DR. SHAPIRO: There's been some flexibility in our agenda, and what I propose to do now is go directly to public comments. We have two or three people who want to speak to us in public comments, then we're going to adjourn the meeting until tomorrow to allow the people who are going to do some writing for us to get down to their work so they won't have to be writing until 2 or 3 o'clock in the morning. So if you don't mind, we'll get to the Biological Materials Report in the morning.

I'd like now to begin our public comments. I'm not sure if Dr. Shellow is still here; is Dr. Shellow here?

DR. MESLIN: I believe he had to leave.

PROF. BACKLAR: I don't see him, no.

DR. SHAPIRO: Okay, Dr. Michael Guarino? Welcome. Walk right up. It's very nice to have you here. Thank you for coming.

MR. MICHAEL GUARINO: Thank you, but I'm definitely not a doctor. I'm here today to represent the Autism Society of America and also as a board member of the Autism Society of America Foundation. I'm here to talk about what you finalized here today, your research findings on persons with mental disorders. But most important, perhaps, I'm a father, the dad of an eight-year-old child who's non-verbal because of autism, and every day I do research on my little girl: from AIT, Auditory Integration Therapy, to behavior modification, occupational therapy, physical therapy, speech therapy, swimming with dolphins, [UNINTELLIGIBLE], music therapy, and the latest, quote unquote, "cure" for autism, secretism. I come in front of you because autism is one of the most complex and elusive neurological disorders facing the biomedical research community. While the Autism Society welcomes the Commission's work on behalf of people with impaired mental capacity, if it's implemented in its current form there will be a dramatic reduction in ongoing neurological research. My two major points have to do with two of the recommendations you adopted today was Recommendation 12 in the report, which talks about [UNINTELLIGIBLE], and that pediatric research was excluded in Recommendation 12. I would just like to see somewhere in the language, if not in the recommendation itself, but it in the language underneath it, so you'd be able to explain that the researchers in autism haven't found what they seek yet, that it's been an issue.

DR. MESLIN: I'm sorry to interrupt. Could you say that last bit just one more time, a little more slowly?

MR. GUARINO: In Recommendation 12?


MR. GUARINO: For pediatric research being done with children with children with autism that is excluded from these criteria.

DR. MESLIN: I understand the point.

MR. GUARINO: Yeah, that's what we were talking about. And the other one was on Recommendation 15. I know that you've worked hard on this and you're talking about possibly not making that recommendation. I think it's real important that families do have that option just still to be at the table with the people. I think that just not to be excluded from them, that's very important. And that's why I came down today. And just don't take the steps just to cut us out. We want to be involved. We're looking for the researchers to help us along the way. We're going to help partner with them. Thank you for your hard work.

DR. SHAPIRO: Well, thank you very much, and thank you for coming today and speaking to us. Thank you also for being so terse and to the point on a long day. That's very helpful. I appreciate -- I very much appreciate that you remained. Thank you very, very much. The next person I have is Dr. David Shore.

DR. DAVID SHORE: At this point, I feel like I'm asking a question from English class during the middle of a math class, but I'll try and get back to what was being discussed this morning. I think probably the best use of my five minutes would be to just try and get on the record and the transcript some brief reactions and a few questions, and some concerns that people I've discussed the most recent draft with at NIH have expressed. First of all, let me say that the people with whom I spoke were very impressed that this most recent version has made the most positive steps of any change during the previous meeting. And for that reason, many people are sad that you are finalizing it at this point, because there was the hope that perhaps NBAC could reach some conclusions that would not be argued with by the scientific community, but we'll have to see what happens in that regard. Certainly, I think you're at the point now where most at NIH would agree with the majority of the recommendations that you have. The major concern that I think people will have is Recommendation 2, the RAPID. If this were to be a board that were to discuss policy issues, rather than protocol-by-protocol or case-by-case reviews, I think we might not have as many concerns. But if it looks like what you're doing is creating a national IRB to take away from the local IRBs their authority to make certain decisions that they now have, I think there is considerable concern that it will take time to charter that group, to staff it, and that the term "RAPID" may not actually apply to the process by which protocols are considered. If the board is to do research, certainly there are groups like IOM that can gather data that can answer some of the scientific questions that have been raised. But I think there is concern about creating another level of bureaucracy that will look over the shoulders of local IRBs.

The third and final major concern that we have is that both the title and the text still focus on mental disorders. And as we have expressed repeatedly, and I know Dr. Shellow was going to comment on, and I believe he's given you some written remarks, of course, most people with mental disorders do not have questionable or impaired capacity, and most people with impaired or questionable capacity do not have primary mental disorders. And therefore we have been arguing over time that to call this a report on mental disorders that may impair capacity is really quite misleading, that you're really talking about people with autism, people with mental retardation, people with Alzheimer's disease, people with brain tumors, and that the conflation -- that's a popular word today -- the conflation between mental disorders and impaired capacity is, I think, inappropriate and unfair. And I would hope that it's not too late to undo that.

Just a couple of little minor points about the text in Chapter 5. I am still looking for the language about consent waivers and the circumstances under which they would be granted, notwithstanding discussions at the previous meeting. I still can't find them. And some of the recommendations that were voted upon today are directly inconsistent with the possibility of allowing consent waivers under the conditions in which they're currently allowed. It's unclear what happens until this RAPID board is created. Do we stop all such research for two or five years, or do we allow it to continue until the board is able to review, protocol by protocol, what will be allowed and what will be prohibited? As was already pointed out, we really don't have adequate competency assessments yet. And, clearly, we need research and time to develop them, and that's happening already. It's not so clear to me what's going to happen in the time that it takes to develop this board, conduct this national IRB function, and do the scientific studies to inform its reports. So, again, I think that this version is clearly getting closer to the versions that the scientific community would be able to support. But I think it helps a lot more for me to focus on the areas of disagreement in this context, than on the areas on which we agree.

DR. SHAPIRO: Thank you very much. Any questions? Yes, Alta?

PROF. CHARO: Dr. Shore, the recommendation -- I think it was 7 -- I no longer have my text in front of me, because I handed in my edited version -- was the one that said that no person with the capacity to consent can be enrolled without having exercised informed consent. The very first sentence of the text that annotates that recommendation repeats that, and then puts in the clause, "except where consent is waived. "Thank you. Now, do I understand correctly that what you would like is to have that sentence expanded to say, " except where consent is waived as per regulatory requirements for consent waivers in general"?

SHORE: I guess it would help if it were up front and a little clearer earlier on that you're not saying everybody with impaired capacity must give informed consent, or their legally authorized representative must. It is clear that the current regs allow for consent waivers under the three or four conditions that you're well aware of. I would hope that that would be made clear, so that local IRBs, which may be concerned about greater than minimal risk, nontherapeutic research did not also get the message that they're not allowed to provide consent waivers in the future.


DR. SHORE: That would help.

DR. SHAPIRO: Thank you. Thank you very much. Excuse me. Bernie?

DR. LO: If I asked you a question about RAPID -- you spoke about your concerns about a transitional period, and sort of a startup period. Assuming that it gets off the ground and is chartered and funded, do you also have concerns about its ability to function as sort of a national IRB clearinghouse? Did I hear you to suggest that you thought that was a less desirable function than the sort of setting of categories that the local IRBs could then use to apply to their deliberations?

DR. SHORE: Well, I have several concerns. For one thing, it kind of turns on its head the whole concept of local IRBs making decisions based upon local standards. And it creates a new centralized bureaucracy to decide what will or would not be approvable. And I think that that's a dramatic difference from what we have now. I think that the potential delays were discussed at a meeting a couple of weeks ago on central review of multisite trials, in which they talked about a situation in Great Britain in which they have tried some of these regional or national IRBs and the response, the back-and-forth between local and national IRBs was described as "chaos." So I would urge you to learn from some experiences in other countries that may have tried something similar and perhaps discovered that this may not be as easy as it sounds.


DR. MIIKE: Just thought I'd point -- the intent was that the -- at least my understanding of what I would like to see is that the national review protocol-by-protocol was an interim measure until more general guidelines could be developed. And so the responsibility primarily rests again with the local IRB. So I don't see it as a permanent situation. It's just that I think some of us were uncomfortable about moving toward that second phase immediately, just to build up the experience, or as Dr. Cassell was talking about, some registry of local board kinds of decisions. So there may be a transition factor. The other side -- another issue is, what's going to happen in the meantime? As I understand it, ours are recommendations. So it's not like we prohibit everything from happening until certain things are put in place. Ours is a recommendation, and we expect a reasonable transition to the kinds of things that we suggest.

DR. SHORE: All right. I think you're certainly right that there are discussions of classes of research, I think under (b), whereas under (a) it clearly starts out protocol-by-protocol. And given our concern about how long it takes to charter a committee, how long it takes to staff a committee, how long it takes to do the research needed, that we're realistically talking about upwards of five years before you can consider enough protocols to perhaps come up with a policy for even one technology. And it's unclear what happens during those five years. Certainly, if you were to make clear in your report that until this newly created board, or national IRB or whatever you choose to label it, that until such a Board has made decisions as to what decisions should be permitted locally and which should not be permitted locally, that the local IRBs can retain their autonomy, that would certainly go a long way towards allaying the concerns. But at present I'm unable to find any language that indicates what will happen during that potentially very lengthy interim.


PROF. CHARO: First, I just want to let you know that some quick redrafting has gotten your concerns about the consent waivers in both the recommendation...

DR. SHORE: Great.

PROF. CHARO: ...on minimal risk research and the text following recommendation 6.

DR. SHORE: Thank you.

PROF. CHARO: On the latter point, though, I've got to say that you're touching on something that's more than just an operational issue, because for those of us that find the current local IRB exercise of authority to allow surrogate decisionmaking under these circumstances to be something that is inappropriate, to have it continue while people work on a board just continues a behavior that some of us feel is inappropriate. And in fact the board is something we see as an avenue to allowing IRBs to do something that otherwise would be inappropriate for them to do. So I think you've touched on something that's more than just a logistical question. I think it goes right to the heart of the debate about the rightness and wrongness of this research.

DR. SHORE: Well, I think that that's why we presented, at the last board meeting, the several pages of examples of what we consider to be important types of research on disorders, again, ranging from autism to Alzheimer's disease and certainly schizophrenia, bipolar disorder, that could not have been done had you in effect ruled out greater than minimal risk non-therapeutic research. And if you want to stop that for five years, I think that you should be aware that the kinds of research that we reported previously is going to be in jeopardy. If that's what you want to do, you can do that.

DR. SHAPIRO: Well, thank you, although I reserve the right to characterize what we want to do myself. Any there is no one else for public comment? What I'm going to do is adjourn the meeting. There's a small group that's going to be doing some writing on the issues. That's what we'll deal with again tomorrow: a response to the President's letter. So I think we'll adjourn for this afternoon and reassemble tomorrow morning at 8 o'clock.