DEPARTMENT OF HEALTH AND HUMAN SERVICES

 

and

 

FOOD AND DRUG ADMINISTRATION

NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH

 

 

convene the

 

 

Ranch Hand Advisory Committee Meeting

 

 

Rockville, Maryland

September 22, 2004

 

 

 

                                                                                       

 

Certified Verbatim Transcript

                                                                                       


TABLE OF CONTENTS

 

Page

 

Opening Session.......................................................................................................................... 1

      Approval of Previous Meeting Minutes................................................................................. 9

Update by the Ranch Hand Study Principal Investigator......................................................... 14

Review of Chapter 19:  Immunology.......................................................................................... 22

Review of Chapter 8:  Covariates............................................................................................. 26

Review of Chapter 12:  Psychology.......................................................................................... 29

Review of Chapter 16:  Hematology......................................................................................... 36

Review of Chapter 15:  Cardiovascular.................................................................................... 44

Review of Chapter 7:  Statistical Methods............................................................................... 54

Review of Chapter 5:  Study Selection and Participation....................................................... 70

RHAC Business.......................................................................................................................... 83

Public Comment Period............................................................................................................. 90

Closing Session........................................................................................................................ 105


LIST OF PARTICIPANTS

 


RHAC Members

Dr. Michael Stoto, Chair

Dr. Paul Camacho

Dr. Ezdihar Hassoun

Dr. David Johnson

Dr. Sanford Leffingwell

Dr. Ronald Trewyn

 

FDA/NCTR Representatives

Dr. Leonard Schechtman

RHAC Executive Secretary

 

Ms. Kimberly Campbell

Management Specialist

 

U.S. Air Force Representatives

Col. Karen Fox

Mr. William Keihl

Dr. Joel Michalek

Mr. William Murray

Mr. Richard Ogershok

Lt. Col. Julie Robinson

Mr. Larry Walden

 

U.S. Air Force Contractors

Mr. Manuel Blancas

UDTech

 

Dr. William Grubbs

Science Applications International Corporation

 

Dr. Judson Miner

Operational Technologies Corporation

 

Mr. Maurice Owens

Science Applications International Corporation

 

Ms. Meagan Yeager

Science Applications International Corporation

 

Guests

Mr. George Hawley

Veterans of Foreign Wars

 

Ms. Diane Mundt

Environ

 

Mr. Kenneth Mundt

Environ

 

Ms. Jaclyn Petrello

Exponent

 

Mr. Fred Razzaghi

Consumer Healthcare Products Association

 

Dr. Robert Sills

National Institute of Environmental Health Sciences

 

Mr. Rick Weidman

Vietnam Veterans of America



DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH

 

Ranch Hand Advisory Committee Meeting

September 22, 2004

Rockville, Maryland

 

Certified Verbatim Transcript

 

 


Text Box: Opening Session


 

 

 

 


 [CONVENE 8:17 A.M.]

 

            M. STOTO:  Everybody and all the equipment is in place, so we’re ready to begin.  I’m Mike Stoto, the Chair of the Committee.  And I’d like to welcome everybody here from the — from the Committee, from the Ranch Hand staff, from the Committee staff and others who are here.  And I think you all have a copy of the agenda before you.  I’d just like to ask everyone to go around the table.  First, the Committee members and then everyone else should introduce themselves briefly.  Robert, do you want to begin?

            R. SILLS:  Oh, there you go.  Okay, thanks.  I’m Robert Sills.  I’m the head of molecular pathology at NIEHS in the Research Triangle Park and my expertise is carcinogenesis and molecular mechanisms of cancer.

            S. LEFFINGWELL:  Sanford Leffingwell, former CDC tech, now trying to make my way in the real world as a consultant.  Some expertise in occupational and environmental medicine.

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

            R. TREWYN:  Ron Trewyn, Kansas State, Vice Provost Research, Dean of the Graduate School.  And back when I used to have to work for a living, same expertise as Robert.  So we’ll have to fight over the cancer chapters.

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

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

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

            J. MICHALEK:  Joel Michalek, Principal Investigator of the Air Force Health Study.

            RECORDER:  Excuse me, can you go to this microphone?  I’m sorry, but I have to record every single word.

            W. GRUBBS:  Bill Grubbs, SAIC, involved with the report.

            K. FOX:  Colonel Karen Fox, medical investigator with the Ranch Hand Study.

            L. WALDEN:  I’m Larry Walden and I’m with the Ranch Hand Study.  I’m a data management specialist.

            R. OGERSHOK:  I’m Richard Ogershok.  I’m the Program Manager for the Air Force Health Study.

            W. MURRAY:  I’m Bill Murray with the Air Force Surgeon General’s Office, Program Support.

            M. OWENS:  I’m Maurice Owens with SAIC.  I’m the Program Manager of the SAIC support contract.

            J. MINER:  I’m Jay Miner, Operational Technologies.  I work with Mr. Ogershok for the Air Force.

            M. BLANCAS:  I’m Manny Blancas, also with Operational Technologies and I also work for Mr. Ogershok in the Air Force Health Study.

            W. KEIHL:  I’m Bill Keihl.  I’m the contracting officer for the Air Force Health Study.

            M. YEAGER:  My name is Meagen Yeager.  I’m a project analyst for SAIC and I work on the Air Force Health Study.

            F. RAZZAGHI:  My name is Fred Razzaghi.  I’m the Director of Technical Affairs at the Consumer Healthcare Products Association in Washington.  Thank you.

            G. HAWLEY:  George Hawley from the Veterans of Foreign Wars.

            M. STOTO:  Okay.  Thank you everyone.  Len, would you lead us through the housekeeping items?

            L. SCHECHTMAN:  Okay.  Thank you, Mike.  Just one thing on the microphones, everyone needs to use them.  We’re recording the meeting and for the — for the verbatim transcript.  And if everyone would also shut their mikes off after they’re finished speaking, then we can recognize the next person who wants to speak and it also won’t interfere with the microphone that’s currently in use.  Thank you.

            Now we have a few housekeeping items that we’re going to be dealing with today.  First of all, we have two breaks scheduled — two coffee breaks — and a working lunch today.  So we won’t be leaving the room; you’re trapped.  Okay.  We’ll also try and hustle along that way and perhaps we can even adjourn a bit earlier to allow everyone to catch their flights.

            What we need to start doing already is start thinking about meeting dates for 2005.  And we’ve looked over the calendar to look for some blocks of time that wouldn’t interfere with holidays and general issues that seem to surface at certain times of the year.  So if you’ll jot these down, you can start thinking about this.  We will follow up with an e-mail from our office to try and nail down the dates as soon as we can.  We’re talking first about a meeting in February, either the week of the 14th or the week of the 21st of February.  And those — the actual days of the week, we’ll have to determine as to which is the most convenient for all individuals.

            M. STOTO:  Should we — why don’t we talk about that a little bit here?

            L. SCHECHTMAN:  Okay.

            M. STOTO:  I remember we discussed this in the past, and we decided that some days were good and bad, and I don’t remember which ones were which.  Was it — was it that Mondays and Fridays were bad?

            L. SCHECHTMAN:  Generally.

            M. STOTO:  Is that the — people had clinical responsibilities or something or ...

            P. CAMACHO:  For me, it’s ...

            RECORDER:  Use your microphone, Dr. Camacho.

            M. STOTO:  Mike, yeah.

            P. CAMACHO:  For me, it’s a matter of semester classes and the teacher’s schedule changes.  So like today, Tuesday would’ve been fine just because the schedule changed at the last minute.

            M. STOTO:  Yeah.  Well, why don’t ...

            P. CAMACHO:  So I don’t know.

            M. STOTO:  Let me just put it this way.  Are there — is there anybody here who has problems with a particular day of the week?

            J. MICHALEK:  Mike, I work ...

            RECORDER:  Mike.

            M. STOTO:  Mike.

            J. MICHALEK:  I work nights:  Monday night and Thursday night.  But the Thursday night is flexible and the Monday is less flexible.  I’m being paid to teach Monday night at the University of Texas.

            M. STOTO:  Okay.  Yeah, I — when I teach, I — it’s often on Monday too, so maybe we should try to avoid Mondays and we probably should try to avoid Fridays.  I think that someone had — maybe Dr. Osei, who’s not here today had — was the one who had a problem with that.  Good.

            L. SCHECHTMAN:  Okay.  So as I said, we’re looking currently at in February, the week of the 14th or the week of the 21st.  The meeting following that, we’re looking at May:  the week of the 1st of May or the week of the 23rd of May.  However, for the week of the 23rd of May, Thursday and Friday are not currently acceptable, so let’s exclude those from our thinking.  Okay.

            Following that in September of ‘05, the week of the 11th or the week of the 18th.  And in November, the week of the 1st, although Monday and Tuesday of that week should be excluded from your thinking at this point in time.  Actually, you might want to think of only Wednesday and Thursday if Friday is also excluded, so we’ll have to work around that.  Anyway, we’ll follow up, as I say, with an e-mail message to try and nail those dates down as best we can with the knowledge we currently have as far as 2005 goes.  And we’ll circulate the information as to how close we can get to the dates that we all want.

            M. STOTO:  Do we have some sense of — do we have some sense of what the agenda will be at these different meetings?  I mean, we’re finishing the draft chapters next month, right?  What’s — what are — what are the main work items for these meetings in 2005?

            J. ROBINSON:  Well, one will be ...

            R. TREWYN:  Microphone.

            J. ROBINSON:  One will be the final report and then I believe we need to have at least two meetings with you every year.  I think that’s what’s in the charter.  So the other one would probably be just to continue to update you on the closure activities, any additional research that would be going on and findings.

            M. STOTO:  So it’s possible we may not need all four of the meetings?

            J. ROBINSON:  Four meetings, right.

            M. STOTO:  Okay.

            L. SCHECHTMAN:  It sounds like we might need three though.  Is that what I’m hearing at a minimum?

            J. ROBINSON:  Two definitely, three possibly.

            L. SCHECHTMAN:  Okay.

            M. STOTO:  Okay.

            L. SCHECHTMAN:  Okay.  Next on housekeeping regards our annual conflict of interest paperwork that you were all recently faced with:  the Forms OG-450 and Foreign Activities Forms.  I want to thank you all for your very prompt turnaround of the COI forms.  Unfortunately, we are faced with them on an annual basis.  And in fact, if things change even between those filings, we’re supposed to ask you to update those filings as well.

            As far as the forms for 2005 are concerned, we’ll be e-mailing those to all the members of the Committee in July of 2005 so we don’t bump up against the meetings as we have in the past.  They’ll be due back to our office, the Office of the Executive Secretary, within two weeks of the mailing.

            And the OGE-450 Forms, which we provided you with a shortcut this time that if in fact there was no change from your previous filing, that you were allowed to indicate that on the form.  That was to help expedite the process because there was such a short turnaround time, but that won’t be available to us in the future.  So we’re going to have to ask you to fill out the OGE-450 Forms in toto.

            M. STOTO:  Can you at least send us the previous year’s copy so we ...

            L. SCHECHTMAN:  Oh yeah.

            M. STOTO:  ... remember what ...

            L. SCHECHTMAN:  Yeah.  Yes, absolutely.  Now as far as the Federal Register notices are concerned for upcoming meetings, due to mandatory departmental requirements, we are required to submit Federal Register notices for upcoming meetings well in advance of any scheduled meetings.  So we’ll need to prepare draft agendas, identify topics, presentations, possible outside speakers, et cetera, by no later than sixty days in advance.  This is the departmental requirement.

            We can submit changes to that agenda that we furnish for the Federal Register notice, however, there — they can only be critical changes and we have to justify the changes.  So those changes, if critical, can be submitted up to 45 days in advance.  So we have a window for any changes that need to happen.  Just a reminder as far as your travel receipts, and expenses and those filings, please turn them in as soon as possible.  And if you mail them, make them to the attention of Kim Campbell in our office.

            M. STOTO:  Okay.

            L. SCHECHTMAN:  And that’s it.  Thank you.

            M. STOTO:  Okay.  Thank you.  I think you all have copies of the agenda before you.  The main order of business today is to review about half a dozen or seven chapters in the report.  Joel Michalek is scheduled to make a presentation about a general update, but has to go to the Pentagon at the time he’s currently scheduled.  So we’re going to ask him to do that presentation in a minute after we’re through with reviewing the minutes.

            We also have time scheduled for public comments.  So far, we have not received any word that someone wants to make a comment.  I’m just looking around now to see whether anybody does want to add themselves to the list?  Okay.  Thank you.

 

Approval of Previous Meeting Minutes

            M. STOTO:  Now for the minutes, the minutes have been circulated.  I’ll ask in a moment if there are changes that people want to make.  I reviewed them and have suggested some changes.  I don’t know whether what you got reflected my changes or not?  Did they go out?  There were — there were a couple of things.  One, in Colonel Berry’s presentation last time, he had a statement about what the law required the NAS study to do that wasn’t quite consistent with the law.  So I gave him the opportunity to change that.

            And secondly, there were lots of — he made a very detailed, and interesting and provocative presentation that we really didn’t have a chance to review as a scientific basis.  So I tried to make the minutes clear that they were his — that that was his perspective rather than the Committee’s perspective.  The other thing was that we had a discussion about this Congressionally mandated study the National Academy of Sciences is supposed to do which ended up with an action item that I was supposed to write a letter to Secretary Principi to try to move that along.

            I ended up thinking that the best way to do that was to invite the Secretary to send a representative to this meeting today to explain what the situation was with respect to that study, which of course, the law calls for the study to have been initiated within, I think, sixty days of passage.  So they’re long overdue on that.  I want the record to be clear about that; that we have taken notice that the Department of Veterans Affairs has not fulfilled this responsibility according to the law.

            I have not heard a response from the — from the Secretary or the Department about that.  I don’t think there’s anybody here from the Department.  I — we continued to hear indirectly that things are moving along, but of course, that may or may not be true.  And what is definitely true is that they didn’t do it according to the time schedule that the law demanded, so I will invite the Secretary and representatives to come next time and explain what the situation will be.  And I think that is important that we continue to do this.

            We’re in the unusual position of our job is to advise the Secretary of Health and Human Services, who doesn’t have a direct interest in this.  This is really the Air Force, and the Veterans Affairs and Congress.  But it might be — it may be of use to call this to the Congressional staff’s attention.  We copied them on the letter and that’s something that ...

            P. CAMACHO:  I don’t know if it’s — what’s the appropriateness of all this; I leave to you.  But the service organizations should be all informed of this directly, if nothing else, in a way to protect our — protect ourselves.  Because to — for me as a member of this advisory board, we have an obligation to the service community, the veterans community, to inform them of things.  Now whether this study continues, whether this — all the data is saved or whether this is thrown off the cliff, it’s for NAS to make that decision.  And if they’re not allowed to make that decision, we’re going to sort of be holding the bag, if you will.  And people are going to say, “Why didn’t you do something about it?”

            So that’s what I — so doing something about it would be writing a formal letter, as we wrote to Mr. Principi, to all the service — major — the major service organizations:  the VFW, American Legion, the DAV, and AMVETS, and then Vietnam Veterans of America and let them disseminate that.  Then we’ve told them this isn’t happening; the study isn’t — NAS is not looking forward to it; this is going to probably drop off the cliff.  Maybe that’s bad; we should be keeping this data somewhere, find a home for it ...

            M. STOTO:  Well, I ...

            P. CAMACHO:  ... whatever.

            M. STOTO:  I’m not sure it’s our role to write to those organizations.  But I wrote the letter to Principi in way that a copy can be sent to those organizations and a copy has been ...

            P. CAMACHO:  Oh fine, but ...

            M. STOTO:  ... a copy has been sent to the Congressional staff.

            P. CAMACHO:  Yeah.  If a copy could also be sent to those — if I provided those list of ...

            M. STOTO:  Right.

            P. CAMACHO:  Would that be acceptable to you?

            M. STOTO:  I mean, we did copy the relevant Congressional staffs already.

            P. CAMACHO:  Yes, but I think also could we go — is it appropriate for us to go one step further and send copies to the ...

            M. STOTO:  It’s appropriate for you to do that.

            P. CAMACHO:  It is?

            M. STOTO:  Yes.

            P. CAMACHO:  There’s no problem?  All right, fine.

            M. STOTO:  No.

            P. CAMACHO:  I’ll do it.

            M. STOTO:  I mean, it ...

            P. CAMACHO:  I’ll do it.

            M. STOTO:  Okay.  Were there any other comments?  Any other discussion about that item?  Any other comments, corrections for the minutes?

            R. TREWYN:  I do have one correction on the minutes.  On page eight, bullet three, it should read, “Provide a breakdown of in-country Vietnam versus ...” not “countries in Vietnam.”  So “in-country Vietnam versus other locations ...”.

            M. STOTO:  Careful reading.

            R. TREWYN:  That was my only edit.

            M. STOTO:  Let me — let me just make the comment again that I think that these minutes were very well — the draft was very well prepared, so thank you very much for your efforts.  So do I hear a motion to approve the minutes?

            R. TREWYN:  So moved.

            M. STOTO:  Ron.  Second?

            S. LEFFINGWELL:  Second.

            M. STOTO:  Sandy.  All in favor, please raise your hand and say yes.

            RHAC:  Aye.

            M. STOTO:  Okay.  I think it was unanimous.  Okay.  Joel, can you make a report now?

 

Text Box: Update by the Ranch Hand Study Principal Investigator


 

 

 


            J. MICHALEK:  How much time do we have:  five minutes, ten, fifteen?

            M. STOTO:  Whatever you need.

            J. MICHALEK:  Okay.  I’ll try to tell you about three things.  Number one, I briefed the National Academy of Sciences in June of this year.  Number two, I attended the dioxin conference in Berlin in September of this year.  And number three, a short summary of our research that’s going on right now today.

            In June, I briefed the National Academy, namely the Institute of Medicine panel, the panel that’s responsible for writing the Agent — the Veterans and Agent Orange books in Columbus, Ohio.  The — I was there to respond to a critique of our cancer paper that was published in the Journal of Occupational and Environmental Medicine in February of this year.  The key person on their committee that was responsible for the critique of that paper is David Strogatz from UC — University of New York at Albany.

            I responded to the questions.  I gave a detailed presentation of the paper which you’ve already seen.  The features of that paper were that we departed from our usual analysis of comparing and using what are called “main effects models:”  high, low and background Ranch Hands against comparison.  That analysis was done already, and published in 1998 and showed no exposure effect.

            On the advice of the Committee, we expanded the analysis, and dropped our model and searched for new approaches using your advice:  number one, to compare Ranch Hand in comparison with the cancer incidence experience against national rates; number two, to revisit the so-called dioxin category analysis with adjustment for years spent in the region and exposure potential to Agent Orange.  That new analysis showed an effect; however, in order to do it, we had to stratify.  And stratified analyses are not as easy to understand as main effects analyses; anyone would know that.

            The point is that the analysis was driven by what we called in statistics a “significant interaction” which meant that the relation between cancer and dioxin changes with years in SEA — years in Southeast Asia.  And that concept leads to the talks I made in Berlin this month.  Also discussed at the meeting in Ohio was the 2002 paper we published in Neurotoxicology on dioxin and peripheral neuropathy.  That paper showed a significant increase in risk of probable peripheral neuropathy with increased dioxin category.

            The very latest National Academy textbook found the analysis less than convincing and so they did not conclude that the data provided a suggestion of an exposure effect.  This committee wants to revisit the paper.  And they’re now re-analyzing that paper and questioning every analysis.  And so they’ve asked us to provide additional detail on the data and the results from that paper.  And we’re working on that as I speak.  That’s really all I had to say about the National Academy meeting in Ohio.  In “Dioxin 2004,” which is one of ...

            M. STOTO:  Joel, excuse me.

            J. MICHALEK:  Yes?

            M. STOTO:  Ron has a question.

            R. TREWYN:  I was just curious whether the — in that presentation they had any criticisms or concerns about the cancer paper?

            J. MICHALEK:  They had no criticism that was — I — that I couldn’t address with the — with the questions and answers, so that I think they’re just meditating at this point.  Obviously, it’s a complicated picture when the usual so-called “main effects models” produced no effect.  And when we additionally adjusted for a factor, such as years in SEA, we see an effect.  That’s new and it takes time to understand that.  And so that’s where it is at this point.

            “Dioxin 2004,” I presented three papers — actually, four; one was a poster.  The presentations were insulin sensitivity, which is a talk you’ve seen already, which is the matched pair design of thirty pairs we sent to the VA Medical Center in Little Rock to further explore the diabetes association we saw in the study.  Cancer in the comparison group:  this is a — the next step in our analysis of cancer.  We discovered in the paper published in February of this year that the comparisons themselves are experiencing an increased risk with years in Southeast Asia and that complicated our analysis of the Ranch Hand cancer experience.  And that was why the paper published in February was complicated.

            The trends we see in the comparison group complicate our attempts to understand cancer in the Ranch Hand group.  The purpose of this paper was to display what we see in the comparison group divorced from the Ranch Hand group, the comparisons only.  What we see in that group is a trend of increased risk of all-site cancer with years in Southeast Asia.  We also see a trend of increased risk of all-site cancer with dioxin in the comparison group.  And further, we see an interaction, meaning that the relation between dioxin in the comparison group changes with years in SEA.  It becomes stronger the longer they’re there.

            In the third and fourth quartile of years in SEA, the associations between cancer and dioxin are increased.  And the p value in that interaction was .006.  It’s not an interaction; it can be statistically ignored in other words.  So as the paper sits right now, we’ve got two series of analyses:  cancer versus years in the region and cancer versus dioxin in the controls.

            I also presented a paper on mortality and the — which is a, for us, a fairly routine presentation because we’ve been doing mortality studies since the beginning, since 1982.  In those analyses, we compare the mortality experience of the Ranch Hand group against all 19,000 comparisons.  The analysis benefits from the large sample size, but it’s hindered by the lack of covariates.  We don’t have smoking and family history of heart disease in the 19,000.  All we’ve got in these analyses are date of birth, rank and military occupation, and those are the main covariates.

            In that series of analyses, you see all — we see again what we saw five years ago:  namely, a significant increase in the risk of cardiovascular death in the enlisted ground crew.  That’s important to us because the enlisted ground crew have the highest dioxin levels.  The complication is that when you view the cardiovascular chapter in the current report, you’ll find very little in the way of a dioxin exposure effect there, which leads to the third part of the puzzle in cardiovascular health, which is our metabolic syndrome paper which was also presented at “Dioxin 2004" as a poster.

            That shows an association between metabolic syndrome and subsequent cardiovascular death in controls as you would expect, but not so in the Ranch Hand group.  There’s a fairly strong interaction there showing that the usual association that one would expect is visible, and clear and significant in controls, but not so in Ranch Hand.  We don’t understand that, so I’ve got three pieces going on with cardiovascular.  You’ve got this change in the expected pattern of metabolic syndrome in cardiovascular mortality.  You’ve got the increased cardiovascular mortality in the Rand Hand enlisted ground crew.  And you’ve got the lack of an exposure association in the current report on the living individuals who showed up at Scripps.

            Right now today, we are very carefully examining every single death in the Ranch Hand enlisted ground crew looking for the possibility that we may have missed something because of competing risks.  Individuals may have died of cancer or the causes and that may be obscuring what we’re seeing.  And so we’re itemizing every single case.  And with members of our staff, we’re reviewing every single record.

            So the third topic was ongoing research.  We have papers in progress on prostate cancer and dioxin, which is a continuation of what I presented at the last meeting using the updated database, which we now have more cases.  So it’s more opportunity for analysis and display of results.  I already mentioned heart disease.  We’re looking very carefully case-by-case at those enlisted ground crew.

            We are responding to the National Academy questions on our peripheral neuropathy paper which was published two years ago in Neurotoxicology.  And we have a paper in progress on cancer in the Ranch Hand group, which is the follow-on to the paper I just described on cancer in the control group.  The new paper on cancer in the Ranch Hand group will build on what we’ve seen already in the control group using the very latest data.

            And by the way, the database has changed since the publication in February of this year.  At that time, we had 355 individuals with at least one tumor out of a total of — well, talking about controls only to give you an idea — 355 out of 1,700.  And now the latest data shows 400 and some — 450 out of 800.  So there’s been a big increase in the number of verified cancer cases in the control group.

            There’s been a big change in the cancer database.  And as I speak, we’re updating the database again because the new cases are being discovered to verify all the time by our staff.  About 33 percent of the cohort have at least one tumor — verified malignancy in other words.  So that’s what I had.

            M. STOTO:  Okay.  Thank you.  I — go ahead, Ron.

            R. TREWYN:  Quick question on the — on the cancer side of it with the years in Southeast Asia; that’s anywhere in Southeast Asia or was there a breakout in that, in Vietnam versus Thailand, wherever?

            J. MICHALEK:  At this point, all we can do is break out Vietnam versus non-Vietnam.  And now that you’ve brought that up, that is a piece that we have put in.  We’re going to — we took it out and we’re going to put it back in again comparing years spent in SEA with cancer risk and comparing those that went to Vietnam, those that didn’t go to Vietnam.  Those are all ready and obviously straightforward.  We do not know where they were in Southeast Asia yet.  We can’t count up days spent in Japan, Okinawa, Taiwan.  We’re working on that now; that’s very labor-intensive.

            Just to give you an idea, imagine 1,800 individuals maybe with ten to fifteen entries in their tour file.  And all of these are written many years ago about units that may not exist anymore and units which require research to understand where they were.  And so it’s a lot of work, but we’re going to get there.  We’re working on it.

            M. STOTO:  I just wanted to make the comment that I think this really illustrates the value of these data that the Ranch Hand Study has gathered that go beyond the original study question about the effects of Agent Orange and other herbicides.  I mean, particularly the studies done in the — in the controls that you’re finding very interesting things.  And that, I think, is something that needs to be clear to people as they’re considering the disposition of the study.

            J. MICHALEK:  Yes.  The underlying kind of concept there, I believe, is questioning your assumptions every step of the way.  We had always assumed from the very beginning that the comparison group was fine, but they were our — they were our standard.  There was no concern about the comparisons.  They were our standard, period, and they were to be the reference.

            Well, as soon as you begin to adjust for factors that we had not previously considered, the models show significant interactions, meaning that there is a change in risk going on, a relative risk going on with factors, such as years in the region and dioxin.  And the models are so strong they can’t be ignored and that’s what we’re finding today:  that our original assumptions may not be true; that the Ranch — that the cohort, the two cohorts are different and we don’t understand why.

            M. STOTO:  Any other comments?  Robert?

            R. SILLS:  Joel, you talked about all sites of cancer.  Is there anything that’s specific about the cancer in the controls and the dioxin groups?

            J. MICHALEK:  I think I can answer that a little later; I have the document on my computer.  The — there was a distinction between the so-called “SEER” cancer sites, S‑E‑E‑R:  Surveillance, Epidemiology, End Results section of the National Cancer Institute.  Those sites include all cancer sites except the cosmetic cancers:  basil cell and squamous cell carcinoma.  And as I recall, there was a difference whether you look at all-site including those or all-site not including those cosmetic cancers.  I’ll have to look at the document to answer your question; I’d rather not guess right now.

            R. SILLS:  If I could, I — can I — can I just make one quick comment?  I think over the years, what have been useful to the Committee is the updates on the findings and the studies you have done to date.  One of the recommendations of the Advisory Committee over the years was to make sure that we publish the data in the peer review press and we appreciate that this advice was taken seriously, which really provides a strength and credibility that supports the document that we’re reviewing today.

            It’s really refreshing to see that as we read the text, we could find publications.  We could find publications that are very current.  So I think as a group, you guys are doing a super job and we appreciate the fact that you’re pulling it together so nicely.  Thank you.

            M. STOTO:  Thanks, Robert.

            J. MICHALEK:  Thank you.

            M. STOTO:  Other comments?  Okay, Joel.  Thank you for your report.

 

Text Box: Review of Chapter 19:  Immunology


 

 

 


            M. STOTO:  So according to the agenda now, we’ll move into the review of Chapter 19 about immunology and Sandy has prepared a review.

            S. LEFFINGWELL:  This has been previously reviewed, so I really didn’t find much to comment on.  That, in fact, is a source of some embarrassment.  One feels obliged to say something just to prove you’ve read it.  And the consequence is that the comments, by and large, border on trivial; they’re an embarrassment.  Nevertheless, let’s plunge forward.  I don’t think there’s anything here that would embarrass either the authors or the Committee if it were released without revision.

            Table 19.2, which begins on page 19-11, is a long table in two parts.  The abbreviations are defined after the second part, which gave me some trouble.  I wondered if we could put at least those portions of the abbreviations that pertain to part one immediately after part one, the “Dependent Variables?”  The only part that’s repeated is “data form” and I don’t think it would cost us much to print that in both places.  Most of it is — pertains only to the “Dependent Variables” part.  Line 466, which is on page 19-14, the comment about “excluded observations” — that’s not the right line.

            M. STOTO:  Actually, before you talk about that line, I don’t know whether someone wants to respond to these one-by-one or as a group?  The other question I have is I — Sandy has written up these notes and I don’t know whether you’ve all received them yet?  Okay.

            J. ROBINSON:  No, I have not received them.

            M. STOTO:  Okay.  So I can — I mean, I can send you my copy here and you probably can e-mail them too.  I wonder what’s the best way to have them?

            S. LEFFINGWELL:  I can get those to her.  I sent them to Kimberly also.

            M. STOTO:  Okay.  So I take it there’s no response to this particular — do you want to ...

            J. MICHALEK:  I’m sorry.  Would you repeat that?

            J. ROBINSON:  In regards to modifying the tables, we’ll need to get with SAIC to determine the impact of that modification.  So I need to actually ...

            S. LEFFINGWELL:  Yeah.

            J. ROBINSON:  ... talk with Dr. Grubbs.

            M. STOTO:  So you’ll take it under consideration?

            J. ROBINSON:  Yes, absolutely.

            S. LEFFINGWELL:  Let’s see if I can find the right line.  Some line, and I’m trying to find it here, there was a mention of the “excluded groups.”  And I wondered if it would be worthwhile stating explicitly that there was no statistical difference between the numbers excluded?  I did a few chi-squares on the data there.  It looked like the — like there wasn’t; I think that’s genuinely true.  And I wondered if just adding that comment would be worthwhile?

            Line 563, Table 19-4.  Okay, 19-4 now is on 613.  Apparently, I had the wrong version either then or now; I don’t know which.  It’s not clear if I’m looking at version 1 now or whether I was looking at version 1 before.  In this table, I was having hectic day when I was trying to go through this, interrupted and kept coming back, and I found myself getting disoriented.  The titles of the sub-tables or the individual tables under 19-4 do not repeat that this is an “Analysis of T Cells or CD3+.”

            And so when you look, for example, at Table — Sub-table (b), it appears that it’s looking at Ranch Hands versus comparisons somehow broken out by occupational group instead of looking at T cells within these groups.  And I wondered if it would be possible to reinsert in the headings for the individual tables what the topic is so that as we go from page to page, there would be less risk of disorientation?  As I say, a careful reader will get around that; that’s not a serious problem.

            M. STOTO:  That sounds like it’s a — it’s a general comment that probably applies to all tables.

            S. LEFFINGWELL:  Yeah.

            M. STOTO:  And it probably is a good idea.

            S. LEFFINGWELL:  And then on — again, I had line 1572, which doesn’t correlate with the line number in the document in front of me.  There was a statement including the phrase “which is designed to” and I think it’s talking generally about the immune system.  And that’s, of course, teleological reasoning.  The purists would say we ought to simply state “which fights invading organisms such as ...” instead of saying “which is designed to fight invading organisms.”  And then in the references, there’s a couple of places where it mentions “(Callithrix jacchus).”  And I wondered if that should be italicized?  And that is really all I found in this.  And as I say, that’s an embarrassment.

            J. ROBINSON:  Well, we appreciate your careful review of the document.  And what we do with all your comments is we take them back, review them and then respond to them with a — working with our contracting authors.

            M. STOTO:  Okay.  Thank you.  Thank you, Sandy.  Any other comments that people had on that — on that chapter?  It sounds like it’s in pretty good shape.  Okay.

 

Text Box: Review of Chapter 8:  Covariates



 

 

 


            M. STOTO:  Can we move on, Robert, to Chapter 8 about covariates?  This was a very exciting chapter.

            R. SILLS:  I know it was.  Well, I got something out of it, so I thought it was a pretty good chapter.  So Chapter 8 on “Covariate Associations with Estimates of Dioxin Exposure” was clearly written and easy to read; tables were chronological with the text; and the text was supportive of the data in the tables.  I agree with the comments — the comment resolutions prepared by the staff.  This chapter accomplished its goals of determining whether the covariates used throughout this report were associated with the estimates of herbicide or dioxin exposures.

            The chapter is consistent with the fact that dioxin was significantly associated with military occupation where officers had the lowest levels, followed by enlisted flyers and enlisted ground crew.  The association between dioxin and health measurements and possible explanations were useful for the reader.  An example which was well written in where it was stated in the summary, line 602 to 605, that “body mass index, HDL cholesterol, physical activity, diabetic class, duration of diabetes and waist-to-hip ratios are likely explained by body fat;” and that “high body fat measurements are known to correspond to higher dioxin levels, lower levels of HDL cholesterol and higher cholesterol-HDL ratios.”

            These types of discussions were very useful and we thank you for providing some explanation to the — in terms of the data that was presented.  I will provide the staff with my minor editorial changes which were made throughout the text.  These include rewording sentences for clarity, possible deletions and maintaining consistency.  These changes will not change the context of the chapter, so I don’t think there’s a need for me to go through each line — each one line-by-line.

            Some are just additional suggestions or to add asterisks to the tables to indicate statistical significance.  And as you go through the tables, it would be nice for to just see stars:  you know, one star meaning “p<0.05;” two stars, “p<0.001.”  I think it — right.  You could, you know, the data’s there, but just by putting those stars in will really make a difference and really would allow one to easily identify significant associations.

            And one last minor point is rather than beginning both the summary and the conclusions sections with, “The purpose of the chapter,” et cetera, I suggest removing this beginning from the conclusion in line 629.  And just state, “It was determined whether the covariates used throughout this report were associated with the estimates of dioxin exposure and, therefore, could potentially be confounding variables in subsequent statistical analyses.”  I also suggest removing “in the report” from that sentence at the end.

            M. STOTO:  Can you say again which line that was?

            R. SILLS:  That’s line 629.

            RECORDER:  Page 629?

            R. SILLS:  Line 629.

            M. STOTO:  That’s the beginning of Section 8.1.

            R. SILLS:  Yeah.

            M. STOTO:  “Conclusion.”

            R. SILLS:  Yeah, on — right.  And I also suggest removing “in this report” at the end of the sentence since it was redundant.  A question to the staff is can a reference section be added to this chapter?  This would be very informative to the — to the readers.  I noticed in a number of the other chapters, there were references.  And for people who are not familiar with this topic, just some general references may be informative.

            M. STOTO:  You mean references to like statistical methods?

            R. SILLS:  Yeah.

            M. STOTO:  Okay.

            R. SILLS:  You know, just some basic information.  So in conclusion, this is an excellent chapter.  It is really great to see the tremendous progress that is being made in reporting this important data from the Ranch Hand Study.  The staff is highly commended for their valuable efforts.  The Ranch Hand Study clearly represents a model for future studies where the American public may be exposed to potentially hazardous substances and agents.  Thank you very much.

            I just want to reiterate this.  I’m — I work at the National Institute of Environmental Health Sciences and I’m with the National Toxicology Program.  And I really — I really know the detail and the amount of work it takes to prepare these documents.  And as I — as I go through these documents, I could just see that attention is being paid to detail and the documentation is clearly done.  And I think when we’re done with this, we’ll have a great product.

            M. STOTO:  Thank you.  Any response from the Air Force then?

            J. ROBINSON:  Thank you very much and we’ll welcome your additional changes.

            R. SILLS:  Good.  Thanks.

            M. STOTO:  Okay.  Other comments from the Committee?  Okay.  Well, we are — the agenda calls for a break between these next two chapters, but we’re still only a little bit after 9:00.  So I propose we go on to Chapter 12.  Dr. Hassoun, can you give us your comments?

 

Text Box: Review of Chapter 12:  Psychology



 

 

 


            E. HASSOUN:  This chapter is very well written, very clear, very easy to understand.  Just a few comments, I’m with Dr. Sills about the tables.  Other than mentioning all the significant values, just define the significant — significance levels in the footnotes:  like “p value<0.05.”  That’s significant.  Because the way it’s written, I mean, in this chapter, probably in all other chapters, for example, if I can look at one of the tables:  “p>0.02;” it’s non-significant.  It sounds like anything less than 0.20 is going to be significant, right?

            J. ROBINSON:  What page is that on?

            E. HASSOUN:  Page 12-16.  I mean, it’s through all the tables; this is just an example.  If we just add asterisks to the tables and define the significance level:  “p value is less than 0.05.”

            J. MICHALEK:  I guess ...

            M. STOTO:  Yeah, go ahead.

            J. MICHALEK:  ... a short comment.  That specification, I think, is given in the “Statistical Methods” chapter throughout the report; “p<0.05" is called “significant.”  You know, we have to make global decisions about this and put things in the — in one place sometimes.  And that’s what we did, I think, on this issue.  Is that true, Bill Grubbs?

            W. GRUBBS:  That is correct.

            J. MICHALEK:  So, and that’s what we did and that’s consistent with the previous reports.  And that’s another issue, you know.  As we think about changing format, we have also the — to realize that the reader might want to compare this report with last cycle report and so we want to keep that task as simple as possible.

            M. STOTO:  So can I — are you asking that they — that they change the table or they just be clear about what the significance is?

            E. HASSOUN:  Exactly, yeah.  Define the significance level.

            M. STOTO:  I mean, it seems — that seems to me to be relatively simple enough to do, to remind the reader in every chapter.

            J. MICHALEK:  Yeah.  All right.  I just reassured that it could be done.

            M. STOTO:  Okay.

            J. ROBINSON:  Again, I just want to say that we take every comment, and we evaluate it and respond to them all.  Thanks.

            E. HASSOUN:  Then page 12-8 about the “Verbal Paired Associates test,” I have a question about the adjustment of the scores to 18.  I mean, you divided the total for the easy items by 2 and adding the total for the difficult items.  Why did you choose to divide the easy items by 2, just to make it 18?

            J. MICHALEK:  Please tell me where are you reading that?

            E. HASSOUN:  12-8, lines 427 through 432.

            J. ROBINSON:  And the specific line is 432.

            J. MICHALEK:  Okay.  Well, this is an algorithm that is cited from the literature or given to us by our consultants at CDC on how to score these psychological tests.  This is not something we made up just for convenience, you know.  It’s ...

            E. HASSOUN:  Yeah.

            J. MICHALEK:  So probably what we need there is a reference.

            E. HASSOUN:  Okay.  Because it says, “In order to mimic the other, I mean, we did so-and-so.”  It sounds like you adjusted it so that ...

            J. MICHALEK:  Yeah.  It makes it appear we made that up in order to mimic the scoring.  Now that I said that, yeah, that’s true.  This language and this algorithm, no doubt, came from our consultant at Scripps — what’s his name, the psychologist at Scripps? — Dr. Carey, who was our consultant on the Wechsler Memory Scale.  And so — and he’s a psychologist, so he’s using his knowledge to write that.

            E. HASSOUN:  For the “Covariates” on 12-9, I don’t know; it’s about alcohol history.  Is that a covariate or a dependent variable?

            J. MICHALEK:  That is a covariate.

            E. HASSOUN:  Yeah, because you used it under dependent variables also:  alcohol dependence and the drug dependence.

            J. MICHALEK:  Now there, that’s a, I believe, an item from the DSM.  The — that’s a standard outcome in a psychological profile and they’re all given:  the alcohol dependence, drug dependence.  Yes, so that it’s also a dependent variable, so that complicates the picture.  Yes, you’re right.  It’s both a — sometimes a covariate and sometimes a dependent variable.

            E. HASSOUN:  And for 12.1.4, the “Statistical Methods,” page 12-10, line 496 — “Unadjusted and adjusted analyses for Models 2 and 3” — can you just add a little explanation for those models?  I saw them; I found them later.  Under “Exposure Analysis,” you described the models:  1, 2, 3, 4.  But in “Statistical Methods,” all of a sudden, you are talking about Models 2 and 3 and I got confused when I read those.

            J. MICHALEK:  All right.

            E. HASSOUN:  So I had to go ...

            J. MICHALEK:  Okay.

            E. HASSOUN:  ... to the ...

            J. MICHALEK:  And that, so they’ve not been described up to this point?

            E. HASSOUN:  Just a little, I mean, just two lines.

            J. MICHALEK:  Okay.

            E. HASSOUN:  You had four methods or four models.  Then the table, Table 12-1, page 12-11, since you decided to put the cutpoints in the table, why not add a maximum scores also for the “SCL-90-R Global Severity Index?”  Like “Cutpoint/Maximum Scores,” which are 1825 or 34, right?

            M. STOTO:  What table?

            J. MICHALEK:  What table is this?

            E. HASSOUN:  Table 12-1.

            J. MICHALEK:  Okay.  All right.  So you want to know the maximum?

            E. HASSOUN:  Yeah.  Since you decided to put the cutpoints ...

            J. MICHALEK:  Yeah.

            E. HASSOUN:  ... on the SCL, why not add in the maximum scores for the WMR?

            J. MICHALEK:  I’m sorry.  All I see in that table are cutpoints for covariates.

            J. ROBINSON:  That’s what she’s saying.  She saying in addition to cutpoints, to “/Maximum Scores.”

            E. HASSOUN:  “/Scores.”

            M. STOTO:  But that’s the definition of the categories, right?

            J. MICHALEK:  My table 12-point for some reason ...

            M. STOTO:  Isn’t that ...

            J. MICHALEK:  Oh, I’m looking at the wrong panel.  Okay.  All right.  I’m with you now, yeah.  So you want to know the maximum possible value of the psychological scales?  Is that right?

            E. HASSOUN:  Yes.

            J. MICHALEK:  Okay.

            E. HASSOUN:  So rather than going back to the text ...

            J. MICHALEK:  Yeah.  Right.

            E. HASSOUN:  ... and read what the ...

            J. MICHALEK:  Yeah.

            E. HASSOUN:  ... normal scores ...

            J. MICHALEK:  Yeah.  I think — yeah; that’s a standard thing to do in reports like this.  I understand that.  We’ve taken note of that.

            E. HASSOUN:  Okay.  Okay.  That’s all what I have for the chapter.  Regarding the appendix, again, it’s nice to define the significance level.  And also for Pearson’s correlation coefficient, the maximum correlation is 1.0 as I know.  Is that right?  It’s 1.0?

            J. MICHALEK:  That’s correct and the minimum is minus 1.0.

            E. HASSOUN:  And the minus values will — would indicate inverse ...

            J. MICHALEK:  That’s ...

            E. HASSOUN:  ... correlation?  Yeah.

            J. MICHALEK:  That’s correct.

            E. HASSOUN:  If we can add that to the appendix also.

            J. MICHALEK:  Okay.  That’s all what I have.

            M. STOTO:  Okay.  Thank you very much.  Can I bring up one point?  This and the immunology chapter were — are the first substantive chapters we’ve reviewed this cycle.  And one of the, I think — I think the major difference is, is that the summary section and tables at the end.  And we had a lot of discussion about that in the last cycle and my sense is that this is relatively nicely done here.  I don’t know whether the two of you agree with that?  And maybe when the others come to review their chapter, they may comment on that as well.

            J. MICHALEK:  Thank you.

            M. STOTO:  Sandy, did you want to say something?

            S. LEFFINGWELL:  Not really.  Yes, I noticed the summary tables and thought they were helpful.

            E. HASSOUN:  They were very helpful.

            M. STOTO:  Other comments from the Committee about this chapter?  Okay.  Thank you.

            S. LEFFINGWELL:  I was curious.  Do the Ranch Hand subjects know which group they are in or do they have fairly high suspicion just from knowing what they did while they were there?

            J. MICHALEK:  Well, they certainly they’re Ranch Handers and the controls know they’re controls.  Is that what you mean?

            S. LEFFINGWELL:  Only in part.

            J. MICHALEK:  Oh, their dioxin levels?  Is that what you mean?

            S. LEFFINGWELL:  Yeah.

            J. MICHALEK:  Dioxin category?  They know their — we told them their dioxin levels.  We gave them that by mail.  And if they’ve read the reports, they’ll know what category they’re in, but I don’t know how many people have read the reports.  We sent them a letter in 1989 telling them they had 12 parts per trillion.  I doubt if that information, for very many people, is at the top of their mind as they’re going to Scripps.  I mean, they don’t — you know, I don’t know how many people study the reports and compare their dioxin level with the reports.  I don’t know.

            S. LEFFINGWELL:  I was just wondering if that could affect things like a global assessment of well-being?

            J. MICHALEK:  That is a possibility, yes.  Good point.

            M. STOTO:  Okay.  Thank you very much.

 

Text Box: Review of Chapter 16:  Hematology



 

 

 


            M. STOTO:  Let’s move on to the hematology, Chapter 16.  Ron?

            R. TREWYN:  All right.  I don’t have these written up since I did the review in the airport yesterday, but have two — I will get them written up — two what I would consider significant issues with this.  And the one is with the introduction and my standard point since 1995 when I first got on here.  This is not a study of dioxin and so the background material, I really believe needs to be more broad and look at other herbicides, other types of species.

            I know there have been studies done on 2-4-D, for example, and there are toxicological studies related to, you know, cacodylic acid, which is a component of Agent Blue and whatnot.  So by having the mode of action and the epidemiology essentially focused exclusively on dioxin, I think misses a significant point that we need.  It needs to be a broader discussion of related chemicals that might be — might be out there, so that was — that was point one.  The other is the issue of ...

            M. STOTO:  Well, let’s talk about that one a little more.

            R. TREWYN:  Okay.

            J. MICHALEK:  That’s a major point ...

            M. STOTO:  Right.

            J. MICHALEK ... because that applies to all chapters.

            M. STOTO:  Right.

            J. MICHALEK:  And unfortunately, these chapter reviews, that’s a major piece of work.  They were — they were done by an outside subcontractor.

            W. GRUBBS:  They’re sitting over there.

            J. MICHALEK:  Okay, and they’re here with us today.  Fantastic.  All right.  So they know how much work this is and so I’m, you know, I have doubts that we’d be able to implement that suggestion in this report and stay on time.  That’s a major piece of work, I think.

            M. STOTO:  Let me — can I make two comments about it?  One is that you’re right, Ron, that this was set up as a study about occupational exposure being part of Ranch Hand.  And, but over time, I think the focus has shifted.  Whether we’d like it or not, I think it’s pretty clear that the focus has shifted in large part because of the — being able to make dioxin measurements and because of the literature has built up over time that suggests that dioxin really is the active component.

            The second point is that when I was involved with National Academy of Sciences review of this — that was admittedly a decade ago — we found very little information of the sort you were asking for about the effect of the herbicides per se.  So I’m not sure that even if we wanted to include that, there would be that much to say.  That may have changed, of course, in years.

            R. TREWYN:  Well, I would just, again, I think some of the findings that the assumptions point you made earlier about your presentation that many of the early assumptions, in fact, are proving not to be the correct assumptions.  And I think I — and clearly, I’m not saying take the dioxin stuff out.  I mean, that is — and I recognize that most of the data that’s out there that one is going to — going to find does relate to that, but I do know there have been studies.

            Like I say, I’ve seen studies on 2-4-D, cancer associations and various things, so I know there are some toxicological studies out there.  And clearly the stuff on cacodylic acid, I know there’ve been evaluations and that was the, you know, the active component in Agent Blue.  So, and again, if I was just — if I was just raising this for the first time in 2004, but I’ve done this a few times, so ...

            J. MICHALEK:  Yeah.  There are some things to say to amplify what you just said.  Remember that there’s a lag, a necessary lag between doing a report like this and doing research.  We had to put the statement of work in place a couple of years ago.  And this is a major contract with a — with a company to produce a big report, so we had to set this thing and fix it.  And you saw the statement of work a long time ago and you helped us review it.

            Since then to address your issue, we have reevaluated the tour data from the Ranch Hand cohort to enumerate the number of days — not that they were in the Ranch Hand unit — but the number of days they were there while there was spraying going on.  We know from the herbicides tapes that there were periods of time when the Ranch Hand unit wasn’t spraying at all.  They were shut down for a month, for example.

            So we’ve enumerated for each Ranch Hand the days spent spraying and we’re finding that covariate has meaningful — produces meaningful changes and results.  So we’re moving in the direction you suggest in the research side of our activity, but you’re not going to see it in this report.

            R. SILLS:  Can I ...

            M. STOTO:  The other thing that you might do is in the introduction, talk about the evolution of the study.

            J. MICHALEK:  Right.

            M. STOTO:  How it — how it’s gone from a Ranch Hand Study to a dioxin study, and why, and what the implications are and how.  That means that when you come to these substantive changes, you’ve focused on dioxin and so on.

            R. SILLS:  So Mike, I — you took the words out of mouth and that was my thought.  I thought the discussion that we just had about how the study’s evolved and the fact that the focus is on dioxin in the report, but I think also to capture the broader picture that was just recommended.  And, you know, you could just do a paragraph.  But in the introduction, it could set it up, set up the document so that it’s clear that, you know, other agents may be involved, but the focus is on dioxin.

            J. MICHALEK:  I think we have that; I was just reassured by Dr. Grubbs.  I think we may have that text already in Chapter 1.  We’ll have to check and see.

            R. TREWYN:  Well, one last point on this, I think clearly for publications that might come out utilizing this, you’re going to have to, I believe, be — use a broader introduction in anything that, for peer review publications, that would have to incorporate that.  And I recognize that, but I also feel obligated since I’ve been tilting at this windmill for a decade or close to it that I would keep doing a — keep doing it, so ...

            J. MICHALEK:  Thank you.

            R. TREWYN:  My pleasure.

            M. STOTO:  Okay.  Did you have other comments?

            R. TREWYN:  Then the other issue, and it gets to the other point of the in-country component in the comparison group.  I think clearly when you get those numbers so you can push the button and separate this out, a lot of what shows up here shows no difference, Ranch Hand to comparisons.  And I believe, again, that might be explainable — might — by the fact that the comparison group is a very mixed population and that the years in Southeast Asia, all those things need to come into play.

            My concern is that if some of the things in this chapter are predictive of some future events that might be coming, we might be missing things by not having that broken out here.  And so to have it that there’s, you know, that there’s no significant difference because I know things like sedimentation rate for certain things are, you know, can be an early indicator of some changes that are going to come up later, so ...

            J. MICHALEK:  Your point is well taken.  We have a paragraph in there explaining now the new analyses showing effects after adjustment for years in SEA and that covariate was not used in this report.

            M. STOTO:  So that’s on like page 3, that section there?

            J. MICHALEK:  The cancer chapter somewhere, yeah.

            M. STOTO:  Okay.

            J. MICHALEK:  Up front, yeah.

            M. STOTO:  But there’s — but there’s on page 3 here ...

            J. MICHALEK:  Oh, which chapter are you looking at?

            M. STOTO:  This is ...

            J. ROBINSON:  We’re still on the last one, hematology.

            J. MICHALEK:  Okay.

            M. STOTO:  Yeah.  Cardiology, Chapter 15, there’s a — there’s a section.  There’s a long paragraph in the middle of page 3, lines 223 to 240, that’s about the Ranch Hand Study and that I think it’s referring to things that have been published in the peer reviewed literature at that point.

            R. TREWYN:  You’re in a different chapter.  We’re still on ...

            J. MICHALEK:  Yeah.

            M. STOTO:  I’m sorry.  This is ...

            J. MICHALEK:  You moved to cardiology.

            R. TREWYN:  We’re in — we’re in 16.

            J. MICHALEK:  I thought we were still on ...

            M. STOTO:  Oh, I’m sorry, 16, yeah.  Oh, okay.  I’m ...

            J. MICHALEK:  You were — we were talking hematology.

            M. STOTO:  Yeah.

            J. MICHALEK:  Again, and there’s a lag going on here between this big report and our research papers.  We have not explored or looked, considered years in SEA, or time spent in Vietnam or number of days of spraying against hematological endpoints.

            M. STOTO:  Right.

            J. MICHALEK:  We’ve only considered cancer, and heart disease and diabetes, for example.  So it’s frustrating, I know.  We’ve got this report that was locked in — into a contract two years ago and we’re — and, you know, that’s the way it is.

            R. TREWYN:  I would say though at least having a sentence or two, you know, in each of the chapters that would relate that; that these things are coming.  Again, for people that are coming in and just picking up, they’re going to read, you know, their area of research is hematology, so they’re going to pick that chapter.  If you don’t have something in there in that chapter that alludes to that issue, then it’s going to be missed.  And I think that at least needs to be done, which is a sentence or two addition somewhere in this.  Okay.

            J. MICHALEK:  Good point.

            R. TREWYN:  And I just had one very minor thing and I’m just curious on 16-1, line 126.  I assume “the dosage and types of species” mean — “the type of species” means animal species?  I mean, you can have chemical species.  You can have a lot of different ...

            J. MICHALEK:  Yeah, it’s animal species.

            R. TREWYN:  Then that should just be stated.

            J. MICHALEK:  Okay.

            R. TREWYN:  And that’s basically it.

            M. STOTO:  Okay.  Thank you, Ron.

            J. ROBINSON:  Thank you, sir.

            M. STOTO:  Any other comments from the Committee on Chapter 16?  Okay.

Text Box: Review of Chapter 15:  Cardiovascular



 

 

 


            M. STOTO:  Let’s go on and talk about the cardiovascular chapter, Chapter 16.  Sandy?  I should say that Sandy stepped in at the last moment when — to do this review when I found out that Dr. Osei was not able to come, so thank you for that.

            S. LEFFINGWELL:  Chapter 15, again, the same whining complaint I made before.  This chapter is in pretty good shape and I don’t think I have anything that’s terribly earth-shaking to say about it.  In lines 398 to 401, give you a page in a moment.

            RECORDER:  What lines did you say, Dr. Leffingwell?

            S. LEFFINGWELL:  Say again?

            RECORDER:  What lines did you say?

            S. LEFFINGWELL:  398 to 401 and that should be page 15-7.  In discussing the ECG variables, the way they’re listed suggests that they are mutually exclusive, but doesn’t say that.  Bradycardia and tachycardia are sometimes considered disorders of rhythm, so I think it would be worthwhile inserting something about mutually exclusive categories to make that clearer.  Line 441 on the next page, 15-8 — hey, how’s this for trivial?  It says the vessel with the “strongest” signal.  Since there are only two vessels, it should be the “stronger” signal.

            Line 563 and following, Table 15-1, the same suggestion; that the abbreviations be put between the tables so that each part is clear.  Line following 615, it’s in Table 15-2 on page 15-16.  One of the variables is “Resting Pressure Index” about halfway down the page.  It — a quick chi-square suggests that there was a significant difference between the number excluded by Ranch Hand versus comparison or by categorized dioxin Ranch Hand versus comparison.  That’s not going to affect the actual analysis of those results.  They were robust enough and, you know, 0.05, about as close as you can get to it that it’s not going to change anything.  But I wondered if mentioning that would be worthwhile?

            Similarly in the bottom of the table, “Family History of Heart Disease Before Age 45,” there was a significant difference between the number excluded in both Ranch Hand and comparison in both “Group” and “Categorized Dioxin” columns.  And again, I don’t think there’s any consequence, any analysis that needs to be done looking for a confounding, but might note it in passing.

            Line 815, which would be — okay, that’s Table 15-3 on page 15-22 — and again, the same comment I made before.  If we could repeat the variable being analyzed in the subtitles, it would help a bit.  Leaping rapidly forward, page 15-86, Table 15-26, again, a kind of a small quibble on the titling of this.  This was abnormal posterior pulses that are being tabulated.  That is evident in Sub-table (a), but not in Sub-table (b); there is no “Abnormal” in the column headings there.

            J. MICHALEK:  That’s because that’s a table of adjusted relative risk.  The actual percent abnormal are given only in the unadjusted tables.

            S. LEFFINGWELL:  Yeah, and it’s still ...

            J. MICHALEK:  That’s throughout the whole report.

            S. LEFFINGWELL:  It’s still abnormal ...

            J. MICHALEK:  True.

            S. LEFFINGWELL:  ... tibial — posterior tibial, not presence or absence ...

            J. MICHALEK:  Oh, I get your point.  Yeah.

            S. LEFFINGWELL:  ... arm, leg index, anything like that.  And the discussion says there were several different abnormalities that would qualify as a score based on the way, form of the Doppler.  In fact ...

            J. MICHALEK:  So what’s your suggestion then?

            S. LEFFINGWELL:  Well, let’s see here.  “Abnormal tibial,” just mention it.  State as the group title, “Abnormal Tibial Pulses,” and then in the same thing where we’ve got normal versus abnormal mentioned in some tables and not others.  If we could mention that it’s “tibial pulse” that’s being looked at and “abnormal tibial pulse” in the sub-table headings, especially, you know, where the sub-tables go over several pages.

            The same general problem seemed to be true in tables beginning on line 2148 and 2198:  Tables 15-27 and 15-28.  Again, it’s abnormal peripheral pulses and if you can state that it’s “Abnormal Peripheral Pulses” in the individual subtitles.  Getting back to the references on line 2784, wondered about italicizing “(Callithrix jacchus)” again?  And on 2816, italicizing “(Orizias latipes);” 2819, this is not your problem.  It’s NLM’s and probably the original publication, but they’re talking about a cytochrome P5401A.  And I’ve heard about cytochrome P450, but I didn’t know we’d gotten up to P4501, much less subtype A.  And I suspect that needs to be typeset.  When I tried to ...

            J. MICHALEK:  No.  I think it really should be P4501A.

            S. LEFFINGWELL:  Yeah.  When I pulled that down from NLM just to see what it was in the original listing, they’ve got it this way in the title that they have posted there.

            J. MICHALEK:  Sounds like a typo.

            S. LEFFINGWELL:  It may be that it was printed that way.

            J. MICHALEK:  Yeah.  Right.

            S. LEFFINGWELL:  But I think maybe it would be nice to correct it for them even if they did make a mistake.

            J. MICHALEK:  Right.  Correct.

            S. LEFFINGWELL:  And back in tables, for F-7, I found it a little difficult reading the table because it’s hard to tell the rows apart.  In Table F-11, there has been an insertion of about a three- to six-point break between categories, which makes it scan much easier.  And I’m wondering if we could so the same for Table F-7?

            J. ROBINSON:  We will ask Dr. Grubbs if that’s possible.

            S. LEFFINGWELL:  And then lastly in column five in one of the tables there, there’s a — it needs to be a little wider to accommodate “ground crew.”  “Ground crew” wraps around to the next line.  Hey, talk about trivia.

            M. STOTO:  Okay.  Thank you.  I gave my hard copy of your comments to them.  And maybe, Kim, you can e-mail them as well?  Yeah.  Good.  Okay.  Any other comments from the Committee?  Robert?

            R. SILLS:  I thought this was a well written chapter also.  There were some minor comments that I wanted to bring up.  On page 15-1, the title says “Mode of Action” for 15.1.1.2.  But when I read that section, it’s really toxicological effects in animals and I really don’t see anything in there that really talks about mode of action.  So I suggest — a suggestion is just to modify that title.

            On page 15-2, I really liked the idea of comparing or — comparing or — the Ranch Hand Study or reference it — referencing it to like you’ve done in here with the International Agency for Research on Cancer, their findings; the National Institute of Occupational Safety and Health; the Dow Chemical findings.  All those findings, I thought were very helpful in terms of putting the studies in perspective.  So I commend you on that.

            Now in terms of the discussion, my philosophy in terms of discussions is I think a discussion should really — I don’t — I — what I want to say is the discussion should really deal with the findings in the study.  And so when I looked at the discussion section here, the first — the first three paragraphs were really about cardiovascular disorders, how you diagnose this and just background information.  And I thought maybe that the first three paragraphs could be put into — could be put into the background of the chapter.

            RECORDER:  What page is this on?

            R. SILLS:  This is page 15-112, -113.  Because there’s nothing, you know, there’s no discussions about data.  And so, and it’s until you get to probably line 2594 that you really start talking about the data.  And I think it would strengthen the chapter by just, you know, getting into the data.  You know, that’s just a suggestion.

            M. STOTO:  I wonder if that’s something that should be considered for all the chapters?  I don’t know whether this is the same issue as other ones.

            J. MICHALEK:  Actually, there’s a history to this as there is to everything else.  We added this several cycles ago to remind the reader of the strengths and weaknesses of the endpoints themselves and what do they mean.  And so that’s why we put them here in the discussion.  And it certainly makes sense to put them in the introduction too; I don’t know.

            R. SILLS:  So the point is, you know, I mean, it took me a long while to start reading about dioxin, about the findings of the study and it would really ...

            J. MICHALEK:  Maybe a little sub-header, leave them where they are, but just put a little sub-header, background information on the measurements themselves.  And then where it starts talking data, you could put a little sub-header that says “Findings.”

            R. SILLS:  Right, but I would prefer in the discussion that ...

            J. MICHALEK:  I understand.

            R. SILLS:  ... right away we start talking about the study.

            J. MICHALEK:  Yeah.

            R. SILLS:  I mean, no not taking, you know, three paragraphs or four paragraphs before you get into the meat of the study, which I think is the exciting data, which is the exciting data.

            J. ROBINSON:  Sir, if I could get a copy of your comments?  Excuse me.

            P. CAMACHO:  I have to ...

            S. LEFFINGWELL:  As a ...

            P. CAMACHO:  I ...

            M. STOTO:  Paul?

            P. CAMACHO:  ... want to side with him because I’m one of the guys a couple of years ago that said that as well.  I’m not — obviously, I’m a social scientist; I’m not familiar with any of this.  But if people looked at this, at least they’d have a clue.  And so if it was just marked like you said — background, what the findings mean, and then discussion of the findings and just two little blurbs there — that would be good.  And then have it — also stick it up front because who’s reading this ultimately and whether they get that?  I don’t know; that’s — I was one of the people two years ago who said a little refresher course wouldn’t be bad.

            R. SILLS:  So Paul, I’m supportive of having it in the document because I agree too.  When I read it, I said this is really good stuff on how, you know, issues surrounding assessment of the cardiovascular system.  But there’s — I think it would be better in the introduction and, you know, we could put a small section on it in the discussion.  But I like to get to the meat of data when I look at the discussion.

            R. TREWYN:  I would just add to Robert’s comments though that I think certainly in the literature that I would review in the discussion, you discuss the results.  But you put them in context of previously published so you don’t start off with everything bundled.  But many of those comments could be interwoven as they apply to the results of that — of that you’re talking about from the study.

            I think having, going back, it’s very common, certainly in the cancer field, that you’re going to see these things brought back up in the discussion.  But it’s only as they relate to the specific result that you’re getting to.  And so I think it’s just a matter of maybe of weaving them in; that you could have the three paragraphs in the background section and then pull those parts that make sense to interpret the results of the study.

            M. STOTO:  Sandy?

            S. LEFFINGWELL:  I think I’d kind of want to keep this in the section.  One of my concerns in the past has been the volume of the individual chapter.  There is no executive summary, per se, in it.  The discussion section comes close to functioning as an executive summary.  And I think if we paired this discussion out completely and left it just in the introduction, then we’d have nothing that served as an executive summary.  And I think for people going through this, it might be nice to have.

            M. STOTO:  Well, there is an executive summary in the overall document, correct?  We don’t have it here.

            R. TREWYN:  But not the chapter-by-chapter.

            S. LEFFINGWELL:  No, not chapter-by-chapter and I don’t know how this is going to be appear to be read by people when it’s ultimately completed.  Some of it, obviously, is being published in peer reviewed journals and I would assume there is a summary in that, but I just don’t know how this is coming out.

            P. CAMACHO:  The big picture.

            M. STOTO:  I mean, this is coming out in a very thick set of volumes and that — and that is kind of on a parallel track to the peer review publication.  And there is an executive summary that will be part of that volume.  So I guess, you know, one question is should some of this material be in that executive summary?  I mean, I think needs this ...

            S. LEFFINGWELL:  That also would be a legitimate question.

            J. MICHALEK:  Yeah.  The executive summary is in review right now by us and you’ll see that at the next meeting, I guess.

            M. STOTO:  Well, I think that there’s pros and cons on this.  And can we ask you to think about this and report back at the next meeting about this, not just with respect to this chapter, but as a general issue about how do you think is the best way to deal with that bearing in mind what you think the audience is for this?

            And I think — I think it’s an important question to raise and I’m not sure we’ve resolved it.  So I’m going to ask that you think about that and tell us how you think it should be done.  Is that reasonable?  Okay.  Thank you.  Do you have more, Robert?  Other comments?  Well, I propose that we take a break for about fifteen minutes, and come back at five minutes to 10:00 and continue.  Thank you, everyone.

[BREAK 9:40 A.M. - 9:55 A.M]

            M. STOTO:  Is everybody ready to start again?  Let’s get started again, everyone, please.  Julie, can we ask that Joel stay for another fifteen minutes?

            J. MICHALEK:  About thirty or forty.

            R. TREWYN:  Yeah, we’ll beat up on him.

            J. ROBINSON:  I have to — I have to check with Colonel Fox.

            M. STOTO:  Because we’re about to talk about the statistical analysis.

            J. ROBINSON:  Okay.

            M. STOTO:  Okay.  Let me — let me call this to order.  There are a number of people who have joined us.

            L. SCHECHTMAN:  Use the microphone.

            M. STOTO:  Thank you.  There are a number of people who have joined us since we started.  And for the record so we know who’s here, if you can ask them — bring the mike around — and ask them to ...

            J. PETRELLO:  Jackie Petrello with Exponent.

            K. MUNDT:  Kenneth Mundt with Environ.

            D. MUNDT:  Diane Mundt with Environ.

            R. WEIDMAN:  Rick Weidman, Vietnam Veterans of America.

            M. STOTO:  Is — yeah, but is there anyone else?  Were any of you intending to speak during the public comment period?  Okay.  Thank you.  We may end up doing that a little bit early, but you’re here.  So I want to give you a warning; I like to give warnings for the people who aren’t here, but I obviously can’t do that.  Okay.  Thank you.  Okay.  I’d like to ask Ron to take over as chair while I review the review for the next chapter.

 

Text Box: Review of Chapter 7:  Statistical Methods



 

 

 


            R. TREWYN:  All right.  So we’re going to now do statistical methods.  And who is responsible for that?  Oh, that’s ...

            M. STOTO:  It is — it is I.

            R. TREWYN:  Okay.  Thanks.

            M. STOTO:  I’d also like to thank Joel for being willing to stay a few minutes longer to talk about this.  This, I think, is really a difficult chapter because it prevents — it presents a lot of technical information and is designed for an audience that may not have the training in that field.  And I think that generally it does a good job.  It’s also complicated by the fact that it has to describe models that have developed over time for a variety of different reasons and that may not be the way that we would do it now if we were starting for scratch.  But there’s good reasons in terms of maintaining the continuity for all this, so again, I think that they’ve done — they’ve done a good job.

            I do have some issues I’d like to raise and I’ve got some editorial comments which I’ll just give you a copy of.  I think one of the points that needs to me — be made is that these models are the ones that have evolved over time and it’s important for historical reasons to keep them in here.  But exactly as I’ve said before, they may not be the ones we would have used now.  And there is this other set of publications in the peer review literature where you use different models for different purposes and for different reasons.  And I think that should — just should be mentioned at the — at the outset here as well.

            The other general point, like I think is that the summary tables that have been added to all the substantive chapters are new and I think a useful innovation, but they’re not really covered in the statistical methods chapter.  So there probably should be some discussion about the general scheme of doing that and how, you know, how that was done.  I had a number of problems with Section 7.2.  Well, let me just say — ask whether you want to respond to any of that before we go on to the next topic?

            J. MICHALEK:  Fine.  I’m ready to talk 7.2 if you want to.

            M. STOTO:  Okay.  I had a number of things about Section 7.2.2.1; this is page 3 — Chapter 7, page 3.  I wasn’t totally clear what this was about to begin with.  And I think part of it is because it may not be titled properly and because it probably brings stuff together from a variety of places that maybe the order isn’t as clear.  I think that probably this is, thinking about it, that the word “elimination” should be added to the title; that this is what we know about dioxin elimination ...

            J. MICHALEK:  Yeah.

            M. STOTO:  ... and the implications of that for the statistical models.  And I think that if you made that change and then you thought about reorganizing some of this material, that might make it clearer.  There’s also some stuff on lines 176 to 183, which is in the next section, in fact, on the next page, which I think belongs in this section as well.  I think it somehow just didn’t make the editorial transition.  And I think that the fundamental point is that you have measures of serum dioxin that were done in 1987 or later and you really want to know about how much dioxin people were exposed to a couple decades beforehand.

            And it’s almost clearly a good thing that we have these measures, but it’s not the same as knowing what they were at the time.  And that has all kinds of limitations and I think that the point of this section should be to make those things clear.  The other point here is that in various places, you make — you essentially make the assumption that if someone has less than 10 ppt measure of dioxin, that’s equivalent to 0 or background and I’ve complained about that in the past.  I don’t think ...

            J. MICHALEK:  But of course that’s not what we intended.  We just put them in a single category; that’s all.

            M. STOTO:  Well, I don’t think that you can change what you’ve done.

            J. MICHALEK:  Yeah.

            M. STOTO:  But I think you need to explain ...

            J. MICHALEK:  Right.  Good point.

            M. STOTO:  ... what you’ve done and this is the place to do that.

            RECORDER:  Dr. Stoto, “less than 10 ppt,” is that line 183 you’re referring to?

            M. STOTO:  No.  Well actually, that is — it is brought up there and that’s in — that’s the part that I said needs to move into this section and so there is a mention of that.  But I think that even beyond that, there’s some discussion that needs to be done.  Boy, you were pretty clever to catch that.

            J. MICHALEK:  I just want to mention that these notes that are being produced, these minutes are critical to us because we can’t keep up with you sometimes in writing notes down.  Well, you can.  Okay, but I’d still like to see the actual minutes of this meeting as soon as possible.

            M. STOTO:  Okay.  So we’ll — I mean, we’ll send it to you in draft.

            J. MICHALEK:  Draft would be great.

            M. STOTO:  Yeah.  Now the next set of comments I had have to do with the statistical models.  And I think that the underlying issue here is the one that already came up today; is that this study was essentially designed as a Ranch Hand occupational exposure study and over time, because of the ability to measure serum dioxin, has changed to some degree.  And the statistical models, Model 1 reflects the original design and the other models reflect, to varying degrees, the new capabilities that are there, but also still reflect the original design.  And I think sometimes the marrying of those two things is uncomfortable.

            J. MICHALEK:  Right.  The underlying assumption is that exposure to herbicides is proportional to the exposure to dioxin.  The higher the dioxin exposure, the higher the exposure to phenoxyherbicides.

            M. STOTO:  Well ...

            J. MICHALEK:  That is an assumption which we cannot measure or assess, but that has to be said in here somewhere.

            M. STOTO:  Well, that ...

            J. MICHALEK:  It’s not said already.

            M. STOTO:  Right.  Well, that’s one point.  That’s one point and I — but I think it’s more than that.  I think that there’s a lot of value in epidemiology of sticking, of keeping the analysis in sync with the design.  And the real value of Model 1 is that it does that.  And, of course, I mean, I — and when you talk about the advantages, I think that you ought to make that clear.  Of course, the disadvantages of that are that it doesn’t take into account this new information that we have.

            J. MICHALEK:  Right.  Potential mis-classification, for example.

            M. STOTO:  Right.  So I think that’s a point that needs to be said.  In Model 2 — Model 2 and I guess some of the other ones — you add BMI as a covariate, which I think is better than not doing it.  But given some of the things that we’ve seen in the peer review publications that you’ve done, it probably isn’t enough.  I mean, the relationship between obesity, and the dioxin elimination rate and the health outcomes that might have a relationship with obesity are very complicated.

            J. MICHALEK:  True.

            M. STOTO:  And at — and, you know, just throwing BMI in as a covariate is probably not adequate enough to do it.  It’s better to do it than to not to do it.  And I’m — and I guess at this stage, I’m not saying that you change these models, but I think that you should talk about the limitations of BMI and its ability to handle those issues.  In Table 7-2, this is the one that talks about the pros, and the advantages and disadvantages of Model 2.  You say at the very end this “does not account for dioxin exposure after SEA” — after Southeast Asia experience.  Well, in fact, that it actually does.

            J. MICHALEK:  Yeah, because that would inflate the dioxin level ...

            M. STOTO:  If someone ...

            J. MICHALEK:  ... and therefore, inflate the initial dose estimate.

            M. STOTO:  Right.  If someone had a job, you know, in 1985 that involved working with a lot of herbicides that had dioxin or worked in a factory and so on, in fact, he would have a higher dioxin level.

            J. MICHALEK:  Exactly right, yes.

            M. STOTO:  And this — and this actually, I think, is a fundamental point because when, you know, in Models 2, 3 and 4 to the extent that they’re talking about dioxin, I don’t understand why we don’t just talk about dioxin.  I mean, if this is — if someone happened to have ...

            J. MICHALEK:  Right.

            M. STOTO:  ... a big exposure to dioxin outside of Ranch Hand experience ...

            J. MICHALEK:  Yes.  Yes.  You put your finger on another issue that we’ve dealt with for many years.  People want — they want us to use the initial dose.  However bad it is, they want it — okay — and so that’s why we did the Model 2 and that’s why we did our cutpoint in Model 3 using the initial dose.  We know it’s only an estimate.  We don’t — we don’t know how good an estimate it is.

            However, we do know that if you — there’s a paper we co-authored with Seveso and we showed that it was not bad, you know.  It’s pretty good.  If you use the — compare the elimination curves of the adults from Seveso with the Ranch Hands, you see a pretty good pattern there.  So we have some confidence in that initial dose estimate.

            M. STOTO:  Well, I mean, at this stage, I’m not saying to change the models.  I don’t think that makes sense, but I do think you need to ...

            J. MICHALEK:  More comment.

            M. STOTO:  ... bring in stuff like this ...

            J. MICHALEK:  Okay.

            M. STOTO:  ... about them.

            J. MICHALEK:  Good.

            M. STOTO:  Model 3, you say here someplace, assumes that the “dioxin body burden has been eliminated with time.”  And I guess I’m not sure that’s true either.

            J. MICHALEK:  Model 3 assumes?

            M. STOTO:  I think that ...

            J. MICHALEK:  Where do you see that?  What page?

            M. STOTO:  I’m sorry.

            J. MICHALEK:  7-6.

            M. STOTO:  Let me see if I can ...

            J. MICHALEK:  Yeah, I see it.  It’s on page 7-6 in the big table there.

            M. STOTO:  Yeah.  Okay.  And I think that what this model assumes is that there’s a first-order elimination rate.

            J. MICHALEK:  That’s correct.  Yeah.

            M. STOTO:  And that — and that the parameter is either constant or varies in way that just adding BMI as a covariate fully adjusts for it.

            J. MICHALEK:  Good point.  Right.  First-order elimination, that’s true, and the dependence of that model on BMI in a predictable way; those are the assumptions ...

            M. STOTO:  Right.

            J. MICHALEK:  ... which, of course, may not be true.

            M. STOTO:  But I think that’s what needs to be said.  You also say that Model 3 may be “less dependent on the accuracy of the estimation algorithm for initial dioxin” because you put things into categories.

            J. MICHALEK:  Put them into bins, right, based on ...

            M. STOTO:  But I think you also should say that you actually lose power by taking continuous variables ...

            J. MICHALEK:  True.

            M. STOTO:  ... and treating it as a ...

            J. MICHALEK:  Yeah.

            M. STOTO:  ... as a ...

            J. MICHALEK:  A discrete.  You might have your best power having a continuous of what?  Do you know what?  What do you call it?  One degree of freedom parameter like a slow slope, true, and that’s a disadvantage.

            M. STOTO:  And then you also say in here about there’s a “prior belief that some Ranch Hands received large doses.”  I mean, I think that’s been documented, right?  That’s just ...

            J. MICHALEK:  Yes.

            M. STOTO:  That’s not just a belief.

            J. MICHALEK:  That’s supported by our interviewing the enlisted ground crew.

            M. STOTO:  Right.  I mean, that may have been a prior belief when the study was designed.

            J. MICHALEK:  Right.

            M. STOTO:  But it’s been shown to be ...

            J. MICHALEK:  Right, supported by the data.

            M. STOTO:  But I think that the biggest problem I have with Model 3 is that it confuses ...

            D. JOHNSON:  How has it been shown?  Excuse me.

            J. MICHALEK:  Well, we, in 1989, we questioned the enlisted Ranch Hand about their activities in Vietnam.  “Did you enter the spray tank?  Did you use it as a hand cleaner?  Did you get it on you clothes?  Did you get it on your face?  How much for how long?”

            M. STOTO:  But you’ve also measured dioxin.

            J. MICHALEK:  And we measured it.  We measured dioxin; then we measured their reported exposure.  And we found a strong association between their dioxin body burden and what they reported on the questionnaire.  And that was done blinded; we did not know their dioxin levels when they responded to that data or that questionnaire.  So that gives us some confidence that some of those people received very heavy doses indeed.

            M. STOTO:  The biggest problem I have with Model 3 is that it makes a distinction between the comparisons and the background category.  And I mean, it’s — and I think that we know now that there are some people in the comparison who actually had ...

            J. MICHALEK:  Yes.

            M. STOTO:  ... substantial amounts of dioxin.

            J. MICHALEK:  True.

            M. STOTO:  And it’s not true that everybody in the — well, that’s just the same.

            J. MICHALEK:  Well, yeah, you’re correct.  And some of those comparisons worked in industries in the United States where they received ...

            M. STOTO:  Yeah.

            J. MICHALEK:  ... doses.  And the comparisons themselves are experiencing approximate first-order elimination and that’s been published too.  So they’re having their own dioxin pharmacokinetics and their own associations between health and the dioxin.  So ...

            M. STOTO:  So again, I don’t ...

            J. MICHALEK:  ... it could be modified.

            M. STOTO:  I don’t think you can take this now out.

            J. MICHALEK:  No.

            M. STOTO:  But I think that it just should be discussed ...

            J. MICHALEK:  Right.

            M. STOTO:  ... as a — now Model 4, let’s see.  This is — this is page 8 and I’m at where you — where you have the definition of “ppt.”  I think you ought to — you need to say in there “for 1987.”  That’s the whole point.

            J. MICHALEK:  It’s — it was in ‘87 as a standard.  So if they had the result measured in ‘92 and if it was above 10, we extrapolated to ‘87 to put — sort of put everyone on the same ...

            M. STOTO:  Right.

            J. MICHALEK:  ... base footing there.

            M. STOTO:  So, but I think the point is that you need to say that it was either “measured in ‘87" or “measured and extrapolated ...”

            J. MICHALEK:  Yes, it needs to be said.

            M. STOTO:  “... to ‘87.”  That’s the whole point.  And then you also make the point that this measure “has less inherent variation than initial dioxin.”  It’s right there in “Advantages,” the first sentence.

            J. MICHALEK:  Yeah.

            M. STOTO:  I don’t think that’s true.

            J. MICHALEK:  No.

            M. STOTO:  It’s essentially the same information.

            J. MICHALEK:  It’s direct.

            M. STOTO:  Yeah.  Right.

            J. MICHALEK:  It’s direct.  It’s measured in today’s or in 1987 serum, whereas the initial dose is an estimate of what it should’ve been in Vietnam.  And we didn’t dosimetry in Vietnam; we had no measure of what was in Vietnam.

            M. STOTO:  I understand that, but there ...

            J. MICHALEK:  It needs to be said.

            M. STOTO:  But there really is no statistical difference between ...

            J. MICHALEK:  No.

            M. STOTO:  ... the measure in ‘87 and the measure in ...

            J. MICHALEK:  No.

            M. STOTO:  ... extrapolated back.

            J. MICHALEK:  It’s a — it’s a linear.  As you know, if you linearized the first-order model, you had a simple in your model.  Right.

            M. STOTO:  If you had, you know, a more complicated model where it wasn’t first order and you had more information, then this might be true.

            J. MICHALEK:  Yeah.  So we want to modify the sentence.  Which sentence now are we talking about?

            J. ROBINSON:  “Advantages,” the first point:  “Using 1987...”

            M. STOTO:  Yeah, it’s in the table, the first ...

            J. MICHALEK:  Yeah.

            M. STOTO:  ... thing under “Advantages.”

            J. MICHALEK:  Yeah.  So you — how would you suggest we edit that?  Do you have an idea?

            M. STOTO:  I just — I just thought — I think I’d take that point out.

            J. MICHALEK:  Okay.  I agree.

            M. STOTO:  Yeah.

            M. STOTO:  In Model 4, let’s see, on line 322, you just — actually, this is not specific about Model 4.  On line 322 and 323, you kind of throw out this thing about BMI being included, but without saying why.

            J. MICHALEK:  Mention the association with the first-order kinetic parameter ...

            M. STOTO:  Right.

            J. MICHALEK:  ... of the slow parameter.

            M. STOTO:  And hopefully, that’ll be now in the initial section that early should’ve been talked about.  You can refer back to that.

            J. MICHALEK:  Okay.

            M. STOTO:  In Section 7.5.5, you talk about the “clinical interpretation of discrete versus continuous data.”  And this is the situation where you have a — sometimes you find a significant difference that is not clinically significant.  And I think that one thing that you can say about that is that one possible interpretation is that there are clinical differences, clinically meaningful differences, in a subset of the population.

            J. MICHALEK:  That would cause a small shift in the meaning.  Right.  Right.

            M. STOTO:  So I think that’s a — that’s a point to make.

            J. MICHALEK:  That’s a good point.

            M. STOTO:  And I’ve got a couple of other minor things that I’ll just give you in writing.

            J. MICHALEK:  Okay.  Great.

            R. TREWYN:  Well, since I’m now chairing this section, let me ask if there are other members of the Committee that would like to comment or have points?

            S. LEFFINGWELL:  On page 7-3, line 139, in the formula for deriving parts per trillion, I don’t like the use of “ppq,” which implies parts per quadrillion, when in fact it’s just a measure of weight.  And I wonder if we might substitute some other term for ppq there and in the table on page 7-8, the fourth line of the table?

            M. STOTO:  I can — I actually had a more general thought about that.  I mean, “ppt” is also used as a variable, when in fact it really is a unit of measure.

            J. MICHALEK:  Right.  It’s really “picograms per gram lipid;” “ppq” is ‘femtograms.”  It’s a — it’s a — what do you call it?

            M. STOTO:  But the point is ...

            J. MICHALEK:  Wet weight.

            M. STOTO:  ... ppt is actually a measure of dioxin burden.

            J. MICHALEK:  In lipid, on a lipid basis.  Yeah.

            M. STOTO:  Yeah.  Right, but the real variable for both of those things is dioxin ...

            J. MICHALEK:  Yes.

            M. STOTO:  ... in different ways.  And that the ppt/ppq is actually just a unit rather than the name of the variable.

            S. LEFFINGWELL:  Well, except “ppq” ordinarily stands for “parts for quadrillion” and femtograms is not a part per quadrillion.  It’s a weight; it’s a single ...

            J. MICHALEK:  Okay.

            S. LEFFINGWELL:  ... class.

            J. MICHALEK:  There are two, in my view, two conflicting expressions of a unit for dioxin in the literature:  one is picogram per gram lipid and the other is ppt.  We tend to prefer picogram per gram lipid in our latest work although, again, this statement of work goes back two or three years ago and so we have this ppt in here.  And ppq is femtograms and ppq is in the literature.

            S. LEFFINGWELL:  It shouldn’t be.

            J. MICHALEK:  I know.

            S. LEFFINGWELL:  It’s a weight.  Its units are mass ...

            J. MICHALEK:  Okay.

            S. LEFFINGWELL:  ... not mass per mass ...

            J. MICHALEK:  I know.

            S. LEFFINGWELL:  ... or mass per volume.

            J. MICHALEK:  So what we really — what do you want us — do you think we should write in parenthesis, put “(ppt=picogram per gram lipid and ppq= ...”

            S. LEFFINGWELL:  I would actually get rid of ...

            J. MICHALEK:  “...femtogram-weight)?”

            S. LEFFINGWELL:  ... ppq in the formula.  And if you feel obliged to refer to previous errors in the literature, do it as a footnote.

            J. MICHALEK:  Okay.  One way is to replace ppq with a lowercase “w.”  Okay.

            S. LEFFINGWELL:  That would be fine.

            J. MICHALEK:  Lowercase “w” is the weight ...

            S. LEFFINGWELL:  That would be fine.

            J. MICHALEK:  ... the wet weight measured in femtograms.

            S. LEFFINGWELL:  I could live with that fine.

            J. MICHALEK:  Okay.

            S. LEFFINGWELL:  I still have trouble balancing the units with that, but I’ll take your word for it that it all works out.

            J. MICHALEK:  It does, yeah.

            R. TREWYN:  Other comments?  If not, I have to at least make one of mine.  On the Model 1, my standard issue of clearly the assumption is comparisons were unexposed and Ranch Hands were exposed, and again, with the new information of location that a significant number of comparisons were stationed in Vietnam.  Somehow, that — those issues need to be — need to be footnoted and outlined here in this section, I believe, so ...

            J. MICHALEK:  Good point.

            R. TREWYN:  And with that, I will turn the gavel back to ...

            M. STOTO:  Okay.  Well, thank you very much, Ron.  And thank you, Joel, for staying.

            J. MICHALEK:  Thank you.

            M. STOTO:  That was a — let me — let me pass over my comments and I’ll e-mail them too when I get back to the office.  Okay.

 

Text Box: Review of Chapter 5:  Study Selection and Participation



 

 

 


            M. STOTO:  We have one more chapter and let’s see who’s — Paul was reviewing Chapter 5.

            RECORDER:  Pull your mike up, Dr. Camacho.

            P. CAMACHO:  I only had a few things to — I — they were all basically questions.  Around line 64, “A veteran who was classified as hostile had refused to participate twice — passively or otherwise — was classified as ‘final refusal.’”  So my question was where’s the difference?  Was there a time-line here or was this automatic that they were thrown?  It seemed to me there were — then where’s the difference between hostile and final refusal?  There has to been some intermediate steps and that doesn’t seem apparent there.

            Ninety-six — “specified that noncompliant Comparisons would be replaced matching variables” or I marked that.  No, excuse me.  Oh, here I am down on 107ish, 105-107, how many replacements?  The question I had was how many replacements were there over the life of the study?  Did replacements have replacements?  That’s the kind of a weird question I had.  So here’s my — here’s my Ranch Hander.  I’m Paul Camacho teamed up with this Ranch Hander, but he falls out.  Paul Camacho has his replacement ...

            M. STOTO:  Why don’t you just stay in the seat there for a few minutes?

            P. CAMACHO:  ... Robert and then what happens when Robert gets replaced?  And is there — was there a rate of how long people lasted in this study?  Was there anybody who started in the beginning and finished at the end?

            W. GRUBBS:  Oh certainly.

            P. CAMACHO:  Yeah, I ...

            W. GRUBBS:  The numbers themselves are in Appendix ...

            P. CAMACHO:  C?

            W. GRUBBS:  Yeah.

            P. CAMACHO:  Okay.

            W. GRUBBS:  You can see that.  And answer your question whether a replacement was replaced with a replacement, technically the — as I understand — the original comparison may have been replaced.  Okay, but ...

            P. CAMACHO:  Okay.  My — then the replacement falls out?

            W. GRUBBS:  Yeah.  If ...

            P. CAMACHO:  He’s not replaced?

            W. GRUBBS:  Yeah.  If an original needs replacement with a replacement comparison and that replacement falls out, he’s not replaced.  The original may still need to be replaced, but not the replacement.

            P. CAMACHO:  Well, that — okay.  But the original is — was there somebody else who fills in?  But I — there’s another clone for Paul Camacho?

            W. GRUBBS:  Correct.  There’s a — there’s a ...

            P. CAMACHO:  That fit ...

            W. GRUBBS:  ... a group of eight ...

            P. CAMACHO:  That fits — that fits the categories ...

            W. GRUBBS:  Right.

            P. CAMACHO:  ... of the first clone?

            W. GRUBBS:  Right.

            P. CAMACHO:  Okay.  That isn’t said there and then I started to think that well, you had these Ranch Handers with no comparisons at all and that started to grow over the life of the study.  And then you’d have more Ranch Handers without replacements comparisons than not and you couldn’t tell that from looking at this.

            W. GRUBBS:  If the original comparison refused, he was attempted to be replaced either by the first replacement comparison or an additional one.  Is that correct, Jay?  Yeah.

            J. MINER:  There was great fear at the ...

            RECORDER:  Please go to a mike.

            J. MINER:  There was great fear at the start of the study that — exactly as Paul described — that the Ranch Handers would have a reason to come to the study, but that the replacements really wouldn’t have a reason to continue on.  So a replacement strategy was developed that used a group of up to eight, I think ...

            P. CAMACHO:  Ten.

            J. MINER:  ... or ten matched individuals to the Ranch Hander.  And then there is a very specific replacement algorithm that is part of the protocol, is part of the report.

            P. CAMACHO:  That ...

            RECORDER:  What’s your name, sir?

            J. MINER:  Judson Miner, M-I-N-E-R.

            P. CAMACHO:  That’s not in this.  In the paragraphs between 105 and 121, it’s not clear there.  It says — it’s not clear; that part is really just not clear.  I didn’t know that the original comparison was replaced by another replacement when his replacement dropped out.  You — he just said that now and I couldn’t — you wouldn’t get that from this section.

            W. GRUBBS:  Okay.

            J. MINER:  Sorry, one more comment.  Anybody that was ever invited to the study always gets invited back, so in fact, you might wind up with both the original comparison and his replacement.  But they’re always invited back.

            P. CAMACHO:  I guess then what I’m fooled by was — but the deceased original, he’s not being invited back.

            J. MINER:  And is not ...

            R. TREWYN:  He might be.

            J. MINER:  And is not replaced.

            W. GRUBBS:  And is not replaced.

            P. CAMACHO:  And is not replaced.

            J. MINER:  Right.

            P. CAMACHO:  So that still — does that, in fact, leave a Ranch Hander hanging without a comparison?

            W. GRUBBS:  There possibly could by design whereby the Ranch — the original comparison is deceased and doesn’t have a replacement comparison or one could not be found.  Everybody refused; that’s another situation where you wouldn’t have a replacement comparison.

            P. CAMACHO:  Yeah.  I didn’t get a sense of the numbers; that was basically my biggest issue with all of this.  It’s really not that clear, especially ...

            W. GRUBBS:  The replacement.

            P. CAMACHO:  To you guys, it’s very clear.  You’ve been working on this thing.  But if some researcher picked this up and just looked at it, they’d get confused.  They’d have to be confused.  Oh, and here the “self-perception,” I — on 129.  Really, I didn’t go page-by-page; I only had a few of them.  On — around 128 and 129, would asking “for their self-perception of health” — I mean, I probably should’ve ask this years ago when I first got on here.  Would asking this question alone create a bias?

            Did respondents — I mean, would it create a bias?  “What’s your health?”  Do I — what are my motivations?  If I’m in a — if I’m looking to get on medication, do I say, “Yeah, I’m sick?”  I’m looking to get somewhere else hoping, should I say I’m well?  I mean, did anyone think about that part of it, the bias of the answer that would come out?  I mean, when you ask people the self-perception answer, they usually have a kind of a motivation to say and it may not always be the truth so to speak.  But they know in their head is whether they’re sick, whether they’re well.  If I’m applying for insurance, I might not say I’m really sick.

            W. GRUBBS:  I don’t believe I could answer that question.  Dr. Miner might have some insight on it.

            M. STOTO:  Well, I think — I think the point ...

            W. GRUBBS:  The question though ...

            P. CAMACHO:  They’re getting it though.

            W. GRUBBS:  The point though is, is there a bias between Ranch Hands and comparisons on their ...

            P. CAMACHO:  The self-perception.

            W. GRUBBS:  ... them stating their health?  Yeah.

            M. STOTO:  I mean, you know, this was all done years ago, so you can’t change what you’re going to say.

            P. CAMACHO:  Yes.  I — you’re right.

            M. STOTO:  But I think that what you can do is say why you did this and what the potential problems — the benefit and problems.

            W. GRUBBS:  Again, due to the protocol.

            M. STOTO:  Yeah.

            W. GRUBBS:  Julie reminded me there is a flow chart in the statement of work.  It’s God awful to look at and to read, but it could be imported as an appendix table and you could see how complicated it is.  That’s a possibility and ...

            R. TREWYN:  Social scientists love those.

            P. CAMACHO:  Yeah.  Threw out the case.  Oh, and cases when the “no replacement” on 205 — when “no replacement was made if formerly invited Comparisons in a matched set were deceased,” et cetera, the case was not thrown out though.  Is that correct?  You didn’t throw that case out of the ...

            W. GRUBBS:  That’s correct.  The Ranch ...

            P. CAMACHO:  ... the file?

            W. GRUBBS:  The Ranch Hand was kept.

            P. CAMACHO:  He remained.

            W. GRUBBS:  Yeah.

            J. MINER:  Yeah.

            P. CAMACHO:  All right.  That should — I think that should be made — it’s not clear.  I would assume if I was — you get the sense, even though it’s not a matched pair study, you get that sense about the matched pairs business.  And he got thrown out, so I dropped the case if I was running SPSS, which is the academic thing.  Sure, I’m going to throw the case out.

            W. GRUBBS:  Dr. Stoto, you can probably comment on this.  The differences and advantages to a matched pair design where you take a Ranch Hand and comparison measurement and get a different ...

            P. CAMACHO:  Well, I’m not saying change the ...

            W. GRUBBS:  No.  No.  No.

            P. CAMACHO:  ... pattern and all that stuff.  I was just saying ...

            W. GRUBBS:  No, not at all.

            P. CAMACHO:  ... some people will jump on this and say, “Gee, didn’t they throw the case out?”

            W. GRUBBS:  Yeah.

            P. CAMACHO:  “Or should they or did they throw the case out?”

            W. GRUBBS:  Right, but there can be a debate as to how do you analyze these data?  Do you throw the case out?  I personally wouldn’t.  But to attack it as a matched pair  design, you’ve got to have the Ranch Hand.  You’ve got to have the comparison.  There’s differences here because you can have multiple comparisons for a Ranch Hand.  You can have Ranch Hands that have no comparisons, so yes.

            M. STOTO:  Well, I think — I think the issue here is not the pros and cons because you did what you did.  But the question is, is that discussed?  And I think it probably should be discussed in the statistical methods chapter.

            R. TREWYN:  Right.  Yes.

            P. CAMACHO:  It could be discussed or it could at least be noted here we didn’t throw the — we didn’t throw the case out.  I — I’m asking, you know, if I’m a reader and I hit line 205, I would come to the end of it and say, “Well, did they throw the case out or did they not?”  Otherwise, I’m going to be searching all the way through the mulberry bush and it’s always going to be in the back of my mind, “Is this table with cases or with the cases minus those guys?”

            M. STOTO:  Yeah.  I guess my recollection is that the ...

            P. CAMACHO:  They kept them.

            M. STOTO:  ... that they kept everybody for the analyses that are reported in this thing.  But maybe some of the peer review papers where they worry about the matching, that’s right.  Yeah.

            W. GRUBBS:  But here the Ranch Hands are kept, yeah, and a — and a simple sentence like that.

            P. CAMACHO:  A simple sentence helps it out ...

            W. GRUBBS:  Yeah.

            P. CAMACHO:  ... a lot better.  I think that’s — I think that’s really it.  I just started hacking through the tables.  Either I — or did I understand either — “Reasons for Refusal by Group,” all that came up.  And finally, I guess it popped into my head finally around 283 — entire — for refusal.  Now did people refuse for the entire length of the longitudinal study or they refused?  Is it clearly refused?  I refused in ‘80.  Then I got to the point — wait a minute — this guy refused in ‘87, but he came back in ‘95.

            W. GRUBBS:  That’s correct.

            P. CAMACHO:  So, you know, we’re figuring that in.  But how — maybe is there a distinction of what he refused two times?  I only refused once.  My data’s more — you know, there’s a confusion about the data here that’s ...

            W. GRUBBS:  The numbers you see in Table 5-3 are just for 2002.  To get an overall picture of refusal rates, you can look at Table 5-5 by study and different reasons.  There have been discussions between the Air Force and SAIC about doing a longitudinal compliance analysis after this report is in so, but that isn’t contained in this chapter.  This is dealing with 2002.

            P. CAMACHO:  Finally, there’s no real — it’s one thing to say a test is significant.  I’m — I guess I’m being picky at this point.  Now 319, 20, 21, 22 — “A test of association for refusal” — something significant.  Did it have a real meaning?  No, I can — it — I started to think of the angels on the head of the pin business, you know, or — and I said, “Wait a minute.  Well, this is significant that I have an angel on the head of this pin, but you know, this is really small potatoes in the whole picture.  And I don’t know whether I got started to say, “I wonder how many times this sort of issue pops in our head?”

            W. GRUBBS:  In writing this chapter, I was thinking the same way you were and I come to age is significant for a reason for refusal.  Well yeah, that makes sense in my head.  That’s, to me, at least obvious.  Race — well, is there significant or not?  If it were significant, why would it be?  Is there some underlying reason?

            P. CAMACHO:  Because you have these kind of numbers, right?  The size, just the numbers, things tend to turn up more significant.

            M. STOTO:  So that statement refers to some — what numbers in the table here?

            W. GRUBBS:  I think in general.

            P. CAMACHO:  Right.  In — yeah, in general about the — that’s what I was getting at, the “in general” idea, but ...

            W. GRUBBS:  For example though, first, the officer versus enlisted is there and inherent — dedication or duty.

            P. CAMACHO:  Yeah, the refusal, more officers were hostile — always.

            W. GRUBBS:  They — yeah.

            R. TREWYN:  That’s part of their nature.

            W. GRUBBS:  Say why is that so?

            P. CAMACHO:  Yeah.  Why is it?  What’s — and it — why is it really significant?  I mean, if it was significant that officers were hostile, but what does it really mean?

            W. GRUBBS:  Is it statistically significant?  Obviously, we can test that.  Is it practically important?

            P. CAMACHO:  Yes.  That — yeah.

            W. GRUBBS:  Yeah.

            P. CAMACHO:  That’s the point ...

            W. GRUBBS:  Yeah.

            P. CAMACHO:  I was trying to get at.  I mean ...

            M. STOTO:  Well ...

            P. CAMACHO:  ... if I’m under the command and the officer’s, she’s hostile, I guess I’m in trouble, but I don’t wander in.

            M. STOTO:  It seems to — it seems to me that what you’ve done is you’ve given us the numbers in the table and you’ve reported whether it was statistically significant.  And the reader can make his or her own judgment ...

            P. CAMACHO:  His judgment.

            M. STOTO:  ... about whether or not he thinks that ...

            P. CAMACHO:  Okay.

            M. STOTO:  ... they think that that’s meaningful.  I mean, I don’t know if you can do any more than that.

            P. CAMACHO:  Yeah.  Yeah.  I think then that I just was, I guess, having a little fun at the end about those hostile officers.  But that — but the piece about — the piece about refusals is, and the replacements, I think is worth giving a tad of explanation to or even the one sentence here and there.  I’m not — that would be it.  And was a — yeah, getting back to my hostility, “87 hostility versus 92 hostility,” if this is really what we’re measuring.  So I didn’t catch about the significance of it, that’s why.  And throughout the study, if every point is, you know, you make every piece significant, does it have real meaning and basis?

            W. GRUBBS:  Regarding the hostility issue, to me it’s final refusal, of course, but it’s a classification as to how they became final refusal.  Did you call them up and they say, “No, I don’t want to go.  I’m sick.  I can’t go?”  Did you call them up and they say, “I’m going to get my lawyer on you?”  Or did you call them up and get their answering machine, they never called back?  It’s just a classification.

            P. CAMACHO:  So was the replacement stuff ...

            M. STOTO:  I mean, it seems to me that the reason for having this is that when you have a, you know, an analysis of X some place later and someone says, “Well, that may just be because you had more refusals of some sort than others.”  And oftentimes, you know, in a study, there’s no way of telling that.  But here, you can — you can then go back to this chapter and then see, you know, is that a plausible explanation.  And, you know, it may be — if the outcome is a psychological outcome, you may think that the hostility was relevant in that way and so on.  So, I mean, I think that this is an important table to have.

            P. CAMACHO:  I’m not arguing about any of the importance of — I’m not arguing about any of the importance of the table.  It was just about who — about the dropout rates and about the — and about that issue and the replacement.  Did the original is being replaced by a second clone?

            M. STOTO:  Okay.  Thank you, Paul.  Any other comments from Committee members?  Okay.  Well, thanks.

 

Text Box: RHAC Business



 

 

 


            M. STOTO:  We’ve got a couple more things on the agenda.  One is the public comments, which we’ll have earlier than originally planned.  But before we do that, I’d like to talk about the assignments for next time and the list I have is the one that I sent out in my e-mail a couple of weeks ago.  I don’t know who — if we have a hard copy of that.  But I have is Chapter 10, neoplasia — cancer, I guess, right?  So let me — let me say these and then I’ll ask for volunteers.  But I’ll give you the whole menu before so you can decide which ones you want to volunteer for.  Chapter 10 is neoplasia or cancer; Chapter 11 is neurology; Chapter 13 is gastrointestinal, used to be hepatic.

            W. GRUBBS:  It’s back to hepatic.

            M. STOTO:  It’s hepatic again?  Okay.  What will it be?  Chapter 14 is dermatology; Chapter 18 is endocrine; Chapter 20 is pulmonary; and Chapter 1 is conclusions and the executive summary — 21; I’m sorry.  And we have all the Committee members, but one — Dr. Osei — here.  And I don’t know what his — he’s on medical leave.  I don’t know whether he’s — how likely he is to be here in November.  So I — let’s not assign him a chapter and if we — if he does come, we could make something with him.  Okay.

            J. ROBINSON:  Well, and I would almost recommend that all Committee members review the conclusions and executive summary.

            M. STOTO:  Right.

            J. ROBINSON:  So that would — everyone would have that.

            M. STOTO:  I think that that’s true.  Yeah.

            RECORDER:  I’m sorry.  Was that Dr. Camacho for Chapter 21?

            P. CAMACHO:  Well, that’s ...

            M. STOTO:  Yeah.

            L. SCHECHTMAN:  Everybody.

            P. CAMACHO:  Well, yeah.

            M. STOTO:  Well, I’m going to — I’m going to ask that Dr. Camacho be the lead for that, but everyone take a look at it as well.  Okay.

            R. TREWYN:  Neoplasia — I’m going to beat Robert to it.

            R. SILLS:  Neurology.

            M. STOTO:  Okay.

            P. CAMACHO:  Dermatology is Dr. Johnson.

            RECORDER:  Dermatology is Dr. Johnson; Dr. Hassoun is gastrointestinal.

            M. STOTO:  Okay.  Now we have endocrine and pulmonary left by my — is anyone willing to do another one?

            S. LEFFINGWELL:  Whatever is left over.

            M. STOTO:  Okay.  Do we have some sense of which of these things are the longest, which are the shortest?

            J. ROBINSON:  Endocrine’s the longest.

            M. STOTO:  Endocrine’s the longest, okay, so I’m going to ask that Dr. Sandy to do that one.  And pulmonary because pulmonary’s going to be a double-up, doubling up for somebody.  Ron?

            J. ROBINSON:  I think dermatology and pulmonary could be put together would be my suggestion.

            R. TREWYN:  Okay.  Good solution.

            M. STOTO:  And since you didn’t do one this time, I think it’s fair to ask you to do two next time.  We’ll do that.  Okay.

            R. TREWYN:  Eight hundred and twelve pages.

            RECORDER:  Dr. Johnson, you’re doing pulmonary and you’re also doing dermatology?

            M. STOTO:  Okay.  And if we learn that Dr. Osei is going to be here, we’ll give one to him.

            D. JOHNSON:  If he’s going to be here, he can take dermatology since I asked for pulmonary first.

            M. STOTO:  Okay, that’s fine.  Okay, and I think these have all been already been sent out before, but may ...

            L. SCHECHTMAN:  No.

            M. STOTO:  No?

            L. SCHECHTMAN:  No.

            M. STOTO:  Okay.  So you’ll take care of sending them to the relevant people?

            L. SCHECHTMAN:  As long as she does that.

            J. ROBINSON:  I have three that can be sent out to you, which are endocrine, pulmonary and — you actually have endocrine already — pulmonary, neurology and gastrointestinal.  And we’re in the final throes of dermatology, and neoplasia, and the conclusions and the executive summary.

            D. JOHNSON:  Is this for the November meeting?

            M. STOTO:  November meeting, yeah.  And the meeting will be November — what date?

            P. CAMACHO:  19th ...

            M. STOTO:  19th?

            P. CAMACHO:  ... which is a Friday, which is nice.

            M. STOTO:  Okay.  So once you send them to the Committee staff and they’ll make sure they go out to the right people.  Maybe if you guys can prepare an e-mail about who’s going to do what?  Okay, and probably should — and with the idea that Chapter 21 goes to everybody and probably I should get a copy of everything.  Does anyone want more than the — than the ones they’re doing ...

            R. TREWYN:  This guy.

            M. STOTO:  ... just to — just to have them?

            P. CAMACHO:  Oh yeah, I’ll take the set.

            M. STOTO:  Okay.

            R. SILLS:  Good idea.

            R. TREWYN:  Yeah.  Yeah.  That’s fine.  Yeah.

            M. STOTO:  Okay.  So we should send everything to everybody ...

            RHAC:  Right.  Yeah.

            M. STOTO:  ... but make clear who is the primary?

            RHAC:  Right.

            M. STOTO:  Yeah.

            R. TREWYN:  That works.

            R. SILLS:  That’s helpful.

            M. STOTO:  Okay.  Yeah, and one of the — one of the jobs, I think, for reviewing the executive summary is making sure that it’s consistent with the chapter that it summarizes and so ...

            P. CAMACHO:  We might as well read the whole book.

            M. STOTO:  ... and so that’ll be the primary, you know, so whoever, you know, does dermatology should also take responsibility for looking at the dermatology section of the ...

            J. ROBINSON:  Conclusions and the executive summary.

            M. STOTO:  Yeah.  Okay.  Go ahead.

            L. SCHECHTMAN:  Just a question for everyone.  Was it useful to have us provide you with the chapters or is that unnecessary?  Do you prefer to lug the chapters from home or ...

            R. TREWYN:  No, having them here.

            L. SCHECHTMAN:  ... having them here?

            R. TREWYN:  Having them here is helpful.

            L. SCHECHTMAN:  Is good?  Okay.  Okay.

            R. TREWYN:  And we bring the ones we — the primary reviewed.

            L. SCHECHTMAN:  Okay, very good.  Thanks.

            R. SILLS:  Just to clarify, so the meeting, the next meeting is November 19th, Friday?  Good.  Thanks.

            L. SCHECHTMAN:  So the travel will be on the 18th and we’ll try and finish up in a manner that allows you to leave on the 19th so you can be home for the weekend.  If not, we’ll let you know.

            M. STOTO:  That’s not Thanksgiving week or anything?

            R. TREWYN:  And Friday night flights out of Washington are generally a mess, so if we can get done early, scheduling with earlier would help.

            M. STOTO:  So it’s probably important to make arrangements if you could — if you guys could get the information out.

            L. SCHECHTMAN:  Yeah.  Right.  Well, we’ll — okay — we’ll take care of that.  We’ll get a jump on it so that we can get flight reservations for you and hotel bookings as soon as we can using the same system that we’ve used before through our office.

            M. STOTO:  And the meeting will be here?

            L. SCHECHTMAN:  Well, we’re trying to get this room.  You know, CDER has first preference for the room and whenever we can squeeze in here, we do.  If not, we’ll have a room in the other — in headquarters Parklawn Building.

            R. SILLS:  I just want to make one point.  Len, you and your staff, especially Kim, have been really good in terms of getting us the materials on time and keeping track with things.  I had to change my travel arrangements today; Kim did an awesome job.  So thanks to you and your staff for keeping everything going and making sure that we’re all taken care of.

            L. SCHECHTMAN:  Thank you.

            R. TREWYN:  And I would just throw out too that the DoubleTree is orders of magnitude better than the one across the street.

            M. STOTO:  Well, thank you for making those comments.  I mean, I — since I come on the Metro, I don’t — I’m not aware of these things.  So okay, any other administrative items of that — of that sort?  Okay.

 

 

Text Box: Public Comment Period


 

 

 


            M. STOTO:  So let’s go to the open session now.  Would you like to comment — make comments?

            R. WEIDMAN:  I can come up there?

            M. STOTO:  Oh yes.  How about if he — can he sit at the — at the table over there?

            R. TREWYN:  Or go to the podium.

            M. STOTO:  Either one.

            R. TREWYN:  I’d make it as tough on him as possible.  You know, let’s just — right, Rick?

            M. STOTO:  Rick, if you would just remind us who you are?

            R. WEIDMAN:  My name is Rick Weidman and I’m Director of Government Relations for Vietnam Veterans of America.  And I’m used to hostile officers, so the method of addressing you is immaterial.  From the point of view of those of us who are former enlisted men, most officers, by the way, are hostile and to one degree or another.  First of all, I want to thank each one of you on behalf of Vietnam Veterans of America and our national president, Tom Corey, for serving on this Committee.  You take a lot of heat simply from some quarters and it doesn’t do, frankly, those of you in academia a heck of a lot to advance your career to sit on this Committee and we’re grateful for your taking the time to do so.

            Having said that, VVA has looked at this, has been involved in one way or another with the Ranch Hand Study for 25 years, I guess.  As looking at, reviewing pictures the other day as we were cleaning out the basement, it reminded me that I had all my hair when this study started and none of it was gray.  And I think that’s true of perhaps others in this room, and yet, we are not much closer to finding the kinds of answers that we set out to find in the first place.

            It is useful to remember the historical perspective on this.  The reason why the Ranch Handers were chosen as the study group was because the Department of Defense and the VA claimed that they had no evidence that anybody else was exposed to any of the herbicides.  And that’s useful to bear in mind because we know that now not to be true by a whole heck of a long shot.  In fact, one can argue that those who served on the ground were much more exposed certainly than those who sat in the front of the aircraft that actually did the spraying operations on Ranch Hand; that’s one.

            Two is that those — that there is even a certain theory that bears some consideration; that those who served in the rear-most areas, such as Cam Ranh Bay and Long Bien, where anything that was green got zapped with an herbicide and the particulates which then became part of the dust and wind, and people inhaled, got on your food, got in your — anything you drank, et cetera, got on your hands.  And when you sweated and wiped your face, you ended up eating it; that this was an exposure that was hard to measure, but it also depended exactly how much you were outside, frankly.

            So there’s a lot of — a lot of things that have changed since the very start.  So the question is — and I was pleased to read the September 2nd memo, Mr. Chairman, that you forwarded to Secretary Principi for a variety of reasons.  We’ve discussed it in the VVA leadership, and our Agent Orange Committee and Healthcare Committee and prior to this meeting.  And there are so many problems that we see methodologically that while much of the data and many of the samples, in fact, will prove to be useful to ultimately what questions may be answered in the future.

            This was started as a herbicide study.  The most eloquent expression of why that is important to bear in mind was given by one of your members in testimony in the year 2000 before Chairman Chris Shays of Connecticut on the Oversight and Investigation Committee dealing with VA, DoD and National Security, the Government Reform Committee of the House of Representatives, when he said, “We have been looking as to whether or not there was harm done by one particular species of beetle bark boring into a particular tree and looking at that so hard that we have not looked around and realized that the forest has died all around us.”

            And that’s why this can’t be anything that is ultimately useful.  In terms of overall answers for Vietnam veterans and their families, cannot be limited to dioxin and the other confounders are useful and necessary to look at.  The Institute of Medicine of the National Academy of Sciences took that into account, not on their latest biannual review that was released a year ago, but the previous one when they accepted a body of material that was given to them by representatives of VVA and decided to consider it in terms of studies done by the Japanese and by others on the effects of PCBs.

            And those of you who deal with molecular know that at the sub-molecular level, PCBs work exactly the same as a dioxin in terms of their effect on the body and the long-term health of the overall organism.  As you move forward and try and make this report as useful as possible, we believe that there are a number of things that even now need to be examined.  One is the assumption that ten points — part per trillion is — anything below that is not harmful.  In fact, we don’t know that.  There is no scientific basis for saying — that is credible — to say that eight is not harmful and ten is.  That’s just one example.

            It is not only a dioxin study.  It is — we have to look at confounders, and we have to look at participants and other kinds of problems that you’re up against.  And without examining and comparing all of those other confounders against a null hypothesis, there is no reason to assume nor is there any, to our knowledge anyway, compelling body of knowledge that has been — has been enumerated either by this body or by the various committees of the Institute of Medicine of the National Academy of Sciences that would say the null hypothesis stands up on all of these other factors.  Because we don’t believe that that is correct and if we’re wrong, we would — we would be delighted to hear back from those of you as individuals or as a body.

            Next major problem that we’ve seen from the start is that there’s no non-veteran cohort group.  Finally, there is some measurement of Southeast Asia time, but we do not know — and nor does anyone in this room nor anybody to our knowledge period — whether or not merely having served in the military during Vietnam, in and of itself, that something happened to individuals either through immunizations or some other method of exposure that makes a difference with their non-veteran peers.  We simply don’t know that.

            And without that third group of the non-veteran cohort group — non-in-country Vietnam veterans, in other words, those who served in the Air Force and had similar duty, but never served in Southeast Asia — and then compare that with those who served in Southeast Asia, and last, but by no means least, the fourth group and the — is the primary group of those who served on Ranch Hand.  If you have those four groups, then you have some shot at telling whether or not the first, those last two groups — those who served in country and those who served on Ranch Hand — whether or not there’s a difference in the health, overall health effects between those and Air Force personnel who did not serve in Vietnam and their non-veteran peers who never entered the military whatsoever.

            And so the whole issue of hostile versus non-compliant, and replacements and replacements of replacements, and replacements of replacements of replacements or whatever the case may be, those are all potential confounders that may or may or not be relevant to the overall validity of the study.  But the question is whether or not the study should be continued and in its current form.  And we think there’s serious questions about that and that’s not because of the talent nor the dedication of either the staff of the — of the Ranch Hand Study, or of the Air Force or of the contractors who have done much fine work within the parameters of the contract that has been drawn for their particular segment of the overall work.  But it is because of many of the things that I’ve mentioned thus far.

            Number one and number two — one thing that is absolutely essential for this work, and the reason why the Congress authorized it and then appropriated funds for it is that Vietnam veterans and their families, the veterans community in general and the American public in general have confidence that this has contributed materially to the answers that have been raised and that are continuing to be there about the health of Vietnam veterans and their families, and whether or not there was significant harm done by virtue of service to their country in Southeast Asia and exposure to these herbicides.

            And it — it’s a balance point there.  Can we spend another $180 million to better affect?  Some of us, the answer is, “Yes, we can spend it to better affect.”  So then the question comes back to, Mr. Chairman, your letter to the Secretary.  In your third paragraph which is, “The Air Force’s funding for the study is due to expire in the recent future.”  We presume you mean “near future.”

            M. STOTO:  Did I say that?  Sorry.

            R. WEIDMAN:  “Without funding, the biological samples will be lost.  The data gathered will be inaccessible to researchers and the investments that thousands of veterans have made of their time will be squandered.”  That is only assuming that the data is not transferred as VVA has taken the position that it should be.  Both the data and the samples transferred to the custody of the National Institute for Environmental Health Sciences and be — and the data — and made available to legitimate researchers and research institutions throughout this country.

            We believe it to be a significant and erroneous action to first make the data public and now “having taken it private again” — to borrow a term from Wall Street — is inappropriate.  And that data needs to be accessible.  If we need to file FOIA, if we need to go to court, we’ll get it open because privacy concerns can be met and still make that available for further scientific inquiry and further scientific mining, if you will, of that data and of those — of those samples that have yet to be — that have yet to be tested and that — and added to that significant — to that significant database.

            It belongs to the American public; the American people paid for it.  And the American people paid for it with the motivation and clear intent of the Congress that it contribute to bringing the answers to Vietnam veterans and their families about the deleterious health effects that may or may not be due to people’s service in Vietnam.

            And therefore it is, by its very nature, a covenant that it be made public, and made available, and that research that is privately conducted — privately conducted, but publicly funded by reputable research institutions through NOFAs, not just RFPs, but NOFAs, so that people can design studies, would be of useful design, come in and test those out, and further mine this data.  And we believe that that is absolutely essential.  And we’ll be working with our friends on the Hill to accomplish that end in the future to make sure that it is publicly available and that there is a successor study of some studies.

            I would also bring to the — to your attention that there is pending a — the whole issue of the National Vietnam Veterans longitudinal study which the contract with IOM has not been consummated for what to do with this data to complete the actions required under Public Law 108-183 in regard to the Ranch Hand Study.  But there’s a report for the National Vietnam Veterans longitudinal study is due to be released and given to the Congress next year.  And currently, not only is it not ready, there is not currently a contract in effect.

            We hold the VA accountable for both of those actions and there is absolutely zero excuse except it’s either one of two things:  either deliberate mendacity or its breathtaking incompetence and there is virtually neither one a judgment that it — one could make on the lack of follow-through and completion of either of those very clear, very straightforward actions that were clearly mandated by the Congress.

            So I wanted to, on our behalf of VVA, to share some of these thoughts, and intentions and judgments with you, and to once again extend to you our thanks for your service on this Committee individually and for those of your predecessors who have tried to do the best they can, and of all the many fine people who have participated in various aspects of the study.  But it has gone awry and it is time to move on in a new context with a new wine skin and new wine, but not throw out the old, but make it available some place else and to put our public resources where we’re going to have more bang for the buck and more yield on the original intention of the will of the people as expressed through the statutes governing this and future research.

            And Mr. Chairman, I’d be happy to answer any questions you or your colleagues may have.  And on behalf of VVA and our national president, Tom Corey, I wish to thank you for the opportunity to make some comments here today.

            M. STOTO:  Well, thanks, Rick.  Let me — let me respond.  First of all, thanks for coming today.  We do appreciate that you do that.  Second, I think it’s important that you made a distinction between whether or not the study should continue.  I think you meant in the sense of gathering new data versus maintaining the information and the samples that — making them available — that currently exist.

            And I’m not sure that we agree as a Committee on the — on the value of extending in the — in the first sense, but that really is not our charter.  But I think that we certainly all agree about the value of the information that’s already been in this — in the material that’s already been gathered and the importance of making that available to legitimate researchers as you were saying.

            R. WEIDMAN:  Did you want me to clarify that, sir?

            M. STOTO:  No.  No.

            R. WEIDMAN:  Okay.

            M. STOTO:  No.  The — I just want to emphasize that we agree with you, at least on the second part, which is that the part that’s within our, I think, within our charter.  The second thing I wanted to say is that — and I said a little bit about this early before you came — that we’re kind of in a funny position.  We advise the Secretary of Health and Human Services and who — and this really is an issue that the Air Force, and even more so now, the Department of Veterans Affairs have the main play in.

            And so I tried to — that letter that may have had grammatical problems was intended to do the best that we could to raise the issue that the Department has not fulfilled its obligations under the law.  And I think that’s the point.  I mean, I — we did that in the context of inviting him to — Dr. — Mr. Principi to send a representative to this meeting.  But the point of that letter, and I’ll be clear about this for the record, was to make it clear that as far as we can tell, the Department was not fulfilling its responsibilities.  So we’re glad that you took note of that.

            And to the extent that we’re concerned about the value of this information that may be lost, we hope that you are able to push this issue further as you seem to want to do.  So I think that the Committee is very much in sync with that.  Okay.  Sandy?

            S. LEFFINGWELL:  The concept of a referent population in the general population as opposed to service people is certainly a — would certainly be a valuable thing if it could be done.  I think that would be a daunting task even if Congress elected to try to fund some future study.  So it may well be that the best hope for that would be to find a repository where the data could be used perhaps for studies in the civilian population.  And this data set might be one referent population for those.

            Quality of the study — this was a very well done study and whether it would be done as well in future studies is a little bit problematic.  That’s certainly an interesting concept, and again, we would appreciate your efforts in making sure that the data are not lost and ...

            M. STOTO:  Ron?

            R. TREWYN:  I just wanted to mention that at least with regard to cancer, there is the effort and some of the publications that are in the works.  It’s not necessarily designed into this study, but they really are looking at the general cancer prevalence in the civilian population and whatnot to do comparisons and are finding significant differences.  So again, I would, you know, compliment the study group on their willingness and interest in taking this as far as they can, utilizing this data for the peer review publications that they’ve got in the works that can really, at least, start to raise some of those questions and get to — get to some of these issues in perhaps some of the most important areas.

            And I think there are then opportunities in a variety of other areas:  cardiovascular and a whole host of others to do the same sorts of things.  And again, I think as long as we’re all pulling in the right direction here.  There were limitations on how this particular study was designed.  There were the limitations in the power that this group had or, in fact, did not have in throughout its history in what we — what this group could do as far as study design and whatnot.

            We were advisory.  We’re given very little clout to make many changes and a lot of that though came out of, I think, the original legislative effort.  So we certainly recognize there are issues.  And again, as long as everybody’s looking for the right direction to move, I think that’s very helpful.

            R. WEIDMAN:  Mr. Chairman, if I could just respond if I may to Dr. — is it Leffingwell, sir?  The research design of the three — of the three elements, minimum three elements — non-veterans; those who served in the military, but not in Southeast Asia; and those who served in Southeast Asia — is not original with us.  That was the original design of the Vietnam Veterans Readjustment Study or National Study of the Vietnam Generation, which was done by Research Triangle Institute, and which at that time concentrated primarily on psychosocial judgment — speak much, apparently not and not very well — on readjustment, psychosocial readjustment of Vietnam veterans, versus those who served in country, versus those who served in the military, versus the non-veteran peers.

            The longitudinal study, while they did self-report healthcare information at the time in the mid-‘80s on the NVVRS as we call it or the RTI study, this time what we want is a — is a complete health study.  And if the individual has died, review of the medical records in order to verify and hang on that some empirical evidence that self-reporting and find out whether or not it was reasonably accurate.

            And so then we will have the closest we’re going to get to a longitudinal study.  The IOM, for the last five reports — both special and biannual — we’ve asked the question to the chair every single time:  “Do you have enough science?”  And the reply has been exactly the same every time:  “We have enough science, we think.  We could always use more.  But what we do not have is a long-term epidemiological study of Vietnam veterans and their families in order to make — to do the kind of job which we want to do and which we believe that veterans and the citizens deserve.”

            M. STOTO:  Okay.  Thank you.  Joel would like to make a couple of remarks in response.

            J. MICHALEK:  Your points were well taken.  I just want to point out that the concept of more than one control group and which control group to choose was considered in 1975 and 1976 when the study was conceived.  We were originally considering a control group of Air Force personnel stationed in Europe and also control groups who we have today who are stationed in Southeast Asia.

            So all of the issues you mentioned around the table and they were discussed many times in 19 — between 1976 and 1980 by ourselves and our peer review panel of the National Academy of Sciences, and in the Armed Forces Epidemiological Board and the University of Texas Scientific Advisory Board.  This was a very painful discussion because obviously, we had a budget limitation.  The study would be three times as big if we had, you know, multiple times larger if we were able to get what we would’ve really wanted, which was multiple control groups.

            We realized we could only have one control group and we also realized that yes indeed, there may have been exposures in Southeast Asia by itself regardless of Agent Orange.  And that’s why the final decision was made to choose the control population we have today, which are those stationed in Southeast Asia.  And every point you’ve made is well taken, the technical points you’ve made.  I guess that’s all I had.

            M. STOTO:  Okay.  Thank you.  I mean, you know, we have to bear in mind that our job is to be an advisory panel on the study that exists and, you know, what should’ve been done is an interesting question.  What might be done is still — I mean, it’s still possible to do some of these things.  And I think it’s important that organizations like the VVA and — is continuing to raise those issues, but it’s fundamentally not a job of our Committee to resolve those.

            R. WEIDMAN:  Mr. Chairman, may I make just one point for the record?

            M. STOTO:  Sure.

            R. WEIDMAN:  When I said it was my criticism of the VA was not of the particular sector.  I think he’s getting — I think he’s getting bad advice and poor service from certain elements within the Veterans Health Administration, so we continue to have confidence in this Secretary.  We do not have confidence in the people who are not serving either he nor the veterans they’re sworn to serve well.

            M. STOTO:  Thank you.  I think that we will extend the invitation again to Dr. — to Mr. Principi to send a representative to our November meeting and see where that stands.  Hopefully, things will have been resolved by then.  But if not — and if so, we’ll hear about how they’ve been resolved.  Otherwise, we’ll keep the issue on the front burner.  Okay.  Are there — anyone else like to make a comment?  Rick?

            R. WEIDMAN:  May I just make one suggestion in regard to your next meeting on November 19th?

            M. STOTO:  Yeah.

            R. WEIDMAN:  And that is to think about requesting of the Secretary and of the VA to have meeting space in 810 Vermont Avenue as a courtesy between departments and in order that more people are more likely to attend than journeying out here trying to find where Fisher Lane is, much less this particular building.  I went to the main building before I ended up here.

            And also at that time, then asking the Secretary or his direct representative to speak.  If you’re in the same building, you’re much more likely to have high ranking representatives of the VA attend this meeting.  Given that it’s on a Friday, and it’s at that particular month of the year and at that particular time of the year, I do not believe that there won’t be a suitable meeting room with — that’s miked, et cetera, available within the headquarters building of the U.S. Department of Veterans Affairs.

            M. STOTO:  We’ll consider that.  I’m not sure what are — what are the logistics involved there, but yeah.  Okay.  Thank you.  Other comments?  Well, let me thank again everybody on the Committee for their reviews, for the people from the Ranch Hand Committee.  Oh sorry, David.

            D. JOHNSON:  One thought I’ve had as we’ve heard — we heard discussions about taking this data and using it for various other studies in the future.  I — this — we don’t want to forget the importance of appropriate consent from those.  I know this has been covered to some degree and it sounds like it’s pretty well covered.  But you don’t want to forget that at any time you go to use this data for other — things other than what it was initially intended to be used for.

            M. STOTO:  Yeah.  I think that could be quite a thorny issue.

            D. JOHNSON:  Right.

            M. STOTO:  I think that ...

            D. JOHNSON:  It has to be looked ...

            M. STOTO:  But that it’s quite explicitly on the National Academy of Science’s agenda if they get that study to do.

            D. JOHNSON:  Right.  Okay.

 

Text Box: Closing Session


 

 

 


            M. STOTO:  Okay.  Again, thank you for the Committee for your reviews; for the Ranch Hand staff and contractors for all the good work that you’ve done; for the Committee staff in organizing us; and for the others who were able to attend.  We’ll see you all in about a month — two months.  Right.  Okay.  We’re adjourned.

[ADJOURN 11:16 A.M.]



CERTIFICATION

 

State of Georgia       )

                                    )

County of DeKalb      )

 

 

            I, Nadine Rivera, do hereby certify that the foregoing transcript, consisting of pages 1 – 105 in total, was personally typewritten by me and is a true, complete and accurate transcript of the proceedings recorded by me.

            I further certify that I am not related to, employed by, or attorney of record for any parties or attorneys involved herein.  I further certify that I have no financial interest in this matter.

            WITNESS MY HAND AND OFFICIAL SEAL BELOW.

 

            This 14th day of October, 2004.

 

 

 

                                                                                    ___________________________

                                                                                    Nadine Rivera

 

                                                                                    My Commission Expires:

                                                                                    August 1, 2006