1 DEPARTMENT OF HEALTH AND HUMAN SERVICES SECRETARY'S ADVISORY COMMITTEE ON HUMAN RESEARCH PROTECTION MEETING TUESDAY, MARCH 30, 2004 The Advisory Committee met in the Commonwealth Ballroom in the Holiday Inn Hotel and Suites, Commonwealth Center, 625 First Street, Alexandria, Virginia, at 8:30 a.m., Ernest Prentice, Ph.D., Chairman, presiding. MEMBERS PRESENT: ERNEST D. PRENTICE, Ph.D., Chair BERNARD A. SCHWETZ, D.V.M., Ph.D., Acting Executive Secretary CATHERINE SLATINSHEK, M.A., Executive Director THOMAS L. ADAMS, CAE, Member MARK BARNES, J.D., L.L.M., Member CELIA B. FISHER, Ph.D., Member ROBERT G. HAUSER, M.D., Member NANCY L. JONES, Ph.D., Member FELIX A. KHIN-MUANG-GYI, Pharm.D., Member SUSAN KORNETSKY, M.P.H., Member MARY L. POLAN, M.D., Ph.D., Member, M.P.H. SUSAN L. WEINER, Ph.D., Member MEMBER ABSENT: E. NIGEL HARRIS, M. Phil., M.D., D.M. EX OFFICIO MEMBERS: RACHEL BRAND, U.S. Department of Justice HOWARD L. BRADLEY, Social Security Administration FRANK BRICKFIELD, U.S. Central Intelligence Agency KATHRYN LYNN CATES, U.S. Department of Veterans Affairs ROGER CORTESI, U.S. Environmental Protection Agency PATTY DECOT, U.S. Department of Defense ANITA EISENSTADT, J.D., National Science Foundation SALLY FLANZER, Agency for Healthcare Research and Quality Food and Drug Administration DAVID LePAY, M.D., Ph.D. DAVID SHORE, National Institutes of Health 2 OHRP STAFF PRESENT: MICHAEL CAROME IRENE SMITH-COLEMAN PAT EL-HINNAURY KELLEY BOOKER JULIA GOREY KARENA COOPER KRISTINA BORROR RINA HAKIMIAN SHIRLEY HICKS JUDITH BROOKS JULIE KANESHIRO GLEN DREW MELINA HILL CARLA BROWN 3 A G E N D A ADDITIONAL BUSINESS: . . . . . . . . . . . . . . .4 Ernest Prentice, Ph.D. Chairman, SACHRP LITIGATION ISSUES PRESENTATION: . . . . . . . . . .5 Haavi Morreim, Ph.D. Department of Human Values and Ethics University of Tennessee College of Medicine BREAK: . . . . . . . . . . . . . . . . . . . . . 57 HIPAA PRIVACY RULE PANEL: . . . . . . . . . . . . 58 Susan McAndrew, Office of Civil Rights, Department of Health and Human Services Susan Ehringhaus, Associate General Counsel for Regulatory Affairs, Association of American Medical Colleges Mark Rothstein, Director Institute for Bioethics, Health Policy and Law Joanne Pollak, Vice President and General Counsel, Johns Hopkins Medicine INTERNATIONAL ISSUES - REVIEW/DISCUSSION: . . . .124 Dr. Mary Lake Polan LUNCH: . . . . . . . . . . . . . . . . . . . . .132 ADVERSE EVENTS ISSUES - REVIEW/DISCUSSION: . . .132 Ernest Prentice, Ph.D. PUBLIC COMMENT: . . . . . . . . . . . . . . . . .167 FUTURE BUSINESS ISSUES: . . . . . . . . . . . . .178 Including discussion on Subpart B Conflict of Interest Decisionally Impaired Subjects ADJOURN: . . . . . . . . . . . . . . . . . . . .245 4 P R O C E E D I N G S 1 (8:40:19 a.m.) 2 DR. PRENTICE: Okay, folks. Good morning 3 everybody. We're getting ready to start again. 4 Another long interesting day. I want to briefly 5 overview the schedule for you. As you can see, we are 6 beginning with additional business. There really is 7 no additional business, except to introduce our first 8 speaker, which I'll do in a moment, but we're going to 9 have an awful lot of other business later on during 10 the day so we're not going to spend time talking about 11 that at all. 12 We will move through the sessions. We'll 13 try to stay on time. As you can see, we're going to 14 have a talk on litigation. We're going to have a 15 panel on the HIPAA Privacy Rule. We are going to 16 change the schedule slightly. Dr. Mary Lake Polan has 17 to go back to Stanford on an early afternoon flight, 18 so what I would like to do is to have her talk be 19 given between 12 and 12:30, so we're going to delay 20 lunch for a half an hour. I hope that's okay. We'll 21 have lunch between 12:30 and 1:30, and then we'll move 22 into the talk on adverse events, which I will give at 23 1:30 to 2. We'll have the public comment period 24 between 2 and 3, so if you have a comment that you 25 5 would like to address to the committee, please sign 1 up. And then 3 to 3:15 a break, 3:15 to 4:00 we'll 2 continue with some future business issues, and then 3 hopefully we'll be able to adjourn on time. 4 All right. Moving right along, it's my 5 distinct pleasure to introduce to you a friend and a 6 colleague, Dr. Haavi Morreim, and she's a Professor of 7 Bioethics in the College of Medicine at the University 8 of Tennessee. She has a very long bio here, I'm not 9 going to read it all, but for over 20 years, initially 10 at the University of Virginia School of Medicine, and 11 thereafter, at the University of Tennessee, she's done 12 an awful lot of clinical teaching and consulting in 13 medical ethics. 14 She chairs the Independent Patient 15 Advocacy Council, created to serve patients enrolled 16 in the Abicor Artificial Heart Trial, and I'm sure 17 that a lot of you have read about that particular 18 trial and the subsequent lawsuit. So Haavi has really 19 gotten heavily involved in bridging ethics and law, 20 shall we say. 21 And a little side note, Haavi is a BMW 22 race car driver, so she comes here eminently 23 qualified, and when you hear how fast she talks, you 24 will understand why she drives race cars. 25 6 DR. MORREIM: Thank you. As a matter of 1 fact, I've really got to live up to that today because 2 I'm not going to be going through all of the slides. 3 I don't know if you all have copies of my slides out 4 there or not, but I'm not going to talk about all of 5 them. There's way more than we can possibly talk 6 about in the approximately 20 minutes that I get to 7 yap before we open it up, and so what I'm going to do 8 is basically just focus on a few slides and highlight 9 some issues. 10 By way of overview, I'm going to look a 11 little bit at litigation trends but not really, 12 because you all can read an article that I sent a 13 while back. I'm going to look a little bit at some of 14 the sequelae that might come about, insurance 15 challenges, a certain special issue, the propensity 16 that we're seeing to settle without litigating 17 anything. And above all, I'm going to focus on what 18 I think are some solutions for protecting IRBs, and I 19 think that's really important. 20 For this stuff, like I said, I've got to 21 just go through retro speed. I'm not going to read 22 this stuff. It's very hard to find out what's going 23 on out there by way of litigation because a lot of 24 this stuff gets settled before it even gets filed, so 25 7 we don't really know what's going on there. For the 1 overview, I refer you to an article that is almost on 2 the ground. It should have been out by now, but it 3 will be very shortly, so you've got the site. 4 Potential sequelae, again those of you who 5 have the outline can read that. Some of the problems 6 include just getting people to serve and stay on IRBs 7 as we find more and more litigation naming IRBs. I'm 8 going to be looking a little bit at some of the other 9 players in research, obviously investigators, CROs, 10 SMOs, clinical research coordinators, other folks, but 11 my focus is going to be on the IRBs. 12 Insurance challenges - what I did here was 13 I took a look. I found a number of people who are on 14 IRBs, both independent and institutional IRBs. I 15 talked to a few investigators, CROs, SMOs, some 16 sponsors and people like that just to get an idea of 17 what was going on in the insurance industry. 18 Basic problems - some very disturbing 19 trends I want to call your attention to. One of them 20 is, particularly for investigators, their medical 21 malpractice insurance is not covering research, 22 increasingly true. Some are. In Tennessee we've got 23 State Volunteer Mutual which is a physician- 24 owned/physician-controlled malpractice insurer. They 25 8 do cover research. A lot of insurers, however, are 1 saying Mr. Doctor Investigator, this isn't medical 2 practice; therefore, it ain't medical malpractice; 3 therefore, sayonara, good luck. 4 We're also finding other kinds of recision 5 actions. We are finding, deeply troubling here, if 6 you'll take a look at this one - refusals to cover 7 pediatric trials. And now we're starting to get to 8 see refusals to cover OB trials, so that an IRB that 9 is reviewing a pediatric trial may have to try and get 10 indemnification from the sponsor, or find some other 11 means. This is a very troubling development. 12 We also are finding some problems getting 13 indemnification for, for example, independent IRBs or 14 others who want to. There are some IRBs who do not 15 like the idea of getting indemnification from the 16 sponsor because it looks potentially like getting into 17 bed. A lot of IRBs do because they don't have a lot 18 of choice in this matter, but now we are seeing 19 sponsors wanting cross-indemnification from not just 20 IRBs, but investigators as well, saying look, you all 21 pay for our problems. If litigation happens, we want 22 you to indemnify us, so that's getting increasingly 23 problematic. 24 Premiums are based on a number of things, 25 9 and if you look at this slide and the next one, we are 1 seeing increases in insurance premiums, but as we see 2 30 to 50 percent rises per year, you have to 3 understand how the premiums are calculated. For a lot 4 of independent IRBs they are based on revenues. If 5 revenues are going up, and they are for a lot of 6 independent IRBs, then of course the malpractice 7 premium is going up as a function of doing more 8 business, so it's hard to parse out the actual rises 9 in costs. Similarly, for an SMO it's based per 10 patient. If they're doing more patients then, of 11 course, they're paying more. Again, it's hard to 12 track, and I really did not have much of a chance to 13 get at the details there. We do know the premiums are 14 going up rather substantially. 15 A major challenge here, and I've gotten 16 this from more than one source, insurers do not 17 understand much about research. They think it's 18 medical practice, or they don't understand where the 19 real risks come from. They think that IRBs perform 20 experiments on people. I mean, they don't understand 21 what's going on. A number of insurers have gotten out 22 of the business all together. There are basically two 23 insurers left, so those are some of the things that we 24 have to at least be aware of. 25 10 Also to be noted is that the increasing 1 costs of insurance really are not built into the 2 overhead costs. For example, NIH grants for sponsors. 3 Where are they going to come up with the extra money 4 to pay for this? 5 In the insurance industry, there are some 6 possible responses, and some of them are already 7 underway. As the economy improves, the entire 8 insurance market is going to improve. The whole 9 insurance market has been in the tank for years. Med- 10 mal has been in the tank for years, well before 9/11, 11 and now it's been in the tank more since then. 12 We're starting to get a comeback on the 13 economy, that's going to help. Brokers are now in the 14 process of trying to educate insurers about what are 15 the risks, where are they located, how to manage them 16 more intelligently than just yikes, raise the premium. 17 And we are seeing some market-based activity going on. 18 We're seeing consortium purchasing on the part of 19 independent IRBs. We're finding insurers now offering 20 special riders to investigators to cover research, 21 things like that. So the market processes are 22 beginning to activate, and we can look forward to some 23 improvement there. 24 Some of the solutions that I'm going to 25 11 offer or recommendations as I focus on Section 5 of 1 our outline, I think that that is going to help 2 considerably. If we can limit insurance risk, and 3 make the insurance risk more predictable, it'll be a 4 lot easier for insurers to have intelligent, 5 intelligible, reasonable pricing on their product. 6 Another challenge here is the temptation 7 to settle without litigating. As your outline 8 indicates, there are a number of reasons why it is 9 very tempting to settle without litigating, including 10 the difficulties of predicting what juries are going 11 to do, and the expense of litigating. 12 Some of the problems of settling, and 13 that's mainly what's going on. Right now even as we 14 speak, the Hutch trial is underway in Seattle. Maybe 15 not exactly even as we speak. It's almost 9:00 here, 16 so it might be a little early out in the Seattle area, 17 but the Wright against the Frank Hutchinson Cancer 18 Institute, that trial is underway. The plaintiffs 19 have made their case. The defense case is now 20 underway, and that is one of the relatively few cases 21 being actually brought to trial. 22 And, of course, then if things go further 23 and somebody doesn't like the outcome, you can be 24 rather confident that appeals will be made and so 25 12 forth. On the whole though, most of these cases are 1 getting settled no matter how flimsy, and that is 2 deeply troubling to me. 3 Part of it may be that insurers who work 4 in research are not as familiar with litigation in 5 this area, partly because it is a rather new 6 phenomenon as, for example, med mal insurers for 7 ordinary medical malpractice. You find that an awful 8 lot of med mal claims don't get settled, they get 9 tossed. They basically just get þþ the plaintiff 10 attorney realizes we don't have a case here, and then 11 the thing gets flat dropped with no money changing 12 hands. It's a very common outcome in ordinary med 13 mal. 14 We don't know how common it is here in 15 research, but it seems to be less common here. 16 Insurers seem more willing at this point to just hand 17 the plaintiff's attorney some cash and make him go 18 away. We don't know. But one of the problems with 19 premature settlement is this fourth one that's 20 mentioned, the third and fourth one, is that you get 21 all these unexamined, unrebutted claims that are left 22 out there hanging as though they might be some sort of 23 standard of care. 24 I culled from some of Alan Millstein - he 25 13 is an attorney who has been very active on the 1 plaintiff's side in litigation. Many of you know that 2 person's name very well here. I culled from some of 3 his complaints some of the so-called responsibilities 4 that IRBs have, and some of them are deeply troubling. 5 The idea that the IRB is supposed to approve all 6 aspects of a clinical trial. Take a look at number 3 7 - ensure that the research complies. How can anyone 8 ensure that all of the factors of the research comply 9 with federal requirements? 10 Number 4- assisting the sponsors in 11 developing protocols. Is that the IRB's job? That's 12 being put out there as though it's some sort of 13 standard. I am troubled by this concept. Take a look 14 at the fifth one - appropriately monitoring the 15 informed consent process and the conduct of the 16 experiment. Yes, there is some opportunity for IRBs 17 to monitor. It is very unclear what kind of 18 monitoring IRBs really are supposed to do. Are they 19 supposed to be in the room every time a consent is 20 done? That's the only way that you're going to find 21 every inadequate consent. I think that's an 22 unreasonable standard to place on IRBs, and make sure 23 - take a look at the bottom one - ensure proper 24 reporting. No IRB can do that. Make sure that all 25 14 the investigators report all the adverse events they 1 are supposed to. How can an IRB do this? These 2 standards have been proffered, they're out there, they 3 have not been rebutted. I find that troubling. 4 Okay. Potential solutions. I'm going to 5 look at four. First of all, arbitration, which I 6 think is a very interesting option, and then I'm going 7 to look at three different models of importing federal 8 immunity. And I think this is a very promising kind 9 of approach. As I say, three different models, and 10 each one of them has a lot to recommend it. 11 First of all, arbitration. There is 12 actually since 1925, the Federal Arbitration Act 13 basically has said the federal government strongly 14 endorses for public policy reasons, strongly endorses 15 the idea of resolving disputes by arbitration, 16 including binding arbitration. State statutes, a lot 17 of them replicate the FAA, and courts have been very, 18 very favorable in upholding and enforcing arbitration 19 agreements; not just any old arbitration agreement, 20 because there are some constraints. The arbitration 21 agreement has to be written in certain ways that are 22 fair, and I'll outline I think what should be an 23 arbitration agreement that might go into a research 24 situation, but there are a number of advantages to 25 15 arbitration. It's simpler, rules of discovery are a 1 lot more relaxed. Time frames are smaller. The 2 expense at least in terms of the litigation process is 3 vastly smaller in most cases. You may or may not have 4 a smaller outcome, but the administrative costs are 5 vastly less than the cost of litigation in most 6 instances. And it's more expeditious. The injured 7 person does not have to wait years, and years, and 8 years before getting perhaps a jackpot, perhaps 9 nothing. 10 Some of the major themes of courtsþ 11 decisions - I went through a number of decisions 12 regarding arbitration contract, and not just in 13 healthcare, but you look at employment, you look 14 across the board, there are a number of different 15 places where you find arbitration contracts. Courts 16 emphasize - a couple of things I'll highlight here. 17 One, they emphasize this is a contract. This is a 18 contract between two parties. And number two, that 19 this is not the þ and this is the U.S. Supreme Court, 20 very important - it is not a waiver of rights. It is 21 merely a different venue for seeking to enforce one's 22 rights. 23 So that as you look at the IRBs, you know, 24 the consent forms and so forth that IRBs have to pass 25 16 on, and they say oh, well, we can't have the research 1 subject waiving rights. Arbitration is not a waiver 2 of rights. It is just a different venue for exploring 3 and vindicating one's rights. Arbitration contracts 4 are not generally overturned unless you have done 5 something that would overturn any kind of contract, 6 like it's fraud, it's undue inducement, it's seriously 7 unequal bargaining parties, strength of the respective 8 bargaining parties, unconscionability, things like 9 that. 10 So here are some recommendations for what 11 might go into an arbitration agreement that would go 12 into research. One is, it's got to be clear and 13 conspicuous, big letters, and maybe even a separate 14 sheet of paper. Very good idea to have a take-home 15 copy of something like this, of the consent form, and 16 especially the arbitration agreement. It needs to be 17 fully voluntary. In other words, it cannot be a 18 prerequisite for getting into this trial, and that 19 would be especially important for things like Phase I 20 trials for people who are very ill. A little bit 21 different for normal healthy volunteers, perhaps, who 22 are being paid for their participation, so we've got 23 a spectrum of considerations to deal with here. 24 I recommend making it fully voluntary and, 25 17 indeed, in one case, or more than one case that I 1 read, a 30-day opportunity to revoke was looked on 2 very favorably by the courts as a reason to enforce 3 this contract. Look, the guy had a take-home copy. 4 This was not in the research context, but the fellow 5 had a take-home copy. He had 30 days to change his 6 mind. The court said what more do you need? Of 7 course it's binding. 8 We also want to make sure that they are 9 fair bilaterally, that you have reasonable time frames 10 and discovery opportunities. And don't make the 11 research subject pay the cost of the arbitration. 12 That'll kill it in a heartbeat. Okay. Make sure that 13 the research subject does not have to pay cold hard 14 cash in order to vindicate his or her rights in this, 15 and make sure that it's implemented carefully. In 16 other words, a legally authorized representative, if 17 not the patient - not just any old buddy who looks 18 like might be a suitable person to sign. 19 Now federal immunity, and I'm going to 20 look at three different types. The basic concept here 21 comes from Old English law going back to the 1200s, if 22 I'm not mistaken; and that is, sovereign immunity - 23 the king can do no wrong. Governments on the whole 24 worldwide do not allow themselves to be sued as they 25 18 go about the business of governing the people, unless 1 the government has drawn some sort of exception, a 2 waiver to sovereign immunity. 3 Our government has drawn a number of 4 exceptions to sovereign immunity, and I'm going to 5 explore several of them. The idea behind sovereign 6 immunity is that as people try, and as government 7 officials try and govern and do their things, they 8 need to have some kind of realm of flexibility for 9 making the discretionary judgments that they have to 10 make without being judicially second-guessed every 11 time they turn around. The government has got to 12 work, has got to function. 13 The idea for an IRB is, the underlying 14 concept, IRBs are federally mandated, federally 15 specified in their activities, and federally 16 supervised. They are, in a sense, quasi-government 17 operators in this way, and there are a number of ways 18 in which we might flesh that out. Oh, and by the way, 19 for the longshot advantages of this - to the extent 20 that we make IRBs at least immune in a qualified way, 21 and by qualified immunity what I'm talking about here 22 is the idea that they're presumed to be immune, but 23 not completely immune. Yes, they could be liable 24 under certain circumstances. That's the qualification 25 19 of the immunity. And to the extent that we could use 1 one or more of these models, we could very 2 substantially reduce the cost of suits because with 3 immunity, what you want first off the bat is for a 4 judge, not a jury, a judge to decide, is this immune 5 from suit? Are these people immune from damages? Is 6 this the kind of thing that renders immunity? If the 7 answer is yes, you don't even go to discovery, which 8 substantially cuts down on litigation costs. 9 Typically, these immunity also have 10 unavailability of punitive damages. And in some cases 11 you also have the option of the defendant gets to 12 recover the legal costs from the plaintiff, and that's 13 a big disincentive. If Alan Millstein stood the 14 chance, or any other plaintiff's attorney stood the 15 chance of having to pay not only his own expenses but 16 the other side's expenses, that would be a significant 17 disincentive to frivolously naming an IRB or some 18 other entity in the context of research-oriented 19 litigation. So let's take a look at the first one - 20 the Healthcare Quality Improvement Act of 1986. 21 The story behind this basically is, you 22 take a look at hospitals and their peer review 23 committees, those peer review committees have a very 24 public policy-oriented job of look at their fellow 25 20 physicians and if they find, for example, the surgeon 1 has a terrible technique. He's killing off people or 2 causing injuries right and left, getting a lot of 3 infections, they might want to review the activities 4 of that surgeon or other kind of doctor, and 5 potentially either curtail, or suspend, or even 6 outright withdraw that person's privileges to practice 7 at that hospital. Peer review does a very important 8 function for quality of healthcare. 9 What was happening is, back in the early 10 80s and before, what was happening is that some of the 11 doctors who were being reviewed and having their 12 privileges either suspended, curtailed or revoked were 13 suing the peer reviewers. They're saying wait a 14 minute, you're not trying to improve healthcare 15 quality. You're just trying to get rid of business. 16 I'm going to sue you on anti-trust grounds, treble 17 damages. This chills peer review, needless to say. 18 So Congress said we need to give these people some 19 immunity to protect this very important function. And 20 so basically, if the reviewers meet these very basic 21 standards, then they are immune from liability. Not 22 immune from being sued, but immune from liability; 23 namely, they were reasonably in the belief that their 24 action was to improve the quality of healthcare or 25 21 promote þþ they reasonably tried to get the facts, 1 they reasoned carefully, gave adequate notice of 2 hearing to the person, and their conclusions were 3 reasonably based on the evidence that they had. 4 Important features - this is a rebuttable 5 presumption. The burden is on the plaintiff. Now 6 remember in typical tort litigation, the burden is 7 also on the plaintiff, but here it's especially on the 8 plaintiff. They have to prove that the peer reviewers 9 were out-and-out unreasonable, not just that they made 10 a mistake, but they were unreasonable. So even if 11 they make an error that's okay, as long as it was a 12 reasonable error, and they then are immune, very 13 important. 14 Judges also, not juries, decide this. 15 You're not leaving this to twelve good and true. 16 You're leaving this to a judge who understands the 17 concept of immunity. Also, there is the prospect of 18 the defendant who prevails collecting attorney fees, 19 which I think is a very interesting thing. And as I 20 say, a very strong potential deterrent to frivolously 21 naming the IRB just because they happen to be 22 somewhere in the picture. 23 Courts have very happily upheld the 24 Healthcare Quality Improvement Act. I have yet to 25 22 find a case, there must be one somewhere, I have yet 1 to find a case, however, where judges have said yeah, 2 these guys weren't very reasonable. Go ahead, 3 collect. I have yet to find such a case. Very strong 4 endorsement by courts here. 5 The basics with IRBs are parallel, 6 obviously. Important healthcare quality and research 7 human protection functions. Instead of due process 8 for the accused, what you're looking for is 9 reasonableness of care in gathering facts and so forth 10 to make reasonable decisions regarding protection of 11 human research subjects. And here's a very rough 12 draft on slide 27 of how you might actually parse this 13 out, and adapt the HCQIA to protect IRBs. I'm going 14 to shoot on from there. Sorry. You've got it in 15 your hands hopefully to read that and go back later. 16 The second one, the Federal Tort Claims 17 Act, which was enacted back in 1946. This is very 18 directly based on sovereign immunity, and as pointed 19 out here, the sovereign immunity, this act waives it 20 so that the federal government will allow itself to be 21 sued under circumstances where somebody else might 22 also be suable, a private person under similar 23 circumstances, but there are very important exceptions 24 that I'll get to in a second. What happens here is 25 23 that instead of suing that individual, typically it 1 would be some government worker, you sue the federal 2 government. You file an administrative claim, the 3 Attorney General says yeah or nay, that this is, 4 indeed, a person who is employed by the government 5 acting within the scope of his employment, and then 6 the exclusive remedy is against the government. 7 Judges, not juries, decide these cases - no punitive 8 damages. And think about when you translate to IRBs, 9 think about the ways in which that will limit the 10 costs for insurers, where they're not worried about 11 this wildcard out there of what kind of multi-million 12 dollar punitive damage suit are we going to have to 13 cough up the money for. That's off the table, once 14 you get into the immunity territory. 15 Exceptions especially focus on 16 discretionary functions. Although the government 17 allows itself to be sued, no can do if we're talking 18 about a government official exercising discretion in 19 ways that have to do with public policy issues, or 20 similarly social-economic, as well as political kinds 21 of policy. Think about the ways in which IRBs 22 exercise discretion, making decisions that are policy- 23 oriented decisions. 24 Okay. Interesting historic example here, 25 24 and it's not historic, it's actually contemporary - 1 back in 1992 the federal government, Congress decided 2 that it's federally funded community and migrant 3 healthcare centers needed protection from the cost of 4 malpractice insurance. It was another of our 5 malpractice insurance crises, and these federally 6 funded centers wound up spending a lot of federal 7 money paying for malpractice insurance premiums, and 8 they were able to do less and less by way of providing 9 care for the people that they were federally funded 10 and set up to care for. And so the Congress said, you 11 know, let's at least try for three years as an 12 experiment pilot project to give Federal Tort Claims 13 Act coverage to the people who provide care in these 14 community centers. 15 Well, three years later they made it 16 permanent, and actually at this point although the 17 healthcare centers can buy GAP insurance coverage, 18 they don't need to buy comprehensive healthcare, or 19 excuse me, malpractice and other kinds of liability 20 insurance. 21 What happened there, and by analog, the 22 idea of protecting IRBs via this kind of thing is that 23 once again, you have something, although IRBs are not 24 federally funded per se, they are federally mandated, 25 25 they are federally specified and federally supervised. 1 They are created to serve the public interest, and the 2 parallels are obviously very strong. 3 The advantages obviously of bringing IRBs 4 literally under the FTCA, and I think this would be a 5 very interesting analogy, you would, if you want to 6 sue an IRB, you have to sue Uncle Sam, and Uncle Sam 7 decides if you get to sue him or not. That would be 8 a fairly significant deterrent to litigation, and 9 above all, it would protect the IRB members. They 10 would no longer even possibly be individually liable 11 so long as it was covered by the FTCA. Some things 12 are not covered by the FTCA; intentional torts. And 13 as I say, there would still be a need for GAP 14 coverage, but it would be substantially less, and 15 substantially more circumscribed. 16 Okay. We then get to the last model which 17 is a little bit more complicated, and I'm still, I 18 confess, kind of sorting my way through the Section 19 1983 and Bivens stuff. And Mark Barnes and I were 20 chatting on the phone about this. I'm trying to get 21 that book you recommended, and I called the library. 22 Yeah, yeah, we have it. I went to the library, nah. 23 So at any rate, what I'm presenting here is the 24 product of several weeks of very intensive work as I 25 26 was invited to do this, and to think about litigation 1 issues, especially with reference to IRBs, and so I 2 have not been able to absolutely clear the plates on 3 some of these concepts. 4 Basically, 1983 and Bivens are sort of 5 dovetailing. Again, you begin with the presumption of 6 sovereign immunity, the king can do no wrong. You 7 cannot sue the government, except. Section 1983 8 actually was enacted in 1871. It was called the Ku 9 Klux Klan Act. It was civil rights litigation, 10 because we were finding after the Civil War, because 11 we were finding that a lot of folks who were acting 12 under the color of state, meaning not government 13 generically, but literally the 50, or at that time 14 maybe, what was it - 48 states, however many states we 15 had at the end of the Civil War, they would act under 16 color of state law and basically ignore the federal 17 protections for minority persons, such as freed slaves 18 and others. And so basically what Section 1983 wanted 19 to do was to make sure that people could enforce 20 constitutional rights, even if they are being trampled 21 on by state officials, such as police officers or 22 state troopers, whoever that might be. 23 Okay. So that's in the ambit of the 50 24 states. A Bivens action is with respect to federal 25 27 employees. You note a moment ago that I said one of 1 the exceptions for the Federal Tort Claims Act is that 2 when you have a federal agent or government official 3 who is exercising discretion, making policy decisions, 4 normally that person is exempt, and the government is 5 exempt from litigation. The exception carved out by 6 the two of these is, if this government actor trampled 7 on a constitutional right that was obviously a 8 constitutional right, and knowable as such to a 9 reasonable person at the time, then there can, indeed, 10 be liability. So it's people acting under color of 11 state or federal law performing discretionary 12 activities, and trampling constitutional rights. 13 The idea here is on the one hand, you 14 really need to protect citizens from overbearing 15 public officials. On the other hand, you don't want 16 public officials to be subjected to judicial second- 17 guessing every time they make a decision, so that's 18 the balance the Feds are trying to create with both 19 Bivens and Section 1983. 20 What we're looking at for IRBs here is 21 kind of the obverse of all that, what would they be 22 protected from if they were brought into this kind of 23 model? So we would look at very similar themes to the 24 ones that I've been drawing for, the Healthcare 25 28 Quality Improvement Act and Hospital Peer Review, and 1 similarly, the FTCA. You're looking at giving IRBs 2 qualified immunity. In this case where they would be 3 liable is only when they are literally trampling on 4 someone's constitutional rights, clearly establish 5 constitutional rights knowable to be such at the time; 6 things like due process, revocation of due process, so 7 that as long as IRBs were engaging in careful 8 procedures and so forth, they would probably be and 9 remain immune from tort litigation so long as they 10 were honoring people's constitutional rights. So 11 that's that idea. 12 And by way of summary, and then we can 13 open it up to discussion, the reasonableness of the 14 conduct across the board here is what tends to secure 15 the immunity. Judges, not juries, determine immunity 16 on this theory for the IRB. The burden would be on 17 the plaintiff to show that the IRB's action was 18 clearly unreasonable or that it trampled 19 constitutional rights, knowable as such to a 20 reasonable person. And immunity, ideally would want 21 immunity from suit. ACQIA gives immunity only from 22 damages. Ideally, it would be nice to have immunity 23 from suit, but one or the other, either way, whatever 24 you can get would be a great help, no punitive 25 29 damages. And then again a very important thing that 1 I would like to see built in is to protect potential 2 defendants by allowing them to collect attorney's fees 3 where the plaintiff's action was unreasonable in 4 naming the IRB. 5 Overall recommendation - one thing I would 6 like very much to see from the administrative end, and 7 this goes back to some of the first things that I said 8 in this brief set of remarks, is that we need to make 9 it a little bit clearer as to what our IRB's 10 responsibilities, particularly regarding ongoing 11 monitoring both of the informed consent process, and 12 of the undertaking of the research itself, especially 13 what are not their responsibilities for ongoing 14 monitoring. This is a very big hole, and IRBs are 15 falling into it, and down and down they go until we 16 get some kind of administrative clarification on that, 17 and hopefully constraint, circumscription of what kind 18 of responsibilities IRBs have there. 19 Also from the administrative level, I 20 would like to see some kind of mechanism to track 21 litigation. It would be nice. I'm not sure that we 22 easily can, but it would be kind of helpful. Also, to 23 encourage in some way a creative marketplace with 24 respect to the insurance issues. And then finally, it 25 30 would be interesting to see the legislature enact 1 qualified immunity. 2 I might mention, by the way, that with 3 respect to this third option for qualified immunity 4 that I mentioned, Section 1983/Bivens kind of thing, 5 there are some arguments, and I've been digging around 6 in this in case law, it is at least conceivable that 7 some courts might grant IRBs Section 1983/Bivens-type 8 immunity even now, because looking through some of the 9 older Supreme Court decisions here - Supreme Courts, 10 for example, in one decision 20 or 30 years ago 11 extended federal immunity to school board officials. 12 In this particular case what happened was 13 some school kids spiked the punch for a meeting of an 14 extracurricular activity, so the school board guys 15 suspended these two students, and the students sued, 16 and the U.S. Supreme Court said in previous cases we 17 have found that state troopers, we have found 18 policemen, National Guardsmen are immune from 19 liability because they are performing quasi-government 20 activities. We hereby find this extends to school 21 board people because they are engaged in quasi- 22 government kinds of activities. They are serving a 23 public policy function, and they deserve immunity. 24 Well, wouldn't it be interesting if a court said IRBs 25 31 are serving a public policy function that should not 1 be chilled, same rationale applied from case, to case, 2 to case. And it's a very familiar set of themes that 3 go across the case law here. And IRBs fit very 4 squarely within an awful lot of the case law regarding 5 all three of these kinds of federal immunity, so I'm 6 going to be quiet and turn it back over to Mr. 7 Chairman. Thank you for your attention. 8 DR. PRENTICE: Thank you, Haavi. You've 9 fully lived up to my expectations. 10 DR. MORREIM: Well, somebody said I speak 11 at 285 words a minute with gusts up to 482. 12 DR. PRENTICE: I've got a number of 13 questions, but I'm going to limit my questions to I 14 think one, with one comment. In looking at your 15 extraction from various complaints, there is one that 16 I would like to amplify on. And I don't know whether 17 you touched on that in your research. That's the 18 Richard Cuss v. Sherman Hospital case in Illinois, 19 where the appellate court basically determined that 20 the IRB had a duty to ensure that Richard Cuss, who 21 was the plaintiff, actually signed the IRB approved 22 consent form. So it wasn't good enough for the IRB to 23 simply approve a consent form, and then inform the 24 investigator he had to use that consent form. They 25 32 actually had to make sure that he, indeed, used the 1 correct consent form. That was settled out of court 2 because the insurance company mandated a settlement 3 when it was remanded back to district court. 4 The question I have concerns your comments 5 on arbitration. I've been involved in one case in 6 California where there was arbitration. It was a 7 research-related case. Arbitration was mandated as a 8 condition for participating in the clinical trial, 9 which goes counter to what you're recommending here. 10 So my first question would be, why would a subject 11 want to voluntarily agree to arbitration? The chances 12 are that if you sue, you're going to get a lot more 13 money if you don't arbitrate, so that would be one 14 question. The second question would be, does 15 arbitration offer any protection for IRBs? 16 DR. MORREIM: Your question or your 17 hypothesis that you get more money if you sue, I'm not 18 sure I would buy that from the data in terms of 19 medical malpractice, if that's an analog. Most 20 medical malpractice cases get either tossed or 21 settled, and so if one is looking at settlement, then 22 in those kinds of cases, arbitration versus 23 settlement, arbitrators are sometimes more generous to 24 plaintiffs than juries are in some cases, and they are 25 33 sometimes more generous to plaintiffs than would be a 1 judge. And I say sometimes. I think we would 2 actually have to track the data, but in terms of 3 collecting money for the plaintiff, given the number 4 of suits that either get dropped or that wind up 5 taking endless amounts of time, and remember the 6 attorney gets a third in liability litigation, 7 malpractice, research-oriented and so forth, so that 8 what the person actually winds up with in the end 9 years out, that's not so clear. Some people hit the 10 jackpot, a lot of people don't. 11 Another factor, and this is one of the big 12 advantages for arbitration, is that smaller claims can 13 actually collect. Typically, the cases that wind up 14 attracting a plaintiff's lawyer are the ones that are 15 big enough to attract the big bucks, and so a lot of 16 the people have small claims that are just not worth 17 bothering with, if you're a plaintiff's attorney 18 because it's expensive to file and pursue litigation. 19 It's very expensive, and so a lot of those cases 20 simply are never taken up. And so somebody who has a 21 small claim has a chance with arbitration, and 22 basically no chance. 23 We also have the expeditiousness of the 24 settlement, that you don't have to spend endless years 25 34 dragging this thing out. There are a number of 1 advantages for prospective plaintiffs. It becomes an 2 interesting question how much "informed consent" would 3 you have to engage in for the arbitration. There are 4 downsides to these, which is why I'm more inclined 5 toward the federal immunity approach than the 6 arbitration approach, but I think we need to put it on 7 the table and look at it carefully, because if you 8 don't get any arbitration - or excuse me - if you 9 don't get the immunity, arbitration may be a 10 reasonable alternative. 11 DR. PRENTICE: What about protection of 12 IRBs? 13 DR. MORREIM: It would seem to me that 14 perhaps you could write that in. I invite others 15 comments on that, but that can be a contract. 16 Arbitration is a contract. And perhaps, you know, 17 another possibility - we talk about indemnification, 18 I guess þþ I don't want to get too far into 19 speculation here, but there are various possibilities 20 that one might write by way of arbitration contracts 21 that would include the IRB within any kind of 22 arbitration agreement. 23 DR. PRENTICE: Okay. One final comment. 24 I would think that if you did have an arbitration 25 35 agreement, a plaintiff would be less likely to include 1 the IRB in any kind of a suit. 2 DR. MORREIM: I believe so. 3 DR. PRENTICE: Okay. 4 DR. MORREIM: Yes. 5 DR. PRENTICE: All right. It's opened up 6 to the floor now. Raise your hands so I can see you 7 if you want to ask a question. Yes. 8 DR. HAUSER: Haavi, that was terrific. 9 RPMs were maximum on that. I have a couple of 10 questions. One is, what type of mechanism should we 11 develop to track litigation, and perhaps understand 12 better the occurrences out there regarding 13 malpractice, and incidents that would give us a better 14 base of knowledge regarding this problem. Do we need 15 to put together some sort of registry or data 16 collection mechanism so that we better understand 17 exactly what we're dealing with, so that better policy 18 can be devised? 19 DR. MORREIM: I would like to see better 20 information. I really would, and I think we need some 21 creative problem-solving in this realm. We might þþ 22 I hate to mandate that IRBs that have been sued file 23 somewhere, but I would sure like to encourage some 24 sort of registry, at least an informal one, where IRBs 25 36 that have been named, or obviously other people 1 involved in research can at least identify that they 2 have been named. Here is the complaints. Complaints 3 tend to be, obviously, public documents, and so if 4 someone has been named in a suit, then your insurer 5 already knows, so it's not like you're spilling the 6 beans. And so I would hope that there would be 7 relatively few disincentives to some kind of central 8 informal registry, but I think we need better data, 9 and I would hope that at least sharing information 10 about what kinds of complaints are being brought out 11 against what kinds of entities, and what happens to 12 them. I think it would be a useful thing. I'm not 13 familiar with the mechanics of assembling such a 14 thing, but I like the idea. 15 DR. HAUSER: The second question I have is 16 around immunity. Have you thought through how you 17 would extend immunity to IRBs, and what the IRB may 18 need to do in order to qualify for that immunity? 19 DR. MORREIM: The ways in which one would 20 extend, if you were to use the Healthcare Quality 21 Improvement of 1986 Act, Congress would enact it. And 22 the wording that I offered as a very rough draft might 23 be the way in which such legislation would be enacted. 24 It would require legislation, at least on the HCQIA 25 37 approach. And the rationales would be pretty much the 1 same, and so you would simply carve it out and say 2 IRBs, because they are federally mandated, their 3 activities are federally specified, and they are 4 federally supervised are immune so long as their 5 decision-making is reasonable according to these 6 standards, so that's how you would do it there. 7 Alternatively, if you follow the FTCA, the 8 Federal Tort Claims Act approach, you would do it, and 9 again it would take Congress if you're going to do it 10 the way that they did it for the federally funded 11 community and migrant healthcare centers, but again 12 you would do it on that model if you took the FTCA 13 approach, and you would write into the legislation we 14 hereby bring IRBs under the FTCA, and they are immune 15 so long as - and that means if you want to sue an IRB, 16 you're suing Uncle Sam. And they're immune so long as 17 they follow these criteria. Obviously, intentional 18 torts are not part of the FTCA. Nobody gets immunity 19 from the feds for intentional torts like battery, 20 fraud, things like that. I don't know if any insurers 21 who are going to immunize you for that either, but 22 those are a couple of approaches that would require 23 legislation. 24 The Section 1983 thing is þþ one way you 25 38 could get there is hope to goodness that some court, 1 like the Supreme, would just declare that IRBs þþ 2 DR. HAUSER: Okay. So the legislation 3 would contain certain qualifications that the IRB had 4 to meet in order to qualify for immunity. That's the 5 substance of the þþ 6 DR. MORREIM: Yes. I mean, you look at 7 FTCA, it's not that they specified a lot of ditsy 8 details for these community health centers to qualify. 9 If they're a federally funded community health center, 10 however those are set up, then they're under. If they 11 choose þþ it was voluntary, by the way, but now it's 12 permanent for those who choose to sign up. And maybe 13 you could make it a voluntary thing. It's hard to 14 picture an IRB not wanting to be brought under that 15 kind of immunity. 16 In other words, I think one thing that's 17 worth pointing out is that for HCQIA, the peer review 18 bodies themselves didn't have to meet some sort of 19 detailed list of qualifications in order to become a 20 peer þþ if it's a hospital peer review body, as the 21 hospital sets these up, then you're under this. And 22 the only criteria are, did you engage in reasonable 23 procedures to get the facts, give reasonable notice to 24 the person you're looking at, et cetera, et cetera, 25 39 fairly broad. 1 DR. PRENTICE: Mark. 2 MR. BARNES: Thank you, Haavi, for all the 3 work that you did leading up to this, as well, because 4 I know in conversations you had with Ernie and me, you 5 were deeply involved in this for a while. 6 Just a couple of points. One is that if 7 one wanted to capture data in regard to what kind of 8 suits are going on out there, there actually is a way 9 that the department has right now to capture, perhaps 10 not all of the data but a good deal of the data, and 11 I think it's worthwhile for us to note that; and that 12 is that under the Healthcare Quality Improvement Act 13 of 1986, that also created a registry of med mal 14 payments in the National Practitioner Data Bank, or 15 NPDB, which is a national registry of any kind of 16 malpractice payments when a physician is one of the 17 co-defendants, a defendant or one of the co-defendants 18 in an action. And any resolution, including 19 settlement of those cases, must be reported to the 20 NPDB with the designated amount of settlement and what 21 the apportioning of liability is between the different 22 physicians, the hospital, and others who are named as 23 co-defendants in the suit. So the federal government 24 keeps this registry right now, and all malpractice 25 40 insurers, all hospitals, all group medical practices, 1 they're all required to report to the NPDB when there 2 is a settlement. 3 One thing that could be done is that it's 4 not in the NPDB methodology now, but it would be 5 possible for the department, which has administrative 6 authority over the NPDB, with full authority to 7 implement the NPDB and design regulations for NPDB 8 under the authorizing legislation, the HCQIA, it would 9 be possible for the department to put some checkboxes 10 or basically to design the system in such a way that 11 research-related claims are flagged, so that there 12 would be a registry of cases and of settlements, and 13 of judgments. That is something the department could 14 do right now. And it may be that we should think 15 about recommending that as a group to the department. 16 HRSA is the entity that oversees the NPDB, so that's 17 one point that I wanted to make. Did you want to 18 respond? 19 DR. MORREIM: You have noted very 20 appropriately an important distinction that we would 21 want to keep track of; namely, where you have med-mal, 22 ordinary medical malpractice, all the NPDB, the data 23 bank keeps track of is what happened in the end. And 24 in the med-mal context, we have had a certain skewing 25 41 of activity to avoid, you know þþ listen, I'll go away 1 quietly if I don't have to pay a settlement so that it 2 doesn't have to go on the data bank. 3 As you have very nicely noted, what we 4 would want to make sure and ask for by way of any 5 expansion is to keep track not just of outcomes, but 6 of just the filings themselves, and the initial 7 filings, which is not something the data bank 8 currently gathers. But you've nicely kept track of 9 the difference there, and I just want to accent that. 10 Thank you. 11 MR. BARNES: And then one other point. 12 And I want to express a point of view which is not my 13 own, but I think it's worthwhile expressing. In fact, 14 I loathe the point of view I'm about to express, but 15 I think that it's worthwhile putting on the table so 16 that you can respond to it; and that is, and we hear 17 this þþ this would be Alan Millstein's point of view, 18 not to speak for him, obviously, but I've heard him 19 say what I'm about to say in different fora. And that 20 would be look, IRBs have been negligent. They've been 21 lazy. They have been þþ investigators have been lazy 22 and negligent. They experiment on people. People get 23 hurt, and the tort system is a good way to punish 24 people who do bad things. It's a good way to punish 25 42 IRBs and investigators who don't play by the rules, 1 who don't inform people of their rights, and so why 2 not let the American tort system let it work, and it 3 will reform behavior. 4 DR. MORREIM: I agree. I loathe the þþ 5 I'll tell you, I think there is a certain theoretical 6 measure of credibility if the tort system actually 7 worked the way it's supposed to. If the tort system 8 actually ferreted out and blamed blame-worthy conduct, 9 yes, okay. And in my writings þþ and Millstein and I 10 have actually appeared on the same platform - that was 11 colorful. And it was right when he had sued and the 12 suit was in process for the Number 5 Patient for the 13 Abicor Artificial Heart Trial, with which I am deeply 14 involved, and that was really an interesting sub-plot. 15 At any rate, I think that one of the 16 biggest problems here is that the tort system isn't 17 working the way it hypothetically ought to. And as I 18 said to Millstein at the time, I have been very public 19 in being in favor of appropriate kinds of tort 20 liability across the board, but it needs to be based 21 on blame and reasonableness, and that is not where we 22 are right now. 23 Indeed, the kinds of immunity that I am 24 structuring or recommending that we structure might 25 43 more closely resemble the way the tort system ought to 1 work, where you're focusing on reasonableness. Now it 2 would be with a certain kind of accent; namely, the 3 plaintiff would have to prove unreasonableness in 4 order to prevail, as opposed to merely having to show 5 something of a softer standard than that. But I think 6 the kinds of immunity that I am proposing would more 7 closely resemble the kinds of things that the 8 hypothetical Millstein argument is trying to achieve. 9 And frankly, I think that some IRBs have been less 10 careful historically than they need to be, and I think 11 some of the both federal actions and the litigation 12 has been a wake-up call, and wake-up calls are useful. 13 The problem is that now that everybody is wide awake, 14 we are at the point where we can þþ this kind of 15 litigation can inspire very perverse activity, time 16 wasting, effort wasting activity. And I commend to 17 your attention the slide that talks about potential 18 sequelae. It's slide number - whatever the heck it is 19 - slide number 5. I think we're going to start to see 20 perverse responses that do not improve human research 21 safety. 22 DR. PRENTICE: Felix. 23 DR. GYI: Thank you for a very 24 enlightening talk. Those are þþ not being an 25 44 attorney, I find those options to be very interesting. 1 From your perspective in having gone 2 through advising subjects and looking at the wealth of 3 information they have to sign prior to entering into 4 a study, I wonder if we are placing the burden on 5 subjects by even looking at arbitration as a feasible 6 alternative, because that's one of those areas where 7 we then go back to the subject and say read some more, 8 adopt, digest information prior to participating in 9 the study. And then, by the way, forget all the 10 things you read in the informed consent form because 11 here's another document for you to digest. I wonder 12 if you might comment on that and see what the utility 13 of something like that is in this particular setting, 14 even though that may be a reasonable legal option. 15 DR. MORREIM: I think that the challenges 16 of achieving another informed consent of sorts are 17 significant, and I think that would be a significant 18 downside. I think probably the best thing to 19 recommend arbitration - again, if we can't secure 20 appropriate kinds of immunity - is that it's something 21 that could reduce some of the onus on IRBs. To the 22 extent that it could at least displace from the 23 litigation forum onto the arbitration forum, to the 24 extent that it could displace a lot of that activity 25 45 into a more confined, a more constrained, a more calm 1 headed forum, I think to that extent - and thereby 2 reducing IRBs' fears of being sued, et cetera, et 3 cetera, et cetera - to the extent that it can then 4 encourage IRBs to be more relaxed in the sense of not 5 getting into perverse responses to litigation, it 6 could foster a better atmosphere for IRBs to work, so 7 that in that indirect sense, benefit patients. 8 Also, I think it is important to remember 9 that arbitration does hold certain very significant 10 potential advantages for the research subject class 11 patient, and it's not like they're giving up something 12 major. Yes, they're giving up some things, but as the 13 courts have pointed out again and again, the person on 14 the patient side, the smaller party, can gain a great 15 deal from arbitration. 16 So many cases wind up, as I pointed out, 17 either not being brought about in the first place 18 because they're too small, or they wind up being 19 endlessly lost in litigation, or the person winds up 20 collecting very little at the end because of all the 21 court expenses that get deduced. There are a lot of 22 advantages. It is true, a very significant 23 disadvantage could be the possibility of informed 24 consent for the arbitration. 25 46 On the other hand, something that can be 1 rescinded within 30-days. It's not like you have to 2 achieve instant understanding this moment before you 3 step out of the office. If this person has a take- 4 home copy, the opportunity to ask questions and 5 rescind the agreement any time within 30 days, that 6 might be a good protector for those up front 7 information costs, if you will, for an arbitration 8 approach. 9 DR. PRENTICE: Celia. 10 DR. FISHER: Hi, Haavi. Thank you very 11 much. I think for me, I have a number of points. 12 They're points and questions. For me what I think is 13 most significant with respect to some of your 14 suggestions is the notion of how to operationalize 15 what an IRB is supposed to insure. And I think that 16 that's something that one could take some kind of 17 short-term action on, what does it mean for an IRB to 18 monitor. So I think those points are something that 19 is very important to follow through because the 20 language is vague at this time. 21 I'd also say that to collect the data 22 might be difficult, because it's my understanding that 23 institutions settle to avoid publicity. Many times 24 the settlements request that this is not public 25 47 information, so to find out about settlements may be 1 very difficult, and maybe you have some ideas about 2 that. 3 I also have a question about talking about 4 protecting an IRB versus talking about individual IRB 5 members, versus protecting the PI, so I can understand 6 the protection of individual IRB members who come 7 under an umbrella of the institution, or the 8 organization to which the IRB is constituted, but I'm 9 not sure, and maybe I'm a loathsome person, but I'm 10 not sure I totally think that þþ I totally agree with 11 the concept of immunity for an IRB, but let me go on. 12 Another question I have is if, in fact þþ 13 I know in your paper you made very important 14 distinctions between medical tort law and how it would 15 be inappropriately applied to research. However, I am 16 confused about the type of research in which 17 participants use their health insurance to pay for 18 their participation, and I'd like to know what would 19 happen in those situations. 20 I'm also not comfortable with the analogy 21 of the IRB to peer review. In my mind, peer review - 22 one of the purposes is to recommend punitive action 23 if, in fact, it is reasonable, or to say that someone 24 has practiced in an ill manner. My understanding of 25 48 an IRB is to ensure subject protection and that to the 1 extent feasible, the proposed subject protections are, 2 in fact, enacted by the PI. And once again, I put in 3 to the extent feasible. 4 I also have difficulty in thinking about 5 the IRB as an arm of the government. I think there's 6 a difference between being regulated by the federal 7 government and being an arm of the government. And I 8 think that there's certainly a chilling effect if, in 9 fact, IRBs are seen from the participant's perspective 10 as having the authority and mandate, and power of the 11 government which, in fact, I don't think was the 12 purpose because they're supposed to be local and come 13 to decisions that reflect the local community. 14 I also agree with Felix that the notion of 15 reasonableness seems to place an undue burden on a 16 participant who not only is basically getting an 17 informed consent to understand what the researcher's 18 responsibilities are, and now is being asked to sign 19 something for arbitration or whatever way you would 20 organize it against an IRB to which they know very 21 little about. 22 And my last confusion has to do with in 23 informed consent. Typically, you are given 24 information that you call the PI if you have questions 25 49 about the research, and you're given the number of 1 someone with the IRB or in Human Subjects Protections 2 to talk about your research rights; yet, the kind of 3 arbitration that you proposed immediately sets up this 4 adversary system, so who is going to be the 5 participant advocate if in fact any time they call a 6 representative of the IRB or the individual who is 7 supposed to talk to them about their rights, that 8 individual has to be protective of potential 9 arbitration that may come down the line. 10 And finally, if in fact there's immunity 11 for the IRB, the IRB has conflicting tensions to begin 12 with. They have a responsibility to their 13 institution, and one of the beauties of the IRB system 14 is that there is supposed to be a wall there so that 15 they can implement subject protections. And I'm not 16 sure, it sounds to me like a lot of what you're 17 suggesting might undermine protections for subjects. 18 DR. MORREIM: Okay. Lots of questions, 19 very good ones. I think we got lots of answers, good 20 ones. First of all, how to operationalize sort of 21 voluntary reporting and so forth; admittedly, a 22 challenge. I would refer us, I guess, at this point 23 to efforts by JACAHO and others to collect information 24 about adverse events in hospitals, you know, patient 25 50 safety movement needs to be a model here. Not all 1 together successful yet, but we are trying to get 2 reports of adverse incidents, you know, sentinel 3 events, things like that from within the patient 4 safety movement. We might be able to pick up some 5 tips from them on how to encourage reporting. 6 I'm thinking that it's likely that 7 voluntary reporting is only going to be þþ is going to 8 be it rather than any kind of mandate. But again 9 note, when somebody has been served with process, it's 10 now a done deal, honey. You ain't going to give away 11 anything by saying we just got served, so that 12 reporting that we've now been served is not nearly as 13 sensitive as reporting we had a boo-boo and nobody 14 knows about it yet. And that's the level we're trying 15 to get reports on for patient safety, so this would be 16 at a lesser level, it seems to me. 17 Secondly, looking at protecting IRBs, very 18 important, versus IRB members and PIs and so forth. 19 Very important to note, and you did not trample this 20 distinction but I want to highlight it. It is one 21 thing to protect IRBs. All the immunities that I'm 22 talking about do not touch Pis, they do not touch 23 sponsors. I am not talking about making drug 24 companies immune from suit, or investigators or 25 51 anybody like that. I am strictly talking about IRBs. 1 And when we talk - and I'll jump to one of 2 your later questions - when we talk about a 3 potentially adversarial setting when somebody phones 4 an IRB to make a complaint; darling, if you're about 5 ready to get sued, that's also adversarial, so the 6 possibility of any kind of adverse action by a 7 prospective plaintiff against the IRB sets up the 8 adversariality that is going to be true, whether it 9 would be resolved in an arbitral forum or in a 10 litigation forum. Either way, if people aren't 11 getting along in the same sandbox, we're going to have 12 some sand flying in each other's eyes potentially. So 13 in other words, it doesn't make the problem worse to 14 talk about arbitration, as opposed to litigation. 15 You've still got the challenge. 16 With respect to the third thing that I 17 wrote down, for patients who are using healthcare 18 insurance to participate in research, I may have to 19 come back to that. I'm not sure I understood your 20 question exactly. You're noting that peer review in 21 hospitals is a potentially punitive sanctioning thing; 22 whereas, IRBs are very different. Yes. That's not 23 where the analogy is. The analogy is they are both 24 engaged in a particular kind of process to safeguard 25 52 healthcare, or in this case, safeguard the well-being 1 of research subjects, patients, research subjects. 2 What activities they do in order to 3 protect research subjects, protect patients are a very 4 different focus, absolutely right. And in one case, 5 you're getting rid of bad apples. In the other case, 6 you are sort of taking a more positive thing, trying 7 to make sure that certain protections are in place in 8 the first place, so that where you see disanalogies, 9 I agree - definitely disanalagous, but the important 10 things are where the analogies do lie; namely, a 11 federally mandated public service/public policy 12 protected function that is going to be substantially 13 chilled, and perhaps significantly misdirected, and 14 perversely misdirected when the individuals, and yes, 15 the bodies as a whole stand to be named in litigation 16 if the litigation is not meritorious. 17 I will say that you rightly distinguish 18 between individual members versus IRBs on a whole, but 19 I can also say that in some of private conversations 20 with various IRB people, including heads of 21 independent IRBs, I know of some who would just get 22 out of the business if they got sued. Or much more 23 significantly, although some individuals might just 24 say I've had it if we get sued, and that would be a 25 53 more personal decision. 1 On the other hand, if it becomes 2 impossible to get insurance - I mean, the independent 3 IRBs serve a very significant function for those who 4 do research outside of the academic health center 5 context. And to the extent that certain kinds of IRBs 6 might find it impossible to exist in a litigious 7 environment, that could be a significant downside for 8 the overall protection of human research subjects. It 9 could add to the complexities under which IRBs 10 function. 11 Furthermore, seeing IRBs as an arm of 12 government - I will say, it's an interesting thought. 13 I'm not sure that this kind of immunity would 14 necessarily prompt patients in their minds to say ah- 15 hah, the IRB is an arm of government. I think a lot 16 of people don't really know much about the IRB. 17 You're quite right in the first place, even though a 18 plaintiff's attorney might later suggest to sue them. 19 They know about it perhaps a little bit through the 20 consent form and a phone number and so forth, but IRBs 21 play such a different role than investigators. And 22 their role in the potential harms - and I think here 23 is kind of a bottom line in my somewhat lengthy 24 response to your many interesting and thoughtful 25 54 questions. 1 I think that the IRBs play such a 2 different role, and as you pointed out, that role 3 needs badly to be further clarified. The injuries 4 that happen to subjects are usually not going to be 5 from inadequate IRBs. They might be from a very good 6 protocol not being carried out very well, so that we 7 need to parse out where are the true injuries most 8 likely to come from. 9 IRBs are a broader umbrella function, and 10 their responsibilities - and yes, their susceptibility 11 to whatever kind of punitive response needs to be kept 12 where the IRBs' responsibilities are; namely, in this 13 broader umbrella area. 14 DR. PRENTICE: Okay. We have three 15 individuals on the list who want to ask questions. 16 We've got a choice here. We can go with the first 17 person on the list, which is Susan, or two of you 18 could yield to the third or the second. And the 19 people on the list are Susan, Mary Lake and Tom, but 20 only one of you can ask a question. We're already 21 three minutes into the break, so what would you like 22 to do? Who has the most important question to ask 23 Haavi? 24 DR. MORREIM: Give each person 30 seconds 25 55 and a give me a minute and a half. 1 DR. PRENTICE: All right. Each person 20 2 seconds, you have a minute and 15 seconds. And then 3 we'll cut our break short. Susan, succinct. 4 MS. KORNETSKY: My question is about 5 arbitration. You had mentioned that this is not 6 viewed as a waiver of rights, and I would just like 7 you to expand upon that. And then also, if HHS - I 8 mean, I want to put you on the spot whether you would 9 look at that the same way. And just a comment; my 10 concern would be that we're going to have to start 11 asking research subjects to bring attorneys to the 12 informed consent session. Between the informed 13 consent, the HIPAA, and now this I would be very, very 14 concerned. 15 DR. MORREIM: Oh, no. I mean all three. 16 DR. PRENTICE: Oh, all three? 17 DR. MORREIM: Yes. 18 DR. PRENTICE: Okay. All right. Mary 19 Lake. 20 DR. POLAN: A really rapid and practical 21 question. As a physician, the disincentives to serve 22 on IRBs are enormous. And if you add the fact that 23 you don't get paid, you have enormous pressures for 24 financial activity in your practice. And then to that 25 56 you add the potential for getting sued layered upon 1 malpractice claims. It's a difficult situation. 2 If you were to prioritize your three 3 levels of immunity in terms of likelihood of seeing 4 one of those eventuate in a practical solution within 5 the next 12 months, what would your priority be, and 6 why? And perhaps the general counsel, somebody else 7 like Mark or the general counsel could weigh-in on if 8 you really wanted to do this and make this happen, how 9 would you do it? 10 DR. PRENTICE: Tom. 11 MR. ADAMS: The thoughts that you have 12 shared with us centered on issues that would require 13 legislation for the most part. The OHRP has as part 14 of its existing mandate the ability to educate the 15 public. Would you see a potential federal role in 16 contacting insurance entities and the broader public 17 to begin to talk about this problem, and basically 18 jaw-bone, if you will, for meaningful change given the 19 fact that historically medical malpractice legislation 20 at the federal level has not fared well? 21 DR. MORREIM: Okay. Quick answers one, 22 two, three. I don't see a whole lot of enthusiasm for 23 arbitration. I just throw it out there, darlings. 24 Okay. Second, disincentives to þþ okay. It's a toss- 25 57 up between HCQIA and FTCA. I'm thinking HCQIA is a 1 lovely model because of granting attorney's fees, no 2 punitive damages, a lot of protection, and it's very, 3 very parallel. It would be an easy thing to sift that 4 out. FTCA, though, has such a precedent with the 5 community health centers. I think that that could be 6 readily adaptable, so I have a hard time choosing. 7 Finally, the federal role for educating 8 insurers, et cetera - my guess is that probably the 9 better educators are going to be the brokers, people 10 who are actually carving the deals in the marketplace. 11 Government might, indeed, have some role. Just help 12 them understand where the risks reasonably are. If 13 somebody can please educate certain plaintiffs' 14 attorneys out there so they understand a little more 15 about research, that would be really nice, but I don't 16 think Uncle Sam is going to be very effective in that 17 respect either. Thank you. 18 DR. PRENTICE: Okay. Thank you, Haavi. 19 That was fascinating. We could listen to you all day. 20 We're going to take a little over 10 minutes. Please 21 try to get back on time because we now have the HIPAA 22 Privacy Rule Panel. 23 (Whereupon, the proceedings in the above- 24 entitled matter went off the record at 9:50:38 a.m. 25 58 and went back on the record at 10:04:26 a.m.) 1 DR. PRENTICE: Okay, folks. If everyone 2 could take their seats. Okay. Now we're going to 3 move into the HIPAA Privacy Rule Panel. I think 4 everybody recognizes the fact that this is an 5 extremely important topic to IRBs, as well as clinical 6 investigators, so it's a delight to have four 7 distinguished panelists who are going to present to us 8 today. What I'm going to do is introduce them 9 individually in sequence, and then at the end of the 10 fourth panelist, I would like all four experts to go 11 up to the table in front of the room where they can 12 respond to questions, so you would hold your questions 13 until after all four presentations are complete. 14 The first panelist is Susan McAndrew, and 15 I'm going to abbreviate her bio in order to be a 16 little bit more efficient and not read everything 17 here, out of time considerations. Susan's a Senior 18 Health Information Privacy Policy Specialist in the 19 Office of Civil Rights at HHS. Ms. McAndrew came to 20 HHS in May, 2000 to lend her expertise to the final 21 privacy regulation, so it's really an honor to have 22 you here, Ms. McAndrew, to talk about the HIPAA 23 Privacy Rule and some of the issues that we are 24 dealing with. 25 59 MS. McANDREW: I want to thank you so much 1 for inviting me here today to talk about the Privacy 2 Rule. I am from the Office for Civil Rights, which is 3 in the Office of the Secretary, that was given 4 responsibility for enforcing and implementing the 5 Privacy Rule. 6 The Privacy Rule stems from legislation in 7 1996 called the Health Insurance Affordability and 8 Accountability Act, hence HIPAA. The regulations were 9 issued first in December of 2000, and then modified 10 substantially in August of 2002. And entities were to 11 be in compliance with the Privacy Protections as of 12 April of last year. 13 The Office for Civil Rights does two 14 things. One, we work with entities to provide 15 technical assistance and to help them come into 16 compliance with the rule. And we also investigate 17 complaints about potential violations of the rule. 18 And to date, we have probably received over 5,000 19 complaints, and the number continues to grow, but we 20 are happy to say that we've been able to resolve about 21 45 percent of those complaints satisfactorily. 22 I wanted to use the time today just to 23 give a very brief overview of how the Privacy Rule 24 works, particularly in connection with research 25 60 endeavors. I'm assuming that a lot of this is known to 1 you all, and so I want to move rather rapidly through 2 it and allow time to talk a little bit about some of 3 the issues that have been resolved to date, and some 4 of the issues that remain. And then the other 5 speakers will þþ the other panelists will have 6 additional perspectives to offer in terms of the 7 issues that the research community is facing in trying 8 to absorb the privacy requirements, and interacting 9 with entities that are now subject to privacy 10 requirements. 11 Basically, the rule operates to protect 12 privacy in two major ways; one, it gives the 13 individual certain rights with respect to their 14 information - that is, they now have a federal right 15 to access their information, their medical records and 16 billing accounts. They have the right to amend those 17 records if they are wrong. They have the right to ask 18 for an accounting from covered entities about how 19 their information has been used. 20 The rule also protects the privacy of 21 identifiable health information by limiting how a 22 covered entity can use and disclose that information. 23 Use is usually a term that we use to describe how an 24 entity will employ the information within itself, a 25 61 disclosure is how it would give the information, or 1 share the information with someone outside of the 2 covered entity. So by controlling how a covered 3 entity uses and discloses information, we can keep 4 that information private. 5 The rule sets out þþ does these controls 6 in a way of providing permissions. We say how it can 7 be used. Clearly, we allow the information to be used 8 for treatment, payment, and healthcare operation 9 purposes. These are the core functions of treatment 10 providers and the insurance industry. We allow þþ in 11 addition to those primary purposes we do recognize in 12 the rule a more limited set of important public 13 purposes, where information can be disclosed or used 14 without the individual's permission. If, in fact, the 15 information is to be used in a way that is not within 16 the scope of one of those permissions, then the only 17 way that information can be used for that purpose is 18 with the individual's written authorization. 19 Research is an area where we have allowed 20 under certain conditions for the information to be 21 shared with others without the individual's written 22 authorization. Otherwise, not that much different 23 from when you would conceive of the need for an 24 informed consent. Other research purposes would go 25 62 forward with a written authorization, and I want to 1 talk about those circumstances just briefly. 2 But before we get into that, the research 3 that is þþ just to step back for a second. The 4 research that's affected by the rule includes both 5 records research, research just on information, as 6 well as research involving human subjects in a 7 clinical trial setting is the most common. But the 8 rule also effects research in a variety of contexts. 9 It's not all research. It's not just research that's 10 subject to the Common Rule. It's not just research 11 that's subject to the FDA protections. It's any 12 research endeavor, and so we have tried to make the 13 provisions of the rule applicable in a generalized 14 way, and not specific to any other environment in 15 which research operates. 16 The counter of that is that the Privacy 17 Rule does not override, does not change the Common 18 Rule, does not change the FDA protections that are in 19 their regulations. And so an entity that is subject 20 to the Common Rule or is subject to FDA's protections, 21 and is also subject to privacy needs to blend all of 22 these obligations in order to continue to operate. 23 So what does it mean to have research with 24 patient permission? Under the Common Rule, this would 25 63 be research that's gone through IRB approval and there 1 is an informed consent. For the Privacy Rule, we 2 parallel that function by requiring that an 3 authorization valid under the Privacy Rule needs to be 4 signed by the research participant. 5 We have made attempts in the regulations, 6 primarily in August, to streamline the authorization 7 process so that it is more likely that the 8 authorization that's needed for privacy and the 9 informed consent that would be needed for the same 10 trial can be merged into a single document. In some 11 cases, the preference may be to have two separate 12 documents. But to make the merger of these two 13 documents easier, we did allow research authorizations 14 and exemption from the usual requirement of the 15 typical privacy authorization; and that is, it doesn't 16 need an expiration date. It doesn't have to be time 17 limited, or even event limited. And we also allow an 18 IRB in the process of merging the documents to waive 19 some of the authorization requirements in order for 20 the two to work better together. 21 We realized that there was going to be 22 circumstances in the typical research setting where 23 informed consent was not needed, and typically þþ the 24 Common Rule has criteria under which the need for the 25 64 informed consent can be waived. In the Privacy Rule, 1 we have tried to adapt those criteria to apply in a 2 setting where you would also be thinking about having 3 to waive the privacy authorization so that the same 4 research can go forward without either an informed 5 consent or a privacy authorization. 6 And there are also a number of activities 7 that were either outside of the Common Rule, or where 8 IRB approval wasn't necessary. And we have tried to 9 provide for some of those activities to also go 10 forward under the Privacy Rule without authorization; 11 including research on decedents, activities that are 12 simply preparatory to research, as well as creating in 13 August of 2002 something we call a Limited Data Set, 14 which allows information that's not totally de- 15 identified by our privacy standards, but do lack any 16 personal identifiers to be used for research purposes 17 without needing individual's authorization for that 18 information to flow for research purposes. 19 So just briefly what these þþ how these 20 four options work for when you can do research under 21 the Privacy Rule without needing the individual's 22 authorization - the first one is, when you have an IRB 23 that has waived the need for the authorization. And 24 that's based on three criteria that are set forth in 25 65 the rule, that the use of the PHI for the research 1 purpose represents only a minimal risk to the privacy 2 of the individual. That the research could not 3 practicably be conducted without waiver of the 4 authorization, and that the research could not be 5 practicably conducted without access to the 6 identifiable health information. 7 A little more on minimal risk. We had a 8 lot of discussion internally about how to þþ in a 9 privacy context what this means. This is similar to 10 our criteria that the IRB uses in terms of waiving the 11 informed consent in the normal research context, but 12 what does minimal risk mean when you're only looking 13 at the privacy aspects, and so we have further 14 identified that. It essentially means that there's a 15 plan in place that will adequately protect the 16 identifiers. There's a plan in place in the research 17 that will remove the identifiers as soon as 18 practicable consistent with the research purpose. 19 There may be times when, in fact, the identifiers need 20 to stay with the data, and that's allowed. And 21 there's a need for written assurances that the 22 information will not be reused or disclosed in other 23 than a research or similar context. 24 So if those conditions are in place, then 25 66 it would be permitted þþ describe circumstances where 1 the risk to the individual's privacy would be 2 considered minimal enough to allow their identifiable 3 information to flow without their written 4 authorization for that research purposes. You would 5 also need then to meet the second and third prongs of 6 the waiver criteria to get the waiver. 7 Just briefly on the preparatory for 8 research. This was essentially a way to allow 9 researchers access to information within a covered 10 entity so that they could prepare their hypothesis and 11 prepare the material necessary to present the research 12 proposal to the IRB for the IRB's review. This was 13 not the research itself, but just certain activities 14 that are preparatory to that research. And that the 15 condition for the access to the information is that 16 the identifiable information is not removed from the 17 covered entity, so it's used only for this limited 18 testing purpose. 19 We attempted to merge the fact that the 20 Common Rule does not cover information of decedents, 21 but the Privacy Rule does, and so we have allowed for 22 research that uses decedent information to go forward 23 without authorization. 24 And finally, the limited data set was 25 67 created in an attempt to track research need for 1 information which is largely unidentifiable, but still 2 contains certain elements. Primarily, the 3 conversations we were having mostly with the research 4 community was the need for birth dates and geographic 5 identifiers to come as part of these data sets. 6 With that degree of specificity within the 7 data, the information is still potentially 8 identifiable, so we didn't want to take it totally 9 outside of the protections of the Privacy Rule, but 10 did allow for research purposes for those kinds of 11 indirect identifiers to remain in the data sets. The 12 balance there was struck in terms of requiring a data 13 use agreement to govern how that information is 14 controlled once it is given over to the researcher. 15 There were a number of other requirements. 16 One of the rights I had mentioned earlier was the 17 right for the individual to know how their information 18 has been used or disclosed, actually disclosed. Here 19 for research, there were a couple of changes that we 20 made in August of 2002, to make it easier for a 21 covered entity that does a lot of þþ participates in 22 a lot of research, to simplify how they account to the 23 individual for the information that's shared with 24 researchers. One was where there's been an individual 25 68 authorization that's been signed, entities no longer 1 have to account for that research. Signing the 2 authorization, the individual knows the information is 3 going for that research purpose. 4 But if you're participating in very large 5 studies, studies of 50 records or more, we have 6 relaxed the requirement so that it doesn't have to be 7 an individualized accounting for that information, for 8 each and every individual. You can simply maintain a 9 list of the studies that you participate in. If the 10 individual wants more information, they can do the 11 contact directly with the research study. 12 Okay. The intersection between privacy 13 and research also required us to address some 14 organizational structures. A researcher can be 15 totally outside of the covered entity, just a third- 16 party researcher that wants the covered entity's 17 records. That's fairly simple to deal with, but we 18 also wound up in a situation where many entities, 19 large university settings and other large teaching 20 hospitals, where they do a lot of research themselves, 21 and have large research staffs, they essentially have 22 an option if they are, in addition to their research 23 and actual treatment provider that bills 24 electronically, they're covered by the rule. 25 69 The rule can apply to the entire entity, 1 including their research, or they can try to separate 2 their treatment function and their research function. 3 And if they hybridize or separate the two, then the 4 rule would only apply in the treatment setting, and 5 the research component of the entity would operate as 6 if it were a third-party. You would still need to go 7 through either the authorization or an IRB waiver of 8 that authorization process in order to move 9 information from your clinical setting into your 10 research setting if you hybridize. 11 DR. GYI: Ms. McAndrew þþ forgive me for 12 interrupting, Mr. Chairman. We have a few minutes 13 left, and I was wondering - there are probably some 14 issues that you'd like for us to address, and there 15 are I think about two minutes left on the time. 16 MS. McANDREW: Okay. I just wanted to 17 point you to some information. We have a website 18 where we have frequently asked questions. We also 19 have in your materials the NIH website where there 20 also are additional fact sheets, and frequently asked 21 questions, as well. 22 Many of the issues that we have addressed 23 today are contained in those materials that are on the 24 web, either in the frequently asked questions or in 25 70 the fact sheets that are available. And I think some 1 of those have been provided to you. Either in the 2 course of the rulemakings or in the subsequent FAQs, 3 we have addressed issues, such as recruitment 4 activities, how entities can recruit either as part of 5 the preparatory for research activities, or in 6 maintaining pre-screening logs, to reach out to 7 potential subjects for research. There are still some 8 discussions around those clarifications, and later in 9 the program there might be additional points raised by 10 the other panelists with regard to that. 11 We have also addressed the IRB's 12 responsibility to review the stand-alone authorization 13 and essentially have said from the Privacy Rule 14 perspective, there is no requirement to review a 15 stand-alone authorization. And I believe the FDA has 16 also subsequently posted clarification that indicated 17 that they didn't believe that their rules governing 18 their IRBs would require the stand-alone 19 authorizations to be reviewed. 20 We have tried to clarify how research can 21 go forward through creating repositories and 22 databases, as well as using those repositories and 23 databases for subsequent research. And there is 24 continuing conversations in that area, particularly 25 71 with regard to at what point the IRBs would actually 1 participate in authorization permissions for the 2 subsequent research done using existing databases. 3 And we have addressed the question where 4 when you are seeking the individual's authorization 5 for research, it needs to be research-specific. And 6 there are also continuing discussions on how that 7 meshes or does not mesh with some permissions that 8 come through the informed consent. But the 9 clarification so far is that the authorizations need 10 to be research-specific. 11 Just some things that we are working on, 12 we have recently gotten from the NCVHS, 13 recommendations based on their November hearings. 14 Those recommendations address some of the issues that 15 were on the prior slide, this slide, including asking 16 for additional clarification on stand-alone 17 authorization, as well as some inconsistencies in 18 preparatory for research in the recruitment area. And 19 we will be working with the NCVHS in responses to 20 their recommendations. 21 In addition, we've had many questions on 22 international research, and we're working with NIH to 23 put together additional fact sheets and FAQs that will 24 attempt to address some of the questions when you are 25 72 collaborating with researchers in other countries. 1 There is guidance that we're working on 2 again in cooperation with NIH about research in the 3 human services context, and there's been some interest 4 by our SAMHSA organization for some fact sheet and 5 FAQs in the area of using mental health records and 6 perhaps substance abuse records in the research 7 context. 8 DR. PRENTICE: Okay. Thank you very much 9 for a nice overview of the HIPAA Privacy Rule. The 10 next speaker will be Susan Ehringhaus. Would you 11 please come up. Susan is the Associate General 12 Counsel for Regulatory Affairs at the AAMC. And prior 13 to coming to AAMC, she was a Vice-Chancellor/General 14 Counsel at the University of North Carolina at Chapel 15 Hill. So welcome, Ms. Ehringhaus. We look forward to 16 your presentation. Let's all bear in mind that we 17 need to have time for discussion at the end of this 18 panel period; otherwise, we're going to cancel lunch. 19 MS. EHRINGHAUS: Well, I have good news 20 for you, and that is I have streamlined my 21 presentation from the version in the book, and I think 22 the audience has copies too, so I'll just skip a 23 couple of pages when I move forward, because I've 24 streamlined it knowing that you have a lot to go 25 73 through. 1 One, I want to thank all of you for your 2 invitation this morning to come and present, and for 3 your attention, and for people in the audience too. 4 The AAMC appreciates a lot the opportunity to 5 participate in these discussions. We've been a 6 participant since now six, seven years, however long 7 it's been. And we continue to want to be a 8 participant as these discussions evolve, and as the 9 impact on HIPAA is felt, and its interpretations by 10 your office and others mature, so thanks to everybody. 11 Truth be known, David Coin the person who 12 should be here. He's the Senior Vice President of the 13 AAMC, and he's out-of-town, so Cathy was kind enough, 14 along with the leadership of the committee to accept 15 a substitute, so here I am. 16 This survey that I'm going to tell you 17 about has been a very interesting project to work on. 18 And, in fact, it was started, it was a brain child of 19 Dr. Coin and Rina Hakimian, who before she was lured 20 away by Dr. Schwetz, she would be up here making this 21 presentation. So, Rina, thank you for all your work 22 on this. 23 I want to start with what should be 24 obvious to everybody, but I just want to affirm that 25 74 I suspect we are all committed to the same kinds of 1 principles; that is, the principle of conducting 2 research on humans ethically and with, obviously, 3 scientific integrity, where the protection of those 4 subjects is paramount, and where the protection of the 5 subject's privacy is also crucial. 6 To that end, we believe that whatever 7 standards are in use should maximize the use of the 8 identified data, and the standards obviously need to 9 clarify and affirm the duty of researchers to 10 safeguard privacy. At the same time, I think it's 11 also true that we want to assure the vitality of the 12 research enterprise, and I've listed some kinds of 13 research there that based on our survey, the kinds of 14 research that are particularly and uniquely affected 15 by HIPAA. And obviously, we'd like to reduce the 16 disincentives that HIPAA represents to researchers. 17 So with that prelude, let me also tell you that this 18 is where I'm going and where I'm going to end up - the 19 AAMC recommendations, and this slide is duplicated at 20 the back, but just bear with me. I just want you to 21 know where I'm heading, and this survey has led us to 22 these recommendations. I'll spend a little more time 23 on them at the end, but these recommendations conform 24 to recommendations that have been made by the National 25 75 Cancer Advisory Board on the basis of its survey of 1 its researchers. 2 So the AAMC-HIPAA survey was launched back 3 in April, the same time HIPAA took effect, the Privacy 4 Rule took effect, and has been open for several 5 months. We essentially shut it down late last year in 6 order to get a picture to present to NCVHS, the 7 Subcommittee on Privacy and Confidentiality, which we 8 did. This is the same data we presented there, but we 9 sought in this survey to create a database of case 10 reports, research functions affected and problems 11 encountered in HIPAA, and to probe the cost broadly 12 defined. A very impressive group of scientific 13 societies on the Steering Committee, along with 14 obviously the 126 accredited U.S. medical schools, 15 participated in this enterprise. 16 You'll see there American College of 17 Epidemiology, American College of Cardiology, other 18 organizations. These are the people we targeted for 19 respondents, and these are the traditional cautions, 20 we want data to be interpreted accurately. It's a 21 relatively small data set. The questions were asked 22 in the earliest phase of HIPAA compliance when many 23 people thought that we were over-interpreting or being 24 excessively conservative. But with those caveats, 25 76 let's see what we found. 1 The types of research affected by HIPAA, 2 serious concern to AAMC is the column on the left 3 there on the slide, the clinical research. Our 4 respondents tell us, 72 percent of our respondents 5 tell us the clinical research has been affected, and 6 you see on down. Health Services, Epidemiological, 7 and patient reported outcomes research - those kinds 8 of research are, we believe, essential to many of the 9 enterprises that we're all concerned about. 10 And in terms of research function 11 affected, you see how high those numbers are. We 12 asked respondents to tell us all that they believed 13 were affected; recruitment, data access, data 14 acquisition, data retention, and so on down the line. 15 But recruitment and data access, again, are areas of 16 significant concern for the AAMC. 17 We learned from our survey that there were 18 a number of different kinds of effects that HIPAA is 19 having on research, and you can read those as well as 20 I can. What I've elected to do is try to give you the 21 words of the researchers, and so I want to share with 22 you some quotes from that survey. 23 This is a sample of a comment dealing with 24 authorizations. "Additional consent form tends to 25 77 confuse more than inform participants, confusing for 1 participants to understand. Subjects are overwhelmed 2 by added length to the consent form." 3 Another perspective, or another set of 4 perspectives on authorizations, this time focusing on 5 informed consent. "My greatest concern is that the 6 requirement for all these authorizations to be signed 7 overshadows the importance of the research informed 8 consent document in process. I'm worried actually 9 that subjects are now paying less attention to the 10 consent process." 11 On recruitment - you see the first one, 12 "Just about made it impossible." Clinic patient 13 recruitment, again a very clear expression of concern, 14 and these are just samples. We had literally hundreds 15 of anecdotes reported in our survey. "HIPAA has shut 16 down our recruitment of subjects for a Phase III Chemo 17 Prevention Trial." 18 Uniformed consent. This one is a plea. 19 "My fear is that they" - meaning the subjects - "will 20 not take the time to thoroughly read the consents as 21 they are overwhelmed by the situation, all the pages 22 to read, and will just want to sign without being 23 fully informed." 24 I think this really is at the heart of one 25 78 of our concerns, that the added þþ that we do not see 1 added privacy protections, and we see confusion and 2 distraction for subjects by us. "The complexity of 3 the authorization form intimidates potential 4 participants. My concern is that by not including 5 those people in the study, we are not including a true 6 cross section of the population." 7 Now we all have heard of the burdens on 8 research resulting from the impact of the Privacy 9 Rule, but here these are in the words of the 10 researchers themselves. Reduce enrollment of 11 patients, difficult to access records and so on. And 12 then the last phrase, "Has created an environment of 13 paranoia, distrust, and frustration at my university." 14 I have to say, I've retired from the 15 University of North Carolina at Chapel Hill after 30 16 years, and I left there in December of 2002, but that 17 was the run-off issue to the HIPAA Rule. And even at 18 that point, the level of frustration and really anger 19 is a little strong, but the level of frustration at 20 these new procedures where the implementing privacy 21 protection could not be discerned was serious. 22 The identification - "those standards 23 increases errors, and severely limited ability to 24 obtain long-term follow-up for patients participating 25 79 in national registries." One of the most important 1 sources of research for the country. 2 And this, if you will read - I'm sorry to 3 be reading any of these to you - is a very interesting 4 comment from a researcher who does highway safety 5 research in connection with location of trauma 6 centers. This suggests that states are interpreting 7 quite conservatively the standards for releasing 8 information. Again, the identification causing a 9 change in a research direction, time and þþ increasing 10 time and money, forced to make decisions about current 11 need for data items when you can't really tell. 12 And then finally, the major difficulty for 13 us has been establishing multi-site trials and getting 14 everyone to collaborate in this newly derived fear of 15 litigation driven system. 16 Healthcare providers, particularly 17 community-based providers are no longer as willing to 18 submit data. Here we have a comment that providers 19 are not willing to submit data to an observational 20 pregnancy exposure registry. Multi-site trials used 21 to be more feasible. The costs we all know about, and 22 interpretations are all over the map. 23 We have a number of lawyers in the room, 24 and we all know that when we are representing an 25 80 organization, we want to make sure from our own 1 perspective that documents measure up to the standards 2 we think they're to measure up to. That process is 3 being duplicated in hundreds, literally hundreds of 4 places across the country every day as we all are 5 reviewing HIPAA authorizations. We are all reviewing 6 these documents, an unnecessarily duplicative effort. 7 The methods in HIPAA that the Privacy Rule 8 offer us for using health data do not offer much 9 solution, or many solutions for us as you can see from 10 this slide. We believe for the reasons that I'm going 11 to quickly go through, that these are not adequate to 12 take care of the problems. You can see that slide. 13 We are concerned about this, that many 14 people are not trying to involve third-parties in 15 resolving problems, that they're simply just throwing 16 up their hands in frustration. 17 If you look at the investigative column 18 and the study coordinator column, those two columns 19 account for certainly the vast majority of our 20 responses. Most of our responses came from 21 investigators and study coordinators. 22 Just a brief word on the National Cancer 23 Advisory Board Survey. They had conducted a very 24 interesting review of their cancer centers, 25 81 cooperative groups and spores, and they came up with 1 many findings that were entirely consistent with 2 our's; a negative impact on informed consent, 3 confusion of subjects, negative impact on subject 4 recruitment, bias, burdens, abandonment, alteration, 5 research direction, costs, collaboration, and 6 inconsistencies. 7 So with that background, let me conclude 8 by going through the AAMC recommendations for your 9 consideration. The first and second of our 10 recommendations really are very much like each other. 11 The first one deals with the process for 12 authorizations and waivers. And we are suggesting 13 that where there is informed consent and IRB approval, 14 that the requirement for authorizations or waivers for 15 research uses be eliminated. And we're doing that 16 because we believe that if the protocol is approved by 17 the IRB and there is informed consent, that the 18 increase in privacy protection that authorization 19 provides is negligible. 20 If informed consent is waived, we believe 21 we should retain HIPAA's specific waiver criteria, and 22 we would retain the requirement for authorization and 23 waivers for research if research is not subject to IRB 24 review. This process that we now have impedes inner- 25 82 institutional collaborations for the reason I just 1 indicated, the necessity to review others' 2 authorization and waivers for HIPAA compliance. 3 Our second recommendation is really just 4 a variation of the first, is to harmonize HIPAA and 5 the Common Rule with respect to privacy protection so 6 that we do not have inconsistent requirements creating 7 confusing, and causing delay. 8 We would also relax the standard þþ we 9 would urge you to consider relaxing the standard for 10 de-identification. One of our basic principles is to 11 maximize the utility of de-identified data. We 12 believe that you can do that by relaxing the standards 13 for de-identification so that you have greater utility 14 for what would be a new definition of de- 15 identification. This is especially problematic for 16 research requiring data contributing to the 17 understanding of disease associations or exposures, 18 and genotype data for rare diseases. 19 We need a de-identification standard that 20 is not based on extreme assumptions, but rather based 21 on realistic appraisals of what researchers can access 22 and what they can't. And we believe that de- 23 identified data can incorporate unique identifiers 24 provided they're not shared with researchers. 25 83 We would eliminate the accounting for 1 disclosures for research. We think these accounting 2 records are really meaningless for the individual. 3 For research involving fewer than 50 subjects, we've 4 got a huge regulatory burden. We have a differential 5 impact on community providers and hospitals. They do 6 not want to go through this according to what they're 7 telling us. We don't want to shrink the research base 8 for epidemiologic and health services research where 9 there's no increase in privacy protection, we believe. 10 For research involving 50 or more 11 subjects, again the list of protocols will be 12 extensive in major research universities. The burden 13 that we've taken on is pretty severe. 14 And then finally, you've heard this from 15 us before, but we believe that the standards for the 16 organizational focus in HIPAA doesn't match the 17 organizational complexity of academic health centers, 18 and we would urge rethinking of that. 19 So there are our recommendations. Again, 20 you see that the first four are consistent with the 21 NCAB respondents. The fifth one simply was not 22 addressed by the NCAB. And finally, we'd just like to 23 end with the same principles we started; that is, the 24 protection of human subjects is paramount, and part of 25 84 that is the protection of the privacy of those 1 subjects. And at the same time, we believe that it's 2 possible to preserve the vitality of the research 3 enterprise and reduce some of the negative incentives 4 that the impact the Privacy Rule has illustrated. 5 Thank you very much. 6 DR. PRENTICE: Thank you, Susan, for 7 sharing the survey data with us. I think we all agree 8 that AAMC data are both disturbing and I think 9 predictable. Our next speaker is Mark Rothstein, who 10 holds the Herbert F. Bail Chair of Law in Medicine, 11 and is Director of the Institute for Bioethics, Health 12 Policy and Law at the University of Louisville. He's 13 also Chair of the Privacy and Confidentiality 14 Subcommittee of the National Committee on Vital and 15 Health Statistics, which is a federal advisory 16 committee. He's here to talk about the 17 recommendations of the NCVHS on the HIPAA Privacy Rule 18 and research. Mark, thank you. 19 MR. ROTHSTEIN: Thank you. I want to 20 thank you for the opportunity to be here. I am going 21 to be presenting the official view of the National 22 Committee on Vital and Health Statistics. Where I 23 stray from the official line, I hope to remember to 24 add the appropriate disclaimers. 25 85 For those of you not familiar with the 1 NCVHS, it is a statutory federal advisory committee 2 that was established over 50 years ago to advise 3 Congress and the Secretary of HHS on health data 4 issues, including those arising under HIPAA. We have 5 18 members, 16 appointed by the Secretary and two by 6 Congress, one from the House and one from the Senate. 7 And we have a variety of workgroups and subcommittees. 8 The last one you see, Privacy and Confidentiality - 9 not in importance, but merely on this list is the one 10 that I have the privilege of chairing. 11 By way of introduction, for those of you 12 not familiar with HIPAA and Privacy issues in general, 13 if I asked everyone in the room could I have a show of 14 hands how many of you are in favor of health privacy - 15 you don't have to raise your hands. I'm sure 16 everyone would raise their hand. I mean, we are all 17 in favor of health privacy in the abstract, but we're 18 also in favor of research, and we're also in favor of 19 unfettered clinical care. And we're also in favor of 20 public health, and we're also in favor of not standing 21 in the way of national security and law enforcement, 22 and other essential access to information. So 23 immediately you see the problem. 24 We must balance two or ten very important 25 86 and well-considered interests, and that's what makes 1 HIPAA so difficult, and it's a problem that anyone 2 who's thought about the issue, let alone regulated in 3 the issue, or recommended in the issue has had to deal 4 with. The Privacy and Confidentiality Subcommittee 5 has held a number of hearings. Those of us on the 6 committee are not busy enough in our day jobs, so we 7 like to go around the country, mostly to Washington 8 and hold hearings in which we hear from different 9 stakeholders related to HIPAA. We did this before the 10 implementation data. Now we're doing it to monitor 11 the implementation activities, and we're conducting 12 hearings, and will conduct hearings in a variety of 13 areas. 14 Our November 19th and 20th hearings dealt, 15 in part, with the issue of research. And let me 16 summarize for you the testimony that we heard. You 17 already heard the testimony about the study that 18 indicated the belief by researchers that the Privacy 19 Rule had detrimental effects on research. 20 I think in fairness, however, some of 21 those negatives views can be attributed to one of two 22 factors. One is that what is being blamed on HIPAA is 23 general dissatisfaction with regulation of research in 24 general. So in other words, people complained about 25 87 HIPAA making us do X, Y, and Z, when they already had 1 to do X, Y, and Z before HIPAA came along, but it's a 2 nice target. That, I think, is an unquantifiable 3 percentage of people. 4 The other complicating factor, and I think 5 this was mentioned very clearly in Susan's 6 presentation, is that the misunderstanding of HIPAA by 7 the possessor's of health data and not releasing it 8 for research purposes - in other words, the 9 confusion/misunderstanding is a limiting factor, as 10 well. And those kinds of things call for, I think, 11 different solutions than some of the other problems. 12 There is wide support we heard in the 13 testimony for aligning the Privacy Rule and the Common 14 Rule, something I want to talk about at greater 15 length. There is still considerable confusion among 16 researchers and IRBs, but that's an improvement. I 17 would characterize our prior hearings on research, the 18 atmosphere as despair and anger, so confusion I view 19 as a positive step in the right direction. 20 There are inconsistencies between the 21 Privacy Rule and the Common Rule. I'm going to try to 22 address some of those that the committee was concerned 23 about. And at all of our hearings, no matter what the 24 subject, we have the same types of comments from the 25 88 witnesses about the need for additional clarification, 1 education and outreach activities. 2 Well, I want to talk about three 3 inconsistencies that the committee was concerned about 4 between the Privacy Rule and the Common Rule. 5 Inconsistency would not be a bad thing, per se, but 6 it's the effect of the inconsistencies, and I think 7 there are three effects of the inconsistencies. One, 8 they can either cause gaps in protection for human 9 subjects. Second, they can create unnecessary burdens 10 on researchers. And third, they can contribute to old 11 favorite, confusion. 12 So one that we looked at is the provision 13 dealing with efforts preparatory to research. And 14 under the HIPAA interpretation from HHS, researchers 15 who are part of the work force of the institution that 16 stores the medical records, so an in-house researcher 17 let's say at medical school and their business 18 associates. After they are allowed to look through 19 the records without any prior authorization or IRB 20 approval, to see if there are enough people with such 21 and such disease that makes it feasible to create a 22 study, which is okay at that point as far as we're 23 concerned. But after that, then these researchers may 24 contact the individuals that they've identified and 25 89 ask them for their authorization to use their 1 protected health information in research. 2 This is before any submission has been 3 made to an IRB for approval or waiver. Now there is 4 an argument that the department has made that somehow 5 this is okay under the Privacy Rule because it comes 6 under healthcare operations, which I think is a rather 7 expansive, shall we say, interpretation of healthcare 8 operations. But irrespective of that interpretation, 9 I think it clearly violates the prime directive of 10 IRBs, and that is, you don't start research unless the 11 IRB has given you approval. And recruitment is 12 research, and when you directly contact individuals to 13 try to ascertain whether they would be willing to 14 allow you to use their protected health information, 15 that is part of the recruitment, and that should not 16 go forward unless the IRB approves. 17 Okay. Here's an example of confusion. As 18 was mentioned earlier, the Privacy Rule permits 19 combined informed consent and authorization documents. 20 It's been my experience that many institutions don't 21 want to do this, and I would invite perhaps Susan or 22 Joanne to explain why the many institutions don't want 23 to do this, but many of the problems that we see in 24 terms of duplication of efforts stem from the fact 25 90 that institutions don't want to have a unified 1 informed consent and authorization document. 2 If you have a unified document, it makes 3 life a lot simpler. I've actually drafted these. It 4 doesn't take too much effort to integrate the HIPAA 5 requirements for an authorization into an informed 6 consent agreement. Perhaps this is one area where if 7 there are institutional problems - in other words, if 8 the institutions feel that it's not really in their 9 best interest to have a single document, maybe we can 10 address those issues and make it more feasible or more 11 reasonable for them to integrate those documents 12 without the concern that they have for other issues. 13 But allowing them to be integrated would help. 14 At any rate, they're not required to do 15 this. The Privacy Rule does not require IRB approval 16 of stand-alone authorizations, and because of that, 17 some IRBs believe they are in fact prevented from 18 reviewing them. Now you have the situation where the 19 IRBs think it's outside of their jurisdiction to 20 review purely HIPAA-related stuff. They can only deal 21 with the IRB, the informed consent document, and the 22 research is delayed, and the researchers don't know 23 who to turn to, and it's a mess. So this is an area 24 where this difference, this inconsistency leads to 25 91 confusion. It's an area, I think, that needs to be 1 addressed. 2 I think one possibility, and it's not what 3 we specifically suggested, so I'm now going beyond our 4 recommendations, is that IRBs be directed and reminded 5 that information that is given to potential research 6 subjects that they will rely on in deciding whether 7 they want to participate in the research should be 8 reviewed by the IRB. And that, perhaps, would settle 9 that, but that's not the þþ I suppose under the 10 Privacy Rule there's not the authority to tell IRBs to 11 do that, and so that inconsistency has emerged. 12 The third area I want to rely on is I 13 think an example of an unnecessary burden being placed 14 on researchers. Under the Common Rule, IRBs may 15 approve research subjects providing informed consent 16 for future unspecified research. Now for those of you 17 who serve on IRBs, you know that IRBs are not crazy 18 about this idea, and often attach rather specific 19 conditions on that, and try to limit the scope of the 20 future research as far as possible. 21 Nevertheless, under the Privacy Rule, as 22 Sue McAndrew explained, generally speaking, 23 authorizations must be for protocol-specific research, 24 and under only a recent interpretation, you would need 25 92 to get a waiver alteration from an IRB or privacy 1 board. These, it seems to me, create unnecessary and 2 excessive burdens on researchers to go forward while 3 adding very little, if any, protection to the privacy 4 interests of research subjects. 5 We also identified other areas of concern 6 from the testimony that we got. One was the issue of 7 indirect participants of research, and I know this is 8 something that has been a concern for a long time. 9 It's also a HIPAA concern, because in many instances 10 the indirect participants are only involved because 11 their health information is disclosed in the course of 12 a study, so we need to address the indirect 13 participants' issue both from the Common Rule 14 standpoint and from the HIPAA standpoint. 15 The second one, Susan just went through 16 the multi-institutional studies. It already was a 17 problem before, and to the extent that HIPAA adds 18 another layer in the sense of getting an 19 authorization, as well as informed consents that vary 20 across institutions, that makes multi-institutional 21 studies more difficult. And we heard testimony that 22 it's impossible now to get smaller institutions to 23 participate in research because they don't have the 24 staffs that larger institutions have. They don't have 25 93 an office of research, and they're just overwhelmed by 1 this new monster, as they see it. 2 Fourth, not on the slide, I would add that 3 we heard testimony from the American Society of Human 4 Genetics on a very narrow issue, and that is that 5 anonymous information is not covered by the Privacy 6 Rule because it's not individually identifiable. They 7 wanted to know whether genetic samples were per se 8 identifiable, because in theory, you could sequence 9 the DNA and limit that DNA to one individual. And I 10 think that's easily resolved by a clarification from 11 the department, because if you adopted that arguably 12 paranoid theory, that would apply to any biological 13 specimen because you could always extract DNA from 14 that, and then you could really never have any 15 anonymous samples, so I think that can be clarified. 16 Okay. To summarize, and I believe that 17 you have copies of the letter that we sent to the 18 Secretary - with regard to research, we had one 19 specific and one more general recommendation, and the 20 specific one is the second one. We said that HHS 21 should clarify that the Privacy Rule neither requires, 22 nor precludes IRB review of stand-alone authorizations 23 for use or disclosure of protected health information 24 for research, and I've talked about that. 25 94 I do want to talk about the other one, the 1 more general one, and I think that's really 2 appropriate for you to consider, and possibly 3 coordinate with NCVHS or other federal advisory 4 committees; and that is, our recommendation that HHS 5 should make further efforts to harmonize the Privacy 6 Rule with the Protection of Human Subjects Rule. 7 We recognize, and I suppose I should now 8 add that this is my editorializing about our 9 recommendation, and it's not part of our 10 recommendation. So I recognize that there is 11 different authority for the Common Rule and for the 12 Privacy Rule in terms of the legal authority for the 13 regulation; that there is, in fact, different 14 coverage. Not everybody covered by the Privacy Rule 15 is covered by the Common Rule and vice versa, and they 16 serve different purposes. The Common Rule has a 17 broader purpose to protect human subjects, the Privacy 18 Rule protects human subjects of research in a narrow 19 sense, but it protects other people in other ways. I 20 recognize all that, but I believe that there is 21 substantial overlap of these two sets of regulations. 22 And I believe that the interests of researchers, 23 research subjects and the public will be furthered by 24 coordination, simplification, and harmonization of 25 95 these rules to the greatest extent possible. And I 1 don't think we've done that yet, or achieved that yet. 2 I think that we need to make sure that 3 every additional burden that we impose has a payoff 4 down the end to the extent possible, additional 5 privacy protections for an individual. So those are 6 the views of the National Committee on Vital and 7 Health Statistics, with a couple of footnotes of my 8 own thrown in. And during the discussion, I'd be 9 happy to answer your questions. Thank you. 10 DR. PRENTICE: Thank you, Mark. We 11 appreciate the information. The next speaker is 12 Joanne Pollak, who is the Vice President and General 13 Counsel for the Johns Hopkins Health System 14 Corporation. As Vice President, she oversees internal 15 audits for the healthy system, as well as HIPAA 16 compliance for the same health system. So welcome, 17 Joanne. We're looking forward to your presentation. 18 MS. POLLAK: Thank you very much for 19 allowing a provider, in essence, to come before you. 20 We have no official capacity here, except that we're 21 living with the rules. And what I'd like to do today 22 and what, indeed, I was asked to do was to talk about 23 some of the practical implications of HIPAA at an 24 institution, since we've really begun to live with 25 96 what the words mean in practice, rather than just in 1 theory. 2 I'm going to talk about three areas. The 3 first has not been talked about today, and that is the 4 area of medical archives in covered entities. The 5 second is the unspecified future research. I'd like 6 to give you some of our experiences with that. And 7 the last really is what's been talked about both by 8 Susan and Mark, and that is the whole issue of whether 9 we should somehow legally and/or practically through 10 amendment of both sets of rules harmonize the Common 11 Rule and HIPAA with respect to authorizations. 12 So first with respect to medical archives, 13 most of you know that medical archives are 14 documentation that is held within an institution that 15 may include the actual medical record of persons who 16 have been in that institution. But more often, it 17 includes records of the physicians who practice there. 18 It can involve letters that go back and forth, not 19 just between patients and doctors, but between doctors 20 and/or between individuals that somehow make their way 21 into the papers of a famous physician or something 22 like that. It can involve photographs of patients who 23 were there in 1890. It can be groups in front of a 24 particular clinic. There could be all types of things 25 97 that when you think about it, you wouldn't readily þþ 1 HIPAA wouldn't readily come to mind. 2 However, for those of us who find that our 3 medical archives do not or should not be out of the 4 covered function of our covered entity, and therefore, 5 are covered by HIPAA, such as our's, we then are 6 subject to the HIPAA rules with respect to these 7 documents, some of which are 100, some 150 years old. 8 Now how do we do that? 9 We have two areas that we have to address, 10 one is access and one is publication. Well, the first 11 is access. And HIPAA, as Susan has gone over, has 12 several ways that you can access PHI, in effect, 13 that's now sprinkled through all these documents in 14 all different places. And most of them relate to 15 treatment, payment, and healthcare operations. 16 Generally, none of those are exceptions to allow you 17 to get into the archives if you're someone from the 18 newspaper, if you're a person who comes in and just 19 wants to go through the archives for historical 20 interest, if you're a historian, if you are someone 21 from another university. You don't necessarily have 22 a research hypothesis, but you want to look at the 23 medical archives. 24 Well, to be able to access those 25 98 materials, we have to fit into one of the access 1 buckets that HIPAA has. Research is the one that 2 we're sort of stretching as far as we can so that we 3 can say that when somebody comes, they are doing 4 research. Now as long as they do not disclose to 5 anyone else that information for other than research 6 purposes, and as long as they follow all the 7 representations that you need to make, you can 8 generally give access to these materials in a 9 meaningful way for the researcher, so we don't want to 10 stop true research. But the more you stretch that 11 definition, the more difficult it gets. And when you 12 get to someone who's just coming in to look at their 13 family history to see if they can find out something 14 about what's going on in their family, or in their 15 nationality, or someone is just coming in because they 16 want to read and they're interested in a certain area, 17 that's not really research, so what does the archive 18 staff have to do? 19 Under HIPAA we are not allowed, except 20 incidentally to disclose PHI. Now remember, this 21 might be Dr. Ossler saying to somebody in 1910, my 22 sister has gout. Now there's no patient involved, but 23 there's an identifiable person and there's medical 24 information, and together that makes PHI. So that 25 99 letter that talks about his sister's gout technically 1 cannot be disclosed except incidentally. And if you 2 can mark it out, then is that reasonable? 3 Well, what we found is that our staff, our 4 medical archive staff is spending hours and days going 5 through materials and marking out the PHI from the 6 documents that are being requested by those who do not 7 meet the research exception. What makes it even more 8 nefarious is that those institutions that don't have 9 their archives in the covered function are not subject 10 to this, and people who want to donate things to our 11 archives are reluctant to do so because they feel that 12 the access will not be broad enough and serve the 13 public purpose of what they intended when they make 14 donations to archives. 15 The last implication that is difficult for 16 us is publication. We have researchers and students 17 who want to do their dissertation. Dissertations are 18 generally published, maybe in a very narrow way, but 19 certainly within HIPPA's definition, it's published. 20 Technically, that researcher may not publish. The IRB 21 cannot waive the right to publish. They can waive the 22 right to do research but they can't waive the right to 23 publish. So, therefore, if that dissertation has to 24 be published even within a small group of people at 25 100 that university, or outside which is generally the 1 problem, then they've got to de-identify the 2 information. 3 What's come up to our privacy board on two 4 occasions recently are where the person writing the 5 dissertation is trying to link the information from 6 prior published research going into our medical 7 records on that very person, and then wanting to 8 publish what their interpretation is, now having 9 looked at the medical record versus the information 10 that was prior published. 11 Now there's a couple of ways you can do 12 it. You can go and try to get permission from each of 13 the people that you are doing this for. Some of them 14 can't be found. Some of them, their families þþ their 15 name was in some book in 1930, but there's nobody 16 around to get that. Who do you go to? 17 The other thing that we've had, and I 18 don't want to miss it, is that we have some wonderful 19 photographs that we like to put in our publications, 20 but people that are technically patients and they're 21 standing outside of a clinic that you can identify, 22 we're not sure they're patients, but under the HIPAA 23 Rule, you've got a full face which is definitely 24 identifiable. You have some medical information, link 25 101 it, it's probably PHI. 1 I sought an outside opinion on this and I 2 didn't get anywhere, and so what we really have is a 3 situation where reasonable people looking at that 4 should be able to figure out whether that would be 5 embarrassing or difficult for an unnamed or 6 unidentifiable person. So I was asked to give some 7 solutions, not just the problems, and one of the 8 things I would suggest, and there may be other ways to 9 solve the problem, would be that only the designated 10 record set in an archive would be subject to HIPAA; 11 meaning, that if you are just moving your medical 12 records over from your provider side to your archive 13 side, that should not þþ you shouldn't escape from the 14 regulation of HIPAA. 15 However, the books and records, and 16 documents and other things really are not, I don't 17 think, what was intended by HIPAA to be protected. 18 But even if it is, we could leave it up to a privacy 19 board to determine whether it's reasonable to release 20 that. So I would suggest, number one, limiting it to 21 the designated record set. Second, using the Privacy 22 Board as the arbiter for taking out as much 23 information as possible, and/or deeming that it's 24 reasonable to publish when it is not something that's 25 102 in the designated record set itself. 1 Another way to solve it might be to put a 2 number of years - this is really in addition to the 3 other solutions - a number of years, something in the 4 letters and documents that are 75 year or 100 years 5 old would not be subject to the HIPAA requirements. 6 Okay. I want to make sure. Okay. The 7 second area is future unspecified research. I think 8 all of our speakers today have spoken about 9 unspecified future research. I would like to talk 10 about it in the practical sense. 11 We've had situations where people have 12 donated their tumors to a cancer registry, and the 13 Common Rule informed consent says that I donate my 14 tumor or my tissue for future research related to the 15 study of X types of cancer. It does not specify 16 exactly which protocol specific research would be 17 done. That goes into the data bank held by Hopkins. 18 There is no need for an additional informed consent. 19 Next week a researcher comes in with the 20 next study. Well, we know whose tissue now is in that 21 tissue bank. What HIPAA requires is for us to go back 22 and get an authorization for everybody who put their 23 tumor in that registry. 24 Now a disembodied authorization with no 25 103 study to go with it, because there's no informed 1 consent required for the study, because the researcher 2 already has the right to use that under the Common 3 Rule. But you need to go back with an authorization 4 and get an authorization from the individual. That's 5 very confusing. What they say is I already gave my 6 consent. Is there something different here? What's 7 going on? 8 Now I think the reason in reading the 9 commentary and explanations is that there's a concern 10 that in that second research, or third research, or 11 20th research project, that that information might not 12 be kept private and confidential in the way that it 13 should, and the person gets a right to know that. But 14 that's really the IRB's responsibility, whenever 15 they're doing that next protocol. To have to go back, 16 and that registry can be used 50, 100, 200 different 17 studies. Every single time we have to go back and get 18 a waiver from the IRB or an authorization from 19 everybody whose tissue is in the bank. To me, this is 20 really overburdening, and is very confusing when the 21 IRB members say to me, Joanne, we already got consent 22 for this. This can't be right, and so it's confusing 23 not only to our participants in research, I think it's 24 confusing to our IRB members themselves. 25 104 The solution has already been mentioned by 1 others here today, and that is that the Common Rule 2 and the HIPAA rule should be harmonized in this area. 3 We should allow the IRB to determine whether that 4 first consent is adequate, and even build in 5 additional protections. 6 One thing I don't want to forget - if we 7 don't change this, what's going on is that people 8 don't want to contribute their tumors and their data, 9 and their DNA to covered entities. And what's 10 happening is that you are getting a whole industry of 11 outside of the universities' data banks, so it takes 12 it out of our control. 13 Now I'm not against outside data banks, 14 but to say that we can't have them because of HIPAA 15 seems very much an injurious consequence. And I 16 believe it was an unintended consequence. 17 Last, and this has also been mentioned, is 18 really why have both an informed consent and a HIPAA 19 authorization? I think that as I've read the 20 commentary and under the Q&As, there really were two 21 reasons why HHS determined that we really needed these 22 two separate things. One was that the privacy rules 23 needed to protect everyone in research, not just those 24 covered by OHRP or FDA federally funded research. 25 105 And, therefore, there was the desire to make that 1 circle much broader. 2 Second, there was the feeling that the 3 IRBs had not paid enough attention to the privacy 4 concerns in the trials. The regulation is right there 5 now. Every IRB is supposed to look at the privacy 6 considerations in every trial, but I think it had not 7 been focused on historically. So what we've got are 8 these two forms. 9 Now, Mark, you asked the generic question, 10 why would you not have one form? Well, we went to one 11 form, and what has happened to us, I could never have 12 predicted. Number one, every single funding agency 13 has a different requirement. One says they want it 14 together, the next one says they want it apart, or 15 they want one section of it moved to another section, 16 or they won't approve the study. 17 It has come to the point where I sometimes 18 spend three weeks to two months just negotiating with 19 the institute within the NIH as to how they want the 20 HIPAA form worded and/or which place it should be. I 21 don't think that is a good result from what was 22 intended to protect privacy of individual 23 participants. 24 It is very confusing when you think about 25 106 it. You can't do the research unless you have the 1 authorization, and yet we say oh, the IRB doesn't have 2 to approve a single research form. Well, excuse me. 3 If you are þþ this is the basis upon which you're 4 allowed to use the data, I don't think you can just 5 cavalierly say oh, the IRB doesn't have to review it. 6 Now I realize from an authority point of 7 view that may not be in the law, but what we've got is 8 this schizophrenic, like people so confused about what 9 they should be doing and shouldn't be doing. And I 10 don't mean to be light about it, because it is serious 11 to make sure that people understand what they're 12 giving their consent for, for the use of their 13 material and information, and how it's going to be 14 used, so I don't mean to make light of it. What I'm 15 making light of is the fact that we think we can 16 somehow separate the very permission to use the 17 information from the research itself. It just doesn't 18 make any sense to me, so even though the FDA says oh, 19 don't worry about it, or the Office of Civil Rights 20 says no, you don't have to do this - somebody in the 21 covered entity has to do it, and the principal 22 investigator has got to negotiate between people, so 23 it seems to me we have created confusion. 24 Solution - I think for those studies that 25 107 are covered by the OHRP and the FDA, we should rely on 1 the Common Rule. We should not have an additional 2 form under HIPAA. For those research - this is really 3 what Mark said - and for those that are outside of 4 HIPAA we could continue to have an authorization and 5 try to simplify it somehow, so that they don't get 6 caught in the same situation. 7 We probably should strengthen the OHRP 8 rules on privacy. So in other words, if we take away 9 the requirement for the authorization for OHRP and FDA 10 trials, then possibly we could strengthen what we 11 require the IRB to do and have in the informed 12 consent. But by bringing it together, it seems like 13 it would be a little bit saner than where we are right 14 now. Okay. Thank you very much. 15 DR. PRENTICE: Thank you, Joanne, for that 16 insightful presentation. Would the panelists please 17 assemble up at the front of the room. Okay. One of 18 the advantages, maybe the only advantage to compensate 19 for the pain associated with being chair of this 20 August group is I get to comment and ask questions 21 first. I'd like to be able to monopolize the entire 22 time, but I'm sure that I would not be able to get 23 away with that, so first a few comments. 24 I was quite surprised that I have not had 25 108 a lot of complaints from investigators at my 1 institution with regard to implementation of the HIPAA 2 Privacy Rule. I thought I'd have a revolution on my 3 hands. Secondly, we utilize a combined Common Rule 4 consent form with HIPAA authorization, and we found 5 that it works quite well. We've not had much 6 difficulty in getting various sponsors to accept the 7 language with exceptions of drug companies, which is 8 where I want to go next, because nobody really talked 9 about pharmaceutical sponsors in this whole equation. 10 Everybody knows that drug companies are 11 not a covered entity. They do not have to comply with 12 the Privacy Rule. We are encountering model consent 13 forms produced by drug company lawyers, as well as 14 contract language that basically says we want the PHI, 15 we want to use it for any purposes in the future that 16 we want to use it for, unspecified research purposes. 17 We want to put it into a data bank, give it to anybody 18 that we want to forever more. And then when we tell 19 them well, yes, we understand you're not a covered 20 entity, but we are. We have to comply with the 21 Privacy Rule. Then we get into protracted 22 negotiations on the language with these lawyers, and 23 it has really become a problem for us. 24 In some cases, they actually compromise 25 109 and agree to the language that's contained in the 1 consent document, but they don't agree to the language 2 contained in the contract because they seem to think 3 that the consent document is more or less a contract 4 between the institution, its investigator and the 5 research subject; whereas, the contract is an 6 agreement between the company and the institution, so 7 we have a lot more difficulty in negotiating the 8 language in the contract. So I'm just wondering if 9 anybody else has encountered this problem, or is this 10 unique to my institution? 11 MS. POLLAK: Maybe I could start in that 12 this is something that we too have encountered a great 13 deal of difficulty with. And actually, with so much 14 resistance from the drug companies that we took it 15 back to the IRB as to whether we as an institution 16 would have a position that if they would not agree to 17 limitation of the future uses either consistent with 18 the consent or authorization, or de-identified or data 19 use agreement, that we then would have to not do the 20 research with them, so that's a very big step. And 21 what we found was when we went back and said we were 22 very dead serious about it, and that we thought that 23 you really couldn't, in effect, have an agreement, if 24 you would, with your participant that this is how 25 110 we're going to use your information, and then turn 1 around and give it to somebody else and let them use 2 it differently under a contract, we were able to 3 resolve. Our major concerns has been using it for 4 marketing and identifying it using the information 5 outside of the sponsor. And when we really talked 6 about what they wanted to do, we usually have been 7 able to get it, either something that we could add 8 into the authorization or using a limited data set, or 9 even de-identified information. 10 MR. ROTHSTEIN: May I comment on that? I 11 just think that the scenario that you raise cries out 12 for sort of a uniform solution to this. I think the 13 worst thing that could happen would be a race to the 14 bottom among institutions who are fearful of losing 15 the research, so I could see a situation where a 16 research sponsor would say well, if you don't agree, 17 I'm going to go to Institution X. They will do that 18 for me, and then there would be tremendous pressure to 19 do that. And I think that needs to be taken out of 20 the equation in determining who actually is the 21 institutional researcher. 22 DR. PRENTICE: And I agree with you. When 23 I left last week to go on a trip, I was negotiating 24 with a company, and basically the position was this is 25 111 our last offer. Either comply or we're out of here. 1 And it's a significant amount of money in terms of a 2 research contract, and we think it's important to be 3 able to offer our patients the opportunity to 4 participate in these kinds of clinical trials, so I 5 think it's something that's very serious, has serious 6 consequences all the way around, and it needs to be 7 addressed. 8 Okay. The floor is now open for everybody 9 else, and we'll take you in order. Bob. 10 DR. HAUSER: Thank you for your 11 presentations, and I think we all appreciate the 12 burdens of the HIPAA Privacy Act. We're obviously 13 concerned with human research protection. And I'd 14 like to ask the panel if they believe or have any 15 experience with whether or not the HIPAA rules have 16 adversely affected out ability to conduct safe 17 clinical research. Are there any safety issues 18 involving human subjects where HIPAA may be a problem? 19 MS. EHRINGHAUS: Well, I'll take the first 20 crack at that. Certainly in our survey the 21 respondents, or some respondents indicated that the 22 use of de-identified data according to the HIPAA 23 Privacy Rule standards increase the possibilities for 24 error in data interpretation because essential 25 112 features had been removed necessarily in order to 1 comply with the standard, so that's what we heard from 2 some of our respondents on medical error. 3 One other thing. Research involving þþ a 4 retrospective review of research, of treatment 5 records, I'm sorry - retrospective research of 6 treatment records of patients in order to identify 7 systemic causes of medical error we also heard was a 8 type of research seriously compromised by the impact 9 of the Privacy Rule. 10 MS. KORNETSKY: Thank you for the 11 presentations. I'd like to ask, Susan - you made a 12 statement that there have been over 5,000 complaints 13 made since the initiation of HIPAA, and I would expect 14 that there probably are a lot of people sort of 15 testing the waters out there, but can you make any 16 comment as to what percentage have to do with 17 research, if any, and what the types of issues that 18 have been raised have been? 19 MS. McANDREW: I can't comment 20 specifically on the number of those complaints where 21 there might be a research disclosure that is embedded 22 in that. I would say that the majority of the 23 complaints þþ if research was an issue, it would be a 24 relatively small percentage of those complaints. By 25 113 and large, the complaints concern healthcare 1 providers, either private practitioners or general 2 hospitals, and the top issues that we get in the 3 complaint mix are impermissible uses and disclosure, 4 but that covers the waterfront, not just þþ I mean, 5 research is just one possible component of that. 6 Access to records is another major source of concern 7 for individuals on the basis of complaints, refusal to 8 be provided access to their records. 9 I would say, however, not in terms of the 10 complaints but in terms of the comments that we got 11 through both the original Privacy Rule that was 12 proposed in `99 and finaled in 2000, as well as the 13 modification, there were significant comments from 14 individuals about the need to protect their 15 information and concern about wanting to have consent 16 and control over how their information is used in a 17 research setting. It was not an insignificant number 18 of comments. 19 DR. PRENTICE: Thank you. Tom, you're up 20 next. 21 MR. ADAMS: Well, it's pleasant to find 22 that someone has had something good to say about 23 HIPAA, so that was a helpful remark. One of the 24 things that came up repeatedly in the testimony here 25 114 this morning was the fact that to harmonize the Common 1 Rule with HIPAA would solve a number of the problems 2 that we had discussed. So I guess, Susan, my question 3 to you is are there conversations which are occurring, 4 or any desire for the department to move in that 5 direction? 6 MS. McANDREW: We are having many 7 conversations in the research area. There was a 8 fundamental decision when we did the August 9 modifications to not totally exempt Common Rule 10 covered research, but to attempt to come to a set of 11 privacy conditions that would apply generally to 12 research, whether it was subject to the Common Rule or 13 not. The department was concerned about having what 14 would be the appearance of different standards. 15 Participants in Common Rule covered studies would have 16 this set of protections as defined by the Common Rule. 17 Other studies outside the Common Rule would have a 18 different set of privacy standards applied to them. 19 And there was a consideration to not go in that 20 direction, to try to treat all research alike. But in 21 that process, to try to accommodate the Common Rule, 22 to make the rule work as smoothly as possible with the 23 Common Rule. And those conversations continue to go 24 on about what is it þþ where are the rubs, and can 25 115 they be smoothed out so that the two rules do work 1 more harmoniously. 2 DR. PRENTICE: Felix. 3 DR. GYI: Joanne, you had mentioned that 4 a recommendation that you might want us to consider is 5 to have OHRP strengthen its rules on privacy. I 6 wonder if you might help us to understand what that 7 looks like, if you could elaborate a little bit more 8 on that. And, Susan, if you could react to that 9 response, that would be tremendously helpful to me. 10 MS. POLLAK: Thank you. I think my 11 suggestion is in the context of not doing what Susan 12 had said; in other words, exempting OHRP and FDA from 13 the rule. Given that, the question is, is there 14 anything in the HIPAA Privacy Rule that is not 15 expressly present in the OHRP rules that would need 16 strengthening, and I think that there probably is. 17 In other words, there is no requirement 18 currently in OHRP to, in effect, disclose the types of 19 information that would be used and how it was going to 20 be used. And I think just focusing on that is helpful 21 to participants, and also making sure that there is a 22 plan for protection of privacy of the information. 23 Now most IRBs do that under that general sentence 24 that's in the OHRP rules right now. And I'm not sure 25 116 it has to be amended. It might come through 1 clarifications from the department as to how they 2 expect institutions to comply with that part of the 3 OHRP rule. 4 MS. McANDREW: I think those were the 5 nature of the conversations that we were having, both 6 running up to the 2000 rule, and certainly in the 7 course of the 2002 modifications, is that the þþ what 8 was currently in existence in terms of specific Common 9 Rule privacy protections, there was a generalized 10 direction, but no specifics. And the question was þþ 11 working with the folks from OHRP, as well as NIH, of 12 what we could do through the Privacy Rule to bring 13 some structure, and eventually we're expecting some of 14 that conversation to carry over into the Common Rule 15 area. 16 MS. POLLAK: Am I allowed to make a 17 follow-up? 18 DR. PRENTICE: Go ahead. 19 MS. POLLAK: One idea might be that the 20 HIPAA privacy regulations if this were amended would 21 specify that an IRBs, the exemption from HIPAA is 22 dependent on the informed consent containing certain 23 things, so that you technically would not then need to 24 amend the OHRP rules, but to take advantage of the 25 117 HIPAA exemption you would have to do certain things. 1 And obviously, my list of what would be on that would 2 be somewhat less than what's in the requirements now, 3 but I think it is a way to sort of finesse having to 4 amend the OHRP regulations. 5 MS. EHRINGHAUS: That's precisely what the 6 AAMC is recommending, to go at it in that fashion, is 7 to make the exemption dependent on a narrower set of 8 requirements. 9 DR. PRENTICE: If you were to amend the 10 HIPAA Privacy Rule in that direction, this is perhaps 11 a question for Susan, how long would that take? 12 MS. McANDREW: It depends. The rulemaking 13 process would þþ I think you would have to consider a 14 year to 18 months for a process, because I think 15 realistically the rule would not be reopened for this 16 one topic, and so what would happen if you were þþ if 17 we were going to go forward with further modification 18 of the Privacy Rule, it would be the vehicle quickly, 19 if not from the outset, for not just the research 20 concerns, but essentially concerns across the board 21 from other venues, public health, law enforcement, 22 individual rights, the whole gamut. 23 DR. PRENTICE: Any other questions or 24 comments? Mark, I was expecting you to sooner or 25 118 later stand up. 1 MR. BARNES: Thank you all for very 2 informative presentations. I just have a couple of 3 questions. The specific questions, and I guess 4 they're really for Susan, but any other panelist who 5 wanted to comment, I'd appreciate their comments, as 6 well. 7 First of all, the question of academic 8 case studies of specific cases. Traditionally, our 9 physicians in our medical centers have been able to 10 take one or two, or even three cases of unusual 11 presentations of disease, or unusual manifestations of 12 disease, or unusual treatment that's given, and they 13 have been able to take those case studies and write 14 them up, and submit them to a peer review journal as 15 a case report without going to the IRB. Most of us 16 thought that if limited to one, two, or even three 17 cases, that these case studies would not be researched 18 because they were not actually an attempt to divine 19 generalizable knowledge from anything. And so our 20 physicians, our clinicians are accustomed to being 21 able to do those things without writing a protocol and 22 seeking IRB approval. And so the question is, if it's 23 not research under the Common Rule, then what status 24 does that activity have under HIPAA? 25 119 It is not operations, it's not treatment, 1 and it's not payment. Do you need an authorization 2 from an individual patient before you can actually 3 write up the individual patient's case and publish it 4 in a medical journal. And, of course, the way the 5 HIPAA de-identification standards are so high, that 6 when one publishes, when one as a clinician publishes 7 a case study, then one is per force identifying at 8 least a range of treatment dates, as well as the 9 geographic identifier of where the person was treated, 10 as well as the identity of at least one of the 11 physicians who treated them. So we have had þþ I 12 mean, many of us actually in the room, I know because 13 I've had conversations over the past year or two with 14 many of the people in the room about this, we've 15 wondered what the status is under HIPAA of these non- 16 research case studies and both the preparation for 17 publication and the actual publication in a medical 18 journal, so that's my first question. 19 The second question is in regard to 20 research recruitment, there was some press coverage 21 actually, at least in the trade press when, Joanne, 22 your institution wrote a letter to OCR asking about 23 whether it would be possible for individuals when they 24 were first admitted to a facility, to a covered entity 25 120 facility to be able to sign an authorization, a HIPAA 1 authorization that would give the institution the 2 right to be able to recruit them, and to look at their 3 study records for eligibility for recruitment. And 4 then actually to contact them for recruitment into 5 studies happening at that institution. And I know 6 that there were press accounts when Hopkins wrote that 7 letter, and I wonder whether there has been a response 8 yet from OCR about that particular inquiry - so those 9 are my two questions. 10 MS. McANDREW: Taking the second question 11 first, perhaps - there was in one of the recently 12 published fact sheets, and I'm going to get it wrong - 13 was it the IRB? No, the database, the database and 14 repository? No. Clinical studies - there you go. 15 There's so many we've published, I can't keep them 16 straight. No. 17 In the clinical studies fact sheet we did 18 generally address the question of being able to use 19 the authorization process with individuals to get them 20 on a potential recruitment log. And we did say that 21 that would be okay with the individuals. You could 22 get an authorization for that purpose, and then use 23 the logs for future þþ to test protocols against to 24 see if there were good study candidates on that list. 25 121 The first question on the case studies þþ 1 I mean, we did recognize that there was a fudge 2 factor, I guess, with healthcare operations, and it's 3 not always a clean line where quality kinds of 4 studies, or investigations being done within an 5 institution would actually develop into something that 6 might be research, or might be at least a contributor 7 to generalizable knowledge, if not the actual study 8 structured to produce that generalizable knowledge. 9 But there were going to be occasions where something 10 could be initiated as a healthcare operation that 11 might suddenly necessitate þþ have sufficient value to 12 require publication. 13 I think the expectation under HIPAA would 14 be that if, in fact, the information in the case study 15 cannot be sufficiently disguised so that the 16 individual is not de-identified, that there would be 17 þþ that person's permission to publish their 18 information would be required in that case. 19 MR. BARNES: And that would mean, for 20 example þþ I mean, in the single case of Anthrax that 21 occurred in Manhattan Eye, Ear, and Throat Hospital in 22 New York, the epidemiological trail or cause for which 23 was never explained, that if that particular þþ and 24 that woman was identified in the press, so it would be 25 122 if that woman's family withheld the right to publish 1 then, in fact, it means that Dr. Michael Tapper, the 2 Chief of Infectious Disease at Lennox Hill who 3 recognized the case of Anthrax that occurred at 4 Manhattan Eye, Ear and Throat Hospital would not be 5 able to publish her case report, even though it would 6 be a matter of vital national security that he be able 7 to þþ and potentially of significant academic 8 importance, that he publish how he recognized the case 9 of Anthrax. I mean, that's the implication. 10 DR. PRENTICE: One last question. That's 11 it.12 MS. KORNETSKY: Yes. But the case þþ I 13 just want to comment. I mean, case studies are 14 usually about rare or unusual types of things, and 15 there's sort of that catchall in HIPAA that any unique 16 identifier so, you know, the proposal that if they 17 can't be undisguised, it just doesn't mesh, because by 18 virtue of doing a case study, that's exactly why 19 they're doing a case study. So basically what you're 20 saying is for case studies, you need to get HIPAA 21 authorization, if I hear you correctly. 22 MS. McANDREW: I mean, that is the 23 individual's information, and the individual ought to 24 have a say in when their information is being used 25 123 outside of their treatment, for a non-treatment 1 purpose. And that's one of the things that the 2 Privacy Rule wanted to give them more say in. And in 3 balancing that need, I mean we did þþ there were a 4 variety of public purposes, and where exceptions could 5 be made. And if there is an argument about some 6 additional set of those exceptions, I mean that is 7 essentially where the argument would be made. But I 8 would contend that that's still the individual's 9 information, and they ought to have some say in how 10 you use it, other than to treat them. 11 DR. PRENTICE: Okay. Mark gets the last 12 comment. 13 MR. ROTHSTEIN: In my view, even if HIPAA 14 had a contrary interpretation, I think certainly a 15 very good argument could be made that it violates 16 professional ethics to publish individually 17 identifiable case information in a widely circulated 18 journal, perhaps, that might get picked up by the 19 press and be on everyone's front page without the 20 consent or authorization of the individual. And 21 that's what I recommend to my colleagues. 22 DR. PRENTICE: Okay. Thank you very much 23 for taking your time to come and talk to us. We found 24 your presentations very interesting. I apologize to 25 124 everybody for the expanded time. I know you're 1 probably hungry, you're probably tired, you need to go 2 to lunch, but Dr. Mary Lake Poland needs to also go to 3 Stanford, so we need to indulge her and listen to her 4 presentation. So, Mary Lake, are you ready? And she 5 promises me that it will not take more than the 6 allotted time period. 7 DR. POLAN: Actually, I think it will 8 probably take less than the allotted time period, 9 because in looking at the audience þþ what I'd like to 10 do while we're bringing this up on the screen is to 11 give you some history. 12 At the last meeting we had presentations 13 on international research, and you heard from David 14 Broasky, Melody Lin, and Helen McGough in terms of 15 issues that they have found to be interesting, and 16 sometimes problematic in terms of international 17 research. 18 Now Susan brought up one of the issues 19 that they're looking at, is international research. 20 And this is an area that I think important that did 21 not rise to the level of a subcommittee. So what I'm 22 going to present to you is not a subcommittee report. 23 This is a series of thoughts. 24 The group got together and we had two 25 125 phone calls, and we talked about and discussed the 1 issues that had come up during the presentations for 2 those of you who were here last time, and we found a 3 series of issues; some of which we felt were 4 straightforward enough to make recommendations on, and 5 some of which really require ongoing discussion, 6 perhaps further input, getting information from other 7 places and other people. So what I'm going to present 8 to you is a series of three recommendations. And if 9 Dr. Prentice is interested and the committee is 10 interested, we could consider those in terms of 11 supporting them from the committee. 12 The other four issues are things that we 13 really can't finalize, that would require more 14 information. And at this time, we do not have a 15 subcommittee, so we really can't go forward with that 16 in any meaningful way. And I suppose that we would 17 probably just wait and see as this process moves 18 forward with the entire committee how important, and 19 what other issues might arise in terms of 20 international research. 21 I also would like to say that 22 unfortunately none of the people who are on the 23 committee are here today, so that I'm going to present 24 the outcome of our discussions. And I would term them 25 126 discussions rather than a subcommittee report. So the 1 next slide shows you three recommendations that þþ we 2 said SACHRP, but actually it is this group of people, 3 and perhaps SACHRP will agree believes will facilitate 4 human research projects throughout the world with 5 optimal efficiency and protection for human subjects. 6 And the first of those recommendations is 7 that resources from HSS to support host country 8 infrastructure development for appropriate initiation 9 and monitoring of clinical studies. For example, such 10 funds could be line items in grant applications to 11 NIH, and could be supported by additional funding 12 through Fogarty. 13 Next slide. OHRP, with appropriate 14 outside support and consultation, should develop and 15 publish guidance for building IRB capacity in host 16 countries. And thirdly, federal matching of private 17 funds from educational institutions and foundations 18 which could be used to build capacity in host 19 countries for IRB development, information technology, 20 and monitoring of clinical trials should be offered, 21 so that it would be a joint resource combination which 22 would allow really capacity building in countries 23 where research is being done outside the United 24 States. 25 127 Now those are the three recommendations 1 that we felt were relatively straightforward. The 2 next four items are more complicated, and these are 3 areas that we did not believe were sufficiently clear 4 to make recommendations. And they are, in order - 5 clarification of OHRP's determinations about 6 regulatory equivalents, and modification of the 7 international FWA document, so that we can clarify 8 whether non-domestic IRBs can substitute equivalent 9 regulatory structures for 45 CFR 46 under the terms of 10 assurance. 11 The current FWA document our group felt 12 was confusing because it implies that both non- 13 domestic IRBs can choose both an alternative 14 procedural standard and an alternative set of ethical 15 principles, but at the same time requires a commitment 16 under the terms of assurance to both 45 CFR 46 and to 17 the Belmont Report. So this is really an attempt to 18 design some guidance that would make clear and perhaps 19 more efficient exactly what the procedure should be. 20 The next point - an evaluation of current 21 training, if any, for principal investigators in the 22 U.S.A. who will undertake international research, and 23 the development of specific training programs to 24 educate them in both regulatory and practical realms 25 128 of international research. We felt that there wasn't 1 really enough structured education on how to initiate 2 and perform this research. 3 Three, collaborations between the federal 4 regulators of international research, including OHRP 5 and FDA to harmonize ethical standards and regulations 6 for international human subjects research, and provide 7 a clear pathway for regulatory adherence. All of the 8 people in the group felt that there was some confusion 9 and some difficulty with multiple different pathways. 10 And the last area that we would think 11 merits additional information and study is a 12 systematic review of governmental and non-governmental 13 institutions, such as the NIH, NSF, USAID, private 14 foundations, and educational institutions, to actually 15 assess the magnitude and type of international human 16 research that they're supporting, given what was 17 presented last time of the enormous growth in 18 international research projects in order to better 19 describe the challenges presented by such research, 20 and to create an educational forum for improved 21 understanding of process amongst all these 22 stakeholders. And that constitutes what we discussed 23 and how we in a consensus way came to formulate both 24 recommendations in areas for potential future study. 25 129 DR. PRENTICE: Okay. Thank you. 1 Interesting recommendations. We do have a little bit 2 of time for questions, discussion, comments. Tom. 3 I'm sorry, yes. 4 DR. POLAN: Oh, and could I just say that 5 Nancy Jones was very helpful in this. She also 6 participated in the process. 7 DR. PRENTICE: All right. Nancy first, 8 then Tom. 9 DR. JONES: Okay. And I would also say on 10 number four, as you're doing a review and assessing, 11 I think international research is only going to grow, 12 and it's important to facilitate it, but also to make 13 assurances of human research protection. And so as 14 part of that, I think it would be good for these 15 different funding agencies to identify their 16 justification for engaging in international research 17 in the first place, why are there special populations, 18 special goals, because some of the ethical concerns 19 have been using populations with a lower standard of 20 care to enroll them, or cost issues, or even that 21 there is less regulatory burden. So I think it's 22 important to have the funding agencies identify what 23 justifications they're using for engaging in 24 international research, and to make that also part of 25 130 the process. 1 DR. PRENTICE: Tom. 2 MR. ADAMS: This is a important area, and 3 it's certainly a growing area. I'm curious as to 4 whether in looking at the first three recommendations 5 you have been able to develop any type of, or have an 6 understanding of the cost implications here. 7 DR. POLAN: That's an easy answer. No, we 8 don't. Because this wasn't a full subcommittee, we 9 didn't have other people come in and give us the 10 information. We had the information that was 11 presented at the last meeting that really talks about 12 the amount þþ the number of research projects and the 13 amount of money that's being spent. And we didn't 14 address, nor did we look at, the cost of capacity 15 building, although that's implicit in some of the 16 suggested areas that might be helpful to look at in 17 the future, and would certainly be important. 18 DR. PRENTICE: Felix. 19 DR. GYI: The fourth bullet talks about 20 funding from just the federal funding side, but it 21 seems to me that there's a lot of research that is 22 being considered by the pharmaceutical industry, as 23 well. And the collaboration at this particular 24 juncture seems to make sense to me, to engage them in 25 131 conversation earlier as opposed to later, because the 1 capacity building affects both sides of that 2 particular coin. And I wondered if your folks had had 3 a chance to discuss what that might look like, and how 4 we might engage that particular sector earlier on as 5 opposed to later. 6 DR. POLAN: We actually did not bring it 7 down to that level, but I think it would be extremely 8 appropriate and important to add it to bullet number 9 4, along with the information on justification for 10 using international research sites. And that is 11 simply an omission that we made, and thank you for 12 pointing it out. 13 DR. PRENTICE: Other questions, comments? 14 Yes. 15 DR. JONES: As you look to subcommittee 16 work, I don't know if I would put this as a top 17 priority, but I think this is going to be a growing 18 issue. Research is going to be expanding 19 internationally. There are going to be a lot of 20 things that would jeopardize human subject protection 21 or national relations, so I think it is important to 22 be proactive and lay guidance down as you go, rather 23 than wait for problems to occur and have huge 24 anecdotes that influence the progress. 25 132 DR. PRENTICE: Other questions, comments? 1 Okay. We are going to adjourn for lunch, and we're 2 going to reconvene the meeting at þþ let's see, it's 3 12:15, 1:15. That will put us slightly behind time, 4 but that's okay. We're not doing too badly. So 5 everybody have a good lunch. 6 (Whereupon, the proceedings in the above- 7 entitled matter went off the record at 12:09:41 p.m. 8 and went back on the record at 1:18:28 p.m.) 9 DR. PRENTICE: Okay. Let's get started 10 again. Welcome back, everybody. I'm going to be 11 talking about IRB review of External Adverse Event 12 Reports, and so that we're clear about what that term 13 means, there are basically two kinds of Adverse Event 14 Reports, those that occur to research subjects at the 15 institution where the IRB has jurisdiction, and those 16 that occur in multi-center trials across the country, 17 hundreds of sites where all IRBs will be given a copy 18 of that External Adverse Event Report according to 19 certain criteria that I'll talk about in a moment. So 20 I'm not going to talk about internal adverse event 21 reports. They do not constitute a problem for IRBs, 22 at least not for academic IRBs. So exactly what is 23 the problem facing IRBs? 24 For those of you who were in attendance at 25 133 the last SACHRP meeting, you know that this topic was 1 discussed. So to refresh your memories, or to provide 2 information for those of you who are not here, IRBs 3 are simply overloaded to the point of meltdown with 4 External Adverse Event Reports for multi-center 5 trials. Now multi-center trials were not the way we 6 conducted clinical research back in the 70s when the 7 regulations were first formulated. 8 Gradually over the 80s and over the 90s, 9 this is the way we conduct research, and it involves 10 hundreds of sites. So consequently, we have seen an 11 escalation of the number of adverse event reports 12 given to IRBs, particularly those that occur in multi- 13 center drug trials. The reports that we're given via 14 the investigator simply don't contain enough 15 information, and IRBs are almost expected to act as 16 quasi-DSMBs, and we're simply not constituted to act 17 as a DSMB. We don't have the expertise to act as a 18 DSMB considering the vast nature of protocols that we 19 review at any given IRB, all the way from cardiology, 20 to psychiatry, to oncology. 21 We think that fear of litigation is 22 probably driving the system. That, perhaps, may be a 23 motivation for pharmaceutical companies to insist upon 24 IRB reports being given to all IRBs of record. And 25 134 the problem continues to grow, and as it continues to 1 grow it consumes already strained IRB resources. 2 To give you an example of the load, Wash 3 U in St. Louis has upwards of 12,000 External Adverse 4 Event Reports sent to them every year, over 12,000. 5 UCLA has somewhere around 7,500. We're a relatively 6 small to medium-size institution. We get about 3,000. 7 What's an IRB supposed to do with 3,000 External 8 Adverse Event Reports? And when you consume or 9 restrain IRB resources, this impacts the IRB's ability 10 to engage in other important activities. And to get 11 back to this fear of litigation. When an Adverse 12 Event Report comes in the door and it's sitting in our 13 IRB office, we worry if we don't act upon it, if we 14 have it. 15 There's no question that some IRBs have 16 over-interpreted the regulations. I go to a lot of 17 institutions across the country, and I find some IRBs 18 have definitely over-interpreted what the regulatory 19 requirements are. Some IRBs are actually reviewing 20 both expected and unexpected adverse events, as an 21 example. And last but certainly not least, OHRP and 22 FDA expectations concerning what IRBs are supposed to 23 do with these Adverse Event Reports have not been 24 clearly articulated in any kind of an official 25 135 guidance document. 1 I've been concerned about this problem for 2 a long time, but particularly for the last eight 3 years. I've written three papers and one book chapter 4 on this issue. It's a topic that's under discussion 5 at every single SACHRP meeting. I've never been to an 6 institution as a consultant where I've not been asked 7 what do we do about our Adverse Event problem? It's 8 time to fix it, so what's the solution? 9 Well, I'm not going to suggest that I'm 10 wise enough to know the solution, but I want to 11 present some thoughts. And these thoughts are based 12 upon my own experience, my interaction with Wash U in 13 a conference call with OHRP staff, my discussions with 14 OHRP staff, my discussions with City of Hope and other 15 institutions. So some thoughts on a possible 16 solution. 17 First of all, I think it would be 18 appropriate for the sponsor and/or their DSMB to take 19 responsibility for triaging these Adverse Event 20 Reports, and don't send them to us unless the protocol 21 requires modification. It's their protocol. They 22 ought to decide if it needs to be modified to reduce 23 risk, or the consent form requires revision to 24 disclose a new risk, or if there's simply a problem 25 136 which affects the study that IRBs ought to be aware 1 of. Instead, we simply get the Adverse Event Reports, 2 and the vast majority of the times, there's absolutely 3 no recommendations whatsoever from the sponsor. 4 Now we need to be very clear that the 5 Protection of Human Subject regulations, the HHS and 6 the FDA, which mirror one another, and the IND 7 regulations, 21 CFR 312 - they do not specifically 8 require all IRBs of record to review External Adverse 9 Events which occur during these multi-center trials. 10 This seems to be an undeclared interpretation that's 11 arisen over the 80s and the 90s, and that's why we're 12 seeing all of these Adverse Event Reports. 13 I know of no official guidance ever issued 14 by OHRP or FDA that would tell us we have to be 15 reviewing all of these reports. And certainly I would 16 invite OHRP and FDA to correct me if I'm wrong in this 17 assumption. 18 Some more thoughts. The IND regulations, 19 21 CFR 312.32(c), it requires the sponsor to notify 20 the PIs of all AEs that meet the IND safety reporting 21 requirements. That means the adverse event has to be 22 unexpected, it has to be serious, and it has to be 23 associated, and all those terms are defined in the IND 24 regulations. 25 137 Now I think that the PI should be 1 responsible for analyzing the Adverse Event Report, 2 and determining whether or not any local action is 3 needed. And if a local action is needed, then 4 obviously the PI needs to submit the changes to the 5 protocol or the consent document to the IRB. And the 6 PI's analysis and determination should be documented 7 and subject to audit. 8 Basically what this means is this, if the 9 PI does not decide that any changes need to be made or 10 any revisions to the consent document need to be made, 11 then they ought to have this analysis documented and 12 simply filed. It would never go to the IRB, but we 13 would audit those files because we're supposed to be 14 monitoring research anyway. 15 On the other hand, in the absence of the 16 pharmaceutical company deciding that a change in 17 protocol or a change in the consent document is 18 necessary, the PI still has the prerogative of saying 19 I don't agree with the company. I think some changes 20 need to be made, so the PI then would only notify the 21 local IRB if he or she decided that there's a problem 22 related to risk or other factor which impacts the 23 study, and the IRB needs to be informed of that, or a 24 change in protocol is necessary as a consequence of 25 138 the information contained in the Adverse Event Report, 1 or the consent form requires revision to either 2 disclose a new risk, or perhaps emphasize a risk that 3 was not sufficiently emphasized in the consent 4 document. And then at continuing review time, the PI 5 should provide a DSMB safety report or a summation of 6 the adverse events. And many IRBs are already 7 requiring that as it is. So now we're moving to final 8 thoughts. 9 I believe that OHRP and FDA should 10 promptly, and it's underscored, it's underlined, 11 promptly issue official guidance that's clear and 12 consistent. You have to have, obviously, consistent 13 guidance between OHRP and FDA, otherwise it's not 14 going to work. And this guidance should facilitate 15 the ability of research institutions, IRBs and others 16 to interpret and apply 45 CFR 46.103(b)5. That's that 17 section that deals with adverse events, which are not 18 called adverse events, by the way, in the regulations, 19 and the equivalent FDA section, 21 CFR 56.108(b)1. 20 You note that in the yellow footnote down 21 here, the requirement is that each institution shall 22 have written procedures for ensuring prompt reporting 23 to the IRB any unanticipated problem involving risk to 24 the subject or others. So the term "adverse event" is 25 139 not even contained in the Protection of Human Subject 1 regulations. 2 There are things that go beyond simply an 3 adverse event. An unanticipated problem involving 4 risk may not result in an adverse event. That's a 5 reportable event under the Protection of Human Subject 6 regulations, but that's internal so we're not going to 7 worry about that. 8 Now I want to make it perfectly clear that 9 the driver in this solution is really FDA, much more 10 so than OHRP, because it is all of the FDA regulated 11 IND drug studies that are producing all of these 12 Adverse Event Reports. 13 What about some roadblocks? Are there 14 some roadblocks to making this kind of a solution 15 happen? Well, I haven't talked to Pharma, but they 16 may object to a triage system where Adverse Event 17 Reports are not sent to all IRBs. Maybe they would 18 object because of litigation fears, I don't know. 19 Patient advocates may express concern over 20 lack of IRB involvement in the review of Adverse Event 21 Reports. And I can certainly understand the position 22 of patient advocates who would say, you know, we're 23 really concerned to let the responsibility simply rest 24 with the physician/investigator. Somebody else ought 25 140 to be looking at that besides the pharmaceutical 1 company. 2 I know for a fact that at some 3 institutions their legal counsel worry about increased 4 liability if the IRB does not look at these Adverse 5 Event Reports, and probably Pis might worry about it, 6 as well. But what about some advantages? 7 Well, there are some advantages. It's got 8 to decrease the cost of Pharma. We're talking about 9 thousands and thousands of IND safety reports. 10 Somebody has to generate all of this paperwork and 11 make sure it gets down to the IRBs, and then they're 12 asking for verification that the IRB got it in some 13 cases, so it would decrease cost of Pharma. 14 There's no question it's going to decrease 15 the cost to the institution, the PI, and the IRB. And 16 once again, I would remind you to think about the 17 workload of the Wash U IRB - 12,000 IND safety reports 18 a year. With this kind of a triage system, I suspect 19 that would be reduced really significantly, which 20 would result obviously in a significant reduction in 21 workload. And if there's a significant reduction in 22 workload, there's more time and resources for other 23 IRB-related activities. 24 Now this is not going to reduce the 25 141 workload so much to the investigator who still has to 1 analyze the Adverse Event Report, but it will reduce 2 their workload in terms of not having to put this 3 through an IRB system of review. 4 Now I like history. I've always liked 5 history, and I want to go back to 1966, some advice 6 from the past. And I'm sure most of you know who 7 Henry Beecher was. He produced that landmark article 8 and published in the New England Journal of Medicine. 9 And what Henry Beecher said, and I'm going to quote - 10 "The ethical approach to experimentation in man has 11 several components. Two are more important than the 12 others; the first being informed consent." And I 13 don't think anybody can argue with that. Then he went 14 on.15 "Secondly, there is the more reliable 16 safeguard provided by the presence of an intelligent, 17 informed, conscientious, compassionate, responsible 18 investigator. IRBs should not be police forces. They 19 were never intended to be a police force." If you 20 read the National Commission's Report on IRBs, we are 21 meant to share the ethical decision making 22 responsibility, and not act as policemen. It seems to 23 me that as a consequence of over-interpretation of 24 regulations, fear that has been produced because of 25 142 multiple shutdowns, fear of litigation, we are 1 beginning to act in some cases as a big brother 2 overlooking the shoulders of investigators. And, in 3 fact, the best protection is clearly articulated by 4 Henry Beecher, an investigator who is concerned about 5 the welfare and rights of his or her research 6 subjects. They're informed, they're conscientious, 7 they're compassionate. They are responsible. 8 So this is the charge that I would like to 9 present to SACHRP. I want to first acknowledge that 10 OHRP and FDA are, indeed, working on development of 11 guidance on adverse event reporting. And I applaud 12 that effort as being long overdue. And clearly, the 13 goal is to protect human subjects. That's our 14 paramount goal as we develop this kind of guidance, 15 but with relief of the AE burden. So the question is 16 what can SACHRP do to facilitate this effort. As you 17 know, we had four panelists talk about the problem 18 last time. We decided to put it on the agenda this 19 time, and we need to discuss where we want to go from 20 here. 21 Okay. Thanks. We're now open for 22 discussion. Somebody else will chair this. Felix, 23 would you like to take over. 24 DR. GYI: Celia. 25 143 DR. FISHER: Ernie, thank you for putting 1 that together and stressing a very important issue 2 that IRBs are facing. I'm just confused, so I want to 3 help my confusion. And these are the areas that I'm 4 confused at, in the order of how this would proceed. 5 DR. PRENTICE: Do I need to get a pen and 6 write this stuff down? 7 DR. FISHER: Okay. Sure. Do you have a 8 paper? 9 DR. PRENTICE: I need a pen. I anticipate 10 the length of your questions þþ 11 DR. FISHER: Right, I'm sorry. One, two, 12 three. 13 DR. PRENTICE: I probably better sit down 14 too. 15 DR. FISHER: That's right. Okay. I'll 16 put them all together. I'm trying to figure out where 17 responsibility would ultimately lie in terms of 18 protections for participants in this model, and so 19 there are probably assumptions that I'm just naive 20 about. One thing, it appears from the model that the 21 funder is ultimately responsible, that they would be 22 þþ because they're integrating the information from 23 multiple sites, they would be receiving information. 24 So my first question is, number one, they 25 144 would be receiving information on any of the three 1 components of the IND, serious, unanticipated. 2 DR. PRENTICE: Yes. They get those 3 reports from the sites. 4 DR. FISHER: Okay. So they get those 5 reports from the sites. 6 DR. PRENTICE: Right. 7 DR. FISHER: They then let every PI know 8 in some kind of regularly scheduled report they put 9 together monthly or quarterly, or whatever it is, a 10 adverse event table, so that all the Pis know? 11 DR. PRENTICE: Not necessarily. You might 12 get individual IND safety reports. You might get some 13 aggregate IND safety reports. They come in all kinds 14 of varieties, but the point is that under the IND 15 safety regulations, the sponsor is required to notify 16 all of the Pis participating in this multi-center 17 clinical trial of adverse events that are unexpected, 18 serious, and related. 19 DR. FISHER: Right. So then, it can or 20 cannot be aggregated. Right? 21 DR. PRENTICE: Yes. 22 DR. FISHER: And so then it appears as if 23 it's up to the individual PI to decide whether or not 24 something needs to be done. And let's say, let's have 25 145 the ten site, multi-site example again. And what are 1 the criteria þþ and number one, what makes the PI 2 qualified to interpret by him or herself across the 3 ten sites that this is the time to report? And number 4 two þþ 5 DR. PRENTICE: Report to who? 6 DR. FISHER: To the IRB, I mean, because 7 you have a number of criteria to which the PI then 8 reports to the IRB. 9 DR. PRENTICE: Right. After they've 10 analyzed the IND safety report, they decide whether or 11 not they need to make a change to minimize risk, or 12 change the consent document. 13 DR. FISHER: Right. But my question is, 14 what is the criteria by which this single PI is going 15 to use when there are ten other sites, and what þþ you 16 know, it seems to be it's resting on the 17 idiosyncracies of Pis at different sites, so that's 18 just one of my confusions, how this would work, and 19 why we would want to put responsibility of multi-sites 20 in the hands of one PI. 21 DR. PRENTICE: It's not multi-sites. 22 DR. FISHER: Okay. 23 DR. PRENTICE: Okay. First let me try to 24 clarify. 25 146 DR. FISHER: All right. 1 DR. PRENTICE: The first level of decision 2 making occurs at the pharmaceutical company and/or 3 DSMB. They have the data. They have the aggregate 4 data. They know a lot more than we do. We don't know 5 anything. 6 DR. FISHER: Right. 7 DR. PRENTICE: So they make a decision and 8 they say okay, we think that a change in protocol is 9 necessary. That rarely happens. We think that a 10 consent form revision needs to occur. That rarely 11 happens. What happens is, they send these reports 12 that really don't have a lot of data for us to use. 13 Then the next step is they tell the PI 14 send it to your IRB. Now the IRB is in even less of 15 a position than the PI to analyze this incomplete 16 report and figure out what to do. 17 DR. FISHER: No, I understand. I think 18 you're describing exactly what the problem is. But 19 what I'm trying to figure out in your proposed model, 20 it doesn't þþ it seems to me the proposed model, there 21 still is no accountability, except within the single 22 PI. So I'm trying to figure out where the 23 accountability lies. 24 DR. PRENTICE: Okay. 25 147 DR. FISHER: Because I would love to have 1 a model like this, so when you say that the funder may 2 or may not have a DSMB, that troubles me, you know, 3 because I would like þþ if the funder is going to be 4 ultimately responsible, I would like the funder to 5 aggregate the data, to have an independent DSMB that 6 they have to be responsible for, who then communicates 7 to a PI, and the PI has a criteria that you have 8 developed for when the IRB is informed. 9 DR. PRENTICE: Yes. That would be an 10 ideal system that would require revision of the 11 regulations. What I'm proposing is not going to 12 require a revision of the regulations. 13 Now you talk about accountability - the 14 accountability would be resting with the PI. That's 15 clear. Right? And we recognize they have an absence 16 of information. Yes, but they're in a much better 17 position to analyze the significance of the adverse 18 event than the IRB ever is, so accountability is with 19 the PI. And if they decide something needs to be 20 done, then they send it to the IRB. Otherwise, we 21 don't get the report at all. It's simply filed by the 22 PI with their analyses. 23 DR. FISHER: I just want to add, I think 24 my discomfort is that having been in some of these 25 148 situations with Pis, there is sometimes disagreement 1 between a PI and a DSMB in terms of what kind of 2 serious adverse event would require a change in 3 protocol. And so I'm still concerned about the total 4 responsibility of changing a protocol or understanding 5 that an event is serious enough, or significant 6 enough, or additive enough to require a change, should 7 rest solely in this PI. So that's my only concern 8 about the model and how that would be addressed. 9 DR. PRENTICE: It's a legitimate concern. 10 DR. GYI: Susan. 11 MS. KORNETSKY: A couple of things. I 12 think what you're proposing is very good, and from a 13 practical level, I think many IRBs have moved to this. 14 I do have two comments though. One is, in order to 15 propose or make this work, I think that one of the 16 things that the IRB needs to do up front is to feel 17 comfortable with some type of data safety monitoring 18 plan. And I think my own experience is when you start 19 asking about those things, because we really are 20 relying on sort of a triage of things, so if we feel 21 uncomfortable, if we feel that it's not independent 22 and it should be, then this won't work. I would add 23 to this that this would work if you ask as part of the 24 application what the data safety monitoring plan is. 25 149 And even ask for some criteria, ask them to say what 1 is going to be reported, how it's all going to work 2 and be communicated. I don't think that's going to 3 alleviate all of Celia's concerns, but that's step 4 one.5 The other thing that I'm just cautious on. 6 I think that this is fine, and I would not want this 7 to ever be interpreted that an IRB, if they chose to, 8 would go beyond this. The reason that I'm bringing 9 that up, and maybe it's specifically because I work 10 within pediatrics, is especially in pediatrics 11 sometimes the number in any one particular institution 12 is very, very, very small. So sometimes it is 13 important to be able to see maybe something that isn't 14 thought to be totally related, but possibly related. 15 So I wouldn't say that we should endorse this or 16 suggest it, but it would be with the caveat that in 17 certain types of populations and vulnerable things 18 that an IRB may want to look at this and make sure 19 that that works. 20 DR. PRENTICE: Okay. Let me þþ I agree 21 totally with your second point. Let me make a comment 22 relative to your first point; that's being comfortable 23 with the DSMB. And yes, a lot of IRBs now are asking 24 about whether or not there's a DSMB, and how often the 25 150 report is going to come in. 1 MS. KORNETSKY: And also, because many 2 studies don't have a DSMB. 3 DR. PRENTICE: That's correct. 4 MS. KORNETSKY: They have a DSMP, a Data 5 Safety Monitoring Plan. 6 DR. PRENTICE: Yes, that's correct. 7 MS. KORNETSKY: Many pharmaceutical, so I 8 think þþ and there's a big difference, because DSMBs 9 by nature are independent, and I think that's the type 10 of thing that everyone feels very comfortable with. 11 And in many studies you're not going to find that. 12 DR. PRENTICE: However, we've got to 13 recognize that DSMBs don't operate in real time. So 14 consequently, investigators are going to get the 15 reports before that DSMB has actually looked at all of 16 the aggregate data, so you do have a time lag there. 17 MS. KORNETSKY: Something really 18 significant within that plan, and we've often asked if 19 there is something very, very serious, is there a 20 mechanism that someone can be notified that a Data 21 Safety Monitoring Plan or Board can pull together. 22 DR. PRENTICE: One would hope that the 23 DSMB would make that decision right away. And you 24 know of circumstances when that's happened. Okay. 25 151 Other? 1 DR. GYI: Bob. 2 DR. HAUSER: This seems to be a problem 3 that continues, and I wonder if the committee 4 shouldn't communicate its sense of urgency to the 5 Secretary. And I would propose that we make a motion, 6 if I may. 7 DR. PRENTICE: I'm not the chair of this. 8 DR. HAUSER: I would like to move that the 9 committee recommend to the Secretary of HHS that OHRP 10 and FDA should issue official guidance that 11 facilitates the ability of research institutions/IRBs 12 to interpret and apply 45 CFR 46.103(b)5, and 21 CFR 13 56.108(b)1 to the review of internal AERs and external 14 AERs. That's my motion. 15 DR. GYI: We have a motion on the floor. 16 What is the committee's desire and pleasure with 17 regard to entertaining this motion, versus hearing a 18 little bit more discussion, because Tom was on the 19 agenda before the motion was made. If you would 20 indulge me for a moment, and if I could exercise my 21 prerogative, I'm going to let Tom speak his mind 22 first, please. 23 MR. ADAMS: I understand the problem that 24 you have outlined, and my point actually could have 25 152 gone toward the motion, and really is a process 1 question for the committee. And this seems to me to 2 be a part of a larger problem that we've heard 3 testimony on earlier today. And that is, there are a 4 number of areas where guidance is needed from OHRP and 5 FDA for IRBs. And it in many ways goes back into the 6 conversation we had regarding liability issues this 7 morning, so my question was going to be should we look 8 at this in a larger picture at other areas that we 9 would like to have guidance, or do you want to deal 10 with it on a piecemeal basis? Either way you get 11 there, but my question basically was going to be do we 12 want to empower another subcommittee to look at the 13 broader issues? 14 DR. PRENTICE: I don't think that we need 15 a subcommittee. I also don't think that we need to 16 incorporate this problem into all of the other issues 17 that we require guidance on. I do, however, think 18 that this is a priority in terms of IRB workload, and 19 as a consequence, we ought to deal with it as a 20 priority. 21 I am not suggesting that we dictate how 22 IRBs should or should not review these adverse events. 23 I've simply presented some thoughts. I know that OHRP 24 has a copy of the slide presentation, as does FDA. I 25 153 know that it has been circulated at FDA, who is 1 looking at the particular issue as we speak, so I 2 would endorse Bob's motion that we make it very clear 3 that this is urgently needed. 4 I went to FDA, I think it was something 5 like seven years ago at the invitation of FDA. That 6 was before David LePay was on board, at least in his 7 capacity, and I spent a half a day talking about this 8 adverse event problem, and nothing happened. So I'm 9 optimistic that something is now going to happen, and 10 it certainly would help the process, I think, if we 11 were to go on record as this is something that needs 12 to be done promptly. 13 DR. GYI: Dr. Prentice, you have opened 14 the door for us to have some dialogue with our 15 regulatory colleagues, and I wonder if this might be 16 an opportune time for us to ask some questions of the 17 FDA and OHRP, see if they have any comments. 18 DR. SCHWETZ: Well, from the OHRP 19 standpoint, we certainly are prepared to move on this 20 as a high priority. And, in fact, our office has gone 21 on record in writing on our website, we have said in 22 public meetings, we said it at SACHRP in December that 23 we accept this triage approach. That's fine with us. 24 For decisions to be made about who should receive 25 154 Adverse Event Reports, that system is fine with us. 1 So from the standpoint of our office, what we need to 2 do is translate that into words. It isn't that we 3 have to spend months trying to get some thoughts 4 together on what the guidance should read. We have a 5 pretty good idea of that. So from the standpoint of 6 us already agreeing with this approach, and having 7 discussed it in December, and having communicated with 8 a number of people at the two institutions to pull 9 this thought together, we're pretty far down the track 10 on that. So we communicated, met with David and 11 others at the FDA to anticipate that this was going to 12 be a recommendation from SACHRP at this time, and we 13 ought to move forward on our own, rather than have a 14 subcommittee of SACHRP put words together for us that 15 then we have to deal with and turn into a guidance. 16 We might as well start at that point ourselves and 17 save the three to six months that it would take to 18 have a couple of subcommittee meetings to hand us a 19 piece of paper that would say things that we already 20 have in mind from the December meeting. 21 So from that standpoint, we're prepared to 22 move on this, but I can only speak for OHRP. The 23 context is a little bit different for the FDA, so I 24 would ask David to comment in terms of the FDA. 25 155 DR. LePAY: Well, thank you, Bern. 1 Certainly, this is a very high priority for FDA. I 2 think we mentioned that the last time around. There 3 are many facets to this. Of course, our regulatory 4 authority extends not only to the IRB community, but 5 also certainly involves sponsors and clinical 6 investigators as well here, so we have to look at the 7 various facets here. 8 I think we have recognized, however, that 9 this is a particular problem for the IRB community. 10 And, therefore, although we recognize that this is 11 going to have to have a more comprehensive look across 12 all of the groups that we ultimately regulate, there 13 are facets that we can work more immediately upon to 14 deal with the IRB community while we are continuing 15 also the interactions that will be necessary with the 16 other stakeholder communities that are involved in the 17 safety reporting and oversight under FDA's 18 jurisdiction. 19 We have had many conversations with OHRP 20 about this. We are continuing to have considerable 21 conversation within FDA. Mark McClellan has certainly 22 made this a high priority for my own operation when we 23 had spoken toward the beginning of this year, and I've 24 been assured by management, even as Dr. McClellan has 25 156 gone on to his new position, that this remains a very 1 high priority for FDA in terms of developing this kind 2 of guidance, and dealing in particular with this 3 issue. So I expect that the þþ I know that this is 4 very much already moving forward at FDA, and we're 5 using the materials that had been generated and the 6 comments that we get from meetings such as this to be 7 able to input into some of our thinking. So again, I 8 can just say this is something that we anticipate will 9 happen. 10 DR. GYI: It sounds like there's general 11 consensus and agreement in principle regarding at 12 least that you folks þþ I'm sorry. There's a motion 13 on the table, so I want to make sure that we at least 14 address the motion, because we've already gone beyond 15 some parliamentary procedures. 16 DR. LePAY: Could you repeat the motion, 17 please? 18 DR. LePAY: Yes, I would like to have Dr. 19 Hauser repeat the motion with the understanding though 20 that there is an agreement between OHRP and FDA to 21 work towards providing guidance with regard to 22 externally reported Adverse Event Reports to the IRB 23 and how that's supposed to be handled. So I just want 24 to make sure that I narrow the definition of what it 25 157 is that we're asking FDA and OHRP to act on. 1 DR. HAUSER: My motion was that this 2 committee, in effect, take a stand and recommend to 3 the Secretary of HHS that OHRP and FDA should issue 4 official guidance that facilitates the ability of 5 research institutions/IRBs to interpret and apply 45 6 CFR 46.103(b)5, and 21 CFR 56.108(b)1 to the review of 7 internal AERs and external AERs. That's my motion. 8 DR. GYI: Second? I'm sorry. 9 MS. KORNETSKY: Does that include the þþ 10 I'm sorry, on the references. The reference to the 11 FDA, does that include devices, drugs, biologics? Are 12 those the appropriate number? 13 DR. GYI: That's 56.108(b)1 is the IRB 14 regulation that speaks to þþ 15 MS. KORNETSKY: Just the IRB regulation. 16 Okay. Then what's we're proposing. Okay. Thank you. 17 DR. GYI: And it's not the 312 or the 812 18 regulation. 19 DR. PRENTICE: Of course, we do know that 20 the regulations require all IRBs to be notified of 21 serious unanticipated adverse device effects, so 22 they're different than the IND regulations. And I 23 think it's also appropriate, Bob, to include IRB 24 review of internal adverse events, as well. You did 25 158 so. 1 DR. HAUSER: Yes. 2 DR. PRENTICE: And let me clarify why I 3 think that's appropriate. If you look at the language 4 in the regulation it says "any unanticipated problem 5 involving risk to the subject or others." Any 6 unanticipated problem involving risk does not specify 7 any kind of a risk threshold. There are some IRBs who 8 have said unless the adverse effect that occurs 9 internally is serious, we don't want to see it. I 10 would suggest that that criteria is way too high in 11 terms of reporting. 12 If you look at the definition of serious 13 in the IND regulations, you're practically on death's 14 door. You have to have a much lower threshold of 15 reporting adverse events for internal ones. So it 16 would be nice if OHRP would look at that issue, as 17 well as FDA, and provide the necessary guidance. I 18 don't think, Mike, that you've done that, as far as I 19 know. So yes, I'd like to combine the two, even 20 though I only spoke to the one issue. 21 DR. GYI: All right. But there is a 22 motion on the floor, and I wonder if anybody is going 23 to second this. 24 DR. PRENTICE: It wasn't seconded? 25 159 MR. ADAMS: I'll second it. 1 DR. GYI: Discussion. 2 DR. FISHER: Okay. My question is to 3 Bern. 4 DR. PRENTICE: Before you get started, Dr. 5 Fisher, we're at a point of time, so I'd like to 6 extend this discussion for five more minutes and then 7 get back on track. 8 DR. FISHER: All right. I'd like to ask 9 Dr. Schwetz, you said something about triage. In our 10 endorsing this motion, are we endorsing what Ernie 11 presented? Okay. 12 DR. SCHWETZ: It sounded to me like the 13 motion is delinked from the triage process that you 14 talked about in the December meeting. 15 DR. PRENTICE: The motion is for OHRP and 16 FDA to issue guidance. Now if they choose to take 17 this model and say we think it's the greatest thing 18 since sliced bread and we're going to adopt it, 19 that's their prerogative. Okay. But we're not 20 linking the motion with the model. That's why there 21 was a big question mark as to whether or not this is 22 a solution. 23 DR. GYI: So any further discussion? All 24 in favor of the motion as Dr. Hauser has presented. 25 160 Opposed? Any abstentions? 1 (Vote taken.) 2 DR. GYI: The motion stands approved, and 3 I will turn the chair back over to you, Dr. Prentice. 4 MS. KORNETSKY: Ernie, could I ask, now 5 that we're through this, one related question. Since 6 Dr. Schwetz has said that þþ at least he has gone on 7 record for sort of that this approach, and if we 8 delinked it, is acceptable. I have not heard that 9 from FDA, so if we had þþ this is our policy and an 10 FDA auditor showed up tomorrow, from your perspective 11 would this be an acceptable approach? 12 DR. LePAY: Again, I've shown this also to 13 our Chief Counsel and am still waiting for some 14 determination on that. And our interpretation, at 15 least, is this is a mechanism that is consistent with 16 the regulations, because the regulations again focus 17 primarily on the IRB having procedures in place to be 18 able to handle these events. It does not specifically 19 discuss the level of review that must go on at the IRB 20 for these events. But again, I can't give you an 21 official statement. 22 DR. PRENTICE: I guess one final comment. 23 Wash U has actually adopted this model, not 24 necessarily the triage at the pharmaceutical company 25 161 level, but certainly placed some responsibility at the 1 level of the investigator. They've already adopted 2 that. The City of Hope has also, as well, and we have 3 not. Okay. We have an electronic adverse tracking 4 system in place where we do have a triage system, but 5 ultimately we make the decision. So if FDA were to 6 adopt this particular model, we would undoubtedly move 7 in that direction and do exactly what Wash U is doing 8 now. Okay. 9 DR. GYI: One more question. 10 DR. WEINER: No. I have one final comment 11 to make; and that is, with respect to the quote from 12 Henry Beecher. There's a missing term in there that 13 troubles me, and that really has to do with the 14 principal investigator being unconflicted. And it's 15 really the check and balance, not just against the 16 professional judgment of what constitutes serious, but 17 also that that judgment comes from someone who is 18 unconflicted. 19 MR. ADAMS: That is þþ I mean, Ernie, just 20 þþ I mean, we've been talking among ourselves and 21 just, I would agree with Susan. There is no question 22 but that IRBs have too many Adverse Event Reports and 23 stomachs that have nothing to do with the drug or 24 device under study. There's too many of those. It 25 162 inundates IRBs. Everything that you say is absolutely 1 true, but I have to say, I would be more comfortable 2 with having a serious adverse event threshold for 3 events than I would having Pis make a decision 4 essentially about whether they've got to go to even 5 more trouble or not, because I think it's for the IRB 6 to decide whether a serious adverse event should be a 7 recognition of risk that would lead the IRB to say 8 there should be a change in informed consent, or 9 reconsent, or anything else. I just think there's an 10 inherent conflict of interest in letting investigator 11 make that determination. 12 DR. PRENTICE: And I appreciate that. On 13 the other hand, I would also suggest that the IRBs are 14 not in a position to do that. They don't have the 15 data. They don't have the expertise. They really 16 don't. 17 MR. CORTESI: Could I add something? 18 There's been a long history of Pis getting the bit 19 between their teeth when they're investigating, and I 20 think that has been shown to be a very real hazard to 21 subjects. And to put that in the PI's court, I think 22 is not going to fly. 23 DR. GYI: Given that Dr. Prentice is 24 chairing and we're taking a free-for-all here, let me 25 163 comment on what you're saying, Mark. I think that 1 there is a real concern that Pis are not going to be 2 able to address this in a way that we are hoping that 3 it will, and I think that that's very clear. 4 I wondered if we're moving away from 5 certain basic elements in terms of what we're 6 discussing about - we're looking at what an IRB is 7 supposed to be doing with this. There's a lot of 8 information that they have absolutely no idea what the 9 impact of that particular event is on the study. And 10 so we're not looking þþ at least if I'm understanding 11 this correctly, this is not addressing the serious 12 adverse events at the local site. The IRB still 13 remains responsible for those types of activities. 14 DR. PRENTICE: All adverse events as far 15 as I'm concerned are the local. Anything that's more 16 than minor risk, they should be reviewing, or anything 17 more than a minor event, rather, they should be 18 reviewing. 19 DR. GYI: And what I heard us do was to 20 ask OHRP and FDA to give us guidance on how externally 21 reported adverse events are handled. And currently, 22 the IRBs are not doing a good job of it anyway. Many 23 IRBs are simply taking it and just not even looking at 24 it until something happens, and that something is yet 25 164 to be defined. 1 I do believe that we need guidance on this 2 so that sponsors will be moved in the direction of 3 helping investigators make some determination that's 4 reasonable and accurate. And I suspect that that's 5 where we are right now in asking OHRP and FDA to take 6 a stand. 7 DR. FISHER: Speaking for the group here 8 a little bit, the peanut gallery here. Just once 9 again, I totally agree with you. I'm glad it's not 10 about internal events. I would be comfortable with 11 this if, in fact, the PI has a criteria that he or she 12 has presented to the IRB, that that criteria includes 13 how independent assessment of risk is going to be 14 made, and that I also agree that I think one way is 15 also to begin to distinguish between the SAEs and the 16 AER. But I think I agree with Susan, and I think 17 Mark, and maybe Susan that to think that Pis are 18 unconflicted is not the experience that most of us 19 had. And so not burdening the IRB, but having a 20 policy to which þþ a safety and independent monitoring 21 policy to which the PI has to insure, I would be more 22 comfortable within this model. 23 DR. PRENTICE: We're getting into the 24 public comment period, and I don't know how many 25 165 people want to speak up, but let me just very briefly 1 describe our adverse event reporting form for both 2 internal and external. 3 First of all, we want a brief description 4 of the Adverse Event Report. We want the investigator 5 to comment on the causality, because if they disagree 6 with the pharmaceutical company's assessment, we want 7 to know why. If they agree, we want them to state 8 that. We want them to tell us whether or not the 9 risk/benefit relationship of the research has been in 10 any way altered by the adverse event. And they simply 11 can't say no. They have to say why. It's not good 12 enough to say no, it's not. You have to tell us why 13 they made that decision. 14 They have to tell us whether or not 15 there's any change in protocol required to minimize 16 risk, to further minimize risk. They can't simply say 17 no. They have to say why. They have to go on to say 18 whether or not the consent document requires 19 modification. Once again, they can't simply say no, 20 it doesn't. They have to say why it does not. 21 That's the analysis that we're currently 22 looking at for our somewhat, probably by the time we 23 go through the triage system, maybe 2000 adverse 24 events. Now what I'm suggesting is the investigator 25 166 should still do that analysis, but that analysis would 1 be audited. And we would simply never get the adverse 2 event unless the investigator chose to make a change 3 in the protocol. 4 So I would still contend, despite the fact 5 that I understand fully that investigators can be 6 conflicted, the entire system of human protection 7 breaks down if we cannot trust investigators, period. 8 It just simply breaks down. And I know that there are 9 maverick investigators, and I know that there are 10 tragedies, but the vast majority of investigators, in 11 my opinion, are ethical, conscientious, and 12 responsible. And to have a place like Wash U have to 13 review 12,000 adverse events every year in order to 14 add this additional level of protection against 15 conflict of investigators is not cost-effective, as 16 far as I'm concerned. 17 DR. WEINER: Just one final comment, and 18 that is that the SAEs are graded in cancer already, so 19 there's a system that exists, at least in that whole 20 research domain. 21 DR. PRENTICE: Yes. You're talking about 22 the criteria for reporting. 23 DR. WEINER: And the timeliness. 24 DR. PRENTICE: Yes. The oncology trials, 25 167 that's not the problem. The problem is the IND 1 safety trials that come from pharmaceutical companies, 2 not the co-op trials. Mr. Chairman, are we done with 3 this session? 4 DR. GYI: We were done 10 minutes ago. 5 Thank you very much. 6 DR. PRENTICE: Okay. Now we're going into 7 the public comment period. We have allocated about an 8 hour. We're 10 minutes into that hour now. Cathy, 9 has anybody signed up to comment? All right. Would 10 anybody care to comment that has not signed up? John, 11 and whoever comes up identify yourself and your 12 institution, please. Come up to the microphone. 13 DR. MATHER: Dr. John Mather with the 14 Office of Research Compliance Review, University of 15 Michigan. It seems ironic but the two public comment 16 periods come right after sessions when the subject 17 matter is relevant to the public commentary. I wonder 18 if in other times we can have public commentary 19 periods snuck in a little bit at other times, as well, 20 because I know there were some others in the public 21 who wanted to comment on a couple of the sessions this 22 morning. And we're waiting now to be able to make 23 those kinds of comments. 24 Notwithstanding that comment, let me just 25 168 commend you for the resolution that you just passed, 1 because when I went back to Michigan last December, I 2 started inquiring into our problem in this regard. It 3 was close to what the University of Washington's was, 4 and it's a big, big struggle. But I do want to make 5 a comment about the issue of the conflicted situation 6 of PI. I mean, I know you're aware in the FDA 7 regulations, you can have an investigator sponsor. So 8 if you're an investigator sponsor where you're just 9 being funded from a drug company, the drug company is 10 not the sponsor. You are the sponsor. So I think in 11 that situation, the remarks that were being made here 12 are even more pertinent in the care to sort out what 13 is conflicted. 14 We also noted that in our conflict of 15 interest committees, we find the investigator sponsor 16 not uncommonly coming because they have either some 17 anticipation of patent, or some other factor that's 18 going on, which really becomes very much more 19 financial rather than a conceptual conflicted 20 situation. It goes from the conceptual to the 21 financial piece of it, as well. 22 DR. PRENTICE: Thank you, John. Paul. 23 MR. GOEBELS: I'm Paul Goebels with 24 Chesapeake Research Review. One comment on the 25 169 liability situation. The informed consents, the way 1 the sponsors like to have them worded anyway is say if 2 you get hurt, we won't pay for anything, but feel free 3 to sue us. So if that's the instruction that's given 4 to the study subjects, and if they actually read this 5 consent, they would think that they haven no recourse, 6 except to employ an attorney. So I'm wondering þþ I'm 7 not sure where I'm going with this, but I'm wondering 8 if there's some way that we could change the 9 conventional wisdom about what should be placed in the 10 informed consent to suggest some intermediate step 11 before you go to the point of nothing left except to 12 sue somebody. Just a little food for thought. 13 Next subject, Dr. Prentice, my ears were 14 burning when you talked about coming to FDA eight 15 years ago and talking the þþ 16 DR. PRENTICE: That's right. You were 17 there. 18 MR. GOEBELS: I was, yes. 19 DR. PRENTICE: Weren't you the one who 20 invited me? 21 MR. GOEBELS: I think so. I might have 22 been the one that said we're going to do something 23 about it. Hopefully, the new regime will be able to 24 do better on that. 25 170 I think I'm very much in favor of the 1 motion that you passed. One thing that I think, 2 looking at it from the standpoint of the sponsors, 3 they have been faulted by FDA for failing to note and 4 promptly report an obtuse adverse event that occurred 5 halfway around the world. So it's not just out of the 6 clear blue sky that they're reporting everything, so 7 that may be a dynamic that also has to be addressed. 8 But I think it would give the sponsor some comfort if 9 there is official guidance that says the IRBs don't 10 have to see all this, because I think they would very 11 much like to get out of the expense of making sure 12 this and then making sure they get confirmation that 13 it's been either received or reviewed. So I think a 14 little guidance will go a long way in this area. 15 Thank you. 16 DR. PRENTICE: Thank you, Paul. Other 17 comments? You're a rather sedate group. Where is 18 Maura Keen? Maura, you're from Minnesota. You're a 19 huge institution. 20 MS. KEEN: I can't comment officially. 21 DR. PRENTICE: You don't have to comment 22 officially. Just tell us what you think your problem 23 is.24 MS. KEEN: I already stated my disclaimer. 25 171 Yes, I'm from the University of Minnesota. My name is 1 Maura Keen, and I manage the IRB operations there. 2 And this is a very serious problem for all of us, the 3 adverse events. We have both internally held INDs and 4 IDEs. We manage those very carefully. We also have 5 a very aggressive conflict of interest management 6 policy and practice so that we do control for a lot of 7 those variables within our structure of our human 8 research protection program. 9 The concern that we have is the when in 10 doubt report phenomena that we are getting from 11 industry, whether it's device trials. We have a lot 12 of those in Minnesota with our device companies. We 13 have a lot of IND-related research that comes from the 14 drug companies, and there is a default that they 15 expect IRBs to respond to these problems and issues 16 that come up because they're looking at us for some 17 liability insurance, and a basis for protecting 18 themselves, as well as the study subjects. And I 19 think that that is a really serious problem that must 20 be addressed. 21 The only flaw that I see in your proposal, 22 and I appreciate your bringing it forward, is that we 23 don't have a deadline built into that. And for some 24 of us who have been around for a long time, we have 25 172 seen this issue come to the fore many times, so I urge 1 you to please take action. 2 While I have the microphone - it's a 3 dangerous thing to let me have a microphone - I have 4 a comment about the international research issues. 5 One of the things that I struggle with, again being 6 close to Canada, we do a lot of research across our 7 northern border. And when we talk about international 8 research in a context like this, there is always a 9 supposition that our research is being handled in an 10 inter-cultural/cross-cultural context that involves 11 third world countries. That is simply not true. 12 Many of our partners in drug and device 13 research, and in social and behavioral sciences 14 research - let us not forget - is actually conducted 15 in very advanced cultures, very advanced communities 16 where they have their own ethical standards, but they 17 don't necessarily mesh with the language that is built 18 into the FWA system, so I would urge when you're 19 talking about international research to remember that 20 many of our partners in those research projects are, 21 in fact, as sophisticated as we are in considering 22 these issues. 23 That doesn't change the fact that we have 24 a lot of burden and concern about research in third 25 173 world countries, but let's remember that we have 1 disequilibrium in the international context. Thank 2 you. Again, unofficially from Minnesota. 3 DR. PRENTICE: Thank you, Maura. Yes 4 Felix. 5 DR. GYI: We've spoken of the adverse 6 event issues as if it's a conflict and tension between 7 IRBs and sponsors. Of course, the investigators are 8 in that mix, as well. But many times we've been faced 9 with the interpretive position of having FDA 10 colleagues tell us that we as an IRB actually should 11 have taken a more proactive stand to seek out what the 12 issues are, and what IND safety reports are with 13 relationship to risk to subjects. And as an IRB we 14 just don't have the capacity to be able to serve in a 15 DSMB mode. And so I see this in not only helping the 16 IRB colleagues and the sponsor colleagues, but also 17 providing some guidance for those folks that are out 18 in the field monitoring the activities of both IRBs 19 and investigators. 20 DR. PRENTICE: Felix, could I ask you a 21 question concerning clarification of the AE problem 22 for academic IRBs versus independent IRBs? I mean, we 23 can easily classify things as internal and external 24 because most of us are not the IRB of record for 25 174 multiple sites, although in some cases we do have that 1 sort of broad-based responsibility. But an 2 independent IRB, you have research sites all over the 3 country, but you are the IRB of record. So in a way, 4 you are the þþ those are internal adverse events for 5 you. Then in addition, of course, you would get the 6 external adverse events for sites that are not under 7 your jurisdiction. So how does the adverse event 8 problem impact an independent IRB like your's? 9 DR. GYI: When an independent IRB is 10 fortunate enough to be the IRB of record for a large 11 percentage of multi-site studies, then there are 12 economies of scale and efficiencies that we could 13 realize in applying information from one site as it 14 relates to impact on the overall research discussion, 15 or looking at the impact on other sites. So when 16 there is a serious adverse event that is reported to 17 a central IRB, I won't pretend to speak for the entire 18 universe of central IRBs, but most of the ones that I 19 communicate with have a similar structure where there 20 is a dedicated activity resource to evaluating these 21 types of events. And that standing adverse event 22 subcommittee addresses many issues like this. 23 We face the same problems as our academic 24 colleagues, in that getting information from halfway 25 175 around the world that has very little other clinical 1 information is very difficult for us to evaluate and 2 quantify in terms of its impact on either information 3 to the subjects who are in the study, or the impact on 4 the redesign of the existing study. I'm not sure if 5 that answered your question. 6 DR. PRENTICE: That helps. What we're 7 finding with our investigators is that, first of all, 8 you can't change a protocol, a multi-centered clinical 9 trial protocol very easily, but it's a lot easier to 10 revise a consent document. And what we're finding our 11 investigators are doing more and more is saying well, 12 okay, I don't really know whether or not this adverse 13 event is really related, but why not just throw into 14 the consent documents one more line, or four more 15 lines. It doesn't make any difference. I don't 16 really care if it increases the length of the consent 17 document. 18 So we're finding that as a behavior 19 pattern for our investigators, so I wonder if the 20 other members of SACHRP would have some comments with 21 regard to þþ particularly our lawyer representative 22 over there as to the utility of doing that. 23 MR. BARNES: Thank goodness the lawyer 24 member is called upon, Celia says. The problem with 25 176 that attitude is that it ends up hopelessly cluttering 1 the informed consent form with risks that are actually 2 not significant, which is itself a deterioration of 3 informed consent, not an enhancement of informed 4 consent. I mean, that's the theoretical legal problem 5 with just adding something when you're not sure 6 whether it's related or not. It diminishes informed 7 consent. 8 DR. PRENTICE: We agree. But on the other 9 hand when an investigator says, you know, I can't 10 think of a reason why I shouldn't put this in a 11 consent document. You know, a consent document is not 12 limited to only serious risk. You know, venipuncture 13 you include the risk associated with a research 14 venipuncture. It's nothing more than bruising, rare 15 possibility of infection, a little bit of pain and 16 discomfort, you put that in. So you can't relegate 17 revision of consent documents to only those risks that 18 might be serious. 19 MR. BARNES: No, but the standard has 20 always been significant risk, not serious risk, but 21 significant risk. That's been the standard in court 22 cases that are challenged. It's significant risk of 23 injury, but the injury might be small, but it's 24 whether the risk of the small injury would be 25 177 significant. 1 DR. PRENTICE: Are we suggesting we don't 2 need to have venipuncture risk in consent documents 3 any longer? 4 MR. BARNES: No, no. That's not what I'm 5 saying at all. No. There is a significant risk of 6 having bruising when you have venipuncture. 7 DR. PRENTICE: I see. A significant 8 probability of occurrence would be maybe a better way 9 to characterize that. 10 MR. BARNES: Exactly. 11 DR. PRENTICE: Okay. Yes. 12 DR. HAUSER: I just wanted to comment. In 13 my motion, I did not include a date. I thought it 14 might be presumptive, or otherwise tactless. But I do 15 think the committee has a sense of urgency on this 16 issue. 17 DR. PRENTICE: Let's open that up for 18 discussion. How would you like to characterize this 19 urgency? 20 DR. HAUSER: Well, that it be done 21 promptly. 22 DR. PRENTICE: Promptly. David, what's þþ 23 David is not here any more. I was going to ask him 24 his interpretation of promptly. Speaking of promptly 25 178 by the way, OHRP, I don't think you've ever issued any 1 guidance as to what promptly means, have you? As you 2 said, somewhere between immediate and never. Is that 3 correct? Okay. 4 All right. Let me tell you what we have 5 to do for the rest of the day, if there are no public 6 comments. And I'm assuming that there aren't any. We 7 need to decide where we go from here. In some cases, 8 we know that we're going to have subcommittees working 9 on various issues. We summarized the SACHRP 10 Children's Research Subcommittee's activities 11 yesterday. They know what their charge is. They're 12 going to go back and meet, and try to interpret, 13 reinterpret the requirements in Subpart D, which are 14 problematic, to say the least, in terms of 15 interpretation, so that's what they're going to be 16 doing at their next meeting. 17 We're going to write a letter to the 18 Secretary recommending the adoption of the non-FACA 19 model with all of its trappings, and I think that's 20 fairly clear-cut. We'll be able to do that once Susan 21 and Celia come up with the exact language of the 22 regulations based upon the review of the Minutes, so 23 you know what you're doing. And then feel free, of 24 course, to consult other members of SACHRP as you see 25 179 fit. But eventually, we want to get a concise series 1 of recommendations that we can send to the Secretary 2 on that model. 3 We will also incorporate the 407 review 4 algorithm which we approved last time, but there was 5 no point in sending that kind of a disjointed 6 recommendation to the Secretary, because it really 7 goes hand-in-hand with a 407 review process, so that 8 would be incorporated into that recommendation. So 9 that's what Subpart D is going to do. 10 Subpart C is going to continue to look at 11 Subpart C in terms of your short-term fixes and your 12 intermediate term fixes, and your long-term fixes, 13 which is probably going to take long past my 14 retirement before you finally get done with the long- 15 term fix. But it's good that you're working on it, 16 Mark. So we're going to expect a report next time 17 from both subcommittees. 18 I think we all agree that the HRPP 19 Accreditation Subcommittee has done a fine job with 20 the limited data available. And you really can't do 21 very much more at this point in time. You may want to 22 resurrect that issue at some point in the future, but 23 you produce a report. So I want to probably start 24 with that report. 25 180 What would your intentions be in terms of 1 that report? Is that something that you would like to 2 send to the Secretary? Is that your intent? 3 MR. ADAMS: My understanding was that all 4 of the reports would eventually go to the Secretary. 5 DR. PRENTICE: If it's considered a final 6 report and you want to send it to the Secretary - yes, 7 that is correct. 8 MR. ADAMS: That would be our intention. 9 DR. PRENTICE: Okay. So far, we have two 10 reports going to the Secretary. We have a Subpart þþ 11 I'm going to use Subpart D, it's easier to say - 12 Subpart D and HRPP. Correct? 13 MR. ADAMS: Right. 14 DR. PRENTICE: Now we also endorsed a 15 recommendation to send a letter to the Secretary 16 asking that this AE problem be resolved in a prompt 17 manner. So we can do that with some additional 18 flowery language added as to the significance of this 19 problem in terms of IRB workload. Okay. So we will 20 send that, as well. So there are now a total of three 21 reports that are going to go to the Secretary as a 22 consequence of this meeting. All right. 23 We had a presentation by Mary Lake Polan 24 on international research. She was concerned about 25 181 the fact that the other individuals that were involved 1 in producing this report were not here, particularly 2 Dr. Lin. She does not object to us accepting the 3 report and its recommendations, or deferring that for 4 future discussion. What is your preference on that 5 particular report? 6 DR. FISHER: I think the points were very 7 well made. I think their implementability is 8 questionable, so I'd like to delay. 9 DR. PRENTICE: You'd like to delay it. 10 Okay. Are there other comments? Felix. 11 DR. GYI: I heard her say that these were 12 simply just thinking out loud points for SACHRP to 13 hear, and that she did not want us to take any 14 additional action at this particular point. 15 DR. PRENTICE: All right. So we will þþ 16 I don't think we need to bring this to a vote unless 17 there's some debate about it. We will delay further 18 action on the international report. All right? 19 DR. JONES: I mean, is that indefinite, or 20 is there þþ 21 DR. PRENTICE: No, it's not. 22 DR. JONES: þþ a strategy to relook at it 23 at a certain time? 24 DR. PRENTICE: I think that what we should 25 182 do is see what Mary Lake thinks about that, and what 1 Melody thinks about that. And then resurrect it at 2 the appropriate time. You know, part of the problem 3 with the international report is the feasibility of 4 implementing many of the recommendations, which are 5 costly. I think it's great. It should be done. The 6 question is how can it get done. And if we were to 7 write this report and send it to the Secretary, quite 8 frankly I don't think it's going to go anywhere. 9 That's my personal opinion, so let's sit down and 10 discuss this some more at the appropriate time. All 11 right? 12 We had a very nice presentation on 13 litigation from Haavi. And, Mark, you were very 14 interested in having consideration of litigation as 15 part of our agenda this time. And certainly, I've had 16 an interest in this for a very long time. She's made 17 some recommendations, some of which, obviously, would 18 require a Congressional action, which I have no idea 19 how feasible that is or is not. But let's talk about 20 the litigation report, and what do you think SACHRP 21 should do? 22 MR. BARNES: Yes, Ernie. I mean, it 23 clearly is an issue that faces all of us wearing our 24 IRB hats and our investigator hats. At the very first 25 183 meeting of NHRPAC which was now, I guess, about four 1 years ago, when we were asked to go around and say 2 what issues we thought were burning issues, my issue 3 was that I thought we needed something like the 4 Healthcare Quality Improvement Act to protect IRB 5 members from suits either by frustrated investigators. 6 And that was not talked about this morning, but there 7 are some IRBs that have been sued by investigators for 8 turning down protocols. So they would be protected 9 from those suits by those investigators, and also 10 suits by disgruntled or even injured subjects. 11 And four years later, it's become even 12 more of an issue than it was four years ago. And much 13 of what we see IRBs doing these days is really driven, 14 unfortunately, by liability considerations, instead of 15 by considerations of what is truly best for research 16 subjects. And so this procedure has become a fetish 17 in some IRB circles, and substance gets relegated to 18 second-class citizenship. And that's not a good þþ in 19 fact, it's a terrible result for ethical conduct of 20 human subjects research. So I hesitate to say that we 21 should have yet another subcommittee on litigation, 22 but I will tell you that there's a lot of talk in 23 Congress right now about Senator Frist and others 24 coming up with a bill that would actually do something 25 184 like extend a Healthcare Quality Improvement Act type 1 insulation from liability to IRB members, as long as 2 IRBs meet basic criteria for having appropriate 3 process in looking at protocols, and reviewing 4 protocols. 5 It does seem to me that þþ God knows 6 what's going to happen in November, but I think it's 7 safe to say that if there is a Republican majority 8 retained in the Senate and the House, that there will 9 be serious proposals for this. And I would hate for 10 this committee to lose the opportunity of weighing in. 11 I think that we could provide some real guidance if we 12 had a report about this, and if we came to a position 13 as to what the problem is, number one. And number 14 two, what some potential solutions might be. 15 I'm not eager to dive into this myself 16 because I've got my hands full with the Subpart C 17 committee, but I think that we could make a real 18 contribution by doing it. And I'm the only lawyer þþ 19 I'll give you an honorary law degree and you can do 20 it. 21 DR. PRENTICE: Okay. Let me make a couple 22 of comments. And I agree with you, I think that this 23 is a problem. I also want to temper our consideration 24 of this problem with the fact that very few IRBs have 25 185 ever been sued. Sometimes they're named as an entity, 1 sometimes IRB members individually are named. There's 2 never been a successful suit against an IRB. There 3 are some suits pending. I know of at least one. 4 There's probably more than one that I don't know 5 about, but there's at least one. 6 If an IRB is sued at an academic 7 institution, unless there is gross negligence on the 8 part of the IRB, which is probably unlikely, the 9 institution's liability insurance automatically covers 10 all IRB members. So this has not been a problem in 11 terms of getting IRB members to serve because of 12 liability concerns in the academic environment, 13 although they certainly ask about it. 14 Secondly, I only know of one situation 15 where an investigator has sued an institution for an 16 IRB for halting or suspending his research project. 17 That was an unsuccessful suit. There may be some 18 others I don't know about, so it's a small number. 19 Let me tell you what I think the real 20 impact of fear of litigation is. It's paperwork. We 21 practice what I refer to as IRB defense-ism, because 22 we're documenting every single thing, because serving 23 as an expert witness, what I do is I get hired to pour 24 through an IRB's records to see whether or not they 25 186 have a defense against the allegations that they were 1 irresponsible, or the investigator was irresponsible. 2 And I see more and more documentation occurring as a 3 consequence of this fear of litigation. But I also 4 want to make the point that there's also a fear of 5 OHRP shutdowns, and FDA site visits. Investigator 6 error, IRB inspections that' driving an increase in 7 the paperwork. 8 We're seeing Minutes that extend to 100, 9 150 pages in some institutions. We've got files and 10 files of paperwork documenting how we reviewed the 11 protocol, checklists that we check off that we found 12 that complies with the regulations, et cetera. We're 13 finding consent documents that are increasing in 14 length every month, every year. I think the record 15 now is something like what, Bern - a hundred something 16 pages. Okay. I think that's a really significant 17 issue, because the more time we spend documenting, the 18 less time we spend on really protecting the rights of 19 human subjects. 20 I just want to bring that up for 21 consideration by the committee. That's a real concern 22 of mine. What do you all think? 23 DR. PRENTICE: Bernie, is the question 24 that the position that we take in response to 25 187 litigation, or is the question should we take on 1 litigation as a topic for discussion? I'm not sure I 2 understand what the question is. Sorry. 3 DR. PRENTICE: No. I'm just making a 4 comment in response to Mark's comments. We had Haavi 5 produce a report on litigation issues. We have to 6 decide what we want to do with it. Do we want to have 7 a subcommittee, or do we want to produce some kind of 8 a report that indicates what the problem is, and 9 possible solutions? Nancy. 10 DR. JONES: It seems like the report that 11 we had today really focused on the IRB's concerns in 12 litigation. And we haven't really heard much about 13 what the subjects' concerns might be with litigation. 14 So I think before we went to make a proposal, that we 15 should also consider that. I'm not sure who the 16 expertise would be to consider that, but I feel like 17 we've so far narrowly focused on litigation, and just 18 the burden it is on IRBs. And I believe we should be 19 broader if we're considering þþ I know it affects 20 human subject research through the IRB, but I think 21 there also might be some other concerns out there. 22 DR. PRENTICE: Well, I think that research 23 subjects who are injured should have the right to sue. 24 They do have the right to sue under the American way. 25 188 I don't think that Haavi's report in any way decreased 1 the liability of the individual investigators or 2 institutions. I think what it was trying to do is to 3 insulate, in particular, IRBs from being named as 4 defendants in lawsuits. I think if an IRB is totally 5 negligent, then the þþ whatever it's called, the 6 acronyms, I can't remember the name - it's not an 7 adequate defense. But if they are performing a review 8 in compliance with the federal requirements, they 9 could have immunity from suits. That would be nice, 10 but I don't think that that alters in any way the 11 subject's right to sue over an injury, so I'm not 12 quite sure what we're going to gain by asking to have 13 a subject's perspective. 14 If you're injured in a research protocol, 15 you want justice, you want to sue. And if you're like 16 me, you want as much money as you can get. Yes, Bob. 17 DR. HAUSER: My sense is, and I don't know 18 how the committee feels, but I feel like I need more 19 information. One of the points that she made this 20 morning was that most of these things probably get 21 settled without ever going to court, and so we may be 22 unaware of the vast majority of activities that are 23 actually occurring. 24 A thought that I had while I was listening 25 189 to her was þþ I asked the question about can we þþ is 1 there some registry or some way to acquire information 2 that is public. Another way to go about it may be for 3 us to survey institutions, and actually try to drill 4 down on exactly what the issues are. 5 I don't know which is the best way to go, 6 whether we should go all ways, but my feel is that I 7 would like to have more data. 8 DR. PRENTICE: Celia. 9 DR. FISHER: I didn't think that Haavi 10 raised many actionable recommendations, or at least 11 ones that I'd be comfortable with, or that were 12 practically actionable. I also agree with Nancy that 13 I would feel uncomfortable in terms of what I believe 14 is the charge of this committee with not hearing from 15 subject advocates, opposing attorneys, whether or not 16 we want to do that. And I'm not sure þþ if it's 17 simply an issue of reducing paperwork for IRBs, which 18 I know is very important, but I'm not sure if that 19 would be a priority if we only have one subcommittee. 20 And I don't feel comfortable that we have enough 21 information to write a report without a subcommittee. 22 The one thing I did think was very useful 23 was þþ and I think this also gets to your risk adverse 24 concern as to why there's so much paperwork, is that 25 190 we might be able to better operationalize and 1 articulate both the breadth and limitations of IRB 2 responsibility. 3 So, for example, in terms of reviewing 4 what a consent form is, requiring storage so it can be 5 auditive of consent forms. Those seem, to me, within 6 þþ and having a yearly report. This is just one 7 example. That's certainly in the purview and 8 responsibility of an IRB. Knowing whether or not it 9 was grabbed away from a participant is not something 10 that an IRB can know, so that's just a very surface 11 example. 12 So another way is to say what is there in 13 terms of misconceptions or lack of clarity about the 14 breadth and limit of IRB responsibility that could 15 help make IRBs less risk averse. 16 DR. PRENTICE: Yes. Tom. 17 MR. ADAMS: Whatever we would come out 18 with, no matter how much work we would do is going to 19 be controversial. And there are going to be about 50 20 percent of the people on the Hill that are going to 21 agree with it, and about 50 percent that won't. 22 It would seem to me listening to others 23 this morning that we might be better off spending our 24 limited resources looking, as Celia suggested, at 25 191 those issues which could use clarification for IRBs, 1 or for investigators as we move forward. So I would 2 like to see us address the liability problem, but 3 address it in a way that we are actually helping 4 people who are doing research rather than getting 5 involved with the trial bar and others. 6 DR. PRENTICE: Do you have any ideas as to 7 what direction you want to go in terms of helping 8 people do research, Tom? 9 MR. ADAMS: Well, we've heard some 10 testimony that there were þþ and I didn't hear a lot 11 of specifics, but that there are areas where IRBs 12 would like to have clarification as to what it is that 13 FDA or OHRP are looking for in the auditing process. 14 And clearly, anything we could do that would help 15 to clarify that would have a beneficial effect 16 probably of cutting back to some extent on paperwork, 17 and cutting back on legal liability. But I think the 18 work of the subcommittee would be to look and explore, 19 and find out exactly where those areas are, and allow 20 us to produce a report that would let us wind up with, 21 ultimately, a recommendation similar to the one Bob 22 made earlier today. 23 DR. PRENTICE: So as I understand what 24 you're suggesting, is that we need clearer guidelines 25 192 on the documentation expectations of OHRP and FDA. Is 1 that what you're saying? 2 MR. ADAMS: That's essentially what I 3 believe that I heard from the testimony. 4 DR. PRENTICE: I'd like to ask OHRP to 5 comment on that. 6 MR. ADAMS: Do you think it's a model of 7 clarity at the moment? 8 DR. SCHWETZ: It's hard to answer Tom's 9 question because what are the issues that you have 10 specifically in mind. We follow a pretty standard 11 procedure in the quality improvement business. We 12 have a list of things that we go through, that we look 13 for, that we advise on, that we would make comments 14 on. So if we have that kind of guidance that is the 15 basis for us going on and reviewing what's going on in 16 an institution. And to some extent, it parallels the 17 visit that þþ the pre-assessment that would be done in 18 preparation for accreditation, so there's that kind of 19 guidance, but unless you can give us specifics of 20 where you would want us to comment on, how to make 21 changes, Tom, I'm not sure what else we could say. 22 DR. PRENTICE: Celia. 23 DR. FISHER: Ernie, I just wanted to þþ 24 some of this þþ are we going to be getting to the 25 193 HIPAA issues, because we do have a recommendation that 1 we'd like to make. 2 DR. PRENTICE: We're not there yet. We're 3 still on litigation. 4 DR. FISHER: Okay. But we will be getting 5 there. 6 DR. PRENTICE: Oh, yes. Yes, we're going 7 to be here until the wee hours of the night. Don't 8 worry. 9 DR. FISHER: And I also assume that from 10 what I gather from the agenda, we're trying to figure 11 out what a third subcommittee might be doing? 12 DR. PRENTICE: Not necessarily. 13 DR. FISHER: Not necessarily. Okay. 14 DR. PRENTICE: We don't have to have a 15 third subcommittee. We have a limit of three 16 subcommittees. What we need to decide is the best 17 mechanism to pursue our charge. That may not be via 18 a third subcommittee. We'll make that decision later. 19 Mark. 20 MR. BARNES: Yes. There's clearly not 21 like a ground-swell of opinion in favor of having a 22 subcommittee to look at litigation issues. If there 23 were, people would have spoken up, I think. I mean, 24 I think it's unfortunate because I think that we 25 194 actually could have a real impact on may well be one 1 of the most important pieces of legislation to be 2 proposed, if in fact it is proposed, which I believe 3 it will be again þþ maybe even proposed this year. 4 But there has to be a willingness of the committee to 5 take it on, and it's going to be a big task to take on 6 that issue in a subcommittee, if there were one for 7 this issue. It would have to do things like reach out 8 to subjects, reach out to subject representatives, 9 reach out to pharma. I mean, it would be a real 10 undertaking. It's almost to the scale of like an IOM 11 report instead of a subcommittee that could be done by 12 this group, because we have limited staff resources 13 and everything else. 14 So with that, I think it's probably better 15 to drop it, if people aren't interested in doing it. 16 I think it's too bad. That's my personal opinion. 17 Because I will tell you, Ernie, every client I go to 18 and talk to the IRB, whether it's from San Diego to 19 Maine, there are people who are not willing to serve 20 on IRBs because they don't want to be sucked into even 21 potential litigation or potential liability issues. 22 I get this every place I do. And there are lawsuits 23 þþ I mean, I'm a member of an IRB that's being sued 24 right now by a disgruntled investigator who is part of 25 195 the coterie of people who think that DPT causes autism 1 in children, the thing that was just withdrawn from 2 the Lancet and people who were the co-authors. Well, 3 we had one of those and we didn't approve the study, 4 and we got sued. 5 This stuff is going on. It would be þþ to 6 me, my personal opinion, it would be folly for us to 7 ignore the elephant in the room because it does drive 8 a lot of decision making. But with that said, it's a 9 huge issue, and it's probably too big for a 10 subcommittee, so I would say let's just drop it. 11 DR. PRENTICE: Let me make a suggestion. 12 Let's drop it for the time being, and when I say the 13 time being, I want to clarify that. We're going to 14 drop it until we consider some of the other issues 15 that we're going to look at, and then we may revisit 16 this. Okay? 17 DR. WEINER: Is it worth going on record 18 to have a general resolution that recognizes the scope 19 and the implications of the problem - not that I can 20 craft one on the spot. 21 DR. PRENTICE: Mark, did you hear that? 22 MR. BARNES: No. 23 DR. PRENTICE: Would there be any benefit 24 to having a general resolution in the record that 25 196 recognizes the scope and impact of the problems of 1 litigation? It's not going to solve the problem, but 2 it is stating the problem. 3 MR. BARNES: Maybe. I mean, by the way, 4 I would term the problem not litigation, but 5 liability, because it's only a fraction of things that 6 actually get to an actual full-blown lawsuit, but the 7 problem is the one of liability concerns for IRBs. 8 But I think that it might be worthwhile to have a 9 resolution that says that the committee recognizes 10 that there are issues here, that there are emerging 11 concerns about the issue of liability of IRB members, 12 and the committee regrets any kind of system in which 13 the result would be that people would defer, or delay, 14 or even decline serving on an IRB because of fear of 15 personal liability. I mean, I think that's probably 16 a worthwhile resolution to have. 17 DR. WEINER: So I second the motion. 18 DR. PRENTICE: There wasn't a motion made. 19 MR. ADAMS: Okay. I'll move that. 20 DR. PRENTICE: Is there a second? 21 DR. WEINER: I second what he moved. 22 DR. PRENTICE: It's getting late in the 23 day. Any further discussion about this resolution? 24 Tom. 25 197 MR. ADAMS: I am in complete concert with 1 the motion that is involved with this issue, and have 2 spent 25 years working on medical malpractice issues. 3 I'm not certain that passing a resolution like this 4 does anything other than make the 10 or so of us feel 5 good about it. So if we're going to get involved with 6 it, then I would much more rather go where you 7 suggested initially, and that is, let's produce 8 something that can at least be useable in the debate 9 which is going to occur. 10 The question really is, is this where we 11 want to use our resources versus something else. But 12 I would be uncomfortable with just passing this 13 resolution. 14 DR. PRENTICE: Yes. 15 DR. SCHWETZ: There's another way to keep 16 the discussion alive while SACHRP continues to think 17 about what you want to do with this fear of litigation 18 right now or in a future meeting. The Clinical 19 Research Roundtable of the IOM continues to discuss 20 those things that have a negative impact on the 21 function of the human research enterprise, and clearly 22 this is one of those aspects that is of concern in the 23 whole enterprise. 24 The possibility is that if SACHRP goes on 25 198 record as recommending that the Clinical Research 1 Roundtable would pay additional attention to this as 2 an issue within the enterprise, that kind of sends the 3 signal to IOM that perhaps they should pull together 4 a committee. It might be outside of the Clinical 5 Research Roundtable. They might look for sponsors to 6 deal with this question among the federal agencies, or 7 elsewhere. But it raises this issue to another body 8 that might have some means of getting at it. 9 DR. WEINER: That's a good idea. I sit on 10 the Clinical Research Roundtable, and would be willing 11 to communicate that. 12 DR. SCHWETZ: Yes, I think between the two 13 of us, we can. 14 MR. BARNES: I'll amend the motion, Ernie, 15 if I may to be that we commend to the attention of 16 the IOM and the Clinical Research Roundtable this 17 issue, and that we forward to them the results of the 18 presentation that we had today. 19 DR. PRENTICE: Okay. Is there a second 20 for that amendment? Okay. When you say forward the 21 results of the presentation, you're talking about 22 Haavi's presentation? Are you talking about the 23 slideshow, or what are you talking about here? 24 MR. BARNES: The slide show and the text 25 199 for the presentation with the questions and answers. 1 DR. PRENTICE: Okay. All right. We have 2 a motion on the floor that's been amended, and 3 seconded. Any further discussion? Those in favor? 4 Any opposed? Any abstentions? 5 (Vote taken.) 6 DR. PRENTICE: Motion carries. Mark and 7 Susan, would you be responsible for making sure that 8 that happens. 9 DR. SCHWETZ: I'm very happy to. I will 10 make sure that Alex Omayo gets a copy of the 11 information, and so does Kata Bond, the chair of the 12 Clinical Research Roundtable. 13 DR. PRENTICE: But somebody has to produce 14 the document. Right? That's what I'm referring to. 15 DR. SCHWETZ: Okay. 16 DR. PRENTICE: So you guys figure out how 17 you want to do that. Right? 18 DR. SCHWETZ: I'll deliver it. 19 DR. PRENTICE: Right. Okay. Yes. 20 DR. HAUSER: Ernie, do you know, or does 21 anyone know whether or not research has been þþ a PI 22 has not been covered by the malpractice insurance of 23 their institution or practice? Is that an issue? 24 Haavi mentioned that during her presentation. Do you 25 200 see that as something on the horizon? 1 DR. PRENTICE: I don't know if it's þþ I 2 know if it not happening. She said that, and I 3 thought I noted that because I never heard of that 4 happening before. Maybe she has some data that I'm 5 unaware of. 6 DR. FISHER: I know, for example, in terms 7 of research psychologists, they've been insured for 25 8 years. I mean, I didn't see it as much a problem as 9 she seemed to think it was. 10 DR. PRENTICE: Could it become a problem 11 in the future? Yes, sure it could. Certainly, I've 12 had Pis express concern over litigation, and basically 13 question why they're bothering to get involved in 14 clinical research. And the ones who take that concern 15 seriously probably drop out of doing clinical 16 research, which is a bad thing. 17 MS. MATHIAS: My name is Charlie Mathias, 18 and I happy to have some knowledge about the 19 University of Oklahoma, what's happened with the 20 principal investigator there as far as his insurance 21 is concerned. He's been put on reserve by his 22 insurance company, so if he þþ this is my 23 understanding. I'm not a lawyer, but if he þþ I 24 believe in the end if there is a lawsuit, what they 25 201 win þþ the plaintiffs win, then the insurance company 1 won't pay. Is that correct, when it's in reserve, 2 they put him on reserve. That's what's happened 3 there, is that they're being notified that they're all 4 put on reserve. 5 MR. BARNES: Apparently, what you þþ just 6 to rephrase perhaps what you're saying, is that they 7 have agreed to defend them, but they have retained a 8 reservation of rights, which means that even though 9 they are paying for the legal defense, they retain the 10 ability at the end of the day, if there is liability 11 assessed against the investigator, essentially to 12 disclaim their underlying liability for the injury 13 that he or she has caused. And that's what insurance 14 companies do when they believe that it's possible that 15 the policy that they've issued actually may be 16 interpreted not to cover the bad activity of the 17 insured. 18 DR. PRENTICE: Tom. 19 MR. ADAMS: My understanding is that we 20 are down to essentially one company that will write 21 CRCs and CRAs at this point. 22 DR. PRENTICE: Really. That's pretty 23 significant. All right. Other comments? All right. 24 We're going to take a 12 minute break, and we're going 25 202 to try to wrap up somewhere around 4:00. Just so I 1 know what's happening, who has planes to catch when? 2 MR. BARNES: Ernie, could I ask a 3 question? 4 DR. PRENTICE: Yes. 5 MR. BARNES: Could we just work straight 6 through, please. 7 DR. PRENTICE: Sure. 8 MR. BARNES: And just finish. 9 DR. PRENTICE: We could if it's okay with 10 everybody. We could do that. As far as the public is 11 concerned, you can do what you need to do and come 12 back. Let's make sure that everybody agrees on that 13 course of action. How many people want to just work 14 straight through? Raise your hands. Any opposed? It 15 doesn't mean you're going to get out before 4:00, 16 Mark. Just make sure you understand that. Okay. 17 All right. You have to give me a moment 18 to regroup here. 19 DR. FISHER: We'd like to make a motion. 20 DR. PRENTICE: What? Go ahead. Make a 21 motion. 22 DR. FISHER: Okay. The motion is that 23 SACHRP endorse the four AAMC recommendations that were 24 made by þþ presented to us by Susan Ehringhaus, and 25 203 it's on page 13 of the Power Point handout. And that 1 we do so within the context that OHRP, in order to 2 attend to all of the issues that not only are being 3 raised in this committee, but all of its 4 responsibilities should not be overwhelmed by issues 5 that arise for them in constantly having to clarify or 6 address some of the HIPAA related issues that are 7 inconsistent with the Common Rule. And that we 8 believe that consideration of the AAMC recommendations 9 may be very helpful in that regard. 10 DR. PRENTICE: Is everybody looking at 11 those four recommendations, page 13? She modified it? 12 Do you have þþ five. We just noticed it. There are 13 five recommendations. Yes. Kelly. 14 MS. BOOKER: Ernie, Susan changed her 15 presentation this morning, and we will have copies of 16 that available to all of you. 17 DR. PRENTICE: Does anybody know what the 18 fifth one was? 19 DR. FISHER: We can't endorse it if we 20 don't know what the fifth one is. 21 MS. BOOKER: Right. Let me see if it's on 22 the Power Point. 23 DR. PRENTICE: It has to be on the Power 24 Point if she talked about it. All right. So her 25 204 order has changed. All right. Everybody look at 1 that. The order is important too, so take a look at 2 that and see whether or not you agree. 3 MR. BARNES: Ernie, these are generally 4 phrased, and so if I could perhaps modify the 5 amendment, or if you would entertain an amendment. 6 And that would be that a small group of us basically 7 be commissioned to look at the testimony, tease-out 8 the elements, keeping in mind these five suggestions 9 as five hard concrete suggestions that we received, 10 and bring a draft letter back to the committee at the 11 next meeting. He wants it more quickly? Okay. Then 12 we produce a letter that would be circulated to the 13 committee electronically for comment so that the 14 committee could make a series of recommendations to 15 the Secretary and, therefore, to the Office of Civil 16 Rights about problems with the implementation of the 17 HIPAA regs in the research context, and suggested 18 solutions. 19 DR. PRENTICE: Mike, is that legal? 20 MS. ODWAZNY: Ernie, I actually think that 21 if the committee wants to make recommendations to the 22 Secretary, the committee has to vote on that in the 23 open meeting process in order to comply with the 24 Federal Advisory Committee Act. 25 205 DR. PRENTICE: Right. 1 DR. FISHER: Can we vote on the four - I 2 mean, I'm sorry þ the five recommendations, and then 3 have two people write up a description of it. Can we 4 do that? 5 MS. ODWAZNY: Celia, I guess I don't 6 understand the distinction. Wouldn't that all be part 7 of the advisory committee's recommendation to the 8 Secretary, even if you did provide additional 9 guidance. It would be coming from SACHRP. It's my 10 understanding it would have to be approved during an 11 open meeting. 12 DR. PRENTICE: Yes. See, what they're 13 proposing, which is why I asked the question, is they 14 want to take these five recommendations and amplify 15 those recommendations, maintain the same concept, the 16 same intent, but amplify on that. And then send that 17 report around via email to all members of SACHRP to 18 comment and theoretically accept or not accept. My 19 understanding is you can't do that. Is that correct? 20 MS. ODWAZNY: That's my understanding, as 21 well. 22 MS. KORNETSKY: I mean, I think what we 23 were trying to do is to vote on this, accept this 24 today and just take the þþ you know, to fill in the 25 206 blanks with the stuff behind it. But if we can't do 1 that, I guess the next best thing is to come back to 2 the next meeting with a draft letter. I think there 3 was some concern about more þþ some urgency to this, 4 and to do it sooner than later, but if we can't, we 5 can't. 6 DR. PRENTICE: Well, considering the 7 likelihood that OCR would move quickly on any of this 8 stuff, I'm not sure that we have such urgency, so I 9 would think that that's an appropriate course of 10 action to take. The reports, the slide presentations 11 made by the individuals, take the AAMC 12 recommendations, expand upon them as you see 13 appropriate, and then bring a report back to the next 14 SACHRP meeting. Who is on this drafting committee, 15 other than Mark, and Celia, and Susan? 16 MS. KORNETSKY: I've done this before with 17 Mark, and usually if he takes the lead, at least does 18 the initial draft, then I will be happy to þþ 19 DR. PRENTICE: I just want to know who's 20 in charge. 21 MS. KORNETSKY: Okay. I guess I'm in 22 charge but he's doing the first draft. 23 DR. PRENTICE: Okay. So it's Susan K, and 24 Mark. Anybody else doing this, just so I know. You 25 207 too? All right. Just them. That's fine. Then we 1 will arrange for you to make a presentation at the 2 July meeting. Okay. 3 Now it's probably logical to move into a 4 related area, and that is research involving tissue 5 and data repositories. We've not had any discussion 6 about that. Apparently, this is one area which OHRP 7 gets an awful lot of questions about. We've had some 8 guidance on this, as you probably know, issued by 9 various groups. I think that PRIM&R is having a 10 conference devoted in part to this. 11 MS. KORNETSKY: I'll clarify. As far as 12 I know, what PRIM&R is doing, they are having a 13 conference, and they are getting together a group of 14 people to stay after the conference, I think with the 15 aim of doing some type of guidance or sort of white 16 paper. I'm not sure yet. I'm involved in that. I 17 don't necessarily think that pre-empts us from doing 18 things. We may benefit by their work. They may 19 benefit by having our interest in it, but I do know 20 that there will be another effort starting May 6th- 21 7th. And that does involve, I think, people from þþ 22 I think Maryann Bledsoe and people from either NCI or 23 NNH or someplace. 24 DR. PRENTICE: So what does the group 25 208 think we should do? Do you want to put this on hold 1 until this white paper is produced, or do you think 2 there should be a complimentary effort? 3 MS. KORNETSKY: I have no idea of the 4 time, but I understand Mark's on that group too. So 5 I have no idea what they have in mind. It's very 6 preliminary. 7 DR. PRENTICE: Yes. 8 OHRP STAFF: I've been asked to 9 participate in that group, as well, just as a liaison 10 member from OHRP. And my understanding in terms of 11 timing is that they would have a report that would be 12 ready to have discussion at the next PEIM&R meeting in 13 October. 14 DR. PRENTICE: In October. You know, I 15 would really suggest þþ we have enough work to do. I 16 would suggest that we defer SACHRP consideration of 17 this issue until the white paper is produced, it's 18 presented at the PRIM&R meeting, and then maybe use 19 that as a platform, if we think it's necessary to go 20 beyond. If not, we can accept that as being adequate 21 to resolve the problem. What do you think? 22 MS. KORNETSKY: I think that's great. I 23 think if they produce a white paper and we want to add 24 or agree with it, that sort of standing behind that 25 209 and moving that forward to the Secretary will 1 certainly help their efforts, than just leaving it as 2 a white paper. 3 DR. PRENTICE: Okay. So is there 4 agreement that that's going to be our course of 5 action? All right. Next topic. It's becoming 6 increasingly difficult to figure out what's research 7 and what's not research, particularly in the realm of 8 public health surveillance. 9 This has become an issue for OHRP. 10 Apparently, the Hastings Center is doing something 11 about this. I don't know how comprehensive their 12 effort is, but they are looking at the issue, so 13 that's the next item we want to take a look at it in 14 terms of possible future activities. Do we want to do 15 anything about that now, or do we want to take a wait 16 and see attitude in terms of what Hastings Center 17 does? Yes. 18 SPEAKER: Hastings Center is looking at 19 improvement of all insurance activity þþ 20 DR. PRENTICE: Okay. So they're only 21 looking at one aspect of what is research. 22 MS. KORNETSKY: I think they're looking at 23 also þþ I don't even know if þþ it will probably 24 cross-over to what is research, but I think they're 25 210 also looking at ethical issues, even if it's not 1 research. Is that correct, Mike? 2 DR. PRENTICE: Let me ask OHRP to comment 3 on the relative importance of this particular issue to 4 them. 5 DR. SCHWETZ: I'll start and ask Mike to 6 add, if there's anything else to add in. This has 7 been an ongoing problem I think from before when I 8 joined OHRP 14 months ago. The question exists along 9 federal agencies, and it also is an issue within state 10 agencies, and perhaps other institutions. I'm not 11 sure, but agencies that are collecting either public 12 health surveillance data or quality improvement data 13 of whatever process they are responsible for 14 monitoring, whether it's how they spend money on 15 health-related care, whatever it might. But the 16 recognition that sometimes these surveillance 17 activities or quality improvement activities involve 18 research that meets the definition of research in 19 humans, identifiable people, generalizable conclusions 20 to improve the process. There are times when there is 21 research within these public health activities, in 22 particular, and it's a gray area of when these kinds 23 of activities have to go before an IRB and when they 24 don't. And there are a lot of confusing signals that 25 211 has to do with the source of funding, what the intent 1 of the work is, whether or not it's legislatively 2 mandated; therefore, it isn't research. 3 There are a variety of criteria that have 4 been used to say no, this isn't research and, 5 therefore, it doesn't have to go to an IRB, but it 6 involves in some cases large numbers of people 7 involved in clinical trials, and they've never gone to 8 an IRB. And we are in the middle of discussions 9 still. The Council of State and Territorial 10 Epidemiologists are in the process of writing a 11 document that in their mind clarifies the distinction 12 between research and non-research activities in the 13 public health area, but we still have an issue. And 14 there are gray areas that people have never reached 15 agreement on uniformly on how to make this decision. 16 As we've talked to people, it isn't just 17 among federal agencies, because a lot of the money 18 goes from CDC to states to conduct these kinds of 19 activities. It's HHS funds being used to conduct 20 these activities at the state level, so it isn't just 21 between us and CDC, or between us and CMS, or one or 22 two other federal agencies. So it's a larger issue 23 that we have activities going on out there that sure 24 look like research, where the institutions call us and 25 212 say we've just received money to conduct this work, 1 and the funding agency says it doesn't have to go in 2 front of an IRB. And if we applied for this money and 3 wrote the protocol, and proposed the work, we would 4 have felt compelled to take it before an IRB, so 5 that's kind of the issue. 6 DR. PRENTICE: Susan. 7 MS. KORNETSKY: From a practical level, 8 this is a huge issue. It's an issue with CDC. It's an 9 issue with internal quality improvement issues, and 10 I'm going to get this wrong. One of the federal 11 agencies, HR - isn't there an HRQA or something? 12 SPEAKER: AHRQ. 13 MS. KORNETSKY: Thank you. I'm sorry. 14 And maybe what I would like to suggest is perhaps at 15 our next meeting get some speakers or a panel on some 16 of these different issues to explore whether this þþ 17 I mean, I know it's an issue, but to sort of set the 18 stage for potentially working on some report. 19 Actually, this will be something very important for 20 guidance. I know we've gone three times. We have 21 three different policies. The whole issue of intent 22 to publish, does that make it research? So I support 23 this very much, but think that we probably need to 24 panel this to sort of open up our thought process on 25 213 how to go forward with it. I'd like to make a motion 1 that we suggest getting some speakers on this topic 2 for the next meeting. 3 MR. BARNES: I would like to second the 4 motion, and also suggest that there are two recent 5 scholarly treatments of this issue, one by Erin Mellon 6 and Nancy Dubler that was published in Gem, I think. 7 And another one by Jeremy Sugarman and two other 8 people. And I would suggest that Erin and Jeremy be 9 two people who would be invited to present, because 10 they're the ones who really have thought most deeply 11 about it. I know Jeremy's is kind of wacky. I told 12 him that. I've told him he doesn't know what he's 13 talking about, but that's okay if it's on the record. 14 I told him, so anyway. 15 DR. PRENTICE: He just moved from Duke to 16 Hopkins. We ought to be nice to him and invite him 17 here. 18 DR. FISHER: Also, AERA, this is a very 19 big issue for people who do research in the schools, 20 because it's not clear what normal educational 21 activities are, and things that are exempt, so if we 22 could have somebody on that. 23 DR. PRENTICE: Okay. Let's get þþ a 24 motion has been made. It's been seconded. There's 25 214 been some discussion. Any further discussion? Let's 1 take a vote. All those in favor of the motion raise 2 your hands. Any not in favor? 3 DR. GYI: I would abstain. 4 DR. PRENTICE: You're abstaining. Okay. 5 You're the first þþ we've never had anybody abstain 6 before. Okay. All right. I think the motion is in 7 order. I agree with it. And by the way, the chair 8 doesn't vote here except to break ties. We've never 9 had a tie yet, but if we ever had a tie, then I get 10 the chance to break the tie. Okay. 11 Cathy, you will obviously þþ I think we'll 12 put this as one of our panels, and we will get 13 together a collection of speakers who can address the 14 issues in consultation with Celia, Mark, and anybody 15 else you need to talk to. Okay. 16 Moving down the line, and by the way, this 17 is not in any order of priority, so don't think it is. 18 There is a lot of concern about applying a biomedical 19 model to behavioral social science and research in 20 terms of IRB review. I can't tell you how many times 21 I've had behavioral social scientists express this 22 concern to me. 23 I know it to be true to some extent on my 24 own IRB, particularly the physician members who 25 215 somehow seem to just take off on these no-risk 1 behavioral social science studies and just chop them 2 up. Whereas, it's a Phase I clinical trial with a 50 3 percent expectation mortality and they just don't have 4 a problem in the world with that. And I've been to a 5 number of institutions with respect to exactly this 6 particular issue, where it's been very clear to me 7 that that's what's happening. 8 I don't pretend to know all of the 9 problems. I am sure that there are people, such as 10 Joan Seiber and others who know far more about it than 11 I do, but we have been asked by, I can't remember the 12 exact name of the organization, something to do with 13 a subgroup of AAU to look at this. So it's on the 14 agenda for your consideration. Should we be looking 15 at the problems and potential solutions in terms of 16 the application of the Common Rule, its interpretation 17 to behavioral social science research by some IRBs, 18 and offer guidance to try to resolve that problem? 19 Yes. 20 DR. FISHER: I would endorse that. I'm on 21 two committees that are very anxious about that. One 22 is jointly social behaviorists, and the other is 23 psychologists. In my own thinking about it and what 24 I hear, is that much of it is tied to clarity of the 25 216 definition of minimal risk. So much of it is tied to 1 evaluation of minimal risk and then above minimal 2 risk. Obviously, in the children's guidelines it gets 3 more sophisticated, so I'm wondering whether it's also 4 tied to the fact that both the Subpart C and the 5 Subpart D committee are looking at this issue of 6 definition of minimal risk. I think it's an issue 7 that we need to take up with respect to Subpart A. 8 We have this risk definition that may or 9 may not be utilized consistently across, and whether 10 once we are working with that, we can tie this into 11 the issue of how one judges level of risk of social 12 behavioral research. 13 DR. PRENTICE: So I take it what you're 14 doing is suggesting that you need to look at the 15 interpretation of some of these terms in Subpart D and 16 Subpart C, and then go from there as a platform to 17 look at Subpart A, particularly relative to minimal 18 risk interpretation. Is that what you're saying? 19 DR. FISHER: I think so. We have already 20 on the children's subcommittee, as you know, we have 21 already looked at the definition with respect to 22 Subpart D. And so my question would be, whether or 23 not it's useful to perhaps have a paper or maybe the 24 subcommittees get together in some way. I'd be happy 25 217 to do that, to look at what the common issues have 1 been in C, and also maybe raise some issues for next 2 time regarding A, because that's where a definition 3 is. And then to see how we would want to move in 4 terms of social behavioral, or how we want to move in 5 terms of consistency of the definition across the 6 different subparts. 7 DR. PRENTICE: Okay. Just for the 8 edification of the committee, when you look at the 9 definition of minimal risk in Subpart A, there is 10 absolutely no clarity as to whether or not it's an 11 absolute standard or relative standard. However, if 12 you go back to the preamble, both the FDA preamble and 13 the HHS preamble when the regulations were issued, the 14 `81 version, it's very clear that they are advocating 15 a relative standard of minimal risk. Now Laura is 16 nodding her head over there, I think. Okay. And 17 something that I found very instructive at the Subpart 18 C subcommittee meeting which I did not know, is that 19 we can interpret regulations in some cases and it does 20 not require some sort of notification of policy 21 making. And I'm going to ask Laura to comment exactly 22 what that process is, but when we interpret 23 regulations, general counsel goes back and looks at 24 the rationale behind the regulations in the first 25 218 place, including the preamble. So I just think you 1 need to be aware of that when you're thinking about 2 reinterpreting regulations. So, Laura, would you 3 expand upon that from a legal perspective? 4 MS. ODWAZNY: Sure. Celia, I had given a 5 little brief discussion of this during the Subpart C 6 subcommittee, so unfortunately you weren't present. 7 But when the General Counsel's office is examining the 8 meaning behind a regulatory provision first, of 9 course, we'll look at the plain language of the 10 provision. However, if it does seem to be unclear on 11 its face, we look at the intent behind the regulation 12 as evidenced in the preamble to the NPRM and the 13 preamble to the final rule. And as Ernie stated 14 regarding minimal risk, the evidence intent is clear 15 in those preambles, so to adopt a different definition 16 of minimal risk, a different interpretation of minimal 17 risk would be, in effect, adopting a different 18 definition of minimal risk, and would require HHS to 19 go through the regulatory process of notice and 20 comment. 21 MS. KORNETSKY: Would you go back and look 22 at the National Commission's report, because that was 23 very clear that it was an absolute. And I know that 24 that was þþ 25 219 DR. PRENTICE: You're talking about 1 Subpart D. You're not talking about Subpart A. 2 Subpart D was very clear, it was an absolute standard. 3 MS. KORNETSKY: Right. 4 DR. PRENTICE: All right. And that was 5 not accepted by þþ I mean, what happened was it þþ 6 when Subpart D came out, there is no definition of 7 minimal risk in Subpart D. Therefore, it refers back 8 to Subpart A. Okay. And if you want to take this to 9 its logical extension, you could say that the preamble 10 in Subpart A applies to Subpart D. Is that not right, 11 Laura? 12 MS. ODWAZNY: Yes, because when Subpart D 13 was promulgated, there was not a distinction made for 14 how minimal risk should be treated for that subpart, 15 as there was in Subpart C. Although Mark has pointed 16 out that it may be difficult to discern the actual 17 difference between the definitions of minimal risk i 18 Subpart A and in Subpart C, there was an intent þþ the 19 intent was there to make a distinction. 20 DR. PRENTICE: Yes. Just so you're aware 21 of the fact that it's not easy, not that we shouldn't 22 change interpretations. As a matter of fact, I think 23 we should. You already know I endorse the absolute 24 concept of minimal risk for research involving 25 220 children. I don't necessarily think that that should 1 apply for research involving adults. I'd have to 2 think about that some more, but just so you know that 3 there's some hoops you've got to go through. 4 Okay. So what you're suggesting is that 5 we kind of defer any consideration of the application 6 of the Common Rule to behavioral social science 7 research until we get a little bit further along in 8 our subcommittee deliberations on C and D, which has 9 some applicability to behavioral social science 10 research. Is that correct? 11 DR. FISHER: Well, I guess I was 12 suggesting þþ that's part of what I was suggesting, 13 but I thought that since Subpart C and Subpart D are 14 both addressing the minimal risk, and both are 15 thinking about it in terms of Subpart A, then it may 16 be a good idea so that we don't necessarily go off in 17 very distinct directions, or at least are informed by 18 each other that subcommittee or just people, you know, 19 depending on how you want to define it - that SACHRP 20 because to look at this issue of consistency across 21 the four subparts with this particular definition that 22 is used in one way or the other, so that's what I was 23 recommending. 24 DR. PRENTICE: Okay. Anybody disagree? 25 221 MS. ODWAZNY: I just wanted to make one 1 point. I understand the desire for consistency, but 2 there was, as I said, the intent that the definition 3 of minimal risk for Subpart C be different than the 4 definition þþ I'm not sure that we're disagreeing. I 5 just wanted to make sure you understood. 6 DR. FISHER: I'm not saying that we are 7 going to þþ what I'm saying is þþ you're not saying 8 that we should curtail any discussion on this. Right? 9 MS. ODWAZNY: No. 10 DR. FISHER: No. Okay. So I understand 11 that you're saying that there may have been an 12 intention for C to be different from A, that A may 13 have a different way of being interpreted for adults 14 than children, but I think as we are thinking about 15 this, we need to have all four in mind to make a 16 judgment about any subpart, so I know exactly what 17 you're saying. I am not attempting to interpret the 18 legality, but I am attempting þþ I think we have to 19 consider the ethics and morality of the application of 20 these terms. Okay? 21 DR. PRENTICE: All right. Any 22 disagreement? All right. Let's move on. We've got 23 some other items that are on our agenda. And I know 24 I added to the agenda, but we do need to also consider 25 222 what's officially on the agenda. And I'm going to 1 take them slightly out of order. 2 Conflict of interest - I will tell you 3 what I think. It's a big problem. Everybody knows 4 it's a big problem. Everybody's mother and brother, 5 and organizations have issued guidance on how to 6 manage conflict of interest, a lot of which has never 7 been implemented. But nonetheless, lots of 8 institutions are looking at this, and they are making 9 progress in terms of dealing with investigator 10 conflict of interest, more importantly - or not more 11 importantly, but more problematically, institutional 12 conflict of interest, and IRB member conflict of 13 interest. 14 I see nothing to be added by SACHRP to 15 this issue until we allow institutions to progress in 16 terms of their modification of their archaic conflict 17 of interest management plans. And I certainly include 18 my own institution in that category. We have been 19 trying to revise our COI policies at a four campus 20 university. It's got to go through Central 21 Administration and a stable of lawyers, and it's been 22 there for about a year and a half. It takes time for 23 these things to happen, so I don't see us going and 24 looking at anything to do with conflict of interest 25 223 yet, but that's only my opinion. Ultimately, the 1 committee decides, so what do you want to do? 2 MR. BARNES: Ernie, my personal opinion 3 is, I agree completely with you. I think that we 4 should hold-off on this. There are many commissions, 5 entities, AAMC, others that have looked at this, and 6 we should wait and see what issues develop. 7 NHRPAC spent dozens, hundreds of hours on 8 the issues of conflict of interest. We gave guidance 9 to the Secretary on it. Our guidance was, as I 10 understand it, factored in by Stewart Nightingale and 11 others when they drafted the preliminary draft 12 guidance that is out there now, so my personal þþ I 13 couldn't agree more. There's no reason for us to take 14 up this issue now. 15 DR. PRENTICE: Anybody disagree? All 16 right. It's put on hold. Next item - decisionally 17 impaired subjects. As you perhaps know, at one time 18 or other a Subpart E was proposed, and then it was 19 withdrawn, very long time ago. I don't know, probably 20 in the 70s, probably `78, `79. However, it's a 21 problem. We all recognize it's a problem because in 22 Subpart A there is only a reference to ensuring that 23 there are additional protections for vulnerable 24 subjects, but there is no specific guidance in terms 25 224 of what those additional protections should be. And 1 certainly, we are charged by the Secretary with 2 looking at additional protections for subjects who may 3 be vulnerable. 4 However, having said that, OHRP is in the 5 process of thinking about what to do about this 6 particular issue. I don't know how far they've 7 gotten, but it's in the plans. Okay. I think it 8 might be premature for us to all of a sudden decide to 9 have a subcommittee to develop guidance on how 10 decisionally impaired subjects should be protected. 11 I think we ought to wait a little while and see what 12 OHRP does. Any comments from the committee? 13 MR. BARNES: Can we hear from OHRP as to 14 what they're doing, before we decide what we're going 15 to do. 16 DR. CAROME: The department is in the 17 midst of deliberations about whether a notice þþ you 18 know, whether there's a need at this time to solicit 19 public comment for whether there should be additional 20 protections for decisionally impaired adults. And if 21 so, what might those protections include. 22 DR. PRENTICE: Felix. 23 DR. GYI: I'll take a stab at it. Given 24 that the department is under discussion about what 25 225 they're going to do, I personally feel that this is a 1 huge issue that we should have on the table at some 2 point. But I do agree with you that there may be some 3 duplication of efforts if we don't know what they're 4 doing, and they're in the process of evaluating what 5 needs to be done as next steps. Perhaps we should 6 table this, as well, until we get a better sense of 7 where OHRP is going with this. 8 DR. PRENTICE: Other comments? Any 9 objections? All right. We'll put it on hold. 10 Where's Mike? It's not on hold indefinitely, Mike. 11 MS. KORNETSKY: Ernie, I would just add, 12 you know, I would hope that OHRP would come back to 13 this group if they are working on things, and let us 14 know when is good timing. I mean, I think it's an 15 important issue, and I would expect that, that that 16 would happen. 17 DR. PRENTICE: Okay. The last þþ I mean, 18 there may be some other areas that we've not touched 19 on that I've not brought up, but I'm just going by the 20 agenda. 21 Subpart B - the additional protections for 22 pregnant women, fetuses are part of Subpart B. It was 23 revised, I don't know, two or three years ago. Quite 24 frankly, it's a mess as far as I'm concerned. It's 25 226 inconsistent, disjointed, it doesn't make any sense, 1 and really hard to understand. 2 I want to make it clear that Subpart B 3 does not define a human embryo. It uses the term 4 "fetus", and the definition of a fetus is from 5 implantation until delivery, which obviously includes 6 technically a human embryo. 7 Subpart B clearly does not apply to human 8 embryos that are on the shelf as a product of IVF. It 9 just does not. And, of course, those embryos are a 10 source of a great deal of controversy concerning stem 11 cell research. 12 Sooner or later, I think it's appropriate 13 for SACHRP to tackle Subpart B. I said sooner or 14 later. I don't know what that means, sooner or later, 15 so I think every time we meet it's appropriate to 16 raise the issue of Subpart B and decide whether or not 17 it's time to do anything about it. So I bring that up 18 for your discussion. Yes, Tom. 19 MR. ADAMS: I'm just curious as to why 20 it's a mess at this point. 21 DR. PRENTICE: I don't know who wrote it. 22 They were perhaps on drugs at the time. It's just þþ 23 and I don't mean to be insulting, but quite frankly, 24 if you are þþ it's sort of like Subpart C in a way. 25 227 If you're enrolled in a research protocol, and the 1 institution has agreed to comply with Subpart B, and 2 you become pregnant and they have not reviewed that 3 protocol in consideration of the requirements of 4 Subpart B, you have to be dropped from the research. 5 That's an issue of justice. That's ridiculous. 6 The requirements for protection of 7 pregnant women are so narrowly restricted to issues of 8 benefit, that it more or less precludes almost all 9 social behavioral science research, so that's one 10 aspect that I find problematic. 11 The other aspect is it's just not clear to 12 me. You know, I know the regulations very well, and 13 I don't have a problem in the world understanding 14 Subpart D. I have a little bit more of a problem 15 understanding Subpart C, and I can't understand 16 Subpart B hardly at all, despite the fact I've given 17 a couple of talks on it. So I just think it needs to 18 be þþ like Subpart C needs to be thrown out and 19 redone. Yes. 20 MR. BARNES: I have a suggestion. I know 21 that Mary Lake Polan is interested in the issue of 22 Subpart B, and I'm pretty sure that Nancy is 23 interested in the issue of Subpart B too. I tell you 24 what I would be interested in, is hearing a 25 228 presentation from the two of them about their views of 1 the status of Subpart B, and what it means, and what 2 problems lurk in the existing text of Subpart B. And 3 I feel like I'm not þþ I'm ignorant about Subpart B. 4 I've read it, and I've applied it a few times, but I 5 certainly am no expert. And I don't feel like I could 6 really come to a rational conclusion as to what even 7 my feeling would be about what this subcommittee 8 should or should not do, or what the timing should be, 9 or anything else without hearing a presentation about 10 it.11 DR. PRENTICE: Okay. That's a good 12 suggestion. Nancy, you were named. What do you 13 think? 14 DR. JONES: Well, I do think there are a 15 number of issues that you could at least begin to 16 examine whether or not those were the pieces that you 17 would like to follow, like using the one that you just 18 talked about - what is research? I would say on 19 Subpart B, there's a lot more things where patients 20 wonder if it's a research technique, because it's a 21 new technique, or if it really is research, because a 22 lot of the areas, like say if you do some of the fetal 23 surgeries, they're all experimental procedures. Is it 24 research, is it not, so you could þþ some of those 25 229 issues, as well as what you talked about. 1 I know our dermatology department is 2 concerned that what is their liability for someone who 3 happens to become pregnant in some of their research 4 protocols. Their concerns that they take, as you 5 said, an overly protective view, and then is there a 6 justice issue? So I think there are a number of 7 issues that you could look at. 8 I would make one other point, even though 9 that Subpart B does not include embryos, that was also 10 in the charter that was given to this committee to 11 consider how should, or should human research 12 protection be extended to the embryo. 13 DR. PRENTICE: I would make the point, 14 it's not clear. The definition of human embryo is not 15 clear in the charter. 16 DR. JONES: It was there in the charter. 17 DR. PRENTICE: It's in the charter, but 18 the definition is not clear. I would defer back to 19 Subpart B, where they define a fetus, which actually 20 includes a human embryo, but an implanted one. It's 21 just þþ we have no guidance whatsoever on that. 22 DR. JONES: Well, I would say that that 23 would be then an important issue to look at, whether 24 or not the definition as it stands applies or doesn't 25 230 apply, if there is something else that þþ 1 DR. PRENTICE: I don't disagree. Just as 2 long as we understand that we've never been given any 3 guidance concerning exactly what that term means. 4 DR. JONES: Correct. But it isn't a point 5 to be considered by our committee. 6 DR. PRENTICE: Okay. What's the feeling 7 of the committee? Tom, you have your light on. Do 8 you want to say something? All right. So hearing no 9 objections, we will ask Nancy and Mary Lake to present 10 on Subpart B. 11 DR. JONES: And could I amend that and/or. 12 I guess there's not enough time for two panels, or 13 would there þþ 14 DR. PRENTICE: Well, actually we're not 15 talking about two panels. We're talking about two 16 individuals right now. If you feel þþ 17 DR. JONES: If we feel that we need to 18 invite a few speakers þþ 19 DR. PRENTICE: Okay. Let's leave it open. 20 That's subject to negotiation. How's that? Okay. 21 You come up with an agenda, and we could talk about 22 it.23 DR. JONES: Okay. 24 DR. PRENTICE: Fair enough? 25 231 DR. JONES: Good. 1 DR. PRENTICE: Everybody agree? Okay. 2 All right. I have one last problem, and I don't quite 3 know what to do about this. We no longer have a 4 specific job for Felix and Tom. Their subcommittee is 5 dissolved. As far as I can tell they've not been 6 relegated to writing any reports, organizing any 7 panels þþ oh, that's right. Bob þþ three of þþ no, 8 Susan's got something to do. Do you guys really want 9 to let them off the hook? Tom is not even listening. 10 He didn't even hear what I said. Let's make him the 11 chair. 12 MR. BARNES: We're the bad children over 13 here, we decided. We have been bad the whole time, 14 and we're sorry. We apologize. 15 DR. PRENTICE: All right. We will find 16 things for them to do. I don't think that we always 17 have to have somebody assigned as co-chairs of a 18 subcommittee, so let's understand we don't have a 19 third subcommittee right now. We may have one as a 20 consequence of our July meeting. 21 And speaking of the next meeting, it is 22 when? Cathy, when is our next meeting? 23 SPEAKER: The 26th and the 27th of July. 24 DR. PRENTICE: And where is it going to be 25 232 held? 1 SPEAKER: At the Sheraton Four Points 2 Hotel. 3 DR. PRENTICE: Same place we were at last 4 time. Okay. The 26th and 27th of July. All right. 5 MS. KORNETSKY: Ernie, can I just þþ this 6 is just þþ I happened to get a blue sheet today from 7 yesterday, and there's an article in here that says 8 HRP regulations review should be complete in months, 9 and talks about an effort on behalf of NIH and 10 Congress. And I'm just wondering if this is something 11 of interest to this group, or if anyone knows anything 12 about this? I don't know if we have someone from NIH 13 here, or OHRP. Yes. 14 MR. SHORE: This refers to the effort 15 that's underway under Amy Paterson and the 16 biotechnology office at NIH. It's part of the roadmap 17 initiative, and you can find a description of it on 18 the NIH web page under the roadmap initiatives. 19 I noticed the term months, and in the 20 discussion of when timely is in terms of whether it's 21 immediate or never, I think months may not necessarily 22 mean two or three months, but less than several years. 23 But that's just my interpretation. 24 Actually, there are a number of things 25 233 that have already taken place that are tied into that 1 initiative; the discussion of identifiability in human 2 subjects, the ongoing discussions about third parties 3 in research. We met with Susan Ellenberg from FDA 4 just last week, and have been looking at some of the 5 guidances that relate to IRB and DSMB activities, so 6 there are a number of things that are ongoing. 7 I don't see any surprise roll-out of a 8 major conclusion about this, because there are just so 9 many different subjects that we plan to look at. For 10 instance, different institutes have their own 11 approaches for reporting adverse events, so it's not 12 just a problem - I shouldn't say not just a problem 13 between FDA and NIH, but there are problems within the 14 NIH Institutes. There's a lot of work to be done. 15 It's an ambitious agenda. Some things, in effect, 16 have already been addressed, others are going to take 17 a lot longer. 18 MS. KORNETSKY: So is this looking at 19 policies within NIH and how you're interpreting 20 certain things, or is this looking at things 21 throughout the whole system? I'm just trying to 22 understand where this effort is. I'm not looking for 23 this committee to do any work or intervene in any 24 areas that we don't need to get involved with. I'm 25 234 just trying to understand what this is, and how it may 1 or may not relate to the issues that we choose to look 2 at. You talked about third-party consent. I mean, 3 these are þþ we just went through a whole list of 4 things that we were going to þþ that's all I'm trying 5 to do, is understand what this is. 6 MR. SHORE: There's been a focus on 7 disparities between the way FDA does things, and the 8 way NIH and OHRP do things. There have been pieces of 9 legislation drafted that have set deadlines for 10 addressing that. You've heard the word harmonization 11 used. I think the current approach is trying to use 12 a somewhat different term; namely, re-engineering the 13 clinical research enterprise. So if you hear that, I 14 think that means what harmonization used to mean, but 15 it's basically the idea that we are imposing a burden 16 on clinical research by having this disparate system 17 of reporting requirements, rules, regulations, et 18 cetera. And I think there's now a commitment to 19 address that. 20 It's between agencies in the sense that it 21 involves OHRP, it involves NIH, it involves FDA. It 22 will probably also involve the VA, CDC, et cetera, so 23 we're just at one stage along the way. 24 MS. KORNETSKY: Is there a role for us? 25 235 That's what I'm þþ it sounds like it's another group, 1 which is fine, actually within the government that are 2 looking at these things, all of which seem to be under 3 HHS rulemaking recommendations. That's all I'm 4 asking. 5 MR. SHORE: I think they are following 6 what goes on here very closely. I think that if you'd 7 like any þþ certainly available to discuss the status 8 of this. And if that's something you want to hear 9 about, I'm sure that that's an appropriate topic for 10 dialogue. 11 DR. PRENTICE: As you're progressing in 12 your project, can I ask what kind of involvement - 13 since we work very closely with OHRP, what kind of 14 involvement does OHRP have in this whole process? 15 DR. SCHWETZ: David, do you want to answer 16 that? 17 MR. SHORE: Well, you've hosted some of 18 the meetings, we've hosted some of the meetings, FDA 19 has I don't want to say hosted some of the meetings, 20 but we've in various stages, and various incarnations 21 and combinations sat down to discuss some of these 22 topics of mutual interest in which in past years, to 23 some extent, maybe we've gone our separate ways. 24 Maybe we've said given the mandate that we have, we do 25 236 things in a particular way for a particular reason. 1 I think what's happened is that it's turned out that 2 that is imposing a burden on the universities, on the 3 IRBs, et cetera. And if there's some way that we can 4 sit down and talk about do they really need to be 5 different? Are there ways in which we can use similar 6 definitions? We can use similar criteria, we can use 7 similar reporting requirements. Then we want to sit 8 down with FDA and the other organizations and see if 9 we can harmonize this. We're going to have to at some 10 point. We want to do it while we aren't under the 11 gun, so to speak. 12 DR. SCHWETZ: It's being driven on more of 13 a topic-by-topic basis, as opposed to having brought 14 together a committee composed of representatives from 15 various agencies or across the Common Rule, and having 16 a game plan of systematically going through one part 17 after another, after another, after another to find 18 out are there any pieces as we go through this 19 systematic process where we have to talk about 20 harmonization. So I think this has evolved as part of 21 the roadmap of NIH, and deliberations within NIH have 22 driven when other agencies get tapped on the shoulder 23 and say we need to talk about this piece or another. 24 Now coincidentally, among the ex officio 25 237 representatives of SACHRP, we are also going topic-by- 1 topic, and it's under that heading that we have looked 2 at what should we be doing now about adverse event þþ 3 collecting adverse event data. And with the GeMCRIS 4 capability, potentially being expanded to collect 5 other kinds of adverse event data, we should have one 6 system of fields to collect information to put into 7 the database, for example. So there are issues of 8 that kind that we're going to look at as a group of ex 9 officio members. 10 DR. PRENTICE: Thank you. Felix. 11 DR. GYI: I hear what you're saying, 12 Susan, and I support the fact that it would be better 13 for us to have information, as opposed to simply 14 coming to find this out haphazardly. And while I 15 applaud our colleagues in the regulatory agencies, it 16 would have been helpful for us to know, as an example, 17 what the level of discussion between OHRP and FDA have 18 been with regard to things like adverse event 19 collecting, so that we don't end up starting from 20 scratch some of the discussions that it doesn't make 21 sense for us to have to explore, so that's þþ 22 MS. KORNETSKY: We went through a whole 23 list of issues, and I think if there are issues þþ and 24 maybe it is they don't want our help or advice, and 25 238 that's fine. But if there are issues that come up 1 that they would like þþ it was surprising. I mean, I 2 didn't realize the extent to which other activities 3 were going on on this. Fine. We just þþ 4 MR. SHORE: Actually, when Amy presented 5 at the last SACHRP meeting on adverse event reporting, 6 she referred to this process. It may not have been 7 clear at the time exactly all the elements that were 8 involved in that, but Amy was happy to present on that 9 topic because that's, in effect, one of the first 10 topics that we have formally addressed in this 11 roadmap, harmonization, re-engineering process. But 12 absolutely, we are delighted to tell you what we're up 13 to, and we're following closely what you're up to. 14 And in that case, the issue of adverse event reporting 15 was on the front burner for both groups 16 simultaneously. 17 DR. GYI: Perhaps a suggestion is simply 18 to have an update of some key topics that might 19 overlap, and have an understanding of where the groups 20 are so that we don't have to repeat the discussions. 21 DR. JONES: Just a little more 22 clarification. Could you tell us what the committee 23 composition is, or is it all within house? Do you 24 have external experts sitting on the committee? 25 239 MR. SHORE: If I trusted my memory better, 1 I would, but how about if I send you a list of the 2 membership of that group, and a description of its 3 mandate. And then you will read about it in the blue 4 sheet from yesterday's issue, and maybe you'll be able 5 to tie together what you heard from Amy at the last 6 meeting with this structure. 7 DR. PRENTICE: Okay. Thank you. 8 MS. KORNETSKY: Ernie, can I bring up 9 another issue? I think this was a revelation. This 10 has implications for our subcommittee. This issue 11 about the minimal risk in an interpretation, and what 12 Laura has told us, is really important for our 13 deliberations. I just want to make sure that we 14 understand this, because my sense is from our initial 15 discussions in the subcommittee that there is a 16 feeling, as has been with many other committees, of 17 moving towards an absolute. And if this definition, 18 and my understanding þþ I know OHRP is different 19 people now, but I have been to many conferences where 20 this has also, at least for children, has been sort of 21 the interpretation, what they have said that the 22 interpretation is. 23 I don't want our committee to be spinning 24 our wheels on recommending a different interpretation 25 240 if this is going to be something that is going to be 1 a big issue. This is the first I'm hearing of this, 2 and it has some significant consequences. And I just 3 think we need to be advised. I understand that the 4 Subpart C, the prisoner group þþ 5 MS. ODWAZNY: Susan, if I can respond - I 6 think that we þþ I can discuss this issue with OHRP, 7 and we certainly can get back to you so that you can 8 be properly informed during your subcommittee's 9 deliberations. I think it's possible that Mike would 10 like to say something now also. 11 DR. FISHER: It's a broader issue because 12 I think that the fact that we've had two meetings on 13 our committee and were not alerted or notified of the 14 fact that there might be very serious regulatory 15 limitations on an interpretation is very important. 16 And I think the reason Susan associated it with this 17 other committee, is because we are so optimistic about 18 SACHRP and the partnership with OHRP in terms of 19 making a difference, and we just want to make sure 20 that our subcommittees aren't going off in directions 21 to which either it's in conflict with what another 22 committee is doing, or it is not feasible based upon 23 legal parameters. So I think the issue is not simply 24 this one. And, of course, we definitely want to be 25 241 informed about it at our meeting, but that it is 1 important to continually be informed by legal with 2 respect to what the limitations are. And that we may 3 decide as C did, that a regulatory change might be 4 something to recommend. But it's important to know 5 not just for minimal risk, but all efforts. So I 6 think we would very strongly recommend having legal at 7 all meetings, as well as subcommittee meetings to keep 8 us informed. 9 MS. ODWAZNY: Sure. I'm sorry if there 10 was some omission and you didn't understand this. I 11 was not present at your first subcommittee meeting, 12 and it's possible that you did discuss this then. 13 From the subcommittee meetings I remember focusing 14 more on the 407 process. 15 DR. PRENTICE: Okay. Mike wants to make 16 a comment, and then depending upon what he says, I 17 have something to say. Mike. 18 DR. CAROME: I think it's OHRP's 19 expectation, Susan and Celia, that any guidance that 20 flows on interpretation of Subpart D is going to be 21 put out for public comment by the office. It doesn't 22 mean we're going to change the rule. It may be that 23 here's a new guidance document, a draft guidance 24 document like we did in the financial 25 242 interest/conflict of interest document that HHS put 1 out. There may be a similar document on how to 2 interpret and implement Subpart D in a draft format 3 that's put out for comment before it's made into 4 formal guidance, separate from putting out any change 5 in the regulation. 6 MS. KORNETSKY: Is that what Laura is þþ 7 is that what you þþ I think we're maybe talking apples 8 and oranges. Is that going to solve the problem where 9 she's saying it's very clear within the preamble that 10 it was relative. I understand that it's going to go 11 out for public comment. It absolutely should, but I 12 thought I was hearing something different. 13 MS. ODWAZNY: As I mentioned, that was the 14 preamble to Subpart A, and there was no different 15 interpretation of minimal risk laid out in the 16 preamble when Subpart D was adopted, but this is an 17 issue that I'll have to discuss further with OHRP. 18 And then we can consider how best to facilitate the 19 subcommittee's recommendations. 20 DR. PRENTICE: I have a different take on 21 this problem, but maybe it's not that much different. 22 There's only one SACHRP, that's us. We've been given 23 a charge, and we're pursuing that charge. And let's 24 take Subpart D, for example. We're looking at Subpart 25 243 D. We're looking at all aspects of Subpart D. We're 1 going to make recommendations to HHS and OHRP as to 2 how that should be interpreted. 3 I would hate to think that there is any 4 other committees who are also doing the same kinds of 5 work that would come up with opposing or different 6 interpretations. I'm all for streamlining, 7 harmonization, et cetera, but I would hope that if NIH 8 is looking at the kinds of issues that we're looking 9 at, then we need to be aware of that, OHRP needs to be 10 aware of that. Is that where you're going, Susan, on 11 this? 12 MS. KORNETSKY: Yes. 13 DR. PRENTICE: Okay. So I trust that 14 that's not the intent, is to re-interpret the 15 regulations, David? 16 MR. SHORE: No. 17 DR. PRENTICE: Okay. Then we should not 18 have a problem. We just want to know what you're 19 doing, but if what you're doing starts to impact on 20 what we're doing, then obviously we need to talk about 21 that. Okay? 22 MR. SHORE: What we're focusing on has 23 more to do with the policies and procedures, and the 24 disparities in the relative regulations, so to that 25 244 latter extent, we're dealing with some of the same 1 problems. We're not looking at the child regs. 2 DR. PRENTICE: Well, we're also looking þþ 3 MR. SHORE: Nor are we looking at the 4 prisoner regs. 5 DR. PRENTICE: Okay. How about Subpart A? 6 MR. SHORE: We're not looking to revise 7 it. 8 DR. PRENTICE: Are you looking to 9 interpret it? 10 MR. SHORE: We're always looking to 11 interpret it. Yes. 12 DR. PRENTICE: Then if you're looking to 13 interpret it, then OHRP needs to be þþ I assume they 14 would be aware of your efforts in that direction. And 15 then in turn, I think that this committee ought to 16 know something about where you're going on that, 17 because one of our charges potentially in the future 18 is to literally look at Subpart A. 19 MR. SHORE: That's what I was referring to 20 when I talked about the identifiability and the human 21 subjects issue which we spoke with OHRP about in the 22 fall, in the winter. And third-parties is on the 23 agenda. 24 DR. PRENTICE: Okay. We're three and a 25 245 half minutes past adjourn time. Any other issues, any 1 other comments? Okay. Yes. 2 DR. JONES: Reopen a closed case, but I 3 just would like to go on record that the litigation - 4 my comments were not to preclude a subcommittee if we 5 felt it was that important to work on, but not to make 6 a decision on the information we had just today. And 7 so if that was þþ 8 DR. PRENTICE: We could still have a 9 subcommittee, but right now we're referring that to 10 the OIM. 11 DR. JONES: Okay. 12 DR. PRENTICE: Okay. And we could change 13 our minds later to do something more. Okay. Listen, 14 I want to thank everybody for a productive couple of 15 days. Thank the members of the public for coming. 16 Meeting is adjourned. 17 (Whereupon, the proceedings in the above- 18 entitled matter went off the record at 4:03 p.m.) 19 20 21 22 23 24 25