**DEPARTMENT OF HEALTH AND HUMAN SERVICES**

**and**

**FOOD AND DRUG ADMINISTRATION**

**NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH**

**convene the**

**[Ranch Hand Advisory Committee Meeting]{.smallcaps}**

***Rockville, Maryland***

***September 22, 2004***

**[Certified Verbatim Transcript]{.smallcaps}**

**TABLE OF CONTENTS**

[Page]{.underline}

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]{.underline}**

Dr. Michael Stoto, Chair

Dr. Paul Camacho

Dr. Ezdihar Hassoun

Dr. David Johnson

Dr. Sanford Leffingwell

Dr. Ronald Trewyn

**[FDA/NCTR Representatives]{.underline}**

Dr. Leonard Schechtman

RHAC Executive Secretary

Ms. Kimberly Campbell

Management Specialist

**[U.S. Air Force Representatives]{.underline}**

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]{.underline}**

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]{.underline}**

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]{.smallcaps}**

***September 22, 2004***

***Rockville, Maryland***

**[Certified Verbatim Transcript]{.underline}**

**\[CONVENE 8:17 A.M.\]**

**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
14^th^ or the week of the 21^st^ 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 14^th^ or the week of the 21^st^. The meeting
following that, we're looking at May: the week of the 1^st^ of May or
the week of the 23^rd^ of May. However, for the week of the 23^rd^ 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 11^th^ or the week
of the 18^th^. And in November, the week of the 1^st^, 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]{.underline}**

**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?

**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.

**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.

**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?

**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[\<]{.underline}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[\<]{.underline}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.

**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.

**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.

**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.

**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.

**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:** 19^th^ \...

**M. STOTO:** 19^th^?

**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 19^th^, Friday? Good. Thanks.

**L. SCHECHTMAN:** So the travel will be on the 18^th^ and we'll try and
finish up in a manner that allows you to leave on the 19^th^ 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.

**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
2^nd^ 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 19^th^?

**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.

**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]{.underline}**

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 14^th^ day of October, 2004.

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Nadine Rivera

My Commission Expires:

August 1, 2006