ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS + + + + + Thursday, June 22, 1995 The Advisory Committee met in the Executive Chambers at the Madison Hotel, 15th and M Streets, NW, Washington, DC, at 9:00 a.m., Ruth Faden, Chair, presiding. Advisory Committee Members: Ruth Faden, Ph.D., M.P.H., Chair Kenneth Feinberg, J.D. Eli Glatstein, M.D. Jay Katz, M.D. Patricia A. King, J.D. Ruth Macklin, Ph.D. Lois Norris Nancy Oleinick, Ph.D. Henry Royal, M.D. Philip Russell, M.D. Mary Ann Stevenson, M.D., Ph.D. Duncan C. Thomas, Ph.D. Staff Present: Gail Geller Steve Goodman Dan Guttman Nancy Kass Steve Klaidman Anna Mastroianni Jonathan Moreno Shobitha Parthasarathy Patricia Perentesis Jeremy Sugarman Agenda Item Page Committee Discussion: Subject Interview Study [Part III, Chapter 16] 5 Committee Discussion: Research Proposal Review Project [Part III, Chapter 15] 89 Committee Discussion: Recommendations for the Protection of the Rights and Interests of Human Subjects 174 Committee Discussion: Contemporary Projects An Ethical Analysis [Part III, Chapter 17] and Findings for the Contemporary Period [Part IV Chapter 19] 241 Committee Discussion Concerning Strategy and Direction: Mechanisms for Sign Off of Final Report and Personal Statements 325 P-R-O-C-E-E-D-I-N-G-S (9:06 a.m.) CHAIRPERSON FADEN: Good morning. We have a day devoted to the contemporary world. Almost the entire day, except for the last hour, which is given over to process, committee business of that sort. We are going to put the discussion on notification on the agenda for Friday. And where, exactly, I can't tell you. But I think we will -- well, we'll work it out. It will be on Friday, and it will definitely get its hour, which it really needs to have. There is supposedly in your packet the discussion about notification that Mary Ann has prepared with Jeff. And then there's a response from Duncan, I believe. It was FAXed to us at the last minute. But in line with the experience yesterday, not everybody gets all the last minute mailings. I want to make sure that everybody has the document, and gets a chance to look at it tonight before the discussion tomorrow. So, if you do not have a document that is from Mary Anne and Jeff, and then with something behind it, I believe from Duncan, then please let Anna know? Okay. And we'll get you the copy. So, if you could just take a minute to check, and make sure you have the document. UNIDENTIFIED: It's one of the -- folder -- documents -- CHAIRPERSON FADEN: All right. If you've got it, fine. If you don't have it, let us know today, so that you can have it in time to look at it tonight. We're going to turn right away this morning to the subject interview study. We had a draft to look at. We've got Steve, Jeremy, Nancy, and Pat, here to brief us again, and answer our questions. We're at the point now where we have to decide about the meaning, as well as the findings. What do we think this means, or says? Or what are the implications of these data, and this project? And not only, you know, what do the data say? So, I'm hoping the discussion will include a time for interpretation. Jeremy, are you going to do a little show and tell for us, first? DR. SUGARMAN: There wasn't much to show, but there's some stuff to tell. (Laughter.) CHAIRPERSON FADEN: Okay. Nothing to hold up? No props, or anything? All right. Well, the floor is yours. DR. SUGARMAN: Okay. The only questions that we have received since we submitted this draft of the chapter of the Committee was some question about what was happening with our analysis of what we call discordance, because the denominators move around a little bit. And after discussing that with Ruth Faden, we thought it might be a good idea just to go through that, so everyone understands what those data mean, and how come the numbers are moving all over the place. If you do look on page 12 of this chapter, and line number 20, I promise it won't be this exciting a conversation later, but there is a mistake in the number there, which might help clarify things. On that line, you have a 412, followed by 76 percent. The correct numbers there should be 313, followed by 58 percent, parenthetically. (Pause.) Okay. Let me remind you about how this analysis started. During the subject interview study, when we talked with people in the brief interview, we asked them whether they thought they were research subjects now, or whether they thought they had been research subjects in the past. Following the interview in the clinic, we then went to hospital records, medical records, research records, and tried to determine whether or not people were research participants. And this was for everybody, regardless of how they answered those questions during the brief interview. The overwhelming majority of folks were concordant, meaning that what they said about research participation, and what we could document were consistent. That they said they were -- they were what we found they were, and if they said they weren't, we found they weren't. But we were left with some numbers of people who were discordant. Some people who believed that they were research participants, and we could not find that documentation, and the other way around. So, if we start at the beginning, and if you remember correctly, when we found there were some people who believed that they were not participants in research, we then went back a second time to try to get more information about that. This analysis reflects all of those data gathering activities. So, if you begin at the second paragraph on page 12, what we described there is that there were 412 of 1,791 respondents, that we found were research participants. Now, if you remember, the first number was 1,882, because we talked to 1,882 people. For whatever reason there are 91 of those people for whom we didn't have, couldn't get enough information to make a judgment at all about research participation. That's how we get to the 1,791. So, 412 people of the 1,791 were, in fact, participants in research. So, if you remember back to approximately a year ago, when we were debating whether we'd find people who were in research by using this method, here's the answer that we were all debating about. It was somewhere between the estimates we had, from our guesses, from three to 50 percent. So, if you go to these kinds of places, the answer now is about 23 percent. Well, then, if we try to look at, and I'm going to skip this middle section here, because I don't think that's the troublesome stuff. There's not a lot of denominators shifting. We then wanted to look at the people who said they were research participants, or had been, but we couldn't find any evidence. CHAIRPERSON FADEN: Can I interrupt for one second, Jeremy? DR. SUGARMAN: Yes? CHAIRPERSON FADEN: You've just gone from 412 in line eight is okay? DR. SUGARMAN: Correct. CHAIRPERSON FADEN: And 412 in line 20 is not okay? DR. SUGARMAN: Correct. CHAIRPERSON FADEN: Can you tell us why? DR. SUGARMAN: Yes. CHAIRPERSON FADEN: Or are you about to tell us why? DR. SUGARMAN: I'm just -- that's -- CHAIRPERSON FADEN: Thank you. All right. I just wanted to make sure. DR. SUGARMAN: That's why I'm jumping to the next number. CHAIRPERSON FADEN: And I want to know all the other places where it's 412 when it has to be 313, like on page 13, line 12? You'll tell us if that's supposed to be -- this is going to be a great mystery. Will it be 412 or 313? DR. SUGARMAN: You can write down your guess on -- (Laughter.) All the other numbers are going to -- should stay the same. The mistake here was just in this one place. CHAIRPERSON FADEN: All right. DR. SUGARMAN: So, now we're just going to think about the people who thought they were research participants, but we couldn't find any evidence of that. So, we -- 541 people told us they thought they were research participants. Okay? For 313 of those people who told us they were research participants, we were able to find documentation of their research participation. Okay? CHAIRPERSON FADEN: Okay. DR. SUGARMAN: Then -- (Whispering.) What's that? No. That's next. Okay. So, that explains how we got that denominator. All right. Is everybody following the numbers? Good. Now, Steve, the next one, is a little bit more interesting. And Steve's going to explain, starting on page 13, in the first full paragraph, line 12, what we did to look at the folks who, we found documentation of research participation, but they said they were not in research. DR. GOODMAN: Okay. The number, the operative number that we start with here is 99, as is in line 13, of page 13. So, that is the number originally felt after Advisory Committee staff review of -- and RTI screening of patients who thought they -- for whom we had documentation of research -- CHAIRPERSON FADEN: I'm still lost, Steve. I've got to apologize. Maybe I'm -- maybe it's because I haven't had -- UNIDENTIFIED: He has it all worked out. CHAIRPERSON FADEN: You have it all worked out? DR. GOODMAN: Line 13. CHAIRPERSON FADEN: Let me try this again. It may be an insufficient intake of caffeine. But you have, one line, on page 20, I mean, on -- DR. GOODMAN: Page 13. CHAIRPERSON FADEN: Page 12, line 20, okay? Going back a page? DR. GOODMAN: Okay. CHAIRPERSON FADEN: Jeremy tells us now that you had 541 people who said that they thought they were in research, right? DR. GOODMAN: Yes. I believe. You just took away my tables. (Laughs.) Yes. UNIDENTIFIED: Yes. CHAIRPERSON FADEN: Or -- wait a second. Let me just try to -- if Steve could -- I just want to see if I understand this. So, these 541 people are people who said to us, "I think I'm a research subject, or I was one." DR. GOODMAN: That's right. CHAIRPERSON FADEN: Okay. Of those 541, you're saying you could find documentation that 313, in fact, were research subjects. But that tells me that that's only among the people who thought they were research subjects. DR. GOODMAN: Correct. CHAIRPERSON FADEN: When you go to page 13, line 12, you're using that same furthermore of the 313? But presumably -- UNIDENTIFIED: It's a different group. DR. GOODMAN: No. It's a totally different group. CHAIRPERSON FADEN: So, it's a total coincidence that it's 313 again? What's -- what should the number be? UNIDENTIFIED: That should be 412. DR. GOODMAN: That's 412. CHAIRPERSON FADEN: Okay. That's what I didn't understand. That one is -- that one remains 412? DR. GOODMAN: Yes. We only change one number. DR. SUGARMAN: We only change the one. CHAIRPERSON FADEN: Okay. That's what I didn't get. All right. So, furthermore, the 412 for him, documentation was found. So, that's 313 plus 412. DR. SUGARMAN: 313 plus 99, it would be 412. CHAIRPERSON FADEN: Okay. So, you're back to the 412 in line eight of page 12? UNIDENTIFIED: That's right. DR. GOODMAN: That's right. UNIDENTIFIED: It's easier to see -- much easier. CHAIRPERSON FADEN: All right. Maybe -- do you want to put your table up, Duncan? UNIDENTIFIED: Okay. Do you want to do it, or shall I? CHAIRPERSON FADEN: Somebody put it up, while they -- ? We need the table in the text. Okay? DR. KATZ: That would mean that 25 percent didn't know that they were research subjects, approximately? 99 out of 412? CHAIRPERSON FADEN: That's what we're trying to figure out. But that's what it sounds like. DR. GOODMAN: Yes. Approximately. DR. KATZ: Is that what the conclusion is? Yes? Okay. DR. GOODMAN: Yes. CHAIRPERSON FADEN: That's what I was trying to get to, Jay. DR. KATZ: No. I know. Okay. CHAIRPERSON FADEN: We're getting there. DR. GOODMAN: So, I won't say any more numbers until Duncan has finished writing them down. But what we then tried to do was study these 99 as intensively as possible, to track them. Try to figure out where they came from, where they enrolled, how serious were the protocols that they were involved in, etc. I won't continue on that. And what will happen as I go through the numbers is that for each stage of the efforts, the -- we get a smaller and smaller denominator, because we're able to find fewer and fewer records. Because, as you know, the original purpose of this study was not really to track this down. CHAIRPERSON FADEN: Right. Okay. Take us through it. (Pause.) You got it? Okay. So now you're going to tell us, Steve, what we know about the 99. DR. GOODMAN: Right. CHAIRPERSON FADEN: Okay. DR. GOODMAN: So, these 99 -- of these 99, when the ACHRE staff went and looked for documentation of research involvement, they could only find the detailed information on 81 in the day that they went back. CHAIRPERSON FADEN: All right. You've got to forgive me, because I'm going to stop you all along the way. Okay? DR. GOODMAN: That's fine. CHAIRPERSON FADEN: We knew that they were research subjects from flimsier documentation? DR. GOODMAN: Yes. From RTI. DR. SUGARMAN: Well, what happened, if you remember the initial -- I don't know flimsy, but -- (Laughter.) CHAIRPERSON FADEN: That's what I'm trying to figure out. When you're saying, is there -- are we right in thinking -- ? DR. SUGARMAN: When some -- some of the times -- CHAIRPERSON FADEN: How valid -- ? DR. SUGARMAN: Well, you know, it's a hard question to answer. When RTI went through the first set of abstractions, they found some kind of documentation of research participation. Some of the discordant responses that we were able to clear up, remember, the last time we talked, it looked like it was up at around 40 percent. CHAIRPERSON FADEN: Right. DR. SUGARMAN: Some of the kinds of things we found on abstraction when either Pat or I re-looked at those records were, sometimes there was an informed consent for research in that patient's medical record, but it was never signed, and didn't have the patient's name on it. Sometimes we found consent forms that were for standard treatment, but not for -- CHAIRPERSON FADEN: I guess what I want to know, Jeremy is, there are 18 people, right? Who are in the original 99, who you couldn't find more detailed documentation about. How should we view them? Should we view them as maybe not -- maybe that's invalid information. Maybe they weren't ever research subjects? DR. SUGARMAN: That is correct. CHAIRPERSON FADEN: How -- so, we don't really know. DR. SUGARMAN: We don't know. CHAIRPERSON FADEN: Okay. So we can't say, I mean, what we really do is take those 18 out, presumably, and say we don't really know what their deal was, because you're saying that the basis on which some of these classifications were made originally by RTI, that's what I'm trying to figure out is, how confident are you that these 18 people ever were research subjects? Or do you want to put them in a category of, we don't really know what the deal was with these 18? DR. SUGARMAN: I don't think we really know. But they're a suggestion that they were. And so, we're giving you the sort of the worst possible case there. CHAIRPERSON FADEN: The -- 18, Nancy, is there are 99 that were discordant, but there are only 81 that Jeremy and Pat could go back and find better documentation about. So, there are 18 that RTI, based on a -- a more quick look, classified as having been a research subject. But when Pat and Jeremy, is that what somebody is saying -- ? DR. SUGARMAN: That's right. CHAIRPERSON FADEN: When Pat and Jeremy went back and looked in detail, they couldn't find anything that bore on that issue. So, we don't really know about that 18. DR. SUGARMAN: Correct. I mean, it's for a variety of reasons. Sometimes their records weren't available the date Pat and I went. And they might have been the day that RTI went, because the patient was there, and the records might have been in the clinic. I mean, so we don't know. CHAIRPERSON FADEN: So, they could all have been really research subjects, and they could none have them been really research subjects? DR. SUGARMAN: Correct. CHAIRPERSON FADEN: We just don't know about those 18. DR. GOODMAN: This is a side effect of the fact that this was sort of an add-on to this study. CHAIRPERSON FADEN: Understood. DR. GOODMAN: And it wasn't -- CHAIRPERSON FADEN: Understood. DR. GOODMAN: So, that brings us down to 81. CHAIRPERSON FADEN: Got it. DR. GOODMAN: Unfortunately, the denominator then shifts further. Because what the next step was, we wanted to know, of those persons, approximately what percentage would be deemed to be in something more than -- in research that was more than minimal risk. With the thought that if they were in what was deemed to be minimal risk research, that was not of serious concern. There were only 63 persons for whom protocols, consent forms, well -- (Whispering aside.) UNIDENTIFIED: Consent forms. DR. GOODMAN: For which consent forms could be found. So that now we're down to 63. CHAIRPERSON FADEN: All right. Can I stop you one more time? Are we right, Steve, in believing that all of these 81 were research subjects? Okay? That when you say you found the - - there was documentation on those 81? DR. GOODMAN: Yes. Yes. Those are pretty definite. CHAIRPERSON FADEN: So we have -- okay. So we know that 81 didn't know they were -- didn't recall being research subjects? DR. GOODMAN: That's right. CHAIRPERSON FADEN: Even though there was documentation that there was? DR. GOODMAN: Right. CHAIRPERSON FADEN: Now, we're down to the -- DR. GOODMAN: So, we're going to have one -- and one last shift of the denominator. 63 consent forms were found, but only 47 persons had their actual protocols reviewed for evaluation of the risk. So, of the original 81, we're down to a sub-sample of 47, hopefully a random sub-sample, but we have no idea. CHAIRPERSON FADEN: Got it. DR. GOODMAN: That actually had the documented dates of participation, and the actual protocol reviewed and evaluated for risk. CHAIRPERSON FADEN: By that committee that you set up. DR. SUGARMAN: Correct. DR. GOODMAN: Right. CHAIRPERSON FADEN: Okay. By your review panel. DR. GOODMAN: So this is, hopefully, but we don't know, a random sample of the original 81. DR. KATZ: Are you suggesting that the 16 who were not reviewed -- should have been reviewed were not reviewed by the -- ? DR. GOODMAN: They were not reviewed. I don't know exactly what the -- CHAIRPERSON FADEN: No, Jay, this is not reviewed by an IRB. What happened is that in this project, we set up our own consultants. DR. KATZ: So, they were not reviewed by the -- ? CHAIRPERSON FADEN: By our own consultants. DR. KATZ: -- by our own consultants. CHAIRPERSON FADEN: Right. And they didn't look at every proposal. They looked at a sub-sample of proposals. And it happens that 47 of them -- 47 of the research projects that our discordant people were in were in the pool of projects that were reviewed by the consultant to the SIS project, for risk. That thing that Jeremy reported last time. DR. GOODMAN: So really, the relevant shift in denominator here is going from 81 -- 47 of those 81 subjects were intensively looked at. So now, we have 47. This is just about the last number. (Laughter.) CHAIRPERSON FADEN: Till we get to the good stuff. DR. KATZ: Could I have another number -- ? Of the -- DR. GOODMAN: I'm afraid. DR. KATZ: Of the ones that were reviewed by the committee? DR. GOODMAN: Yes. The 47. DR. KATZ: The 47. How many totally were more than minimal -- ? DR. GOODMAN: Well, that's the next number. (Laughter.) That is the last number. So, of -- but I just wanted you to get your footing on the 47. So, we have 47, that is some hopefully random sample of the 81, because most of the reasons that these weren't obtained were logistical. And of the 47, 21 were deemed to be more than minimal risk. So that, which is a proportion of about 45 percent. Where is my calculator? (Pause.) CHAIRPERSON FADEN: Got it. DR. GOODMAN: 45 percent. So, what Jeremy then did was, went back to the actual individual records of each of those 21 to see what we could tell. Just the forms, Jeremy tells me. And this narrative summary Jeremy will go through. It's the first paragraph on page 14. And this is as detailed a profile as we could get of those 21 subjects, who were at more than minimal risk, of the 47. DR. SUGARMAN: Yes. I probably won't rehearse this whole -- all this language that you've already read. But -- DR. KATZ: Could I ask one more question before we -- DR. SUGARMAN: Lots more. (Laughs.) DR. KATZ: Because I had another figure in mind. DR. GOODMAN: Okay. DR. KATZ: It is, of the 412, were all of those reviewed by your review committee? DR. SUGARMAN: A proportion of those were. And we have that information described a little bit earlier. Hang on one second. (Pause.) 200 -- in footnote, or endnote 8, we describe that, and that refers to the language that appears on page 12, line 18. And it's 236 total consent forms were evaluated by the panelists, of 412. CHAIRPERSON FADEN: And they -- just remind us -- and they remind us, they were randomly selected? DR. SUGARMAN: They were the ones we could get on short notice. CHAIRPERSON FADEN: Okay. So, they were a convenient sample. DR. SUGARMAN: A reminder for what happened with this analysis is, once we -- we didn't go into the project to examine the question of discordance. We would have designed a different study. But having found the discordance, we wanted to learn as much about it as we could. And therefore, by adding on each of these steps in this analysis, we -- and doing it in a quick time period, is why we got 236. Basically, that was due to Patt and Praveen hounding the institutions to please send us the blank consent forms for all the projects that we had identified people to be on. And then this review committee reviewing them. DR. KATZ: Yes. And of those 212, how many were more than minimalist studies? Is that easily obtainable? CHAIRPERSON FADEN: It's right in the text, Jay. It's line 19, page 12. DR. KATZ: Is that -- CHAIRPERSON FADEN: Yes. Page 12, line 19. DR. KATZ: That's half of the 212, right? DR. SUGARMAN: Correct. DR. KATZ: Okay. Thanks. DR. SUGARMAN: What we were trying to do, and obviously this is a confusing passage here, and we're trying to seek a way to communicate this in an understandable fashion, we want it in this draft purposely, to give you all of the data, decided which of these you thought was important to go in the final report, what you thought would be in notes, etc. But we wanted to give you the analysis so you could work with it, realizing that we will pitch the average reader, if we provide shifting denominators. And that's not our intent. DR. GOODMAN: It is interesting to note that virtually the identical percentage of protocols among these -- these subjects, the ones who were -- didn't know they were in research, were deemed to be minimal risk, than in a total sample. CHAIRPERSON FADEN: Right. DR. GOODMAN: I mean, they were both almost exactly 50 percent. Another hopeful suggestion that maybe this wasn't -- weren't selectively selected. CHAIRPERSON FADEN: Right. Okay. So, now we're on page 14. And Jeremy, you're going to quickly tell us about these 21 people? DR. SUGARMAN: I can. Nothing changes from what's in the text. So -- CHAIRPERSON FADEN: Why don't you review it real quickly. Because I think people didn't -- because the text was confusing, I'm not sure people really knew who these 21 were, by the time they got to read it. So, this is important for us to make sense out of the discordant problem. DR. SUGARMAN: Okay. So, the 21 folks who were in -- who were judged to be more than minimal risk studies, they came from four of the five geographic sites sampled in the SIS. And they occurred at each kind of institution that we sampled: the university hospitals, government hospitals, government-military, VA hospitals, and community hospitals. They were from each of the types of clinics: radiation oncology, medical oncology, and cardiology. They ranged in age from 21 to 91. About half were men, and half were women. The majority, 16 of the 21 were white. And they had a range of education levels, all the way from an eighth grade education through professional degrees. Sixteen of the 21 had consent forms signed. That was the -- we actually found the consent form for research in their record. It's not to say that they weren't available for the others. We just found 16. All but one of them was enrolled in what we were classifying as therapeutic research, at the risk of getting into that debate. But compared to a diagnostic project for some other type. Eleven of them, sort of about half, were randomized controlled clinical trials. Four of them involved modifications and regimens for treating cancer. So, there was sort of an available treatment. It wasn't sure which treatment would be used. Three were with new drugs, during or following anesthesia. Three drugs were used for conditions, for other types of conditions unrelated to, say, oncology, cardiology, and one was primary prevention trial. The other studies that -- besides these 11, were Phase II trials. And there was question about what a salvage regimen is. These were folks who were generally in -- who had malignancies. And there were types of regimens that were not necessarily shown to be effective, but had been used as part of care. And these investigators were studying whether or not these salvage regimens, as are known in the field, were helpful in either providing palliation, or some type of curative effort. There were some -- three of them were for testing new devices or procedures, and adding additional -- there was one that added an additional maneuver during an otherwise performed diagnostic exam. And one was a basic science study. Sixteen of the 21 involved just modifying a procedure or treatment that the participant would have underwent anyway. And in at least four instances, based on the description we had, and the consent form, the respondents would have likely been quite ill at the time of enrollment. CHAIRPERSON FADEN: There's one piece of information, Jeremy, can you -- and there probably are others, that I would really like to see here. And that is the temporal question of how long ago they were enrolled in these trials. DR. SUGARMAN: That actually was answered in -- that's on page 12 -- I'm sorry. Where is it? I've got it here. CHAIRPERSON FADEN: For the 21? UNIDENTIFIED: For this particular sample. CHAIRPERSON FADEN: For this particular sample. DR. SUGARMAN: Oh, for this particular sample. CHAIRPERSON FADEN: Yes. For these particular 21 people, okay? Who were in more than minimal risk studies, who didn't know that they were in such -- didn't recall being in such studies. Let's phrase it that way. How long -- what can we say about whether they were enrolled in these studies 12 years ago, or last year, which would have some bearing on how we would interpret -- DR. SUGARMAN: Well, we do have a profile, I don't know if it's there, of the entire sample, of the 81 -- I'm sorry, of the 63, which we only were able to get protocols on 47. I don't know if -- I thought I saw that reported. Yes. It says half. This is page 13, line 16. And this of -- not of the 21. This is of the total sample. 52 percent had enrolled just in the previous year. Two thirds within two years. 75 -- this -- some of this information is not there. I'm just giving it to you. CHAIRPERSON FADEN: Is not there. Yes. DR. SUGARMAN: Half within a year. Two thirds within two years. Three quarters within four years. And no one was longer than 11 years. And there were just a few -- two or three stragglers at that level. CHAIRPERSON FADEN: We -- we clearly need that. That's very important for making sense out of this. Can you do it for the 21? DR. SUGARMAN: He has it. DR. GOODMAN: The longest was 12/7/87 was the date of enrollment for the longest participant. Oh, no. I'm sorry. There's -- one is 6/21/85. One is 12/7/87. And then we skip to 1994 dates and '95 dates. CHAIRPERSON FADEN: So you're saying that of the 21, all but two had -- were enrolled in '94 and '95? DR. GOODMAN: Three. CHAIRPERSON FADEN: Is that correct? DR. GOODMAN: We have one in '87. One in '90. One in '85. Two in '90. One, two, three, four. And one missing. One missing. So, four of those participants occurred before 1994. CHAIRPERSON FADEN: Well, and how much before '94? What's the -- ? DR. GOODMAN: '87. '85. '90. CHAIRPERSON FADEN: From '85 to when? DR. GOODMAN: There's one '85. CHAIRPERSON FADEN: One '87. DR. GOODMAN: One '87. Two 90's. CHAIRPERSON FADEN: All right. So, from '85 to '90 we have four people. And then how many do we have from '94 forward? DR. GOODMAN: We would probably -- CHAIRPERSON FADEN: No, because I think there's one missing. DR. GOODMAN: Sixteen, and one's missing. CHAIRPERSON FADEN: So, how many do we have? 21 minus five? UNIDENTIFIED: Sixteen. CHAIRPERSON FADEN: Sixteen? So, 16 are from 1994 forward. Okay. And that, too, obviously we'll need to have in the text. DR. ROYAL: Jeremy, you made it sound like you found the consent form in the medical record for the 16 out of 21 patients. When you didn't find the consent form, did you as the investigator whether or not they had a copy of the consent form? DR. SUGARMAN: When possible. Some of those consent forms weren't necessarily in the medical records. We took a fairly aggressive stance when Patt and I went to the institutions. DR. GLATSTEIN: Patt is ruthless. (Laughter.) DR. GOODMAN: She is the Jim David of the interview study. (Laughter.) CHAIRPERSON FADEN: No higher compliment, Patt. No higher compliment. DR. SUGARMAN: So, actually at one of the institutions that I visited, I went into their research office, where they keep the consent forms, and we went through the files in that way. And another institution didn't have that procedure in place. So, you know, in -- in the interest of keeping the institutions, and the particularities of the institutions confidential, as we have said that we would, the specifics of where each of us went will not be known, and how it was. But when possible, we went to investigators to find that out. CHAIRPERSON FADEN: Okay. (Pause.) Now, I, again, it's a shame, there's so much else going on in the subject interview study that it's kind of -- we shouldn't just focus on this. But because the text was not self-explanatory, for those of us who haven't been following every nuance, this was very, very helpful. DR. SUGARMAN: Okay. CHAIRPERSON FADEN: At least it was really helpful for me in getting straight on what we found here. DR. SUGARMAN: Is there -- does anybody have a suggestion about how we could re-do this section, so that it is understandable? Just a table? Let's say, the table changes after -- CHAIRPERSON FADEN: That's okay. I would just put the table -- I think we need the table -- DR. SUGARMAN: Within the text? Table after table? DR. GOODMAN: Probably just a flow chart, showing where the patients dropped out. DR. SUGARMAN: We'll have an insert with a flow chart. CHAIRPERSON FADEN: Yes. That'll be really, really helpful. Can we have a few minutes of discussion, not more on this part, and then go on to some of the other parts of the SIS? I think that would be real important. Jay? DR. KATZ: Just one. In order to think about the question you just asked, I want to ask you another question. What do you make of -- you've been working, what do you make of these findings that you've just reported to us? What -- because once I know what you're thinking is, maybe others, too, maybe we can figure out how to construct -- DR. SUGARMAN: Right. I think that's a good segu‚ into the overall SIS, and how these data fit within that, in the context of what we did. I think if you look at the data as a whole, one thing we learned from the subject interview study is that the overwhelming majority of people we talked to think research is a good thing. And that is sort of what we hear overall. And we hear that from people who are both participants in research, and for those who don't participate in research, but are at institutions where there's a lot of research activity going on. At the same time we hear that there's some confusion about things like terminology. There's confusion about the term research. There's confusion about the term experiment. And these clearly have meanings that don't fit with the way that we in the research world dichotomize some of these aspects. They hold some folks in it seems whole different kinds of paradigms which are quite confusing. And in the context of that confusion about what these words mean, and their interest in participating in these things, we find that some people who are not on research even think that they are. They believe that research is such a good thing, and what that means, we don't really know. But we know that should they hold research to be such a good thing, there's something about them that says, I'm on research. I want to be on research. Or I think I am on research. So, some of the things that take place in the normal care of patients in hospitals makes them think that they are in research. Additionally, we find this group that is discordant. And they don't know that they're in research. But again, it's in the setting of a lot of confusion about what that process entertains. Now, from the in-depth data, we also learn that people have an awful lot of trust in sort of the process that's at hand. They trust their physicians. They trust their institutions. They trust the whole enterprise of research. And the trust question really is something which I think demands a lot of attention. Something we didn't anticipate learning when we set out to do a subject interview study. It means that there should be good reason people trust us. And it also means that people may need to trust us in this process of when they're sort of sick, and engaged in research. So, it's in that context, Jay, that we have that -- this finding of discordance. And they're willing to accept the advice of physicians, and folks who seem to know about what's going on with them. And the final thing I would say is that in the consent process, when we talked to people in the in-depth study about the consent forms, is that the consent forms didn't mean that much to a whole lot of people. And it may not matter as much to them as it matters to us. And if they sort of had a yellow form for research, or a pink form for therapy, that might be important to people who make forms in hospitals, but it may not be important to people who are sick. CHAIRPERSON FADEN: Eli was waiting to get. And I see Lois. DR. GLATSTEIN: Do you have enough information to be able to take the discordant group, and analyze it by educational status? DR. SUGARMAN: Yes. I believe it's right there. Not - - I don't think with a number of 21 that it would make sense to even, you know, do any regression, or anything like that. But what we do know is, their educational level ranges really from eighth grade to all the way to professional degrees. DR. GLATSTEIN: Well, I meant for the whole group. Not the 21, but the whole group. The whole group of discordance. DR. SUGARMAN: Yes. I think we did put that into a model. CHAIRPERSON FADEN: The 81. DR. SUGARMAN: Yes. We did -- we could do a distribution. We did put them into a model. And I think, Eli, your point is right on. I think the only thing that -- (Pause.) UNIDENTIFIED: Off the top of my head, I don't recall. I don't know. DR. SUGARMAN: We put -- we ran a bunch of models to explore those data. And there wasn't really anything systematically going on with them. We can run that again. Because prior research has obviously shown that educational level in sort of understanding and retention of information and consent forms, correlates with educational level, and just about nothing else. So, that -- it's -- those prior studies really dealt just with the consent forms. CHAIRPERSON FADEN: Well, what you're saying is that in our data, it doesn't look as if the people who didn't remember, or never knew, we don't know which it is, that they are current research subjects? The 81? Not the whole group of 81? They were not disproportionately poorly educated? Is that what you're saying? DR. SUGARMAN: I believe that's correct, and we can check. DR. GOODMAN: Well, it was such a small number, it may be a little bit -- CHAIRPERSON FADEN: I know. But as close as we can, it doesn't look like the data -- that's what we need. That's I think the underlying question is, in line with what you'd anticipate, are they disproportionately poorly educated, relative to the whole sample of people. Lois, and Henry? Lois? MS. NORRIS: I have a feeling that perhaps this question can't be answered. But do you suppose with respect to the different definitions attributed to the various research terms, the mere fact you asked the question leads people to believe that they must mean different things? And therefore they have to give you an answer indicating that they mean different things? DR. SUGARMAN: Well, I think your question is great, and points out one of the sort of hazards and limitations of doing survey research. I mean, we're basing this discordance response on one or two questions. Do you believe you're a participant in medical research? MS. NORRIS: Well, I'm not talking about discordant. I'm talking about research, experiments -- DR. SUGARMAN: No. I understand that. But even when we started, when we started to ask folks about this question, we asked him a question about whether they thought they were in medical research. Okay? So -- CHAIRPERSON FADEN: I wanted to just follow up on that. So, for -- I mean, is it possible that had we asked the question, are you currently in a clinical trial, they might have said yes. DR. SUGARMAN: Correct. That's where I was going. CHAIRPERSON FADEN: Because they don't think a clinical trial, and medical research is the same thing. DR. SUGARMAN: So, you know, we could have gone through and asked that question again five or six times. You know, and like, that's when I was saying that we -- the discordance issue came up later. Had we, you know, another study could look at this discordant question in great detail, to be able to go back to research, or you know, to respondents, and say, okay, let's explore this a little further. Additionally, Nancy did some analysis of the in-depth data that, you know, remember that for the in-depth interviews, we recruited people who answered yes, okay? So, we're not going to be able to address those kinds of people who didn't know they were, because we didn't talk to them, again. But for the folks that we did talk to, she looked at some of those data. Do you want to go over that? DR. KASS: Yes. As Jeremy said, we -- our criterion for interviewing someone was that he or she believed that he or she was in research. Later, we found out that we couldn't find documentation for 16 of these people. So, I actually did a very thorough analysis of who these 16 people were, and why it was that they thought they were in research, and we couldn't find documentation. For seven, we actually thought that probably there was some reason why the documentation could not be found. But the way they described it, I mean, there was one person who was talking about, he was either receiving aspirin or placebo for his study, and he got the pills in the mail, and it seemed clear that he really was in research. But there were an equal number, I think it was seven again, where my sense was that those people probably were not, but they said things like, what I was getting was new. Or, I was getting tests for this. And that was their -- that's what research meant to them. And so, if there was something innovative being done, then they thought that that meant research, and that's all they needed. DR. GOODMAN: Just to complement that, I think with respect to these patients, the fact that 16 out of 21 were getting what might have been only minor modifications on what would have been normal therapy, points to the fact that maybe they didn't see this is particularly new, or novel. And that's why perhaps they didn't perceive that they were in research. DR. KASS: Yes. And I would say similarly, just to follow up on that, from Eli's earlier question about the education, I think what's true is that we didn't see striking differences in many of the demographic characteristics that we expected to for the discordant. However, the one difference that was striking was that all but one of those 21 were in therapeutic projects. And that's very different than the demograph -- than the distribution of type of research project from the sample, as a whole. So, that was a striking difference. CHAIRPERSON FADEN: Could you, for the 21, I know this is labor intensive, but for the 21, could you take a look and see, chiefly the ones that were in clinical trials, whether they were the people -- that they answered that clinical trials were different from medical research, or not? I mean, we have this rival hypothesis, right? That maybe some of these people said no, I'm not in medical research, because they were in a clinical trial, and they don't think that clinical trial is the same as medical research. I don't think it's going to account for a lot. But since we have these data, could we take a quick look, and see? DR. SUGARMAN: We can look at those data. Remember that subjects received randomly one of four terms. CHAIRPERSON FADEN: So, if they had that one. Good point. DR. SUGARMAN: They -- everybody was asked about medical research, and another term. CHAIRPERSON FADEN: Right. So, if we can look at it -- DR. SUGARMAN: Experiment, investigation, study, or trial. So, we can look at that. CHAIRPERSON FADEN: I wouldn't just restrict it to clinical trials. Just look and see if these were people who attributed radically different meanings to the different terms, so that Lois' -- essentially Lois' question, we can get a little bit more information about the likelihood that the discordance may have been because the term medical research to them meant something very special, and different from what we used it to be, which was a short-hand for anything. Clinical trial, epi-study, anything. DR. SUGARMAN: Okay. CHAIRPERSON FADEN: Henry's been waiting. DR. ROYAL: When you were talking about the discordance of people who believed that they were in research, but turned out not to be in research, one of the comments you made was that people have the impression that research is good, and maybe want to believe that they were in research. I wonder if the opposite might be true, in the group that didn't believe they were in research. CHAIRPERSON FADEN: Oh, good point. DR. ROYAL: You have the brief interview which gives the opinion of research. It would be interesting to see if they had a lower opinion of research than the rest of the people. DR. SUGARMAN: Okay. Yes. I think we can do some fairly quick analyses. (Laughter.) CHAIRPERSON FADEN: The problem is, everybody is turning back into a pumpkin shortly. We're going to lose everybody. DR. SUGARMAN: Yes. We can do some of these. Those are not too burdensome to do. We have the data. CHAIRPERSON FADEN: That's a great idea. And that would be for the whole 81 that we could look at, right? Not just -- DR. SUGARMAN: We could look at the 99. CHAIRPERSON FADEN: The 99 and the 81. I'm really sorry. Ruth, and then Jay. DR. MACKLIN: So, I'd like someone to correct me if I have a mis-impression here. But Jeremy said a few moments ago that this, the study was not designed to look at these discordants. And you would have designed it differently if you had. I'm just wondering how much can be gained from looking at all these things, and trying to make these correlations, when you weren't really, or don't have the opportunity to ask these questions. I mean, I can think of 100 explanations for why people might think they're not. And we've heard several here. And I can think of others. I mean, I don't know if it's going to be valuable for our work, since we can always speculate about reasons why people do or do not believe they're in research, or do or do not remember. And there are lots of other variables we haven't looked at. Now, let me just give one quick example here. One, on page 19, somebody says here, this is on the trust thing, "I do not feel like the drug would be on the market if it were going to harm me, and if it would help in any way." Now, we don't know whether that was a drug that was on the market that's being compared to two other drugs in combination. But for much research, there aren't drugs on the market yet. That's the whole point. They're not on the market. They're in the research -- So, there's a whole lot we don't know. And I'm just wondering whether it's fruitful to try to give something that could be an explanation here for these discordances, that just may not be valid. DR. GOODMAN: I agree with you. I mean, I don't think we're going to be able to give much weight to different -- you know, subtle differences, if there are any, in opinions, or -- or terminology, or whatever. And we can do it, and -- and you can look at it, and you can put whatever -- you wish. I do think that most of what you're going to be able to do is in the realm of speculation, though. CHAIRPERSON FADEN: The study was designed to look at discordance. Not to answer the why, but to see how much there was. DR. SUGARMAN: How much -- how much -- how much -- CHAIRPERSON FADEN: I think we have to be careful with equations. That was one of the major objectives of the study. DR. SUGARMAN: Right. But not to explore in detail the nature of discordance. That was never our intent. To go -- go out, and to be able to, you know, examine. Because we, if we were, we would have -- CHAIRPERSON FADEN: I want to draw a distinction between rates of discordance, and explanations for discordance. Okay. The study was designed to determine rates. DR. SUGARMAN: Correct. CHAIRPERSON FADEN: Okay. UNIDENTIFIED: Fair enough. (Laughs.) CHAIRPERSON FADEN: We -- we didn't have the resources and the time to do everything you would want to do, if you would want to explain the why. DR. SUGARMAN: Correct. CHAIRPERSON FADEN: That would have included being able to interview these 81, for example. DR. SUGARMAN: To go back to them again. CHAIRPERSON FADEN: Right. Go back to these 81 again. DR. SUGARMAN: And to ask another set of questions. CHAIRPERSON FADEN: And do this -- DR. SUGARMAN: Also to go back to the other group again. CHAIRPERSON FADEN: The people who thought they were in research, and they weren't. DR. SUGARMAN: All sorts of discord -- CHAIRPERSON FADEN: Right. Exactly. So, you would want to do what Nancy did with the people who correctly thought they were in research -- DR. SUGARMAN: But also with -- CHAIRPERSON FADEN: -- with these other two groups. That we couldn't do. DR. SUGARMAN: Right. With the knowledge, with their medical information in front of you. CHAIRPERSON FADEN: Right. DR. SUGARMAN: Knowing, reviewing their research in detail. CHAIRPERSON FADEN: Exactly. DR. SUGARMAN: We didn't have that sort of -- DR. MACKLIN: But I guess what's -- what's been happening in the last few minutes is a quest for the explanation. I mean, I agree that having the data, and making these correlations is fine. But there's too much information left out. I mean, I would be leery of making a conclusion, drawing some conclusions, by way of explanation, that are purely speculative, and for which we have absolutely -- we haven't looked at, and there's no evidence to be able to document one or the other. CHAIRPERSON FADEN: I just want to make a distinction between pure speculation, and when you've got a hypothesis, a working hypothesis, about what might explain a finding. And you have some information, some data that might bear on how likely or unlikely that working hypothesis is. And I think that's what we're trying to do with things like education, and what they thought of research, and things of that sort. It may not resolve everything. But if one reasonable hypothesis is what Henry has proposed, for example, that the people who thought they were in research, but they really weren't, were people who thought research was really a wonderful and great thing, we have some data that bears on that hypothesis, and we could snoop around and look at it. So, I -- I don't want to say, you know, I agree with you, that we can't -- couldn't sort of give a definitive interpretation of what went on, but we can illuminate a little bit, you know, our speculations. I've got Jay, and Nancy, and Duncan. DR. KATZ: One comment about these questions. I think Ruth Macklin's point is very, very important. We should very much keep in mind, now who -- can you recommend it next time, when the study is done of 1,700 informants, that they be subjected to five year psychoanalysis, because only then will we be able to get the right answer -- (Laughter.) -- a proper answer to these kinds of questions. CHAIRPERSON FADEN: God help us. DR. KATZ: But my question is -- your recommendation, my question is, of those people who said that they were in research, and irrespective of whether they were in research or not, did by any chance the question come up with all of them, do they think that research is the best possible kind of treatment? Do they have that information? DR. KASS: That exact phrasing of the question I think did not happen. However, the question, why did you decide to be in the research, was asked. And the question, what do you think about research, was asked. And I think through that, we typically learned that people thought that research was cutting edge. It was the right way to get good treatment. I mean, again, as -- as we had -- DR. KATZ: That's not quite, you know, on point. Because then they could still think it was research. And they were getting the best kind of treatment. But I was more interested in the question where there's an equivalency that they see between research and the best possible kind of treatment? DR. KASS: Yes. No. I think for many people, there was that belief. DR. KATZ: There was that belief. DR. KASS: When -- when we get into this section here, where we're discussing distinctions between treatment and research, what was so striking was that in certain ways, people had very clear distinctions, in terms of being able to say, that particular intervention I got was the research piece. And yet, they would go on to describe that as their means of having treatment. CHAIRPERSON FADEN: I've got Nancy, Duncan, and Pat. DR. OLEINICK: I certainly agree that with this small number, small sample, that it's going to be impossible to draw any definitive conclusions as to the explanation for this discordance. But I -- but as we said, there are some hypotheses that seem somewhat trivial, and that can easily be eliminated. I mean, it isn't part of the country. It isn't the type of the hospital, and so forth. But I think it's important that we make some statement. And I said this in my comments, because otherwise, the reader is going to start drawing conclusions that are probably going to be invalid. And because of the -- you can't really say. I mean, it may not be any kind of a problem at all. And yet, there might be something there. But I think that whatever can be said ought to be said. Because otherwise you're leaving the un-informed reader to draw conclusions based on a very small sample, which may not be valid at all. DR. SUGARMAN: I think those are good points. And we'll just need your guidance about which of the conclusions you think are reasonable to make. Keeping in mind both Ruth Macklin's comments, Jay's endorsement of that, and your statements. I mean, I think -- I think everyone's saying the same sort of thing. We don't want to make overarching conclusions. But we need to at least be fair to the data. DR. GOODMAN: Also, I want to add to that, with regard to even the issue of rates, I think we really have to put a big qualifier on that. This is rates having to do with a single question. UNIDENTIFIED: Um hm. Good point. DR. GOODMAN: And you know, if this had been really designed to get at the rates, particularly knowing what we know now, we might have wanted to go back to them, or ask them the question a variety of ways. I think we really -- we have a rough idea of what the rates are. I don't know -- CHAIRPERSON FADEN: Can you give us -- can you give us the rate, against the most relevant percent? The issue is, what the right denominator is. With all the qualifiers you've just said, Steve, you've got 81 people, out of the denominator of -- is it 412 for which you had documentation? DR. GOODMAN: Right. So that's about -- CHAIRPERSON FADEN: Who did -- who were discordant that way. DR. GOODMAN: That's right. So, that's about -- CHAIRPERSON FADEN: So, what percentage -- DR. GOODMAN: Twenty percent. And it should be contrasted with the very similar percentage of people who thought they were in research, who in fact were not. CHAIRPERSON FADEN: Okay. So, it's both -- DR. GOODMAN: Which is both about 20 percent. CHAIRPERSON FADEN: Okay. That's very helpful. Thank you. Duncan? DR. THOMAS: There's an interesting section starting on page 16, which describes the reasons for people, why they decided to participate. I seem to recall, we collected a lot of information about -- from those who declined to participate, as well. And I thought I had seen an analysis of that in an earlier draft, although I may be deluding myself. Do you have any information on that? DR. SUGARMAN: Yes. Give us -- give us a minute to find that. (Pause.) Okay. You -- you did see these data. You saw the -- the sort of raw counts of these data, when you -- on the percentage forms, the last time you received the -- these are the final numbers, within the survey instrument. Steve will be looking for some of the bi-variant stuff, while I'm talking through this. Okay. For the people who said that they were approached about being a participant in research, but declined to participate, we asked them a series of questions. CHAIRPERSON FADEN: How many people were there? Roughly? Do you have an N around there? DR. SUGARMAN: The N is somewhere around -- what is that total? 22 -- 42 -- about 100. About 100 people made a decision not to. CHAIRPERSON FADEN: We should stick this in the -- DR. SUGARMAN: Okay. The first question was, being -- and these are all, contributed a lot, contributed a little, did not contribute. Again, feel free to write down your answers. (Laughter.) If you made that decision. Being in the medical research project would have been unpleasant. Eighteen percent said it contributed a lot. Twenty percent said it contributed a little. But the majority said it didn't contribute, 60 percent. (Pause.) (Whispering aside.) I can. I'm just going to give them a host of data. The medical research project was too risky. About 50 percent contributed a lot or a little, and 50 percent said didn't. I just can't sum it up that fast. Taking part in a medical research project would have cost you money. That wasn't a contributing factor for 88 percent of folks who decided not to contribute. You did not want to be treated like a guinea pig. Fifty-five percent said it didn't contribute. But 34 percent said it contributed a lot. Taking part in a medical research project would have been inconvenient. And it's across the board. Forty-three percent said it contributed a lot, 23 percent said it contributed a little, and 30 percent said it didn't contribute. You wanted your medical decisions made by your doctor and yourself, not by researchers. Fifty-six percent said that contributed a lot. You wanted to know what treatment you were getting. Sixty-four percent of folks said it contributed a lot. Your doctor thought it was a bad idea. And 85 percent of folks said that didn't contribute. Being in the medical research project was not the best way for you to get better. And it was across the board. Forty- five percent said it contributed a lot. Forty-three percent said it didn't contribute. CHAIRPERSON FADEN: Jeremy, one of the reasons why I think it would be important to put in this is to illustrate the fact that, for whatever it's worth, out of the 1,800 -- 100 people had an opportunity to be in research, and refused. That's -- that's meaningful, in and of itself, especially against an historical comparison, where you know, it's counter-factual, but my guess is, 40 years ago, it's not likely that people would have known that they could refuse, in lots of contexts, because they wouldn't -- it wouldn't have been presented to them as a choice. DR. SUGARMAN: Well, we can -- we can do these. And as everyone's thinking through, heaping on additional analyses, we are -- let me just remind you that three months ago, we planned the analysis. And we went through the directions of the kinds of things that we would submit to analysis of these data. Each time we do another analysis, we're providing you with more text, additional information. And the scurry to get it right, and to correct things in the text, is -- is quite important. So -- CHAIRPERSON FADEN: I will promise to work with you, to sort of highlight the core things. I think it's becoming clearer, and I think other members of the committee would, too, it's not that we're looking for, you know, multiple regressions, and more runs. It's rather to pull out the kind of core -- DR. SUGARMAN: No. I understand -- CHAIRPERSON FADEN: -- big, big issues. DR. SUGARMAN: I understand. CHAIRPERSON FADEN: But Pat's been waiting to comment, I think, on right this question. MS. KING: I'm really getting very disturbed, because everybody is gleeful, because we've got a study. And all of the things that we're all trained to do as academics is leaping to the fore. And we can just -- want to massage this data, and really get into it. That's what I sense around the table. At this point that, to me, though, is not what we should be doing. This study supports conclusions -- CHAIRPERSON FADEN: Correct. MS. KING: -- for recommendations. And so, every -- it's -- we should not be talking about what it would be nice to find out, because we would learn something that we might find interesting. I think that with a month to go, you have to be hard nosed about, and we can't even do it until we get a clearer sense of the recommendations this afternoon. Anything that doesn't link up with those recommendations, at this point, as tough as it may be, ought to be cut. And the data preserved for maybe somebody else going back to massage it. And that's the point that I want to make. Because that requires what Jeremy, I think, is trying to get us to, too. It's more important that what we have be done right, in terms -- and - - and support whatever we finally say, than it is to be able to say something in addition that we might have missed. And that's what I really want to urge. That we use their time, that's left, to make the statements that we're going to make, make them well. I can't say this strongly enough. Because I just sense us moving in a different direction, because we're getting excited. So, I support -- (Laughter.) Well, we are. Everybody's so exciting, you know? CHAIRPERSON FADEN: You're right. MS. KING: -- we've got some information. Well, and I think that's wonderful. But I think that Ruth's caution, endorsed by Jay, and what I hear Jeremy said, needs to be said over, and over, and over again, before we start doing something we like doing, rather than turn to this nasty work that we were doing yesterday, and we'll have to do this afternoon. CHAIRPERSON FADEN: I think your caution is well taken. And Jeremy, and Nancy, and Steve, and Patt, are much relieved to hear you say this, I don't doubt. (Laughter.) And the key thing is pulling out, and bulleting, in ways that are available for the readership of, you know, the general audience readership of this report. The key points that the data that we've collected lead us to. I think that's easily done now. There's so much richness in this study, we can do that. And there'll be a whole army of people who will follow us. The data are a matter of public record, once we're done, which is one of the nice things about -- DR. SUGARMAN: And I'm glad you're all jazzed by these data. (Laughter.) I mean, I really -- I am. CHAIRPERSON FADEN: I'm going to -- well, let me just say, let Phil have the last word, and then we're going to have go on to another. DR. RUSSELL: I'd like to pin Jeremy down as to what recommendations do you see coming from these data? You're closer to these data than anybody, in the sense of what they really mean. And what -- DR. SUGARMAN: Steve is the statistician. He's really close. DR. RUSSELL: Where do we go next? DR. SUGARMAN: I would turn to sort of the end of your chapter, page 29 it begins. Actually it starts on 30, but under the heading of distinguishing medical research, and medical care. We found, based on our look, these are some of the reasonable data that might work with your policy recommendations. It is clear that there has been a long standing dichotomous treatment in legal, regulatory, and bio-ethics communities, particularly about research and treatment. There was some uncertainty both in the sort of brief interview, and the in-depth interview, about what that means. That this might not be such a meaningful distinction to people who were enrolled in research, or are patients receiving their care. Now, that's not to say that there's anything not useful about the very important philosophical, and regulatory, work that has been done to distinguish research and treatment. And believe me, that those of us who have been looking at this have thought hard about those things for a long time, and have gotten up in front of groups of people, and carefully delineated the sort of differences for those two things. Despite that, with this setting of confusion, some sort of distinction, if that's a distinction we need to hold onto, then we need to do something, or make some suggestions about either making that clear to people who might not think this is so clear, or that important, as we might. Or, sort of scrap the idea. And I think your ideas about how that fits in with the research proposal review projects, and other aspects, might be helpful there. And if it is important, because of the philosophical and legal arguments, and the way some -- some informed consent grew up in the courts, and other grew up through major bodies, etc., etc. Then we're going to need to find ways of making that known to participants. With trust, I think that the language there is -- is pretty strong. The trust has to be responded to with caution and humility. People really trust the research enterprise. And they trust the regulatory bodies. And they trust their doctors. And it is going to be crucial to communicate in some way that that trust is not -- you know, trust is probably a good thing. That people trust their physicians, etc., is probably a good thing. Helps people get better. What we have to make sure is that that trust is not used in ways to encourage people to participate-undermined in some way. The vulnerability in the context of serious illness, it was clear through the in-depth interviews, that some people didn't feel as if they had much choice into where they were going to go. And in fact, that might be true. In some treatments, there are no drugs available, and that they have a choice of -- of getting on to that research project, or not. Or not having another therapy. But the caution there would be, I think, just to make sure that people understood all the other options of both what it means to -- if this is the only sort of active intervention that's available, what's associated with that active intervention. This is nothing new. What are the side effects. And what are the alternatives, although that's sort of consistent with current regulatory things. What can I do for you, in addition to doing this research project? Comfort, care, palliation, quality of life. The consent forms, a lot of people didn't care. And the people who did care did interesting things with them. They took them home. They tried to understand them. They'd have other people explain things to them. And I think we know from the small empirical data of what IRB's do, IRB's spend an awful lot of time looking at consent forms, debating about the readability of the form. Debating about whether this form was good. And I think we should know that, with people not attending to them are carefully as we might think that they do, that we ought not put a lot of weight into just jazzing up consent forms some more. In terminology, I think we learned a lot. We learned a lot, starting with the focus groups we had around the country with physicians, that the term experiment is an approximation of what science is about. Research is a term that has to deal with sort of the progress. And the actual process of an experiment, or an experimental trial, the scientific nature of it, is captured in that word experiment. Except experiment is loaded, as well. Sort of, some negative stuff that goes along with it. So, I think that in -- in trials, or investigations that are really experiments, we're trying this, or this, that this, in fact, is an experiment. That other words, like in a clinical investigation, or clinical study, are almost meaningless terms that sort of mask the idea of what's going on. And medical research is something that's generally perceived to be good. And we don't have qualifiers for knowing sort of what the actual is. But if you want to communicate that this is something distinct from care, then probably the term experiment, for at least those sort of treatment trials, or some of the diagnostic testing, the term experiment is probably a more realistic word to use. And so, you might consider using the correct terminology, or figuring out what terminology would be most appropriate for the people you're trying to enroll. And finally, most people reported that they were in research for what we'd consider the right reasons. They wanted to help others, and they wanted to advance science. And with all the other kinds of things we do, in the setting of some confusion, people are willing to help other folks. It's sort of not heard that much. But they really are willing. And folks, even initially, when approached, some people described, I'm just doing this for myself, at first, but over time said, I'm doing this really for other people. And they found some meaning in participating in research. Now, I don't know if I'm -- am I still pinned down? Or can I -- ? DR. RUSSELL: Pretty slippery to me. (Laughter.) CHAIRPERSON FADEN: That's very helpful. We need to go on to other things. But I was commenting on the side, I remain amazed that this was pulled off. I'm delighted that it was pulled off. I think the Committee just should feel wonderful about this. But even more wonderful, the four of you should feel -- DR. SUGARMAN: Can we just feel tired? CHAIRPERSON FADEN: Yes. Tired. You'll feel wonderful a couple years from now. Right now, you just feel exhausted. Pat, did you want to comment? MS. KING: This is a question, and a comment, as well. One of the things that Jeremy said is that, which I found very interesting, which I think actually does go to how recommendations are shaped, is that you said that contrary to those of us who worked on the theory side, the legal, and regulatory side, that what you find when you actually go out, and talk to those who are on the receiving side, I don't want to use this word discordance. There are differences. And I think this is very important. This is actually - - and I don't know, it doesn't require massaging of the data. What it requires is a full explanation in the text of what you think you might mean. One of the things that struck me, for example, is, there was a great deal of debate about what the NIH and other agencies should regulate. So, we define research in a way that was good for the regulators. So that we have a very theoretical view of what constitutes research, you know? It has to be a written protocol, hypotheses, etc., etc. One of the debates at that time was, that's well and good. But this is going to cause confusion in the field. Because from the patient's perspective, if you do act A, and you have a written protocol, from the patient's perspective, it's no different than doing act A without this developed hypothesis, etc., etc., etc. This is not to say we should do away with the definition of research. But it may have implications for training. And education of those who actually work in the field, about what they present, and how they talk about it. Because it -- because this may be, this is speculative, this may be a source of the confusion. That everybody operates with a definition of research on the giving side that may not work on the receiving side. I'm interested in your thoughts put on paper, because this does not have to backed with research. This can be speculative for me, about how the legal and regulatory structure may be undermining what its goals are. Because we want to know that. And so, you started with that. And if you can flesh that out, I, for one, would be interested. Because I think that does go to what this committee can do, in suggesting that certain things be pursued in the future. DR. SUGARMAN: I think, actually, going back to when we were designing this study, and that we went around, and talked to researchers at major research institutions, they still have trouble understanding what constitutes research. And I know from reading the recommendations that this is consistent with some of the findings, not directly from the SIS. But I can say that is concordant, or consistent, depending on which term you prefer. With the idea that they struggle with this question on a daily basis. There are modifications in regimens that occur with drugs, with radiation therapy, with oncology, with surgery. It's gone on since the earliest accounts, and Sue could speak to this, of what medicine was about. And that certain things get tried. And it's once one wants to gather data in a systematic fashion. And have it be generalizable, that it becomes research. Some people shudder at the thought of that, because it then heaps on them a whole set of other regulatory stuff, that they see that, you know, that they would otherwise be able to do. MS. KING: To avoid. DR. SUGARMAN: To avoid, or to do. Or to even, you know, nuance their care, consistent with their patient's value system, and all those sorts of things. So, I think it's a problem for people in the field. If you went into operating rooms, is that exactly the way it says -- textbook surgery, sir? It says to put a stitch here, over there, you know? That -- that goes on every day. So, I think -- CHAIRPERSON FADEN: We're going to give you the transcript, Jeremy, of what you -- MS. KING: Yes. If you could put that -- if you could put some of that -- CHAIRPERSON FADEN: So you could stick it in the chapter. That was good. DR. GOODMAN: One comment to that which came up in our discussions, which is that although this is speculation, it's unclear what -- what the goal should be, in terms of patient's awareness. I mean, we could say that for terminal patients, 100 percent of them should be aware that they're going to die within three months. But patients have various coping mechanisms when they're very ill. And particularly when they're getting treatments which might be therapeutic treatments in the context of research. It's not necessarily clear to us that the goal should be 100 percent of patients being able to articulate in a certain way that they were engaged in research, and not in treatment. That may not be particularly beneficial to certain kinds of patients. So, I think we have to be very careful in saying what -- what is overall the optimum target. And maybe this is getting at what -- part of what you were saying. MS. KING: This is getting at some of the things I want to say. Because that connects up to where you -- where you go. Not just where you failed, but some thoughts about where we're going to go with our recommendations. DR. SUGARMAN: Sure. Well, we tried to start that discussion. And what we said were, policy implication, the last section of the chapter, and are happy to elaborate on any of those that are consistent with where the advisory committee is going. CHAIRPERSON FADEN: I think what Steve -- what just said is terribly important. I mean, what we do -- so, what's the meaning of it? Is it clearly a bad thing that these people didn't know that they were in research? DR. GOODMAN: Or chose not to know, or forget, or whatever. CHAIRPERSON FADEN: Or chose not to know, or forget. One take of it would be obviously yes, okay? And then there is, but wait a minute, okay? And you know, I have a view that says overall, I think it's not a good thing. But you're right. To look more subtly in terms of the clinical context, and explore it a little bit more. And say, okay, now what -- what are the dynamics here? And all that kind of stuff would enrich considerably, particularly for the non- technical reader. Nancy wants to comment. Bill's on the list. We may never end this discussion. I've got you, Jay. DR. KASS: The only piece I will add to that is, I think it's important from a policy perspective to distinguish what we want to make sure patients do. I think Steve is right in saying, it is not our place to tell people how to interpret their illness. Anything like that. It is not our place to, you know, ram down their throats a certain belief system. However, it is our place to give an honest presentation of certain things. And for very ill people, it's very easy, I think, to make promises that perhaps we can't live up to, because of the place they're in. And that is our responsibility. CHAIRPERSON FADEN: Put that in there too. (Laughter.) We're getting a lot of this stuff. I've got Jay, Sue, Henry, and Phil. And then I really feel like we need to call it on this. DR. KATZ: If I could be brief, is that it's difficult just as I listened to Pat a moment ago, I started to agree with her. Then I disagreed with her. Then I agreed with her again. Because the complexity of the sentence. I just want to refer you to one sentence, I think that she was also referring to, on page 30, line six. Although the legal, regulatory, and bio-ethics communities, tend to treat research and treatment dichotomously, from the perspective of patients separating research from treatment often is not meaningful. A correct statement, within the scope of the chapter. But the problems begin, that one could say, from the perspective of physician investigators, separating research from treatment often is not meaningful. It's the Kinderschule. It's where these patient- subjects are being educated. Kinderschule means, you know, the nursery where you begin to learn. These patient-subjects are educated in a setting where by and large the distinction between research and treatment is not considered to be very meaningful. And they really have no background, no education, by and large, I'm exaggerating a little bit, of speaking to, and reflecting on, the difference between treatment and research. So, it's complex and -- but that's what the problem is. DR. SUGARMAN: It's very complex. And I think that getting at the problem, too, whether physicians and researchers know the difference, can be for two reasons. One, because they weren't educated to know the difference. And one, because maybe that's not even -- misapprehends a reality of what goes on in the care of patients. And so, I think we can clear up some of that confusion by educating people. We can't go back and make sure their Momma's raised them right. But we can go back and sort of inform sort of discussions about making these distinctions clearer. When they do, in fact, exist. But some cases, I think we're going to be banging heads. CHAIRPERSON FADEN: I've got Sue, Henry, and Phil. And then I'm going to call it. So, anybody else who wants to make a comment, pretend it's relevant in the next discussion. (Laughter.) We're formally going to end this discussion with Phil. Sue, Henry, and Phil. DR. LEDERER: I guess I was thinking ahead. One of our recommendations is for public education. And given one of the findings that you have, I guess I'm thinking about the people who are not pleased with the state of medical research in general. Do you think that based on your experience with this study, that we might advise that education be tailored to particular groups that have had different experiences with the medical research enterprise? DR. SUGARMAN: I'm not -- can you just rephrase that? DR. LEDERER: Well, I guess I'm thinking about your section here, the state of medical research. DR. SUGARMAN: Yes. DR. LEDERER: And there is a particular group whose opinion of medical research in general is less promising than most of the other people. DR. SUGARMAN: Yes. DR. LEDERER: And we have a recommendation for public education. And I'm just asking whether you think we should revise that recommendation, given -- your findings, to say that the government has more of a responsibility to reach out to certain groups who, because of their experience, might -- DR. SUGARMAN: I see. I see. MS. KING: This is in reference to African-Americans having less trust? DR. LEDERER: Yes. DR. SUGARMAN: Yes. I think we -- looking at those data, as we have them, it might make sense, you know, broad public education campaigns, if they're not targeted in different ways. And then finding out what that means to different people, and using language that different folks are going to understand at different levels is important. Remember that 90 percent thought that research was favorable, very favorable, and somewhat favorable. So, we're starting with, you know, it's only ten percent of folks we're getting at. And it's so easy, and the good stories are on sort of the bad experiences. And there are lots more good stories about the good experiences. But -- DR. LEDERER: That's very impressive. But I think that, you know, given the experience in this country, it's not surprising that, among some groups in the population, they would have different experiences. And that we might -- the government might have different obligations to those -- DR. SUGARMAN: Sure. I think it would be prudent and appropriate to pursue that. DR. GOODMAN: I also think that, obviously, people's attitudes towards medical research is reflective of their attitudes towards many institutions, and targeted campaigns. Although I basically agree with you. I don't know that you can necessarily shift their opinion towards the institution of medical research, which they may feel very divorced from, or alienated from, in -- in isolation from their distrust of many of government, or social activities. DR. SUGARMAN: And we don't have information to support all of these claims that we're making from all over the place. CHAIRPERSON FADEN: Henry, Phil. And Lois, is this right on this point? MS. NORRIS: Very brief. I fear that targeting any specific population might increase, rather than diminish distrust. MS. KING: Well, what Sue is talking about there is -- there is writing in the field, that the role of Tuskegee, for example, in creating mistrust among other things, in the African- American community, of the medical establishment, is fairly significant. And it is on the research side, because Tuskegee is considered an experience. It is, I would argue, what we can do to try to do something about that, because it may not be -- it may be a healthy paranoia. But it may be an unhealthy paranoia, as well. It would be important to call attention to that. That different groups do, in fact, have different experiences in medicine. It's not just the other institutions. It is within medicine itself that might account for some of the differences. CHAIRPERSON FADEN: Can we hold this discussion off until we get to recommendations? We have the public education recommendation. And then we can continue to pursue whether we want to recommend that there be targeting of campaigns within a larger public education campaign, or not. Henry, and the Phil. And then we're done. Oh, fine. Thank you. Phil? DR. RUSSELL: I would just like to comment that, when you get right down to it, you're dealing in terms of people who are disoriented as to where they are, and what they're -- how they're being dealt with, amount to about three percent of the total. So, you've got a 90 percent success rate in one way -- from one way of looking at it. So the -- that although has some importance, I think it doesn't immediately cry for a major systems fix. It does -- on the other hand, some of the observations that cut across the whole population, such as the communication issues, and the issues of trust, and vulnerability, and so forth, are very, very important issues that kind of jump out at you. But dealing with those is very difficult, except in an educational mode. CHAIRPERSON FADEN: How did you get the three percent, so we know, Phil? How did you get the three percent? DR. RUSSELL: We got down to 16 out of 412. CHAIRPERSON FADEN: (Pause.) Sixteen? DR. RUSSELL: There was the -- as you kept peeling the numbers away, explaining more and more the -- there was a final number of about 16 -- DR. GOODMAN: Right. But those -- DR. RUSSELL: No explanation of why -- DR. GOODMAN: But remember, some of them were lost, or not records that we couldn't review. So, the number may not be quite that small. But it is -- it isn't -- it isn't large. DR. RUSSELL: It's pretty small. CHAIRPERSON FADEN: You know, this is going to be a problem all the way through, as to how we present this, and what we want to say. So, probably as a matter of fairness, we should, with that flow chart, we probably need to be thinking through how we want to keep framing this, you know? Because there are different ways of slicing this, obviously, all the way through to the three percent, or whatever figure it comes down to. And as a matter of fairness, we need to put the whole display out there, so people can see at what point they're worried. So, the readers can make their own judgment about where this is. Thank you all very much. This has been terrific. And now we stay with the contemporary world and move to another project. But I'm thinking we're way off schedule. Should we have a break now and just go straight through on the other project? How about if we make it a very short break. Well, you know what, nobody is allowed to leave the room. (Whereupon, from 10:28 a.m. until 10:39 a.m. the proceedings went off the record.) CHAIRPERSON FADEN: Okay. Committee, if we could come to the table. It got quiet. Okay. All right. We're at RPRP time. Jay, let me make sure that Jay is here. We have the RPRP Chapter and we have Jay's careful report of his work. We need to talk about this chapter. Talk about the chapter that follows it, which is an attempt to kind of put things together. I don't even know where to start. We have got Gail, Sara and Shobitha here. So if we need to have a sort of discussion about how things were done, they are here to answer that for us. My own preference is that we get to the content of the chapter and of Jay's report of his findings, and what do we want to make out of this is really what I think we need to be talking about. I hope that we now all understand, unlike the SIS where we didn't all understand how it was done. I hope at this point we all understand how the RPRP was done, since we did it basically. The core thing for us today and the rest of the day is to figure out what do we think this all means. We have got the collective summary of the collective findings. We have got Jay's report of his analysis. We have got text here. So now is the time to say I don't like the text or I like the text, I want to do this or I want to do that. So I would like to start, if it's all right, with just an open discussion of the status of the RPR chapter and Jay, I don't know how we want to do this, but if it's all right, we'll just put the two together, and people can ask you questions and we can talk about how they should be combined or what should happen or whatever we want to do with them. Okay, Nancy, please. Thank you for starting. DR. OLEINICK: Okay. The first item that I would like to discuss is why these are two separate documents. What are the plans for eventually putting them together into one document? I mean Jay has done a very thorough analysis of the data that he collected. From my reading of it, most of that analysis is certainly appropriate to the data collected by the group as a whole. I am not quite sure why we are looking at two separate documents. CHAIRPERSON FADEN: Ruth? DR. OLEINICK: So I guess I'm asking Jay. MS. MACKLIN: I'm going to add something to that too. I agree with Nancy that what Jay has done is not only a masterful piece of work, but a good analysis of it. I want to know what putting it together will mean. Part of this is asking Jay, and part is asking the experts who know how to put these things together. It seems to me there are two differences. At least I note two differences between what Jay did and what the committee did in its study. One is that as Jay describes his questions, the questions he asked, they focus on informed consent. What can I learn about the contemporary informed consent process? How adequately does the process protect the rights and interests of research subjects? Now those are critically important questions. The Committee's study also tried to get at those questions, but not only at those questions. Therefore, in putting the two together, I think we have to be alert to the fact that Jay's study focused on one aspect, but not the other aspect that the Committee looked at. That is, the first half of our coding form had to do with the documents, what was in the proposal, what the IRB review, whether the IRB re-reviewed it, et cetera. So in putting the two together, it seems to me we have to separate the questions that Jay asked and possibly put that together with our informed consent inquiry, because Jay asked I think half, a very important half, but half of the questions that the other proposal was designed to study. The other thing that I don't know and I don't know if Jay knows or if anyone knows, is what the overlap was in the samples. Jay did what, 103, 102? The Committee looked at what was the total number, 125. From those, we have the assessments, the overall assessments in terms of numbers. Again, in order to know, and this is I think a more methodological and statistical question, how do we put together two studies when we either don't know or don't yet know and can we find out. So that is my second question about putting it together. I think it would be ideal to put it together. Should I stop talking? CHAIRPERSON FADEN: Let's stop for a minute and see if we can at least get the answer to this question. Jay, I know has been trying to give information to the staff about the studies he had and then the staff has been trying to put it together to see. The problem is that these things have been called different things at different times, so it wasn't as simple. It sounds like a simple clerical task and I should be able to match up and match up, but it's not a simple clerical task because somehow things got assigned different titles or names. Sara, Shobitha or Gail, can you enlighten us as to a best guess? At the mike, please. We need somebody at the mike. You might as well come up who knows. Come on, Gail, we'll see how many times this comes up. Do you have a ballpark estimate, even if it isn't precise? MS. PARTHASARATHY: We went back and looked at the fours and fives, those studies that Jay gave fours and fives to out of the original 50 that he had studied in greater detail. Of those, he had given 11 fours and fives. Of those 11, we had reviewed 10 in our sample. CHAIRPERSON FADEN: That's not very helpful. I mean is that as far as we have gotten? MS. PARTHASARATHY: That's as far as we have gotten. CHAIRPERSON FADEN: Why is that? DR. KATZ: I will give you ballpark figures. I think of about, and that's just about, of the 102 that I reviewed, my estimate would be that between 60 and 70 are part of our review also. It is my general impression, plus or minus, I don't know what precisely -- CHAIRPERSON FADEN: One standard deviation. DR. KATZ: That would be my ballpark. CHAIRPERSON FADEN: Let us work with that. We are going to have to do a lot better than looking at those 11. I mean, we're going to have to do something more to substantiate Jay's sense that it is 60 or 70 percent. But for discussion purposes, we'll go with -- and you are probably right, Jay, it's in that ballpark of overlap. DR. GELLER: And everyone understands the reason for the discrepancy. CHAIRPERSON FADEN: It is not even worth going through. It is a whole combination of things. I mean it has to do with the fact that the projects -- DR. GELLER: It's very simple, but that Jay was sent all the proposals early on. Many of which ended up being deleted from our sample because our cell size decreased. DR. THOMAS: But I don't understand what is so difficult about matching them up. DR. OLEINICK: Yes. They were all assigned a number. DR. KATZ: The names changed. CHAIRPERSON FADEN: They were not all assigned a number when Jay got them. DR. THOMAS: Isn't it still a clerical -- MS. PARTHASARATHY: In addition to that, the grant proposal may have been called one thing, whereas the IRB application the title was something different or the title changed in the process of the proposal. Jay wrote down one as a title and we wrote down something other than that. Our original titles are from the grant applications. DR. THOMAS: Yes, but Jay still has his documentation. Don't you? Can't you just send back the face pages or something in your search for them? DR. KATZ: It'll take time, but it can be done. CHAIRPERSON FADEN: The point is, there's no question we have to do it. I am not sure why it hasn't happened, but it will happen. It isn't easy, but it's certainly doable. It is in the range of doable. But let's say that it's somewhere around 60 or 70 percent. Ruth, had you finished your comments? DR. MACKLIN: Well, I finished that, but what I'd like to -- I mean, I finished what I was going to say about what I saw to be the questions that have to be addressed in blending the two. Then the question I have, the bar chart, figure 2 on page 11, I would like to see a chart like that for Jay's so we know here what we are comparing and how to think about it. I mean, numbers would be just as good as the chart, but the bar graph is a nice thing. I don't think anyone can -- spot, but do we have some sense of how this lines up? CHAIRPERSON FADEN: We could probably construct it with numbers. Jay, you have got it. This is the chart, if you could go to page 11 of the RPR one, which breaks out the ratings by minimal risk, less than minimal risk. I don't know if this one is easier to do or the pie charts on page 12 are easier to do. DR. MACKLIN: It doesn't matter which is easier, but you know what I want. CHAIRPERSON FADEN: I know what you want. DR. MACKLIN: What I want to see compared. DR. KATZ: I would think again approximately, and I don't think how important it really is that my figures of 3, 4, and 5 are higher than the Committee review's finding. That you know if you look at the total figure is of the more than minimal risk study, I thought that 75 percent were problematic. While the Committee found 50 percent problematic. But what difference does it make whether 3 million Jews were killed or 5 million Jews were killed in the Holocaust. You know, it's a matter of just numbers. So that's not too significant. CHAIRPERSON FADEN: I think there's a way to do it quickly. MS. KING: You don't want that on the public record. CHAIRPERSON FADEN: Can we just, if you look at page 3 of Jay's analysis, where he says statistical results, and you look at the pie chart on page 12 of the RPRP, you can get a pretty close sense of how similar or dissimilar. I mean we can easily produce pie charts for Jay's work as well, but if you look at the first paragraph under Statistical Results of Jay's Analysis and the pie chart. Actually, I'm sorry, it's the first and second paragraphs. The first thing that I think you can find tremendous agreement, is that Jay found that about 60 percent of his studies were no or minimal risk and so did we collectively. So the breakdown of -- actually, we had it the other way around. We had perhaps 48 percent minimal risk, but it's in different populations and it's in the ballpark. So basically, we're not having a wide disagreement about what proportion are minimal risk and what proportion should be more than minimal risk. Parenthetically, it's about the same proportion that they got in the SIS. So it looks like we're getting a sense of in the research world out there, what proportion of studies seem to be below, more than minimal risk and what percent less. It's somewhere around 40-60, 50-50. So that's the same. So that part is good. Then if you move on in the second paragraph, the one that says of the 41 studies, that can be compared directly to the righthand chart, the greater than minimal risk pie chart. Have I got that right, panel, on page 12? The righthand pie chart is the greater than minimal risk. The labels are not in the proper place. DR. MACKLIN: I'm sorry. This is the problem. Because what Jay's second paragraph says, and that's what he was looking at, acknowledged he was looking at, is that he gives the percentage that raise ethical concerns about informed consent process. What the Committee's overall assessment was was overall. At least in the reviews that I did with my co- reviewers, we had discussions about how the overall rating, the four and five, should reflect the informed consent process, the whole thing or the first part in the coding form. That was very significant, because my discussions with the co-reviewers were if we were only looking at the informed consent, we would have given lower ratings to very many more of them. But because we had the other piece of the coding form and another criterion for being able to assess it, we actually raised the rating. CHAIRPERSON FADEN: That's a very good point. So when we combine it, we have to make clear that there are differences in the criteria. MS. KING: These issues raise questions that we ought not pass lightly about whether they should be combined. CHAIRPERSON FADEN: Would you like to -- MS. KING: I'll raise it, because what we state is in the beginning of the chapter about our review process, how many members of the Committee reviewed each section, so I think that the only parts that can be combined, so this makes this issue tough, are those protocols that Jay reviewed that were reviewed by somebody else as well. It doesn't mean he doesn't go in the report. That is not what I am saying. What you may need to do is say what the committee did, and one committee member did something differently. Then try to talk about the two different issues, because I think that Ruth's last point is very telling. If your ratings, if you can't make an assumption that the way you arrived at rating was roughly the same in every review, then it seems to me that you are not saying anything. CHAIRPERSON FADEN: Unless you do what I think was suggested earlier, which I can't remember by whom, that Jay's analysis be embedded in the part of our analysis that talks about the informed consent process, which is what Jay focused on. MS. KING: But Ruth just said undermines that as well, because what she just -- her last statement was, unless I misheard, her last statement was if we had looked only at the informed consent, we would have, we might have. So I think that that is what triggered me. DR. MACKLIN: Pat is right because we don't have an overall rating of four, three, four or five for the informed consent process alone. It is not as if our process enabled us to give a number to the first part, a number to the second part. CHAIRPERSON FADEN: But there are different ways to -- I would like to let Jay talk, but there are different ways to incorporate Jay's work, not all of which require the statistical treatment. Jay has done a wonderful job of invoking the kinds of problems in the consent process that we have identified as a collective committee as well. That part certainly, I mean one option is to pull in that qualitative discussion that Jay has. Where we talk about confusion in terms of research and treatment say that Professor Katz in his review similarly found such problems and here are examples he -- I don't know. I'm just suggesting there are other ways to combine this rather than having side by side pie charts if the side by side pie charts are misleading. Let's get Jay in. DR. KATZ: I don't know. Yesterday and today I'm always picking up on what Pat is saying. Because I think Pat raises the fundamental question, should the two reviews be combined or not. There's a long history, but no need to get into it as to why these turned out to be two separate reports. I think ultimately, it became necessary. Before we even think about combining them, I think after reflecting about both reports, it might be better to take a look at the report of the chapter report, and ask ourselves the question how satisfied are we with that report by and large. Because if we are by and large satisfied with it, it doesn't make any sense to combine my report and the Committee's report, because my report -- and that's one thing I discussed with Ruth two or three weeks ago over the telephone, I thought that the tenor of the chapter differs significantly from the tenor of my report to you. Which tenor do we want to adopt? I would not want, personally, though anything you may want to use from my report is as far as I'm concerned, Committee property and they can use it. The way in which they may use it may still not satisfy me and I have to go further than that. So that's really not the point. I really don't want my report to be copyrighted. It is the Committee's property. But I think we first have to look at the Committee report, I think, and see how satisfied we are, and then go on and maybe raise questions about the way I see the issues. As you know, I said that in the other comment, I would not like these two things become sort of be combined in a form that leaves you sort of a middle ground. Is goulash all right? So that's the only comment that I have. CHAIRPERSON FADEN: I think your point is well taken. How different do people think the two documents are in tone or tenor or whatever, and how satisfied are we with the tone or tenor of either or both? I think that's very important. It is open. Somebody comment. Help. MS. KING: To make sure we get the process straight, I think it would be useful, I agree with Jay. I think it would be useful to start with the draft Committee Report. CHAIRPERSON FADEN: Okay. MS. KING: The issue that is open is, when we explain what we did in that chapter, whether we have an additional paragraph that says Professor Katz conducted an independent study, and then describe what he did, and then as we go through, describing what was found. The second issue, procedural question becomes, to what extent do we highlight the similarities and the differences between what the Committee concludes and what Jay concludes. Should that only be in the findings or should that -- this is a third procedural point, should that be in the conclusions as well? This is anticipating a discussion for this afternoon. One of the ways to do it of course is to always identify a separate view clearly. The fact that there are two tones, and I would agree, I find the tones different, that that is a way to account for the two tones and not try to meld them. I think that we undermine the Committee's work by trying to fold in Jay's work and undermine it in a way, because we tried to have some constraints in terms of checks and double checks within the Committee operating that you can't necessarily say operated outside of that process. CHAIRPERSON FADEN: Let's have it up. I've got Ruth. I'm going to start to take a list. I'm looking for hands. Ruth, Nancy. DR. MACKLIN: I would certainly be prepared to strengthen the severity of the tone of the Committee's. Increase the severity of the tone of the Committee's report on the informed consent conclusions, since our general tone is a combination of both, our look at the process, the IRB, et cetera. I think the biggest difference, quite frankly, in Jay's and the Committee's report is not so much of a tone. Jay has a word like "radical." We don't have "radical." I mean those words. But I think the biggest difference comes near the end where Jay talks about the Federal regulations are in need of "radical revision", that's the Federal regulations. That is, he's built in the conclusions here that we later address in the recommendations. Since Jay recommends a national body and we recommend, the Committee's report recommends a national body, I think we have to look hard at the differences in what is being proposed in Jay's and in the Committee's proposal for a national body, since that is a very big difference. CHAIRPERSON FADEN: Okay. I have Nancy. There's a proposal on the table which goes to the procedural point that we focus on our chapter first, our collective chapter in its own right and by contrast. Ruth has put on the table that she would support strengthening the criticisms of the informed consent dimension of the Committee's review in the Committee's chapter, with whatever implications that has for incorporating or combining with Jay's or not. Nancy. DR. OLEINICK: I think what we have to aim for is clarity of presentation of the results of this study. It seems to me that it would be clearer to try wherever possible, to incorporate what Jay has found into the body of the report. Otherwise, you have two separate reports. Then have to have a third chapter in which you are discussing the differences and similarities of the two, and what one can make of them. I would like to see it all in one. I agree with Ruth that the biggest difference is in the recommendation that falls out. The chapter that is the Committee study doesn't really deal with the whole question of recommendations. That has been saved for recommendations. So if we pulled out of Jay's chapter the whole question of recommendations and leave them for later, then I think it can be melded. CHAIRPERSON FADEN: Jay. DR. KATZ: Could I just, from my perspective clarify something that Nancy raises. This is not a report in its present form. That if I have to write something separate, that I would plan and would even ask you to incorporate in the final report. This is a report to you. I combined some things that goes to the recommendations section to the chapter section, in order to inform you. CHAIRPERSON FADEN: For this discussion. DR. KATZ: For this discussion of where I was coming from. Depending on how this chapter ultimately will look and also I have of course problems, as you can imagine, with some of the findings and recommendations in the light of my report, I may have, as I said, to write a concurring dissent or something like that, or may not have to. But that will be much briefer and that will be much shorter. This is not what I would want us to include in the final report. CHAIRPERSON FADEN: That's helpful. So we should understand this as a report to the Committee of where Jay's findings are. So sort of separating conclusions, this is not one integral document that stands or falls. I have got Pat. MS. KING: The only point that I wanted to make and I found the pages, is this like the subject interview, constitutes "a study" that the Committee undertook. In the study, we outline our methodology. CHAIRPERSON FADEN: That is correct. MS. KING: This is in my mind, a soft study, in the sense that everybody worked hard on the forms and developing it and everything. But everybody reviewed out of their own framework. Then there was a check on that by how we match people up and then how you coordinated your individual reviews at the end. My concern is, and people are going to talk about what we did in terms of our findings, how good was the methodology, et cetera. But I am comfortable with the methodology. We did what we needed to do to get what we wanted to do. What I am worried about it undermining that now, because when you review what comes out of this, I think it is acceptable to say that one person on the committee reviewed all of the things separately and reached a different conclusion. I don't like mixing a lot of this because I think you undermine what you say you did in getting to the information that we want to articulate. I want to make clear that that is my concern. CHAIRPERSON FADEN: I understand. MS. KING: I am not taking a point on the other parts. That part of the report on six and seven, pages six and seven that concern me. CHAIRPERSON FADEN: Of the Committee chapter? MS. KING: The Committee chapter, that I am concerned about. CHAIRPERSON FADEN: Eli. DR. GLATSTEIN: I found this whole exercise to be very educational. I did not anticipate nearly the degree of the problems that exist. But I think that the bulk of the problems can be restricted, not all of them, but the bulk of the problem I think can be restricted to a very specific type of study which we call the Phase I, where there is a great tendency not to explain the detail of what is really being sought, namely toxicity, because the dose is not known. The tendency is to grossly exaggerate the expectation for therapeutic benefit. This, I think, if there's some way of getting the investigators together to point it out to them, I think most of them would actually, I think most of them would respond in a favorable way. I don't think the guys know what they are doing. I think they are actually so concerned with -- and Jay points it out -- the patients aren't being invited to participate. They are being recruited. That's the word that he used. I think that is the right word. There is such an emphasis on recruiting patients to this study that some of these things are being sold like used cars. I don't believe the investigators realize they are doing it. CHAIRPERSON FADEN: Can I ask you, Eli, what your general sense is of the tone, or whatever the message of the chapter as it is written? Are you comfortable with it? Would you strengthen it? Would you qualify it? I'd like to hear from everybody on that. DR. GLATSTEIN: I'm content with the tone of the chapter. I think Jay's stuff needs to be folded-in in some way, either by a separate document or just included as a study within a study. I think that we have to be sure that we all agree on the recommendations we want to make on this. CHAIRPERSON FADEN: Right. That we will be talking about shortly. DR. GLATSTEIN: That I think is the key. CHAIRPERSON FADEN: We will get to the recommendations shortly. But right now I am trying to surface reactions to the chapter so that we're down to the wire. We've got to know. Phil. I really would love to hear from everybody, if we could do that, because this is our document. Mary Ann. DR. RUSSELL: We have two studies that were done differently. They each have their value. They have to be interpreted separately. I don't think we can combine them because of what Pat said, the integrity of the process. However, they have to be juxtaposed, because they pertain to the same issues. Jay's work was additive. It added another dimension. I think we just need to either make it another part of the chapter or put it on behind it or in front of it or in some way juxtapose it so that the reader sees Study I and then Study II, conclusions from one, conclusions from the other, and then goes on to the recommendations. I do not think we can meld the studies and mix the text. I think they have to be totally separate. CHAIRPERSON FADEN: What about your reactions to the Committee chapter? Are you generally comfortable with it? That is what I am going to ask of everybody. Are you generally comfortable, or there is stuff you want to see changed or added? Thank you, Phil. Mary Ann. DR. STEVENSON: I think actually for me the findings of the chapter are actually there, but I think that the prose in the summary is so unfocused and qualified that in fact the tone becomes very reticent. What I ended up doing is redlining about 50 percent of the summary and just making statements and forget the qualifiers. Don't apologize for the IRBs. I mean, let's just say what we're going to say. So I think it is there, but it is obscured by all the excess prose. CHAIRPERSON FADEN: So you would like to see it strengthened? DR. STEVENSON: The way I strengthened it was just actually getting rid of 50 percent of the verbiage, because I think it's there, but it's watered down by qualifiers and explanations that are unnecessary. So in essence, yes. I think it should be strengthened. But I don't think it takes a lot of work to strengthen it. It's getting rid of qualifiers. CHAIRPERSON FADEN: And you have got it marked up? DR. STEVENSON: Yes. DR. KATZ: Can I just add something for one second to this, because that also compelled me to really, maybe it's bad and maybe it's good, but I literally spent three, four, five hours on each protocol and consent form, reading it and re- reading it, and going through the protocol and going to the consent form to really figure out what it was all about as best as one can in their problems. But I did it also in part after I read the summary. To me, I don't know whether Mary Ann will agree with me. The problem with the summary at the moment is, that it reminded me, I think I mentioned it to one or two of you, of Heisenberg's uncertainty principle that you could know the speed of the electron or the position of the electron, but not both at the same time. That one paragraph, I was somewhere. Then the next paragraph I was in a different dimension. When I focused on the position, then I was off again. Maybe that can be rectified. CHAIRPERSON FADEN: It's easily rectified. It's a matter of how strongly and with what we want to say things. I have got Henry and Pat. DR. ROYAL: I think the chapter would be strengthened and should be strengthened. So I agree with including Jay's material. I don't that it can be melded. I mean I think there has to be a section probably that Jay writes. I mean, I think that the real strength in Jay's writing is not the statistical analysis, if we don't combine the two. CHAIRPERSON FADEN: We don't need it, yes. DR. ROYAL: That that's no great loss. But his qualitative analysis I think is very important. CHAIRPERSON FADEN: Yes. I agree too about that. I think that's provocative language and the examples that Jay selected are very powerful. DR. ROYAL: Just one other comment about the tone. One of the things that I liked about the tone of this chapter is when it describes human radiation experiments. It actually defines them as any federally funded or performed investigation where the exposure of human subjects to ionizing radiation is an element of their research design. A very interesting alternative to a human radiation experiment. CHAIRPERSON FADEN: That's good. DR. ROYAL: I think that's a much better description of what a human radiation experiment is. CHAIRPERSON FADEN: Can I take it as we go around that when people say strengthen, that the force of that is that the summary ends up reading more straight forwardly critical? I want everybody to understand that that is what will happen. MS. KING: Straight forwardly critical of documentation? CHAIRPERSON FADEN: Of what we found. Critical that what we found is -- MS. KING: I am next on the list right? CHAIRPERSON FADEN: Yes. You are next. You go ahead. MS. KING: What my problem was was before I got to the summary. I'll point to two where I think this could be a question of the way it was written or it could be a question of issues of more substantive import. Page 20, for example, when we talk about voluntariness. One of the things as I understand that we found were that documentation about procedures was a problem in terms of review. But when we start at the bottom of page 20, one problem of voluntariness is that of undue inducements. We all know that. We thought that this was particularly critical and proposes a complex and greater than minimal risk research that offered the prospect of benefit to subjects. Then we give an example in a non-therapeutic neuroscience study involving former cocaine addicts still in treatment, the level of compensation was 100 dollars a day. This was thought to be inappropriate and potentially coercive. I mean, it does not strike me without more that it is potentially coercive or inappropriate. So either this requires an explanation. And this feeds into something that is worrying me about the study. That is, undue inducements is a big issue, what it means in research in many contexts. It is a big issue because now it is clear what we mean by coercion, because people have different views about specifics about coercion. So when we use an example, minimally if we don't explain why we think this is inappropriate and potentially coercive, I think we have a problem. But there would be a second problem. This is what is worrying me about the points I made earlier about methodology. That is, when we conclude coercive and inappropriate, that is a judgement call about what you see here. I really think that we have to be careful about these judgement calls. This is when the study starts to look less -- I'm not saying the Committee can't have a judgement. I hope we do have judgements. But what it means is that how you reach that judgment I think has to be more clearly specified. The other example that I had was the emergency room situation about obtaining consent in an emergency room. Anybody who has done this research, we know that emergency room consent is a major major issue in biomedical research. What we did here was talk about -- this is page 21 -- what I had trouble with was it does not surprise me if we take a look at documentation about consent forms in this context, that we would see problems. But what this doesn't present here is, one of the problems of the emergency room context. Again, we have made a judgement, I think, without specifying something that is enormously controversial. I don't know what we're doing here. I read this again carefully. I kept saying if we're just troubled by it that's one thing. This is the bottom of page 21, Ruth. If we're just troubled by it and the consent procedures in the emergency room, I don't have any problem with that. What ways we are troubled, why we are troubled, and why we found this study is problematic is what I kept looking for. I found that that was not spelled out in enough detail. I don't know how I would react if I saw it spelled out in greater detail, but I know I kept saying, how can we make these conclusions with respect to these instances. So what I am concerned about is tightening up not the summary, because I think the summary will flow from the middle part, it was tightening up and being very careful in the middle part, when we reach these conclusions from the data, from the reviews about what we draw out of the problem spots and why. CHAIRPERSON FADEN: Henry. DR. ROYAL: One thing about the inducements that struck me was I noticed in the SIS study we paid people 25 dollars for an hour. Here we are complaining about someone paying someone 100 dollars for a day. One of the justifications in the SIS study presumably is parking and transportation. But it is unclear with this cocaine study whether it was reimbursement of expenses or whether or not it was a -- DR. MACKLIN: You can't obviously, it would require more time and more -- I'm sorry, I spoke out of turn. DR. ROYAL: I'm agreeing with Pat that this needs to be fleshed out. Exactly what is troubling us -- DR. MACKLIN: But you can't just compare the 100 with the 25. I mean, Eli and I reviewed this protocol. These were people in a rehabilitation treatment center. They didn't have to go anywhere. They didn't have to park. They didn't have to drive. They were there and they had nothing -- DR. ROYAL: Ruth, you can't tell that from what is written here. I'm telling you that someone who reads this is going to say -- DR. MACKLIN: Is going to say 100 dollars is not a big deal, what are you fussing over. DR. ROYAL: Plus we paid someone 25 dollars for an hour. DR. KATZ: What's surprising that that's the same study. I didn't refer to it, but that's the same study. The real question I had about was the inducement of being given cocaine. Wasn't that in that study? DR. MACKLIN: Yes. They injected it into the brain. DR. KATZ: Why wasn't that mentioned rather than the money? I mean it also gave the money for future purchases, but - - CHAIRPERSON FADEN: I think the main point here is that that section needs to be, from my point of view, that section needs to be revised, not so much to clarify that example, but to emphasize that it was very, very difficult to make any judgements about voluntariness from the documents. That is the real concern that came out of our review. The key point is that if IRBs don't have any more information than we have when they are charged with looking at questions of voluntariness, they are not very well positioned, based on our experience, to make that assessment, because the IRB materials and the research proposals generally are not illuminating on the questions that you would like to see addressed on issues of voluntariness. That is the core issue. We did have this one, and we can explicate it. But I think we have to rewrite that section, in my mind, to emphasize that that's the major finding we had on the voluntariness question. The reason we didn't have more examples is because by and large we didn't have any evidence that would speak one way or the other. The example that is in there that is a good example was an exception in the other direction, where there was careful attention paid to issues of voluntariness in a context in this case of recruiting employees. So there was a concern to communicate your job is not at stake and things of that sort. It was done quite well. But my own sense in that section, so the failure there is in part, Henry and Pat are quite right. The example on its own is not persuasive. But it's a kind of second level message. The real message is look, we couldn't make much out of whether these people were consenting voluntarily or not from the information that was provided. MS. KING: I couldn't agree with you more, Ruth. I would say in addition that even though we note here the limitations in the methodology, being that this is a review of documents, that is not only not reflected in this section in the way we write about it, it is not reflected in the other sections as well. The fact that you only read documents in terms of making an assessment is a general limitation that I think needs to be repeated in most of the sections. CHAIRPERSON FADEN: I think we have to be careful here, because what I am hearing from Mary Ann is stop all the qualifying in the summary, where there is a lot of qualifying about this is only from documents. This is only from documents. Now I am hearing you say, remind everybody it's only from documents. MS. KING: I was awaiting my turn to speak after Mary Ann, because I did disagree with her. I disagree with her because I think a documents review is a documents review. One of the things we don't want to lose sight of on almost every issue is that when we talk about consent forms, we are really concerned about the process of consent. When we review a consent document, we review the document. So what we have to say about consent, for example, is in fact qualified by the fact that we only see certain things present or absent from documents. But I agree with Mary Ann, and maybe this is where we are in agreement, that there are in the summary, the summary kind of goes blururururururur all over like this. She and I agree with that. When I say it wavers back and forth, I will give you some examples. My problem was that -- well, this is a specification. It says the system is not working as it should. That bothered me because as it should is a comparative. It should be clearer. But it says perhaps an alternative mechanism should be developed. That is when you started to go -- the summary seemed to go in a wavy fashion. I didn't think we disagreed about that. DR. STEVENSON: I don't have any problem. My concerns were not about apologizing for documents or no documents. I think we should say what we did and how we did it and what its limitations are. My problems were once we established that, say what you are going to say. That is where I felt -- CHAIRPERSON FADEN: Okay. That's fine. I think we can do both. I have a need. We have to do something like the following. The point that Pat just raised that the system is not working as it should. That is a critical phrase. It is a finding phrase. We are going to get to it in findings. We are either going to like that phrase or we are going to not like that phrase. We are going to come up with some other phrase. If we do, it's got to go back into this chapter. So that's going to change. I am concerned about time. We were going to go on to the joint -- the chapter that sort of responds to both. Do we have enough of a sense of this chapter? Has everybody commented? Duncan, would you comment on your general sense of this chapter? We need to hear from everybody. DR. THOMAS: I think the conclusions can be strengthened, qualifiers removed. I don't see that, at least until we get to recommendations, that Jay and the rest of us are all that far apart. Jay has some excellent language, in particular, the section of his report where he talks about the specific problems. He enumerates five classes of problems, each of them illustrated with specific examples, which I think we could all of us sign onto. I would like to take ownership of that piece if Jay is willing to sell it to us. CHAIRPERSON FADEN: I sounds to me something like the following, in a rush to get to the other agenda items. Is I think the summary description of the findings of the contemporary period is where we can get clear on what our voice is on this issue. It sounds as if the Committee chapter, the view is that the Committee chapter basically is okay. The conclusions need to be strengthened. The methodological qualifiers made plain, but then the interpretation more straight forward and more critical. That we would like to incorporate a part of Jay's work, if Jay is agreeable, clearly identified as Jay's work, demarcate it and separate in the chapter in some fashion so that the reader has benefit of the collective review. Then Jay's review as well. But not the conclusions and the recommendations part. That's a separate debate. Is that agreeable to you, Jay? DR. KATZ: With one amendment, I mean possible amendment. It's perfectly all right with me for me not to be identified separately on anything and everything that the Committee wishes to own. I don't have in this respect any type of ownership. I am a member of this Committee. I only need to be identified, although I will not object to that, the work that I have done only is an expression of the work all of us have done in the past year. It has been hard work. So the only thing I really would like to be identified by personally is if it's the Committee pleasure, if it adopts the national human experimentation board in one way or another, I wish I could be identified, because I have argued for that since 1974. That's the only thing. But I just want to say about the rest of it, I don't need to be identified. CHAIRPERSON FADEN: Pat. MS. KING: Ruth, this is a question. Would it be appropriate for this chapter as opposed to the meld chapter, as an organizing principle to have the major conclusion the one you stated for voluntariness? By that I mean that the principle point that we draw from here is that based on documents there are certain critical issues, voluntariness, the use of the term treatment, that based on our review of the document and issues we could not respond to in all of those areas, that no IRB could really give adequate review, and no agency could monitor and find out, have a clue about what was going on because of the inadequacy of the document. I am looking for an organizing principle. I actually think that is the organizing principle for this chapter. If we disagree with that, we need to know because that is leading me into the recommendations from what I think about -- CHAIRPERSON FADEN: I think the disagreement that I have with you, Pat, is I think that is not an organizing principle. But that is one of the major conclusions of the RPR. But it is not the only one. MS. KING: Well, what would the other conclusions be? CHAIRPERSON FADEN: We have very substantive criticisms or conclusions, let me step back, that lead to criticisms about informed consent, and about the use of subjects who are not competent without proper authorization, or would appear to be not. MS. KING: But that's a document. CHAIRPERSON FADEN: But Pat, there are differences. There are two different problems with the documents. One set of problems we identified, and we tried to distinguish that in the report, but it did not come through. One set of problems with the documents is that the documents were silent on certain important issues. The two key ones being voluntariness and subject selection, which we believe are very important to the ethics of research. You are supposed to be assured that voluntariness, that there is voluntariness and that the subjects are neither under-represented or exploited or all that stuff. What we found was the documents were by and large silent on those two topics. There is another issue which is the consent, the adequacy of the disclosure in the consent form, about which the document is the issue. There we have the document. The document was revealing. We evaluated the document against the information in the full grant proposal and often found the document wanting. That is not an issue about inadequate documents. It's an issue about jobs not being done right. Now the next leap is from there to what can you say about the whole informed consent process that we had a whole bunch of bad consent forms. Bad for different reasons. That's where the subtlety comes in. But that is a different kind of problem from saying that the IRB materials didn't give us anything to work with. We always had the consent form and we always had the grant proposal, almost always. So we could look at the two and say against what the investigator says in his or her application, is what the investigator is saying on the form to the subject straight and adequate. There we reach some judgements. There, that's it. That's a basis for stopping. The next order question is did the investigators supplement the information in individual exchange. That of course we can not speak to. But we have the consent forms. We maybe have to make it plainer. We tried to separate in the chapter those two things. Where we had concerns about what we saw, and where we didn't have anything to look at. It's very important that we somehow find a better way of making it plain. So our concerns about the consent stuff are substantive, not gee, we don't know what is going on out there. They presumably suggest something about what's happening between investigators and subjects, although not necessarily. I mean, we don't know whether subjects are being told more or less than what is in these forms. All we have are forms. That is a limitation, but the forms are telling in many circumstances. DR. MACKLIN: But it may be useful, I mean when we say all we have are forms, and when Pat said before, well we only looked at documents. One way to think about this is what is available to the IRB that was not available to us. Now the only thing that is available to the IRB, certainly not running out and watching the informed consent process, what is available is the presence of the investigator to answer certain questions. There I think we have to make an inference about the kinds of questions an investigator can answer in advance, or maybe answer in a forthcoming way. I mean it is certainly possible that if some things are missing, the investigator can answer. For example, how are subjects going to be recruited into this experiment? If that's not in the document, in the IRB, that's surely a question that someone can ask and will ask in the IRB. But on the other hand, the question, the thing that you posed about the undue inducement and whether 100 dollars is too much and all that stuff, that you are only are going to get from the documents. MS. KING: I am glad Ruth Macklin spoke, because it helped me because I was trying to think and listen at the same time. Maybe I stated my point inadequately, because I am always trying to connect things to recommendations. I think the point, and Ruth helped me, the point is that based on review of documents, and this is what I am going to keep saying, because that's what we did -- documents, we conclude that on the documents that the IRB, so it doesn't matter whether it's absent or there, that the IRBs in our view don't have what they need to make the kinds of judgements we expect them to make. CHAIRPERSON FADEN: In two arenas. MS. KING: In two arenas. The second point is, there is not a sense of review in monitoring process. Anything that you would recommend can only take two forms. It's essentially going to be, if you are a regulatory agency, you are going to review documents or you are actually going to try to do something to watch processes. Typically, it is going to be a review of documents in the limited sample about processes. It means the second thing that we care about. That is, that monitoring the system to figure out how the system is working also can't go on as well. It doesn't mean that the documents were correct. The system is operating right, by the way. But it does mean that you can't get any clue if the documentation itself is inadequate. Those were the points that I was trying to state before. Those are the things I think organize the chapter, but they emphasize that we understand the limit of documents themselves. I am worried about the fact that this report gives a great deal of emphasis to the documents reflecting consent, as it should. On the other hand, the subtle implication of that, that has been widely communicated is, it's more important to get the damn document straight than to actually figure out what the subjects themselves understand. So this is a very subtle set of messages that are going on here. We do want the documents straight. But I don't want to fall in the same trap that a lot of other groups have fallen into, about giving over-emphasis to the documents. CHAIRPERSON FADEN: We don't want the message to be clean up your consent forms and everything is fine. MS. KING: Right. CHAIRPERSON FADEN: I agree with you. MS. KING: So I am trying to think about the way you organize the chapter so we get to these endpoints, because it's those two endpoints that we want to make recommendations about. CHAIRPERSON FADEN: Phil and Jay and Mary Ann. DR. RUSSELL: Jay's data shows some evidence of clustering that there are more problematic protocols in the area of Phase I trials of treatment for carcinoma. The document implies but doesn't state that there were problems across all of the areas where we drew the performance problem. We went to great pains to get distribution across agencies and across intra-mural extra-mural. Yet the document is fairly silent on do these problems cluster at all. CHAIRPERSON FADEN: And they did not. DR. RUSSELL: They did not. That should be very explicitly stated that they did not cluster. That there were fours and fives in all the agencies and up and down and so forth. CHAIRPERSON FADEN: They didn't in any real importance. DR. RUSSELL: I think that is important though. CHAIRPERSON FADEN: Jay, you happen to be next. DR. KATZ: I thought so. CHAIRPERSON FADEN: It means that we can't point a finger and say it's the intramural system, it's the extramural system, it's universities. It's whatever. There were some more in one, more in the other, but we can't say one group has got it right in every respect and one group is screwing up in every respect, or that cardiologists have got it right and the oncologists have got it wrong. It was also by specialty. It didn't fold out so that you'd say one group is really -- and that we should emphasize. That these are system- wide difficulties. DR. RUSSELL: Maybe a little worse in one area or another but they certainly are system-wide. CHAIRPERSON FADEN: Exactly. But not in a way that you'd say we have identified a target group and everybody else is doing fine. That is an important message that again, all these things we need to organize the chapter, have to get the key points out. The same for the SIS. Jay. DR. KATZ: Just very briefly. Pat made an important observation. Of course as I tried to say, as we tried to say in the Committee report, you only have documents available. The charge is often made and it's made repeatedly when my work is discussed, you don't know what went on in the actual oral interchange. I addressed it briefly, but you can never answer that question because we don't know. But the point is, the way I categorize these studies, when we talk about randomized clinical trials and two arms that have significantly different implications for the patient subject, if nothing is mentioned about this, passed over in silence in the informed consent form, I think that tells us something. The same thing also with the problematics of the Phase I studies and the other categories I am talking about, and also the discrepancy that I also highlighted between what IRBs know and what patients know. The twain at times never met. So I think one can not say anything with absolute certainty about these documents, but they have a certain, if one examines them closely, they have a certain amount of persuasive power about what is not documented in forms that we want the IRBs to carefully review and they spend too much time on them to begin with, because the result doesn't justify the time spent. So let me stop. CHAIRPERSON FADEN: We have Mary Ann and Eli and then perhaps we can go to the combined chapter before lunch, which would keep us on schedule. Then we could go to findings, which would be really exciting. Like this is intrinsic, an end in itself. Being on schedule is valued merely because it is valued when you are chair of a committee. It becomes its own thing. Mary Ann. DR. STEVENSON: Yes. Just picking up on Pat's comment. The SIS study showed that the quantity and quality of the consent documents don't necessarily affect the attitude of the subjects towards the research process. So the subsectional regulation of the documents may still fall short of the goal that we're trying to reach in that process. I guess we do end up commenting on that in the next chapter. CHAIRPERSON FADEN: And one of the things I think -- that's right, it's in the next chapter -- we also have to do a better job of is pointing perhaps at how circular this is in so far as the consent forms end up being not particularly relevant, not well organized, not hitting the high points. That encourages people from not paying attention to them. I mean it sort of all feeds into itself. As long as there's sort of legalistic documents that detail a whole bunch or risk, isolated independent risks without context, without meaning, who would look at them? It doesn't serve the sort of ethics considerations they are intended to serve. It doesn't educate. So I think in a way, it's not as disparate as it sounds. Part of why maybe people don't look at them and don't value them is because of the fact that they aren't very helpful. They don't touch the really important issues that a patient would care about, rather than the lawyer for the hospital cares about. DR. GLATSTEIN: That is exactly right. I think that needs to be emphasized, that all these consent forms these days go through the attorney's office, which complicates it even more. It makes it very difficult to have a direct simple conversation with a patient that reveals. Everything is obfuscated. At the same time, I want to call the attention, I think the report needs to call attention that some of the consents are really excellent. We're not saying that. But some of them were. CHAIRPERSON FADEN: We do say it. We should say it more strongly. Okay. We will say it more strongly. I mean the point -- and that's an important message, I think, because what it says is, and Jay says it in his real well. It can be done. DR. GLATSTEIN: That's right. Everybody isn't off the track. CHAIRPERSON FADEN: And it can be done. It's not like we're asking for people to do something that is not humanly possible to accomplish. DR. GLATSTEIN: That's right. CHAIRPERSON FADEN: And that's very much more sellable than saying nobody got it right, which suggests that maybe it can't be accomplished in an effective manner. MS. KING: There's a second thought here. The requirements of a monitoring process may be different than the requirements of a process in which you really want informed patients. That is the point we want to make. There is a little bit of war going on here. I mean the reason we have informed consent documents primarily is a legal one. This is what Eli is saying. CHAIRPERSON FADEN: The documents? MS. KING: The documents. That is the regulatory function. Now the documents for some patients are also, even the best documents, for some patient subjects have another function. Some patient subjects like to read it. Some will absorb it. Some will be better informed. Some will be appreciative of having had something to refer to, to take it home, to do many other things. So the documents serve two purposes. In that sense, they work toward both ends. What we are worried about is getting an imbalance in the goals that we are -- and this is what we should be saying. What we are worried about is trying to maintain some equivalence between our goals so that we serve both. I think what we are now saying is that -- what we're worried about, not saying -- is that the consent process to some extent veers too much in the direction of the regulators and less in the direction of serving patients. Ruth said it better than I did. But it's the tension between the two ends that we should document, because there are two things going on here. The beauty of this section of the report, maybe we should turn to Chapter 17 -- CHAIRPERSON FADEN: We are ready to. MS. KING: Is that we look at a regulatory aspect and we look at documents to a large extent, we look at patients when we looked at the survey, and at the interview sample to a large extent. The real beauty is that we have an opportunity now from looking hard in both directions, to see what implications that has for us when we take a look at it. One of them is the tension. There is a tension between these two that we recognize, tried to separate and bring it back together. I don't think people think of it that way often. CHAIRPERSON FADEN: That was a lovely segu‚ thank you, into Chapter 17. DR. STEVENSON: The pie graphs on 12 and 13 are inaccurate. They don't jive with the numbers in the text and I think they are presented in a confusing way. Easy to fix, but need to be done. CHAIRPERSON FADEN: They weren't. That's quite right. Thank you. You know what that is? It's a testament to your careful reading. It's so validating. We are such an anal committee, it's so exciting to have a bunch of colleagues all of whom are equally. MS. NORRIS: May I make one more along that line? CHAIRPERSON FADEN: Of course. MS. NORRIS: I find the bar graph extremely confusing because of the three-dimensional qualities. CHAIRPERSON FADEN: So we'll fix that all up. We should acknowledge the hard work of our staff members in putting this together. This all looks like it just comes out of air, but it does not. It comes out of people's weekends and evenings, as does the whole thing for all of us. Okay. We will have something to say, which is kind of nice. All right. Chapter 17, which Pat has just taken us right into, as obviously an underdeveloped document at this point. The first issue is do we need it. It sounds as if yes, we definitely need it. So what needs to be done to it to make it a good document? The floor is open. Ruth. DR. MACKLIN: I had a couple of comments and I hope some positive suggestions. The first paragraph describes the two studies briefly. Then the last sentence says direct comparisons of the results should therefore be avoided and the whole rest of the chapter makes direct comparisons. I would strike that sentence rather than try to avoid the direct comparisons. I mean I think it's evident what you say about the methodologies, et cetera. I think makes that point. My second comment is about on page three, trust and language I don't think belong in the same section. There are two issues. There's an overlapping issue because some of the language relates to the question of trust. But since language is a very important issue, I think it should be dealt with separately, and perhaps fleshed out a little bit, because we had a lot of things that dealt with language. I mean, the meaning of these different terms, experiment, treatment, et cetera, I think deserves a discussion of its own. I would disagree with the particular word that's proposed here, neutral word like intervention. I don't think that neutral word is a very clear word. It may be a weasel word to talk about intervention. So we may be able to come up with something a little bit better there. On the discussion of altruism, I mean there were a number of different discussions. Jay said something about it. We have discussed it all along. Whatever we say about altruism, I think the line, the sentence on line 7, that is a reason to participate even not a direct benefit in the same sense of others, it's not a benefit at all. I mean, a feeling of altruism that a subject gets may be a benefit to the subject. But altruism is not a benefit. Altruism is a motive or a reason. CHAIRPERSON FADEN: What line are you? DR. MACKLIN: On page 6, line 7. I mean I'm just trying to clean up some of the points that we should, because it gives a misleading impression that altruism might be listed among the benefits. It is only if someone actually feels some altruistic feelings. But a motive is different from the feelings. So that's my point there. I don't actually know where the discussion of language, just to go back a little bit. Trust and language. Many things in this chapter address the question of language. I'm not sure they all have to be in the same place, but I think we have to pull out what we want to say about language per se, and what we want to say about language under the different headings. CHAIRPERSON FADEN: Could I ask a question of the committee? I know Jay is waiting. But this is a general question about how to view this chapter. One conception of this chapter is to comment on -- is to provide an integration of the findings of the two chapters. Therefore, it would only discuss those findings or implications on which or from which there is something to say from both projects. So for example, the specific discussion about the fact that people have different meanings attached to the word experiment versus clinical investigation, that is a finding unique to the SIS. By one conception of this chapter, ought not to be repeated here because it is discussed in the SIS chapter. So one view is this is the chapter that tries to look at the intersection of the two chapters and works that way. Another conception is this is where we pull together what we want to say on the contemporary world, in which case we'll pull in anything important we want to comment on, including the work that Wilhelmine did for us, the chapter that we have reviewed but aren't discussing publicly, just because of time, but it's out there, on the status of agency oversight. So the issue is just first to get clear on which chapter this is. If this is just to pull the SIS and RPR overlap and comment on that and deal with on the one hand, it looks like consent forms don't matter. On the other hand, the chapter says consent forms are terrible, what's the Committee take on this. So which would we like it to be? Jay and then Pat. DR. KATZ: I was thinking about that. This chapter if it is kept here, it would need a lot of tidying up and work, though that could be done. But clearly, can we discuss even this chapter before we concluded our findings and the recommendations for the contemporary world, because in a certain sense, it also in part foreshadows what is coming there. It includes material that has already been discussed in the previous two chapters. So the question still is do we ultimately need it. We may need it. I have no opinion on the subject. But there's another thing involved here. This chapter in a certain sense also summarizes a chapter we haven't discussed. It's not on the agenda, namely, the review chapter on the common rule, which is the chapter before. CHAIRPERSON FADEN: Right. That's what I just meant. DR. KATZ: And I would say whenever it comes up, either it should be eliminated in its present form, and do anything that needs to be done in the appendix the federal regulations, current federal regulations need to be reprinted, because I find no analysis in that chapter at the moment. CHAIRPERSON FADEN: That chapter is not an analysis of the common rule or even about the common rule. DR. KATZ: What is it? CHAIRPERSON FADEN: It is a chapter about how the different agencies currently conduct oversight of research in human subjects. DR. KATZ: That's contained, that's set forth in the common rule regulations. CHAIRPERSON FADEN: No. It is not. No. Not at all. No. This is how each agency responds to its obligations to monitor its human subjects protection system. So it's an attempt to survey and then provide to the public how NIH does it, how the FDA does it, how Defense does it, how the VA does it and so on. Not the common rule, but rather do they audit, how many people do they have auditing, what do they look for, how frequently they do it. DR. KATZ: Then I misread that. But I guess I misread it also in part because one thing that is missing and of course I referred to it, and probably we can't do much about it, is an analysis of the current federal regulations. That is really in a certain sense too bad, but we didn't think of it, because it's a crucial issue on which good people can differ. CHAIRPERSON FADEN: What we do is we present it. So what we should indicate in that chapter is it's presented but not appraised or evaluated or analyzed in that chapter. It's not the Committee's critical appraisal of the common law. It's an entirely descriptive chapter. The common rule is here. Here is how the agencies implement their sense of duty under it. So we should make that clear, Jay. That's important. Because we wouldn't want to take it as either an endorsement or whatever. Pat. MS. KING: Having read the recommendations and the findings in this area, one of the things that struck -- and these chapters, one of the things that struck me was that the connections were not made clear between what we might recommend and what we found. So I found the need for a chapter like this one, that pulled together all of what we have looked at, because it's all what we know. What we have looked at with respect to the contemporary world, and to organize it in a form around some things. I'll come back to that in a minute. To organize it in a way that leads more clearly into the recommendations. I should say that I am not happy with some of the recommendations. So it may be that some others would disagree with my view about my views about the recommendations. Even if you do, it is my view that whatever recommendations we do agree to, need that integrating factor. My concern is that, and this is a chicken and the egg, I don't know how to organize this chapter. One possible way to organize it to get into recommendations is the way it is done here, by some themes like trust. But if we develop those themes like trust, for example, trust, if patients still trust their physicians, a lot of which we learned about and rely on them, then that plays into several recommendations, from education of physicians, and what are the kinds of things we need to know about. That is a little bit where you talk about language, because it means that how you communicate and what your understanding about going on is important. So one way to organize it is here. I don't think this is necessarily a bad way to organize. I can't actually assess it. Another way to organize it, and I take no pride of authorship because I thought about it as I was listening at the table, but as another possible direction with a lot of refinement, is to try to organize it by the goals of what we see the human subjects protection system to be. This goes back to that question that's not yet -- doesn't have any content. That phrase that doesn't have any content yet, which is, the system is not working as it should be, which Ruth alluded to earlier, that appears time and again in the documents and in the recommendation. It's not flushed out. Now if it's flushed out, if we have a sense of what the system should be, then we will have a sense of what goals we are trying to achieve. One way of organizing this material is around the goals that you are attempting to achieve. I can't give any kind of sense of which direction we should go in, because it depends on what we do with this, what this system -- it is not working in the way it should be, means yet. We need to discuss that. But I thought I would lay out the two possible ways of organizing some of the material. CHAIRPERSON FADEN: It sounds as if either way though, to get to the question I put to the Committee, and I'd like to hear what other people have to say, that the purpose of this chapter is to foreshadow and prepare the ground for the recommendations. So it is only -- as it happens, it will integrate the RPR and the SIS, but its real purpose is to foreshadow whatever recommendations provide the evidence for the Committee having made the recommendations that it is going to make. That is very helpful in terms of defining what the purpose of the chapter is. Is everybody in agreement about that, as to what the purpose should be? I have got Eli and Ruth. Oh, I'm sorry, Duncan. Duncan, Eli, and Ruth. DR. THOMAS: I agree completely with Pat. That should be the purpose of this chapter. The chapter at the moment does not do it. I was very disappointed by the chapter. I find it totally redundant. It didn't to me, accomplish any synthesizing purpose. There was nothing new here. Every point that was made here, although it was good and needed to be said, had already been said in the previous chapter. So for me, I didn't get any synthesizing material out of it. So I would ask myself do we really need it. The only reason I can see why we would need it would be to provide the justification for recommendations. The recommendations to some extent, the way we have structured them right now, do come with their own justification. By and large that justification could refer back to the two separate chapters quite effectively, without the need for this. If we are going to have this chapter, it has to be done well. CHAIRPERSON FADEN: That raises a very practical -- DR. THOMAS: If it can be done, I am all for it. But if it can't be done well, then let's not do it. CHAIRPERSON FADEN: So if worse comes to worse, we won't have it. I mean, if we can't pull out a really good one of these, we obviously won't do it. But your point is well taken. As it is written right now, it would not be worth publishing. Eli and then Ruth. DR. GLATSTEIN: Briefly, I just want to say I think that if it can be, as has been said, if it can be done well, I think it does serve a useful purpose. This is where Pat's crystallization of the tension between the legal regulatory function and the communicative process in language, excluding jargon, really should come to life. It should come to life in this chapter, already based on what we have learned from the other two. I think that that's at the heart of trying to address the issues of the documentation of the informed consent, that we're spending so much time on. I think this is where it honestly belongs. CHAIRPERSON FADEN: It seems to me also that this is the place where we make the case for why this approach, the approach that the two chapters represent for taking a look, an evaluative look at the human subjects system, is to be preferred over the paper auditing look. DR. GLATSTEIN: There is one other point I wanted to raise about the studies, the review study, review project, that I don't think we've talked about. I don't think it will take a great deal of discussion. But one of the repetitive problems that I saw was the business of the so-called cooperative study groups in a central conference room writing a protocol with a consent form being shipped out to a bunch of institutions that belong to that group, but then no ability to modify that consent form at the local level. I think that is an issue that from a standpoint of doing national studies, I think that has to be addressed in some form. We haven't talked about that, but I believe that that needs to be brought up there, because I don't know where else you can bring it up. CHAIRPERSON FADEN: Very good. Ruth. DR. MACKLIN: I'm now led to comment on something Eli said. But let me go back first to Pat's and Duncan's comment. I think Pat's suggestion is the one clear way to have this chapter go beyond the other two without redundancy. That is, to focus it and organize it around the protection of human subjects. That is, the purpose for which we have these regulations, the concerns that this Committee has, what we found to be the flaws. Done in that way, it won't be merely redundant, even though it will repeat some things. But the organizing principle here, the themes came kind of random. First you talk about this, then you talk about that, then you talk about another thing. But the way Pat is suggesting it, not only has the purpose of moving towards the recommendations, but also underscores the motivation for all this work, namely, the protection of human subjects in just those areas. So if those are the themes, or that is the organizing principle, I think it then has an analysis that goes beyond the repetition. CHAIRPERSON FADEN: And are we, just to make sure we're all reading from the same book here, by the goal, you are thinking about the standard way in which one presents the goals of human subject protections? DR. MACKLIN: Yes. Yes. I don't want to take the time now to go over them because we are bound to quibble a little, but I think that's the point here. It will also go directly to the concern, the interpretation and elucidation of the phrase that Pat is talking about here, that things are not working as they should. Why are they not working as they should? They are not adequately protecting human subjects. CHAIRPERSON FADEN: The whole chapter itself is set up then as the groundwork for the recommendation, for the finding. MS. KING: But the more important thing is that in the interest of protecting human subjects, the various ways in which we try to protect them, there is some tension among them. That is what Eli is talking about. I liked his example of the multi-center studies, because I sat in on some of those. Everybody thinks it is critical to have a standardized consent form. That's the lawyers talking. Don't deviate consent form. Use the same consent form every center across the country. No deviation. They are arguing from the need for standardization. DR. GLATSTEIN: They are afraid of a class action suit. MS. KING: And they say I am protecting subject this way because it's the regulatory focus on protection. Other people are saying, but I live in the part of the country where I need to be able to explain to subjects not quite this way, but that way. They are right too, because they are trying to protect their subjects in a different way, through a different route. It is the tensions that exist in our effort to protect that we use multiple pathways to achieve this overall goal. CHAIRPERSON FADEN: I don't know exactly how this is to be done, but it's looming larger and larger as an important task. That's helpful in a way. That on the one hand, you have got the organizing principle of the goals. Then there is also the means. One means is documentation and oversight. The other is communication and effectuation of the principles. We need to illustrate the tension between the means that are directed at achieving the goals and the means that are directed at documentation for purposes of oversight and legal regulatory. Something like that. DR. MACKLIN: There is one more point. I didn't quite finish. That's all right. This exchange actually adds to it. I have some uncertainty about when Eli said it doesn't leave any room for changing things at the local level, the way I think about that is for improving those pieces of garbage that -- DR. GLATSTEIN: I'm not arguing at all. DR. MACKLIN: Then what Pat said, that is changing at the local level means improving it. On the question of local variation, I don't even know what to say about that, Pat. I mean why should local or regional be so different. This really does go to the question that Jay has been pushing on whatever we are going to say about some national body. Because here we have the tension, and the current system is set up so that local IRBs make some kind of determination based on I don't know what difference in the local region. But at the same time, I can see this as leading to profound injustices or at least inconsistencies throughout the country in the way in which subjects are protected. DR. GLATSTEIN: Do you think that doesn't exist now? DR. MACKLIN: I think it does exist now. I think it does. I think it does exist now, but I guess I'm adding to what Ruth said, one more piece. That is problematic. That is, whatever the virtues are of leaving of the semi-autonomous IRBs, that is, not imposing consent forms et cetera, on all of them, there is also down side as in fact we saw in the RPRP when we had exactly the same protocol. But one site did it very well and the other site did it very badly. That is what concerns me about having the variation in the local IRB. That is can lead to just this sort of variation. MS. KING: Let me respond. I am not suggesting for some of the difficulties that Ruth points to, that this Committee ought to resolve that, ought to resolve the tensions that I am alluding to, because I think that resolution is difficult. I can actually think of examples where I might want variation at a local level, depending upon the nature of the subjects, the subject population that we're using in one location versus another. But I do think that the bigger point about there being tension between the different ways you try to protect patient subjects ought not be lost, because quite frankly, the legal regulatory side is winning. I mean the tensions are being resolved in one direction, in my view. So my only point here was that in calling attention to the tensions, that we need to remind the regulatory and legal people who have so much clout in the system that we don't want to lose sight of the forest for the trees. So that's more the purpose that I am trying to get. What I want subsequent groups to work on, Ruth, is thinking more clearly about these tensions and how to do something about it. Because I think that the question you just raised is the old issue of what is equality. You know, treat similar entities similarly. But then the big question that comes in, what are similar entities and what is similar treatment. That is the issue you are talking about when you are talking about local and variation versus consistency often. That is a tough, tough, tough question. CHAIRPERSON FADEN: Can I do this? I think it would be preferable from my point of view if we broke for lunch now, assuming we can break a little early. We just checked. Assuming that we've had enough discussion of Chapter 17, enough to know that it's got to be completely rewritten, which means that this will be one of the -- this will be the only document basically, that will be almost a whole cloth. So the plea will be for people please to read it very carefully and send back very detailed comments. We'll exchange them, everybody back and forth, because this is such a critical document on the one hand. On the other hand, it's got to be well done before the next Committee meeting. When you get it, if you could kick it to the top of your pile, that would be appreciated. Jay. DR. KATZ: Ruth, indulge me just for one minute. We might want to consider, and you might want to consider because I am referring to something in my report, that if we follow Pat's suggestion about talking about tensions, that really begin with the tensions that I address in the beginning of the chapter about investigators, what they are about, what they want to accomplish, the sincerity and dedication of their mission. Therefore, there have to be inherent tensions between the acquisition of knowledge on one side and the protection of subjects of research on the other. They are inevitable. Then we can go on to talk about what can we do to minimize and in what ways, these inherent tension in the human experimentation process. Because neither regulators have addressed this issue as efficiently, neither have we as physician scientists. CHAIRPERSON FADEN: I think that is a lovely way to start. It also pre-stages what we want to be saying about education and sets the larger context. I'm sorry. Henry. DR. ROYAL: I just wanted to add one thing to this concept of tension. It relates to the statement that the IRBs are not doing as good of a job as they should be or something to that effect, as if there is some adequate level that we are shooting for, and once you make it to that level you are okay. The thing I like about the tension idea is that it's not like there's this adequate level. It's that this whole process needs constant attention and constant care because these tensions exist. CHAIRPERSON FADEN: Right. That is very nicely put. DR. GLATSTEIN: I'd like to add one point to that. When you write these consent forms, and I usually write them, try to write them in as simple language as you can, then they almost always are viewed by the hospital attorney, whose looking at this not as a position of trying to protect the patient rights, but trying to protect the institution from liability. That is the tension. MS. KING: This calls forth something that is actually missing. All of our recommendations are addressed to the biomedical community. If you keep talking about -- I mean, I'm thinking about what he is talking about in the education part. We need to educate the lawyers too. DR. GLATSTEIN: Absolutely. CHAIRPERSON FADEN: They are in there. But we can put them in. They are in there as university officials and administrators. It's there, but believe me, I'm sure we should probably just call them lawyers, I agree. Let's do this. It's now 12:10, which is 20 minutes before we were supposed to break for lunch. So instead of coming back at 1:45, can we come back at 1:15? Is that okay? We will thank you. We'll come back at 1:15. We'll go right into findings and recommendations for the contemporary human subjects arena. (Whereupon, at 12:13 p.m., the proceedings were recessed, to reconvene at 1:24 p.m., this same day.) A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N 1:24 P.M. CHAIRPERSON FADEN: Would the committee please come to the table? Okay, let's see what he said. There you go. We're in complete agreement on restaurants if nothing else. Hopefully, other things. Can't do much better, right? Well, we've dispensed with the important thing, which is options for dinner. All right, we're going to start. (The proceedings went off the record for a brief recess.) CHAIRPERSON FADEN: All right, we're going to do findings and recommendations for the human subject protection world. So we need to pull out the findings chapter first, which is Chapter 18? Chapter 18. And there are not many findings which may, in and of itself, be worth discussing. Do we need more? They are to be found on page 17. There is a finding on intentional releases. We're going to do that tomorrow. So we're not looking -- we're staying with -- we were thinking contemporary human subjects research. We're going to stay with that today. So finding 15 will be discussed tomorrow on intentional releases. There are only two findings, and they are findings 16 and 17. And there was a correction, which is a minor correction. It's about what we want to say with respect to the percentage of research that appears to be minimal risk or a little less. But let's just take the two findings as we've got them: finding 16 on page 17 of the findings draft, and draft finding 17, which are pages 17 and 18. Let's start with 16. Okay, 16 is open for discussion. I feel like I'm auctioning. All right, do I hear one? Do I hear -- Jay? DR. KATZ: In 16, I have to refer to 17 too, is -- are at least as likely as other areas of research involving human subjects to conform to prevailing standards of research ethics. And the comparison is fine, but do they conform to prevailing standards, both of them conform to prevailing standards of research ethics? And it goes then to 17. It does not appear to be working as it should. I would put a period after working. That would be my recommendation. CHAIRPERSON FADEN: Let's get to 17 in just a minute. DR. KATZ: Yes. Yes, but they are sort of interrelated. CHAIRPERSON FADEN: I don't think so. The sense of 16 was intentionally ambiguous, the language, on how well, if at all, either are working. DR. KATZ: Yes, I see. CHAIRPERSON FADEN: But simply to say at least -- to be at least as likely as other areas without saying -- so they both could be working a little well or awfully, but it's the same or they're both working wonderfully and it's the same. Maybe there's better language. But the only thing that's intended to communicate here is based on the SIS and the RPR. There is certainly no indication that radiation research is causing more human subjects problem, and some indication that they may be -- that that field may be a little less problematic. DR. KATZ: Would you put the period after "subjects" in 16. CHAIRPERSON FADEN: Let's read it. "The Advisory Committee finds that today human -- appears to be at least as likely involving to do something, has to do something." DR. KATZ: Yes, you are right. It doesn't do anything. MS. KING: It seems to me the problem is not -- the problem is the word "research ethics" as opposed to -- what is it that they're to conform to? CHAIRPERSON FADEN: All right, let's change the -- MS. KING: Are they to conform to regulatory and one view is that they reform to regulatory requirements. There is a view of research ethics that's quite different and, in some ways, goes beyond what the regulations would require. So I think we have to discuss what it is that we thought we were asking them to conform to. The little text seems to indicate that we had regulatory and governmental policies in mind. And to my way of thinking, that's not necessarily -- with research ethics. CHAIRPERSON FADEN: All right. So the problem seems to be what we want to say -- this is about -- let me just step back. It's strong on both the SIS and the RPR. So we know in the SIS, there was also a comparison of radiation research with non- radiation research with the same absence of a finding of any difference. And that wasn't guided, the SIS, in any strict sense by the regs. We were looking for things like did people who were radiation subjects more likely than other subjects or less likely to say they had been coerced or forced into it or manipulated or, you know, it's drawing on more than just the RPR. But I'm -- whatever turn -- MS. KING: Well, I don't have any direction one way or the other. I'm just asking -- CHAIRPERSON FADEN: Right, right. MS. KING: -- what are we doing because research ethics is a broader, more ambiguous phrase than is regulatory and the regulatory structures. So whatever it is that we are comparing it to, I just think we need to be clear about it. CHAIRPERSON FADEN: I saw Ruth and Phil. DR. MACKLIN: Yes, I was just following on that point. The justification, I don't have a quarrel with the way the finding is worded. The justification talks about levels of review, more safeguards than levels of review. My question is are the safeguards and level of review, do they speak only to the risk levels, or do they speak to other things? I think we should specify what they -- what those layers of review -- CHAIRPERSON FADEN: What we have learned is that some of the radiation review committees look at the consent forms quite hard, not only on the level of risk. So it really is, and there is some institutional variation from what we've been able to learn in that. But it is not simply only the dose risk stuff that is subject to an additional level of review by radiation safety committees. But that would vary by institutions. We could certainly expand on that. Wait, I've got Phil. Patty, is this right on this point because I've got Phil, Henry -- MS. KING: Yes. We seem to be talking here about practices, in which case the -- should talk about practices. Do we review -- did both the -- did both studies of ours actually take a look at practices, and it's from an examination of practices that we conclude practices, with respect to human radiation research, appear to be no different than other practices? Is that a more accurate statement of what we looked at? CHAIRPERSON FADEN: Well, we looked at -- we looked at what we looked at. In the RPRP, we looked at the documents, which were not practices. They're documents submitted to the committees describing the risks and benefits and blah, blah, blah. In the SIS, we looked at how the subjects in different kinds of research feel about being research subjects. And what we heard was not different in the different groups. So it's not practices in either case. In one case, it's the perceptions of subjects. In the other case, it's the adequacy of documents and the apparent adequacy of the consent form. I've got Phil and Henry. DR. RUSSELL: The finding is much more grounded in the results of the proposal review. That's where it's explicit and was looked for explicitly in the study. CHAIRPERSON FADEN: It was looked at explicitly in both. The SIS -- DR. RUSSELL: It wasn't emphasized as well in -- CHAIRPERSON FADEN: It should have been. It should have been. I mean, the SIS was designed to make sure we had three comparison groups: radiation oncology and cardiology and medical oncology. So it was specifically set up to see if subjects in radiation oncology research were different from, and the issue was different from, other oncology people or alternatively different from people who aren't cancer patients. So it was set up with that -- you know, I don't mean to interrupt. But basically, it's both. In both, there were no differences except a slight hint in the RPRP that the radiation stuff looked a little better. DR. LEDERER: And also in the SIS, wasn't it, that the people who were in radiation -- CHAIRPERSON FADEN: A little bit. DR. LEDERER: -- oncology were slightly -- CHAIRPERSON FADEN: Slightly, yes. Yes. So I mean, that's why "that at least as" is in there to suggest that it might be more. But I think what we're struggling with is the latter part. We're all agreeing the finding is clear. Whatever it is, the human radiation world is doing at least as good as it on it. So what is it? DR. RUSSELL: We're struggling with what they conform to. MS. KING: Well, what we should -- what we should do is to say that -- what we did. If we're having this much trouble with the language -- CHAIRPERSON FADEN: Right. MS. KING: -- we should say the committee's review of documentation and study of perceptions of subjects indicate in these two areas, because we want to be specific -- it does indicate in those two areas, we couldn't discern a difference between -- or at least as likely as. That phrase is okay with me. CHAIRPERSON FADEN: It's intentional because it's communication in the direction. MS. KING: But we should say what we did, what we did. CHAIRPERSON FADEN: Okay. Can we say the Advisory Committee finds that the human radiation research reviewed by the committee appears to be at least as likely as other areas of research to have adequate documentation and consent forms, and they have positive reactions among its subjects, or something like that? And that would be very literal. MS. KING: That's what I was going to say. But it's a precise statement. We can't talk about everything because we didn't look at everything. We can't look at the whole world and say -- CHAIRPERSON FADEN: I don't know that this is the whole -- I mean, we can say that. That's literal. It's a little less exciting, but we can say it. So is that the preference, just change it and say that? Okay. So it will change "at least as likely as other areas of research involving human subjects." And then from that point on, to conform to prevailing standards of research ethics will be substituted by a description of the -- two phrases that capture the RPR and the SIS. Is that okay? MS. KING: If you need a jazzier statement, because I understand your concern about a jazzier statement, the central point of this is -- the question was is human radiation research different from all of the research of human subjects? Our conclusion is not that we can figure it out. If anything, human radiation looks better. CHAIRPERSON FADEN: Right. MS. KING: So you could say, you could have a broader statement that says, based on everything the committee looked at, which protects you or whatever, then human radiation research is not -- does not appear to be different -- CHAIRPERSON FADEN: Or is at least -- MS. KING: -- is at least -- well, is at least is is kind of -- well, maybe you just want to say as far as you see no reason to distinguish if, in any direction in the explanation, it might be better. I mean, that's -- I can't do words. I've never been able to craft words on the table. CHAIRPERSON FADEN: Okay. MS. KING: But that, to me -- CHAIRPERSON FADEN: Okay, so the alternative formulation is the Advisory Committee finds that based on its two projects, human radiation research appears to be no different than other areas of research involving human subjects with respect to practices or something. MS. KING: Something. We've got the general idea. CHAIRPERSON FADEN: Right, we'll try that one too. Henry? At least as -- you see, I like the at least as likely myself. DR. ROYAL: Well, why don't -- why can't you say it in the positive way like maybe more likely to -- CHAIRPERSON FADEN: I think that's over-reaching what we found. I mean, at least as likely -- DR. ROYAL: So at least as likely -- CHAIRPERSON FADEN: -- means it's surely as good, and the suggestion that it might be better, whereas -- right. Well, we're trying to communicate that we have some evidence to suggest that it might be -- DR. MACKLIN: As likely, if not more likely than. CHAIRPERSON FADEN: Okay. DR. MACKLIN: That accomplishes the positive tone. As likely, if not more likely than -- CHAIRPERSON FADEN: Right, that would be fine too. But then we're still stuck with what the "it" is. It is as likely, if not more likely, than other areas of research to have appropriate -- to have adequate practices with respect to human subjects. I mean, it's still -- you qualify it now with the "based on." I'll try to play with it. If worse comes to worse, the fall-back position is we stipulate the two studies and get the less jazzier statement. So we'll try for a jazzier versus literal, okay? And if we can't come up with a jazzy formulation, we'll do the literal formulation. Let's go to 17. Jay has a proposal already on 17 that we stopped the period after "working." Phil? DR. RUSSELL: Jay's proposal says that the whole system is not working. I don't believe the data supports that. I think the data indicates that the system, in some instances, works very, very well. We have a very complex and a very difficult and high at-risk protocols that, by the criteria we established, came out very well. So that indicates that a large number of the protocols reviewed came out very well. So it's kind of a is the glass half empty or half full issue. And since the issue of what the fix is for the system relates to the finding, I would say that we have to have a precise finding, that the system has deficiencies and parts of the system are not working. And I would guess that it's kind of IRB-specific. Some work very well and some don't. We haven't validated that. CHAIRPERSON FADEN: Yes, that we haven't looked at. DR. RUSSELL: But nonetheless, we do know that in some instances the system works very well. And furthermore we have, I think, evidence from the patient or the subject survey that there's a high level of satisfaction and a high level of success of the system. So what we have to do is be precise in saying what's -- where the system or how much of the system is not working rather than condemn the whole system. MS. KING: First of all, we have to be careful talking about the -- CHAIRPERSON FADEN: We've got Henry and we've got -- Pat, did you want to be on the list? MS. KING: Yes, I will. CHAIRPERSON FADEN: Okay, and Ruth. Henry? DR. ROYAL: The thing I don't like about the working/not working paradigm is again, it sort of makes it sound like you've reached this certain line. And then once you've reached the line, you can all sort of relax and things are fine. I wonder if this finding could be written in the context of human research is complex and parts of the system should be improved or somewhere along those lines, or can be improved or requires constant attention. You don't like any of that stuff? CHAIRPERSON FADEN: It doesn't say very much. DR. ROYAL: But working and not working doesn't say very much. CHAIRPERSON FADEN: That may be true. I mean, that may be the problem of trying to get it down to one sentence, but -- DR. ROYAL: But the concept that I'm introducing is that it's not this threshold thing where you cross this line and you're now working, or if you're under the line, you're not working. CHAIRPERSON FADEN: Well, but I think the argument is - - I mean, I would agree with you that we want to emphasize, and I think that's the force of some of the recommendations, draft recommendations later, that for us to have a system that's adequate, it needs constant care and attention. DR. ROYAL: Right. CHAIRPERSON FADEN: That's clear. But it needs -- the way I think of is it needs constant care and attention to be working at an acceptable level. There is a notion -- I mean, not that I could give you precisely what the failure rate -- DR. ROYAL: Yes, I didn't know what the presumable level was. That's the problem. CHAIRPERSON FADEN: Well, that's a judgement call like anything else. It's like when you're running an air traffic control system. How many near misses are acceptable? You'd prefer one, but it's a unit system. So if you have a couple near misses and 100,000 flights a day, you say okay, that's within tolerable levels. If it drops below that, you say we've got to take a hard look because our air traffic controllers aren't being trained right or our equipment is no good. I mean, nobody can give you a fixed thing. But that's sort of what I have in mind here. I mean, not necessarily with these words, but the notion is do we think - - people are going to ask us, okay, what do you think? How are things going? Okay, and the issue here is this finding is that answer. DR. ROYAL: But isn't the answer that we're trying to give is that we should be doing more than what we're currently doing? CHAIRPERSON FADEN: That's one possibility is that more attention -- that we're not happy with the way things are and something needs to be done. That could be a finding phrased in that way. This is where I think, by the way, committee work on the language is real, real critical. But that's -- okay, so we've got three options here: the way it is now, Jay's formulation that stops after does not appear to be working, and then the third formulation which is the committee isn't satisfied and thinks more needs to be -- stuff needs to happen. We wouldn't say "stuff" though. We'd say something else in terms about -- I've got Pat and Ruth. MS. KING: Maybe we should be talking about what our reaction was to the data. But I have to say that based on what I read and my own knowledge of the system, which is not as extensive as the rest of -- some of the rest of the people in the system, I was pleasantly surprised. I think it's working better than I would have thought. That is not to say it's working great. I'm just saying that, from my background -- this is what I measured it against and this is what a finding has to say to me. It has to give a measure that you're shooting for and you've got to make some judgement about how close you're coming to it or not coming to it. That's -- however you formulate it, that's what we're talking about. My measure is or the primary goal of the system for me is to keep people from being harmed. This is a game -- this is a distinction between ethics and regulation, and we have to figure out what we mean here. I think that the system is doing pretty well in terms of protecting people from physical harms. It is not doing pretty well as far as we've turned out from protecting people's dignitary interests. That requires a way of thinking about dignitary interests in relation to physical harms. A regulatory system is not going to be equally concerned with both I don't think. I thought the system was working better. It is a bureaucracy. I haven't seen a perfectly functioning bureaucracy ever. Does it say that this system could stand improvement? Absolutely. I don't mind anyway not talking about the improvements that I would find desirable and like to see. But I'll tell you, I'm not comfortable with saying it's not working, because I think it is working. I think it is doing basically a good job given the task that it has. So this finding concerns me because my initial reaction is different, I think, than the initial reaction of others. But it has to do with what your expectations were. I'll stop there. CHAIRPERSON FADEN: Okay. But this is what we needed to get at: everybody's views and then see where we are. I've got -- DR. ROYAL: Can I ask Pat -- CHAIRPERSON FADEN: All right. DR. ROYAL: -- what it is that we could have found that would have made her say that the system wasn't working? You said that things were better than you expected, but what was it that you expected that would have made you say that it's not working? MS. KING: Coercion, exploitation of subjects, not deficiencies in consent forms unless I could track deficiencies in consent forms to some impact other than one that relates to ideal communication or better communication between subjects. We didn't turn up -- we didn't turn up those kinds of things. DR. ROYAL: And we didn't turn them up in the subject interview study because we -- MS. KING: We didn't turn them up in the document study, the way I read it, either because the problem is what we turn up in the document study -- this is why I asked before what we think we've turned up. I think that what we turned up is that documents are silent. Ruth explained it much better than I did this morning. Documents are silent in areas where they should not be silent. And two, documents where they speak, don't speak adequately. I don't quarrel with those findings. It is where you go with those findings. Would I like a system that had documents that covered what it should cover and documents that were better in terms of what was explained in the consent form? Absolutely. Does the absence of that say that the system is functioning at a terrible level? To my mind, no. Is it functioning -- am I willing to say inadequate? I'm looking for a weasel word. I'm not sure that I even -- it's not working as -- it's not working ideally in protecting -- I keep trying to say this. It's not working ideally in protecting dignitary rights, if you have a right to have certain kinds of information. I would agree with that. But then in other ways -- and then I have to ask myself a second question. And that is, in a bureaucracy, as distinct from what ethically might be required because we made compromises, am I -- do I expect to accomplish the ideal within a bureaucracy? No, I don't. So I start with this dichotomy between what I -- the way ethicists talk about protecting human subjects and the way that it was possible in designing the system, right. CHAIRPERSON FADEN: Okay. I've got Ruth, Mary Ann and Sue so far, and I'm looking -- DR. MACKLIN: Phil made the point that we didn't look at the whole -- well, maybe Pat made that point. Pat started by saying we didn't look at the whole system, so how can we talk about the system? And then everything that followed in her comments used the word system. MS. KING: Correct me every time I use that statement. DR. MACKLIN: Well, but you did say -- yes, and Phil wanted to reword -- I don't think you captured his words in giving these alternatives, by talking about parts of the system, which I think is the only accurate way that we can talk about this. For example, one thing we didn't look at at all, and we're not set up to do it and I'm not saying we should have, is violations of some sort that get reported through a bureaucracy and what gets done about it. I mean, reports -- we didn't look at that, and that certainly is part of what one might look at as the system. Because if there are wrongs or harms and people get away with them and nobody does anything about it, then that would be a pretty bad way that the system is working. So when Pat refers again, not only to the system, but to the bureaucracy, here I think we're thinking about the entire structure and the super-structure, which is very, very complex. We only looked at a teeny little bit of that. So I think we have to be careful, and particularly following Pat's good lead, if we're going to put this into the recommendations or lead to the recommendations, we should be much more precise rather than global in our statement. Now that goes to what evidence we use and what specific recommendations we're going to make. I don't want to take this any farther except to have a gentle objection to something that Phil said, which was "Well, the subject interview study showed that people were basically satisfied." If slaves were treated very well, were happy slaves, it doesn't show that their rights weren't being violated. So the fact that subjects are, by and large, happy because they trust their doctors or they believe they're getting treatment, doesn't quite go to the question of whether the rights and interests of subjects are being protected. All it says is that they're happy and there may be terrible violations, but nonetheless, they're happy. So I wouldn't use as a piece of evidence that any part of the system is working well, whether people are satisfied or happy. What I got out of that study was that people's trust in their own doctors or in the idea that they're being protected at -- conjoined with perhaps a little desperation because of their diseases, which may have been in stage, made them grateful both to their doctors and to a system that allowed them to get this. So I just want to be cautious what we infer from their satisfaction. CHAIRPERSON FADEN: Mary Ann? DR. STEVENSON: Yes, I mean both 16 and 17 are totally based on our small sample, our two contemporary projects. We should make that clear. But one statement we made in the RPR chapter was that there were no gross violations of human rights and no findings of excessive -- exposure to excessive risks in a non-therapeutic setting. So why don't we say that? That's what we found in terms of the Advisory Committee finds the current system for protection of human rights and interests is working in as far as -- and then those things. However, and then there are the deficiencies that we've also found. But at least it defines where we think it's working and where we think it's not working. CHAIRPERSON FADEN: Well, that's an interesting way to set it up. That sentence is in the RPRP. DR. STEVENSON: Yes. CHAIRPERSON FADEN: Right. I know the sentence. So the finding is -- DR. STEVENSON: And at least it's consistent with what we've already said. CHAIRPERSON FADEN: And the finding is that we didn't find, you know, any horrible horror stories. DR. STEVENSON: Right. CHAIRPERSON FADEN: But we found some very troubling things. DR. STEVENSON: Right. CHAIRPERSON FADEN: Here are the findings. Does that - - DR. MACKLIN: Yes, but I think those words -- I think that's terrific. Those words "no gross violation of human rights" are things that are in there because that really says why it wasn't a terrible thing. But then we'd have to say what we did find wrong and how it should be fixed. CHAIRPERSON FADEN: Right, right. DR. KATZ: What's a gross violation, by the way? DR. MACKLIN: What's a gross violation? DR. KATZ: Yes. DR. MACKLIN: Coercing people in some way that we may be able to find evidence that they were coerced into being subjects or total absence of informed consent. Those would be gross violations. CHAIRPERSON FADEN: And what we can say is "no evidence of." We can't say that -- we have to be careful. That statement should be amended to say "no evidence of gross violations." That doesn't mean -- MS. KING: Because we know that the system does have some gross violations, not that we uncovered, but -- CHAIRPERSON FADEN: Right, but you have to say "in our sample." MS. KING: In our sample. CHAIRPERSON FADEN: And the reason why this has to said too is just the observation we made earlier. Since we have very little information that bears on voluntariness, we don't really know whether any subjects in the studies we reviewed were subjected to, you know, gross pressures that might rise to something like that description. But we certainly found no evidence of gross violations, no evidence of. So that would have to be -- so we're back to what does "no evidence" mean, that issue we've been arguing. "No evidence" means what? It doesn't mean it's there or not there? It just means we found no evidence of it. But we could lead with that sentence and then go on that the committee did find, however, serious deficiencies with -- MS. KING: In the following areas. CHAIRPERSON FADEN: -- in the following areas. DR. KATZ: Is there a contradiction between the two or not? CHAIRPERSON FADEN: No. DR. KATZ: There's not? CHAIRPERSON FADEN: I don't think so. Is there a -- do we think there's a contradiction? DR. LEDERER: It's what we say in the RPRP. CHAIRPERSON FADEN: Right. DR. STEVENSON: But everything is consistent. That's why I found this a contradiction to say one thing in the RPR and then say it's not working. DR. KATZ: But it still might be a contradiction of the RPRP, so -- CHAIRPERSON FADEN: Is the word -- DR. KATZ: I'm asking. I somehow have not thought it through and it somehow sounds somewhat contradictory, but I'm not certain about it. CHAIRPERSON FADEN: But when you say there ware serious deficiencies in the documentation, that doesn't necessarily mean that there are gross violations of human rights. That means there are serious deficiencies in the documentation. It says there are serious deficiencies in the consent form. That may or may not be part of what ends up being a violation of human rights. We don't know. But I think that's the sense of it, I guess. That's the sense of it. Do we want to draw out -- so is the word "serious deficiencies" an okay word? Then we can decide what we found serious deficiencies in. Do words matter here? So if we say serious -- if we lead with the sentence from the RPRP and then we say "serious deficiencies" I think we've pretty much mined the serious deficiencies areas for the RPRP. We're clear on that, right? The documentation is absent on two points and the consent forms, serious deficiencies in the consent forms. Now what about the SIS? Is there evidence of serious deficiencies in something that draw from the SIS study? MS. KING: I don't know why it strikes me -- serious deficiencies seems to work better with documentation and less well with the subject interview study because what I find troubling in the subject interview study is exactly that. It is troubling. It is very hard for me to say -- I don't have enough information about defects. And the areas which I find troubling, for example, the kinds of things we talked about before, it is this confusion between, for example, research and treatment. I don't -- somehow deficiency doesn't work as well. CHAIRPERSON FADEN: Right. MS. KING: It needs a different word to describe what I consider very serious. But it's much tougher to get your fingers around in terms of -- CHAIRPERSON FADEN: Well, one strategy -- MS. KING: -- these indicators or signs of. CHAIRPERSON FADEN: So one strategy is a three -- sort of the finding is in three parts. The first says we didn't find evidence of any gross violations of human rights. We did find serious deficiencies in the two things from the RPRP. We also found cause for serious concern about -- and that would be confusion between research and treatment and -- MS. KING: That bothers me. That's the one that resonates with me a lot. CHAIRPERSON FADEN: Right. Cause for serious concern, something -- is that all right. Does that -- something like that? Sue, you were next on the list. I'm sorry. Henry, did you want to comment? DR. ROYAL: Well, if the -- I don't know what the things that are going to be listed for the SIS. CHAIRPERSON FADEN: Well, we should talk about it. DR. ROYAL: If it's confusion about the terms, I'm wondering if we want to say that there are serious misunderstandings about treatment versus research. CHAIRPERSON FADEN: Evidence of serious misunderstandings between the relationship of research -- DR. ROYAL: But it may be that if there are other things from the SIS study, maybe the other things aren't misunderstandings. But if they are misunderstandings, that might be a better word. CHAIRPERSON FADEN: Well, the problem is we don't know. I mean, what does the word "misunderstandings" mean? I mean, it sort of conveys inadvertent or -- no, it's fine? Serious misunderstandings about the relationship of research to treatment. DR. KATZ: Is that for subjects or also for physicians? CHAIRPERSON FADEN: For both. DR. KATZ: Well if it is for physicians, then it's such a fundamental problem. If that's the confusion, if you want to say that that is a serious deficiency, that goes to the heart of the research enterprise. I don't know what you're saying. DR. LEDERER: But we had learned that from the subject interview study. CHAIRPERSON FADEN: No, I think it could be learned from -- I mean, where we learned it at all, and I'm not sure that we have a whole lot of direct evidence of it, is in the RPRP in some of the consent forms. DR. KATZ: But if that is what you are identifying, my God, what are we saying? I'm confused, so -- CHAIRPERSON FADEN: If there are -- I think Jay's point is well taken. If there really is a serious misunderstanding about the relationship between treatment and research, that's a pretty foundational criticism. That's really the core of it. DR. RUSSELL: The review of the documents didn't indicate any confusion in the minds of the writers. CHAIRPERSON FADEN: Yes, it did sometimes. DR. RUSSELL: No. I think it could equally be interpreted as the inability to convey or to explicitly differentiate between. You don't know what's in the mind of the writer. You know he didn't get it right, but -- DR. KATZ: Phil, assuming you're correct, but at least let me state it differently than what it was stated just before because it was stated the way it was just, then it's a very telling indictment. CHAIRPERSON FADEN: Well, we do have evidence -- DR. RUSSELL: It may indeed be true, but the evidence is only in the writing and we don't -- DR. KATZ: Yes, but then it has to be -- the way you put it, is has to be put differently in the findings than proposed. MS. KING: If I might, this depends -- something is foundational in relationship to something. And from my way of thinking, it's only a foundational problem if we identify the problem and the consequences of the problem also turn out to be serious. That is not everybody's formulation, but that is mine. So for example, there could be misunderstanding, but it is not led to -- we don't know this by the way, and we don't know the opposite either. As far as we -- we didn't pick up it leading to something that I would consider a gross violation of human rights or one of these other things. So in that sense, a person like myself, who always focuses on regulation and policy, that's not foundational. If I, on the other hand, were an ethicist or a person who wrote about these things all the time, which I do not -- I mean, I get to wear both hats -- then it might be a foundational issue because in thinking about how I think about human subjects research, one of the critical distinctions one ought to be able to make is a distinction between research and medical care. CHAIRPERSON FADEN: How about this sentence, this clause? The committee also found evidence of misunderstanding about the relationship between treatment and research and the perceptions of the subjects interviewed and in the research documents reviewed? MS. KING: Good. CHAIRPERSON FADEN: We did find that, okay? So the three things we're going to say is no gross violations. On the other hand, serious deficiencies in the documentation on the voluntariness and subject selection and serious deficiencies in the consent forms, and also evidence of misunderstanding about the relationship between treatment and research, both in interviews with subjects and in the research documents reviewed. Is that okay? So that's the finding, which is not -- which is okay. I mean, it's sort of descriptive. All right? The text -- DR. ROYAL: Does it still say distinct title to protection of rights? CHAIRPERSON FADEN: I would think so. I mean, that's the heading and then that's what we found that it bears on protection of the rights and interests of human subjects. That's what we found. We didn't find any horrible things, any evidence of really horrible things. We didn't uncover another set of -- I mean, the bottom line is to tell the public that we didn't find another series of plutonium experiments. And that doesn't mean they're not out there. We just didn't find evidence of anything like that. Now you say our methodology wasn't set up to do it, but actually the subject interview study was more likely to pick up something than the RPRP. They're all projects that are obviously already approved. So invariably, somebody has reviewed them. I mean, if there's somebody out there doing research and not telling anybody, we wouldn't have had a mechanism for really finding that -- that out. So we have make sure we say that somewhere. But basically, we didn't find any evidence of that. And then these other two things. Okay, can we go to recommendations? MS. KING: Can I ask you a question? CHAIRPERSON FADEN: Yes. MS. KING: And maybe taking recommendations would take us there, but it's critical to the findings. Somewhere I read a reference to the role of IRBs in looking at the science side of proposals -- CHAIRPERSON FADEN: Right, yes. MS. KING: -- and going to the study section. This is something near and dear to my heart about the system being backwards. Is there anything about where we do the review for the science, for the risk benefit assessment? Is there anything in our findings that come out of the two studies that I might have missed, that might give us some data with respect to that issue? Because if there is, somewhere it should be in a finding. CHAIRPERSON FADEN: It can go in the -- it can go in the documentation on the merits. Because one of the other findings of the RPR was that there was often insufficient evidence for the IRB to make a determination about scientific merit. Okay now, based on the documents. I mean, often the documents were not adequate to make a judgement for -- but the issue that's disputed there are IRBs supposed to be doing that or not? IRBs are clearly supposed to be doing voluntariness issues and clearly supposed to be doing subject selection issues. And then there's this controversy about whether IRBs are supposed to look at the science or not. All we can say from the RPR stuff is that we've found lots of proposals that didn't provide sufficient evidence, information, so that if somebody wanted to do a scientific review, they couldn't have done it based on the documents. Does that make sense? MS. KING: It makes sense. Is there some way we can talk about the fact that it's very hard to assess the adequacy of consent forms? Does our data support to assess the adequacy of consent forms and the array of risk and benefits unless one has an understanding of the science? I mean, part of the problem is things that IRBs are charged with doing -- CHAIRPERSON FADEN: Right. MS. KING: -- depend upon -- CHAIRPERSON FADEN: I think we can put that in the explanation. MS. KING: Okay. CHAIRPERSON FADEN: Okay, but I think you're right. DR. MACKLIN: But I think I'd put it the other way around. I'd emphasize that one of the charges to the IRB is to look at the benefits in relation to the risk. CHAIRPERSON FADEN: Right. DR. MACKLIN: And unless you understand the science and know whether there is going to be any benefit and if so, what, you can't even do the basic activities. CHAIRPERSON FADEN: Right. DR. MACKLIN: And that may begin to clear up something near and dear to my heart as well, and something that has remained, for some reason, not adequately addressed. CHAIRPERSON FADEN: So what we could say under the serious deficiency clause, there were serious deficiencies in the two areas we identified, documentation-wise, voluntariness and subject selection and the consent forms -- serious deficiencies in the consent form. There was also often inadequate information based on which one could make a scientific review and this was problematic both for making judgements about risk benefit and for assuring that the documentation and the content of the consent form was accurate. Okay? And then we can go on to, there was also evidence of misunderstanding about the relationship between research and treatment. DR. MACKLIN: Ruth, you're now talking about the paragraph that appears under findings. CHAIRPERSON FADEN: I know. It's becoming the finding. DR. MACKLIN: Pardon? CHAIRPERSON FADEN: It's becoming the finding. DR. MACKLIN: Well, but some of that has to be in the paragraph, not in the finding. Otherwise we're taking up all this -- yes, no? CHAIRPERSON FADEN: Well, that's the tension. You know, if you can't come up -- that's exactly what we were struggling with. If you can't come up with a one-sentence, jazzy sentence -- DR. MACKLIN: No, but this is the gross deficiency. If we're talking about deficiencies, we're documenting the deficiencies, okay, where there are no gross violations but there are all these deficiencies. What are the deficiencies, all the things -- CHAIRPERSON FADEN: Oh, so you would put that in the text? You want to put all that in the bottom text? We could do that. DR. MACKLIN: Yes, deficiency would be the end of the findings. DR. RUSSELL: Put the deficiencies and the findings generically and then specify -- CHAIRPERSON FADEN: All right. So, we found no evidence of gross violations. On the other hand, we found serious deficiencies and reason to be seriously concerned. Okay? And then -- DR. MACKLIN: And everything that follows is a reason for that. CHAIRPERSON FADEN: Okay. DR. MACKLIN: Now are those that we've just enumerated going to be in addition to the paragraph that's there or are will we -- CHAIRPERSON FADEN: We'll rewrite that paragraph. DR. MACKLIN: Okay. CHAIRPERSON FADEN: We'll rewrite that paragraph now in the light of what we just discussed. DR. MACKLIN: Right. But that means don't omit things that are in there that still should be in there. CHAIRPERSON FADEN: Yes. But it will be a rewriting of that paragraph to make sure that we've hit. So the finding itself will be we didn't find any evidence of violations, evidence of gross violation of human rights. But we did find evidence, serious deficiencies. In what though, is the problem? Serious deficiencies in documents and evidence of serious misunderstandings about there nature of research and relationship of research and treatment. DR. MACKLIN: But we found other deficiencies as well. For example, the one that's already in there that we didn't just discuss, the diminished capacity for the process -- CHAIRPERSON FADEN: Right. DR. MACKLIN: -- of consent, etc. CHAIRPERSON FADEN: Right. DR. MACKLIN: I mean, I think we should still state it generally. Serious deficiencies -- CHAIRPERSON FADEN: Serious deficiencies in what? DR. MACKLIN: -- in some aspects of the system for protecting -- CHAIRPERSON FADEN: Good. DR. MACKLIN: -- human subjects. CHAIRPERSON FADEN: I'm going to write the sentence right now. DR. MACKLIN: All right. We don't want to talk about the whole system, but we want to talk about aspects or parts of the system. CHAIRPERSON FADEN: All right. Can we do this? DR. MACKLIN: And that's all we can -- CHAIRPERSON FADEN: Right. The Advisory Committee finds -- did not find any evidence in its review, okay, of gross violations of human rights. The committee did find evidence of serious deficiencies in some aspects -- DR. MACKLIN: Some aspects, some parts. CHAIRPERSON FADEN: -- some parts of the system. Is that all right to say "system" now? DR. MACKLIN: Yes, because if you're talking about parts it is. CHAIRPERSON FADEN: Okay, some parts of the system for the protection of human subjects. So that's the finding, okay? And then the rest is rewriting. Jay? DR. KATZ: I've got to say something to you, not for purposes, at least from my perspective, for further discussion. To me, the ambiguities in this sentence are significant, and I will have to say something about the ambiguity. And I may have to say something. That's what I feel. I must bring to your attention. To give just two examples from my paper, one of the studies that I commented on was reviewed by a more distinguished member of this committee. And independently, he and his co-reviewer came to the same conclusion at the end of my clinical study where -- and no treatment was compared with a very aggressive treatment. In the situation where clinical experience suggests that you -- that it's just as good an option to wait and do nothing and see what would happen. There was no information in the informed consent form about any kind of -- what the implications were of being assigned to one treatment arm or the other, with respect to quality of life, all kinds of other things. Even though the protocol mentioned it, it wasn't really, unless you're an expert, not sufficient information for them to possibly consider all the pros and cons of -- not about the project itself, but what needed to be communicated to the subject. Another example that's more frequent in the exclusion criteria for non-therapeutic studies, it was specifically mentioned that if you are within six months of death, you cannot participate in this study, but which means if you are seven months from death or eight months from death or a year from death, you could be included. And this was also -- and they were looking really a little bit for more terminal kinds of patients for the studies. Are these, I do not know, gross bushel, feather-weight kind of violations of human rights? And I don't want to go into this anymore. You have it in my report. I just want to say that depending on what the wording is, and most likely irrespective of the wording, I will have to dissent on this. And in all fairness and out of respect for you, I want to bring that to your attention. But I don't think we should discuss it anymore because I think we have so much more to do and we've gone as far as we can. CHAIRPERSON FADEN: The issue you pose is whether the examples you've provided in your -- DR. KATZ: What? CHAIRPERSON FADEN: One of the issues you pose for the whole committee, Jay, is whether the examples you've provided in your review or the experience out of the committee's collective work requires -- is constant with this formulation, particularly the formulation on gross violations of human rights. Are we all -- so we're all clear on what's at issue here, are we comfortable with the statement that we did not find evidence, admittedly it's a loose term, of gross violations of human rights? We clearly found things that troubled us a lot, okay? But what Jay is bringing to our attention is are we all comfortable in saying that first sentence? We should all be comfortable with that because that is part of what's at issue. Ruth? DR. MACKLIN: Certainly, the two examples Jay -- the first example that Jay gave would be an example at least of the serious deficiency, at least, possibly worse. I didn't get the second example, and I'd like to hear Jay elaborate it -- I mean, state it again. This was the question of not within a certain number of months of death. I mean, what -- could you just please -- DR. KATZ: Using terminal patients for research that have, in addition to everything else, grave implications for quality of life. CHAIRPERSON FADEN: Jay, we need you to be on the mike, please. DR. KATZ: Oh. That using terminally ill patients for research, it's tremendous implications for quality of remaining life. DR. MACKLIN: Right, but the answer to that has to depend on what they're told. I mean, if in fact they are told all of these things, what these implications -- DR. KATZ: But they're not told. I mean, that's the point. I mean -- MS. KING: We don't know what they're told. DR. KATZ: They are not told in the consent form. That has to be able to -- we can't -- we have to rely on what we've got. CHAIRPERSON FADEN: Let me suggest one amendment just to what we're doing here, and I don't think it will affect Jay's decision about what he does personally. And Jay obviously can speak for himself. The first sentence could be deleted, okay? It's highlighted as a finding. That is, the Advisory Committee did not find any evidence in its review of gross violations of human rights. The finding could simply say, the committee finds evidence of serious deficiencies in some parts of the systems for the protection of the rights and interests of human subjects. I mean, do we want the first sentence or not? DR. MACKLIN: And then take it out of summary as it now appears on page 28? CHAIRPERSON FADEN: It could. That's right. We could. Do we need to say it? I mean, we certainly could have other language that says we found examples where it worked well. We've found -- in other words, instead of a global statement, we can replace the test in the RPRP and in the summary statement of what we did find, the kinds of things Phil was raising. We found examples of very difficult, complex studies that were handled quite well. We found that 100 patients in the SIS had no trouble -- well, I don't know if they had trouble, but they certainly said no when they had the opportunity to be research subjects. We know at least for some people, they feel empowered enough to refuse to be research subjects. So we could highlight what we found that was encouraging without commenting on this issue of whether we found or didn't find only because of the misleading character of it. And then the finding could be the committee found evidence of serious deficiencies. Yes? MS. KING: I don't mind changing the first sentence, but I don't like leading the way you lead the second sentence. I think we need some committee statement that says what our overall impression of that part of the system that we examined looked like. And the reason I say that is we are not operating in a vacuum. The system for review out there has many critics from the perspective of it's too much, too cumbersome, too bureaucratic, let's do away with it. It's a burden on clinical research. It's got critics from another perspective that says not enough, we're not paying enough attention to certain of these details. We clearly are falling into that category because we conducted studies that gave us information that we found troubling. But I want to be able to say, which I firmly believe as an individual, and maybe the committee is somewhere close to this, that -- I want to say something about the fact that the system is doing a job. It's not doing as well as we want it to. It's doing a job that's necessary. We need to keep it in place, and we need to continue, Henry's words. This is a work in progress almost and we are continuing to try to improve it. But we are trying to weigh lots of things here, and there's some way to convey that nuanced judgement. If the first sentence makes people uncomfortable, I'm willing to do away with it. But I want a substitute sentence that says -- CHAIRPERSON FADEN: I understand what you're saying. MS. KING: -- something like that. CHAIRPERSON FADEN: I understand what you're saying. I think that's well taken. I'm not even sure that this sentence speaks to that -- MS. KING: Right. CHAIRPERSON FADEN: -- because you may not need the whole apparatus of the IRB system to keep from having gross violations of human rights. I mean, I don't know. MS. KING: Right. CHAIRPERSON FADEN: That's a good -- that's a good point. Mary Ann? DR. STEVENSON: Well, picking up on what Pat's saying, and also something she said before lunch, one thing that the regulatory aspect of the present system is very committed to and probably has achieved fairly well is keeping patients from physical harm, particularly in the setting of non-therapeutic research. And that was the other part of the RPR statement was gross human violations and exposure of patients to excessive harm. Now you could lead with that part of it if we feel comfortable. CHAIRPERSON FADEN: That would be -- that would work. DR. STEVENSON: And you'd say -- and whatever, we found that -- CHAIRPERSON FADEN: We did not find any evidence of -- DR. STEVENSON: -- of patients being exposed to -- CHAIRPERSON FADEN: -- of subjects being exposed to -- DR. STEVENSON: Right, harm. DR. MACKLIN: Without any compensation benefits. DR. STEVENSON: Right. So I mean, again, that's in the RPR chapter. CHAIRPERSON FADEN: That I'm more comfortable saying because -- DR. STEVENSON: Right, because all our deficiencies are really in the area of ethics, not in the area of risks or harm, physical harm. CHAIRPERSON FADEN: Well, the Advisory Committee did not find any evidence of subjects being exposed, being subjected to excessive levels of harm without offsetting that. DR. STEVENSON: Right, or state at the current -- I think it's important to say something about the current system. I think it's actually useful to have those words. I think people are looking for that. And if we don't use it to some degree, people will realize we're avoiding it. I mean, I think you can say -- CHAIRPERSON FADEN: Well, you could turn it around and say that the Advisory Committee found evidence that the current system appears to be succeeding in -- DR. STEVENSON: In the area of -- CHAIRPERSON FADEN: -- protecting subjects from being exposed to. Okay? Would that be -- DR. STEVENSON: Right. CHAIRPERSON FADEN: Okay? DR. STEVENSON: However -- CHAIRPERSON FADEN: However, the committee did find -- okay? The current system appears evidence suggesting, which we did, that the current system appears to be effective in protecting subjects. And then we've got severe harm or whatever, high levels of harm without offsetting -- DR. STEVENSON: Right, therapeutic -- CHAIRPERSON FADEN: -- benefit. And then, however, the committee did find evidence of -- okay? DR. STEVENSON: Okay. DR. MACKLIN: Let me just ask this question. I don't think there were -- somebody reviewed all these things, maybe Gail knows, in the RPRP study, it had a question: "Are subjects being subjected to high levels of risk, greater than minimal risk?" And then there was a question about the -- yes, did the benefits compensate for those risks. Did the benefits do whatever, you know, for those risks? Now in many cases, the answer was yes, high levels of risk. And in many cases, the answer was maybe. And I want to know first, were there any cases in which the answer was no? CHAIRPERSON FADEN: But the point is we've got to be careful about the phrasing. It was more than minimal risk, not high risk. DR. MACKLIN: Right. No, no, more than minimal risk. And then the question, were the risks offset? CHAIRPERSON FADEN: Right. But the point is, Mary Ann's formulation says high risk, not more than minimal risk, okay? The formulation and the finding would be, you know, we didn't have studies flagged in the RPRP where somebody said this is an unconscionable level of risk, this is appealing is, this is near murder, this is whatever. So we certainly had instances where people said this is more than minimal risk, and it's not clear to me that this -- that the benefits to the subjects are appropriate. What all this would say, this is up there with the gross violations of human rights, that we didn't find indications of people being subjected to very high levels of risk without offsetting benefits. DR. MACKLIN: Well, but now we get to Jay's example. CHAIRPERSON FADEN: Right. DR. MACKLIN: In other words, if these are patients who are in this terminal period, and if those are the ones that could be said to be subjected to high levels of risk because they're being zapped -- CHAIRPERSON FADEN: Okay, so maybe the formulation isn't correct. DR. MACKLIN: Then we have to ask about the compensating benefit when one is so near death. CHAIRPERSON FADEN: Henry? DR. ROYAL: Phase I studies also -- CHAIRPERSON FADEN: Maybe we can say this. So maybe we have to step back. Maybe the world isn't looking very good. I mean, we have to sort of get clear on what can we say. I mean, we can say we found evidence that some good protocols and that people can say no. Maybe that's all we should -- that's what we should say. Go back to saying what we did find without trying to generalize because the generalizations maybe are not supportable. DR. KATZ: But you must state -- too is that in medical research with respect to this kind of gross physical injury, that's been relative -- except for the Nazis, that's been relatively near in the history of medical experimentation. CHAIRPERSON FADEN: Generally. DR. KATZ: Generally. I mean, so in the sense that these -- work now -- CHAIRPERSON FADEN: That's not a good answer. DR. KATZ: We don't need them for that purpose. CHAIRPERSON FADEN: I mean, there is some real hard thought. I mean, you have had people die in medical research. It has not been -- DR. KATZ: You still do now. CHAIRPERSON FADEN: But we could -- the first sentence could lead with what we found. And again, we're back to it's hard to get the generalizations, but we can say we found evidence that some research products are -- you know, the documents are good and the consent forms are good and that the subjects -- sizable numbers of patients approached feel like they can say no, have said no. However, the committee did find -- and we can say that as the lead sentence. But to make generalizations about the whole system starts to become -- on the positive side, starts to become problematic. MS. KING: I have no trouble with not making generalized statements. There is an implication of not being able to do it, though, that I should -- they will carry us into recommendations. And that is, you can't start talking about then tinkering with the whole system and having high level review of the whole system when you can't make some statement, it seems to me. CHAIRPERSON FADEN: What we're finding is we can make statements about the deficiencies. We're having trouble finding statements about the correct wording. MS. KING: No, but this is very carefully qualified. We are finding deficiencies in two respects. This is the state of our evidence: documents and subject interviews. And it's a big leap from -- unless we put something in here to say that, because the documents weren't written right or people have some perceptions that we are troubled with, that on this evidence, we make recommendations and national committees. That is why I think that we should be making the struggle here to have some evidence to support that recommendation. Because in my mind, if you can't -- if that's what this means, then I have a hard time justifying calls for that kind of level one. CHAIRPERSON FADEN: You see, I see it the other way around. The fact that we're struggling to find evidence that's generalizable about how -- the good things is indication enough. I mean, what we have evidence of here, when we say serious deficiencies and Pat's way of formulating it is always to reduce it to the documents, is that the documents are only pieces of paper that don't reveal anything about what's really happening. That to me is -- MS. KING: No, they do reveal what is really happening. But the tendency of the committee has been to do just the opposite, is to take the document and run with it. The document is just the document. And it points to me the areas that need serious examination. I don't have any quarrel about that. CHAIRPERSON FADEN: Well, who's going to do it? MS. KING: But the problem is that examination does not mean that you've found the consequences of these documents, lead to such egregious consequences that a massive look at this is called for. Because for a policy recommendation, I'm interested in consequences. I can find something wrong with almost anything you give me on a piece of paper. And the -- I can. (Laughter) MS. KING: And the issue is, one of the consequences that flows from that -- I'm conceding some consequences. I haven't heard such egregious consequences, that some of the recommendations we're going to discuss, not all, some of the recommendations we're going to discuss will justify those recommendations. DR. MACKLIN: But Pat, we have to go back though to the question of whether the IRB gets any more information or is likely to get any more information than is in these same documents we're looking at. I mean, there are two questions here. What would be additional evidence? One might be some account of adverse outcomes. That is, the study was conducted and then there were all these horrible side effects; that is, the pieces of paper that go to the IRB about adverse effects or deaths under a study. But in many cases, what we're talking about here as pieces of paper that we looked at, are pretty much the basis for the IRB's judgement. Certainly when we're talking about risks and benefits, that's what we're talking about. Now granted, there are some things omitted that the PI can say to the IRB that we weren't privy to, namely how are you going to recruit these subjects? Are these subjects being coerced by this, that or the other thing? But if we're talking about risks, benefits, quality of life, those are things that we're looking the pieces of paper that the IRB was. MS. KING: I keep emphasizing we looked at documents because you, yourself, said we did not look at the enforcement procedures. We are going to look at documents and make extrapolations from documents about things that are missing there and things that are done wrong. And you have a big jump to say it takes a national level body to rewrite, in essence, documents. You want to be able to say something different, but we didn't look at the rest of these things. CHAIRPERSON FADEN: Let's do this. We're now going to recommendations, and we are really short on time. We're dancing around the key recommendation. This finding -- we know the second half of the finding. We're not sure about the lead sentence of the finding. We will come up with some formulations for the lead sentence and circulate them around, okay? Is that agreeable to everybody? The second sentence that says serious deficiencies and how the serious deficiencies would be explicated. That's really the important stuff in the perspective of the committee. But it's also important to have a right characterization of the good news, as it were, and we have to figure out how to do that. Can we move to the recommendations? There are very many of them. And I am concerned because we did say that at four o'clock we would turn to process issues for the committee. And so we need to do that. We're on page -- this is Chapter 19, and it is the section, and it is a long one. We're at Chapter 19, and we are beginning -- page 13? Thank you, page 13 -- 12, right. It starts on 12, line seven, is the heading: "Recommendations for the protection of rights and interests of human subjects. And please note that it goes all the way to -- there's a lot here. Let's see where it goes to, page 30. So we've got 18 pages of recommendations and about an hour and a half. Now we may spill into tomorrow, but we're, you know, cutting things close in every dimension. We keep getting stuff stuffed into tomorrow. We could take the -- the recommendations are organized under headings. If we could just take a sense of the committee about where people are with the various -- Ruth, do you have a suggestion? DR. MACKLIN: This is going to be a proposal, that we start with recommendation ten on page 16, because these are pretty much the things we've been talking about: let the findings go to the -- education and presidents and deans and stuff. But what goes back to the finding is I think the important stuff here, and likely to be a little more controversial. So I'd suggest we start with ten and look at ten. CHAIRPERSON FADEN: Fine. All right, let's -- the floor is open for ten. Ten is the changes and then 11 is the call for -- which is what Pat has been speaking to, the call for a national body. So let's do ten first. Comments on the meeting summary recommendation which is lines ten, 11 and 12 on page 15. And that's explicated by 10(a), 10(b) and 10(c). Okay, let's go on to 10(a). You may go back to the lines ten, 11 an 12 after we've done the whole thing. Maybe we should get the details and work out with Lois -- MS. NORRIS: Recommendation 10(a)(2), I would like to see expanded somewhere, perhaps in the text, to say that this recommendation really comes into play with respect to the Phase I and, to some extent, Phase II trials because that's where I see the real problem. CHAIRPERSON FADEN: So you would like to make it clear that the particular area where this needs to be worked on is this area, the Phase I and Phase II trials, especially Phase I, which is something that Eli had said earlier? We're on 10(a) which is -- MS. KING: 10(a)(1),(2) and (3), if my memory serves right are all deficiencies that flow from documents and the way information is pertained to documents. So I don't -- I may have problems with the heading of this in terms of mechanisms to provide for -- the overall heading of the recommendation. But ensuring the we provide information in a different way with respect to those issues seems consistent with defining - - when you say "mechanisms for ensuring that the information provided to potential subjects identifies." It's what we mean by "mechanisms" that confused me. CHAIRPERSON FADEN: Well, I think we're saying that we can't stipulate what they are yet. We can't now say what the -- solution should be. We just don't have the time to do that. Somebody has got to figure out how to do that. We are pointing out where there are problems and not -- and we're saying that somebody has got to do this. And the issue is who's going to do it. But we can't stipulate -- I mean, I don't think we can sit here now and get mired into how do we want to do this? Change the federal regulation, send a dictate out to all the -- I mean, I think we can't do that. I don't know. Is that your problem with "mechanisms" or do you want to -- MS. KING: Well part of this, yes, because of the federal regulations already provide what should be in the -- gives the subject headings of what should be in the informed consent forms, for example. And then there are supplementary, as I understand it, guidance to IRB about special areas of research. Some of what we were talking about seems to call for changes, probably not at the regulatory level because they are written in more general language, many of them. But additional guidance to IRBs to say when you review informed consent forms, you should ensure that the informed consent form has the agency's -- and research, for example, in the form. The other aspect of this is not captured by this. What you -- it seems to me it's a separate question to say that I now want a mechanism or a way of checking to see it was done. CHAIRPERSON FADEN: I think that comes later. MS. KING: Okay. CHAIRPERSON FADEN: That comes later. MS. KING: But when I say "mechanisms" here, that's what I'm -- it sounds -- CHAIRPERSON FADEN: Right. MS. KING: I think of this as not being a grand process to get the consent forms changed. CHAIRPERSON FADEN: It's not only the consent forms. It says that the information provided to potential subjects. That doesn't mean only and solely in the consent forms. It means the information provided to subjects. So it may require, in some cases, monitoring, you know, asking for all kinds of creative things that people had bene doing, particular at high risk studies which we can't get into here. But it may require asking for a script for an oral disclosure in a particularly troubling study. It may require in a particularly high risk study that IRBs do require a tape recording. It depends on what's at stake, or an ombudsperson or -- and we can't --there are all different mechanisms that people have used as the stakes go up. I don't think we can go through that here. We're flagging the problems. MS. KING: Our documentation does not reveal, if I remember correctly from reading the chapters, that this is not done is -- so part of the connection is -- in getting to -- I'm not quarrelling with what you're recommending -- is making the connections with what we recommend with what we have found. But where are the connections so that -- CHAIRPERSON FADEN: In the text that follows. If you don't think it's good enough, then we need to change it. We found reason to be concerned. That doesn't mean that we found for sure that it's the case. We found reason to be concerned. So somebody after us is going to have to establish whether our concerns are right, okay, and we have reasons to be concerned by what we've found. We obviously did not have access to what exactly is going on. So somebody has got to find out if our concerns, in fact, are accurate and reflect what's really happening and if they do, which is likely, at least in some cases. And they've got to figure out how to fix it. And then I don't know what else you do -- MS. KING: Well, let me ask you, is that then what our recommendation should be that we should identify the source, which is the subject of another -- the proper authority the subject of another recommendation, identify an entity that says we have noted these deficiencies which we have described in our chapters. We think they're serious, etc. And we think that there should be a follow-up to see if, in fact, they are -- have general applicability. And if so, correct it. Because it seems to me this specifies a great deal more. So I'm asking a little bit about what exactly is the intent of our recommendation? I don't know. This is the question. CHAIRPERSON FADEN: Ruth? DR. MACKLIN: One intent it seems to me is to flag items that have not received sufficient attention and that could, or that did, in the RPRP study raise issues of concern to us. Now when you point out that the current federal regulations deal with some of these, they don't deal explicitly with these items. So what it's flagging are things for which even if it's only in the documents, because maybe that's all we looked at, to which there has been insufficient attention paid, and where the current federal regulations are silent? CHAIRPERSON FADEN: Look, I think the process is what you're describing, Pat, and maybe it's not clear. You have recommendation 10 which lays out in three areas the committee's concerns, the areas the committee is recommending need to be carefully looked at because we're worried. We have cause to be concerned based on our work. Recommendation -- MS. KING: But -- CHAIRPERSON FADEN: Let me just finish. Recommendation 11 says the best way to follow-up is through this national body. Now you may disagree with tat, but we're basically saying -- MS. KING: I'm not disagreeing. I'm trying to get a clear sentence to say we recommend structural, substantive changes, and then we specify. And so what I'm asking is what is our intent because the way you described it a few minutes ago was what we were saying -- one of our intents is to say this is what we uncovered. We think it is of serious concern. We want somebody else to examine what we have uncovered and do something about it. That is different than -- CHAIRPERSON FADEN: All right, so the -- MS. KING: -- recommending structural changes. So I'm just trying to get clarification on what you are trying to do. CHAIRPERSON FADEN: What I'm understanding you're saying is the issue is whether in lines two, three and four of page 17, the leads should be we found these areas. We think they're very serious. We think they probably will require changes, but we can't be for certain and somebody has to do the next step. DR. KATZ: Put a bridge between what you were saying and what Pat was saying, that the most the committee can say is we have reason to be concerned. It needs to be investigated. It may eventually -- dependant on what the investigation uncovers, it could either lead to changes in thinking or changes in the current system, or to more wide- ranging changes. Anything, perhaps not even mention it, going to anything like that now, of course, just reason to be concerned and we need another investigator. CHAIRPERSON FADEN: All right. DR. KATZ: I don't buy it, but -- MS. KING: I'm trying to get that sense of where the committee is because I think it makes a difference in what we're saying here. I'm just not clear about what we're saying, whether we are recommending that changes be -- trying to specify changes, whether we are recommending that what we have uncovered is strong -- suggests serious problems that need to be further looked at. I am not clear about the thrust. The wording, I can't focus on the wording because I'm not sure what -- CHAIRPERSON FADEN: I understand what you're saying, Pat. I think the bottom-line issue is this. Do we think the evidentiary base is strong enough to call for changes in these four areas? Let's just start with the four areas. Or do we think the evidentiary base is strong enough to say that it's worth investing a fair amount of time and money to decide whether something needs to be done about those things. That's the bottom line question. So which way are we? How strong do we think our evidentiary base is? Strong enough to say you've got to do these things, or strong enough to say somebody has got to investigate further, and it looks like you're going to need to do these things. Okay, is that what you're asking? All right. So let's see, where is the committee on that issues? And that would affect the wording of two, three and four. I take it that the issues themselves, one, two, three and four, seem not to be a problem. People seem to be reasonably okay with these being -- in this -- under this heading of the IRB system, the stuff that comes out of our experience and our research. Now the only issue is, do we think the evidentiary base is strong enough to say fix it, or do we think it's only strong enough to say pursue it? I think fix it. All right, how many people want to -- I mean, is there anybody that wants to hold back from the fix it? DR. MACKLIN: Let me -- I just want to say this one thing. I'm not sure that all the evidence comes from our studies. That's my only hesitation. But what Pat says, and I entirely -- I don't remember how you put it, but that this is a letter of great concern or this is an old bugga-boo about the risk benefit. All we found was that the committee, in its review, this is number four on page 18, could not make the judgement of what was scientifically meritorious. CHAIRPERSON FADEN: Go ahead. DR. MACKLIN: We didn't -- I mean, it's entirely possible that at every single IRB, which we know is not the case -- at every single IRB, the principal investigator gets up there and makes a case before the IRB that convinces them about the scientific merit, but we know that's not the case. But we know from ancillary evidence that that's a problem for IRBs and they don't even know what their role is. CHAIRPERSON FADEN: Well, notice four only says "resolution of the roles of IRBs." It's basically saying on four, it's fix it. Somebody get clear. Send a clear message to IRBs. Have a -- figure it out so it's -- once and for all know what they're doing here. But four is a little different from one, two and three. DR. MACKLIN: The other point I guess I wanted to make is that some of the -- let's look at one. They allocate their time so as to enable adequate review of the studies. What was there in our studies? I mean, I'm saying there's ancillary evidence for this, and in fact, there's ancillary evidence for something we haven't heard anything about, which is inquiries into the IRB chairs. But we have evidence from this, everybody's got evidence for this, and we know it from all kinds of other fora. We didn't actually look at this question. We didn't look at this question, did we? I mean, I don't know how we can say it's evidence from our studies. And yet, I think there are things that we know enough about that IRBs don't have adequate time, right, to -- CHAIRPERSON FADEN: Well, let's look at this. Let's go line by line. The first line -- okay, Nancy and Duncan, do you want to get into this? DR. THOMAS: No, we're just puzzling what she meant by inquiries to IRBs. CHAIRPERSON FADEN: Okay. That's when we sent out the letters. The first line comes from us, okay? We found out that most of our problems come from higher risk research. The second sentence also comes not only from our common experience, but our experience here. We learned -- if we didn't know it before, we leaned that it takes a lot of time to do a careful review of a complex study. We learned that together if we didn't know it previously because we actually reviewed all of these. Now Jay has counted four or five hours for -- everybody's experience. I mean, it's not that Jay is a slow reader. It takes a long time to do this, okay? DR. KATZ: Thank you. (Laughter) CHAIRPERSON FADEN: You're welcome. The last sentence, the Advisory Committee you heard from several IRBs is the most -- but we did, when we surveyed the IRBs, one of the major complaints they came back with is we don't have the time to do a good job on the tough protocols. So everything here comes from our experience. It's true we're also enriching it with what we know from our other lives. But everything there comes from something we did. DR. MACKLIN: Okay, I think -- I mean, I'm convinced now by what you say. I'm just worried, but maybe it's only a question of spelling it out in this paragraph. What I would not like to see happen -- you see, I threw out this challenge here playing the devil's advocate. I would not like to see someone who reads those reports. Where did they come to these conclusions from? You've got a four-line -- MS. KING: That's a very important question because people won't pay attention to your recommendations if they can't answer it. DR. MACKLIN: So that's why Ruth began to elaborate the answers which are not in here. CHAIRPERSON FADEN: I just read it from here. I just read it straight from the text. Now maybe it's not persuasive the way it's presented. That I don't doubt for a minute. DR. MACKLIN: The last sentence in this paragraph, yes. But then you also pointed to all of the hours that it took us to -- CHAIRPERSON FADEN: Right. We could put that in. I'm sorry, you're right. You're quite right. DR. MACKLIN: It's only a question here of supporting these claims that this came out of our experience, rather than simply out of our heads. And I think that that's what Pat is concerned about. CHAIRPERSON FADEN: And maybe we -- certainly, to be honest, should say where we think that there are other sources of information that also support that these recommendations are appropriate. Either other literature or whatever. So we don't have to -- we can say -- it comes out of our experience, but it's constant with what is available in the world out the, so that we don't look like we're claiming as if we made this up de novo where nobody every thought of these issues before. And we can certainly do that in terms of -- arguments. We can put that in the -- for you -- But I want to get back to Pat's challenge, which is -- and we're never going to get anywhere if we don't sort of go -- we've got to go further. On 10(a)(1), (2), (3) and (4), two options are the saying, the fix it option or somebody else go and investigate it an option. Now (4) is a kind that somebody else investigated option because we're not taking a position. We're basically saying this is a muddle. We found it a muddle and somebody resolve it. But (1), (2) and (3) could be fix its. Can anyone tell me which way we want to go with the committee, Nancy? DR. OLEINICK: I would like to answer the muddle in four. DR. MACKLIN: Okay. DR. OLEINICK: Okay, which is from my own experience that if a protocol that goes to the IRB at an institution is obviously subsequently going to be submitted to an outside agency such as the NIH for funding, it will probably have a scientific review. So that may be some way in which the IRB doesn't have to worry about it. Maybe they do, maybe they don't. But I think there's concern raised for protocols that will not be submitted for external funding. And there, who is going to review them becomes even a greater problem. CHAIRPERSON FADEN: So we should point out that in some cases, the IRB is the only review, right? DR. MACKLIN: Right. CHAIRPERSON FADEN: All right. Maybe I should separate this. For (1), (2) and (3), can I do like a show of hands? How many people want to fix it? This is not unlike the stuff in the recommendations with respect to uranium miners. You know, do you want to say give it to everybody or recommend that people think about whether it should be given to everybody. I mean, that's basically -- MS. KING: No matter what we say, whoever receives this will stop and fix it. CHAIRPERSON FADEN: That's correct. MS. KING: The part of the issue -- part of what my problem has been is I don't not think -- I agree with the rest of the committee that I think these are real problems. I have -- some are more serious, I think, than others. But the issue for me is not that everybody doesn't know that the IRBs are overworked and overloaded. What we need to be doing is talk, if you can, about why the fact that they're overloaded, in our view, has presented a problem. And what we need to be telling them is that they've got to explore ways. My problem is mechanisms for ensuring that someone -- because actually one of the reasons is there's no funding. There is -- there are a whole lot of reasons why IRBs are overloaded -- CHAIRPERSON FADEN: Right. MS. KING: -- and don't have time to focus on -- and some of them are not going to be fixed. My view is to lend support to, and we won't be the first people who pointed out some of these problems either, is to lend support to the view that these areas are becoming serious and trying to explain why we think they are serious. Because that's the way we can be helpful in maybe getting something done. And I would move in that direction. I don't see that as fitting into your alternatives of fix it and not fix it. I'm not against fixing it, Ruth. I'm against how we talk about the problem to somebody that's going to have to receive it. CHAIRPERSON FADEN: All right, now I'm really confused. I mean, what I just heard you saying sounded like more arguments for why this is a problem. Explain more clearly why it's a problem. Why should anybody care that IRBs are overloaded, and give some indication as to what -- MS. KING: Well, in my world that would be the first thing I would say. I would say I have X dollars, X people. This is a problem. Why should I fix -- CHAIRPERSON FADEN: That's right. That's fine, and we certainly ought to do a better job of persuading why people should worry about this. But I thought we were back on this -- still back on this issue of which way we want to. Do we think our evidentiary basis is strong enough to say this is -- that we feel this is already enough of a problem that they need to be addressed, or that somebody needs to check out to see if we're right about the fact that IRB should spend -- would need more time to work on higher risk studies. It seems to me we don't need it. That's clear already, okay? And can't we just say that? The problem is figuring out - - the problem that some other group has to figure out is how best to help IRBs be able to spend more time on higher risk studies, which is what we didn't have the time to do. We can talk about why it's important, but we don't have the time here to come up with the creative solutions. That's what we've got to pass. But we don't need another group to go check out that IRBs have trouble dealing with higher risk studies. That's what I'm trying to distinguish. The same with two, I think we have enough evidence that this is a problem. The distinction between research and treatment is a problem. And now we have to say somebody else, not us, has got to figure out the most creative ways for dealing with the fact that, as Jay has pointed at, it's a problem in part because it's a problem inherent in the enterprise, the ambiguity between research and treatment. And what's needed is some tough thinking about how to deal with it, not somebody else to verify that there are problems in confusing research and treatment. That's kind of what we've got to pass on in (1), (2), and (3), it seems to me, is the hard work, okay? In other cases, maybe there's something else. Ruth? DR. MACKLIN: I wanted to ask you, you are now making an argument for the fix it and not someone else study it. I mean, it sounds like that's what you're saying. CHAIRPERSON FADEN: That's right. I'm saying -- we're saying to somebody else, "Fix it." DR. MACKLIN: Right. CHAIRPERSON FADEN: We've identified a problem. We think we have enough evidence to say there's a problem. DR. MACKLIN: I just wanted -- CHAIRPERSON FADEN: We don't have the time to come up with a solution. Maybe we're weaseling out. Maybe we're lucky. Maybe we're just, you know, not up to the task. But we petered out just in time. (Laughter.) You know, no -- we found the problems. We don't have the time to come up with the solutions, but we found some real problems and we feel comfortable we've got enough evidence that these are real problems. DR. MACKLIN: But it does go to the question of the recommendation itself. That is, not the A, B, and C. CHAIRPERSON FADEN: Right. DR. MACKLIN: Because if, for example, one way that IRBs can devote more time to the high risk studies is to alter the system that requires full IRB review of every protocol except those that fit under expedited. As a possible mechanism, that surely requires a change in the current system. CHAIRPERSON FADEN: Exactly. DR. MACKLIN: So -- CHAIRPERSON FADEN: That's why that language is the way it is. We can't here stipulate what the changes should be, but the changes need to happen -- DR. MACKLIN: Right. CHAIRPERSON FADEN: -- I think is -- is -- MS. KING: That recommendation says -- recommends changes, and so part of this is we are not recommending changes. We are recommending that others come up with changes, or we are recommending that we can no longer buy -- we are not recommending a systems change; that's the problem. What we keep -- because we don't have a concrete recommendation. DR. KATZ: We do -- actually, that's what I don't understand is unless I don't know something. It goes back to the recommendation about approving that the research is scientifically meritorious. At Yale, I think as long as I was under the IRB, Yale did not review the scientific merits because it was a can of worms. It gave informal advice to researchers because we had such distinguished scientists on it, and it would say, "Look, you really ought to look into this, that, or the other thing." But if the feeling was that it is a can of worms, it would also take an inordinate part of additional time to evaluate the scientific merits. Does Johns Hopkins review scientific merits? Is -- CHAIRPERSON FADEN: When I chaired the IRB, they did. DR. KATZ: You did. (Laughter.) CHAIRPERSON FADEN: It was -- I can't say any more of it than that. DR. KATZ: Well, they must vary, then, you know, and there must be great variations. So now -- DR. GLATSTEIN: That's, I think, the heart of the problem with the IRBs. There is enormous variation, and some of the institutions are doing a bang up job and some are not. I think there's confusion as to what their role is supposed to be is -- CHAIRPERSON FADEN: That's what -- DR. GLATSTEIN: -- we call attention to. I think that there are some specific recommendations that can be made. One is simply to streamline the process for the minimal risk group, classify it as minimal risk, identify it up front and streamline the process. I think that there is a need to widen the IRB to more non-medical people to represent the cause better for the patients, because we're not -- that's clearly -- right now, the consent form is supporting, to some degree, the physicians' communication process. But as I said before, even to a greater degree, the institution's potential for litigation, and that needs to be addressed by someone who is impartial, and neither the institution nor the doctors are impartial. CHAIRPERSON FADEN: That's part of what we're dealing with here. How about -- DR. GLATSTEIN: Well, why can't we specifically say some of this? CHAIRPERSON FADEN: Right, we should. We should say it in that last chapter that we're going to write. I mean, that's the kind of context that I think we need to put in, the impartiality, the inherent ambiguity. That's the beginning of the interpretation. Can I do this? How is this for a resolution on the problem that Pat has put before us? I see the point that she's making, because we don't say how to fix it. We say what the problems are. Can we say that we recommend that for a moment we'll leave open what government agency is this issue going to be directed, come up with some kind of a process for identifying the appropriate structural and substantive changes that need to be made to resolve the problems we have identified and then implement those -- then implement those changes, which is really what we're saying. Okay? What we're saying is, "Government," okay, "you come up with some kind of mechanism for finding out how to change the system to fix these problems and then you implement those changes." DR. RUSSELL: We don't have to specify a single agency either. CHAIRPERSON FADEN: That's right. I don't know how -- I mean, because it is an -- because we have discovered it's a universal -- we discovered it's a government-wide -- we are government, almost government-wide. It's all of the agencies involving human subjects who would share in this, would have an interest, obviously, in this. So that's the language we want. Are we getting it? Good. DR. MACKLIN: Ruth? Mary Ann and I would like to propose, if you are -- I'm sorry we whispered there before -- that four -- number four be strengthened not to say someone else should resolve it, but rather to recommend that IRBs have a role or establish a mechanism which means either they do it, they bring in consultants. Some institutions have a Research Review Committee, which -- which reviews them beforehand. So rather than say, "Someone decide whether IRBs have to deal with this," if this committee is agreed that they do have to deal with it, they either do it directly or establish a mechanism for ensuring the -- that the research is scientific. CHAIRPERSON FADEN: That would be -- that's -- let's see if the -- all of us agree. So the proposal is to turn around saying, "The committee believes that IRBs should have a role here, and you've got to fix it so they can do it." Okay? Is anybody in opposition? DR. KATZ: How soon? Maybe take some -- that paralyzed my -- (Laughter.) But, look, that's -- you know, you -- to put this task on IRBs, the duplications of effort of 100 IRBs addressing these same kind of issues that you are talking about, is -- is so cost- ineffective to begin with. And secondly, IRBs do not really have the time and even the capacity and authority to really review these kinds of complex issues. They can take care of some more mundane kind of issues. If you have anything -- if you just have some minor things in mind -- or if we have just some minor things in mind, so be it. But anything major to put that task on the shoulders of 100 IRBs -- CHAIRPERSON FADEN: I think that what we used to do in our committee, Jay, is the following distinction. The scientific review -- I mean, we may still do it. I just am not serving on it at the moment because I'm doing this. (Laughter.) Among other things. But the way we used to do it is say, look, it's not like you are a study section that's got to decide relative to other things, is this -- you know, whether it should get a 100 or a 500. Is this good enough science to put human subjects at inconvenience or risk? That's all the IRB has to do. Is it past the threshold that justifies the involvement of human subjects. Even if it's zero risk, it is an inconvenience. It's a disturbance. It's an irritation. So is it good enough science that it is appropriate to ask a human being to give of his or her time or body? Okay. And not whether it is absolutely the best design possible, okay? Is it going to give -- does it have a good enough crack to illuminate an area of research that is worth bothering a human being to ask to volunteer? And that's -- that's different, I think to me you can't do. That's why when I was chairing it I thought you had to do it or you couldn't possibly -- DR. MACKLIN: And there are different mechanisms. It doesn't -- the whole IRB doesn't have to sit there and discuss it. You could ask for a written report from a consultant. You could have the primary reviewer find somebody else to do it. Some institutions have a science research committee that -- that all proposals must pass before they go to the IRB. So there are different ways to do it that need not take a lot more time. CHAIRPERSON FADEN: Phil? DR. RUSSELL: Perhaps the recommendation should not be directed at the IRBs but at the institutions which support IRBs, which have IRBs, so that the onus, then, is on the schools or the hospitals, or whatever the organization is, to fix it. CHAIRPERSON FADEN: That's an interesting point. MS. KING: That's very tricky because the government's authority over an institution with respect to non-federally funded research has always been an issue. When you -- DR. RUSSELL: Say again. MS. KING: The government's reach of regulation to institutions is clearest when the government funds the research. By assigning the institutional assurance, you agree to treat your non-government funded research in the same way. That is a very tricky issue. CHAIRPERSON FADEN: But I don't know what -- how that -- I mean, would -- MS. KING: So if you lay questions on institutions -- the research that gets the good science review is federally funded. CHAIRPERSON FADEN: No, I think what Phil is saying is you could have, for example, an IRB defer to a departmental committee that looks at science. In other words, some universities have structures where a department decides -- you know, they look at everybody's new research and give some sort of okay that the science is good, and the IRB could defer to that, or universities could -- MS. KING: I thought you said direct universities. DR. RUSSELL: No, I said it -- direct the recommendation toward the institution, not to the IRB itself, so that the institution can fix the problem. CHAIRPERSON FADEN: In other words, the general assurance, for example, could say the scientific review that the IRB needs to be relying on will be made by this institution, not necessarily by the IRB but by the department, committee, or -- I mean, I don't -- DR. RUSSELL: Or by a separate committee. DR. MACKLIN: There is one little problem with that, and that is one of the existing mechanisms that people use to weasel themselves out of this is the department chair signs off on it, and that department chair signs them blindfolded. CHAIRPERSON FADEN: Okay. DR. MACKLIN: So if you leave it to the dean and the -- CHAIRPERSON FADEN: Let's do this. In the interest -- we've got to go on. The sense -- the question is, does this committee want to change four and say that it's -- we want IRBs to be directed, IRBs or in -- you can say IRBs or through whatever mechanisms the IRB and the university work out, and then it becomes one of those, okay, our recommendation to government is figure out some process to come up with a way to -- MS. KING: I asked this question in finding. I think that what you want is a finding that goes to the point you just made when you said that you have to ask from the point of ethics whether there's enough scientific merit here to warrant subjecting human subjects to risk. And I think what you want to do here is in the light of that finding say that it is -- and then, when it is no longer acceptable, then this capacity is missing in some IRBs, and that you then put this in the same category as you have some of these other recommendations. And the reason I suggest that is we haven't really discussed all of the variations. We don't really know all of the considerations about cost, except what we do know is you can't make a good ethical judgment without doing the -- that is what we know. That's what our experience is. That's what you stick with. CHAIRPERSON FADEN: Good. We can do that. So I take it that we've got 10A done. Okay. That's -- we're going to go to 10B. Okay. So we have now moved to a different set of concerns that emerged from the committee, okay? And what this says is we -- we bumped up against two big policy issues, or whatever you want to call them, two big issues that were problematic. And the question is, how ought they to be resolved, and there are clearly others in other areas of research that we didn't -- that didn't fall under our name. But these were two that we bumped up against, and we say somebody has got to figure this out, and the recommendation says it has got to be figured out in some sort of a public forum. Nancy? DR. OLEINICK: On line 13, why -- I don't -- the wording is, "In particular, exposure to radiation." I am not sure why we are singling out radiation here. CHAIRPERSON FADEN: Because the -- DR. OLEINICK: No, the issue is just risk to -- to healthy children. But it's not just from radiation. CHAIRPERSON FADEN: No, no. We should word this better. The reason it came to our attention is that there is a controversy ongoing currently, and it's in the literature, and it was sent to us -- we circulated it to everybody -- about people who want to do basically development -- I guess development of diagnostic technologies work or tracer studies with (quote) "normals" -- healthy kids. And there's this whole debate in the literature about whether if you take a healthy child and have them involved in a research project that offers no prospective benefit to them, okay, in which they're exposed to trace levels of radiation, whether that falls under the provision and the current regs of less than minimal risk, no more than minimal risk, whichever way it goes, which is the condition under which you can use children as research subjects without offsetting medical benefit. So here is a specific -- yeah. We need to rewrite it. The reason it came up -- now, you're right. There's a larger question about what this whole thing means in other areas of work, but it came to our attention out of the specific problem, community people I guess, who are interested in doing tracer research. DR. GLATSTEIN: I respectfully suggest that the same issue with -- as far as children and exposures are concerned -- relates to potential use for genetic therapy. I don't think we have any idea what genes that might be turned off in adults may not be turned off in kiddies, and I think that that's -- it's the same basic issue. CHAIRPERSON FADEN: It is the same. The only reason it's -- it's because that's how we got to it. We got to it because it's the radiation illustration of that problem. They are obvious -- DR. MACKLIN: What if we just changed the wording? Would they have been unhappy if we changed the wording "including, but not limited to"? CHAIRPERSON FADEN: Fine. MS. KING: I think that what we intend here is that we need a -- a way to change the Common Rule so it means that we need to call attention to the fact that this involves several agencies or all agencies governing -- that deal with research. CHAIRPERSON FADEN: Yeah, that's a good point. We should make the bureaucratic implications of this clearer. And two is the -- another policy issue that we bumped up across in our own experience in the several studies we had what looked like incompetent adults who were being used in research projects that offered no prospective benefit that were more than minimal risk, about which as far as we know the current regulatory system is silent. And so the issue is if we need a national debate or some sort of public policy to decide, is it okay? Or, under what conditions? Maybe it's never okay. You know, this gets into the gross violations of human rights. Some people might say this is a gross violation of human rights. I don't know. So is this recommendation okay? Is 10B all right with the modifications that have been suggested with respect to one in terms of "including, but not limited to" and explaining in the text that this is a recommendation that would require attention, goes to the limitations or ambiguities in the Common Rule, that kind of stuff. It's in the text but we can make it clearer. DR. MACKLIN: But isn't the -- isn't there another category there also? Not only those who are temporarily incapacitated, but what about those who may be permanently -- CHAIRPERSON FADEN: Well, that's why it says "including, but not limited to." It's both. What we want to do is, rather, highlight that it's -- DR. MACKLIN: Okay. CHAIRPERSON FADEN: -- it is also people who are permanently, or for a long time, in that state, as well as people who are temporarily in that state. And either way, we've got this issue about what can you -- what can you do to them? And the particular concern is when there is more than minimal risk and there's no way that they could benefit, and we had a couple of those. Not many, but we had a couple. It wasn't clear whether they were competent or not. If they had been clearly incompetent, then the issue would have emerged, is this ever appropriate to do? Even if they have a third party authorization. It's a good question. All we could see was that they might or might not be competent. They were Alzheimer's patients. We couldn't know how diseased they were. They were -- you know, that kind of thing. We didn't have the level of -- so is 10B okay? We've got to save time for the more -- Oh, I'm not going to, by the way, call for a break. I'm just going to assume that we're going to work, and if people need to get up, which you people have no hesitation in doing -- (Laughter.) -- then you can get up. There are cookies here and -- All right. So now we're into 10C. MS. KING: I had a question about two, and that is other -- maybe I should look at this, but other than the oral history project, I wanted to know what evidence that there was of inadequate use of sanctions. You what connection between violations of standards for research involving human subjects and sanctions for those violations. I'm trying to get a better sense of why we think the current system in place is -- and the use of sanctions in enforcement is inadequate. This is an evidentiary question. CHAIRPERSON FADEN: Okay. That's -- MS. KING: From the committee's work or experience or -- or -- and I see that we have past ethics. But I'm really asking that we examine the current system in any way and reach some reasons for concluding that what we want here, clear connection is not working. That's really what I'm -- CHAIRPERSON FADEN: That's a very good point. And we probably need to do a little work on that one. What we do have is our own experience from the historical investigation -- MS. KING: Right. CHAIRPERSON FADEN: -- in which we've seen how difficult it is to decide whether anybody should be sanctioned -- and, if so, how -- when the rules weren't clear. MS. KING: Right. CHAIRPERSON FADEN: Now, the issue -- including the rules about sanction. And the issue is today are the rules clear, and you're saying we don't have any evidence that there is direction on that. MS. KING: Yeah. I wanted to know why we decided to do some of those things. CHAIRPERSON FADEN: In two. MS. KING: In two, right. CHAIRPERSON FADEN: So we will go back and look at the work on the contemporary stuff. It talks about contemporary oversight in C. But, you know, you're right. This may or may not stand, depending on whether we can pull in any contemporary evidence. What we know from the historical evidence is it's real important that that be -- MS. KING: Agreed, agreed. CHAIRPERSON FADEN: -- but we don't know whether, in fact, it is or not. I mean, I don't know what those sanctions are. MS. KING: The reason I asked this is the recent, quite well criticized case as a matter of fact, that the university is screaming and yelling that HHS took against the University of South Carolina -- CHAIRPERSON FADEN: Right. MS. KING: -- in actions near and dear to my heart that seems to work. CHAIRPERSON FADEN: Right. MS. KING: So I was curious about what are the kinds of evidence that we have -- CHAIRPERSON FADEN: Right. Good point. MS. KING: -- for the contemporary period being inadequate. CHAIRPERSON FADEN: We will keep this in or not keep this in and circulate that. I take it that -- that basically what 10C(1) would be, and it could be -- 10C(1) essentially says what we learned from the RPRP and from the subject interview survey was really, really useful. And it could be, of course, done better if it was with more planning and more thought and more whatever, but it's the kind of thing that needs to be done -- this is your point, Henry -- on an ongoing regular basis. You can't pretend it's fixed once you write the regulations and it's done, and merely making sure that the general assurances are right every time the general assurances need to be renegotiated are not going to get you this kind of insight into the system. So it's basically saying, "This level of oversight is required," the level that looks at outcomes and products and not a level that looks at you've got 14 members on your IRB and you have one community member and it's not worth -- DR. MACKLIN: Yeah, I entirely support this. I think the -- I have a minor suggestion of a change in wording, very minor. Under 10C(1), the last line there going onto the next page says, "To determine the extent to which the rights and interests of participants appear to be protected." I know why that's in there, but that's a little weak because to seek to -- a study to show -- so I would suggest just to say, "To seek to determine the extent to which the rights and interests of participants are protected." And that way it says you are seeking to determine it. But to say they appear to be protected, you can shove out all of those documents Pat keeps talking about. CHAIRPERSON FADEN: And we would hope that this -- they would be -- that the system that would come in and do this regularly would be able to do more than we did and be able to say that rather than what we did. You're right. That's much better. Okay. Now we go to recommendation 11. We probably should see if we can get Jay in here, because I know he has a strong interest in this recommendation, as do others of us. But nevertheless, this is, as he pointed out earlier -- DR. GLATSTEIN: While we're waiting for Jay, there is another thing that we've -- we've seen some individual patients who have legitimate complaints that they think they are experimented on but they were treated and weren't part of an experiment as we're using the term. We have also seen that we've sent letters to some IRBs to question the papers that came out of the institution, report their experience with a new technology, and we've -- then, we got a response that that wasn't considered research, and I don't think it is research. But from the patient's point of view, the doctor is putting into practice a technique which -- with which he has no background or familiarity other than what he has read. CHAIRPERSON FADEN: Right. Right, right, right. DR. GLATSTEIN: And I think this is a real issue. It is not research according to our committee. But at the same time, I think we have to have something that addresses this issue because I think it is a real issue from the recipient's point of view. CHAIRPERSON FADEN: What we should do I think -- first of all, we have to make sure that gets written up and stuck some place, so that's still a problem. Certainly, in the summary chapter, when we talk about all of the inherent ambiguities, it is not only a difference between -- one of the reasons why research and treatment is so confusing is that some things could be brand new. And being introduced without a research context, that just adds to people's confusion. We need to say that in the -- DR. GLATSTEIN: When a new technology gets introduced in an individual practice or hospital, there is obviously a learning curve associated with it. And somehow we've got to convey that that's -- we don't consider that research in the purview of the committee, but it is certainly a risk to the patient. CHAIRPERSON FADEN: It's very well taken. DR. GLATSTEIN: And my -- we have seen so many examples of it here, and I think we need to have something in there, maybe not so much from a recommendation point of view or finding point of view, but in discussion we have to -- we have to touch on this point. CHAIRPERSON FADEN: What it raises is what -- you know, what patients really are concerned about is being subjected to new stuff in an inappropriate fashion, and they don't really care whether the new stuff is being, you know, done in an experimental -- in the trappings of a data-gathering context or not. From their point of view, it's new stuff and it causes unknown risk. DR. GLATSTEIN: Well, if Hopkins reports a series of 50 cases that's one thing. But if it's the first case that Joe Dokes does in the Pennsyltucky -- CHAIRPERSON FADEN: Right. DR. GLATSTEIN: -- and in -- (Laughter.) -- from that point of view, it is his research even if it isn't research as we think of it. CHAIRPERSON FADEN: Yeah, that's quite -- it's important. So we have two sources of that. DR. GLATSTEIN: It touches on what we do, but I think it's very important from a patient's viewpoint. DR. MACKLIN: I agree entirely. But the question is there is no federal jurisdiction for that -- DR. GLATSTEIN: No. DR. MACKLIN: -- is there? DR. GLATSTEIN: I don't think there is. I think all we can try to do is try to educate the patients on this point. CHAIRPERSON FADEN: Is public education -- I mean, we got -- we skip the public education part and we skip the recommendations about educating the research community and university lawyers and university administrators and physicians. DR. GLATSTEIN: Frequently, this isn't even related to institutions. It's private practice. CHAIRPERSON FADEN: Right. But if you trained young medical students to be -- and hopefully, you know, to sort of get into the culture of what -- of young physicians, that you've got different responsibilities when this is something that is conventional practice. Or when it's being newly diffused into your practice, that your obligations are different, and they may be, in fact, more akin to your obligations when you're enrolling somebody in research, even if you no longer do research or never did research because you only do private practice and you're not interested in writing up a thing. Okay? But that could be something -- DR. GLATSTEIN: Might refer to it as the exportation of research, because that's sort of what it is. DR. LEDERER: Or it's the relationship between medical research and the practice of medicine. It's how -- DR. GLATSTEIN: Yeah. DR. LEDERER: -- it goes to -- CHAIRPERSON FADEN: So we need to get that in both the setup for Chapter 17 and then in here as well, in the education part. And you're right, Ruth, it doesn't fit with the regulatory sectors; the reach isn't there. But it certainly would fit with the education part. DR. GLATSTEIN: He's back. (Laughter.) CHAIRPERSON FADEN: Sorry, Jay. We were trying to hold off the discussion until -- DR. KATZ: Sorry. I need to go downstairs. CHAIRPERSON FADEN: No, that's fine. We had plenty -- we have so many things to discuss, it was not inconvenient. We were waiting to discuss recommendation 11, which is the national body for oversight of research and resolution of ethical issues. DR. KATZ: Well, what you said -- you know, depending on how we come out on the wording of what is problematic -- CHAIRPERSON FADEN: Well, we've just gone through -- DR. KATZ: Yeah, I know. But it's not quite -- but it means -- for the committee's purposes, the national body at this point may be much too much to recommend. CHAIRPERSON FADEN: Well, that's what we're trying to -- that's exactly what we're going to determine. I mean, the committee has just endorsed, and pretty much not too different but better language, 10A, B, and C, three areas that we say need to be fixed. DR. KATZ: Yeah. CHAIRPERSON FADEN: And then, this document says a national body is the best way to fix it. 10A says -- the introduction to 10 is now going to be reworded to say, "Government, come up with some kind of mechanism to come up with -- that will come up with the changes that are needed in order to solve the problems identified in 10A, B, and C." 11 says, "We think the mechanism you ought to use is a national body." Okay? That's the logic here, so the issue is, does the committee think that's -- that we ought to go and recommend this as the mechanism that the government should use to identify the changes needed in 10A, B, and C. DR. MACKLIN: Well, you pulled Jay back in the room, but now Phil is not here, and Phil speaks against this. And I don't know if he has said it adequately to the whole committee, but he has said it in the past time. CHAIRPERSON FADEN: Anna, you may need to send Jeff if it's a bathroom issue. (Laughter.) DR. KATZ: But as a member of the committee, I can't recommend it at this point as I -- DR. MACKLIN: But we have to hear the arguments for and against right now, and that's why I -- I'd rather that Phil come back because he is very eloquent on this point. CHAIRPERSON FADEN: I hear the arguments. What are the arguments against, and what are the arguments for is the issue. The problem is we've identified problems under 10A, 10B, 10C that need to be fixed. Somebody has got to decide how to fix them, all right, so the issue is do we want to be silent on the question of who should decide how to fix them, okay? Or do we want to make a recommendation -- you know, silent and just say, "Government, you decide. You pick whatever mechanism you want for deciding who should fix these things." Or should we make a recommendation about who should fix these things? MS. KING: There is a third way. CHAIRPERSON FADEN: Okay. MS. KING: And the third way is that in recommendation 10, in the commentary to the text, we could make suggestions about what kinds of mechanisms might work -- I mean, what kind of structure, where it could be located, which is neither a recommendation nor silence. That has been done by some other committees. That's -- CHAIRPERSON FADEN: All right. So let's -- MS. KING: -- where you put things that fall in the middle. CHAIRPERSON FADEN: So let's -- and also, let me get our options out, okay? One option is we don't -- we don't comment on how the -- what process the government should use to fix these problems, so we're silent. Another is we make some observations about how it might be done. The third is we make a recommendation to the government about how we -- who we think should decide how to fix these problems, and that recommendation could be this standing body, or it could be the alternative which is an ad hoc body that just is given the responsibility of dealing with these questions and then goes home. Okay? Or it could be some other recommendations. We might have a standing internal to the bureaucracy, in-house committee or something or other. So those are the options, and I just want there to be an explicit decision by the committee which way we go. Jay? DR. KATZ: Well, look I -- at the moment, I think, as I said just a moment ago, from the perspective of the committee as a whole, I don't think it makes too much sense to -- where we are at to ask for that kind of national board. But I still personally feel differently for two reasons, one about which there is disagreement and is namely how fundamentally is the system flawed at the moment? I think it is; others feel it is not. And that is in terms of our evaluation of the system, and the -- let me put it aside. We've talked about this enough. But as I said earlier, there is a fundamental tension in the conduct of research that the federal regulations have not sufficiently addressed, and surely haven't been addressed in any kind of official way. Namely, how to balance the dignitary interests of subjects of research against the need to -- for the acquisition of knowledge. That really plagues the human experimentation enterprise. It will have to continue to plague the human experimentation enterprise because it cannot be resolved. The only thing one can do is with respect to what kinds of issues, like the most recent one right now -- can you do research on head trauma patients in an emergency room, where there cannot be any informed consent? Who has the authority to decide? And I can give other examples. Decisions have to be made about how to balance the need to advance science against the dignitary interests of subjects of research, and we do take, in terms of national policy, consent seriously. And supposedly, bioethicists take informed consent seriously. And informed consent can only be taken seriously up to a point. These are very, very important issues that need to be thought through, and not just thought through because there is a bioethics literature on it, but somebody with some -- or some group with some kind of authority has to decide these things. And that's why I am in favor of it, but it's -- CHAIRPERSON FADEN: Can I agree with you and say that our committee, in 10B, has identified two such issues. And I -- I disagree with your interpretation that the committee doesn't have a basis for making the recommendation that you are in favor of. DR. KATZ: Okay. But then -- CHAIRPERSON FADEN: The committee has identified two issues that are parallel to the issue you've just described -- DR. KATZ: Okay. All right. CHAIRPERSON FADEN: -- in its own experience. That, in my mind, say somebody has got to -- these are the tough social policy issues, and I certainly want to see them debated in a public forum and resolved, maybe not for all time but resolved in such a way that the public has a voice, or at least a mechanism such as we have provided, for commenting. And then if, you know, three years from now we reverse our position on whether you can do research on people who are incompetent that doesn't rebound to their benefit, so be it. But I think we have identified -- DR. KATZ: Good. Well, then, I'm delighted to join you. CHAIRPERSON FADEN: Right. And so in that sense I would take, you know, exception with the fact that the committee doesn't have evidence, not on the first point where there is not agreement but on the second issue. That's the point of 10B. Phil? DR. RUSSELL: I think we should be very careful and separate the two issues, one on -- Jay did -- just addressed, which is national policymaking and addressing the sticky issues that we -- that keep being confronted. We need to separate that quite totally from an operational bureaucracy that -- that tries to fix what -- the operations in the field, in the decentralized IRBs. I'm very concerned about building a hierarchical bureaucracy that tries to, by administration, modify the operational effectiveness of the IRBs in the various institutions. Bureaucracies are cumbersome. They are -- they have serious limitations, and they are very inefficient. They -- and as you build a hierarchy, they tend not to get a lot smarter at the top than at the bottom. As a matter of fact, if you look at the -- (Laughter.) -- it goes up for a while and then comes back down again. So the -- and there is no evidence at all that the -- that these issues are -- operational issues are addressed better inside the Beltway than outside the Beltway. CHAIRPERSON FADEN: So you want to make a distinction between policy issues and operational issues. DR. RUSSELL: Absolutely. CHAIRPERSON FADEN: Okay. DR. RUSSELL: I think we need to address the -- CHAIRPERSON FADEN: I want to get back to that. Let's hear from other people. DR. RUSSELL: -- operational issues in a decentralized mode. To make the IRBs work better, we need to address the policy issues kind of one by one in a -- CHAIRPERSON FADEN: Let's see -- we'll keep that in mind as we hear from other people, because that is -- it's worth returning to. DR. MACKLIN: I want to endorse that completely, but -- and look at the wording in recommendation 11 that is -- Phil just used the word "operational" and "policy." Well, operational can be policy, too. The way the words are in here, oversee and help resolve the difficult -- difficult ethical choices. Oversight is the one I think -- is the operational one, and the oversight I entirely agree is bureaucratic and ends up looking at things like pieces of paper, checklists, whether you have a quorum at your meetings, and all kinds of other -- excuse me -- bullshit. Whereas, the difficult ethical choices confronting contemporary researchers are not matters of policy so much as they are matters of ethical quandary requiring thought and resolution, and surely a bureaucracy is not the right group or organization to address that. So if there -- I mean, there are something like a commission, a federal commission, or something, that would look at the kinds of issues in the way that the National Commission did but on specific issues. I'm just suggesting there should not be one recommendation for oversight and then the federal -- the ethical choices. CHAIRPERSON FADEN: Could I ask -- maybe we ought to -- since, in my mind anyway, 11 is related to 10, okay, what I am hearing so far is -- from at least -- well, only from two of you, I want to hear from everybody else -- is that a national body to deal with 10B is -- seems appropriate, where 10B is interpretation and application of ethical rules and principles. These are the large policy issues. Pat? Pat and then Eli. MS. KING: I had promised myself I wouldn't go talk on this one, but -- DR. ROYAL: Jay has a pill for you. (Laughter.) MS. KING: One, I think that some of the things that are talked about in 10B need to be done. CHAIRPERSON FADEN: Right. MS. KING: So my next question is, what can I do in my view that will help ensure that they be done? In my view, the best way to kill it is to call for the creation of a national permanent body. If anybody hadn't noticed, we're getting rid of them beginning with the Energy Department, some would like to start with. I mean, some of this needs to be couched in reality. What we want is we think the issues are important. It seems to me we are operating in an environment where it is very hard to talk about mechanisms with any assurance one way or the other. What I would do would be to urge that alternative ways of achieving certain characteristics. It seems to me what we've wanted was independence from any particular agency -- seemed to be one of the characteristics. Ruth mentioned public forum. I'm actually not sure how I feel about that. That cuts several ways, by the way. But that -- that we talk about is what the -- what the characteristics are -- would be important to have in such a mechanism. And my own way would be to suggest that should a bioethics commission be created, that the policies -- some of the big policy issues that we've identified, so I could research those kinds of things. There are -- some of the things Jay mentioned -- incompetent subjects be handled as a part of an agenda for that group. Or, that a consideration be given to establish, in connection with the common rule participants, an advisory committee -- some of the mechanisms to establish an independent advisory committee, not a presidentially-appointed committee, none of that kind of stuff. There are independent advisory committees appointed in government all of the time. Some are ad hoc, some are more or less permanent, but you identify your characteristics and you say the issues -- and you say why the issue is important and we would like them to be handled in this area. That would be my approach, rather than trying to specify what is least likely to happen -- a presidentially- appointed board. CHAIRPERSON FADEN: Eli and then Ken. DR. GLATSTEIN: I would strike the business of, as it's worded, the overseeing of federally conducted research. I'm not sure how that would be done, but I would support the idea of having some sort of commission to resolve difficult ethical choices as they are -- as is stated there, and also to serve as some sort of sounding board for the individual IRBs. I am convinced that one of the problems with the IRBs is that they are all operating in local vacuums, that they have no one to turn to themselves when they have a problem. And I think that's why there is such great variation from place to place. In a place like Yale or Hopkins, where the quality of the staff is top flight, I don't think it is quite the same as it is in some of the other institutions where the quality is a notch or two below. And I think that's a big problem. When you get to individual hospitals, I think the fall- off is considerable. And I would like to -- I support this idea, the concept, but I think it is -- the strength of it, I think, is to serve as some sort of referral base to which the IRBs can turn, because I think that's really one of the fundamental problems here. CHAIRPERSON FADEN: Okay. Ken and Lois. MR. FEINBERG: I think it's a mistake for a commission to recommend the appointment of a commission, and -- CHAIRPERSON FADEN: Gee, you think so? (Laughter.) MR. FEINBERG: What I would suggest is some recommendation along the lines that the government take steps to assure that ethical research issues will be given priority and visibility. And then, in the explanation lay out all sorts of possibilities as to how it can be done. I just think that -- that for this commission to recommend a specific way to do it is a mistake. In the recent report on how to improve science, how to improve the sophistication of how the courts should treat science and medicine in the courtroom, there was a recommendation that -- basically, that the government explore different avenues as to how that can best be assured. I think that -- that something general, with then an explanation of all sorts of ways to do it, but we're not flagging any specific bureaucratic way is the -- is the most likely way to assure that the recommendation will be given careful consideration. And just leave it to other people to decide which of the options, and there may be 10 of them, which is the best way to assure that this subject matter won't get lost. CHAIRPERSON FADEN: I've got Lois, Sue, and Ruth. MS. NORRIS: I just wanted to say that Eli has identified what I consider some of the primary purposes of whatever body we're talking about, and I have to rely upon the Kens and the Pats and the people who have experience with policymaking and the appropriate things for us to be doing. If we have to lay out a menu of choices in order to get someone to do something, that's fine with me. CHAIRPERSON FADEN: But you agree with Eli about the IRB -- MS. NORRIS: Indeed, I do. I think -- CHAIRPERSON FADEN: -- consultation role. MS. NORRIS: Yes. I think that's very important. CHAIRPERSON FADEN: Sue? DR. LEDERER: I guess I, too, want to endorse what I take to be now Ken and Pat's suggestion for laying out the alternative mechanism by which people could implement what we see as problem areas. But I felt I had to object to Eli's characterization that people in other institutions other than our scientific elite institutions don't know ordinary rules of good behavior, like you don't experiment on people -- DR. GLATSTEIN: I didn't mean to imply that. It just -- DR. LEDERER: I mean, these are -- we're not talking about extraordinary ethics here. We're talking about ordinary rules of decency. DR. GLATSTEIN: Well, I think -- I didn't mean to imply that the top flight institutions are immune to making blunders. But I think there is a -- they are the biggest ones in the news because they get the attention. And numerically, I'm not sure that that is true. CHAIRPERSON FADEN: I've got Ruth and Pat. I'm just trying to keep track of it. DR. MACKLIN: This is actually a question more to Ken in -- I mean, I can understand the spirit of the layouts and ways to do it, and don't tell them exactly how to do it. But if we want to be alert to some failures in either -- even the very attempt to put together a bioethics commission -- and there was a distinct failure about three years ago -- and also the difficulties that some committees have had in working and coming to some kind of either consensus or conclusions because of a political system that ended up paralyzing such committees, the question is, can we somehow recommend -- is there a way to recommend the kind of independence that a committee should have of a political process that will paralyze it? So we might as well not mention anything at all. Can't do that? MS. KING: No. CHAIRPERSON FADEN: Well, except I thought you did, Pat, say you could -- say that one of the critical attributes is independence. MS. KING: You can say that one of the critical attributes is -- CHAIRPERSON FADEN: And you can -- MS. KING: -- Ruth asked another question. She said, "Can you make an it independent of the political process?" and I said no, because the -- the people who appoint to the bodies are part of the political process. And as long as you control appointments -- as long as the political process controls appointments -- MR. FEINBERG: That's an awful morally elite position you're taking. The -- independent of the political process. I mean, it -- DR. MACKLIN: Well, what I mean -- you know what I mean. I can say -- I mean, I didn't mean morally elite, but some political processes end up paralyzing because they insist on people with certain points of view being appointed to the committees. And if people with those specific substantive points of view are appointed to the committees, the committees can go nowhere because they're paralyzed by the fact that there are people -- MR. FEINBERG: It might not even be a committee. DR. MACKLIN: Right. MR. FEINBERG: There are other ways to do this. CHAIRPERSON FADEN: I've got Pat and Jay. MS. KING: One is a comment. I don't know if the committee -- I'm trying to remember the book. There is a recent IOM publication where there was an examination by -- I don't know if you've read it, but we have -- we just got it. There is I think, if I'm not -- I know it was discussed. There are discussions of the sort that we are having now that might be beneficial in terms of a lot of the pros and cons of public versus private groups resolve, these kinds of issues, etcetera, that you might find useful. The second point that we ought not lose sight of is the point made by Phil, and that is that we -- we are completing two things. We tend to talk about both. They should be separated. One is the functions that we want satisfied, and two is the mechanism, and we are -- and Eli has introduced a third function, which is what made me think of the IOM -- fourth function, which made me think of the IOM report. And it is not clear at all that in terms of certain kinds of work with IRBs -- there are lots of problems, like coordination, one IRB knowing what the other has done so you'll reinvent the wheel. Lots of issues, that it's not even clear you need an independent body of this type to accomplish it all. But what you need is a coordinating function. That might work quite well in existing bureaucracies. So one of the things it seems to me that in the writing of this we need to do is to -- to follow clearly Phil's suggestion. I'm not trying to call it operational versus policy, but the kinds of -- CHAIRPERSON FADEN: What I want to do is go back to 10A and 10C. 10B everybody is saying the policy one, we need some sort of independent group to be available to debate, and at least temporarily address and provide policy guidance on these big issues of ethics rules and principles. We have 10A, if we can just go back to that for a minute. 10A is where we laid out the -- some of the very specific things, and we said, "Somebody go fix this -- these eight" -- you know, this is on page 17 -- 10A(1), 10A(2) -- this is one function. Find the solutions to these problems, right? Do we have a recommendation about what kind of entity we think, or what kind of strategy the government should adopt for coming up with solutions to helping -- to figuring out how IRBs can deal with finding enough time to review detailed studies, finding a way to clearly distinguish research from treatment, and so on. Is that in the oversight category or the operational category? Phil says no, no national body, or is that -- what do we do about that? MS. KING: I don't see that you need a national body to do something like that myself. You know, bureaucracies have their good points as well as their bad points. And I don't see why this requires some outside body. What it does require is some coordination between the agencies that sponsor research, but I don't think that -- I don't -- I think the national body -- a body to deal with those big issues, where we need a huge resolution and full exploration of how you deal with therapy versus research, some of those kinds of questions. Which leads me to say that maybe what we should do is point this -- as Ken said before, point to what the problems are, suggest that there are different mechanisms for dealing with different kinds of problems. Our interest is in seeing that these issues are resolved. We don't have time to explore. We might have done some -- we don't have time to explore. We might explore this in more detail. But we do -- we do have a clear understanding of what we think problems are, so we are going to go with what we -- what we know. CHAIRPERSON FADEN: I know that. What I was trying to do is that middle part. Do we have any suggestions to impart for the stuff that's under 10A, as to what would be a fruitful way to pursue it or not? If you want to go with the route that says we're going to lay out a menu of options, do we want to provide any guidance within that -- MS. KING: An interagency task force composed of the agencies that do research ought to be able to do something like this, I would think. CHAIRPERSON FADEN: The 10A series. That would be your suggestion. Ken? MR. FEINBERG: Again, I don't -- I think in our discussion of the recommendation we make Phil's point that when it comes to certain aspects of this, it should be decentralized, it shouldn't -- I mean, all of that is fine as -- as sort of a blueprint to guide policymakers. But I think the recommendation itself should just, again, be a generic recommendation that says that the government should take adequate steps to make sure these issues are prioritized and visible and that -- that -- CHAIRPERSON FADEN: That they get done. MR. FEINBERG: -- that they get done. And then, in the explanation, I am all for going with the experts around this table who say here is some do's and don'ts that should guide the government in deciding how to make a priority -- CHAIRPERSON FADEN: That's what I'm trying to get out from the group. If we go with this approach, I'm trying to get out from the group what are some of the guiding thoughts you would like to leave the government with as we tell them, go, come up with adequate steps to ensure that these problems get fixed. Ruth? DR. MACKLIN: One through four under 10A are really a mixed bag, and I don't think you can have one recommendation. CHAIRPERSON FADEN: Okay. DR. MACKLIN: So, I mean, let's look at each one. CHAIRPERSON FADEN: Fine. DR. MACKLIN: Number one, the mechanisms for ensuring that they appropriately allocate their time. Probably to be able to do that, it might require a -- some changes in the current requirements for IRB review of every protocol. I mean, however that gets fixed. I don't want to name a mechanism, but that's -- the current regulations say, "Here are the ones that are expedited. Here are the ones that require a full committee review," etcetera. If you want an alternative mechanism like subcommittees of IRBs to deal with informed consent documents, subcommittees to deal with other things, that's a kind of a mechanism, but it has to be dealt with at the level that says everything has to be -- go through full IRB. That's number one. I mean, I'm not -- these are just my -- Two -- I'm sorry. No -- yes. CHAIRPERSON FADEN: You're right. DR. MACKLIN: In two, it seems to me the kind of information -- and by the way, so, too, is three, the mechanism for providing the information provided to potential subjects. This is the kind of information that is currently in the federal regulations under the heading "informed consent," elements to be -- items to be disclosed to subjects. You know, the purpose, the blah, blah, blah, blah, here is the -- and then they have additional elements. Where they put them, additional or whatever, this is in the current regulations. This is saying, "These are the elements to be disclosed in informed -- in the informed consent process," whether they're in the form or not. Everything under two fits in that category. In other words, it is telling people how to convey information to subjects. And everything under three, that's simply the federal agency or agencies that support it. So this is adding information that has to be disclosed to subjects, and it seems to me that can fall right within the current federal regulations. You don't need any other mechanism for that. You just need to add these items. Four is a little different. But I'm only saying we -- I don't think we have these as a blanket solution or a recommendation. Each one requires a different one, and I've only suggested what I think is feasible for one through three. CHAIRPERSON FADEN: Can I just try and -- Jay is waiting patiently. I think -- I want to get on the table a brief discussion on 10C, and if the committee has any thoughts or wisdom it would like to impart on this issue. If C is -- if we are saying in 10C somebody -- the government -- somebody needs to institutionalize a regular look at the system, and it ought to involve something like a better version of the RPRP and the SIS. Have we any suggestions about who ought to be doing that? On the independence ground or independence criteria? And the other question -- I have, obviously, views myself but I want to hear -- MS. KING: Well, you can put -- I think that that could be handled in the existing agency. You can call for -- don't laugh -- GAO audits. You can call for all this kind of -- I mean, there are mechanisms -- (Laughter.) -- here. There are existing mechanisms that do this kind of work. If we think that the existing -- that those sorts of things don't work, we need to write why we think the theory is different. I have not been persuaded that it is not different. We could conduct this kind of work. I don't think that HHS and -- along with some of these agencies, couldn't conduct the same kind of work if they had the money to do it. I don't think that you've got to have the -- if you're saying -- if you think that we need independence, that the findings won't be interpreted well by people who get their paychecks from the Federal Government, then you can always ask for an advisory committee to the agency to help them design the study or interpret the study. But I don't think it -- it is outside of sort of the existing way of handling this kind of problem. That's my own -- that's my own sense. CHAIRPERSON FADEN: I think what I -- the sense that is coming to me from the group is that recommendation 11 -- the dominant view is that recommendation 11 should be replaced with a general recommendation that says, "You better make this a high priority, and you'd better take adequate steps to do this soon, and here are some thoughts about the different ways you can do it." But what we're saying is, "You ought to do this." Okay? MS. MASTROIANNI: Well, wouldn't another alternative be, then, to break down 10A and go through the -- CHAIRPERSON FADEN: I think it would be in the text within it. I think we -- MS. MASTROIANNI: Okay. CHAIRPERSON FADEN: The committee isn't going to have a chance to go through each one of those, no. I think basically it would -- we could never do that, but just -- with the only exception of 10B where there is a clear view that everybody has about how that needs to be done. The 10A and the 10C stuff, there -- I think there would be disagreements in the group about how that should be done, and we can just say that that is -- some general guidance there. 10B we put in the explication under this recommendation, say that the committee feels strongly that this particular arena needs independence and public accountability. This is dealing with large issues of social policy. The others, there are different ways in which they could be approached, and all we're saying is that we want to hold you accountable, government, for making sure that you fix these problems that we identified in recommendation 10. Is that the general sense of where we are? So that we can go on. DR. MACKLIN: I just -- I would like, though, to follow -- I mean, unless someone opposes it, to look again -- just look at 10A and possibly also 10C, to see whether these recommendations are grouped. I mean, I've -- it seems to me, and maybe this is my slender knowledge -- that 10A(1) and (3) are grouped, and they -- it makes a natural grouping because -- I'm sorry. Am I look at the wrong one? No, no, no. B -- I'm sorry -- (2) and (3) are grouped; (1) is different. In other words, if we don't give some guidance in -- I mean, laying out menus is one thing, but suggesting what we think is a wiser way to go based on what we know works or doesn't work, or what mechanisms currently exist, if we can suggest something that requires less creation of new mechanisms, it's not only more likely to be accepted, but it may fit in very well with those existing mechanisms anyway. So that's why I'm -- I was following up what Anna suggested. DR. LEDERER: I think that's a good idea, too. CHAIRPERSON FADEN: Excuse me, Sue? DR. LEDERER: I think that the -- I think separating 10 is a good idea, precisely for the reasons that I guess Anna suggested, and Ruth as well. CHAIRPERSON FADEN: Do you mean making them different recommendations, instead of 10A, 10B, 10C? We can certainly do that. We can certainly do that. Jay has been waiting patiently, so -- DR. KATZ: Well, I -- I yield 60 seconds of my 90 seconds to anyone; 30 seconds -- the only thing I wanted to say -- it may already be past this. I haven't been able to follow everything. But the last thing I would recommend is the appointment of another national ethics committee under guidance of -- not going under the guidance of Ken's that a committee shouldn't recommend the appointment of another committee, but we've had enough ethics committees already. The Presidential Commission, they did a wonderful job sort of formulating the principles that should govern research and all kinds of other things. So -- and that's not what is needed. Whether anything else is needed is another question, and -- but I would strongly urge us not to recommend the appointment of another -- of a successor national ethics commission. CHAIRPERSON FADEN: Okay. We're now at 10 of 4:00. The issue is whether we should try to do another recommendation or we should go to the process issue. I think we should go to the process issue, and I'm going to violate my own rule because I need to take a break. (Laughter.) So if we could take a five-minute break and then come back, we'll see what we haven't discussed and I'll try to figure out what to do. (Whereupon, the proceedings were off the record from 3:52 p.m. until 4:03 p.m.) CHAIRPERSON FADEN: Would the committee please come to the table? Anna and I are having a minor panic attack because we are sitting here trying to figure out how to get this done. We've made this wonderful progress in the past two days, which is just great, and then I sit there with the calendar and the hyperventilation starts again. You know, how are we going to get this through. We know that we're leading people. So we have a lot to discuss in the next hour about the mechanics of how we're going to do this, how we're going to sign off on this report, and let's just point out that there are -- there is the main report, which is what we've all been struggling with; there is the executive summary, which doesn't exist yet; and then there are the companion volumes which are largely just what they sound -- supplementary detailed documents that will be published for the scholars and the bureaucrats, and so on, who care about the details that have driven us all crazy over the past year and a half but don't make it to the main report. I'm looking for Jay. Oh, here comes Jay. We also have the issue that has emerged about dissents or concurring statements or how they are to be handled, so maybe we should take that one first, okay, and deal with that. But I just want to make sure -- we only have an hour. I don't want to take more than -- I don't want to have this spill over into tomorrow. So I just want to make sure that we don't take more than 15 or 20 minutes on this issue of dissents and the process for dealing with those, and then preserve enough time to think about and talk about how are we going to get through the next -- Anna will tell us how many weeks -- working backwards from when the thing has got to go to the printer. I mean, the bottom line is it's got to go to the printer by a certain date. Anna will tell us what that date is, and we -- and how that dates fits in relation to the last meeting, and then we'll work backwards. The printer is going to be -- what is the National Academy of Sciences press? Joseph Henry Press, the National Academy of Sciences, will -- will publish the report as a book, which means that it will be better looking than a GPO publication. The GPO also probably will do a run, but it will come out as a report by National Academy of Sciences press. It will show up in bookstores and things like that, so the implications are very nice for the packaging, I guess, of the report. But that means we have a deadline that's working with a printer. The constraint, of course, there was -- just to let you know, there was some interest on the part of commercial presses, but they can't work fast enough for this kind of a document given that we need every day we can need, whereas National Academy of Sciences press is sort of set up to turn stuff around, not quite as quickly as GPO but quicker than Oxford or something. MR. GUTTMAN: Take your time, but the marketing survey for the National Academy is -- the marketing survey can see -- we have to go meet with them. Among the questions are, "Will this volume be the best in its field? Why should it be purchased over the competitor's?" CHAIRPERSON FADEN: That's an easy one, relatively easy. (Laughter.) MR. GUTTMAN: Why should they purchase it? CHAIRPERSON FADEN: The more difficult one, okay? (Laughter.) But over the competitor's is -- well, the last time they had an advisory committee on human radiation experiments they did a lousy job. All right. We should go to the issue of dissents. All of us have seen a flurry of memos that went forward. I didn't mean to isolate Jay, but Jay indicated for some time now that there was a possibility that he might want to write a statement that could take the form of something that might be a dissent, and we've heard indications that Pat might want to dissent from some finding or more than one finding. It's not clear. So the three issues that are out lined are the committee's process for addressing this, and then placement and the responses -- I don't know where to start, but to put it open for the committee to consider. So the floor is open. DR. KATZ: Well, it's -- to me, it's simple. But it's just me and I present to you and I -- and set it forth in the -- in my two and a half page memo. So it seems to me that there can't be any question, and Ken said the same thing in his memo, that if anybody plans partially to dissent that that has to be included in the report. Hopefully, all of us will be careful in what we intend to dissent from, and if we do it we do so with an economy of words. So that issue that dissents have to be included I think is almost not debatable. Surely, dissents shouldn't be reviewed, in my mind, by the -- by anyone -- the committee or individuals -- reviewed by the committee. After all, it is writing the majority report, and that would be majoritarian tyranny. It -- the dissent is reviewable only by the dissenter. To be sure, and I hope what I would do if I write anything, as quickly as it's finished I want to send it to everybody on the committee for those who -- for reactions, because I may hear something that may want to -- that would induce me to modify my position, and maybe some -- some members of the committee would want to join me in whole or in part. Third, it doesn't make any sense to me, and I've never seen it, should be rebuttals to the dissent. We had the majority statement, and it stands on its own, and the dissent should stand on its own. And finally, I think that the dissents ought to come -- dissents ought to come immediately following the sections of recommendations. And those are my views. CHAIRPERSON FADEN: I've got Ruth and Ken. DR. MACKLIN: Yes. Well, I would certainly agree with Jay that a dissent is, by principles of freedom of speech and constitutionality and everything else, something that has to be allowed. My own view is that dissents should be on principle grounds, since that is what a dissent is. If I had a dissent from something the committee said on principle grounds, I would certainly want to write it and would have the right to do it. I don't happen to have any such, at least so far, on principle grounds. I would also agree -- I mean, I guess I'm unclear what Jay means by not be reviewed by the committee. Surely a statement that's a dissent should not be censored by the whole committee. That would be majoritarian tyranny. But I don't agree that the committee or members of the committee could not or cannot have a comment. I wouldn't use the word rebuttal, but comment, since the comment or the response, which may not be a rebuttal, may be in the form of an explanation or an explication and not of a direct rebuttal. So the fact that the committee has had its say in the chapter is fine. But if someone then says something by way of dissent to what was in the chapter, then the chapter itself does not reply or comment on the dissent. Therefore, just as the dissenter has a right to issue the dissent and have that be included, so, too, does anyone on the committee or the committee as a whole should be granted the same right to comment on the dissent. CHAIRPERSON FADEN: Ken? MR. FEINBERG: Three quick points. First, I don't share the view expressed in Jay's memo that a dissent adds luster to this report. I think we have debated and caucused and discussed countless issues here, and I am still hopeful that at the end of the day Jay will not find it necessary to file additional views. I don't think that that helps the report, and I continue to hope, that pursuant to Jay's own comment, that after he circulates his views and awaits comment from the members of this committee, that he may think twice about the necessity of filing additional views. Secondly, we should be careful about throwing around words like "dissent." I await with great interest, if Jay decides that he wants to file some personal views on issues. There's a big difference between labeling something a dissent -- that is, I oppose and am in opposition to what the committee is doing -- and filing supplementary views, concurring views, to emphasize certain points that a committee member feels, based on personal conscience, it is important to spell out. And I think it is one thing to say, "I've read the report, and I disagree with the report. I think that all of my committee members are basically incorrect -- their views -- and I am going to file a dissent." It's another thing to say, "I've read the report. It's a thoughtful report. I want to add some supplementary views of my own based on experience," and what have you. That is vastly different, it seems to me, in terms of the overall thrust of the report. And finally, Ruth is absolutely -- DR. KATZ: That would be satisfactory to you? I mean -- MR. FEINBERG: Well, it's not -- it is more satisfactory than dissenting views. DR. KATZ: Yes, good. MR. FEINBERG: I think much more satisfactory. And third, I -- final point, I think Ruth is absolutely right. I think that -- that the process must work, that Jay circulates his views, everybody reads them, and can't -- can suggest changes, for Jay unilaterally to decide whether he wants to accept those changes, and then the committee, if it feels necessary, in the majority report makes reference if it wants to Jay's views and says what it wants to say. My own view is, final point, that I think -- my own personal view is that I would be much less eager to respond to supplementary concurring views than views labeled "I dissent," and I hope that everybody will keep these thoughts in mind. DR. KATZ: Well, can I just in one second respond to you? Is because it got so confusing with the personal statement kind of issue and I'm -- I probably then overreacted and then put it in terms of dissent. My hunch would be at the moment if I have to do anything, it would be rather -- it would be -- most likely be in the form from what I've heard so far in saying that perhaps the -- perhaps saying that I concur. But in my view, the committee didn't go far enough and then say why. It's more likely going to be of the kind that you have less trouble with than being a dissent. CHAIRPERSON FADEN: Pat? MS. KING: Well, I do plan to dissent, and I do know the meaning of dissent, Ken. And I want to say that the questions of placement and what the committee wants to do I think are appropriate for discussion. I think it's quite hard to try to tell other people what to do with their views and principles, so I'm not going to try to do that. What I'm interested in is the committee process for those who intend or who are thinking about writing a dissent. You can't write one until you get a report. So while you are talking about how you want to respond to whatever is written, I want to talk about when we get what we're responding to so we can make a decision about what is going to be the content or the subject. The other -- the other question, it seems to me, for the committee is placement, because in my experience this is a discussion for the committee, where the statements are listed on the table of contents and where the statements appear. And whether the statements are labeled dissent, concurrences, whether that's a committee decision, or whether that's the decision of the person who drafts the comment, and whether the person's name appears, or whether the person's name does not appear. CHAIRPERSON FADEN: You mean in the table of contents. MS. KING: In the table of contents. CHAIRPERSON FADEN: Right. MS. KING: And I have seen it done -- CHAIRPERSON FADEN: Various ways. MS. KING: -- various ways. CHAIRPERSON FADEN: I have as well. MS. KING: Typically, what I have seen in all of these kind of committees is a listing on the table of contents of dissenting views and a placement of dissenting views at the end of the report, without a listing of person's views -- I mean, the person's names, and often not dissenting statements, even though they constitute a dissent. That sometimes they are labeled statement of individual members of the committee. CHAIRPERSON FADEN: That's where the term "personal statements" emerged. MS. KING: Right. So it seems to me that those kinds of issues are appropriate. I hope that you leave to me my question about what I'm going to do as I will leave to everybody else. But I think that there are questions of how fast the whole report appears, because having had experience in responding to reports, you can't respond responsibly until you see the whole report either. So if that's what we are encouraging, that's what I would also like to emphasize. I don't care about the others. People can write as many responses as they want. The committee can respond to what I have to say as a group or not. I don't care about that either. I would make one final statement, and that is the -- this report has -- because of the way we have operated, unlike some other committees, does not have a mechanism for taking account of differences internal to the report, and that ought to not be lost sight of. And there are not questions of supplemental findings versus dissent, etcetera, etcetera. There are questions about where there is consensus. You can have -- I said this yesterday when Ken was not here -- you can have consensus or unanimity on outcomes, and you can have lack of unanimity on how you get there. The way our report is structured for those people who as a matter of principle have a hard time with how we get there, there are no ways to permit you to do that easily because we have findings, and we have recommendations, and we have chapter discussions. So all of these things should be kept in mind when we are talking about how you do this. Different groups handle these kinds of problems differently, so perhaps what we should be talking about is what exactly will be objected to and how we might handle that, because my own objection doesn't go to recommendations so far; it goes to some other things about which I feel quite strongly, obviously strongly enough to -- to raise the whole question. So I think at this -- I've thought about this. It seems to me that where we are in the report is it's kind of really hard to do what some committees do, which is as you go along in the report, because you either take votes for -- because you have clear understandings of where there are differences, then you can write in as you go along. But we've all seen -- most of the committee, the overwhelming majority of the committee thinks this way. Others think this way on this issue, and it is all written in as the question in the text, and I have been asking myself whether that is possible at this stage. But in many places, it is not really truly comfortable in that real sense, because we didn't sort of do it and then keep accurate track of it. But it is a problem. CHAIRPERSON FADEN: Okay. I've got Ruth, and Duncan, Ken, and Henry. Ruth? DR. MACKLIN: I think I spoke already, but let me just ask Pat. I mean, I really want to understand this. If there were a way at this stage for you to express your disagreement or dissent, whatever, within the place or places in the text where it appears, would you do that? For example, if there were in one chapter a place where there could be this wording you just referred to, namely. However, one member of the committee -- and then you say what that is. Would that be -- MS. KING: That is actually what I thought was going to happen the last time we met. But that's impossible to do with the finding. Where you have a serious disagreement with a finding that goes to some core recommendations, that's the point I was making yesterday. When we left this issue last month, for me anyway, Jonathan Moreno and I were talking about ways of working in my differences into the chapter. A finding makes that very difficult, unless you do a vote, and I'm not asking for that. I'd rather write a separate one-pager or two-pager, whatever. But, yes, I have struggled with this question, and I thought that -- about how you take account of differences in views or strongly held views, and I didn't come up with a good solution at this point other than writing. I don't think it will do a lot of damage to the -- to undermine the report. CHAIRPERSON FADEN: You know, the issue of -- these findings force things. MS. KING: Right. CHAIRPERSON FADEN: Which is the point you're -- MS. KING: The point of having it. CHAIRPERSON FADEN: The point of having findings, and that's why we're struggling so hard over them is because they force the view. The problem is that it makes it harder to weasel. MS. KING: Right. CHAIRPERSON FADEN: And that's the idea, so you've got a dilemma and I appreciate the problem. Duncan, Ken, Henry. Duncan? DR. THOMAS: It's obvious that our personal statement can't be finalized until the report itself has been finalized. But it is also true that a personal statement can have a powerful effect on causing the committee to rethink certain issues, and I would like to ask those that are contemplating a personal statement if they wouldn't do the rest of us the privilege of having a preview of what it is that they're considering writing. At this point, with both Jay and with Pat, I'm having some difficulty anticipating the exact nature of their objections. And to see it in writing would be very helpful, because it would help crystalize my own thinking about how I might wish to revise the chapter, not necessarily to accept them, and it may be that at the end there will still be a fundamental difference of opinion. But it would be very helpful to me if we could have something like this which does not commit them to either the shape of the final comments or even the existence of a final comment. But it would really be nice to have that in writing before we go to the next meeting. CHAIRPERSON FADEN: I'd like to comment on that, but I want to get Ken and Henry out. MR. FEINBERG: Duncan has expressed exactly what I was going to say -- namely, I'm not prepared yet to concede that if Jay or Pat or anybody else has supplementary views or dissents, or whatever, the internal process of tempering language, trying to accommodate language, trying to work very hard at getting them on board, so to speak, they have a unilateral right to say, "You didn't go far enough. We want to file supplementary views or dissenting views, or whatever." But I completely agree with Duncan that I think the committee has to work to try and see if we can get them on board on something that is so important. The problem that may come up, and I anticipate this being talked about by the Chair, we don't have the luxury of time. I'm very concerned, and that's I think why Duncan mentioned the idea of some anticipatory language that would come, is to talk about the majority report going and then dissenting views or supplementary views, and then trying to work out temporizing language, or what have you. You know, to the extent that there is time to do that. But I completely agree with you, Duncan, that I would like to try and see if we can't have one report with no supplementary views if we can. CHAIRPERSON FADEN: Henry? DR. ROYAL: I'm in favor of trying to work out our differences, but I guess I don't understand the strong feelings about people expressing a different point of view. It's a very long report. We're talking about very complex issues, and the fact that a committee member might have a different point of view about a certain section of the report I would think would be the expected outcome as opposed to some abhorrent outcome. And I guess I don't -- I don't like the suggestion that you're somehow, you know, disloyal to the committee by writing something that really may enrich the report as opposed to detract from it. So I'm certainly in -- I'm in favor of trying to work out our differences. But if we can't work out our differences, I don't necessarily see that that means that someone writing a personal statement is going to detract from the report. CHAIRPERSON FADEN: I think we're all in agreement that we can only go so far, right. We're going to do the best we can, and there are differences, I think, as Ken indicated, and I think Pat alluded to this as well, different kinds of personal statements have different kinds of effects, potentially, on the report. Some could be enriching. Others could be quite harmful. DR. ROYAL: But you have to trust us. I mean -- CHAIRPERSON FADEN: Yeah. I mean, that's the -- DR. ROYAL -- we understand that statements can be enriching or they can be harmful, and you have to trust us to make sure that we can tell the different. CHAIRPERSON FADEN: I think that's an issue about which there is no alternative. (Laughter.) So we're all, I think -- DR. KATZ: That's what the process is really all about. I -- CHAIRPERSON FADEN: So that is where we are now, and I think, Duncan, your point surely, I agree, it would be helpful. And I'm not sure that things are going to change so radically much that if people could jot down something that was quick that would be most helpful for the rest of us. The problem we're going to move to immediately now is the time one. This is the segu‚, you know, into the timing because we need to -- all of us need to know when to expect this, so that all of this can -- can happen. I'm not sure there is much else to say on the personal statement issue. DR. KATZ: Could we ask some practical questions, or is it -- CHAIRPERSON FADEN: Sure. That's what we're moving to. DR. KATZ: Yeah. The question is, some of the chapters we've now received. Which ones are considered already final? Are they considered final final? None of them are -- when are we going to get -- CHAIRPERSON FADEN: Well, they might be final if you all come back saying, "This is great." This is -- you know, we're going to get to that right now. DR. KATZ: Oh. CHAIRPERSON FADEN: If you all send back to this -- the ones you're getting now, "This is terrific. I love it," and everybody says, "It's terrific. I love it," it's final. But if -- it's out for that. Okay? That's what it's out for. Can I make one comment before we go to the practical stuff? Just to remind everybody this was circulated. This is the -- an alternative recommendation on uranium miners. We will try to get it in tomorrow to revisit it, but please, you know, we get so many loose pieces of paper, so put it wherever it is you're going to -- whatever you're going to take back to your hotel room, put that -- put that with it. Okay. I'm sorry. Anna, can you work us backwards and see where we are, and then we can get back -- MS. MASTROIANNI: Okay. We have three pieces -- three big documents that we're talking about. One would be the executive summary, one is the actual final report that you all have been working with, and then there is a series of three supplemental volumes. The outline of the supplemental volumes is in your folder. The executive summary and the final report are currently scheduled to go to the publisher on August 14th. The supplemental volumes are scheduled to go to the publisher on August 30th. So what I would like to do is explain a couple of the stages. In addition to signoff, we also have a copy editing process which will be ongoing, as well as a final proofreading before it goes to the publisher, and then we have the actual publication. So looking at the calendar, we have a group -- what I think -- what I need to know from you is, are you updating those big, thick binders as things come in? Or is there a reason to resend out or the -- the people that need to see -- what I should probably do, then, is -- I'm getting varying responses, actually. What I can do is -- what I'm going to do tonight is to run through the final report table of contents and figure out which versions are the most recent and when you're getting the next ones, and then at least I'll have it here and I'll know what you're getting, exactly what you're getting in the next few weeks, and we'll -- I can hand this out so that you can even go to your notebook and check and make sure that you have the most recent versions, because some of them may not change and I will also note whether they're planning to be changed in the next two weeks. We have -- the issuance of the report is not something I think we've mentioned before, have we? CHAIRPERSON FADEN: It will be issued some time between after Labor Day and September 15th. MS. MASTROIANNI: Okay. And as I mentioned for the final report, the thicker volume, it has to go to the publisher on August 14th. The -- it has to be absolutely finalized, then, by August 4th, so that we can do the final proofreading and copy editing. We have a meeting scheduled for July 17 to 19. That means there is a space of about 15 days to put in our final final changes before it gets to the copy editor. So it's not a lot of time, but it's some time. We are planning to do weekly mailings, not surprisingly. Tomorrow we will have a handout with various chapters, which I don't know what they are off the top of my head, honestly, but we will have a packet for you to walk away with. And then we will send out another one next week, and we will send out another one -- and the last mailing is scheduled to be July 7th, so you'll probably get that on Saturday if not -- for some of you get them on Mondays. Hopefully, there won't be very many things in there, but, you know, I don't know what to tell you. I -- we do our best. So that's -- that's the time table for the final report. For the executive summary, as I said, that actually has not been written at all yet. It's currently scheduled to go to the publisher on August 14th. So we may get an extra week out of that, and the big question that we're grappling with is, when do you -- what is it? We'll deal with that. But when do you all need to get your last crack at the executive summary? CHAIRPERSON FADEN: Maybe your only crack, actually. MS. MASTROIANNI: Your only one. We haven't actually determined -- we are going to talk about that. Maybe we could revisit that tomorrow. I thought we would -- CHAIRPERSON FADEN: The thought was that it should be like 40 pages. You know, in other words, 40, 50 pages if you could get it, the kind of thing that is a short piece that the person -- and, frankly, so that it doesn't sound -- and it will probably be a little bit longer -- so that it doesn't sound like it's, you know, my God. It's mostly going to be the recommendations and findings chapters. I mean, it's going to be, you know, what we did, the case studies we covered, and the recommendations -- and the findings and recommendations. So it's not going to be like surprises. Now, people could still have objection to phrases. You know, as much as possible, we'll use language that has already been approved by the committee in a chapter rather than -- but the packaging always can have a different implication. So that's why we have to look at it. There should be no new news in there, but it -- it may sound different when it is compressed. So that's the deal. But it's basically a context, in a short number of pages, for the findings and recommendations is what the executive summary will be. MR. GUTTMAN: Well, haven't we -- it's not surprising. People suggest everywhere from a maximum of 50 down to like two pages if you really want to get the attention of decisionmakers, right? So that is -- MS. KING: Fifty is a bit long to me. CHAIRPERSON FADEN: We can talk. That's shooting at the top, right. MS. KING: But that's in part because the recommendations are too long. So somebody -- I mean, there are too many recommendations is what the problem is. And it's probably too late to cut and prune, but maybe it is possible to -- to do some work of combining. CHAIRPERSON FADEN: Well, that's part of why when the suggestion was to take apart recommendations, part of my hesitation is that some of them are bundled, perhaps -- maybe not in the most rational way, so that all that can show in the executive summary is the lead one, and the A, B, and C part isn't in the executive summary. But there is a reference to where you can find the A, B, and C. The bundling is for purposes of getting it -- you know, here is the -- here are the pithy 10 recommendations, because if we start making 10A(1) and 10B(1), then you've got a problem. But if they're bundled inappropriately, then that would be a mistake, too. But that's -- so that's it for the executive summary. But I think we need to work back a little bit on the dates. It's a little less clear. MS. MASTROIANNI: The executive summary? CHAIRPERSON FADEN: Well, no, on the whole report. I think it was Jay asked the question, are these final chapters? And the issue is every chapter that you get now -- MS. MASTROIANNI: From now on. CHAIRPERSON FADEN: -- is hoped to be -- MS. MASTROIANNI: Okay. CHAIRPERSON FADEN: Right. So what we're hoping is that people will not write back, "I hate this. It's disgusting." Now, if you write back, "I hate it, and it's disgusting," we've got a big problem. Okay? But we're now really into the Ken formulation. Can you live with it? All right. That's really where we are with these chapters. Can you live with it? If there's a section you can't live with, please let us know immediately and we'll try and fix it. But that's the sense in which these -- the ones from now on are intended to be received. MR. GUTTMAN: Just to the expectations in terms of what -- what level of -- Steve and, of course, Ruth can correct me -- but the chapters that you should pay attention to if you still have energy to pay attention to anything, the observational experiments, particularly the Marshall Islands. Steve has got to figure out what to do with new information. It's obviously something that hasn't received the attention that it should. The children, as you know, have been reorganized, and therefore hasn't gotten the focus. The Atomic Vets -- Phil Russell gave me his comments, and Ruth said that if Phil says it about the military he knows something. But so that has to be incorporated, but that -- that is going to be changed. The one you're getting tomorrow is not yet reflecting Phil's comments. CHAIRPERSON FADEN: Then, maybe we shouldn't send it out. MR. GUTTMAN: Well, for practical -- CHAIRPERSON FADEN: I think, Dan, that's a real issue. MR. GUTTMAN: Okay. Well, that's my question. CHAIRPERSON FADEN: Absolutely don't distribute it because it -- if you've already gotten serious changes from Ken, the committee can't resend it twice. MR. GUTTMAN: Okay. Fine. That's it, okay. CHAIRPERSON FADEN: Okay? What goes -- every chapter that you get now is going to be staff's best effort. MR. GUTTMAN: Okay. CHAIRPERSON FADEN: Okay? At that chapter, and all we're looking for now is, can you live with it? MR. GUTTMAN: Okay. CHAIRPERSON FADEN: Okay? If you can make -- if you can't live with a section of it, you've got to let us know right away and we'll try and fix it. That means that, you know, you -- Pat always wants to see, and with good reason, the report from beginning to end. That's going to be a little difficult to do until real close to the game, but what you're getting now, okay, will be -- you know, from now on we will -- you don't -- there will be a difference made. When you get the children's one, that's different because that's a stage behind. DR. THOMAS: You're still accepting comments on children's? CHAIRPERSON FADEN: Right. In other words, we will -- we're accepting comments on everything, but I think we'll -- what we should do is identify -- what we should do is identify on each chapter when you get it whether it is the staff's best effort, it has been around enough, all we're looking for is, can you live with it? Or, it's a primitive chapter, relatively speaking, it's behind schedule, of which there are a few, one of which is children's. Another which is going to be this chapter 17 that is going to be completely rewritten. And recommendations and findings, of course, everybody should always read, you know, with a fine-tooth comb because they are recommendations and findings. But we will probably -- we'll come up with a system where our chapters are stamped, okay, with something that says this is, you know, final in quotes, so read it and see if you can live with it, versus this is, you know, the stage before final. It is going -- there is going to be rewrite. Would that work, so people can know as they get it and, you know, so Atomic Vets should hold back. DR. ROYAL: It would be good to know before we get the chapter that said "final" on it that that was going to be the final chapter. CHAIRPERSON FADEN: I'm confused about -- DR. MACKLIN: Are there any that we now have that are considered -- MS. MASTROIANNI: I will go through this tonight and tomorrow morning, and I can get a -- I'll get a -- DR. KATZ: Are some considered final already? I mean -- MS. MASTROIANNI: I can tell you that tomorrow. CHAIRPERSON FADEN: All right. Maybe we should do final with a little "f." Say provisionally final. Let's just call them that, because I don't want to suggest that any of these are final in the sense that -- especially for the public record, because then they get taken to be the report. So there is nothing out there that is truly final final. But we're trying to make a distinction between provisionally final and -- DR. ROYAL: Why don't you say final draft on it or -- CHAIRPERSON FADEN: Final draft versus preliminary draft, just for purposes of a distinction. Okay? Final draft versus preliminary draft will be the designation. Does that work with everybody to convey the difference? Okay. Jay? DR. KATZ: And tomorrow we will hear which of the chapters might be considered for the moment final draft. Be sure that if you do that that you put the date behind this. CHAIRPERSON FADEN: So you know you've got the right one. DR. KATZ: Because sometimes I may have the wrong draft. CHAIRPERSON FADEN: That's what I'll do. DR. KATZ: And then, from then on, I guess we will get all of the chapters, and hopefully -- do you think these might -- sequentially or -- CHAIRPERSON FADEN: Not perfectly. We'll try the best we can but not perfectly. DR. KATZ: Okay. CHAIRPERSON FADEN: But what I would ask you to do is when you get your final draft, to stick it in the book. I mean, if you want to send your comment back on it, if you could possibly hold on to it, that would be very useful and -- or just xerox the pages we have changes or write a cover memo, because that's going to stay the provisional -- the final draft until we get everybody's together. That would be how you could build your book from beginning to end is what I'm suggesting. DR. KATZ: I plan to start now with book number 37 and -- but and -- and it will include in it what you tell us tomorrow and whatever you send us from them on. And I understand this correctly. MS. MASTROIANNI: Right. And for those of you -- right. And for those of you who haven't been keeping up filling in the notebook, we'll prepare a whole new one. DR. KATZ: Now, when does the -- when does the book have to go for copy editing? MS. MASTROIANNI: August 4th. CHAIRPERSON FADEN: August 4th. MS. MASTROIANNI: Right. So we have to work -- is that correct? Now, when is it? When does it go? Steve, come on. For final proofreading and -- MR. KLAIDMAN: August 4th is final proofreading. About July 15th for copy editing. MS. MASTROIANNI: Okay. But -- MR. KLAIDMAN: Copy editing is an ongoing process. DR. KATZ: Can I finish my time? CHAIRPERSON FADEN: Finish your time. DR. KATZ: Is that -- is the August 4th date when the report will really be final final, or is there an earlier date -- CHAIRPERSON FADEN: No. DR. KATZ: -- when it -- when we can't make changes? CHAIRPERSON FADEN: What I think we will need to do -- we'll work out a calendar -- is we will need a date at which point there is a from beginning to end document that is called -- which everything is final draft. DR. KATZ: Yeah. CHAIRPERSON FADEN: Okay? When that's done, at that point we'll have to give those of you who want to write whatever we call these things, okay, some period of time, given what's left, to write your personal statements to -- DR. KATZ: And get back to all of you. CHAIRPERSON FADEN: Right. Get back to all of you, and then that will -- a chance for the individual committee members or the whole committee to decide what they want to do with each of those. So we're going to have to work that out. MS. MASTROIANNI: My current estimate is that that -- you should have everything by July 8th. That will be -- DR. KATZ: That would be the time of day, so we have to think July -- CHAIRPERSON FADEN: It's as close as we'll be able to get it. MS. MASTROIANNI: Because we're still accepting comments all the way through the end. CHAIRPERSON FADEN: But it will be as close as we'll be able to get it, and we're going to have to ask those of you who want to write statements to do it based on that draft because we can't do it any other way. Okay? And if there is -- you know, if it turns out that you're writing on something about which there are going to be changes, we'll have to be working until the last second back and forth. But my guess is it's not going to change a whole lot after that, so by July 8th or 10th or something like that, everybody should have a beginning to end book. DR. KATZ: But that will change somewhat, if I understand it correctly. CHAIRPERSON FADEN: Well, hopefully not a lot. DR. KATZ: Not a lot. CHAIRPERSON FADEN: What we will do is alert you if there is a huge brouhaha about a particular chapter. We will let you know, okay, that that chapter or that section of the chapter is in contention. And if you're -- and please know that, okay, so we'll find a mechanism to let you know if there's active rewriting going on in any part of that document. Would that work? So you'll know if anything in that document is the subject of active debate or rewriting. Otherwise, we'll take it that that document is pretty much going to be the final report, and then we'll set in deadlines for personal statements, responses, whatever, working without the -- the whole idea, of course, is that we have it when we meet in July, that we have this thing. Plus, people's statements, so that there can be a discussion about everything. MS. KING: I will not have my statement in July because I have my own committee to chair, as you know, just before that. This has run into it. I can't even look at it until after that. CHAIRPERSON FADEN: We'll have to figure this out. MS. KING: I can make my statement in time for all of this stuff to get to -- I cannot make it before the July meeting because I've got my own July meeting. CHAIRPERSON FADEN: Well, we're going to have to do something to deal with this practice of the committee being able to -- to read it before it goes to the printer. So we're going to have to work in something. MS. KING: I can get it to you before the committee has to go to the printer in time for you to circulate it among the other committee members, but I'm saying it won't be before the July meeting because that's impossible. CHAIRPERSON FADEN: All right. Well, we'll just have to work with this. DR. KATZ: You know, you really have to think about this because I -- if we get the thing by July 8th, the entire draft let's say -- CHAIRPERSON FADEN: You're going to be getting it all along. DR. KATZ: We'll be getting it all along, but there is not much time between now and July 8th, and -- CHAIRPERSON FADEN: I know, and we'll probably fail. DR. KATZ: -- and the meeting is on the 17th, and I want to give the whole report a very careful reading. So to -- CHAIRPERSON FADEN: Jay? DR. KATZ: -- do the best -- no, no, I'm not suggesting -- CHAIRPERSON FADEN: I can't -- we can only do so much. We're all going to try to -- I mean, there's only -- only what we can do is what we can do. DR. KATZ: But can't we set perhaps different -- I'm not -- I'm not complaining. Can't we perhaps set different deadlines for us, then, and figure out what the deadlines need to be in order to be -- to comport also with what -- CHAIRPERSON FADEN: We can try. I'll have -- Anna and I will sit down, and we'll try to work out the best we can work out with the calendar. We'll try to do it as close as we can. DR. KATZ: And at least look at this. That's the only thing I'm suggesting. CHAIRPERSON FADEN: That's all we can do. And also, I want to emphasize that while there is certainly great meaning to reading it from beginning to end, it is coming. I mean, you know when you get the draft and you read it, even if you read Atomics Vets before you read Contemporary Stuff, you know what it says. So although certainly there is a great value to being able to see it as an integral whole, it is not as if, you know, this is going to be new stuff to anybody when you get it in July. So when you say the deadline is you're going to get it July 8th, and you only have X number of weeks, that's not really how it's going to come. It's going to come in pieces every day. Now, the worst part of it -- my real fear, Jay, is -- maybe from my point of view is we're not going to make it by July 8th, and that people don't have the time to read the stuff as it comes. I mean, this is going to be like a hellish couple of weeks, and people had other lives planned. This extension was, you know, not anticipated. So people are out of the country, or people are, you know, on vacation, or people have made other commitments for -- you know, other professional commitments. So the scariest thing to me is that -- is just the whole thing, you know, making it under this very tight -- tight deadline and people feeling as if they've had a chance, really, to look at it. DR. KATZ: Do we need the July meeting? CHAIRPERSON FADEN: Well, that's an interesting question. You could -- we could decide -- that's a very good point. We could decide we don't want the July meeting and everybody could take the three days and hold up in a room and read or something. I mean, we could say we don't need the meeting, and we do the signoff by -- DR. MACKLIN: What would be the task for the meeting? Would it be discussion of the chapters on which there has been comment? Will there be more discussion on the recommendations and findings? CHAIRPERSON FADEN: Well, it's an interesting question. I mean, what was envisioned is that we would particularly go on the recommendations and findings and make sure that those were -- that there would still be adjustments that needed to be made to get collective agreement on those for which there were going to be collective agreement -- hopefully most, if not all, all of the recommendations. DR. GLATSTEIN: After today, I think we probably will have to have some. But -- DR. KATZ: Do we need three days? CHAIRPERSON FADEN: We may not need three days, but we use all of the time we get. MS. KING: I don't know how many days we will need, but I'd stake a lot of years of experience on the fact that when we read the (quote) "final chapters" (end quote) that more holes will appear than you will anticipate. And what we will be doing -- (Laughter.) No, what we will be doing -- I'm quite realistically -- what we'll be doing is the best, quickest way to have a suggestion to fix a hole. I mean, it's not -- and that's what you need. You could delegate that to somebody if you want to. Then you wouldn't need a meeting. But my sense is that probably is not a wise thing to do given the state of the report about those holes. But my experience says they're going to show up, and it's not necessarily they will show up in the findings and recommendations. They may show up lots of places, and we'll be spending all of the meeting going through one by one fixing the holes quickly, as quickly as we can. CHAIRPERSON FADEN: Right. What's the best way to patch up this problem? MS. KING: Right. CHAIRPERSON FADEN: I do think -- I mean, my own view is that the recommendations and findings will need -- you know, we may sit there with four of them where there are five different people fighting over the exact word for this finding and doing that face to face. We resolved a lot today, today and yesterday, by being all together in one room on findings and recommendations. DR. GLATSTEIN: Yes, but we have quite a bit to go. CHAIRPERSON FADEN: That's right. And even though we feel like, at least I feel like we've made real progress in the findings and recommendations that we've reviewed so far, there is a world of difference between that feeling and its getting down on, you know, the paper, and then people will have reactions to the paper. So my own sense is that we do need those days. I don't know about three days, but I do think that we need -- and then we have how many weeks afterwards? Two weeks? MS. KING: Two weeks. CHAIRPERSON FADEN: Two weeks to -- for the staff -- largely staff at that point. I mean, at that point, there should be no more -- you know, unless a committee member takes on a special task of saying, "I will fill this hole with a paragraph," and we'll say, "Okay, Henry, bless you. Go fill in the hole with a paragraph," and that's it, then by and large it will be staff work in those 10 days, entering the changes for the copy editing or proofreading, and all that kind of stuff. So it's a huge job. Dan, did you want to say something? MR. GUTTMAN: Just a small point. I wanted to just say, are you looking at the potential stylistic changes to the ethics chapters? Because that may run into -- CHAIRPERSON FADEN: What stylistic changes? MR. GUTTMAN: The readability. Sara Flynn has looked at the ethics chapter. We've had some questions from the people who have been reading the main key ethics chapters who are confused by them, which is important if we're going to write a report for people. And so one of the questions is changing and flipping around the order -- CHAIRPERSON FADEN: Oh, the order. I mean, this is not a -- yeah. I -- this is -- I don't think this -- MR. GUTTMAN: It's trivial, but it's important in this context. CHAIRPERSON FADEN: Yeah, that's going to come out. There is a discussion going about whether the order of the ethics chapters should be flipped, so that you start with the practices and standards chapters because that's more available and more engaging than the chapter that starts with the history of ethics -- of human subjects' policies and the various agencies, which is duller and drier. So that's an issue of order that the staff is playing with as to which way would be better. I don't know if -- if anybody would like to weigh in on that, that's fine. But it's -- you know, it can be just as easily flipped back over again. DR. MACKLIN: You're talking about flipping and you're giving half titles. CHAIRPERSON FADEN: I'm sorry. If you look at -- DR. MACKLIN: Would someone please be precise? I've got the table of contents. What do you want to flip with what? CHAIRPERSON FADEN: Flipping Chapter 2 and Chapter 1. MS. KING: But Dan said something -- order doesn't concern me. Dan said something else. Maybe I didn't hear him right. MR. GUTTMAN: No, no. Here is the question. What happened -- there are several things involved. One is that the chapter, the so-called John Harkness chapter, I think people think is terrifically interesting and readable and engaging, and, therefore, it might be a nice first chapter except that you -- what you have to know to get to that. There are things that -- in other words, in the process of trying to rewrite it, things that people have spent a lot of time focusing on may or may not get lost, so we just wanted to alert the committee. MS. KING: So it's not a question of the chapters as written not being understood by people who read them. It's a question of making sure they can be understood after we flip them. CHAIRPERSON FADEN: Well, it's both. Basically, what it is is Sara's job is -- as you all know, is the editor of the volume, has strong suggestions about how to make the chapter more readable. DR. MACKLIN: Is this taking them out of chronological order? CHAIRPERSON FADEN: No, because Chapter 2 starts with the 1940s. It starts at the same period as Chapter 1. Current Chapter 1 and current Chapter 2 start at the same point.l MR. GUTTMAN: I think Sara's basic point is -- CHAIRPERSON FADEN: I don't think we should use -- MR. GUTTMAN: -- that people and practices are more interesting than documents. CHAIRPERSON FADEN: But that's basically -- so it's her job. I mean, it's basically she's doing her job and trying to give us a report, and we'll -- and so the staff is playing around with it. And, you know, I -- the anxiety that I'm hearing or sensing is it's problematic because those chapters had pretty much been, you know, reviewed and whatever by the committee, so we don't want to be radically transforming them. And that's always the thin line between, you know, an editor who is a writer who isn't as interested in what we've haggled over as in people who close the book after the first two pages, which was the concern that animated her when she started reading about memo so-and-so to so-and-so in April of '47, followed by another one in May of '47, and saying, "Gee, I don't know about this. This may not keep people going with this report very long." So that was her concern. All right. You can say -- yeah. MS. MASTROIANNI: About the supplemental volumes. They are due to the publisher on August 30th. CHAIRPERSON FADEN: Oh, we forgot about that. MS. MASTROIANNI: And we're copy editing kind of as they go along over the next couple of months. They are in the process, some of them, of being sent to the agencies for any fact checking that is necessary, so that the version that you get is as close as we can get it, but there still may be some factual changes. One I think you've already received. I mean, I can go through this again tomorrow. You will be getting another one tomorrow. It's really up to you when you want to get comments back to us. I would say within the next month. Yeah, you received the table of contents. I'm sorry. No, the only thing that you have -- no, there is only -- there is only one that you will be receiving tomorrow. I'm anticipating the distribution tomorrow. CHAIRPERSON FADEN: Lois, did you want to comment? MS. NORRIS: Will the final draft have gone through Sara before we get it? CHAIRPERSON FADEN: Yeah, that's the idea, that when you -- if you get something that says "final draft" that's the committee -- the draft -- the staff is done with it. MS. NORRIS: Okay. So my -- I guess my question is, if we at that point see line edit types of things, do you want those comments? Or ignore them? CHAIRPERSON FADEN: Yeah, yeah, sure. Sure. MS. NORRIS: You can put them in. CHAIRPERSON FADEN: Sure. Especially if you happen to be a good editor, yeah. Oh, absolutely. If you happen to be the kind of person who edits as you write, that would be great. MS. NORRIS: Okay. I just didn't know whether that's burdensome for you because -- CHAIRPERSON FADEN: No. MS. NORRIS: -- someone is going to catch that ultimately anyway. CHAIRPERSON FADEN: Right. But what we want to distinguish is where, you know, you really think it's -- where you've got a big problem. If you don't have a big problem -- and then, also with the understanding that if your change doesn't get in you could live with it. So if there's some change that you make that you say, "Unless this change goes in I'm going to be apoplectic," that -- you know, that would be fine. We have all of these tests. Now we have the apoplectic test. Let me say one thing I forgot to mention about the supplementary volumes. This is a real tension because we're short on time. Obviously, my own priority is to spend much more time struggling over the report than the supplementary volumes. It is, however, also the case that the supplementary volumes go over the authorship of the committee, so that we have some responsibility with respect to the supplementary volumes. You are, obviously, free to exercise your sense of responsibility with respect to the supplementary volumes however you choose, but they don't come out as authored by anybody. They come out as supplementary volumes, supplementary report of the committee. So we are all collectively responsible for what's in the supplementary volumes. You'll see as you get them that they are heavily technical and detailed in character, but I just -- you get the sense of what I'm saying. They're out there for whatever -- and there will be a call at the July meeting of approval of the supplementary volumes, which I have to do to get it out. MS. NORRIS: But they won't all be done. CHAIRPERSON FADEN: Not all, not at the July -- but then for those that are not done they will be signed off. There will be some sense of signing off by E-mail or fax or something, but you will be asked to say, "This is okay with me." And that's a problem because it's -- it's a committee product, even though it's not, admittedly, products that we have agonized over. They are committee products, and we should be mindful of that, that you will be asked to do that. I'm sorry. Eli? DR. GLATSTEIN: From most of the titles there, from Volume 1 at least, the things that we've touched upon had some background on, except for 1(d). I don't remember seeing anything on that. CHAIRPERSON FADEN: 1(d) is the California case study, and that's the -- MR. GUTTMAN: This is a revision of what you had -- the draft that was sent out to you six months ago. MS. MASTROIANNI: You'll be getting that one tomorrow. DR. GLATSTEIN: Okay. CHAIRPERSON FADEN: At one point, there was a thought of having it be a chapter in the report, but it is much different, you know, since then. And then the problem is all of this work was done, so what are we going to do with it? When we decided not to do the case -- the institutional case study approach and eliminated it, then it just seemed like a terrible thing not to -- MR. GUTTMAN: It got some good reviews from some of the serious scholars in the California system -- you know, critical commentary as well. DR. OLEINICK: We did another one. Wasn't there one done on Oak Ridge? They decided to just self-destruct, okay. MR. GUTTMAN: It has been incorporated. They cannibalized. DR. OLEINICK: Good, okay. Fine. I'm not asking to see anything -- (Laughter.) -- I can assure you. MR. GUTTMAN: In fact, we snatched parts of the -- (Laughter.) -- for the rest of the report. CHAIRPERSON FADEN: You wouldn't want to see it. MS. MASTROIANNI: I assure you also that the final report will be formally copy edited, so the version that you will see may not have been copy edited. It may have been edited but not the comments and the grammar and all of that. CHAIRPERSON FADEN: Which is why, Lois, your point is still useful. MS. MASTROIANNI: Right. CHAIRPERSON FADEN: Those kinds of comments are still useful. Sara is editing on a large scale but not copy editing, and that's a task that will be done by somebody else who has recently been hired for that purpose, so it -- Sara is writing for -- is editing for style and not for the smaller stuff. DR. KATZ: Can you also give us tomorrow two days -- is the date when if there aren't any -- except for statements -- the date you would like to receive them at the central office, and so that it can be circulated. And also, the date when it finally has to be in in order to make the -- to make the volume. Possibly, I don't know, there may be some leeway here because it comes at the very end of the report. There may not be. But anyway, we need those -- all of us need those dates. And if you could let them -- MS. MASTROIANNI: We'll have to work those in. DR. KATZ: -- and think about it. CHAIRPERSON FADEN: It may be, for what it's worth, that you may not be able to walk away with this tomorrow. It may have to be faxed to you on Monday. DR. KATZ: Oh, okay. CHAIRPERSON FADEN: It may not be possible for Anna to pull this out and make sure it's right by the time we leave tomorrow, so better to get it right and get faxed to us on Monday than have to get another one of those things that things are replaced, right? This piece of paper with this other piece of paper when you don't know where the other piece of paper went to. Thank you all very much. We start -- to remind everyone, tomorrow I believe we start at 8:30 rather than -- right, rather than 9:00. (Whereupon, at 5:00 p.m., the Advisory Committee meeting was adjourned, to reconvene at 8:30 a.m., the following day.)