1 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES SECRETARY'S ADVISORY COMMITTEE ON HUMAN RESEARCH PROTECTION MEETING FRIDAY NOVEMBER 3, 2006 The Advisory Committee met in the Galaxy Room in the Sheraton National Hotel, 900 South Orme Street, Arlington, Virginia, at 8:30 a.m., Ernest Prentice, Ph.D., Chairman, presiding. PRESENT ERNEST D. PRENTICE, PH.D. Chair BERNARD A. SCHWETZ, DVM, PH.D. Ex. Sec. CATHERINE SLATINSHEK, MA Ex. Sec. JEFFREY BOTKIN, MD, MPH Member MYRON GENEL, MD Member NANCY L. JONES, PH.D. Member DANIEL K. NELSON, MS, CIP Member NEIL R. POWE, MD, MPH, MBA Member JAMES H. POWELL, MD Member FRANCINE C. ROMERO, PH.D., MPH Member SAMUEL TILDEN, MD, JD, LLM Member EX OFFICIO MEMBERS MARGUERITE BARRATT NSF HOWARD BRADLEY SSA KATHRYN LYNN CATES, MD USDVA ROGER CORTESI EPA SALLY FLANZER AHRQ DENISE H. GEOLOT, PH.D.,RN,FAAN HRSA PETER T. KIRCHNER, MD DOE JEFFREY W. RODAMAR Dept. of Ed. DAVID SHORE NIMH LINDA TOLLEFSON FDA 2 ALSO PRESENT KELLEY BOOHER Office of Human Research Protections MICHAEL CAROME OHRP JULIA GOREY OHRP JULIE KANESHIRO OHRP IVOR PRITCHARD OHRP KEVIN PROHASKA OHRP IRENE STITH-COLEMAN OHRP 3 A-G-E-N-D-A Remarks, Ernest Prentice, Ph.D., Chairman, SACHRP. . . . . . . . . . . . . . . . . . . . .4 Report of Subcommittee on Research Involving Individuals with Impaired Decision-Making Capacity, David Strauss, M.D., Co-Chair . . . .6 BREAK Panel on Research Involving Individuals with Impaired Decision-Making Capacity . . . . . . 55 Robin Elliott, M.A., Executive Director, Parkinson's Disease Foundation. . . . . . . . 58 Representative Anne Blanchetai Donahue, J.D., Vermont House of Representatives. . . . . . . 83 Sharon M. Grandinette, M.S., President, California Association of Physical and Health Impairments . . . . . . . . . . . . . . . . .104 Public Comment. . . . . . . . . . . . . . . .170 Wrap-up and Adjourn . . . . . . . . . . . . .191 4 1 P-R-O-C-E-E-D-I-N-G-S 2 8:35 a.m. 3 DR. PRENTICE: Good morning, 4 everybody. Why don't we get started with our 5 agenda. As is customary, I'll provide an 6 overview of the meeting today. We are going 7 to begin at 8:35 with a report on our newest 8 subcommittee on research involving decision- 9 impaired individuals. That would be given by 10 David Strauss and I'll introduce him in a 11 moment. 12 Then we'll have a short break. 13 We'll reconvene for our panel and I will 14 introduce all of those individuals at that 15 particular time. We'll have a comment period 16 from the public between 12:00 and 12:15 and 17 then a wrap-up and try to adjourn by 12:30. 18 If you will recall, we talked 19 about the charge given to the Secretary's 20 Advisory Committee on Human Research 21 Protections yesterday and it involves 22 vulnerable subject populations. 5 1 Over the last three and a half 2 years we have examined additional protections 3 for children, additional protections for 4 prisoners who are involved in research, and 5 our latest endeavor is looking at additional 6 protections for individuals who have some form 7 of cognitive impairment. 8 I'm really kind of excited about 9 this latest subcommittee. I think it's long 10 overdue. It's going to be a very, very 11 important endeavor. I am delighted that the 12 chair of this particular subcommittee is Dr. 13 David Strauss and I would like to introduce 14 him at this time and then have him come up and 15 give us a report on the initial steps in 16 formulating this subcommittee and their 17 charge. 18 Dr. Strauss is an Associate 19 Clinical Professor of Psychiatry, Director of 20 the Office of Human Subject Research and 21 Psychiatry at Columbia. He is also Chairman 22 of the IRB at the New York State Psychiatric 6 1 Institute. 2 He is Co-Director of the Ethics 3 Public Policy and Human Rights Core of an NIH 4 funded HIV Center for Clinical and Behavioral 5 Studies, and recipient of two NIH grants on 6 Research Ethics Training and Enhancement of 7 Human Subjects Oversight for Psychiatric 8 Research. 9 He consults. He teaches on a wide 10 range of activities dealing with research, 11 ethics, and regulatory compliance. He is 12 currently a member of the NIH Research Ethics 13 Study Section and is also on one of our 14 subcommittees, that is the subcommittee 15 dealing with Subpart A. Now he's on two 16 subcommittees. We are really getting our 17 money's worth from you, David. 18 David, it's our pleasure to invite 19 you to come up here and address SACHRP. 20 DR. STRAUSS: Hi. Good morning. 21 Thank you, Ernie. It's really an honor and 22 privilege to be here. I was speaking this 7 1 morning with Anne Donahue who is a Vermont 2 state legislator and I was reminded of my 3 first encounter with this whole business or 4 the whole conflict related to research 5 involving subjects with impaired decision 6 making. 7 I was an eager young attending 8 psychiatrist on our brand new schizophrenia 9 research unit. For reasons unclear to me I 10 was asked to give a tour to a New York state 11 legislator who was visiting and wanted to see 12 what kind of monies we had invested in our 13 research operation. 14 Now, coming from work as a 15 clinician primarily into this new job as a 16 clinician on a research unit, I was very much, 17 let's say, protections oriented and so I 18 proudly announced to the state legislator that 19 we never include subjects with impaired 20 decision making or subjects who lack capacity 21 in any of our research studies. That is how 22 concerned we are about their rights and well 8 1 being. 2 He stopped dead in his tracks and 3 he said, "But isn't that exactly why we funded 4 this operation, for you to help those people 5 who are most in need of help?" It made the 6 point to me that I was focused perhaps too 7 much on one side of the story. 8 I think the challenge that we are 9 talking about here today is how to strike a 10 proper balance between protecting the rights 11 and welfare of people who have impaired 12 decision making formulating what kinds of 13 appropriate protections are in order, while at 14 the same time recognizing the really critical 15 clinical and research needs of those 16 populations. 17 I say those populations because in 18 fact, we really need to be broad in conceiving 19 of those people, those groups of people whose 20 decision-making capacity, whose ability to 21 freely and in an informed way consent to 22 research is impaired or absent. 9 1 This is the charge that we've been 2 given in this new panel. I don't know that it 3 makes sense to read it but let me just say 4 that the goal really is for us to develop 5 recommendations for consideration by you, by 6 SACHRP, about whether guidance or additional 7 regulations are needed for research involving 8 individuals with impaired decision-making 9 capacity. 10 It makes specific reference to 11 relevant provisions in Subpart A and the 12 related FDA regulations and asks that we 13 develop one of a few products. Like I said, 14 recommendations on the interpretation of 15 specific Subpart A provisions in order to 16 enhance protections, and/or recommendations 17 for a new subpart under 45 CFR 46. 18 By way of background, 46.111(b) 19 says when subjects are likely to be vulnerable 20 to coercion or undue influence such as 21 children, prisoners, pregnant women, mentally 22 disabled persons, or economically or 10 1 educationally disadvantaged persons, 2 additional safeguards have been included. 3 Within the criteria for approval 4 under Subpart A, that is really the extent of 5 guidance that we are provided. Additional 6 safeguards have been included. Let me 7 emphasize that fact that how one goes about 8 providing those additional safeguards is 9 really not presented within the body of the 10 regulations or in formal guidance, No. 1. No. 11 2 is we really don't have a working or 12 operational definition of what it means to be 13 mentally disabled. 14 Right there I think the challenge 15 to the field is what kinds of additional 16 safeguards are we really interested in. How 17 would we go about structuring those, No. 1. 18 But perhaps even before that, how do we define 19 those who are in need of protection and what 20 does it mean exactly to be mentally disabled? 21 Also within Subpart A under 22 membership criteria it says, "If an IRB 11 1 regularly reviews research involving a 2 vulnerable category, that consideration shall 3 be given to the inclusion of one or more 4 individuals who are knowledgeable and 5 experienced with these subjects." 6 So when we think about the 7 structure of the IRB working with these 8 populations, we are only told that 9 consideration shall be given. I think one of 10 the other things we need to think about is the 11 structure of review for these populations that 12 we are talking about providing additional 13 protections for. 14 Again, in the approval criteria it 15 says that subject selection is equitable and 16 would be particularly cognizant of special 17 problems with vulnerable populations. 18 I think it's interesting that if 19 we think back actually on the kind or the most 20 notorious stories, the most notorious cases in 21 a fairly notorious history of human 22 experimentation in the United States, many of 12 1 those stories do involve these populations 2 that we are talking about today. 3 We think about Willowbrook, for 4 example, as among those stories, those horror 5 stories, about exploitation of people who 6 couldn't protect themselves. We think about 7 the studies in the Jewish Home for the Aged. 8 We think about more recently the study in 9 Florida that recruited pregnant women during 10 labor into a series of research studies. 11 Each of these notorious cases 12 suggest to us that this is an area where we 13 need perhaps the most thoughtful guidance or 14 the most thoughtful regulatory additions. Yet 15 for many years, and until now, there has 16 really been no guidance, which is not to say 17 there hasn't been efforts added. 18 In the criteria for informed 19 consent, the regulation tells us that we are 20 required to obtain the legally effective 21 informed consent and that we have to seek 22 consent only when we can minimize the 13 1 possibility of coercion or undue influence. 2 There's also reference to legal 3 authorized representative. But beyond this, 4 beyond these considerations, the regulations 5 and guidance is completely silent on the issue 6 of how we involve people who cannot consent 7 for themselves in most kinds of research 8 activities. 9 It is left in many cases to the 10 state and in most cases, the states haven't 11 acted in a constructive way to guide 12 researchers and IRBs into who may be included 13 in research studies and what kind of research 14 may be done with those who actually lack 15 capacity to consent. 16 The guiding principle behind all 17 this, of course, is this notion from the 18 Belmont report which says, of course, that 19 some people are in need of extensive 20 protection to the point of excluding them from 21 activities which may harm them, and other 22 persons require little protection beyond 14 1 making sure they undertake activities freely 2 and with awareness of possible adverse 3 consequences. 4 Again, the principle is quite 5 clear but we have to think about how the field 6 has been operating absent coherent regulatory 7 principles and guidance on how to behave. 8 Actually, what's important and what's 9 interesting is now for the first time there is 10 increasingly systematic research looking at 11 how IRBs apply these regulations. 12 Dr. Gary Chadwick is involved in 13 one project looking at surrogate consent 14 across the country. We have actually very 15 little data in hand about how IRBs are 16 actually applying this principle in practice. 17 From the front line what you often 18 hear frankly is that absent any ideas about 19 how to proceed, IRBs are often conducting no 20 research with subjects who lack capacity. If 21 you take a look at the VA regulations, and the 22 VA does have a policy on surrogate consent, 15 1 even there there is no clear definition of 2 what it means to be decisionally impaired. 3 They use the term mentally disabled but there 4 is no definition there either for what that 5 means. Clearly we don't mean mentally 6 disabled in the way that, for example, the 7 Social Security Administration might conceive 8 of it being unable to work. That is mentally 9 disabled but it's not defined further. Nor 10 are any mechanisms for how one goes about 11 assessing who is and who is not mentally 12 disabled. 13 The point here, of course, is that 14 we need to define the vulnerable group and 15 recognize that there are classes of 16 individuals who may have impaired decision- 17 making abilities but there are separately a 18 class of individuals who have impaired 19 decision-making abilities but who nonetheless 20 may be able to make decisions for themselves. 21 There is interesting research, for 22 example, that shows that even psychiatric 16 1 patients who are involuntarily hospitalized 2 for care and treatment, in other words, who 3 are hospitalized against their will because 4 they are felt to be unable to care for 5 themselves in the community, have been 6 demonstrated from research to have certain 7 capacities including, in some instances, 8 capacity to consent to research studies. 9 Capacity is a very task specific thing so we 10 really need to think about capacity to do a 11 specific thing so we can recognize that there 12 are people who have impaired abilities to make 13 decisions but who may nonetheless retain 14 capacities to do certain things including 15 consent to research. 16 Finally, the smallest group, of 17 course, are individuals who lack the capacity 18 to consent to a research study. We really 19 need to have a coherent framework for thinking 20 about in what circumstances, at what level of 21 risk, for example, is it reasonable to conduct 22 research with people who can't make a decision 17 1 for themselves. 2 I talked about this actually in 3 August when I was here. We have to think 4 about decisional impairment, at least as a 5 starting point, from a very broad perspective. 6 There are many different kinds of ways that 7 people can have impaired decision-making. 8 For example, there's decision- 9 making impairment which can be seen a 10 situational, like I mentioned before, 11 approaching a woman who is in the midst of 12 labor and asking her to consent to a research 13 study is unwise for a number of reasons, but 14 one can certainly say that it is unlikely that 15 she can make a considered and voluntary 16 decision about research. 17 So there are situational 18 impairments. The emergency room is another 19 one where the context doesn't necessarily 20 permit the careful decision that may be 21 required for informed consent. Prisons and 22 other institutions are also situational 18 1 contexts in which subject's voluntariness may 2 be compromised. 3 Part of the original thinking of 4 the National Commission in its original 5 Subpart E recommendations, of course, had to 6 do with the idea that we wanted to protect 7 people who were institutionalized as mentally 8 infirmed both because they were mentally 9 infirmed, whatever that meant, and because 10 they were institutionalized recognizing, of 11 course, that being locked in a prison or being 12 hospitalized are not necessarily environments 13 which engender a sense of self-determination 14 or economy. 15 Those situational impairments are 16 different from disorder-related impairments 17 which are intrinsic impairments, let's say, 18 related to stroke or traumatic brain injury or 19 coma. 20 We also have to think about global 21 versus specific kinds of impairments. As I 22 said earlier, someone who is brought into a 19 1 hospital following an overdose, a sedative 2 overdose, may be globally impaired. A patient 3 with paranoid psychosis may be quite impaired 4 in certain domains but nonetheless, be quite 5 capable in many other domains. 6 We have to think about impairment 7 as also being static or progressive or 8 episodic. For example, severe mental 9 retardation we would see in many instances 10 static impairments, not expected to change 11 significantly over time. 12 Alzheimer's is an illness, of 13 course, in which we see progressive decline in 14 decision-making. And manic depressive 15 disorder is one in which quite typically we 16 see quite dramatic shifts in episodic 17 impairment and return to normal function. 18 I didn't mention this here. Maybe 19 we'll talk about this a little bit more later 20 but there are also, of course, conditions in 21 which what we witness is the regaining of 22 decisional capacity where subjects who, for 20 1 example, experience a traumatic brain injury 2 or other kinds of trauma to the brain and who 3 regain capacity over time. 4 It is important to talk about 5 these things because each of these areas that 6 I mentioned are areas where it is critical 7 that we learn about the nature of the disorder 8 and be able to bring to the field important 9 new research opportunities. If we impair the 10 ability to do any research with these 11 populations, and I would say that sometimes 12 absent guidance that is what has happened, 13 then we are really shortchanging ourselves. 14 Then there is acute versus 15 persistent impairment. Someone who is hypoxic 16 and confused or delirious from a fever may 17 have impaired decision-making ability. That 18 is quite different from someone, for example, 19 with autism. 20 The other points that I think I 21 would like to make today is that we do need to 22 recognize that mental illnesses are diseases 21 1 which affect the brain. There have been real 2 changes really since the National Commission 3 first took on this concept of protecting 4 people with impaired decision-making ability. 5 We need to recognize, and we do 6 recognize now, we do know now, that we are 7 talking about brain illnesses in all these 8 categories that I spoke of before. There has 9 been quite dramatic development of new and 10 more successful treatments for brain disorders 11 with many new treatments on the horizon, the 12 ability to study these things. Sometimes the 13 ability to study these things in the most 14 impaired subjects is increasingly important to 15 consider. 16 We have witnessed the end of the 17 asylum, so maybe the term in the late 1970s of 18 those institutionalized as mentally infirmed 19 had a particular poignancy where patients at 20 that time and previous to that were being 21 warehoused in large mental institutions. 22 That is no longer the case in most 22 1 instances. Hospitals or what they are now 2 called, psychiatric centers at times. The 3 level of care and treatment in most instances 4 is quite different. 5 We have witnessed a real birth of 6 patient rights movements which talk about 7 empowerment and partnership with physicians 8 and with the medical establishment and with 9 the research community. There is a new 10 relationship between science and subjects that 11 didn't exist 30 years ago. We have to be 12 mindful of this. 13 It certainly is the case that the 14 federal government, or under the auspices of 15 the federal government and the OHRP and OPRR 16 before that, there has been a quite dramatic 17 reinvigoration of the IRB system and the 18 system for human subjects protections. 19 One only need to attend the annual 20 PRIM&R meeting, professional meeting of IRB 21 groups, to see the massive increase in 22 interest and membership. It is a field that 23 1 is really thriving now with new levels of 2 professionalism and involvement in protecting 3 the rights and welfare of research subjects. 4 We have mandated investigator training. 5 I think more important is that it 6 might have been said 30 years ago that the 7 need to study the brain was present but we can 8 really see right in front of us some dramatic 9 benefits to research on the brain in every 10 condition that affects the brain. We don't 11 have time to talk about those today but it is 12 an exciting decade where we can expect to 13 learn a lot about how the mind works. 14 Eric Kandel, the Nobel Prize 15 winner, talks all about this new science of 16 mind and how he predicts that we will really 17 understand some basic mental processes as 18 never before including memory and affect in a 19 way that interventions will be possible. 20 It means we need to be able to learn about 21 this. 22 As I mentioned before, 24 1 increasingly now we are seeing real tensions 2 between access to experimental treatments and 3 these mental illnesses and brain disorders and 4 the need for protection. We need to make sure 5 that we are cognizant of the proper balance 6 there. 7 As I said, obviously there have 8 been other attempts, NHRPAC and NBAC before 9 that. We need to really consider what 10 happened in the past in those fields when they 11 have issued guidance and regulatory 12 suggestions. 13 We need to learn from history. It 14 is critical that we consider all perspectives. 15 We need to be careful in defining the 16 vulnerable groups. One of the things that 17 happened with NBAC was that NBAC equated 18 having a mental illness with having impaired 19 decision-making abilities. 20 Having a mental illness is not the 21 same as being mentally disabled or having 22 impaired decision-making abilities and so 25 1 perhaps suffering from a lack of input or 2 perspective on that topic its recommendations 3 were met with a fair degree of hostility from 4 the community of patients and researchers. 5 Like I said, it's important for us 6 to understand impaired decision-making in all 7 its dimensions. I think that we need to be 8 really careful in evaluating the risks and 9 benefits of regulatory change and guidance. 10 By that I mean we need to really be mindful in 11 a pragmatic way of how people in the front 12 line, IRBs, IRB members and research 13 investigators will apply the principles or the 14 regulations or the guidance. 15 We really need to be thinking 16 front line in terms of how these things will 17 be translated. It is not really a time for us 18 to be talking about concepts or principles. 19 It's really a time for us to think about how 20 we can create a meaningful practice of 21 research protections in these groups. 22 The folks at OHRP, Ernie, Bern, 26 1 and others have been thinking about the 2 membership of this new subcommittee. I 3 thought we should be called the Decisionally 4 Impaired Subcommittee but Cathy Slatinshek 5 said that was a bad idea. 6 We really want to make sure that 7 we have real clinical and scientific expertise 8 related to the disorders affecting the central 9 nervous system, critical care medicine, and 10 healthcare literacy. We have been working 11 hard sending out feelers, evaluating a lot of 12 helpful input from many of the members of 13 SACHRP and others around the country. 14 What is really kind of interesting 15 to me is not just that there is a lot of 16 interest and involvement in this subcommittee 17 but so many people who otherwise say no 18 because they are too busy to everything have 19 said, "This is an important enough issue for 20 me that I will make it my priority if asked to 21 serve." 22 There is a lot of interest and I'm 27 1 not talking just within science. I'm talking 2 about really in all communities that we have 3 made contact with. It's not surprising but it 4 is nonetheless important to note. 5 We have decided, of course, that 6 we really need to have strong input from those 7 in the patient and family advocacy field. It 8 is critically important really. These are in 9 many ways the most important stakeholders in 10 this enterprise. 11 Their perspectives are ones that 12 all too often are not taken into consideration 13 in some of the activities that occur. We need 14 to make sure their voices are heard. I say 15 their voices because it is a mistake to think 16 that these communities represent a single 17 perspective. There are many perspectives in 18 this area. 19 There is a really growing field of 20 empirical research ethics. We know a lot now 21 that we didn't know 15 or 20 years ago about 22 informed consent in these populations. It's 28 1 been studied. It's been well-funded in recent 2 years by NIH. There are many seasoned 3 investigators who can speak from data what it 4 means to have impaired decision-making 5 ability. We can learn from them and I think 6 we need to in this process. 7 Legal aspects are critical here. 8 Among other things the committee may come up 9 against this whole notion of legally 10 authorized representatives. It may come up 11 against state laws on surrogate consent. We 12 want to make sure that we have very helpful 13 legal thinking in this process. 14 Then finally, of course, because 15 ultimately the value of our products will 16 depend on our ability to be pragmatic and make 17 these work within current regulatory and IRB 18 systems. We want to make sure we have 19 expertise and research oversight and human 20 subjects protections. 21 In terms of process, we have 22 assembled a long but by no means a complete 29 1 list of contenders and in the next couple of 2 weeks we will be making final decisions and 3 perhaps sending out invitations. So that is 4 by way of background where we're headed, our 5 thinking on this. 6 Ernie, shall we open it up for 7 questions and discussion? 8 DR. PRENTICE: Yes. Thank you 9 very much, David. I'm taking the Chair's 10 prerogative. I often ask the first question. 11 You talked about the requirement for 12 additional protections in the federal 13 regulations, specifically 46.111(b) and 56. 14 111(b). Those regulations have been in effect 15 since 1981. 16 I'm curious to ask you two 17 questions. One is to what extent do you think 18 IRBs who are involved in reviewing research 19 that includes decisionally impaired subjects, 20 have been applying additional appropriate 21 protections. If so, what are the common 22 methods that they have used to provide such 30 1 protections? 2 DR. STRAUSS: Well, I certainly 3 haven't done any systematic investigation of 4 this but let me tell you what I think. I'm 5 sure there are others here, if that would be 6 okay with you, who might want to comment on 7 that who perhaps have other perspectives on 8 that. 9 My sense is that to a large extent 10 research facilities that work with populations 11 of the sort that we are talking about will 12 provide additional protections in the consent 13 process. Originally, or at least until 14 recently, I would say that would primarily be 15 in the form of requiring an independent 16 assessment of capacity. 17 That would be, I think, the most 18 commonly applied additional protection. I'm 19 sure the folks from OHRP and Compliance can 20 speak more to this issue. The requirement is 21 that institutions have policies with regard to 22 what kind of additional protections will be in 31 1 place. 2 The requirement, for example, of 3 an independent assessment of the capacity for 4 subjects who may have impaired decision-making 5 I would guess is the most common kind of 6 additional protection. 7 More recently again, and probably 8 following on some of the empiric literature, 9 many institutions, and I'm talking about 10 outside NIH and outside the major academic 11 centers, have been applying specific tasks, 12 for example, to assess capacity. They may 13 require a mini mental state exam. They may 14 require a kind of questionnaire so they are in 15 that form of consent enhancements. 16 Then I think there is another 17 category that is applied. I can certainly say 18 that at my institution probably what we do is 19 we really have a sliding scale in many ways in 20 terms of risk benefit thresholds and so we 21 adjust our approval threshold. In other 22 words, our view of what is reasonable shifts 32 1 depending on our sense of the vulnerability of 2 the subject. 3 We think about how to approve 4 research based on the subjects who are likely 5 to be enrolled. The more vulnerable the 6 higher our threshold for approval but I would 7 be interested to hear, if you would, Ernie, in 8 what others perhaps who have other 9 perspectives on that might say. 10 DR. PRENTICE: Let me ask one more 11 follow-up question pertaining to vulnerability 12 tied to an acceptable risk benefit 13 relationship. As you know, the proposed 14 additional protections for individuals with 15 impaired decision-making capability, Subpart 16 E, largely reflected the Subpart D categories 17 where if there is an absence of direct subject 18 benefit there is a limitation on risk. 19 In Subpart D, as you know, it is a 20 minor increase over minimal risk and there was 21 a similar type of risk threshold in Subpart E. 22 Could you comment on perhaps what your IRB 33 1 thinks about risk limitations tied to 2 vulnerability? 3 DR. STRAUSS: Again, this is my 4 personal perspective on it. I think it's 5 limiting in many ways. I think in certain 6 instances what winds up happening is that you 7 wind up, let's say, over-protecting groups 8 that don't require protection and under- 9 protecting others that do. 10 I guess my point is that I think a 11 categorical approach in that way is 12 restrictive and ultimately not helpful. In 13 other words, impairments are neither present 14 nor absent. Vulnerability is neither present 15 nor absent. 16 It occurs along a spectrum and so 17 by virtue of having to take those subjects and 18 that research and box them into a particular 19 one of two categories you are limiting 20 essentially, forgive me, wisdom of an IRB who 21 is closer at hand and may be in a position to 22 tailor more appropriate safeguards. 34 1 DR. PRENTICE: Okay. Jeff. 2 DR. BOTKIN: That was a very 3 helpful presentation. Thank you. I have a 4 question about what we should consider the 5 spectrum of decisional impairment. I tend to 6 think about this in the context of 7 vulnerability due to the inability of people 8 to make decisions either because they can't 9 understand the information or can't make a 10 rational decision based on that information. 11 It seems to me that there is a 12 spectrum of vulnerability due to people's 13 perhaps other impairments. Not the inability 14 to make decisions but perhaps the influences 15 that are psychological, psychiatric in nature. 16 I'm thinking specifically here of issues like 17 paranoia or people who may be excessively 18 dependent on caregivers or perhaps enhancing 19 therapeutic misconception. 20 Or perhaps even people that have 21 memory impairment who can make a perfectly 22 rational decision today but you ask them next 35 1 week how the research is going and they have 2 no recollection that they are part of a 3 research enterprise. 4 Is it your sense that the kind of 5 measures we might be talking about or IRBs 6 might be utilizing or encouraging 7 investigators utilized to assess decision- 8 making capacity encompass these types of 9 deficits as well that seem to me to be 10 potential significant source of vulnerability 11 for folks? 12 DR. STRAUSS: I think so. Again, 13 this subcommittee will, of course, take its 14 charge from you and from the parent committee 15 but I think at the start, we need to cast a 16 wide net and to make sure we survey the whole 17 landscape and then think about what we can 18 best accomplish from a pragmatic perspective. 19 Yes, I mean, I certainly think 20 those areas that you mentioned are areas that 21 are critical. If we are only talking about a 22 kind of points to consider or a method of 36 1 enabling IRBs to focus on these kinds of 2 issues, then we'll have accomplished 3 something. 4 What you raise, I think, speaks to 5 the issue also of expertise on the IRB because 6 an IRB can't arrive at those kinds of 7 understandings of complexity of decisional 8 impairment without appropriate expertise. 9 DR. PRENTICE: Other questions? 10 You have obviously looked at the charge and 11 this is a very complex charge, in my opinion. 12 How long do you think it's going to take to 13 actually develop a series of recommendations 14 that would fulfill the charge? Do you have 15 any idea? I mean, years, decades, a lifetime? 16 MR. NELSON: David, before you 17 answer, I'll caution you when I was sitting up 18 there launching the Subpart A subcommittee and 19 Ernie asked me the identical question, I very 20 flippantly and too fast said, "When we have 21 completely revised the subpart or when UNC 22 wins the national basketball championship, 37 1 whichever comes first," and that came within 2 the year and he didn't let me off. Be careful 3 how you answer. 4 DR. STRAUSS: All right. 5 Obviously I have no idea. 6 DR. PRENTICE: Good answer. 7 DR. STRAUSS: I think part of the 8 reason of bringing together this subcommittee 9 will be to gather the necessary expertise in 10 the room. I think once we do and once we 11 refine a reasonable aim in terms of product 12 and process we'll be able to report back or 13 ask this committee how far you would like us 14 to go, where you would like us to focus and so 15 on. 16 But these preliminary ideas, I 17 think, again, are with the aim of casting a 18 fairly wide net. We are unlikely to change 19 the world even in two years of the standard 20 subcommittee process but I think we may 21 recognize several key areas where change on a 22 short time table is critical. I hope that we 38 1 can accomplish at least that within the 2 typical scale. We haven't yet met so it is 3 hard for me to say what we'll learn in that 4 process. 5 DR. PRENTICE: There are obviously 6 two ways your committee could go in terms of 7 a final product. One is recommendations on 8 guidance and the other is recommendations that 9 there be a new subpart. 10 Would you comment on what you see 11 as the advantages and disadvantages, the pros 12 and the cons of either one of those outcomes 13 recognizing the fact, of course, that you 14 haven't had the benefit of any subcommittee 15 deliberations on that but I know you've been 16 thinking about that. 17 DR. STRAUSS: I think that there 18 are problems in terms of interpreting the 19 regulations which cut across the kinds of 20 situations and disorders that investigators 21 and IRBs grapple with. 22 The issue of vulnerability, for 39 1 example, in its broadest form, I think, or 2 remedies regarding vulnerability will overlap 3 significantly with some of the kinds of things 4 the committee will consider. If we look at 5 111, again the reference there is to people 6 who are, for example, economically 7 disadvantaged. 8 We may see in the process of 9 thinking about additional protections for 10 people who have impaired decision making that 11 the kinds of recommendations we will want to 12 make will have importance for some of those 13 other categories of vulnerable subjects as 14 well. 15 We want to be careful not to 16 define a new subpart that is too specifically 17 focused on a certain category of research 18 subject. In terms of whether a subpart versus 19 guidance is necessary, you know, I'm sorry to 20 be dodging these questions, although I guess 21 when in Rome. 22 I think the starting point for 40 1 some of the discussions has to be what has 2 gone wrong before. Lots of really smart 3 people, well-intentioned smart people, have 4 gotten together and tried to tackle this 5 really critical issue and have produced 6 documents and recommendations which have not 7 made it to the field. 8 I think we really need to 9 understand why that has occurred. I think 10 whether the problem is that the Subpart E 11 concept was too restrictive, whether it was 12 too proscriptive, you know, I think that we 13 need to begin by learning what went wrong 14 before. 15 I don't want to prejudge that so 16 I'm not starting out personally with any 17 preconceived notion. I do feel that a Subpart 18 E that would look like Subpart D might be 19 overly restrictive. 20 DR. PRENTICE: Other questions? 21 Yes. 22 DR. SCHWETZ: David, a question 41 1 from Rome. You refer to casting a wide net 2 which means you will capture a lot of 3 different forms of impairment. The extent to 4 which subjects in a given category of 5 impairment might be vulnerable to risk of 6 research is one consideration that might set 7 a priority for the subcommittee. 8 Unfortunately, the areas that are popular for 9 research don't necessarily match up with that 10 so you are trying to pursue questions relative 11 to risks represented by research when, in 12 fact, the area of emphasis of research today 13 is different than it was five years ago, 10 14 years ago, and will be different than what it 15 will be five years from now because things are 16 either popular or have lost popularity 17 unrelated to whether or not these are 18 important to the health of the people who have 19 these impairments. 20 How would you envision the 21 subcommittee making a decision? Do you track 22 where the research is and look at the risk 42 1 there, or do you look at the vulnerable 2 populations and assign priorities among them 3 as you are trying to narrow what you capture 4 in the big net? 5 DR. STRAUSS: I am going to answer 6 that indirectly but get to the point. It 7 surprises me often when I talk with 8 investigators at some institutions, or at my 9 institution, that they think of assessing 10 capacity as the thing you do when people may 11 have problems with decision-making rather than 12 recognizing that there is an affirmative 13 obligation on the part of the investigator to 14 always make sure that the subject has 15 understood the risks and benefits and 16 alternatives and the choice they are making to 17 participate in a research study. 18 The scenario, of course, is that 19 the investigator presents the consent form, 20 maybe even reads it to the subject. The 21 subject looks at it, signs it, and hands it 22 back, end of story, rather than there being a 43 1 real engagement or dialogue, questions and 2 answers and an assessment on the part of the 3 investigator that the subject knows what he or 4 she is agreeing to take part in. 5 Obviously that kind of assessment 6 of capacity is required. I think it is always 7 required during consent. To answer your 8 question, my thought is that it is conceivable 9 to think about guidance in this area of 10 informed consent that applies in all cases but 11 reflects a kind of changing intensity 12 depending upon the nature of the condition and 13 what is learned during the initial assessment. 14 In other words, the protections 15 have to be tailored in many ways. The 16 practice has to be tailored to the individual 17 subject always. I guess I would wonder if 18 guidance or even a subpart would be better not 19 directly related to particular disorders or 20 particular categories of illness, but 21 recognizes that across the board there's a 22 spectrum with which people can make decisions 44 1 for themselves. 2 I think ideally what we do is we 3 create mechanisms whereby investigators and 4 IRBs, and I'm going to use this word but I 5 don't mean it exactly, are sensitized to the 6 issues and have tools for thinking about it 7 and applying the principles. That is vague, 8 I understand, but again -- 9 DR. PRENTICE: Okay. As you know, 10 we have ex officio members represented on all 11 of our subcommittees and we've got Dr. David 12 Shore from NIMH who has obviously been 13 involved in this whole issue for a very long 14 time. David, would you like to make any 15 comments? 16 DR. SHORE: It depends on the 17 meaning of the word "comments." 18 DR. PRENTICE: This is Rome. 19 DR. SHORE: I actually have been 20 listening carefully and I think based on the 21 discussions that we had at the last SACHRP 22 meeting that I feel even more strongly than I 45 1 did then. 2 As David has suggested this 3 morning that adopting a new set of regulations 4 will have potential adverse consequences for 5 the kinds of research that are most needed at 6 this point. I think that Dr. Strauss' summary 7 was outstanding and I wouldn't have said 8 anything differently had I been up there. 9 DR. PRENTICE: Yes. 10 DR. BARRATT: Let me just add, Peg 11 Barratt from NIH, that David is going to be 12 helping us with leadership on an NIH-wide 13 consideration of these issues so we'll have 14 our own process to try and gather from across 15 our large organization some input for this. 16 DR. SHORE: We have a subcommittee 17 that is going to look at a number of issues 18 including the previous points to consider 19 document on issues of questionable decision- 20 making which was designed to be a sliding 21 scale flexible document. 22 Since it was prepared, as you may 46 1 recall, as a result of a panel in which you 2 participated back in 1997/98, we think that it 3 is probably due for something of an update but 4 for the most part it is a pretty good starting 5 point for us. 6 DR. PRENTICE: Okay. Great. 7 Thank you. 8 Jeff. 9 DR. BOTKIN: I've got two 10 questions I want to pose here. One is the 11 scope of the work of the committee, or the 12 subcommittee. I'm wondering whether much 13 consideration to the question of how to 14 potentially enhance decision making capacity 15 by those who may be deemed as having 16 incapacity. 17 Part of the issue is who has 18 capacity and who doesn't and then you treat 19 them in one way or another. It seems to me 20 there is an opportunity to say by having 21 enhanced decision-making support for certain 22 categories of individuals who might otherwise 47 1 be considered incapacitated you might bring 2 them above that threshold in some fashion. 3 That may well be a naive kind of question but 4 it seems to be perhaps part of the scope of 5 the subcommittee to say are there different 6 ways to approach these patients that would 7 enhance their abilities. 8 The second question I had, and 9 this is I guess a theme for me during this 10 meeting, is characterizing the nature of the 11 current problem. I think there is clearly a 12 lack of conceptual clarity about the regs. 13 IRBs want more guidance about how to do this 14 right and that is intrinsically important and 15 makes the whole effort worthwhile, but I'm 16 wondering what your sense is of the community 17 who does this kind of research, perception of 18 the current situation. Are the risks too high 19 for this group of patients because of how IRBs 20 are dealing with this issue? Are IRBs being 21 excessively restrictive in not permitting 22 important research to go forward? Is it both? 48 1 I wonder whether you have a sense of what the 2 attitude in the field is about current 3 oversight. 4 DR. STRAUSS: It depends who you 5 ask. I suspect it's both. I mean, one of the 6 reasons why I point out the historic changes, 7 the changes in quality of care, and really, I 8 think, especially the changes in the quality 9 of research oversight as a result of the 10 field, the human subjects protections field 11 that we are part of. 12 I think things have probably 13 shifted recently. The loudest complaints, of 14 course, come from two groups. I think 15 researchers who feel that important work that 16 they would like to do can't be done. Many 17 institutions, I can speak around New York 18 State, just don't know what to do with 19 subjects who cannot make decisions for 20 themselves at all and so do nothing. IRBs are 21 reluctant to allow them to do anything absent 22 clear guidance. 49 1 We also hear very vocal complaints 2 from research or disease advocacy 3 organizations whose job it is to try to move 4 care and treatment forward but feel some 5 important research was being hampered. 6 I think there is also a community 7 of people who worry about risks to subjects as 8 being too high. Again, I think there are more 9 mainstream and let's say, more fringe groups 10 that voice opposition to research with some 11 quite important and legitimate concerns and 12 others are antagonistic to the enterprise so 13 I think it covers the broad spectrum. 14 But my sense is now that certainly 15 in the academic communities among IRBs and 16 researchers that people feel that there is 17 inadequate guidance and as a result, research 18 is not occurring. I think that is probably 19 the shift that has occurred. I don't think we 20 have Willowbrook anymore. 21 The first question you asked is so 22 not naive I can't even begin to say. I should 50 1 have mentioned it specifically but of course, 2 I think that is critical, the idea of can we 3 enhance capacity. Now, look, I mean, that 4 could take the form of something fancy but it 5 could simply take the form of a better consent 6 form. 7 At my institution, it's silly but 8 we started requiring a consent cover sheet 9 before every 10-page consent form. It's 10 outlined and bulleted. It tells you what you 11 need to know. On the front of it it says, 12 "This is merely a guide to what you are about 13 to experience," so to speak. 14 The details are within and we will 15 go over those with you but this is a kind of 16 quick and dirty preparation. It's not a 17 paragraph, it's bullets because we think that 18 helps. 19 Even little enhancements probably 20 go a long way and I suspect that there is 21 probably, again, looking at multi-center 22 industry sponsored clinical trials in serious 51 1 psychiatric illness, I'll tell you that most 2 of the consent forms that come to us from 3 outside haven't considered enhancements so I 4 think that is critical. On our long list of 5 potential candidates we have a couple of 6 people whose research areas include that. 7 DR. PRENTICE: Mike. 8 MIKE: David, that was a superb 9 presentation. The Subpart A subcommittee is 10 now going to consider IRB membership criteria. 11 I have a suspicion that will overlap a great 12 deal with the functions of your subcommittee 13 because I suspect there is an enormous degree 14 of variability upon the expertise that is 15 available within various IRBs. 16 Your IRB, I presume, is extremely 17 competent because it's comprised totally of 18 researchers who are involved in this, or 19 people who are conversant in this area but 20 that's not true outside of that. I wonder 21 would you comment on particularly how the work 22 of your subcommittee may interact with the 52 1 efforts of the Subpart A subcommittee in terms 2 of committee membership and education of IRB 3 members. 4 As an aside I would ask you is 5 there any data on how many subjects sign 6 consent after reading the executive summary 7 without reading the full form? I have a 8 suspicion what the answer might be. 9 DR. STRAUSS: You know we would be 10 sending the wrong message if we didn't try to 11 harmonize recommendations within SACHRP 12 subcommittees themselves so I think that we 13 will have to work closely with Subpart A on 14 those issues. Right now I sit on Subpart A 15 and will be co-chairing this new subcommittee. 16 Whether it's possible for me to do 17 all those things going forward we'll see. The 18 perks are substantial but you know. No, I 19 think it would be so silly for us not to work 20 closely together on those kinds of 21 recommendations regarding membership. 22 Like I said before, I think we 53 1 have yet to consider whether we are going to 2 have a separate subpart or whether what we are 3 going to present will either be an addition to 4 Subpart A or an elaboration of the form of 5 guidance of Subpart A. That remains to be 6 seen so we will need to work closely. I know 7 the co-chairs of the Subpart A subcommittee 8 and I am fond of them so I think they'll be 9 good. 10 In terms of how often subjects 11 just read the cover sheet and don't read 12 further, I actually don't think that happens. 13 The cover sheet provides really inadequate 14 information to make your decision. It really 15 is a guide. It tells you the kinds of things 16 to look out for with it. 17 The investigators really have to 18 go through the consent form and then sign the 19 capacity assessment. I mean, you can also ask 20 how often do people understand the consent 21 form. That is another issue. 22 MR. NELSON: Just a quick follow- 54 1 up, Ernie, if I may. I am speaking on behalf 2 of the Subpart A subcommittee. We would be 3 delighted to have David find the time to stay 4 on our subcommittee as well as chairing this. 5 I wanted to get that on the record today. 6 Not only for the liaison and the link between 7 these activities but because of his great 8 contributions to our work. 9 On the question of membership, it 10 is an area where you have to be careful what 11 you ask for. At least what you put out there. 12 I would opine that one of the reasons the 13 earlier efforts in this area that David 14 referenced already did not take root in the 15 IRB community is because they were perceived 16 as in some respects overly prescriptive in one 17 area was quite specific recommendations or in 18 fact, requirements for, for example, numbers 19 of members in certain categories. 20 By the time you get all your 21 categories represented you have a board of 50 22 people, etc., etc. We'll look forward to 55 1 certainly David's subcommittee thoughts in 2 that regard. 3 DR. PRENTICE: Okay. Nancy, would 4 you defer your question to later? Thank you. 5 We are five minutes over. We are going to 6 reconvene at 9:50. Thank you very much, 7 David, for a very informative presentation. 8 DR. STRAUSS: Thank you. 9 (Whereupon, at 9:35 p.m. off the 10 record until 9:51 p.m.) 11 DR. PRENTICE: If people would 12 assume their seats, please. Okay, folks. If 13 everyone would assume their seats, please, 14 we'll try to get started. The microphones are 15 not terribly loud today, so I would encourage 16 everyone to speak directly into the microphone 17 to get the volume up. 18 Now we are going to move into our 19 panel discussion on research involving 20 individuals with decisional impairment. And 21 we have three panelists, and let me tell you 22 what the format will be. I will ask each 56 1 panelist in sequence to come up and give a 2 presentation that should be roughly, well, no 3 more than 20 minutes, if possible. Then I 4 would ask that individual to go back down to 5 the audience and sit down. I think you'll be 6 more comfortable doing that. And then, at the 7 end of the presentations of all three 8 panelists, we'll ask all three to assemble up 9 there at the table, along with David Strauss, 10 who will serve as a moderator. I would like 11 to ask you to hold your questions until the 12 end of all three presentations, if you would. 13 The first panelist is Robin 14 Anthony Elliott, who is the Executive Director 15 of the Parkinson's Disease Foundation. I will 16 give you some information from his bio. I 17 won't read all of it. It is rather extensive. 18 He has been the Executive Director 19 of the Parkinson's Disease Foundation since 20 October, 1996. He is often cited as a leader 21 amongst Parkinson's organizations for 22 prompting collaborative efforts, including 57 1 negotiating a merger with the Chicago based 2 United Parkinson's Foundation in 1998. 3 He has played an instrumental role 4 in the creation and organization of the World 5 Parkinson's Congress in 2006. He was very 6 active in development, communications, and 7 not-for-profit management in New York City for 8 more than 30 years prior to his tenure in 9 Chicago. 10 As you'll find out from his 11 accent, he grew up in Southern England, 12 received his formal education at Bradfield, 13 and then Oxford University after that, and 14 Columbia University here in the U.S. 15 So Robin, thank you very much for 16 agreeing to come to SACHRP and speak with us 17 today. 18 MR. ELLIOTT: Again, thank you 19 very much, Dr. Prentice, for this privilege. 20 I should say that my role with the Parkinson's 21 Disease Foundation are much less deeply and 22 extensively qualified as all the people you 58 1 heard from earlier today. 2 I am a generalist, and a person 3 with great interest in healthcare, health 4 policy, and a certain background also in some 5 of the ethical aspects of this kind of thing, 6 but I feel very humble in the face of people 7 who have worked either in social work or 8 allied health professions, psychiatry, and the 9 other very important front line areas of this 10 sort that are central to the problem that has 11 been addressed by this committee and this 12 subcommittee today. 13 Having said that, as a generalist 14 I have the privilege of talking with all sorts 15 of people, and in the couple of weeks I've 16 had, since being notified of this opportunity, 17 I have taken the opportunity to speak with 18 colleagues in medicine, and clinical research, 19 and in some of the social work disciplines to 20 kind of prepare myself for this. 21 It has been a very interesting and 22 enlightening experience, which has actually 59 1 refired my own curiosity about how one can 2 create and refine systems to meet 3 simultaneously the needs of science and the 4 protection of people, especially human 5 subjects and research, which is the central 6 thing before this committee, so it has been a 7 great experience doing this. 8 I should also say, having looked 9 at my printed slides this morning, I have been 10 traveling in Japan, and some of this had to be 11 done long distance. The committee, I hope, 12 will forgive the occasional assaults both upon 13 the English language and on logic and other 14 things as we go through this, a couple of 15 corrections I'll make on these slides, which 16 I can assure Ms. Hill I shall give you full 17 written correction for after this meeting, for 18 the record. 19 We had a preparation for this 20 discussion in a conference call about a week 21 ago. I raised the question with Dr. Prentice 22 and others whether it would be appropriate for 60 1 a person in my position to talk specifically 2 about a particular disease entity, recognizing 3 that the more general subject before you, of 4 course, has to do with research in general 5 across the entire spectrum of disorders that 6 may involve cognitive impairment. 7 And I was assured by the chair 8 that this kind of, maybe more parochial focus 9 would, in fact, be appropriate, so I'm taking 10 advantage of this, and speaking specifically 11 about the issue as it pertains to Parkinson's, 12 but maybe opening the door for the fact that 13 any given disease area properly described and 14 properly examined by people will provide a 15 portal or a window into the way that these 16 issues would also play out in other disease 17 areas. And I assume this is something that, 18 as we proceed with the discussion, that you 19 will see. 20 I would like to start with just a 21 little description here of Parkinson's. For 22 those of you in the audience who are not 61 1 directly familiar with it; for those who are, 2 forgive me if I run through this quickly. 3 Parkinson's is termed a movement disorder, and 4 has been so for 20, 25 years or so. And it is 5 characterized, medically, by criteria of a 6 movement nature. That is to say, resting 7 tremor, slowness of movement, sometimes called 8 bradykinesia, and rigidity. All of those 9 three criteria that are used as the hallmarks, 10 the clinical hallmarks of Parkinson's, are of 11 a motion motoric nature. 12 What is particularly interesting 13 in terms of the subject before you today is 14 that, increasingly, Parkinson's is being 15 viewed, not just by the world and by the 16 patients who live with it, but by the doctors 17 who study it, as more of a full-body disorder, 18 one that really is multi-dimensional, that 19 extends beyond the motion directing areas of 20 the brain such as the substantia nigra and the 21 dopaminergic system, that is faulty in the 22 creation of Parkinson's, but also extends into 62 1 other areas of the human system, which means 2 that there are symptoms associated directly 3 with the Parkinson's itself that go way beyond 4 the motoric, and include the examples I've 5 given here - fatigue, organomic disfunction in 6 the area of gastrointestinal and other areas, 7 depression, psychosis, cognitive decline, and 8 potentially, dementia. 9 Cognitive decline is now 10 considered one of the descriptive features of 11 Parkinson's disease, and not something that 12 simply happens to older people as they get 13 older, and maybe experience co-morbidity with 14 other conditions such as Alzheimers. 15 Parkinson's itself is, in fact, associated 16 with this, and I'll come to you a little more 17 with that later. 18 Parkinson's, just to give you an 19 idea of the whole frame work here, affects 20 some 1 to 2 percent of the people over the age 21 of 60, which is 500,000 to a million within 22 the United States. That is rather a wide 63 1 range. We don't have a registry, which is why 2 it's a wide range, but it is a significant 3 number of people. 4 Back to the point of half a minute 5 ago. More than 80 percent of people with 6 Parkinson's do, in fact, experience some level 7 of cognitive impairment within 15 years of 8 diagnosis. It is one of the most common 9 facets of the condition. 10 And if you then compare this in 11 Parkinson's with people age-matched controls 12 in the general population, the rate of 13 cognitive impairment is indeed significantly 14 higher in people with Parkinson's than in 15 comparable non-Parkinson's populations. 16 One of the senior clinical 17 researchers, who I spent some time with in 18 Japan three days ago in preparation for this, 19 told me that his own studies in Chicago have 20 shown something like eight or nine times 21 difference. I'm told that that is maybe a 22 little high - five to eight to nine times the 64 1 incidence - which clearly is a very, very 2 distinct difference, and one that many, many 3 people with Parkinson's do suffer this. 4 It is also of note on this slide, 5 the last point on this slide, that the kinds 6 of cognitive impairment that are experienced 7 in Parkinson's are not identical with those 8 that are experienced in other neurologic 9 conditions, most particularly, Alzheimers. 10 Clinicians tell me that such areas as loss of 11 executive function and competence in visual 12 spacial distinctions may be impaired more in 13 Parkinson's than memory, for example, which 14 is, as I understand it, the hallmark of 15 impairment in Alzheimers. 16 So, we are dealing here then with 17 a cognitive impairment, but a cognitive 18 impairment that is unique and different from 19 the cognitive impairments experienced in other 20 neurologic conditions. 21 I took some time, prompted by the 22 people who guided me excellently in this 65 1 preliminary conference call we had a week or 2 so ago to reread the Belmont report. It is a 3 masterpiece, I must say, a masterpiece of 4 ethics and erudition, and a concern for all 5 the various elements here. 6 I was thinking about it in terms 7 of application to Parkinson's. The principles 8 there certainly resonate as brilliantly now, 9 in 2006, as they did in 1979 when they were 10 prepared. The three hallmarks, the criteria 11 here for ethical treatment and approaches in 12 this area that we are dealing with. Respect 13 for persons, which they describe as a cardinal 14 principle that plays out in the process 15 through the practice of informed consent. 16 This area No. 2 of beneficence, 17 which is essentially a way of describing the 18 risk benefit analyses that we need to apply 19 always in looking at how we measure one value 20 against another in determining what is the 21 right and the appropriate way of treating and 22 respecting the rights of people with cognitive 66 1 impairment. 2 And, finally, justice through 3 fairness in participant, which plays out in 4 participant selection, that people should not 5 be unduly burdened, that people should not be 6 unduly exploited, that privileges should not 7 be extended to one group at the expense of 8 others, for whatever reason. 9 This is going to be one of my two 10 or three recurring themes in these few 11 minutes, this idea of what constitutes, then, 12 fairness. I think one of the things that 13 clearly influenced the Belmont people, because 14 they were primarily concerned with the issue 15 of human protections, and very properly so, 16 but one of the things that maybe they spent 17 less time on, less concern with, and maybe the 18 context of the times wasn't the same as it is 19 today, is fairness as applied to opportunity. 20 It is quite as important that 21 people have the opportunity to do something in 22 the right circumstances, and with full 67 1 assurance that they are able to express their 2 preferences here; it is quite as important 3 that they have those opportunities, as it is 4 that they be protected from things that would 5 happen to them of an adverse nature. 6 And so there is this sort of 7 double focus of fairness or justice is, I 8 think, a recurring theme throughout this 9 meeting today, and was referred to earlier by 10 the excellent presentation by Dr. Strauss in 11 several of his comments, and I think is going 12 to be very much like motif of the rest of our 13 discussion today. 14 A point here in terms of how, 15 within Parkinson's, then, what the cognitive 16 impairment, how this issue plays out in 17 considerations about clinical trial 18 participation. This first point, terribly 19 important, came through every conversation I 20 had over the last couple of weeks, that mild 21 to moderate cognitive impairment may not 22 interfere with participation in Parkinson's 68 1 clinical trials. It may not at all; it may 2 be something that, with the right kinds of 3 appropriate controls, here, and assurances of 4 informed consent that, in fact, it might be 5 something -- it is certainly something that 6 should not be a barrier to participation. 7 The word "spectrum" was used 8 earlier this morning. There is clearly a 9 spectrum in the area of cognitive impairment, 10 which can stretch from something extremely 11 mild, to something that is very serious in the 12 area, obviously as we move into dementia, but 13 not all cognitive impairment is dementia. 14 This is clearly very obvious to everybody in 15 this room. 16 It is obvious to all of those who, 17 well, in IRBs in other areas who try to 18 implement these practices, but it is something 19 that clinicians I have spoken to feel 20 sometimes the concern about dementia, for one 21 reason or another, being an excluding 22 criterion for involvement can sometimes spill 69 1 over into forms of cognitive impairment that 2 are much less serious, where the person 3 retains much greater control over their 4 autonomy, and ability to decide what or what 5 not to participate in. 6 And this distinction, this 7 recognition of the spectrum and the different 8 points on it is completely crucial. One of 9 our most serious and wonderful advisers in 10 Parkinson's is a man in this area, Washington 11 area, Ph.D., wonderful background in health 12 delivery, is deeply interested in research, as 13 many people who are educated and who 14 understand the purposes of this and see what 15 opportunities there are, this person would be 16 certainly a very good candidate, and presents 17 himself as a candidate for trials, and has on 18 several occasions. I think he has 19 participated in no fewer than three trials. 20 This person probably at this point does, in 21 fact, experience impairment by this own 22 admission, and by those who are much more 70 1 qualified than I to judge who know him. 2 This is something that clearly his 3 executive function is something he's wrestling 4 with. And yet, would one say that he should 5 not be considered for this by virtue of this 6 particular mildly disabling condition? And 7 most of us, and certainly including the 8 subject himself, would say, no, and he is 9 first in line for consideration for a trial in 10 the next couple of months. 11 Obviously, more serious 12 impairments require special safeguards, and 13 the issue of legally designating 14 representatives is one that is being talked 15 about already today. In my own conversations 16 with the experts, the role of the caregiver 17 comes up again and again and again. The 18 person, most typically a spouse, but doesn't 19 have to be, who is living with this person who 20 is sharing in the burdens and the other 21 aspects of daily life; this person does have 22 clearly a role to play, and the people who can 71 1 think through how this could be routinized and 2 made a formal part of the process, clearly 3 that is something that we should all be 4 looking at. 5 I have reference here to something 6 I know really very little about, and it was 7 introduced to me only when I started this 8 modest piece of research for this undertaking, 9 the idea of a prior-signed document indicating 10 willingness to participate in trials. I had 11 been told by at least one lawyer, this is 12 probably not a great idea; I leave it to you 13 to decide whether it has any value at all. 14 If somebody, when they are of 15 sound mind, but already have the symptoms and 16 the diagnosis of a particular medical 17 condition, whether they are in a position at 18 that point to say that they would like to be 19 available for participation subject to 20 whatever constraints and other involvement 21 that would be required at a later stage of 22 their condition, whether that would be 72 1 something that would hold up in court, I don't 2 know, but it was mentioned to me, and I 3 mention it to you, for what it is worth. 4 I mention here - here is one of my 5 assaults on the English language, for which 6 you will forgive me - I see we have an 7 exclusion criteria; it's supposed to, of 8 course, be criterion. And there is another 9 error in this piece, too. 10 What this line should read, at the 11 end of this slide, is that the references here 12 to dementia in Parkinson's trials, 13 interestingly, being something that, of all 14 the 47 open trials that we have listed on a 15 website that we manage called Pdtrials.org, 16 Of all of the 47 trials that are right now 17 open for Parkinson's, every single one of them 18 that involves intervention excludes somebody 19 with a diagnosis of dementia. 20 There are two problems with this, 21 it seems to us. First of all, one 22 understands, of course, why, in most cases, 73 1 dementia would be an excluding criterion. This 2 is not something that I am challenging for a 3 minute. But by saying -- the act of almost 4 reflexively including this as an exclusion 5 criterion means two things. 6 First of all, quite obviously, 7 when the subject to be studied is one that 8 involves potential treatments that could 9 retard the process of increasing dementia, 10 that would be, by itself, almost by definition 11 would be inappropriate. 12 But also, back to the point I was 13 alluding to a few minutes ago, just the 14 reflexive inclusion of dementia reflects 15 often, I am told, a tendency among the 16 clinical scientists, the sponsors of trials, 17 maybe including government, for all I know, a 18 kind of general mindset that is saying, people 19 with impairment, probably, "Let's not worry 20 with that; it's an extra problem we don't need 21 to take on, so let's not do that," which, 22 going back to the ideas of justice in the 74 1 Belmont report, really violates to some degree 2 - if I'm describing it not in a caricature way 3 - it violates the notion that an individual, 4 in fact, should have the opportunity to 5 consider this, and if the individual is under 6 the appropriate safeguards and constraints 7 able to consider this, it certainly should be 8 something that should be built into the 9 system, and not excluded reflexively as a 10 matter of course. 11 Type of trial, this would be 12 observational. Interventional, I apologize 13 for that, too. The same point made a different 14 way; we need to look, of course, at what kind 15 of trials one is looking at in making it a 16 factor in deciding how one then proceeds with 17 making judgment as to whether somebody should 18 be included or not. 19 Two rather important things on 20 this slide, Nos. 2 and 3. First of all, the 21 whole notion of a moving target. One of the 22 people I talked to, a neurologist who works a 75 1 lot with dementia, made sure that I understood 2 that, particularly in long-term trials in 3 Parkinson's disease, we are talking primarily 4 here just about Parkinson's, since cognitive 5 impairment is a progressive condition when it 6 happens, it means that, for long-term trials, 7 you are dealing with, clearly, a situation 8 that will change over time. 9 It is three to five to seven 10 years, if that is the duration of a very long- 11 term trial, during that period, there is 12 reason to believe there would be a significant 13 deterioration or progression of a condition of 14 this sort, and the process of being able to 15 understand that re-consenting may be required 16 at appropriate moments needs to be built into 17 the system itself. 18 The last point, which, 19 interestingly was raised, maybe not 20 surprisingly to you, by patients as well as by 21 one social worker we work with, the idea of 22 the therapeutic value of participation in 76 1 trials. 2 This person, the social worker I 3 was referring to, has had a lot to do with 4 working with clinical trials in Parkinson's, 5 and with the people who participated, said 6 that she has come up again and again and again 7 with the experience of somebody whose life 8 was, maybe not fundamentally changed, but 9 improved, enriched, to the benefit, not only 10 of their general mood and feeling about life, 11 but their competence in functioning in that 12 life and in their family. 13 This notion of being able to 14 contribute to science, of being part of an 15 autonomous contributing agent, as the 16 philosophers call it, in this process, is 17 something that itself has therapeutic value. 18 I find this, I guess intuitively clear, but 19 also really quite exciting, and something that 20 seems to me should be within the mindset and 21 review of this eminent committee. 22 Research needs. There were three 77 1 areas in which I'm advised we need to be able 2 to -- we need to be planning for maybe making 3 more of the data that we have and the things 4 that we should be doing in an area I guess 5 broadly that you define as research. 6 One is defining and measuring the 7 nature and characterization of the many forms 8 of cognitive impairment. In a condition like 9 Parkinson's, what precisely defines this? 10 What is the spectrum here? What are the 11 stages? Both qualitative and quantitative, 12 what are the elements here that need to be 13 defined? I am advised that we don't have 14 thoroughly pinpointed or examined to the 15 detail every aspect of Parkinson's impairment 16 and dementia, and this could be done. 17 And the issue of databases, there 18 are several databases within Parkinson's, one 19 of which I've mentioned, one of the largest 20 ever produced which now goes back, I think, 21 almost 20 years, a group called DATATOP, which 22 was examining the potential neuro-protective 78 1 effect of an MAOB inhibitor decades ago. 2 There is a database here, a population 3 database, that apparently was characterized 4 for a number of things, including cognitive 5 impairment, when it was first created. And 6 the idea of going back into that and seeing 7 what we can learn about the progress of this 8 condition, I should say this aspect of the 9 condition, the cognitive impairment condition, 10 is something that should be encouraged. 11 And of course, the third point has 12 to do with developing treatments. This is 13 something, in Parkinson's, there is no 14 specific treatment for Parkinson's specific 15 cognitive impairment or dementia. Parkinson's 16 - there is an indication that was given to, a 17 drug that is used commonly in Alzheimers, 18 Exelon, an indication that was approved 19 several months ago for Parkinson's, and it 20 apparently is moderately or mildly effective 21 in some people for some of the time. 22 Clearly, we are very, very short 79 1 of therapies in this area, and the simple fact 2 has really nothing to do with the work of this 3 committee, because I think it is somewhat 4 beyond your scope, but we do need, in these 5 areas, new treatments. 6 But, in a sense, it's not beyond 7 the scope because, of course, these treatments 8 will never proceed unless we have 9 opportunities, to use this word again, for 10 people with Parkinson's to participate in 11 trials that can actually enrich and improve 12 their lives. 13 I have taken the liberty of 14 suggesting five areas in which there is value 15 in spending some time and attention having to 16 do with cognitive impairments in Parkinson's. 17 One is better defining the terms in which a 18 cognitively impaired person may be able to 19 participate in a trial based specifically upon 20 our knowledge of how this is in Parkinson's. 21 No. 2, to develop models to manage 22 participation by cognitively impaired people 80 1 with Parkinson's, protecting rights while 2 providing opportunities, and the issue of how 3 the care-giver comes in as a role, and so 4 forth. 5 And finally, developing policies 6 and programs that engage potential trial 7 participants, family members and care-givers, 8 physicians, and other allied health 9 professionals. This is, in more than one 10 sense, a community endeavor, this business of 11 trying to draw this balance between the 12 various interests and ethical claims here. 13 And all of these groups, in one way or 14 another, need to be part of the way in which 15 we engage and define and refine the issues. 16 So I think I had one what they 17 call, I guess, take home message here in 18 addition to the one that is being stated more 19 eloquently than I have been able to do so 20 about the balancing of claims between science 21 and individuals, it is to maybe just probe 22 half a level down into that and say that, in 81 1 looking at the whole question of how one 2 approaches the rights and responsibilities of 3 people in clinical trials, the issue of 4 opportunity to contribute in some way, the way 5 that people can be part of science, people can 6 help in their own therapy, apart from other 7 things; people can be listened to as well as 8 talked to, and interpreted in appropriate ways 9 in finding some way in which this system can 10 be refined. It seems to me it is a 11 refinement. Obviously, all the fundamental 12 pieces are there; they were there in the 13 Belmont report, and they are there clearly in 14 everything I have heard today about the way 15 this committee goes about its very, very 16 important work. 17 But the question of opportunity, 18 the question of people being able to be part 19 of this process to the extent possible, and it 20 will vary case to case, be able to be agents 21 in their own health and in the contributions 22 they make to their community is something that 82 1 we, the Parkinson's Disease Foundation in this 2 particular nexus that we occupy, which is 3 between science, on the one hand, and patients 4 on the other, we feel is the appropriate 5 watchword for the rest of these discussions. 6 I thank you very much for this 7 opportunity; it has been a great treat and a 8 privilege. 9 DR. PRENTICE: Thank you very 10 much, Robin. We really appreciate your 11 presentation - very informative. 12 Our next presenter is Anne 13 Donahue. Let me tell you a little bit about 14 Anne. Anne is a member of the legislature in 15 the state of Vermont. And, actually, she is 16 now running for her third term. Good luck, 17 Anne. 18 She's been a member of the Human 19 Services Committee in the state legislature, 20 which did extensive revisions of the law on 21 advanced directives for healthcare. 22 She has also introduced 83 1 legislation that would establish common 2 standards as the basis for medical 3 guardianship, or court-ordered treatment for 4 those lacking cognitive capacity. And as a 5 graduate of Georgetown University Law Center, 6 and also Boston College. 7 Thank you, Anne, for agreeing to 8 come to SACHRP and speak with us today. 9 MS. DONAHUE: Thank you. This is 10 a phenomenally interesting, challenging, 11 complex, and important topic before us today, 12 and I'm honored to be able to share my 13 thoughts with you. 14 I bring four perspectives to this 15 table. First, I am a person with a serious 16 mental illness, currently in remission. That 17 means I'm a person who has directly 18 experienced the effects of a psychiatric 19 illness on the ability to make informed 20 choices. Because mental illness can move 21 between relapse and remission, it also means 22 that I can reflect on that experience from the 84 1 position of being, for lack of a better term, 2 well. 3 Secondly, I enter this discussion 4 as a person who has been an advocate within 5 the consumer community for some 10 years. One 6 of the most contentious topics for that area, 7 for advocates, is the treatment of an 8 individual who is deemed not competent to make 9 his or her own treatment decisions, but for 10 whom the recommended treatment is against the 11 expressed wishes of the individual. 12 As an advocate, I also initiated 13 state oversight for electroconvulsive therapy 14 in Vermont. My personal medical journey, my 15 uninformed consent to ECT, and its devastating 16 consequences in my life, bring the reminder 17 into today's discussion that all ethical 18 dilemmas are also shaped by the daily 19 experiences of individual human persons. 20 And all politics is local. I'm a 21 state legislator, and in 2005, we grappled 22 with the issues of capacity, informed consent, 85 1 and the breadth of decision making by an agent 2 when we rewrote the state law on advanced 3 directives for healthcare. 4 Finally, for the past eight years 5 I have been the editor of Counterpoint, which 6 is Vermont's quarterly mental health consumer 7 newspaper. A year and a half ago I followed 8 the fallout of an explosive headline on the 9 cover of the local daily newspaper that said 10 that our state hospital patients were being 11 proposed as research subjects. It was an 12 imprecise truth, but it illustrated a still 13 raw nerve. 14 So first, some perspectives as a 15 person with a psychiatric illness. Mental 16 illness often has a course of recurring and 17 subsiding. Modern treatments have brought 18 both success and limitations. An outcome of 19 both of those factors is that impairments that 20 affect decision making are not static. 21 I speak to you today with a 22 certain degree of rational competence that I 86 1 convey and articulate a level of intelligence 2 and sophistication. And as placeholders in 3 time, I can tell you that I graduated from law 4 school with honors 25 years ago, and I 5 received a national award for public service 6 in the halls of the U.S. Supreme Court 15 7 years ago. 8 Yet, interspersed between then and 9 today, this same person that you see has been 10 curled up hiding under a hospital bed in a 11 psychiatric ward, has tried to drown herself 12 in a bathtub in a drunken stupor, has been 13 carried off by an airport medical team, 14 unresponsive, refusing to hear or speak, has 15 raced at high speeds on back roadways, or with 16 eyes closed on interstates, trying to provoke 17 a physical injury that she believed would 18 allow herself to be cared for, cared about, 19 has run away from police and hidden in the 20 woods, has sat sobbing uncontrollably on a 21 public sidewalk. 22 But that is not the person I am. 87 1 I know myself, and I can therefore say, who I 2 am is not who I appeared to be at those other 3 times. When I went through the many cycles of 4 beginning to respond to treatment, relapsing, 5 and then beginning to respond, there were 6 times that I would wonder, "I'm not sure. Am 7 I back? Is this the real me, the well me, who 8 I am?" 9 And I came to learn that there was 10 a way I could tell. If I had to ask, if I 11 wasn't sure, then it wasn't. When I'm the 12 person who is me, I always know it with 13 certainty. And I can look back and say, not 14 only was that person who was another person 15 under the control of an illness of the brain, 16 but that person did not act like me and, more 17 importantly, did not think like me. 18 That person has neither the 19 ability nor the right to speak for me, or make 20 decisions for me. I am a person who loves 21 life. And by definition, a person who wants 22 to die, who would choose death, if she was 88 1 able, in order to escape the unendurable 2 cauldron trapped inside her mind, does not 3 hold the same persona, is not the same being 4 as the one who loves life. 5 During some of those times I was 6 probably legally competent, but at other times 7 not. That is purely a legal standard, and a 8 line in the sand for something that has every 9 possible gradation. So although competency 10 and capacity are terms of art in treatment 11 discussions, the term used in the charge to 12 this panel, decisional impairment, is a 13 descriptive term that makes it much easier and 14 more accurate to discuss the levels of 15 impairment that may be created by a mental 16 illness. 17 So it isn't just about being a 18 spectrum. It is also about being a spectrum 19 in motion. And the level of impairment in the 20 decision making ability is also tightly 21 interweaved with the kind of decision that is 22 being presented, creating a matrix that is in 89 1 constant evolution. 2 Within that matrix, we need to 3 understand psychiatric disabilities, not only 4 from medical or personal perspectives, but 5 also within the political and social context. 6 The consumer movement was birthed by those who 7 emerged from some of our worst institutional 8 abuses and gained angry voices. 9 It started primarily as a civil 10 rights movement, arguing for the right of 11 individuals to make their own choices in the 12 face of a society that was perceived as 13 impinging on those choices, solely for reasons 14 of social control. 15 This context means that judgments 16 about decision making capacities are sometimes 17 tied to internalize beliefs about altruistic 18 versus oppressive motives. From a provider's 19 perspective, a patient's consent to 20 recommended a treatment demonstrates the 21 ability to understand the risks and benefits 22 appropriately, and thereby establishes that 90 1 the patient is competent to make the decision. 2 On the other hand, if a person 3 with a psychiatric diagnosis is refusing 4 treatment that the medical professional has 5 identified as appropriate, then the patient is 6 identified as lacking sufficient insight to be 7 competent to make that decision. 8 Equally committed individuals 9 making their own assessment of risks and 10 benefits of treatments based on their lived 11 experience of psychiatric care lobby on behalf 12 of the rights of others to make their own 13 decision, but only as long as that decision 14 matches the advocate's judgment of the better 15 course of action. 16 During the debate on ECT in 17 Vermont in the late '90s, advocates suggested 18 that the targets of ECT were mostly 19 vulnerable, elderly women unable to defend 20 themselves against the persuasive power of 21 physicians. They believed that these 22 patients, if empowered to make their own 91 1 decisions, would realize that the risks of ECT 2 far outweighed the benefits. Therefore, 3 consent proved lack of competence. 4 If the issue had been reversed, 5 the implication that age and sex were proxy 6 indicators for competence would have been 7 angrily denounced. But the potential for 8 these social assumptions to have an undetected 9 effect on objective assessments create a 10 powerful added risk factor that must be 11 monitored as part of the challenge in 12 assessing the impact of decisional impairment 13 in psychiatric patients. 14 Despite the desire and advocacy 15 for appropriate protections, there is little 16 consistency in legal approaches, at least in 17 Vermont law, the criteria for commitment to 18 involuntary hospitalization as a danger to 19 self or others, in other words to be deprived 20 of liberty, is unrelated to a determination of 21 capacity to consent to treatment. 22 The separate legal process for an 92 1 order for involuntary medication of a person 2 who has been committed to a hospital does 3 include the requirement that a court rule on 4 the competence to make a treatment decision. 5 On the other hand, under 6 guardianship law, there's no statutory 7 guidance on how decisions should be made for 8 the court orders or guardian decisions on 9 medical interventions for a person who has 10 been found unable to protect their own health 11 or safety due to a mental illness. 12 In the law on advanced directives 13 for healthcare, the revision passed in 2005, 14 which includes experimental treatment by 15 reference, defines capacity on two levels 16 connected to the specific decision being made. 17 The individual needs only to have a basic 18 understanding of what it means to appoint an 19 agent. 20 In contrast, making a healthcare 21 decision requires a basic understanding of the 22 diagnosed condition and the benefits, risks, 93 1 and alternatives. If that ability is impaired, 2 the advanced directive and the authority of 3 the agent are triggered. 4 By right, an advanced directive 5 can be revoked at any time, including by a 6 person who lacks capacity. What if a person 7 wants to be locked in to his or her own 8 informed decision, rather than retaining the 9 right to revoke the directive when incompetent 10 and, therefore, potentially being subjected to 11 the decisions of a relative or guardian 12 instead of their own choices. 13 The term Ulysses Clause within an 14 advanced directive comes from the Greek myth 15 of Ulysses, who commanded his ship's crew to 16 leave him tied to the mast regardless of what 17 he said otherwise in order to escape the 18 influence of the song of the sirens that he 19 knew would overcome him, and lead him to 20 direct the ship into the shoals. 21 Vermont created a unique hybrid 22 solution to the controversial issue of 94 1 permitting the use of a Ulysses Clause in an 2 advanced directive. It significantly raised 3 the threshold of protections for the decision 4 to surrender one's right to revoke an advanced 5 directive when incompetent. 6 The option can be activated only 7 through the intervening actions of a named 8 agent. There are added witnessing 9 requirements, and the directive can only be 10 triggered if the loss of capacity 11 determination has been made by two clinicians. 12 Could a person consent in advance 13 to agree to be part of a research opportunity 14 prior to a loss of capacity? Perhaps, if the 15 specific risks and benefits and the proposed 16 treatment were known in advance. But if one's 17 capacity is lost, the person's consent is no 18 longer valid, then the advanced consent is 19 worthless. 20 A Ulysses Clause in an advanced 21 directive, as an example of an alternative in 22 consent to treatment points to the 95 1 opportunities, not necessarily a specific 2 example, but the kind of thinking and 3 opportunities for creative problem solving in 4 approaching research for those with 5 intermittent decisional impairments. 6 We also need to distinguish 7 between past and current reality in the 8 perceived need for special protections carved 9 out for psychiatric treatment. That was a key 10 debate in 1998 when I had my own state 11 representatives at the time introduce 12 legislation to place the practice of 13 electroconvulsive therapy under state 14 oversight in Vermont. 15 The provider outcries had merit. 16 Why was this single area of medical practice 17 being singled out? Wasn't that creating a 18 special category of oversight for a 19 psychiatric treatment a concession to and 20 potential future contributor to the 21 discrimination against psychiatry? 22 My experience in the practices of 96 1 Vermont hospitals at the time demonstrated an 2 inadequate standard of care. I had signed a 3 consent to ECT after being shown an 4 informational videotape that said that 5 lingering allegations about the risk of memory 6 loss were nonsense. 7 I suffered a devastating loss of 8 years of my life memories that were verified 9 by medical evaluation. My own decision 10 process to consent to ECT is reflected in my 11 journal entries. I wrote that I was afraid 12 that accepting ECT treatment was merely a cop 13 out from addressing difficult life issues, but 14 also that I felt relief in the decision just 15 by the mere fact of doing something, anything 16 different to try to get relief. 17 As journalist Larry Tye said in a 18 new book on ECT, "Can consent be truly 19 informed when a person giving it is sick 20 enough to need electroshock?" And might that 21 question apply to more types of psychiatric 22 treatment than we recognize? 97 1 Yet if my mix of uncertainty, or 2 if the intense desire for relief from pain as 3 a basis for consent are considered 4 unacceptable influences or impairments of 5 capacity, then research for many conditions 6 unrelated to mental health would be put into 7 question. 8 In the same way, if we are to be 9 consistent, then it's hard to find the logical 10 support for either special statutory schemes 11 addressing only psychiatric medication, or 12 open-ended guardianship laws that may allow 13 virtually unfettered discretion in making 14 medical decisions for persons with mental 15 illness. 16 There is one other layer to add to 17 the matrix. If a decision is being made by a 18 person on behalf of someone else, the standard 19 for replacement of the individual's decision 20 comes into issue. 21 For court-ordered psychotropic 22 medications in Vermont, if a person has 98 1 previously expressed preferences regarding 2 medications at a time when competent, those 3 wishes must be followed initially. A so- 4 called substituted judgment standard in which 5 a fact-finder bases a decision on what the 6 person would have wanted if competent. 7 But this standard immediately 8 shifts to a decision to be made in the best 9 interests of the patient if evidence 10 demonstrates that following the patient's 11 preferences has not resulted in significant 12 clinical improvement in the past. 13 In Vermont's advanced directive 14 statute in contrary, a best interest 15 consideration is only permitted if the agent 16 has exhausted all means of trying to interpret 17 what the person would have wanted under the 18 circumstances. 19 A guardian is held to a 20 traditional legal standard of care, but 21 without any standards on factors to gauge in 22 making a substitute decision. In considering 99 1 research, any potential use of a substitute 2 decision maker needs to address how the 3 decisions would be made in relationship to the 4 risk benefit analysis. 5 But ethical considerations are 6 also uniquely tied to the history of stigma in 7 psychiatry. I'll give you a quote: "How do we 8 know what makes them screwy until you treat 9 them?" Unfortunately, that's a 2002 remark 10 from a federal judge on the United States 11 Circuit Court of Appeals during oral argument 12 in a case from Vermont involving an advanced 13 directive for healthcare, and the inclusion of 14 psychiatric illness. 15 Public understanding of mental 16 illness is still far from where we would wish. 17 Those with a psychiatric illness have a right 18 to the same quality of care based upon the 19 same quality and priorities for research as 20 other disabling illnesses. 21 Preserving individual rights does 22 not need to be an obstacle to the ability to 100 1 identify new and better treatments. However, 2 resistance emerges anytime it is perceived, 3 rightly or wrongly, that civil rights 4 protections may be reduced. 5 A year ago, a new contract was 6 signed for psychiatric services provided at 7 the Vermont State Hospital by the academic 8 medical center affiliated with the University 9 of Vermont School of Medicine. And it noted 10 an expectation for research in the area of 11 public sector psychiatry, including a 12 reference to experimental investigational 13 treatment. It caught the stakeholder 14 community completely off guard. 15 Letters to the editor of my 16 newspaper Counterpoint made comments such as, 17 "We might all want to ask ourselves why the 18 state and university insist on conducting 19 experiments on patients at VSH." And there 20 was a fierce campaign to have all research 21 language removed. 22 In opposition, the university's 101 1 director of public psychiatry urged that it 2 would be caving in to stigma against research 3 to withdraw the language, and that it was a 4 critical opportunity to develop a new message 5 about the appropriate place and value of 6 research. 7 Ultimately, the wording of 8 experimental and investigational care were 9 removed. The incident was unfortunate in that 10 the opportunity for dialogue about psychiatric 11 research was lost by the failure to have it 12 discussed before the language appeared in a 13 contract. It illustrates the tremendous 14 importance of communications and dialogue with 15 all stakeholders in order to foster trust. 16 I was recently surprised in some 17 conversations just before this meeting, of at 18 least one comment by a practicing inpatient 19 psychiatrist in opposition to almost any 20 research involving patients with decisional 21 impairments beyond demographic data 22 collection. 102 1 He said, "We have been doing 2 without it for this long, so I don't see why 3 we would want to embark on that slippery 4 slope." I disagree. I don't have a solution 5 for that slippery slope, or how to create the 6 balance, but I do not believe the answer is to 7 rob for myself, or for future generations, 8 from moving more quickly to better 9 opportunities for survival, recovery, and 10 quality of life. 11 The President's 2003 New Freedom 12 Commission Report has made consumer directed 13 and recovery oriented care the 14 transformational principles of mental health 15 care across the nation. In the same report, 16 but much less widely publicized, was the 17 recommendation to, "accelerate research to 18 promote recovery and resilience, and 19 ultimately to cure and prevent mental 20 illness." 21 I believe we need to transform the 22 ways we think about the affects of mental 103 1 illness on decisional capacity, so that the 2 multi-dimensional matrix of factors that apply 3 to all human subject research opens the door 4 to creativity instead of fear, and we work 5 together on solutions, rather than letting 6 history or other unique challenges be barriers 7 to moving us forward. 8 DR. PRENTICE: Thank you very 9 much, Anne, for a very compelling 10 presentation. And we applaud your courage for 11 talking about your personal journey. That 12 kind of perspective is extremely important for 13 members of SACHRP who don't work every day 14 with individuals who have such problems. 15 I would like to move to the next 16 presentation, which will be given by Sharon 17 Grandinette. And let me tell you a little bit 18 about Sharon. I'll read a few abbreviated 19 comments from her bio. 20 Sharon is a special education 21 consultant and trainer who owns and operates 22 Exceptionally Educational Services located in 104 1 Rodondo Beach, California. She has worked 2 with children, adolescents, and young adults 3 with special needs for over 26 years. 4 She has worked in the public and 5 county schools, as well as in private special 6 education school settings as a special ed 7 teacher, program specialist, and 8 administrator. For 14 years, she focused her 9 work on children and adolescents with 10 emotional disabilities and mental health 11 needs, but since 1989, her efforts have 12 centered on children and adolescents with 13 acquired brain injury or other neurological 14 disorders. 15 She is also currently president of 16 the California Association of Physical and 17 Health Impairments. Welcome, Sharon. Thank 18 you for taking your time to come and speak 19 with us today. 20 MS. GRANDINETTE: Thank you. It 21 is an honor to be here today, and although my 22 background is education, I've had the unique 105 1 opportunity of following many of the children 2 that I've worked with over the years into 3 their adulthood, and so I hope to bring a 4 perspective from not only the children's 5 perspective, but obviously ongoing. 6 My goal today with you is to help 7 you understand what we call acquired brain 8 injury, and how it affects decision making 9 skills. Some statistics first. With regard to 10 brain injury, brain injury is the leading 11 cause of death and disability, not only in our 12 country, but world-wide. And we need to look 13 at what difficulties of research access that 14 we may have with the brain injury population. 15 As the other presenters before me 16 have done, we need to define the population. 17 Brain injury is a very broad category, and 18 there are varying levels of severity. We have 19 mild, moderate, and severe levels, and with 20 people who have mild injuries, which is 21 approximately 75 percent of the individuals 22 with brain injury, they certainly look like 106 1 walking, talking, functioning in