                         UNITED STATES OF AMERICA



             ADVISORY COMMITTEE ON HUMAN RADIATION EXPERIMENTS


                             (PUBLIC MEETING)



                             The Madison Hotel
                            Executive Chambers
                         15th and M Streets, N. W.
                             Washington, D.C.


                                  Friday,
                              March 17, 1995

                                 8:00 a.m.


          ADVISORY COMMITTEE MEMBERS PRESENT:

          RUTH R. FADEN, Ph.D., M.P.H., Chairman
          ELI GLATSTEIN, M.D.
          JAY KATZ, M.D.
          PATRICIA A. KING. J.D.
          SUSAN E. LEDERER, Ph.D.
          RUTH MACKLIN, Ph.D.
          LOIS L. NORRIS
          NANCY L. OLEINICK, Ph.D.
          HENRY D. ROYAL, M.D.
          PHILIP K. RUSSELL, M.D.
          DUNCAN C. THOMAS, Ph.D.
          REED V. TUCKSON, M.D.

          STAFF MEMBERS PRESENT:

          DR. JEREMY SUGARMAN
          NANCY KASS
          DR. STEVE GOODMAN
          SARA CHANDROS
          GAIL GELLER
          ANNA MASTROIANNI
          DAN GUTTMAN
          MONICA SCHOCH-SPANA


                               A G E N D A 
                                                                       PAGE

     UPDATE ON SUBJECT INTERVIEW STUDY

          Jeremy Sugarman, Nancy Kass, Steve Goodman                    511


     UPDATE ON RESEARCH PROPOSAL REVIEW PROJECT

          Sara Chandros, Gail Geller                                    561

     
     Break


     RECOMMENDATIONS:  LOOKING FORWARD                                  620


     Lunch


     RECOMMENDATIONS:  LOOKING FORWARD (continued)                      699


     Break

     
     MEETING ADJOURNED

                           P R O C E E D I N G S

                                                                (8:10 A.M.)


          CHAIRMAN FADEN:  We are a little late but we're going
to go ahead.  We are having a contest between one side of the
table and the other.  Oh, you're sitting on the wrong side. 
Okay.  Now, we're even.

          Good morning.  We'll start right away.

          Steve, I can't recall if you've sort of been formally
introduced to the Committee members or not.

          DR. GOODMAN:  Once indirectly.  I don't know if they
remember.

          CHAIRMAN FADEN:  Well, we're going to start the morning
with reports on the two empirical contemporary projects that are
ongoing.  We've got Jeremy and Nancy whom all of you may be
familiar with and we've been joined by -- well, I know you're
familiar with Steve Goodman, who is an epidemiologist and
pediatrician and statistician and -- have I missed anything?

          DR. GOODMAN:  Good guy.

          DR. SUGARMAN:  Whom we've co-opted into helping us deal
with the data from the subject interview study.  We're really
very lucky.  And he's like all the rest of us who thought this
was something you could do a few hours a week and now it's taking
over his life.  So, we appreciate Steve's allowing us to snooker
him into doing this, along with Jeremy and Nancy.

          Okay.  We have stuff to talk about; right?

          DR. SUGARMAN:  We have stuff.  First of all, I'm
basically going to walk through the handout that we gave you
yesterday at about 4:15, so if you could find that, it will be
helpful as we go through this material.

          Basically, I'm happy to report that of the 19
institutions that were selected for participation in the subject
interview study we have succeeded in getting IRB approvals from
16 of those institutions.  They are balanced in a way better than
we could have hoped four universities, four VA hospitals, four
community hospitals and four governmental hospitals.  

          The three institutions that did not come on board,
Baylor and Dallas, didn't come on board because the oncologists
voted that they didn't want to participate.  And the Seattle,
University of Washington, are tied with the same IRB in the
person who is designated as the titular PI at that site.  His
mother was sick, as I described last time, and he tried to do an
expedited review over the last few weeks and that didn't fly.  So
their IRB approval, sometime during the next meeting of the
Advisory Committee, and that was a little late to get data.

          In terms of the brief survey, surveys are being
completed or in progress at 13 of the 16 institutions.  Since
three of the institutions' IRB approvals just came in this week,
we have conducted as of yesterday 1458 interviews, the brief
survey, and we're going to report later on today on 943.

          In terms of the in-depth interviews, realizing that
these follow the brief interviews, 18 of the 100 in-depth
interviews have been completed and we will be giving you some
information about the process of the in-depth in just a minute.

          We did proceed with doing some on-site observations to
see how the surveys were being conducted in each of the
institutions.  Some of the Advisory Staff went out and with their
Tony the Tiger glasses on and sat in waiting rooms around the
country and they observed the clinic atmosphere, how clearly the
brief survey was explained, how people were recruited, how
informed consent was obtained, the privacy of the process -- so
it was almost helpful if they couldn't observe some of these
things -- and the relationship between the RTI, the interviewers
and the clinic staff and with the patients.

          Overall, they found that the interviews were conducted
well, they found a couple of instances where things could be done
better.  More private space, for instance, might be needed.  We
gave that feedback to the contractor and we've been assured that
they're making the corrections in each of those institutions.

          In addition, we called some of the people who said they
were willing to be called back and asked them what they thought
of the process.  And overall, the results were very positive.  

          We called 10 people at least from each of the five
geographic sites and they seemed fairly happy.  Their only
complaint is that this five to 10 minute interview is more like a
10 minute interview or a 15 minute interview and they would have
liked to have been told that up front.  And that was a fair
request.  And so, we've asked that in the future, for recruiting
folks for this study, that they actually tell them -- give them a
more realistic time estimate.

          With respect to research determination and assessment,
Pat Perentesis on the staff visited with the site coordinator at
each of the five sites.  She helped them design an
institutionally specific mechanism for making the determination
of research in the way that I outlined during the last Advisory
Committee meeting and they are in the process now at each
institution, clinic by clinic, going through and trying to
determine whether people are research participants.

          The next hurdle we have is to now get an abstract of
the protocols from each of the studies that people are enrolled
in, whether they knew it or not, and that's going to be something
we're going to be concentrating on over the next couple of weeks.

          What we anticipate doing is calling the investigators
and asking them to send us those and following up by letter.  We
then will come up with a mechanism for assessing these protocols
in a much more abbreviated fashion than the research proposal
review project.  Basically, what we need to know is what kind of
study it is; is it therapeutic, diagnostic or epidemiologic or
other; where it took place, which one of the medical clinics;
what was the approximate level of risk to participants; what was
the level of benefits to participants.

          In terms of analysis, we will present sort of some
frequency analyses today but once the interview phase of
collecting the data have been cleaned, RTI will deliver data
tapes to us and Steve Goodman will be supervising an analysis of
those data, consistent with the analytic plan, and he'll describe
that in a minute as well.

          Do you want to give an update on the in depth?

          MS. KASS:  Yes.  The only addition I will make to what
Jeremy said related to the qualitative part, the in-depth part,
two things, actually.  First of all, I would like to introduce --

          CHAIRMAN FADEN:  I was going to say can we introduce
Monica?  Yes.

          MS. KASS:  -- to the Committee, Monica Schoch-Spana. 
If you could stand up for a second?

          CHAIRMAN FADEN:  This is another person that we seduced
and snookered and misled into joining us, joining the enterprise.

          MS. KASS:  Monica is an anthropologist who is going to
help us with the qualitative piece, who's now going to work full-
time for the rest of the Committee's existence to help us with
this component.

          To tell you how quickly all of this is moving, from the
time when this memo was written until now, there actually have
been many more in depth interviews done.  We now have done 79,
even though your memo says 18.

          CHAIRMAN FADEN:  79?

          MS. KASS:  There's 79 that are completed.

          CHAIRMAN FADEN:  In-depth interviews?  Sorry.

          MS. KASS:  In depth interviews.  Yes.

          CHAIRMAN FADEN:  That's terrific.

          MS. KASS:  Which we're very pleased about.  And these
are from 11 different institutions.  We wanted for some of the
Advisory Committee staff to do some of the interviews so that we
would have even a better handle on the data so that we would have
first hand experience of going into the hospitals, doing it in
the settings or doing it in the patients' homes.

          And so we decided that among us we are going to conduct
20 of the interviews.  And so the subcontractor will probably
only conduct a handful of the remaining interviews because we now
have changed, as it says in your memo, to do 100 total, rather
than 125 total.

          Shall I go on with the recruiting scheme?  Okay.

          The other major thing that we have done is to try to
figure out how we are going to code these interviews.  As any of
you will know if you've worked with qualitative data before, the
main way you analyze these data is to try to figure out what
kinds of themes keep emerging, and then group the quotes from
each of the transcripts by those themes.

          So the first step of the analysis is that Monica is
going to read every single interview transcript front to back so
that she has a sense of the overall data.  Then we have picked
out 10 codes or themes that we think, from having read the first
10 interviews, are the kinds of themes that keep emerging and
reflect the kinds of things that we hope we have learned the
Committee is interested in.  And I will run through these with
you.  They are also in the handout.

          I guess this is also a time to tell us if there are
particular things that you want to make sure that we look for
that aren't included in this list.  And remember that these are
broad codes.  The way that it works is that coders are hired to
read the transcript.  And whenever a particular passage seems to
be associated with one of these themes, that passage is coded to
be labeled with this theme.  And a particular passage could be
coded with several themes, as several themes are included.

          And then later, with the help of a computer, the
computer spits out all of the quotes that had to do with, for
example, voluntariness or all the quotes that had to do with
consent.  And that way one reader can look at everything that had
to do with the particular topic and get a feel for what was
mentioned.

          So, the codes are, first, a general appraisal of
research.  This is any time anyone talks about attitudes, about
research in the big picture, sort of in the abstract.

          CHAIRMAN FADEN:  Nancy, if we could have everybody
directed to the diagram. It's in the middle of the fat thing that
you have.

          I'm sorry.  I didn't mean to interrupt.

          DR. SUGARMAN:  It's attachment 3.

          MS. KASS:  Yes.  It right in the middle of the large
handout that you have from us.

          CHAIRMAN FADEN:  And it starts, "In-depth interviews,
global focus."

          DR. SUGARMAN:  It's before the table shells.  And if
anyone filled in their table shells correctly, you'll be getting
some free Danish.

          MS. KASS:  Okay.  Thanks.

          So the first code has to do with when someone talks
about research, not in terms of their personal experience, but in
what they think research is general.  If they talk about their
attitudes, if they think research is a good thing or a bad thing,
if they think research helps to advance science, something like
that.

          The next code is their personal experience with
research, particularly if they say things like I felt this way
when I was in the study or they treated me this way.

          The third code is their reasons for participating. 
There are specific questions about this, but also if in the
course of the discussion a participant says something like, well,
I was really hoping that this would be my chance to get better or
my chance to have a cure or the doctor really recommended it so I
thought it would be a really good idea if I went in.  Anything
like that will be coded with this term, reasons for
participating.

          The fourth code is voluntariness, which obviously has a
lot of relevance, I think, to the Committee in terms of the
history of why we are here.  And this both reflects the choice to
join the study, whether there was a choice, the decision to
participate in terms of the choice versus pressure aspect.  And
also, any choice or pressure to stay in the study.

          So, any time there's discussion about whether or not
they thought they could leave, whether they thought that there
was pressure to join, whether they heard about it and it was
really their own free will by which they decided to join, all of
that gets coded with voluntariness.

          The fifth code is consent, and that has to do with the
consent process.  It has to do with the form itself, but
obviously it's broader than that.  It has to do with someone from
the study team talking to them, giving them information, what
they were thinking about.

          The next code, which is somewhat related, is their own
personal decisionmaking process.  And this actually is a code
that we added after having read through the first 10 transcripts. 
It seemed like, from whatever conclusions you can draw from a
small number, that there were some people who thought about it,
weighed the options, needed more information, and there were
other people who acted.  The information seemed not to make much
difference.  For whatever their own complex of reasons was, they
knew they wanted to be in the study. 

          And so this process and how they thought about it is
what this code reflects.

          The next code which also emerged from having read the
first set of transcripts is trust. There were many people, even
in the first set of transcripts, that said things like, "I trust
my doctor" or sometimes, unfortunately, I think, in terms of
accurate understanding, "I know I couldn't have the placebo.  I
trust my doctor.  He wouldn't do that."

          But things that reflect trust in the system or "I
couldn't be harmed in research.  They wouldn't do that to me." 
Something that reflects I have faith in the people who run this
kind of thing or I have faith in the medical profession.  So
there's a code that reflects this issue of trust.

          The next code we are calling, for lack of a better
term, blurred boundaries.  The main reason we put this is was
initially a concern that we had I think both from the literature
and also from a few things that we had read that often people
don't distinguish clearly what is research and what is treatment. 
Obviously, particularly, for clinical research.

          We have included in this anything similar to that that
we would call a blurred distinction, such as the doctor versus
the investigator, being a research participant versus being a
patient, being at a research institution versus a non-research
institution, side effects of the medical condition versus side
effects of a research intervention.

          So anytime it seems to us that those things are being
blurred in a discussion, we want to capture that and look at it
separately.  

          The last two codes are, first terms.  As you know, this
is part of the brief interview that we asked people to
distinguish among four different terms.  And we already have
gotten a few interesting things that fortunately consistently
have shown up in the brief survey, which Jeremy will talk about
in a minute, and in the in-depth.  But there really do seem to be
differences in the way people understand these terms and we want
to capture that. 

          And then the last one is radiation, obviously.  Any
time anyone mentions the word radiation we're going to code it
and look at the context in which it was raised, whether it was
simply descriptive, whether they tried to express some kind of
reaction that they had that they think perhaps is attributable to
the radiation.  Any time it comes up we're going to flag it and
look at it.

          CHAIRMAN FADEN:  This has probably provoked enough that
maybe we should take just five or 10 minutes, Nancy for questions
on this coding and on the qualitative and then we'll return to
the plan.

          Is that okay, Jeremy?

          DR. SUGARMAN:  Yes.  I think so. I think it would just
be helpful for the folks not familiar with -- and tell me if I'm
wrong -- with qualitative research, which these codes do and how
they're used. And then why the data are coded.  Would that be
helpful?

          CHAIRMAN FADEN:  Sure.

          MS. KASS:  Okay.  Again, what we will do is take all of
the 100 or 100-plus transcripts, read them in their entirety and
block off sections of text that we think apply to any of these
codes.  And again, portions of text can be coded with nothing if
it's just sort of extraneous stuff.  That, again, gets captured
in the total read but we think doesn't apply to one of these.

          It could be coded with one code or it could be coded
with several codes, again, just depending on what it is that the
participant says.

          That all gets entered into a computer with these handy
new software packages.  We then call up any code that we're
interested in.  And again, if any of you has an interest, if you
want to read everything that someone said about radiation, for
example, or anything anyone said about voluntariness, we'd
request that from the computer.  

          And if there was a section in an interview 2 and a
section in an interview 6 and a section in an interview 12, all
of that gets grouped together.  It's put in a printout.  It
actually is also printed out, if anyone cares, with the other
codes that that particular passage was coded with.  And then you
have a whole set, a printout that is anything anyone said in the
entire part of this part of the project about that particular
subject.

          After that, the analysis starts to happen and we try to
draw some conclusions, both from the overall picture and from
these particular components.

          CHAIRMAN FADEN:  And I think the point that really
needs to be underscored is that these are very broad.

          MS. KASS:  They are very broad and they are
deliberately broad.  There are different philosophies about
coding and different mechanisms for doing it.  We decided, both
because we're under time pressure and because we want to get some
of these broad areas covered that we would do this broad type of
coding.  

          Another philosophy is that you have about 100 codes
and, for example, the 15 possible reasons that may be mentioned
about why people participate each would be given its own code. 
And we want to look at it in the aggregate after we make these
broad distinctions, and that's why we did it this way.

          CHAIRMAN FADEN:  Ruth?

          DR. MACKLIN:  This is really just a very brief
question.  Did any of these codes -- and I think particularly in
the consent and the voluntary -- capture the subject's perception
of alternatives different from whether they had a choice not to
participate, the coercion factor, but that is legitimate standard
practice or what other things come in?  I didn't hear you say it,
so I'm looking at those.

          MS. KASS:   Yes.  No.  That's a good -- I think you're
right. I think actually we should add that as a completely
separate thing.  Even though it will probably come up in some, to
highlight it, to see whether they either repeat that it had been
mentioned by an investigator or they were thinking of it
themselves.

          DR. MACKLIN:  Well, from the terms being used -- I
mean, in the follow up to the research in the lengthy interview,
is the term used by the interviewer or does the subject have to
initiate the language?

          MS. KASS:  Because the questions don't follow a rigid
set of questions, it doesn't necessarily come up but it is in
their guide so they are supposed to cover it.   It sometimes will
come up in the course of conversation even before the interviewer
initiates it when the patient is going through is or her
decisionmaking process.  The patient may say, "I was thinking
about joining the study because what I would have had otherwise
I've been through before and it didn't seem to have worked." 
Something like that.  And then that hopefully would be coded
alternatives because that's how the patient is conceptualizing
it.

          That's a good suggestion.

          CHAIRMAN FADEN: Nancy and then Sue.

          DR. OLEINICK:  Is there any way from this exercise of
discerning whether the subject's perception of being informed is
in fact -- the fact that they would have been informed
sufficiently to make that decision?  In other words, you're going
to get some information, some of the phraseology that's going to
talk about yes, it was explained to me and I agreed to do it. 
But I don't know exactly how one would do this but I wonder if in
any of this information we would expect to see phraseology that
would suggest that it was a misperception.  Does that come out of
that or does it come out of the kinds of questions in the short
interview where you're asking them to describe the study?

          MS. KASS:  Well, if I'm understanding you correctly, it
sounds like part of what you're interested in is some kind of
validity check.

          DR. OLEINICK:  Right.  Exactly.

          MS. KASS:  And that is a piece that we are not doing
except the piece that we have is we will have abstracts of the
proposals.  So that will tell us what the proposal is about. 
However, we won't have a tape of the conversation.  And in
certain ways, if this were an absolutely complete study, what we
would have is a tape of the interaction between the investigator
and the potential, at that point, participant.  But instead, what
we will have here is the piece where the participant is recalling
what he or she had heard and had been exchanged.

          CHAIRMAN FADEN:  I think that's important to emphasize
that the study can't speak to the quality of the information that
was provided.  It speaks to the status of the understanding that
the subject has.

          DR. OLEINICK:  And the perception of understanding.

          CHAIRMAN FADEN:  Right.  That's right.  

          DR. OLEINICK:  Whether the subject thinks he or she
understands.

          CHAIRMAN FADEN:  That's right.  And also if there was a
gross -- like if the person said, well, I'm in the study because
I think it could cure me and from looking at the abstract, we
could pick up some misconceptions if they were very gross.  And
from the abstract it's clear that it's research that's not
possible to offer a prospective benefit.  We don't know.  We will
never know whether that the subject's overlay or whether they
were somehow led to believe that.  That we wouldn't be able
impact.  We would simply be able to see that there's some problem
here because the patient has -- the subject has a discrepancy. 
But that would be the only -- is that a fair characterization?

          I figured we would do this.  We're probably never going
to get done, so we've got Sue and Duncan and maybe one or two
more and then we'll go back to the quantitative.

          DR. LEDERER:  Do you have a sense that the subjects
have given any thought to what would happen if a bad outcome were
to occur?

          MS. KASS:  In the transcripts I have read so far, not
at all.  

          DR. LEDERER:  Because something you said made me think
of that when you said that nothing -- I mean, my doctor wouldn't
let anything bad happen to me.  I mean, there's certainly an
outcome of that.  But if a bad outcome were to occur there's not
much --

          MS. KASS:  Have you seen any discussion of that?

          CHAIRMAN FADEN:  Monica, could you come to the table? 
Thank you.

          MS. SCHOCH-SPANA:  Of the first 10, there hasn't been
any commentary specifically to that issue, so we might have to
postpone discussing that.

          MS. KASS:      Yes.  I think that's a good question. 
What has been overwhelming so far, and I'm almost hesitant to say
this because it is 10, but it really is the opposite.  It is the
trust that comes through so clearly and very positive
experiences.

          Again, obviously, it's a bias.  We are selecting people
because they are in research.  We are not selecting people
because they've rejected being in research.

          DR. SUGARMAN:  Also, the code of personal experience
with research would pick up those sorts of things.  So if you
think some of those experiences will be good and some of those
experiences may be bad or adverse in some way, so it will be the
interpretation of that in context of that person's interview that
we'll be able to get at that.

          DR. LEDERER:  I guess I was thinking of the language of
some consent forms that say explicitly that the university will
not be held -- will not pay for treatment if they don't get
outcomes.  

          MS. KASS:  I'm glad you mentioned it and we'll
certainly look for it.

          CHAIRMAN FADEN:  Duncan?

          DR. THOMAS:  These coding schemes seem to be, at least
at this stage, basically used as a sorting device.

          MS. KASS:  Exactly right.

          DR. THOMAS:  Nothing more than a big pair of scissors. 
Smart to compare scissors to it.

          MS. KASS:  But it's a lot more convenient to have it
considered.

          DR. THOMAS:  Did I understand you to say that now the
analysis piece begins?  And the question is does that analysis
piece entail attempting to assign codes to what people actually
said in a manner that could then be linked with the short
interview to provide us more insight into an analysis of actually
what happened.

          DR. SUGARMAN:  We're going to illustrate that for you,
actually in the next section here.  When we review the
quantitative, we're going to give you a hint at how that might
work.

          CHAIRMAN FADEN:  And the fact is, I don't know what
Jeremy is referring to, Duncan, but if that doesn't work, we'll
have a speaker come back.

          DR. SUGARMAN:  Yes.  Because we're going to have a
section.  What we hope to do is provide you with a review of the
brief data, the sort of very preliminary data, and then talk
about analysis while Steve is here.  And then, once we've seen
the sorts of analysis that we're going to do, maybe we could deal
with the whole analysis questions together, if that would be all
right.

          MS. KASS:  the one thing I can tell you briefly in
direct answer to your question is that when we get a complete
transcript that's come from the transcriptionist, it comes with
what's called a contact sheet that has on it eight to 10
demographic variables, so that at least that particular
transcript is being read knowing some of the demographics of the
person.  

          And again, qualitative data has a lot of analysis done
in the reader's head, and so part of it is understanding -- okay,
this is an African-American man in his 60's who's saying this and
you read it knowing that.  And the next one is a white woman from
Texas who's in her 70's and you know that.  And you start to make
some conclusions by reading these chunks of data that you know
come from this person and that person and this person and that
person.  And that is on initial way that the data are linked from
the two types of surveys.

          DR. THOMAS:  It isn't evident to me why you want to do
this that way.  In other words, we're not particularly interested
in this case in knowing whether or not race is a factor in how
people respond to these things.  But supposing there were, that
would seem to me to build in certain biases in your analysis. 
And that we'd be better off doing that coding blind and then
seeing whether or not there's an association.

          DR. SUGARMAN:  Yes.  The coders won't have access to
the brief interviews when they're coding.

          DR. THOMAS:  No.  We're talking about the in depth
interviews.

          DR. SUGARMAN:  Right.

          DR. THOMAS:  And why the coder ought to be provided
this background information in the first place.

          DR. SUGARMAN:  Should be provided.  So you're making an
argument that the code should --

          MS. KASS:  Should not.

          DR. SUGARMAN:  Should not or should?

          DR. THOMAS:  Should not.

          DR. SUGARMAN:  Okay.  They're not.

          DR. THOMAS:  But they are being provided the
demographic information and I'm just trying to understand why you
do even that.

          CHAIRMAN FADEN:  No.  I think we're distinguishing
between the coders and the professionals who are analyzing the
data.  

          Monica could speak to this better than I could, but
it's my understanding -- obviously, when you're doing
ethnographic work, you will know who you're talking to.  It's a
different -- you've got to suspend, think of this as an
anthropologic project.  It's ethnography. We're not sitting here
trying -- this is not quantitative data we're trying to -- you
know, sort of pull out the variables and then stick them in and
model this.  

          This is -- when an anthropologist talks to his or her
respondent, you know who you're talking to generally.

          MS. SCHOCH-SPANA:  Correct.

          CHAIRMAN FADEN:  And you're forming impressions in a
gestalt fashion.

          MS. SCHOCH-SPANA:  Right.  Well, to speak to your
concern, the coders are going to be coding the transcripts blind. 
That is, they won't be focusing on the demographics of the
respondent.  I'm the staff member that's been entrusted with
reading the transcripts in their entirety and I do have the
contact sheet associated with the transcript that includes
demographic information.  But I think because we're using
multiple tools to both code and analyze the data that includes
both being blind to demographic information and then being
attentive to it, that we're getting a nice balance and trying to
control the detrimental effects of bias and still be sensitive to
differences across income groups and age groups.

          CHAIRMAN FADEN:  Maybe if it's all right, if we don't
hear, let's go on with the quantitative stuff in more detail and
then try to put everything in.

          DR. SUGARMAN:  Okay.  In order to facilitate a quick
review of the quantitative information, we've provided you with
the frequencies put directly onto the survey forms so you
wouldn't have to keep bouncing your heads back and forth.

          We're going to actually start on page 21 of the survey
instrument form, which is the demographic information.  Although
this is the latter part of the interview, we thought it would be
helpful to tell you who it was we were hearing from.

          Let me just emphasize as I go through this information
that these are preliminary data.  The data tapes have been
cleaned somewhat.  They're not in their final clean form.  We are
going to be receiving another whole bunch of data and we
shouldn't even pretend to leap towards conclusions based on the
data that are presented here.

          And it's -- I know you always like to dive in to do
that and try to make sense of all these numbers, but if you can
try to hold back for another few weeks, that would be helpful,
because it's harder to unlearn those things later.

          Basically, what we're finding is that the mean age is
about 60 years old.  We have a good balance between men and
women.  There is representation from various groups.  We have
black or African-Americans, 139 of these respondents, and 757
whites and 45 Latino.

          These data don't completely reflect the sampling in
Texas and we anticipate that we will be able to provide more
Latino representation based on those data.

          We actually have a highly educated sample.  If you take
all those confusing numbers under F-5 and lump them into at least
four things instead of however many are there, 11, about 118 of
those folks don't have a college education, so about 10 to 15
percent have a high school education; 281 have finished high
school or some kind of vocational school; 225, about a quarter,
have some college; and about 25 percent are college educated or
beyond.

          People tend not to be employed about 60 percent.

          DR. MACKLIN:  [Off mike.]

          DR. SUGARMAN:  I think that's a reasonable way to
interpret these data.  I wouldn't want to imply causality from
one to the next yet, but that makes sense to me.

          Let's see.  What else.

          Most folks believe that their health is good or fair
and they tend to be insured.

          Now let's flip back to the beginning of the survey
instrument to Section A.  And you'll recall that Section A are
general attitudes towards research.  And we find that overall
most people feel pretty positive throughout and that's
summarizing the items on pages 1 and 2.

          We then ask people to make distinctions between some of
the terms.  Now, there are four versions, as you'll recall, of
the survey instrument, each one asking about a different term, so
each respondent compares medical research to something else.  But
what we find over the group is that medical research seems to be
different than clinical investigation, clinical trial and medical
experimentation.

          At the risk of doing what I said not to do, clinical
investigations and clinical trials seem to be perceive to be the
lowest risk or sort of the most beneficial in the group; medical
research in the middle; and medical experimentation to be
somewhat riskier.

          What do you do with these data?  Well, Nancy now will
give you a couple of excerpts from -- these are unlinked to the
particular respondents to this, but these are just our first
transcripts back, to show you what some of the people said about
each of the terms.

          MS. KASS:  I'll give you quotes from two different in
depth transcripts about the same topic of terms.  The interviewer
says -- there's a card that the respondents are given with these
four different terms on it and the interviewer says, tell me if
you see any difference among them. And the respondents said
medical experiment would be medications more than research as
such, and there's a little bit more questioning.  And then the
interviewer says, if a doctor said to you, look, we've got these
four different kinds of medical research happening, which would
you like to participate in, the respondent very quickly said the
study.  And then the interviewer said, and why would you feel
that way?  And the respondent said, less risk, parentheses,
laughter.

          And then the interviewer says, so you think there are -
- there's one with more risk?  Which one would probably have more
risk?  And the respondent says that would be the medical
experiment.

          And then, similarly, another person said medical
experiment means that you don't know the results or what you're
testing and that's what the word experiment means.  And that you
have an idea or theory or hypothesis and you're trying to prove
or disprove it.

          Clinical trial is another stage of that. You've got
some results and you've got some information.  It's based on a
very small scientific sample and you're trying to see whether
those results hold.

          CHAIRMAN FADEN:  That's a very sophisticated person.

          MR. GUTTMAN:  Who were you interviewing?  Dr. Katz?

          (Laughter.)

          MS. KASS:  The only thing that I'll say about the
reassurance -- you know, I assume most of you have conducted
research.  When you get your first set of data and you're
actually really anxious because you go in sort of -- you've asked
the questions because you expect that you might find something
and you're not really sure. And when both the brief survey and
the in depth survey had really consistent results in this, it was
for us personally very reassuring.

          DR. SUGARMAN:  The other reassuring part skips to page
4 where there was a huge discussion back in July and August when
we were initially in the process of designing this experiment
about if we went into these particular waiting room, would there
be anybody who was in fact a research subject.

          Now, what I can tell you is what people perceive.  And
from the data we have so far, it's that 12 percent of the 943
respondents believe that they are currently participants in
research.  An additional 15 percent believe that they have
participated in research in the past.  So that gives us about 25
percent or so of the population that has some experience to base
their thoughts and attitudes on and we can see if those differ
with the other groups.

          That breaks down in terms of what types of research
project.  And this is from the patient's perception.  One hundred
fifty-two of the respondents of the 943 believe that they are in
a treatment trial; 40 of those people believe that they are in
some kind of diagnostic trial or study; and 63 believe that
they're in a epidemiologic study.  So we have no reason to
suspect that those numbers, the proportions, will differ greatly
later.

          So, we're going to skip several pages now through these
items which then explore what people think of their participation
based on treatment, diagnosis and epidemiologic study, and
generally, most people seem to be positive.  Again, some of them
-- most of them had altruistic motivations for participating in
research.  

          And although the urge is to dive in and go through each
of these items, we're going to let you do that in the privacy of
your home or office because I think really going much further
with these data would be quite tenuous because the numbers get
extraordinarily small.  But the patterns generally are revealing
that there may be now -- there are minorities of respondents that
may be highly significant, but the overwhelming trends seem to be
quite positive and we'll just need to wait to explore that
further.

          DR. KATZ:  Jeremy, can I ask --

          DR. SUGARMAN:  Sure.

          DR. KATZ:  Sorry.  Ask one quick question.  I didn't
quite understand.  All these people that you interviewed of
course are participants?

          DR. SUGARMAN:  These are people who believe -- well,
everybody who --

          DR. KATZ:  Is in the research project or not
necessarily?

          DR. SUGARMAN:  The overall 943 are people that were in
waiting rooms, either in cardiology, radiation oncology or
medical oncology waiting rooms.  And one of the questions that
we're talking about, when we asked them about these particular
reasons for participating, are the group that suggested or
believe that they are research participants.

          DR. KATZ:  So later on you'll tell us something about
whether their perceptions are correct being --

          DR. SUGARMAN:  About research.  Yes.

          DR. KATZ:  That's still to come.  Okay.

          DR. SUGARMAN:  Yes.  That's still to come.

          DR. KATZ:  Okay.

          CHAIRMAN FADEN:  And everybody in the qualitative
interview believes they're a research subject.  Is that correct?

          DR. SUGARMAN:  Correct.

          MS. KASS:  That's right.

          CHAIRMAN FADEN:  So everybody in the in depth part of
this thinks they're a research subject.  Whether they actually
are or not is something --

          DR. SUGARMAN:  Skipping to Section E, reasons for not
participating, these were a group of people who didn't answer the
first set but had been asked to participate in a research project
before but they said no.  And we asked them some questions about
why they decided not to participate.  And the only
generalizations I'd like to make now is that most of those folks
thought it would be inconvenient and they didn't like the
uncertainty or the inconvenience of participating in research. 
They wanted to make their own decisions with regard to care or
have their physicians do something like that.

          I'm going to stop right there and let Steve talk about
analysis.

          DR. GOODMAN:  Yes.  I'll direct your attention to the
table, the shells, that are in the latter half of this.  It's
Attachment 4.  As you see, we've completely eliminated any
temptation to over-interpret the data by putting no data in these
at all.

          This is obviously just the beginning of an analysis. 
This is just a welter of cross-tabulations by a variety of
factors.  And this is what the subcontractor will provide to us
and from which we will take off on.

          Now, this is obviously restricted to lots of two-by-two
comparisons and there are lots of questions being posed by this
research that are going to involve a lot of substratification. 
That is, we'll want to know questions by whether they were in
former research or current research; by whether they were
radiation, not radiation, et cetera, et cetera.  It's not going
to be restricted to just these two by two comparisons, but this
will begin to give us a sense of what the data look like.

          The parameters that we'll be using for the overall
analysis will be the same sort of things we see here, just in
combination.  That is, the geographic site of which there are
five; the hospital, of which there are four; whether they're in
research or not; and among those who were involved in research,
whether they're current and former; whether they're in radiation
or no radiation.  

          There are obviously a host of patient characteristics
which are all listed here in the demographics; race, income,
insurance, education, sex and age.  And the outcomes are both the
outcomes of the attitudes to the questionnaire, as well as the
concordance, whether they know that they are on research or not. 
And then, of course, there's the relationship of some of these
with each other.

          Now, obviously, the final analysis will not be
necessarily in the form of these tables, which will be virtually
impossible to interpret with a brief inspection.  We will be
using those horrible things called models to start to sort out
the independent contributions of things.  And, we'll go back and
forth between both interpretable data displays and the models.  

          The models will be used both as exploratory tools to
try to sort out which factors are related to what, as well as
what you might call confirmatory tools to sort of summarize very,
very complicated patterns. Although, my experience is that in the
end you can often sort of present a lot of the message in very
unsophisticated ways.  That is, you can have a final model but
you can show how it looks in terms of some simple two by two
tables.

          In fact, my goal in almost all research is to reduce
all of the numbers to a single two by two table, so we will be
trying to do that here, as well.

          Now, the one thing we actually had not talked about
specifically which Dr. Thomas just brought up, was specifically
linking the specific interviews in the in depth interview to
specific brief interview results.  And I think that's a very
interesting suggestion.  And we certainly, I think, will have the
ability to do that.  So I think we'll think about the exact
logistics of that, but it's certainly not impossible.

          I would say in terms of the Committee, if there -- I
mean, I've outlined the general sort of things that will go into
the models.  If for the purposes of your making recommendations
there are certain questions that you want to make sure,
absolutely sure that we have nailed down within a month of your
final report that you need for those deliberations, of course, if
you give those to us, you can absolutely ensure that they'll be
addressed.

          I think we have just about every -- you know, we will
look at just about every combination of factors we can think of
that will be of interest, but we obviously want to make sure that
we don't miss some.

          DR. SUGARMAN:  If you express any ideas as you
deliberate about policy that you would like to test, rather than
just simply conjecture, we can sort of look at those
specifically, if directed.

          DR. MACKLIN: I don't know anything about this kind of
data analysis, so these may be very stupid questions.  Well, the
first question is stupid.

          DR. GOODMAN:  I'm sure, they're not.  If they're
simple, they're probably very hard.

          DR. MACKLIN:  What are these things called?  Shells?

          DR. GOODMAN:  Yes.

          DR. MACKLIN:  On page 40 --

          DR. SUGARMAN:  Was that your question?

          (Laughter.)

          DR. MACKLIN:  No.  I know how to listen.  I guess maybe
it's 40, but the one that has two choices; radiation research
patients and non-radiation research patients.

          DR. GOODMAN:  Yes.

          DR. MACKLIN:  The three categories are oncology,
cardiology and radiation; right?

          DR. GOODMAN:  Yes.

          DR. MACKLIN:  So that you have lumped together in the
non-radiation research people who would be in cardiology,
cardiology patients and oncology patients.

          DR. GOODMAN:  That's right.

          DR. MACKLIN:  My question is if you find some kind of
differences, significant differences between the radiation and
the non-radiation research patients, how do you know without
further division that there might not be a greater difference
between the cancer patients and the non-cancer patients --

          DR. GOODMAN:  Well, obviously --

          DR. MACKLIN:  -- or would it matter?

          DR. GOODMAN:  Well, it certainly could matter.  And
this is just an examples of the type of divisions.  We could, of
course, produce a table with that split out.  And, of course,
that will also come in in the models where there'll be a specific
term for type of research.  I mean, oncology, radiation oncology,
oncology and cardiology, will be a separate term.  If anything
came up -- if we actually haven't produced a table of that
already broken out.

          The thing is, many of these headings can be broken out
into a number of subheadings, so we didn't want to produce every
possible table here that we could possibly produce, but that is
one of many very good points about subdivisions that we'll have
to look into.  Because obviously --

          DR. MACKLIN:  So we'll be able to look at it, even
though you're not representing it here --

          DR. GOODMAN:   Absolutely.  These are really
prototypes.  They're, A, not necessarily complete; and B, we will
be going -- as I said, we'll be going back and forth between the
models and these tables.  And it may be that if we find that
there is a particularly important contrast among non-radiation
research participants, which is possible we would only see in a
model, although we could see it here if we just produced that
table.  We would then go back and look at just the two by two,
this type of cross-tab, to see what the raw data actually looked
like.

          The disadvantage of any one of these tables is that any
two by two contrast, that is, one thing by another thing, doesn't
then control for all the other things that are different.  So
there's always a loss of balance between a loss and a gain in
simplicity.

          DR. MACKLIN:  One other quick question.  And this is on
the -- when you're comparing the current and the former research
participants.

          DR. GOODMAN:  Yes.

          DR. MACKLIN:  Isn't there a problem about recall?  That
is, the longer ago in the past the person was a subject of
research, the last recall there might be about some of these. 
And if someone answered, "Don't remember," that's one thing.  But
if the person thinks he or she remembers --

          DR. GOODMAN:  Right.

          DR. MACKLIN:  -- then -- I mean, it's really a question
of what do you do with that kind of factor when -- and is there
just for example, any indication of how long ago the person was a
research participant?

          DR. GOODMAN:  Yes.  I believe there's a specific
question that addresses that.  And it's a good point.  We can
include that, as well.  Like within five years or greater than
five years, and see if there's an appreciable difference between
those types.  Again, --

          DR. MACKLIN:  But in any case there's the problem of --
I mean, suppose you found some significant differences in the
consent process between the current research participants and the
former research participants.  How do these mechanisms enable you
to determine, if at all, whether the person is mis-remembering or
just simply doesn't recall, or whether there was a clear consent.

          DR. GOODMAN:  There is, I would say, based on this we'd
have to use surrogate measures.  There's no direct way of knowing
that aside from perhaps getting clues from in depth interviews. 
We could use a length of time since the research as a surrogate
and see if we see data patterns that suggest, that are
inconsistent or whatever. 

          Of course, you have problems associated with that, like
people who were involved in research a long time ago are likely
to be systematically older and have other characteristics that
might be different.  So, obviously, the degree to which we'll be
able to sort things out is to some extent limited and we'll have
to use very indirect methods to determine that.

          DR. SUGARMAN:  And also, if you'd look at the types of
items, the types of questions we're posing, we're not asking
people to report to us what they remember about say the side
effects of the medication or that they forgot some things over
time.  We're trying to be careful in the design of the instrument
not to do what we know people do.  We know people forget things. 
And so that would be -- we could prove a scientific sort of so
what.  And I think we weren't interested in that question.

          There is an empirical literature on informed consent
that shows, gee, if you ask people what they know at the minute
they can date for consent, do they forget things over time.  And
it's no surprise that they do.

          Likewise, we're not going to look and say did you think
the consent form was readable.  We know that consent forms are
readable and that's been proven.  So we've tried to eschew asking
those kinds of questions.  So there may be some recall bias but I
think it's effect may be minimized by the statement.

          CHAIRMAN FADEN:  Duncan?

          DR. THOMAS:  There's a block of tables on the
concordance of indicators of medical research participation. I
understand from the script from the beginning that you're
actually planning to code the protocols in terms of things like -
- tied kind of like risk and benefit.

          Is there any plan to try to compare the concordance in
terms of the patient's assessment of risk and your judgment of
risk and did it have a benefit.

          DR. SUGARMAN:  Yes.  We can do that.  The reason for
that -- and it's an appropriate question -- is that these shells
will be filled in by RTI when they provide us with the data tape. 
Advisory Committee staff are doing and coordinating the efforts
of retrieving the protocols and then getting a mechanism outside
of the contractors.  We're keeping that in house.  

          So we'll have a separate database which we'll be
merging so that there'll be no possibility of having that
analysis presented from the subcontractor.  It's going to lag by
a few weeks because we're going to have to do that.  And that's
the only reason that's not here.

          CHAIRMAN FADEN:  Henry?

          DR. ROYAL:  When we've been reviewing protocols, it's
often been difficult to be very quantitative about the benefits
and the risks with the information that we have.  What
information are you going to have to do this quantitation about
the control in terms of approximate level of risk and benefit and
what sort of semi-quantitative units are you going to use?

          DR. SUGARMAN:  This is the stage that we are working on
now.  We are probably -- what we hope to do is do something like
low, intermediate or high risk and to force consensus of a group
or what I'm probably going to do is get experts in each of the
specialties to do the risk/benefit calculus and to have them sort
of do it independently and see what consensus is like.

          CHAIRMAN FADEN:  I think Henry's point is all we're
going to probably have is the abstract.

          DR. SUGARMAN:  Correct.

          CHAIRMAN FADEN:  So we may only be able to do a best
guess of -- you know, more than minimal risk, minimal risk, or
something.  You know, higher, lower, relative.  Because we're
going to have very little information.  And this is the roughest
sort of a thing. The only agenda -- remember, this was stimulated
by -- I forget --

          DR. SUGARMAN:  Committee discussion two months ago.

          CHAIRMAN FADEN:  I know.  But I'm trying to -- okay. 
So we can credit or blame one of us who suggested that it would
be really interesting to know if people don't know or a wrong
understanding, but don't know that they are a research subject. 
Whether that's more likely to occur in minimal risk studies, the
studies that are not very significant consequentially in terms of
people's lives.  So that's really all we're looking for here is a
rough cut to test -- to explore the hypothesis that if we have
anybody who doesn't know they're a research subject who is one,
which we don't know yet, whether that pool of persons is more
likely to have been enrolled in a lower risk study than a higher
risk study.

          So that's all we're trying to do here.  And as a
consequence, since the research aim is relatively modest, we
don't -- you know, it's not a very precise sort of risk/benefit. 
It's not for the purposes that we're doing in the research
protocol review project where we're trying to determine whether
the research and the project itself is an ethical one.

          So I think that's important to emphasize and we should
make clear that that's all that we're trying to do here.  And
therefore, it's not -- it would be nice if we had more
information but we're trying to make a guess based on the
protocol.

          DR. SUGARMAN:  Yes.  If you just found -- just to
demystify a little bit.  If you found that in these data that
there were a group of people that were discordant, they were
research subjects but in fact they didn't think they were, and if
it turned out that all of those people were in survey studies,
it's a problem we would like them to be aware of but it's not as
big a problem as if they were sort of engaged in something that
posed them at great degree of risk and there was some
intervention versus a placebo or something.

          So that's all we're trying to get at there, so that we
know what to do with those concordance and discordance numbers
rather than just have them be out there with no -- not to hang
them on anything.

          DR. MACKLIN:  I just wanted -- just a quick point about
what Jeremy said and who you're going to tell what the level of
risk is.  I can't cite the study or where or when it was
published, but I know I remember something about it, and that is
that experts in a particular area tend to rate the risks lower
than non-experts in that area, even among physicians.

          So, for example, neonatologists who work with three
pound infants will rate the risk of inserting some catheter in
this teeny little infant much lower than someone who works with
adult patients.  I mean, just something like that, but among
specialists and subspecialists.  

          So that could skew the data if in fact that is correct. 
That could skew the level of risk if you pick the experts to make
the judgment.

          MR. GUTTMAN:  There's a whole science of expert bias
which we have not yet called on.

          DR. GOODMAN:  The division we've made -- I mean, this
is a very rough cut, but even if we didn't go to the abstracts,
the division into epidemiologic diagnostic and treatment is
obviously a very rough cut at level of risk.  And in fact,
looking at the patterns of reasons why they -- that we've already
seen in terms of reasons why they are in studies, we see exactly
what you would expect from these sort of studies right now where
issues regarding risk and treatment didn't seem to play any role
in the people who signed up for what they perceived as
epidemiologic investigations.

          DR. MACKLIN:   Could I -- just sort of to understand
what you meant, are you implying that diagnostic studies would or
do in general carry lower risk?

          DR. GOODMAN:  Than treatment.  This is a trick
question.

          (Laughter.)

          CHAIRMAN FADEN:  Don't answer it.

          DR. MACKLIN:  I mean, at least for some.  I mean, I'm
thinking of ones I've seen in my own institution.  I'm also
thinking that some that we've seen in the protocol review where
they were purely diagnostic, no direct benefit to patients. 
They're sticking wires into people's arms and they're making them
exercise on treadmills until they drop.

          I mean, --

          DR. GOODMAN:  I would say very rough, very rough.

          DR. MACKLIN:  So some -- I mean, I understand what you
mean, you know, a diagnostic study.  But some of them in
cardiology, and I don't know about oncology.  Somebody could
speak to that better perhaps.  But I mean, among the things both
that we've seen here and that I've seen as a member of an IRB, I
don't think you can make a quick --

          DR. GOODMAN:  Oh, no.  That was really -- I mean, when
I said rough, I meant rough and on average.  But I've seen
screening studies that posed a much greater risk to participants
than some treatment studies.

          CHAIRMAN FADEN:  We probably could go on all day about
this.  The problem is, of course, we've got to do all our other
work.

          I have to just say on behalf of all of us, I think this
is extraordinary.  We have how many?  Fourteen hundred something,
1400 of the short interviews done and 79 of the long interviews,
which is totally news to me.  It's really remarkable.  And when
we started this, this sort of issue, there was the general view
abroad this could never be done.

          So, there's an accomplishment in the process of the
doing which is really worth noting.  We're all very delighted
that we'll have this information in time to use it for our
deliberations. 

          So we'll be seeing stuff presumably between now and the
next meeting from the four of you and then at the next meeting we
will have a go at maybe filled in shells as opposed to empty
shells or the impressions based on 10.

          DR. SUGARMAN:  If over the next couple of weeks you do
have ideas for analysis, we do need to hear from you rather soon,
like within the next week or so, so that we'll have time to plan
for that analysis if you want to look again over the analytic
plan now that the idea of making policy recommendations and the
like is close approaching.  We're happy to do any of those
analyses.  We're just going to need to know early.  So just
please send them my way and I will get them distributed to the
right people.

          CHAIRMAN FADEN:  Thank you all very much.  That's
great.

          DR. LEDERER:  Is there going to be a draft, a chapter
draft of this material due by our next meeting?

          CHAIRMAN FADEN:  I don't know.  We're shooting for
April.  What we don't know either is whether we're going to have
this project and the project that we're about to discuss will be
one chapter or two chapters.  We'll see how that will go.  We
don't know yet.

          I think it's really -- we should --

          DR. KATZ:  Is it possible as certain sections or
certain issues are being analyzed to a reasonably good extent,
that this be faxed to us?

          CHAIRMAN FADEN:  Anything you want.

          DR. KATZ:  This could be part of the policy because
then it can --

          CHAIRMAN FADEN:  Yes. Of course.  I mean, I think the
issue is --

          DR. KATZ:  -- come part of the forward thinking.

          CHAIRMAN FADEN:  Yes.  I think we have to think of a
reasonable way to do this.

          DR. KATZ:  Yes, yes.

          CHAIRMAN FADEN:  Something that's provided to
everybody. And then people have particular interests or want to
help work.  If Committee members want to work on analyzing
particular themes or particular subsets of the quantitative data,
that's terrific.  Plus, we will need to be pulling stuff out and
getting it to you quickly so that you can have it available as we
think through future recommendations.

          But the bottom line is we will have input before our
deliberations from these data and we will have the perspectives
of people who are currently subjects of research, which was the
goal of this whole enterprise was will we really be able to hear
from people who are current research subjects without putting an
ad in the newspaper and seeing who shows up.

          So we've reached out and we've found such people and we
will have data from them.  So that's just great.  It's really
great.  It's really wonderful.

          Nancy is reminding us that the numbers that we've heard
are the number of people who think they are research subjects.
And the big piece of the puzzle is the confirmatory process; how
many of these people correctly appreciate that they are research
subjects.  We'll see what happens, won't we?

          And the fact that we've got a very nice balance for
university hospitals, for community hospitals or military
installations or VA hospitals, allows us to be able to explore
whether the experiences are different for people who are
receiving their medical care and being recruited into research
from institutions.

          We should underscore that one big limitation of these
data with respect to the contemporary situation is that we are
only then getting information about research subjects who are
being recruited in context because they are getting medical care. 
So research with people who are healthy, the kind of research
that's done on healthy subjects, we don't get in this pool.  I
don't know that we even pick up any quote in normal controls in
this context.  I doubt it.  And certainly research that's done
exclusively on healthy populations, community research or
research where you're recruiting healthy people, we miss that
entirely.

          So that's something that we're going to have to just
acknowledge straight out.  That this is focusing on clinical
research and not on research involving healthy subjects.  And
that's very unfortunate because, as we know from our historical
investigation, the issues are somewhat different and also
important when the subjects are not patient pools, not coming
from patient pools but coming from other communities -- not
communities, other contexts.

          Okay.  We're going to move on now to an update on our
research proposal review project, where we are.  We're generating
the data as opposed to the customers or clients for the data. 
So, if we don't like the pace at which the data are being made
available, it's our fault and no one else's.

          Sara and Gail are with us?  Great.

          Now, we should look at a document that was distributed
the first day.

          MS. CHANDROS:  There's two documents.  One is -- it has
"handout" in the upper right-hand corner and it's going to be the
basis of my presentation.  And the second one is -- it lists the
frequencies of all the responses on the coding form that we have
to date.

          CHAIRMAN FADEN:  Can we give everybody just a second to
see if they can locate it there?

          MS. CHANDROS:  Sure.

          CHAIRMAN FADEN:  This is always risky, very risky,
right?

          (Pause.)

          Okay.  Sara and Gail, could we get started?  thank you.

          MS. CHANDROS:  Okay.  Thank you.

          We have as of March 13th, which is -- as far as the
analysis in this memo goes, we have 59 radiation reviews
completed and entered into the database and two non-radiation
proposals.  Right now, -- and since then, I've also gotten five
or six back that aren't factored into this analysis, and 20 are
in circulation amongst reviewers.

          So, we now have a chunk of information that we could
begin looking at numbers, but the bad news is that this
represents only about a third of the proposals that the Committee
planned to review itself.

          There is approximately an additional 48 radiation
proposals that need to be completed and entered into the database
and between 50 and 60 non-radiation proposals.

          In order to meet the stated goals of the project,
something is going to need to change or we need to either change
the sampling scheme, modify it to get done something reasonable,
or modify the mechanism for conducting the reviews, or both.

          I want to briefly present two ideas to the Committee
that you can discuss and decide how you'd like to proceed.

          In Table A on the second page of the update handout,
there's a table, a familiar table.  It now includes the numbers. 
The numerator is the number of proposals in each category by
biomedical category and agency that have been reviewed, and the
denominator is the total number available to be reviewed.  

          The shaded cells, which I know are a little dark on
your copies, are done.  We've completed those and there's nothing
more to do in those.

          One, our goal has been to fill each cell with between
three and 10 studies.  As a compromise, the Committee might want
to consider at least prioritizing.  Make sure we complete five in
each cell with the hope that we could finish everything, but if
we don't, at least we have some sort of even distribution and we
can say something about each of the categories and have it to be
as balanced as possible.

          Another possibility is to increase the number of
reviewers working on this.  The Committee has been dedicated to
at least one person from the Committee reviewing each proposal. 
And what we could do is unpair Committee member who are currently
working together and match them with a new member of the staff. 
We'd have to train and include more staff people.  Now, maybe
even hire new people with the proper expertise, because we need
scientific -- people with scientific background on one side and
ethics or IRB experience on the other side.  

          But we could increase the number of reviewers doing
these per week because we know they go slower than we originally
anticipated.

          So that's the second option.  Or, the Committee might
want to consider doing both of these to get done something
reasonable so that we can have -- so we can make conclusions
based on a reasonable number of proposals.

          Moving on, based on the 59 studies that we do have
completed, I can characterize those generally right now.  And we
don't wont to necessarily draw conclusions based on this, but I
want to show you what the numbers look like right now.

          We've been using an overall rating system of 1 to 5
where 1 is excellent, outstanding proposals, and 5 is ethically
unacceptable or very problematic and troubling.  Twenty-seven of
the 59 studies viewed as of March 13th received an overall
assessment of 1.  That's almost half.  Seventeen of the studies
were given an overall rating of 2; seven received a 3; five
received a 4; and three received 5's.  

          That means a total of eight out of 59 studies overall
gave reviewers the impression that there are real troubling
ethical concerns.  When we look back at each of these eight, each
of the eight involved greater than minimal risk to the research
subjects.

          In general, concerns over these proposals revolves
around the level of risk and the disclosure of this risk to the
patients -- I mean, to the research subjects.  So, still, these
eight studies and any more that come up that receive ratings of 4
or 5 will be reviewed again by the subcommittee to first confirm
this rating, to see what the core ethical concerns are, and then
decide what to do from there.

          Again, based on these 59 studies, some trends have been
emerging and a lot of them are consistent.  The percentages have
persisted.  If you look at the second handout, these percentages
are relatively constant with what I reported at last month's
meeting.  So we're finding -- with some confidence, we can say
that we're seeing some consistencies.   It's still too early to
draw conclusions based on these, I would say, but I want to talk
about some of these trends very generally.

          Some of the numbers that we see are percentages stand
alone as being interesting and some of the reviewers' comments --
we also asked each reviewer to comment on their answers, and some
are particularly poignant or consistent, and that's what I'm
going to report on.

          In terms of the scientific merit of these research
proposals, reviewers were unable to determine if 15 out of 59
studies were what we would say are worth doing.  And we want to
point out since IRB's and agencies are looking oftentimes at the
same materials that the committee reviewers and staff reviewers
have in hand and also have the same types of expertise, a
question that comes out of this is what sorts of outside
consulting do IRB's or agencies utilize in order to get at these
scientific questions for expertise that they don't themselves
possess.

          Another question of scientific merit that has come up
is sample size.  Whether the sample size that is proposed in
these studies is adequate to get at the research questions.  And
in approximately five studies, the sample size was small because
they knew that there aren't enough subjects to recruit into the
study, but this might jeopardize the results that would come out
of doing this research.  And on the other side, so many subjects
were proposed to be recruited into studies that reviewers felt
that it was too excessive.  Not all these people needed to be
included in the research to get at the answers.  So we're seeing
those kinds of problems on both sides.

          Regarding the selection of subjects, some preliminary
observations.  Five out of 59 studies specifically stipulated the
inclusion of economically disadvantaged research subjects in the
population.  And similarly, five out of 59 studies proposed that
students would also be included in the research.

          Of the questions that are related to these populations,
we could ask whether they're being overly persuaded by financial
compensation to participate in research.  So far, out of the
studies that do offer compensation to research subjects, 23 out
of 25 were deemed appropriate, so it may be that this question is
adequately addressed in the proposal, that it may not be a
concern.

          One number that stood out as particularly pointed by
itself, 35 out of 59 studies explicitly exclude pregnant women
from the research.

          Of nine studies that involve children who are old
enough to read and therefore thought old enough to give assent,
only five proposals include assent forms, so four did not include
assent forms in the materials that we received, so they could not
be reviewed.  If they did exist, they couldn't be reviewed.  And
the question is do they exist at all.

          Ten -- fourteen studies were found to include subjects
who have questionable capacity to give informed consent for
various reasons and out of 10 of these, these limitations to give
consent were not addressed at all or were not adequately
discussed.  And three out of 12 of such studies adequately
discuss how consent will be obtained in these cases; whether
proxy consent will be utilized.

          Now, an interesting point with the discussion of the
balance of risk to benefits in the research proposal document as
opposed to the consent forms.  In approximately half, 17 out of
35 of research proposals, the balance of risk to benefits was
partially or inadequately addressed.  However, looking at risks
individually, 41 out of 50, they were adequately addressed.  And
looking at the potential benefits, 35 out of 46 proposals discuss
these adequately.  So, somewhere when they're discussed together,
it seems not to be as complete.

          And then, finally, in the evaluation of consent forms,
which is a separate section of our coding form, reviewers felt
the reading level, 31 out of 59 consent forms, was appropriate. 
And based on the reviewers' comments, there seems to be a
fundamental conflict between including just the bare -- making it
very readable and therefore not including enough information
about risks and potential benefits and other information that
would be relevant to the subject.

          And on the other side, in putting too much detail,
telling everything possible.  But then it's too technical and
very difficult to read and understand and would also be
intimidating.

          Also, a number of the consent forms were very lengthy,
which would also decrease readability.  And in several cases,
there are also language barriers and ethnic specific barriers
that may have been a problem in certain environments, in certain
populations.

          Something I pointed out at the last meeting and seems
to be consistent is the problem of the use of boilerplate or
standard language on consent forms, literally in small print, on
a smaller font.  Some of the most important information is
included on consent forms such as alternatives to participation,
cost to the subject, confidentiality and that participation is
voluntary, and these look like -- reviewers commented that these
look like they could easily be overlooked and not noticed by
subjects.

          In 23 out of 54 consent forms, reviewers were concerned
that risks and burdens were not adequately addressed.  Ten
studies were identified as involving potential social risks.  And
the consent forms for these 10 studies, only one of them
discussed that risk.          In 13 out of 56 studies potential
benefits to the subject are not adequately addressed and only 18
out of 40 adequately discusses the balance of the risk to
potential benefits in the consent forms.

          Those are, in a nutshell, some of the major -- most
important trends we see emerging that may now lead into what
sorts of questions the Committee really wants addressed by the
research proposal review project.

          And this is another thing. I want to encourage the
Committee to discuss today or to keep comments coming in to us
about what types of questions you need these analyses to address
in order to be able to draw conclusions and make recommendations. 
We're at the point where we need to go beyond simply calculating
the percentages and looking at reviewers' comments and deciding
how they're going to fit together and what the core concerns are
or what issues does the Committee want to place priority on.

          So, I know Jay wants to --

          CHAIRMAN FADEN:  Could we do this?  I know Jay wants to
-- in retrospect, I'm sort of sorry that we didn't stop after
your initial discussion of the fact that we're behind schedule,
and address that issue before we got into the suggested findings. 


          If Jay would not mind and if you all would not mind, we
can return to that and to the issue of how we're going to get
focused.  I know even these preliminary findings are very
intriguing.  We might want to pursue them and discuss them. 
Maybe we could do that after we hear from Jay.  And they're sort
of all of a piece, if that's okay, and take 10 minutes or five
minutes to concentrate on what do we want to do about the fact
that we are behind schedule in completing these reviews.  

          On the one hand I think it's clear from what Sara's
already suggested to us that the information we're gleaning from
these reviews is potentially of great importance and we are
learning from these reviews.  And we would like to get this
project completed so that we can have a high rate of confidence
in what we're seeing.

          On the other hand, we're having problems getting this
done at the pace that we would like to get it done and that's a
human factor issue entirely.  So there are two proposals that
Sara briefly went over that have emerged in discussions by the
staff and subcommittee and they're not mutually exclusive.

          One is -- and we don't have the table for the non-
radiation research, but in a few cases, they are as well -- the
potential number of studies that could be evaluated per cell is
greater than five.  So one proposal that's out there is to say
let's concentrate first on making sure that we have five projects
reviewed in each cell.  

          If there are, for example, four left to do in that cell
and we already have four, randomly select one to make five.  And
then if we can get five in each cell and we still have time, we
would look at the remaining two in that cell or whatever it
turned out to be.  If not, we just won't look at them.  We just
will say, okay, it is now -- whatever.  

          How many projects would that save us, Sara?

          MS. CHANDROS:  Twenty studies.  That would eliminate 20
from the sample.

          CHAIRMAN FADEN:  For radiation or non-radiation?

          MS. CHANDROS:  Just radiation.

          CHAIRMAN FADEN:  And then the non-radiation, what would
we guess?

          MS. CHANDROS:  Possibly a similar number.

          CHAIRMAN FADEN:  So instead of having a total of --
what was our goal originally?  How many radiation studies did we
want to review?

          MS. CHANDROS:  We have --

          CHAIRMAN FADEN:  The total?

          MS. CHANDROS:  There's now about a total of -- I think
it's --

          CHAIRMAN FADEN:  107?

          MS. CHANDROS:  Yes.

          CHAIRMAN FADEN:  Okay.  The total.  So instead of
reviewing 107, we would review -- what is 107 minus 20?

          (Laughter.)

          MS. CHANDROS:  87.

          CHAIRMAN FADEN:  Thank you.  We would review 87 instead
of 107 radiation ones.  And if we pulled it off, we would go
ahead for the whole 107, but if not we would randomly pull the
ones that we did.  And we'd have 87 in the pool as opposed to
107.  And in the non-radiation, what?

          MS. CHANDROS:  It would be about 15 in the non-
radiation.

          CHAIRMAN FADEN:  So what would the sample size go? 
From what to what?

          MS. CHANDROS:  We have 48 or 50.  About 35-40.

          CHAIRMAN FADEN:  I'm sorry.  How much was the original?

          MS. GELLER:  The total was about 145 radiation.

          CHAIRMAN FADEN:  No, no.  In the non-radiation.

          MS. CHANDROS:  Non-radiation?  It's been 50 and 60.

          CHAIRMAN FADEN:  We don't know exactly?

          MS. CHANDROS:  Well, it may be as low as 48.  We've had
to pull a lot of studies --

          CHAIRMAN FADEN:  48 minus 15 would be the worst case
scenario.

          MS. CHANDROS:  Under 35 -- 33.

          CHAIRMAN FADEN:  33.  So we would have 87 radiation and
33 non-radiation?

          MS. CHANDROS:  Right.

          CHAIRMAN FADEN:  What would you say?  That's too low on
the non-radiation side.  We'll just take the radiation side down
by 20.  Twenty would help.

          I mean, if we could eliminate 20 reviews, that's a lot. 
So that's one proposal that we should discuss.  

          And the other one is right now we have paired,
sometimes paired Committee reviewers and that turns out to be
inefficient because if the position we want to take is that every
project has to be looked at by at least one Committee member, we
could decouple some Committee member pairs, assign you, if you
are now currently assigned with a fellow Committee member, and
team you with a staff member.  And that would allow the Committee
to look at more.

          So, this one, the second one, everybody seems to think
is fine.  Nobody -- I'm looking for body language.  Nobody has
any trouble with that one.  So the second one goes.  I don't know
how much that will save us.  I mean, how much it will save us
from the perspective of Committee members having to look 

at -- 

          MS. CHANDROS:  That would give us about six extra
reviews per week, based on what people said that they originally
could do.

          CHAIRMAN FADEN:  It's not going to solve the problem by
itself probably, or maybe. We don't know.  It depends on how
quickly it goes.  But we're all agreed that that one is okay?

          Okay.  So, that one's all right.  So now we're into the
other proposal, which is do we want to lower our radiation
sample.  The non-radiation one may be too low, but for the
radiation one, are we willing to say we will shoot for five in
each cell and max out at five rather than go up to ten in each?

          Duncan?

          DR. THOMAS:  I really can't answer this without knowing
the timetable and what its impact on the timetable is.  My big
concern is getting a draft that we can react to, a substantive
draft as opposed to just tabulations, that we can react to at our
next meeting.  Because without that, we're not going to be in a
position to finalize it at the May meeting.

          CHAIRMAN FADEN:  Right.

          DR. THOMAS:  Now the subtext of this is if we're still
doing reviews up to May 10th or whatever that date is, and at
that late date we're trying to finalize the text and we learn new
things from ongoing reviews, that's, I think, quite unacceptable. 
We have to decide that the data collection is finished before the
report is finished.

          CHAIRMAN FADEN:  I agree.  I mean, -- so let's just do
this out loud together, because I don't think it's real
complicated.

          On the one hand, Sara has indicated that it looks like,
at least so far, based on 20-some last time and based on 59 this
time, we're not finding any differences, but you never can tell
when something could happen.  So, if we were to -- if the draft
that we will have by the April meeting would not be based on all
the reviews.  That would be unrealistic.  But if we closed out
reviews by the end of April, that would give us four more -- how
many more weeks?

          We could have a draft but it would be based on however
many are done for April.

          How many more weeks are there?

          MS. CHANDROS:  Six. 

          CHAIRMAN FADEN:  Six more weeks. So if we reviewed for
six more weeks, if we go with the original end, how many would we
have to do a week?  And if we threw out 20 studies, -- Jeff's
sitting there with his calculator.

          How are we doing?

          DR. SUGARMAN:  Six weeks; correct?

          CHAIRMAN FADEN:  Six weeks.

          DR. OLEINICK:  It's impractical, though, to think about
doing reviews the week of the Committee meeting because we have
so much other reading and --

          CHAIRMAN FADEN:  All right.  So we'll say five more
weeks.  So we'll say it's five functional weeks.  

          How many are left, Sara, to do overall?  If we go with
the original end and then we'll knock 20 out.

          DR. MACKLIN:  And the original end goal is what?

          CHAIRMAN FADEN:  Take the 48 figure for the non-
control.

          Jeff, it's 48 plus 107.

          MS. GELLER:  155.

          CHAIRMAN FADEN:  155.  Okay.  We'll just say 155.  So
155 divided by 5 is 31 a week.

          MS. CHANDROS:  No, no.  155 is the total.  Minus 59.

          CHAIRMAN FADEN:  Minus 59.  Excuse me.  155 minus 59.

          MS. CHANDROS:  So 94 is the --

          CHAIRMAN FADEN:  94 divided by 5.  19 a week.  We would
have to plug out 19 a week if we are to do -- and if we subtract
20 from that --

          DR. MACKLIN:  How many have we been doing a week just
to get a comparison?

          MS. CHANDROS:  It's varied from week to week.

          MS. GELLER:  The original plan was to do 20 a week.

          MS. CHANDROS:  20 to 25, but we haven't achieved that.

          DR. MACKLIN:  There are two factors for being behind. 
One is that we started five or six weeks after the projected
start date and the other, I guess, it's been a little bit slower.

          CHAIRMAN FADEN:  I'm sorry we didn't do this
calculation beforehand, but basically, it looks like if we don't
reduce the sample size, we have to do 19 a week if we're going to
finish these all out by the end of April.  And if we took out the
20, we would have to do 16 a week.

          DR. KATZ:  But you have to leave the slippage in the
assignments because in addition to everything else in the next
four weeks we have to read back chapters.

          CHAIRMAN FADEN:  That's exactly right.

          DR. KATZ:  And all other -- and think about things. 
And I'm sure, speaking for myself, only speaking for myself, but
I'm sure probably for some of the other Committee members, too,
we have other kinds of obligations.  And in a sense, the final
Board draft has to take some precedence.

          CHAIRMAN FADEN:  No.  Like for this.  I realize that. 
So the notion is if we drop by three a week -- that may not seem
much, but obviously I'm advocating doing this because I think
there's a practical -- there is no magic to this.  If you're
drawing inferences based on 107 projects or 87 projects, I'm not
sure that it matter a whole hell of a lot.  Right?  We're at
still a fair number of projects that we're looking at in an
unusual and unprecedented fashion.  So if we can pull out and go
three fewer a week, let's do three fewer a week.

          That's still 16 per week.  That means that everybody
here, if everybody were to pull their weight, would have to do
one per week and a few of us would have to do several a week in
order to get the 16 done, now that we're decoupling Committee
member pairs.

          So it would mean that we're all here obligated to do at
least one a week for the next five weeks in this collective
fashion and we can pull off something I think worth reporting on.

          DR. OLEINICK:  May I just make a comment from my own
experience?  The first few protocols that arrived, the pack of
material was like such.  I've discussed this already with Sara. 
There was just a huge amount.  And much of it was redundant.  But
it took a great deal of time to go through and find out that it
was redundant. Don't know -- even though it looks like it's the
same, it's not necessarily the same.

          It has gotten better in the more recent ones, so I
would encourage you please to make sure that at least we have a
proposal.  One package, as you know, came without a proposal.  

          CHAIRMAN FADEN:  Some came with two or three.

          DR. OLEINICK:  And some came with two or three.  But
that saves the Committee and whoever is reviewing it, the
Committee or staff member, a great deal of time.  And I think --
you know, there are occasions where I could have done another
review in the time that it took just to sort out stuff.

          DR. MACKLIN:  Along those lines, another thing that
takes a lot of time -- I mean, Sara has been doing a wonderful
job, so this is not my complaint or I think anybody's complaint,
and it is better after we made our initial complaints.  There are
still things that take too much time and make for a great deal of
difficulty in sorting out the materials.  And those are projects
that we get that are either multi-center or program project
grants.  Because with the multi-center one, either we end up
using more coding forms and doing one coding form for each IRB
submission, which is really two different protocols in a sense. 
I mean, the proposal is the same, but the IRB's --

          CHAIRMAN FADEN:  We should just pick one.

          DR. MACKLIN:  So I think we should pick one, if you get
ones with several centers, or else what we've been doing is
checking.  I mean, those of us doing the coding forms have said,
all right, the first column is --

          CHAIRMAN FADEN:  Petition A and -- I think you're
right.  We'll just pick one when we got one of those.

          DR. MACKLIN:  So even if you got more, I suggest you
just wipe one out.  The other similar or analogous problem is
with the program project grant where the protocol is a huge
protocol that may have many substudies.  Then you've got the
substudies, all of which are being done by different people, and
their consent form, their level of consent form is different. 
So, I mean, that, too.  It's like having five different proposals
when we look at things like the IRB application.

          So unless we are interested in covering that kind of
material and reporting on it, which I don't think we are -- I
mean, we'll have enough information about inter-institutional
differences.  I suggest here, too, it would just simplify it,
because both reading it and then deciding with a co-review, what
should we do about this, should we do all of them, should we do
some of them, should we just use this one as the model -- takes a
lot of time.

          MS. CHANDROS:  As you said, we've been trying to do
that and we'll continue to pull those out.  In some cases with
the multi-centered projects, deliberately we want to review two
side by side.  I think each of those counts as an individual
proposal.

          CHAIRMAN FADEN:  As long as they count individually we
don't care because that's one of our numbers. If they get counted
as one, we don't want to do it.  That's basically what's going to
happen.

          DR. MACKLIN:  That has not been the process of
individuation that I've seen so far.

          CHAIRMAN FADEN:  So we're now into a thing where it's
one study per review.  And if it turns out that a thing generates
two separate studies, send it to a different group so that people
can get on it.  It's a huge job for Sara and it's overwhelming. 
We're trying to do the best we can, but at this point we really -
- every piece of paper we don't get is like 10 minutes time saved
trying to figure out what piece of paper.  And that's
conservative.  So, efficiency demands it.

          MS. GELLER:  I know that this alters our random -- or
efforts at random election, but is there any reason to consider
consciously deleting from now on, if we're going to pick some in
each cell, the ones that are program project grants?

          DR. MACKLIN:  No.  I thought the suggestion here was to
pull something out of the program project grants rather than look
at the whole thing.  That makes it much more complex.  Just pull
one item out rather than eliminate the whole thing.  Pull out one
grant element.

          CHAIRMAN FADEN:  I think if we're going to pare down,
Gail, we should only do it by randomly collating.  We've got four
left in a cell which is randomly selected.  

          Also, I think on the comparison one, we think the
number is 48 for the non-radiation.  We might, if it's all right
with the Committee, and maybe we could just run it by Duncan just
to make sure it's okay.  If there is a case where there's like 10
in one cell and we don't have the table in front of us and we
could go to six in that cell, we could get it down to maybe 40
comparison ones.  That would probably be all right.  But even
eliminating eight of the comparison ones would make life a little
easier.

          So if it's all right with the Committee, could we pare
it down to 40 comparison ones and 80 -- whatever it turns out to
be, so it's sort of still preserving something like a two to one
ratio.  Eight-seven radiation ones and 40 non-radiation is enough
to give you a feel.  And we'll just look at the cells from the
non-radiation ones.  That will take the number down to maybe 15.1
a week or something and save us a little bit.

          Well, it will take us down to less than 15 a week. 
Every one we can do and still feel like we have confidence in
being able to say something. Plus, we have -- Jay's going to
report on his own analysis on these same projects and we'll have
a rich base.

          Ruth?

          DR. MACKLIN:  There's one other methodological point
and I want to hear what Duncan says about this.

          When I saw the preliminary assessments and the figures
-- oh, by the way, let me just preface by saying that the least
meaningful thing we're doing with these is giving the overall
rating.  

          There are many of this number, of this final number. 
And the reason I think it's the least meaningful is sometimes it
may get a lower rating because the consent form and process are
miserable but the research is fine.

          In other cases it may get a low rating because it's a
risky protocol and the ratio, the risk/benefit ratio is not
favorable.  And those are comparing two very different things.

          CHAIRMAN FADEN:  Well, we will obviously pull out the
eight or 10 or 15 that fall into that category.

          DR. MACKLIN:  Right.  I mean, so the reasons matter
more than the numbers but this -- actually, that was just
prefacing my observation here.

          I was surprised to see so many out of the total that
received an overall assessment of one, since among the ones that
I've reviewed, which is nowhere near the number that Jay has, but
it's somewhere in the vicinity of 20, I think, only two were done
with my co-reviewer.

          And I should add that I'm not the one pulling them
down.

          (Laughter.)

          In at least as many cases my co-reviewer has proposed a
lower number.

          CHAIRMAN FADEN:  I think what we should do is clearly
emphasize --

          DR. MACKLIN:  So we need now to mix up the pairs,
because I've done quite a number with three other Committee
members.  

          And now I think we have to separate those and fix it up
a little bit. And I'm wondering if it destroys things or helps
things to do it deliberately.  In other words, if you could look
at the ones done where you've got the guys who said one, and pair
them up with the guys who had more of the lower ratings, would
that help as a matter of methodology and statistical accuracy for
you to rate a reliability --

          CHAIRMAN FADEN:  We're not doing that.  I think more
than that it's important for us to realize that the 1's and 2's
should be smushed.  That there's really -- these are global
impressions.  It would be very troubling to me if one person's 1
was another person's 5.  But if one person's 1 is another
person's 2, I really don't care.  I mean, that's sort of my view
about this.

          If one person's 4 is another person's 5, you know, big
deal.  The notion is are they more or less okay or are they more
or less a problem.  And I think that's how we'll need to report
this.  I think that's how we'll need to present it.  And we
probably should take a look to see if there is any, you know,
real serious problems.

          We hope that the pairs would work that out. If indeed
you thought something should get a 1 and your colleague thought
it should get a 4, that that would precipitate -- you know.

          DR. MACKLIN:  But that would lead to another review.

          CHAIRMAN FADEN:  Right.  That's what I'm saying. 
That's our mechanism.  That if you had a disagreement that broad,
our system was such that you were supposed to then take it back
to the subcommittee and say, look, we really disagree about this.

          DR. KATZ:  Has that occurred yet?

          CHAIRMAN FADEN:  Has that occurred yet?

          MS. GELLER:  Actually, in my experience, I gave a
proposal a 2 and my co-reviewer gave it a 5, but I was completely
educated in discussing --

          CHAIRMAN FADEN:  That's different.

          MS. GELLER:  That's a different case.

          CHAIRMAN FADEN:  I think that's a different matter.

          MS. GELLER:  Right.

          CHAIRMAN FADEN:  I mean, after you've discussed it, if
you still disagree --

          MS. GELLER:  Right.

          CHAIRMAN FADEN:  So the issue is have we had any
instances.

          MS. CHANDROS:  There's one study that remains to be re-
reviewed.

          CHAIRMAN FADEN:  Okay.  So basically, if we're having
disagreements, I think that that was the internal check.  So if
people are pulling it down a little bit or it's, gee, I didn't
realize that was so risky.  This is not my technical area.  Or I
didn't realize that here was an instance in which you needed
assent.  I didn't know about assent from children under 7.

          That is mutual education and that's what would go on an
IRB and that's fine.  Okay?  Obviously, -- you know.

          So I think that that's how we should be thinking about
it.  I would hate for us to come out there and say, you know, 20
percent or 30 percent got A's and then a bunch got D's. I think
when we report this out, it's the ones that -- might take a look
at the 3's maybe to get a sense of it, but the 1's and 2's.  The
4's and 5's we're particularly looking at to make sure that a
larger group of people agreed that these are seriously
problematic studies.  And then the 1's or 2's I would report out
as no major problems.  Forty percent or 50 percent of the
projects that the Committee looked at, the Committee saw no major
problems and they seemed to be ethically acceptable and no major
problems.

          Lois?

          MS. NORRIS:  Are you finding on the overall assessment
that most of the downgrading is being explained under comments?

          MS. CHANDROS:  Yes.

          MS. NORRIS:  Okay.

          MS. CHANDROS:  People have been pretty good about
talking about what the major concerns are and what caused them. 
And mostly, like I said, it was either disclosure of risk, which
has to do with the consent process, or the actual risk in the
design of the study, which has to do with the science of the
study.  So it has been both, as Ruth pointed out.

          CHAIRMAN FADEN:  Duncan, and then I wonder if we could
go to Jay's report.

          DR. THOMAS:  Yes. I'm all for scrambling the review
teams for just the reason you described. Unfortunately, we've
lost an opportunity to do a proper inter-variability study.  In
part because it was my impression that we were each of us going
to be sending back our original independent reviews first as well
as consensus.  Having lost that, it's difficult now to design a
proper randomization scheme, setting aside the difficulties of --
you know, just the fact that we have to pair a Committee member
with a staff member, ethics systems assignments and so on. 

          So we can't do it properly at this point but it still
should be subject to some sort of analysis when we're finished.

          CHAIRMAN FADEN:  That was an intentional decision.

          DR. THOMAS:  I had forgotten that.

          CHAIRMAN FADEN:  We'd given up on trying to do that
that way because there were a complex of logistic and another
sort of reasons.

          Okay.  If there's silence it's because we're all trying
to figure out where we're going to do those 1.2 reviews a week,
plus the chapters that we said we were going to get finished.

          MS. GELLER:  What about -- do we have sufficient staff? 


          CHAIRMAN FADEN:  Excuse me, Gail?

          MS. GELLER:  Do we have sufficient staff on the staff
side?

          CHAIRMAN FADEN:  We may have to hire some staff
consultants on the staff side.  And we would look for people with
IRB experience and also the matching.  So if Ruth's been coupled
with science types, we have to -- science and physician types, to
use her as an example on the Committee, we will be looking to
either find within the staff or to hire a staff consultant person
who has the right medical or science background to replace one of
you who fits that category but hopefully who has IRB experience,
as well.

          And we'll have to scramble.  But the Committee judgment
and staff is retained by the fact that every pair includes one
Committee member so that every project is looked at and evaluated
by a Committee member with a colleague who may be staff.  Who
from now on will be staff and in the past sometimes was staff and
sometimes was another Committee member.

          We should have thought about this in the beginning and
realized that there was not a good use of Committee resources to
couple Committee member with Committee member and attempt to do
these many reviews, given everything else we're asking of each
other and the short time frame.

          DR. THOMAS:  It's another thing you know for the next
Committee.

          CHAIRMAN FADEN:  Right.  Next time we do one of these
we'll know how to do this better.

          Jay?

          Do you mind if we just go to Jay's because I think --
then we can look at the substance issues the stuff suggested by
Sara and Jay's findings, perhaps, of a piece.  So, --

          DR. KATZ:  Look.  As a general comment, I really think
we are on top of it with respect to the evaluation of present
practices and its implication for the future.  I mean, before the
afternoon is over, we talk about it and figure out what we can do
about that.  Because in response to Duncan's question, it will be
late before this phase will be completed.

          With respect to my review, and I'll try to be as brief
as possible.  It may in part have to remain a private review by
one Committee member because, of course, it has shaped my
thinking about the pertinent implications for the future in light
of the work that I've done.  But I'm not sure whether I can
really complete it because I've already spent an inordinate
amount of time on doing what I've done.

          I've read 120-130 research protocols so far.  Fifty of
them, of which I want to briefly report to you, I've read two or
three times or more and formed some judgments about them.  

          Of course, with apologies to Duncan, on the next page I
did a statistical analysis.

          (Laughter.)

          Okay.  Fifty protocols. I identified 30 of them as
being in a certain sense trivial experiments, survey studies,
questionnaire studies, most minimal minuscule kind of risks or no
risks.  And we have 26 and 4.  Four raised some minor ethical
problems.  But since they were the kind of study about which one
could be quite forthcoming, everything seemed to be reasonably
all right.

          It may be a testimony to the fact -- to two facts.  One
is that investigators are more careful now because it has to go
through IRB review so they do their utmost to decrease the
physical risk issues.  And that's of course true throughout.  And
also, many of these studies are also tracer studies.  

          And it seems to me, I get the impression that with
respect to tracer studies, the radiation community has really
developed standards and safety standards that are very carefully
followed.  And therefore, we don't have to be that much concerned
about.

          Now, 20 studies to my mind created problems, except the
first four.  Four were very, very good.  These were risk studies. 
They were complex studies raising questions, quality of life
issues.  Raised questions about should one leave matters alone,
stay with standard treatment rather than becoming a participant
in a research protocol.  There were these kinds of studies which
I will eventually try to specify more.

          Four were very, very good.  Two particularly are
outstanding.  And I've never seen informed consent forms like
that.  That in a very complex kind of situation, the
investigators were really able to present in understandable
language risk, benefits, complications, alternatives.  I've never
seen anything like that before.

          Sixteen were problematic.  Six of them according to our
ratings I would approximately give a 2 or 3.  Five I would give a
4, and five I would give a 5.  

          So now my statistical analysis.

          (Laughter.)

          If you use a denominator of 50, 34 are problematic or
16 percent of them, a remarkable figure.  And problematic -- 2, 3
-- 12 percent; 4, 10 percent; 5, 10 percent.

          If you use the denominator of 20, which I would use as
my denominator --

          CHAIRMAN FADEN:  We discussed this, by the way.

          DR. KATZ:  We discussed this.  Yes.  Twenty percent are
very good; 30 percent are 2 and 3; and 50 percent are 4 and 5. 
I'm sure some of you will comment on my statistical analysis.

          Look.  Time is short.  I want to just give you a few
descriptions of what I've learned from reviewing these protocols
and I will try to be brief for the sake of time.

          Take one study.  It is a chemotherapy study that tried
to compare intensive versus milder treatment for Stage 4 low
grade follicular lymphomas.  The question was do milder
treatments work just as well as more aggressive kind of
treatments.  In the informed consent form, the risks, side
effects and discomforts arms of the -- it was a randomized study
-- for both arms of the research study were combined.  No
distinction were drawn between the milder one and the more
aggressive treatment.

          There was no discussion of the quality of life or even
no mention -- when I say no discussion, there was nothing there -
-  of the quality of life issues of one treatment research arm
compared to the other.

          There was no discussion of the medical discomforts
which the randomizations imposed on the subjects.  There was no
discussion about the question of alternative -- of conventional
treatments rather than participating in the experiment, even
though in the research protocol it was noted that conventional
treatments, some conventional treatments really had a very high
success rate, 60 to 80 percent in some instances.  And none of
this was mentioned.

          I could tell you more but I want to go on.

          CHAIRMAN FADEN:  Jay, just to give an insight, was that
one that you rated a 4 or a 5?  Do you recall?  Just to give us
some insight.

          DR. KATZ:  Either 4 or 5.  Yes.

          CHAIRMAN FADEN:  One was definitely a 4?

          DR. KATZ:  Or a 6.

          (Laughter.)

          One is a study is chemotherapy of cystomas.  And let me
only mention one thing about that.  In an earlier informed
consent form, it was mentioned -- and it used a very powerful
chemotherapeutic agent.  I'm trying to be careful and not
identify agents because of the confidentiality issues.  Highly
toxic agent which they were giving to a maximum kind of dose.  In
an earlier consent form it was noted that there was a 10 percent
mortality with that particular treatment.  It was ultimately left
out of the informed consent form altogether and just some general
mention of toxicity.

          And in that particular protocol, it was one of the
bigger ones that Sara sent us, there was one death report after
another included, though it didn't really fully explain where it
all came from.

          Another study, treatment of Hodgkin's disease, grade
122A, and children under the age of 18, a randomized clinical
study comparing low level radiation therapy versus low level
radiation therapy and an intensive chemotherapeutic agent.

          One of the chemotherapeutic agents causes -- has a 3 to
5 percent incidence of cancer within three to five years after
administration and there was again nothing mentioned about the
pluses and minuses of taking radiation alone versus radiation
plus intensive chemotherapy, including the fact that in general -
- and I have discussed it with three persons very knowledgeable
in the treatment of Hodgkin's disease and research of Hodgkin's
disease, they wouldn't use that one agent in their combination
chemotherapy because of its incidence of three to five percent of
causing leukemias.

          The general -- it was mentioned in the informed consent
form that, of course, that malignancies can occur as a result of
treatment, but nothing was said about this particular agent,
which generally was the culprit for these consequences.  Nothing
was said about ordinary treatment, which by and large for
children, as I understand it, whenever possible -- and it's not
always possible -- is radiation therapy.  They try to avoid
particularly with younger children.  Chemotherapy, the toxicities
involved, et cetera, none of this in the informed consent form.

          Let me just give you one more. Actually, that was a
frequent issue in various combinations and permutations.

          Talking about Phase 1 treatments, Phase 1 research --
I'm getting contaminated -- as if it were a Phase 2 or a Phase 3
treatment.  In one protocol, which was highlighted both in the
protocol and in the informed consent form as the frontline
treatment for advanced breast cancer it was never described in
the research protocol as research.  Always it was treatment,
treatment.  Much investigation was used for a very interesting
reasons because one of the drugs involved was investigational and
therefore the insurance company wouldn't pay for it, so they
wanted to make clear that the patient research subject would have
to pay for that particular medication.  That was the only mention
of investigation in the informed consent form.

          Otherwise, it was a toxicity study.  They were using a
new combination of chemotherapeutic agents where it was known
that using them in combination increased myelotoxicity and they
wanted to find out what the MPD was with respect to this
combination.   That was the purpose of the study. 

          It was described in the protocol -- I mean, in the
informed consent form, as being treatment, even though they said
in the protocol, this is not treatment.  This is going to
establish toxicity.  Once we've done that, we will do a Phase 2
study to determine efficacy.

          Two of the commentators, probably members of the IRB,
said, you know, there's nothing confusing about this protocol
because this is not a Phase 2 study, it's a Phase 1 study.  The
methodology is wrong because it's a homogenation of Phase 1 and
Phase 2 issues.  And one of the investigators was concerned about
it, not only for scientific reasons, but for fairness to the
other investigators at the institution because they have been
instructed that they must clearly distinguish between Phase 1 and
Phase 2 studies.  And therefore, they felt this group of
researchers should also.

          Nothing was done about that.  And neither of the two
commentators who were concerned about the Phase 1/2 complication,
made any suggestion that the informed consent form had to be
changed to identify that issue.

          I could go on and tell you -- give you many more
examples, but I think this gives you a flavor of what my findings
were and what they are based on.

          CHAIRMAN FADEN:  We are open for questions and they can
go to Jay or Sara.

          DR. RUSSELL:  I wonder if most or all of the ones, the
five that fall into this general category of high risk treatment
for malignancies, is that where our big problem lies in general?

          DR. KATZ:  I would -- yes.  I think probably four or
five or maybe all five are within the area of malignancy.  And
there's some very interesting additional issues involved. 
Namely, how do researchers and IRB's deal with situations of
hopeless prognosis.  

          None of these I have now -- yes.  So that is a problem.

          DR. RUSSELL:  I don't think the numbers, whether they
change or not for the next 50 are going to make any difference to
the fundamental problem of the Committee on how to address this
set of issues.  And it seems to me a very specific set of issues
around the quality of life, the issues that relate to adding one
poison on top of another poison for these kinds of therapy.  And
I think from a philosophical and recommendation point of view, we
need to wrestle that one right, because the numbers, if they go
up or down, don't make any difference.  The problem that has been
identified is out there.

          DR. KATZ:  But what should we disclose to the subjects
of research in these kinds of situations.

          DR. RUSSELL:  Well, I think there's two issues.  One is
what should be arrayed for the IRB in the protocol to make
judgments regarding risks and benefits and so forth.  That's one
part.  And according to this evaluation, half of them don't make
the grade.     And then the other is how do the risks/benefits
issues get explicitly laid out in the consent forms.

          One of the things I see is, from past experience, is
that the issues of risks and benefits are woven through a
discussion.  There isn't a paragraph that says these are all the
risks and then these are the benefits, and then here's an
analysis of the equation.  That is usually not done.  It's woven
through.

          So, consciously making a risk/benefit analysis by way
of science takes a little intellectual work.

          DR. KATZ:  Yes.  You can't identify the threads because
it's so interwoven.

          DR. RUSSELL:  They're interwoven.

          DR. KATZ:  Yes.  And that's the problem.  And, by the
way, you raise another important issue that I've also paid some
attention to.

          The IRB's I think are not sufficiently informed by the
investigators about what the issues are and the IRB's seem to
accept that or not comment on it, by and large, and on the basis
of incomplete protocols make judgments about the acceptability of
the protocol.

          CHAIRMAN FADEN:  Henry and Ruth.

          DR. ROYAL:  I just wanted to say that I completely
agree with Jay's comment about the quality of life issues.  They
are extremely -- to me they're even more important when someone
has a limited life expectancy.  I mean, if you're going to live
six months, you'd like to know what those six months are going to
be like if you participate in the research or if you don't
participate in the research.  The protocols I've seen don't give
a very good description of what to expect.

          I think the problem with chemotherapy is that there is
evidence of the more intense the chemotherapy is, that it in fact
does help.  And that's sort of the dilemma that they're faced
with.

          When I say there's evidence, there have been some
successes and so that's the motivating force.  That even though
you know that it might be an uncomfortable experience for the
patient, it's possible that you might shift things around a
little bit and have more survivors, less morbidity long-term. 
One of the problems that I didn't like is not only don't they
describe the quality of life issues very well, but they also
don't give the patients any reasonable expectation of what the
benefits might be.

          Are we doing this intensive chemotherapy because we
think that there might be a chance of a cure?  If we think that
there might be a chance of a cure, what percentage are we talking
about?  Are we talking about a gain of 2 or 3 percent or are we
talking about a 50 percent chance of cure?  If we're talking
about prolonging life, are we talking about two or three months
or are we talking about year?  What's your expectation?

          I mean, I know that you can't answer it exactly but
what would be a reasonable expectation.  And maybe they're not
even talking about extending my life.  Maybe they're not talking
about a cure.  Maybe they're just talking about improving the
quality of my life.  But the benefit is really never explained in
any way that you could make an intelligent decision about whether
you should participate.

          CHAIRMAN FADEN:  Ruth?

          DR. MACKLIN:  Yes.  There are certain things we cannot
tell from this review about the IRB process.  And I suspect that
it's very, very involved and that in some cases -- I mean, Jay
just made the remark that the investigator isn't telling the IRB
about certain things.  I don't think we know whether one of three
things is happening.

          A, the investigator is telling either the IRB or a
primary reviewer because we don't have any evidence about what a
reviewer in the IRB who is assigned to review the protocol is
saying over and above what kind of pieces of paper we have.  So
we don't know whether the investigator is saying more orally, if
the investigator is present.

          B, if the investigator is saying something to the
primary reviewer who then conveys it.  Or C, even if these things
are said, the IRB is approving it anyway. So -- even with the
information.

          So, I mean, in a sense, we have to be agnostic about
that.

          Now, just as a piece of ancillary information, I was
struck, quite surprised to learn in a bio-ethics discussion group
over the Internet that a distinct minority of IRB's have as their
procedure that the investigator, the principal investigator, come
before the IRB.  I was struck by this since they do in my own,
and I know they do in others, come to present the protocol and
answer any questions.  

          And the overwhelming response among the people who
replied to this -- Jeff probably has seen the same thing -- was
that it takes too much time, wastes too much time.  Investigator
comes; runs off at the mouth.  Investigator comes and is
disdainful of the IRB members as being a bunch of dummies who
don't know anything about research.  

          And among the respondents of this -- it there was a
very small number.  I think two out of 20 or so said that the
investigator comes before the IRB.

          Now that's ancillary information to what we're having
but it tell me something.  And if it's so, it sort of may
explain.  I mean, they of course then go on to tell the primary
reviewer -- the process of primary and secondary reviewers.  But
that's only going to be as good as -- if the people who think
that too much time is wasted when the investigator comes to the
IRB, they may also think that too much time is wasted.

          So I think there may be a huge variability out there
and we don't know what to attribute.

          CHAIRMAN FADEN:  I think that's the core issue.  What
we know is that these are approved protocols that people have
been authorized to go ahead and do these studies based on the
description of risks and benefits and the consent forms that have
been approved.  It's remotely possible that some of them have
been revised, but basically they were approved and people were
given authority to go ahead and do this to people, enroll them in
these studies.

          It is a black box and we can all have inferences and
guesses based on our own experience as to why when things have
gone wrong.  And in these eight cases or 10 cases or however we
slice it, things apparently have gone wrong, why they went wrong.
          But we just had to be very clear that what we can say
is these are projects that have been approved by IRB's in the
format which we got them and we are concerned about these.  We
can all have educated guesses about why they ended up the way
they ended up and maybe even enough so that we can make
recommendation about how things might be improved.  But we do
have to be careful -- I think Ruth is right -- to say we can't
know for sure why they ended up.  And there may be different
reasons every time.

          Jay?

          DR. KATZ:  Well, I know one thing for sure -- a number
of things for sure.  I know for sure that the IRB are charged
with the responsibility.  And one of their primary
responsibilities is to review the informed consent form and to
approve the informed consent form.  On the basis of my review,
they're doing a lousy job in 50 percent of the cases.  This I can
document to my satisfaction.  That we know.

          We also know -- I also know that if after all our
majestic principle is principle one of the number code, then the
voluntary consent of the subject of research is absolutely
essential, that in the present day and age, that principle is not
being implemented.

          And I'll leave for this afternoon or next time, but I
hope we'll have some time this afternoon, to discuss what my
views are on where do we go from here in terms of future
recommendations.  But it's a very important issue.

          CHAIRMAN FADEN:  No.  I think that however we want to
slice the percentages, Jay, the point -- your point is well
taken.  What we have here are approved protocols.  That's the
power of this analysis.  They have been approved and people have
been authorized to go ahead and do this study with the consent
form that we have, unless we've been given bad information, and
with the risk/benefit balance as it's described. 

          So this is not -- and that's powerfully important
information.  These are approved projects and they are allowed to
go forward.  People are actually doing them.  And that's
different from other kinds of contexts where you're looking at
things in prospect.

          I wonder -- just real quickly.  I know we have a lot to
talk about.  The four that thought were very good, were any of
them complicated chemotherapy trials?

          DR. KATZ:  Yes.  One.

          CHAIRMAN FADEN:  See, I think it would be very nice to
put side by side to show to the world, look, it can be done well;
right?  It isn't being done well.  And in important instances. 
But it can be done.

          DR. KATZ:  I'd like to give you one of them and see
whether we can circulate it to the Committee.  I find it very
impressive if we can sort of keep it and do that.

          CHAIRMAN FADEN:  And that may give us insights into
recommendations, too, like here.  It can be done well.

          Yes?

          DR. RUSSELL:  How many of the inadequate consent forms
seem to you to result from this tension between readability and
explicit specificity of all the -- you know, there's endless
discussion on all -- and whether the argument comes down on the
readability and simplicity and reasonable brevity versus the
specificity and detailed exposition is going to determine whether
the consent form is looked on by an independent evaluator as
adequate or inadequate.

          How many of these seems to be a result of that in
particular?

          DR. KATZ:  I don't -- you see, I don't think so. And
I've thought and written just a little bit about it.  Most of the
consent forms are three or four pages and double spaced.  And the
one that are nine and 10 pages are the worst ones. But the
problem is, and that is that I would say that in defense of
IRB's, though they do it all so slavishly, they are constrained
by the federal regulation's requirement to go through A, B, C, D,
E, F criteria.  Even though I think many of them in my view don't
need to be mentioned or need to be mentioned only most briefly,
and the kind of issues I've identified, I think they can be
written in two or three sentences to give the person who signs it
an idea of what is at stake.

          So, I think a good informed consent form by deleting
lots of unnecessary information and including some necessary
information that would give the person an idea of what this is
all about would not make the informed consent forms longer.  But
let me in two minutes and then I'll shut up, or less than two
minutes, tell you an anecdote.

          Okay.  Last week I talked to a distinguished medical
research scientists and I gave him two hypotheticals based on my
review and said I want to ask you three questions.  Do you think
that -- one, do you think the following information should be
given to subjects of research.  And he said, yes, of course.  In
order for them to arrive at a considered judgment as to whether
to participate or not.  And I gave him the information and he
said of course, they need to know this.

          Two, do you think this information can be provided in
simple enough language.  The answer was yes.  The third question
was would you provide the subjects with this information. And he
said no.  And why not?  Because too many subjects might refuse
participation and it may take too long to accrue the requisite
number of subjects.

          Then I asked him another question.  Do you have any
experience with this happening when you've really informed the
subjects of research.  He was very thoughtful person and he was
quiet.  And he said, you know, Jay, I've never thought of it. 
I've never tried it.

          DR. OLEINICK:  Can I ask just one other question of
Jay?

          CHAIRMAN FADEN:  Yes.

          DR. OLEINICK:  Of the protocols that you reviewed that
you rated 4 or 5, I think you alluded to one and I'm just asking
you is the number larger than that, of a research project that,
even with the best consent form in the world, shouldn't be done? 
Do we have any of those?

          DR. KATZ:  I have a number of them.  I have a number of
them in the other 50 that I haven't gone over yet because, you
know, I've never had that experience of, in a relatively short
period of time, really seeing a mass of -- reading a mass of
protocols.  And some reason or other -- by the way, these are
consecutive.  I didn't make any selection on the basis of --
because they seemed to be more problematic than others.  The
first 50 in order of -- that I received them.     

          But I'm now in the second bunch, I'm getting more
protocols that deal with situations of hopeless prognosis where
the patient subjects are really very, very sick.  And I wondered,
after reading three or four of them, should these -- and these
are really heroic treatments that the patients are being exposed
to.  There's no mention in the application to the IRB the
question should we do this kind of research; should we leave them
alone.  There's surely no mention in the informed consent form
about the alternative of no treatment except, you know, it's
mentioned somewhere in passing, but in a meaningful kind of
fashion.

          Because one might wonder if the persons really knew
what is in store for them undergoing what the investigators had
in mind in the hope of finding -- I mean, these are well
intentioned people -- of finding a cure, then many of them -- a
number of them at least, maybe not many of them, but who knows
how many might say it's time to pass on.

          CHAIRMAN FADEN:  I have Henry and then I think maybe we
should take a break since this is break time.  But Henry, Gail
and Sue, and then we'll stop.

          Henry?

          DR. ROYAL:  Jay made all of the points much more
eloquently than I could.  Thank you.

          CHAIRMAN FADEN:  Gail?

          MS. GELLER:  I would like to add to the list of things
we don't know about the IRB's whether they've decided it's within
their purview to make some assessment of scientific merit.  And
it's relevant because I think in some cases where some of the
risk/benefit analyses are absent, it really may be -- and it's
particularly true perhaps in some of these very complicated
cancer treatment cases, it may really be because there's been
some decision that the study section will decide.  That it's just
not -- I mean, I have certainly experienced it in my own
institution this debate and I've certainly had discussion a lot
with you, Phil, where something that strikes you particularly is
the scientific merit issue.  And I know that there are some IRB's
that have decided that it's not within their purview.

          DR. RUSSELL:  And there are situations where there's no
other organization or system to lay it off on but not within the
purview of the IRB and there isn't any funding agency that picks
up that responsibility or there isn't an internal requirement
within the institution to do it.  You could envision the funding,
the private source, would have no oversight of the science.  If
the IRB doesn't pick it up, there's nobody else.  It will drop
right through the cracks.

          CHAIRMAN FADEN:  Sue?

          DR. LEDERER:  I have two brief questions that maybe
Sara and Gail could answer.  I wondered if there's any
distinction in the protocols which we have reviewed between
research involving healthy subjects and those involving sick
patients.  

          And my second question is you note that the level of
proposed payment is a concern. Is it a concern for the reviewers
or for the IRB's?  And secondly, is the absence of compensation
ever flagged as a concern?

          MS. CHANDROS:  I'm going to answer your second question
first.  When I've reported on those numbers, I think it was two
out of 25 studies raised concerns in our reviewers.  We don't
always know how the IRB deliberations went.  Sometimes we have
correspondence and minutes but that wasn't the crux of what we
asked for so we don't reliably know how they responded to the
compensation.

          The absence of funding?  I don't remember.  I haven't
really focused on it but I don't remember seeing that in any
cases, but it's something we can look for and reviewers might
want to, now that you've alerted it.  Reviewers can keep that in
mind also.

          Regarding the distinction between healthy patients or
sick, we did the therapeutic diagnostic, that breakdown, but we
know that doesn't always reliably -- therapeutic studies involves
at least some sick individuals we would think.  Diagnostic
studies could be either.

          The proposals themselves, I think those distinctions
are made when the subject population are reported.  We have a
tally.  If you look at the percentages in the second handout I
gave out, there's a tally that says how many studies explicitly
state whether healthy individuals, whether hospitalized
individuals are included.  So we do have figures on those.

          CHAIRMAN FADEN:  We haven't broken it out yet.

          MS. GELLER:  And we certainly have the capability to do
that if that's important.

          CHAIRMAN FADEN:  This is the only source of information
we have about research with healthy subjects.

          DR. RUSSELL:  But the small numbers, have we identified
any number of high risk normal subject protocols?

          CHAIRMAN FADEN:  We haven't looked for it yet. What we
need to do at this point is we need to very quickly take a look
and see how many studies we have that involve normal persons.

          DR. RUSSELL:  Not a lot of them.  And I don't think --

          DR. KATZ: I haven't found any.  I've been looking for
that in the 120 I've looked at.

          DR. RUSSELL:  There aren't an awful lot.

          DR. KATZ:  Yes.  I haven't found a lot.

          CHAIRMAN FADEN:  It may be that we'll do 100 of them
and there won't be a study that has maybe a few normal controls,
quote/unquote, but we may not have any.

          DR. OLEINICK:  We're picking oncology and cardiology.

          CHAIRMAN FADEN:  Well, not in the other ones we aren't. 
In this one we're just taking it --

          DR. OLEINICK:  Yes.  That's right.

          DR. KATZ:  We have a number of normal volunteers.

          CHAIRMAN FADEN:  Volunteers.  Right.  So we have to
pull those out and see.

          DR. RUSSELL:  But they're mostly in the small, in the -
-

          DR. MACKLIN:  But Ruth is right.  I think that the ones
that have normal controls, there are some that have normal
controls that do involve, at least I can recall one or two, that
are risks that are more than minimal --

          CHAIRMAN FADEN:  To the healthy person.

          DR. MACKLIN:  -- to the healthy controls, the normal
controls within a study that is comparing the healthy controls to
the patients.

          CHAIRMAN FADEN:  And the epi studies may well have
populations that are not hospitalized or not ill.  But whether we
have a study where it's only being done on healthy persons that
involves medical like interventions, I don't know.  We haven't
seen vaccine trials or anything like that.

          DR. LEDERER:  Well, the studies stipulate students or
specify students and they presumably --

          CHAIRMAN FADEN:  So we need to focus -- that's the
message.  We need to pull that out and take a look and see
whether we've got -- because again, looking at our history, we
know that there are reasons to think that things may have been
different in the past.  So the question is are things any
different.

          MS. GELLER:  I would like to be a little bit clearer
about Sue's point about cost.  Are you interested in
compensation?  Not to the cost to the subject?

          DR. LEDERER:  No.  I'm interested in compensation.

          CHAIRMAN FADEN:  So the issue is is there any one of us
who said, "They should have paid somebody?"

          DR. LEDERER:  Right.  

          CHAIRMAN FADEN:  It's like the flip over.  How come
they're not paying this person to do this as opposed to -- is
that right, Sue?  Rather than -- as opposed to the issue of
they're paying them too much?

          DR. LEDERER:  Right.

          CHAIRMAN FADEN:  There's kind of a flip over as to
that's a huge imposition and should they at least be paid for
their child care or something.

          DR. LEDERER:  Well, because it suggests that if they're
getting a high rate of compliance, I mean, why are people
agreeing.

          MS. CHANDROS:  Actually, there is one study where the
issue, the cost to the patient and the compensation kind of
overlap.  One reviewer noted that the subject was required to pay
for the experimental medications, they or their insurance.  So
that was the flip side. 

          But yes. Not only are they not being paid but they're
being asked to pay.  And it's particularly problematic, I think,
in these very complicated high risk cancer treatment protocols
where cost becomes a part of the risk/benefit calculus.  I think
greater prominence if you have four months left to live and
you're asked to spend everything you have.

          CHAIRMAN FADEN:  What has happened clearly is the group
- we need a break.  We're breaking down into too many two-way
conversations.

          Thank you all very much.  This is clearly important and
we've made a dent in it.

          (Whereupon, a recess was taken.)

          CHAIRMAN FADEN:  Do we have any -- yes.  We have some
Committee members, but not many.  I wasn't paying attention in
terms of the agenda.  We have to return to the backward looking
recommendations or the recommendations to the past, but I think
this experience, the discussion this morning, has us all thinking
about the future and the current situation.  And I'm inclined to
think that maybe we should spend some time on contemporary,
future oriented recommendations since we're all thinking that way
and then just make sure that we return to the discussion about
situation 1, 2, 3 and 4 that we were having yesterday after
lunch.    

          I just think people's minds, at least my own mind right
now is so filled with thoughts raised by Sara's and Gail's
presentation and by Jay's presentation especially that I kind of
think it's weird.  So does everybody -- that we focus on the
future ones for right now?

          Again, remembering that these are initial passes, quick
cuts, ideas being thrown out and mostly to stimulate discussion.

          What did I do with my copy of it?  Here we go.

          It's something called Final Chapter: Coming to terms
with the past; looking ahead to the future.  And if we could just
-- it starts on page 21 and the format is there are headings and
there's a little rationale and then the draft Committee
recommendation is in bold. 

          I think the purpose now is not to nitpick about
language but basically is this general thrust appropriate.  Is
this an area about which we want to make a recommendation and is
this framing of the recommendation going in the correct
direction.  

          And the headings -- we start with recommendations with
respect to openness.  Those recommendations don't flow directly
from the discussion this morning.  

          I'm wondering if we should skip ahead while we're
thinking and go to page 27 and then go back to the openness
recommendation, because we're all thinking about the conduct of
research, based on the discussion this morning, a discussion of
what people would propose, remembering that this is just a very
rough, very rough cut and we don't have our findings findings but
we've heard some preliminary findings now from the contemporary
projects.

          All right. So we're on page 27.  I don't know how to do
this except by sort of marching through.  March through some of
these and then if people want to stop at some point and say this
is okay.  But what I really think needs to be here is something
more along the lines of this or this is inadequate.  

          We can start to discuss ideas that haven't been written
down and see if there's a Committee sense, a Committee feeling
that that idea is worth pursuing and then we'll try to get
written language either from the Committee member who proposes it
or from the staff.

          So, we're on page 27.  The first area -- this is under
the heading Preliminary Recommendations for the Prospective
Review and Conduct of Human Subject Research, so this is right on
the point of this morning's discussion.

          And the first recommendation that's proposed here
addresses the question of -- addresses the importance of finding
mechanisms to more clearly distinguish research from treatment in
the process of soliciting consent from potential subjects.

          The specific proposal is kind of ironic because we
heard from Sara this morning concerning the tiny boilerplate. 
The argument here is the opposite, massive overplate boilerplate
that would be required which is very plainly signalled to anybody
looking at it this is not like the consent form you sign for
surgery.  This is not a consent form you sign for admission to
the hospital.  This is something different.  

          This is a consent form for -- and then based on the
subject interview study, whether the term should be medical
research, medical experiment or clinical study is something that
is in itself worth debating.  And we could wait for the results
of the subject interview study to get clear on what we want to
say, but we already know that if you call it a clinical -- we
already suspect, based on the subject interview study, that if
you call it a clinical investigation you will get a different
reaction from people than if you call it a medical experiment.

          And so we have to be thinking about that and there may
be recommendations about educating about the public about what
these terms mean and so on.  This is a recommendation that's very
particular or boilerplate.  It would be for the opposite purpose
of standardizing the message to potential subjects about whether
this is research or this is treatment.

          Henry?

          DR. ROYAL:  In the footnote, it says that you want to
clearly communicate that the primary intent is research to
advance medical knowledge and not to enhance the welfare of a
particular patient.

          I think that, yes, that's the word we want to choose. 
But the other thing that I was hearing about the subject
interview study was the amount of risk was also varied, depending
on what word you used.  And it's not clear when we select the
word, how that factor is going to fit in.  Is it better to pick a
word that makes it sound more risky or is it better to pick a
word that makes it sound less risky?

          CHAIRMAN FADEN:  I don't know.  I mean, I think we have
to think about that.  I don't know that we can prepare that right
now.  Or maybe part of it is we need a massive educational
campaign that goes out to people in some way to educate people
that these terms don't really mean anything differently.  I don't
know, but that's a very good point.  What we do know is that it
doesn't all mean the same thing.

          DR. OLEINICK:  But maybe we should be using more than
one term.  That it should be saying:  "This is a research
project.  An experiment is described here which will involve a
clinical investigation," or some such as that, just so that
whatever term they use, it's there.

          CHAIRMAN FADEN:  Another recommendation might be get
rid of all these terms.  Call them research projects and don't
let people use words like study, which tend to be more
reassuring, or clinical investigation.  That sounds more
reassuring.  And just emphasize that the key issue is to
communicate to people clearly what's in that footnote.  That this
is primarily being done to  address the scientific question and
not to treat you.  And that if there's a potential benefit to you
that might flow from that -- but rather than pick the right term,
simply say don't use any of them unless we have a standardized
thing that everything is called a research project.

          DR. ROYAL:  I'm wondering if in that standardized
heading that says "This is a research project," whether it should
go on to say that has minimal risk, substantial risk, right in
the title.

          CHAIRMAN FADEN:  In the big bold stuff at the front?

          DR. ROYAL:  Yes. So that it clearly communicates that
it's research and it really gives people some idea right up front
whether we're talking about something trivial or something that
might have significant risk to it.

          CHAIRMAN FADEN:  It's worth considering.  But is there
some general sense of agreement that there should be -- that this
recommendation is worth pursuing with respect to distinguishing
research from treatment in some standardized way that's bold,
that makes the form look different and doesn't have obfuscating -
- this is a clinical investigation study; welcome. You've been
chosen.  Sort of like when you get -- I keep thinking about the
Sweepstakes.  I haven't been fortunate to be selected by somebody
for a one in 10 million chance of getting a condo or some swamp -
-

          (Laughter.)

          So, we need to make sure that this is treated at a much
more -- and I think it is generally.  I don't mean to be so
facetious.  But that general sense that we have to be real clear
about this.

          Yes.  I see Lois and then Phil.

          MS. NORRIS:  Yes.  This is really pretty picky, but I
think sometimes language which is expressed at the top of a form
in bold face tends to be overlooked.

          CHAIRMAN FADEN:  Oh, really?

          MS. NORRIS:  People go immediately to the body of the
form and look for the things that apply to them as individuals. 
So I don't -- maybe that's my own way of doing things and maybe
other people don't do it that way, but people tend to overlook
the titles and they tend to overlook the captions on the top of
the form and go to the guts.

          CHAIRMAN FADEN:  I think that's a good point.  And
obviously, we can suggest that somebody empirically test this. 
Just like the subject interview studies are empirically testing
that these terms mean something different.  

          But we could have a recommendation that says, look,
whoever this recommendation is directed to, this is the objective
and you figure out the best way empirically to accomplish this
objective.  Here are some suggestions the Committee has.  We
don't have the time to run these little tests but we've
established, as other people have established, that you can
approach answers to these questions empirically.  Figure out
which would work.

          But something that had a boilerplate instruction:  This
is consent to a research project, not for a -- and then in the
body it's repeated again.  The purpose of this is -- what a
research study is.  This is the purpose of which you -- but
whatever.  I think your point is well taken.

          We should probably resist making very particular
recommendations unless we're sure that that very particular
recommendation is exactly as it should be.  

          Lois, I think you're right to say that we can lay on
somebody else that the recommendation is to figure out how best
to do it.  This is the problem. Here are some suggestions worth
trying out.  The message is clear.  Figure out a way to make sure
that people are not going to be confused about the difference
between research and treatment when they're approached in the
context of clinical care.

          That's great.  That's very important, Lois.  Thank you.

          Phil?

          DR. RUSSELL:  I'm a little behind the curve here.  I
was wondering how -- what the intent was in terms of
operationalizing these recommendations. Who are these
recommendations to and are we making a recommendation to all the
advisory committees of the world or are we making a
recommendation to a specific federal officials for operational --
I mean, what's the operational context for these recommendations?

          CHAIRMAN FADEN:  It looks like Ruth wants to speak to
that, and also Jay.

          Let me just say that I think we can direct it to
whomever we want.  

          DR. RUSSELL:  Yes.  But to be effective we have to --
but the onus for operationalizing it --

          CHAIRMAN FADEN:  I agree.

          DR. RUSSELL:  -- on some individual, whether it's the -
-

          CHAIRMAN FADEN:  So we need to be thinking about that.
But I'm just saying by way of backdrop, there's a way in which
all of this is delivered obviously to the Interagency Working
Group and to members of the Cabinet that we know about which
agencies they are, but we can also be more particular and
specific and go outside of government or within government, too. 
And that's obviously part of what we need to be thinking about. 
But we're not constrained.  We can recommend to whoever we want. 
Whether they listen to us or not is a separate order of problem.

          DR. RUSSELL:  I'm just concerned that we --

          CHAIRMAN FADEN:  Right.  I agree.

          DR. RUSSELL:  -- are specific when we make the
recommendation, not just throw them out for the world.

          CHAIRMAN FADEN:  Somebody out there, please fix this. 
Right.  Somebody out there please fix it would not be a good
idea.

          Ruth and Jay, I think.

          DR. MACKLIN:  I had the same question that Phil asked
but I think we should be more specific since we can address
anyone.  But what underlies this question, this is not a question
that applies only to this one, obviously.  It's the next one,
communication of medical benefit.  

          In all of these we're recommending something about the
consent form, which is a piece of paper.  I mean, we can say
something about the consent process, but the piece of paper.  I
think we have to ask whether -- it could be to OPRR or whoever
that we place in the federal regulations.  But I think the
underlying question is not only to whom, how it would be
implemented and to whom, but also whether we are taking a stance
that there be uniformity in all federally funded research, which
moves things a bit beyond where they are right now with the IRB
process, which is presumed to be semi-autonomous.

          Now, we're calling for more consistency among IRB's,
and particularly in light of some of these findings.  And I think
we have to recognize that the implications of that are more than
-- I mean, in addition to the implementation are that there be a
kind of higher level uniformity that meets certain standards
between and among IRB's in order to be acceptable.  And that does
take us beyond what the current situation is with IRB's and it
may be not very pleasing to some people who think there should
continue to be that kind of autonomy.

          CHAIRMAN FADEN:  Jay and then Dan.

          DR. KATZ:  Well, Phil just raised what to my mind is
the most important question and I've thought a little bit about
it.  I believe -- I would answer your question that the federal
regulations need to be radically revised.  I think they are
inadequate.  They are cumbersome.  They put requirements for
IRB's that I have questions about and they don't emphasize
sufficiently the important points that to my mind they should
emphasize.

          I've made the suggestion, and some of you have read it,
that we really need a national human investigation board that
really wrestles with these issues of informed consent forms, of
giving better instructions and continuing instructions to IRB's,
that reviews at times what they are doing, that has some overall
administrative function.  That's the direction in which I would
go.  And these recommendations are couched in terms of, many of
them, in terms of the IRB should do X, Y and Z, but I don't think
that's going to be too helpful because why should they accept our
recommendations.  And who will see to it that they follow
whatever we may wish to recommend?

          CHAIRMAN FADEN:  Dan and then Phil.  Did you want to
respond right away?  Let Phil respond.

          DR. RUSSELL:  I think that I'd like to make two
comments.  One, a search for uniformity across the federal
government is more likely to bring down the average than bring it
up.

          (Laughter.)

          And it will prevent leadership.  I think we've found
excellence in the system.  Trying to make the system uniform is,
I think, probably hopeless to begin with and almost certainly
don't bring the total thing down.  

          The other -- and I tend to say the same thing about
adding another centralized level of the bureaucracy.  That I
don't think it's going to solve the problem.

          DR. GLATSTEIN:  No one wants to pay for it; right?

          DR. RUSSELL:  Well, again, that's an issue of political
acceptability and the reality of the times, too.  So, while I
understand your intent, and I fully support it, I'm not sure that
operationalizing it in that way is exactly the right choice.

          DR. KATZ:  Do you have an idea?

          DR. RUSSELL:  Not yet.  Not one that I'm going to lay
out on the table.        

          (Laughter.)

          CHAIRMAN FADEN:  You know, Jay, I think it would
probably be helpful if we circulated to all the Committee members
your article and I think that lays out the major case, the case
for the position that you're proposing, well.  And we should all
take a hard, hard look at it, because I think there's an awful
lot that is meritorious of what you proposed.

          And maybe you want to take a look at it, too, and see
if in the light of these findings, you would like to supplement. 
That would be very helpful.  We could circulate the article, plus
whatever in addition --

          DR. KATZ:  I'll try to get something to the Committee.

          CHAIRMAN FADEN:  That would be very critical, so that
we can pursue this further.

          Dan and Eli.

          MR. GUTTMAN:  Yes.  And Anna made a comment which
probably deal with this more carefully.  One of the things that
was quite interesting when these were discussed on the staff
through E-mail, was there were a couple of comments saying it's
really interesting. It jumps out that all these recommendations
are that government should do less.  You know, we should have a
new centralized this or more regulations, whereas this is all
about individual --

          VOICE:  -- behavior.     

          MR. GUTTMAN:  Right. And none of them were citizens
should do X.  So it may be Pollyanna-ish, but just to think about
a supplement, not certainly exclusive, but you know, maybe
anybody who would go into an experiment may want to ask the
following questions.  You know, just to cast some of these in
that -- as a think directly at -- if we're talking about who the
audience is; right?  And if it is the public as well as the
Secretary of the agency, what a citizen might look at as a
recommendation to say, you know, this is what you should do if
you're going to be involved or your family member.  That kind of
stuff.

          DR. RUSSELL:  There are some things that the federal
government does very, very well and there are some things that it
does very, very badly.  I think we ought to just differentiate
between the two.

          CHAIRMAN FADEN:  I know what you're talking
about.    

          Eli and Sue?

          DR. GLATSTEIN:  Well, along the same line, it seems to
me that the key to being able to supervise some of this is to tie
conditions to the funding of some of this research.  It could be
done through structures like the NCI or American Cancer Society
whereby funding would not be granted unless the institution can
show that it has these kinds of programs in place; educational
programs for the IRB.  And there should be probably an ACS type
of national conference on responsibilities of IRB's, a function
of that sort of thing.

          I think it can be done.  The problem of trying to do it
through the government is that in a time of reducing the budgets,
there's not going to be any money to hire new people to carry out
these kinds of additional functions.  And in the case of the
institution, NIH, it's not been a regulatory agency.  That's not
its function.  And that sets up for some real problems.

          CHAIRMAN FADEN:  So that goes to some core issues.

          DR. GLATSTEIN:  But if you tie it to funding and put
the pressure on the institutions --

          CHAIRMAN FADEN:  You also, then -- and this is later. 
Then you also have to tie it to some kind of outcome performance
measure to be able to -- there has to be some way --

          DR. GLATSTEIN:  That, I think, can fly.  It is not
perfect but there isn't going to be a perfect solution for this.

          CHAIRMAN FADEN:  Okay.  Sue and Ruth.

          DR. LEDERER:  My question is actually for Phil.  His
answer, I think, would be useful to helping me think through some
of these issues.    

          Do you think that the federal regulations that created
sort of the IRB system are not effective in improving the conduct
of human experimentation?

          DR. RUSSELL:  No.  I think the work.

          DR. LEDERER:  So you said -- well, I guess I was going
back to your comment about --

          DR. RUSSELL:  The question is -- we have a system in
place and the system clearly works when it's being run by a
concerned and educated and affected people because some of the
outcomes is very, very good.  Then the question is what about the
bottom five percent or 10 percent or 20 percent of high risk? 
Why isn't the system working in those instances?

          And the question then comes, is it a -- can you change
the outcome by tinkering with the system, by putting additional
bureaucratic constraints on it or bureaucratic pressure on it. 
Can you change it by changing some of the rules and regulations?

          In other words, can you fine-tune the system to make
the outcome better or is there something intrinsic about the
operation of the system, the people and so forth, where the
target is.  And I tend to believe that any more regulations --
simplifying regulations, I'll go along with.  Adding more
regulations and adding more bureaucracy is probably
counterproductive at this point.

          We need to figure out how attack the problem of
educating the people and putting more responsibility into it. 
It's already bureaucratically onerous for a lot of the people
involved.  The time issues that they --

          DR. KATZ:  Phil, I would exempt 50 percent of protocols
from review.  I think we can specify --

          DR. RUSSELL:  And figure out how to cut out the
workload and focus on the risk/benefit issues for the important
once.  There's ways of doing that.  And simplifying the
regulations, changing the focus and so forth, that's certainly
probably a productive way to go about it.

          But I think the education at the operational level is
equally as important.  And how does the Committee reach out to
that world and get that message through is what Eli addressed
here.

          CHAIRMAN FADEN:  We haven't mentioned education
recommendations that come in later with the certification
proposal, et cetera.

          DR. RUSSELL:  But they're totally related.

          CHAIRMAN FADEN:  It's all of a piece.  I think this is
all of a piece.  And the issue is how much can we -- how specific
can we get as a Committee in our recommendations versus --

          DR. GLATSTEIN:  Well, most of those IRB's are comprised
of people that want to do a decent job but there's a tendency to
get carried away because the workload is really enormous.  And
there's also an underlying sympathy within the IRB for the
investigators.  You know, everybody's got it's own work that they
want to carry out.

          CHAIRMAN FADEN:  Sure. Absolutely.

          DR. GLATSTEIN:  And there's an underlying theme that
the study is so good, you know, we've got to make a little extra
allowance for this.  Sort of ends justifies the means kind of
thing.

          I didn't honestly think there was this much of a
problem until we started this protocol review and I'm surprised
it's as pervasive as it is.  But that's the way it is and I think
that there is a need to address this problem more directly.  And
I think the only way it's going to work is to put the pressure on
the individual institutions to make the IRB more important than
it has been, emphasize the education, and tie it to funding.  And
I don't think there's going to be a better way to do that.

          DR. LEDERER:  But not by stipulating that greater
citizen involvement be necessary for IRB operations?

          DR. GLATSTEIN:  Well, that's another way of improving
the problem but I don't think it's going to be enough by itself. 
And who's going to do that?  I think you have to make the
institutions do it themselves.  And I think the only way that's
going to fly is by tying it to funding.

          DR. RUSSELL:  Many of these problems that are addressed
here are not the kinds of things that citizens, lay citizens, can
deal with.  The risk/benefit issue is very professionally
specific here.

          DR. GLATSTEIN:  Most of them have one or two lay people
on the board.  Maybe they need to have more.

          CHAIRMAN FADEN:  Well, it's also tied to training. 
This is all of a piece.  If you can say that to the range of
everybody out there, look, if you are being approached to being a
research subject, here are the things you want to ask and here
are the kinds of answers you should be receiving.  You can
provide that training to people who are not professional bio-
medical investigators before they go on IRB's.

          There actually have been some studies that have shown
that you can prep patients and effectively change the exchange
between patient and doctor by a session in advance of going into
the doctor's office that says, what do you want to find out;
let's practice it; blah, blah.  And you can bring people's
abilities to become assertive in a specific context.

          You can't do that for every potential person who might
be approached as a research subject, but you can certainly do it
for lay members of IRB's.

          DR. GLATSTEIN:  The IRB's need guidance, too, actually.
that's the point.

          CHAIRMAN FADEN:  Yes.

          DR. LEDERER:  I know.  But for me, one of the lessons
of this Committee has been sort of the distrust in expertise and
sort of strengthening the powers of experts.  It doesn't strike
me as something that's going to please American citizens on the
whole.

          DR. GLATSTEIN:  Maybe it will be that there needs to be
broadening of membership of the IRB's to include more lay people. 
I don't have a particular problem with that, although I would
hate to see more of them in majority.

          CHAIRMAN FADEN:  I have my list and there's Ruth and
Henry who have been waiting patiently.

          DR. MACKLIN:  What this conversation, discussion,
suggests is that these recommendations are not directed towards
only one body or group and that we might want to give a little
thought to whom they might be directed and name those individuals
or agencies.  

          As Anna and Ruth know, in the report that the IOM did
on Women in Research, many gave a lot of thought to addressing
recommendations to IRB's, investigators, IRG's, funding agents,
et cetera.  The IRG's being the study sections. Because some of
them really have more impact if they're going to be implemented.

          Now, Jay's question will always remain, "Who's going to
listen?"  You know, if there's no teeth in it and who's going to
listen, that may always be a problem.  But people might listen
better.

          I mean, as Dan pointed out, one sent to citizens.  And
maybe some of these recommendations might even have to be broken
out in certain ways; citizens or prospective research subjects
should be thinking of doing (a) or (b).  And then Eli's point
about the funding agency.  So that they don't just get lost as
recommendations made in the air but that they be targeted.  And
it's certainly possible that any one of these recommendations
might be directed at different bodies or agencies who may have
different tasks to do with respect to them.

          So I think we should try to give a little thought to to
whom they might be addressed and to whom that might -- and how
that might be effected.

          DR. GLATSTEIN:  Well, if you try to get funding for
animal work, you have to show that you live up to certain -- the
institution has to show that it has an animal program and lives
up to certain standards.  I don't see why you can't do the same
with the IRB's.

          DR. FADEN:  I think what we're getting to is -- if we
could move ahead.  And I want to move ahead on Look Backwards. 
And there is, if you march through it, there's -- maybe what we
could do is start right now for getting a sense of whether these
are the right Committee views and tentative agreement that these
are areas about which we want to make recommendations.  And then
we can refine it.

          So one is on the distinguishing of research and
treatment.  There was consensus that this was one.  Just moving
through.

          The next is on this articulating the medical benefit
issue.  Jay has given us some wonderfully compelling examples of
the problem that remains with respect to the appearance of more
benefit than perhaps or in fact is there.

          The area that's identified on page 29, Back to Basics,
emphasizing why consent is being sought. A nothing, I think, that
has emerged in the discussion that the consent forms are -- ones
say too much and say too little, is what this is intended to
capture. We've lost -- perhaps lost sight of what are the most
essential elements that we are trying to communicate.  In some
cases, at the expense of veracity.  

          The notion behind this is if you give somebody tons of
details about the risks of the therapy and they don't understand
that it's an investigational drug and this is a Phase 1 trial,
who cares kind of thing.  We drown them in detail about what
could happen but they think it's the latest and best treatment.

          DR. GLATSTEIN:  The Phase 1 program was largely
supported by drug companies.

          CHAIRMAN FADEN:  Which raises some points.

          DR. GLATSTEIN:  Yes.

          DR. RUSSELL:  There's no lever here.

          CHAIRMAN FADEN:  You see, if you put the leverage on
the university or the research institution that says, okay,
you've got to meet these standards regardless of where the source
of funding is, performance outcomes.  So figure it out.  But we
should identify that.

          DR. GLATSTEIN:  That's right.  I think those kinds of
things I think can be built in.  And I think you'll find most of
the academic programs will respond very quickly to that.

          DR. MACKLIN:  But now, here's the problem. And I think
-- I don't know if this --

          CHAIRMAN FADEN:  The problem or a problem?

          DR. MACKLIN:  No, no.  A big problem.  It's not just
the drug companies who supply consent forms.  It's also, for
example, as Eli would know better than I, the cooperative
oncology groups.

          Researchers come to the IRB and they say, sorry, I've
got to have this 15-page consent form because ECOG requires it. 
Sorry, I've got to have these lists and lists and lists of things
because ECOG requires it.  The researchers who are doing studies
for drug companies say the drug company won't let me do the
research or better, better -- and this is where the hook is --
the institution won't hold me harmless or the drug company won't
hold the institution harmless if you change the consent form.  In
which case it's the company's lawyers and the lawyers for the
institutions who are saying, don't change a word.  Otherwise, if
there's some adverse event then the researchers are going to be
held liable.

          DR. GLATSTEIN:  That's a very legitimate problem.

          CHAIRMAN FADEN:  I think that's very helpful.  We need
to flesh that out.

          DR. GLATSTEIN:  But I think that in terms of
cooperative study groups, cooperative study groups get their
funding predominantly from the NCI and I believe that you can get
the NCI to make some suggestions on altering the consent form
process.  Not the consents, but how the consents get written. 
There's no reason why the individual institutions, the members of
the individual institutions can't write the consent form
themselves and make sure that it includes all the materials that
the group as a whole requires and just simply change where the
writing takes place.  It could be peripheral and still
centralized.  

          DR. MACKLIN:  But isn't that the problem, Eli?  That
now the current requirements for the cooperative groups are that
they tell the researcher -- they give them a model form and then
they say --

          DR. GLATSTEIN:  It's done by committee.  And that's the
problem.

          DR. MACKLIN:  -- anything that's every come out that
would go into a patient package insert should go into the consent
form. And that is clearly a higher standard than anyone ever --

          CHAIRMAN FADEN:  I think we should march on.  But I
think the recognition is that Ruth's point is to something very,
very powerful, which is whether it's a cooperative clinical
trial, it's a ACOG or ECOG group of whatever, if the funding is
federal, you could fix it at the basic level.  I mean, there's a
connection.  And this Committee needs to be mindful of pointing
out that you've got to have a large scale effort directed at
getting the priorities straight, whether we want to call it back
to basics or whatever.

          When the funding comes from drug companies, the
complications with respect to implementation jump orders of
magnitude.

          DR. KATZ:  Could I ask Eli a question?

          CHAIRMAN FADEN:  Okay.  And we don't want to be naive
and pretend that it's not an issue that you're involved in the
counsel's office of a private industry that has a different set
of considerations and are speaking to different kinds of
incentive structures than those investigators whose research
comes from the public sector, even if it's filtered through a
cooperative clinical group like the ECOG and like organizations.

          So you're pointing us to -- in terms of again, to whom
this is directed.  It is very important.

          Jay and --

          DR. KATZ:  Eli, I want to ask you a question in terms
of that.  Would you support a proposal which the National Cancer
Institute could also involve drug companies to, but generalizes
it.  That assuming that a research protocol has been approved for
three years, a particular research study, that if in the second
or third year the investigator will simply data that because he
or she has followed the informed consent process, patient accrual
has slowed down significantly, that automatically the research
will be funded for an additional three years.

          DR. GLATSTEIN:  No.

          DR. KATZ:  That's the crux of the problem of the
industrial research.  But would you support it?

          DR. GLATSTEIN:  I think I probably would. But I'm not
sure that I'm in the majority of the investigators.  I don't have
a problem with that.

          DR. KATZ:  Not the investigators.  The investigators
might even possibly like it, but -- 

          DR. GLATSTEIN:  I think they probably would.

          DR. KATZ:  -- but what about NCI?

          CHAIRMAN FADEN:  You know what?  The very interesting
question is you'll reduce the number of projects that can be
funded as a consequence.

          DR. KATZ:  You may.

          DR. GLATSTEIN:  But the problem is money.  Right.

          DR. KATZ:  And inviolability of subjects of research.

          CHAIRMAN FADEN:  That's the tradeoff.  That's the
tradeoff.  If you believe that behind some of this is the
pressure to get enough subjects into your --

          DR. GLATSTEIN:  But if in fact the laws were changed so
that the insurance companies paid for clinical research that
included the Phase 1 and Phase 1 drug studies, then I think you'd
have a basis for payment right there.  I don't think you'd have.

          I mean, a guy pays his money for 25 years for insurance
and comes down with cancer.  When he really needs it and he wants
to go on a clinical study, he may get the same treatment, a
standard treatment versus a standard treatment plus something
new.  If he goes on a randomized study, the insurance company
won't pay even though it's standard treatment.  And it's a little
crazy.

          But if that were changed, I think that would cover the
money.

          CHAIRMAN FADEN:  Well, we're an inventive Committee.

          (Laughter.)

          And at least all of the stuff is getting -- Ann and I
are taking notes and probably other people are, as well, as we're
going to try to feed this back in some fashion.

          DR. ROYAL:   Because money speaks, a number of people
have suggested that one way to get people to behave better is to
work through funding agencies.  It's not clear to me that that is
a good idea because I don't think that the funding agency -- the
funding agency has a conflict of interest.

          The funding agency is in business to do research and
there's a disincentive for them to do anything that would
seriously impair their ability to do research.  So I would be in
favor of a more independent body.

          DR. GLATSTEIN:  Well, in tying it to funding, all I
meant to imply by that was the ability of the funding agency to
spell out in some detail, for example, what sorts of methods they
use to maintain IRB education on some of these points.

          Do they have or is there a regular program for making
sure that each person that goes on the IRB has the background and
so forth that we were talking about earlier.

          DR. ROYAL:  But there is a disincentive.  They're not
going to do anything that's going to make their job, their
primary mission, more difficult.

          DR. GLATSTEIN:  Well, I don't think they really have
to.  All they have to do is point out that the individual
institutions have to make the changes.  They are simply
establishing some guidelines.  And those guidelines shouldn't be
translated into a great deal of expenditure vis-a-vis the sorts
of things taking place in Washington right now about mandates.

          CHAIRMAN FADEN:  I think there's a different -- your
proposal or your -- I don't think you want to call it proposal
yet, but your position you're articulating with respect to the
independent body is regarding the sort of overall oversight
responsibility for --

          DR. GLATSTEIN:  I mean, when this cancer treatment
evaluation program evaluates a protocol, that's about a four or
five month process which goes back and forth to the investigators
to make changes and so forth.  And I don't understand why it
wouldn't be possible to build in some of these other requirements
during that process.

          CHAIRMAN FADEN:  That's right.  That's true.

          DR. ROYAL:  I guess one of the earlier proposals in the
Openness Section is the central registry concept.

          CHAIRMAN FADEN:  Right.  We'll go back to that.

          DR. ROYAL:  And as a potential independent way, or more
independent way than the funding agency, I think one of the
reasons why the system doesn't work as well as it could is that
there's just no feedback loop. 

          And one way you could do an expedited review is to just
have -- you're already sending the consent forms to the central
agency for preservation, and theoretically you don't need a lot
of expertise to read the consent form because that form is
intended --

          CHAIRMAN FADEN:  For lay people.

          DR. ROYAL:  -- for lay people.  And,    I mean, I
really have been surprised at the variability of the quality of
consent forms that we've seen with contemporary research and I
would think that you could get quite a big bang for your buck
just by having a group of people who are interested in the issue
of how well you communicate risk and benefits to patients, and
they could read the consent form and decide for themselves
whether or not they would be able to make any sort of intelligent
decision based on the information that's provided.

          You don't know how accurate that information is, but at
least you can separate those studies out from which someone could
make an intelligent decision.

          CHAIRMAN FADEN:  So you're thinking about some sort of
a mechanism whereby --

          DR. ROYAL:  Well, one of the other suggestions was
already to send in consent form.

          CHAIRMAN FADEN:  Right.  Exactly.  So off of that
mechanism there's some periodic review that's pulled out?  This
is what I'm thinking about in terms of performance outcomes. 
Some way of looking at the output.  The process that we have now
all looks at the input, sort of sets up the regulatory side; you
should do this, you should that, you should do the following
thing.

          What this Committee has done, which is what we could
attempt -- not that it's not been done before, but certainly not
on this scale -- is looked at the output, what comes out from
this regulatory thing through which everything is pushed.  And we
learned -- we're learning a lot.   So what you're suggesting is
some sort of regularizing of that.  A look see.  A kind of let's
take a look at that from time to time.

          DR. ROYAL:  And I actually think that having this
feedback loop, if some outside agency says the consent form could
be better, and means could be better in the true sense of
communicating with the patient; not better to protect you from
medical/legal consequences or whatever or to meet the federal
registry's requirements that aren't necessarily communicating
anything to the patient.

          I think that for the amount of effort that's put into
it, that you're liable to get the most amount of benefit, and
that would be a starting point.  If that didn't work, then things
like sanctions and stuff would be appropriate.  But I wouldn't
start this off as being -- setting up this agency that's going to
sanction you.  It's really setting up this agency that's going to
help you write better consent forms.

          DR. GLATSTEIN:  But the point I'm trying to get at is
that there is an agency that exists now.  These protocols and
their consent forms have to go through the -- at least if they're
funded by NCI money, they go through the NCI now and the protocol
doesn't begin until the NCI signs off on that consent form.  And
they usually make a bunch of changes.

          Now, it's clear they're not making the right changes.

          CHAIRMAN FADEN:  Right.

          DR. GLATSTEIN:  It's clear that the orientation is not
-- that they have, is not really aimed at patient rights and
patient protection.  I hadn't realized there was this big a
problem but there obviously is.

          And that's where I think you could tie it.  And I think
it represents no additional bureaucracy because that bureaucracy
is there and functioning at this moment.

          DR. RUSSELL:  I want to clarify something in regard to
that.  The Defense Department has two levels of review with the
committees, with community members on it and so forth for all of
the high risk -- the normal risk protocols go through one level. 
If they're greater than minimal risk they go through two levels
of review.  And obviously at NCI the same parallel committee
structure is in place.

          Is that a committee review or is it an administrative
review?

          DR. GLATSTEIN:  That's a committee review.

          DR. RUSSELL:  There's a second level committee that --

          DR. GLATSTEIN:  Yes.

          DR. RUSSELL:  -- does the same thing.  Now, one of the
questions I would have from the analysis is are there problematic
protocols, the ones that seem to be the most problematic, have
they undergone two levels of review or a single level?  That's
one question.

          CHAIRMAN FADEN:  Well, we could go back and try to --

          DR. GLATSTEIN:  Take a quick look at that.

          CHAIRMAN FADEN:  We could take a quick look.   I also
should emphasize we should remember that these studies that we're
looking at, these research projects, come from -- how many
different agencies?  Four?  Five? 

          VOICE:  Five.

          CHAIRMAN FADEN:  Five. Okay.  So when we think about
mechanisms, we haven't yet gone back and tracked to see which
ones are coming from which agencies.  But we have to remember
that while NCI may make a -- if it looks like they're all cancer,
which we don't know yet, that are problematic, then of course NCI
would loom large.  but even NCI is not the only place that funds
cancer research in the federal government.

          So we have to step back and realize that our research
projects -- this is the other thing that's kind of unprecedented.
We're looking across the federal government at humancentric
research.  We are not looking solely or exclusively at research
funded by NIH, although obviously NIH is in there. We've got all
the other people.

          And so we need to look better to see connections when
we start thinking about mechanisms and to whom to direct this. 
As we look at it by who's funding these projects, it may emerge
that the recommendations disproportionally go to one agency or it
may not.  It may be that -- you know --

          DR. GLATSTEIN:  Within the NCI it's called the Cancer
Treatment Evaluation Program, CTEP.  

          CHAIRMAN FADEN:  Right.  And we have to see how many
fall within that.  That's just by way of background so we can all
remember that the projects we're looking at, we haven't broken
them out yet by agency on this issue.  They come from across the
federal government.

          DR. GLATSTEIN:  The other question I have was whether -
- the issue is fundamentally a quality assurance, quality control
issue with regard to the human volunteer system and how do you
make a system like that work better.

          One is you keep your hand on the money and don't let
the money out until all the arguments are satisfied, and the
other is the accreditation systems within the medical treatment -
- our medical treatment world.  We have the JCAH.  Are they
focusing at all on the IRB and the process by which --

          DR. RUSSELL:  We have not seen any evidence of that.

          DR. GLATSTEIN:  I don't think so.  Do they --

          CHAIRMAN FADEN:  I don't know the answer to that.

          DR. GLATSTEIN:  They do look at the existence thereof
and they look at whether it's -- but I don't know that they --

          DR. RUSSELL:  They look to see that there is one.  They
don't look to see if it's doing a good job.

          DR. GLATSTEIN:  Right.

          DR. MACKLIN:  But that would only cover hospital based
IRB's; right?

          DR. RUSSELL:  Exactly.  But there's also a parallel
system being built in.  But my point is that's another pressure
point that you can put on the -- whatever system.  I would
venture to say that a very, very large number of our high risk
protocols we're concerned about are going to fall under the
purview of either that system or a similar system for the HMO's.

          DR. MACKLIN:  Does that focus the question?  Does JCAH
at all have anything to do with the veterans system or --

          DR. RUSSELL:  All hospitals.

          DR. MACKLIN:  Is it every hospitals?

          DR. RUSSELL:  Military hospitals included.

          DR. GLATSTEIN:  Every hospital that seeks
accreditation.

          CHAIRMAN FADEN:  They're pretty powerful.  It reaches -
-

          DR. RUSSELL:  That seeks accreditation.  Yes.  That's
true.  I don't know what percentage of --

          CHAIRMAN FADEN:  Are unaccredited?

          DR. RUSSELL:  There are some.

          DR. GLATSTEIN:  There are some, but not very many.

          CHAIRMAN FADEN:  This is all very important, but if we
could just march through a little bit and get a feel for where
else things are going.

          Can we assume that we want a subset of our
recommendations to speak to the issue that's raised on page 29,
line 16?  This comes out of our historical experience, making
sure that the range of purposes for which research may be
conducted the range of sources for funding somehow has to emerge
as an issue.  This obviously comes out of our looking at some
historical ones.  Whether this is a problem today, I don't know.

          Pat?

          MS. KING:  Is this intended to cover the end payor
situation where the researcher also has a financial interest?

          CHAIRMAN FADEN:  Yes, it was.  I don't think it's been
spelled out.

          MS. KING:  Because it should be spelled out.  And I
think that it actually came out in the report, but I'm very much
aware of how controversial such a recommendation is.  So I just
point that out.  But I think that we need to clearly address it. 
We have to give some reasons for why we have come down on one
side of the issue.

          CHAIRMAN FADEN:  We may have to pull that off to the
side and see.  It may be inappropriate.  And I spoke too quickly. 
This issue, abstracting the question of financial interests of
the investigator, speaks out of our historical experience being
the base for saying something about it.  The particular question
we haven't hit as a Committee in any of our other work.  So I
have to maybe go back as to whether we should be really pursuing
it or not.

          And let me say as a general backdrop, I think obviously
the strength of our Committee is to speak from what we have
learned together as a Committee, so our recommendations -- and we
have so much.  We have contemporary data that we are amassing and
we have historical analysis that we have conducted, so we have a
very rich base from which to speak with some authority about our
recommendations.

          So we should probably concentrate our energies on
making recommendations that come most strongly from our
collective learned experience.

          MS. KING:  I think I agree with that.  But I would note
that in the future, the financial conflicts are the major issue
in terms of language here about purposes for which the research
is being conducted, just as the period of which we come out of it
may have been the multi-purposes in terms of military purpose
versus benefits, et cetera.

          CHAIRMAN FADEN:  That's a good point.

          MS. KING:  So you can argue both ways about whether --
we have something to say about it from our past experience that
perhaps has implications for what happens to subjects when there
are other purposes going on that they're not aware of.

          CHAIRMAN FADEN:  That's a good point.  We'll flag that
and separate it.  Perhaps provide background for Committee
members who aren't familiar with that issue in there.

          If we could just march -- I don't know.  If this is
bad, tell me.  If we don't -- I'm just trying to give a little
help to staff the most.  If we could march through this and get
some sentiments.

          On page 39, "Avoiding -- line 8.  "Avoiding
Presumptions of Agreement."  Several Committee members commented
that they're irritated -- their irritation at continuing to see
consent forms written in the first person.   I will have this
happen to me; I will have that happen to me.  It's a tiny point.

          DR. MACKLIN:  It's even more that "I understand that. 
I understand that.  I understand that."

          CHAIRMAN FADEN:  And it sets up a presumption that you
already agreed and makes it really weird to say no. It makes it
very awkward, so that it's -- I was surprised to see so many of
these still remaining, like this one here.

          DR. LEDERER:  Do we have any input from the subject
interview survey about that?

          CHAIRMAN FADEN:  Not yet.

          DR. LEDERER:  But is that a question we could get?

          VOICE:  I don't think it is.

          CHAIRMAN FADEN:  I don't think we get anything that
particular.  Because again, as Nancy was -- and Jerry, you were
pointing out, the whole thing was crafted to minimize asking
questions where recall would be really a problem in getting an
answer.  So that's always an issue because you're asking people
to recall things that happened to them in the past.  The more
detail-ish you get, obviously the more it could just be the
forgetting curve problem and not a real problem.  So we tried to
concentrate on areas that were less vulnerable to disputed
interpretation because of the passage of time.

          DR. LEDERER:  So what's the evidentiary base for this?

          CHAIRMAN FADEN:  The protocol review project.  We're
getting consent forms in the research projects that we're
reviewing that are written in this form.

          DR. LEDERER:  And we have evidence that people do feel
more constraint?

          CHAIRMAN FADEN:  No.  That's the presumption on our
part.

          DR. LEDERER:  Okay.  That's what I'm asking.

          CHAIRMAN FADEN:  I'm sorry.   

          DR. LEDERER:  It's the presumption rather than actual
empirical evidence.

          CHAIRMAN FADEN:  We have evidence that these forms are
still -- no.  We have empirical evidence that people are writing
forms in this way.  And it is the judgment of some Committee
members that that's offensive and/or inappropriate.  But no
empirical evidence.  And that would be important to establish.

          DR. ROYAL:  When you say it's a judgment of the
Committee members, I'm just trying to better understand the issue
because I know that in my own IRB at one time we were told to
write in the first person and then another time we were told to
write in the second person.  And so I'm wondering if there are
any sort of global recommendations about first or second person. 
That issue has not been explicitly addressed in any organized
way.

          CHAIRMAN FADEN:  I don't know.  Maybe we can look
again.  I don't know if anybody's ever done an empirical study in
which people have been given forms in the first persona and in
the second person and measured their sense of --

          DR. ROYAL:  But has anyone ever made a recommendation
that carried any weight in any of the federal agencies?  Do they
care?

          CHAIRMAN FADEN:  I don't know.  I don't know of any.

          DR. RUSSELL:  Part of the form have to be in the first
person.

          CHAIRMAN FADEN:  I agree. 

          DR. RUSSELL:  It has to be there someplace.  It may be
one sentence, but part of it has to be in the first person.

          DR. KATZ:  Unless there's some objectification observed
in the research, what about putting it in the third person,
calling them its.

          (Laughter.)

          DR. MACKLIN:  Some consent forms mix up the persons. 
They say the purpose of the procedures, subjects will be asked
to, et cetera, et cetera.  Then they go to you and then they go
to I.  So I mean, that's really pretty confusing when they mix it
up like that.  But I think the uniformity is desirable, but after
what Phil said before, I'm a little concerned that too much
uniformity may drag us down.

          CHAIRMAN FADEN:  No, no.  I think we all have to think
about that.  It's an interesting challenge.

          Six is a placeholder.  We have been asking chairs of
radiation safety committees to provide us with any suggestions
they might have on how their committees have approached the issue
of communicating risk in relation to radiation and we have been
very fortunate in every respect. People answer us when we send
these letters out.  They actually write back, which is terrific. 
I mean, when we write to chairs of IRB's and ask questions and
they write back, and we write to chairs of radiation safety
committees and we're getting answers back.  People are sharing
with us what their committees have thought about these issues.

          DR. KATZ:  Well, you've gotten answers?

          CHAIRMAN FADEN:  Yes.  Oh, yes.

          DR. KATZ:  Many of them?

          CHAIRMAN FADEN:  Yes. And we're starting to look at
what people have been trying to do.  Obviously, we have
colleagues sitting around the table who have struggled with this
and we are now trying to augment your impressions with
suggestions that are coming from chairs of radiation safety
committees who say this is how we have worked it out for your
committee's consideration.

          And I don't know that we'll come up with a uniform
recommendation or even that we should try, but at least we can
give some guidance as to how people are approaching this problem;
how much of a problem they think it is; and --

          DR. KATZ:  Can we get copies of these things?

          CHAIRMAN FADEN:  Yes.  We'll send them around.  They're
just starting to come in.  And also, some of the suggestions that
are in here come from chairs of IRB's who wrote to us and said we
could use some help of the following sort.  Could you please --
if your Committee could say certain things, that would be very
helpful to us.  So that's available, too.

          Pat, and then Henry.

          MS. KING:  This is just a comment, because I'll wait,
as always, to see the justifications.  But being a potential
subject and not a member of an IRB, I can't see that it makes a
lot of difference to me whether I'm addressed in the first person
or the second person.  And I don't know if I'm the only person
who feels that way but that raises for me a question of de
minimis recommendations.  I mean, in terms of do we want to make
a recommendation about everything.

          And so, I may be wrong about this one.  There may be
substantial reasons for going to discuss one person versus the
other person.  But it's a concern for me that arose when I --

          CHAIRMAN FADEN:  I think what you're saying is well
taken.  And my personal view is that we would be better off if we
had, you know, 10 big deal recommendations than if we had 332
recommendations.  And that some of the smaller ones could be in
the commentary underneath some bigger one, so as not, you know,
pulled out by itself and given equal weight.

          So if we could, thinking about how this report comes
out, this Committee sees 10 important things and these 10 things
were done, the world could be better, it would be a whole lot
easier to communicate than if we have 2,226 specific
recommendations that we would like to tinker with. 

          So I'm in general -- I assume by the nods of heads
around the table that the Committee overall would prefer a
structure that took more of that character than some other.  So
that's a point well taken.

          Henry?

          DR. ROYAL:  I wanted to bring a paper to the attention
of some Committee members, if you're not aware of it.  But there
actually is a paper written by Frank Casternovo about
communicating radiation risk.

          MS. MASTROIANNI:  Yes.  I think it was sent out early
on.

          CHAIRMAN FADEN:  But we thought we sent it out to
everybody.

          DR. ROYAL:  No.

          MS. MASTROIANNI:  Early on?

          DR. ROYAL:  What they did is they actually did a survey
of IRB's.  Asked them to send their preferred language and then
the sent all the preferred language out to the radiation safety
committees and they all voted on what they thought was the best
language. 

          So there actually is some information available from
the literature.

          CHAIRMAN FADEN:  We'll circulate that.

          MS. MASTROIANNI:  I thought we had circulated that.

          CHAIRMAN FADEN:  I did, too.  I'm sorry.

          And so what we were getting from people would be
augmenting that.  We'll see where we're going.

          Actually, your point -- Phil's point about checking to
see how many levels of review the more problematic studies have
raised, to me that's obviously very important to draw the
parallel to the isotope. What has the experience that evolved in
the radiation research area where there is two levels of review
and if we are in fact -- we have adduced that.  If we can adduce
any evidence that suggests that that second level of review
actually has the effect of improving the ethics of research,
that's worth noting.  And that would be important to pull out and
see if a specialty review really does pay off from the
perspective of improving the ethics of research.

          Okay.  On page 31, we begin recommendations specific to
certification and training.  And if we -- they are kind of a
piece that begins with the notion, this notion of certification,
which actually emerged as a recommendation that was sent to us by
an IRB chair.

          MS. NORRIS:  Was that only one?

          CHAIRMAN FADEN:  Pardon?

          MS. NORRIS:  That was only one, from one IRB chair?

          CHAIRMAN FADEN:  One IRB chair.  Other people suggested
we need education but he was the only person who linked it to
something formal like certification.  But the idea here being
that -- and many of us know that there is a question about the
line that begins, "It is."  We started out with just being
shocked.  Some people.  Not everybody.  That why wasn't the
Nuremberg Code better known, so on and so forth.  

          And the issue is how many people today know what the
Belmont Report is and know the principles that lie behind
research of human subjects today, including IRB members, since we
don't have a whole lot of evidence that the research community is
more knowledgeable today about the underlying principles of
research involving human subjects than previously.  Nor do we
have evidence to the contrary, except anecdotal, from people
telling us.

          This is intended to say, look, out of our experience,
there's a gap in principles from today until tomorrow, and if the
people who are supposed to actually live by them don't know about
them, they couldn't possibly honor them.

          So the idea here -- at least they might honor them,
just out of some other set of moral convictions, but they're much
less likely to honor them if they don't know that they're
supposed to live by them.  So the idea is as simple as that. 
Whether certification is the right mechanism or not is a separate
order of issue, but the notion is a simple one.  That we've
learned from the past that just because somebody says there's a
code out there, doesn't mean that anybody knows about it.

          DR. KATZ:  Are you serious about this proposal?

          VOICE:  I hope not.

          DR. KATZ:  I mean, it's -- I have to interject. 
Particularly, I want to get the deans, the presidents, the CEO's,
IRB members.  I mean, it is -- I wouldn't want to train them.

          CHAIRMAN FADEN:  You're a university president.  Tell
us.  Is this terrible and awful or what?  How would you respond?

          DR. KATZ:  Let me put teeth in it.

          DR. TUCKSON:  Let me, before I get any more people
yelling at me, seize the ground.  First, now I'm nervous because
-- well, I'm glad he's leaving.

          (Laughter.)

          Because I'm going to disagree with him.

          I want to take a larger perspective on this.  I think
that from -- it's hardly a juxtaposition between -- I read -- I
went back and re-read all that -- a lot of that stuff between the
AEC and the Department of Defense and Shipman versus Shields
Warren and going back and forth and reading all that stuff.

          And then I read this part and it seems to me that I
think one of the most important things that could come out of
this is that the government changed its behavior and that the
public is sure and is assured that this isn't just a rhetorical
exercise, even if it was a remedy that had to do with money, and
that's good.  We could say, well, we sure got their attention. 
But that there was something in place that changed the culture of
the way in which government behaves.  

          I know that -- I'm a member of the IOM and I know that
for some reason -- I never asked.  I'm a fairly new member to the
IOM but I'm always with you, so -- but some reason, when it's
time for conflicts of interest, enormous energy is spent in
meetings regarding discussions of conflict of interest. 
Something changed their corporate culture to the point that for
an hour before discussions would occur, regularly you must sit
there.  And there is a lawyer.  In fact, the Executive Director
of the place sits right there with you and everybody must
disclose who they are and who their grandmother got stock from
and it's very serious.  

          And as a new member of that culture, I am extremely
aware that I am not supposed to screw up regarding conflicts of
interest.

          (Laughter.)

          And it seems to me that it is such similar mechanisms
that the government widely defined says we do know about
something called the Belmont Code and we do know something about
the Nuremberg Code and we are aware of the standards of the day. 
And one thing for sure.  Within the agencies and with our
relationships external, you cannot misread how doggone serious we
are about protecting the lives of American people and being
ethical about it.

          So, I would just first come down on the point that I
know it is possible to do this and I know that it is important to
do it.  And I know that if there's any recommendation that we
will make for the future, these are the most important
recommendations that we will make for the future in my opinion.

          Now, at the level of technical detail about
certification, I'm prepared to listen to other conversation. But
I'm getting, to end my long-winded analysis on this, specifically
I'm asking that the issue -- before we get to certification at
the institutional level, I think there needs to be a government
discussion around the way in which government culture will be
dealt with and what are the issues in how the government handles
these matters internally.  And then, secondly, how does
government then affect the behavior down the line with those
external to it.

          So, I'd like to open up that bigger issue.

          CHAIRMAN FADEN:  Thank you.  Reed, I think you've
captured -- corporate culture, it is an issue of culture.  This
recommendation is intended to address changing the culture, as
it's written now, of the biomedical research community.  I'm not
sure about whether it's more important to change government
versus the biomedical research community.  I think you clearly
need to be addressing both.  

          But I think you can talk to the government from today
until tomorrow.  If the biomedical research community doesn't
have the view that this is one of our primary obligations and
just like you're an IOM member and you'd better get your conflict
of interest stuff straight, if you do research on human subjects,
you've got to get this stuff straight and you better be damn sure
you don't screw up this end of it.

          DR. TUCKSON:  But Ruth, I would just say this.  I think
we cannot accept that you can't change the culture of the
government.

          CHAIRMAN FADEN:  No.  I'm not.  I want to change that,
too.

          DR. TUCKSON:  I mean, -- I understand.  Yes.  Because I
think that's both important.  Because first of all, it is, --
again, I have no idea of what conversations are going on between
the Department of Defense and somebody else.  I don't know if
there's another Shipman writing a letter to another Shields or
whether some knucklehead in the Air Force is going to decide
we're not going to flag down the planes because we don't -- in
other words, I just think that there's something in the word
we're about to enter so complex and the issues are so unknown
that I think that it just -- maybe what you've said means we have
to be even more Draconian.

          CHAIRMAN FADEN:  Pat, then Henry.

          MS. KING:  I don't disagree with changing the culture
that Reed talked about, but I feel strongly that certification
doesn't do anything but relegate something off to another expert
who's in charge of the problem.  And I'll try to speak to that.

          I was struck by a comment about the IOM.  I, too, am a
member. Probably between the two of you.  And I've been struck
with how perfunctory some of those conversations can be.  I've
also been struck that in a different -- I just came through one
that was totally different from a perfunctory approach where we
got beyond financial conflicts of interest and really got people
to talk about what their biases were, what their predispositions
were when coming into a new area.

          It was a wonderful conversation and went well beyond
what I've also participated in, the very perfunctory ones.  I own
stock in this and, you know, I'm a consultant for that.  But it
doesn't really tell you a lot of meaty stuff in addition to that.

          I was struck by that because what we really want to
happen in IRB, for me, is for people to have a conversation where
they are not barriers but conversation about why it's important
to everything that they do that they be aware of the fact that
you get consent.  You do a lot of things that we all take for
granted.

          And I don't think that we have to talk about codes in
order to do that.  That was my point yesterday.  You don't need
to know the terms of the Nuremberg Code or the Belmont Report --
which I happen not to like a lot and I helped draft it, but I
don't like it at all, so I want to be on record as being very
happy to let people forget the document itself, but not some of
the principles and the ideas that I think that we were trying to
capture in the document.  Probably do a better job today doing
that.

          And I think of certification as another way to do
credentialism, which is another way of being expertise in
satisfying requirements and open up cottage industry.  I would
much prefer seeing requirements that required or suggested to
IRB's that they retreat and go off and discuss problems or that
they start every year by trying to duplicate the IOM message.  

          Credentialism is a way to meet a requirement.  You go
off to class with X, Y and Z and you come back and somebody
certifies that you went.  I think what we want to do is think
about suggestions.  And I think of them sort of as suggestions
for IRB operation to help accomplish a goal that we all think is
important.  And maybe IRB's will do it differently, but there has
to be ways of working on the integration in IRB's so that the
ethics person is not the ethics expert, because that's not what
you want.

          CHAIRMAN FADEN:  Pat, I think what you're doing is the
opposite of what I want.  You're not casting the net widely
enough.  You can educate IRB members for today and tomorrow. 
It's the whole rest of the community that's the problem.

          If I chair an IRB --

          MS. KING:  Oh, we're not disagreeing on that, Ruth.

          CHAIRMAN FADEN:  That's what this area is directly
towards. It's not explicitly or primarily even IRB members.  It's
the whole biomedical research community.

          I chair an IRB and even if I've got the most wonderful
members and we are honest and we discuss, if the rest of the
community thinks we're a pain in the butt committee, the sole
purpose of which is to pass paper through, so that you can get a
stupid stamp so you can send your -- I'm exaggerating for
purposes of effect here, but that the end result is just so I can
get the stupid form signed so I can get my grant application in
on time.  That's not going to accomplish what we want to
accomplish.

          MS. KING:  I'm not disagreeing with you, Ruth.

          CHAIRMAN FADEN:  So that was what this was speaking to.

          MS. KING:  I'd be perfectly happy with the wider net. 
But I think that when you talk about the wider net, that the
credentialism is even more of a problem.  Because what you really
want people to do is not to have to jump through another hoop
which they -- I don't want them to jump through a hoop because I
teach some of those hoop courses that people come to, and you do
to.  And to get eight people to buy into why this is an issue is
easier when we have the people who are there because they are
motivated to come, than some of the encounter who say I need a
continuing education credit.  That is my experience.

          I think that the kind of things that we want to think
about is getting people to see it as a part broadly of the
biomedical enterprise that you have to do certain things.  That
takes us back to where people are educated.  Not their
credentialism.  And credentialism, I think, doesn't help.  It is
often a serious handicap to what we're trying to achieve, which I
think -- that's my view, anyway.  But Reed says that what we're
trying to do is change the culture.  We want people to think more
broadly, focus more broadly.

          So, I don't like this one.  I'll talk about the next
one when we get to it.

          CHAIRMAN FADEN:  Right.  You don't like the
certification element or whatever we want to call it.  The
general goal seems to be one that people are agreeing to. 

          I saw Henry and Jay and Sue.

          Henry?

          DR. ROYAL:  I'm sort of surprised at the amount of
debate that this has brought up.  Maybe it's because we all have
a different view of what we mean by credentialing.  And maybe
it's also -- it doesn't seem like such a big deal to me because
when you write the material, I mean, you have to -- I mean, it's
not a big deal. It means that you have to spend an hour reading
something to -- and then we actually have a little exam that you
take that takes 15 minutes to show that you read it and you have
some idea of what you're doing. 

          And if that's what we're talking about, making sure
that people understand what the basic principles are of
conducting research ethically and we're talking about a one or a
two hour thing for a new investigator in some sort of annual
recertification thing, that might just consist of passing out
some written material that they sign it and they say, you know,
I've read it.  Then they can't go and say later on, well, you
know --

          CHAIRMAN FADEN:  I never heard of it.

          DR. ROYAL:  Yeah.

          CHAIRMAN FADEN:  They didn't know about it.

          DR. ROYAL:  It seems like a very simple thing to do. 
But maybe that's not what certification is meaning in this
context.  I don't know.

          CHAIRMAN FADEN:  Well, there's two.  I mean, I see your
response here, but there are two issues here.  One is linked to
the issue that we have heard, is "I didn't know I was supposed to
do this."  And it gets very difficult to hold people accountable
because you say, well, where was the breakdown.  Did the
administrator not effectively communicate this?  Is it the
person's fault?  Is he or she culpable for not knowing that she
was supposed to do this?  So it's this narrow accountability
problem.  And then there's the broader one of changing the
culture and whether sitting down for an hour and reading
something and signing it changes the culture is doubtful.  It may
serve the other purpose, though.

          But let me ask you.  Do you think people learn
something from that?  Do they learn how to handle radioactive
materials as a benefit, able to do it, or do you feel like it's a
Mickey Mouse kind of thing?

          DR. ROYAL:  It depends on how well it's done.  I think
it can be very useful.  As a matter of fact, there is a paper
about using fluoroscopy where some hospital instituted a program
of education for using fluoroscopy because in a hospital,
fluoroscopy can be used by anyone, not just a radiologist.  And
the actually got comments back from physicians who were being
required to do this about how useful of a program this was.

          So, I think if it's done right, it can be --

          MS. KING:  But people have a reason to buy into the
program when they themselves have something that they can see is
a clear benefit for themselves as well, which is --

          DR. ROYAL:  But the clear benefit here is that you've 
going to be allowed to do research.

          MS. KING:  I don't think that's the way people approach
thinking about ethics and ethical principles.  But I'll keep
quiet.

          CHAIRMAN FADEN:  Well, don't keep quiet.  We want to
hear from everybody.  But we've got Jay and Sue waiting, so I
mean --

          DR. KATZ:  You know, there is something nice, Ruth,
about the spirit that you're proposing.

          CHAIRMAN FADEN:  I didn't propose.

          DR. KATZ:  Well, --

          CHAIRMAN FADEN:  I'm not saying that I don't like parts
of it.

          DR. KATZ:  But I wonder about certification . And
indeed we've become the most over-certified kind of body.  I get
asked to be certified in all kinds of things and I just say it's
too late for that.

          (Laughter.)

          And to pick up on something that Henry said, there
might be something nice.  Forget about certification.  There
might be something nice, even if it's just to some extent even
symbolic at this time to have a few hours a year of compulsory
participation in some seminars.  Maybe even with a little exam
attached to it.  Particularly if the requirement is that all the
senior people, first of all, the senior investigators have to
attend that seminar and learn something about the ethics of
research.  It might have a salutary impact on the younger people. 
Maybe it can be done in a double mirrored room where the
presidents and junior investigators can sort of listen in to
what's going on.

          And to do something that you think through.  I'm really
not trying to be funny, but serves the purpose behind it.  To do
something that can be both meaningful and symbolic and that
there's at this point there's something to be learned here.

          The major problem I have is to go back to juvenile who
asked who shall stand guard over the guardians.  Who will be the
teachers of these people?  Surely, you very well can appreciate
if I were the teacher it would be quite different message
conveyed than some other people also impressing the same issues
as I would be the teacher.

          But that's inevitable.  But this is just, I think, --
however wonderful, it's just too much in its present form.

          CHAIRMAN FADEN:  Sue and Reed.

          DR. LEDERER:  Well, I guess I can't sit here any longer
and say that if people knew the history that that would also
change the culture.  And I think that knowing the history is an
earlier recommendation, I think, in the Looking Forward.  But I
also wanted to make the point that it seems as though --

          CHAIRMAN FADEN:  That's well taken.  That's the notion
behind introducing Nuremberg.  Not because it's a code but
because we've got to have people understand where we came from.

          DR. LEDERER:  But I'd also like to make the point that
it seems that aren't there already sort of accreditation for
people who use animals in research?  Don't they have to take some
sort of course in the ethics of using animals?  They have to
account for the animals that they use. And that we could ask
whether that has changed the culture of using animals in this
country as research subjects and use that as a model.

          DR. GLATSTEIN:  Actually, I don't think we have -- I'm
not aware that that's true, but if it is true that in England it
takes you much longer to treat animals than to treat patients. 
There's about a six month check-up that they put you though,
whereas, all you've got to do to treat patients over there is
register with the General Medical Council.

          DR. LEDERER:  I understood that in this country that if
people are going to use a particular animal species, for example,
you had to take a course in --

          CHAIRMAN FADEN:  I don't think so.

          DR. GLATSTEIN:  I think that's desirable but I don't
think it's necessary.

          DR. RUSSELL:  The Laboratory Animal Review Board system
changed the culture.  The veterinarians that monitor it and
manage the care have made a tremendous impact on the medical side
of the culture.  But the sea change came when they put in the
system of a review board for protocols.

          CHAIRMAN FADEN:  Your phrase of sea change is kind of
interesting.  If you're arguing that a sea change occurred when
the federal regulations came in in a big way, then maybe it's
sort of time for looking for another sea change.  Whether the
answer is regulatory or certification or whatever, I mean, it's
been 20 years and we now know things aren't perfect.  There are
still issues.  And we're looking for -- what we're struggling for
are the means issues.  

          DR. GLATSTEIN:  But the idea that I had originally for
educating the IRB's is the same thing as here.  You could leave
out the certification process but still a required amount of time
every year for each individual, including the people that remain
there, to go through an informative process.

          CHAIRMAN FADEN:  If a person is suggesting that the
president of the university and the deans and the chairs of the
departments were speaking to the thing that Jay was mentioning,
that unless you get people in leadership --

          DR. GLATSTEIN:  Yes.

          CHAIRMAN FADEN: -- to give evidence that this is
serious, important and high priority and they care about it and
it's really part of being a professional in our institution, it's
hard accomplish this sea change or whatever.  Maybe sea change is
too dramatic a metaphor.  But I think that was the force of this
person's wanting to sound to elevated and go all the way up to
the president of the institution.  That that was the issue. 
          

          Whether certification is right or not, but it's sort of
like whether that IOM stuff is too helpful or not, but Reed's
mention that when the Executive Director comes down it clearly
communicate that this is serious and we take this seriously. 
It's part of what this person I think who wanted to put this
forward for our consideration wanted to communicate.  That's the
help he's seeking.  How can I get my institution to overall
support me as an IRB chair in taking all this stuff really,
really seriously.  Which is not to say that there aren't tons of
people out there who already take their obligations seriously,
but it's not in this person's very, anyway, diffused enough in
the culture.

          I don't know how to do it.

          Reed and -- I'm sorry.  Ruth and then Reed.

          DR. MACKLIN:  I think both sides who've been arguing
about this proposal are right.  I mean, both sides are right.

          (Laughter.)

          The reason I think both sides are right is this.  When
Pat and Jay talk about certification.  Once you have
certification, the emphasis is on the piece of paper.  And having
the piece of paper and waving the piece of paper and then asking,
do you have this credential, and it tends to elevate what you
have far more than it deserves.

          So, for those reasons I think the certification -- you
notice how quickly certification got picked up as credentialize,
although it says certification.  So a little certificate --

          MS. KING:  No.  I mean, as some people here now,
there's a big discussion now about whether bio-ethicists should
be certified.  And the people in the field are studying this.  I
mean, I think it's a revolting notion.

          (Laughter.)

          What it does is it erodes the idea that someone can get
a certificate and then go out and charge money to be a bio-
ethicist.  And that really is the bottom line.  I mean, I can
charge for counseling patients.

          DR. MACKLIN:  And charge to train them.

          MS. KING:  Exactly. I mean, that's the revolting part. 
What's the good side?  What's in between it?

          DR. MACKLIN:  What Eli just said -- and maybe there is
a kind of mechanism that fits in with the culture of medicine. 
Now, I mean, some may think this, too, is Mickey Mouse because
you don't get any guarantee that people learn anything.  But
there are CME requirements and people -- many people take those
seriously.  I mean, if those are treated also and dismissed in a
way -- I mean, I don't know what else to say.  People don't want
to continue to learn things.

          But putting it more under the heading of CME, where
people do have to come and sign in because, you know, -- I mean,
it doesn't prove that they learned anything.  It proves that they
sat that; right?  And maybe they slept and maybe they were awake
but they also can't say I didn't know or no one told me because
they were there in that room.

          I've been surprised.  My institution, my IRB has
actually had an educational program running for several years now
and we've had different levels of attendance at different times. 
The first time we had general education sessions very many people
came.  We learned a few things.  One thing we learned is take the
administrative aspects out and put that somewhere else because
there are going to be a lot of IRB administrators who come and
people want to know how many pieces of paper and when are they
due and all of that stuff and how many copies have to be there,
how long ahead.  Set that stuff aside.

          Then there are people with very specific interests,
such as pediatricians, people who do pediatric research, people
who do AIDS research that have to meet certain other kinds of --
so, we've had some specialty sessions for people like that. 

          The attendance has been reasonably good.  And what has
been gratifying is people are really interested in the ethical
underpinning when they actually hear it.  When they view it as
more forms, more pieces of paper and more regulations, their eyes
glaze over and they have more pieces of paper.  But if someone
mentions what the Nazis did and why do we care about research
ethics and why do we have these things -- and I always begin with
a little bit about Tuskegee and a little bit about Willowbrook
and a little bit about Nazis, and people then see that this has
to do with how doctors treat people and how researchers treat
people.

          So, I think putting it into the educational mode
without the certification and that stuff -- and people don't want
to be educated.  You can't drag them kicking and screaming.  But
it can accomplish both the end of saying I didn't know.  And then
if it's done well, people may actually be interested.

          CHAIRMAN FADEN:  Reed's been waiting.

          DR. TUCKSON:  A couple of comments.  First, I think
that Ruth is really right on when she says -- I know that as a
function of participating on this Committee and by being made
aware of the history I know that I have already removed the
person that was running my IRB and we've got a whole new process,
a whole 'nother level of intensity.

          I do know that I personally am communicating with my
campus that says I, as the president of the university, am saying
this is damn well important to me and it will be damn well
important to you.  And I've learned that that is important that
the person on the top communicates that through.

          I think that I came to that conclusion not with
sanction, not with certification, but just with information, just
as a human being.  And so I didn't have to have anybody to force
me to do it, but I was aware of information, which is an
educational role that I think has to be played.

          I think that one of the ways that perhaps this gets
done then and would be in one of our recommendations, might be
that we might recommend that through the appropriate mechanism,
whether it's the National Academy of Sciences or whatever, that
there be some convening of appropriate leadership of American
universities for the purpose of discussing how to best accomplish
a generally, I'm sure, mutually agreeable goal.

          So that maybe we should not have to think about trying
to figure out all the mechanisms here in isolation but to write
our recommendations in such a way that there could be no doubt
that we are expecting clearcut guidelines, but maybe we do it in
consultation with folk so we put this on the positive as opposed
to the negative.

          However, I think the second issue we must be concerned
about as we put forward our ideas -- and Ruth used an important
word in the contemporary political landscape, this word
regulation.  Now, with the government and the Congress that will
receive our report anti-regulation, and nobody's going to want to
do anything that's going to add to government bureaucracy, I
think that that's going to be very important in terms of whether
or not our report will be received and acted on in an effective
way within the agencies and within the Congress.

          And so I think that perhaps we may have to find
ourselves  moving more in that direction.

          The last thing I'll say is -- and it will be just
counter to all that I just said -- is that I think back and as a
university president, again, what gets my attention.  I remember
that the way we conduct our vivarium, the way that the Department
of Agriculture review, when they will snatch my license in a
minute if we don't meet some very clearcut issues, is an
extremely important way of getting my attention.  And it takes
all the crap out of it.  And those little rats will have their
little cages cleaned, thank you very much, because those doggone
Agriculture people come in there and review that stuff every --
whenever.  And if there's not enough -- so, I'm just saying that
that gets it done.

          CHAIRMAN FADEN:  Well, that goes to the other
recommendations.  What you're suggesting is you can't throw that
stuff out.

          DR. TUCKSON:  Yes.

          CHAIRMAN FADEN:  Let me just move in the other
direction.

          Pat?

          MS. KING:  I want to add a different -- I always see
red when I see certification, so -- I have this -- and it now
relates to the second point, now that we've talked about the
biomedical community and a high awareness of ethics.

          I'm always reminded about how I got started in this
field.  I had no background in philosophy, ethics.  I have a law
degree and it made me more acceptable because I had a law degree. 
And when I teach people who want to know about ethics now, I
don't start with principles of philosophy and all that kind of
stuff.  I start with trying to empower them.  And I think that
one of the things that's been lost in the IRB process is just not
the broader biomedical community.  Also what has been lost is
that one has to have peculiar knowledge in order to be effective
in a setting like that. 

          And we have a requirement of public members on IRB's
for a purpose.  We have never ever really done anything with it. 
And that, to me, is a part of the culture change. I don't think
that one has to have a J.D. degree to ask a common sensical
question if one has lived in the world.  And I take a lot of IRB
review -- not the science review, but the consent process and
people's perceptions of risk, et cetera, not to be a function of
biomedical knowledge.

          And part of the culture change that we're talking
about, I think, has to be in a culture change about understanding
that at this aspect of the enterprise there are knowledges --
that's a terrible word -- that's valuable to bring to the
enterprise and that people who we now ask to sit should be
empowered in ways so that other people pay attention to them.

          The worst thing in the world -- and I've endured this,
of course, as those of you who know me though, this has never
stopped me.  But to be the only person outside of a field when
you're then asked to review something is a very difficult thing -
- difficult position to be in when you risk being put down
because you don't have certain kinds of knowledges.

          So part of the culture change is not that we're talking
ethics.  Part of it is that we're talking about human endeavor, a
societal enterprise.  A society in which biomedical enterprise is
highly valued.  And part of the value, its continued perception
as being valued, is dependent upon the broader community's
continued belief that this is valuable.

          What is being undermined -- that's why you have to have
appreciation for some of that outside knowledge.  What is being
undermined with some of these conflict of interest rules -- I
mean, the reason people have latched onto the conflict of
interest rules is because they sort of sit as a glaring issue
that creates problems of trust and distrust in the broader
community.  You don't get your biomedical funding because people
have suspicions about your motivations, et cetera.

          And I don't know how to get that group, but I don't
want to leave the cultural issue defined in terms of I'm
expanding the culture of the biomedical community, because a lot
of the tension is these are people from the outside who have no
understanding of the biomedical enterprise imposing rules and
regulations on the entire enterprise.  Why don't they just go
home.  Thank you.  Give me the money and go home and let me go do
what I have to do.

          The culture question somehow has to deal with that, as
well.

          CHAIRMAN FADEN:  Yes.

          DR. TUCKSON:  Can we at least at some point in one of
our recommendations, if it's possible to cause the relevant -- a
relevant set of material to be available to those who would like
to do it right because they want to do it right.

          Somehow or another it seems to me the background stuff,
the things -- the curriculum that people are teaching, the things
that Pat is talking about, the things that Ruth would recommend,
that you would recommend, Ruth.  But at some point it's a small
recommendation but I don't know if it's our job to compile such
or to cause or direct or ask somebody else  to do it.  But that
we would have something to say that it ought to include -- this
is a small point but I think it's important.

          Again, if you want to get folks to do the right thing,
make it easy for them to do it.

          CHAIRMAN FADEN:  Right.  That's not a small point. 
It's actually a large point.

          DR. TUCKSON:  And what I find myself doing now is --
and actually, I've already -- I'm asking folk individually.  I'm
getting ready to ask Ruth.  You know, it's like give me the stuff
you think I need to teach our medical students.  Give me the
stuff that I need to give to my newly constructed IRB.  What
would you have them read as a minimum bibliography, and so forth
and so on.

          And so if I'm asking it, others would probably want
that.

          CHAIRMAN FADEN:  Yes.  There's no question about it. 
And I think that's very important.  And I think all of this stuff
is very important.  And that's not here at all in any form, so we
need to get that in there.

          In case people are getting hungry, we should probably
break now.  We're probably in need of food to keep on going.

          We're going to break, come back at 1:30.  Let's come
back at 1:25 so we can really start at 1:30.  I mean, if we could
really start at 1:30.  And we're going to maybe take another half
hour to sort of go at this stuff and then switch to situation 1,
2, 3, 4 from yesterday.

          (Whereupon, the luncheon recess was taken at 12:25
p.m.)































                             AFTERNOON SESSION

                                                                [1:45 P.M.]

          CHAIRMAN FADEN:  It's now quarter of 2:00 and we have
until 4:00.

          DR. RUSSELL:  P.m.

          CHAIRMAN FADEN:  P.m.  Yes.  We have until 4:00 p.m. 
Here's what we need to do, okay?  Now, whether we can do it all,
I don't know, so we'll have to prioritize it.

          It would be nice if we took a quick look, just a sense
of the group reaction, at some of the other Forward Looking
recommendations that are here.  We also, however, have to return
to situations 1, 2, 3 and 4, where we left them yesterday
afternoon.

          DR. GLATSTEIN:  Was it yesterday afternoon?

          CHAIRMAN FADEN:  That was yesterday afternoon.  Three
we hadn't yet gotten to, which is the notification one.  We have
material on that and we really do need to have a collective
discussion.  The people that are working on the notification part
of our charge, both Committee and staff, need guidance and we
need to debate as a Committee what direction we want to take the
notification steps.  And that has to be clearly -- time must
really be set aside for that.

          So, I'm thinking, since it's quarter of 2:00, do people
object to our not having a formal break?  People can get up; the
coffee is there and food is there.  But we're only talking about
going for two hours.  It seems like we can go for two hours and
15 minutes without having a break.

          So, having dispensed with break, it seems it should be
doable.  Maybe what we should do is take only a half hour, no
more, to continue to leaf through and brainstorm about the future
of oriented recommendations.  At 2:15 we will stop and return to
the discussion we had yesterday afternoon.  If for some reason
that discussion does not take up the rest of the afternoon, we
can return to Forward Recommendations.

          Within the Forward Recommendations, Phil, I don't know
whether you're reading to have us take a look at some of the ones
that were directed at research involving soldiers or not.  We
could get that page xeroxed and circulated.

          DR. GLATSTEIN:  It's being xeroxed now.

          CHAIRMAN FADEN:  It's being xeroxed now?

          DR. RUSSELL:  The one I gave you last night?

          CHAIRMAN FADEN:  Yeah.

          DR. RUSSELL:  That's fine.

          CHAIRMAN FADEN:  Is that fine?  So maybe -- the concern
I have is that Phil is going to be in Australia at the next
meeting.  We all had a trip planned years and years and years
ago.  He'll have to miss the meeting next time.  So if we're
going to look at any recommendations that speak specifically to
research involving soldiers it would be a good idea if Phil was
present when we had that discussion.

          So let's spend 15 minutes perusing this through and
then 15 minutes looking at the recommendations which we have not
yet seen, but they're being xeroxed as draft ideas to discuss and
see if this is worth pursuing for research involving soldiers. 
And then we're going to return to the Backward Looking stuff.

          We were involved I think in what was a terribly
important discussion and I hope that our notes will do it
justice.  We had not gotten to two topics that are really
important to get just a sense of the group for, one, still
staying with human subject research.  There are recommendations
on pages 34 and 35 and 36 which gets into accountability,
oversight and sanctions and I don't know whether we can do
anything with them right now other than -- it would be nice to
spark a little debate and discussion about whether the Committee
wants to comment on these questions.

          DR. GLATSTEIN:  I'd like to comment on periodic audits,
IRB performances.  I have no problem, but who's going to do it. 
Who's going to pay for it. And the problem is with what's
happening in the Congress right now with reductions of budgets, I
can't see that anyone's going to be able to afford new people to
do this.

          CHAIRMAN FADEN:  Well, I think there's sort of two
issues.  One is do we think this is an important function.  If we
think it's an important function and it ought to happen, then do
we -- but do we make that recommendation, given the climate.  Can
we think of some other way or can we think of the most resource
minimal way to accomplish the same objective given the current
constraint.

          I'm not -- I understand what you're saying.  I mean, I
don't know how to factor in the political --

          DR. GLATSTEIN:  I mean, we're going in the opposite
direction to what everything else is going if we make this
recommendation.

          CHAIRMAN FADEN:  Right.  On the other hand, you heard
Reed's statement that nothing galvanizes his approach as a top
university administration more than the fact that they're going
to -- when they come to inspect the vivarium, if the rats don't
have their square feet, they don't get their permission to
continue to get animal funding research.

          So, to throw that mechanism out altogether would be
problematic.  On the other hand, you're right.  We're swimming --
maybe we're swimming against -- I don't know.

          MR. GUTTMAN:  We're going upstream.

          CHAIRMAN FADEN:  Thank you.  I always look for Dan when
I'm trying to think of metaphors.  Okay.

          I see Phil, Pat, Henry.  And I am going to be a little
more -- and Lois. I'm going to be a little more like -- a few
comments on this one; let's go to the next one.  Just to get a
sense of the group so the staff knows.

          Phil?

          DR. RUSSELL:  In those instances where there are two
levels of review in place, such as the Cancer Institute and
military for high risk research or greater than minimal risk
research, there's functionally already a way of evaluating the
performance.  And what's probably missing is a feedback to the
IRB.

          The investigator sends it to his IRB and gets through;
goes to the second level of review, doesn't get through; comes
back to the investigator.  And it isn't used to evaluate the
performance.  It may have to come back through the whole loop
again.

          DR. OLEINICK:  Well, it does go back if it's not
approved.

          DR. RUSSELL:  If it's not approved.  

          DR. GLATSTEIN:  It's typically approved with revisions,
subject to revision, so that there isn't a complete circle.

          CHAIRMAN FADEN:  And so one discussion is let's look at
all the mechanisms that are in relation to that and see what we
can add on.

          DR. RUSSELL:  It's a possible mechanism for improving
the feedback to the local IRB's.

          CHAIRMAN FADEN:  Pat?

          MS. KING:  I thought that HHS was initiating its own
review of the IRB process and the review process.  If I'm right
about that, one way to deal with this would be to find out more
about what they're doing and endorse it to answer, in part, a
little bit of Eli's question.  If I'm wrong about it, then you
can scratch this.

          CHAIRMAN FADEN:  I think I know what you're talking
about, but let's not confuse issues.  Let's find out more and
make sure we're thinking about the same thing.

          Henry?

          DR. ROYAL:  Item Number 4, cumulative tracking of
radiation exposure.  I think the benefits --

          CHAIRMAN FADEN:  Where are we?

          DR. ROYAL:  Page 36.

          CHAIRMAN FADEN:  Yeah.

          DR. ROYAL:  I think the benefits to be accrued by that
are questionable and with the resources that it would take.

          CHAIRMAN FADEN:  I will look at where that came from. 
We'll start a dialogue with the originator.

          DR. THOMAS:  Well, I'd like to be in on that dialogue. 
I don't know where it came from.  I don't know who's developing
it.  But I actually think it has some potential if only for
epidemiologic studies.

          CHAIRMAN FADEN:  Okay.  I will try to find, for at
least two of you, will try to find where this came from, but we
can think about it.  I have no thoughts because I don't know
anything about this area that would speak to whether -- I don't
know enough certainly to know whether this is a useful or not
useful suggestion.

          MS. MASTROIANNI:  E-mail will start between Henry and
Duncan and we'll try to coordinate that.

          CHAIRMAN FADEN:  Lois?

          MS. NORRIS:  I'll try to keep this short.  I recognize
that we have to be cognizant of political realities.  But on the
other hand, I think if there are recommendations which we feel
are sufficiently important, that we should nonetheless go ahead
and make those recommendations.  To say that we don't think it's
going to be done or we don't think that it's politically
acceptable at this time is limiting and I don't think we should
be limited entirely by that.

          The other thing is with respect to the on-site audits. 
It seems to me that if we have a system in this country which has
on-site audits for the animal review boards, I think it's
appropriate then that we should give equal consideration to human
subjects.

          CHAIRMAN FADEN:  We'll find out more about that.

          MS. KING:  We don't have a human subjects lobby.

          (Laughter.)

          That's a facetious comment.

          CHAIRMAN FADEN:  It's not irrelevant.  Practically
speaking, we function as that at the moment.

          MR. GUTTMAN:  In fact, we asked this over at the
Defense Department.  They said they're now putting on Internet
all of their animal experiments.  Of course, we said what about
human experiments.  Nobody care about those.

          CHAIRMAN FADEN:  Ruth?

          DR. MACKLIN:  One thing I don't see -- it's not in
here, and one thing that I don't know that has ever been done,
although there is likely to be great resistance to it, is a
monitoring of the actual consent process.

          The federal regulations as currently written permit
IRB's to engage in monitoring activities.  It doesn't specify it
but they do say something like that.  And yet everyone shudders
at the thought that members of a committee -- we're not talking
about whole committees trooping anywhere, but that a member or
selected members of a committee might be authorized to observe
the consent process.

          I'm also not only not suggesting, although I don't
think anyone has suggested, that they go into doctors' private
offices.  But these are -- very many of these are hospitalized
patients.  The IRB is either a hospital IRB or a medical school
IRB of which the physicians are on staff.

          It seems to me not unreasonable, especially in teaching
institutions where many people troop to the bedsides and do
things of much greater indignity to patients in the training
mechanism, like doing pelvic exams on women, et cetera, et
cetera, sometimes when they're unconscious and they're under
anesthesia, seems to me not unreasonable to suggest a monitoring,
a periodic monitoring.  And this can be done openly with
notification to investigators that from time to time someone from
the IRB may show up and announce himself or herself and
acknowledge or identify himself or herself as a member of the IRB
to engage in a monitoring of the consent process.

          And that might include who gets the consent, do they
send a resident in there, "Hey, consent this person."  That's now
a verb.  "Consent this patient."

          (Laughter.)

          Whether it's a research fellow who is presumed to know
something about the research; whether it's the physician, et
cetera.

          So I think the time has come to suggest something like
that.  I mean, with a Committee like that could at least have the
imprimatur of suggesting that monitoring is not an intrusion on
the doctor-patient relationship.

          CHAIRMAN FADEN:  Again, this is an interesting
suggestion.  Monitoring doesn't only -- we're not -- it's to whom
the recommendation is directed and how it's executed.  If it's
done that way, it's different than if the federal government
sends a team of people.

          DR. MACKLIN:  Oh, but that's right.  This -- well,
talking about auditing of records is very different from giving -
- from -- I mean, Ruth, are we asking for any of these to whom
are they directed?  And what I'm suggesting here is that this be
directed to IRB's if we're going to direct anything to IRB's. 
And I think we are about consent.  That this expand the -- not
expand, actually, enable the IRB to do something that is within
its current charge.  We don't need anything different in the
federal regulations, but that an explicit mention that it would
be an appropriate thing for the IRB to do, to engage from time to
time in a monitoring of the process for consent.

          DR. KATZ:  But, Ruth, I think you appreciate as well as
I do that in these situations it's not the dignity of the patient
that's involved but the dignity of the investigator.  I've talked
with a number of heads of IRB's about that issue and all of them
were opposed to it for one reason.  They say that is an
indication that we do not trust the investigator.

          And when I said, look, it's not a matter of trust, it's
a matter that the issue of how to obtain -- how to make
disclosures and obtain consent.  It's very, very complex and we
have to learn about what's going on so that we can improve the
process.  It had very little impact on them because they felt
it's an insult to the moral integrity of the investigators.

          CHAIRMAN FADEN:  That's the argument generally provided
for any kind of monitoring of IRB functions or what investigators
do.  This is a system predicated on trust.

          DR. GLATSTEIN:  Undoubtedly true.  But if it's required
by the funding institution, they'll put up with it.

          DR. ROYAL:  I don't think that having someone stand
there while consent -- which is much of an audit -- while consent
is being obtained, because who knows what the consent -- how that
changes the process.  And it also would be inefficient.  You'd
have to sort of get everyone together at the same time.  But I
think going to talk to patients who have been enrolled in a
research patient and say, "Did you understand that it was
voluntary?  Who got your consent?"  And doing that kind of an
audit would be a good thing.

          The other thing is if investigators were required to
give you a list of the patients that they talk to to enroll into
a study, that would give you some idea of what percent of
patients agreed and did not agree to participate in research
subjects.

          And I think that there are probably some investigators
who have very high recruitment rates.  And every time that they
don't recruit a patient they sort of feel that they've failed in
some way.

          If you actually are logging and keeping track of their
failure rate, if a patient told them no, they might think that's
a good thing because they know that the IRB is then not going to
question them about them coercing patients.  

          So, suddenly this thing which they've always regarded
as being a bad thing and a failure, it's okay that an occasional
patient --

          CHAIRMAN FADEN:  That's fascinating, actually, because
you know the whole review process when you put in for competitive
renewals is predicated on, not only because of the issue that Jay
raised which is can you get your sample approved in the time
frame that's necessary but also the bias issue.  If you have a
refusal rate, then immediately your research is suspect because
you've got some sort of refusal bias.

          So the whole incentive structure, not only the money
but the science side of the incentive structure works against
your approaching this in such a way that you would feel okay
about having somebody say no to you.

          If there's a little way you can make it feel okay
wouldn't hurt, you know.

          DR. ROYAL:  And it doesn't require much effort.  We're
just asking for a list of names of patients and whether --

          CHAIRMAN FADEN:  Maybe not the list of names because of
the privacy issue but some sort of a -- I don't know.  We can
work on it.  That's interesting, kind of interesting.  It's a
very interesting suggestion, as these all are.

          I want to draw your attention, only because we've got
to march on, to the -- in fact, march backward with this.  We're
going to look at particularly notification which we have as yet
left unexamined communally.

          The last recommendation that I want to do is some
directed research involving soldiers that aren't in this package,
because we will lose Phil next week. But I also want to spend
like five minutes on the class of recommendations that don't bear
on human subject research that's in here but that speak to
openness, the other history of a rather big territory to which we
lay claim in this Committee.

          The last one on sanctions -- and I don't know if you
want to discuss this now, but we're going to take a look at it. 
Sanctions are -- it's presented here as the end of a loop.  That
basically you have to have a complete process. 

          It speaks out of our history because, remember, we have
addressed the question of whether we can reach judgment about
culpability about individuals, let alone address questions of
sanction.  And we have said that for lots of reasons this is
really difficult and inappropriate to do.  And the line is but
we've got to do this in the future.  

          In the future we've got to make it clear that it's
possible to draw such judgments and apply sanctions in an
unambiguous straightforward seamless web of obligations, duties,
sanctions, audits, violation sanctions.  That's what this is
intended to capture but it may do it poorly.

          I see Pat and Duncan.

          MS. KING:  I think of this as being very hortatory --
is that the correct word?  You know, involving good people.  I
think it would be a better approach to call attention to the
sanctions that we would find acceptable, rather than short of
like this general call for -- see, I think that people, if you
violate some of these human subject rules, then you don't get
funded again.  That's where it hurts.

          DR. GLATSTEIN:  That's right.

          MS. KING:  And so we should be explicit about what we
think is warranted.  I don't mean give specifics, Ruth, but be
willing to go on record as standing behind strong sanctions or
egregious behaviors and listing the kind of sanctions that we are
talking about because unless we're willing to do that, then
whatever else we recommend doesn't really amount to a hill of
beans.

          And quite frankly, we see a lot of problems out there
now just because the likelihood of being caught and the
likelihood of having something bad happen to you is so minuscule
that people can run big risks.

          CHAIRMAN FADEN:  Well, that's why the notion of some
sort of oversight mechanism, whether auditing --

          MS. KING:  Well, then, the sanctions must be willing to
say you lose your -- it's poor science, I have always thought, to
conduct a research study in a way that jeopardizes the human
subjects.  And you ought to be sanctioned for it that way.

          DR. GLATSTEIN:  Yes.  If you'd refuse any application
for at least a five year period, that hurts.

          CHAIRMAN FADEN:  That's right.

          Duncan and Ruth.

          DR. THOMAS:  Mine was in a similar vein.  I support the
notion of sanctions but I find the language too nebulous. It
doesn't tell me what types of sanctions nor does it tell me who's
being sanctioned.

          Types of sanctions could range anywhere from funding,
an excellent suggestion.  There are some publications which I
believe you already have, but it's not probably uniform across
journals.

          CHAIRMAN FADEN:  We know from Wilhelmine's project that
there are some sanctions already in place and we will be able to
fit this against the sanctions that are there and how much is
known about how frequently they are applied, imposed.

          And, of course, the big hole is if no one knows if a
bad thing happens unless there's a crisis or a controversy and
the connection breaks, that's where some sort of monitoring or
oversight or something has got to be there.  Otherwise, as you
were saying, to surface someone to whom a sanction is
appropriate.

          MS. KING:  I haven't thought this before but there are
two ways to get compliance.  One is monitoring.  And I'd have to
think about this, but the federal government has gone to this. 
The other way is that you place incentives in place to get people
to whistle blow.  That you don't look for your -- in fact,
they're having great success with whistleblowing now because they
pay them money.  I'm not suggesting that.  But part of this is is
there something to work on the other side in terms of getting
those people who've been asked to participate in research, some
way to get them to talk about and to surface their concerns.

          A lot of them are still quite cowed.

          MR. GUTTMAN:  You mean get paid to be a subject and
then you also get paid to blow the whistle?

          MS. KING:  You can't pay subjects.  Are you kidding?

          CHAIRMAN FADEN:  Ruth?

          DR. THOMAS:  Well, let me just finish.

          CHAIRMAN FADEN:  Sorry, Duncan.

          DR. THOMAS:  The other types -- I think there are a
wide range of sanctions open to us.  I agree that one of the
things that we can do is make a catalogue of what's already out
there.  I can imagine various forms of professional
stigmatization, whether it's just bad publicity or actually
involving the professional organizations in stronger measures,
right up to on the line to civil and criminal proceedings.

          And then I further want clarification as to whether --
as to which of these sanctions are appropriate for investigators,
for institutions, for IRB's, for government agencies and so
forth.

          CHAIRMAN FADEN:  Okay.  That's -- so, level of detail. 
I'm not sure how far we can go, but we'll try it, more detail. 
Clearly what we're hearing is the Committee wants to say
something about sanctions with strong language and wants
specifics.

          Ruth and Eli.

          DR. MACKLIN:  In the last few years since the federal
government has gotten interested in scientific misconduct,
there's now a growing track record of sanctions, of denial of
grants, pulling money away from people, saying you can't be a PI
for the next X number of years in violation of one or another --
either regulation or accepted rule of scientific conduct.

          So the current activity and the flurry working through
local institutions, whistleblower -- allegators is what they're
called.  The people who make the allegation.

          (Laughter.)

          The people who make the allegations that scientific
misconduct have occurred -- don't pay them any money.  But that's
a process that has taken place.

          CHAIRMAN FADEN:  Yes.  The allegators.

          DR. MACKLIN:  Now, one consequence of this which is in
a way interesting is that there are now more sanctions and more -
- there are more sanctions imposed and more whistleblowing,
against people who violate scientific misconduct than those who
might violate rules or jeopardize human subjects.

          They're not even jeopardizing the animals here.  I
mean, it's plagiarism.  It's the government's money.  It's
falsification of data and all that stuff.  There's a great deal
of attention to that.

          So, I mean, this seems to be a perfect time to say,
well, maybe we care about people, too.

          Now, one more thing.  And that is, what should be the
institutional mechanism to review this misconduct.  Every
institution now has to have some layer of committees in more or
less compliance with the ORI or the OSI now, the Office of
Scientific Integrity or the Office of Research Integrity. I
forget which.  It was one, then they changed it to the other. 
But some layer of review of allegations of misconduct.

          Now, some people have argued that if you've got some
kind of violation of human subjects research that's not
scientific misconduct.  That's some other kind of misconduct. 
And therefore, -- I mean, maybe human subjects research
misconduct or whatever, but it's not, narrowly speaking,
scientific misconduct which raises the question whether those
bodies that are already in place are the right ones to look at
it.

          The question is are IRB's the right committees to look
at it.  That's not what they're structured to do.  That's not
what they have traditionally done.  And I think I told this
story. I will make it very, very brief.

          In the first year or two that I was on an IRB at Albert
Einstein and some researcher at the institution was doing blatant
-- no one questioned that he was doing things wrong.  He was
doing blatant violations of all kinds of things and people knew
it.

          And the question came up should the IRB censure him.
Not report him to anyone, but just censure him. And I brought up
a little statement.  I was asked to do it because I was new on
the Committee and I was an editor.  But I wrote this little
statement that accused him -- in fact, that was ultimately what
the IRB was going to sign -- that accused him of unethical
behavior and unprofessional conduct.

          And they said, oh, you can accuse him of the unethical
behavior but not the unprofessional conduct.  That's a red flag. 
You accuse a doctor of unprofessional conduct and he's finished.

          And as it turned out, the IRB refused even to censure
him for anything.   

          I tell the anecdote because maybe the times have
changed.  Maybe they have not.  But maybe the IRB is not the
right mechanism.  And since any place that gets research funds
now has to have these other committees in place, that might be --
if we want to be a little more specific than what's here.

          CHAIRMAN FADEN:  They're already there, basically?

          We're going to let Eli have the last word on this and
then I'm just going to --

          MS. KING:  Can I follow up to Ruth?

          CHAIRMAN FADEN:  Yeah.

          MS. KING:  In the consent form discussion which I
missed this morning, what we might consider doing is informing
subjects, which we do at some places, that if they have problems
with what has occurred to them, they can go someplace.  But in
addition, we should inform -- subjects should be informed of the
possible sanctions that can be brought to bear to encourage them
to think about this as being serious.  Because I think that they
will need that.  Most subjects are not going to go do this.

          CHAIRMAN FADEN:  Right.  But if they're told that
actually if you do this something will happen?

          MS. KING:  Right.  So we might want to think about that
next time we take a look at the consent form issues.

          CHAIRMAN FADEN:  Okay.  Eli?

          DR. GLATSTEIN:  Before we move back to the other
subject, I want to address Items G and H on page 37.  And this
has to do with research with soldiers and oversight of
intentional releases.

          It's hard to anticipate when we're going to have
another resurgence of issues of national security, but I would
certainly like to make it not impossible but damn difficult to
see some of the things ever repeated that have been done.

          And I would like to see a restriction in there that
deliberate exposures of soldiers to atomic weapons, atomic
explosions, would require an authorization from the President of
the United States, the highest elected official in the country. 
There may be some reason why he would permit it, but I think it
requires an elected official to approve that.  I don't want to
see this left in the hands of admirals or generals.  And by the
same token, intentional releases, I don't want to see it left in
the hands of someone who is running a nuclear power plant.

          There may be urgent situations where there's no time to
do something, but if there's a planned release, I want to see
some restrictions on there that that just can't be done at
somebody's whim, no matter how well motivated that individual
might be.

          CHAIRMAN FADEN:  Well, the intentional release, that
falls into a whatever right now.  We'll need to work with that. 
We do have something on soldiers.  Why don't we just go to
soldiers right now and add Eli's concern, the discussion of what
Eli has presented to us just now.

          We're all looking at you, Phil, so not to put you on
the spot here, but the notion is -- the suggestion that's coming
out, Eli, you're saying that there ought to be some clear
recommendation that basically says in this kind of a context you
can't --

          DR. GLATSTEIN:  Shouldn't be allowed unless there's a
written authorization by, I think, the highest elected official
in the country.

          DR. RUSSELL:  At the present time, that kind of an
authorization is delegated to the Secretary of the Army.

          CHAIRMAN FADEN:  The issue is not whether there should
be above ground nuclear testing.  That obviously isn't.  The
issue is whether you --

          DR. GLATSTEIN:  That's not our business.  This is about
ordering people to go someplace on a non-emergent basis.

          CHAIRMAN FADEN:  So it's not wartime.  So you're
talking about --

          DR. GLATSTEIN:  Not wartime.  It's not when there's
been a nuclear accident and somebody has to do it and it falls to
the military to do it.  That's not the issue. This is forcing
people, ordering them to attend some atomic explosion --
exposure.

          DR. LEDERER:  Is this only radiation related exposures,
or would you include other things?

          DR. GLATSTEIN:  That's all I have in mind.

          DR. ROYAL:  I'm confused about what level of exposure
we're talking about.  Soldiers get ordered all the time to do
things which have some risk to them. And whether or not you have
in mind that the trigger should be the magnitude of risk that
they're being exposed to or that you really mean that the trigger
should be radiation, per se.

          DR. GLATSTEIN:  I have in mind an atomic explosion, a
non-trivial exposure.

          DR. ROYAL:  Well, but as you get away from ground zero,
you go from a point where there's a high exposure to the point
where you get close to background radiation.  

          DR. GLATSTEIN: I find the business of ordering people
into ground zero or near ground zero, depending on how you want
to define that.

          CHAIRMAN FADEN:  Dan, did you want to come in on this?

          MR. GUTTMAN:  Yeah.  This is probably going to
complexify it, but we've been thinking about this.  And somebody
has talked to Phil and some of the people.  And just a couple of
little points that may or may not be relevant.

          One is, I understand the tests, each test series, was
in fact authorized by the President.  It isn't clear the
President knew or had before him that troops were going to be
marched in.  All of that was public.   We actually found
congressional correspondence with the Joint Committee on some of
this.

          The second point, and this is the one that was a
surprise to me. And General Russell will probably be able to tie
in better.  As it turns out today, surprise, we were talking
about whether the risks, as we look at the atomic vet story, who
was in charge of looking at that set of risks back then.

          And as we've been discussing at great length, you've
got this peculiar situation where some of the folks were
experimental and nine out of 10 were the similarly situated
people who weren't experimental.  And I guess the perspective we
have and the story that's drafted is that the people who could
have called the whistle -- blew the whistle on the risks were
wearing multiple hats.

          They were both the doctors, not only the generals but
the medical people.  Today, -- and Phil, is this correct, what we
were told?  Is that if you were going to develop a weapon you'd
have to do in effect a health assessment for the soldier who were
going to use it.  And we were talking about -- remember that
discussion?  This may seem like a quirk and an oddity but in fact
in some ways since that period the system has now begun to look
at it.

          And Phil, do you remember that one?

          DR. RUSSELL:  Yeah.  There is a very complex system in
place which deals with the experimental development of equipment,
weapons being one of them.  Some of the problematic ones as far
as soldier exposure are things like smokes and obscurants. 
That's a good example because the system or the weapon has to go
through a st of human interface evaluations, which is done by the
research people.  The medical community only gets involved as a
part of that safety evaluation.

          If there's a database available in which the safety can
be evaluated, then that's done by the safety people.  And it
usually requires as part of the safety evaluation a clearance
from the medical community.  There's basically no research
involved.

          If the information is available in which, for example,
radiation, that standards are in place and if there's a source of
radiation in the equipment or if it's a laser, for example, where
there's a substantial danger to the user, physical data and the
physiologic data are pretty much available. But if there isn't,
then there has to be experimentation, some of which may involve
human volunteers.

          But the fact is that there is an incredibly complex
system in place to deal with the safety issue of the new
equipment.

          CHAIRMAN FADEN:  Can we go to the core question?  The
core issue is whether that mechanism answers Eli's concern.  I
mean, that's the issue.  Would it not allow what happened then to
happen again?

          MR. GUTTMAN:  Can i just capsulize it?  Because there
are two steps here.  One of the things I think looks like it
happened back then, either because of the times.  Everything was
happening in a rush and everybody thought whatever, but there was
no -- that the failsafe mechanisms, the risk review mechanisms,
as Phil said, there were may places where things could have been
checked and they didn't work.

          So one is do you today have a risk review mechanism
that can at least find facts if somebody would say, well, gee,
there may be a risk here.

          DR. RUSSELL:  That's a very extensive question.

          MR. GUTTMAN:  And then, too, Eli's question is in an
area that is going to be as sensitive.  And there are so many
players and so many parts of the bureaucracy.  What triggers at
what point what kind of risk or what kind of -- you know, it is
radiation or atomic bombs.  Do you say that can still only be
done with an approval that's non-delegable?  I mean, from the
highest level.

          So, there are two questions.  One, you have to have a
risk review mechanism, otherwise it doesn't really matter.

          CHAIRMAN FADEN:  And then there's a way that they
cannot say that the call has to be made higher than that?

          MR. GUTTMAN:  Right, right.  And is that the way to
fully phrase the question.

          DR. RUSSELL:  I really don't understand your last
question because the issue of exposure to radiations is so dealt
with in the radiation safety issues that I don't see the kind of
problem that might be --

          CHAIRMAN FADEN:  Let me unpack this for the rest of us. 
Phil, is your response to Eli's concern about specific repeating
of what happened in the '50s, it couldn't happen because --

          DR. RUSSELL:  The system is different.

          CHAIRMAN FADEN:  -- the system is different.  And it
couldn't happen because now we have all these standards for
radiation.  

          DR. RUSSELL:  For radiation.

          CHAIRMAN FADEN:  For radiation exposure.  You've got
all these standards and marching to ground zero would clearly
exceed those standards.  And so the risk mechanisms of the Army
wouldn't allow that to happen.

          DR. RUSSELL:  Well, there's a little cultural change,
too.

          CHAIRMAN FADEN:  And cultural change.  That's sort of
what I hear you saying.  And the issue is they exceeded the risk
standards it looks like sometimes in the past, too.  So what's
are the issuances?

          MR. GUTTMAN:  They were waivered.  They're waivered.

          DR. GLATSTEIN:  What's the assurance that there won't
be a return to the previous system?

          CHAIRMAN FADEN:  It might be that if you want something
that speaks to this particular situation, although I don't know
how likely it is that we're going to have that again.  Maybe the
more forward looking thing is to anticipate.  

          DR. RUSSELL:  The fact is we've got a different --

          CHAIRMAN FADEN:  I don't know.  My mind doesn't -- to
get to the waiver questions and to get waivers, you can't waiver
radiation.  Only the President could waive radiation --

          DR. RUSSELL:  We're no longer in the business of
testing atomic weapons.

          CHAIRMAN FADEN:  Right.  We're not now.

          DR. RUSSELL:  Not above ground or not ever, not
anyplace right now.  Hopefully, never again.

          CHAIRMAN FADEN:  Right.

          DR. RUSSELL:  So it's not a realistically addressable
issue in my mind.  Now, are there other kinds of --

          CHAIRMAN FADEN:  Hazards.

          DR. RUSSELL:  -- hazards that are -- and I've mentioned
a whole set of them that the military has come up against and
they've been, I think, dealt with by a very complex bureaucratic
system for evaluating and so forth.

          MR. GUTTMAN:  Let me try -- can I try another way
around it?

          DR. RUSSELL:  Can you get by that?

          MR. GUTTMAN:  Let me try some other approaches.

          CHAIRMAN FADEN:  That's the key question.  I mean,
isn't it the issue that you can get by it?

          MR. GUTTMAN:  Yes.  Let me try a couple of other
approaches here.

          CHAIRMAN FADEN:  Why do we need to?  Can't we just
stick to that question?  Can we find out if you can get by it? 
And if you can get by it, who has the authority to say you can
get by it and is this Committee comfortable or maybe we don't
have the expertise, but we can say, look, somebody's got to look
at the rules by which you can get by it.

          MR. GUTTMAN:  Let me give you an example.

          CHAIRMAN FADEN:  Okay.  An example.

          MR. GUTTMAN:  This may be the real world.  Part of what
happened in the past is in some ways I think quite relevant to
the present.  And the basic institutional questions are laid out. 
And one of the things if you look back in the past is you had --
there were two levels of check going on at the bomb tests and
there was the internal Defense Department where theoretically you
had doctors who were radiation experts who were going to say, you
know, you can't do this.

          Then you also had the AEC and its biomedical experts. 
And one of the things that happened -- this gets to the waiver
and the check.  The AEC standards were routinely waived for the
troop maneuvers.  And in fact, the interesting story is that in
relation to the international standards with our partners the
Canadians and the British, they didn't like what any standards
were.

          So, in other words, the situation, to focus even more
finely -- and maybe this is -- I don't want to use the word
Persian Gulf or anything like that, but you may have a situation
where there's another agency with expertise.  That in these
situations which are as important and as focused and as
sensitive, you may have multiple standards set; right? 

          And so the question is does the Defense Department
become the arbiter of risk in the face of a countervailing
alternative.  What's that balance?  Let's say the AEC is there
tomorrow and says our standard is 3.9 but it's a military
operation.  What happens if the DOD makes a call or --

          DR. GLATSTEIN:  I don't want it to be the DOD.

          MR. GUTTMAN:  Well, I don't want to talk about that.

          CHAIRMAN FADEN:  But that's what Eli wants to talk
about.

          MR. GUTTMAN:  But I'm saying in the real world --

          DR. GLATSTEIN:  I want it to be an elected official.

          DR. RUSSELL:  Let me ask you this.  Who has the waiver
authority?

          MR. GUTTMAN:  These are the questions.  

          DR. RUSSELL:  No.  Who was the waiver -- what's the
historical record on who was the waiver authority?  Who signed
it?

          MR. GUTTMAN:  Well, very interesting.  It looks like it
was a delicate dance of elephants.

          (Laughter.)

          The AEC saying, you know, in terms of -- well, gee, we
really don't want to get into this.  This is political.  But,
hell, these guys are going to do it. But on the other hand, we
look like we're abdicating and we're going to get blamed if this
is a mess.

          You know, it's really internal arguments enclosed --
this was all done in secrecy.  So that's part of the system.

          DR. RUSSELL:  You didn't answer the question.

          MR. GUTTMAN:  Not the President.  It was the AEC.

          DR. RUSSELL:  The AEC had the waiver authority.

          MR. GUTTMAN:  I don't know if they had the authority,
but they did it.

          DR. RUSSELL:  The AEC did it.

          MR. GUTTMAN:  Yeah.  Now, whether they legally did it -
-

          CHAIRMAN FADEN:  A civilian agency.

          MR. GUTTMAN:  Huh?

          CHAIRMAN FADEN:  A civilian agency.

          DR. RUSSELL:  A civilian agency.  I rest my case.

          CHAIRMAN FADEN:  That's very telling, but it actually
also speaks to Eli's question.

          DR. GLATSTEIN:  The concern is what happens when we get
another era of paranoia.  The concern is what happens if we get
into another Cold War and we're more concerned about these issues
than we are at the moment.  I want to put some real restrictions
on that.

          CHAIRMAN FADEN:  All right.  What I think is we need to
do some hard work here.  We clearly don't even have the sort of
backward story set up the right way to do the forward story on
this narrow point.  It's a terribly important point but you're
making it very narrow.  And that's as it should be.

          So, let's focus on -- we'll try to work on trying to
get something that captures the spirit of what you say, Eli.  We
may not all agree about the President, but the idea is somebody -
-

          DR. GLATSTEIN:  I want to put -- and I see an analogy
with respect to intentional releases --

          CHAIRMAN FADEN:  Okay.  Right.

          DR. GLATSTEIN:  -- that could come from nuclear power
plants or something of that sort.  And I want to make that
difficult, too.

          CHAIRMAN FADEN:  Now, the question of whether --

          DR. RUSSELL:  Let me make one point here.

          CHAIRMAN FADEN:  All right.

          DR. RUSSELL:  I think there's a generic issue that who
is responsible within the military system for the health and
welfare and well-being of the service members, and not on the
battlefield but in a broader sense, and that generally is --
who's responsible for feeding them and clothing them and so
forth.  And that kind of authority and responsibility are
invested in the service secretaries.  And that's why you see the
secretary of the service being the approval authority, final
approval authority for all of the high risk kinds of volunteer
issues.  Because it's just part of the culture, part of the way
the services work.

          Fundamentally, the civilian control over the military
extends down that chain and I think Eli is a little bit extreme
there because the delegation of this authority is virtually two
steps from the Office of the President.  And that's --

          DR. GLATSTEIN:  That's not close enough.

          DR. RUSSELL:  Well, that depends on the frequency and
the level of the issues.

          CHAIRMAN FADEN:  Right.  I think that's right.  And we
can't have this be like an every day event.  

          DR. GLATSTEIN: I can't imagine that it would be.

          CHAIRMAN FADEN:  Right.  So the issue is, though, can
you signal -- let me separate those.

          One issue is this issue of where to place the President
in all this, and another is this sort of general issue of what's
in place now, who has waiver authority, how does this work out,
what are the protections.  And we're speaking and thinking in the
context of around nuclear testing but presumably there are other
hazardous contexts.

          DR. ROYAL:  Why don't you think about it in terms of
waiving the usual occupational safety standards?

          CHAIRMAN FADEN:  I was about to do just that.  Right. 
I was about to do just that.  That you have mechanisms and a
civilian counterpart. And you could sit there -- and don't know,
but I have a feeling that there's a whole world out there about
which I know nothing, so I'm hesitating.  All I'm suggesting is
we want -- the Committee needs to deliberate recommendations on
this topic.  We don't have anything before us right now and
that's in large part because we haven't done the work that needs
to be done.

          MR. GUTTMAN:  Well, actually, we are now because Phil
has got this work refocused and we're collecting the standards
and so forth.

          DR. RUSSELL:  There's a huge system of bureaucracy out
there that we don't know very much about.

          CHAIRMAN FADEN:  Well, that's part of the problem.  The
point is we've got to figure out to do.

          We're going to forward.  The IR stuff there is similar
sort of scrutiny.  We've tried to do that as well.  I hate to
push us on but I think discussions in ignorance are often
useless.  And since we have so little information, most of us --
I include myself in this, on this point right at the moment, I'd
like to hold back and let us have a good discussion on this next
time where we've had a background paper or document or something
that can educate us.

          DR. OLEINICK:  Okay.  So we're going to be educated
then not only about the issue of risk, which is one issue, but
the other is the ability of the soldier to volunteer for an
experiment.

          CHAIRMAN FADEN:  Right.  And let's look at these three
recommendations.  

          DR. GLATSTEIN:  Where did these come from?

          CHAIRMAN FADEN:  Well, Phil and I talked about them and
I tried to capture, so I did the typing.  Okay?

          (Laughter.)

          I told Phil I was the scribe.  We had lunch. I told him
-- we talked about it and I tried to capture his suggestions. 

          And you looked at them, Phil, so I guess I haven't
violated them too much.  They're at a much different level than
the discussion about -- take a quick look at it.

          And again, the language isn't at issue here. We're
going to work on the language. But it's these kinds of
recommendations.

          I'll just direct this to Phil -- and we can do this
briefly.

          Could you speak to the middle one?  Because this is
something -- I thought that was very interesting, the one about
the investigative officers.

          DR. RUSSELL:  This speaks to the issue of the interface
between training and human experimentation.  We felt that the way
to assure that the current regulations, which are very detailed,
very comprehensive, and if followed were pretty good, are
followed in the best possible manner to educate the people
involved.

          Well, it turns out that there's a very large community
out there outside of the medical community that gets involved in
these issues.  They have to be instilled in the officer education
programs up through the system, so that's a recommendation that
they embed concerns about human volunteer issues and experimental
issues in the education of officers.

          Most officers go to school at least four times during
their careers, a basic course.  There's an advanced course,
there's an Army staff college or equivalent and a senior service
school, Army War College, Navy War College.  So, you have that as
part of the curriculum of all of those courses, some education in
this with regard to these regulations.  It  would probably do a
lot more than revising the regulations.

          DR. OLEINICK:  It seems to me that if this kind of --
these regulations could be transferred into the civilian world,
it solves our major problem.

          DR. RUSSELL:  Well, we're always ahead, you know.

          DR. GLATSTEIN:  With one proviso and that is if
everyone could agree on what is research.  Because my concern,
that some of the issues of what you and I call research, would
not necessarily be classified that way by a professional military
man.  Not every professional military man, but by some.  And it's
this confusion of roles, again, that makes me very concerned.

          DR. RUSSELL:  Well, that goes to recommendation number
one, which says to ask the secretaries to review their policies
and procedures that speak to distinguishing between research and
the usual business of the military.

          I don't know that if the subject is sufficient by
complex that being more prescriptive and telling them to go back
and look at the issue is very difficult.

          CHAIRMAN FADEN:  I see Ruth.  And I'm going to be real
Draconian here.  Ruth and Henry, and then --

          DR. ROYAL:  I don't want to talk.

          CHAIRMAN FADEN:  Okay.  Ruth?

          DR. MACKLIN:  This is just a question and I apologize
because I forgot the answer when we discussed this once before. 
And it goes to Eli's question.  The last sentence in paragraph 1,
medical interventions that are intended to protect the troops. 
What was the category?  Wasn't that the category under which the
Gulf War -- I can't even remember what the material was that the
soldiers were given, the substance that they were given.

          Wasn't it under this category, medical interventions
that are intended to protect the troops?  And quite apart from
the question of whether it was procedurally correct, would that
count as research or would that count as medical intervention?

          DR. RUSSELL:  Medical intervention to protect the
troops.

          DR. THOMAS:  Even though the intervention is still
unproven?

          DR. RUSSELL:  It was proven to the extent that it could
be scientifically proven without challenging with nerve gas.

          CHAIRMAN FADEN:  It isn't, again -- let's try to be
straight.  There really wasn't anything you could have done in
that kind of time frame.  I mean, I shouldn't say that with such
authority, but it's something that I've looked at.  I've become
persuaded that this was a rock and a hard place issue rather than
a clear example of something gone wrong.  At best it's a mess and
a muddle.

          DR. THOMAS:  And if it can be followed up by an
epidemiologic -- hypothetically, if it were to be followed up by
an epidemiologic study to find out whether it was effective,
that's still not research.

          DR. RUSSELL:  There weren't enough casualties to count.

          CHAIRMAN FADEN:  Let's go to Ruth's question.

          DR. MACKLIN:  The question of whether anything else
could have been done is a separate question from whether it
should have been considered research. I mean, -- or whether it
was an innovative --

          CHAIRMAN FADEN:  I understand what you're saying.

          DR. MACKLIN:  Yes.  I mean, -- and Eli asked who judges
that or who determines that.

          DR. GLATSTEIN:  Yes.

          DR. MACKLIN:  Now, whatever the muddy -- I mean, to
even to say there wasn't anything else that could have been done,
that may be to justify it, but not to answer the question whether
it was research or not.  That is, one might justify a research
maneuver on the grounds that we don't have anything else.  This
is research. Therefore, we're going to be doing it because it may
be the only way to protect them.

          CHAIRMAN FADEN:  I think the question is is it research
when you use an unproven material, regardless, or whether you're
trying to answer a scientific question.  That gets into what's
research, too.

          DR. KATZ:  You can't call it research.

          DR. OLEINICK:  This was not research.

          CHAIRMAN FADEN:  It's not research.

          DR. KATZ:  It was not research.  I've reviewed many of
the documents.

          CHAIRMAN FADEN: It did use an unlicensed product for
that use.  That's true.  So the question is if you count it as
research --

          DR. MACKLIN:  Did anybody have any interest in whether
it worked or not?

          DR. RUSSELL:  It was not addressable under those
circumstances.

          DR. KATZ:  That was really the big question that
remained moot.  In this kind of a situation, should or should not
data have been collected after the event.  It never became an
issue.

          CHAIRMAN FADEN:  I think what we should do there is we
need to look at this.  We need to provide documentation that
these recommendations are generally in line with the sorts of
things the Committee would like to consider.  I think we can
provide to those of us who are not.  And I certainly don't know
what the authority or language or meaning of the term "medical
interventions that are intended to protect the troops" are -- is. 
What does that mean?

          I think it's like language that means something in the
world of the military.  And so for the rest of us, we need to
understand better what that means.  And that I think goes more to
your question than using the example of the Gulf War, because
then we go off on a red herring.

          So let's try to find out what that term means for those
of us who are not familiar.

          DR. RUSSELL:  Let me address one more question that I
think is very important.  There's a civilian counterpart to the
comments that were made by Duncan and Dr. Katz, and that was if
you gather data after the use of a medication or a medical
intervention, is that therefore defined as research and therefore
you have to use -- and I put to you that we have a legal
requirement in the United States for post-licensure surveillance
of all drugs and vaccines.

          Now, -- so you cannot use the data gathering --

          CHAIRMAN FADEN:  After the fact.

          DR. RUSSELL:  -- after the fact, as defining a
research. It isn't.

          DR. KATZ:  Ruth will cut our heads off, so let's talk
about it afterwards.

          CHAIRMAN FADEN:  The reason I'm trying to avoid it is
because I know the kinds of issue it will raise.

          DR. KATZ:  Well, let's make it research.

          CHAIRMAN FADEN:  Look.  I'm going to do --

          (Laughter.)

          DR. RUSSELL:  We will all agree on that.

          CHAIRMAN FADEN:  I'm getting more Draconian by the
minute, so here's what we're going to do.  Okay?  If you don't
like it, you can leave.

          (Laughter.)

          Here's what we're going to do.     

          DR. GLATSTEIN:  Tough lady.

          CHAIRMAN FADEN:  We are not going to talk about this
any more.

          (Laughter.)

          Until next time.

          DR. RUSSELL:  Come on, Ruth.  I'm just getting warmed
up.

          CHAIRMAN FADEN:  No.  What we have to do, even though -
- we got consensus that we got so much else to do and we've got
to get -- what I'm trying to do is just give staff enough of a
feeling so they can take this further so we can go beyond it.

          We have not looked at all, and we need to, at the
recommendations on openness.  They'd be on page 21.  And we'll
spend a short period of time going through those and then we're
going to move to notification, which we didn't touch at all last
time and we have to do something with before the next meeting. 
If we don't exhaust the notification issue before 4:00 o'clock,
we will return to situation 2, which was left in distress.

          But we haven't talked at all about situation 3.  But
before we do that, can we look at the preliminary recommendations
with respect to openness very quickly, and just so the staff can
get the same kind of sense of the group about what looks
promising and what doesn't look promising, as we did for the
research involving human subjects.

          So on the openness business, the first one is the
recommendation that Henry alluded to before lunch, the notion
that a registry be created in which information is routinely
preserved on funded -- approved and funded research, for a series
of purposes, not the least of which is so that if there's ever,
God forbid, a committee like ours again, they don't have to go
through boxes.  And hopefully, technology should make this a lot
easier.

          DR. OLEINICK:  I am certainly not against this
recommendation.  I would like to know whether there is any
thought to going beyond the studies, just those funded by the
federal government, and asking particularly those funded by
pharmaceutical houses.  And there's a lot of human subject
research funded that way.

          MR. GUTTMAN:  The answer is that's what they had in the
'50s, believe or not, and it got abandoned.

          CHAIRMAN FADEN:  Oh, really?

          MR. GUTTMAN:  The Navy pulled some of its.  The
National Academy of Sciences sponsored something that included,
for example, the Damon Runyon Cancer Fund and all that kind of
stuff.

          DR. OLEINICK:  Yeah.  All those foundations.

          MR. GUTTMAN:  All that foundation stuff.  Yeah.

          CHAIRMAN FADEN:  No problem.  We can recommend
whatever.

          DR. OLEINICK:  We can recommend it and somebody along
the line can decide not to.

          CHAIRMAN FADEN:  And yet they probably could say you've
got to drop this stuff off if you want your drug approved. 
Before you get approved, you've got to drop this stuff into the
registry.

          I would imagine there are mechanisms.

          MS. KING:  Well, actually, other than a federal
handbill, you need legislation.  So your recommendation has to be
for legislation.

          CHAIRMAN FADEN:  Good point.

          DR. LEDERER:  Does this registry include the names of
research subjects?

          CHAIRMAN FADEN:  Research subjects?

          DR. LEDERER:  Yes.

          CHAIRMAN FADEN:  I don't know.  We have to think about
that.

          MR. GUTTMAN:  I'll tell you where that goes under,
technically.  The question -- the big -- is in all the studies
not done by direct government workers.  All the data is kept by
the private institutions.  And it turns out there's just no rhyme
or reason as to whether it's kept or whether the government has
access or whether through the government the citizen has access. 
That's separate.  It doesn't cover the drug companies but it
covers the other government funded people, contractors.

          CHAIRMAN FADEN:  Sue's question is whether you want the
names of research subjects in such a registry.  And if you don't,
what are the implications.

          MR. GUTTMAN:  I know.  But what I'm saying is going
through the loop or the chain, if you knew that that set of data
was kept somewhere; right?  That's the first question.  You know,
then you could say this is at Johns Hopkins.  Go to Johns Hopkins
on these subjects.  Right now there's no requirement that Johns
Hopkins keep --

          CHAIRMAN FADEN:  Ruth?

          DR. MACKLIN:  I just wanted to -- maybe Dan just said
it and I missed it, but if as Nancy is recommending this is
something that includes all research since I mean, a lot of the
drugs are going to be FDA approved and therefore come under some
federal purview, is this the kind of information or material that
drug companies are likely to view as proprietary after the fact
and, therefore, make a big stink about?

          MR. GUTTMAN:  It depends on the level of detail.

          DR. OLEINICK:  Yeah.  I would think that would be the
amount of detail.  I mean, --

          DR. MACKLIN:  It may not depend on that at all.  What I
mean is it's not only the trade secret business, but if there are
lots of charges floating around that drug companies conducted
research that had different results or iffy results there in some
of them, raw data or some of the earlier data that eventually got
reported or reported out.  So the question here is whether or not
they're going to claim, on whatever grounds, that the whole
matter, the whole ball of wax is proprietary and therefore
resistant.  In which case the Supreme Court of the United States
is going to uphold it.

          MR. GUTTMAN: There's whole set of questions having to
do with the non-directly related.

          CHAIRMAN FADEN:  Yes.  We will look.

          DR. OLEINICK:  I think that needs to be looked at.  We
might want to actually interview somebody from a drug house, or -
-

          CHAIRMAN FADEN:  We can get staff moving on that and
try to figure out where we stand on that issue.  There obviously
are also redaction options for proprietary information and I
don't know what relief might be found in that kind of a
mechanism.  But okay.  Those are both important points.

          This is the sort of thing we need to hear. People are
generally thinking this is a good idea.  What are your concerns;
what are your reservations; what are the worries.

          Lois?

          MS. NORRIS:  Are you going to look at a response to
Sue's question as to whether it's appropriate to list
individuals?   I think that would require very careful study.

          CHAIRMAN FADEN:  It does.  Because on the one hand, if
you think about our experience, people can't find out.  If you
can't look by people it's problematic.

          MS. NORRIS:  Well, you've got confidentiality problems.

          CHAIRMAN FADEN:  So either way it's problematic and
probably there is a creative solution, but I'm not sure that
we'll come up with it. It's a very important issue to flag.  Very
important issue.

          Other things that come up generally, it looks like
people think this is not a bad idea but it needs development,
refinement, stuff like that. Is that right?  

          MS. KING:  I actually would like to hear somebody talk
about -- like from HHS, which has the largest bulk of -- storage
of protocols, what are some of the problems here.  Because, you
know, a lot of ideas, which I'm sure we're the first people to
think of this idea.  And I'm really curious about what have been
some of the obstacles other than funding.

          CHAIRMAN FADEN:  For?

          MS. KING:  For doing it.  For establishing some kind of
central repository.

          MR. GUTTMAN:  Well, we can check.  Actually, some of
this is now being automated on line, which is happening in some
of these places sort of spontaneously.

          MS. KING:  We don't have to make the recommendation. 
Make the recommendation that what has started go forward.  That's
a different kind of recommendation.

          DR. ROYAL:  But it would be a good idea to talk to
people who have experience with a central registry and find out
what sort of problems they've been having.

          CHAIRMAN FADEN:  And there are lots of central
registries for lots of other sorts of things, so it's both for
people who haven't tried it what do they think are the obstacles,
and for people who have central registries for one thing or
another, what works and what doesn't work.

          So, you know, both would be -- it's not like the world
has never had a central registry for any information.  There's
also kinds of central registries, just not for this kind of stuff
yet.  Those are good points.

          The next one, the next recommendation calls for the
preservation of our collection of all the information and
material that the Advisory Committee staff have sort of
painstakingly accumulated  accessioned is the term.  Accessioned
into our system. 

          So this is a recommendation that calls for the
importance of keeping the entire collection of this Advisory
Committee intact for the historical record.

          Is there any discussion of this, other than the obvious
-- my obvious view that this is terribly important?  Does anybody
--

          DR. GLATSTEIN:  That is be kept as a separate
collection?

          CHAIRMAN FADEN:  Yes.  That's it.  As a distinct,
separate historical -- for obvious historical reasons we already
experience that hopefully other people will want to look at as an
experience.

          Sue, did you want to --

          DR. LEDERER:  I guess I understood that that was part
of the FACA regulations.  Is that not so?

          MR. GUTTMAN:  We're talking about something very
practical and when the collection gets broken apart and, you
know, dissipated or whether there'd be a distinct -- nothing is
clear in today's budgetary world and all these other kinds of
worlds.

          DR. LEDERER:  No.  I mean, I have no objection to it. 
It's a good idea.

          CHAIRMAN FADEN:  So that is a recommendation we
currently have.  I don't think it's a trivial one, by the way. 
It is not obvious what happens to our stuff, so there's a great
concern.

          This next one is for an ombudsman for citizen access to
historical archives.

          MR. GUTTMAN:  Let me just take two seconds on this. 
This is in a world where we all know more regulations and all
that are not something anybody wants.  The basic thrust of this
is that the Committee staff and Committee, I guess, -- clearly
there was a disconnect.  The federal records system was broken. 
There was no connection between the vast amounts of material in
the warehouses and what you have in the front counter.  Anybody
who went through the Freedom of Information Act was just going to
get somebody who turns around, looks at the warehouse and says,
"I don't see a box that's got that label on it."

          Now you're beginning to get roadmaps, as the DOE says,
and we are now aware there are terrific efficiencies.  So, for
example, you've got lots of classified indexes of documents that
you could declassify.  You've got a lot of records that aren't in
the National Archives system, which is relatively well organized
or in record centers, other places that are totally inaccessible
to the public. 

          The question here is what's the best way to use the
public energy that's been identified for the people out there and
the way in which we now can see how things can be locatable
without spending more money but just continue to get things out
in the public.  And sort of what's the mechanism.  I don't think
it's an interagency -- when you go through the Freedom of
Information Act, there's stuff at one agency, so there's no kind
of central person saying, "Well, bits of that is over here and
bits of that is over there."

          So the notion of this is that there's an opportunity,
hopefully at low cost, to bring the public into kind of cleaning
out the records.  It's just tell the public here is this vault. 
We'll get rid of the two classified documents in it and you guys
can go through it.  And so that's the notion.  It's a way of sort
of sorting through all the ick.  Having some mechanism.  We use
the word ombudsman because we're not trying to think of a
committee or commission, just a very practical solution.

          DR. LEDERER:  Is there a precedent for this kind of
significant discussion?

          MR. GUTTMAN:  Well, the closest thing to a precedent
that I know of is this law with the State Department.  You talk
with the person -- there's a committee of historians that helps
the State Department try to get out its basic historical
documents. The CIA, actually, has prevented the publication
basically of a recent volume.  But that's the closest, the
closest thing we've got to independent -- that's not the word I
want to use -- search of documents.

          The full record has yet to be made public.  Basically,
the notion is taking all the energy of all these people out there
who would like to get into these documents but all we can do is
file a Freedom of Information request and wait a decade.  And
we're saying it's not necessary.

          CHAIRMAN FADEN:  Wait a decade?

          MR. GUTTMAN:   Yeah.  We're saying it's not necessary. 
The warehouses can be opened up.

          CHAIRMAN FADEN:  Pat, did you want to respond?

          MS. KING:  I don't have -- I mean, anybody who has any
experience with FOIA knows the inadequacies of FOIA.  So the
justification makes a lot of sense to me.  What I have a problem
with -- and so I can't render judgment.  Unless we've got
something concrete to propose, we're whistling in the wind.

          MR. GUTTMAN:  I know.

          MS. KING:  I mean, this kind of stuff has been around
for a long time.  Now there are two ways we could proceed. One,
there are groups and organizations -- and I'm sure Dan knows them
better than I do, who have some experience with trying to get
information out of the government through FOIA requests who might
be able to give us some ideas for some very specific things to
do.

          I would not be in favor of just a general open-ended
thing unless we got some specific say, even though I absolutely
agree with you.  I want to make this part clear.  I absolutely
agree with you that our stress on openness and accountability in
the government seems to me to carry with it a parallel obligation
to be able to get the information you need.  But I'm so serious
about that, unless we can say something specific, we ought not
say anything.       

          MR. GUTTMAN:  We've got two things here.  One is we can
say quite clearly -- and a little bit is here -- that there is no
reason in the world why Oak Ridge's classified vault should still
be classified.  Either the documents that are really legitimately
classified should be removed and the public should be let in, or
they should let the public into the whole thing.

          And there are places like that, because of this
experience with the agencies, we will have the ability to
identify.

          CHAIRMAN FADEN:  That's a different thing.  That's very
different.

          MR. GUTTMAN:  I understand.  That's different.  But
what I'm saying but then the point is how do you build on that. 
As we go forward, we can identify more and more so that there'll
be less need for this government information bureaucracy.

          MS. KING:  But we're saying something else.  If you
like specify the collective collections that we know about, that
is still backward looking, although we have an interest in the
task.  What we also want to be able to do is say that, thinking
forward --

          CHAIRMAN FADEN:  Exactly.

          MS. KING: -- that we will take care of some of the same
problems.  And so it's got to be specific.  You know, the
likelihood that this will gather dust, all this will gather dust,
is larger than I'd like to think about sometimes.  But on the
other hand, that one little bit says somebody may listen to you. 
So if they look at it, you've got to tell them something
specific.

          MR. GUTTMAN:  You're right.  The answers is we've been
talking and the problem is all these people with these interests. 
There's nobody that's got a particular easy idea.  They say it's
a good, good point.  Sounds like a nice -- what can I say.

          CHAIRMAN FADEN:  Was there other comment on this?

          MR. GUTTMAN:  We'll have to think about it.

          CHAIRMAN FADEN:  Because if not, we've got -- this is
an issue that there's very specific particular collections that
we know about.  That's one thing.  But the forward looking one,
if we could sharpen it up, there's a general sense that sure, we
can speak to this because we have had this experience.  So we can
say, look -- you know, this is not an easy thing to do and there
has to be some way to make this better.

          MR. GUTTMAN:  So just think of a way to put it in some
terms that actually somebody can either say yes or no to.

          CHAIRMAN FADEN:  Right.  That if somebody wanted to do
it, they could do it.

          MS. KING:  That they could do it.  That is the guide.

          CHAIRMAN FADEN:  The point is we've got two levels of
problems.  One is will anybody listen to us.  And the if they
listen to us, is it something they could actually do.  And those
are like the two tests that have to be -- the first one we have
just to hope somebody -- that the force of our recommendations
are powerful enough that people who are well-intentioned with
some authority will pay attention to them.  And then the other is
are the recommendations something somebody who wanted to, had a
will, could actually seek guidance from and implement.

          Okay.  The register of offices of records and other
federal entities.  This gets into some smaller --

          MR. GUTTMAN:  Yes.  These are more along the lines of
what I was saying to Pat.  These are the particulars.

          CHAIRMAN FADEN:  I think we can move out of this
because these are the particulars.  And we also have a general
sense, I think from the group, that we would prefer, as we said,
10 big recommendations than smaller things.

          MR. GUTTMAN:  We can put all these particulars under
one big recommendation.

          CHAIRMAN FADEN:  Exactly.  Exactly.

          DR. LEDERER:  Which is maximizing public access to all
of this historical information as it's generated.

          MR. GUTTMAN:  And we'll give 10 examples.

          CHAIRMAN FADEN:  So that's what we're looking for is a
report that words it that way.

          All right.  Now, with that, if we could switch -- okay.

          Did you want to say something, Duncan, before we switch
or are we ready to switch?

          DR. THOMAS:  You're going backward now?

          CHAIRMAN FADEN:  I was going to notification.

          DR. THOMAS:  I just want to put two other thoughts on
the table before we leave this group.  I don't see anything here
expressly, unless that's what's implied under recommendation 3,
on subject of future -- any future restrictions we might wish to
suggest to the use of secrecy.

          CHAIRMAN FADEN:  There's an openness requirement --

          DR. THOMAS:  Things on declassification.  Maybe it's
here and I missed it.  I don't see it.

          CHAIRMAN FADEN:  Yes.  And there's also a whole section
on classified research.

          DR. THOMAS:  It seems to me there are other points we
might want to make under that broad heading of number 3.  

          The other thing is I don't see anything in here in the
spirit of situation 4, retrospectively, guaranteeing
prospectively the citizen's right to access to the government's
on records on himself or his next of kin in the event that he's
dead.

          CHAIRMAN FADEN:  Good.  Also, I was grumbling.  There
were recommendations on classified research we need to talk about
which, the special subset of issues dealing with what we have
learned about, to the extent to which we've researched, what
human subjects today can still be classified and the oversight of
those and what we want to say about that.  So that will come back
to the Committee, as well.

          I'm sorry to be so directed, but the notification
issues is plaguing us and we really need to air it in full in the
full Committee. So, just to refresh everyone's memory, yesterday
when we left off we had -- we were into the world of human
radiation experiments, the biomedical experiments in particular.
And we had -- the draft, as its currently constructed, identifies
four particular situations, two of which we have discussed
extensively, situation 1 and situation 2, not reaching resolution
but discuss it extensively.

          Then on page 7 there is italicized situation 3.  And
this language, to remind everyone, comes directly from the
charter.  We begin on page 8.  There's essentially a very long --
not long, long-ish memo.  It goes from page 8 through -- let's
see.  Where does it end?

          DR. GLATSTEIN:  20.

          CHAIRMAN FADEN:  20.  On this issue of notification. 
The origin is in the Executive Order in the charter.  The
language is on page 8.  We were specifically asked in our charter
to comment on whether there should be notification of particular
subjects of an experiment or their descendants, of any potential
risk or the need for medical follow-up.  And the context is to
protect the health of individuals.

          So the language, just because this issue has already
come up multiple times, there may be other reasons the Committee
may want to consider notifying people, but the Committee charge
speaks specifically to FERC and we must answer that charge.  We
must address that.  Whether we choose to address other
justifications for notification is up to the Committee, but we
have to say something about this.

          So, looking at this question of protecting the health
of individuals, we started thinking -- and this was a long time
ago, so we may not all remember -- well, how might -- who would
be -- we can't look at every experiment.  We can't pursue every
one.  So who might stand to be at -- most likely to be in this
category of still being able to benefit by some protection of
their health if they were notified today.

          And obviously, the first response was subjects who were
young.  Even when we're talking about studies that went on a long
time ago, many of the people who were older persons at the time,
older, adults, will no longer be living or will be of an age
where they, if they had an ill effect, it has already
materialized and done its damage in most cases.  Which is not to
say you still couldn't have a person who was 30 then be around
and essentially benefit, but when it comes to an allocation of
resources question, we decided to focus on research projects done
in our historical period, '44 to '74, where there's the greatest
likelihood that his protection of health benefit might be
extended.

          So, we identified research involving children and
started a project trying to look at research involving children. 
We identified research involving -- in which fetuses were exposed
to ionizing radiation generally because of some research project
in which their mothers, while pregnant, were exposed.  And so
while we were looking at the issues for the children born who
were fetuses when exposed, we also looked at the pregnant women
themselves to see whether there was any issue there.

          We also -- so those were the two groups, or rather
three groups; children, pregnant women and people who were
exposed while they were still fetuses.

          And then we had the issue of prisoners, the prison
studies.  Because these were young men and because we knew
something about the kind of exposure they had had.  This is the
testicular irradiation studies.  And we got people starting to
work and think, both staff members and Committee members, on this
question of how to understand the charge with respect to
protecting the health of people and to see if any recommendations
could be brought to the full Committee.

          And I don't know how to do this.  Whether we should
have little reports from the different people involved, or how to
proceed.

          DR. THOMAS:  Just to complete that, the fourth group
was the genetic studies.

          CHAIRMAN FADEN:  Yes.  And then there was yet another -
- well, we haven't looked at studies for that.  We asked Duncan
to do some thinking about that part of the charge that speaks to
-- or their descendants.  So the issue is if there are any second
generation issues that would raise protection.  But there we
didn't look at studies as such, but asked Duncan to give us some
thinking about what we would have to consider and what might
likely -- might be a reasonable recommendation.

          So, I don't know exactly quite how to start. I don't
know how many have had a chance to read this material.  You have
here little short reports on each area, each of the four subject
groups, and the future generations question.

          The first one, the first specific one that appears is
children.  We're going to inject back in here -- we should just
start.

          Henry?

          DR. ROYAL:  One of the things that I was surprised at
when I saw this document was the one in 1,000 figure shows up
again.  Because I had thought that at the last meeting that we
had discussed that.  And I had thought that we had come to the
conclusion that that was not a particularly defensible criteria.

          So I guess I need to be brought up to speed about
whether or not that's something we have or have not decided.

          CHAIRMAN FADEN:  The question was raised -- I have no
idea.  I think we need to discuss it as a group.

          I did ask -- I guess through Gary to ask Jeff Botkin
his reasoning.  Please give us his reasoning for the one in
1,000.  And I think the first thing Jeff said is he was only
thinking thyroid kids.  So, he's not suggesting this is sort of
for everybody.

          And his reasoning, I think, is expressed now, although
it may not be adequate, on page 11, lines 13 to 18.

          DR. ROYAL:  Of the 25 to 37 percent probability --

          CHAIRMAN FADEN:  That seems to him to be -- to get a
value judgment in there wouldn't be transferable to anything
else.

          DR. ROYAL:  The fair thing to do would probably be for
me to write some reason why I don't think that this is a very
wise thing to do and to circulate it among the Committee.   

          The wise thing to do that I'm referring to is the one
in 1,000.  I would like to make up a table of the possible harms
and benefits that would occur if you started screening people for
thyroid cancer who had a one in 1,000 chance of thyroid cancer.

          CHAIRMAN FADEN:  You mean in excess, an excess case of
risk.

          DR. MACKLIN:  What are the harms?

          DR. ROYAL:  In the older -- in older populations,
somewhere between 20 or 30 percent of people have thyroid
abnormalities detectable by ultrasound.  So to find your one case
in 1,000 that's going to be your excess thyroid cancer, you're
going to have somewhere between 200 and 300 people who have other
abnormalities of their thyroid.

          So you're going to identify maybe 300 people who have
abnormalities of their thyroid.  Then in order to determine
whether this is a benign abnormality or a malignant abnormality,
you're going to have to do some invasive study, potentially do a
surgical procedure to biopsy the nodule.

          So you have to realize it would confuse some of the --

          DR. MACKLIN:  No.  I'm not confused. I just want to --

          CHAIRMAN FADEN:  Yes.  Go ahead.

          DR. MACKLIN:  -- pursue this. 

          CHAIRMAN FADEN:  And I also hope people will want to
look at Jeff's text on page 12.  The actual memo is in there.

          DR. MACKLIN:  I just want to address the question of
harms and benefits.  The question of notification in order to
protect health has to be distinguished from harms and benefits or
harm/benefit ratio in doing procedures. 

          Now, notification is one thing.  What you do about it
and whether people are prepared to go ahead and undergo biopsies
or whatever else is a second thing.

          So, the question whether people might be harmed by a
biopsy or any other diagnostic procedure is once again a question
of informed consent if it's put properly, of course, that people
then have to decide, do I want to undergo this procedure for
this.

          But the notification doesn't mandate undergoing the
procedure.

          DR. THOMAS:  I disagree.  This is one point that Henry
and I are in clear agreement on and it's one which we have
discussed before.  And I think Henry cogently the last time made
the case why the one in 1,000 figure is, although it has its own
justification which has now been written down for us in this
section on page -- line 13 to 18, it's a justification for the
wrong thing.  And it isn't really relevant to the real issues at
hand.

          And Henry has touched on it.  We discussed it in brief
at -- I think it was the January -- maybe it was the February
meeting.  I'm losing track.  I ripped it out of an old copy,
which I happened to bring along.

          We had three paragraphs that might be worth circulating
again, under the heading of Medical Monitoring, back in the days
when we were discussing that.  And the issues are the same for
medical monitoring as they are for notification.

          CHAIRMAN FADEN:  Sure.

          DR. THOMAS:   So, if anybody wants to refresh their
memory with what the issues are, they're here.

          Now, to address --

          CHAIRMAN FADEN:  Well, let me just step back one
second.  Medical monitoring was not the same as notification.

          DR. THOMAS:  No.  They're not the same. That's what I'm
going to say.

          Ruth makes a good point that to notify somebody is not
necessarily to proceed on to all of these other steps which have
their other concerns.  But there is nevertheless, I think, some
potential hazards, just in the pure act of notification.

          DR. MACKLIN:  Meaning psychological?

          DR. THOMAS:  Yes.

          DR. MACKLIN:  But that's paternalistic.  We don't know
whether people might, if they find out say -- who are you to
decide what kind of emotional harm I might have.  If I was
exposed to something, you could at least do me the courtesy of
letting me know and not decide I'm going to get emotional
anxieties.

          DR. THOMAS:  Well, I just feel like we're in a somewhat
different ethical position.  If somebody approaches us and says,
I want to know, then of course there's no excuse for not telling
them. But if --

          MS. KING:  But nobody's going to approach us because
the whole point is they don't know enough to approach us.

          DR. THOMAS:  I'm getting to it. But then if you out and
you tell somebody who says I would rather not have known, now I'm
not yet persuaded that that's a compelling reason not to go out
and tell anybody, but I am concerned that there will be at least
a few people who won't turn around to us later and say maybe the
vast majority say thank you for telling me, but even if there's a
few people to whom we cause severe psychological harm as a result
of telling that, I don't want that on my conscience.

          MS. KING:  Before you go to the next step, let me say
this.  This is not the only arena in which this occurs.  And this
is not the only time we get this issue.

          The issue is one that can be handled by processes that
have been used in other areas.  There's a risk in not notifying. 
Ethics.  People want to know.  they don't want to be patronized.

          There's a risk in not notifying and there's a risk in
notifying.  Even if you got closer connection to the disease
because of the reasons that you're talking about.

          In the genetic area, as well, what they do is they
start to make provision for how you approach people about trying
to inquire whether they would be interested in knowing or not. 
And that is what I think that we need to be talking about as
opposed to coming down firmly on the side of notification or non
notification.

          DR. THOMAS:  Bingo.  Exactly.  What I'm trying to
communicate is not that we should be simply saying we should
notify, we should not notify, but that we have to do it
consciously so that we have the right mechanism in process.  And
I think the genetic model is exactly what I had in mind.

          Now, you ask somebody first do you want to know.  And
then you have the proper support services in place in the event
that they accept. I mean, these are the kinds of things I think
we need to think about.

          DR. RUSSELL:  We can't do that in this situation, can
you?

          CHAIRMAN FADEN:  Let me just interrupt.  We have two
orders of problems here.  I mean, I don't know whether we want to
go to the theoretical question or the practical issues before us.

          If you take the children one -- and Gary tried to draw
this.  Gary Stern has had the unfortunate task of having to pull
this together in an area that is totally outside of his expertise
and he's done a really masterful job.  And it's been an case of
the blind leading the blind here, again, and I am sort of backing
off trying to figure out how to proceed here.

          So I personally wanted this discussion with everybody
all together because I think we need to have it.  So, let me just
lay out.  One issue is if you want to have some sort of threshold
for deciding whether we should even be in the business of having
this debate about whether to notify people or not notify people.

          DR. ROYAL:  Isn't establishing a threshold
paternalistic?  I mean, --

          CHAIRMAN FADEN:  Well, that's what I was about to say,
Henry.  Let me just complete this.

          You either say you notify the whole world, even if
there's a one in a zillion chance that they might be at excess
risk for something or you say that as a matter of human resources
and public policy we cannot notify everybody; it doesn't make
sense.  And of course, so you get into an issue of a threshold
question. We've got to decide at what point do we even think it's
worth debating whether we should be notifying people or
approaching them as to whether they want to know.  Because there
are costs attached to this that go to the public purse, quite
apart from the sort of human issues that we're talking about
here.

          So then there's the question whether that should be one
in 1,000; whether you could have a general one in the excess risk
case; whether you have to look at a disease condition by the
disease condition and so on.

          Then you hit the threshold for even debating this.  And
then you have to say, okay, well now we get into this; what about
the harms, the follow-up procedures and Ruth's point versus
Duncan's point versus Pat's point.

          There is also the issue here in this particular case --
and this is very important and we haven't yet gotten to, which is
all of a piece because it can make it moot.  That if you look at
Jeff's analysis all the way through and his colleague, Greg
Moskun, what Jeff and Greg do is they go through this exercise.  

          If you look on page 12, lines 7 to 16, and they say,
look, let's assume, Henry, let's just grant it for a moment that
one in 1,000 makes sense.  Maybe it should be one in 10,000;
maybe it should be one in 100,000; maybe it should be one in 100;
maybe it should be one in 50.  But let's for his argument's sake
say let's say it should be one in 1,000.

          He then looks at the numbers and says it looks like we
have 570 people who if they are still alive were exposed to I-131
as children in research projects.  That would meet that
criterion.

          But guess what?  And this is where the next issue comes
out.  Depending on your view about lifetime risk versus how the
risk curve goes, if people have gotten -- those people that would
have gotten thyroid cancer as a consequence or thyroid disease,
odds are already have it.

          That doesn't mean that somebody still out there
couldn't still have it, but if you read that to say there's this
next issue about the question of the latency period between
radiation exposure and expression of an illness.  And if you look
at the fact that for the people we are more like 40 to 50 years
out, the actual likelihood that somebody doesn't know that they
have thyroid cancer is way lower, or that they have it and it's
asymptomatic is way lower.

          So, after all of this -- and this is very contentious
and we need to discuss it -- Jeff's conclusion is on protection
of health grounds -- there may be other grounds -- it doesn't
make sense to notify people.

          That doesn't mean there may not be other reasons to
notify them, but his reasoning, which we need to address.  So if
this reasoning is persuasive in this case at least, we don't have
to look at the one in 1,000 issue.  We don't have to think about
how to notify people.  Because he is basically concluding don't
notify anybody for a reason that's totally different, namely,
that most of these people are already ill and have become
symptomatic and should have received treatment if anybody got
ill.

          MS. KING:  Does health include reproductive health?

          CHAIRMAN FADEN:  I would think so.  Except in this case
--

          MS. KING:  I think that -- well, I think that part we
need to check out.  Because what concerns me is the unknowns.  We
know -- we think we have all the answers now.  We think we know
what all the links are.  But everything continues to move and
we're going to acquire different information -- medicine will in
the future. And the only repository where we're likely to know
that I was exposed at one time to SUS and I have to worry about
it in a reproductive context in the individual.

          And that's why I think that the other big issue is
reproductiveness.

          CHAIRMAN FADEN:  I would like to --

          MS. KING:  So if we could just out what he meant, it
would help.

          CHAIRMAN FADEN:  No.  He was speaking only about
thyroid cancer.  He took the view that with I-131, exposure at
the doses that these children were exposed to, the only
consideration that really loomed as worth addressing was diseases
of the thyroid.

          Now, it's a separate issue whether -- I have no
technical expertise.  So if somebody would tell me that there's a
reason to think that I-131 exposure might be related to
reproductive cancers --

          DR. ROYAL:  There are studies of much larger doses of
I-131, treatment doses of I-131 and then subsequent studies about
pregnancy and outcome that have been unable to show any adverse
outcome in several hundreds.

          CHAIRMAN FADEN: So we can pursue that.  But let's for a
moment table that and let's just look at the issue that we've got
here.  And I want to get some sense of the group about where we
are.

          And I don't need to say that we shouldn't be taking the
larger questions on.  But frankly the pace that we're in, if it's
out for this other reason, let's go on to the next one and look
at the fetus one.

          DR. ROYAL:  The only thing is I would wish that the
logic not necessarily be what the logic is.

          CHAIRMAN FADEN:  Okay.  But I'm not sure that the
conclusion -- that everybody --

          DR. ROYAL:  The conclusion is fine.

          CHAIRMAN FADEN:  But I'm not sure that everybody buys
this reasoning for the conclusion.  So, if everybody doesn't then
we have to go back to your argument, for your reason for the same
conclusion.

          Do you see what I'm saying, Henry?

          DR. ROYAL:  I see.

          CHAIRMAN FADEN:  I want to see if this reason for the
conclusion is persuasive.  Then we don't have to fight these
other battles.  If it is not, then the Committee has to address
these other battles.

          Duncan?

          DR. THOMAS:  Yeah.  I'm not yet completely persuaded
that the reasoning is sound on the grounds that -- and I'd like
the opportunity to go back and review the data recently, but it's
my impression that at least the risk for thyroid cancer is
continuing to rise in atomic bomb survivors, even now, 45 years
after -- sorry, 50 years.  The data is 45 years old -- after the
exposure.

          If that's the case, it may not be true that given that
an individual has not yet contracted thyroid cancer he is
therefore unlikely to in the future, almost certainly the
probability that he will in the future is continuing to decline
as time goes on, but I'm not yet comfortable saying that it has
reached zero.

          For that reason, I think we have to deal with Henry's
point, which is that this rationale that's provided here does not
address Criterion D.  It labels it.  I mean, it points out what
are the criteria.  Well, -- and he gives some details on A, B, C.
But then he never actually comes back and revisits D, which is
the crucial question, in my view.

          CHAIRMAN FADEN:  Would somebody here who knows more
than I do tell me whether it helps to know if you've got thyroid
cancer early or hypothyroidism early?  Does it help?   Eli?  Are
you better off knowing?

          DR. GLATSTEIN:  Oh, hypothyroidism isn't --

          DR. ROYAL:  The way thyroid disease has been
traditionally detected in the past is someone gets a lump in
their neck and then the diagnosis is made and certainly if the
thyroid cancer has not spread at that point, that's much better
than if it had spread.  But the issues, and it's an issue with
many cancers, not just thyroid cancer, is that now that we have
more sophisticated diagnostic tests, we're able to detect cancers
when they're at a microscopic stage.  

          And it turns out that many, many people -- and I do
mean many, many people.  For example, if you look at men aged 70,
maybe 50 percent of them have microscopic prostate cancer.  The
whole issue comes out if you start looking for it, you're going
to end up starting treating people for their microscopic prostate
cancer and it never would have harmed them in their entire life
or their remaining life.  But they're going to now have to
undergo surgery and have all the associated morbidity of being
treated.

          DR. MACKLIN: Can I just ask why?  I mean, where's the
logic in that?  If as you're now saying as a knowledgeable person
there's more morbidity -- no, no.  The treatment is unnecessary
if it's at a late stage.  It's a slow growing cancer.  It's a
microscopic level.  So why isn't the standard of care leave it
alone?

          DR. ROYAL:  Because there's going to be some dividing
line between -- you know, there's a continuum between microscopic
and macroscopic.  And where to draw that dividing line is a
constant debate.

          DR. MACKLIN:  Right.  It's always hard to draw lines.

          CHAIRMAN FADEN:  I'm kind of confused about this
question on the -- if we have this problem, if there is this --
let me step back so I can articulate it now.

          It is acknowledged that the risk doesn't disappear. 
And you're saying there's a suggestion that it's lifetime,
although the risk reduces as the time lengthens past this 10 to
30 year or whatever period   is.

          So maybe the first issue is, whatever the number should
be, shouldn't the analysis be what's the likelihood of there
being an excess cancer 40 to -- 30 to 40 years out.  Because
these studies are at least all 30 years ago.

          So how many excess cancers would be left to be picked
up?  And they turned out to be very small.  Quite apart from your
point, Henry.

          I mean, the prostate issue is one which everybody is
analyzing like frantically in the outcomes world because it's so
fascinating.  And yet I do my own little private survey whenever
I'm at a dinner party with outcomes researchers. I ask them
whether they have their PSA levels checked and they all do.

          (Laughter.)

          Now, I always have -- and that's probably an
exaggeration because my sample is very small.  But the point is
that there's that human desire that even if on a macro level it
may turn out that it doesn't cost out to do this, on an
individual human level if there's a teeny, teeny cancer --

          DR. ROYAL:  I'm not even talking about cost.  

          CHAIRMAN FADEN:  I know.  But if there's a teeny, teeny
cancer, people somehow want to do something about it. Now, they
may be wrong or misguided.  Maybe that's a wrong value.  But we
don't have enough information yet that we can hammer people over
the head and say, if you've got a microscopic thing we shouldn't
do anything about it.

          DR. ROYAL:  But one of the arguments that Jeff makes
for having notification is that it represents 37 percent of all
of the cancers.  But if you start adding in the 15 percent of
people who have microscopic cancer, then it's a very small
fraction.  So then the justification you have to make is if 200
people out of 1,000 have cancer including the microscopic cancer
because they've been exposed to radiation, it's going to be 201
out of 1,000. Do you really want to subject that patient
population  that has 201 out of 1,000 to some kind of different
medical follow-up than the ones that have 200 out of 1,000.

          CHAIRMAN FADEN:  I want to call on Pat.  But what I'm
trying to get out of this Committee now is what does the
Committee want to know in order to make this decision.  And it's
not clear to me that we've got it yet.

          Pat?

          MS. KING:  Well, the first thing I want to know, and
maybe we can ask this here because I can tell you the rest of it. 
And that is what is it in this range of people that we might not
possibly notify do we think it is that they don't know.  Is it
that they were in a research protocol?  Is it that we want to
tell them they were in a research protocol where they were
exposed to radiation -- that involved research and they were
exposed to radiation?

          I mean, I need to start at the beginning.  What is it
that we think these children don't know?  Do we think that they
don't know they were in a research protocol?

          CHAIRMAN FADEN:  We have no idea if they know or not.

          MS. KING:  Well, I think that Ruth is right and we
ought to keep the question of notification separate from what is
coming behind it.  Because my way of thinking about this is today
we make assumptions that people know that they are involved in
research protocols.  That's what the consent process is supposed
to be about.

          We make assumptions -- you notice I'm careful.  I'm not
saying they know.  I just say we make assumptions that they have
been told about the risk of participating in the research and
they have some awareness of the risks.

          So, today, we proceed on these assumptions that people
have this knowledge.  So if anything comes up in the future they
will have to make certain kinds of these crazy decisions or sane
decision or whatever that we're now discussing.

          My first question is why can't I put the people that I
can detect or find on the same footing as somebody who would
participate in research today?  This leaves aside all this
information about what the risks of the disease are, what the
this, what the that and all this kind of stuff.  That goes to the
question of money you're going to spend, to me.  Whether you're
going to spend any money on medical monitoring or medical follow-
up.

          And so I can't escape the theory.  If I had been in a
research protocol as a child and I had been exposed to radiation,
I quite frankly am not interested in you all's one in 1,000.  I
would like to know that I had been in such a protocol and that I
had been exposed.

          Now, if you want to tell me that the exposure is not
dangerous in your view, dah da, dah da, dah da, I'm willing to
listen to all that, too.  But I would want to know.  There are
people out there who would not want to know.  I think that that's
right, too.

          Now, I want to know why -- what are the objections to
telling them without getting into medical monitoring, what
anybody who participates in research would have a right to know
today.

          DR. THOMAS:  The difference is that you've already done
it to them.  Remember, I'm not saying that you shouldn't tell
them.  But knowing that there possibly are a very small
percentage of people out there to whom these things have been
done that don't want to know about it, then I still have a
problem trying to figure some way of telling the 99 percent of
people who do want to know without harming the one percent that
don't want to know.

          If I could figure a solution to that problem, I would
be all for it.

          DR. MACKLIN:  But wouldn't the ones who do want to know
be equally harmed if they knew that there was information out
there and that you were not telling them?

          DR. THOMAS:  On a net benefit basis there's clearly
ways to tell everybody.

          CHAIRMAN FADEN:  All right.  Let him explain what the
problem is.  There is a problem and it's a human problem and it's
a practical problem and it's a economic problem.  In most of
these studies we don't know the names of these people.  We don't
know who they are.  It's going to take a lot of work to find out
who they are.  It's going to take a lot of effort to find out who
they are.

          So if we have -- and we want to do this, but I just
want to lay out what's at issue.

          In principle, Pat, I think you're right.  The problem
as a practical matter is that --

          MS. KING:  It's not a practical problem.  And you've
answered in part, as far as I'm concerned, your question.  And
that is, if you have to make a cost/benefit judgments, which is
what you're talking about, the starting point is, for me anyway,
those people for whom we have -- when we have come across names. 
If we have information about them in the course of our work where
people were exposed and we feel that they may not be aware of it,
then my own view is that they should be notified.

          The incremental cost effort it would take to search for
people to notify -- and that's a different thing, so we ought to
specify what notification means. Sometimes notification means you
tell them or have tried to find them.  Some means you have to go
find them, you have to go find the names and then go find them to
tell them.  And that may require some highest stage of effort to
protect.  So you want a showing that says we have a stronger
reason for expending this amount of money to go out and now look
for --

          That is the approach I would take.  I mean, because
part of what we're deliberating here is how to think about this.

          CHAIRMAN FADEN:  Right.  And we were starting at the
opposite end. And maybe that was my mistake.  I was starting with
the charter, where the charter gives you what would be arguably
the strongest justification for expending money to find out who
these people are and locate them.  And that is, if you could
still offer the benefit of some kind of protection of their
health, either preventing cancer, which is unlikely, or an
illness or more likely getting early treatment, improving quality
of life, whatever.

          So that was the strongest justification.  And going the
other way, your reasoning from the opposite direction.

          MS. KING:  I'm reasoning from the other end because as
always you know I think that we need to know why we're doing
things.  And part of it is to reaffirm what lies behind even
thinking about notification from the very beginning.  And it's
always -- it is not always to prevent a disease because using
that as a basis puts it into an arbitrary time frame in the sense
that the judgment that you make is based upon current knowledge,
the best you can do at the time.  But we all know that that is
exactly what that is and there may be other reasons for
notifying.  There may be reasons for not notifying.

          So I always start with the case and then let it drop
off as these other considerations come into existence.

          And it may be that if we started that way, we really
wouldn't have very much left.

          CHAIRMAN FADEN:  Which way?

          MS. KING:  If we started moving down -- how many
people's names have we come across in the records.  And have we
moved -- have we identified any possible diseases or connections
where people might still be alive?

          CHAIRMAN FADEN:  Well, that's -- I mean --

          MS. KING:  But it would answer these disturbing issues
going around the room in the background when we're talking about
we're at cross-purposes in our discussion.

          CHAIRMAN FADEN:  There's a way to put the discussion
together, which is to say, look -- and I see Reed and Henry.  One
way is to say, look, we have this morass on this protected health
business; the numbers, the crossovers, whatever.  

          If you went to a pure autonomy basis, kind of an
argument, the one that you're floating, and you try to combine it
with the public health whosy-whatsy, there is a happy coming
together, which is it happens to be that people who are most
likely to be still alive are the people we're talking about in
the first place anyway.  

          And you simply say, let's bag this whole thing.  Let's
notify the 800 people that all totalled fall into this category
of people who were children and fetuses at the time they were
exposed.  They're most likely to still be alive.  We can't do
everybody, even if it's a reasonable slice into it as possible.

          The justifications are both that we would like to honor
everybody by letting everybody know that it's an overwhelming
task and we can't do it, we have another agenda, which is these
are people who can still use the information.  Maybe the best use
of that information is to ignore it.  But put it together and
say, okay, this is -- that's a strategy that puts the two
together.  We are not talking about thousands of people in any
event.  

          There are -- in the children, the case of the children
study, 607 of them, in the case of potential children.  Oh, no. 
It would be more than that.

          I'm sorry.  You're right.  These -- it would be all the
children, but it would be all the people who were children.

          MR. GUTTMAN:  But basically, just to get to the
practical, though, there are a couple of populations  like
Vanderbilt, obviously, which a large -- where at one time there
were lists of names.  Maybe there are still.  That's a question. 
In most of the cases, it's from journal articles, so that at the
best you would be doing is going back to the university or the
researcher --

          CHAIRMAN FADEN:  And say, "Do you have the names?"

          MR. GUTTMAN:  Presumably -- the situation we have in
this whole loop situation is presumably most of these cases there
are patient files in hospitals but they're not linked to whether
or not anybody was in an experiment.  And if there is a patient
file, if there's no consent or if there's no notification that
somebody's in an experiment in the first place, then it might be
separating at birth in terms of the connection.

          MS. KING:  I understand.  And I understand what Ruth's
was, too, but on the court it looks different and has a different
tone and it doesn't sound as though you only notify when there's
health interests, which I think is the critical difference.

          We were also saying where there's something out there
that we haven't uncovered yet and there is data or there are
names, unlikely, that the desire is to notify or at least inquire
whether they would like notification.  That's a different kind of
-- that's the only reason I did it the other way, Ruth.  And I'll
shut up now.

          CHAIRMAN FADEN:  Reed and Henry.

          DR. TUCKSON:  Let me just ask actually Henry or Duncan
if it matters.  If it was possible to send a notice to a person
who's name we knew for sure was studied and be able to say to
them, we have information that suggests you might have been, if
you would like to know more about that, you can do the following.

          In other words, if there's a way that we could fashion
it such that the individual would have some opportunity to decide
to want to know about it, if you say it to them in a way that
doesn't give it a certainty that you have been, it's just a
likelihood that you might have been.  Leave it open.  And then
give that person the choice about whether they decide to know or
not know.

          Putting them in the same category, say, of somebody
who's -- you know, again, with a disease they would get --
Parkinson -- they'll get something when they're 80.  And whether
or not they have gene, you can decide whether you want or not
know whether you have this gene or not.

          DR. THOMAS:  I think I would be quite comfortable with
that situation.  What I don't want to have happen -- that's why I
keep making these points, is I don't want a letter to arrive at
my desk saying your dear mom did something really foolish to you
when you were a kid. She enrolled you in this stupid study.  And
as a result of this, you may be at increased risk of some disease
for which there's no cure.

          We can check you out and tell you whether you have it
now and make you dread it for the next 50 years, but as a result
of the fact that you're going to get this disease, you know, your
insurance coverage has been dropped and all these other horrible
things are going to happen to you.

          I mean, that's what I'm -- I'm making a separate case.

          DR. TUCKSON:  Okay.  But do it the other way. 

          DR. THOMAS:  But if you did the way you propose, you
would give the person the option.

          DR. TUCKSON:  Right.

          DR. THOMAS:  I actually posed this question to Cooper
Brown yesterday or the day before because he had raised it in his
public testimony. And he said, well, we actually took a survey of
our membership.  Now, admittedly, his membership is not
representative.  These are the people who already know that they
are members.  So it's not quite the kind of data we need to
resolve this question, but at least it's some data.

          He says, our membership wrote back to me.  The vast
majority of them would like to know.  They were glad to have been
informed.  So that makes me feel a little bit better.  But I
still continue to worry about that small minority of people.

          DR. TUCKSON:   So the answer, -- I mean, I'm just
trying to make sure I understand.  And maybe Henry can.  If you
write it to them such that it is not given with the degree of
certainty, it is given that we have information that suggests you
may have been exposed to such.  We don't know for sure.  We will
do nothing unless you come to us and ask for more information and
track this down.

          You may be very comfortable in never knowing.  There's
no obligation for you to ever do another thing.  We won't do
anything unless we hear from you.

          DR. THOMAS:  What you've essentially done is describe
the paradigm that's used in genetic notification.

          CHAIRMAN FADEN:  Let me point out -- let me just ask
Dan.  How many people's names do we have, roughly, names of
subjects, before we get into too --

          MR. GUTTMAN:  In the children area, I don't think many
other than the ones that are in the Vanderbilt case and are known
to people.

          CHAIRMAN FADEN:  In general.  This is across the board?

          MR. GUTTMAN:  Sporadic.  I mean, we have lists of
dozens of TBI patients from the 1940's.  It's random.  We've got
assorted random lists.

          CHAIRMAN FADEN:  I've very sympathetic. I just want us
all to understand what we're doing here in terms of -- we might
have the names.  We have no idea where these people are now in
many cases.  And there's an effort that -- I don't know how many
names.  We have 100 names?

          MR. GUTTMAN:  No.  We have many more than 100 names.

          CHAIRMAN FADEN:  Do we have 1,000 names?

          MR. GUTTMAN:  Probably more.

          CHAIRMAN FADEN:  It's important.  We're trying to
figure out what we're dealing with here.

          MR. GUTTMAN:  I understand.  

          CHAIRMAN FADEN:  Not children, just overall.

          MR. GUTTMAN:  We have more than 1,000 names.

          CHAIRMAN FADEN:  I'm just trying to get a sense of
what's happening.

          MR. GUTTMAN:  Let me try the other problem, though. 
The other problem is that if you wanted to do it, let's just
focus on children.  You know where these things took place.  At
the least you could go back to those institutions or the
investigators.  Some further effort with some further success.

          DR. TUCKSON:  But what I'm hoping -- and I understand. 
I think I understand what you're doing and I think that I'm
influenced by Pat's point, if I understand some of the
implications of her point.  And that is, we have already raised
the ugly monkey.  

          Now, whether or not practicality will permit you and
how you deal with the practicality of the cost benefit issues,
the one thing for sure is that in the record of our deliberations
is we raised the question.  And the question then becomes how do
we resolve it intellectually, first. 

          Then, secondly, gets to practicality.  We may decide
that -- let's say we may decide first that it's important
philosophically, ethically to notify, given the following
caveats.  Secondly, we decided the cost benefit of doing so is
impractical, therefore, we decided not to do it.

          But while I appreciate the practical point, I don't
think we can evade.  Once having raised it, we've got to deal
with it.

          CHAIRMAN FADEN:  That's what I'm trying to do.

          DR. TUCKSON:  Well, I thought you were trying to
basically say --

          CHAIRMAN FADEN:  No.  What I'm trying to do is figure
out -- see, I think there's several levels of practical.  One is,
okay, if we took the strategy that -- we had the general
principle that people should know that they were subjects of
research.  We don't know whether anybody was or wasn't but it
seems reasonable at the very outset to presume that people who
were children and fetuses are less likely told at the time that
they were research subjects, just as in today are less likely to
know that than someone who was 30 or 40, although they may not
have known either.

          So that's -- yes.  You start to build up the arguments
for why you're zeroing in.  This is the multiple arguments for
landing on the same people as the people where you might want to
say we can't.  There is limited resources so on whom would we
want to concentrate if we were going to do this.  And there are
sort of multiple arguments coming together.

          Henry, and then Eli.

          DR. ROYAL:  I just want to make certain that my
position has been stated clearly.  The statement that's on the
piece of paper here regarding notification in order to protect
the subject's health, and that was the issue that I was
addressing.

          I personally would be in favor of notifying people
whose names we have and that we can notify.  I think that we
would have an obligation if we notified those people to let them
know something more than just that they were in a radiation
experiment.  That we would have to make some recommendation to
them or give them some information that would allow them to know
whether or not they should have anything special done because of
the fact that they were involved in a radiation experiment.

          So I think that we're going to have to be prepared to
do that.  I mean, just to -- I would be very much against
notifying people and then having them go to their family doctor
and perpetually get misinformation.  So I think the notification
is tied in with an obligation to notify them about the
circumstances of the experiment.

          CHAIRMAN FADEN:  If we know them.

          DR. ROYAL:  Well, we know --

          DR. MACKLIN:  Well, you know something.

          CHAIRMAN FADEN:  Whatever we know.

          DR. ROYAL:  I can tell you that we know a lot more than
family doctors are likely to know.

          CHAIRMAN FADEN:  Yeah.  Okay.

          DR. GLATSTEIN:  There's precedent for this.  I mean,
realistically there's the experience of Michael Reese Hospital,
which is not necessarily an experiment but a planned form of
treatment that they used to give kiddies with radiation to reduce
the size of thymus gland at the time of birth.  And once they
recognized -- it came 20 years later -- that there was a finite
risk of malignant disease associated with that, the institution
that delivered the treatment tried to chase down as many of the
survivors as they could, get them to come in for follow-up or
urged them to see a physician if they had moved away. But the
onus was on the place that delivered the treatment.

          And I think that that's the only way that it can really
be done effectively.  There should be a list in those
institutions.  I don't think it's our obligation to chase down
every list of people who have ever received radiation.  The onus
should be on he institution to do this and check that out. I
mean, that's the way it's been done and I don't see anything
wrong with it.

          DR. ROYAL:  But I think the issue that the Committee
has to answer is if we have a name, how are we going to notify
it.

          DR. TUCKSON:  Or do we push and encourage in very
strong language and say that as an ethical matter it is our
conclusion that every institution that conducted such research
has an ethical responsibility to go through their Rolls.

          DR. GLATSTEIN:  Yes.  I would say that.

          DR. TUCKSON:  And will find those folks.  If that's
what we believe.

          DR. GLATSTEIN:  Do as much as they can.

          CHAIRMAN FADEN:  Do we believe this, given the
radiation research project that was conducted from 1944 to 1974?

          DR. TUCKSON:  The institution has the moral right --
responsibility, to go back and do that work.  That starts to get
at mechanism.  It shouldn't be a government apparatus, perhaps,
to do it.

          DR. GLATSTEIN:  Yes.

          DR. TUCKSON:  That's an interesting way to solve the
problem but it still -- but we still haven't decided whether you
should opt to do it.

          I'll just tell you this.  Pat, I don't know.  I'd be
interested, Pat, in your view on this.  I know -- Duncan's point
I really do appreciate.  I appreciate what Henry is saying.  I
mean, I'm an African-American.  Surprise.

          (Laughter.)

          I'm going to be really doggone honest with you.  Our
experience in this country -- and I don't think, by the way,
there's any homogeneity among the African-American community on
this either, so I want to be real clear about that.  But black
folks, most of the folks I know would be pretty damn mad if the
United States Government did some stuff with their kin and then
somebody made a decision that said, well, it was too much -- for
a whole lot of other reasons, you don't even have the opportunity
to know because of a whole lot of other complicated -- look, I'm
tired of that.  And I'm going to tell you.  It will be real hard
for me to go see my momma and my folk if I sat around this table
and said, well, it was too complicated for them to know.

          And people who have been poor, prisoners -- I mean,
it's just rough to try to get past that one.

          DR. MACKLIN:  This whole discussion has been cast in
terms of risks and benefits, possible harms and wanting or not
wanting to know some of the harms that could come from the people
who don't want to know.

          The other analysis, and I don't think Pat used the
word, but it's what she and I have in mind here is whether people
have a right to know.  And when people have rights, sometimes the
exercise of rights actually results in some harm.  There's not a
perfect fit between having rights and having benefits that accrue
to those rights.

          So we haven't yet discussed whether or not -- but I
think Pat was going very strongly in that direction in making the
analogy with present research subjects.  If we could agree -- I
don't know if we can in two seconds, but if we could agree, it
might be worth just a straw vote, on whether or not people have a
right to know whether they were subjects of experiments in the
past, then we don't totally dismiss the question of whether there
might be harms, but we have a very different take on it.  We
don't sit around weighing.  Because in order to override a right
you need some very strong evidence of likely and probable harm
that would overcome the right.

          So, if anyone wants to put forward -- and I'll be glad
to do it.

          (Laughter.)

          People do have a right to know if they were in
experiments.  That doesn't answer the question of whether some
people might be harmed by being informed but it puts a very
different cast on the discussion.

          MS. KING:  And it also doesn't answer -- it does not
carry the necessary implication with what others must provide and
give in order to be able to exercise your right.  In fact, that's
one of the big issues in this country and that is lots of us have
lots of rights and very little wherewithal to carry them out. 
That is a fact of life.

          But I quite agree with Ruth and I am not advocating
spending a lot of money trying to locate people.  I do think,
though, that it's an important principle to have out on the
table.  And I think if we would be like philosophers -- and I'm a
lawyer, remember, so this isn't perfect.  When people think about
rights they often think about corollary duties.

          So, Henry -- I mean, not Henry, Reed's idea about
having institutions think about having moral obligations, which
may resonate with some institutions more than other institutions
is worth saying, even if we don't say somebody should pay us, a
law to make you do it, because some of those institutions will in
fact take their obligations seriously, but some institutions it
won't be as onerous as it will for others.  And some will try to
do the best they can do.

          And I would want to facilitate that or foster that. 
And I think that's important.

          Now, when it comes to -- when you told people what is
theirs and you get to the point of what can we do for you after
we've told you something was yours, I think where we started is a
real appropriate set of considerations, which is the hard
question for the Committee.  Are there any people in any risk of
disease that we can think of, based on the work that we have
done?   And thyroid seems to be the only candidate that we've
come up with so far where we would be willing to do something
more than that.  Where we might be willing to offer either a
greater search -- that's one way of looking at it -- or to offer
a greater benefit, some kind of follow-up or health examination,
if that's what we'd like to recommend.

          But I like it like that.  Then we can quarrel about the
--

          CHAIRMAN FADEN:  I'm just trying to lay this out so we
can tell where it's going and understand where the discussion is
going.  And I understand that.  So if we're arguing that we want
to acknowledge that former subjects of research -- and for what
it's worth, I want to get clear.  Are we now thinking exclusively
of human radiation research?  Because that's all we're talking
about.

          Okay.  This is another one of these things that will
reverberate potentially.  People have a right to know whether
they were research subjects or not.  And we don't know whether
these people do or not.  We don't know if they know or not, for
all the same reasons that we've been talking in situation 2 about
a presumption favoring government culpability.  The guess is that
some of them probably didn't know.  And certainly the children,
the people who were exposed as fetuses don't know.  So we say
there's a right to know.

          But you're also, though, not saying yet what the
Committee would recommend by way of who and with what level of
effort people are now obligated or have a duty to assist people
in the exercise of that right.

          MS. KING:  I'm saying that.

          CHAIRMAN FADEN:  Okay.  That's what Pat's saying.  So
Pat's saying we can have a position that says people have a right
to know without necessarily saying that there's a strong duty on
the part of somebody to make sure they find out.

          MS. KING:  I think we do that all the time.

          CHAIRMAN FADEN:  Okay.  I just want -- then it becomes
-- because the reason I'm saying that is because eventually we're
going to get back to where we started, with some nice additions
like tell the institutions insofar as possibly they can, try to
find the people.  But they're going to seek guidance.  They're
going to say, well, you know, just anybody?  Any research
project?  Or -- we have limited resources and can't track down
everybody.  Can you give us some guidance as to where it would be
most appropriate for us to put our resources to try to locate
people.

          I mean, you can see this sort of dynamic operating if
you just endorse the principle but then have no strict, firm
views about how far people need to go to assist other people in
respect to that right.

          DR. MACKLIN:  This is all kind of -- it's like the New
Yorker's view of the world.  It's all institutional centered. 
Part of, I think, what's implicit in what Pat is saying is that
sometimes people know darn well what they want to know, but
they're told by the institution you don't have a right to get
this information.  It's their patient files with the detailed
history they're legally entitled to.  That's one thing.  But
suppose it's Dr. So-and-so who has notes.  So that there's a lot
of this which is self-enforcement.  And that's the gap.

          MS. KING:  Thank you.  That's exactly what I feel.

          I mean, it sort of like goes back to the discussion
about animals.  You know, this Committee and the federal
government can't do everything.  Sometimes you have to make it
possible for other people do to things and the animals versus
humans was a good analogy for me because it shows you what the
power from the outside has done.

          DR. GLATSTEIN:  Well, maybe a lot of those institutions
faced with a potential lawsuit would be very willing to do a
simple diagnostic procedure.

          CHAIRMAN FADEN:  Can I relate this to the -- can we try
in the last five minutes we have left to try to connect this
discussion to the responsibility under the charter, which was to
indicate whether anybody should be notified?  Which is different
than saying that somebody is supposed to take some assertive
steps to find them.  Okay.  Because I don't think it answers that
problem.

          All we're saying is people have a right to know and
reasonable efforts should be made to try to -- no roadblocks
should be put in the way, first of all, of someone trying to find
out if they were research subjects and they should get assistance
from institutions.

          Secondly, reasonable effort should be made in
institutions who have been notified that they have to conduct --
or human radiation research has been conducted, that they should
try to find people.  There's still the issue is there anybody out
there and by what criteria, where an active effort has to be
made, ought to be made, to find them or not.  Are we just going
to just drop that and say we're going to take this other
approach?

          MS. KING:  I would not drop it.

          CHAIRMAN FADEN:  Okay.  So we're back to -- we still
have the issue we started with.

          MS. KING:  And I think that the provision of a  health
benefit which is why it's in the charter and why the charter
doesn't have this other stuff, is a reason for requiring more,
given the whole -- where we're going.

          And the issue I can't resolve, because it's where I
need Duncan.  When I say I couldn't resolve it, I can resolve it
and get some more information.  It's where I started to need to
hear again Duncan and Henry talk about how to make connections
between what has happened to people and what kind of likelihood
of them having an increased risk.

          And I actually think that's complicated, but if I heard
them, I'd have some guidelines.  Because then you would be able
to assess what it means, I think, to have declining likelihood
that you're going to have cancer.

          And my other question that I need an answer to is --
and Henry answered it, I think, but I just want to make sure it's
true for other diseases. And the other thing that's worrying me
is reproductive health, if we've got cases where there's
something other than the he mentioned.

          But I'm willing to take a crack at that.  Make a
decision about that.

          CHAIRMAN FADEN:  Duncan has -- we're at 4:00 o'clock
and we obviously have advanced the discussion of notification but
not in the direction that perhaps was originally envisioned.

          DR. THOMAS:  Well, no.  We've advanced it a lot.  I
mean, we've gotten consensus that there is a right to know
whether you're a participant in a research project, and agreement
that that right should be -- does not necessarily carry an
obligation to tell.  And that any program to inform a person that
they're a research subject should be done in such a way as to
respect the rights of those who would prefer not to. know. And we
had a very practical suggestion.

          CHAIRMAN FADEN: I would just change the middle of your
summary, Duncan. Which is not that there's not an obligation to
tell.  There's an obligation to tell someone.  There may be
limits that are practically put on how far, how much effort, or
how far someone has to go to seek out.

          Certainly if you are asked as an institution, "Was I a
research subject?" you would have the duty to answer that
question.

          DR. THOMAS: I'm not sure.  But you said it very well
when you said no roadblocks.

          CHAIRMAN FADEN:  Right.

          Ruth, could you clarify on that one subject?

          DR. MACKLIN:  What?

          CHAIRMAN FADEN:  Did you want to clarify?

          DR. MACKLIN:  All I wanted to say here is that to say
there's a right to know is not to specify the steps that have to
be taken in order to satisfy the right.  But it's at least to say
if a person asks and someone has the answer, they're obligated to
tell.  But it's in between the questions of what steps you have
to take, how much effort you have to make, and how you get around
the problem as with the genetic circumstances so that you don't
do what's called imposing unwanted information or truth-dumping
on people.

          DR. THOMAS:  With respect to whether or not there ought
to be an active program of notification for the purpose of
protecting a person's health, that turns on the questions of
first of all, is there any increased risk in the first place and
secondly, whether or not if a person is at increased risk,
whether we can do them any good.

          And those are the questions that are not well known to
us.  I think we've explored them pretty thoroughly.  We don't
have a clear answer to that.

          DR. GLATSTEIN:  You can't answer the second question
until you know the answer to the first one.

          DR. THOMAS:  No.  I think they're two separate
unrelated questions, Eli.

          MS. KING:  One of the things we have resolved, Ruth, is
with that kind of contact, I think it has implications for which
way you lean.

          CHAIRMAN FADEN:  Exactly.  That's where I was trying to
go.  I some ways, though, if you say, okay, there is a background
right to know which we would all like to respect.  Instead of
obsessing very narrowly about whether the protection is this or
that or the other thing, you can say look, let's just find a
category of people where there's even a slight possibility where
there's a health protection.  And since we think they have a
right to know anyway, we can make an effort to find them, still
with that proviso that says you may be ineligible.  That kind of
thing.

          DR. THOMAS:  I don't see the point of an active program
of notification, just to tell people that they were participants
in a research subject even.  But it's not going to do them any
good to know this other than --

          CHAIRMAN FADEN:  It's saying that you can relax your
sensitivity range or something with the air you breathe, because
you can say that's not the only reason why you might want to give
this information -- give them access to the information.  If you
had endless money, you'd find everybody.

          I mean, if you take the principle of the right-to-know
right, if this could be done in a heartbeat because everybody's
name and address was in some computer filing and we could just E-
mail them, we'd do it tomorrow.

          So the issue is ideally, if notification was real easy
to do, we'd find everybody.  But we can't find -- if you follow
the logic of this, if we could find everybody in a keystroke, we
would write a letter to everybody saying you may be in a research
project.  You might want to know this.

          The point is we can't find everybody by a keystroke, so
you get into that gray area of trying to figure out, well, can we
identify any groups of people. It's justifiable to expend extra
effort to find them rather than just seek -- help them, should
they seek assistance.  I don't know.  

          It's 4:00 o'clock.

          DR. THOMAS:  Before everybody drifts off, I just have
one last comment.

          CHAIRMAN FADEN:  Why don't you have the last word.  The
last comment and then --

          DR. THOMAS:  All I want to do is invite people, please,
to look carefully at the section on genetic risks, page 16 to 20. 
This is something that I drafted in a hotel room without any
access to literature.  I feel very insecure about what I've
written here.  I'm particularly insecure about the final
conclusion, which I'll let you read for yourself.

          But this is something that we should begin to think
carefully about.

          CHAIRMAN FADEN:  Okay.  Well, thank you for that.

          Reed, can you officially -- sorry to close on such a
whatever note, but we have accomplished a lot at this meeting.

          DR. TUCKSON:  Ruth, for the record, you continue to do
a marvelous job.  I hope you feel good about it, Ms. Chairman.

          CHAIRMAN FADEN:  Thank you.  That's very nice of you to
say.

          (Whereupon, the proceedings were concluded at 4:10
p.m.)



     





          

     