 12 DR. BIANCO: Well, I think that to go -- 13 one segment is institutional conflict of interest, and 14 most institutions are working on this -- these 15 policies, but we actually have been doing that for 16 about a year and a half. And a key part of that 17 policy is the actions of senior officials. They are 18 working on behalf -- they are representing the 19 university with actions. 20 Now, in the VPR -- Vice President for 21 Research -- is an interesting position when it comes 22 to oversight for research. We accept equity in 69 1 startup companies. We advocate for intellectual 2 property transfer and then licensing back to do 3 clinical trials, sponsoring clinical trials. 4 Now, look, all of those things the VPR is 5 going to have to recuse himself when it comes to these 6 things. By lowering the IO and having the IO focus on 7 compliance and not be holding, in any way, shape, or 8 form, or not caring about what the institution's 9 holdings are, eliminates the perception -- perception 10 is what we deal with mostly -- there are very few 11 actual conflicts -- it eliminates the perception of 12 conflict of interest in the public's mind and in the 13 Minneapolis Star Tribune's mind. It's an extremely 14 important point. 15 The second point I'd like to make is it 16 provides cover for the VPR. I'm using the term 17 "cover" in a positive sense. The faculty thinks they 18 can -- you know, they have the option of going to 19 appeal -- and I'm not talking about classic appeal of 20 IO decisions, but they can go to the VPR and discuss 21 the problems with me or the IRB or the animal care 22 community. That's very important -- for the faculty 70 1 to feel that they can do that. I totally support 2 that. 3 I mean, the footprints on my back are 4 fine. I don't have any problems with that. 5 (Laughter.) 6 But it's an important organizational 7 venting for faculty. 8 CHAIRMAN PRENTICE: Tom? 9 MR. ADAMS: Thank you. I, too, have 10 enjoyed the conversation thus far. We talked a little 11 bit about certification. Clearly, certification for 12 people who are involved as clinical research 13 associates, clinical research coordinators, is -- is 14 well established. 15 When you take that to PIs, that's really 16 not the case. I mean, we've got basically in the 17 country about 425 to 450 PIs who have achieved 18 certification from the three major certifying groups. 19 And so I guess my question is: what could the 20 institutions do to encourage PIs to at least achieve 21 that base level of knowledge that certification would 22 indicate? 71 1 MS. BROOKSHIRE: Well, I can say at UCLA 2 you cannot be an investigator if you haven't been 3 certified and gone through training. We actually at 4 UCLA have our home-grown -- home-grown certification 5 process. It's very involved and extensive, and it's 6 available on our website. 7 We also encourage other accreditation and 8 certification, but you cannot be an investigator 9 without having gone through that. And IRB members 10 cannot be on the boards without also having 11 successfully gone through -- we have both biomedical 12 and sociobehavioral components of the certification. 13 And the IO has to go through the certification as 14 well. 15 DR. BIANCO: I think that -- a couple 16 comments on that -- I suffer no delusion that 17 responsible conduct of research certification has any 18 value for a faculty member. Usually their beeper is 19 going off every five minutes; they're not paying 20 attention anyway. 21 So -- and I don't mean to be cynical. 22 That's just the way it is. So what we have kind of -- 72 1 what I'd like to concentrate on is really the line of 2 first offense for subjects, and that's the nurse 3 coordinator position. Education and training, working 4 with our monitor, certification perhaps of that 5 position, I think will lead to more faculty awareness 6 of the need to educate themselves. 7 Perhaps I'm being delusional, but I -- we 8 are focusing on nurse coordinators right now. 9 Certainly our faculty, as UCLA, must be certified. 10 But these are -- I mean, let's look at the other side. 11 These are physicians that practice medicine. They are 12 certified and CEUs and they're well trained, and they 13 really do have the patients first in their minds, and 14 I believe that wholeheartedly. 15 But they're not trained to organize their 16 data properly, to make sure they're using the right 17 version of a consent form. Those sorts of things are 18 crucial to protect human subjects, and that comes down 19 to the nurse coordinator in my view. 20 MS. BROOKSHIRE: I have to say that anyone 21 that's involved in the protocol and works with 22 subjects has to be certified. It's not just the 73 1 principal investigator. But ultimately it's -- 2 whatever happens, the responsibility lies on the PI. 3 CHAIRMAN PRENTICE: Dick, I'd like to 4 reinforce what you said. We have a required training 5 program for all study personnel, whether they're a PI, 6 secondary investigator, protocol coordinator, even 7 somebody who analyzes the data. They've got to be 8 listed on a protocol. They have to go through the 9 CITI training program, which Paul is going to be 10 talking about a little bit later. 11 However, aside from that required 12 training, we focus our efforts on the protocol 13 coordinators. They're the ones that attend our in- 14 services. Quite frankly, we can't get the 15 investigators to come. They are too busy. You know, 16 they're operating on people, they're saving lives, 17 whatever else they're doing. They don't have time to 18 come to these sort of "lunch and learn" sessions. 19 So, we find if we can educate the 20 coordinators, they in turn can get to the 21 investigators. So, I certainly support what you're 22 doing. 74 1 Felix, you're next. 2 DR. GYI: I just wanted to add to Ada 3 Sue's comments. I think part of the problem that we 4 have is in applying a vernacular that was perhaps 5 crafted at a point in time when it made sense. 6 Currently, to call something an institution really has 7 a lot less meaning. 8 What do we mean by an institution and an 9 Institutional Review Board as Chesapeake that's 10 decentralized, the institution that has oversight over 11 research that's conducted over multiple sites, or are 12 those individual sites individual institutions that 13 have to have institutional responsibility and IOs at 14 those institutions? 15 And perhaps we ought to think along those 16 lines to help us tease out some of these issues, 17 because sometimes we get caught up with just calling 18 it one thing and then applying it across the board. 19 CHAIRMAN PRENTICE: Susan? 20 MS. KORNETSKY: I just want to go back -- 21 thank you, both -- and I've been listening to the 22 discussions about IOs and where they should fall 75 1 within an institution. And you are both from very, 2 you know, state -- very large institutions, and I 3 think we've brought up the issue that they're all 4 different variations on the theme. 5 And I would just like to stress that it's 6 important. I don't think there's any one particular 7 model. And in my own institution, we don't even have 8 the different levels. There aren't as many levels 9 that exist in your institutions to be able to even 10 drop it to a certain level. 11 So I think it's really important to look 12 at the outcome. I think you've all brought up very 13 important issues about what needs to be avoided, where 14 the conflicts are, and I think there -- I get 15 concerned that we would think about becoming too 16 prescriptive, that it's either here or it's there or 17 it doesn't work, because, you know, Ada Sue has a 18 model, we have other models that -- you know, where 19 administratively we report one way, the chair reports 20 to another direction. 21 So I just want to -- I just want to really 22 point that out, that the end result is what's 76 1 important to me, that we achieve all of the things 2 that you've avoided and not necessarily to be 3 prescriptive, that it can -- it can or can't be at the 4 highest level or should be lower. 5 CHAIRMAN PRENTICE: Yes, Nancy. 6 DR. JONES: I just wanted to comment back 7 on ¦ I did the education component that you've talked 8 about, and I do agree that, you know, in terms of once 9 the wheels have been churning, and you're trying to 10 comply and get the research going, that the 11 appropriate place to focus are on the nurse 12 coordinators and the different points there. 13 But my concern is that a lot of times when 14 we have been doing all of these subparts, and we keep 15 on saying the investigator should know how to balance 16 this risk, or design the research in this way, so that 17 there is less, you know, inherent risk or understand, 18 you know, the component analysis now that we've just 19 said is a new part. 20 And so while I agree in terms of the 21 practical aspects that the nurse coordinators are 22 essential for the daily functioning, you are still 77 1 going to miss that component of designing better 2 research and helping the researchers, you know, write 3 the protocol in the best way to enhance -- 4 DR. BIANCO: I did not mean to suggest 5 that we are ignoring the faculty member. 6 DR. JONES: Right. 7 DR. BIANCO: And I think that what we have 8 done, and I -- and many places have done it -- is used 9 the scientific review committees who have served in 10 that function. The GCRC at the University of 11 Minnesota and the Cancer Center have peer review -- 12 true peer review of each proposal, and they will -- 13 and they're not shy about commenting on study design, 14 statistical issues, non-IRB issues, and certainly IRB 15 comments on those subjects, too. So there is an 16 educational process there, too. 17 CHAIRMAN PRENTICE: Mark? 18 MR. BARNES: I wonder -- I mean, I think 19 that everybody here who has had a practical experience 20 agrees with your point that the nurse coordinators 21 tend to be the place where there's sort of the 22 pressure point that's most effective. 78 1 But I wonder whether you guys, in your 2 institutions, have experimented with models or tried 3 to do some things with educating doctors when they can 4 be educated and have time to be educated, which is in 5 medical school, internship, and residency. 6 There are some universities -- some 7 medical schools that have begun, you know, different 8 kinds -- in fact, all of them have some kind of ethics 9 or kind of public policy lecture programs for their 10 medical students, but some have more elaborate 11 programs than others, and it's been my experience in 12 teaching in the program at Yale Medical School that -- 13 about these sort of research issues to the first year 14 medical students is that that's a time when they 15 really are able to focus and learn, and they might not 16 understand all of it, but at least they understand the 17 rationale for the regulatory structure. And I wonder 18 whether you've had experience with that. 19 DR. BIANCO: Yes. But, you know, with the 20 -- I think residency is probably a better place, 21 because first year medical students, as you know, 22 they're a little bit overwhelmed right now. The 79 1 curriculum is too large. To add more curriculum is 2 difficult. 3 But I think residents, especially in -- 4 well, obviously, in teaching institutions, that needs 5 to become a core part of it. And certainly there's 6 more and more focus on ethical behavior, how to 7 communicate with patients, and I think it's a natural 8 outspringing of that. How do you conduct research? 9 How do you respect the subject? How do you avoid 10 coercion? All those sorts of issues, absolutely. 11 MS. BROOKSHIRE: I am a part of that and 12 participate in the residency program as well as all 13 other ethical presentations that are required, both in 14 the medical school and on the upper campus for social 15 behavior research. Last year I did over 60 16 presentations, and oftentimes that didactic one on one 17 is very, very helpful, especially when it's 18 discipline-specific. 19 But they're really geared to the ethics of 20 research, and I'm part of that. But, you know -- 21 DR. BIANCO: Remember now, we have to 22 stick within 80 hours per week. 80 1 (Laughter.) 2 MS. BROOKSHIRE: Yes. 3 CHAIRMAN PRENTICE: Any other questions? 4 Okay. I want to pursue the idea of an IO conference 5 a little bit more fully. 6 MS. BROOKSHIRE: Can it be mandatory? 7 (Laughter.) 8 CHAIRMAN PRENTICE: Well, you know, I like 9 -- I like Minnesota, not in the wintertime, but 10 summertime it's okay. Hawaii is better, certainly. 11 We could have a conference for IOs in Hawaii. We'd 12 probably get a, you know, pretty big attendance. 13 (Laughter.) 14 But in terms of how this would be done, I 15 attended one IO conference at Wright State University 16 for animal care and use IOs. I don't know if you were 17 there or not. Do you remember that one, though? 18 Okay. 19 And I thought it was quite well done, 20 quite successful. I mean, we didn't have like 500 IOs 21 there, but we probably had 40 perhaps, which is not a 22 bad turnout. It seems to me that -- that if the AAMC 81 1 offers a conference, or PRIM&R offers a conference, 2 that's pretty much like any other conference. You're 3 not going to draw the IOs. 4 What about OHRP sponsoring a conference 5 where OHRP issues a direct invitation from the 6 Director? I'm going to ask you to comment on this in 7 a moment, Bern. From the Director of OHRP to every IO 8 by name, because you already know who they are. 9 You've got these FWAs where it specifies who the 10 individual is. 11 And if you get that kind of an invitation 12 from the Federal Government -- I mean, I'm not 13 suggesting you're going to get 100 percent attendance 14 or even 90 percent attendance, but I certainly think 15 you're going to get more attendance than if you have 16 a private organization that would sponsor such a 17 conference. 18 So, Bern, I'd like to invite you to 19 comment on that. 20 DR. SCHWETZ: Thank you, Ernie. Let me 21 first thank both of you as the leaders of this 22 discussion this morning. It's been an earful, and I 82 1 might even comment on whether or not OHRP should be 2 the last word. 3 (Laughter.) 4 But reaching the IOs is almost as 5 difficult as reaching the investigators for OHRP and 6 our training programs. We put on 10, 12 conferences 7 across the country throughout the year, and as we try 8 to figure out -- and sometimes we directly ask how 9 many of the audience are investigators, sometimes 10 we've gotten as high as 10 percent. We consider three 11 or four percent a good turnout of investigators, and 12 usually it's less than that. 13 And I don't ask how many institutional 14 officials there are, because it would be less than 15 that, obviously, even if you consider the percentage 16 of them at which there is an IO present. 17 So how to reach them is -- is a difficult 18 problem for us, both investigators and IOs. One thing 19 that we have been doing as we put on our training 20 programs is to target investigators more directly than 21 we have before by simply having an invitation for 22 people to attend our -- our regional or national 83 1 training conference. 2 We could target IOs in the same way and 3 make specific outreach to the IOs to attend our 4 training programs when we hold them. That would be 5 one possible way to reach out. 6 I just recently was invited to the AAMC 7 meetings that had all of the research deans in 8 attendance, and was able to have audience with them to 9 talk about my feeling of how they could help us more 10 to protect human subjects. If we could get -- if 11 there is an AAMC meeting at which IOs and research 12 deans attend, I would be very happy to -- to have 13 audience with -- any time, any place, even if it's in 14 Minnesota in January -- to reach out to that audience 15 by whomever would bring them together. 16 Should OHRP do it? We can. We would most 17 likely do it in partnership with other federal 18 agencies, if we did it, because I think for us in OHRP 19 to do this alone would -- would not be as powerful as 20 if we did it in partnership with the FDA, or if we did 21 it in partnership with other federal agencies who also 22 are dependent on some structure within the research 84 1 institutions to provide the effect that we want from 2 the institutional officials. 3 So I -- I think we need to think more, 4 Ernie, about what -- what is the most effective way of 5 reaching out to the institutional officials. A one- 6 time meeting would be better than nothing. An 7 organizational structure, wherein the institutional 8 officials agree to meet on a regular basis and deal 9 with the issues of institutional officials, would be 10 even better. 11 And I don't -- I'm not going to propose 12 how that would be -- you know, how it should be 13 partnered up with anybody -- with any other existing 14 organization, but it is pretty scary, Dick, to hear -- 15 and I don't question -- I don't doubt at all what you 16 said. It kind of confirms what I was afraid of -- 17 when you say that the institutional officials are the 18 weakest link in this. 19 And there are -- everything is downstream 20 from the institutional officials. And that -- that -- 21 I was hoping that there may be a piece of this that 22 would say where OHRP should be focusing our efforts in 85 1 view of the fact that the institutional officials are 2 not a strong link in this system. But if, in fact, 3 they're the weakest link, that means everything that's 4 downstream from the institutional official is 5 something that we have to focus on to protect human 6 subjects. 7 And all of those things that are 8 downstream from you as an IO, you know, part of that 9 relates to the burdens that we create on this 10 enterprise. That may be part of the reasons why young 11 physicians are reluctant to remain as investigators 12 once they get a taste for it. But also that -- as you 13 well know, that part that's downstream from you, 14 independent of the burdens on the enterprise, that's 15 also where the specific risk to human subjects lies. 16 And I guess we -- we have to keep working 17 to reach the institutional officials, but it isn't 18 right at the sharp edge of where the harm is created. 19 You're right, the culture of institutions -- we see 20 one of -- I think one of the most dangerous things 21 that we see, one of the most upsetting things, in 22 institutions is this -- this culture of indifference. 86 1 That it doesn't matter particularly from the high- 2 level management of an institution what goes on at the 3 level where the risk is, because there isn't an 4 institutional commitment. 5 And, clearly, the IO is part of that, and 6 it's hard to blame investigators for not being 7 particularly concerned when the dean isn't, the 8 institutional official isn't. 9 So I -- Ernie, we can talk more about how 10 we reach out to them, and there are several models 11 that we could use to -- to reach the institutional 12 officials. But I would like to hear some additional 13 thoughts, having all of these nuggets on the table, 14 any additional thoughts that the SACHRP has on what 15 OHRP should be doing to help bring focus to resolving 16 some of this problem? The models are out there. 17 DR. BIANCO: Can I just comment? It's not 18 so much I believe the weakest link; it's that I don't 19 think we're -- we're maximizing what we can do with 20 the IO. I don't think it's effective as we really -- 21 what the design is supposed to be. And I think that 22 to me is the issue; we're not making the most of that 87 1 structure. 2 I think that the best thing to do -- and, 3 I mean, certainly OHRP's involvement or SACHRP -- I 4 mean, when I get a call for -- even -- I'm a 5 blabbermouth, I'll go anywhere to talk about this. 6 But you get a call from SACHRP or OHRP to come to 7 Washington, you come. You come. There's just no two 8 ways about it. You clear your schedule and you come. 9 That -- OIs think like that. That's one 10 of the reasons they're in the positions they are 11 sometimes. But I really do think the best method is 12 if we organize ourselves, and we do it ourselves. 13 Maybe the -- maybe have an initial meeting sponsored 14 by AAMC and maybe, you know, all of the principals, 15 and then let it continue -- have the IOs form an 16 organization themselves. 17 CHAIRMAN PRENTICE: Yes, Mark. 18 MR. BARNES: You know, one thing to bear 19 in mind is that -- is that the members of AAMC are 20 sort of the top of the pyramid here, because they're 21 the ones that actually -- you know, that focus more on 22 who the institutional official is and what it is and 88 1 that sort of thing. 2 But just as -- as Felix was saying about 3 how most of the -- I mean, and as you were saying, 4 Ernie, most of the research that's -- the clinical 5 research that's done is done outside of the academic 6 medical center setting. 7 And so there is sort of the academic 8 medical center setting, then there is the independent 9 IRB setting, with private practice research, but the 10 broad middle range, which is the vast majority of 11 research, is the community hospital research where 12 people who are physicians, who are members of a 13 voluntary medical staff are using the community 14 hospital IRBs as their IRBs of record for the studies 15 done in their private offices, or partly in the 16 private offices and partly on the in-patient side. 17 It's precisely those community hospitals 18 where the institutional officials are, in my 19 experience having advised community hospitals, there 20 is not even any institutional recognition of what the 21 IO's role is, of what they're supposed to be doing. 22 It's just like something that somebody has to sign, 89 1 and so they sign it. Those are the people, I think, 2 whom you want to -- whom OHRP should want to target 3 more than anyone else. 4 Those are not members of AAMC in most 5 cases. They don't know what they're supposed to be 6 doing as IOs. And that, I would venture to say, is 55 7 or 60 percent of the clinical research around the 8 country are those -- it depends on those kinds of IRBs 9 and those people. 10 So the bottom line is that, when you talk 11 about -- I think it's -- it would be important to co- 12 sponsor something with AAMC, but I think that's only 13 about 25 percent of the picture. I think that if 14 those IOs did get a personal letter, you know, 15 addressed to them, which is on -- I'm sure on your 16 database you have all their names and everything -- 17 they would be surprised to be hearing from you, first 18 of all, and that's a good thing, I mean, that they 19 would be surprised to -- to hear from you, because it 20 will -- it will shake them up. And if they were 21 invited, than either -- I mean, I'd venture to say 22 that most of them are either going to show up or 90 1 they're going to send like a top assistant to show up 2 to find out what this all about. That would be a 3 very, very useful thing and very supportive of the 4 IRBs in those institutions as well. 5 CHAIRMAN PRENTICE: Yes. You know, I 6 agree. I remember the agenda from the Wright State 7 Conference to some extent. And it was specifically 8 designed for IOs. Every session was designed to 9 address some kind of an issue that was pertinent to an 10 IO. I mean, it was not an IRB 101. It was not your 11 typical OHRP conference where you've got some stuff 12 there that might be of interest to IOs. But for the 13 most part, you know, it's going to go over