[CONVENE 8:17 A.M.]
M.
STOTO: Everybody and all the equipment is in place,
so we’re ready to begin. I’m Mike
Stoto, the Chair of the Committee. And
I’d like to welcome everybody here from the — from the Committee, from the
Ranch Hand staff, from the Committee staff and others who are here. And I think you all have a copy of the
agenda before you. I’d just like to ask
everyone to go around the table. First,
the Committee members and then everyone else should introduce themselves
briefly. Robert, do you want to begin?
R.
SILLS: Oh, there you go. Okay, thanks. I’m Robert Sills. I’m the
head of molecular pathology at NIEHS in the Research Triangle Park and my
expertise is carcinogenesis and molecular mechanisms of cancer.
S.
LEFFINGWELL: Sanford Leffingwell,
former CDC tech, now trying to make my way in the real world as a
consultant. Some expertise in
occupational and environmental medicine.
L.
SCHECHTMAN: I’m Leonard
Schechtman. I’m the Deputy Director for
Washington Operations at the National Center for Toxicological Research with
FDA and I’m the Executive Secretary of the Ranch Hands Committee.
R.
TREWYN: Ron Trewyn, Kansas State,
Vice Provost Research, Dean of the Graduate School. And back when I used to have to work for a living, same expertise
as Robert. So we’ll have to fight over
the cancer chapters.
P.
CAMACHO: Paul Camacho from the
University of Massachusetts.
D.
JOHNSON: Dave Johnson, Executive
Medical Director for the Division of Environmental Health, Florida Department
of Health.
E.
HASSOUN: Ezdihar Hassoun at the
University of Toledo, College of Pharmacy, Associate Professor.
J.
MICHALEK: Joel Michalek, Principal
Investigator of the Air Force Health Study.
RECORDER: Excuse me, can you go to this microphone? I’m sorry, but I have to record every single
word.
W.
GRUBBS: Bill Grubbs, SAIC, involved
with the report.
K.
FOX: Colonel Karen Fox, medical
investigator with the Ranch Hand Study.
L.
WALDEN: I’m Larry Walden and I’m
with the Ranch Hand Study. I’m a data
management specialist.
R.
OGERSHOK: I’m Richard
Ogershok. I’m the Program Manager for
the Air Force Health Study.
W.
MURRAY: I’m Bill Murray with the
Air Force Surgeon General’s Office, Program Support.
M.
OWENS: I’m Maurice Owens with SAIC. I’m the Program Manager of the SAIC support
contract.
J.
MINER: I’m Jay Miner, Operational
Technologies. I work with Mr. Ogershok
for the Air Force.
M.
BLANCAS: I’m Manny Blancas, also
with Operational Technologies and I also work for Mr. Ogershok in the Air Force
Health Study.
W.
KEIHL: I’m Bill Keihl. I’m the contracting officer for the Air
Force Health Study.
M.
YEAGER: My name is Meagen
Yeager. I’m a project analyst for SAIC
and I work on the Air Force Health Study.
F.
RAZZAGHI: My name is Fred
Razzaghi. I’m the Director of Technical
Affairs at the Consumer Healthcare Products Association in Washington. Thank you.
G.
HAWLEY: George Hawley from the
Veterans of Foreign Wars.
M.
STOTO: Okay. Thank you everyone. Len, would you lead us through the
housekeeping items?
L.
SCHECHTMAN: Okay. Thank you, Mike. Just one thing on the microphones, everyone needs to use
them. We’re recording the meeting and
for the — for the verbatim transcript.
And if everyone would also shut their mikes off after they’re finished
speaking, then we can recognize the next person who wants to speak and it also
won’t interfere with the microphone that’s currently in use. Thank you.
Now
we have a few housekeeping items that we’re going to be dealing with today. First of all, we have two breaks scheduled —
two coffee breaks — and a working lunch today.
So we won’t be leaving the room; you’re trapped. Okay.
We’ll also try and hustle along that way and perhaps we can even adjourn
a bit earlier to allow everyone to catch their flights.
What
we need to start doing already is start thinking about meeting dates for
2005. And we’ve looked over the
calendar to look for some blocks of time that wouldn’t interfere with holidays
and general issues that seem to surface at certain times of the year. So if you’ll jot these down, you can start
thinking about this. We will follow up
with an e-mail from our office to try and nail down the dates as soon as we
can. We’re talking first about a
meeting in February, either the week of the 14th or the week of the
21st of February. And those
— the actual days of the week, we’ll have to determine as to which is the most
convenient for all individuals.
M.
STOTO: Should we — why don’t we
talk about that a little bit here?
L.
SCHECHTMAN: Okay.
M.
STOTO: I remember we discussed this
in the past, and we decided that some days were good and bad, and I don’t
remember which ones were which. Was it
— was it that Mondays and Fridays were bad?
L.
SCHECHTMAN: Generally.
M.
STOTO: Is that the — people had
clinical responsibilities or something or ...
P.
CAMACHO: For me, it’s ...
RECORDER: Use your microphone, Dr. Camacho.
M.
STOTO: Mike, yeah.
P.
CAMACHO: For me, it’s a matter of
semester classes and the teacher’s schedule changes. So like today, Tuesday would’ve been fine just because the
schedule changed at the last minute.
M.
STOTO: Yeah. Well, why don’t ...
P.
CAMACHO: So I don’t know.
M.
STOTO: Let me just put it this
way. Are there — is there anybody here
who has problems with a particular day of the week?
J.
MICHALEK: Mike, I work ...
RECORDER: Mike.
M.
STOTO: Mike.
J.
MICHALEK: I work nights: Monday night and Thursday night. But the Thursday night is flexible and the
Monday is less flexible. I’m being paid
to teach Monday night at the University of Texas.
M.
STOTO: Okay. Yeah, I — when I teach, I — it’s often on
Monday too, so maybe we should try to avoid Mondays and we probably should try
to avoid Fridays. I think that someone
had — maybe Dr. Osei, who’s not here today had — was the one who had a problem
with that. Good.
L.
SCHECHTMAN: Okay. So as I said, we’re looking currently at in
February, the week of the 14th or the week of the 21st. The meeting following that, we’re looking at
May: the week of the 1st of
May or the week of the 23rd of May.
However, for the week of the 23rd of May, Thursday and Friday
are not currently acceptable, so let’s exclude those from our thinking. Okay.
Following
that in September of ‘05, the week of the 11th or the week of the 18th. And in November, the week of the 1st,
although Monday and Tuesday of that week should be excluded from your thinking
at this point in time. Actually, you
might want to think of only Wednesday and Thursday if Friday is also excluded,
so we’ll have to work around that.
Anyway, we’ll follow up, as I say, with an e-mail message to try and
nail those dates down as best we can with the knowledge we currently have as
far as 2005 goes. And we’ll circulate
the information as to how close we can get to the dates that we all want.
M.
STOTO: Do we have some sense of —
do we have some sense of what the agenda will be at these different
meetings? I mean, we’re finishing the
draft chapters next month, right?
What’s — what are — what are the main work items for these meetings in
2005?
J.
ROBINSON: Well, one will be ...
R.
TREWYN: Microphone.
J.
ROBINSON: One will be the final
report and then I believe we need to have at least two meetings with you every
year. I think that’s what’s in the
charter. So the other one would
probably be just to continue to update you on the closure activities, any
additional research that would be going on and findings.
M.
STOTO: So it’s possible we may not
need all four of the meetings?
J.
ROBINSON: Four meetings, right.
M.
STOTO: Okay.
L.
SCHECHTMAN: It sounds like we might
need three though. Is that what I’m
hearing at a minimum?
J.
ROBINSON: Two definitely, three
possibly.
L.
SCHECHTMAN: Okay.
M.
STOTO: Okay.
L.
SCHECHTMAN: Okay. Next on housekeeping regards our annual
conflict of interest paperwork that you were all recently faced with: the Forms OG-450 and Foreign Activities
Forms. I want to thank you all for your
very prompt turnaround of the COI forms.
Unfortunately, we are faced with them on an annual basis. And in fact, if things change even between
those filings, we’re supposed to ask you to update those filings as well.
As
far as the forms for 2005 are concerned, we’ll be e-mailing those to all the
members of the Committee in July of 2005 so we don’t bump up against the
meetings as we have in the past.
They’ll be due back to our office, the Office of the Executive
Secretary, within two weeks of the mailing.
And
the OGE-450 Forms, which we provided you with a shortcut this time that if in
fact there was no change from your previous filing, that you were allowed to
indicate that on the form. That was to
help expedite the process because there was such a short turnaround time, but
that won’t be available to us in the future.
So we’re going to have to ask you to fill out the OGE-450 Forms in
toto.
M.
STOTO: Can you at least send us the
previous year’s copy so we ...
L.
SCHECHTMAN: Oh yeah.
M.
STOTO: ... remember what ...
L.
SCHECHTMAN: Yeah. Yes, absolutely. Now as far as the Federal Register notices are concerned
for upcoming meetings, due to mandatory departmental requirements, we are
required to submit Federal Register notices for upcoming meetings well
in advance of any scheduled meetings.
So we’ll need to prepare draft agendas, identify topics, presentations,
possible outside speakers, et cetera, by no later than sixty days in
advance. This is the departmental
requirement.
We
can submit changes to that agenda that we furnish for the Federal Register
notice, however, there — they can only be critical changes and we have to
justify the changes. So those changes,
if critical, can be submitted up to 45 days in advance. So we have a window for any changes that
need to happen. Just a reminder as far
as your travel receipts, and expenses and those filings, please turn them in as
soon as possible. And if you mail them,
make them to the attention of Kim Campbell in our office.
M.
STOTO: Okay.
L.
SCHECHTMAN: And that’s it. Thank you.
M.
STOTO: Okay. Thank you.
I think you all have copies of the agenda before you. The main order of business today is to
review about half a dozen or seven chapters in the report. Joel Michalek is scheduled to make a
presentation about a general update, but has to go to the Pentagon at the time
he’s currently scheduled. So we’re
going to ask him to do that presentation in a minute after we’re through with
reviewing the minutes.
We
also have time scheduled for public comments.
So far, we have not received any word that someone wants to make a
comment. I’m just looking around now to
see whether anybody does want to add themselves to the list? Okay.
Thank you.
Approval of Previous Meeting Minutes
M.
STOTO: Now for the minutes, the
minutes have been circulated. I’ll ask
in a moment if there are changes that people want to make. I reviewed them and have suggested some
changes. I don’t know whether what you
got reflected my changes or not? Did
they go out? There were — there were a
couple of things. One, in Colonel
Berry’s presentation last time, he had a statement about what the law required
the NAS study to do that wasn’t quite consistent with the law. So I gave him the opportunity to change
that.
And
secondly, there were lots of — he made a very detailed, and interesting and
provocative presentation that we really didn’t have a chance to review as a
scientific basis. So I tried to make
the minutes clear that they were his — that that was his perspective rather
than the Committee’s perspective. The
other thing was that we had a discussion about this Congressionally mandated
study the National Academy of Sciences is supposed to do which ended up with an
action item that I was supposed to write a letter to Secretary Principi to try
to move that along.
I
ended up thinking that the best way to do that was to invite the Secretary to
send a representative to this meeting today to explain what the situation was
with respect to that study, which of course, the law calls for the study to
have been initiated within, I think, sixty days of passage. So they’re long overdue on that. I want the record to be clear about that;
that we have taken notice that the Department of Veterans Affairs has not
fulfilled this responsibility according to the law.
I
have not heard a response from the — from the Secretary or the Department about
that. I don’t think there’s anybody
here from the Department. I — we
continued to hear indirectly that things are moving along, but of course, that
may or may not be true. And what is
definitely true is that they didn’t do it according to the time schedule that
the law demanded, so I will invite the Secretary and representatives to come
next time and explain what the situation will be. And I think that is important that we continue to do this.
We’re
in the unusual position of our job is to advise the Secretary of Health and
Human Services, who doesn’t have a direct interest in this. This is really the Air Force, and the
Veterans Affairs and Congress. But it
might be — it may be of use to call this to the Congressional staff’s
attention. We copied them on the letter
and that’s something that ...
P.
CAMACHO: I don’t know if it’s —
what’s the appropriateness of all this; I leave to you. But the service organizations should be all
informed of this directly, if nothing else, in a way to protect our — protect
ourselves. Because to — for me as a
member of this advisory board, we have an obligation to the service community,
the veterans community, to inform them of things. Now whether this study continues, whether this — all the data is
saved or whether this is thrown off the cliff, it’s for NAS to make that
decision. And if they’re not allowed to
make that decision, we’re going to sort of be holding the bag, if you will. And people are going to say, “Why didn’t you
do something about it?”
So
that’s what I — so doing something about it would be writing a formal letter,
as we wrote to Mr. Principi, to all the service — major — the major service
organizations: the VFW, American
Legion, the DAV, and AMVETS, and then Vietnam Veterans of America and let them
disseminate that. Then we’ve told them
this isn’t happening; the study isn’t — NAS is not looking forward to it; this
is going to probably drop off the cliff.
Maybe that’s bad; we should be keeping this data somewhere, find a home
for it ...
M.
STOTO: Well, I ...
P.
CAMACHO: ... whatever.
M.
STOTO: I’m not sure it’s our role
to write to those organizations. But I
wrote the letter to Principi in way that a copy can be sent to those
organizations and a copy has been ...
P.
CAMACHO: Oh fine, but ...
M.
STOTO: ... a copy has been sent to
the Congressional staff.
P.
CAMACHO: Yeah. If a copy could also be sent to those — if I
provided those list of ...
M.
STOTO: Right.
P.
CAMACHO: Would that be acceptable
to you?
M.
STOTO: I mean, we did copy the
relevant Congressional staffs already.
P.
CAMACHO: Yes, but I think also
could we go — is it appropriate for us to go one step further and send copies
to the ...
M.
STOTO: It’s appropriate for you to
do that.
P.
CAMACHO: It is?
M.
STOTO: Yes.
P.
CAMACHO: There’s no problem? All right, fine.
M.
STOTO: No.
P.
CAMACHO: I’ll do it.
M.
STOTO: I mean, it ...
P.
CAMACHO: I’ll do it.
M.
STOTO: Okay. Were there any other comments? Any other discussion about that item? Any other comments, corrections for the
minutes?
R.
TREWYN: I do have one correction on
the minutes. On page eight, bullet
three, it should read, “Provide a breakdown of in-country Vietnam versus ...”
not “countries in Vietnam.” So
“in-country Vietnam versus other locations ...”.
M.
STOTO: Careful reading.
R.
TREWYN: That was my only edit.
M.
STOTO: Let me — let me just make
the comment again that I think that these minutes were very well — the draft
was very well prepared, so thank you very much for your efforts. So do I hear a motion to approve the
minutes?
R.
TREWYN: So moved.
M.
STOTO: Ron. Second?
S.
LEFFINGWELL: Second.
M.
STOTO: Sandy. All in favor, please raise your hand and say
yes.
RHAC: Aye.
M.
STOTO: Okay. I think it was unanimous. Okay.
Joel, can you make a report now?
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<0.05.” That’s significant. Because the way it’s written, I mean, in
this chapter, probably in all other chapters, for example, if I can look at one
of the tables: “p>0.02;” it’s
non-significant. It sounds like
anything less than 0.20 is going to be significant, right?
J.
ROBINSON: What page is that on?
E.
HASSOUN: Page 12-16. I mean, it’s through all the tables; this is
just an example. If we just add
asterisks to the tables and define the significance level: “p value is less than 0.05.”
J.
MICHALEK: I guess ...
M.
STOTO: Yeah, go ahead.
J.
MICHALEK: ... a short comment. That specification, I think, is given in the
“Statistical Methods” chapter throughout the report; “p<0.05" is
called “significant.” You know, we have
to make global decisions about this and put things in the — in one place sometimes. And that’s what we did, I think, on this
issue. Is that true, Bill Grubbs?
W.
GRUBBS: That is correct.
J.
MICHALEK: So, and that’s what we
did and that’s consistent with the previous reports. And that’s another issue, you know. As we think about changing format, we have also the — to realize
that the reader might want to compare this report with last cycle report and so
we want to keep that task as simple as possible.
M.
STOTO: So can I — are you asking
that they — that they change the table or they just be clear about what the
significance is?
E.
HASSOUN: Exactly, yeah. Define the significance level.
M.
STOTO: I mean, it seems — that
seems to me to be relatively simple enough to do, to remind the reader in every
chapter.
J.
MICHALEK: Yeah. All right.
I just reassured that it could be done.
M.
STOTO: Okay.
J.
ROBINSON: Again, I just want to say
that we take every comment, and we evaluate it and respond to them all. Thanks.
E.
HASSOUN: Then page 12-8 about the
“Verbal Paired Associates test,” I have a question about the adjustment of the
scores to 18. I mean, you divided the
total for the easy items by 2 and adding the total for the difficult
items. Why did you choose to divide the
easy items by 2, just to make it 18?
J.
MICHALEK: Please tell me where are
you reading that?
E.
HASSOUN: 12-8, lines 427 through
432.
J.
ROBINSON: And the specific line is
432.
J.
MICHALEK: Okay. Well, this is an algorithm that is cited
from the literature or given to us by our consultants at CDC on how to score
these psychological tests. This is not
something we made up just for convenience, you know. It’s ...
E.
HASSOUN: Yeah.
J.
MICHALEK: So probably what we need
there is a reference.
E.
HASSOUN: Okay. Because it says, “In order to mimic the
other, I mean, we did so-and-so.” It
sounds like you adjusted it so that ...
J.
MICHALEK: Yeah. It makes it appear we made that up in order
to mimic the scoring. Now that I said
that, yeah, that’s true. This language
and this algorithm, no doubt, came from our consultant at Scripps — what’s his
name, the psychologist at Scripps? — Dr. Carey, who was our consultant on the
Wechsler Memory Scale. And so — and
he’s a psychologist, so he’s using his knowledge to write that.
E.
HASSOUN: For the “Covariates” on
12-9, I don’t know; it’s about alcohol history. Is that a covariate or a dependent variable?
J.
MICHALEK: That is a covariate.
E.
HASSOUN: Yeah, because you used it
under dependent variables also: alcohol
dependence and the drug dependence.
J.
MICHALEK: Now there, that’s a, I
believe, an item from the DSM. The —
that’s a standard outcome in a psychological profile and they’re all
given: the alcohol dependence, drug
dependence. Yes, so that it’s also a
dependent variable, so that complicates the picture. Yes, you’re right. It’s
both a — sometimes a covariate and sometimes a dependent variable.
E.
HASSOUN: And for 12.1.4, the
“Statistical Methods,” page 12-10, line 496 — “Unadjusted and adjusted analyses
for Models 2 and 3” — can you just add a little explanation for those
models? I saw them; I found them
later. Under “Exposure Analysis,” you
described the models: 1, 2, 3, 4. But in “Statistical Methods,” all of a
sudden, you are talking about Models 2 and 3 and I got confused when I read
those.
J.
MICHALEK: All right.
E.
HASSOUN: So I had to go ...
J.
MICHALEK: Okay.
E.
HASSOUN: ... to the ...
J.
MICHALEK: And that, so they’ve not
been described up to this point?
E.
HASSOUN: Just a little, I mean,
just two lines.
J.
MICHALEK: Okay.
E.
HASSOUN: You had four methods or
four models. Then the table, Table
12-1, page 12-11, since you decided to put the cutpoints in the table, why not
add a maximum scores also for the “SCL-90-R Global Severity Index?” Like “Cutpoint/Maximum Scores,” which are
1825 or 34, right?
M.
STOTO: What table?
J.
MICHALEK: What table is this?
E.
HASSOUN: Table 12-1.
J.
MICHALEK: Okay. All right.
So you want to know the maximum?
E.
HASSOUN: Yeah. Since you decided to put the cutpoints ...
J.
MICHALEK: Yeah.
E.
HASSOUN: ... on the SCL, why not
add in the maximum scores for the WMR?
J.
MICHALEK: I’m sorry. All I see in that table are cutpoints for
covariates.
J.
ROBINSON: That’s what she’s
saying. She saying in addition to
cutpoints, to “/Maximum Scores.”
E.
HASSOUN: “/Scores.”
M.
STOTO: But that’s the definition of
the categories, right?
J.
MICHALEK: My table 12-point for
some reason ...
M.
STOTO: Isn’t that ...
J.
MICHALEK: Oh, I’m looking at the
wrong panel. Okay. All right.
I’m with you now, yeah. So you
want to know the maximum possible value of the psychological scales? Is that right?
E.
HASSOUN: Yes.
J.
MICHALEK: Okay.
E.
HASSOUN: So rather than going back
to the text ...
J.
MICHALEK: Yeah. Right.
E.
HASSOUN: ... and read what the ...
J.
MICHALEK: Yeah.
E.
HASSOUN: ... normal scores ...
J.
MICHALEK: Yeah. I think — yeah; that’s a standard thing to
do in reports like this. I understand
that. We’ve taken note of that.
E.
HASSOUN: Okay. Okay.
That’s all what I have for the chapter.
Regarding the appendix, again, it’s nice to define the significance
level. And also for Pearson’s
correlation coefficient, the maximum correlation is 1.0 as I know. Is that right? It’s 1.0?
J.
MICHALEK: That’s correct and the
minimum is minus 1.0.
E.
HASSOUN: And the minus values will
— would indicate inverse ...
J.
MICHALEK: That’s ...
E.
HASSOUN: ... correlation? Yeah.
J.
MICHALEK: That’s correct.
E.
HASSOUN: If we can add that to the
appendix also.
J.
MICHALEK: Okay. That’s all what I have.
M.
STOTO: Okay. Thank you very much. Can I bring up one point? This and the immunology chapter were — are
the first substantive chapters we’ve reviewed this cycle. And one of the, I think — I think the major
difference is, is that the summary section and tables at the end. And we had a lot of discussion about that in
the last cycle and my sense is that this is relatively nicely done here. I don’t know whether the two of you agree
with that? And maybe when the others
come to review their chapter, they may comment on that as well.
J.
MICHALEK: Thank you.
M.
STOTO: Sandy, did you want to say
something?
S.
LEFFINGWELL: Not really. Yes, I noticed the summary tables and
thought they were helpful.
E.
HASSOUN: They were very helpful.
M.
STOTO: Other comments from the
Committee about this chapter?
Okay. Thank you.
S.
LEFFINGWELL: I was curious. Do the Ranch Hand subjects know which group
they are in or do they have fairly high suspicion just from knowing what they
did while they were there?
J.
MICHALEK: Well, they certainly
they’re Ranch Handers and the controls know they’re controls. Is that what you mean?
S.
LEFFINGWELL: Only in part.
J.
MICHALEK: Oh, their dioxin
levels? Is that what you mean?
S.
LEFFINGWELL: Yeah.
J.
MICHALEK: Dioxin category? They know their — we told them their dioxin
levels. We gave them that by mail. And if they’ve read the reports, they’ll
know what category they’re in, but I don’t know how many people have read the
reports. We sent them a letter in 1989
telling them they had 12 parts per trillion.
I doubt if that information, for very many people, is at the top of their
mind as they’re going to Scripps. I
mean, they don’t — you know, I don’t know how many people study the reports and
compare their dioxin level with the reports.
I don’t know.
S.
LEFFINGWELL: I was just wondering
if that could affect things like a global assessment of well-being?
J.
MICHALEK: That is a possibility,
yes. Good point.
M.
STOTO: Okay. Thank you very much.
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: 19th ...
M.
STOTO: 19th?
P.
CAMACHO: ... which is a Friday,
which is nice.
M.
STOTO: Okay. So once you send them to the Committee staff
and they’ll make sure they go out to the right people. Maybe if you guys can prepare an e-mail
about who’s going to do what? Okay, and
probably should — and with the idea that Chapter 21 goes to everybody and
probably I should get a copy of everything.
Does anyone want more than the — than the ones they’re doing ...
R.
TREWYN: This guy.
M.
STOTO: ... just to — just to have
them?
P.
CAMACHO: Oh yeah, I’ll take the
set.
M.
STOTO: Okay.
R.
SILLS: Good idea.
R.
TREWYN: Yeah. Yeah.
That’s fine. Yeah.
M.
STOTO: Okay. So we should send everything to everybody
...
RHAC: Right.
Yeah.
M.
STOTO: ... but make clear who is
the primary?
RHAC: Right.
M.
STOTO: Yeah.
R.
TREWYN: That works.
R.
SILLS: That’s helpful.
M.
STOTO: Okay. Yeah, and one of the — one of the jobs, I
think, for reviewing the executive summary is making sure that it’s consistent
with the chapter that it summarizes and so ...
P.
CAMACHO: We might as well read the
whole book.
M.
STOTO: ... and so that’ll be the
primary, you know, so whoever, you know, does dermatology should also take
responsibility for looking at the dermatology section of the ...
J.
ROBINSON: Conclusions and the
executive summary.
M.
STOTO: Yeah. Okay.
Go ahead.
L.
SCHECHTMAN: Just a question for
everyone. Was it useful to have us
provide you with the chapters or is that unnecessary? Do you prefer to lug the chapters from home or ...
R.
TREWYN: No, having them here.
L.
SCHECHTMAN: ... having them here?
R.
TREWYN: Having them here is
helpful.
L.
SCHECHTMAN: Is good? Okay.
Okay.
R.
TREWYN: And we bring the ones we —
the primary reviewed.
L.
SCHECHTMAN: Okay, very good. Thanks.
R.
SILLS: Just to clarify, so the
meeting, the next meeting is November 19th, Friday? Good.
Thanks.
L.
SCHECHTMAN: So the travel will be
on the 18th and we’ll try and finish up in a manner that allows you
to leave on the 19th so you can be home for the weekend. If not, we’ll let you know.
M.
STOTO: That’s not Thanksgiving week
or anything?
R.
TREWYN: And Friday night flights
out of Washington are generally a mess, so if we can get done early, scheduling
with earlier would help.
M.
STOTO: So it’s probably important
to make arrangements if you could — if you guys could get the information out.
L.
SCHECHTMAN: Yeah. Right.
Well, we’ll — okay — we’ll take care of that. We’ll get a jump on it so that we can get flight reservations for
you and hotel bookings as soon as we can using the same system that we’ve used
before through our office.
M.
STOTO: And the meeting will be
here?
L.
SCHECHTMAN: Well, we’re trying to
get this room. You know, CDER has first
preference for the room and whenever we can squeeze in here, we do. If not, we’ll have a room in the other — in
headquarters Parklawn Building.
R.
SILLS: I just want to make one
point. Len, you and your staff,
especially Kim, have been really good in terms of getting us the materials on
time and keeping track with things. I
had to change my travel arrangements today; Kim did an awesome job. So thanks to you and your staff for keeping
everything going and making sure that we’re all taken care of.
L.
SCHECHTMAN: Thank you.
R.
TREWYN: And I would just throw out
too that the DoubleTree is orders of magnitude better than the one across the
street.
M.
STOTO: Well, thank you for making
those comments. I mean, I — since I
come on the Metro, I don’t — I’m not aware of these things. So okay, any other administrative items of
that — of that sort? Okay.
M.
STOTO: So let’s go to the open
session now. Would you like to comment
— make comments?
R.
WEIDMAN: I can come up there?
M.
STOTO: Oh yes. How about if he — can he sit at the — at the
table over there?
R.
TREWYN: Or go to the podium.
M.
STOTO: Either one.
R.
TREWYN: I’d make it as tough on him
as possible. You know, let’s just —
right, Rick?
M.
STOTO: Rick, if you would just
remind us who you are?
R.
WEIDMAN: My name is Rick Weidman
and I’m Director of Government Relations for Vietnam Veterans of America. And I’m used to hostile officers, so the
method of addressing you is immaterial.
From the point of view of those of us who are former enlisted men, most
officers, by the way, are hostile and to one degree or another. First of all, I want to thank each one of
you on behalf of Vietnam Veterans of America and our national president, Tom
Corey, for serving on this Committee.
You take a lot of heat simply from some quarters and it doesn’t do,
frankly, those of you in academia a heck of a lot to advance your career to sit
on this Committee and we’re grateful for your taking the time to do so.
Having
said that, VVA has looked at this, has been involved in one way or another with
the Ranch Hand Study for 25 years, I guess.
As looking at, reviewing pictures the other day as we were cleaning out
the basement, it reminded me that I had all my hair when this study started and
none of it was gray. And I think that’s
true of perhaps others in this room, and yet, we are not much closer to finding
the kinds of answers that we set out to find in the first place.
It
is useful to remember the historical perspective on this. The reason why the Ranch Handers were chosen
as the study group was because the Department of Defense and the VA claimed
that they had no evidence that anybody else was exposed to any of the
herbicides. And that’s useful to bear
in mind because we know that now not to be true by a whole heck of a long
shot. In fact, one can argue that those
who served on the ground were much more exposed certainly than those who sat in
the front of the aircraft that actually did the spraying operations on Ranch
Hand; that’s one.
Two
is that those — that there is even a certain theory that bears some
consideration; that those who served in the rear-most areas, such as Cam Ranh
Bay and Long Bien, where anything that was green got zapped with an herbicide
and the particulates which then became part of the dust and wind, and people
inhaled, got on your food, got in your — anything you drank, et cetera,
got on your hands. And when you sweated
and wiped your face, you ended up eating it; that this was an exposure that was
hard to measure, but it also depended exactly how much you were outside,
frankly.
So
there’s a lot of — a lot of things that have changed since the very start. So the question is — and I was pleased to
read the September 2nd memo, Mr. Chairman, that you forwarded to
Secretary Principi for a variety of reasons.
We’ve discussed it in the VVA leadership, and our Agent Orange Committee
and Healthcare Committee and prior to this meeting. And there are so many problems that we see methodologically that
while much of the data and many of the samples, in fact, will prove to be
useful to ultimately what questions may be answered in the future.
This
was started as a herbicide study. The
most eloquent expression of why that is important to bear in mind was given by
one of your members in testimony in the year 2000 before Chairman Chris Shays
of Connecticut on the Oversight and Investigation Committee dealing with VA,
DoD and National Security, the Government Reform Committee of the House of
Representatives, when he said, “We have been looking as to whether or not there
was harm done by one particular species of beetle bark boring into a particular
tree and looking at that so hard that we have not looked around and realized
that the forest has died all around us.”
And
that’s why this can’t be anything that is ultimately useful. In terms of overall answers for Vietnam
veterans and their families, cannot be limited to dioxin and the other
confounders are useful and necessary to look at. The Institute of Medicine of the National Academy of Sciences
took that into account, not on their latest biannual review that was released a
year ago, but the previous one when they accepted a body of material that was
given to them by representatives of VVA and decided to consider it in terms of
studies done by the Japanese and by others on the effects of PCBs.
And
those of you who deal with molecular know that at the sub-molecular level, PCBs
work exactly the same as a dioxin in terms of their effect on the body and the
long-term health of the overall organism.
As you move forward and try and make this report as useful as possible,
we believe that there are a number of things that even now need to be
examined. One is the assumption that
ten points — part per trillion is — anything below that is not harmful. In fact, we don’t know that. There is no scientific basis for saying —
that is credible — to say that eight is not harmful and ten is. That’s just one example.
It
is not only a dioxin study. It is — we
have to look at confounders, and we have to look at participants and other
kinds of problems that you’re up against.
And without examining and comparing all of those other confounders
against a null hypothesis, there is no reason to assume nor is there any, to
our knowledge anyway, compelling body of knowledge that has been — has been
enumerated either by this body or by the various committees of the Institute of
Medicine of the National Academy of Sciences that would say the null hypothesis
stands up on all of these other factors.
Because we don’t believe that that is correct and if we’re wrong, we
would — we would be delighted to hear back from those of you as individuals or
as a body.
Next
major problem that we’ve seen from the start is that there’s no non-veteran
cohort group. Finally, there is some
measurement of Southeast Asia time, but we do not know — and nor does anyone in
this room nor anybody to our knowledge period — whether or not merely having
served in the military during Vietnam, in and of itself, that something
happened to individuals either through immunizations or some other method of
exposure that makes a difference with their non-veteran peers. We simply don’t know that.
And
without that third group of the non-veteran cohort group — non-in-country
Vietnam veterans, in other words, those who served in the Air Force and had
similar duty, but never served in Southeast Asia — and then compare that with
those who served in Southeast Asia, and last, but by no means least, the fourth
group and the — is the primary group of those who served on Ranch Hand. If you have those four groups, then you have
some shot at telling whether or not the first, those last two groups — those
who served in country and those who served on Ranch Hand — whether or not
there’s a difference in the health, overall health effects between those and
Air Force personnel who did not serve in Vietnam and their non-veteran peers
who never entered the military whatsoever.
And so the whole issue of hostile versus non-compliant, and replacements and replacements of replacements, and replacements of replacements of replacements or whatever the case may be, those are all potential confounders that may or may or not be relevant to the overall validity of the study. But the question is whether or not the study should be continued and in its current form. And we think there’s serious questions about that and that’s not because of the talent nor the dedication of either the staff of the — of the Ranch Hand Study, or of the Air Force or of the contractors who have done much fine work within the parameters of the contract that has been drawn for their particular segment of the overall work. But it is because of many of the things that I’ve mentioned thus far.
Number
one and number two — one thing that is absolutely essential for this work, and
the reason why the Congress authorized it and then appropriated funds for it is
that Vietnam veterans and their families, the veterans community in general and
the American public in general have confidence that this has contributed
materially to the answers that have been raised and that are continuing to be
there about the health of Vietnam veterans and their families, and whether or
not there was significant harm done by virtue of service to their country in
Southeast Asia and exposure to these herbicides.
And
it — it’s a balance point there. Can we
spend another $180 million to better affect?
Some of us, the answer is, “Yes, we can spend it to better affect.” So then the question comes back to, Mr.
Chairman, your letter to the Secretary.
In your third paragraph which is, “The Air Force’s funding for the study
is due to expire in the recent future.”
We presume you mean “near future.”
M.
STOTO: Did I say that? Sorry.
R.
WEIDMAN: “Without funding, the
biological samples will be lost. The
data gathered will be inaccessible to researchers and the investments that
thousands of veterans have made of their time will be squandered.” That is only assuming that the data is not
transferred as VVA has taken the position that it should be. Both the data and the samples transferred to
the custody of the National Institute for Environmental Health Sciences and be
— and the data — and made available to legitimate researchers and research
institutions throughout this country.
We
believe it to be a significant and erroneous action to first make the data
public and now “having taken it private again” — to borrow a term from Wall
Street — is inappropriate. And that
data needs to be accessible. If we need
to file FOIA, if we need to go to court, we’ll get it open because privacy
concerns can be met and still make that available for further scientific
inquiry and further scientific mining, if you will, of that data and of those —
of those samples that have yet to be — that have yet to be tested and that —
and added to that significant — to that significant database.
It
belongs to the American public; the American people paid for it. And the American people paid for it with the
motivation and clear intent of the Congress that it contribute to bringing the
answers to Vietnam veterans and their families about the deleterious health
effects that may or may not be due to people’s service in Vietnam.
And
therefore it is, by its very nature, a covenant that it be made public, and
made available, and that research that is privately conducted — privately
conducted, but publicly funded by reputable research institutions through
NOFAs, not just RFPs, but NOFAs, so that people can design studies, would be of
useful design, come in and test those out, and further mine this data. And we believe that that is absolutely
essential. And we’ll be working with
our friends on the Hill to accomplish that end in the future to make sure that
it is publicly available and that there is a successor study of some studies.
I
would also bring to the — to your attention that there is pending a — the whole
issue of the National Vietnam Veterans longitudinal study which the contract
with IOM has not been consummated for what to do with this data to complete the
actions required under Public Law 108-183 in regard to the Ranch Hand
Study. But there’s a report for the
National Vietnam Veterans longitudinal study is due to be released and given to
the Congress next year. And currently,
not only is it not ready, there is not currently a contract in effect.
We
hold the VA accountable for both of those actions and there is absolutely zero
excuse except it’s either one of two things:
either deliberate mendacity or its breathtaking incompetence and there
is virtually neither one a judgment that it — one could make on the lack of
follow-through and completion of either of those very clear, very
straightforward actions that were clearly mandated by the Congress.
So
I wanted to, on our behalf of VVA, to share some of these thoughts, and
intentions and judgments with you, and to once again extend to you our thanks
for your service on this Committee individually and for those of your
predecessors who have tried to do the best they can, and of all the many fine
people who have participated in various aspects of the study. But it has gone awry and it is time to move
on in a new context with a new wine skin and new wine, but not throw out the
old, but make it available some place else and to put our public resources
where we’re going to have more bang for the buck and more yield on the original
intention of the will of the people as expressed through the statutes governing
this and future research.
And
Mr. Chairman, I’d be happy to answer any questions you or your colleagues may
have. And on behalf of VVA and our national
president, Tom Corey, I wish to thank you for the opportunity to make some
comments here today.
M.
STOTO: Well, thanks, Rick. Let me — let me respond. First of all, thanks for coming today. We do appreciate that you do that. Second, I think it’s important that you made
a distinction between whether or not the study should continue. I think you meant in the sense of gathering
new data versus maintaining the information and the samples that — making them
available — that currently exist.
And
I’m not sure that we agree as a Committee on the — on the value of extending in
the — in the first sense, but that really is not our charter. But I think that we certainly all agree
about the value of the information that’s already been in this — in the material
that’s already been gathered and the importance of making that available to
legitimate researchers as you were saying.
R.
WEIDMAN: Did you want me to clarify
that, sir?
M.
STOTO: No. No.
R.
WEIDMAN: Okay.
M.
STOTO: No. The — I just want to emphasize that we agree
with you, at least on the second part, which is that the part that’s within
our, I think, within our charter. The
second thing I wanted to say is that — and I said a little bit about this early
before you came — that we’re kind of in a funny position. We advise the Secretary of Health and Human
Services and who — and this really is an issue that the Air Force, and even
more so now, the Department of Veterans Affairs have the main play in.
And
so I tried to — that letter that may have had grammatical problems was intended
to do the best that we could to raise the issue that the Department has not
fulfilled its obligations under the law.
And I think that’s the point. I
mean, I — we did that in the context of inviting him to — Dr. — Mr. Principi to
send a representative to this meeting.
But the point of that letter, and I’ll be clear about this for the
record, was to make it clear that as far as we can tell, the Department was not
fulfilling its responsibilities. So
we’re glad that you took note of that.
And
to the extent that we’re concerned about the value of this information that may
be lost, we hope that you are able to push this issue further as you seem to
want to do. So I think that the
Committee is very much in sync with that.
Okay. Sandy?
S.
LEFFINGWELL: The concept of a
referent population in the general population as opposed to service people is
certainly a — would certainly be a valuable thing if it could be done. I think that would be a daunting task even
if Congress elected to try to fund some future study. So it may well be that the best hope for that would be to find a
repository where the data could be used perhaps for studies in the civilian
population. And this data set might be
one referent population for those.
Quality
of the study — this was a very well done study and whether it would be done as
well in future studies is a little bit problematic. That’s certainly an interesting concept, and again, we would
appreciate your efforts in making sure that the data are not lost and ...
M.
STOTO: Ron?
R.
TREWYN: I just wanted to mention
that at least with regard to cancer, there is the effort and some of the
publications that are in the works.
It’s not necessarily designed into this study, but they really are
looking at the general cancer prevalence in the civilian population and whatnot
to do comparisons and are finding significant differences. So again, I would, you know, compliment the
study group on their willingness and interest in taking this as far as they
can, utilizing this data for the peer review publications that they’ve got in
the works that can really, at least, start to raise some of those questions and
get to — get to some of these issues in perhaps some of the most important
areas.
And
I think there are then opportunities in a variety of other areas: cardiovascular and a whole host of others to
do the same sorts of things. And again,
I think as long as we’re all pulling in the right direction here. There were limitations on how this particular
study was designed. There were the
limitations in the power that this group had or, in fact, did not have in
throughout its history in what we — what this group could do as far as study
design and whatnot.
We
were advisory. We’re given very little
clout to make many changes and a lot of that though came out of, I think, the
original legislative effort. So we
certainly recognize there are issues.
And again, as long as everybody’s looking for the right direction to
move, I think that’s very helpful.
R.
WEIDMAN: Mr. Chairman, if I could
just respond if I may to Dr. — is it Leffingwell, sir? The research design of the three — of the
three elements, minimum three elements — non-veterans; those who served in the
military, but not in Southeast Asia; and those who served in Southeast Asia —
is not original with us. That was the
original design of the Vietnam Veterans Readjustment Study or National Study of
the Vietnam Generation, which was done by Research Triangle Institute, and
which at that time concentrated primarily on psychosocial judgment — speak
much, apparently not and not very well — on readjustment, psychosocial
readjustment of Vietnam veterans, versus those who served in country, versus
those who served in the military, versus the non-veteran peers.
The
longitudinal study, while they did self-report healthcare information at the
time in the mid-‘80s on the NVVRS as we call it or the RTI study, this time
what we want is a — is a complete health study. And if the individual has died, review of the medical records in
order to verify and hang on that some empirical evidence that self-reporting
and find out whether or not it was reasonably accurate.
And
so then we will have the closest we’re going to get to a longitudinal
study. The IOM, for the last five
reports — both special and biannual — we’ve asked the question to the chair
every single time: “Do you have enough
science?” And the reply has been
exactly the same every time: “We have
enough science, we think. We could
always use more. But what we do not
have is a long-term epidemiological study of Vietnam veterans and their
families in order to make — to do the kind of job which we want to do and which
we believe that veterans and the citizens deserve.”
M.
STOTO: Okay. Thank you.
Joel would like to make a couple of remarks in response.
J.
MICHALEK: Your points were well
taken. I just want to point out that
the concept of more than one control group and which control group to choose
was considered in 1975 and 1976 when the study was conceived. We were originally considering a control
group of Air Force personnel stationed in Europe and also control groups who we
have today who are stationed in Southeast Asia.
So
all of the issues you mentioned around the table and they were discussed many
times in 19 — between 1976 and 1980 by ourselves and our peer review panel of
the National Academy of Sciences, and in the Armed Forces Epidemiological Board
and the University of Texas Scientific Advisory Board. This was a very painful discussion because
obviously, we had a budget limitation.
The study would be three times as big if we had, you know, multiple
times larger if we were able to get what we would’ve really wanted, which was
multiple control groups.
We
realized we could only have one control group and we also realized that yes
indeed, there may have been exposures in Southeast Asia by itself regardless of
Agent Orange. And that’s why the final
decision was made to choose the control population we have today, which are
those stationed in Southeast Asia. And
every point you’ve made is well taken, the technical points you’ve made. I guess that’s all I had.
M.
STOTO: Okay. Thank you.
I mean, you know, we have to bear in mind that our job is to be an
advisory panel on the study that exists and, you know, what should’ve been done
is an interesting question. What might
be done is still — I mean, it’s still possible to do some of these things. And I think it’s important that
organizations like the VVA and — is continuing to raise those issues, but it’s
fundamentally not a job of our Committee to resolve those.
R.
WEIDMAN: Mr. Chairman, may I make
just one point for the record?
M.
STOTO: Sure.
R.
WEIDMAN: When I said it was my
criticism of the VA was not of the particular sector. I think he’s getting — I think he’s getting bad advice and poor
service from certain elements within the Veterans Health Administration, so we
continue to have confidence in this Secretary.
We do not have confidence in the people who are not serving either he
nor the veterans they’re sworn to serve well.
M.
STOTO: Thank you. I think that we will extend the invitation
again to Dr. — to Mr. Principi to send a representative to our November meeting
and see where that stands. Hopefully,
things will have been resolved by then.
But if not — and if so, we’ll hear about how they’ve been resolved. Otherwise, we’ll keep the issue on the front
burner. Okay. Are there — anyone else like to make a comment? Rick?
R.
WEIDMAN: May I just make one
suggestion in regard to your next meeting on November 19th?
M.
STOTO: Yeah.
R.
WEIDMAN: And that is to think about
requesting of the Secretary and of the VA to have meeting space in 810 Vermont
Avenue as a courtesy between departments and in order that more people are more
likely to attend than journeying out here trying to find where Fisher Lane is,
much less this particular building. I
went to the main building before I ended up here.
And
also at that time, then asking the Secretary or his direct representative to speak. If you’re in the same building, you’re much
more likely to have high ranking representatives of the VA attend this
meeting. Given that it’s on a Friday,
and it’s at that particular month of the year and at that particular time of
the year, I do not believe that there won’t be a suitable meeting room with —
that’s miked, et cetera, available within the headquarters building of
the U.S. Department of Veterans Affairs.
M.
STOTO: We’ll consider that. I’m not sure what are — what are the
logistics involved there, but yeah.
Okay. Thank you. Other comments? Well, let me thank again everybody on the Committee for their
reviews, for the people from the Ranch Hand Committee. Oh sorry, David.
D.
JOHNSON: One thought I’ve had as
we’ve heard — we heard discussions about taking this data and using it for
various other studies in the future. I
— this — we don’t want to forget the importance of appropriate consent from
those. I know this has been covered to
some degree and it sounds like it’s pretty well covered. But you don’t want to forget that at any
time you go to use this data for other — things other than what it was
initially intended to be used for.
M.
STOTO: Yeah. I think that could be quite a thorny issue.
D.
JOHNSON: Right.
M.
STOTO: I think that ...
D.
JOHNSON: It has to be looked ...
M.
STOTO: But that it’s quite
explicitly on the National Academy of Science’s agenda if they get that study
to do.
D.
JOHNSON: Right. Okay.
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.]