DEPARTMENT OF HEALTH AND HUMAN SERVICES

Text Box: Opening Session

[CONVENE 8:08 A.M.]

M. STOTO: Are you ready? Well, let’s get started, everyone. I’d like to welcome everyone; thank everyone for coming. I guess the first order of business is introduction of the Committee members. So what I’d like to do is just go around the table, have the Committee members introduce themselves and then go around the room so we know who else is here. I’m Mike Stoto from the Rand Corporation and Harvard School of Public Health and I am the Chair of the Committee. Robert, do you want to ...

R. SILLS: I’m Robert Sills. I’m the head of molecular pathology at NIEHS.

D. JOHNSON: I’m Dave Johnson, the Executive Medical Director for the Division of Environmental Health, Florida Department of Health.

P. CAMACHO: Paul Camacho from the University of Massachusetts in Boston.

E. HASSOUN: Ezdihar Hassoun, Associate Professor of Toxicology, the University of Toledo, College of Pharmacy.

R. TREWYN: Ron Trewyn, Vice Provost Research, Dean of the Graduate School of Kansas State University.

J. ROBINSON: I’m Julie Robinson. I’m the Branch Chief for the Air Force Health Study at Brooks City-Base.

J. MICHALEK: Joel Michalek, Principal Investigator of the Air Force Health Study, Brooks City-Base.

L. SCHECHTMAN: I’m Leonard Schechtman. I’m the Executive Secretary of the Ranch Hands Advisory Committee and the Deputy Director for Washington Operations at the National Center for Toxicological Research at FDA.

D. BUTLER: David Butler. I’m a Project Officer with the National Academy of Sciences, Institute of Medicine. I’m Study Director for the AFHS Disposition Study.

G. KAYAJANIAN: I’m Gary Kayajanian and I’m an individual scientist. I evaluate human cancer data. I’ve done this for dioxin and arsenic and have found that high doses of dioxin — not too high — are actually beneficial with respect to cancer, significantly reducing cancer levels.

K. CAMPBELL: I’m Kim Campbell. I’m the Management Specialist, FDA.

M. OWENS: Maurice Owens with SAIC. I’m the Program Manager of our Air Force Health Study support contract.

J. MINER: I’m Jay Miner. I work for Operational Technologies, a support contractor for Program Management for the Air Force Health Study at Brooks City-Base.

M. MONTGOMERY: Lieutenant Margaret Montgomery. I work as the Deputy Program Manager at Brooks City-Base.

M. BLANCAS: Manny Blancas, Operational Technologies also. I work alongside Dr. Miner at Brooks City-Base.

M. YEAGER: My name’s Meagan Yeager. I am an employee of SAIC and I work on the Air Force Health Study.

W. GRUBBS: Bill Grubbs, SAIC. I work on the Air Force Health Study in support of the report.

M. STOTO: Okay. Thank you, everyone and again, welcome. Len, do you have any household — housekeeping items that — excuse me.

L. SCHECHTMAN: Household as well, yes. Just one; that we’ll have our usual working lunch around the noon hour. Should the day extend, the food will remain so that we can munch and continue to work. I also have the conflict of interest statement that I’ll read for everyone to hear for the record. The following announcement addresses the issue of conflict of interest with respect to this meeting and is made a part of the record to preclude even the appearance of such.

Based on the agenda submitted for today’s meeting, all special government employees have been screened for the — for their financial interests related to the topics at hand. FDA has determined that all financial interests and firms regulated by the Food and Drug Administration present no potential for a conflict of interest at this meeting. In the event that the discussions involve any other products or firms not already on the agenda for which a participant has a financial interest, the participants are aware of the need to be excluded from further participation. Such an action will be noted for the record. In the interest of fairness, all other guest participants are asked to address any current or previous financial involvement with any firm whose products upon which they wish to comment.

M. STOTO: Dr. Kayajanian has asked to speak during the comment period which we’ll certainly allow him to do.

G. KAYAJANIAN: I’ve secured a patent for the use of dioxin at modest levels as a cancer prevention agent based on not only the study data from the Ranch Hand Study, but from other human and animal studies.

M. STOTO: Thank you. Okay. So the agenda today is mainly to go through the chapters. We’ve done this in a couple of passes before and this is the remaining set of chapters. They’ve all been assigned to one reviewer with the exception of the last two — the conclusions and the executive summary where we were all asked to take a look at those — and then we’ll have a break for comments around mid-morning.

Approval of Previous Meeting Minutes

M. STOTO: And so the next item now is approval of the minutes. I think in your — in your folders is a version of the minutes. I have already been through it myself and have requested some changes. What I didn’t do in my review was to look at the detailed comments on the — on the chapters; those are the ones I reviewed myself. And so I’d like to ask those of you who did that if they have any comments on that, and of course, on the minutes as a whole as well? Joel?

J. MICHALEK: May I have a copy of the minutes? Do you have them with you?

M. STOTO: Oh yeah. Okay. I’ve got — I’ve got two right here, so ...

D. JOHNSON: I’m sorry. You asked for comments on the minutes and what else?

M. STOTO: The minutes, just especially if you were in charge of reviewing a particular chapter. I think it’s important that Joel and others from the — from the study have a chance to review the minutes for technical content. I mean, obviously, they’re our — they’re our meetings. It’s our responsibility for the minutes, but I would find that my — I could discharge that responsibility better if I asked that. In fact, it even says in the minutes that we — that we — that we should do that. So I don’t know what we can do in the future to make sure; maybe that the Air Force people get the minutes at the same time they’re sent to me? Oh, you did?

L. SCHECHTMAN: Yes.

M. STOTO: Okay. So then — so then if you have any comments, you’re welcome to make them too.

J. ROBINSON: We do review them and have submitted our comments.

M. STOTO: Okay. So they — but the comments probably should come back to me so I know that the changes really are technical and appropriate rather than ...

J. ROBINSON: Okay.

M. STOTO: Yeah.

J. ROBINSON: No problem.

M. STOTO: Not that I suspect you of anything, but just — but in terms of our responsibility. Okay. Were there any other comments that people wanted to make? Okay. Would someone like to move that we approve the minutes?

R. TREWYN: So moved.

M. STOTO: Dr. Trewyn. Second?

D. JOHNSON: Second.

M. STOTO: Okay. Thank you, Dr. Johnson. All in favor?

RHAC MEMBERS: Aye.

M. STOTO: All opposed? Abstentions? Thank you. It carries unanimously. Again, I want to — I want to thank our scribe for doing a nice job with this. This new system is working out very well. Okay. We’re — it’s our pleasure this morning to have Dr. David Butler from the National Academy of Sciences, Institute of Medicine to be here. He is going to staff the study that was mandated by — I don’t know; I forget the name of the law — last year and that we have been talking about in the last couple of meetings about the disposition of the Air Force Health Study.

Text Box: Update on the Air Force Health Study Disposition Study

D. BUTLER: Just taking a moment here to get all set up and to review just what we’re going to be taking a look during the course of this study. Very briefly, this study comes out of a Congressional mandate that was contained in the Veterans Benefits Act of 2003 which was signed in December of last year. That law mandated several elements for the National Academies to address and I want to go through these.

I’m not a big fan of reading slides, but in this case, I want to make an exception because the material that’s here is going to be the motivating and guiding factors for the National Academies’ study. It’s important that we try to answer all of these questions to the best of our ability. And since we’re going to be looking for input throughout our study process, I want to make sure everyone understands just what it is that we’re going to be doing.

First, the scientific merit of retaining and maintaining the medical records, other study data and laboratory specimens collected in the course of the AFHS. Second, whether any obstacles exist to retaining and maintaining those materials, data and laboratory specimens, including privacy concerns, obstacles both logistical and ethical. Third, the advisability of providing independent oversight of the medical records, and other materials, and of any further study of such records, data and specimens.

By “further study,” we understand this to mean either in the course of an investigation of the health of the veterans, the impacts of herbicide exposure during the war, or more generally, of health questions that might be addressed by the data and specimens. And if such studies are to take place, the mechanism for providing such oversight. Fourth, the advisability of extending the study itself, the potential value of doing that and the potential cost. And if the study is to be extended, the committee’s input on which federal or non-federal entity is best suited to continue the study.

Finally, the advisability of making the laboratory specimens collected available for independent research, including the value and relevance of such research and the potential cost of such research. To that end, we are putting together a study. We have now signed a contract with the Department of Veterans Affairs to conduct the work. I am in the process of putting together that committee. Very briefly, that process consists of my soliciting input from a number of different individuals, and sources on potential committee members and potential areas of expertise the committee should cover.

We are soliciting committee members in the following areas: those with expertise in environmental medicine issues and issues relevant to the health of Vietnam veterans; individuals who are familiar with the conduct of longitudinal epidemiologic studies and decision-making that goes into maintaining the records and biologic samples; individuals with expertise in the long-term maintenance and analysis of biologic specimens; biostatisticians who will — can give us input on issues related to sample size and future potential of these data to yield informative studies of veterans health or of aging and military populations; and finally and very importantly, bioethics because issues of informed consent are very important to the future study of these materials.

We are seeking input in two primary areas at the moment. First, are materials for the committee’s consideration. All National Academy of Sciences studies are science-based. The panel of experts we’ve put together can’t just kibitz what they think we ought to be doing. Any recommendations and conclusions they generate must be founded in the science. To that end, we are seeking materials for the committee’s consideration on those issues.

The other thing are — is suggested topics and speakers for our spring 2005 workshop. We intend on putting on a workshop in March or April of this year in Washington, DC where we will gather additional information for the committee’s consideration. And what we’re looking for are people that can come and provide some perspectives to our committee for their consideration. The National Academies has very strict requirements for perception of conflict of interest with our committee members for any study.

One of those restrictions prevents us, for example, from soliciting individuals who work for government agencies on this particular project since our sponsor, Department of Veterans Affairs, is a governmental agency. However, we’re aware of the fact that there are several very knowledgeable individuals in the federal government who might be able to provide us with some good input on this study. And I encourage everyone here today to get back to me on any recommendations they might have for either individuals, or institutions or areas of expertise that we should be soliciting in this workshop. Information on this study is not yet ...

M. STOTO: David, that workshop will be open to the public too so people can ...

D. BUTLER: That’s correct; this is a workshop that will be open to the public. We will make public announcement of it. I will make sure that Mike, that Dr. Schechtman is — are informed about the study so we can get good participation in it.

M. STOTO: And we’ll make sure that word gets around to the Committee about that?

L. SCHECHTMAN: Absolutely.

D. BUTLER: We do not have this up on the National Academies’ web site yet because I still have a few more administrative hoops to jump through internally. But information on this study and on all other National Academies’ studies will be posted on our “Current Projects” web site that’s reachable via a button from our home page. And as I’ve mentioned before, the full text of our reports, including our rather large series of veteran’s health reports, is available at the National Academies Press site. In addition, we maintain the site, veterans.iom.edu, which is a one-stop shopping location for information on all our studies, not just on Vietnam veterans, but more generally of our studies of veterans from all conflicts. I’d be happy to take questions.

M. STOTO: Okay. Thank you very much. Ron?

R. TREWYN: Yeah. David, you commented that you should be contacted if we have recommendations, but I don’t note an e-mail address or anything on here for you.

D. BUTLER: That was — yeah. And that you’re right and it was an oversight. I have established an e-mail address for this study. It is afhs_study@nas — for National Academy of Sciences — .edu. And that’s going to be the best way to get in touch with me on this study.

M. STOTO: Anyone else?

D. BUTLER: Thanks very much.

M. STOTO: And we’re delighted that this is finally moving here. This is something that’s been of great concern. And the issue that you’re studying has been of great concern to the Committee as well as whether or not the study was actually going has been a concern. So this is — this is great news that it’s finally moving. Paul, did you want to ...

P. CAMACHO: I’m sorry, Mike. I just have — are there any possible roadblocks that you can see preventing you from actually moving forward?

D. BUTLER: None that I know of.

P. CAMACHO: So the check from the VA is in the mail?

D. BUTLER: It’s in the office. That’s correct; we have a signed contract with the Department of Veterans Affairs and we have full funding for the study.

P. CAMACHO: And you have full funding? So nothing logistically in terms of that funding or money is going to stop this?

D. BUTLER: Nothing that I know of.

P. CAMACHO: Okay. Thank you.

M. OWENS: What do you envision as the period of performance of the study, Dr. Butler?

M. STOTO: The transcriber can’t hear you.

M. OWENS: What do you envision as the period of performance of your — of the study evaluation?

D. BUTLER: We’re moving expeditiously to push the study forward. I anticipate a report no later than this time next year.

M. STOTO: Rick, did you want to ask a question?

R. WEIDMAN: Yes sir, I did. And the question is for Dr. Butler as to the size of the contract — both the parameters — are they broad enough for you to do the kind of job and assessment of where the data as well as the tissue samples, blood samples, et cetera, should reside in the future, number one? And number two, were there — was it big enough? Was there enough cash American provided by the VA in the contract for you to be able to fulfill the scope of the contract?

RECORDER: Excuse me, sir. State your name for the record.

R. WEIDMAN: My name is Rick Weidman, Vietnam Veterans of America. In other words, is there enough money there to do it right?

D. BUTLER: Yes. We believe that we have sufficient funds in our contract in order to answer all of the questions that the committee was asked to address. I don’t have the exact figure in my head; it is approximately $850,000.

M. STOTO: Okay. Any other questions?

P. CAMACHO: When is this — when is the actual — this is actually for you, Michael. As the answers come out ...

M. STOTO: Joel.

P. CAMACHO: Joel, as the answers — as the answers get to the table November ‘05, what does that do to your logistics of the Air Force Health Study regardless of what he says? You know what I mean? Are you breaking down already by that time?

J. MICHALEK: We — we’ve already pretty much decided to stop doing research on January 1, 2006 and to spend the last few months of the study in shut down. So the end of 2005 is putting us at a position where it seems awkward in terms of, you know, if there’s an active decision to continue the study, there’s going to have to be some very proactive measures taken by the government because we’re in a shut-down mode starting January 1, 2006.

P. CAMACHO: But you’re — when you say “shut down,” are these the quality or the maintenance of the specimens?

J. MICHALEK: Well, the maintenance of the specimens will be there until the last day. I mean, there’s going to — there are freezers; there’s a building; they’ll be locked up. There’s an uninterruptible power supply. There are six million documents stored in a locked building. We have a chain of custody. It’s all in place; it’ll all be there. But what I’m saying is that as we move toward the last few months of the study, the staff will start to leave because they have — they have families, you know. And so we’ve received no direction other than we will shut down October 1, 2006. And until we’re told otherwise, that’s the markdown of the plan. And so you’re going to start running into logistical problems as you get closer and closer to the end as you would in any project.

J. ROBINSON: We have developed a shutdown plan. We haven’t heard any word from anyone that they are going to be leaving at that time or when, but you know, that is a potential issue. I think we have enough flexibility to work with whatever the recommendations are.

D. BUTLER: We’ll move expeditiously to complete the study as soon as we can. I have a long track record of not being able to guess how long it takes to put a study through our scientific review process and reluctant to commit to days — to dates. But we’re aware of the time pressures related to the project and we’ll do what we can on our part to complete it expeditiously.

M. STOTO: Okay. Thank you very much. Next on the agenda, we have a presentation from Dr. Michalek, who’s now the — in charge of “investigating principles” according to the agenda.

J. MICHALEK: I was not aware — tell me again what it is that you wanted me to say. What’s the topic?

J. ROBINSON: I think, Joel, what they’re looking for is just an update since the last meeting; that you’ve been to the APHA meeting.

Text Box: Update by the Air Force Health Study Principal Investigator

J. MICHALEK: Okay. All right. Since the last meeting, we have revised our paper on cancer in the control group. It’s a talk I gave in Berlin in September of this year, and subsequently, I gave the same talk at APHA in Washington last week. The document has been revised and resubmitted to the Journal of Occupational and Environmental Medicine. The paper shows an association between cancer and dioxin in the control group. It also shows an association between cancer and years in the Southeast Asia region in the control group.

The reasons for these associations are unknown and it says so in the discussion. The paper is in submission after several revisions. We have a separate line of work going on in the Ranch Hand cohort taking account of what we know about the control cohort. The picture in cancer is complicated to say the least because of the trends we see in the control group. The Ranch Hand paper will probably be ready before the next Advisory Committee meeting.

Separately, we are summarizing our work that we gave to Congress on the potential years of life lost that shows that participation in the study did not statistically prolong anyone’s life or improve their health measurably. That’s being summarized in a paper. And finally, we’re doing a case-by-case review of the Ranch Hand enlisted ground crew who have died of cardiovascular disease trying to understand the patterns we see. And I shouldn’t have used the word “finally” because there’s more.

The Centers for Disease Control has completed 500 randomly selected assays of the TEQ, which for the first time give us the measurements on 36 dioxin congeners, and furans and PCBs. And we’re summarizing those data with CDC right now for — in a manuscript. And that’s basically where we sit at this point compared to the last time we met.

M. STOTO: Okay. Any questions or comments?

J. MICHALEK: Yes?

R. WEIDMAN: Joel, are the studies available on a web site anywhere?

RECORDER: Use a mike, sir.

R. WEIDMAN: Are the — are the studies available on a web site and link into recent studies that, in fact, have been published after being peer reviewed?

J. MICHALEK: We have a web site for the project which lists the citations of all our published papers. The paper I just mentioned is not on the web site because it’s not published yet, but it is cleared for public release — the paper on the control group.

R. WEIDMAN: Okay. How would one get that if I may ask, sir?

J. MICHALEK: Send me an e-mail.

R. WEIDMAN: Okay. Thank you.

J. MICHALEK: Okay.

M. STOTO: Okay. Thank you very much, Joel.

J. MICHALEK: Thank you.

Text Box: RHAC Business

M. STOTO: I realize that there was one thing that we — housekeeping item we should talk about and that’s the plan for meetings for next year. Len, can you say a little bit about that?

L. SCHECHTMAN: We’ve been, of course, surveying the Committee members for their availability at different times for the meetings that we’ve planned. We’ve been in touch with Julie and Joel regarding the possibilities of future meetings. We had initially planned for up to four meetings for the next year. We got a message back from Julie that perhaps the Air Force would only need as many as two meetings.

Considering that and the possibility that we might also need a wrap-up meeting in terms of the members of this Committee and how to — how to wind down our own activities as well as consider next steps if next steps become available to us, we thought a third meeting after the two technical meetings that we would have regarding Air Force — Air Force Health Study issues could happen as well. So we will continue to work those dates, and survey the members and consider the possibilities of availability for all those meetings.

M. STOTO: Well, it seems to me like that third meeting should be after the Academies’ report.

L. SCHECHTMAN: That would — that would make the most sense, sure. Yeah, so ...

M. STOTO: But not too much — not too much after because ...

L. SCHECHTMAN: Yeah. I mean, and basically in order to hold a third meeting within the calendar year, we’re talking November already. So we’re talking a week or two perhaps after the completion of the — of the Academies’ study. Hopefully, we’ll have enough information fed to us by Dr. Butler and his group so that we can have — provide input and call a meeting around those issues.

M. STOTO: Okay. Okay. Thank you very much.

Text Box: Review of Chapter 18: Endocrine

M. STOTO: Well, let’s move into the discussion of the individual chapters now. And the first chapter is Chapter 18 about the endocrine outcomes. And Sandy Leffingwell was the reviewer, but obviously, he’s not here. He did, however, write up his comments. He’s really very good at that; I have to note for the record. And I think they’ve been circulated now.

It looks like — does everyone on the Committee have this kind of grid? It says “RHAC Comment,” but my understanding is that it really is Sandy’s. You don’t — you don’t have it? Okay. And, you know, since he’s not here, I propose that we just take a minute to read through this, see if there’s anything people want to add or whether the Air Force would like to react to it.

R. WEIDMAN: Mr. Chairman, if there are copies available for the peanut gallery?

M. STOTO: Do we have more copies? Thank you. I guess I would — it looks to me like the two comments at the bottom of the first page, about lines 300 to 314, look like they may deserve some comment; others look like helpful editorial suggestions.

J. MICHALEK: On lines 311 to 314, I think it’s always a good idea to place the Ranch Hand dioxin levels in context with other cohorts. I think that’s a good idea.

M. STOTO: Okay.

J. MICHALEK: And that will just take a sentence or two.

M. STOTO: So would anyone else like to raise any issues or comments?

J. MICHALEK: I think the point he makes in the first — in 163 to 165 is congruent with our own paper on insulin in the 30 matched pairs we sent to Little Rock, Arkansas. In the — in the review provided by Dr. Kearn, he points out that “during the process of developing diabetes, an individual maintains glucose levels, but only through very high levels of insulin until the point is reached that insulin production fails and diabetes results.” So I think the text from that article could be lifted out of our published paper and put into the document to address his comment in line 163 to 165.

M. STOTO: Okay. Good.

J. MICHALEK: So in other words, I — I’m just perusing these. I think they’re all — most of them can be addressed with minor edits in the chapters.

M. STOTO: They look — they look to me like very helpful comments ...

J. MICHALEK: And they’re all helpful, yes.

M. STOTO: ... that strengthen it. And so I — what I would suggest is that we include this as an appendix to the — to the minutes, and you have a chance to review them more carefully and respond to any if you — if you think that’s necessary. And also, we should thank Dr. Leffingwell for doing such a thorough job.

J. MICHALEK: Nicely done.

M. STOTO: Okay. Other — anything else on this — on this chapter? Rick?

R. WEIDMAN: Mr. Chairman, obviously I speak out of ignorance having not had the opportunity to read any of this. But the question I have is a — is a general one about the — about the whole chapter on endocrine assessment. I cannot tell you the number of our members and associates who have one part or another of their endocrine system that’s a mess. And I’m not talking about resulting in diabetes; I’m talking about thyroid, parathyroid, adrenal gland that fires all the time. There may be a symbiotic interplay between that and chronic acute PTSD.

We don’t know that, but we do know that there have been so many weird diseases, Lupus-like things that have resulted. And indications back from the doctors who examine these folks say it’s because their endocrinal system was way off. So my — and question back to you and to Dr. Michalek is, was this examined a full range and not just endocrinal abnormalities that led to diabetes, number one? And number two, did it — did you explore other conditions and other disorders that may result from the endocrinal system being off from the — from the outset ...

M. STOTO: Joel, can you respond?

R. WEIDMAN: ... e.g., resulting in parathyroid?

J. MICHALEK: I’m sorry. I don’t have the endocrine chapter in front of me. Does someone have a copy of it that I can look at? Just want to browse it quickly. The chapter covers thyroid conditions as well as diabetes and hormones. The connection between the endocrine results and other conditions, such as PTSD, and psychological abnormalities and hematological abnormalities has not been done. This is the point I’ve tried to make before in that the research in this report is one-directional and was written following an analytical plan derived three or four years ago and approved by the Committee.

It’s written in a fairly straightforward way and meaning that there are many other paths that could be followed in subsequent analyses in other research of the type you described. We are attempting to do that in-house. This kind — these kinds of questions that you raise could be addressed on the data, but they’re not addressed in the chapter. There are very few analyses in the report that cut across chapters. In fact, I don’t know of any.

R. WEIDMAN: Mr. Chairman, a follow-up question. Is in your database, do you believe that there is sufficient data to be mined to pursue those other lines of inquiry?

J. MICHALEK: The answer, of course, is yes. The other sorts — the other paths that one could follow are almost uncountable. And so that, yes; it would require, and would and could easily be done. The data sets are complete; they are correct. They’re verified and would be the source for future research along the lines you suggested.

M. STOTO: I’d like to make some comments about keeping with the agenda and doing our job. What the Committee is supposed to be doing now is reviewing these chapters, and normally, we don’t take comments from the public. I mean, if it helps to review the chapters, I’m helping — I’m happy to do that. I think the kind of comment that Rick made is actually quite a good idea that might be brought up in terms of the National Academy of Sciences committee.

I mean, that’s potentially a topic that could be addressed with further analysis of these data and, you know, the Air Force will certainly have a chance to do it on its own between now and 2006 or maybe not. But I think that’s the kind of question that could be brought up there and I would suggest that you do that.

R. WEIDMAN: I’m sorry. In which context, Mr. Chairman?

M. STOTO: For the National Academy of Sciences panel because that’s what we’re talking about.

R. WEIDMAN: Oh, the new panel?

M. STOTO: Right. Because one of — one of their questions is what kind of studies can be done using these data; that would be important to know. So Gary, if you have a comment about this chapter?

G. KAYAJANIAN: It’s very brief.

M. STOTO: Is it about this chapter?

G. KAYAJANIAN: Yes.

M. STOTO: Okay.

G. KAYAJANIAN: A suggestion; since you looked at the comparison group breaking down cancers as a function of length of duty tour, it might make sense to do the same thing for the other effects, such as the endocrine effect. Longer stay, more harm; that’s a straightforward question to ask.

M. STOTO: Thank you.

G. KAYAJANIAN: End of comment.

Text Box: Review of Chapter 20: Pulmonary

M. STOTO: Okay. Let’s move on to Chapter 20 now. This is one of two that Dr. Johnson has responsibility for reviewing. It’s about the pulmonary outcomes.

D. JOHNSON: I thought the chapter was well written, and agreed pretty much with the conclusions, and the summaries and so forth, the discussion. I have a few comments. On page 22 — or 20-2, page 2, on the epidemiology, it appeared that the one paragraph at line 171, “Overall, with the exception of the recent Seveso reports,” it seemed like that maybe should’ve been included over when — with the other paragraphs that were discussed in previous studies. It’s kind of sandwiched between talking about ...

M. STOTO: It’s 20-3, right?

D. JOHNSON: That’s page 20-3, yeah. I’m sorry. But it needs to be put over on page 20-2 or considered to move it over there. It seems — it seems a little out of place when I was reading through, but then it goes back and talks about Seveso report — Seveso reports and sandwiched between two paragraphs talking about the current AFHS Study.

So then in line 166, it says, “In all examinations, a slight reduction in FVC,” is that a significant reduction in all examinations? Because if so, that would be inconsistent with the conclusion, I believe, which I’ll go to in a minute. So I just wanted to clarify if that’s a significant slight reduction in all examinations?

M. STOTO: Joel, do you want a copy of this?

J. MICHALEK: Yeah, I’d like to have a loose-leaf copy in front of me.

M. STOTO: Here.

D. JOHNSON: On page 4, line 214, it says, “No evidence of an herbicide.” This is a minor — is that a — is that — it didn’t sound right to me, “an.” It should be “a herbicide,” I think, and again, on line 217, “a herbicide,” not “an herbicide.”

M. STOTO: Depends on if you pronounce it “er-bi-cide.”

D. JOHNSON: What’s that?

M. STOTO: Depends on if you pronounce it “er-bi-cide” rather than “her-bi-cide.”

D. JOHNSON: They’re not herbs though. I don’t believe you pronounce them “er-bi-cides.” Those are “erbs” and this is “herbicide.” You’ve heard it both ways? Okay.

M. STOTO: My kids make fun of me for pronouncing ...

D. JOHNSON: Then leave it as is.

M. STOTO: ... nothing H’s.

D. JOHNSON: It just didn’t sound right to me because I say “her-bi-cide,” so leave it as is if you like. I — this is as much a question as a comment. On page 48 in the second paragraph in the discussion talking about the FEV₁ and the FEV₁, FVC that was “observed in older participants is consistent with published data. The decreased FEV₁ and FEV₁ to FVC ratio that was observed is consistent with published data. As expected, race was significantly associated with pulmonary function. FVC and FEV₁ were lower among Blacks compared to non-Blacks.”

My question in this — that discussion right there, they’re saying that there’s lower values and they — these were to be expected. But I thought the report talked about percent predicted and so percent predicted already takes into account race, and height and gender. So I just — I wasn’t sure what that was referring to there in that discussion.

J. ROBINSON: We’ll check it out. We will check it out.

D. JOHNSON: On page 49, 1141, it says “there is no evidence to suggest that dioxin exposure is associated with ill effects on respiratory health.” I think if you look back at the discussions or the results, that should be “no consistent evidence” because there were some associations found here and there. Obviously, when you look at the whole picture, it’s not consistent. It doesn’t support ill effects on respiratory health, but the same language — “consistent evidence” — is used in other paragraphs and I just thought that should be there.

So then finally if you go to the conclusion, sort of a similar comment. In the second paragraph of the conclusion on page — what page is the conclusion? — 56, it’s a short conclusion. The second paragraph says, “Statistically significant findings indicating adverse effects on Ranch Hands were limited to pneumonia and FVC. A significantly greater percentage of Ranch Hand than Comparison enlisted flyers had a history of pneumonia. Ranch Hands in the low dioxin category had a significantly lower mean FVC than Comparisons. No other statistically significant findings adverse to Ranch Hands were observed.”

Okay. That’s supported in the results, I believe. But then the last paragraph says, “From the results of the 2002 data alone and in conjunction with results from earlier AFHS follow-up examinations, there is no evidence to suggest that dioxin exposure is associated with ill effects on respiratory health.” Again, I think the word “consistent” needs to be in there because otherwise, it seems to me that it’s not — it conflicts the previous paragraph that says we found this and this. Obviously, in the overall picture, that’s not enough to support ill effects on respiratory health, but I think the word “consistent” needs to be put in there.

J. ROBINSON: Thank you, sir.

M. STOTO: Okay. Thank you very much. Are there other ...

RECORDER: Cut your mike on, Dr. Stoto.

M. STOTO: Thank you very much, Dr. Johnson. Are there other comments or questions that the Committee would like to raise?

J. ROBINSON: Dr. Stoto, Dr. Grubbs can address the question regarding the FVC.

M. STOTO: Okay.

W. GRUBBS: Yes, Bill Grubbs. The FVC was just for age and height and not for race. Those are the standard adjustments for the percent of predicted and that’s documented in the — I can give you a line number here — but it was age and height adjusted and not race.

D. JOHNSON: Okay. I — doesn’t it also mention though that the FV — one of them — FVC was lower in the elder as expected in older people?

W. GRUBBS: That we can check. I was just mainly commenting on your comment on the race.

D. JOHNSON: Well, there were several. The, you know, I think — I thought typically the predicted values took into account height, age and I thought race. I think ...

W. GRUBBS: Height and age, I agree with.

D. JOHNSON: Okay.

J. ROBINSON: We’ll follow up on that and ...

D. JOHNSON: I don’t think it’s a critical point. It’s just I didn’t quite understand the point about those comments or how it matched to the data because you were using percent predicted, which takes into effect those — the age.

J. ROBINSON: Thank you.

M. STOTO: Okay. Thank you for the — for the response. Other comments from the — from the Committee? Do you have a comment on the chapter, Rick? Okay.

R. WEIDMAN: When you say “respiratory health,” are you including or not including cancers that may develop in the lungs and the respiratory system?

J. MICHALEK: I believe respiratory cancer was studied separately in the cancer chapter, not in the pulmonary chapter. The pulmonary chapter is primarily based on pulmonary findings at Scripps Clinic among living people who attended the clinic. The cancer chapter uses data collected from all medical records on the lifetime history of cancer, including lung cancer.

M. STOTO: I think that’s a good point. I mean, “respiratory health” is a rather broad statement here and I don’t know — I don’t recall what the results were with respect to respiratory cancer.

J. MICHALEK: I mean, we’ll have to ...

M. STOTO: Yeah. I mean, if ...

J. MICHALEK: ... look at that.

M. STOTO: I mean, if in fact you didn’t find anything there, then I think the statement is fine. But if — but if there is some evidence there, this — you may want to temper the statement in some respect. Thank you.

R. WEIDMAN: Respiratory cancer is currently service connected presumptive for those who served in Vietnam. If in fact that you’re finding that there is no adverse health effect, including cancers of the respiratory system, this is a blockbuster finding.

M. STOTO: Well, what we’re commenting on here is the Ranch Hand Study and the number of cancers may not be sufficient to have power to find — I mean, I’m aware of that — of that finding across the board. So I think that what this should comment about is what the Ranch Hand found on that regard because that’s what this paragraph is about. Okay. Thank you.

Now the — according to the order here, we’re due for public comment, but that’s not until 10:20. We’re moving with a lot of speed. So what I’m going to do, because that’s been posted in the Federal Register at that time, move through the chapters now and about that time, come back and give you a chance for your comments.

Text Box: Review of Chapter 11: Neurology

M. STOTO: So that moves us to Chapter 11, Neurology, and for which Dr. Sills is the reviewer.

R. SILLS: Thank you, Mike. Here we go. So Chapter 11 on neurological assessment in the Ranch Hand Study is a comprehensive examination of cranial nerve function, peripheral nerve status and central nervous system coordination. The results and conclusions are supported by detailed statistical analysis of various neurological assessments. The staff is commended for summarizing the group and dioxin analysis for neurology variables on page 11-116 to 11-125.

The summary tables successfully capture the statistically significant neurological endpoints which were detailed in the results section. So as I went through the results section, I was hoping to see somewhere where you could really summarize the data and make sense of it very easily and I think you guys did a really nice job with that as I got to the discussion section.

Although a number of endpoints are statistically significant, I agree with the concluding paragraph on page 11-127 which states that, “In conclusion, based on these results, the evidence is too weak and sporadic to support that there was any significant clinical evidence of dioxin effect on cranial nerve function.” And I’m not too sure you want, you know, it may — the word “sporadic” is — I’m not too sure we want to put that in there. It may be better to just say, “the evidence is too weak to support that there was any significant clinical evidence of dioxin effect on cranial nerve function.”

M. STOTO: How about — how about “the evidence did not support?”

R. SILLS: And I like that.

M. STOTO: Yeah. I mean ...

R. SILLS: I think that’s a better way to say it.

M. STOTO: ... and it’s less judgmental.

R. SILLS: Yeah. That’s good, Mike. And which is first stated in the conclusion, that “Based on the results of the analysis of pinprick, balance and patellar reflex in the follow-up examination, there is some limited support of an association between dioxin exposure and neurological disease in the peripheral nerves.” One question I have for the staff is that there are other endpoints of apparently greater significance, such as Achilles reflex, coordination, et cetera, which is not mentioned in the concluding paragraph on page 11-127. And you may just want to revisit this to make sure that the criteria used for including clinically significant neurological endpoints is consistent.

In conclusion, this chapter is well written and easy to read. In addition, I appreciate the way the tables were set up. It was easy to determine significant p values. Thank you for the well prepared document.

J. ROBINSON: Thank you.

M. STOTO: Okay. Thank you very much. Would the Air Force like to respond to any of that?

J. ROBINSON: We will need to go back and look at the Achilles reflex and coordination, why they were not included in there. So, and we’ll document that when we address all the Ranch Hand Advisory Committee comments, so we’ll have a response there. And we’d certainly be happy to send that out to you.

M. STOTO: Okay. Thank you. Did you want to ask something, Joel? Other comments from the Committee? Questions? Okay. Other comments from others? Looks like we did that one very expeditiously. So thank you very much, Robert.

Text Box: Review of Chapter 13: Gastrointestinal

M. STOTO: Let’s move on now to Chapter 13 about the GI outcomes and Dr. Hassoun is the reviewer.

E. HASSOUN: Mainly, the chapter is very well written and easy to understand. And first, I have a general comment about the title of the chapter. It’s “GIT Assessment.” Although it says “GIT Assessment,” there has been a focus on the liver only. There has been a mention also for peptic ulcer in the introduction and somewhere else, like in 1992 follow-up studies and the — yeah. The last time you mentioned peptic ulcer was in 1992 follow-up and then there has been no mention about peptic ulcer. I don’t know whether if you have studied that or ...

J. MICHALEK: It looks like peptic ulcer was not included in this chapter.

M. STOTO: Was it included some place else?

J. MICHALEK: Cycle 4, I believe, 1992 report.

M. STOTO: But was it examined at — in all of them?

J. MICHALEK: It was always coded, I believe, in our medical record data. We have data on peptic ulcer; yes, we do, but it’s not in this chapter, not in the report. Apparently, this was a decision made a while back when we reviewed the analytical plan for the report. I can’t recall the details on that and why this variable was not included.

M. STOTO: Okay.

J. ROBINSON: But we’ve captured your comment and we can go back and look at why it was not.

M. STOTO: Okay. Was it — was it significant in the past? Is it ...

E. HASSOUN: There is no — there wasn’t a significant difference, but there should be a mention of this; I mean, why it’s being excluded from further studies. That’s what I mean.

M. STOTO: I imagine that’s kind of an acute thing that you wouldn’t expect to see many years after Vietnam service. But, in fact, you wouldn’t see ulcers, but that it would — an association would be years of service.

J. MICHALEK: Both dioxin, yeah. I don’t remember the reason why.

M. STOTO: Well, so if you can just help us remember why that decision was made, that would be good.

E. HASSOUN: Then page 13-9, Table 13-1, statistical method in the statistical analysis, I could see that you divided the table into two parts. And the second part is not very well related; I mean, for the first part. I would suggest that the table should be divided into two tables. The first one is 13-1; the one that starts with “Covariates” would be 13-2. And I could see that you used “(a)” and “(b)” as the postscripts for “Covariates” and “Exclusions” and you used “(a)” and “(b)” in the text — in the table text. And this is very confusing. It’s better if you used like asterisks or double asterisks just to distinguish between different (a)’s and (b)’s.

And if you are going to use two tables, we need to define the “U” and “A” — the “U” and “A” in the first table, the “D/C.” And then in the second table, we need to define the “No” and — oh, it’s already defined. It’s defined, okay, on page 13-12, it seems. Page 13-16, current cigarette smoking, you mention that current cigarette smoking had many effects. And then on page 13-17, you mention that “lifetime cigarette smoking history was not significantly associated with any of the dependent variables.” Lifetime — I wonder if lifetime included current cigarette smoking also? So I don’t understand how the lifetime should — I mean, how do you explain that current cigarette smoking is not associated, while lifetime is associated?

J. MICHALEK: It’s actually the other way around. Pack years ...

E. HASSOUN: It’s not as ...

J. MICHALEK: Yeah. Yeah.

E. HASSOUN: Yeah. It’s the other way around.

J. MICHALEK: So you’re asking for some discussion of that ...

E. HASSOUN: Yes.

J. MICHALEK: ... right there, a sentence or two? Okay. We will attempt to do that.

E. HASSOUN: And just for curiosity, about wine — lifetime wine history, just “wine consumption increased, alkaline phosphatase levels” — or when “wine consumption increased, alkaline phosphatase decreased.” Does it mean that wine protected against liver disease?

J. MICHALEK: We’re just reporting an association.

E. HASSOUN: Association, but ...

J. MICHALEK: We don’t claim to understand all of these. We’re just reporting what we see; that’s what we see.

E. HASSOUN: That’s all the comments with regard to the chapter. Let’s go to Appendix F. A definition for Pearson’s coefficient should be added, the maximum and the minimum, and a definition for the p value is less or equal to 0.05 should be added. And oh, there is a symbol in the table that I didn’t understand. What are these dots and dots equal? I don’t know. Yes, I mean, dots. There are dots right there. Oh, is it? Oh, it’s supposed to be “n” or what? I don’t know. Equals? Okay.

J. ROBINSON: Okay, equals.

E. HASSOUN: I think that’s all what I have for comments.

M. STOTO: Go ahead, Bill.

W. GRUBBS: I can address the lifetime smoking/current smoking. If you look at the list of covariates, current cigarette smoking is a covariate for all the liver enzymes in all the current lab measurements. Lifetime cigarette smoking is only done on the historical variables, the medical records variables. So lifetime cigarette smoking is only a covariate for a limited amount, not all 60 of the endpoints there. So when the statement’s made that “no covariate associations were seen based on lifetime,” it’s that it was only done on maybe five variables and those were historical variables, like presence of hepatitis, cirrhosis, things like that.

M. STOTO: So that can — that’ll be explained in the text? The question about adding the definition of Pearson’s chi square and so on, I mean, that probably is something we should address more generally across the board because that — those appear in other chapters as well. Yeah. I mean, I guess I would — I would propose that these things be — all be referenced and important ones described in the — I don’t know which chapter it is; it deals with statistical methods.

P. CAMACHO: We had a big discussion actually several times about this; who’s the audience? Because I know as a sociologist, some of this stuff is really Greek to me and I haven’t figured it out. So I asked for some explanations and I was basically told by Ron that it was obvious; that I — but that I wasn’t prepared as a, you know, as a doctor to read this. So that’s the argument; it’s really who is our — and on the serious side, who’s our audience and do we refer them? Do we put these explanations in one section or do we refer them to other areas?

J. MICHALEK: The statistical methods are in — described in the statistical methods chapter. The Pearson’s chi-square is but one example. There are many other far more complicated methods used in the report, such as the proportional hazards model with arbitrary rights censoring, and the logistic model, and it just goes on and on. So that’s why the statistical chapter is the place for it. So to add — to finish the thought, to add these statistical descriptions to all the chapters would add extra text to the chapters and I think that it’s best placed in the statistical methods chapter at this point.

P. CAMACHO: Maybe then — maybe then it’s something to replace this statement as made.

J. MICHALEK: “Go to Chapter 7;” refer the reader to Chapter 7. A single sentence in every chapter, right.

M. STOTO: Okay. Do you have more? Okay. Well, thank you very much. Does the Air Force have any further comments to make about those?

J. ROBINSON: No sir.

M. STOTO: Okay. Anything else from the other Committee members, comments from the other Committee members?

R. TREWYN: I think we’re going way too fast.

M. STOTO: What? Are you afraid you’re not going to get paid enough or ...

R. TREWYN: I’ll slow us down. I’ll slow us down.

M. STOTO: And I don’t see any questions from the — from the audience. So Dr. Hassoun, thank you very much for your review of that chapter. Let’s go back to Dr. Johnson for his second review of the day and this one has to do with Chapter 14 on dermatology.

R. SILLS: Mike, I have just one question. As I look at all the conclusions for the various chapters and I compare it to the first chapter, the conclusions, I think that was the endocrine section. And it nicely summarized the data in terms of dioxin exposure and just the different models: Models 1, 2, 3 and 4. And I thought it was very helpful and I don’t know if it’s — if it’s possible to — that there’s consistency between in terms of how the conclusions are drawn for each part, each chapter. You know, I mean, that’s something maybe we want to think about in the future or as we go through the chapters that, you know, if the conclusions are important that, you know, when you get to the conclusions, you can see similar topics being discussed.

M. STOTO: Let me — let me add a comment, then ask the Air Force to respond to that. I agree with you that it’s very important that the — that the summaries are done in a parallel — in as parallel fashion as possible. And I think that where it’s going to come out more — most dramatically is when we get to the executive summary and the conclusions chapter, which I think pretty much pulls out of these — text out of these chapters. So and we’ll certainly have an opportunity to discuss it at that point and that may lead us to — it may lead the Air Force to go back and want to revise the wording of the conclusions in these chapters. Do you all have anything you want to say about that at this time?

J. MICHALEK: Only that we’ve been attempting to do exactly what you said and we’ve been sensitive to that as we tried to edit the concluding sections. And the executive summary was intentionally made to be totally consistent with the chapter summaries so there would be no conflict between the executive summary and chapter conclusions. So there’s a lot of cut and pasting, in other words, from conclusions to executive summary.

M. STOTO: And I — it’s hard to be consistent when you’re writing these things because the data are so different, and methods, the outcomes studied and so on. But I think that’s an important goal we should — we should all have in mind.

R. SILLS: As Paul was saying, is we need to remember who’s, you know, I mean, that Vietnam veterans, the general public may have an interest or will have an interest in these documents. And it would be good to talk in the concluding statements to have statements in terms of dioxin exposures; “there was an effect” or “there was no effect.” You know, just that important information should be captured in the chapter, in the conclusions.

M. STOTO: Okay. So let’s come back to this when we — when we come to the conclusions chapter. Okay. Thank you. Dr. Johnson has been at bat, I mean — I mean ...

D. JOHNSON: On deck.

M. STOTO: ... on deck and now he’s — now he’s at bat, I should say.

Text Box: Review of Chapter 14: Dermatology

D. JOHNSON: Okay. On the dermatology chapter, I think generally, again, it was well written, science-based. The conclusions were supported by the data and the results, I think a lot of work went into this and people should be commended for all the hard work they’ve put into this. I have a few comments to make on it.

I think if you start from the beginning, the introduction, when I was reading this, from the first time I read it, you know, you start reading there and it opens — the background talks about “data collected regarding the occurrence of acne, the occurrence of acne in relation to time of duty, and the location of acne in the temples, eyes or ears. And the following conditions were reported: acneiform lesions, acneiform scars,” et cetera. And then it goes into talking about chloracne and the epidemiology of chloracne.

So I — my — the one comment I want to make is that as I read through this, I was a little bit unclear at times where we would talk about acne, and then we’d talk about chloracne and then — and it wasn’t really clear what we were focusing on and what we were looking at. Maybe up front, somehow up front if it could — if it could be said that, “It’s well established that chloracne is associated with dioxin. We looked at acne because” — whatever reason we looked at acne — to try to capture acne that might have been missed if you just looked for chloracne because chloracne is difficult to diagnose by retrospect — retrospectively on questioning.

You know, that would just kind of make it clear up front. It would’ve been easier, I think, as we went — as I went through it to kind of keep that straight because you go from one time talking about acne and you’d be talking about chloracne back and forth, so I think that comment. And then on page 3, line 195, it says you were talking about the different results, the veteran studies. And then on line 195, you say, “Also, in a 1998 publication, the risk of acne on the temples, eyes and ears was not related to serum dioxin levels.” Again, I think that’s referring to the distribution of chloracne.

But I think if you added “AFHS 1998 publication” so we’d know that that was referring to an AFHS study. Because in the next line, you say, “In the 1994 report published by the Institute of Medicine, a committee concluded that there is sufficient evidence of an association between exposure to dioxin and chloracne.” Well, I didn’t know if that’s referring to the data in this study or not, so I think you might want to add that that’s the Seveso study there just for clarification.

And just as an example then, down on line 214, -15 and -16, well, where I — it gets — where I think it needs to be clarified a little bit more on the discussion of acne and chloracne, it says, “Data on the occurrence, time and location of acne were analyzed to assess the possible historical diagnosis of chloracne. No significant difference was observed between groups for reported occurrence or duration of acne.” You can find several examples through there of where you kind of go back and forth, so I just include that as an example of what I just talked about.

On line 246, the occurrence of “reported” acne, there’s a few places. I didn’t go through and try to find all of them, but I just think it needs to be “reported.” It needs to be stated at times that this is based upon reported results just so that you’re aware of what you’re looking at. This is not based upon a review of medical records; it’s based upon self-reports. And just here and there, I put in — put that in, not to say that self-report is not good, or whatever or not necessarily to point out the bias. We know there’s a potential for recall bias, but just so that you’re reporting what it actually is.

M. STOTO: Do you have — do you have — you’ve marked up your version there with places they ...

D. JOHNSON: They’re penciled in.

M. STOTO: So maybe after you’re done, you can give that to them and so they have an opportunity to see those specific locations. Did you have any comments about — responses to this?

J. ROBINSON: Just with everything, you know, you always give us wonderful comments and areas that we need to look at. And since it’s a team approach to making and assimilating these changes, corrections, alterations, I hate to speak for the group. So what we always do is we take this back, and we look at it, and then respond to your comments, and always address what our response has been. And frequently, it’s we take that and make those alterations to the document to make it clearer to the reader.

D. JOHNSON: That’s — and I would say my comments are, I think, are more for clarity. I mean, there’s not — I’m not saying that there’s inaccuracies or errors; it’s more for clarity. On line 461, “Younger participants reported lifetime.” And then on line 466, “Non-Black participants had a longer mean;” “reported a longer mean” instead of “had,” just here and there. Then finally, I did want to comment here at the end on the conclusion again if I could. The conclusion talks about — it starts the first paragraph, generally talks about acne.

RECORDER: What page, Dr. Johnson?

D. JOHNSON: Page 67, it talks about acne in the first paragraph. And I won’t read the whole paragraph, but it talks about some positive results or not — some associations. And then in paragraph two, “A higher percentage of Ranch Hands in the background dioxin category than Comparisons had acneiform lesions, but no other significant findings were observed.” Again, we’re talking about acne. And then we — then we mention chloracne: “In summary, there were no findings of chloracne identified in the Ranch Hand and Comparison groups.” Okay. Then it says, “The reasons for the higher occurrence of acne in Ranch Hand enlisted groundcrew are unknown.”

I think it might be clearer from a science-based standpoint to say at that point that there was an association — there were associations found between acne and there’s some — there were some associations found with acne. And then no — and it needs to be made clear that it’s been fairly well established scientifically that dioxin is associated with chloracne and not acne. Quite a few other studies have shown that that’s not consistent to have dioxin and acne, but rather dioxin and chloracne. But yet, this study did find some associations with acne if I — if I — if I understood it correctly.

You know, there’s other potential confounders of oil acne, tropical acne and mechanical acne. These type of things make it, you know, so that the statement’s — the statement’s correct. The statement is correct; I’m not saying it’s not correct that “the reasons for higher occurrence of acne in Ranch Hand enlisted groundcrew are unknown.” I would agree with that. But yet, it’s sort of an association was found and so it should probably be mentioned or maybe stated that way.

And then finally, “Physical examination for acneiform lesions, acneiform scars, comedones, inclusions cysts, depigmentation and hyperpigmentation revealed no pattern suggesting a relation with dioxin.” I thought that was — I thought it would suggest — I think that it should be said “revealed no pattern suggesting chloracne.” And these are — these are suggestions for clarity.

M. STOTO: Go ahead, Joel.

J. MICHALEK: This is not the latest version of the chapter. I mean, we can make — at least I don’t see the edits in here that we talked about on page 459, talking about the climate. I thought we had edited that paragraph and I don’t see that edit in this version.

M. STOTO: That one that I gave you was one that I asked my secretary to print out and maybe she printed the wrong one because we had two versions of them. Yeah.

J. MICHALEK: So this is not the draft? All right, so there is another draft called “draft final report” that does have edits for this material.

M. STOTO: But I think that Dr. Johnson had the latest one, right?

D. JOHNSON: I’m not sure that I do. I — somebody said something to me before this meeting that there is a later draft. I can’t remember who said that to me, but ...

W. GRUBBS: Maybe I can shed some light on this.

M. STOTO: Okay.

W. GRUBBS: There is — the copies that you are reviewing are what we call the “second drafts” of the report. Okay. The second drafts have been progressing along as you know. For the draft final report — if you want to call that a third draft, we call it the “draft final report” — that would include changes to the conclusion, for example, and the executive summary that would have been also reflected back in the third drafts and the draft final report of the chapters.

So what Joel — what Joel is saying that this isn’t the final draft, this isn’t the draft that he’s familiar with, they are — they are currently looking at a draft final report which may include edits from the conclusion which have been placed back in the chapters. Does that make sense?

J. ROBINSON: It’s just an issue of timing, and that basically, the changes that were made to it were done after I had sent it out to you. So the comments that you have made were not addressed — were not addressed, so in that third version, let me say.

W. GRUBBS: Yeah. I think the better thing to do is when you review the conclusions and executive summary, make comments on that as to appropriateness of what should and shouldn’t be in there. And then those comments can be placed back in the chapters because as Julie said, they are — the conclusions, the executive summary are a compilation of the individual things.

M. STOTO: Okay. So when we — when we review the executive — the conclusions and executive summary and we ...

W. GRUBBS: And comments are made, and the Air Force said, “Yes, we’re going to respond to those comments,” we will respond to them in the conclusions and executive summary and also put them — put the same language back in the chapters.

M. STOTO: Okay. Now, I mean, but there’s some substantive points that Dr. Johnson raises now that I think that should be discussed now. I think the — I think the — they come down to the confusion between acne and chloracne and maybe whether or not chloracne is considered a subset of acne. Is that — am I right about that?

D. JOHNSON: Well, chloracne is, you know, has been associated with dioxin exposure and dioxin-type compounds. And it has a specific distribution and it’s not the same as just acne vulgaris or other forms of acne. And there are other causes of acne, like I mentioned, oil acne. People work around oil; people work in a tropical climate; people working with, you know, mechanical acne, all those things.

M. STOTO: Yeah.

D. JOHNSON: So there are — there’s some other causes, but I think prior occupational studies have not associated dioxin with those types of acne. It’s more specifically chloracne.

M. STOTO: Yeah.

J. MICHALEK: There’s a history to this. We have a paper published in like 1997 which show the — which show no association between acne and dioxin. The reason we studied acne is we are using historical reported information and that an individual himself would not know whether he’s reporting acne or chloracne. All he can do is say, “Well, I had pimples on my face.” The question is where were those pimples located and did they have a pattern suggestive of chloracne? Chloracne is difficult to diagnose as I understand. So this is — this is historic.

J. MINER: Biopsy and pattern-based.

J. MICHALEK: Yes, biopsy and pattern-based. So this is all described in our published paper and we attempted to describe it in previous Air Force Health Study reports; that we are left with studying what we would call acne. And we’re trying to infer, based on location of on the body, anatomical location, whether it’s suggestive of prior chloracne. And that needs to be spelled out in here, I think, following your comments. I’m agreeing with your comments.

M. STOTO: Okay. That — I think that — I think that makes sense. So basically, you could do examinations of these people when they came in, but that was probably too late to tell whether or not the chloracne ...

J. MICHALEK: Right. Imagine that, of course, I don’t have to say anymore.

M. STOTO: Yeah, and — but I think it is important to spell that all out.

D. JOHNSON: I don’t know that it needs to be in the conclusion. Maybe the conclusion’s fine as is because you don’t know what caused this association. However, at some point, maybe in the discussion, maybe just discuss a little bit more what happened there.

J. ROBINSON: I think that’s an excellent point. Just to let you know, the only change that we made once we got the — our comments back from SAIC is in the areas of 1417 through 1425. And in there, it talks about, “however, there may have been a difference in climactic and living conditions between Ranch Hand and Comparison enlisted groundcrew.” Our physician had some concerns about the accuracy or the supportability of that statement and so we made some modifications to that paragraph. From my — I brought my review chapters with me and that was the only change that we made, so it’s 417.

D. JOHNSON: What line? Which line?

J. ROBINSON: 417, where it talks — 1417, excuse me.

D. JOHNSON: 1417?

J. ROBINSON: 1417, it’s page 14-59.

M. STOTO: I — coming back to the question about acne and chloracne, I think that it’s important to have a paragraph or so toward the beginning explaining that distinction and a brief reference to that in the conclusions chapter — conclusions section because, you know, that’s the thing that gets pulled out into the executive summary and so on.

D. JOHNSON: Sure.

M. STOTO: Don’t you agree?

R. SILLS: Yeah. I just want to underscore what Dr. Johnson said and Dr. Stoto said about chloracne because in terms of dioxin exposure, that’s a general thought about dioxin exposure. It’s an important finding that’s reported; that chloracne is associated with dioxin exposure. So I think it’s critical, as Dr. Johnson said, to really define, you know, how, you know, or define acne and chloracne and how you used it in the — in the documents so it’s very clear to somebody who’s picking up the document for the first time. And as Mike was saying, really capture it also in the conclusion, you know, the issue about chloracne versus acne.

M. STOTO: Okay. Thank you. Other comments from the Committee? Questions? Further response from the Air Force? Comments from the audience? Okay. What I propose to do now is go on and do Chapter 10 on neoplasia. And then after that, take a break and then come back and do the conclusions and executive summary. Does that make sense for the — for everyone? Ron?

Text Box: Review of Chapter 10: Neoplasia

R. TREWYN: Well, since we’ve had all these nice complimentary components coming up and I have about a decade long reputation of not being — taking that approach, I don’t want to disappoint people by thinking I’ll — I’m falling into this pattern, so I’m not. We have a handout.

M. STOTO: In other words, we’re going to need a break after yours?

R. TREWYN: We’re going to need a break. So I always believe if you’re going to pick a fight, you start in the first sentence and pick a fight. So nothing wrong with it being well written; it was probably well written. I was just, as I say, underwhelmed by the content. We had a discussion the last time about the fact that a lot of the numbers have been modified; that based on the Southeast Asia effect, looking at national cancer incidence and whatnot that the group in publications has found some significant results. Those are not reflected in this chapter. My view, they need to be reflected in the chapter and that’s going to be essentially in the general discussion. That’s my major point. Okay. So ...

J. MICHALEK: May I ask you a question?

R. TREWYN: Yeah.

J. MICHALEK: Are you talking about published findings or all findings?

R. TREWYN: All findings. I was familiar with the big paper that was published, reference 179, I think it is. We’ve gotten a 92-page first draft of that. It’s been shortened. In my view, any data that has been generated relating to cancer where you’ve already got the methods worked out, they may differ from the models that are — that are in these — the generally published stuff or you’ve — where you’ve got methods worked out. You’ve assessed the data; you’ve got results related to cancer. That should be in this chapter.

That it should not — as I make the point — if it was done incorrectly for the first 15 to 20 years, it doesn’t mean you have to for the last five years. That if there are new observations, it’s scientifically unsound to do that. If you’ve made new observations, recognize that by reassessing, reanalyzing, you get significant findings. All of those findings should be in this chapter in my view.

M. STOTO: Well, and this is — this is a significant issue. I think that there are a couple of things to discuss. You know, one is to the extent that things have already been published, they need to be cited and made clear. And I — are you saying that that has not been done or ...

R. TREWYN: That really has not been done. There is a minor, or 18 lines or something hidden in the epidemiology section; that reference 179. That’s not adequate based on the significance of that publication.

M. STOTO: Okay. So one thing is to consider whether or not the reference to that study and related studies should be beefed up maybe?

R. TREWYN: Right.

M. STOTO: Or — okay. The second issue is I think that you were suggesting that studies that have been done and maybe have been submitted, but have not yet been published should be mentioned here?

R. TREWYN: Absolutely.

M. STOTO: Well, I guess that’s not so absolute in my mind because if that happens, then they can’t be published in the peer review literature according to the normal rules of the ...

R. TREWYN: You do that all the time in federal reports. Any grant that you get, you put all the data in your technical report, okay, and then collect and work on getting publications over what — whatever period of time. I think to leave this out — the analysis out of this report is really, in my view, it’s not sound science to do that.

M. STOTO: Well, I mean, is it — I guess there’s a difference between the technical report that goes back to the sponsor and something that’s published as it is a formal publication. And I think that many of the journals would take the position that if it’s — if results like that are published here, they may not be — they can’t be published in a journal. I don’t know whether that’s an issue here, but I think that’s something.

J. MICHALEK: Does this count as a publication? I mean ...

M. STOTO: That’s the question.

J. MICHALEK: Yeah, because it’s a federal report and not a journal article.

M. STOTO: Yeah.

R. TREWYN: My argument would be that it would not count. And again, whether every journal would agree with that, I don’t know. But I think, again, just having received lots of federal grants over my career, that, you know, you put everything, all of your data, all of the methods you applied, all of the data into the, you know, into your report. And it can sometimes take years to get peer reviewed publications out on it and you wind up in the publications generally removing a lot of what is potentially consequential information. And in my view, in this study and in this report, leaving out any significant observations would be — would be problematic and a mistake. And that’s ...

M. STOTO: Okay. I mean, the other — the other issue here is whether or not it make sense to do an analysis in the cancer chapter that’s different from the analyses that’s done in all the ...

R. TREWYN: Right.

M. STOTO: ... Models 1, 2, 3, 4. And, you know, that I mean, that’s an issue that I’ve taken a position on; that I’ve been convinced that this is the right approach. That the purpose of this series of reports is — that a main value of this series of reports is the consistency across all these, across the series. And that because there is also the opportunity to publish in the peer review literature, that’s okay. And that I’m not 100 percent comfortable with it, but that’s the position I’ve been ...

R. TREWYN: Well, I would ...

M. STOTO: I would accept.

R. TREWYN: I would certainly like to — and this is where I think we may want to spend some time today is really discussing this because certainly with regard to this chapter. Well, the last time I tried to raise some of these points about this reanalysis effect, it’s probably much less relevant in the other chapters where there has not been an opportunity to take advantage of these new learnings and apply them where I know that a lot of this has been done, even if a lot of it has not yet been published.

And I think, again, in my view and I really do think we should have a — potentially a substantive discussion of this because I think one could, you know, I was at the meeting in 1999, as were you, Michael, where the — where the observation came up. I believe that was one of your first meetings or where the — where the discovery came that a significant number of the comparison group individuals were in fact stationed in Vietnam, meaning they were probably exposed to herbicides. Potentially in some of these cases, many of those bases were sprayed. There wasn’t a blade of grass growing in or near most of those military bases.

I guess one could question, one would never, of course, suspect that there was an attempt early on to mix exposed individuals into the control group. But I think now that we have the observation or did since 1999 to then exclude the analysis of breaking those out, which I know there’s been a lot of work put into doing that, of then looking at where the individuals were in Southeast Asia. Were they in Vietnam, not in Vietnam? And then the group certainly has run a lot of these analysis. And if the analyses have been run, again, it’s my argument that those should be all included in this chapter, which I recognize makes for a substantial lengthening of an already lengthy chapter.

J. MICHALEK: Unless we were simply to summarize in a few sentences or in sentences in the introduction what we’ve — what the other publications are saying. You’re talking about summarizing data that’s in submission to journals right now. Perhaps that could be done in some sentences instead of a tabular form.

M. STOTO: Yeah. Have you made presentations at meetings about these things?

J. MICHALEK: Yes, multiple times.

M. STOTO: So I guess that what I would propose to put on the table is that there be a — maybe a substantial section in the — in the — in the epidemiology section at the beginning. And maybe in, you know, reflect again in the conclusions ...

J. MICHALEK: Right.

M. STOTO: ... that say that there’s because of what Ron said about the controls having served in Vietnam.

J. MICHALEK: Right.

M. STOTO: There have been a series of studies done looking at these data in a different way.

J. MICHALEK: Right.

M. STOTO: Some of those have been published and they found X, Y and Z. Some of them have not been published yet, but have been presented at meetings and they are suggesting A, B and C.

J. MICHALEK: Actually, the abstracts have been published.

M. STOTO: Abstracts? Okay.

J. MICHALEK: For example, the dioxin conference data I described on the comparison group is summarized in an abstract in the proceedings. So perhaps that could be referenced.

M. STOTO: Right. And so I think that — I mean, I guess I would propose that if we did that and then said and now we’re going to proceed with this analysis that’s parallel to all the other analysis in this report, would that ...

R. TREWYN: And I’m not sure. I’m still — I would still argue for the inclusion. And I think part of the reason is because certainly, at least my understanding of some of this data, it really does document some substantial increases in cancer, certain types of cancer for some of these individuals.

If that’s the case, I believe it’s incumbent upon this group to at least argue that that data should be included into — in the report. Because again as we’ve talked about the audience, if Vietnam veterans are among — and their family members are among the audience for which this is being published, to leave out very, very consequential information would seem to me to be inappropriate, just ...

M. STOTO: Comments from others on the Committee about this?

P. CAMACHO: What’s a good compromise? Is there a compromise in any way?

R. TREWYN: Considering that we’re only advisory and I’ve been voted down on this Committee before, this is — I am just expressing, you know, my view. And it’s part of the reason as I got into this, I decided I certainly needed to have written — some written comments to hand out so there’s no mistake about my particular position in this.

P. CAMACHO: What’s the — what’s the cost, Joel? What’s the cost of getting some of this in? Is that — is it a cost issue and time?

J. MICHALEK: I think Bill Grubbs can tell about the cost. You’re talking about a new round of analysis with ...

P. CAMACHO: Are we just talking ...

J. MICHALEK: ... one or two additional statistical models.

R. TREWYN: No. I’m just talking about incorporating. Again, I’m not talking about rerunning anything that you haven’t rerun for write-ups, for presentations, publication. It’s including things that you’ve already done. So it would, in fact, add by having to put that into at least this particular chapter.

J. MICHALEK: Oh, okay. Now I get it, okay.

R. TREWYN: That ...

J. MICHALEK: You didn’t want to reanalyze our data?

R. TREWYN: No.

J. MICHALEK: You wanted to add more detail on in-house research in the introduction and discussion? Is that correct?

R. TREWYN: That’s — that is correct.

J. MICHALEK: Okay. That is material that would not be — that’s something we could do in-house and not by SAIC. I could — we could write paragraphs for insertion in the chapter to summarize in-house research.

P. CAMACHO: Does that make you happy?

R. TREWYN: That — yeah. And that was really ...

P. CAMACHO: It improves the situation?

R. TREWYN: ... is the issue that I was arguing for; is that stuff that where the analyses have already been done, again, not asking to go out and reanalyze, to have to do anything beyond, recognizing though there is a substantial amount. And so it really could double, triple the length of this chapter. Who knows?

J. ROBINSON: And in regards to, you know, cost involved, it’s something that we would have to discuss with our program manager ...

R. TREWYN: Certainly.

J. ROBINSON: ... you know ...

R. TREWYN: Understood. I ...

J. ROBINSON: ... to look at that issue.

P. CAMACHO: But see ...

M. STOTO: I can — I just want to clarify. I thought I understood and was agreeing with what you were saying until the last sentence. It seems to me that it can be — is a lot of work that’s been done and it can be included. And it’s a question of paragraphs and maybe pages ...

P. CAMACHO: Right.

M. STOTO: ... but not doubling the length of the chapter, which is what I thought I heard you saying.

R. TREWYN: Well, when you consider that the one — the very first draft of the — of the — what is reference 179, when that was provided to us electronically — I’ve got it printed out here — it’s 92 pages long. I can see why that was shortened by the — by the journal. But by the time you include — if you include the actual analysis of the data as was done in this case, it, again, it adds content depending on the depth that you — that you included.

J. MICHALEK: But the 92 pages was double-spaced, 12-point font.

R. TREWYN: Sure.

J. MICHALEK: And now you’re talking single-spaced, 10-point font.

R. TREWYN: Sure.

J. MICHALEK: So you’re down to four or five pages if you try to put most of it in there.

R. TREWYN: Yeah, and again, I don’t — whatever it winds up being, it winds up being. And I don’t — it — I’m not saying you have to double the length of this chapter. I just believe if you’ve got data that you have analyzed from this particular study and it’s relevant to the issue, that we should not be encumbered by models that may not be adequate for interpretation and we should put all the data in.

M. STOTO: And because there are publications and quasi-publications that we can cite.

R. TREWYN: Exactly.

M. STOTO: Okay. Paul?

P. CAMACHO: Finally, I have to agree. It’s one — on one hand, we’re thinking of who’s going to read this and it’s going to be professionals. But on the other hand, this whole thing is about the — a very emotive and sociopolitical issue of herbicide use and the consequences of that herbicide use on our troops. And not to — not to look at the crystal ball, but we see something about that with the Gulf I War veterans and we’re absolutely going to see it with this Iraq-Afghanistan war, the same kind of exposure issues to something.

M. STOTO: Right.

P. CAMACHO: And so you’re going to be asked to respond to that. And it’s really as much of a sociopolitical, emotional, national issue as it is anything medical. And that’s the point.

M. STOTO: Okay. Other comments?

R. SILLS: In terms of what Ron said, I think I like your suggestion, Mike; is to go ahead and include in the introduction and in the discussion a lot of the studies that have been published so that — so that the reader could have access to that data and be able to compare with what is published so that we have a balanced report and that people could have — make the best assessment. So, you know, since a lot of that work has been done, it’s just summarize it in a section and include in the report, in the chapter.

M. STOTO: Okay. Thank you. Other comments from the Committee? Jay?

R. TREWYN: And I would also mention that I — that was on my first two paragraphs. I have additional comments, so ...

M. STOTO: We’ll come — we’ll come back to the other comments. I just want to deal with this issue first.

J. MINER: Dr. Miner. We have had a precedent for sticking findings from our outside studies in reports before. We did that with the cardiovascular disease, for instance. I think in the ‘92 report, we — when we found that there was increased cardiovascular disease in the enlisted ground crew, we made a sentence in the report that stated that to let the know — let the reader know that that was going on. So I agree that we can make some comments about that.

Now there are some things here though that I would like to specifically address; one, your desire to say what the mandate of the study is. For the record, since we have a lot of new individuals, I would like the read the purpose of the investigation from the protocol, the purpose of the investigation. “The purpose of this epidemiologic investigation is to determine whether long-term health effects exist and can be attributed to occupational exposure to Herbicide Orange.” And I’ve read this to you before in earlier things.

So the comments that whether herbicide sprayed, and then I think the Air Force has used as a surrogate for exposure to Herbicide Orange, we use dioxin. And so that’s why it’s so dioxicentric and so forth. Now should way back when all the herbicides — I don’t know; you’ve always wanted a study that included all the herbicides, but that’s not what this study was. And so for the Committee, that’s why it’s dioxicentric. And for the record, that’s why it’s dioxicentric because the purpose the study was to study Herbicide Orange.

M. STOTO: Okay. So this refers to the third paragraph in Ron’s comments, right? And this is an issue that I flagged actually with respect to the executive summary as well. So did you want to say anything more about that, Ron, or anyone else?

R. TREWYN: Yeah. Let me just — let me throw in one thing because not — it — I’ll have to admit it’s been a while since I’ve looked at that, the original Congressional language back when this was all started way, way back. I thought it was — I remembered it as being broader than just Orange. But if that’s the original mandate by Congress was to only look at Agent Orange ...

J. MINER: Well, that was the Air Force protocol.

R. TREWYN: Okay. Air Force protocol. All right.

J. MINER: That’s what we’ve been doing. That’s what we were charged to do.

R. TREWYN: Okay, but then I — because I do recall it, actually, and it goes back a few meetings ago. I think we did look again at the — at the Congressional mandate, and I — as I recall, the language was broader than that. It was to look at herbicides sprayed in — utilized in Vietnam and that then, in fact, would have included things beyond just Agent Orange.

M. STOTO: Did you have a comment?

D. JOHNSON: More of a question for Ron. If this was added — the data that you’re talking about — other than just being more inclusive, all-inclusive into the data, will it change any conclusions or findings or — by adding that data?

R. TREWYN: Yes, it will. It will add significance to the cancer incidence, not necessarily just with regard to the Ranch Handers though. It will — but it will add significant — significance to the data by doing these analyses in the — in the various forms and I think this is comparing to the national cancer incidence. But also by breaking out where and time in Southeast Asia and location, it does make for a significant increase in the cancers in some of those groups. So therefore, it is highly relevant.

D. JOHNSON: So it would change — well, it would change the conclusions or just add significance?

R. TREWYN: Well, in some cases, it may just confuse the conclusions. But it would be, I think, a more accurate reflection of the — of the outcomes; that there were adverse health effects for individuals based on service in Vietnam or in Southeast Asia. Again, and going back to the original thing, now it may not be as clean as between a comparison group and the Ranch Hand group. It clouds some of that, but it helps clarify, I think, the significance of the — of the outcomes; that there were adverse health outcomes.

M. STOTO: It seems to me that the, you know, the summary on pages 137 through 139 is the summary of these — this analysis. We’re basically studying this Ranch Hand cohort versus a certain control and doing certain analyses that are — that are agreed upon and they change. Adding the stuff that Ron suggests will put that in the context that may make it easier or harder to understand.

But I — but I think that, you know, these are — these summaries on those pages that I mentioned, that’s the summary of this — of these data, and analysis and that’s that. And then what this — and then, of course, then we get into the conclusions chapters and how we interpret those findings may be different depending on this context that these other analyses suggest. Is that reasonable to everyone? People seem to be nodding yes here because that — you don’t know whether that’s reflected in your ...

D. JOHNSON: So you don’t really know until you look at it whether or not it’s going to change associations? Either add associations or remove a significant association, you don’t know yet?

J. MICHALEK: But you — if you’re talking about unpublished results, then you’ve already alluded to other risk factors in Chapter 7 that this report does not address, such as when they were there.

M. STOTO: Well, no. What I’m saying is that Table 10-43, right, that’s not going to change? That table will not change?

J. MICHALEK: It will not change because this report was written under an analytical plan described ...

M. STOTO: Right.

J. MICHALEK: ... to you three years ago.

M. STOTO: And this is — this is the — this is the summary of the analysis that we all agreed to do?

J. MICHALEK: It is.

M. STOTO: Okay. Now the conclusions, Section 10.5, might in fact be somewhat different if these are data are interpreted in the light of all this other information that Ron brings up.

J. MICHALEK: I believe that is true.

M. STOTO: Okay. So does that answer your question, David?

D. JOHNSON: I think so.

M. STOTO: Yeah. So I guess what I would — I would propose is that we have a chance to see again by mail the changes that are made in this — in this section, particularly that.

J. MICHALEK: I’d like to clarify once again, are you asking to summarize all published and unpublished research in this report, in the introduction and the summary?

M. STOTO: That’s relevant.

J. MICHALEK: That’s relevant. In other words, relevant to cancer?

M. STOTO: Yeah.

J. MICHALEK: You are. Okay.

M. STOTO: And — but to summarize it.

J. MICHALEK: Summarize it, not to do it. I mean ...

M. STOTO: Right.

J. MICHALEK: ... summarize it; yes, of course. We’re not talking about another 20 tables. We’re talking about a summary.

M. STOTO: Right.

J. MICHALEK: Is that true?

M. STOTO: That’s right.

J. MICHALEK: Okay.

M. STOTO: And I would add to modify the conclusion ...

J. MICHALEK: Accordingly.

M. STOTO: ... accordingly.

J. MICHALEK: Yes. That’s what you’re saying?

M. STOTO: Yeah.

J. MICHALEK: All right.

M. STOTO: Is that — Ron, is that ...

R. TREWYN: Yeah. I mean, I’ll certainly start with that. I would — I guess I would think, you know, relative to the, you know, the next round of reviews of significance, you know, for what — for cancer cause and whatnot, for example, that the Institute of Medicine might be doing. I would think at some point access to the tables in the actual analyses that were done, if they don’t wind up being published anywhere because you do wind up a lot of these things being thrown out.

I guess my strongest preference would be that all of the analyses that have been done either as an appendix or something should be included. But if I’m going to lose that battle, I’ll lose that battle. And my fallback would be at least having the summary in there would be — would certainly be very helpful.

M. STOTO: I mean, that material has actually been presented to the Institute of Medicine already if I recall.

J. MICHALEK: Not all of it. The ...

M. STOTO: Okay.

J. MICHALEK: There’s material that we’re researching right now that may never be published. It took five years, for example, to get our peripheral neuropathy paper published. It took seven years to get our dermatology paper published. It took three years to get our cancer JOEM paper published. We’re — we only have a year left. And so there is merit, it seems to me, to put these findings in the report that are not published yet in Cancer because we only have a few months left.

M. STOTO: Okay. Let me — let me ask this. Does anyone know what the schedule is for the Institute of Medicine’s report? Is there one more report due? David, do you know that? It may not be your project, but you might know the answer.

D. BUTLER: We are presently completing Veterans and Agent Orange Update 2004. It’s in the scientific review process. The Congress has mandated that we continue to publish studies every two years through 2014.

J. ROBINSON: And just to broaden Joel’s comment about it may never be published, any research that has been completed will be published. If it is not in a peer reviewed journal, at least as a technical report in the Air Force.

M. STOTO: Okay. Well, that’s important. Thank you for that. Okay. So, and then of course, depending on the results of the new IOM committee, there may even be a suggestion that the study be continued in some way and analysis be done. So it’s not like these things are being buried is the bottom line. That’s the key; that’s the key thing. Okay.

R. WEIDMAN: I was just going to say, Mr. Chairman, with all due respect to the gentleman from SAIC, is that when the original — sir?

J. MINER: I’m not from SAIC.

R. WEIDMAN: Well anyway, whoever you are, sir. The — when the protocol was first put together on ...

M. STOTO: Could you save it for the — for the ...

R. WEIDMAN: Yes, I can.

M. STOTO: Because that’s where it’s relevant there. Okay. Thank you. Okay.

R. TREWYN: Me again?

M. STOTO: Back to you on the other specific issues.

R. TREWYN: Okay, and again, I will just run through very quickly what’s down here and it does help clarify a bit why it is so dioxicentric. But my assessment is still that because the Congressional mandate was herbicides, that wherever there is — for example, in toxicology — where there are literature studies, at least reference to those studies that show that other components. It doesn’t have to — have to be any long citation, but I think things like 240, cacodylic acid and whatnot where toxicology studies have been published. Those are components of the herbicides; they should be included; likewise, epidemiology.

Getting down to the summary of previous analyses that clearly — and this gets to, I think, the point, Michael, you’ve been — were making; that restating what the findings were in those studies is certainly very appropriate. But then with new information, at least mentioning that that could impact or have a bearing on how that data would now be assessed is the point of this; that to just say that’s fact when you have new information that may, in fact, cast some light on that, that should at least be — should be raised.

Let’s see. Okay, and the parameters of the 2002 are similar, sort of where I mentioned the 92-pager. Clearly, there are many other — now another paper submitted and additional data. So that goes down through the methods, results, discussion and summary; that at least some reference to all of that should be in there.

And then getting down to the final points, that then again, because it’s really the cancer chapter where this stuff — where all these analyses have been run. This would be the one chapter where there’d be a huge, potentially a significant increase in the amount of material. At least, that should be laid out where appropriate in the introduction, in the summary and conclusion chapters of — the relevance of that could be fairly short, but it needs to, I think, be mentioned.

And then the last point here is that I was, in fact went back through. I saw a number of 2003 references: references 171 through 177 on cancer relationships that have been published by other individuals. So I went back into the — into the report to find the context in which those were described and I couldn’t find the — any discussion or any — even that they were mentioned.

And I think there are — as I got looking, I think there are a number of things out of the 186 references at the end. I think there — it goes on, then it starts out and you get up through about 90 or 100-and-some where it’s fairly clear that this list is growing. Then all of a sudden, it jumps up to the last ones. I think there’s a bunch of things in the references that are not incorporated into the text anywhere. And I guess that should be addressed and I would hope that hasn’t happened in a lot of other chapters.

M. STOTO: Okay. Bill?

W. GRUBBS: I can — I can address that. I can check that out. Our mandate was to include all publications up through 2003. So from the initial literature review, we had to update that — update the literature based on those new references, 2003. The — they have been incorporated in there; the numbers just may be off and we’ll check that out.

R. TREWYN: Okay.

M. STOTO: Okay. Thank you.

R. TREWYN: So I knew mine would take a little longer than the others, so somebody had to — had to slow this thing down a little bit.

M. STOTO: Well, no. We appreciate your thoroughness on this. I mean, this is an important issue. Other comments from the Committee about this chapter? Questions? Others? We’ll come back to this issue about the purpose of the study when we deal with the — I think it’s the — it’s the executive summary where that — where that comes up again. Okay. Let’s take a 15-minute break and come back at about 10:25.

[BREAK: 10:10 A.M.-10:25 A.M.]

M. STOTO: Okay. If everyone’s ready, Paul’s finishing his yogurt. Len has some information about next year’s — okay. Okay.

Text Box: Public Comment Period

M. STOTO: So then with that being the situation, we are now in the public comment session. I know we have one, Dr. Kayajanian, has asked to speak. Are there others here who want to speak in this public session? Rick Weidman, okay. Well, go ahead. I just want to remind both the speakers that the primary topic for today’s agenda is reviewing this report from the latest cycle of the exams and analyses. So we’re happy to hear comments on other topics, but we — there may not be a lot of discussion on things that are not relevant to the report that we’re reviewing today.

G. KAYAJANIAN: Thank you. My comments are on two things that probably are not as germane as the Chairman would like to today’s discussion — two papers and slides that were presented by Dr. Michalek earlier this year in Berlin: one deals with the cancer incidence in the comparison group based on length of duty tour and the second deals with heart disease mortality primarily in the comparison and Ranch Hand studies. Let’s deal with the first one first.

There was a reason that Dr. Michalek looked at the comparison group to find out whether there were some factors that were tied to cancer that weren’t dioxin. And he organized 400 — 1,481 individuals into four exposure groups so to speak based on length of time, length of service and looking at two indicators, two broad indicators: SEER cancers, which would be total non-skin cancers plus melanomas, and then the larger group of total cancers.

He found something very interesting; that in the longest duty tour group that had from 3.6 to about 15 years in service, there was a significant increase in SEER cancers compared to the shortest duty tour. But when he looked at all the cancers, he didn’t find that increase and that seemed to be a mistake. And the reason it seemed to be a mistake is that if you looked at the non-SEER skin cancers — the basil and the squamous cell cancers — he actually would’ve found had he reported it, a significant decrease based on length of duty.

So you asked the question, how come? And the reason how come is that there was a certain standard used for including or excluding cancers from the analysis. In order for a cancer to be included in the analysis, it had to have occurred 15 years after the duty tour ended. And in point of fact, if you look at — as I did a few years ago — the occurrence of skin cancers in veterans that had no dioxin body burden, non-detect levels, what you found was that you didn’t find any cancers in the first ten years; years 11 to 15, you found two; 16 to 20, you found 12; 21 to 25, you found two; and 25 — 26 to 30, you found one.

What that meant was that there was a significant peak 20 years after the duty tour began; 16 to 20 years after the duty tour began that was clearly not associated with dioxin because there was no dioxin measured in these veterans. The practice that was used by Dr. Michalek excluded 40 percent of the skin cancers from his analysis and you would assume excluded them to a far greater degree in the category of longest tenured servicemen.

Everybody in that duty tour would not have counted in that segment with more than 3.6 years of service; would not have counted any cancers occurring 18.6 years after the duty tour began. So there’s a skewed result and all those cancers that were excluded by this method should’ve been included. And I suspect that when they are included, you’ll find the same kind of curve for basil and squamous cell cancers as you do for the other cancers. That’s the first comment.

M. STOTO: Why don’t we — we’ll give Dr. Michalek a chance to respond to that one first if that’s ...

G. KAYAJANIAN: Sure, that’s fine.

J. MICHALEK: First of all, I want to respond in writing to Dr. Kayajanian in detail later. Obviously, I’m not going to do it now. But I’ve read his document carefully and I can prepare a point-by-point response in writing.

M. STOTO: Why don’t — why don’t — why don’t we do that? I mean, and also include both his comments, which we have in writing already, and your response as appendices to the minutes.

J. MICHALEK: Very good.

M. STOTO: And you’ll — and you’ll send that?

J. MICHALEK: Yes. I’d like to point out that the material that Dr. Kayajanian is citing is from an older version of our paper where we were using a 15-year lag in assessing cancer. We subsequently dropped that approach and so these exclusions that you’re talking about do not occur in our most recent version of the paper. Secondly, in the most recent version of the paper, the basil and squamous cell incidence does increase with years in the region as opposed to the numbers you’re citing just now. But rather than get into a point-by-point rebuttal right now, I want to tell you that I will respond in writing to these — to these points very carefully.

G. KAYAJANIAN: What I would sort of ask is that you also deal with the issue of counting cancers from the beginning of the duty tour as opposed to the end of the duty tour.

J. MICHALEK: The latest version of the paper doesn’t count cancer from the duty tour at all. It counts cancers from the beginning of medical follow-up which occurred at baseline in 1982. So the material you’re citing is old versions of an article we wrote many months ago. The most recent version is far different from the document that you’re citing.

G. KAYAJANIAN: I understood the paper was presented at the 2004 Berlin conference.

J. MICHALEK: It was presented at “Dioxin 2004.” The material presented at 2004 reflects the most recent version of the paper, meaning that the period at risk is measured from the medical follow-up of the study which began in 1982, not from tour.

M. STOTO: Let me — let me see if any Committee members have any comments on this? Questions? Okay. Let’s go on to the next one then.

G. KAYAJANIAN: The second paper deals with veterans with metabolic syndrome. And there’s a multi-variate relative risk presented for coronary heart disease, cardiovascular disease deaths and for total disease deaths. And what — what’s reported in the slide set given then is that the comparison group has a multi-variate relative risk of 2.1 with a confidence interval — 95 percent confidence interval from 0.7 to 6.7.

The Ranch Hand group has a multi-variate relative risk of 0.5, one-quarter of the comparison group, with a 95 percent confidence interval range of 0.1 to 1.8. What that means is that the comparison group and the Ranch Hand group are significant — show a significant difference: 2.1 is above the 95 percent confidence interval for the Ranch Handers and the Ranch Hand value of 0.5 is below the 95 confidence interval for the comparison group.

What, I mean, that finding wasn’t drawn from — by Dr. Michalek and his colleagues in the paper that accompanied the slide set. And I guess the suggestion that I would have is that one look more carefully at the comparison and Ranch Hand groups, dividing them, say, into the seven exposure categories that I used in my 2001 paper, and see whether these values drop sharply within the comparison group as you go from non-detect to, say, 8 to 10 parts per trillion.

This is the same kind of pattern that I saw for prostate cancers in Black men where you’ve got a very, very sharp drop in incidence as you went from the lowest to the highest exposure groups. The same observations that I cited for cardio — for chronic heart disease apply also for cardiovascular disease: a significant difference in the two groups. And I would suggest the same process be used to analyze the difference.

In the case of all-cause mortality, you have a multi-variate relative risk for the comparison group of 1.9 with a range of 1.1 to 3.4. And for the Ranch Handers, 1.1 with a range of 0.5 to 2. So the Ranch Handers aren’t significantly — don’t show this effect to a significantly reduced degree, but it’s close.

And I would suggest you try to find out whether it’s real, whether it really might be different by doing the same kind of analysis, breaking the comparison and Ranch Hand groups down into — I did seven, but you’re welcome to use whatever number of dioxin levels you want — to see whether as you increase the dioxin diagnosis, you reduce this effect: very simple, very straightforward, can be done, I think, rather easily. That’s it.

M. STOTO: Okay. Thank you very much. Joel, do you want to respond?

J. MICHALEK: Once again, we’ll respond in writing. The relative risk that Dr. Kayajanian referred to are those relating the development of metabolic syndrome to cardiovascular death among comparisons and then separately among Ranch Hands. The point is that we see the expected pattern among comparisons; that is that those that are developing metabolic syndrome are at a much higher risk of cardiovascular death than those that don’t.

That’s what you would expect to see and we see it in the comparisons. We do not see it in the Ranch Hand veterans. That’s the point of the paper; that there is what we call a “three-factor interaction” in the data and that’s what he’s pointing out. He’s asking further that we study that interaction as it may relate to dioxin and that has not yet been done. And I will explain all of that in my rebuttal.

G. KAYAJANIAN: Thank you for your time.

M. STOTO: Okay. Thank you. Other comments or questions from the Committee about that?

G. KAYAJANIAN: You were — you were right.

M. STOTO: I mean, we have — we have something in writing from you. Is that the same as what you were just addressing now? I just want to make sure.

G. KAYAJANIAN: Yeah. I sent two letters and there was a one-page addendum that I guess didn’t get sent to Joel by fax in late September.

M. STOTO: Okay.

G. KAYAJANIAN: And to — completely to Dr. Schechtman a couple of weeks back when I asked for time.

M. STOTO: I just want to make sure the record is complete.

G. KAYAJANIAN: There’s a written record in ...

M. STOTO: So if you don’t have it ...

RECORDER: I just want to make sure that what’s in the “Public Comment Section” is what you want appended to the minutes?

G. KAYAJANIAN: I’ll provide you with ...

M. STOTO: He’ll check that now, plus Dr. Michalek’s response.

G. KAYAJANIAN: It was phrased differently and it ...

M. STOTO: But the content is ...

G. KAYAJANIAN: The content’s the same. It was phrased differently; it was presented differently here, but it’s the same. The argument’s there; the argument’s on there. Thank you.

M. STOTO: Okay. Thank you. Rick, would you like to make a comment?

R. WEIDMAN: Very quickly, Mr. Chairman, first of all, I would like to again thank you for all of your hard work and that of all of your Committee members for trying to make this study as relevant as possible. As you come into the home stretch of three more meetings before the end, at least as we know it now, I would remind all of the members of the Advisory Committee as well as our good friends, Dr. Michalek and those at the Air Force, as well as the contractors that work closely with them, that the judgment on the final report of the Ranch Hand project, it will be on the scientific validity. But it’s going to be read by many more people other than scientists.

It is, in fact, a final report that will be read by many lay persons and policymakers, both in the Congress, and in the Administration and in the general veterans community. It will also, I can assure you, be read with great interest by our friends in Vietnam and the People’s Republic government. So it will have a very wide audience. And the more you include, as an example as Dr. Trewyn suggested in the epidemiological area, other confounders, the more highly regarded and the more accepted that the report will be.

And what I’m suggesting is that you be inclusive. I would point out that the Institute of Medicine — the panel in 2001, David? — or it was 2001, I believe, accepted 600 published studies, peer-reviewed studies on PCBs that we submitted to them as part of their report. Because the 1991 law — not your original protocol that was developed from ‘78 to ‘82 for the Ranch Hand Study — but the law, the 1991 law which is still in effect which is the broad context within which Ranch Hand operates as well as all other activities pertaining to toxins to which American service personnel were exposed in Vietnam states herbicides and other toxic substances to which service persons were exposed.

And that’s why under that rubric, it is why IOM accepted those PCB studies. So the confounders and inclusive information on the broad — in the broad context is important to remember and not to limit it just to Agent Orange. And we would strongly urge you to look at it from that point of view as you move forward.

You do not want to be lumped into the same category as the Gulf War case studies done under the supervision of Bernard Rosker, which frankly, most people in the — in the veterans community and on the Hill regard as a colossal waste of $180 million that was virtually useless in terms of being able to discover any connection between exposures that might’ve occurred during Gulf War — the first Gulf War — and deleterious health conditions that those service members are experiencing today.

And there is much more careful work that has been done. There’s been tremendous work by this Advisory Committee and a — and a real effort to try and make sure that this is an intellectually and otherwise honest report. And all I’m saying is as you go into the final stretch, that you be as inclusive as possible about confounders and other conditions. And in the interest, not give into the temptation in the interest of speed and/or brevity, not include things that would make the report stronger and more widely regarded as a definitive document. And that is — that is — I would urge on behalf of Vietnam Veterans of America and our national president, Thomas Corey. Thank you for your time, Mr. Chairman.

M. STOTO: Okay. Thank you very much. You raise some interesting points there. But I think that the discussion that we had about including the other material on cancer in the — just before the break is an example of the kind of thing that needs to be done to make this report really serve its purpose best. So I think that we should be open to the possibility of doing that wherever that makes sense to do.

The second thing is that you raised a — you touched upon the question about what’s the purpose of the study and that’s going to come up again when we — I just want to flag it — when we discuss the executive summary and the conclusions. So we may ask you to say a little more about that at that time

R. WEIDMAN: Thank you, sir.

M. STOTO: I have one more thing I wanted to say. Oh yeah, the other — the other thing that this raised in my mind is that this is the final study in this series. But it really is the study of the 2002 exam, not an overall summary of the whole Ranch Hand Study. And I don’t know whether there are any plans to do that or that may not be on the issue of, you know, today’s issue. But I think that’s something that we, at some point, need to consider. Does anyone want to respond to any of those things?

R. WEIDMAN: If I may comment, Mr. Chairman? The only thing I can say is on Capitol Hill and in the veterans community, this report will be regarded as that. Whether you all regard it and structure it as that or not is that it will be the final statement on which the entire process over the last 22 years will be — or actually more than that; I had all my hair when you started this.

J. MICHALEK: This — yeah.

R. WEIDMAN: But the whole process will be judged based on this report, I believe, sir — fairly or unfairly.

M. STOTO: Yeah.

J. MICHALEK: Well, Mike, just to amplify what you — I mean, to elaborate on what you just said, the — it’s true that most of the analyses in the big report you’re looking at right now are based on what happened at Scripps Clinic or what was observed at Scripps Clinic. However, the cardiovascular, cancer and diabetes information is historical. I mean, it’s a medical record review — medically record — medically verified outcomes from 30 years of medical follow-up.

So those analyses include all findings collected since Vietnam and that should be highlighted in whatever communication comes out of this report; that there are areas in the — in the report that Rick just pointed out that should be highlighted as a — as longitudinal over the entire health history of these men. And, but the rest of it is strictly what happened at Scripps Clinic in 2002 and 2003.

M. STOTO: Well, I mean, I think that that’s a point that needs to be made in the conclusion in Chapter 21, and the executive summary and so on. But it still does leave open this question about whether it makes sense and it is possible to do an overall wrap-up study. Paul had a comment.

P. CAMACHO: No, I had nothing.

M. STOTO: Oh, Jay, go ahead.

J. MINER: Dr. Miner, again. Yes, the reports pretty much have been directed to reporting the findings at each Scripps Clinic exam with a few exceptions that Dr. Michalek has just mentioned. So in light of that, and I think based on some of the comments from the Committee here, that the Air Force is actually going to do a longitudinal overview, which is supposed to incorporate all of the findings of all of our physical exams and all of our papers that are published, and discussed and so forth. And so that is on contract.

M. BLANCAS: Being negotiated.

J. MINER: Oh, I’m sorry, being negotiated right now with SAIC. So we hope to have an overview that is readable, and means something and doesn’t just include — not to beat a dead horse to death here; I guess that’s a veterinary joke — but not just our findings on dioxin, but any others that we have done.

R. TREWYN: What’s the time-line on that? Any idea? I mean, I know it’s not negotiated yet, but I guess is that something that the outcome of that would be anticipated to be done before this group wraps up its life?

J. MINER: Yes.

J. ROBINSON: Well, the study, you know, the last day on record is 30 September ‘06, so ...

J. MINER: We have two years ...

J. ROBINSON: So we have two years.

J. MINER: ... to do this report, yes.

J. ROBINSON: And two years of time as well.

J. MINER: Still involved, I hope. Absolutely.

J. ROBINSON: So next year is the last year.

J. MINER: And the second comment, I’d like the ...

M. STOTO: I want — I want you to ask that question on the mike, Paul.

P. CAMACHO: Oh. Oh.

J. MINER: Okay.

P. CAMACHO: So the question is, is this Committee connected to this summary study that’s now being negotiated?

J. MINER: I certainly hope so, yes. I mean, it’s up to you guys.

P. CAMACHO: Well, I don’t know who makes — who makes that decision?

M. STOTO: Well, why don’t we say that I think the Committee feels that it would very much like to be involved with the review of this.

J. MINER: And we certainly would like to have you involved with that.

P. CAMACHO: That’s — we’d like to be involved, but ...

J. MINER: A second ...

M. STOTO: I mean, I — all we can speak for is ourselves, I think, in this.

R. TREWYN: It’s if Len will invite us back again, which he may not want to.

J. MINER: The Congressional mandate in 1991 perhaps has been broadened, but what was the title of that — the Agent Orange Act of 1991 initially or no?

R. TREWYN: I believe it was phenoxyherbicides, yada-yada-yada. It was — it was broader than Orange.

J. MINER: But the title of the book that you all produced was Veterans and Agent Orange: Health Effects and Herbicides Used In Vietnam?

M. STOTO: Let’s come back to this — the purpose when we review this next chapter.

P. CAMACHO: There’s also — the word “Agent Orange” was the compromise word because Agent Orange was the largest of all of the different forms of that phenoxyherbicide that was used. So it came to be, but it was jargon that included, in my — to my knowledge, included white, and blue and various forms which were really just a concoction, the recipe that you used on this barrel for this mission at this time. And it was based on what was there and if they needed — if they needed — had more of this, then they threw in that.

So it was rather like sorceress/apprentice mix when they loaded the planes up. I mean, this wasn’t scientifically done. They just started dumping barrels and putting it into the plane base. It wasn’t all that scientifically done. Once the barrels were shipped, they opened the barrels, they loaded it up. But they loaded it up into combinations as to what they had on hand at the base.

J. MINER: Well, the only thing that they couldn’t do was mix the water solubles with the Agent Orange because it would gum up the spray nozzles. But otherwise, what was there was used.

M. STOTO: Okay. Let’s move on to the review of Chapter 21 if we could.

R. WEIDMAN: Thank you, Mr. Chairman.

M. STOTO: Thank you for your — for your comments and for the responses from the Air Force. We also thank you, Dr. Kayajanian. I don’t think I did that — mentioned that.

Text Box: Review of Chapter 21: Conclusions

M. STOTO: Now for Chapter 21, I didn’t assign an individual to review it, but I asked that each person who reviewed certain sections pay special attention to their corresponding parts of this. I — and so I propose that we just sort of go through this page-by-page and then see if there are comments that need to be — or maybe we should do section-by-section. So did anybody have comments about the introduction section? This is Section 2.1. Do people have their copies with them? David, did you have a ...

D. JOHNSON: Minor comment on line 40. I thought, “Throughout this report, dioxin levels,” is that serum dioxin? They’re all serum dioxin? Is that correct?

J. MICHALEK: What line is that?

J. ROBINSON: 40.

D. JOHNSON: 40. Serum dioxin?

M. STOTO: Turn on your mike, please.

J. MICHALEK: It should be serum dioxin, yes.

D. JOHNSON: And then down on line 53, it says, “The use of dioxin as a surrogate,” that’s a little — again, that — you might want to say “use of serum dioxin levels as a surrogate.”

J. MICHALEK: Yes.

D. JOHNSON: That was — that was the extent of my comments.

M. STOTO: Yeah. Now that — the last bit of that sentence is that whether it “can be attributed to an exposure to Agent — to Herbicide Orange,” in fact, is the fundamental point that’s come up a couple of times here. The purpose of the study essentially, that’s not covered in the conclusion although it is in the executive summary. And so I propose that we have that discussion when we talk about the executive summary unless people thinks that this needs to be in the conclusions?

J. MICHALEK: I think personally both chapters should be concordant. They should not disagree. I mean, the chapters should not contradict each other.

M. STOTO: Well, it’s not so much that they contradict each other. It’s a — it’s a question of that the purpose of the study is not addressed here in this — in the conclusions chapter.

J. MICHALEK: This is — since this is the chapter that many people will read first, I think you’re right. It should be mentioned at least what the purpose of the study is ...

M. STOTO: Yeah.

J. MICHALEK: ... as it would be in any clinical trial.

D. JOHNSON: Well, I think the purpose needs to be not what you can go back, and look historically and say, “Well, this is what it really meant.” At this point, it has to be what was done.

M. STOTO: Yeah, so ...

D. JOHNSON: So it has to — so you can’t go back and say, “Well look, this line back 25 years ago said it really included this, this and this.” That wouldn’t be very helpful to put that in here right now, but it needs ...

P. CAMACHO: But I think — I think you can get around that by saying, look, in the very first paragraph or first two paragraphs what happened after — what came about. You’re missing, for me, a paragraph that says, well, there were adverse effects and there was a great political, social discussion about this to Congress about the health of our soldiers.

Therefore, this was this Congressional mandate, and that mandate was turned over eventually to the Air Force, and the Air Force protocol narrowed things down to this, and this is what we were charged with looking at. And that way, I think you cover your butt. We’ve — quite frank on this because people are going to look at this. This left everything out. Remember, civilians are going to look at this; civilians with 25 years of anxiety or — and discussion about this.

In Massachusetts, we just did a quick thing back in the early ‘80s on children and deformed — deformities that they may have had, blah-blah-blah. The emotion was fantastic. I did — I put together for Frannie Dorris, the state senator I worked with, 13 hearings. Each one of those 13 hearings around the state of Massachusetts, the Commonwealth of Massachusetts, was packed with people and people still call and have references to that.

So to leave that out is really to, I think, to expose yourself to criticism to where people want to be acknowledged. And there’s a whole constituency that wants to be acknowledged. Because right here, you’d say, “This came — dropped out of the sky.” Whoever thought of doing some exposure?

M. STOTO: Before you — before you respond, can I add something to that? And ...

P. CAMACHO: And then you narrow down, sir ...

M. STOTO: ... I — I’m — I just — what ...

P. CAMACHO: ... you know, to say this is what we ...

M. STOTO: What I’m going to say is ...

P. CAMACHO: ... were charged with looking at.

M. STOTO: ... consistent with both what Paul and David said. First of all, there’s in the executive summary, there is, in fact, a statement of the purpose in the first — in the first paragraph, which I think is incorrect on epidemiological grounds. But what I would propose that we do is that we have a paragraph on this in the summary and conclusions and that it begins with the context that, you know, at the — at the time in the — in the — in the — when was it, the late ‘70s really when the study was started? — there was concern about the health effects in Vietnam veterans of a variety of things.

And one of the studies that was launched at that time to address this issue was the Ranch Hand Study. And the reason if I recall because I was — I was — I was even younger than Rick was at the time — was to study the — was that the Ranch Hand people had this high exposure to herbicides, in particular Agent Orange, that was thought to be — would make it a good candidate for an epidemiological study.

And so in that context and for that reason, the purpose of this study is — and then quote the protocol exactly because the, you know, the context is what it is. But the protocol says what the purpose of the study is and it says it clearly. And I think we need to stick with that. So, and I think that’s what you were saying.

D. JOHNSON: Well, I — yeah. You just — you can’t say the purpose of the study is to do a lot of things it didn’t do, which is, I mean ...

M. STOTO: Right.

D. JOHNSON: ... the purpose of the study was — well, what did — what did the study look at and this is what — this is what ...

M. STOTO: Yeah.

D. JOHNSON: ... this analysis — the purpose of this analysis was.

P. CAMACHO: It’s sort of a — it’s sort of a funnel that you come down to and it was — it was decided.

M. STOTO: And one other thing I would — I would add is that, in fact, the serum dioxin measurement technique was invented after the study was started, which allowed for certain analyses that were consistent with the protocol, but more particularly, envisioned at the time that the — that the protocol was put together. And I mean, that’s been discussed and does that make ...

J. MICHALEK: Yes, it does. Dr. Camacho mentioned a Congressional mandate. All I have is a letter from the Secretary — I mean, the Domestic Policy Council, the President to the Department of Defense to launch the study. I do not have any documentation on a Congressional mandate to fund the study. Do you have such a thing?

P. CAMACHO: Well, we — I can look around and search around for it, but there’s a lot of Congressional hearings. What I’m referring — really referring to is a whole network, a Hill series of Congressional hearings and political action that was all surrounded by this. And it did get down in a funnel effect that eventually came out. The — there were several studies launched and the Air Force Study was the one that survived, let’s say, and the protocol came to what you read. But there was much more of a broader interest, but we are charged with looking at what we had come down to. But I’m just saying put a context on it and bring us down to what the Air Force Health Study looked at.

J. MICHALEK: I understand. I was just looking for documentation; that’s all.

P. CAMACHO: I’ll search for it.

J. MICHALEK: Okay.

J. MINER: You know, and if you remember too what context it actually was in, it was the Agent Orange Working Group ...

J. MICHALEK: Yes.

J. MINER: ... which was put together. It was a government-wide body, heads of — heads of DVA and yada-yada.

J. MICHALEK: CDC, NIH.

J. MINER: And CDC ...

J. MICHALEK: Yeah.

J. MINER: ... and so forth. They were the ones that actually were charged with coming up with a plan to look at the problem with the veterans. And they recommended to the President and then the President gave us the charter to do it. We did not receive, as near as I can tell, a directive from Congress to the Department of Defense to do this. It came — Agent Orange Working Group to the White House and then to DoD.

J. MICHALEK: Well, I understand. What I was looking for was the — was the legislation or whatever it was to put the line item in the federal budget for our program. There must be something in writing to put that line item in there to fund the study from the very beginning.

M. STOTO: And that just could — it could be just the appropriations bills.

J. MICHALEK: Yeah.

J. MINER: I have — I do have the ...

J. MICHALEK: Do you have such a thing?

J. MINER: Yeah, I do.

J. MICHALEK: Great. I didn’t know that; I didn’t see it.

J. MINER: But it was done — it was done on the Air Force side of the house to fund the study. The initial funding was taken out of — out of — out of — out of Defense Health Programs; it was Program 8 money. And then the Air Force Systems Command commander, it found for the — made a program objective memorandum for the budget to be included as a line item in the — in the DoD budget. And it was — it was — it was ...

J. MICHALEK: Well, I think that history should be in there in a few sentences; it’s just important.

J. MINER: Well, we have that.

J. MICHALEK: But it’s not in the report; it doesn’t say that in here.

M. STOTO: Yeah.

J. MINER: No.

M. STOTO: The other point I would add is that this probably should be in the introduction of the report in more detail. Yeah.

P. CAMACHO: Put it in the introduction, in the summary and in the conclusions.

M. STOTO: We don’t have — we don’t have Chapter 1 here. I don’t know whether it’s there or not, but I don’t recall that it is. Okay. Thank you. So let’s move back to the discussion of the chapter itself. Any comments on Section 2, “Study Performance Aspects?” I had one comment; is that on page 2, line 64, you talk about “passive refusals” and “hostile refusals.” It probably would make sense to define those terms

P. CAMACHO: Or at least make the — at least make the reference because we went through this the last meeting. At least make a reference where somebody can look up the difference between the passive, and hostile and ...

M. STOTO: Yeah.

P. CAMACHO: ... all the refusal pieces.

M. STOTO: Okay.

P. CAMACHO: In general, I would’ve said that there probably should’ve been more “see,” you know, “see Chapter 8, Appendix this” or “Appendix this” in parenthesis a lot more. Because the lay person going through this — where — and if you just spell it out to them, they’ll know and then, you know, they’ll get that. So it’s more — it’s like more of a citation problem.

R. TREWYN: So actually, a social scientist can add value here. This is good, Paul.

M. STOTO: Okay. Jay, go ahead.

P. CAMACHO: Thank you. That was a good — just when you thought there was no more room ...

J. MINER: Yeah. Just one more follow-up on the — on a little bit of a history of the start of the study because it was General Dettinger who was testifying in front of a Congressional committee and they asked him had any of the Ranch Handers been harmed by their spraying activities in Vietnam? So he, General Dettinger, called down to the epi folks and said, “Well, let’s send a questionnaire out to all the Ranch Hand people and ask them if they — if they’re sick or not.” And of course in the ways of epidemiologists, they said, “What are you thinking?” So that’s kind of how the epi division got involved with working on the protocol and then the protocol got vetted through a whole number of places.

M. STOTO: That’s when I was involved a little bit in that.

J. MINER: Yes.

M. STOTO: Okay. Thank you.

R. WEIDMAN: Mr. Chairman, another historical note if I may? The Air Force at that time was maintaining they did not know and had no record of who was exposed. And it was only some four years later that it came to light that they had the herbs tapes all along. And once that came — became public, then it became a different situation. But I must say that it was in the context of much organizing in the veterans community and friends on the Hill pressing with the belief that there may, in fact, be some deleterious health effects of exposure to Agent Orange.

And that culminated in — and it’s even cited in the protocol — an event that happened at the White House during Vietnam Veteran’s Week in 1979. The resolution that created and called on President Carter to declare that week Vietnam Veteran’s Week was the first action of the Vietnam Veterans in Congress Caucus which was organized in the fall of 1978.

And in 1979, David Bonyer led the way in introducing, but with all of the Vietnam veterans, Congress and the caucus behind him, and Senator John Hines on the senator’s — on the Senate side, the Vietnam Veterans Comprehensive Readjustment Act of 1979. You all are familiar with the vet centers; that was one of the provisions in there was to create the vet centers as an autonomous entity within the VA. But another provision dealt with deleterious health effects of Agent Orange.

At the same time on a concurrent track, the Air Force moved forward through executive action. And Jay, as you’re precisely correctly as is the colonel, is it was done by executive action. But it was done in the context of a growing movement and strong sentiment on the Hill that something had to be done. Like almost everything else, it swims in a sea of the sociopolitical context here in Washington as apotheosis and a central crux of what is being felt out in the nation. Thank you for just a moment of add to that historical context, sir.

M. STOTO: Okay. So that’ll be reflected appropriately in the introduction and ...

J. MINER: A point of clarification. I would like to strongly say that the — no; no, that the Air Force did not have the herbs tapes.

M. STOTO: Thank you. Back to the report. Other questions, comments on Section 2?

D. JOHNSON: I’m just wondering did I hear this right? It sounded to me historically that Agent Orange was a key focus ...

M. STOTO: I think — I think ...

D. JOHNSON: ... is what I just heard.

M. STOTO: Well ...

P. CAMACHO: It — Agent Orange was the most used of several products, if you want to call it that, and it was the most common. It caught the news, you know, and I mean it started it. It’s what the media picked up on and they just, for some reason, somebody said it’s “Orange” or it sounded good.

R. TREWYN: Eleven million gallons out of 19 million or something like that.

P. CAMACHO: Or Orange.

M. STOTO: Okay. Section 21.2, any other comments? Section 21.3 is “Statistical Models;” I had two comments. One is that we made — I made a recommendation last time that there — there’d be some notation that, in fact, these were the models that are being used for longitudinal purposes, but other models have been used in different settings and in the published literature. And that probably should be mentioned briefly here as well.

R. TREWYN: And I would just add to that based on our earlier discussion because ...

M. STOTO: Right.

R. TREWYN: ... the neoplasia stuff will be expanded, that at least some reference. Again, it doesn’t have to be lengthy, but to those is very appropriate.

M. STOTO: That’s a good example of it, yeah. The other — the other point I make is that — and this actually opens up something bigger — but I had — there’s a lot of tables here and this is not what I had thought they were going to be in terms of tables. What I thought it was going to be was the summary tables from each chapter.

J. MICHALEK: What chapter are you looking at, 21?

M. STOTO: Chapter 21.

J. MICHALEK: Mine doesn’t have any tables.

M. STOTO: Well, but ...

J. MICHALEK: Oh, Appendix G.

M. STOTO: G?

J. MICHALEK: Appendix tables.

M. STOTO: It’s 100-and — over — well over 150 pages of them. And what I guess what I had thought we had — we had talked about was that the summary table from each chapter, the one that basically only shows the significant results, be what’s included in this — in this conclusions chapter. And then and if that’s so, that means the Statistical Models Section here needs to explain that kind of table and why, how that was chosen and so on. So that’s really two points. Is that — Ron agrees with that or do you want to comment on that?

J. MICHALEK: So what you’re suggesting is a change of the appendix for this chapter to those tables — I mean, only those results that are significant? Is that it?

M. STOTO: Well, for instance, in Chapter 18, that would be Table 18.47 — 18-47 in the summary table, right.

J. MICHALEK: I just want to look at it. I understand that.

M. STOTO: Right. And in Chapter 20, it would be 20-19.

J. MICHALEK: Those tables take up a lot less space, so ...

M. STOTO: They sure do.

J. MICHALEK: ... that’s great. Yes.

M. STOTO: And it wouldn’t involve redoing anything.

J. MICHALEK: No.

M. STOTO: But you’re just taking a different ...

J. MICHALEK: Cut and paste those tables in the appendix instead of the other ones. Right.

M. STOTO: Okay. Any other comments on Section 21.3? Okay. Let’s move on to the results — “Clinical Results,” Section 21.4, beginning with point — “General Health Assessment.”

P. CAMACHO: In the first paragraph, you need to make changes that you’re going to make in the appendix.

M. STOTO: Say it again in the mike.

P. CAMACHO: You have to make a few changes there under the main introduction that reflects what you’re going to change in the appendix.

M. STOTO: Reverse the tables; that’s right.

P. CAMACHO: Yeah.

M. STOTO: Okay. Comments about the “General Health Assessment?” “Cancer?”

R. TREWYN: Just the same as before. Once these other parameters are included, then that has to obviously go in here as well, so the summary relevance.

M. STOTO: Okay. And I guess that ...

J. MICHALEK: What you mean is to edit this chapter to include published and unpublished results found by our group in-house in addition to what’s in this big report? Is that right?

R. TREWYN: Yes.

M. STOTO: Basically, I think that what we decided earlier is that the — whatever chapter, what’s the neoplasia chapter?

R. TREWYN: Ten.

M. STOTO: Chapter 10 would be modified so that the epi section would have a summary of these published and unpublished studies. And there would be a reference to that in the conclusions chapter — conclusions section that basically puts the results of this current analysis in context. And that whatever changes you make to the conclusions should be made to this as well.

J. MICHALEK: Be aware this chain of ...

M. STOTO: Right.

J. MICHALEK: ... of added ...

P. CAMACHO: Yeah, chain of events.

J. MICHALEK: There’s a cascade, yes.

M. STOTO: So basically, to that ...

J. MICHALEK: We know that.

M. STOTO: ... to that end, every, any conclusion, any suggestion we made today or previously about the conclusions would impact this. Right. Okay. “Neurology?” Any comments on “Neurology?” Turn on your mike, please.

R. SILLS: The conclusions pretty much capture the summary findings in the chapter.

M. STOTO: Okay.

J. MICHALEK: Well, since you’ve raised the issue of published findings outside the big reports, there’s the 19 — or year 2002 paper in Neurotoxicology showing the increased risk of peripheral neuropathy. That paper’s already mentioned in the introduction to the neuro chapter, but is being — currently being reviewed by the IOM. In fact, the IOM now has our database. They’re reviewing not just the paper, but the data itself. Do you want that level of detail in here about that?

M. STOTO: I guess the question I would ask is whether it impacts the interpretation of these results? I think that what the cancer story was that, you know, some people would think that — would think differently about what these results from the current analysis means given what we know from these other studies. So if — I don’t know the details of this particular one, but that’s the question I would ask. I mean, would people understand these results differently if that was part of the context?

R. TREWYN: And I would just like to second that; that I think if from the publications that are out there that are derived from the data that came out of this study, if — even if they aren’t directly linked to the particular models that we’ve been utilizing all the time, if they do influence the findings in whatever area, that should be added as part of the conclusion, part of the result of this overall effort. I think then it becomes very relevant.

J. MICHALEK: I understand that.

M. STOTO: Okay. That’s — Robert?

R. SILLS: So Joel, were there additional findings in the paper that you’re talking about here?

J. MICHALEK: Well, the models that were used in that paper are similar, but not quite the same of what’s used in the big report. There were more detailed adjustments for diabetes, for example; exclusions for the use of — medication use; consideration with and without analyses; analyses with adjustment, including veterans who were taking certain meds and excluding veterans taking certain meds.

Those analyses were — most of our articles provide analyses that are carried out with greater detail and a level of analysis than what’s in the big report. And the findings in that paper were statistically significant and were initially dismissed by the IOM are now being reconsidered. So it might be interesting or know — to the reader to know that; that there’s an ongoing critique, critical review by the IOM of not only our reports, but our data. In other words, this is still a point of discussion in the IOM on these issues.

M. STOTO: Do those — do those other analyses, are they consistent with the findings here or do you find different results?

J. MICHALEK: They are consistent in “Neurology,” yes.

M. STOTO: So what you might say then is to say that we’ve looked at this in other — in other ways ...

J. MICHALEK: Ways.

M. STOTO: ... and have found essentially the same results.

J. MICHALEK: Yeah.

M. STOTO: Those analyses are the — the IOM is looking at these analyses as well.

J. MICHALEK: Okay.

M. STOTO: Does that — does that — does that make sense?

R. SILLS: Yeah. I think that’s important because in the neurology section, there are two places where the IOM evaluations are referenced in the text. And it would be good to have the new findings or the — or the new conclusions that are going to be drawn from the IOM reevaluation to be included in the text.

M. STOTO: Yeah. I mean, I take seriously the comments that a number have made: that this thing is going to be read; this will be the only thing that people read in — from the whole Ranch Hand Study. So I think that the extent that we can reflect these ideas in there, that would be important.

R. SILLS: The only other point I want to make is when I read the conclusions versus the executive summary, it’s pretty similar. And I’m trying to figure out if we should try and differentiate them or, for example, executive summary, have it be clearer in terms of risk and no risk in terms of the various endpoints we’re looking at.

M. STOTO: I mean, I had — I had a question like that about the executive summary too, but let’s deal with the conclusions chapter first and then come to that. Is that okay? Yeah. Okay. More on “Neurology?” Anything on “Psychology?” Okay. Anything on “Gastrointestinal?” Nothing. Okay.

E. HASSOUN: It’s consistent.

M. STOTO: Turn on your mike, please.

E. HASSOUN: Actually, it’s consistent with the chapters that I have been reviewed.

M. STOTO: Okay. Was it — did anything come up in the discussion this morning that would mean a change here too?

E. HASSOUN: No.

M. STOTO: No? Okay. “Dermatology?”

D. JOHNSON: I think the comments were made this morning about the conclusion would apply here too.

M. STOTO: Okay.

J. MICHALEK: I’d like to point out that the document you’re looking at now does reflect the edits that we made. If you look at line 237 to 244, these — this is the text that Dr. — Colonel Robinson referred to earlier today. And so you are seeing the very latest thoughts we had on the acne in the enlisted ground crew; they’re given right there on lines 237 to 244.

M. STOTO: Okay, but the clarification between acne and chloracne needs to be in here.

J. MICHALEK: Still needs to be amplified, yeah.

M. STOTO: Okay. Good. Thank you. “Cardiovascular,” any comments on that? That was the one that Sandy Leffingwell reviewed, I think, yeah. Paul, go ahead.

P. CAMACHO: The last — the — 28 — 68, 269, can we restate that or is that what you mean? “As the dioxin level increased, the percentage with abnormally high blood pressure decreased.” I mean, I’m — if I’m a civilian, I’m going to say, “Hey, it’s good for the blood pressure.”

J. MICHALEK: That’s another example of the complications of the study. These men, many of them are on anti-hypertensive medication. We know there’s an increased risk of hypertension with increased dioxin from our in-house research. The straightforward analysis of blood pressure is complicated because of the fact that they’re taking meds and so the reader wouldn’t know that unless they were told. And so this is one small example of the level of complication of the report; you put your finger on it right there. It should say, “However, many of these individuals were taking anti-hypertensive medications.”

M. STOTO: Right.

J. MICHALEK: And how that affects the result, I don’t know at this point. But certainly, I think it should be mentioned. Sixty-five percent of them, by the way, have a history of hypertension.

M. STOTO: Okay. Robert?

R. SILLS: I think wherever possible, you know, I mean, it should be — some of these sentences should be expanded since we know that, you know, that the Ranch Hand group, some of them were taking drugs which would lower their blood pressure, you know, indicate that information here. Because when I read the sentence, you know, the first thing I would take away from this is dioxin, you know, played a role in terms of decreasing the blood pressure.

J. MICHALEK: This comment reflects back to the chapter itself and has wider implications for the whole report. We’re talking now about material that was not included in the original statistical plan — the consideration of extra meds being taken and possible confounding. The effect of possible other confounders is mentioned in Chapter 7 as is the legacy of these statistical models. And this is just one example of that, I think.

M. STOTO: We’re not — we’re not asking for new analyses here. We’re just basically asking for comments that may — that many actually exist in the chapters itself that will help somebody who only reads this chapter.

R. TREWYN: Right. Because again, I think this is an issue where because it says “conclusions,” you don’t just have this black and white “here were the results” in a void; that there are ways of helping people understand what the implications are. And so just then putting some of these in a broader context so it reads as a standalone and you can sort of make sense out of it; that it doesn’t have these contradictions that people are going to say, “What in the hell was this all about?”

P. CAMACHO: You know, the civilian version of what in an argument would be the conclusion and what you guys mean medically as a conclusion are very different. I’m going to conclude, if I’m a civilian, that this — I ought to take a little dioxin pill to lower my blood pressure. I’m sorry, but that’s what people on the outside are going to think. And then they’re going to say, “But what’s this about?” So you have to say something there, reword that.

J. MICHALEK: So ...

P. CAMACHO: Or bring up ...

J. MICHALEK: So your point is well taken. We need to scrub the whole report for these kinds of issues and make sure that we’ve got them covered, like you say, with the — whatever information we’ve got.

M. STOTO: Yeah. My sense is that you actually have done a good job with that in the — in the main chapters, but the key thing is that they get reflected in the conclusions. The other thing along those lines is that the introduction probably needs to say something about how this is an analysis of the latest round of this study. Yeah, and, you know, I made a comment about that with respect to the statistical models, but I — it really is broader than that. And so, but you know, in a situation like the cancer, and the hypertension and so on, if you have other — and the neuro, peripheral neuropathy, if there are other things that have been published that you can cite, they probably should be cited here as ...

J. MICHALEK: All right. Well, there you’ve put your finger on another issue. I mean, maybe I’m giving too much detail, but the Model 4 depends on the initial dose and we already caveated the pharmacokinetic model in our estimate of the initial dose in Chapter 7. Should that kind of information be brought forward into this — into this chapter ...

M. STOTO: Yeah. I mean, it’s ...

J. MICHALEK: ... to warn the reader about their initial dose estimate?

M. STOTO: That’s right. I mean, if that — if that — if this finding is based on something you have reason to think may not be the, you know, lead to the most appropriate interpretation.

J. MICHALEK: It’s not the latest information.

M. STOTO: Yeah.

J. MICHALEK: The model we’re using, the first-order model is not the latest information.

P. CAMACHO: And a — and a general statement about all the potential confounders ...

J. MICHALEK: Yes.

P. CAMACHO: ... here.

M. STOTO: Okay.

J. MICHALEK: Variable elimination rates, and the biphysic model and dose-dependent model that’s not being used. I mean, all this should be mentioned at least and cited.

P. CAMACHO: Especially tailored for civilian understanding.

J. MICHALEK: That’s another problem.

P. CAMACHO: And that might be hard.

M. STOTO: Well, I mean, I guess I would say that for the — for this chapter, this is — this is a scientific report. I think we need to think of that issue for the executive summary.

J. MICHALEK: The purpose of — yeah. The executive summary is supposed to be written in lay language.

M. STOTO: Right. So, and I think that’s one of a number of issues we’re going to have to deal with when we talk about the executive summary, like the ones that one of you guys raised earlier. Okay.

E. HASSOUN: And are you going to add something about the hypertension in this section or ...

M. STOTO: Well, I think that this should — yeah.

E. HASSOUN: Yeah. If you’re going to do that, then we have to go back to the “Psychology Assessment” and we need to add something on page 21-5, line 193, “More Comparisons than Ranch Hands had high scores on the SCL-90-R,” the same thing. We need to justify for that, the symptoms.

M. STOTO: Well, is there — is there material in the chapter that clarifies?

E. HASSOUN: Probably not; you’ll have to go back.

J. MICHALEK: Another point well taken; that some of these apparently contradictory findings could be due to lack of adjustment or something else. For example, the medication used in blood pressure, there might be something corresponding. It’s like that we don’t know about that would explain why one group, why we’re seeing a pattern opposite than what we expected. That’s the problem with epidemiology; it’s basically an uncontrolled study. We do our best to control for confounders, but there may be some that we missed. That’s a so important point that needs to be mentioned again.

M. STOTO: That’s a good point. Actually, so the statistical section, Section 3, does talk about adjustments. So maybe you could put something in there that says that, you know, we adjusted for the stuff that we thought was relevant, but there could be some unknown — okay.

J. MICHALEK: Yes. That’s in Chapter 7, but at least a sentence in Section 3 ...

M. STOTO: Yeah.

J. MICHALEK: ... if it’s not there already.

M. STOTO: Yeah. You have all this extra space now that we took — with the short version of the tables, we can add a couple of sentences here and there. Okay. Anything else on “Cardiovascular?”

J. MICHALEK: Again, your point about other published research would seem to be relevant to cardio. We’re seeing the significant increase in risk of cardiovascular death among the enlisted ground crew. That’s outside the scope of the Scripps data, which is what the subject of this report is, but I have to tell you that it’s a finding and it’s highly significant. It will be published soon. Perhaps should we mention that? Are you suggesting that we mention these other cardiovascular-related findings that we have?

M. STOTO: I think so; I would say that, you know, other analyses have shown the same thing or they’ve shown a different thing. I think that’s ...

J. MICHALEK: It’s a puzzle, however, because we see the increased risk in cardiovascular death. However, we see no increased risk of any other cardiovascular endpoint at Scripps Clinic in the enlisted ground crew. So we would present the — this puzzle to the reader right up front. Is that the idea?

P. CAMACHO: Yeah. I think that’s safe.

M. STOTO: I would — I would — remember, this is a report about a particular analysis; that here’s what we found in this analysis. But it would not be honest to not say that there was some other results in some other ...

J. MICHALEK: Okay.

M. STOTO: I mean, it’s not — it’s not the job here to kind of straighten that out.

J. MICHALEK: It’s not; we’re just going to communicate what we know.

M. STOTO: Yeah.

J. MICHALEK: Is that the idea?

J. ROBINSON: Just a point of clarification regarding that line 268, 269, Dr. Grubbs said it was adjusted for medication.

P. CAMACHO: This is the — oh, you guys are talking about in the findings?

J. ROBINSON: Pardon?

P. CAMACHO: This was the second draft. I’m looking at the second draft.

J. ROBINSON: Oh, this was under the “Cardiovascular Assessment” and the issue about “the percentage of participants with abnormally high systolic blood pressure.”

P. CAMACHO: Yeah, 268, 269. Right.

M. STOTO: In other words, the answer isn’t as simple as Joel said?

J. ROBINSON: Right.

J. MICHALEK: You know, there’s a difference. Well, you were talking about ...

P. CAMACHO: All I’m saying is correct it so that the average reader ...

J. MICHALEK: Right.

P. CAMACHO: Correct it enough so that some — whatever you do, correct it so that people won’t be taken aback or put it in some context.

M. STOTO: Yeah, but they were talking about having a statistical adjustment having been made, not adjusting the text.

J. MICHALEK: And when you get to statistical adjustments there, what Dr. Grubbs referred to is given by the stat plan to do what’s called a “main effects model” with an adjustment by covariate. There may be other effects there that are missed with that approach, such as interactions. You may see things with exclusions. None of that was carried out in our big report because this was a straightforward analysis; whereas, other more exploratory analysis may uncover something that wasn’t seen in this chapter. And all of that is already said in Chapter 7, but perhaps a one-sentence reminder would be relevant.

M. STOTO: Okay. Anything else on “Cardiovascular?” “Hematology?” Nothing on “Hematology?” “Renal?” We’re marching through the body here. “Endocrine System?” And how about “Immunology?” Okay. Or “Pulmonary?”

D. JOHNSON: Again, it’s almost the identical conclusion; that there are some comments I made this morning.

M. STOTO: So they get — they should be carried over?

D. JOHNSON: Yes.

M. STOTO: Okay. The section on “Strengths and Limitations of the Report?” Of course you can say it ...

P. CAMACHO: Is it ...

M. STOTO: ... if you turn your mike on.

P. CAMACHO: ... you know, given all the little gasps of air, should we take Section 2 — 21.5 and actually put it ahead of things?

M. STOTO: That’s an interesting thing. I mean, this is the — scientifically, this often comes at the end. But I think that in this context, it might actually make sense maybe after the “Statistical Models,” but before the “Clinical Results.” Is that what you had in mind?

P. CAMACHO: Yeah. Well, just — I’m just saying its place, this is in this summary; that its place, the “Strengths and Limitations of the Report,” that “Study “Performance,” you’ve got 2 — 21.2. And maybe you put it just before the “Statistical Models” or just after the “Statistical Models,” before “Clinical Results.” Should you move it before “Clinical Results?”

R. TREWYN: Well, and again, based on, you know, there are going to be adjustments made regardless on it based — and if we can summarize some of those prior to people doing the locked step through each of the systems, the bodily systems, it may help; it really might help. And I agree that quite often, this is where it would belong. But it might in fact, in this case, be better because then even by coming after the “Statistical Models,” then some of those things, even some of the additional statistical approaches utilized in some other studies can be — can be raised in here and brought in. So it may, in fact, help clarify as you — as you walk through each of these and then only need a sentence here or there in each section.

M. STOTO: Okay. I think — I think that makes sense. The other — the other comment I had about that was the second paragraph applauding the Advisory Committee and things like that. Of course, it’s true, but I’m not sure I would call that a strength or a limitation; that might be more in the way of an acknowledgment.

J. MICHALEK: Sort of like an acknowledgment paragraph instead of here?

M. STOTO: Yeah.

J. MICHALEK: Okay.

M. STOTO: I actually realized I had a comment when I — when I read the executive summary first; that that applies to this as this whole thing as well. We lay out the different models in the statistical section and then the results are written up in a way that doesn’t make reference to those models anymore. And you have to go back and you can figure out which ones you had in mind. And I guess I thought it would be better to say, you know, when you found a result, this was a Model 1 result; this was a Model 2 result and so on as opposed to using these kind of euphemisms for those models. I don’t know whether others have ...

J. MICHALEK: Actually again, you guys highlighted an issue because we were trying to make this readable to someone who could just pick it up and look at it and the same with the executive summary.

M. STOTO: But I mean, I don’t think that that works.

J. MICHALEK: No, it doesn’t.

M. STOTO: I mean, that’s ...

J. MICHALEK: But putting in models in parenthesis after nearly every sentence would encumber the text and in a way the reader maybe ...

M. STOTO: Well, but the alternative is that you’ve done that in a kind of a code that’s harder to interpret.

J. MICHALEK: Yeah.

R. TREWYN: Well, one of the things to think about is if we wind up going to the approach, because right now the conclusions and the executive summary look so much alike that you wonder what’s the purpose. And if we really do differentiate so that we’re considering this as more the scientific conclusions for the somewhat, at least marginally knowledgeable reader, whereas, the executive summary might be more for the lay public to take it into a — the broad view. I don’t know.

But at least if we — if we do come up with something that these aren’t just replicating one another, which makes little sense to just have two things that say the same thing, so if we can address those to two different audiences, whichever the right approach is, that might help.

M. STOTO: Yeah. I think that — I think that might help. And if we thought about this as the scientific one, it may make sense to include those models. The other thing is that with the new versions of the tables that we’re talking about, I think they say which model it comes from, don’t they? Well, maybe if that’s true and if we refer to the — maybe what we should do is to say in each section, you know, when we talk about “Dermatology,” see table dah-dah-dah.

J. MICHALEK: Or see page such-and-such.

P. CAMACHO: Yeah.

R. TREWYN: Yeah.

J. MICHALEK: Yeah.

M. STOTO: Well, I would say refer to the table because the table ...

J. MICHALEK: Oh, the table? Oh, okay.

R. TREWYN: The summary table.

J. MICHALEK: Oh, all right.

M. STOTO: The summary table because that then has that information. What I, you know, what I guess what I didn’t like was statements like “contrasts of the Ranch Hands with comparisons” or when “comparing categorized level of dioxin.” I know that refers to Model 1 ...

J. MICHALEK: Three.

M. STOTO: ... or Model 3 or so on. But to just have it there, even though it’s in English doesn’t really carry — doesn’t really make the report readable. But if you had that, and you refer to the table and the table said which model, that might — that might say ...

J. MICHALEK: Okay.

M. STOTO: ... serve the purpose. Does that — okay. Where have — did — have ...

P. CAMACHO: We need to do the summary.

M. STOTO: Okay. So we’re at the “Summary” now. Comments on the “Summary?” I had some comments, but I want to let — give others a chance. This — what struck me as odd here was that this kind of singles out diabetes and I think that — but it doesn’t say why. And I think that the reason is that the authors think that that’s the strongest result from this thing here and maybe the most — and maybe the most ...

J. MICHALEK: Well, this sentence will be changed now that you want the other information in there on cancer. So there might be some edits to this based on the addition of unpublished and published results in cancer.

P. CAMACHO: He meant not only strong in significance, but its impact on public health.

M. STOTO: Well basically, you know, we did this whole study and then in the summary, all you talk about is diabetes. In the conclusion, there’s only one sentence about diabetes. And it seems to me that the summary is that we looked at lots of things, and that we think that the ones we want to highlight are diabetes and maybe cancer will come in there now too. But I think you have to say why that’s the summary.

J. MICHALEK: Again, you put your finger on a tough issue here in summarizing several hundred analyses by statisticians and medical doctors.

M. STOTO: Yeah.

J. MICHALEK: And a medical doctor looks at this and sees diabetes and at this — in this version anyway, diabetes as the disease, the actual disease associated with exposure. And the rest are chemistries or isolated findings and physical examinations. That doesn’t impress a doctor as much as disease.

P. CAMACHO: No, but if you say that ...

M. STOTO: Exactly.

P. CAMACHO: If you say — if you say in writing what you just said there ...

J. MICHALEK: That’s enough.

P. CAMACHO: Well, it’s — yeah, it’s ...

J. MICHALEK: Okay.

P. CAMACHO: ... better.

J. MICHALEK: Very good. All right.

M. STOTO: Yeah. The point is that you’ve studied a lot of things. On many of the things that were significant or laboratory ...

J. MICHALEK: Yes.

M. STOTO: ... results, we’re reporting them. But in terms of what’s most important, you’ve made a judgment that’s diabetes because it’s a disease.

R. TREWYN: Adverse health outcomes are such-and-such from this study based on, you know, I mean, that gets you in so you’ve covered that base. Well again, the summary is that there are other statistically significant — but we aren’t writing this for statisticians.

J. MICHALEK: It’s not always clear what those isolated laboratory findings mean medically ...

M. STOTO: Okay.

J. MICHALEK: ... in terms of a person.

M. STOTO: And it’s not like you’re hiding them. You’re reporting on them, I mean, including in this chapter. But you’re saying that, you know, you’ve made a judgment that it’s appropriate to make a judgment here; that the most meaningful from in clinical terms seems to be the diabetes findings. But that needs to be explained why that was really shown here. Okay. Other comments on the “Conclusions,” Chapter 21? Going, going, gone. Okay.

Text Box: Review of the Executive Summary

M. STOTO: Now let’s turn to the executive summary and so we’ve said a couple of things already. You know, one is the need to distinguish the executive summary from the — from the — from the conclusions. And basically right now, it’s the same text with the — in large part with the — with the headers taken out, which I don’t think does the job very well. And then we — I think we made some other comments too that were — that were relevant for the executive summary. Oh, of course, the other thing was including the purpose ...

J. MICHALEK: Right.

M. STOTO: ... being clear about that. Okay. Does anyone want to have any — raise any more issues there? Rick?

R. WEIDMAN: I think the discussion earlier is apropos. Your conclusions would be more your scientific findings about what you found based on the data that you’re summarizing in this document. The executive summary, if I may suggest, will be used by policymakers in the same way that the executive summary is used on the GAO report and that will be — must contain a good overall picture of both the grays as well as the blacks and whites, if you will, of the conclusions of the report.

In other words, a summary about generally what was most important, why is it most important, what did you find, and how did you get there and to do so in laymen’s terms. So therefore, in the way in which it’s written would be significantly different than your conclusions. Your conclusions, you don’t have to regurgitate all the data, but merely refer back to the chapters where you discuss that in detail. But I think you need to say, if I may suggest, something in general about how you got to what were the major conclusions and how you made those judgments.

M. STOTO: Let — go ahead, Paul.

P. CAMACHO: If you go — if you take that idea which we’re all sort of coming to, you actually may be able to move many of the things here, the language here, into the conclusion section. And remember, if you’re saying, yes, okay, the executive summary is actually going to be this — something that’s potentially used for policy — then we’re cutting it down significantly in size. I’d say if it’s eight pages here single-spaced, you’re going to go to four.

The guys that — somebody is actually going to take this, and look at this and say, “What kind of a judgment are we going to make in terms of political action on Capitol Hill for veterans — the Department of Veterans Affairs,” et cetera? Those guys that will — they’re going to tell some staff person to take the four-pager and reduce it to a one-pager. That’s just sort of the way it is and you have to like, on a silver platter, “This is what you’re going to say, Congressman. This is what the, you know, this is what Mr. Principe has to know and this is what should be done.” Now I don’t know if we’re in the “what should be done,” what should — I don’t know if we’re at the “what should be done.” That’s left for somebody else, but we’ve got to lay it out very cleanly.

M. STOTO: Can I propose a new outline for the executive summary? I’m just making it up so this is obviously — paragraph number one is the purpose of the study which includes a statement about the historical context. Paragraph number two is about the study design and execution, basically focusing on the Ranch Hand and comparisons involving historical records, and medical exams and how many — roughly how many people were involved.

Paragraph number three is about the statistical analyses that were used with reference to the fact that other models were used in other publications and why these particular ones were used. Paragraph number four is the strengths and limitations of this — of this study. Paragraph number five is that lots of different parameters were studied and the ones that were statistically significant were X, Y, Z, and maybe essentially just list them across all the — all the outcomes. And then paragraph number six is and that given all these, the ones that we think are most clinically significant are — is diabetes for the reasons that we — that we just discussed a minute ago and then that’s it.

P. CAMACHO: You don’t have to throw away all this work. You can move a lot of this work into the conclusion.

M. STOTO: A lot of it’s already there.

P. CAMACHO: And a lot of it’s already there.

M. STOTO: Yeah.

P. CAMACHO: So then you get a ruthless editor and ...

J. MICHALEK: I would only ask that we get to see these minutes as soon as possible because all your — I didn’t write — I mean, I’d like to see all your word-by-word comments e-mailed to us right away because we’re running out — we don’t have a lot of time left.

M. STOTO: Okay. Can you maybe transcribe that part of the — I mean, I don’t ...

J. MICHALEK: I’d like to see if we can get ...

M. STOTO: ... think my words are so golden, but ...

L. SCHECHTMAN: Allow me — allow me to just state how we handled it the last time.

J. MICHALEK: Okay.

L. SCHECHTMAN: We were able to send a draft, an early draft of the minutes to the Air Force so that they could inject, consider and so on, the comments of the Committee. So that while we were working on finalizing the minutes, they were able to see the comments early on in draft form and we’ll do the same thing this time.

M. STOTO: Well, I actually proposed something slightly different. In that particular list that I made those six paragraphs, that that — if you can just transcribe that section and get that to them.

J. ROBINSON: I captured it.

M. STOTO: Oh, you got it? Okay. Okay.

D. JOHNSON: I have a — it’s sort of a suggestion, a hybrid suggestion, I think together. The — I understood there was some talk here about putting in language because it’s going to be used as policy and that sort of thing, decisions. But at the same time, I actually was thinking myself a little, I got the impression myself this was sort of a final-final and then there’s some discussion here about it not really being a final-final.

This is just the 2002 just like there’s a ‘92; there’s a ‘95; there’s a ‘97. So how were those executive — how were those executive summaries formatted? And shouldn’t this look like one of those as opposed to making this look like a final-final? If we’re going to have a final-final, let’s have a final-final and make this look like an executive summary like the other executive summaries.

M. STOTO: That’s, I mean, certainly we should look at those. And I don’t know, do you have any ...

D. JOHNSON: I mean, if we want to make it a final-final, okay. But if it — we don’t want it to be the final-final, then let’s have it look like the others.

M. STOTO: Well, I think there’s two ideas here. One is that this is — this is an — this is a report from one phase rather than the overall. I think that point needs to be made clear and that probably should be in here. I mean, that’s part — maybe that’ll be part of the context in the first paragraph in what I had. The other point is what’s the right model for writing an executive summary? And if we have a better idea now, I would prefer that we use that ...

D. JOHNSON: Okay.

M. STOTO: ... and not stick with it just for consistency’s sake. But we may have, you know, this may have been done well in the past and we’ve forgotten how to do it, so we certainly should look and see whether there was a good model there before. Yeah.

W. GRUBBS: The format of the executive summary that you see now is similar to what it was in 1997 and 1992, I believe. I’m not completely sure, but I believe it was done in the interest of full disclosure, not to leave anything out, rather to put more in than to get a synopsis ...

J. MICHALEK: Yeah.

W. GRUBBS: ... and so forth. So it is similar in format to the ‘92 and ‘97. In fact, in the first draft of the 2002 executive summary, I took the 1997 executive summary from the shelf.

M. STOTO: Well, I guess that I feel that since we have the comparison — the conclusions chapter, the full disclosure point is not so ...

D. JOHNSON: Well, I think your — I think your point’s well taken and I agree with it; just if there’s a better way to do it just because we did it that way in the past ...

M. STOTO: Yeah.

D. JOHNSON: ... there’s no reason you can’t change it. However, what are we — as we write this, if we’re thinking — if we’re kind of thinking and discussing as if it’s the final, that’s going to come through in the text, I mean, and people are going to see it as the final if that’s what we’re kind of thinking. But if we set out to write an executive summary for 2002 knowing that there’s going to be another final report ...

M. STOTO: Yeah. No, I actually — I think this was written as the 2002 report. I mean, I think that comes through. But stating that clearly in the — in the opening paragraph, I think, would be important.

R. TREWYN: What’s going to be done with the — excuse me — what’s going to be done with this next one, this longitudinal summary? How is that going to be utilized and if this Committee is going to be involved in assessing this before the end? If that is the grandiose summary of all that’s, you know, good in the world from this effort, I guess we need to know that. That would then be summarizing everything that’s gone on from beginning to end, I guess.

D. JOHNSON: But yet, if there’s not going to be some other, then we were going to — we’re going to just — we’re going to sort of include it in here anyway. If this is sort of the final, we’re going to tend to put in our — the final-type view. But if we know there’s not going to be another executive summary for the whole study, it might change our approach to this possibly.

P. CAMACHO: I think your point is well taken, sir, but I kind of — we’re going to move some of this stuff unless you want to have the executive — a summary, you know, and then you’ll have the ultra-executive summary. I can’t — I can’t see it, but I think it’s a better way of doing things.

D. JOHNSON: I don’t understand.

P. CAMACHO: I think — I think the suggestion that the Chairman has made is actually — I think we should go with it. My personal opinion is to — is to go with it.

D. JOHNSON: What? Can you clarify what that — what you mean by that?

P. CAMACHO: The six points — the six points that he outlined as to how the executive summary should be written.

D. JOHNSON: Okay.

P. CAMACHO: And push — just because it is different and push a lot of this stuff, keep in. And you could say in that executive summary that our — we changed — that we actually changed our formatting a bit to make it more clear and most of the things that people would — found in the earlier reports in the summary, we’ve now put in the conclusion. And I think you save yourself with that.

D. JOHNSON: I don’t ...

P. CAMACHO: I think it’s better. That would be how I would think.

D. JOHNSON: No, I didn’t mean to say that those — that format wasn’t good ...

M. STOTO: Yeah. I think that I heard you saying ...

D. JOHNSON: ... and the stuff that’s in there wasn’t good.

M. STOTO: ... addressing something slightly different.

D. JOHNSON: Yeah, slightly different than that.

M. STOTO: Yeah.

D. JOHNSON: So yes, I agree with ...

M. STOTO: Okay, and I think — I think the key thing is to — is to make it clear that this is the report from the 2002 round of examinations and related things rather than the — do you want to say something? Did you have a comment first, Robert, on this — on this topic or ...

R. SILLS: I was just going to say that I think it’s important we also indicate somewhere in there, and maybe it’s in the section where you say the, you know, “the diseases which are clinically significant in terms of dioxin exposure in terms of Agent Orange,” is also — is also to indicate, you know, that there are a set of other diseases which may not be — may not, you know, play a role in terms of risk following dioxin exposure; not only just say these are — these are diseases that are significant, but then we looked at these other diseases or these disease conditions which may not — which may — which may not play a risk in terms of exposure.

M. STOTO: And, you know, another related ...

RECORDER: What line was that, Dr. Sills?

R. SILLS: Oh, I was just making some general comments.

RECORDER: Oh, okay.

P. CAMACHO: Will there ...

M. STOTO: Just a second; I mean, I think another related point needs to be made clear is that just because this study didn’t find a relationship doesn’t mean there isn’t a relationship. I mean, that’s only limited to statistical power for giving outcomes. So we’re just reporting about this — these analyses. Okay. Speak into the microphone, please.

P. CAMACHO: Will there be another round or opportunity for us to look just at like, say, the executive summary and the — and the conclusion? That sounds like those are the two biggest issues.

M. STOTO: What’s the — what’s the publication schedule?

J. ROBINSON: Well, we have to — we have markers for reviewing all the chapters. We have to review Chapters 1 through 8, draft final report by the 9^th of December. And then I think it’s, you know, a month later, we do the next eight chapters and then the final set are due in the first of February. The final publication will be ...

W. GRUBBS: Julie is correct there. We’re staging the report in three stages. A lot of these last chapters we will attempt to revise based on your comments as forwarded by the Air Force so they have a clean copy to look at and then we’ll have something. We expect to be able to turn those comments around by February 7^th. And then according to contract, we have 30 days to get a final report, which would put it the first week in March.

M. STOTO: And when does it say — our first meeting next year will be later than that, right?

L. SCHECHTMAN: We originally talked about a February meeting, but that’s no longer the situation. So the first meeting in 2005 may occur in May.

M. STOTO: Okay. So the question is there some window of time in the winter when we might have a chance to review these things in writing — the executive summary and the conclusions chapter?

J. ROBINSON: I don’t see why not.

M. STOTO: Yeah.

J. ROBINSON: We’d be happy to forward them through Kimberly ...

M. STOTO: Okay.

J. ROBINSON: ... to you.

M. STOTO: And then we can comment in writing on them. I mean, I guess if there was a need to have a telephone — what do you call it? — a conference call, could that be arranged if necessary?

J. ROBINSON: Certainly.

M. STOTO: Yeah. I’m not — I’m not — I’m not sure that we’re — it’s going to be needed, but if it would ...

W. GRUBBS: And Mike, our plans would be to have a revised conclusions and executive summary by January 7, 8, 9 — somewhere in there — with comments back from the Air Force by the first week in February. So that would be the time frame.

M. STOTO: So it would be basically the month of January?

W. GRUBBS: Yeah.

M. STOTO: The second half of January.

W. GRUBBS: Or you could contribute your comments to the Air Force ...

M. STOTO: Okay.

W. GRUBBS: ... to give to SAIC.

M. STOTO: Does that make sense?

L. SCHECHTMAN: Okay. So if there is no feeling that it’ll be necessary to have a physical get-together; I mean, this can be done over the phone in a tele-conference, which we could arrange very easily with enough tie lines.

M. STOTO: I think we need a January meeting in the Caribbean to discuss this.

L. SCHECHTMAN: That is not a problem; don’t write this down.

M. STOTO: Okay. Rick, did you want to make a comment?

R. WEIDMAN: Just a question then and for Joel, the executive summary, will that be at the front of the report?

J. MICHALEK: That’s where we put it in all the reports; it’s right up front.

R. WEIDMAN: Okay. So you’ll do that again?

J. MICHALEK: Yeah.

R. WEIDMAN: One of the things that you may want to think about and consider is once again, the GAO reports, you can fault particularly GAO reports. But in terms of clarity and understanding, they do the executive summary; then they list in bullet form the major findings; and then they go into methodology in the text; and have conclusions at the end where they go through the whole nine yards of everything they looked at and what did they find on that whether they found significance or not.

Essentially, the conclusions then back up the major findings in the executive summary is that one page. As succinct as you make it, that then is what the policymakers — whether it be the Secretary of Veterans Affairs, or a senator or a member of Congress — will look at. And what they’ll ask their staff is, “Is this supported by the data as presented in the overall report?”

And so that’s as succinct as — and yet complete as you can make that executive summary at the beginning, the better off you are for your credibility on Capitol Hill and in the veterans community in general, and then list after that — bang, bang, bang — your major findings, and then refer to the conclusion and methodology in the various chapters if I may suggest.

J. MICHALEK: It seems consistent with the ideas of Dr. Stoto. It sounds ...

M. STOTO: I think the only difference is the order in which things are presented and I have — I don’t feel strongly about that. And there’s also a press release too, which I presume will be done which ...

J. MICHALEK: Yes.

M. STOTO: ... may have a different — most likely have a different order. Ron?

J. MICHALEK: Yeah. So we’re talking about a hierarchy of writing styles from the conclusions to executive summary to the press release to make it more and more accessible to the lay reader. And we’re eliminating more and more jargon by getting it down to plain English and that’s not easy, but that’s our challenge. That’s what we do.

M. STOTO: Right.

R. TREWYN: Since I just can’t resist taking at least one more shot here in the — in the present since Dr. Miner had pointed out that the Air Force arbitrarily decided to eliminated eight million gallons of herbicides in their analyses out of the 19 million to only focus on Agent Orange, I think it though would be problematic having the very last sentence saying, “Diabetes represents the most important dioxin-related health problem” since the charge was not to do dioxin, just ...

M. STOTO: That’s a good point. I had a couple of technical points that may actually not apply anymore given the change that we — that we suggested, but I’ll just mention them. In the — in the first two lines, it says it’s “an investigation to determine whether adverse health effects exist in Air Force personnel who served in Operation Ranch Hand.” Well, of course, they do. The issue is whether or not there’s more of them. But I — but I think that if we — if we replace it by the — if we quote the protocol, we’ll be better off there.

In the second paragraph, it talks about “matched with a randomly selected Comparison” and I think that probably is not right. I don’t think that “randomly selected” is appropriate there. And then again, this may — this may not be — I think this text will probably go. But just later in that paragraph on line 16, you say “consent forms were signed” and I think informed consent is more than signing a form. And I think that the key thing is that the participants gave informed consent to be — to be participants; that’s the relevant issue there.

In — down toward the bottom of the first page, line 41 and 42, “This model required no assumptions about serum dioxin elimination.” Well actually, I think it assumes that everyone has the same constant.

J. MICHALEK: What line is that?

M. STOTO: 41 and 42; it’s talking about Model 4 “required no assumptions.”

J. MICHALEK: Are you talking about the executive summary?

M. STOTO: Yeah.

J. MICHALEK: 141?

M. STOTO: No.

J. ROBINSON: Line 41.

M. STOTO: 41, yeah.

J. MICHALEK: 41, sorry. Okay. Okay. Sorry. Okay.

P. CAMACHO: “This model required ...”

J. MICHALEK: Yeah. You’re right. It’s ...

M. STOTO: The issue ...

J. MICHALEK: Yeah.

M. STOTO: In fact, the next sentence does say what — the point, so that contradicts the next sentence. But that — this may all go away.

J. MICHALEK: Yeah. Yeah.

M. STOTO: And the other point I would’ve added if this paragraph were to stay is that we want to say something about the covariate adjustments being made, but ...

J. MICHALEK: Yes, covariate adjustments — the lack of thereof, possibly missing a covariate and biasing the results ...

M. STOTO: Yeah.

J. MICHALEK: ... therefore? All studies have that limitation; we’ll mention that. It should say, “As in all studies, the possibility exists that we missed a covariate.”

M. STOTO: Right.

J. MICHALEK: That’s always true.

M. STOTO: David?

D. JOHNSON: Back to the comment I was making earlier, so, “Diabetes represents the most important dioxin-related health problem,” what would you say there if you don’t say “dioxin?” And I have a couple of follow-up comments on that. I mean, it says earlier on in the executive summary that dioxin is used as a surrogate for herbicide exposure.

R. TREWYN: Right.

D. JOHNSON: Do we really mean that? Because all of the models that we have, three of the models — 2, 3 and 4 of the models — are really based upon dioxin. So do — are we really using it as a surrogate because the analysis really looks at dioxin? I mean, may — I’m just putting — I’m saying that, but I’m also asking is that what you all agreed?

R. TREWYN: Well, it’s been one of my arguments since 1995 when I first came on the — on the Committee that it has gotten too focused on dioxin as the causal agent. And if it — if an effect is not caused by dioxin, it’s not an effect. I mean, you — that it has become slanted in that direction and I think that’s dangerous. And I think we have an opportunity here to at least utilize the reference to dioxin in the appropriate way; that it is in some instances an indicator of exposure to dioxin-containing herbicides.

We don’t want to then interpret that it was some health effect was necessarily caused by dioxin; it may have been. Even if it was dioxin in combination with 24D and 245T in Agent Orange, it’s — again — it’s just in the utilization of how it’s described, I think what the issue is here.

M. STOTO: There’s some indication for diabetes that — for Model 1.

R. TREWYN: For Model 1.

M. STOTO: Right. So I guess I would say that, you know, diabetes is the most important, most clinically relevant finding from the study.

D. JOHNSON: For herbicides then?

M. STOTO: No, it’s from the study. And that — out of that, of course, is a nuance statement in which we — which we described. That’s part of the introduction paragraph; that this is a study that was done because of concerns about health effects in Vietnam veterans which have been seen as related to herbicides, and particularly, Agent Orange. It’s a study in people who were highly exposed to herbicides and we have exposure methods that are based on dioxin which is not the same as herbicides. That’s all it ...

D. JOHNSON: Well see, I’ve only been to three meetings and you all have been doing this for years. But my general impression, the thrust of the conversations ...

M. STOTO: Yeah.

D. JOHNSON: ... have been dioxin, not herbicides.

M. STOTO: Yeah, and then Ron is right; is that over time — for over time, dioxin has seemed to be — has become — seen to be a good measure, a proxy measure for exposure to herbicides.

J. MICHALEK: There is some data here that I haven’t told you that would throw some light on what you’re saying, which is another example of the in-house research not being reflected in the big reports. By the way, it never has been reflected in the big reports. It’s not a fault — it’s not specific just to this one; it’s specific to all of them. The point is that the — relevant to your point on dioxin, dioxin correlates with the number of days spent on the Ranch Hand Unit and the expected duration. The longer they’re there, the higher the dioxin levels.

It also correlates with when they were there. Individuals who were there early in the war have higher dioxin levels than those that were there later in the war, which correlates with what we know from the National Academy books; that the dioxin — that the herbicides were more heavily contaminated earlier in the war. This information is new; it’s not published. I have it on my desk. That would support the comments made by all of you or alluded to by all of us that why we were studying dioxin so much. The point is it’s a direct measure that we can measure it in blood.

Secondly, it actually relates to what happened operationally in Vietnam during the war in these men. That’s the piece that is currently embedded in a paper that we’re writing on cancer and when they were in Vietnam. So the whole — what I’m trying to say is there’s a lot of information here that’s not reflected in the report, which throws lights on all of your comments just now.

M. STOTO: Yeah. Well, this is for the topic and a complicated one. And I think, you know, to one — what I would say is that to some degree, the study is what it is. I mean, it was — it was a study that was — had a certain history, and it came to be done a certain way, and this is the way it was analyzed, and that’s that. But it’s done in a context and we now have — and it was done this way because people assumed that serum dioxin would be a good proxy for measures for exposure to herbicides, which was thought to be the thing that was dangerous. And we — and so what you’re telling us is actually evidence now to support that.

J. MICHALEK: Yes; that the early phenoxyherbicides were not Agent Orange. They were — Dr. Miner knows this; is it blue and purple?

J. MINER: Purple and pink.

J. MICHALEK: Purple and pink. They contain dioxin at far greater concentration than Agent Orange did and the data support that; that we see in opposite to what you’d expect from pharmacokinetics; that people that were there longest ago have the higher levels, which is against the grain of a pharmacokinetic model with a body elimination.

So this is a very strong suggestion that, yes indeed, this dioxin measure is reflecting exposures to any phenoxyherbicide, not just Agent Orange. It’s reflecting exposures to those that took place between 1961 and ‘65 when the concentrations were increased relative to ‘67 through ‘68.

D. JOHNSON: That is interesting. I think though in reading the chapters, the language and the conversation, that doesn’t come out. It’s dioxin. For example, the discussion we had earlier about dermatology and chloracne, if we’re not talking about dioxin, then that changes that conversation a little bit because maybe herbicides have something to do with chloracne. But we were talking about dioxin and that’s what all of the conversation, the language points to throughout. So that ...

J. MICHALEK: That’s because of the choice of statistical modeling was in terms of dioxin for Models 2, 3 and 4.

M. STOTO: Well, let me — I forget ...

D. JOHNSON: But then at the end — I’m sorry — but then at the end, to say — to change all of what you’ve been kind of discussing through the articles and say, “Diabetes represents the most important herbicide related to health problems,” it’s a little tough to make that leap right at that point when you haven’t been talking about it all along.

M. STOTO: See, I wouldn’t say “herbicides.” I would say, “The most important problem found in this study.”

D. JOHNSON: Okay.

M. STOTO: Which then, of course, sets aside this whole complicated thing about what this study is all about.

D. JOHNSON: Right.

M. STOTO: But I would then — I forget which the — which chapter is which at the beginning, but there’s some study — chapters about the study design and there’s also chapters about the dioxin levels and so on, right? So I mean ...

J. MICHALEK: Yes, there is.

M. STOTO: I mean, it seems to me that if you could bring some — bring some of this information you just said into those chapters, that would help us to understand exactly what the study is about and how to — how to interpret it.

R. SILLS: Mike?

J. MICHALEK: It’s already published, 1989. Skin exposure reported by the — by the enlisted correlates with dioxin levels and that skin exposure was to any herbicide whatsoever, not just Agent Orange. So — in overall years of the war — so everything you’re saying is supported by the data and we need to amplify that, is what you’re saying, in the text to remind the reader of these things.

R. TREWYN: And this goes — and this really does get back to my very first point and why I was raising it. I think when there is information that really came out of this study or whatever, it needs to be part of the overall description and place things in context. Because clearly, many of these publications — that some that have been out for quite some time — really help illuminate the conclusions and the observations. They put it in a context that makes it more understandable.

And by going through in locked step and not utilizing that because I can even go in this second paragraph. This information, again, it’s — this is for the 2002 executive summary. But prior to this being done, at least from our perspective on the Committee, the recognition that a significant number of the comparison group were stationed in Vietnam versus not off in Thailand or whatever, that puts a different spin and a different understanding on what the conclusion — what the appropriate conclusions are from this.

And I think, and again, now we actually do have some data that shows that by taking that into consideration, it changes the outcome. You know, you’ve got your analysis from the study as you structured it, but as more information comes in, it’s better to be inclusive and have that information in there so ...

M. STOTO: So ...

R. TREWYN: ... it helps the interpretation.

M. STOTO: So it — I think that — I think what happened is that the study was set up on certain assumptions. And the assumptions was that the — were that the people in the Ranch Hand Study were exposed to the bad stuff and the — and the comparisons were not exposed to the bad stuff and ...

J. MICHALEK: The comparisons weren’t exposed to anything in particular that’s bad; that was the assumption.

M. STOTO: Right, and now what we — what we’ve learned over time is that the comparisons might have been exposed to some of the bad stuff.

J. MICHALEK: Something else.

M. STOTO: Right, and that, in fact, the — that the Ranch Hand people were exposed to dioxin and so that all — that all fits together. And I think that whole story is important to tell as part of the methodology.

D. JOHNSON: Well ...

M. STOTO: And because it has implications for how you interpret the results.

D. JOHNSON: Leaving though — leaving dioxin and going to a category of herbicides might, you know, it clouds the issue quite a bit too. Because if you’re dealing with one, you know what you’re dealing with — a particular exposure — and you’re studying that to see if there’s any associations with that exposure. You go to — if you start looking at it in terms of herbicides that could be how many different chemicals, how do you make sense of any of that?

M. STOTO: But at — but at this stage, we can’t redesign the ...

D. JOHNSON: Right.

M. STOTO: ... study or the analysis.

D. JOHNSON: I agree with that.

M. STOTO: So I think that what we have to do is report the results and give enough information so that people can understand the context and interpret it as they — as they see fit, you know.

R. TREWYN: I would just add too that my — one of the points here is you get down to if it’s your $144 million bought you that dioxin caused — causes diabetes, that doesn’t serve this group well. It doesn’t serve anybody, you know, well. It’s what did we learn out of this? What’s the value? What was the value of this longitudinal study, you know, at some point and maybe this is the next phase that gets to that.

But I think, you know, one hopefully can lay out a broad picture here, and some lessons learned, some observations that will help people in the future do a better a job either evaluating, reevaluating the data that’s there, doing whatever. But I think, again, you get down to this is what it got you.

M. STOTO: Well, I think that some of those things are not the purpose of this study. I mean, this — I mean, this report, I should say. This report is to analyze the data that comes out of the 2002 exams and to interpret those results. And to interpret those results, you need to know other things. And I think it’s important that we bring those other things in, but in — as an aid of — to interpreting these as opposed to reporting those things per se.

Now it may well be that this new study, this new thing that we talked about will be an opportunity to talk about some of these other things as well. They’re important; I don’t mean to say they’re not important. But I think that the focus here needs to be on what are — were — what were the results from this set of analyses; how do we — what the meaning is.

D. JOHNSON: Well ...

M. STOTO: Is that ...

D. JOHNSON: Right, and I certainly didn’t mean to say that we should change it — not the study. I — but if you’re trying to explain to somebody what does this — what does all this mean, it starts to become confusing as you start throwing in all these other potential exposures. What would that mean? Or then is this — is this study looking, just trying to find associations with people who used herbicides?

Are we just saying then there’s an increased association of some cancer with people who used herbicides? And if that’s the case, it — that’s the case. But it — but it doesn’t really necessarily help me understand the results because that could be one of how many chemicals? I’m just — I’m kind of asking here.

M. STOTO: I think that ...

D. JOHNSON: Because I think that ...

M. STOTO: I think it helps you understand the results in the sense that you’re a little bit less — a little bit more wary about them.

D. JOHNSON: So is that — then is that what we are doing here; is we’re looking for associations with herbicide use in general? Is that — is that what this is?

P. CAMACHO: What about — what about we’re sticking to what we looked at, dioxin, but we’re informing people that these — there were other exposures. There were other things that people were exposed to; and we just want to acknowledge that and let them know that; and that and other new findings are coming about that weren’t in the protocol of the study. So by us mentioning this stuff, we’re informing people of the limitations that our findings have.

D. JOHNSON: Is our — that there’s confounders.

P. CAMACHO: That there are confounders.

D. JOHNSON: Yes. Absolutely.

P. CAMACHO: Is that — so I mean, does that sort of thing satisfy your concerns?

D. JOHNSON: Well, I — hopefully, I’m bringing up these concerns; it’s not my own personal concerns. I would hope ...

P. CAMACHO: Yeah, I understand. No. No.

D. JOHNSON: ... that it would be everybody’s thoughts. So you don’t have to really — I’m really not asking for you to satisfy my concerns, but it seems as if we’re talking about writing up something to help people understand the results. And if we — and I wasn’t quite understanding where you were going with it because if you say — is that our — is it dioxin or is it herbicides with these associations? What are these associations with: using herbicides, or with dioxin or both? And I guess my — these questions have kind of come up here listing the distinctions.

J. MICHALEK: Yeah. Let’s look at the history of this a little bit. Model 1 is the plain vanilla, old-fashioned epidemiology, Ranch Hand versus control stratified by occupation. Separately, every epi study is supposed to include an exposure metric. We tried to make one in 1982 based on herbs tapes. We think we failed because the herbs tape data was too crude at the time.

Subsequent, the CDC developed an assay for dioxin in people and we collaborated with them to measure dioxin. In spite of all of its caveats, it is a direct measure and we think we know some of the caveats. And so we included it as a surrogate exposure measure and we have three models based on it. The dioxin measurement is a direct measure; however, it carries with it a long list of caveats: differential elimination, possible dose-related elimination that we haven’t fully explored yet, unknown initial dose, the possibility that dioxin is a, in the control group perhaps, a surrogate for other things.

If you have a large body burden of dioxin, you would probably have a large body burden of furans, and PCBs and other things because you are a poor eliminator. And so by seeing a trend in the dioxin — of dioxin and health in the control group, we may be reviewing dioxin as a surrogate for markers other persistent organic pollutants that are related to health. The story is much more complicated, in other words, than was originally stated in our protocol.

We didn’t know all these things when we wrote the protocol. We didn’t know that — we had not even imagined that the control group would express heterogeneity like it does or that the enlisted ground crew would be the most heavily exposed. In the protocol, we thought the enlisted flyers were the most heavily exposed and it says so in there. So there were assumptions we made along the way.

There are complications we’ve run into that we revealed in our publications and reports, all of which have been — are out there, but haven’t been brought fully to bear in our interpretations like you said. And so I think by including these things, that’ll help Dr. Johnson and all of you address the uncertainties you see in these interpretations.

M. STOTO: Yeah. I mean, if you go back to the protocol, I mean, it says, “This is a study of health effects in Air Force personnel following exposure to Herbicide Orange, the purpose of which is to determine long — whether the long-term health effects can be attributed to occupational exposure to Herbicide Orange.” So, you know, okay, so that’s the purpose.

And then, I mean, that’s — whenever you do a study, you have to find groups with the appropriate — with exposures and there’s compromises involved in that. And so this study reflects certain compromises that were made, and certain assumptions about those things, and then new techniques that were developed along the way, and new things that were discovered that relate to those compromises — those assumptions, and compromises and so on.

So, you know, in the end, what we have is a series of statistical results that come from this whole long history of things. And in order to understand what they mean, it’s important to understand what was the purpose? What were those assumptions? What were the — what are the compromises? What did we learn, and so on and so forth. I mean ...

D. JOHNSON: So really what you’re saying is that we are looking for associations of working with the herbicides in Vietnam? That’s what we’re looking for — associated illness in those people?

J. MICHALEK: That was the original goal, yes.

M. STOTO: That was the original goal and then what we have is some necessarily imperfect approximation to that.

J. MICHALEK: It also needs to be said this is apparently the best anyone could ever do. We applied all available resources, and all available thinking and ...

M. STOTO: Whether or not it’s the best, this is what we — what we’ve got.

J. MICHALEK: ... whatever. I think this is what we’ve got. You know, I think it’s, yeah, in retrospect, I don’t think we could’ve done any better.

M. STOTO: Well, that may be true, but that doesn’t matter. I mean, this is what we have and we have to interpret these results. And I think all that stuff is relevant to the interpretation of these results.

R. TREWYN: And I would just want to try to synthesize the summary of the discussions. In 1999, my last meeting on the first four-year term that I was on this group, it really came down to the fact that, geez, maybe Model 1 is the most informative of the models if one then takes Model 1, and in the comparison group, breaks it out according to in Vietnam/not in Vietnam and then rehashes the numbers.

You might really get to the biggest health effects for service in Vietnam or as — come as close as you could to that, which I think we — my point was what drove all this in the very beginning was are there adverse health outcomes for those who served in Vietnam? The question that was ultimately asked wasn’t quite that question, but the — at least Model 1 gave an opportunity, and still does and is starting to show that by breaking these out in the appropriate ways — the comparison group — that, in fact, some of that data is coming forward and is helping understand this. So ...

M. STOTO: I think it’s really complicated.

J. MICHALEK: Yes.

R. TREWYN: Well, we can have our working lunch.

M. STOTO: Well, okay. Let’s — I mean, we pretty much have finished, I think, with this. I — let me see if there are other comments about the executive summary that we — that we can — that we can address other than redesign the study. Do we have any more Committee business before we break for lunch? I mean, I — let’s try to finish up. We’re basically — let’s try and finish up our business and then break for lunch if that’s okay.

Text Box: RHAC Business [continued]

L. SCHECHTMAN: Okay. In terms of forthcoming Ranch Hand Committee meetings, Julie has ...

J. ROBINSON: I did have one point of clarification and I may not have understood the intent when you asked how many meetings. I thought you were only addressing 2005 as opposed until the end, conclusion because I certainly didn’t want to imply we were not going to meet in 2006, which I think is very important to do.

L. SCHECHTMAN: Okay. Maybe we need to have some discussion on what kind of agenda items would occur at the 2006 meetings. I mean, I know this would just be off the top of one’s head at this point, but I mean, we were considering two technical meetings in ‘05 and ...

J. ROBINSON: Correct.

L. SCHECHTMAN: ... then the Committee wrap-up meeting or whatever we want to call it at this point in time. That would not necessarily be an Air Force Health Study technical meeting, but would be Committee business related to the study shutdown if you will. But you’re saying now that perhaps ‘06 meetings, that there might be some more technical meetings to finish?

J. ROBINSON: I would — I would think that that is not beyond possibility. I mean, we have — we don’t know what the IOM study’s going to show.

L. SCHECHTMAN: Right.

J. ROBINSON: So we have those issues; parallel to that is what we’ve constructed for our own disposition of the Air Force Health Study within the Air Force. We have the longitudinal study that we’re going to initiate. We also have, I think, something that’s going to capture some of these historic issues of the study; is that we’re going to do a historic perspective of the study.

I mean, we’ll cover things such as selection of the comparison group, you know, and why certain groups weren’t selected and a variety of other things that we really haven’t, you know, codified right at this moment. So I think there definitely is plenty of opportunity for technical meetings. There are — you would probably want to know what has been published: where we’re at as far as the articles that are going to be published in peer-reviewed journals versus in the Air Force technical reports, and kind of, you know, those unknown variables.

J. MICHALEK: Right. You’d probably like to — you may not today — in-house research, in other words, which is going to be reflected, like Julie said, in journal articles and in-house reports — more and more in-house reports as we get closer to the end.

R. TREWYN: I would just like to add that I think in the past, that has been very helpful to get some — in fact, so you don’t have to stand up there, Joel, and say, “What do” — “What do you want me to present?” I think getting some of the overview of new data in these different perspectives when you’ve done those presentations in the past, it has been helpful to then put the overall study in a better context. And I think that would be useful and for publications, presentations and whatnot to at least give us a little overview. At least from my perspective, that’s always been very helpful.

M. STOTO: And I agree. Other comments on this?

L. SCHECHTMAN: Okay. So based upon communications that we’ve had up to now with the Air Force, based upon comments here at this meeting today and surveys of availability, and so on, so forth, I can offer at least some current information as to blocks of time rather than specific dates that we’ve all, at least for now, come to some agreement on. And this, of course, does not include the additional technical meetings that were just proposed by Julie and Joel for ‘06.

We had originally talked about a February 2005 meeting. The Air Force has determined that that won’t be necessary at this point in time. But here we’ve discussed the possibility of holding a tele-con during that period of time instead, so we’ll arrange ...

M. STOTO: If necessary.

L. SCHECHTMAN: ... if necessary, so we’ll schedule that based upon the information that’ll be forthcoming. And Dr. Stoto and my office will take that into consideration and view the possibilities of such a tele-con. In May 2005, we’re currently looking at two blocks of time: May 1 through 6 and May 24 to 27. Of course, we’ll choose one date within one of those blocks of time at this point.

M. STOTO: May 1 is a Sunday.

L. SCHECHTMAN: Okay. Well, that — we just talked about the week, the block; I mean, there’s nothing firm about these specific numbers.

M. STOTO: Okay.

L. SCHECHTMAN: Okay. Okay, and in September of 2005, we are looking at May 12^th through — I’m sorry — September 12^th through 16 and 19 through 23 as the blocks. Dr. Camacho has communicated to us the possibility of scheduling conflicts during the month of September related to the beginning of semester-related activities. Is that right?

P. CAMACHO: Yes.

L. SCHECHTMAN: So we’ll have to take that into consideration as well.

P. CAMACHO: I prefer the later block in May than the earlier block in May as well because that would mean I’d still have to find — you’re approaching that.

L. SCHECHTMAN: Can you put that mike on?

P. CAMACHO: I’m sorry. I also would like — I’d rather, if I had my druthers, I’d rather the late May period than the early May period because you — if you teach, you have — you’re finding the beginning of the semester and the end of the semester become very important as — for students.

L. SCHECHTMAN: We’ll also check calendars as to professional society meetings, holidays and so on. So we’re going to be doing a lot of juggling during these periods of time in trying to accommodate as many folks as we possibly can. Then we’re getting into November of 2005. We originally talked about the block of time, November 1 through 4. However, in view of the NAS study and the possible availability of those results come November of ‘05, it’s been suggested that our November meeting follow the availability of those NAS study results.

So that meeting then may occur either later in the month of November, perhaps in December of ‘05, or again, avoiding holiday periods of course. But may, by virtue of calendars and availability, have to be pushed into the beginning of ‘06 some time, perhaps January, February, even, you know, January through March. Again, we’ll have to survey for availability of the Air Force and the Committee members to make that determination. And we’ll continue to communicate with the Air Force as to the ‘06 technical meetings and then survey members as to their availability with that as well.

M. STOTO: So I propose that we set a date based on when we anticipate the NAS report will be done and have people hold that. But if it turns out that we need to postpone it, we postpone it.

L. SCHECHTMAN: Okay. So I guess the order of the day would be flexibility at this point, which is all we can ask. We have obligations regarding Federal Register notices. We need to send in the information regarding such an assemblage at least 60 days in advance of a meeting, which seems to be rather impossible regarding this November, December, January or February meeting that we’re talking about following the NAS study results.

So we’ll perhaps find a way to propose — okay, so where was I? I’m probably not going to say the same — thank you; oh yes, 60 days. So we’ll try and figure out a way to schedule the dates for that meeting in a way that allows us to pull one date, replace the other. We’re not sure as to how that works. We have to have a very strong justification for making any amendments regarding Federal Register modifications once they’re set. Because although we don’t consider them set in stone, the FR notice does. Okay. So we’ll do the best we can with that and hope that we get some real heavy duty cooperation from everyone. Thanks.

Text Box: Closing Session

M. STOTO: Comments? Other issues that need to be raised? I think we can have lunch now, but let me first thank the folks from the Ranch Hand Study and all the contractors for the good work that they’ve done in pulling this all together; the Committee members for their reviews and comments; and the other staff, of course, for getting us all here and getting us the right material; and then the others who made contributions to the meeting by comments. Thank you. So we’re adjourned; I don’t think we need a motion for that. Enjoy your lunch.

[ADJOURN 12:36 P.M.]

Update by the Air Force Health Study Principal Investigator.................................................. 15

Nadine Rivera