[CONVENE 8:19 A.M.]
M.
STOTO: Good morning, everyone. I’m Michael Stoto, the — this is my first
time as Chair of this Committee, although I’ve been on it. I’m pleased to be here. Thanks to everybody on the Committee for
joining us: to the people from the Air
Force and the staff, and the staff of the Committee at the FDA for coming, and
other guests. We — this is the first
round of reviews of the chapters from the 19 — 2002 examination and we look
forward to seeing that material.
I
think that what we should do is begin by having the Committee members and then
the others introduce themselves so we know who's here. We’ll talk a little bit about the agenda,
and some housekeeping issues and then we’ll go into the — we’ll go into the
substance of the meeting. We’ll have a
presentation by Joel Michalek; we’ll talk a little bit about a meeting that he
went to. And Colonel Berry will speak
about some thoughts about what might happen next with these data.
So
I’ll start the introductions. I’m Mike
Stoto. I’m a statistician and
epidemiologist. I work at the RAND
Corporation now in the Washington office and I'm also on the faculty at the
Harvard School of Public Health in biostatistics. I have been involved with the Ranch Hand Study in a number of
ways over the years. For a long time, I
worked at the National Academy of Sciences and was the Study Director for the
first round of studies that the Institute of Medicine did about Agent Orange —
health effects of Agent Orange. And in
that — in that context, we looked — obviously looked very carefully at the
Ranch Hand Study. So Ron, do you want
to go next?
R.
TREWYN: Sure. Ron Trewyn, Kansas State University. I was involved on the Ranch Hand Study from
1995 to 1999. They made sure when my
term was up, they got me off the Committee for raising too much cane and
whatnot, but I guess then a couple of years after that decided that having
somebody raising cane was okay and brought me back on. So here I am and I’ll try not to cause too
much trouble today after we get past Chapter 1.
M.
STOTO: Thanks, Ron.
D.
JOHNSON: Dave Johnson. I’m with the Florida Department of Health. I’m the Executive Medical Director for the
Division of Environmental Health at headquarters in Tallahassee. This is my first involvement with the Ranch
Hand Study.
S.
LEFFINGWELL: Sandy
Leffingwell. I’m an occupational
physician formerly with CDC, now with a consulting group, HLM Consultants, near
Atlanta
M.
STOTO: Let’s see. Paul, do you want to go next as a Committee
member?
P.
CAMACHO: I’m Paul Camacho. I’m from the William Joiner Center at U
Mass-Boston; I’m a sociologist.
E.
HASSOUN: I’m Ezdihar Hassoun from
the University of Toledo, College of Pharmacy, Associate Professor of
Toxicology.
J.
MICHALEK: Hi, I am Joel Michalek,
Principal Investigator of the Ranch Hand Study; been with the program since
1978. Thank you.
M.
STOTO: Len?
L.
SCHECHTMAN: I’m Leonard
Schechtman. I’m with FDA’s National
Center for Toxicological Research. I’m
the Executive Secretary of the Ranch Hand Committee.
M
STOTO: And you're going to keep
Paul under control today?
L.
SCHECHTMAN: That is correct. Right.
M.
MONTGOMERY: I’m Margaret
Montgomery. I work at — on Ranch Hand
at Brooks City-Base.
J.
ROBINSON: I’m Julie Robinson. I’m the Branch Chief for the Air Force
Health Study at Brooks City-Base.
D.
BERRY: I’m Dr. Dan Berry, Colonel
Dan Berry. I’m at Brooks and I’m the
Division Chief for the Aeromedical and Medical Information System Division and
Ranch Hand comes underneath my division.
R.
ATKINSON: I’m Dr. Richard
Atkinson. I’m Director of the Obesity
Institute here at the MedStar Research Institute in Washington and have worked
on virus-induced obesity, which we’ll be talking about later.
M.
OWENS: I am Maurice Owens. I am the Program Manager of the Ranch Hand
support contract. I'm with Science
Applications International Corp.
M.
BLANCAS: I’m Manny Blancas. I’m a contractor in support of this whole
Program Management at Brooks City-Base.
J.
MINER: I’m Jay Miner. I also work in the Human Assistance Program
Office, contractor support. In my
previous life, I was one of — one of the principal investigators for this study
when I was on active duty.
W.
GRUBBS: My name is Bill
Grubbs. I work for SAIC; I work on the
statistics for the report here.
M.
YEAGER: My name is Meagan
Yeager. I also work for SAIC in
technical support.
K.
CAMPBELL: I’m Kim Campbell. I’m a Management Specialist for the National
Center for Toxicological Research.
M.
STOTO: Okay. Well ...
L.
SCHECHTMAN: The note taker.
M.
STOTO: And the note taker?
N.
RIVERA: I’m Nadine Rivera. I’m your writer/editor.
M.
STOTO: And Nadine did an excellent
job, I should say, of the minutes for the last meeting.
L.
SCHECHTMAN: Yeah.
Approval of Previous Meeting Minutes
M.
STOTO: Actually maybe, you know, we don’t have it
on our agenda, but I suppose that we have to approve the minutes from last
time. Are there copies of them? They were distributed, right? And I know that I reviewed them and sent
comments in, and we asked Dr. Michalek to review them and send comments. And I reviewed his additions, which I think
helped quite a bit in that. Did anyone
else have comments on the minutes?
R.
TREWYN: The changes were brilliant
and I move approval.
M.
STOTO: Okay. Is there a — Dr. Trewyn — is there a second
to that motion?
S.
LEFFINGWELL: Second.
M.
STOTO: Dr. Leffingwell. Okay.
All in favor say “aye.”
RHAC
MEMBERS: Aye.
M.
STOTO: I think it’s — I think it’s
unanimous. Okay. Thank you very much.
L.
SCHECHTMAN: Mike, if I can just add
a comment. I think we’ve finally turned
a corner ...
M.
STOTO: Yes.
L.
SCHECHTMAN: ... regarding the
minutes ...
R.
TREWYN: How many years?
L.
SCHECHTMAN: ... and the reporting
requirements. Yeah, I guess it’s a lot
of years. So, and we thank Nadine for
her outstanding efforts and we'll look forward to her working with us again in
the future.
M.
STOTO: It is a — it is a real
challenge, I mean, the technical material, the wide range of technical material
that’s covered. To reflect that
effectively is a challenge and it was done quite well I have to say. Okay.
The
agenda today will be primarily devoted to reviewing chapters; this is the first
of three rounds of reviews. We have
more of the kind of background chapters as opposed to the results chapters, but
we do have two results chapters to look at this time. So I think it's — we’ll be able to sort of learn how to do this
as a group. And so when we get to the
real meat of the substance — the substantive chapters in the next meeting, we
will have — be able to do that more effectively.
Before
we have the two reports, two — I guess two housekeeping issues: one is that the agenda that was prepared
doesn’t include a time for public comment, but we have — but we’re required by
law to do that. So I would say that we
tentatively plan to do that at the end of the agenda at around 3:00. I’d like to ask if there’s anybody here who
would like to comment now? I don’t see
anybody who’s not associated with the staff or the Committee, but we'll just
make that — that’ll be our plan. If
there’s — if there’s someone who wants to comment, we’ll — 3:00 will be the
time to do that or earlier if we get through the material earlier. Okay.
Len, do you want to talk about the dates?
L.
SCHECHTMAN: Just one housekeeping
item: we have now a need to nail down
the date for the next meeting, which will be in the month of September. Dr. Michalek indicated that there was an
upcoming important meeting that he and perhaps other members of the group will
be interested in attending and so that the originally proposed date is no
longer possible.
We
had a couple of responses back to our e-mail requests regarding availability in
the month of September and we need to have a look at our calendars today, now
if possible, so that we can in fact nail down that September date. We can't push it off later than September
because then the chapters start backing up on us and we have a schedule in
which we need to get these finished and out the door. So where are we in terms of availability? Who did respond by the way?
P.
CAMACHO: I thought I did.
L.
SCHECHTMAN: Okay. And do you remember the date you gave?
P.
CAMACHO: I said whatever date you
want.
L.
SCHECHTMAN: Good.
P.
CAMACHO: They're all bad.
L.
SCHECHTMAN: Good. They’re all bad. Okay.
P.
CAMACHO: A Friday or a Monday is
easier; Fridays actually are very good days.
L.
SCHECHTMAN: Okay.
M.
STOTO: What’s the currently
scheduled date that we have to move it away from?
P.
CAMACHO: I think the — I think it
was the 8th.
L.
SCHECHTMAN: Yeah. It was originally, I believe, also the 8th
of September. Isn’t that right,
Joel? Right.
M.
STOTO: Okay. So that was ...
L.
SCHECHTMAN: And that was a
Wednesday. So there are some religious
holidays in the month of September which we have to work around. There’s also Labor Day, which is the 6th
of September. Well, yes?
M.
STOTO: I recall that when we talked
about scheduling last time, there are certain days that people couldn’t make
it. And presumably, the day of Friday,
the people who ...
P.
CAMACHO: Yeah. Somebody can blame me. I selected Friday because I also teach
nights and especially in September — well, like this is the end of April. I've got finals, and the review for finals
and students go nuts. That’s why I was
the guy who selected the Friday.
L.
SCHECHTMAN: Right.
P.
CAMACHO: I had my choice, so I
don't really have to go along with what everybody else says.
L.
SCHECHTMAN: Right.
M.
STOTO: Because I think — I think
...
P.
CAMACHO: Friday is a nice day for —
actually, a nice day for me.
M.
STOTO: Yeah, but I think that the
people who aren’t here today always can't come on Fridays.
L.
SCHECHTMAN: Right.
P.
CAMACHO: Yeah.
L.
SCHECHTMAN: I think actually at the
previous meeting, we agreed that to rotate it:
some Fridays and some ...
M.
STOTO: Right.
L.
SCHECHTMAN: ... what were they —
Tuesday, Wednesdays? — at the time, so ...
P.
CAMACHO: That's why we selected the
Wednesday the 8th.
L.
SCHECHTMAN: The Wednesday the 8th.
M.
STOTO: Well, how about one week
after that — Wednesday the 15th?
L.
SCHECHTMAN: Okay. That doesn’t work because of a religious
holiday conflict. There’s also the 22nd
and the 29th of September, which are Wednesdays.
M.
STOTO: Either one of those is okay
with me. Do people have their ...
L.
SCHECHTMAN: No. The 22nd of September is a
possibility. Actually, that may be
preferable because the next week is getting real close, that much closer to the
next meeting. So if ...
M.
STOTO: Yeah.
L.
SCHECHTMAN: ... September 22nd,
Wednesday, is good, we can at least, as of today, nail that down. And if you find when you get back to your
respective offices that there is a problem, we'll renegotiate.
M.
STOTO: Okay. So the people here don’t have a problem with
that and the people who can’t come on Fridays hopefully will have ...
P.
CAMACHO: We’ll work it out.
M.
STOTO: Is that okay?
S.
LEFFINGWELL: Fridays are good, but
not every Friday.
R.
TREWYN: Well, that’s what they’re
saying.
M.
STOTO: No, I’m saying the people
who aren’t here have a problem with Friday.
R.
TREWYN: So ...
M.
STOTO: Yeah.
R.
TREWYN: ... the 22nd
works for me.
M.
STOTO: 22nd? Okay.
Well, let’s tentatively say that and you can get that out to everybody
just to check it, including the people who aren’t here. That would be good. Okay, well good. Anything else? Well then,
Colonel Berry, would you like to come and — up to the table and ...
D.
BERRY: I sure would. Actually, I think that I can come over here
where the computer is ...
M.
STOTO: Okay.
D.
BERRY: ... and kind of turn slides
at the same time.
M.
STOTO: Oh, I’m sorry. No, Dr. Michalek is next with the brief
report according to the agenda.
J.
MICHALEK: Actually, this is real short. Mike, when was that meeting? Was it last month or six weeks ago? Mike — Dr. Stoto and I attended a meeting in
Washington, DC sponsored by a medical institute. Do you remember the name of that? U.S. Medical ...
M.
STOTO: U.S. Medicine Institute.
J.
MICHALEK: U.S. Medicine
Institute. The title was the — “What is
the Value of Long-Term Studies?” And it
was a very well administered panel discussion of experts in the field and many
high-ranking people from the Department of Veterans Affairs and Department of
the Army. And I heard nothing but
enthusiasm regarding long-term studies, of which this is a prime example. And I heard comments too about the Ranch
Hand Study and I heard absolutely nothing negative about the Ranch Hand Study;
everything was positive. And those
comments were coming from very high-ranking people at the VA.
And
I think the bottom line was probably well stated by the Surgeon General of the
Army, General Peake, who was there. And
he said that studies like the Ranch Hand Study should be part of our regular
routine of business in the Department of Defense. And I thought that was a remarkable statement coming from the
Surgeon General of the Army and so I had a great time. And maybe Mike, you could add something to
what I said?
M.
STOTO: Well, I thought it was an
excellent session. I — it turns out I
was the one who made the presentation about the Ranch Hand Study and it was a
little uncomfortable for me to be speaking about somebody else's data, but I
...
J.
MICHALEK: You did a great job.
M.
STOTO: Thanks. And I think that what Joel said was right;
it was a tremendous amount of support and people seeing the value of studies of
this sort. Whether that makes a
difference in the end, who knows?
J.
MICHALEK: Yeah.
M.
STOTO: But it’s good to know that
the support is there.
J.
MICHALEK: I think, by the way,
there were some Congressional staffers there at my table anyway and I heard
similar words from them from different committees of Congress, so I was
surprised. I mean, I just sat back and
relaxed and it was — it was fun to watch Mike present our material instead of
me present it and I enjoyed it. And so
— and I enjoyed watching the reaction of the audience too, which was all
positive, so it was a gratifying experience to say the least.
M.
STOTO: I tried to watch Joel’s face
in case I was making mistakes, you know. Okay.
Thanks a lot. Colonel Berry?
J.
ROBINSON: Dr. Stoto, I’d like to
make just a couple more introductory comments ...
M.
STOTO: Okay.
J.
ROBINSON: ... regarding Colonel
Berry. He's already mentioned that he
is the Division Chief for the Aeromedical and Medical Information System
Division under which the Program Management for the Air Force Health Study
resides. Besides being a physician,
he’s also an engineer. He has a Ph.D.
in biomedical engineering and a master’s degree was in biomathematics, so
obviously a lot of experience with biostatistics. As a matter of fact, his thesis was a biostatistical analysis of
cardiac disorders. He’s Board certified
in two specialties: preventive medicine
with a sub-specialty in aerospace medicine and also family practice. He’s been very supportive to our program
over the years and I’ll turn it over to you, sir.
D.
BERRY: Thank you very much. Dr. Stoto, members of the Ranch Hand
Oversight Committee, ladies and gentlemen, thank you very much for having me
here today. I really appreciate
this. As Julie mentioned, I am the
Division Chief for the Aeromedical and Medical Information System Division. We develop new medical equipment; we develop
new computer information technology, computer programs. We also have some studies; we have four
studies. One of my studies is the West
Point Study; then I’ve got the Air Force Special Operations Command Crew
Selection Study; the Air Crew Medication Study; and the Ranch Hand Study.
Three
years ago when I came — and by the way, you may want to just turn around for
the Committee members because it’ll be easier for you to see right here behind
you. Unfortunately, you’re so close to
it, it may be difficult to see. But I
encourage you to take — make yourself comfortable, be able to take a look right
here.
About
three years ago, I came to the Ranch Hand Study and really have had a very
pleasurable time working with the people on the Ranch Hand Study. I’ve come to enjoy the veterans, the people
who run the program, the people at SAIC and Scripps, the people of the Surgeon
General's staff that work on Ranch Hand.
About
two years ago when we were getting ready for the last cycle of physical exams,
I was one of the individuals who went to La Jolla and had the entire battery of
tests done on me prior to the Ranch Hand veterans arriving, thus ensuring that
a comprehensive and high-quality exam was done for all of our
participants. I also participated in
the actual exam process as a health monitor and as a principal investigator for
the physical exams at Scripps.
Ranch
Hand successfully completed the last physical exam study on May 5, 2003. That’s 21 years: 13,183 physical exams, $125.9 million, 21 years, 42,953 records,
26,500 x-rays, 66,597 specimens. The
Ranch Hand Study is recognized as the world's premier epidemiology study with a
higher rate of follow-up and more data points than even the world famous
Framingham study. But not only is the
science good, but the program has been run well.
The
Ranch Hand Oversight — I mean, sorry — the Ranch Hand Program Element Monitor
at the Surgeon General’s Office sent congratulations to the study team. Out of the 187 research and development
projects, there was only 24 that met the program or exceeded the program goals
and Ranch Hand was one of those; $125.9 million spent on the Ranch Hand Study
has purchased these exams: the 13,000
physical exams, the records that I just mentioned, the specimens and the other
data. This data is valuable.
Recently,
SpecPro indicated that a pharmaceutical company would pay about $400 million to
get their hands on a long duration program with the amount of data that Ranch
Hand has. While you and I realize the
value of the Ranch Hand data, many people do not. The Ranch Hand Study participants are very concerned about the
termination of this study; that they feel that they have donated not only their
time, but a part of themselves to this study.
When
I was out there during the Ranch Hand physical exam cycle, they would come up
to me between their tests and they would talk to me about their concerns with
the valuable data being lost or destroyed.
They want this data to be used.
As I listened to them, I also became convinced that it is up to us to
ensure that this valuable treasure is not lost or destroyed, but is used to
benefit others.
Currently,
Congress is looking for where to place the data. They have designated the National Academy of Sciences to do the
study. This study will only address
where the data will go, not how the data will be used. Remember, the data specimens are
perishable. Even with refrigeration,
the items will not last forever. Thus,
it is important to consider that the clock is ticking. This treasure will not last forever. The other concerns for the time is
momentum. If nothing is done with the
data for the next five or so years, people will forget about it. It will likely become a buried treasure
never to be used by — to benefit anyone.
That would be a real shame.
But
from even a more practical standpoint, if no study is started on the data
before it is stored with another agency, it will probably just be stored
forever or at least until the samples deteriorate or money for storage is
terminated. Thus, the clock is ticking
down to the date of September 30, 2006.
If no practical use can be found by then, the chance of putting Ranch
Hand Study data to practical use becomes reduced significantly.
The
best way to ensure that the data will be used in the future is to do a small
demonstration study to demonstrate the value of utilizing the Ranch Hand
data. This demonstration study would be
the “foot in the door” to open the way for more studies. We need to find a demonstration study that
would not destroy or use up the data; that means that the study should mostly
use the information stored on the computers and in the records or be able to
take a very small fraction of a specimen while preserving the greater majority
of the specimen.
The
demonstration project should not be funded by Ranch Hand money. The project should be of value to the
veterans, to the military and to all of society. The project should have appeal both to Congress and to
society. If such a project could be
accomplished, it could very well lead to future use of the Ranch Hand data either
through private funding or through Congressional support. It would also provide satisfaction to the
study participants to know that they were able to contribute to a worthwhile
cause and that their data was not lost or destroyed.
There
is a worldwide epidemic of obesity.
More people are fat today than ever.
In the United States, the prevalence of obesity has doubled in adults
since 1980 and has tripled in children over approximately this period. About 31 percent of all U.S. adults are
obese with a BMI of 30 kg/m2.
This slides shows that we are in the middle of an obesity epidemic. The trend of obesity continues to rise and
there’s no leveling off of the curve.
The
long-term implications of obesity on health, including cardiovascular health,
diabetes and cancer, is significant and leads to an increase in federal
spending on health care for military personnel and veterans. In the United States, obesity caused about
$100 billion a year; 51.6 percent — I’m sorry — $51.6 billion is in direct
health care costs. Obesity is now
listed as the number one cause of preventable death. Sorry, just one moment here; I’m going the wrong direction on the
slides. In fact, it even surpasses
smoking as a cause of death.
But
is obesity truly preventable and what are the causes of obesity? Is it eating too much? Is it eating the wrong foods? Is it not getting enough exercise? Up until about the last ten years, people
generally believed that it was simply an equation of calories in minus calories
out. If you eat too much and you
exercise too little, then you have an excess of calories and you gain
weight. If you eat less and exercise
more, then you lose weight. That
sounded very good, but unfortunately, it turned out to not be quite that
simple.
In
the court system, the health insurance industry has won repeatedly the right to
not have to pay for weight loss programs.
The reason they have won is that they have proved that no dietary
program or exercise program causes long-term weight loss. People eventually go back up to their set
point. Studies have shown that even
with reduced food intake and increased exercise, that the weight starts to come
back and the body’s metabolism adjusts to the new conditions.
Well,
what other factors are associated with the cause of obesity? Is it stress? Is it neurotransmitters, eating disorders, changes in the food we
eat from the fast food industry, a different lifestyle where we work at a desk
rather than manual labor? Is it
genetics? Well, the answer to all of
these is yes, but this still does not explain the recent epidemic pattern that
is emerging in obesity prevalence worldwide.
The
cause of this rapid rise in prevalence of obesity across the world is not
clear. The usual explanations of
increased food intake and decreased activity seem inadequate to explain the
simultaneous increase in many countries regardless of the stage of economic
development. The World Health
Organization and the International Obesity Task Force have documented that the
increase in prevalence of obesity in different countries have not been uniform
over time.
For
example, England had a rise of approximately 125 percent in obesity from 1980
to 1995, but Sweden had a rise of only 6.5 percent from 1980 to 1990. Since 1990, obesity has increased dramatically
in Sweden. China had a prevalence of
obesity of only 1.3 percent in 1992, but also had a dramatic increase in the
last ten years. Paraguay and Panama
currently have prevalence of obesity greater than in the United States despite
levels of development that are less than in the U.S. now or in the 1980s. Such a spotty record of increase in obesity
do not fit the simple behavioral pattern, but could be compatible with an
infectious etiology.
There
are seven viruses reported to produce obesity in animal models. Four of the seven produce damage to the
central nervous system, but three adenoviruses have been shown to produce
obesity. And preliminary evidence
suggests that they may be — there may be a peripheral mechanism of action. The SMAM-1 is an avian adenovirus that
produces obesity in chickens and is associated with obesity in humans. Human adenovirus 36 is of particular
interest as it has been shown to increase adiposity and paradoxically reduce
serum cholesterol and triglycerides in chickens, mice and monkeys.
Studies
in humans show that individuals who have antibodies to adenovirus-36 are
heavier and have lower serum lipids.
The prevalence of antibodies to adenovirus-36 is 30 percent in obese
individuals in the U.S. and 22 percent in individuals in Australia, while only
10 percent of non-obese subjects in the U.S. were antibody-positive for
adenovirus-36. In twin pairs discordant
for adenovirus-36 antibodies, the antibody-positive twins are heavier and
fatter than the antibody-negative twins.
A
retrospective study of rhesus monkeys — and by the way, these aren’t rhesus
monkeys; this is the picture I could find — a retrospective study of rhesus
monkeys was performed at the Wisconsin Primate Center using an informational
database on serum storage banks similar to the databases stored in the Ranch
Hand II program by the way. In these
monkeys, weight was measured and blood was drawn every six months for seven
years. All of the monkeys became
adenovirus-36 positive over the seven years.
Weight decreased in the year prior to seroconversion by 0.04 kg, but
went up by 1.8 kg from baseline after seroconversion. Serum cholesterol went up by about 5 mg/dL in the year before
seroconversion and decreased by 35 mg/dL or about 23 percent afterwards.
If
you inject adenovirus-36 into animals, they become infected and they gain
weight. However, you cannot ethically
inject humans with adenovirus-36 to infect them so as to prove the
adenovirus-36 causes obesity in humans.
To demonstrate the weight gain in humans, you would need to start a
study with people who have been — who have never been infected with
adenovirus-36. You can test for
antibodies to adenovirus-36. If the person
does not have any antibodies to adenovirus-36, then you know that they have never
been infected.
You
could then take this group and measure their height and weight and calculate
their body mass index. Then every few
years, you could take a blood sample to test to see who has become infected
with adenovirus-36 by natural means. You
would know that they had become infected if the antibody test had turned
positive. You could then compare how
much of their weight changed after being infected as compared to those who had
not become infected.
A
study like this would take several years, however, the Ranch Hand II Study
already has all of this data. A
demonstration study could be done on this data by reviewing the records for
height and weight and simply testing a small scraping of fresh frozen plasma
specimens. Thus, the demonstration
study would assay for virus antibodies from all Ranch Hand II time periods and
correlate the changes in weight, serum lipids and other variables that are
contained in the database.
Dr.
Richard Atkinson is here with us today.
He is the leading researcher in the field of adenovirus-36 and
obesity. He is willing to work with us
to help us with the demonstration project.
His study would be very straightforward and would use only a small
scraping off the fresh frozen plasma; would gather weight and lab data from the
records; and would thus leave the Ranch Hand database intact for future
studies.
If
this study demonstrated conclusively that adenovirus causes obesity in the
population that has been infected, it would most likely lead to a vaccine
development program for adenovirus. An
adenovirus vaccine would prevent adenovirus-induced obesity. While adenovirus-induced obesity is — only
represents a part of the total number of people with obesity, being able to
reduce this one form of obesity would be a great benefit to the military and to
society at large. The significance is
tremendous.
The
potential for the development of a vaccine for adenovirus-36 which would
prevent a percent of all obesity in the military as well as in the civilian
world would improve military readiness, reduce the cost of military weight
management programs, and decrease the cost of the taxpayer money supporting
military health care costs that are directly related to obesity.
SpecPro
is an Alaska Native corporation and it has requested funding for this study
from Congress. Thus, no funding will be
needed from the Ranch Hand Study dollars.
This study will benefit society as obesity is a growing concern that
affects a large portion of our society.
Both our society and the military would benefit greatly if this study
can be used as the impetus to develop a vaccine for adenovirus-36, which would
prevent a certain percentage of obesity.
This study would be very rewarding to the Ranch Hand Study participants
who desire to see their data used to benefit others.
Finally,
this study would benefit the Ranch Hand program by demonstrating the value of
using the study data for future health science studies, increasing the
probability that this data will be used in the future and not lost to eternal
storage or destruction. In order to do
this study, we will need for Congress to approve the funding; the Institutional
Review Board — IRB, that is — to approve the protocol; and for the Ranch Hand
Oversight Committee to approve the study.
Since
I am a member of the Brooks IRB, and have discussed the concept of this
protocol with the committee already and the IRB members are in favor of this
study, I do not see any problem with getting the protocol approved by the IRB. SpecPro has been very successful in getting
Congressional funding. SpecPro, by the
way, is the company that already works with Ranch Hand and they do all the
coding. They work right there at Brooks
City-Base. Even though they’re an
Alaskan company, they’re right there with us and I would give their chances of
getting the study funded about 70 percent.
Thus,
for this demonstration project to be a success, what I need from you is your
approval to proceed with the study to demonstrate the value of the Ranch Hand
Study data, to prevent it from being lost forever in a warehouse never to be
used to benefit others. We know how
much the participants of the Ranch Hand Study want their data to be used
because of all that they have given to this study over the years. Therefore, we request your reproval — your
approval of this study contingent upon Congressional funding. And I'd like to open it up for questions at
this time.
M.
STOTO: Okay. Thank you very much. Do people on the Committee have questions or
— about the presentation? Paul?
P.
CAMACHO: What’s the committee? Who — what Congressional committees did you
— have gotten aware — or staff people are already aware of this?
D.
BERRY: Actually, right now what’s
happened is SpecPro has gone to their senator from Alaska who they’ve worked
with before. They’ve gotten
Congressional funding for the Ranch Hand program before and they’re going
through the same route before. And so I
believe it’s the Senate Appropriations Committee who they’re working through —
Senator Stevens.
R.
TREWYN: Therefore, I’d give it more
than a 70 percent chance.
M.
STOTO: Okay. Sandy?
P.
CAMACHO: Yeah, but they have to
have a — the appropriations of the money is one thing and the authorization is
another. So if you’ve got a — like
Veterans Affairs Committee would say we would like to see this done and we
appropriate $10 million. Then they go
to appropriations and under the sector of appropriations, the sub — appropriate
subcommittee would say, “Okay, we're kicking in the money for it.” So authorization is one thing; who’s the
authorizing committee?
D.
BERRY: I don't have that
information. However, I do know that
SpecPro is ...
P.
CAMACHO: Armed Services.
D.
BERRY: Pardon?
P.
CAMACHO: It could be Armed
Services. It could be anybody really,
but ...
D.
BERRY: It could — it could be.
P.
CAMACHO: ... Armed Services or
Veterans Affairs would be two targets.
D.
BERRY: The thing about it is, is
SpecPro is really an expert on this. As
being a military member, I’m not allowed to work with Congress or lobby
Congress for money or anything like that so I have really stayed out of the
part of how they’re going to get funding.
However, I do know that they have been extremely successful in the past
in getting funding. Does anybody else
here have any further information as far as what committees it goes — what
their work — what SpecPro’s working through?
I don't have a good answer for you on that one.
M.
BLANCAS: The only thing I can add
is they were successful in getting ...
L.
SCHECHTMAN: Microphone, please —
mike.
N.
RIVERA: State your name, sir. Thanks.
M.
BLANCAS: The only thing I can add
is they were successful in getting $1 million-plus for this particular program
when we started the Cycle 5 exam because ...
W.
GRUBBS: Cycle 6.
M.
BLANCAS: Cycle 6 exam and the
proposals came in a little bit over our budget. And we were found ourselves in a shortage of funds and SpecPro
went through their channels through Senator Stevens and was able to get $1
million-plus. So I know personally they’ve
succeeded in the past.
W.
GRUBBS: State your name.
M.
BLANCAS: The name is Manny Blancas.
P.
CAMACHO: I know it’s come — going
to come back. They went — they talked
to — I remember when that occurred and we, individually, people went and talked
to like ranking member Lane Evans and went — and to Pat Ryan and to Chris
Smith's committee over there. So, I
mean, if you said, “Well, is anyone on the Committee willing to help to the
degree that it’s all ethical, legal, to help?”
Yeah, fine. But I’ve got to —
we’d have to know, you know. I think we
can — I can pick up a phone and talk to some staff people out of the Veterans
Affairs Committee and probably get through to Lane Evans; you can do any of
this.
D.
BERRY: Outstanding.
P.
CAMACHO: But you have to have it —
you know what I mean? The Committee ...
M.
STOTO: Well, let me ...
P.
CAMACHO: I don’t know what you can
do ...
M.
STOTO: I guess I’d like ...
P.
CAMACHO: ... there ethically and
all of that. What’s our role?
M.
STOTO: I'd like to suggest that
that probably is not our role to be — to be lobbying for or against this with
the Congress. I think that what we
should be discussing is the scientific merits of this. Yeah.
I’ve got a couple of questions I’d like to raise about it. Let’s hear the other — Sandy, do you want to
...
S.
LEFFINGWELL: I wondered — this is a
small scraping, but what fraction would that be of the stored plasma? How many such small scrapings in successive
studies could this system sustain?
D.
BERRY: Could Dr. Atkinson answer
that question for us, please?
R.
ATKINSON: Yeah, Richard
Atkinson. I talked with George
Berberich from SpecPro who I guess knows about these samples. And just a couple of things: we were a little bit concerned about trying
to scrape the samples because it’s possible that the — there may be different
layering and so forth. So my suggestion
would be that the samples be thawed, but as I understand it, I don't know
exactly how much it is. But it’s — I
assume they probably drew a couple of, three red-top tubes and you've got
somewhere between 2 and 20 milliliters of plasma.
To
do our assay, we would ideally like to get about 500 microliters of
plasma. We can probably — or serum,
either one — we could probably do it with about 300 microliters. So it’d be a fairly small fraction of this
and we've submitted a grant that if it gets funded, we’re going to develop an
assay that would use even smaller quantities probably in the range of 10 or 20
microliters. But again, Dr. Berberich
and I talked about if these samples are going to be used in the past, you don’t
want to be thawing them every time somebody’s got a good idea.
But
on the other hand, they’re — if they're currently stored in a big — as one
tube, or flask or whatever — it would make a lot of sense to when the very
first time they're thawed, to aliquot them into a bunch of probably
half-milliliter tubes increases your storage space a bit. But then if anybody comes along, they can
just get one tube and it's a much more efficient process. So that would certainly be the way that I
would suggest, and as I say, we could get by with a minimum of probably 300
microliters and we’d really like to have 500.
M.
STOTO: Ron, did you want to make a
comment?
R.
TREWYN: Yeah, I just want to
mention that I know that the National Cancer Institute over the years had
funded a lot of tumor banking programs and really moved away from that because
what was happening was nobody was ever using the specimens. And I think clearly these specimens are there
and one of the key elements really will be demonstrating some use, getting some
use of these because eventually, they won't be any good. And what had happened in these old programs
is they’d wind up just having to dispose of them and this stuff is there. I think figuring out a pilot study certainly
makes a lot of sense.
M.
STOTO: Okay. Paul?
P.
CAMACHO: This still brings up a
big, general — very general issue. Is
it the role of this Committee not to approve or disapprove of any particular
study, but to say we can — we approve or disapprove of the concept of continued
use of this data? I don’t know for sure
what the Committee’s position or individuals’ positions are. As a member of the Committee, I think that
the data should be available down the road.
I as an individual have mentioned this to different veterans groups that
I know, to people on those committees that I mentioned. But it's still left — it still leads to that
issue about the privacy issues. And a
couple of meetings back about two years ago, we had a ...
M.
STOTO: Yeah.
P.
CAMACHO: ... big discussion of
that.
M.
STOTO: I want ...
P.
CAMACHO: And I don't know what our
position legally is in that or ethically is.
But can this Committee as a committee make a general statement to the
public and to the Congress that we think the data should be — you know,
everything we — should be done to make the data available for appropriately
reviewed studies, et cetera?
M.
STOTO: Well, I’d like to pick up on
that; I — and to suggest a framework for thinking about this. I mean, I think that in a lot of respects,
this looks like an excellent opportunity and it’s something that’s consistent
with what a lot of us want to do. So we
need to take it very seriously. On the
other hand, I've got some concerns about this.
I guess the first one I think we have to think about is what is our
charge relevant to this issue versus the National Academy of Sciences’ charge?
First,
we're an advisory committee, not an oversight committee as Colonel Berry mentioned. I think that makes a big difference and I’m
not sure we have any charge at all in this.
So I think we need to look at our — at our charter and see what that —
what that is. The other thing is that I
don’t believe that I — that you’ve characterized the National Academy of
Sciences’ committee charge correctly either, but I don't — I don’t — I don’t
have that in my head. So we need to
look at that and to see — look carefully at that.
I
mean, the fact that they're there and are thinking about issues at least very
closely related to this, and I think, I mean, they actually were charged with
something much more closely aligned with what do we do in the future than this
Committee is. So we need to look at that
carefully. I guess the second question
is do we — is doing a demonstration project really the best thing in the best
interest of further use and availability of the Ranch Hand Study or not?
I
mean, you've made a good case for that, but I could also imagine the opposite
case. For instance, we would have to
think through, you know, what would we preclude by doing this study? One aspect of that is the assays that we
were talking about before; how whether — and it would be — would be — would be
lost or things like that. Another issue
would be the informed consent issues.
The participants have given their consent for use in the Ranch Hand
Study, the study of the effects of herbicides.
They’ve
— in the second, in the last round, they were asked about military health
studies. And although you’ve made a
case that this is an issue of interest to the military, I think it really is
broader than that and whether that — this can be considered under that consent
is — needs to be explored. And if they
need to be consented again, what would that mean? I mean, do we want to go back to them every time we want to do a
study? No, almost surely we don't. I mean, can we — can we do a blanket
consent? I mean, there are some
complicated issues there I think that need to be considered and I believe that
will be considered by the National Academy of Sciences. So it may be premature to make a decision on
our hand, on our part before that.
The
other issue I think we need to think about is how the scientific community will
view this. I mean, you know, one way is
saying, well this — I guess the idea of a demonstration project is that this
will show the value of these data. But
if we didn’t pick the right topic, that may not work quite as well. And so I guess that leads to the question of
whether this is the right topic of all the things that were possibly done. Is this — is this the best one; and you
know, I guess how we got to this; whether the — what kind of sample size we'd
need for this? Is this hypothesis
really a viable one? And I’m — I have
absolutely no expertise in that myself.
I don’t know that any of us do.
P.
CAMACHO: But that takes us back, a
little back to the detail; this is where my beef of this is. About three — two or three years ago when we
had a meeting and all those privacy issues came up about what data was up on
the screen through the — through the net, et cetera, my thinking was
that even I don’t — being uncertain what our charge is, at least we should’ve
said or should we still say that there ought to be a general Congressional level
discussion about this?
If
you’ve got a study of $125 million in 21 years, that we should have had people
from a general — to me, that translates as a joint hearing with Veterans
Affairs and Armed Services Committee just laying out all the issues you’ve talked
about. Let them hear about it and down
the road, somebody won’t be able to say, “You guys should've done this or you
guys should've done that.” We’ve raised
the issue as a committee. We suggested
they have some kind of hearing, get experts and arguments from all sides: three, four panels, a hearing; that's
it. We’ve done — in other words, at
least it would get laid out and nobody can say, “You should've done this; we
did that.” I went through this about
two years ago.
M.
STOTO: And isn't that — isn’t that
what Congress actually asked for in the National Academy of Sciences study?
P.
CAMACHO: They sort of did, but I
didn’t — they asked those guys to do a study; I wanted a much more open deal
about it. But that’s the way — I know —
I know — do you think that National Academy of Sciences study will do it?
M.
STOTO: Well, I think it’ll come
closer to ...
P.
CAMACHO: Then our hopes are pinned
on them.
M.
STOTO: I thought we need to — we
need to — we need to look exactly at their charge, but I think it is closer to
doing that than Colonel Berry’s notes suggested of their charge by my
recollection.
P.
CAMACHO: I know they’ve — there’s
one section in that hearing that was like an omnibus bill; it was 108-183. And in that section, there were — I was
looking actually at an entirely other section on that for another issue — but
they’ve got — they have five or six charges, the National Academy of
Sciences. Number five is the one that
provides a window for should other studies be considered and that’s the only
window that I saw.
D.
BERRY: I believe you’re absolutely
correct on that. I think that
basically, they’re going to be saying, “Yeah, we think further studies should
happen.” I don't think that they're
going to be proposing any specific studies coming out of this and the concern
is on timing with this whole thing once — you know, the last physical exam
happened last year. And by the time it
switches over to wherever the National Academy of Sciences says it should go,
even if they should say that they approve that future studies should be done,
there's no studies that's going to be lined up then.
Well,
if you start the process then and it’s still another year from the time, you
know, you get Congressional funding and then it goes another year and
everything, we’re talking about three or four years down the road for the first
study. If you wait that long, chances
are that this is going to happen the same as what’s happened with like the
cancer studies and other things like this:
people don't use it; all this information is wasted; $121.9 million is
wasted. If we don’t get something going
fairly quickly, I’m afraid we’re going to lose this completely.
You
brought up some very good issues, privacy issues. The Institutional Review Board is going to have to look at this
to make sure that the informed consent, whether it can be a one-time consent or
a multi-consent, would be the best. But
they are charged with making sure there's privacy for the patients. And the other issue is, is this the best
study? Actually, what would be ideal in
the future is that once funding comes through, that everybody can submit their
proposals, and that there can be a review board, and the review board can look
through all these proposals and then decide which has the best scientific
merit. And if that could be approved by
the National Academy of Sciences or some type of panel like that, it would be
ideal.
Unfortunately
for that to happen, what you have to have is a funding source that’s already
out there. Congress has like got to
come and say, “Here’s a big pot of money.
We think this is a good idea to go ahead and do studies. Now go out and get the best ...”
M.
STOTO: I don't think that that’s
true. I think that there is a big
funding source down the street here called the National Institutes of Health
that has — what is it — $20 billion a year budget? And they — scientists know that if they can put together a good
proposal that makes sense scientifically, they can get funding from already,
you know, authorized and appropriated funds from NIH.
Now
I think what is likely is that if scientists were aware of this resource that
the — that the Ranch Hand Study data and samples would provide and if those
data could be available to scientists, it would be relatively easy for people
to make a compelling case to NIH and other established funding agencies or
research funding agencies that a project should be funded. And those arguments would be made on
scientific grounds. And so it's not
clear to me that someone has to go to Congress and ask for more money for this.
D.
BERRY: Well, the point I’m getting
at is that if — and I like your idea very much with going to the National
Institutes of Health. I think that’s a
— it’s an outstanding idea and that, it would be a scientist going and asking
specifically ...
M.
STOTO: Exactly.
D.
BERRY: ... just as what we’re
talking about here ...
M.
STOTO: Exactly.
D.
BERRY: ... a scientist coming and
asking specifically. What I was
thinking of in the model was though rather than having a scientist come and
ask, that there be a pot of money that would be already there, whether it’s
National Institutes of Health or whoever has that money, and then we could get
a whole bunch of proposals in. We — I
mean, not necessarily myself, but whoever’s in charge of reviewing that — and
could pick the best project at that time.
But your idea of also having scientists go ahead and present ideas to
the NIH or someone like that, I think, is an outstanding idea too. My concern is, is if something doesn’t
happen fairly quickly, that there's going to be no further research on this.
P.
CAMACHO: So, but it’s unclear who
has jurisdiction over all this data.
And how can they just determine we want to pass it over to NIH? So what's the National Academy’s — they come
out with an answer yet? They were
supposed to have hearings and ...
M.
STOTO: No. They — but that — those are the issues that
they’ll be looking at. I checked with
David Butler yesterday and the funding from VA for the activities of that
committee haven’t — hasn’t yet come through.
And it’s been promised, but it hasn’t been delivered.
P.
CAMACHO: So if you’re sitting on
the — they’re all sitting on the money over there?
M.
STOTO: Yeah, so ...
P.
CAMACHO: That’s the bottom line.
M.
STOTO: But they’re charged with
doing this, if I recall, in a really pretty short time: less than a year, six months even. So ...
P.
CAMACHO: But they’re not going to
go anywhere until the money gets there?
M.
STOTO: Exactly. So I guess that what I — what I would
propose is that we table this until our next meeting in September and that we
look at, you know, what is our charge, and what responsibilities and
authorizations do we have with respect to this versus what the Academy is doing
and, you know, and think about some of these things. I mean, I think it’s a — it’s certainly an opportunity that we
don’t want to dismiss easily and it may be one that we want to take very — take
advantage of.
P.
CAMACHO: Yes.
M.
STOTO: But I think it’s — we’ve got
to be a little bit careful about how we do it, particularly because there’s
this other committee that has a Congressional mandate that’s working in a very
similar area. So maybe at that point we
could — I guess the Academy's thing won't be done at that point, but at least
we’ll know what they’re doing and to what degree they’ll be able to address
this. And maybe we can get someone from
that committee to come and talk about this as well. Joel, did you want to ...
J.
MICHALEK: I just want to say the
obvious for the record. First of all, I
think the concept is excellent and the whole idea is important. And I wanted to warn everyone that if this
is to happen, and I hope it does, that it should and must happen before the
study ends. Because as soon as we — the
people who run the study — walk out of that building, you're going to have
thousands of data sets, tens of thousands of computer programs and gigabytes of
data sitting there which are not documented well. And the people who know where everything is, and can get to it
quickly and get to the job at hand most expeditiously — in fact, are waiting to
do so — are there now today and they won't be there after the study ends. And so this is — there’s a short fuse on
this.
M.
STOTO: But it’s — but it is
two-plus years rather than one-plus or — I mean, it’s not October 1st,
2004.
J.
MICHALEK: That’s true. It’s October 1, 2006; however, there are
many complications, you know. There’s a
number of us who are civil service employees.
We have pension plans. We have
...
M.
STOTO: Yes.
J.
MICHALEK: We have all the
bureaucracy associated with civil service in our — in our — in our tenure. There are contractors there who have similar
things. And it’s a — it’s a, you know,
a complicated picture of what it takes to keep a staff on board and all of that
is starting to impinge on this now today.
M.
STOTO: Right, and if the National
Academy study were to be 18 months rather than six months, I would not — I
wouldn’t bring up what I said. But I think
that if it’s six months from a date that soon, I think that we can ...
P.
CAMACHO: That’s six months from the
time you get the money.
M.
STOTO: Right. You know, I’m hoping that that’s soon.
M.
OWENS: Section 106 of the 2003
Benefits Act ...
N.
RIVERA: Microphone, please.
M.
STOTO: Do you want to speak with
the microphone?
M.
OWENS: We’re working? Okay.
Section 106 of the 2003 Benefits Act said that the Secretary of Veterans
Affairs has 60 days to get a study to the National Academy of Sciences or like
body and then the report was to be done in 120 days thereafter. So it was six months since the start of the
legislation, the signing, which was December 16th. So that puts you to June 16th. And Dr. Butler, when he made a presentation
at the last meeting, he was — expressed concern about the schedule for the
study because it is a lot of thorny issues having to do with confidentiality
and other things.
M.
STOTO: Right.
M.
OWENS: My name is Maurice Owens
with SAIC.
M.
STOTO: Right, and we — and we — and
we do know that the Secretary has not produced on that 60-day?
M.
OWENS: Yes. Correct.
J.
MICHALEK: I also want to — may I
say something quickly?
M.
STOTO: Sure.
J.
MICHALEK: I want to warn you about
some realities regarding consent. A
good example are 600 Ranch Hand enlisted personnel to whom we sent a short
questionnaire; it took two years to get the responses back. Now what we’re talking about here is a
consent form that would probably have to be witnessed and perhaps notarized. And you’re going to have to send a — if you
contemplate doing such a thing — sending a hard copy consent form to people on
the order of say 1,000 people. This is
a very arduous task to get that out in the mail and get them back.
And
once again, we have a time-line here that is becoming a source of anxiety and
it’s becoming less and less realistic in terms of a scientific time-line, which
to get a project like this done is already exceeding the time left on the
project obviously. And so to put this off
for a few months, all you're doing now is shorting the fuse even shorter. And so we're going to reach a point here
within a few months where we’re going to have a real serious question about
whether we can do anything and so I’m raising a level of anxiety here that all
of us feel as scientists. Thank you.
M.
STOTO: Ron?
R.
TREWYN: Yeah. I just want to say I do think though we are
really an advisory committee. And I
think we can certainly — and I, as I recall the National Academy charge, it was
— it was “what” and also some “how” to go with that; that they would have to
look at how would you implement this and how would you make it happen. And I think ...
M.
STOTO: It did include a look at the
ethical issues.
R.
TREWYN: Exactly, and I think figuring
out is there some way that this Committee in our advisory capacity, you know,
because I believe we have advocated that studies — that this data should not be
lost, the specimens should not be lost; that if we can interface with the
National Academy committee, try to relay the exigencies here, and the things
that we need to just push forward as fast as possible and try to build those
linkages, maybe have somebody from that group — the staff person or whomever —
come to our next meeting so we can really make sure that this is moved forward
expeditiously, I think would be — would be very wise.
P.
CAMACHO: Mike, can we — can we do,
go sooner than that; that we don’t have to have a meeting? Can we write — can we draft a letter over
the next month, in a couple of weeks, and get that to you and send that letter
to Principi if he’s the — supposed to be the guy that’s to fund this?
M.
STOTO: Saying what?
P.
CAMACHO: Saying “get the money
out.”
M.
STOTO: Oh, I think we can do that.
P.
CAMACHO: All right. I’ll ...
M.
STOTO: Yeah. Let me ask ...
P.
CAMACHO: Can I volunteer to do a
draft in your — in your name or do you want to?
M.
STOTO: Okay. Let me — do other people on the Committee
have comments about that?
D.
BERRY: I had one more question I
just wanted to ask. If SpecPro is going
after this money from Congress and if Congress should approve the money — you
know, we can’t do anything if Congress doesn’t approve the money; it’s just
dead in the water — but should Congress say, “Yes, go ahead with this study,”
and they fund it, how would we work that with the Committee at that particular
point?
M.
STOTO: I don’t know. I think that’s why I want — I said we need
to look at our — at our charge. We’re a
committee that advises the Secretary of Health and Human Services.
D.
BERRY: I understand. Okay.
M.
STOTO: And that complicates things
a lot beyond what the specific charge is, so ...
D.
BERRY: Okay.
M.
STOTO: And we certainly are not a
committee that advises Congress ...
D.
BERRY: I understand.
M.
STOTO: ... although as much as we’d
like to do that.
P.
CAMACHO: Yeah, but as an advisory
committee, we can express our concern. I don’t see anything wrong; I really
don’t see anything wrong with sending a letter to Secretary Principi and cc'ing
...
M.
STOTO: Yeah.
P.
CAMACHO: ... Chris Smith of the
Veterans Affairs committee. I mean,
this is a — it seems to me as my — I see my view differently because I’m a
social scientist; I’m not a medical scientist and so there's a lot of activism
behind this. And to me, this is all a
very important issue for the — for our force structure, the health and safety
of our troops down the road, and the health and safety of our veterans now. And as an advisory board member, I don't
have any qualms about saying, “Oh yes, we should send letters,” and get them
out the door. And so somebody — let
somebody else say “you can’t do that” rather than us worrying about it; that’s
how I see it.
M.
STOTO: Okay.
P.
CAMACHO: And I would really like
the Committee to get a letter together in the next couple of weeks, send it off
to Principi saying, you know, “We’ve charged — the law was this; they were
charged with doing that, but there’s a funding — and you were supposed to put
the money up and the money isn’t up yet.”
And how many months have gone by?
Several now.
M.
STOTO: Sandy?
S.
LEFFINGWELL: Principi is Veterans
Affairs, right?
M.
STOTO: That's right.
S.
LEFFINGWELL: Okay. Yeah.
We could probably get by with that.
I’m not quite sure whether the Hatch Act is still in effect or not, but
we are technically federal employees on this Committee and I don’t think we’re
allowed to lobby Congress.
M.
STOTO: Yeah. That’s right. And so I think that actually the other protocol is that we really
only are supposed to talk to the Secretary of Health and Human Services.
S.
LEFFINGWELL: Yeah.
M.
STOTO: So what we did once before
and what I suggest we do again is that we write a letter to Secretary Thompson;
that we copy Secretary Principi and the Congressional staffers; and that we say
that we've had a presentation about a potential use of these data that we think
is very promising. We don’t think it’s
appropriate for us to make a judgment about this given our role; and in fact,
that the National Academy of Sciences is about to convene a study to look at
exactly — at very similar issues, but we understand that the funding has not
been provided as of yet; and we urge Secretary Thompson to communicate with
Secretary Principi that this funding be delivered soon. Does that — does that make sense for the ...
S.
LEFFINGWELL: Yeah.
P.
CAMACHO: Yeah. No, that’s what — that’s — you're saying
legally that's the route we have to go?
M.
STOTO: Yeah.
S.
LEFFINGWELL: Yeah.
M.
STOTO: And I also think that I would
— I would propose that I just write this letter myself on behalf of the
Committee so we don’t have to go through a ...
P.
CAMACHO: It's safer than you
reviewing it?
M.
STOTO: Me review, yeah. And of course, I’ll send you copies of what
we are going to do. Sandy?
S.
LEFFINGWELL: Now a next step in —
past that if there is to be one, and I’ll leave that to your judgment, if we
need a resolution at the next meeting, then it would be helpful to have
statements of the National Academy of Sciences’ charter and perhaps other
briefing material.
M.
STOTO: Plus our charter.
S.
LEFFINGWELL: I wouldn’t know how to
draft a resolution here and now.
M.
STOTO: Yeah.
S.
LEFFINGWELL: And that would be
something we’d have to figure out.
M.
STOTO: Yeah. So maybe what we should do is make a plan to
invite somebody from the NAS committee and bring, you know, a copy of their
charge plus our charge and a plan to do this.
S.
LEFFINGWELL: Or even send it out
ahead of time.
M.
STOTO: Okay. Yes?
D.
ATKINSON: Atkinson again. Just a little bit of practical stuff
regarding the time-line and the fuse getting shorter. I certainly agree about NIH funding and those sorts of things,
but the practical realities are NIH has deadlines of October the 1st,
February the 1st and June the 1st. It wouldn't be possible to get anything in
obviously for June. If the decision is
going to be put off until September, it wouldn’t be possible to get to October. Now you’re talking February the 1st.
The
grant of 2005, the grant doesn't get reviewed until about July — June or July
of 2005. The initial — less than 20
percent of NIH grants are approved on the first round. It’s, in fact, I was Chair of the Nutrition
Study Section at the NIH and that was 20 percent then; I think it's even lower
than that now. So it’s distinctly
possible that even with approval, the study would run out.
M.
STOTO: Well, I suspect that the
Academy will consider that and take — and think about some way to actually get
funding for the maintenance of the samples, and the staff and all that kind of
stuff. I mean, I think that what you
said is even very optimistic about getting NIH funding.
D.
ATKINSON: Yeah. Exactly.
M.
STOTO: So we can’t — you can’t
count on NIH funding for the infrastructure.
D.
ATKINSON: Right, but there are
other sources of funding. For example,
the Department of Defense has a number of ...
M.
STOTO: Yeah.
D.
ATKINSON: ... different avenues to
get funded and there are other kinds of ways to get funded ...
M.
STOTO: Okay.
D.
ATKINSON: ... which also take
forever.
P.
CAMACHO: So you’re going to do a
letter?
M.
STOTO: I’ll do a letter.
L.
SCHECHTMAN: Okay.
M.
STOTO: I’ll — and I’ll circulate it
to people for comments.
L.
SCHECHTMAN: Okay. And after that letter has been approved
Committee-wide, what we will do is we’ll put that on our letterhead to go
forward to the Secretary rather than it be RAND company letterhead.
M.
STOTO: You bet.
L.
SCHECHTMAN: Okay.
M.
STOTO: RAND would not like
that. And not that they’d disapprove of
the content, but I mean, it just would be inappropriate for an individual
employee to be making — writing a letter to the Secretary. Okay.
D.
BERRY: Dr. Stoto and members of the
Committee, I want to thank you very much for having me here today to talk with
all of you.
M.
STOTO: Okay. Thank you very much. Okay.
M.
STOTO: So now we’re onto reviewing
the chapters. Let me get my information
here. Chapter 1, Ron and Paul are —
have been asked to review and let me try to make up some — propose some ground
rules here; and that is that we focus this discussion on substantive issues as
opposed to editorial comments. I
suspect that the people who reviewed it may have some editorial comments and
that they — and can they be communicated to Colonel Robinson or somebody? Somebody we can — we can — somebody will
take them in writing and that we actually spend our time talking about
substantive issues here.
J.
ROBINSON: And that’d be great. If you have a section that you would like to
refer to, if you could give us the line number. I have it — I’ll have the chapters up on the screen behind you
and then that would allow everybody to refer to it or see it if they wish, sir.
M.
STOTO: Okay. And then I guess that we also maybe broadly
interpret substantive issues at this point.
If we’re — if we’re running behind schedule, then maybe we’ll cut back
on that, but ...
R.
TREWYN: But how about if we get
toward the end of the day, and we’ve got time to then go back, and run through
these and get to some of this other stuff, we can do it?
M.
STOTO: We could do that. Okay.
R.
TREWYN: Yeah. I have no problem with that.
M.
STOTO: Is that okay? Does that make sense to people? And I — and I guess that what we’ll — the
other thing that we’ll do is just have the reviewers just give their comments
and then just have an open discussion with everybody about that. The goal of this really is to come up with a
report that does a good job of (a) describing what was done. And most of the things that we’re reviewing
today are actually describing what was done as opposed to having any results,
but there are two chapters that deal with substantive results where we’ll have
more of a — some kind of scientific discussion about what that means. And we’ll set the tone and develop an
approach to doing that that will carry over hopefully to the next round when we
do those things again. Does that make
sense to everybody? Well, since you are
here, I’ll ask you for the comments on Chapter 1.
R.
TREWYN: All right. What I’ll try to do is skip by. I’ve got a number of editorial things and
I’ll get with Julie later on these. But
there are — I think there’s — there may be two issues that come up throughout
here that I do think are substantive and one of them runs throughout. But I guess I could start it sort of in
Section 1.3–“Study Design.”
M.
STOTO: You know, another thing is
that we have two versions of these chapters now. So we’re — should we refer to the later one?
R.
TREWYN: The later. I — yeah; I brought the first one, but I did
all my editorials on the second version on every one of these that I looked
at. So anyhow, in “Study
Design”–Section 1.3, the issue comes up that back in 1999 when we were at my last
meeting the first time around is a — is a point in time when we discovered that
the comparison group consisted of individuals stationed in country, in Vietnam
and individuals not stationed in Vietnam.
I did not see that laid out at all in here. And I think it’s a critical issue, and one that clearly the team
is looking at and crunching numbers and whatnot.
And
it was really my view that at least a brief statement under the “Study Design”
section perhaps toward the end of that section where it finishes up with “all
19,078 veterans in the comparison population,” with that statement, that
something — a brief statement there about the composition of that, whatever the
proportion is of in country stationed because the issue here is exposure to
herbicides.
And
clearly, those in country with the way all the bases were sprayed a lot and
repeatedly, that clearly that comparison group had some exposure to herbicides
that those stationed in Thailand, which is where I think the majority of the
other part of the comparison group was, and so I’m going to have a number of
points throughout this section that relate to that topic. And I think that is a substantive topic
based on the fact that you’re finding differences when you use the comparison
group in country versus out of country.
Is that correct?
J.
MICHALEK: That’s true. There’s an increased risk of cancer with
increased days spent in Vietnam among the comparison group, which was
unexpected.
R.
TREWYN: Right.
J.
MICHALEK: There’s also an increased
risk of cancer with years spent in Southeast Asia, which was unexpected when
the study started.
R.
TREWYN: Right.
J.
MICHALEK: And that influences the
way we look at cancer in the Ranch Hand group.
R.
TREWYN: Right.
J.
MICHALEK: Only now are we realizing
this after 15 to 20 years.
R.
TREWYN: And that’s why I think it
may be possible if we at least target the time-line of that; that one will
understand that the comparison group was mixed in the early studies, but at
least for this last one, that you’re really looking at that and then when appropriate
going back, I believe. And so I think
somehow though, we need that laid out here in the introduction so it’s
understandable because there are going to be a lot of publications coming out
related to this and it’s a critical element.
M.
STOTO: Right. The comparison group is what it is. It’s important to be clear on what it is.
R.
TREWYN: Right.
J.
MICHALEK: Right. Yeah.
M.
STOTO: Other comments or reaction
to that? Okay.
R.
TREWYN: And then I would just say
that then obviously as one gets down into the particulars further on in that
study under Section 1.6 with “Study Design,” again, as I’ve made the argument
over the years, there is a tendency and clearly and beyond Model 1 that a lot
of those do relate to dioxin. But the
charge really is herbicide exposure and so again this issue; there are portions
throughout here where I think that the comparison group being broken out needs
to be laid out in Table 1-1 and a variety of these other places. And I’d be happy to sit down separately, and
go through and point out where I’ve got scribbles, and why I’ve got them there.
J.
MICHALEK: That’s it; I need to see
your markup.
M.
STOTO: Do you think that it would
make sense to at some point say — just give a breakdown of where the other
comparison groups served?
R.
TREWYN: Yes.
M.
STOTO: I mean, which countries in
Vietnam versus others?
J.
MICHALEK: It is being collected as
we speak. Remember, the material that
Dr. Trewyn is mentioning was only discovered recently, actually after we wrote
the stat plan for SAIC to write this big report. So we’re sort of behind the curve here, but we’ll do our
best. And that has to be said, by the
way, in the report.
M.
STOTO: Right.
J.
MICHALEK: That some of these things
we’re talking about aren't even published yet.
M.
STOTO: Right. Okay.
R.
TREWYN: Anyhow, I’ll be happy to
work with you. Then there’s — then
there’s one other issue and I guess this starts out a bit with a question. In Section 1.6.3–the “Air Force Exposure
Index” — and since you wanted lines, on line 293, it talks about calculated —
“the exposure index was calculated from military records to measure the
potential exposure of a Ranch Hand to any of four dioxin-containing
herbicides: Orange, Purple, Pink and
Green.”
Because
so much of the report is based and so much of the work over the years has been
based on the dioxin aspect of this, this particular statement implies that the
same thing could be done for non-dioxin-containing herbicides. If you can do it from the records for the
dioxin-containing, then presumably those records have the data for the
non-dioxin- containing. And therefore,
it might be possible to determine — say with the latest 2002 specimens just
with a quick analysis — are there any possible significant health problems
associated with exposure to the non-dioxin-containing ones: white with picloram, blue with cacodylic
acid or just even the combination because so much of this has focused
particularly on the dioxin component.
And
clearly with cacodylic acid being an arsenic-based, that’s probably not a real
healthy thing to have a lot of exposure to.
And there are data, I believe, that picloram has adverse health
effects. If somehow in the 2002 one
could say from the records if somebody was exposed to a lot of Agent White, a
lot of Agent Blue, and clearly, there’s also data on just the 24D having some
cancer association in agricultural workers.
So anyhow, my question is — and this would be a new analysis potentially
— but is there the potential to look at those other groups just to see here at
the tail end are there some adverse health parameters that would show up in
those exposed to the other agents?
M.
STOTO: Let me just say one
thing. I mean, I think that last point
you made is important; that this is not so much a comment on the report, but an
opportunity for other research — potential opportunity.
J.
MICHALEK: Yeah. These are thoughts we’ve had. The existing database is not going to be
helpful regarding that level of detail.
I’ve tried to make this point before that the actual day-to-day records
are — exist. We didn't have these in
1977 when we designed the study. They
exist; they are being held by Dr. Jeanne Stellman at Columbia University; she
has them. It tells how many gallons of
pink were sprayed each day at each base.
We never had this detail before.
She has those records. That
would allow us to provide a, for the first time, an exposure index for the
non-dioxin-contaminated herbicides.
R.
TREWYN: But you're saying it was
done for the — for the dioxin-containing.
The statement is “was calculated from the records.”
J.
MICHALEK: All the records have are
what’s in the herbicide tapes and those tapes are not specific to a base or an
individual. What I’m trying to tell you
is this is new information that is held by Jeanne Stellman, which is specific
to the actual day and base that an individual was at during the war. We’d never had that before; she has it.
M.
STOTO: So my recollection is that
this index ...
J.
MICHALEK: The old index, you mean?
M.
STOTO: ... the old index was not
supposed to be very good?
J.
MICHALEK: No, but we think the
information held by Jeanne Stellman is relevant.
M.
STOTO: So this — I mean, this
section is here really for historical reasons?
J.
MICHALEK: Yes.
M.
STOTO: And Stellman will ...
J.
MICHALEK: Stellman has the ...
M.
STOTO: ... presumably ...
J.
MICHALEK: ... the details.
M.
STOTO: ... do research looking at
the more detailed approach.
J.
MICHALEK: She — now Stellman’s
point of view is far different. She
cares about the Army ground troops and so she doesn’t realize the value of what
she's holding as regards to the Ranch Handers.
So we need to — I’m trying to stimulate a discussion with Jeanne
Stellman. If you could be helpful
there, that would be fantastic.
M.
STOTO: Okay, but that — but that’s
not an issue about ...
J.
MICHALEK: No.
M.
STOTO: ... this work? Okay.
Others?
R.
TREWYN: And what I’d like to do,
since Paul was also a reviewer, is let him and I’ll glance through it since
I’ve got so many scribbles to see. I
think most of my others are editorial.
P.
CAMACHO: I didn't have that many
scribbles. I thought it was ...
N.
RIVERA: Turn on your microphone,
Dr. Camacho
P.
CAMACHO: I didn’t have that many
scribbles. I thought it was fairly well
done with all of the provisos; there were plenty of them. I took a good criticism as a social
scientist. I don’t look into too — my
version of statistics and their version, it’s a lot — it’s a lot
different. And I wondered sometimes
should our end notes have a quick refresher course in this thing, but then
again, this is not — we're not writing an SPSS manual. It means you’d have to sort of sit on it and
let it ride.
But
some of the things of who the — who the audience is was the — was the
discussion. Is it strictly experts who
would know all these techniques or expected to know or is there some of the
audience lay persons, Congressional staff, whoever? And so the whole style should — we’d have more footnotes or
possibly an appendix giving a summary and a quick thumb nail, such as SPSS
manuals have or even more brief, and a — and a summary of where a bibliography
of where a reader could go to find the explanations for the different
statistical techniques.
I
don’t know if that’s really in our charge or not, but it seems to me it’s a
possibility to be considered: just a —
it would just be another appendix listing all the statistical techniques that
were done, and a quick bibliography and perhaps a paragraph or two giving a quick
— if that — to the degree that it’s possible — a quick explanation of just
what, in common sense terms, what does this technique do.
M.
STOTO: Comments on that?
J.
ROBINSON: Just to clarify who it
was primarily written for was epidemiologists — that’s line 17, 18 — clinicians
and biostatisticians. So it really
isn’t ...
P.
CAMACHO: It doesn’t have any —
we’re in the ...
M.
STOTO: So this is ...
P.
CAMACHO: ... realm of the ivory
medical tower?
M.
STOTO: So this is intended as a
technical report essentially? Okay.
P.
CAMACHO: Lay people, the average
human is not of our concern yet?
M.
STOTO: I think it would be — it’d
be too much to ask for a, you know, a mini-statistics textbook here. But perhaps there could be some references
put in at this point to some that would help people to — both the introductory
level and standard text at this point.
I mean, I could ...
P.
CAMACHO: An appendix, bibliography
of sorts.
M.
STOTO: I think having been teaching
this stuff, I don’t think it’s very easy to write a simple version of
these. So, but I do think things do
exist.
P.
CAMACHO: And so we have a
bibliography?
M.
STOTO: A bibliography is what I’m
proposing, yeah.
P.
CAMACHO: I mean, I ...
M.
STOTO: I recently put together a
bibliography of some introduction to epidemiology that I — that I can share.
P.
CAMACHO: Okay. I’m happy.
R.
TREWYN: Let me throw out one more
point. It’s probably related to that
because on the first page of the introduction where it talks about in this — “In
this report, the use of the term “dioxin” refers to TCDD.” And that's probably okay to do that, but one
would really need to, in every other chapter, to have that referenced because a
lot of the people you’re expecting to read this may only be interested in the
cancer chapter, the cardio chapter, whatnot.
And
if they just see dioxin, they’re going to have the issue of, “Well, there’s
lots of different forms,” and so one would, I think, almost throughout. But a bibliography with terms and so it’s
very clear what’s defining it. So most
people aren't going to read this from front to back, I don’t think. And if they are, they’re more masochistic
than your average person.
M.
STOTO: It’s always a challenge of
how much of the introduction to repeat in every chapter.
R.
TREWYN: Right.
M.
STOTO: So, but that may be an
important thing.
R.
TREWYN: Dioxin itself — I mean, but
if you’re going away from TCDD, which is very specific to the, you know, to the
specific form of dioxin in the abbreviated form to just generally since there
are I don’t know how many different chemical forms of dioxin, but it’s a lot
and that’s critical. So I would just
think for the scientists reading it if they just picked up the cancer chapter,
they’re not going to — if they just see the term “dioxin,” but maybe if you’ve
got that in a — somewhere in a bibliography, whatever, that this is what we're
meaning throughout this report, that would take care of it.
M.
STOTO: Would it — would it work to
write maybe like a one-page summary of the methods to go in the front of each
of the substantive chapters that would include things like this?
R.
TREWYN: Possibly.
M.
STOTO: Could that — could that be —
maybe there’s even a — maybe even this — there’s a summary here that can be
pulled out and done. Is that — is that
a reasonable thought?
R.
TREWYN: I just think it’s worth —
yeah; they need to look, I think, look at some options where it might cause
confusion long-term if people are pulling out individual chapters. I think that could be helpful
M.
STOTO: One of — one of the things
that we were talking about earlier is the different statistical models that are
used in the chapters. And, you know,
another thing that might be included there is that we use four statistical
models all the way through here and just summarizing what they — what they
are. So this is — this is basically a
page or so that would appear at the beginning of each substantive chapter that
would say things like that. Is that —
people are shaking their heads here for the recorder positively — is that
okay? You think that makes sense or —
go ahead, David.
D.
JOHNSON: We were talking about — we
were talking about Chapter 9.
M.
STOTO: Yeah.
D.
JOHNSON: We were talking about four
models and a — and a description of them, I think, could’ve been — the
description could've been clearer. Now
you’re talking about putting it in one place and then referring to that?
M.
STOTO: Well, it already exists now
in one place; I don’t know which chapter.
But what I’m suggesting is that we write a standard one-page description
of the methods of the study that includes things like focus on TC — dioxin
means TCDD, and the four statistical models and there’s probably, you know, a
number of other things that we could say, and repeat that at the beginning of
each of the methodological — each of the substantive chapters, excuse me, the
substantive chapters so that if someone picks up just those substantive
chapters, they’ll be okay. And of course,
it’ll refer back to the detail — in the detail.
J.
MICHALEK: Well, I think the reason
we’re being quiet is number one, if I were writing this report personally in
Microsoft Word at my desktop, there would be no issue. But this is being done under contract by
SAIC Corporation under our contract.
And so what you’re asking for is a change and that has to be discussed
with our Program Management. And so
that’s a — that’s a caveat that applies throughout the whole report.
We
have a built-in process of peer review and edits to these chapters that are fed
back to the contractor, SAIC. And we've
been doing this routinely and you see the comment resolutions. And we’ve been — we’ve been on this since
the beginning with you. But when we
consider what might be considered a major change to chapter format, then we
have to worry about the contract and what we’ve asked SAIC to do. And so I don’t have anything more
definite. Julie, do you have anything
to add on that?
M.
STOTO: Well, can I — I’m aware of
those concerns and I think the Committee is as well. So that’s part of the reason I tried to suggest something that’s
relatively simple ...
J.
MICHALEK: Right.
M.
STOTO: ... having one standard page
that can be thrown in all those chapters rather than do something specific to
the chapters. I think that doing
something chapter-specific would be prohibited.
J.
ROBINSON: We will take everything
you say under consideration and, you know, the ramifications from a Program
Management standpoint would definitely have to be discussed. But we, you know, we don't want to stop ...
M.
STOTO: Right.
J.
ROBINSON: ... discussion or the
ideas that you are recommending for modifications. I think we all know what the limitations are and what — we can
get back to you.
J.
MICHALEK: Very good; I agree; that’s
great.
M.
STOTO: Sandy?
S.
LEFFINGWELL: The idea of looking at
Thai versus Vietnamese controls seems reasonable. I kind of wonder though if it turns out we don’t see much after a
few rounds, whether we ought to perseverant in that. My recollection of the CDC’s efforts to look at ground troops was
they found after — not after; they got rather far into it actually — that the
distribution of dioxin among veterans in Vietnam did not differ significantly
from that among civilians in CONUS. And
we may find the same is true among ground controls in Vietnam and Thailand.
R.
TREWYN: Except they're finding big
differences.
M.
STOTO: Well, that’s — this — that’s
certainly what CDC — how CDC interpreted those data and other people ...
P.
CAMACHO: If the only thing you can
get is a history here, you might ...
M.
STOTO: ... interpreted them
differently. But I think that that’s
not relevant to the current ...
P.
CAMACHO: Yeah. Somebody’s going to start throwing ...
M.
STOTO: ... the current charge.
P.
CAMACHO: ... grenades at that
because you’re talking about a lot of people.
But remember, it’s ten to one in the rear; ten — there’s nine guys in
the rear to every guy in the bush.
There's 555,000 guys in Vietnam; there’s only really 55,000 guys in the
jungle.
M.
STOTO: Well, I propose that we ...
P.
CAMACHO: Yours truly happened to be
one of those poor wiggling beasts carrying 110 pounds in the DMZ. So that’s, you know, it’s just sort of you
talk about casualty rates or anything like that, it’s enormous because it’s all
out here and there’s nine guys at the club drinking beer that came from the
rear.
M.
STOTO: Well, I propose ...
P.
CAMACHO: I hate to say it, but you
know, they’re working on trucks; they’re all doing their legitimate jobs. But when they sprayed that stuff, it just
came over and like the DMZ would get sprayed.
So your unit’s walking through it and some others; then there’s a whole
bunch of guys that aren’t. So I
understand the overall — you get into trouble with that though and that’s why
the veterans community suddenly goes berserk or when somebody — something like
this happens and then they start making phone calls all over the world. I’m just pointing that out.
You
have to think about who’s — it’s just like who gets shot, you know? The fact of the matter is, for instance —
and I’ll keep quiet — the Marine Corps represented 13 percent of the ground
troops; they took 37 percent of the casualties. There’s nine — eight and nine guys in the rear to every guy in
the jungle. So the casualty rate of the
units that were in the jungle was enormous, just huge. I was in the 9th Marines. I apologize; I only got shot once, crashed
in a helicopter once, then I got shot once, but we’re in the jungle with
dysentery very, very whatever, you know.
M.
STOTO: Okay.
P.
CAMACHO: All the other.
M.
STOTO: Paul, I’m going to suggest
that ...
P.
CAMACHO: So I’m just saying, those
guys are out there in a copious circle with that one; that’s why I just ...
M.
STOTO: But fortunately, it’s not
relevant to what we have to do at the moment, so I would propose that we side
step it for now.
P.
CAMACHO: Gracefully side step it.
M.
STOTO: Okay. Thank you.
Any other comments on this chapter?
Okay. Well, let’s move. Thank you, everyone.
M.
STOTO: Let’s move onto Chapter 2 and that is Dr.
Hassoun. Turn your mike on, please.
E.
HASSOUN: It was very well written,
but I have a couple of comments and I have some editorial changes that I’ll get
those later. And regarding the — it’s
the dioxin — the dioxin assay, but I couldn’t see any method that — I know
that’s being done in CDC. But I
couldn’t see any description for the method used for dioxin assay in the serum: how it was extracted or did they use HPLC or
— I’d like to see the detailed description of the method and ...
J.
MICHALEK: Yes. They used HPLC. I don’t think we’ve included the lab method description in any of
our reports actually. We referenced the
Patterson article, which is in the analytical chemistry journal. To the reader who wants to know the methods,
they can go there and so that’s why we never wrote the lab method in this
report.
M.
STOTO: Do you recall where — do you
recall where that is as it appears?
J.
MICHALEK: Oh, it should be
somewhere referenced. I don’t have the
chapter in front of me. Julie has that
chapter.
M.
STOTO: So Patterson is referenced
in 1 and 2 as well.
J.
MICHALEK: His reference is the
methods that you’re looking for — Annals of Chemistry 1986.
M.
STOTO: Okay.
J.
MICHALEK: Two Patterson papers
referenced, right. Those are the
fundamental chemistry papers.
M.
STOTO: I mean, could — would it
possible to write another sentence or two that would clarify that?
J.
MICHALEK: Put that in your markup;
I’m sure that can be, you know ...
E.
HASSOUN: Okay.
M.
STOTO: Yeah.
J.
MICHALEK: ... considered somehow.
M.
STOTO: Okay. Good.
E.
HASSOUN: Then we move to the
figures. The first Figure 2-2 and
Figure 2-3, I understood those. They
were comparison and dioxin-exposed, but what are these figures — Figure 2-4?
J.
MICHALEK: Can we see Figure 2-4?
E.
HASSOUN: What’s the difference
between Figure 2-4 and ...
J.
MICHALEK: I need to see those on
the screen; just a second.
E.
HASSOUN: Are you talking about — in
Figure 2-4 — are you talking about the 94 participants in the comparison and
the 12 Ranch Hands or ...
J.
MICHALEK: Scroll down and let me
see the words.
M.
STOTO: Do you — do you want to look
at the hard copy?
J.
MICHALEK: You do have it
handy? Okay. I think Figure 2-4 is the same as Figures 2-2 and 2-3; they’re
just put on the same scale. See, the
scale — the scale on Figure 2-2 runs all the way out to 600 for the Ranch
Handers and out to 30 on the controls on Figure 2-3. And the attempt was on Figure 2-4 to put everything on the same
scale so you see up there, run out to 60 in both histograms to give you a
better look at what the — how the distributions compare on the same scale;
that’s all. It’s the same data displayed
differently.
M.
STOTO: That’s described at the —
and on — in lines 146 through 150.
J.
MICHALEK: And on line 161.
E.
HASSOUN: Yes, but I like to see
some description for these figures and your conclusions. What do they mean? I mean, I couldn't see anywhere.
J.
MICHALEK: Oh, how to interpret
them?
E.
HASSOUN: Yes.
J.
MICHALEK: Yeah, a sentence in the
discussion would be helpful. Obviously,
you’re looking at Figure 2-4; it means that the Ranch Handers have a body
burden that the controls do not. And so
— and that we believe, although we can’t confirm, that they obtained this body
burden through their exposure to Agent Orange because we weren’t there in
Vietnam. There was no dosimetry in
Vietnam; we can’t prove it, but we believe it because of the history of this
unit. So that could be said in the
discussion. That’s one sentence or so
added to the discussion, yes.
M.
STOTO: You might say this
“suggests.”
J.
MICHALEK: “Suggests,” yeah; that’s
a word we use a lot.
E.
HASSOUN: I think that’s all what I
have. Regarding the appendix, I think
we are not in a position to discuss that or review that because these are
standard procedures that are being followed.
We can’t go back and change them.
M.
STOTO: Exactly.
E.
HASSOUN: So ...
M.
STOTO: The only question is does
this adequately describe what was done?
E.
HASSOUN: It does.
J.
MICHALEK: Very good. Thank you.
M.
STOTO: Okay. Thanks.
Any other comments from other Committee members on this, other
additional response? Okay. We’ve caught up in terms of our time. I guess I’d propose that we do Chapter 3 and
then take a break if that’s okay.
R.
TREWYN: This should take under five minutes.
M.
STOTO: Okay. Who’s Chapter 3?
R.
TREWYN: That’s me.
M.
STOTO: That’s you. Good.
R.
TREWYN: And this is going to be a
surprise that it’s going to be fast, but it will be. And I’ll — yes, I will speak into the microphone. And really this, while I’ve got a few
comments written, and this would be questionable whether this is substantive or
editorial since I’ve only got one really comment that I need to make. It’s on line 39 and the statement is “All
participants were asked questions to update their histories since their last
interviews.” And I sort of wrote down
the comment at the time, “Were they provided copies of their last
interviews?” Because that seemed like,
you know, that was an obvious question.
Well,
once I read the rest of the chapter, the answer was yes by the bounded whatever
recall sorts of things. But when this
comes on to the New York Times bestseller list and everybody’s reading
it, I’m concerned everyone is going to have that same question. So why not just add to the end of that
particular sentence “and were reminded of information already reported.” Then they don’t have to read on to know that
answer. And that’s it; I'm done.
M.
STOTO: You might also say “their
medical histories.”
R.
TREWYN: And the medical, yeah.
M.
STOTO: They learned to fly or, you
know ...
R.
TREWYN: Yeah. Yeah.
Right. Right.
M.
STOTO: Okay.
J.
MICHALEK: Very good.
R.
TREWYN: So now we could be ahead of
schedule.
M.
STOTO: Yeah. Okay.
We are ahead of schedule, yeah.
Okay. Well then, let’s take —
let’s take a — can we take a 15-minute break?
Let’s come back at around 10 after — 10 after 10:00 or — okay.
[BREAK 9:56 A.M.-10:12 A.M.]
M.
STOTO: Okay. Let’s get started. I have to — I have to file an official complaint about the coffee
cups here. This is the second one that
has leaked on me. I don’t think it’s
me, but okay. So Chapter 4–“Physical Examination”
is Dr. Johnson.
D.
JOHNSON: Okay. As a — as a new member, I just want to
start, open by saying I appreciate the amount of — tremendous amount of work
that’s gone into this study. I think
it’s well written. There’s a consistent
application of science and the report’s science-based throughout, so I mostly
have minor suggestions. Chapter 4 was
to be reviewed in conjunction with Appendix B and I’m kind of looking — I'll be
talking about both of those together. I
don’t have all that much to say.
I’ll
mention that on line 12, the “Air Force carefully prescribed the details of the
above examination elements in the Examiner’s Handbook,” which is
Appendix B, which was being reviewed with this. If you go to page 4-2 on these tables, I just had a couple of
questions I think we have time to go into a little bit. This is borderline substantive.
It
says — it lists under “Elements and Comments,” it has the “internists” and then
it has “Board certified internists.”
And I’m not — to me, does that mean that the radiologists, and the
dermatologists and the psychologists, all these are not Board certified? I mean, why do we say “Board certified” for
just the one internist? It appears
there’s been some discussion about that in the past and so ...
M.
STOTO: Anyone want to respond?
J.
ROBINSON: Good point.
D.
JOHNSON: Okay.
J.
ROBINSON: We'll revisit that.
D.
JOHNSON: Okay.
J.
ROBINSON: Yeah. It was originally “medical diagnostician”
and it was changed. We had a — we have
Dr. Fox, who’s not here today, that pointed that out. So we can certainly clarify that for the neurologists, et
cetera.
D.
JOHNSON: So you’re going to change
it to make them all Board certified or you’re just going to ...
J.
ROBINSON: I think they’re all —
they were all ...
D.
JOHNSON: Are you just ...
J.
ROBINSON: ... Board certified.
D.
JOHNSON: So you’re going to add
that or just take off Board certification?
J.
ROBINSON: We can add it or we could
make a statement at the bottom. We can
look at that ...
D.
JOHNSON: Okay. Right.
J.
ROBINSON: ... and say that they
were all Board certified.
D.
JOHNSON: Okay. And then it says “internist with
subspecialty in pulmonary disease;” that would just be a pulmonologist, I
believe. It’d be consistent with
radiologist, dermatologist. And then
under the “chemistry” study, it says “syphilis” and it — I thought it might be
worthwhile — are you doing the RPR, or the FTA there, or both or you might put
it in parenthesis?
J.
ROBINSON: Yes. I thought we had clarified that, but ...
D.
JOHNSON: I just kind of looked at
this because if you look at a table, they — usually tables, you want to be
self-explanatory. And then further down
under “Hematology,” it says “differential segs.” I thought you might want to go ahead and instead of abbreviating,
saying “segmental neutrophil.”
J.
ROBINSON: Okay.
D.
JOHNSON: And then also “mean
corpuscular volume had cubic micra.”
I’m not used to using micra.
It’s “cubic micrometer” or “micron” and if micra is acceptable, then I,
you know, that’s fine. I’m just not
used to micra; I haven’t seen that before.
J.
ROBINSON: All right.
D.
JOHNSON: Next page, 4-3,
“differential lymphs.” That could be
“lymphocytes,” I think, at the very top.
And then down at the bottom, it has just — this is getting pretty minor
here — “absolute” should be over with the other absolutes. It’s in the left-hand column down under “T
& B lymphocytes.” You have the
absolute on the left side for just one thing and then all the other absolutes
are on the other side. But in any case
...
J.
ROBINSON: Okay.
D.
JOHNSON: ... this list is
inconsistent with the list in Appendix B and I just wanted to point that out;
that it started as it says that it’s described in Appendix B. If you look at the list of lab tests that
are done in Appendix B — I didn’t go through in detail and make all the checks
— but it was apparent to me that they’re not the same; that there’s 137 listed
here and there’s, if you look at Appendix B ...
M.
STOTO: 83.
D.
JOHNSON: There’s 83 and —
approximately 137. I went through and
just kind of quickly counted them. So
that, you know, I — is that an issue? I
don't know, but they’re not — you’ve got two different lists of lab procedures
that were performed. On page 4 ...
M.
STOTO: That — excuse me — that is
an issue if you’re ...
D.
JOHNSON: Right.
J.
ROBINSON: Yes. Yes.
I’ve made a — we'll correct that.
D.
JOHNSON: Okay.
M.
STOTO: Okay.
J.
ROBINSON: We’ll make them
consistent.
D.
JOHNSON: Okay. Just moving — just keep moving on? Am I going to move on?
J.
ROBINSON: Yes sir.
D.
JOHNSON: Am I going too fast? 4-4, it said “additional QC included the
following elements.” Now I didn’t — I
wasn’t able to see the different forms that were used when I reviewed this and
what elements were done. So that — it
comes — when I get to the handbook, I’ll mention that again. The actual physical form is not included, so
you can’t really look and see what the clinicians were using when they were
checking off all their findings. And so
it’s hard for me to see how it was standardized by the description in the
handbook, but I’ll come back to that in a second. On line ...
M.
STOTO: Before you get — before you
go on beyond that, I mean, as a non-clinician, I clearly don’t understand what
all these things imply. And I guess my
question is are they standard enough that a clinician would understand what
they all are and basically be able to reproduce this or do we need more
details, references, “values” — things like that?
D.
JOHNSON: That would get — I was
just about to get to that. If you get
into the Examiner’s Handbook, it tells you what the examination was that
was done, the conduct of the examination.
And there's not enough data here to make a — to get, collect
standardized data and I just had — I made a few comments. If you want to — want me to wait just for a
second before I get to that?
M.
STOTO: No, I guess that is the same
issue. So why don’t you make the
comments?
D.
JOHNSON: Right now?
M.
STOTO: Yeah.
D.
JOHNSON: Well, just for example, it
says “the general physical examination will” — “shall include an” — now the
other point I wanted to make though is this is the — this Air Force — I’m on
Appendix B now — Air Force Health Study Examiner’s Handbook, now I’m
assuming this was used throughout the study, was given to the examiner to read
before they did their exam? Is that
correct?
J.
ROBINSON: Yes sir.
D.
JOHNSON: So I think it would be,
even though I had some changes throughout this where I thought the wording
could’ve been better and there could’ve been some things made clearer to
include in the report at this point, you wouldn’t — I wouldn’t think it would
be good to change any of this because you need to — you need to see what was
used. You need to be able to see what
the document was with all its faults and so I really don’t know that it’s a
good idea to change any of this.
M.
STOTO: This is very archival and
you’re exactly right. I think that it
has to be — it’s whatever they used, they used and we need to ...
D.
JOHNSON: That’s what they used and
that’s what needs to be in the report.
M.
STOTO: Yeah.
D.
JOHNSON: We don’t want to edit it
at this point.
M.
STOTO: Yeah.
D.
JOHNSON: But, so all of my comments
are really just not that — for example, it says “the general physical
examination, waist, hip” — number 11 — “waist, hip, chest and neck measurements
in sonometers.” Now is that
circumferential and where are they going to take those measurements to make
that consistent? “Vital signs, height
in centimeters” — was that with shoes or without shoes? Just, you know, little things like this on a
neurological exam, an assessment of coordination. Well, assessment of coordination, if that’s all the guidance they
had, I don’t see how it could’ve been consistent. But there must've been a form they used or a more — there must
...
R.
TREWYN: We’re getting lots of nods
from the audience.
J.
ROBINSON: Yeah. Do you have the forms? I can send a .pdf file of the forms that the
clinicians used. The neurologists had
two- or three-page forms that they used.
R.
TREWYN: Well, it’d be part of
Appendix B.
D.
JOHNSON: That’s my question.
M.
STOTO: Yeah. The issue is not sending it to us.
D.
JOHNSON: Yeah, but I don’t think we
want to ...
M.
STOTO: Yeah.
D.
JOHNSON: Again, we wouldn’t want to
change them at this point or edit them.
M.
STOTO: Right.
D.
JOHNSON: But they should — if
somebody wants to look back and see what was done, they’d probably need to see
those forms.
M.
STOTO: You know, the other, I
guess, the other alternative is it’s, I imagine, there are a large number of
forms of that sort and it could be quite voluminous. And I wonder if they could be made available on the web with a
reference in here to people?
R.
TREWYN: Well, until they close down
all our shop and there's nothing, no web left.
J.
ROBINSON: Dr. Grubbs thinks that
the forms will all be part of Appendix B.
M.
STOTO: Okay.
D.
JOHNSON: Okay.
J.
ROBINSON: It’ll be included. They just were not included here.
D.
JOHNSON: Okay.
M.
STOTO: Okay.
D.
JOHNSON: So with that on Appendix
B, I don’t see reason to take our time to go through some edits in the wording
because we’re going to leave it. But I
will point out that a couple of things like it says on page — well, under
“pulmonary function testing,” number 7 under “Conduct of Exam,” it says
“products will include as a minimum forced expiatory volume at one second;”
that’s FEV 1.
The
“total vital capacity,” which I’m thinking that you meant to say “forced vital
capacity,” which is FVC, and the ratio of the two measurements which you could
put in parenthesis “FEV 1 over FVC.” Is
that what — is that what it’s supposed to be?
So that's an actual error, but again, you can’t change it at this
point. So I don’t know.
R.
TREWYN: But it may be clear on the
form.
D.
JOHNSON: It may be clear on the
form.
M.
STOTO: Well, yeah. See, there’s two — there’s two things: one is it may be clear on the form; the
other one — and that’ll be included — the other one is that presumably will be
an issue in the chapter where that relates to respiratory outcomes.
P.
CAMACHO: Can you do an errata page
...
M.
STOTO: No, because the forms are
...
P.
CAMACHO: ... here in the — in the —
in the report?
M.
STOTO: No, I don’t think that that
makes sense.
P.
CAMACHO: Okay.
M.
STOTO: I mean, if they — even if
they did the wrong thing in the forms, we need to say what they did.
D.
JOHNSON: Right.
M.
STOTO: But I think what — where the
data that was derived at that point is used in the analysis, at that point, I
think there needs to be a discussion about precisely what values were — what
was done, the implications of that, and so on and so forth. Does that ...
J.
MICHALEK: Yeah. The FVC that you’re referring to in the
ratio are, I think, produced automatically by the software of the
instrumentation.
D.
JOHNSON: Right. Right.
J.
MICHALEK: And so what that manual
is doing is trying to describe what’s going to be automatically produced by a
computer output anyway and that needs to be said somewhere. Maybe it’s in the pulmonary chapter; I don’t
know the details of the method for the FVC and any instrument that was used.
M.
STOTO: I mean, it seems to me that
is where it should belong and maybe it’s there. I mean, we haven't looked at that.
J.
MICHALEK: Right.
D.
JOHNSON: Well, that was just
wrong. I don’t think it’s called the
“total vital capacity.” It’s called the
“forced vital capacity.” But, you know,
you could — you could — you could discuss a lot of things in this manual: it says “neurologic exam;” it says
“assessment of the cranial nerves 1 and 7.”
Well, an examination of cranial nerves 1 and 7, now you can’t — that’s
not enough information to collect data systematically for a study, so I’m sure
there must’ve been more information here to explain how that was collected.
J.
MICHALEK: It’s discussed in the
neuro chapter, so correct. Yeah.
D.
JOHNSON: The forms — I think the
forms might help clarify because they probably had forms they had to fill out
for ...
J.
MICHALEK: Yes.
D.
JOHNSON: ... specifically for each
thing.
J.
MICHALEK: That’s true and it’s also
true that the Examiner’s Handbook, unfortunately, was not a document
that was reviewed as carefully as the other, as the report itself.
D.
JOHNSON: That’s apparent.
J.
MICHALEK: It’s a — yeah; it’s a —
Bill Grubbs might have something to say about that.
P.
CAMACHO: Is this — is it possible —
one more, two sentences I have — is it possible to go back and put some of
these comments, like the software comment, back in the intro chapter? It just maybe occurred to me that it’s just
not really changing the structure of anything.
But as we find mistakes in the other chapters, that we might — the idea
of that software thing ...
J.
MICHALEK: Yeah.
P.
CAMACHO: ... put that back in the
intro chapter.
J.
MICHALEK: That sounds like a good
idea to me to at least add a few words to reassure the reader that things were
under control even though there were typos and misprints or whatever in the Examiner’s
Handbook. Yeah.
M.
STOTO: If it refers to the Examiner’s
Handbook, I think it probably should be in Chapter 4 ...
J.
MICHALEK: Right. Yeah.
M.
STOTO: ... which is what comes
out. And I think the other thing is
that the substantive chapters — the pulmonary chapter, neurology chapter and so
on — there needs to be a discussion of precisely what measures ...
J.
MICHALEK: Methods.
M.
STOTO: ... came out of that that
were put into the analysis.
P.
CAMACHO: Yeah. The only thing I brought up, the intro
chapter, like what are they going to read?
Remember when that came — comment came from outside of the room earlier
anyway?
M.
STOTO: Yeah.
P.
CAMACHO: But they might all read
the intro chapter and so it just occurred to me that you might want to throw
the stuff in both places. I don't know;
you guys make up your choice. And I’m
sorry; it brings up the D2 stuff.
Target in D2, was that expected value?
J.
MICHALEK: I don't know where you’re
getting that.
M.
STOTO: Paul ...
P.
CAMACHO: I had to jump back and I’m
going to do it ...
M.
STOTO: ... let's hold off on that
one for now.
P.
CAMACHO: All right. I had to jump back because I forgot to bring
that up.
M.
STOTO: I think that it’s important
to — Chapter 4 describes the physical examination methodology and it has the
appendix to it; that’s the handbook.
And I think that it would be appropriate to say in Chapter 4 that the
handbook, you know, was a working document and assure people that the right thing
was done somehow in some crafty words.
I think that needs to be done in the substantive chapters. I don’t know what I would say in the
introduction about these issues. I mean
...
P.
CAMACHO: It seems to me that you
would have all the other, you know, the other qualifiers. I mean, the whole intro chapter is a chapter
about qualifications of the study and that’s ...
M.
STOTO: I guess I don’t think that
this is a — such a thing though.
P.
CAMACHO: Right.
J.
MICHALEK: A few words; now I’d need
to re-read Chapter 1 in light of these comments, but I think looking for places
in Chapter 1 to reassure the reader of the scientific integrity and quality of
the study should be done. I mean, it
may be a few words here and there to indicate the level of quality control, and
peer review and everything else should be made in Chapter 1.
P.
CAMACHO: And that more details are
in the other chapters.
J.
MICHALEK: Yeah. Right.
M.
STOTO: Okay. Okay.
Now you had another point, Paul?
P.
CAMACHO: Yeah. I’m — because when he said Appendix D, there’s
a phrase in — there’s a phrase in
Appendix D-1 that just says “target.”
You have the values and one of the columns is target; I had it marked. “Target,” is that expected values?
J.
MICHALEK: Bill Grubbs can correct
me if I’m wrong.
P.
CAMACHO: And then actual are actual
values?
J.
MICHALEK: Target was the — I think
that was the value of the coefficient of variation that we expected or wanted?
P.
CAMACHO: The expected value?
J.
MICHALEK: Or wanted or desired and
the — not true? Bill, did I say that
right?
J.
ROBINSON: No.
W.
GRUBBS: The target — Bill Grubbs —
the target is, I believe, I’d have to study it a little bit more in detail too.
J.
ROBINSON: Right.
W.
GRUBBS: But I believe it’s the
target that was desired or what was put in the system as the standard by
Scripps Clinic. This, for example, for
the low, their target during that time period — 5/6 to 9/4 — was 4.2. They actually achieved a coefficient
variation of 1.5, so that’s their standard I would ...
P.
CAMACHO: So the target is some — a
value, a significant threshold value?
W.
GRUBBS: It’s a coefficient of
variation.
J.
MICHALEK: It’s a level; it’s a
measure of quality control that is desired by laboratory technologists to
achieve. And it’s actually achieved, as
in many cases, better than that, which is a reflection of expertise and the
latest equipment that they used at Scripps.
W.
GRUBBS: Targets are often done by
manufacturer standards. Here’s our
control lot; here’s the expected value; here’s the expected standard
deviation. You take the ratio and get a
coefficient of variation. And one
point, for example, in the first line there — 1.5 — is what was actually
achieved on the data collected.
J.
MICHALEK: In this table, the lower
numbers are better and so a 1.5 means much better quality control than a — than
a 4.2. And so this is a tribute to
Scripps. Maybe that should be said up
on the top paragraph there.
M.
STOTO: I think it does need to be
clarified; that ...
J.
MICHALEK: Yeah.
M.
STOTO: ... basically they — I think
what you're saying is this will not be regarded as acceptable if the actual
value was higher than the target value?
J.
MICHALEK: It’s the other way
around. We want the lower CVs, yeah.
M.
STOTO: It would not — it would not
be acceptable if it were ...
J.
MICHALEK: Right.
P.
CAMACHO: But you wouldn’t
know. That’s where I got confused.
M.
STOTO: That’s right. You wouldn’t know that from the sentence, so
that can be clarified. Yeah.
E.
HASSOUN: What about higher
values? I mean, if the values were
higher than the ...
J.
MICHALEK: Well, then it’s a — I
think there’s another example there and that would be a point of concern, but I
don’t think you’ll find very many like that.
W.
GRUBBS: If there is, it’s very
sporadic — very.
P.
CAMACHO: 13.0 is the closest.
J.
MICHALEK: Well, then you’ll have to
— you’ll ask yourself what is the industry standard and is 13.5
acceptable? And so some of these, it
probably is. In many cases, the
standards set by our statement of work were very stringent and so a slight
departure from those is probably not out of range of what people do in hospital
laboratories. Did I say that right, Jay
Miner? Yes.
M.
STOTO: Now that I look at this more
closely, it’s also not clear to me what “high,” “medium” and “low” mean in this
context.
J.
MICHALEK: Yeah. Those are the standards they used to
calibrate their equipment. This is not
— this is not patient data. These are —
these are manufactured specimens that are used to calibrate equipment: “high,” “medium” and “low.” So there’d be a manufactured specimen for
250 mg/dL of cholesterol, for example, that they purchased, and they run it
through the equipment and they'd better get something close to that when they
measure it. And so that’s how they do
lab QC.
M.
STOTO: Okay. Well, I think that could be clarified too
for ...
P.
CAMACHO: But then it — then it's
not clear at all.
J.
MICHALEK: A few sentences would fix
that.
M.
STOTO: Okay. Jay?
J.
MINER: Jay Miner. If we could go back to the Examiner’s
Handbook again, that was put out as part of the statement of work to give
overall guidance to Scripps Clinic and SAIC.
SAIC then put together a biomedical test plan which went into great
detail to achieve each one of the items in the physician’s handbook. So yes, each physician was given that to
review, but the actual training was based on the biomedical test plan.
D.
JOHNSON: Well, maybe in the intro
then on line 12 where it says “the Air Force carefully prescribed the details
in the Examiner’s Handbook in Appendix B,” you might want to add to that
that ...
J.
MINER: Right.
D.
JOHNSON: ... this — what you just
said.
J.
MINER: Yeah.
M.
STOTO: Exactly.
R.
TREWYN: It wasn’t — it wasn't
prescribed in detail in ...
D.
JOHNSON: In the handbook.
M.
STOTO: And to make it available
what Scripps used either as an appendix or on the web somehow.
W.
GRUBBS: I’m not totally sure, but I
think there might be a reference to the biomedical test plan; if not in Chapter
1, in Chapter 6–“Quality Control.”
There’s some reference. This is
...
M.
STOTO: Well, it wouldn’t hurt to
have it here.
W.
GRUBBS: It’s a key document, yeah.
J.
MINER: Yes. And indeed, we could put that on the web, I
think, as a ...
M.
STOTO: I imagine it’s a pretty hefty
thing. Yeah. Okay. Other comments?
D.
JOHNSON: Well, I have a
couple. These are getting closer to —
I’ll just read, since there is time, I’ll quickly go through them. There are about four or five of them. On line 86 ...
J.
ROBINSON: In the physician's
handbook?
D.
JOHNSON: No, of the Chapter 4, back
on Chapter 4.
J.
ROBINSON: Now part, line what?
D.
JOHNSON: Okay. These are — these are minor things, so I’ll
go very quickly. Line 86, it says that
“Alcohol was prohibited for 24 hours before the first day of the exam.” That’s not very clear as, you know, that’s
probably spelled out someplace else.
Line 99, the “Board certified internist” again. I don’t — just for consistency, sometimes we
use “Board certified;” other times, we don’t.
It seems it might be clearer just to say “internist” with a capital
“Internist” or something because that’s what you used with cardiologist, with
dermatologist.
Because
it makes you think as you read through it, some of these people are Board
certified internists and some of them aren’t.
So that was my only — the same point.
Line 107, it says “On the first examination day, participants were asked
to collect their first urine void of the day at the hotel.” Well, that just needs to be — it makes it
sound like you’re telling them that day on the first day that — well, the — in
the morning, you should’ve collected your first void. So that just needs ...
M.
STOTO: Too late.
D.
JOHNSON: These are just ...
J.
ROBINSON: Good point.
D.
JOHNSON: And a similar issue on
105, 106 — line 105, 106. They said
“They were paid their stipends and reimbursed for travel at this time.” And I’m not clear what that time was. Does that mean after the psychological test,
everybody received their stipend?
R.
TREWYN: No, if they passed.
J.
ROBINSON: At the end of all the
testing.
D.
JOHNSON: That would clearer to say
that. And I imagine you want these kind
of comments? You might not want them
right now; I don’t know. Okay. And one final thing ...
J.
ROBINSON: It’s a matter of time.
D.
JOHNSON: One final thing on line
121, it says “the Air Force was provided 35 cc of serum and 10 of whole.” I would go ahead and put “10 cc of whole”
just for clarity: whole blood, add your
units on line 121 to 10, add cc to 10 cc’s.
So, but very good; it's well written.
J.
ROBINSON: Thank you, sir.
D.
JOHNSON: A few minor things.
M.
STOTO: Yeah. The fact that we are talking about such
details really says a lot about how good the material is.
D.
JOHNSON: Yes, it was good.
M.
STOTO: Right.
D.
JOHNSON: It’s good.
M.
STOTO: Okay. So now we’re ready to move to the first of
the two substantive chapters for today and Dr. Leffingwell is the reviewer for
Chapter 17.
N.
RIVERA: Dr. Leffingwell, pull that
microphone closer to you.
S.
LEFFINGWELL: Okay. I got along fine with this until we got up
to about line 247. Let me get the paper
out in front of me so I can refer back and forth; that would be page 17-5 and
that sentence sort of hung me up for a minute and then I got back to the lines
preceding it. I finally figured out
that this wasn’t a creatinine clearance measure; it was an estimate. And I think perhaps the text should be
clarified to indicate that it’s an empiric formula estimating creatinine
clearance, not actually a calculation of it.
When
I was trying — while I was trying to figure that out, I went back to see if
there would be any way of actually calculating a creatinine clearance. And I don’t suppose they recorded the time
of last voiding before they collected whatever specimen was analyzed? You can’t do creatinine clearances with less
than 24-hour collections if you know the time, but there’s an error with
that. The two references — where are
those given? — 52 and 53 or 53 and 54 were Lam and I think Soto. And apparently, the actual formula comes
from Cockroft-Gault, which was not cited.
Lam
certainly did some important validation work and that reference should be
retained. I have not gotten yet the —
either the Soto or the Cockroft-Gault reference. I think Soto did something similar to Lam and so it’s worth
keeping. I think all that’s needed then
is simply add the Cockroft-Gault reference.
Any further comment or discussion of that section before we go on to
339?
Line
339 is on page 17-9. And I just
wondered would any — how many of these results would still remain significant,
this is the whole section really, if a correction from multiple sampling were
applied? I think it’s generally agreed
that that’s an overly stringent thing and a lot of good results go away if you
try to do that. I’m just kind of
curious what would happen if a Bonferroni correction were applied?
M.
STOTO: Well, that’s an issue for
the whole report, not just for this ...
S.
LEFFINGWELL: Yeah.
M.
STOTO: ... issue here.
S.
LEFFINGWELL: Yeah.
M.
STOTO: And I think that we’ve
discussed that before.
S.
LEFFINGWELL: Yeah.
M.
STOTO: And I think it’s a sign of
old age that every member having discussed things, but not how they were
resolved. You want to say something
about that?
J.
MICHALEK: Only that the current
textbooks argue against using the Bonferroni if you look at Rothman’s book, for
example.
S.
LEFFINGWELL: Yeah.
J.
MICHALEK: We have done thousands of
statistical testing in this report, not counting the rest of the study. I think the best context for the multiple
comparison procedure is in the control clinical trial where you have a — you’re
required by FDA to prescribe a primary endpoint and you are prescribed to
specify primary contrasts with placebo and control. And there in that restricted setting, you do Scheffe’s method or
something like that, but not in a study like this.
S.
LEFFINGWELL: Okay. That makes sense.
M.
STOTO: You know, I agree with that
as a — as a statistician, but you might actually cite that in the methods.
J.
MICHALEK: That’s a good idea. A sentence to that effect in the methods
chapter would be helpful.
M.
STOTO: Yeah.
J.
MICHALEK: Yeah, to reference
Rothman’s textbook. Yeah.
S.
LEFFINGWELL: Skipping over the next
thing on the part — thing I handed out to 369 to 73, since the critical
variable in this is the serum creatinine and then they’re using age and weight
to estimate the lean body weight and creatinine generation, I wondered if the
estimate of creatinine clearance had an independent structure? It would be sufficiently independent of
serum creatinine to warrant separate analysis.
It’s a transformation; it’s one over the creatinine with some other
factors thrown in, but I just wondered if that was really appreciably different
from creatinine?
J.
MICHALEK: You would know the
medical context of that better than me.
And because one variable is a reciprocal of the other, that means to us
that they’re highly related statistically and so the reader should — the reader
— the smart reader would know that purely from a statistical point of
view. Mike Stoto might have something
else to say.
M.
STOTO: It seems to me that is it an
issue of maybe which one is better as opposed to — and I think you’re saying
...
S.
LEFFINGWELL: Possibly or possibly
both should be presented. The addition
of age and weight as a way of estimating 24-hour creatinine generation or
excretion might be enough extra information to really make it an independent
variable.
M.
STOTO: Okay. Okay.
S.
LEFFINGWELL: I just don’t know.
M.
STOTO: I mean, I don’t know about
these measures, but from what I understand you to be saying now is that it
would be a different — it would be a kind of adjustment by bringing age and
weight.
S.
LEFFINGWELL: Yeah. Yeah.
M.
STOTO: And I guess also what I
would say, consistent with what we just said about the multiple testing, we
look at lots of different versions of things.
So I guess I would be in favor of including it then ...
S.
LEFFINGWELL: Okay.
M.
STOTO: ... if it has a — the
potential for being more explanatory.
It’s easy to do and we’d just decide that we’re not worried about
multiple testing.
R.
TREWYN: Of course from Joel’s
comments, it indicates that only statistical people can read this in a smart
fashion. It would be a smart reader
from what I ...
S.
LEFFINGWELL: Okay. Skipping merrily along to the next page —
lines 471 to 508, et cetera — we have, for each of these variables,
analyzed rather extensive tabulation, most of which turned out to have no
significant associations. And I’m just
wondering if it would be easier on readers to summarize the positive findings
and relegate the balance of that to an appendix for those people who are really
intent on looking at it all. I find it
difficult going through something like this just staying awake, much less
understanding it.
J.
MICHALEK: This is a fundamental
format decision that we made a long time ago.
S.
LEFFINGWELL: Okay.
J.
MICHALEK: And you review the report
as a — as a — as a catalog of data to be browsed. And we tried to trim back the writing this time to emphasize only
the significant findings and then just to — if it’s not significant, just say
so and move on to the next table.
M.
STOTO: I have to say though, we — I
mean, I recall discussing this as well in the past. And although it may not have been what I would’ve suggested at
the beginning, that’s what we, I think, makes sense at this point. But this new table that you’ve given us
here, this 17-point question mark/question mark, I think is a — is a quite good
idea about how to address this. So that I guess it’s the third page of the
handout you sent around.
S.
LEFFINGWELL: Yeah.
M.
STOTO: And one of the concerns that
I had with these chapters in the past, and I think we discussed this too is —
let me see; which chapter? — the summary table, like Table 14 — 17-14 and I
guess other ones after that are basically significant, or not significant or a
— or a p value is given. And the
concern I have with that is the p value is meaningless in cynical terms. And what this new table that Sandy suggests
does is it, if I understand it, it picks out the ones that were — had p values
lower than 0.5 and then says what’s the clinical value that goes with
that. Is that what you — is that what
this is?
S.
LEFFINGWELL: We’ve got two separate
tables here and they came from different parts of the document. The first page, “Dependent
Variable-Covariate Associations,” has a different source than the other
one. And yeah, I think that’s about how
— what I did. I believe that’s correct.
M.
STOTO: Yeah.
S.
LEFFINGWELL: Now another
possibility: if the decision is to keep
the entire data in the body of the text, you might do it in a newspaper style
and lead off with the big news in the first paragraph and instead of saving it
for the summary. That’s a judgmental
call. The table, however, here did
illustrate another problem. For “kidney
stones and kidney disease,” for example, there was a p value given for
correlation with age. When we get down
to “blood urea nitrogen,” the tables do not contain any information on the
values of the increase with “born <1942.”
Similar, there’s a gap with the serum creatinine age, creatinine
clearance age, urine albumin to creatinine ratio, and urine-specific gravity.
J.
MICHALEK: Sorry. Could you repeat that about born before
1942? What was your point there?
S.
LEFFINGWELL: Okay. You have a correlation with age and the
dichotomous variable is “born <1942 or >1942.” There are values given: 12.6 percent versus 8.3 percent under
“kidney stones.” Under “age,” kidney
disease had 39.7 percent born before 1942 versus 33.6 1942 or later. When you get down to “blood urea nitrogen,”
there’s a significant correlation, but we don’t know what the percentages are
for before 1942 or later. It wasn’t
given.
J.
MICHALEK: I wonder why that wasn’t
given? Bill Grubbs, do you know
why? Now you’re getting these from the
covariate association chapter? That’s
where you’re getting these numbers from?
S.
LEFFINGWELL: Yes. Sub-section, yeah.
J.
MICHALEK: Yeah. It could be we just inadvertently missed
that one in the covariate associations.
S.
LEFFINGWELL: And there are several
of those things where it’s question mark versus question mark ...
J.
MICHALEK: Yeah.
S.
LEFFINGWELL: ... over in the
right-hand margin ...
J.
MICHALEK: Yeah.
S.
LEFFINGWELL: ... where ...
J.
MICHALEK: Well, this is obviously a
very thorough review of our own stuff and I appreciate it very much. I mean, thank you for all this hard
work. I mean, it’s another cut at our
work here so ...
W.
GRUBBS: Joel, if I can make a
comment?
J.
MICHALEK: We’ll just have to follow
up on what you said. I don’t know if we
can answer it today. Yeah?
W.
GRUBBS: If I can make a comment; Bill
Grubbs, SAIC. The table you have on the
dependent variable covariate associations, I believe, is summarizing what’s in
Appendix F-9 in terms of which ones were significant — the text as you have
attempted to do that in words basically.
We've actually discussed amongst ourselves and the Air Force about even
streamlining the text there to give trends and stay away from the numbers
because they are all in the appendix.
What
you have here is a thorough review.
It’s a summarization of what is in the appendix. The questions we've had internally is, is
this really relevant to the question of dioxin versus the dependent variable
and should it be in the text, in the appendix?
Should it be a focal point of the chapter? And we’ve gone back and forth in discussions in terms of
expanding it, streamlining it, just referring to the table, any number of
different ways.
M.
STOTO: Well, let me comment on
that. Looking at the — at least with
respect to the fourth page of this, the second table that Sandy put together,
the one that begins with “kidney stones” and shows that kidney stones, you
know, 16½ percent of the people with a low dioxin measurement had kidney stones
versus 10.7 with a medium and then the last one is cutoff. I mean, it seems to me that that adds value
beyond saying that the p value was 0.008.
In fact, it shows that kidney stones are less likely with high
dioxin. Is that right?
S.
LEFFINGWELL: Yes.
M.
STOTO: And it seems — that said
something that you wouldn’t have guessed.
J.
MICHALEK: But that's unadjusted.
M.
STOTO: Okay. It’s unadjusted, but okay. So ...
W.
GRUBBS: Dr. Stoto, I agree with
you. The question we were discussing
here, I believe ...
M.
STOTO: Yeah.
W.
GRUBBS: ... plus what we’ve done
five years ago is where’s the appropriate place to have this? We have this in a table. As you’ve seen going through the tables, all
those numbers are there. That final
summary table that I believe you’re talking about is an attempt to just put,
you know, make it as concise as possible and not necessarily as detailed as
possible.
M.
STOTO: I know — I know that’s what
we’re talking about. And I’m saying
that I think that the significant/non-significant p value doesn’t give enough
information to really interpret the results.
And I think that the summary tables or the summary of the report would
be more useful if they included a table like this one, this fourth page of
Sandy’s thing, in addition to what’s there.
P.
CAMACHO: This is another example of
why perhaps in the intro, you have a page of bullets that address that, you
know, little things that’ll address that issue.
M.
STOTO: Well, I mean, I think that,
you know, when this comes out, there'll be a — there’ll be an executive
summary, and there’ll be a news release and stuff like that. That’s where you pull these things out. But in terms of summing up, I think what
we’re talking about here is summing up these substantive chapters. And even though these numbers are someplace
else in the report because that’s how Sandy found them — he, I mean, they’re
there. I think that the numerical
differences add substantially beyond the p value and only for the ones that
they’re significant. That’s my suggestion.
P.
CAMACHO: But you should tell people
that.
M.
STOTO: Oh yeah.
P.
CAMACHO: I mean, I think the
appendix — I mean, the intro in some ways is the best place to tell — I — is an
additional place to tell people.
J.
MICHALEK: Well, just to carry that
thought through a little bit more, there are over 300 endpoints in the study and
so you can — you can overwhelm. If
you’re talking about tabulating, this is a great table. I’m not arguing against it; it’s a nice
table, but it's only one chapter and it happens to be a chapter with only a few
endpoints. Endocrine, for example, had
what, 50 endpoints?
W.
GRUBBS: Forty to 50.
J.
MICHALEK: Forty to 50 endpoints,
400-page chapter. You know, some
judgment has to be made obviously about what to tell the reader in the
introductory chapter. Otherwise, the
introductory chapter becomes a catalog of results.
M.
STOTO: Well, let's set aside the
introductory chapter for the moment.
J.
MICHALEK: Okay.
M.
STOTO: Let’s decide what to do
about the substantive chapters and then we’ll come back to the introduction
because they’re two separate issues.
J.
MICHALEK: Okay.
M.
STOTO: So can we talk about the
substantive chapters? I mean, do people
feel that something like this would be of a valuable addition to the
substantive chapters? And by this, I
really am saying this is — we would only put something in this table if it is
significant in the — in the analysis.
So it — so there could be 40 endpoints, but it may be only some of them
will be — have significant differences and only then ...
J.
MICHALEK: Well, that’s true. Yeah, and many chapters would have none.
M.
STOTO: Right.
J.
MICHALEK: Like psych, for example.
M.
STOTO: Yeah.
J.
MICHALEK: Yeah.
M.
STOTO: Comments?
S.
LEFFINGWELL: Obviously, I kind of
like the format on page 4, but that’s, you know, pride of authorship and we
oughtn’t go too far on that. I did put
asterisks out here and ...
M.
STOTO: Well, we should — we should
— we should give you credit for having done it and show that it can be done
without a tremendous amount of effort.
S.
LEFFINGWELL: I did put some
asterisks out there under the direction thing and I don’t have a footnote that
goes with the asterisks. But the intent
there was to point out that the direction of association would indicate a
change in the direction of greater health with exposure. And I think that’s worthwhile for readers
remembering just as a kind of a way of illustrating there is a lot of random
variation here that may genuinely not be associated with exposure either way.
J.
MICHALEK: All right. It may not be random. I mean, you know, that’s a good point, Dr.
Leffingwell, that we have realized in the last few years that this control
group is not the solid rock of pure healthy men. These men have been exposed to other things too and we don’t know
what and we don’t know why. But they’re
expressing their own trends of health in the adverse direction that we’re just
now understanding, so ...
S.
LEFFINGWELL: Yeah.
J.
MICHALEK: ... it’s a good, I think,
a good exercise to do. I’m not arguing
against it.
S.
LEFFINGWELL: Want to do a chapter
on hormesis?
J.
MICHALEK: Hormesis is an issue,
yes, and that would keep us going for another 15 years. Yes, and I also suggest that this is a — to
extend this table is something that I could do, for example, at my
desktop. Personally, I could make such
a table for every chapter and relieve the contractor, in other words, of that
responsibility and I could do it.
R.
TREWYN: So moved.
J.
MICHALEK: And yeah, and maybe it
could be put out as a separate document, you know.
S.
LEFFINGWELL: I did transmit the two
I sent to Kimberly, so ...
J.
MICHALEK: Okay.
S.
LEFFINGWELL: ... if you want to
import those or do something with them.
J.
MICHALEK: That’d be great; that
would be helpful, yeah. It could be a
separate document from the big report, something you could hand out to people,
you know, as a supplement perhaps.
M.
STOTO: Okay.
J.
MICHALEK: And so yeah; it’s neat.
S.
LEFFINGWELL: Then going on, 1088
simply supplies the reference for Cockroft-Gault. I’m sorry; I tried to get that and bring it up with me and I just
couldn’t get it in time to bring it.
And the last section on 1096 is a favorite rant of mine and I will spare
you the — I really would like to get rid of “conservative” though.
J.
MICHALEK: I don’t see that word up
there, but oh.
R.
TREWYN: I think “clinically
liberal.”
J.
MICHALEK: I don’t know a good
synonym for that word. What would you
suggest other than the word “conservative?”
M.
STOTO: Well, he has a suggestion
right there.
J.
MICHALEK: What’s that?
M.
STOTO: Well, you can read it. It’s in the third column of his handout.
J.
MICHALEK: Oh okay.
M.
STOTO: But that — but that’s a
point that really probably goes across many chapters.
S.
LEFFINGWELL: I wouldn’t wonder.
M.
STOTO: Yeah, so that I think that’s
— I’d make a recommendation that someone look carefully to that all the way
through.
J.
MICHALEK: You know, and I looked at
this. I thought when I first glanced, I
thought this was just a copy of a comment resolutions that we did with SAIC
already, but it’s not. This is from Dr.
Leffingwell’s comments.
M.
STOTO: Right.
J.
MICHALEK: That’s brand new to me
...
M.
STOTO: Well, I think he did a ...
J.
MICHALEK: ... because it has the
same format, you know. It looked just
like one of our own.
M.
STOTO: Yeah. I mean, he did — he did ...
J.
ROBINSON: Joel, what I did is I ...
J.
MICHALEK: Yeah. Yeah.
J.
ROBINSON: ... sent it to Kimberly,
our format, in case anyone wanted to use that.
J.
MICHALEK: Oh, that’s why it looks
like ours. Yeah. Okay.
M.
STOTO: But he made up these new
tables and that’s his own format for those tables.
J.
MICHALEK: Yeah, that's nice.
M.
STOTO: Okay. Anything else?
S.
LEFFINGWELL: And then I didn't have
any comments on the appendix to that —
F something or other?
J.
ROBINSON: F-9.
S.
LEFFINGWELL: F-9, okay.
M.
STOTO: Appendix F is just a set of
tables, right?
S.
LEFFINGWELL: Yeah.
M.
STOTO: And so you derived things
from that from — okay. Okay. Well, good.
Well, thank you.
R.
TREWYN: And we’re finished with
lunch.
M.
STOTO: I hope everyone enjoyed
their lunch.
M.
STOTO: And then Chapter 6–“Quality
Control” is Paul. Are you ready to
discuss that?
P.
CAMACHO: I didn't get the message.
M.
STOTO: Yeah.
R.
TREWYN: We’re moving through these.
M.
STOTO: You didn’t get that
message? Okay. Yeah.
P.
CAMACHO: I’m sorry. I didn’t — I definitely — somewhere I missed
that. I apologize if that’s the
case. I was out last week, and then I
get into my office this week and I saw the Chapter 1; I saw the appendix. I looked at those.
W.
GRUBBS: Dr. Camacho, the Appendix D
that you referred to goes with 6.
P.
CAMACHO: I only saw Chapter 1 and
Appendix D on my e-mail. I’m very
sorry.
M.
STOTO: If he’s not ready — yeah; so
if he’s not ready, he’s not. So maybe
we can — I don’t expect that’ll be a very controversial one, so maybe we can
just put that off until next time.
E.
HASSOUN: I just have one comment
about this chapter.
M.
STOTO: Oh, so maybe you have some
comments? That’s good.
E.
HASSOUN: Yes, only one on page 6-5,
line 193: “No participants felt that
the experience was unsatisfactory.” But
if you look at the figure, you could see some unsatisfactory, like with
technicians’ blood draw and the clinic out-briefing, you have like 0.2 percent
and 0.5 percent unsatisfactory.
W.
GRUBBS: That the use of the term
“experience” in that sentence that you’re referring to, if you go back to the
sentence before then, it said “overall clinical experience.” So the — no participants felt that the
experience — it means the overall clinic experience.
E.
HASSOUN: Okay.
M.
STOTO: So should that be clarified?
W.
GRUBBS: It can be, yeah, but it’s
in the sentence before that. But we’re
just conserving words, but we’ve got plenty of paper so ...
M.
STOTO: Well, I mean, if we’re
already using plenty of paper, okay. So
maybe we don’t need to — have you had the — did you have a chance to look all
the way through it ...
E.
HASSOUN: Yes.
M.
STOTO: ... before? Okay.
So maybe we don’t need to bring it up again next time.
P.
CAMACHO: Or affect my lunch.
J.
ROBINSON: Yeah, that would be up to
the — you sir and the Committee.
M.
STOTO: Okay. Yeah, maybe — yeah. Why don’t you take a look at it, Paul?
P.
CAMACHO: You know, I’m sorry. It is — it is ...
M.
STOTO: Yeah.
P.
CAMACHO: It was there. When I — when I came back Monday, I just
quickly looked at it.
M.
STOTO: Okay. Why — maybe you can take a look at it now
while we’re reviewing the next one because I think we’re going to be done by
lunch ...
P.
CAMACHO: Right.
M.
STOTO: ... to be honest with you.
L.
SCHECHTMAN: Slow down, slow down.
M.
STOTO: Okay. Okay.
That may be a time for — that may be a good time for public comment.
M.
STOTO: “General Health” is Dr.
Johnson, Chapter 9.
D.
JOHNSON: Okay. I’ll go through it — I’ll include some of my
...
M.
STOTO: Let’s go through this one
line-by-line now.
D.
JOHNSON: Okay. I’ll go a little bit slower. Okay.
The “Organs/Diseases” title on line 69.
It doesn’t fit the paragraph very well, but apparently, that’s used in
every chapter so we’ll leave that. And
the next page, if you go to line 117 — are you there? — it says “The
reliability and reproducibility of the serum dioxin assay were established.” That should be “was” and that’s — I don’t
have too many edits like that, but that’s very basic. No?
W.
GRUBBS: Reliability and
reproducibility ...
M.
STOTO: You have to speak on the
mike.
D.
JOHNSON: Reliability was and the
reproducibility was.
W.
GRUBBS: But together, they weren't.
D.
JOHNSON: Okay. All right, my mistake then. Okay.
Down at the bottom, line 147, it appeared to me is if that would’ve —
might be better under the next title “Summary of Previous Analyses” because it
goes into — it gives a little summary of the results in 1982, 1985, 1992 and
1997. And right after that, you go into
a summary of previous analyses. And
actually, line 146 might be a good place to stop. These are suggestions; this is not — this is not critical. But also in that same paragraph ...
M.
STOTO: Can I ask about that? Do I recall that this epidemiology section
was written by that group that you contracted with? It includes Diane Mont and ...
W.
GRUBBS: Correct.
M.
STOTO: ... and so on. And then I imagine that 9.1.2 ...
W.
GRUBBS: Is from previous reports.
M.
STOTO: So that’s taken out of — so,
but that’s not part of what Diane did?
That’s part of what you guys did then?
So you understand the distinction?
They contracted with someone to write an overall summary of the
epidemiological findings.
D.
JOHNSON: Okay.
M.
STOTO: And she included this
summary of these findings there and then — of the Ranch Hand Study — and then
9.1.2 is actually — is that taken from the previous reports?
W.
GRUBBS: That’s correct. The — up through line 153 is a review of the
literature, all literature, including the Air Force Health Study reports. From 154 on are basically the summary or
conclusion section of previous reports to give the reader an idea of what’s
gone on with the Air Force Health Study.
So you will, in particular chapters, see references to the Air Force
Health Study results in the literature section, the background section.
M.
STOTO: So presumably, that chapter,
that paragraph 147 to 153 should be consistent with the next thing?
W.
GRUBBS: That’s correct.
M.
STOTO: And I guess you could ask if
you’re going to have the next thing, do you even need it there?
W.
GRUBBS: That’s a good
question. It is part of the literature
and the task had been a complete summary of the literature on dioxin so ...
M.
STOTO: But you don’t want though, I
mean, this — now that I’m thinking about it, 9.1.2, that’s the major Blue
Book studies, right? The ones that
— this is a summary of ...
W.
GRUBBS: Correct. Correct.
Yeah. A summary of previous
reports, yes.
M.
STOTO: ... of the previous reports
that were like — of the kind that we’re reviewing now?
W.
GRUBBS: That’s right.
M.
STOTO: The stuff in the previous
paragraph, if Joel and company published an article in Epidemiology and
so on, that could be in there?
W.
GRUBBS: That’s correct.
M.
STOTO: So you know that maybe here
they’re the same, but in other — in other chapters, there might actually be
more information?
W.
GRUBBS: That’s correct. There’s references Michalek and colleagues
studied the effects of psychology endpoints, “blah-blah-blah” ...
M.
STOTO: Yeah.
W.
GRUBBS: ... which aren’t part of
the report, but it would be an article that Joel wrote.
M.
STOTO: So that that would argue for
keeping it — both things in there? Is
that ...
W.
GRUBBS: Yeah, and it very well
could be a reiteration of what you see there.
It’s just — it’s, if you will, an abstract, taken from an abstract of a
report.
M.
STOTO: Okay. Is there any — does that — does that make
sense to everybody? Does that ...
D.
JOHNSON: So you want me to leave it
as is?
M.
STOTO: Yeah.
D.
JOHNSON: Is that what you’re
saying? Okay. This is — this is word-smithing so, and I don’t have a lot of
it. But I’ll — since we have time, I’ll
mention it. If you look at starting at
line 150, “Apart from the AFHS examinations, only a few published reports
relate clinical and laboratory indices other than those described above to
serum or adipose dioxin levels.” I thought
that was confusing the way it read. And
I thought it would be better if you said “only a few published reports other
than those described above relate clinical laboratory indices to serum and
adipose dioxin levels.” I think that’s
what they’re saying there.
And
then “These published reports, which relate specific health outcomes with
evidence of prior exposure to dioxin, are discussed in subsequent
chapters.” I had to read that several
times to figure out what they were trying to say because the way they had the
different segments put in there, but okay.
Line 167 — or 168, you say “sedimentation rate abnormalities,” and
later, you put in parenthesis that that’s “(>20 mm/hr).” I thought you should — that's the first time
I saw it here — I thought you should put it there and either leave it in the
other places or drop it in the other places.
On line 181 — are you ready to go?
J.
ROBINSON: What line now — 181?
D.
JOHNSON: 181: “The (geometric) mean erythrocyte
sedimentation rates did not differ significantly” between — I mean, between
what? I wasn’t sure what that’s
referring to there. Actually, I’ll just
make a — I won’t do too much of this.
I’ll make a comment that I felt, even though again, it was — I didn't
find anything wrong. The size was good,
and sound and so forth; that wasn’t a concern for me. This — these two pages here and these summaries or the next
several pages in the summaries were very — quite choppy, and full of facts and
not easy to follow. So it’s just one
fact after another and so I ...
M.
STOTO: Were they?
D.
JOHNSON: It was — it was difficult
reading and I don’t think you need to change it really for what it is. It just gives you a lot of different
facts. But it’s — it — each — all of
these sentences could have a paragraph with them telling you what they’re
talking about, but — and there’s just one after another, but ...
M.
STOTO: Were these — were these
taken pretty much verbatim from the previous reports?
W.
GRUBBS: With some minor style
edits, yes.
M.
STOTO: And so that might suggest
why they’re choppy like that ...
W.
GRUBBS: Yeah, it’s ...
M.
STOTO: ... if they were just
grabbed out of something.
W.
GRUBBS: Yeah, a piece here and a
piece there.
M.
STOTO: Yeah.
D.
JOHNSON: Exactly, and it’s — and
it’s ...
M.
STOTO: So maybe what you could do
is to say, basically say that these are taken from these previous reports and
...
W.
GRUBBS: Yeah, as an up-front ...
M.
STOTO: Yeah.
D.
JOHNSON: But if you’re trying to
grasp the overall picture of what it’s trying to say, it’s difficult to follow
because there’s just one fact after another that’s just kind of placed in
there. But that’s just a comment;
that’s — I don’t know that that really needs to be fixed necessarily.
R.
TREWYN: I just want to back up to
one thing; I hadn’t looked at this section.
But I have a question on the sedimentation rate abnormality since that
happens to be something I get a run on, I mean, every other month. And the cutoff that they’ve got for me is at
10 and in the clinical stuff. So where
did the 20 cutoff — I mean, anything above 10 shows on the sheets that that’s
considered abnormal. Where did the 20
come from?
W.
GRUBBS: I’d have to go back and do
some research on that. If you remember
in 1982, Kelsey-Seybold Lab did the — did the exams for the Air Force. And since 1985, Scripps has been doing
it. But even within Scripps at from
exam to exam, the cut point may change.
So you may be using a lab that has a cut point of 10; they may be using
something with 20. It — and it’s
entirely possible different labs have different cut points so, but I could find
out. I think I could find out what the
cut point is for the one that you mentioned.
D.
JOHNSON: Okay. I’m going to mention this once, and again, I
don’t think it’s going to be something you want to change. But on line 215, it says “In general, body
fat and erythrocyte sedimentation rate exhibited significant positive
associations with initial dioxin.” When
I’m — when I’m reading this, I guess everybody assumes that positive just means
a direct relationship. They’re going up
and it doesn’t have any other connotation as opposed to it’s a good thing or a
bad thing. And it’s — I don’t — I think
just leave it because that’s used a lot where you say a “positive association.” If that’s general accepted terminology
throughout all this report, I think that’s fine.
But
I just — now on line 232 though, it says “In summary” — “In summary, with the
exception of erythrocyte sedimentation rate” — so it says “with the exception
of the ESR, the data analyzed in the general health assessment did not reveal
any adverse health effect consequent to herbicide exposure or to the body
burden of dioxin.” So I take that to
mean indirectly that the ESR did have, did show health effects that were
consequent to herbicide exposure at a body burden and I’m not sure you want to
make that statement there.
So
I would suggest you change it to “did not reveal any association between
adverse health effect and herbicide exposure.”
So my suggestion is on line 233, you say “health assessment did not
reveal any association between adverse health effect and herbicide exposure or
to body burden of dioxin.”
M.
STOTO: So that — so you’re making a
— in the context of a statistical association rather than a causal
relationship, I think, is essentially what you're saying?
D.
JOHNSON: Right.
M.
STOTO: Which is appropriate for
these kind of data.
D.
JOHNSON: For this data.
M.
STOTO: Yeah.
R.
TREWYN: Right. Because as written, it means — it’s saying
that ESR is an adverse health effect, I think, is the way that ...
D.
JOHNSON: Right.
R.
TREWYN: ... it reads and that's —
it’s just a measure of ...
D.
JOHNSON: Right.
M.
STOTO: Well, that’s a different
issue, but that’s ...
R.
TREWYN: Right, but I think that’s
the way it reads.
M.
STOTO: Yeah.
R.
TREWYN: And I don’t think that’s
what’s meant either.
M.
STOTO: Can we come back to that
positive association on 215 and ...
D.
JOHNSON: Well, it's used a lot.
M.
STOTO: Yeah. That’s why — that’s why I want to come back
to it. I mean, there’s a couple of
possibilities. One would be to say
rather than say “positive,” use “direct.”
D.
JOHNSON: That’s more ...
M.
STOTO: I think that would be — that
would be ...
D.
JOHNSON: I think I’ve seen that
more.
E.
HASSOUN: It’s more scientifically
used — “direct association.”
D.
JOHNSON: “Direct association”
meaning — “direct” meaning they’re both going up in the same direction ...
E.
HASSOUN: Yes.
M.
STOTO: Right.
D.
JOHNSON: ... as opposed to a
positive.
M.
STOTO: The other thing would be to
explain someplace what’s meant by “positive.”
That would be the easier thing to do, but I think that the preferable
thing would be to replace “positive” by “direct.” Does that — you want to comment on that?
R.
TREWYN: I agree. I think that makes it clearer because there
are other connotations to positive.
D.
JOHNSON: Right.
R.
TREWYN: And it means it’s a good
thing.
D.
JOHNSON: A good thing, a positive
association.
M.
STOTO: Right.
R.
TREWYN: Okay, and I don’t — that's
clearly what it means; is there is a direct correlation.
D.
JOHNSON: Right.
R.
TREWYN: I think it's better to
change it myself, but that’s ...
D.
JOHNSON: So we’d need to go through
and — because it’s used other places — and use “direct” instead of “positive.”
W.
GRUBBS: Out of curiosity, how would
you rephrase “negative association?”
D.
JOHNSON: It’s “indirect.”
W.
GRUBBS: It’s the other direction?
J.
MICHALEK: Wait a minute; it’s
called “inverse.”
D.
JOHNSON: Inverse; I’m sorry,
inverse. That’s correct, inverse.
M.
STOTO: Yeah. There’s also the issue, I suppose, that in
some cases, a high number is good. In
other cases, a low number is good.
J.
MICHALEK: Well, that’s a point that
I’m sensitive to whenever I read this too.
D.
JOHNSON: Yeah.
J.
MICHALEK: Because I get confused
about what’s good and what’s bad.
D.
JOHNSON: But that’s where “direct”
would be — wouldn’t make that qualification.
It’d just say that there’s a direct ...
J.
MICHALEK: Right. I think the word “adverse” should be in
there somewhere now and then to remind the reader of what’s good and what’s bad
clinically.
M.
STOTO: Well, I think that comes in
the — in the — in the, essentially, the discussion. You say there’s a — there’s a direct association or an inverse
association and that means ...
J.
MICHALEK: Well, sometimes there
needs to be a medical doctor has to say what’s good and what’s bad on some of
these chemistries because a reader like me doesn’t know.
M.
STOTO: Yeah.
J.
MICHALEK: And we’ve caught some of
those in the writing, but whatever you catch is good, you know.
M.
STOTO: Right. Well, I think that comes in the discussion
rather than in the presentation of the — of the results.
J.
MICHALEK: No, I think it’s now and
then, they’re in the — in the results itself.
The reader should know, I think, what’s good, what’s up or down, bad and
...
M.
STOTO: You're right. Okay.
I — you’re right.
J.
MICHALEK: Yeah.
M.
STOTO: Yeah.
D.
JOHNSON: I can — I can appreciate
that, but going back to what we were talking about though, it says “body fat
and ESR exhibited significant positive associations with initial dioxin.” That indicates a good relationship and it’s
not. It’s negative because it’s going
up, which is ...
J.
MICHALEK: I agree.
D.
JOHNSON: ... which is adverse.
J.
MICHALEK: Yeah.
M.
STOTO: I mean, this ...
D.
JOHNSON: So that’s where “direct”
would be better.
M.
STOTO: ... this is an issue with,
you know, Scripps attesting to screening.
People said, “I got — my test was positive for HIV. Hurray!”
You know that is an issue in — particularly in less educated people.
D.
JOHNSON: Okay. So ...
J.
MICHALEK: “Beneficial” could be in
there now and then. If you see a change
in a beneficial direction, it should say that somewhere, you know.
D.
JOHNSON: So it’d be a direct
relationship, which was — indicates a beneficial effect?
J.
MICHALEK: It’s possible it could be
a direct and beneficial; it could also be direct and adverse, yeah.
M.
STOTO: Well, you see, I guess I
would stay away from using “beneficial” because ...
D.
JOHNSON: Right.
M.
STOTO: ... even though there may be
a, you know, some good thing might be — have a direct association with level of
dioxin exposure, I don’t think it’s likely that dioxin really made somebody
healthier.
D.
JOHNSON: Want me to move on? In line 206 going back, you’ve got the
“(>20 mm/hr).” And if you want to —
I’m for you; you can leave it in there if you want because it helps for
clarity, but it’s — then it becomes redundant.
Okay. I think I wanted to point
out that through all of these reviews, “erythrocyte sedimentation rate
displayed a significant positive association” — there it is again — but I just
wanted to point out that that seemed to be one of the inconsistent things and
I’ll come back to that in just a minute.
But
down on line 268, there’s a problem with that sentence structure, I
believe. Correct me if I’m wrong; it
says “Longitudinal analyses showed that Ranch Hands, particularly the two
enlisted strata, had an increased percentage of abnormal erythrocyte — ESR —
rates than did comparisons.” Now
there’s something missing there. It
should be “had a higher percentage of abnormal erythrocyte — ESR — than did,”
or instead of saying “than did,” say “compared” or “contrasted to
comparisons.” But the sentence is not —
there’s a problem with that sentence structure.
J.
ROBINSON: And you’re suggesting
that we say?
D.
JOHNSON: You could say “had a
higher percentage than did,” but the way it is now it says “had an increased
than did.”
J.
MINER: “An increased percentage.”
D.
JOHNSON: What’s that?
J.
MINER: “An increased percentage” —
the Ranch Hands had an increased percentage.
D.
JOHNSON: Than comparisons?
J.
MINER: Right, than comparisons.
D.
JOHNSON: No. Well, even “had an increased percentage than
comparisons” doesn’t work either. You’d
have to add “higher than.”
J.
MINER: “Relative to.”
J.
MICHALEK: “Relative to
comparisons.”
D.
JOHNSON: That would work too, but
there needs to be a change.
J.
MICHALEK: Right.
D.
JOHNSON: And then — and then on
line 271, “This increased risk to Ranch” — this gets to that association,
causation sort of thing. It says the
results — “This increased risk that Ranch Hands raises the possibility of a
subtle inflammatory, infectious or occult malignant disease process related to
the body burden of dioxin.” Well, what
risk are we talking about? I think — I
think if we said “This increased occurrence of elevated ESR in Ranch Hands
raises the possibility of a subtle inflammatory, infectious ... associated with
the body burden.”
J.
MICHALEK: Very good; that's a fresh
edit of an old sentence that’s been around for 15 years.
D.
JOHNSON: Oh, okay. And then on 274, we get into “In conclusion,
a poor or fair self-perception” and it goes into “Longitudinal analyses
indicate an increased percentage of abnormal ESRs.” Is that in conclusion of all of these paragraphs or is it just a
conclusion for 1997 because it’s ...
M.
STOTO: I’m sorry, which line are
you ...
D.
JOHNSON: Starting on line 274, it
says “In conclusion.”
J.
MICHALEK: I think that was intended
only for the 1997.
D.
JOHNSON: Okay, but then it goes on,
on the line starting at 277 there. It
says — and here’s where I want to just bring up a point about ESRs, erythrocyte
sedimentation rate. “Longitudinal
analyses indicate an increased percentage of abnormal ESR rates or ESR in Ranch
Hands over Comparisons in the 15 years of the AFS — HS, and a relation between
abnormal ESR and levels of dioxin during” this period. So right there it’s saying that — well, it’s
— to me it’s saying that consistently over 15 years, you’re seeing a
relationship with ESR and with — okay — with dioxin over that time frame.
The
point I want to just bring up just is that from the rest of this report, no, it
doesn’t mention ESR again. Here, it
summarizes ESR as being found and it — and it — and I didn't go through each
one. But on more than half of these, it
mentions ESR. It showed an association
and then it’s dropped at this point.
And in the — and for 2002, ESR is never mentioned again.
J.
MICHALEK: That's because — I’m
sorry — that’s because we moved ESR from “General Health” to “Hematology,”
didn’t we?
J.
ROBINSON: Yes. It got moved.
J.
MICHALEK: Yeah.
D.
JOHNSON: Then it might just — you
might just want to say that.
J.
MICHALEK: Yeah.
M.
STOTO: Absolutely, yeah.
J.
MICHALEK: And so that disrupted the
flow of the writing.
D.
JOHNSON: Because from — yeah; in
2002 and the rest of the description, it’s not mentioned.
J.
MICHALEK: Right.
M.
STOTO: Well, this ...
W.
GRUBBS: We did say that in
“Hematology.” We can, of course, say it
in “General Health.” Yeah.
J.
MICHALEK: Right.
R.
TREWYN: And I was just going to
add, and Mike may remember this and many wouldn’t, but we had used — we did, in
the late 1990s, did more battles over ESRs.
Our M.D. from Northwestern — I can’t remember her name — but had an
absolute kitten over ESRs, and that it was meaningless, and you didn’t know
what it meant and was fighting to get that all taken out. But yet, it really does show a lot of
correlation in many of these parameters, so even though they don’t understand
why. So ...
D.
JOHNSON: Right. Yeah.
I don’t know that ESR necessarily shows you anything, but it’s just
strange that it’s dropped at that point in this chapter.
R.
TREWYN: Right. Right.
J.
MICHALEK: It just needs to be
explained.
M.
STOTO: I think — I think at a
minimum it needs to be explained why. I
wonder if this — maybe the discussion also of the previous ESR rates belongs in
the new location rather than here or maybe in both places?
J.
MICHALEK: It sounds good to me;
move the whole ESR thing to “Hematology.”
M.
STOTO: Yeah. Right.
I mean, we obviously may want to ...
J.
MICHALEK: That way it’s ...
M.
STOTO: ... note that, you know, in
the previous reports ...
J.
MICHALEK: Yeah.
M.
STOTO: ... it was in something
else, but that should be the background to the — to the new ESR results.
W.
GRUBBS: I can attest that the ESR
is in “Hematology” in its detail. But
whether or not it should be in “General Health,” I’ll ...
M.
STOTO: I’m not talking about
whether — I don’t want to bring up this issue again about which chapter ESR
should be in. But I’m just saying that
...
W.
GRUBBS: No, but I’m ...
M.
STOTO: ... the historical results
about ESR should be in the same chapter as the new results for ESR.
W.
GRUBBS: Okay. They are in “Hematology.”
M.
STOTO: Okay.
W.
GRUBBS: But again, whether they should
— for the archives — whether they should be in “General Health” or not ...
M.
STOTO: Right. Right.
I think my inclination would be to drop it here except for an indication
that we used to consider it here, but it’s now considered someplace else.
D.
JOHNSON: Well, because the rest of
the discussion’s more on the other dependent variables ...
M.
STOTO: Yeah.
D.
JOHNSON: ... in the — but I ...
M.
STOTO: Yeah.
D.
JOHNSON: Okay. Line 283, it says “Dependent Variables” —
that section. And I just thought it
might be good to go ahead and list those dependent variables here — there. It just says “The general health assessment
was based on data from 2002" and it seems like that’s the right place to list
what the dependent variables were.
Going down on line 302, it has a body mass index calculation as the
weight divided by the height squared.
And then you've got this reference, I think, in parenthesis which could
be confused as a factor. I thought you
could move that — move that down to the end of the sentence.
J.
ROBINSON: Could you give me the
line again? I'm sorry; I was still ...
S.
LEFFINGWELL: 302.
D.
JOHNSON: 302.
M.
STOTO: On the 28 — line 283, coming
back to that, isn’t it that, in fact, that just was a lead in to the next two
sections?
W.
GRUBBS: Exactly.
D.
JOHNSON: Okay. All right.
M.
STOTO: What you do — what you do is
that then say what they — what they are.
D.
JOHNSON: Right, what they are. I’ve seen it other places in this chapter
where they just list out the four — the four different dependent, but that’s
fine too. And the same thing on line —
did you get that?
J.
ROBINSON: Yes sir.
D.
JOHNSON: Same thing on line 306,
you’ve got “(118).” It looks like it’s
part of the factor; you might just move that to the end. The “(118)” reference, move it to the end of
the sentence. Next page, line 7,
nothing; line 8, it was nothing; line 9, nothing; line 10, nothing. Now on page 9-11 is where I kind of — this
is probably the bigger, the other large thing that I just wanted to bring up
and it’s already discussed, I think, in Chapter 17.
The models, the explanations of these
models, I found myself looking at this for the first time. Like you said, I haven’t looked at this
before and I’d have to go to the — and I know there’s been discussion about
this. I can tell there’s been a lot of
discussion about what to put in these tables.
But usually when I go to a table, I like to look at the table and the
table be self-explanatory. And I can
look at it, and there’s some summary there and I know what I’m looking at. I had to go back and forth between the text
and the tables to try to figure out what was in the tables. And when I went back to the explanation of
the models, they weren’t very clear.
For
example, it says, “Model 2 explored the relation” — this is line 440. It says, “Model 2 explored the relation
between the dependent variable and an extrapolated initial dioxin measure for
Ranch Hands who had a 1987 dioxin measurement greater than 10 parts per
trillion.” Well, for you all who’ve
been working the study, that’s clear.
But ...
R.
TREWYN: Makes perfect sense.
D.
JOHNSON: ... for someone who’s
trying to look at this data and understand it, if you said something more like,
“Model 2 explored the relationship between the dependent variable and the
initial dioxin level at the time of potential exposure to dioxin when they
began as a Ranch Hander.” Is that what,
you know, is it being extrapolated back to when they first started their
exposure?
R.
TREWYN: When it was first measured.
D.
JOHNSON: When it was first — no.
J.
MICHALEK: Extrapolated to Vietnam;
extrapolated to Vietnam.
D.
JOHNSON: If you’re taking it in
1987 ...
R.
TREWYN: Yes, that’s correct.
D.
JOHNSON: And that’s — for someone
who’s not used to looking at the data, that’s not clear and it’s similar with
Model 3 explanation. I added — I think
you could do your own words, but just, “Model 3 divided the Ranch Hands
examined in Model 2 into two categories based on their initial dioxin measures.” It’s just not kind of — you could say that
“Model 3 created categories of Ranch Hands based on the initial dioxin levels
and examined the relation between the dependent variables and these
categories.” It would’ve been more
clear to me if you would’ve said something a little more descriptive.
R.
TREWYN: Right.
D.
JOHNSON: Now I don’t know if you
care. I don’t know that it’s critical
to make those changes ...
M.
STOTO: Well ...
D.
JOHNSON: ... because the data’s there if you want to spend the few hours
going back and forth and figuring out what it means.
M.
STOTO: ... the challenge — the
challenge here is that there is a set of standard statistical models that are
used all the way through here that are described first in Chapter 7, which we don’t
have. And then there’s a — there’s a —
there’s a section here on page 9-7 about statistical methods, but they’re not
described here.
So
maybe there could be — there could be a paragraph about the four models here so
at least it would be in this chapter or maybe in that — the methods chapter —
the methods section that we talked about earlier adding to all the — all the
chapters or something like that. The
other — the other thing is to say, use some standard wording that every time
you actually use those, you ...
D.
JOHNSON: Use the same words.
M.
STOTO: ... throw out the same
language.
D.
JOHNSON: Right.
M.
STOTO: Right.
D.
JOHNSON: Right.
J.
ROBINSON: In other words, fill up a
boilerplate that could just be inserted into each of the clinical chapters?
M.
STOTO: Yeah.
D.
JOHNSON: So along the same lines
looking at the tables — and I know, again, you’ve tried to trim these down so
that they’re easy to understand, but they’re — they may be so trim that they’re
difficult. For example, if you just —
if you just said, “Model 1:
Self-Perception of Health of Ranch Hands Versus Comparisons Unadjusted
for Covariates,” that would be so much easier than having to look back and say
— finding the text that’s unadjusted for what and I know you mentioned you
didn’t want to list everything.
And
looking back at the title of the table and its analysis because as you go
through and if you go down to the same model, line 447, “Ranch Hands-Initial
Dioxin-Unadjusted.” Well, if you’d said
“Ranch” — “Self-Perception of Illness in Ranch Hands Versus Initial Dioxin
Unadjusted for Covariates,” that would be so easy just to look at that table
and understand what you’re looking at as opposed to having to go back and look
at another chapter or look in the text to determine. And so that — I won't go through all of — all of it there, but I
don’t think those changes would be that difficult if you decided you wanted to
do it to make the tables much easier to read.
M.
STOTO: And particularly with
respect to new ones that are in the new chapters as they’re being written to
try to be consistent in the wording and the way you described these
things. Now ...
J.
MICHALEK: Could we put — could we
put one of those tables up there on the screen so we know what we’re looking
at?
M.
STOTO: Yeah. You know, when you do the same statistical
models over and over again, it’s hard to be exciting and you’re writing
it. And it reminds me of a story about
a statistical book that was — a whole book that was written about robust statistical
methods. And the editor didn’t like
using the word “robust” over and over again, so she changed it to things like
“oak-like” and ...
D.
JOHNSON: 477 — line 477's a good
one because I wanted to make another ...
J.
MICHALEK: So what was the recommendation
for this table? But it already says
that.
D.
JOHNSON: Well, it does. But it does there, but as you get through
these, you start reading them, you really have to do a lot of thinking to
figure out ...
J.
MICHALEK: “Unadjusted for
Covariates,” that would be the addition?
M.
STOTO: Yeah.
D.
JOHNSON: But then you go down about
three or four from that, and you have to look back at the title and see are
they still talking about self-perception.
And so if each table had a — had a title that was descriptive, it would
make it very easy, much easier to look at the data.
M.
STOTO: Yeah.
J.
MICHALEK: All right. Let me play devil's advocate for a
second. It does say “Self-Perception of
Health” right there, right?
M.
STOTO: You know, maybe the problem
is that ...
J.
MICHALEK: Maybe put that all in
caps?
M.
STOTO: Yeah. Maybe the problem is that just the typeface
there is ...
J.
MICHALEK: Put that all in ...
D.
JOHNSON: No, but I think if you
start — if you’re not used to looking at the data and you start looking — say
if you go down to model — go down to a couple other of them; that one’s right
there on top of it. And so you’re
saying it’s right there and you’re not really sure. For example, if you go down to model — line 477 — see “Model
2: Ranch Hands-Initial
Dioxin-Unadjusted.” So then you’re —
then you have to assume that, okay, we’re talking about self-perception. Is that what we’re talking about?
J.
MICHALEK: Yeah. We’re still on the self-perception table.
D.
JOHNSON: Yeah. We’re — yeah. So you can figure it out if you — if you start looking at it, but
if it just said, “Self-Perception of Ranch Hands Versus Initial Dioxin,” you
would know what that table’s about. And
the further you get away from that title, the less you’re really sure what
you’re talking about. But I understand
your point too because I figured that out that it’s there if you go back and
look at the original 9-3.
But
say, look again at 477. It says — it
says, line 477, “Ranch Hands-Initial Dioxin-Unadjusted.” And then it says “Analysis Results for Log2
(Initial Dioxin).” And it — and it says
“Adjusted Relative Risk.” Now I still
haven’t quite figured out: you’re
unadjusted for the covariate; you’re adjusted for BMI? Is that what you’re adjusted for there? Because it doesn’t really make that — it
says “Adjusted for BMI.” Okay. And then in some tables, you’ve got — it’s
consistent where you’re adjusted and you’re adjusted and other ones it’s
adjusted and non-adjusted. And then it
says “Relative risk for a twofold increase in initial dioxin.” What does that mean?
R.
TREWYN: Where are you?
J.
ROBINSON: Line 480.
D.
JOHNSON: Oh well, yeah, 480.
J.
MICHALEK: Well, that’s because a
unit change in log2 means a doubling of dioxin and so ...
D.
JOHNSON: So, but what is that table
telling me? It says the p value is
0.314 for adjusted relative risk and it says — what is that p value referring
to? It’s — and ...
J.
MICHALEK: It’s referring to the
1.10 relative risk is not significantly different from 1.0.
D.
JOHNSON: But what is that? What is that? Are we talking about what’s the p value? What is significant or not significant
there?
J.
MICHALEK: The relative risk is not
significant.
D.
JOHNSON: Relative risk for what?
J.
MICHALEK: The relative risk for a —
for a — for adverse — for an adverse response on self-perception of health
versus a unit change in log2 dioxin. A unit change in log2 dioxin is equivalent to a
doubling of dioxin.
D.
JOHNSON: So ...
J.
MICHALEK: For every doubling of
dioxin, there’s a 10 percent increase in risk of adverse response on
self-perception of health and that increase is not statistically significant, p
value 0.314. Obviously, this report is
not written for the lay reader.
D.
JOHNSON: Well, I mean, even for the
scientist.
J.
MICHALEK: It’s written for you and
...
D.
JOHNSON: If you look at — it’s just
hard to make that — what you’re really saying, significant or not significant,
is it the low, medium, high? Is it a —
is it a — is it longitudinal across those or is it — what are you comparing?
J.
MICHALEK: You’re comparing a fair
or poor self-perception of health with — go to excellent and you’re saying an
increased risk of fair or poor self-perception of health with a unit change in
log2 dioxin. However, that
inflated relative risk is not significantly different from 1. So we have an increase in relative risk, a
10 percent increase, but the confidence interval and p value show that that's
not a significant increase.
D.
JOHNSON: Well, I mean, with the —
with the — with the 1 and the relative risk for a twofold increase in initial
dioxin, it’s just I could not get all of that out of there; I could not.
J.
MICHALEK: Well, that’s because you
have — you know the — you have to know that we’re using a continuously
distributed independent variable, namely log2 dioxin. Mike Stoto, is there another way to say
this?
M.
STOTO: Well, I think the way to
handle this is to have sentences for the titles of the tables rather than
phrases.
J.
MICHALEK: Than these phrases?
M.
STOTO: Yeah. I — and it gets to be repetitive.
J.
MICHALEK: Yeah.
M.
STOTO: But I do think that people
do look at the tables without reading the text that goes around it and so I
would propose that we — that we do that.
D.
JOHNSON: Tables are usually
stand-alone when you look at them.
R.
TREWYN: Yeah, and I would certainly
agree with that. And as long as, you
know, Joel is there to explain it to everyone when they read it, which is
probably not practical for on down the road, it makes sense what you said. But it — it’s — you aren’t going to get it
and I think most when you scan through these articles, you’re going to look at
the tables and, you know, the scientists are going to — going to assess the
results in the tables and you almost need to know — you need a little bit more
there to know what it — what it’s indicating.
J.
MICHALEK: I also have to say for
the record, and you might not like this, but you approved these table shells, I
believe. Is this true, Bill Grubbs, that
these tables were given to the Committee for approval a long time ago? Jay Miner, is that true? I’m not sure who remembers then.
W.
GRUBBS: The tables have looked
relatively similar since 1992 ...
J.
MICHALEK: Right.
W.
GRUBBS: ... to these.
J.
MICHALEK: And we attempted and
there’s a history to this in other words.
And Dr. Johnson, you’re new to this I know; that these tables ...
D.
JOHNSON: These are questions, okay
...
J.
MICHALEK: Yeah.
D.
JOHNSON: ... from someone looking
at it new.
M.
STOTO: Well, I don’t think we ...
J.
MICHALEK: You’re looking at it as a
fresh — in a fresh view. Go ahead.
M.
STOTO: Two things: one is we are not asking for the fundamental
structure ...
J.
MICHALEK: Right.
M.
STOTO: ... of the tables to be
changed. We’re just — we’re just
talking about elaborating ...
D.
JOHNSON: On the labels.
M.
STOTO: ... on the labels that go
with it. I won’t say the other thing,
which was those guys back in 1992 may or may not have made the right decision.
J.
ROBINSON: I’ve made a note in
regards to that.
M.
STOTO: Yeah.
J.
ROBINSON: And we’ll take it back
for — and this applies to all the tables across all chapters ...
M.
STOTO: Exactly.
J.
ROBINSON: ... and looking at the description of them.
J.
MICHALEK: And we try to make the
report so one report can be compared with another and so we have a legacy, in
other words, of trying to compare if someone might want to compare this report
with the last one and so on, so ...
M.
STOTO: Right, and that's important
and I understand the value of that so ...
J.
MICHALEK: Okay.
R.
TREWYN: What you’ll find out after
a few more meetings is the Advisory Committee really is just advisory, and they
listen to a few of our suggestions and ignore others. And that’s why, you know, if you're a — if you’re a pest long
enough, you know ...
J.
ROBINSON: Actually sir, we have to
document each of these and what ...
R.
TREWYN: I’m used to it.
J.
ROBINSON: ... what the outcome was
so there will be record of our action.
D.
JOHNSON: Well, part of my
difficulty was — part of the difficulty as a reviewer was even if you decided,
“Okay; well, I’ll go back to the text,” when you went back to the description
of the models, they weren't that clear either.
And so it was very difficult to go back and forth and try to make sense
of the — of the data.
J.
ROBINSON: And I’ve also made a note
of that about expanding the explanation
...
D.
JOHNSON: Of the models.
J.
ROBINSON: ... of each of those
models.
D.
JOHNSON: Okay.
J.
ROBINSON: And kind of making a
boilerplate that can be put into each chapter, so that’s also noted.
D.
JOHNSON: All right. I’ve only got just a couple others. The — on line — on line 516, you said that
they were “nonsignificant for Models 1 through 4,” a “p >0.10.” I wasn’t sure why you used 0.10 there
because 0.05 is used throughout the rest of the document for the most part.
W.
GRUBBS: I can address that. What we did there just as a global
statement, every p value that you see there is greater than 0.10. If every p value happened to be greater than
0.23, we would say “p >0.23" for each analysis. So it’s giving you the minimum across all
tables.
D.
JOHNSON: The only problem with that
is don’t you have to kind of make a decision of what level you want to consider
significant?
W.
GRUBBS: Well, the non-significant —
when it says “not significant” — that means it was not significant at 0.05; p
equals 0.05.
M.
STOTO: So maybe what you’re saying
is that the minimum p value ...
D.
JOHNSON: Right.
W.
GRUBBS: That’s exactly what I’m
saying.
R.
TREWYN: Well, just put “minimum” in
there and that answers it.
M.
STOTO: I think that would be
clearer. Would that — does that ...
W.
GRUBBS: If you look, for example,
on line 615 ...
D.
JOHNSON: I mean ...
W.
GRUBBS: ... it says “p
>0.20" for each analysis, again, giving a summary of what the minimum p
value was across all the eight different contrasts.
M.
STOTO: So that was not an a
priori decision?
W.
GRUBBS: No, it’s
empirical-based. Yeah.
D.
JOHNSON: It’s just saying that
they’re all not significant at that level.
W.
GRUBBS: Or higher, yeah.
M.
STOTO: That’s a database
statement. I think if you — if you
phrase it as “the minimum p value” and this set of calculations was 0.10, that
might make that a little bit clearer.
D.
JOHNSON: What do you call “not
significant” though throughout this study?
Are you going to 0.05?
W.
GRUBBS: 0.05.
D.
JOHNSON: 0.05? It seems like it might be better to take —
better was my thought — to be consistent and say “0.05" and not “0.10,”
but ...
M.
STOTO: Well, I think this is a —
they’re trying to make a different statement here, I mean, because they
summarize the significance at the 0.05 level and elsewhere. But this is just — this is just an empirical
statement about the p values.
D.
JOHNSON: Okay.
M.
STOTO: I’ve never seen anyone use
that before; I’m not sure.
W.
GRUBBS: It’s better than rounding
up the p value, ten different p values.
M.
STOTO: Yeah.
D.
JOHNSON: I thought it might be
helpful to bold your — in your tables, bold the p values that were
significant. I’ve seen that done a lot.
M.
STOTO: The table — the first line
on table — on page 915, there is one that’s bold and italics. Well, it’s “all.” There was — and the same thing, the last table on page 914. Is that “all?”
W.
GRUBBS: Yeah. Dr. Stoto, if you’ll note in Model 1, “all”
is always bolded and in italics just to set it off from “officer,” “enlisted
flyer,” “enlisted ground crew.”
Throughout each table in Model 1, “all” will be bolded.
D.
JOHNSON: Okay. Should I keep going? Sure.
On page 926, I have several minor edits. But if you let me do those, then I’m complete; then I’ve done the
whole document if you want me to finish them.
There — I don’t know if I should even say this: 760, line 760, “helped to clarify” instead
of just “helped clarify,” but that’s just a style preference. But then in 768, it said, “Officers
perceived their self — perceived their health to be more often in the
“excellent” or “good.” “ I thought it
would be more appropriate if you said, “Officers more often perceived their
health to be in the “excellent” or good.” “
M.
STOTO: Yeah.
J.
ROBINSON: What line?
D.
JOHNSON: Line 768.
M.
STOTO: That is a substantive
difference, I believe.
D.
JOHNSON: Yeah. “Officers more often perceived their health
to be in the “excellent” or good.” “
M.
STOTO: Because we’re talking about
variation across officers rather — across subjects rather than over time ...
D.
JOHNSON: Right. Right.
M.
STOTO: ... within — yeah.
D.
JOHNSON: So, and then on the next
line 769, “such as the varying levels of education.” That makes you think that it’s changing as we speak, but so I
just thought “various” would be a better word there. And line 776, “perceived themselves as ill.” And then line 790, “During the course of the
AFS — HS, however, self-perception of general health has shown mixed
results.” “During the course of AFHS
since 1987" — no. “However, during
the course of AFHS since 1987, self-perception of general health has shown
mixed results.” And ...
J.
ROBINSON: I’m sorry; line 770?
R.
TREWYN: 790.
D.
JOHNSON: 790. “However, during the course of this — of the
AFHS since 1987, self ...”
M.
STOTO: Or 1982.
D.
JOHNSON: Or 1982. I’m sorry; since 1982, my apology. Because what happens here on a couple of
these paragraphs, you — you’re not sure if they’re talking about longitudinal
or you’re talking about the last one.
And so back on line 798, is that the appearance of illness or the
stress? Are we talking about 2002 exam
or are we talking about ...
M.
STOTO: I think what this is — this
is about, the analyses, the results of the analyses have varied from time to
time. It’s not variation within the
men. Isn’t that right? This is not a longitudinal statement about
the subjects. They’re saying that
sometimes when we analyzed these data, we got some things. But when we analyzed the — what you would
think are the same data, we got different results. Is that the point?
D.
JOHNSON: Well, if you look at line
7 ...
J.
MICHALEK: I’m not sure now
actually. We need to study this
paragraph.
D.
JOHNSON: It kind of goes back and
forth between talking about longitudinal ...
J.
MICHALEK: Yeah, I agree it does.
D.
JOHNSON: ... results and talking
about ...
J.
MICHALEK: It’s hard to tell.
D.
JOHNSON: Hard to tell what you’re
talking about. So for example, on 794,
you say “But in the 1985, 1987" and so forth and it goes on to explain
that. And then in the next paragraph,
“The appearance of illness or distress as assessed by the” — and are you
talking about all of them or you’re just talking about 2002 at that point?
J.
MICHALEK: That needs to be
clarified, yes. If we mark that up,
that would be great: starting with line
797 or 796, right in there.
D.
JOHNSON: And on 799, it says “a
finding similar to results reported in earlier studies.” Now are you referring to other studies or
you’re referring to prior follow-up exams?
And if you’re referring to studies, you might want to reference there.
J.
MICHALEK: What line is that again?
D.
JOHNSON: 799.
J.
MICHALEK: 799 — 790 or I don’t see
“other studies.”
D.
JOHNSON: Oh, I’ve got a ...
M.
STOTO: In “earlier studies.”
J.
MICHALEK: “Earlier studies?”
D.
JOHNSON: Oh, wait a minute. I’m looking at a different ...
R.
TREWYN: Yeah, this is the ...
D.
JOHNSON: I’m looking at the second
draft. Are you looking at the first
draft? Something’s different,
okay. When did that start happening?
J.
MICHALEK: We have different versions
of the document going on here.
M.
STOTO: Well, you know, one of the —
one of the things that was raised in the Air Force comments on the earlier ones
is the use of the word “studies.”
J.
MICHALEK: Right.
M.
STOTO: And ...
J.
MICHALEK: As opposed ...
J.
ROBINSON: I can get you copies of
the ...
D.
JOHNSON: Okay.
J.
ROBINSON: ... most recent drafts.
D.
JOHNSON: Well, if you go to 800, go
to line 800.
J.
ROBINSON: Where are we?
D.
JOHNSON: 801.
M.
STOTO: But I think ...
D.
JOHNSON: So it’s, “between the
Ranch Hand and Comparison groups, a finding similar to results reported in
earlier studies.” Now ...
M.
STOTO: But there’s — I think
there’s a general point here that refers to all the way through the report, not
just this.
D.
JOHNSON: Right.
M.
STOTO: And ...
J.
MICHALEK: “Earlier phases of this
study.”
M.
STOTO: Yes.
D.
JOHNSON: Is that what that’s
referring to?
J.
MICHALEK: Yes. Yeah, that’s what they meant.
D.
JOHNSON: Earlier, one of the other
comments for the Air Force, they said they wanted to call them “follow-up
exams” or something like that.
J.
MICHALEK: Yeah. We — yeah.
We’re having disagreement among ourselves about what to do about that.
D.
JOHNSON: Oh, okay. Well, I didn’t know if you were talking
about other studies or if you were talking about other parts of this study.
M.
STOTO: This needs to be resolved as
part of that same issue ...
J.
MICHALEK: Yes, it does.
M.
STOTO: ... because it’s the same
issue.
J.
MICHALEK: “Earlier phases of this
study” would be ...
D.
JOHNSON: Yeah.
J.
MICHALEK: ... really helpful, I
think.
D.
JOHNSON: The same thing if you go
down about another six lines, “These results are generally consistent with
earlier study results.” So it’s the
same thing.
J.
MICHALEK: Yeah.
D.
JOHNSON: And one more comment, I
think, is one I’ve got on line — my line 820, your line 822. It says that “one third” — it says,
“Therefore, more than one-third of AFHS participants” — you’re talking about
obesity being 30 percent: 35 percent in
this cohort and 30 percent in the nation.
And it says, “Therefore, more than one-third of AFHS participants are at
significant risk for health complications associated with obesity.” What — are we back to “significant?” Is this — did we evaluate that
statistically?
J.
MICHALEK: No. This was his — this was the clinician at
Scripps who wrote this. This is his
impression.
D.
JOHNSON: So we need to just say “at
risk.”
J.
MICHALEK: Yeah, because
“significant” means a p value and we don’t have a p value for that.
D.
JOHNSON: Because that’s the way the
rest of the report was pretty scientific, so that wouldn’t be — and thank you
for hearing those. I hope they’re
suggestions to be used as you would like to use them. And you want to see my — you want me to give you my notes? Okay.
M.
STOTO: Okay, so thank you very
much. Now we have — Paul, are you ready
to give ...
P.
CAMACHO: Yeah. I ...
M.
STOTO: ... comments? Did — should we do that now and then have
lunch or maybe get — we can do it over lunch?
How do — what do people prefer, one or the other?
E.
HASSOUN: I have one question about
this same chapter.
M.
STOTO: Okay.
E.
HASSOUN: We discussed about
alcohol: page 910, line 397.
J.
MICHALEK: Line 397?
E.
HASSOUN: The new one or the latest
addition or draft.
J.
MICHALEK: The October 15 draft?
E.
HASSOUN: January 28th
draft.
J.
MICHALEK: Oh, the January 28th
draft?
E.
HASSOUN: 397.
J.
MICHALEK: 397, just a second.
M.
STOTO: Can I make a suggestion that
in the future when we have the first and the second draft, they be clearly
indicated? I don’t know how we can do
that, but ...
J.
ROBINSON: I’m trying to make it as
— sir, I’m trying to make it as — you know, I had the little definitions and
usually it will say “Draft 2." And
what ...
P.
CAMACHO: On the file.
J.
ROBINSON: On the ...
P.
CAMACHO: But sometimes what
happened, I caught myself doing that. I
printed it out ...
J.
ROBINSON: What I can do is I will
retitle the file ..
P.
CAMACHO: ... and I had to be sure
which version I printed out.
J.
ROBINSON: ... to make it very
clear. I’ll make a very long title.
M.
STOTO: Well, the other thing is in
the footer, you’ve got the dates in the footer and you might also add “first
and second draft” or something like that.
P.
CAMACHO: Yeah.
J.
MICHALEK: Yeah.
M.
STOTO: “Draft 2.”
J.
MICHALEK: So tell me the question
again.
E.
HASSOUN: “The highest percentage of
participants who perceived their health as fair or poor was among
nondrinkers.” Does it mean that alcohol
protects against dioxin effects or — I — because we — you haven’t discussed the
effects of alcohol. You discussed the
causative effects of — from smoking and obesity. I didn’t see ...
J.
MICHALEK: Well, this is purely —
yeah; that’s complicated. This is
purely a descriptive, factual sentence which does not explore the possibility
of confounding. It could be those
non-drinkers are do something — are doing something else. They might be heavy smokers or something, so
you bring up a good point, and simply putting out these are raw numbers and no
value judgment is made here about drinking.
It’s just simply these are the percents and ...
M.
STOTO: Why is that needed at all?
J.
MICHALEK: Well, this gets into the
whole idea of covariate descriptions and do we need them. And for a while among our own group, we
thought we should drop all of this discussion.
And then we thought, no, we’d better leave it in. What do you think?
M.
STOTO: Well, I think that if it’s —
if it's left in, it needs to be put in context to say — make the point about
some people have got covariates.
J.
MICHALEK: This is a tough issue
because in some chapters, we have many, many more covariates than just those in
this chapter, like there might be a — right, Bill? In some chapters, we have ten, twenty covariates?
W.
GRUBBS: Oh yes. In cardiovascular, there’s fifteen ...
J.
MICHALEK: Fifteen covariates?
W.
GRUBBS: ... alone. Yeah.
The — it goes on for, I think, five pages. We have taken the — after this chapter, I think even actually
after the third chapter that we did, we took to a different style of writing
where we didn’t state percentages. We
didn’t state p values. We just talked
about general trends. As alcohol
increased, such and such increased.
J.
MICHALEK: And then looked to rework
the tables.
W.
GRUBBS: Right.
M.
STOTO: Okay. This is in a section that’s about — it says
it’s about dependent variable covariates.
W.
GRUBBS: That’s correct. And if you note in the first paragraph there,
it says it’s “unadjusted for other covariates.”
J.
MICHALEK: In other words to answer
your question properly, one would have to carry out a careful statistical
analysis of drinking versus self-perception of health, which is outside the
scope of this report because we’re interested in dioxin versus self-perception
of health, not drinking versus self-perception of health so ...
R.
TREWYN: It just means you have to
drink to feel good ...
J.
MICHALEK: Yeah.
R.
TREWYN: ... is what this is telling
you.
J.
MICHALEK: Right, and so to put ...
R.
TREWYN: We all know that.
J.
MICHALEK: ... this is context and
to do it carefully is prohibitive.
M.
STOTO: Well, I ...
J.
MICHALEK: It is.
M.
STOTO: The point — the point of
this here — being here is that it helps to interpret ...
J.
MICHALEK: It does.
M.
STOTO: ... the results that come
later in the chapter.
J.
MICHALEK: And I’ll note in going
back to the history of this, we thought that in the early days of the study,
putting this in strengthened the study.
It shows that our endpoints are related to known risk factors. It shows the things we’re measuring are
measured properly. And in this case,
you get a contradictory result that non-drinkers are worse off than the
drinkers and to know why would require some work.
M.
STOTO: Well, maybe one approach
might be to — I’ll suggest two things:
one is to just put a note at the beginning of this section here about
why this is here. Okay.
J.
MICHALEK: All right, remind the
reader why we put it in there.
M.
STOTO: That’s right, and two is to
do it as apparently is the case for the new chapters and focus less on the
specific numbers, but more on the direction of these effects because we’re
really not interested in the numbers here.
And we’re really interested to what degree these associations exist
because they might complicate or simplify the section if you put it that
way. Does that make sense to you? Does that make sense?
J.
MICHALEK: Yeah, to warn the reader
that many of these associations were not carefully explored like this one.
M.
STOTO: Yeah. That’s right. The point was not to study these things.
J.
MICHALEK: Right.
M.
STOTO: The point was to summarize
them because they’re important in interpreting the other results. Sandy?
S.
LEFFINGWELL: Or you include this in
the opening sections in your chapter on hormesis. Let the record show I’m smiling when I said that.
M.
STOTO: Okay. Thank you.
Sorry that I didn’t know you had a comment on that. So all right, is
that — other comments on this?
R.
TREWYN: I guess I have a question
for Joel if I may, thinking about one of our off-line discussions here and
thinking in terms of Model 1. Since I
know some of the work that’s being done with the comparison group in country
versus out of country, the question I have is, is in this report, will that
analysis show up anywhere in this report?
J.
MICHALEK: It will not and it cannot
unfortunately. So you bring up a good
point and that is that the current research we have, the current results are —
they are not reflected here and they — and they can’t be because this plan was
written four years ago and so yes, frustration. Yeah, it’s a point of frustration.
R.
TREWYN: Yeah, and again, just
thinking in terms of some of the — when this room used to be packed with
veterans groups, and other advocates and whatnot all screaming that this is a
cover up and et cetera, I mean, somehow we have to at least advise, I
think, in this of what’s being done in some of the forthcoming publications
that do take advantage of that. But
those — I mean, you’ve run those numbers.
You’re showing some of that in some material for publication, correct?
J.
MICHALEK: Yes. For example, we know that years in SEA is a
risk factor for cancer in the control group and that’s going to be submitted to
a journal soon. It’s on my desk and no
one knows about it except probably us in this room.
R.
TREWYN: Right.
J.
MICHALEK: And, but that we also
know that years in SEA doesn’t correlate with diabetes in the control group and
that’s a fact known only to us. And so
we’re just beginning to understand these things, which is a reason to continue
this.
R.
TREWYN: And I guess then the key, I
mean, it’s I think — and I’m not sure how to advise, but I think we at least
need to have this under consideration because somehow that information
somewhere has to be footnoted. It has
to be, you know, where it stands currently.
It’s not part of the official study as this was laid out, but new
information has led to this and this is being worked in the background.
And
if you’ve got statistically significant correlations that are coming out and if
that doesn’t show up somehow or isn’t referenced here, we wind up back with the
same issue, I think, that assuming at some point we do have the room again
packed with veterans that — it's information you've got in your kit and so how
should that be put in here somehow? I
don’t know.
M.
STOTO: Well, I would suggest this;
that it be dealt with in Chapter 1 in the introduction, particularly in Section
1.1. That talks about the purpose of
this report and, you know, we ...
J.
MICHALEK: Talk about its
limitations, yeah.
M.
STOTO: Right, and/or what this
report is not. I mean, I wouldn’t say
it’s a limitation. It’s just not what
the ...
J.
MICHALEK: It’s not a reflection of
current research.
M.
STOTO: Yeah. So I mean this is — and I would add to the
purpose of this report that, you know, we — that these models have been used
historically. These statistical models
have been used historically and what we’re doing here is using the same models
for comparison purposes, you know.
Since that has all been done, the new ways of analyzing the data, new —
in fact, even new data have come to light and those things are analyzed and
being presented in other venues. Jay?
J.
MINER: Yes, and we do have a
“Future Directions” chapter that perhaps this all could be ...
M.
STOTO: I think it could be there
too.
J.
MINER: ... summarized in.
M.
STOTO: But I — but I also think
that it belongs right here in Section 1.1 of Chapter 1.
P.
CAMACHO: See, when you said this is
really not a study for the average person, the room is going to get — when this
is all done in 2006, there is going to be a packed room and I’m just — I know
there is going to be. And so that’s why
— well, why not defend yourself a little now, a little prevention now? Because I’m not saying they’re not going to
be screaming anyway, but you — you’re going to have to protect yourself a
little and by saying exactly what you were really supposed to be doing as
opposed to what other people out there wanted you to do because the perception
is not going to — I don’t think the perception is going to change. Right, Ron?
Are you ...
R.
TREWYN: And I think ...
P.
CAMACHO: We’re on the same page, I
think, on this.
R.
TREWYN: Yeah, and I think that’s
correct. And I guess I would also throw
in that the studies that are — that will be published on this are obviously
being funded under this program. And
somehow, therefore, I think the information were at some — where we are with it
at some point — even if it isn’t Model 1 where the real issue comes up — I
almost think that data needs to be in here somewhere: whether it’s in the “Future Directions,” you know, whether it’s a
separate section that shows that here’s some stuff that wasn’t originally
called for, but we discovered in process, and therefore, here’s where the data
is, or you put all of the preprints and reprints and stuff appended to it
somehow. I think it needs to be tied to
the report for the veterans community to understand that this is a sincere
effort that is going on to put all the data out into the — into, you know, into
print.
M.
STOTO: In fact, you can even
reference your web site which does have the list of publications.
J.
MICHALEK: Or just ...
M.
STOTO: Okay.
J.
MICHALEK: Of course, that web site
will go away on October 1, 2006 unless we’re told otherwise.
M.
STOTO: Why don’t you make that
comment too in the report and see how that goes?
J.
MICHALEK: Good point. Good point.
M.
STOTO: Okay. Paul, why don’t we go ahead and ...
P.
CAMACHO: Yeah.
M.
STOTO: You think we should — maybe
we should ...
L.
SCHECHTMAN: We didn’t eat yet. We’ll make that our working lunch.
M.
STOTO: Okay. Why don’t we take ten minutes, grab lunch,
come back and discuss this over lunch — this being Chapter 6.
[LUNCH RECESS 12:01 P.M.-12:20 P.M.]
![Text Box: Review of Chapter 6: Quality Control/Appendix D [continued]](./2004-4041t1_files/image011.gif)
M.
STOTO: We're going to get started
again. Okay. I think that everyone is back now so we’ll get started again. Right.
The last chapter we have to review is Chapter 6 that deals with quality
control and Paul Camacho.
P.
CAMACHO: I have a side bar before I
start. I was at the Army War College a
couple of — a week and a half ago and I ran into a fellow from the National
Academy of Sciences. And then we struck
up a conversation, and I mentioned the Ranch Hand Study and how it was going to
— all that data was going to drop off a cliff.
The guy’s name is Bruce A. Braun, B-R-A-U-N. He’s the Director of the Board on Army Science and Technology at
the National Academy of Sciences.
It
turns out he has a counterpart who is the Director of Air Force Science and
Technology at the National Academy of Sciences and that guy’s name is Michael
Clark. I gave the numbers out, phone
numbers out. He expressed, Braun
expressed a great deal of interest in housing the data. I mean, that’s on a quick, you know, issue;
that it turns out that this department of military science and technology has
been an entity in the National Academy of Sciences for a long time. I mean, I didn’t know this, but you know, so
that's that. You’re going to follow
that up to wherever it leads.
Let’s
do the Chapter 6 trick here. Whose —
the CAPI system, is that part of SAS?
That would be a question I ask.
Is that a SAS ...
J.
MICHALEK: No, that’s a software
used by NORC, National Opinion Research Center.
P.
CAMACHO: That’s who designed it?
J.
MICHALEK: Maybe they bought
it. I don’t know.
P.
CAMACHO: Okay. It’s a standard package somebody has?
J.
MICHALEK: Yeah.
P.
CAMACHO: You wouldn’t ...
M.
STOTO: It’s not so much a — it’s
not so much a package, but an approach.
Yeah, there’s — I mean, there’s — I’m sure there’s different software
solutions that do it.
P.
CAMACHO: Yeah, that should be
explained here because it almost looked like one of the guys put his own little
data entry, you know, front end on something.
M.
STOTO: Did you want to say
something, Jay?
J.
MINER: Yes, I do. Jay Miner.
The CAPI system, we requested the NORC develop that. They used a standard toolkit to develop it,
but was specifically developed and designed for the Air Force Health Study.
M.
STOTO: So I think that just can be
elaborated.
P.
CAMACHO: That just should be said
because you wouldn’t know, oh, they — some guy wrote the software, put a nice
front end on the thing and we called it “CAPI.” I mean, honestly, not everybody would know this stuff.
J.
MINER: But the total CAPI is used
over lots of different things, but ours ...
M.
STOTO: And it couldn’t — it
couldn’t hurt to elaborate on that.
J.
MINER: Right.
J.
MICHALEK: The acronym is C-A-P-I.
P.
CAMACHO: Yes.
J.
MICHALEK: “Computer-assisted
personal interview.”
P.
CAMACHO: Yeah, but then you — I can
design one for visual basic, you know, if I went into that. So who assessed? I saw at the end, you know, there was a reference in the — from
the old version to the new version about the lines around 58, about the field
manager who supervised them, the interviewers were graded. And this was all done by the field manager,
I take it, right? Okay.
And
the SAS variables being compared to the CAPI and these using a standard
utility, the files were converted from vertical format to horizontal
format. You mean cases? The way the case — the case — each case is
stored? That’s what a — you know, I
know what an ASC tool file is. I did a
lot of these conversions, so that’s the only — you know, I’m not complaining. I just want a clarification.
W.
GRUBBS: I think they said vertical
to horizontal.
P.
CAMACHO: Yeah.
W.
GRUBBS: I think vertical, the data
as it comes in is a line per response to a question, 9,000 of those, and then
each case is a row. So it’s transposing
...
P.
CAMACHO: So they did — they did a
data transformation?
W.
GRUBBS: Yeah. It’s like this and they go ...
P.
CAMACHO: Yeah, and it comes this
way so the case is a row-by-row ...
W.
GRUBBS: Exactly.
P.
CAMACHO: ... instead of a column.
W.
GRUBBS: Exactly.
P.
CAMACHO: Right. I don’t know if you really have to do
that. I didn’t say anything about that,
but ...
M.
STOTO: Yeah, I agree. I don’t think that really is necessary.
P.
CAMACHO: I don’t, no. I just — but I just wanted to know since you
asked.
M.
STOTO: Yeah, if there was any
manipulation that took place in that stage.
P.
CAMACHO: No, it’s just a
conversion. Somebody else said — can I
— the Figure 6-2, is there — there's no — you guys do everything. Where’s the out? How do you get out of the box once you get in, you know what I’m
just saying? There’s no — just for the
heck of it, somebody might say you’re a — I mean, yeah. You got in; you got into the hotel; you
can’t get out. There’s only one arrow
in.
J.
MICHALEK: Yeah.
P.
CAMACHO: Where’s — where do you get
out just for the heck of it?
J.
MICHALEK: Good point.
P.
CAMACHO: I’m just telling you by
the time ...
M.
YEAGER: Yeah. It’s after “QC Scanning of Form.” The ...
J.
MICHALEK: Right over here ...
M.
YEAGER: Yes.
J.
MICHALEK: ... is that the end of
it?
M.
YEAGER: Yes.
P.
CAMACHO: That’s the end of it?
M.
YEAGER: That’s the end.
P.
CAMACHO: You wouldn’t know that
from here because the arrow takes you down to the back to the discrepancy and
you’re not ...
M.
YEAGER: That’s only if there’s a
problem found.
P.
CAMACHO: Okay.
M.
YEAGER: But you're right.
P.
CAMACHO: Yeah. Otherwise, somebody’s ...
M.
YEAGER: We can add another arrow.
P.
CAMACHO: ... you know, going to
accuse you of being in “Roach Motel,” you know.
M.
YEAGER: Don’t want that.
P.
CAMACHO: I’m just saying.
E.
HASSOUN: I would suggest that we
have another arrow — down arrow ...
P.
CAMACHO: Or an out to that.
E.
HASSOUN: ... parallel to that.
P.
CAMACHO: Yeah, because that’s not —
that is not an end result from my memory, right? I mean, as far as standard little chart things, this — that oval
is not an end piece.
J.
MICHALEK: Oh, I see; that’s — yeah.
P.
CAMACHO: You know, just for the
heck of it, I — you know, you asked me.
You know, that’s not — or at least it doesn’t look it this way. You’ve got it down and — but I see the word
“final database” in the next chart and I’m a happy camper.
J.
MICHALEK: What — what's the ...
P.
CAMACHO: You know, but when I look
at “Scanning Form End,” you know, “Scanning Form Complete,” no, boom; problem’s
found. Okay. That’s, you know — and all these judgments at the end of page —
around the lines of 350 are by the interviewers. It’s the — all are judgments of the interviewers getting together,
that whole little sector. Did you go
back to people? Did anyone say, “Call
back,” you know, “Call back one of the participants?” That wasn’t necessary.
Did — right? You didn't do that?
W.
GRUBBS: What line?
P.
CAMACHO: Around 346 to 352 where,
you know, the form was rejected, exact data element, all — that whole section. Those were all judgments about what — these
errors were resolved by judgments of interviewers, right? And you didn’t call me, Paul Camacho, back
up?
M.
YEAGER: Do you want to ...
M.
OWENS: I don’t want to get that
one.
M.
YEAGER: Okay. Most of the errors, things had to go back
were a doctor neglected to bubble a circle, but he put a comment in. So most of the — most of the adjudication
was done by the individual doctors. If
it had been necessary to call one of the participants back, the Air Force would
have called the participant.
P.
CAMACHO: Would have?
M.
YEAGER: Yes.
P.
CAMACHO: Okay.
M.
STOTO: Maybe — I don’t think it
would hurt to clarify that; that most of it was based on going back to the
records, but if — did you in fact have to go back to any of the subjects? There was the business about the ...
J.
MICHALEK: We would — I don’t
remember that, but we can check that out.
M.
STOTO: Right.
M.
OWENS: A lot of the — hit the
microphone — a lot of — Maurice Owens speaking — a lot of the quality control
work that went on there was done by design at the clinic before the
participants left, so yes, there was going back and forth in some cases with
participants.
M.
STOTO: Okay.
M.
OWENS: I mean, that’s the idea to
not wait until the situation cooled off ...
M.
STOTO: Well, that ...
M.
OWENS: ... before you try to ...
M.
STOTO: That’s a very ...
M.
OWENS: ... catch it.
M.
STOTO: That's a very positive thing
then you want to ...
P.
CAMACHO: Right.
M.
STOTO: ... capture.
M.
OWENS: So there probably was some
cross-talk, and on occasion, a physician would probably come up later after the
participant has left and we conferred with the physician. And the physician couldn’t recall exactly
what the circumstance and might have called the participant.
P.
CAMACHO: Well, that — see, you’d
have a — it’d sound a lot better if you said, you know, that was done right
there on the spot.
M.
OWENS: It — yeah.
P.
CAMACHO: And you — if you had to,
you went back to the participant.
M.
OWENS: Yeah. The majority of these quality control steps
were taken on the spot while the participant was still at the clinic ...
M.
STOTO: Yeah.
P.
CAMACHO: I wouldn't be afraid to
say that, right?
M.
OWENS: ... because they’re a
real-time basis.
M.
STOTO: No. I mean, you know, it’s not a question now
whether you did the right thing or not; you did what you did. But I think you should take credit for what
sounds like a pretty good thing.
J.
MINER: There were instances — and I
wish Colonel Robinson were here — but she could address going back to the
hotel, getting a participant, dragging him back out to the — to the clinic and
actually getting another value.
M.
STOTO: You may want to phrase it
slightly differently when you write it up, yeah. Okay. Paul?
P.
CAMACHO: Yeah. No, that was just about it. And then I just put on the side here around
line 367-8-9, the missing values stuff.
I assume standard missing values, you know, you just ...
J.
MICHALEK: Code.
P.
CAMACHO: ... excluded the ...
J.
MICHALEK: Go ahead. What was your question?
P.
CAMACHO: Yeah. I just — what was the procedure, just the
standard missing values? You excluded
that guide?
J.
MICHALEK: In the statistics?
P.
CAMACHO: Yeah.
J.
MICHALEK: In the statistics? There would be a missing value code in the
file, such as “8-8-8-8-8." And
that way, the statistician would know that that’s a missing value. And yes, those would be excluded from the
statistical analysis and the counts of such things are given in every
chapter. And there’s very little
missing data in this report. If you
look at the — look at the chapters and look at the — look at the — where they
enumerate the missing values near the definition of the variables, you’ll see
there’s very little missing data.
P.
CAMACHO: Well, that’s what I would
— you know, that's to your advantage, so ...
J.
MICHALEK: To say so.
P.
CAMACHO: Yeah.
J.
MICHALEK: Yeah.
M.
STOTO: But it does say that now
here in 372 to 73.
P.
CAMACHO: Yeah, but there were no —
there were no — clinical laboratory data were excluded. But then you — I don’t know. You could just add it or you don’t have
to. You asked me to look at it.
J.
MICHALEK: Yeah.
P.
CAMACHO: I just — so that’s really
all I — all I had. And that was from
“10/31/03 Draft.” There’s a “12/08/03
Draft,” but I — that’s the one I — got put on my desk and I do apologize. I just got back, and I looked at that and I
just saw my name higher up. And I ...
M.
STOTO: Okay. Well, you did a — you did a nice job in the
— pulling that together in a short period of time, so I appreciate that. Are there other comments on that chapter?
E.
HASSOUN: Just one thing: it needs to be clarified, page 6-4, line
130. It reads “NORC” — I have the later
draft — “schedulers telephoned” and, you know, “the 15 participants who should
have been asked these questions, but were not.” It’s unclear — “but were not and to collect that information.”
P.
CAMACHO: “But were not and to
collect” — no, that’s just ...
E.
HASSOUN: I thought that you meant
...
M.
STOTO: I’m sorry. Can you — can you say again what — which
lines you’re referring to?
E.
HASSOUN: 6-4, line 130, 133.
M.
STOTO: Okay.
J.
MICHALEK: Okay. Well, how should it read?
M.
YEAGER: Take the “and” out.
J.
MICHALEK: What? What?
I can’t hear you.
W.
GRUBBS: The “and” should not be
there.
J.
MICHALEK: Oh, okay. I couldn’t hear you; I’m sorry.
E.
HASSOUN: “Were not ...”
J.
MICHALEK: “But were not and to
collect” — take out the “and.”
E.
HASSOUN: “Were not to collect the
information.”
J.
MICHALEK: Would you please read the
sentence as it should be read? I mean,
we can’t put it together from here.
J.
MINER: We will fix it.
J.
MICHALEK: Okay. The sentence is incorrect.
P.
CAMACHO: Hey, they’ll stop lunch if
we stop.
M.
STOTO: Yeah. Okay.
I don’t — I don’t think — I think we’ll trust them to fix that, but
clearly, I think that needs to be addressed as a problem in English. Let me do — I think we’ve got two things
left to do now. Any more on that just
to be sure? Oh, Sandy? Yes?
S.
LEFFINGWELL: There is some — it’s
trivial, but there’s some punctuation questions on that. “Field Manager” is capitalized as is “Data
Collection Task Leader,” but “interviewer” is in lower case; “researchers” as
in “Air Force researchers” is in lower case; “NORC designers” is lower
case. I don’t know why “Field Manager”
and “Data Collection Task Leader” are in caps.
M.
STOTO: What I — what I would
suggest is if other people have editorial comments of that sort, then you just
write it down and give it to the ...
J.
MINER: Right.
M.
STOTO: Give it to whom?
J.
MINER: Give it to that young lady
right there ...
M.
STOTO: Okay.
J.
MINER: ... in the blue suit. [Referring to 2nd Lt. Margaret
Montgomery]
M.
STOTO: Okay. Good.
M.
STOTO: So I think we’ve got two
more things on our agenda: one is to
see if there are any comments from members of the public who are lurking in the
corners of the room behind their chairs or columns? I guess the answer to that is no.
M.
STOTO: The other is to talk a
little bit about assignments for next time.
I think we’ll do two things: one
is, I’ve asked Kim to try to put together a roster of the Committee that
includes some areas of expertise so I can do a better job of making these
assignments than I did — than I did last time.
So I guess you’ll send an e-mail and ask for people to do that, and of
course, there are people who are not here today.
Secondly,
my understanding is that in the next round in the meeting in September, we’re
going to have psychology — is it psychology or psychiatry? — psychology,
hematology, immunology, cardiovascular disease and maybe endocrine among the
substantive chapters. So it’s psychology,
hematology, immunology, cardiovascular and endocrine. And then in addition, there probably will be a chapter about the
study selection participation and the statistical methods. I'll begin by volunteering to do the
statistical methods myself. I don’t
know whether other people want to take a stab and take a ...
R.
TREWYN: Hematology.
P.
CAMACHO: I'll look at the
statistical one too if you want, but that’s probably ...
M.
STOTO: Okay.
N.
RIVERA: Speak up, Dr. Camacho.
M.
STOTO: Yeah.
N.
RIVERA: What did you say?
M.
STOTO: Okay.
P.
CAMACHO: Yeah, but I’ll look at the
statistical one too if you want me to ...
M.
STOTO: Okay.
P.
CAMACHO: ... because I have no
medical background.
R.
TREWYN: You’re a sociology guy; you
ought to be able to do the psychology stuff.
J.
MICHALEK: Psychology would include
memory loss.
P.
CAMACHO: You want me to do the
psychology stuff?
J.
MICHALEK: The psychology chapter
will include the memory stuff.
E.
HASSOUN: Psychology — I’ll take
psychology.
P.
CAMACHO: Okay. So the Wechsler thing — the stuff that we
did?
R.
TREWYN: Yeah.
M.
STOTO: Okay.
N.
RIVERA: Dr. Hassoun, what chapter
did you volunteer for?
E.
HASSOUN: Psychology.
M.
STOTO: And then we’ll try to get
some of the people who aren’t here to fill in the gaps. Sandy, did you want to — were you ...
S.
LEFFINGWELL: Didn’t have any
particular one, but if you want me to do one, I’ll take it.
M.
STOTO: Well, I think we’ll call —
we’ll hold — we’ll keep you as a ...
R.
TREWYN: Keep him in reserve.
M.
STOTO: “In reserve” is the term,
yeah. Okay. Any final comments? Ron?
R.
TREWYN: Yeah. I want to back up again. I’m just — when you start working on the
cancer chapter — don’t know where that is in the process right now — but since
that’s one where I know this comparison group split makes a heck of a
difference, I — when we get out there, I'm certainly going to be arguing to do
— to not keep all the comparison group together and show no effect if splitting
them out in country/out of country shows a significant effect.
It’s
a learning along the way. It may be a
deviation from what's been done before, but I think if we’ve got something that
we know shows a statistically significant, you know, effect in this study and
we don't show it as part of the study, I think we’ve not done what we need to
do. And so I will, at least when we get
out to that, I’m going to certainly be arguing that that should be looked at
...
P.
CAMACHO: Yeah.
R.
TREWYN: ... for what it's worth.
P.
CAMACHO: I agree with him. You can put any proviso you want around it,
you know; be sure and do that. But if
you don’t do that, the room's going to get filled up at the end of the — down
the road. That’d just — people are just
going to throw rocks and they’ll go nuts; I just know they will. I just know what the community's going to
do.
M.
STOTO: Is cancer the only one that
we need to do that for?
J.
MICHALEK: So far the answer is
yes. We have checked birth defects,
diabetes and cancer, and that effect shows only in cancer. But the first thing we checked was birth
defects and diabetes.
M.
STOTO: Okay. So in other words, you can — you can make a
case for doing it in one and not another?
J.
MICHALEK: Cancer only? Yeah, so far. Well, you have to be careful here. These — each one of these questions is a research topic ...
M.
STOTO: Right.
J.
MICHALEK: ... I mean, about the
effects of all these things in a control group. And so our quick look says, you know, that there — we can’t see
anything in birth defects and we can’t see anything in diabetes. But it may still be there and we just need
more work on it; that’s all. So our
current knowledge is that there is no Southeast Asia effect of diabetes in the
control group. There is an effect on
cancer, a very strong one, and there’s an effect of days in — just being in
Vietnam is a risk factor for cancer in the control group; that's all going to
be published soon. And so you’re right;
the current report, it was written — the plan was written four years ago and
that's the way it is. Yes?
J.
MINER: Yeah. Jay Miner.
There are ways to handle this.
In the past as I remember, we had a finding in cardiovascular deaths
that we put one sentence in the report years ago. It’s possible we can put a sentence in that says — and then have
an appendix to be added to the report that the one sentence would refer them to
and ...
M.
STOTO: Okay, so particularly ...
J.
MINER: ... handle that. We will look and see how to — how to do
that. We have to be kind of careful by
adding a scope of work and dollars to this particular piece so, but we’ll ...
P.
CAMACHO: Yeah. On the other ...
M.
STOTO: They’re happy if you add
dollars, but I don’t think you have them.
J.
MINER: We’ll find a way to get it
mentioned.
M.
STOTO: The fact that it’s about to
be published, I think is, again, very positive because then you obviously have
something to cite. You may then can
include it in the — in the literature review at the beginning and to the
discussion at the end.
P.
CAMACHO: And if you didn’t have —
you should have something in there that says you didn't see the effect because
I know the birth defects thing, it’s just going to cause the community to
scream. Now we’re not here to placate
that community; however, why get shot at if you don’t have to be shot at? So if you have a sentence saying “we didn’t”
— “when we separate it out, we did not see an effect,” then you've protected
yourself, you know, because I know there’s people out there that they don’t —
it’s a conspiracy that you did not find an effect. So, you know, just protect yourself — that’s all — and that can't
really screw up the dollar scope.
M.
STOTO: Okay. Well, thank you everyone. We’ll see you all — oh, you want to ...
P.
CAMACHO: Wait a minute.
M.
STOTO: We’ll see everybody ...
P.
CAMACHO: Hold it.
M.
STOTO: Yes?
J.
MINER: What time was the public
session as printed in the Register?
M.
STOTO: It wasn’t in the Register;
I don’t know. It was not on the agenda.
J.
MINER: It was 1:30 to 2:30. Just as a point of order, you might want to
have somebody hang around here in case someone shows up at 1:30.
M.
STOTO: I hear you.
W.
GRUBBS: It says “approximately
1:30.”
M.
STOTO: Right. Okay.
Thank you.
P.
CAMACHO: The other — your — in ...
J.
MINER: But it does say “approximately
1:30.”
P.
CAMACHO: The round-up here, Mr.
Chairman, you’re going to do a letter that’s going to go to the Secretary?
M.
STOTO: A letter to Secretary
Thompson suggesting that he bring this up with Secretary Principi; that to
basically give the money to the Academy so they can get started on this thing
because it’s important.
P.
CAMACHO: Yeah. All right, that’s in there. All right.
Thank you.
M.
STOTO: We’re still here. You can ...
D.
JOHNSON: Well, I was — again, it
was what — again, that since I’m new on the Committee, I was listening to that
discussion earlier. And it seems to me
there’s some urgency to do something with the money and — but it seems also so
that to me, then it falls back there’s an urgency to find out what is our — I was
hesitant to comment because I wasn’t clear what our role was. So it would be — there’s an urgency to find
out what is our real role, and then once we know what that is, what is the
process we’re going to use to, you know, to pick or to choose?