REPORT FROM THE HUMAN SUBJECTS SUBCOMMITTEE:
           RESEARCH WITH DECISIONALLY IMPAIRED SUBJECTS
     DR. CHILDRESS:  Thank you.  I would second your expression
of appreciation to Jonathan and now to Eric, who has joined us,
but also to members of the subcommittee who participated very
helpfully in this process.  
     I would like to have one item passed out.  It is a response
I just received this morning from the National Institute of
Mental Health to the November draft of the report.  Enough copies
were provided to make available to everyone. 
     Let me offer my comments under three headings.  Why, how and
what, or a priority processing of the product if you prefer the
latter.  
     Why?  Why did we give this topic priority?  It has been on
our agenda since the very first meeting of the subcommittee last
December a year ago and then it was added to the commission's
agenda as a whole at a subsequent meeting.  
     Why?  There is a long history of discussion of this
particular set of research subjects, particularly following the
work of the national commission whose recommendations of special
protections were not adopted.  Many researchers, many subjects
and their families,  believe that additional guidance is needed
to make sure that subjects with questionable decision making
capacity are adequately protected and also to ensure public trust
as essential to enable appropriate and valuable research to go
forward. 
     There are various proposals in the literature.  For example,
if one looks over the last two years at the large number of
articles on this topic with recommendations of various kinds of
guidelines.  
     How?  How do we get to this point and what process we are
following?  Well, we have heard from a number of investigators,
subjects, families of subjects, policy makers, commentators and
others, both those who were invited and those who volunteered to
contribute either written materials or public testimony. 
Certainly one valuable session, very valuable session was the
large public hearing we held in mid-September.  
     In addition, we have had contract papers from Rebecca
Dresser.  A very large and helpful paper that then Jonathan
Moreno used as a basis for the draft that you have before you.  A
draft that has gone through several different versions already. 
     In addition, you will be getting later today -- there was a
confusion bout whether we could get copies made and when -- a few
additional pages prepared under contract with Paul Appelbaum to
go into those sections in Chapter 1 with appropriate
modifications having to do with the different disorders that are
particularly relevant to our discussion and the promise of
research in this area. 
     In addition, we are exploring the possibility of another
paper looking at measurement of competence, kinds of value issues
lurking in that discussion.  And also a literature search on
research involving greater than minimal risk.  These are things
that we will come back and discuss. 
     Another important part of the process is attending --
several subcommittee members attended a National Institute of
Health sponsored inter-institute conference looking at possible
guidance for investigators and IRB's in the area of research
involving subjects with questionable competence or questionable
capacity.  This was a very important meeting.  
     A report will be coming out of that by the end of the month
and we will make that available to everyone.  But those of us who
participated in the meeting were able then to make
recommendations for the revision of the draft and the draft you
have before you includes in bold a lot of those additions as well
as other additions that were made and suggestions not only from
subcommittee members but from other commissioners.
     What do we have?  What product?  Well, as I noted this draft
builds on all the written and publicly presented materials I
noted.  
     There are problems.  We think it has made -- we made
considerable progress with this report but as people who have
read it within the commission and outside have noted one of the
big questions that arises is whether we have established an
adequate connection between the first several chapters and the
conclusions and recommendations.  I think all of us agree, no, we
have not done that. 
     One important possible contribution of this meeting would be
for us to get clear about the kinds of recommendations we want to
make because that would then lead us -- give us a way to
restructure the report.  I think much of the analysis, thanks to
Rebecca and Jonathan and others, is in very good shape but now we
really need to know how to structure this depending on the
recommendations that we want to make. 
     So I would -- I guess another aspect of that would be how
much we want to recommend in terms of regulation and how much we
want to recommend in terms of guidance.  So one strong
recommendation from the NIH conference in early December was no
more regulation but we are actually in the current draft
proposing regulations and we need obviously to keep that in mind. 
     Well, let me stop there and see if there is anything
Jonathan would like to add and then we will open it to
discussion.
     DR. MORENO:  Just very briefly.  On page 150 on my copy the
final line is missing.  It was dropped between my computer and
the NBAC distribution process.  The word "and" appears on that
summary of recommended framework.  After that word "and" should
be the phrase "health care professional monitor."  It is
reflected in the text but it did not -- it got dropped.  That
last line got dropped.
     DR. CHILDRESS:  Say that again, Jonathan. 
     DR. MORENO:  Sure.  The last line in the summary of
recommended research on page 150 in the right column you will see
the word italicized "and" which is followed by nothing. 
     DR. CHILDRESS:  Right. 
     DR. MORENO:  I did not mean that to be a fill in the blank
test for members of the commission.  It occurs to me at this
moment that might not be a bad idea.  The last line should read
"and" and the last line is "health care professional monitor."  
     MR. CAPRON:  Health care professional monitor.
     DR. MORENO:  Health care professional monitor.  That is not
a monitor for health care professionals.  That is a health care
professional to monitor research with respect to the well-being
of the subjects of research for this category of research.  This
is reflected in the text.  It just got dropped from this page.  
     That is all, Jim. 
     DR. SHAPIRO:  Jim, why don't -- if there are any comments
any of you have let me turn the chair over to Jim for the rest of
this discussion.  
     DR. CHILDRESS:  All right.  The floor is open for
discussion.  Again I would like to have all of the suggestions
you have for the revision of the report.  We do not have a lot of
time so some of those you may want to submit by e-mail.  I think
it would be particularly helpful if we could look at some of the
recommendations, the ones that are given here, and the kinds of
modifications you would propose for them.  That will help us then
think further about the revision of the report.  
     DR. EMANUEL:  Jim, in this summary of the recommendations
there is no potential benefit, no potential benefit issue, and
the use of advanced directives.  I have for reasons you and many
others in this room know about serious concerns about that as an
operative principle.  We have a lot of data that it does not work
in other areas.  We are now going to import something which does
not work somewhere else into this area and I am concerned about
that.  
     I think the intention is understandable and right but the
potential operation is likely not -- for lots of reasons not to
meet that.  So I am not -- I think this is a very important step
that, you know, needs elaboration and consideration.  I am very
unclear as to why it is there.
     DR. CHILDRESS:  Thanks.  We will get response from others.  
     I share many of those reservations, as Tom mentioned,
regarding the report this morning.  This is a work in progress
and the fact that it appears in this form does not suggest or
should not be taken to suggest unanimity among the subcommittee
members about particular matters here.  So this is one that is
still under discussion.
     Eric?
     DR. CASSELL:  I just want to register I share the same
concerns.  
     DR. FLYNN:  Could we hear -- 
     DR. CHILDRESS:  Laurie?
     DR. FLYNN:  I do not mean to interrupt.  I just would
benefit from hearing a little bit more discussion from Zeke or
Eric as to the concerns they have seen in other areas and the
dangers they see in trying to import this into this arena.  
     DR. EMANUEL:  Well, I mean the sort of end of life area
where the advanced directives have had the most run for the
money.  There are a number of problems which have been
identified.  Failure to fill them out.  Failure to understand
what you have filled out.  Failure to implement them at the
appropriate time.  Questions about stability over time.  And I
think relying -- and they have never been tested in the area of
research.  They have been -- I mean, we have looked at them in an
area that has a lot more salience maybe for people.
     I think as a mechanism we have had, you know, maybe 20 years
of experience with them and I generally think the conclusion in
the field even by myself, who is an ardent advocate, is we
trusted them too much.  At best they are part of a process.  And
we end up, like many things, relying on a document that does not
seem to reflect the process.  Most people do not use them even
after extensive publicity.  I mean, it is hard to understand how
much publicity.  You know, most people do not do it even if they
want them.  
     So it is -- I mean, I think as we heard from the people in
the New York group the idea that people are actually going to do
this is, I think, clearly unrealistic.  You just have to
understand that if you put this into place you cannot have any
greater hope than five or ten percent of people are ever going to
do this.  I think we must be very clear about that.  
     It is not because only five or ten percent of people may
want to participate in research.  I mean, if there is anything we
know, there is a big gap between attitude and action here.  
     DR. CHILDRESS:  I have Eric and then Alex. 
     DR. CASSELL:  And then the other issue of it is then they
are not heeded.  The evidence shows that then the people for whom
they were written, that is the physicians in care, do not pay
attention to them.  
     Now the conclusion that is usually drawn is that is because
they are bad guys and they do not want to pay attention.  I think
that is not it at all.  They do not know how.  They do not know
how not to treat.  They do not know how in this kind of thing to
apply a directive written way ahead to a piece of research which
will not really precisely the way it was that that directive was
written for so we have this problem. 
     There is another aspect of this which is we keep talking
about more communitarian view of what the process is and then
when we come to write a recommendation we are right back to
trying to do it as though there was no community whatsoever and
we have not protected this person totally against without having
put some kind of standard in that would allow the research to go
on and protect the individual.
     Now, I do not know -- you could come back to me and say,
"Well, Eric, can you solve that?"   Well, I do not know whether I
can but I know that is -- even if I cannot it is not a reason to
keep putting back into place something that did not work before.  
     DR. CHILDRESS:  One criticism of the draft notes that we
make the family a part of the health care team, that is care
giving a part, but we then take the family away from this
individual.  
     But let me just, before turning to Alex, raise one question
for Zeke.
     Your comments were stated in general terms.  Do you take
them to apply to what one might call procedural events,
directives, as well as substantive ones, that is to ones that
recommend a designated decision maker versus the advanced
directives that set out standards for decision making?
     Your comments were just stated in general terms?  You apply
them equally to both?
     DR. EMANUEL:  As you know from my writing I think yes.  I
mean, I think the answer is if you look at substantive decisions
we have lots of problems but clearly people do not feel about it. 
If you look even at procedural ones, appointing a proxy, you have
a different set but also a set of -- first of all, people do not
actually fill the documents out, number one.  Two, when they fill
them out they actually do not talk to someone so that you are
sure that the attitudes are on the same wavelength.  
     Many of the -- I mean, a lot of this happens informally and
people think what has happened informally is what happens
formally.  
     If I could have a parenthesis because Eric prompted
something which I think is extremely important and actually I
think cuts across the report we heard this morning and this,
which is our understanding of informed consent and what we really
want to achieve.  I mean, this is a process for something we want
to achieve that is different.
     I think Rhetaugh raised the issue.
     If I could just for a minute say something.  Informed
consent occurs over a spectrum.  The detailed elaborate
delineation where you have really gone through it with someone
and it is an extensive process and not just a form is an ideal.  
     DR. DUMAS:  Right. 
     DR. EMANUEL:  In both the settings that we are dealing with
we cannot reach that ideal for many reasons it seems to me
because we are asking prospectively way before the event and so
we will not have a lot of the information.
     We are going to have something less than the ideal and the
question there for us is what are we satisfied with and what role
is consent supposed to play in that process.  
     I think -- I mean, I am like Rhetaugh.  We should never give
up informed consent as a standard but we also should not fool
ourselves that just because we have this piece of paper we have
gotten informed consent and we have respected autonomy in that
way.  There are other things that need to be considered and I
think -- I am just worried that again we may -- we may feel
better but we actually have not improved the system and improved
the protection and really respected autonomy any more by just
having this form.  
     DR. CHILDRESS:  After again Alex and Bernie, I am going to
also ask Trish, who has been one of the major advocates for some
kind of research advance directive in our subcommittee, to offer
some views because we are hitting mainly the critical points and
I want to get the positive ones.
     Alex, and then Bernie, and then Trish. 
     MR. CAPRON:  Zeke, I share many of the concerns about
advance directives in end of life care that you have articulated. 
I do think it is worthwhile not being confused by the similarity
of the phrase "advance directive" to import all of those problems
to this area for several reasons.  
     Before I get to the reasons let me make one other
preparatory comment, which is the problem always of the best
being enemy of the good.  I fully share with you and have spent
years and years writing about the difference between the consent
form and so forth and informed consent.
     Our ideal ought to be an ongoing process of conversation
between investigator and subject.  Where that is not achieved the
question is what do you do instead.  Is it better to go ahead
with an experiment that has no potential benefit to a mentally
impaired subject who has never been asked whether or not if
unable to give contemporaneous consent he or she would want to be
involved or is it better to go ahead where there has at least
been the conversation and there was an apparent agreement to go
ahead?  That is the question.  
     I am not telling you that the answer is ineluctable but it
does seem to me that if you -- it is possible to distinguish
those two categories of subjects and I, for one, would think it
is at least better, if not perfect because we do not know how
good the consent process was, to go ahead where the subject has
had it raised that there may be kinds of research that has no
potential benefit to you.  You do not have to participate in
that.  Some people choose to and some people do not.  We are
giving you an opportunity now to indicate your wish on that
because at the point where it becomes relevant you may be in a
phase of your illness where we cannot ask you or where you cannot
answer us.  
     Now, I would argue that there is reason to believe that is
preferable to going ahead when we have no -- we have never asked
the question and we have never had that kind of directive. 
     Then the second question, when we face that issue someone is
going to have to be involved in the decision process with the
investigator.  Do you have someone whom you would be most
comfortable playing that role?  It might not be your mother or
your father or your brother or your child.  It might be someone
else or it might be among those people, one particular one of
them. 
     Again we might from the outside say that the choice of one
of those people is not the best choice in the world and that
there are psychological reasons why that person was chosen even
though she or he is not the most informed or rational of all the
people who could have been chosen.  But again is there not
something to be said with finding out what that person believes -- who he believes to be the person who is best able to step into
the shoes and make a decision of the type that he would want to
have made?
     Now those are both things which you can achieve
contemporaneously.  The latter you do not really need but you
might need it during like I am in surgery and I want my wife to
be the one they come out and ask whether they should do something
they were not anticipating.  Fine.  You can do that in the
informed consent or you could do it in an advance directive.  
     With these patients that we are talking about here those
same kinds of considerations arise.  
     It seems to me the fact that physicians caring for patients
at the end of life in half the cases do not even know that there
is an advanced directive, that many people do not think about
their own dying process and, therefore, do not fill out
directives, that when the directives are written they are often
written in terms that are too vague to apply.  
     Did he mean no food and fluids if we could get him over the
hump here?  Did he mean -- what is heroic methods?  Those are not
really very strong objections to the particular advanced
directive for research that we are talking about here.
     So I would hope that we would not throw out this concept
simply because of a bad experience in another field and that we
would not throw it out because it is not as good as the perfect
ongoing process of discussion and fully informed consent going
back and forth.
     DR. CHILDRESS:  Let me add one other point to that because I
am not sure this came in Zeke's original statement.  That is we
are in this particular draft limiting this requirement to greater
than minimal risk.  That is very important because -- 
     MR. CAPRON:  Of no benefit. 
     DR. EMANUEL:  No, no, no.  
     DR. CHILDRESS:  It applies to greater than minimal risk in
nonpotentially beneficial research.
     DR. EMANUEL:  Wait a second.  As I read the chart on page
150 it says --
     DR. CASSELL:  That is minimal risk. 
     DR. KRAMER:  Where are you?
     DR. EMANUEL:  It says minimal risk.  
     MR. CAPRON:  No, no, minimal has an X in it. 
     DR. CHILDRESS:  The X is there.  No, no, that is --
     DR. EMANUEL:  X means that is minimal risk, right?  
     DR. CASSELL:  It just means the unknown. 
     MR. CAPRON:  No, there is no -- we have not specified the
requirements where it is minimal risk. 
     DR. CHILDRESS:  That is right.  
     MR. CAPRON:  Greater than minimal risk on people who are not
going to get any benefit. 
     DR. CHILDRESS:  See that is very important because --
     MR. CAPRON:  And we know this kind of research has gone on
and we are disturbed by this type of research. 
     DR. CHILDRESS:  And, see, that is a -- I am assuming that
you are -- so I am assuming that you were building it into the --
would that lead you to state your views differently now that we
are clear about what we mean here because we are limiting this to
greater than minimal risk nonpotentially beneficial research?
     DR. EMANUEL:  Well, I think there are two separate things. 
One -- sorry, I misinterpreted the chart.  I apologize.  I did
not interpret -- 
     MR. CAPRON:  It is a fault of the chart.  It is easy --     
     DR. CHILDRESS:  Instead of X put --
     DR. EMANUEL:  It is my fault.  I was -- I understand the --
let me separate it.  I understand the motivation in this category
of greater than minimal risk or no potential benefit to want
higher levels of protections.  I still object or still find the
idea of trying to use advance directives -- not going to reach
the objective.  
     What I heard from Alex and what I hear around the table is
we share the concern.  We need protections for people.  The
question is whether this answers that concern and whether this is
the procedure that is going to answer that concern.    My sense,
again importing some information from other areas, is it is not
going to.  
     Two things in response to Alex.  First, I agree end of life
may not be a perfect analogy here.  On the other hand one should
not be starry eyed, optimistic, as if there is no carry over.  It
is completely different because we have a lot of experience there
and we have no empirical experience in this area.  
     Second, I am not sure I would pose the question as Alex did,
which lets you -- I mean, the way Alex posed it was very stark. 
Either you talk to them and get their prospective consent or you
do not and you just do it to them.  Those are not the only kinds
of protections.  I would not -- I mean, if you ask me that
question my reaction to the question is you have posed the wrong
question.  You have posed a false question. 
     DR. CASSELL:  Could you elaborate on how?  I mean, what is
the alternative?
     DR. EMANUEL:  Well, I mean, it seems to me that if you have
got --
     DR. HOLTZMAN:  He wants you to be closer to the mike. 
     DR. EMANUEL:  I is coming. 
     (Laughter.)
     DR. EMANUEL:  I mean, first of all, 
     (Laughter.)
     DR. HOLTZMAN:  You better say the right thing. 
     (Laughter.)
     DR. EMANUEL:  First of all, I mean if -- here, I think, it
crucially depends -- I think as Eric was trying tko suggest --
what kind of understanding of that research you have, whether it
-- people who are concerned about this group that is going to be
experimented on have been involved in the process of planning the
experiments.  I think those are other substantive protections
that, in fact, lower my overall concern for the need to be sure
you have got this full-blooded or as close to full-blooded
consent as you have. 
     I think there is a trade off here in my own mind between the
kinds of protections you have, how sure you are that there is no
benefit to the subject, how sure you are that this is greater
than minimal risk.  Whether, in fact, the research results -- the
community of concern thinks that the research results are going
to be very important to them.  These are lots of things that come
into it and it is not just consent. 
     MR. CAPRON:  But there certainly are needs for other
protections.  The question I think we have based upon experience
that we have looked at in the psychiatric facilities is the
willingness of researchers to (a) describe research or potential
benefit that does not seem to be very likely to have any benefit
but (b) the question of where that trade off comes.  And you can
have had other people with similar illnesses agreeing and you can
even have a legally authorized representative agreeing.  
     Our sense was you should not do something to somebody which
has greater than minimal risk and by the design, even the
designers would say, it is not designed to do them any benefit
and any benefit would be totally adventitious and unexpected
without that person having said if the time comes I am willing to
be in that kind of an experiment because I, like you, Mr.
Researcher, value the outcome of research enough to subject
myself in a state in which I am not capable of protecting myself
and not capable of indicating that I want to withdraw, and
everything else we think of as normal protections that people
have I, myself, am willing to take that risk in order to advance
science.  
     It is here, unlike -- I mean, I do not know what I feel in
the end about all the losses that will -- if we cannot get access
to every human tissue without consent -- I mean, you know, I do
not know where I come out on that yet.  You all will still have
to convince me.  But I do know what I think about living human
beings who cannot protect themselves and are going to be used in
greater than minimal research.  I do not want it done unless they
have said it is okay with them.  That is just the bottom line on
this point.
     DR. CHILDRESS:  Before I turn to Bernie, Trish and Eric, let
me just note Harold and Eric Meslin had called my attention to
what appears to be an error on 145 under four, "and IRB may
approve this category of research only if the potential subject
has given informed consent." I think the "and" should be "or." 
Has actually given advance directive to be consistent with --
     MR. CAPRON:  It says "or."  "Or if incapable has executed an
advanced directive," doesn't it?
     DR. CHILDRESS:  On 145? 
     MR. CAPRON:  145, second line -- 
     DR. MESLIN:  Second line of four. 
     DR. CHILDRESS:  Mine does not. 
     MR. CAPRON:  Oh, no.  Look at the top of the page.  
     DR. CHILDRESS:  I know but --
     MR. CAPRON:  Oh.  Oh, I am sorry.  I was looking at the top
of the page.
     DR. CHILDRESS:  Look down under number 4. 
     DR. SHAPIRO:  Could you read that again?
     MR. CAPRON  That is potentially beneficial. 
     DR. CHILDRESS:  That is right.  We do not require --
     MR. CAPRON:  Three --
     DR. CHILDRESS:  -- an advance directive for potentially
beneficial.
     MR. CAPRON:  That is right. 
     DR. CHILDRESS:  But it says it under number four.  At least
our draft says it.
     MR. CAPRON:  Oh, I am sorry.  I am sorry.  I understand. 
     DR. SHAPIRO:  Can you repeat that?
     DR. CHILDRESS:  Yes.  It should be -- the "and" should be
"or." 
     MR. CAPRON:  The thing that we have been discussing is point
number three and you are now switching to point number four.  
     DR. CHILDRESS:  Well, this is just to get this clarification
in.  Thanks to Harold and Eric for calling it to my attention. 
     Bernie?
     DR. LO:  Yes.  Let me also speak as someone who has tried to
work in the field of advance directives and end of life care and
it has been disappointing to say the least that it has not worked
out better.  So although I think we cannot translate all that
experience, there actually are some pertinent differences, and
one being, I think, that some of the people you are talking about
as potential subjects may have a remitting and relapsing course -- I mean, there are moments of whatever you want to call it,
remission or treatment -- may be able to be quite decisionally
capable and actually have some sense of what it was like to
relapse.
     But I am very skeptical about many people filling these out. 
I mean, some will.  I guess you want to give that opportunity. 
But I guess my suggestion would be that what you are really
doing, I think, with the current proposal is saying for all
intents and purposes research that does not provide benefit and
is more than minimal risk is probably not going to happen.  It is
going to -- you are going to have to work very, very hard to find
that small group of individuals who are willing to fill out that
research advance directive and you probably will not.  That may
be fine if that is what you want to do.
     I have some other comments that have to do with sort of our
conceptual thinking behind why we -- why are we so willing to say
that a piece of paper which is really just a signature and a
notarization and may not express any more understanding,
commitment or having thought through a decision, I think it
really goes back to this notion of informed consent.  I would
like to suggest that informed consent is important but we should
not try and make things sound as if they are very much like
informed consent when they are not.  
     I think the real issue is that it is not that we get consent
or not, that we do not want to do things to people that they
would not want us to do or they did not even know about and it is
just very uncomfortable.  If they consent we figure, well, they
let us do it so that is okay.  But I think there are other
degrees of respecting autonomy, many of which I think  you have
worked into the report.
     One is failure to assent even if the patient is uninformed
has to be respected.  I think that is very important and I would
say that you actually have to seek affirmative assent.  You
cannot just say they did not object so we will do it.  You have
to say is it okay if I draw your blood.  
     I think that is -- you know, we were talking about
incremental improvements this morning.  I think that is an
incremental but substantial improvement over what happens now
where you just get the blood drawn because, you know, we want to
draw your blood and you do not object. 
     I think the other thing we tend to do is we try to fit
everything in some autonomy model even when it does not.  Most of
these decisions for people of questionable capacity really have a
lot more to do with what someone else thinks is in their best
interest.  
     I think one of the things that I like about this draft that
I think we need to sharpen even more is a willingness to say that
family members by default, unless shown otherwise, are the
natural surrogates to whom we turn for decisions about is it in
this patient's best interest to be a research subject.  That is a
big change.  I mean, if we are willing to say that leaving aside
the -- it depends on whether it is benefit and risk.  
     But, you know, Alex, to go back to what you always reminded
us sort of the history of this.  I mean, there is a school of
thought that, you know, it was very, you know, cogent, I think,
that said, no, that you cannot do anything to a subject without
their free and voluntary consent.  It goes right back to the
Nuremberg code.  So that if we are really saying a family member
may consent or may give permission under certain circumstances,
again that is -- and if we really involve the family members in a
meaningful decision as best they can make it, again I think that
is an incremental but substantial improvement. 
     As long as I have the floor I am going to just sort of sneak
in another point that is unrelated.  
     I was impressed that a lot of the recommendations are let's
have the good people in the IRB settle this one for us at the
local level. 
     (Laughter.)
     I guess I am really skeptical.  I mean, it may be -- 
     (Simultaneous discussion.)
     DR. LO:  Should we do a global search and replace?  This is
a really tough question.  We do not really have a good answer yet
on how to solve it.  We are still thinking but in the meanwhile
we are going to pass it on and we hope these poor overworked,
under trained, unpaid people in the IRB will do a better job than
nothing at all.  But I think we really should be fairly honest
and say if we are saying the IRB should decide on a case by case
basis and recommend, that is really not a very robust guarantee.
     DR. DUMAS:  I agree. 
     DR. CHILDRESS:  Trish, and Eric, and I think I saw David's
hand. 
     Trish?
     MS. BACKLAR:  First of all, I want to say that it is a shape
--
     DR. SHAPIRO:  The microphone.
     MS. BACKLAR:  First of all, I would like to say that it is a
shame that we are calling this an advance directive because I
think that it is a very -- the document that we describe as a RAD
in here is really very different from the kind of advance
directive for end of life care. 
     Secondly, I see it much more as a kind of ongoing contract
with the researchers which can change as time goes along so if
the subject objects at any time they can go out.  Plus it
involves certain safeguards like a surrogate decision maker. 
Plus I do not know if we actually filled this out -- I have to go
back and look and see exactly what Jonathan said.  
     But there should be also some kind of outside health care
provider who is also involved and is not part of the research so
that it is not simply an agreement to be in a research protocol
and it certainly should not be done ahead of being -- I mean, it
should be part of the informed consent process.  The surrogate
would be part of the informed consent process.  All the
safeguards would be built into a contract to protect the person
who may have fluctuating incapacity.
     DR. CHILDRESS:  Have you taken out -- I guess one question
would be then what role advance plays in this at all?
     DR. CASSELL:  What role has what?
     DR. CHILDRESS:  What role advance plays in this?  I mean,
this is just before the research but it is hardly advance in the
same sense that we are talking about so maybe we have the wrong
language here.
     MS. BACKLAR:  Correct.  Maybe -- because since you notice in
the RAD it really has to be tied to a specific research protocol. 
It is not just for any research that may come along. 
     DR. CHILDRESS:  But then that is -- then perhaps we are
misleading.
     MS. BACKLAR:  Right. 
     DR. CHILDRESS:  The report needs to be altered then and
basically get rid of the language about research advance
directive.
     DR. EMANUEL:  Could you just tell me -- say I have a waxing
and waning condition.  I do not know.  Manic depressive disorder
or something. 
     MS. BACKLAR:  Right. 
     DR. EMANUEL:  How exactly -- and the researcher wants --
     MS. BACKLAR:  The research --
     DR. EMANUEL:  -- the researcher wants to get me at the
depressive moment.  Okay.  That is whatever the research is.  It
has got to get me at that moment.  Now how is it going to do it? 
I mean, basically what you have described is informed consent.  I
do not see how it is anything different than informed consent. 
An advance directive --
     MS. BACKLAR:  I tell you what is advance about it.  
     DR. CHILDRESS:  It may be an improvement --
     MS. BACKLAR:  The advance part of it is in a sense the
person is preparing in case they lose capacity and at a time that
they lose -- they should lose capacity for decision making if
they are in the research protocol, which might involve coming off
medications or various things, that for sure they have with them
a surrogate and an outside provider.  So in a sense that is the
advance part of it.      While they have capacity to make
decisions for themselves they will.
     DR. CHILDRESS:  But we could simply require those mechanisms
without connecting it with the notion of an advance directive.  
     DR. EMANUEL:  I also might mention that does not apply well
to the dementia category, which at least from a numerical
standpoint --
     MS. BACKLAR:  I understand that. 
     DR. EMANUEL:  -- is a much bigger category.
     MS. BACKLAR:  Well, we -- what I was thinking of is setting
up a model out of which one might change in terms of the
different categories.  You will notice in the beginning we
categorize people with capacity.  We have four kind of models. 
This was really set up thinking of people with fluctuating
incapacity.  
     DR. CHILDRESS:  Anything else at this point, Trish?
     MS. BACKLAR:  Not at the moment. 
     DR. CHILDRESS:  Okay. 
     Eric?
     DR. CASSELL:  Well, it is King Solomon's headache revisited. 

     (Laughter.)
     Bernie is absolutely right about a very crucial issue.  Here
it is we want to move forward, the decisionally impaired problem
is here, we have got to solve it, and then we come right up
against it and we are going to use the same mechanism that did
not work before, and we are going to use the same IRB.  Bernie
and I are jumping up and down and saying, "education, education,
here, there and everywhere," but we are not educating them.  We
are going to go in there and talk about an advance directive and
we cannot even agree on what that is.  
     And then even here in number four where an "and" is being
added -- gee, that -- wait a minute.  That means that --
     DR. CHILDRESS:  No, the "or" replaces an "and."
     DR. MESLIN:  It is being replaced.  
     DR. CASSELL:  The "and" replaces the "or," right?
     DR. CHILDRESS:  No, the "or" replaces "and." 
     MS. BACKLAR:  "Or" replaces the "and."
     DR. CASSELL:  Oh, thank God for that.  That is okay. 
     (Laughter.)
     DR. LO:  We solved that problem. 
     DR. CASSELL:  So that is solved.  
     Now all we have to do is solve the problem of we do not know
what an advance directive is and we are depending on an IRB. 
     I do not want to go back and say, "Well, that is it.  We
gave it a run and we are not going to do it."  The Edsel was not
a good car and that is all there was to it. 
     MS. BACKLAR:  And we still have not agreed about risk.  
     DR. CASSELL:  So then the question is what is the
intermediate solution.  Is there an intermediate solution?  Well,
there is a research solution to it, among other things, where we
strongly urge the National Institutes of Mental Health to put out
an RFP on researching the issue and we request them to come back
to us with this saying we cannot resolve this issue because there
are too many questions of fact that have not been solved for us. 
Otherwise we are just writing a bunch of stuff that we know as we
write it does not work.  I do not want to do that.  
     I do not want to come back and say, "Well, it does not work
but we are going to write it down anyway," or end up with a good
workable report where all the way through the body of the report
it is a great report and then we get to the conclusions on which
policy is based and we are back where we were.
     DR. CHILDRESS:  David, do you have anything to add to that
sobering thought?
     DR. COX:  Yes, with some trepidation actually.
     So this is an area where I have very little personal
experience but I have found listening to the discussion it leads
me to the following questions:
     I am very keen on, you know, not instituting things that
knowledgeable people who have personal experience say has not
worked.  But I ask the question why hasn't it worked?  
     So that I can think of two reasons why it might not have
worked.  First, that there is sort of factual practical things
that makes it not practical.  And another thing that I think is
more likely why it does not work is because people do not value
the principle on which it was based to begin with.     Now if
people do not value the principle that it was based to begin with
we can have any process that we want to put together and that
will not work either.  
     So because it strikes me -- again, being naive in this area
and I say that -- that this should not be so complicated.  All
right.  So when things smell like they should not be real
complicated and are real complicated it heads me towards the fact
that some people do not value it.
     So I really very much like the idea of going back because
there is lots of experience in this in asking why it did not
work, okay, and what we have to do to get fixed to get it to
work.  And that the -- rather than making another set of
recommendations sort of addressing that fact right up front.  And
then, okay, if it is not valued by certain people have them come
out of the closet and so on, all right.      Or if they say it is
not that we do not value it but that it conflicts with some other
value that we have that precludes us doing it.
     Now, again, I say that I do not have any background in this
area and maybe this is not relevant but just listening to the
discussion --
     DR. CHILDRESS:  Let me add one point before getting to Eric
and Bernie.  
     When we ask the question would it work here, has it worked
in another area, I think we do have to ask work in relation to
what.  The critical question here, and I think we saw it in the
exchange between Zeke and Alex is work in terms of facilitating
research, work in terms of protecting subjects and their
autonomy.  
     I am not putting those in cast but work -- it was
differently -- there was a different emphasis in your comments as
to whether it would work or not I think and it seems to me that
the fundamental attention that we have to face in this area
because it can -- it can certainly be said it works if only one
percent fill out a form it works in one sense but it will not
permit research to go forward.  So a lot depends on what you are
emphasizing, I think, in terms of what works. 
     DR. EMANUEL:  Wait a second. 
     (Simultaneous discussion.)
     DR. EMANUEL:  I am a little uncomfortable here by people
saying that if we have the form filled out that is the only way
in which we have protection of --
     (Simultaneous discussion.) 
     DR. CASSELL:  No, it falls on the straw man.
     MS. BACKLAR:  It has nothing to do with just filling it out.
     DR. EMANUEL:  As an integral, essential, inescapable part.  
     DR. CHILDRESS:  It is a sorting device.  
     DR. EMANUEL:  No.  I am hearing if you do not have this
consent you are out.  You are not protected.  We have no
assurance of protection and you are out.  
     DR. CHILDRESS:  No, we did not say that.  
     Alex, explain it.
     MR. CAPRON:  Well, if you do not have this -- if you -- put
it this way:  We would have many more advance directives for end
of life care if the public and physicians knew that every medical
technology had to be used on every patient who did not fill out
an advance directive, which I would regard -- most of the care
that would be provided beyond a certain point would not be
beneficial to those patients.  It would be in the same category
as this.  People and doctors, if they knew they had to labor over
every patient until physiologically they had total collapse of
the patient, and unless there had been an advance directive we
would have a lot more advance directives.    
     I have a sense that if researchers believe that their IRB's
will not allow them to do research of a certain category unless
they have discussed that category of research with the subject in
advance at a time when the subject can make a choice, and as you
and Bernie have pointed out this is much more applicable to
people who go in and out of periods than to someone who is on a
course because the person who goes in and out has some sense of
what you are talking about.  The person with Alzheimer's -- it is
a harder prospect to know.    But the incentive will be there to
have those conversations and to have that sorting.
     Now once you get a person who is in the category that they,
themselves, have said it is all right it is not as though you
have carte blanche with them of course.  But the understanding is
that no research institution will allow the research to go on at
a greater minimal risk of no potential benefit on those people
for whom that -- I prefer to think of it as prospective consent
instead of an advance directive.  Prospective consent and
appointment of their surrogate.  
     They have not gone through that process or they went through
it and they said no, they were not interested, or whatever
reason.  If you do not have that from them they are out.  They
are protected in a sense that they will not be subjected to that
except by someone who is willing to break the law. 
     DR. CASSELL:  I want to see examples of the advance -- I
mean, the advance consent, which I think is a good distinction.
     DR. CHILDRESS:  I am sorry, Eric.  I missed that.  
     DR. CASSELL:  I would like to see copies of what you mean. 
I mean, you can write a general, very general statement of
somebody approves the research, they really would like to be a
member of a research project even if they cannot consent at that
time, very general statement and then I understand what the
person is doing but the more concrete you get the less valuable
the thing is and the more broad it becomes the more question
there is are they really consenting to the --
     MR. CAPRON:  And the key thing that you are trying to
distinguish as I have understood what we were about here is
whether or not you would agree to be in a consent protect that
would expose you to greater than minimal risk and that has to be
explained with the kind of things that could happen and make it
concrete but would not be designed to benefit you at all.  
     And that is the determination that is so crucial here
because that kind of research is done by researchers and it
should only be done when the person has said, as the researcher
is saying, I value scientific knowledge enough to go through a
process with no prospect of being benefitted by it as opposed to
with the lure of some potential therapeutic payoff for me.  And
that is why we distinguished it.  We do allow a surrogate in the
potentially therapeutic because we say there the fact that you
have not gone through this process and have not made that
determination ought not to be a total barrier to your getting
that benefit of the innovative treatment or whatever is being
done here. 
     But where that is not a prospect what is the justification
for using the person?  It is just pure use of a person who has
not been given the opportunity to say yea or nay to that.  Not
everybody can be presumed to be willing to go through pain and
suffering in order to advance science.  
     DR. DUMAS:  Yes, right, very true.  I do not understand why
--
     DR. SHAPIRO:  Microphone. 
     DR. DUMAS:  I do not understand why it is so difficult.  You
know, I sit here and I think these things seem to be in general -- they are addressing problems that we talked about a long time
and they seem solvable.  I do not understand why it is so
complicated.  I have a feeling that it is not really that
complicated.  Why are we doing this?  What is going on?  What is
going on?
     DR. CASSELL:  It is complicated.  Rhetaugh, it is
complicated because we are trying to say we want to find out what
this person would think to be in their best interest as they know
those interests.  
     DR. CHILDRESS:  This is not the --
     DR. DUMAS:  Well, you do not ask that question.
     (Simultaneous discussion.)
     DR. CHILDRESS:  That is the case here. 
     DR. DUMAS:  No.  You ask that person -- you tell that person
something about the research you are doing.  You ask them if they
are willing to participate.  You explain as best you can what the
implications are and you extract a yes or a no, or I cannot
answer, or something like that.  I just do not -- I do not know
where we are in here.  I know there is some underlying issue here
that is not on the table. 
     (Simultaneous discussion.)
     DR. CASSELL:  The requirement could be for a drug company,
Rhetaugh.
     DR. CHILDRESS:  It may be that our chart is not as clear as
it should be because, Eric, I am not sure how you would say in
terms of non potentially beneficial research with greater than
minimal risk that this is a best interest consideration.  I mean,
how could --
     DR. CASSELL:  Well, it is like the people who participate in
Phase I trials.
     DR. CHILDRESS:  They may want to but how do we say do it as
a best interest consideration?
     DR. CASSELL:  Well, because the person thinks that in most
instances that some good should come of all this.  
     DR. CHILDRESS:  That is true for those who consent but I do
not think you want to say that to the person who does not have
the capacity to consent and that is the category we are talking
about.
     MR. CAPRON:  Eric, it does not fall within the usual
understanding of best interest.  It seems to me that a person can
make a statement that they have interests other than their
physical well-being and you could say that is part of their best
interest.  But usually when we talk about best interest and about
people who are incapable of deciding we are talking about
something more immediate.  
     It seems to me that the person who has a dread disease and
says you want to do a study unconnected from my disease or
connected but of no benefit to me and I am willing to participate
is saying I am trading off in a larger existential sense my own
personal benefit for some greater good and I am trying to give
some meaning to my life right now that I am still a person
capable of doing something useful for others even though I have
this dread disease. 
     DR. CASSELL:  Well, I --
     DR. CHILDRESS:  But that is not --
     MR. CAPRON:  And you can say --
     DR. CASSELL:  Well, let's back off back to the other issue.  
     MR. CAPRON:  But the --
     DR. CASSELL:  Supposing there is no problem about that and I
agree with all of it and then back off to the other category.  We
have no problem except that one?  Is that our only problem?  
     DR. CHILDRESS:  That appears to be the case actually.  
     DR. DUMAS:  I think it is immoral to persuade somebody to
participate in a project that you know is not going to do them
any good and that has more than minimal risk.  
     DR. CHILDRESS:  Larry has been trying to get in and he has
not spoken.  Let me get him and then Bernie and then Trish. 
     DR. MIIKE:  Am I close enough?  I guess I am. 
     What is the universe we are talking about here because
elsewhere in the report you say that if your research can be done
in other subjects then they are not to be done in the
decisionally impaired?  So what we are talking about is an area
of research in decisionally impaired subjects where there would
be greater than minimal harm.  What kinds of research are we
talking about that would still escape the prohibition about if it
can be done in other groups?
     DR. CHILDRESS:  Bernie, did you want to respond to that? 
     DR. LO:  Yes.  I mean, I think there is a couple of things
we -- we sort of jumped in the middle of the end of the report
and there is a beginning of the report I think we need to set up. 
First there is a long-term benefit to people with things like --
with conditions such as depression, dementia, to have research
done that does not give them direct benefit but illuminates the
condition they have, the etiology, things like that.  
     The problem is that some of the things which are not very
risky to people who have decision making capacity can be quite
risky in some sense to people who do not so that is things like
CAT scans, MRI scans, PET scans, which for people who are aware
present most of the time very little risk.  To someone who does
not understand what is going on it can be very frightening.  One
might, depending on how you construe greater than minimal risk,
might say that.  
     What is missing out of, you know, the way this has fallen
out is the notion that was there before that has been in previous
writings on the subject that it makes a difference whether the
research is pertinent to the condition that the patient has or
not.  
     Now one thing you have done, which I have not thought
through yet, is when you say that it makes a difference whether
you could do the research on subjects who are able to give
consent or not.  But, I mean, if you want to study, for example,
what the glucose metabolism is in people with severe depression
that is refractory to other medications because you want to see
if a different area of the brain is involved because that might
eventually lead to new drugs but it is not going to benefit that
particular patient and the test, which is getting a fancy x-ray,
may scare them.  
     It is hard for me to imagine how you do that research if you
say it is only going to be on people who have given a research
advance directive or whatever you call it.  Realistically we are
not going to do that research.  If we are willing to say that we
do not care, we are not going to do that research and accept the
downstream consequences that is okay.  But I think to say that,
you know, we can make this -- I mean, I would like to believe we
can make it happen because we are going to be committed, we are
going to realize it is important and we are going to mobilize the
activists, I am not sure it is going to happen. 
     MR. CAPRON:  Would you be of the view that Eric expressed
that the statement you have just made is an empirical statement
that ought to at least be studied before we reach the conclusion
negative to the use of the directives?  In other words, if you
are saying that this is a requirement which is a veiled way of
stopping all research not of benefit, that is a disturbing claim. 
I am not convinced of it.  
     DR. EMANUEL:  I think that has to be the presumption, Alex,
given the history and the burden --  I agree with you.  We need
to have empirical studies.  It is an issue of fact.  It is an
issue of fact but the history of the use of advance directives
has to suggest to you that it is unlikely and that the burden of
proof is, you know, quite -- 
     MR. CAPRON:  I mean, because in most states you do not need
an advance directive to get appropriate end of life care and if
you do not get appropriate end of life care it is for reasons
other than the fact that you do not have an advance directive. 
     DR. LO:  Alex, wait.  New York is a state and Missouri is a
state where that is -- legally you need an advance directive to
get life sustaining treatment withheld or withdrawn generally. 
     MR. CAPRON:  No, you do not.  You need clear and convincing
evidence of your views which does not include an advance
directive. 
     DR. LO:  Okay.  But most people do not -- 
     (Simultaneous discussion.)
     DR. LO:  Most people -- 
     (Simultaneous discussion.)
     DR. LO:  Well, the law requires clear and convincing
evidence.  Most people do not give it.  What happens in New York
is that doctors want the law because it is the most ethical thing
to do.
     MR. CAPRON:  Right.  That is my point.  That is why you
could say that "advance directives" have been a failure and why
everybody in the country does not have one because the message is
out there to people and their doctors that these decisions are
going to get made anyway.
     As I say to you, do a thought experiment, if the experiment
I described before was the case where everybody got the full
court press everything medicine could do until they fell apart
biologically or physiologically you could be damn sure that there
would be a lot more people having advance directives and every
doctor would raise it with any patient who he thought was within
ten years of death because he would not want to be stuck having
to do that.
     DR. EMANUEL:  Alex --
     MR. CAPRON:  But that is not the case.  That is why advance
directives have not worked here.  We all avoid thinking about
death, et cetera, et cetera, et cetera.  That is not the case
with these patients if they are in contact with a researcher. 
The researchers say to themselves I can only recruit this patient
if I have had this discussion.  If I have said, "Are you willing
to go into such an experiment, an experiment that would not be
for your own benefit, and that might cause you more risk because
you --" all the kinds of reasons that you have given, "-- or are
you not?" 
     DR. EMANUEL:  Alex, is that the right model?  Is it the
model that I have a stable of patients with manic depressive
disorder and I have experiments waiting to bring them in or does
the situation actually work in a different way, which is I come
up with an idea for a study because of, you know, whatever is
going on in the literature and then I look for the patients that
are going to fit the study.  If it is that second model you have
a problem and you have a problem --
     MR. CAPRON:  You have to --
     (Simultaneous discussion.)
     MR. CAPRON:  -- to their physician to give the consent. 
     DR. EMANUEL:  Wait a second.  You have a problem because the
idea of an ongoing relationship between researcher and subject
that you suggest where this is going to be prospective consent is
not operative.  It simply is not going to work.  So then we are
going to step back -- these research advance directives are going
to be general things not made with the specific researcher who is
going to do your experiment at all and they are going to become,
you know, some kind of carte blanche. 
     DR. CASSELL:  Mr. Chairman, could I ask for clarification?
     DR. DUMAS:  Wrong, no.  No.   
     MR. CAPRON:  Wrong. 
     DR. CASSELL:  I just want to clarify the question we are
discussing.  
     DR. CHILDRESS:  Use the microphone. 
     DR. CASSELL:  I take it that we have made a change in
therapeutic research even where risk is present, that the family,
for example, or a representative can now consent whereas before
that was not the case, I mean, in previous lifetimes that was not
the case.  We put that in.  We have added the family or legally
appointed representative.  Now we are arguing only about one
area, nontherapeutic risky research.  That is the only thing we
are discussing. 
     DR. CHILDRESS:  Greater than minimal risk, nonpotentially
beneficial research. 
     DR. CASSELL:  Right.  But we have as a commission come to
believe that we can protect our subjects by having their family
or equivalent there in other circumstances where it is
therapeutic and there is risk.  So now we are only about
nontherapeutic risky experiments with minimal risk.  Is that the
question?
     DR. CHILDRESS:  That is what I understand this to be. 
     DR. CASSELL:  If that is the case and we are going back and
forth, we are discussing a matter of fact, a question of fact. 
If that is the question then from my point of view it ought to be
left impossible to resolve and we ought to set in motion
something that will help resolve it where that is really
clarified so that we can find out this question.  Otherwise we
are just guessing.  You are saying yes and he says no.
     (Simultaneous discussion.)
     DR. EMANUEL:  No, no, I am not -- 
     DR. CASSELL:  He says yes and you say no.
     MR. EMANUEL:  I do not think it is just a matter of fact
because as I have heard the discussion for one second, Alex is
prepared to say even if my prediction or Bernie's prediction or
anyone else's prediction that you will not get people to fill out
advance directives, that the system will not work, he is prepared
to say fine, it will not work.  But I am not prepared to change
the standards.  He does not care what the facts are, right?
     (Simultaneous discussion.)
     DR. CHILDRESS:  But again our work has to do with values not
simply with --
     MR. CAPRON:  That is right.
     DR. EMANUEL:  No, no, no, will not work in the following
sense.  People will not fill out advance directives and the
researcher --
     (Simultaneous discussion.)
     DR. CHILDRESS:  It works from Alex's standpoint. 
     MR. CAPRON:  It works.  It prevents research on unconsenting
subjects that exposes them to more than minimal risk and no
benefit.  It works. 
     DR. CHILDRESS:  It works.  
     MS. BACKLAR:  I think, Zeke, you are talking about something
quite different.  First of all, I do not really see an analogy to
end of life advance directives.  That is because if you make out
an advance directive about what will happen to you when you die
you do not know what that is going to be.  You have no way of
knowing right now how your end of life is going to be.  So it is
always conjecture and there is always going to be some kind of
reluctance to make out something of which you know nothing.
     This we are talking about something like a psychiatric
advance directive.  You may not have had precise experience but
you should have had some experience perhaps in losing capacity to
make decisions for yourself.  All you are doing is with a
specific protocol putting in place certain protections for
yourself should you lose capacity during that research process. 
And that will be those protections of a surrogate and an outside
health care provider.  
     DR. CHILDRESS:  But I just might note we can put --
     MS. BACKLAR:  And the ability to drop out whatever happens. 
If you object you get out of it.
     DR. CHILDRESS:  But see this is why I think, Trish, as you
and I have discussed several times, it is really important to
distinguish the notion of advance directive from all these other
protections and as long as you can inflate them then a lot of
this debate is going to go on. 
     MS. BACKLAR:  Okay.  I am willing --
     DR. CHILDRESS:  We could require these protections -- 
     MS. BACKLAR:  -- the reason --
     DR. CHILDRESS:  -- whether we have advance directive or not. 
     MS. BACKLAR:  The reason that I see --
     DR. CHILDRESS:  Right. 
     MS. BACKLAR:  -- this kind of contract as a good thing in
the partnership between the researcher and the subject is that it
is a way of getting those protections all into a package.  That
is all.  And that the surrogate is there and part of that consent
process, understanding what is going on, plus the outside
provider, that is it.  Just a sort of package to ensure
protection.
     DR. CHILDRESS:  But in our study we have a lot of contracts
that are regulated in various ways and we could simply require
these components you have mentioned and that would be separate
from the question of whether you have to have an advance
directive before you enter it.
     MS. BACKLAR:  Right. 
     DR. CHILDRESS:  That is -- I think we have to keep those
separate.  If we do not clarify those in the report we will be
going around and around on this.  
     But Steve wants to get in. 
     DR. HOLTZMAN:  Again I am not terribly familiar with the
area but it will not stop me from talking.
     If I understand what you are doing here, when there is
potential therapeutic benefit, even if there is greater than
minimal risk, you are saying that a third party who cares about
the individual can do a cost benefit analysis and make certain
assumptions about that individual that they would have certain
values involving benefit to themselves and risks.  Whereas you
are saying it is not  legitimate for a third party to make that
kind of cost benefit analysis where the benefit are not benefits
specifically to the individual.  It seems to me that is the
bottom line.  
     The question I have -- you are talking about an empirical
study of whether or not there would be enough subjects for that
kind of research.  The question I would have is are there
significant classes of disease in which it is in the nature of
the disease that the individual will never be in a position to be
able to give such an advance directive?  
     If that is the case and if there is valuable research, which
is in its nature is not beneficial to the individual but to
understanding the disease, hence directly to the individual, and
involves potential harm or less than minimal risk and that is
understood as Bernie has said it, where it might be not risky to
me but risky in another sense, right, then effectively this is
saying that research will not be undertaken.  
     If I understand Alex, Alex's position is that is the morally
right thing.  That research ought not be undertaken.  Okay. 
     So I am not sure that it so much an empirical question about
whether the advance directives -- that is a question of how much
of that kind of research we are going to forego.  
     DR. EMANUEL:  Can I clarify the empirical question?  I think
that is a good point and here is the empirical question:  If we
survey these people and they said -- when they are competent and
they said, "Yes, I would like to participate in research," and
then they did not fill out an advance directive.  That would show
that advance directives, in fact, did not work in exactly the way
Alex wants them to work, which is a true expression of person's
preferences.  Is that right?  That is the study we need.  That
data actually is a relevant piece of data.  Separating preference
from action here.  
     DR. LO:  Let me just quickly respond to Steve's comment are
there classes of patients who would never be able to complete
this prospective consent.  It seems to me people who never had
decision capacity -- so people born with severe developmental
disorders who never have the capacity to make an informed
decision.  It seems to me those people would be excluded from
this class of research.  My point would be they would also,
therefore, be cut off from any benefits that might flow from this
greater than minimal risk, not beneficial to that individual
research, because you will not understand some basic things about
the causes of the epidemiology and causes of illness. 
     DR. FLYNN:  Can I just speak to this because I do have a lot
of concern that we are not aware of what this research really is. 
There is a huge set of investigations going on now that look at
the basic biological processes that underlie severe mental
disorders.  Most people who are involved in that research I think
are capable of and do, indeed, participate in giving their
informed consent.  
     But those who are potentially the most important to study,
those who have almost no remission of their symptoms, those who
are multiply impaired, those who have had virtually no way to
give their advance consent or participate in a process are some
of the folks whose participation is most crucial to understanding
and being able over time to ameliorate and ultimately conquer
these disorders.
     It is important that we build protections for these folks. 
It is completely unacceptable to me that we would set up in place
a standard that would essentially stop such research if there
were -- if that is where we think we are going.  I do not think
we want to do that.  I think we want to look at feasible and
useful ways of creating a participation for those subjects that
assures the research goes forward because it is crucial and at
the same time protects them. 
     I think that is what Trish was trying to bring to us in
looking at as one tool the research advance directive.  But we
certainly do -- and I was very troubled to see that families were
removed from that potential role with some of these populations.  
     But I do not want to have the conversation continued with
some assumption that we are willing to give up this research
because we cannot seem to find a way to adequately protect
subjects and yet let this important research go forward. 
Remember greater than minimal risk is not necessarily
extraordinarily risky sets of experiments. 
     DR. CHILDRESS:  It seems to me that this is one place, let
me get some feedback, where we could profit a great deal from
some input from investigators and others over the next few weeks
and I am not necessarily talking about a study but get some
feedback on this.  One of the -- as you recall from the
discussion with the Genetics Subcommittee this morning, the
possibility of putting out -- we are not ready for that yet
because we need to get recommendations further along, but putting
out a draft report and getting feedback.  
     In part of that I think we do need to get feedback on this
from people who work in the field, including the kinds of
comments that Laurie has offered.  That is one thing I think
would be very useful for us.  If there is agreement we will work
out some way to do that.
     Alex?
     MR. CAPRON:  I think we have heard enough that before that
report goes out we have got to go back to the drawing board to a
certain extent because like the Tissues Committee we simplified
and Larry was urging simplification before, and no more than so
many categories, but we may have gone beyond Einstein's dictum
that we should make things as simple as possible and no simpler.
     Because the desire not to distinguish between more than
minimal risk and things which impose severe pain or threaten life
or function, bodily functions, and the different -- the failure
to differentiate between those of permanent loss of decision
making capacity when our real focus in this has been those who
have some diminished but often fluctuating and often varied
capacities, the capacity to decide some things and not others.   
     And our failure to distinguish between institutionalized and
non-institutionalized individuals may have led us to reach
conclusions where I would be certainly open to the notion that
there can be a definition of the benefit of -- prospective
benefit to a group of people of whom the individual is one. 
Where if you had some -- both extraordinary proof that there was
no other way of getting this information rather than just as an
avenue of convenience, indication of the great value of the
information and some surrogate process beyond the individual's
relatives because we know that there are many relatives who are
very protective.  
     We also know that for some long-term institutionalized
people there are relatives who have relatively little attachment
to the individual and who are not really likely to exercise the
kind of concern that we are expecting from them.  
     This may just be a topic where the devil is in the details
and we have got to go back and attend to those details a little
bit more and we do not want to paint with too broad a brush.  I
continue to think we should go into it with a very strong
presumption that the efforts should be addressed towards getting
people to seek that consent and to go through a process of
finding subjects at times when they are able to consent, Zeke,
and working with people longitudinally instead of just saying,
"Gee, I need subjects and I want them to be depressed and so I
will get them when they are depressed right now rather than
having to take the greater effort to work with them over time
until they come to a point where they are not depressed and can
anticipate a future episode and how they would be willing to
react at that time."  
     DR. CHILDRESS:  So this is kind of conceptual normative work
to be done?
     MR. CAPRON:  I think it is -- yes, conceptual normative. 
     DR. CHILDRESS:  What else do we need to do?
     MS. BACKLAR:  Perhaps we actually need to do some boxes. 
God help us. 
     DR. CHILDRESS:  These are not boxed boxes but they serve the
same purpose but we may need more complicated one along the lines
of Zeke's several categories.  We will influence Jonathan soon
enough. 
     MR. CAPRON:  Jim, there is another generic question that --
usually I do not think it makes sense to spend a lot of time as a
whole group wordsmithing, but I have been bothered with the draft
as it now stands by the term that we have used, the adjective we
have used to describe decision making capacity, which is
questionable.  And we are searching around.  At other times we
say decision making capacity is in doubt.  
     There is something about -- and if other people do not share
my sense I will simply -- I mean, it is not something I feel
strongly about.  It is just it bothers me.  The word
"questionable" is usually used in context where you are making an
adverse judgment about the person involved.  I mean, he is --
     DR.            :  Questionable character. 
     MR. CAPRON:  A person of questionable character.  A painting
of questionable authenticity.  I mean, et cetera, et cetera.
     I know it does not mean to attach to the individual but in a
way it rubs off a little bit.  If anybody creatively could
suggest how we -- without saying a person who may lack decision
making capacity or whose decision making capacity may fluctuate
or whatever -- even uncertain it strikes me is a better word than
questionable.  But, I mean, I have made the point and --
     DR. CHILDRESS:  I think that is --
     MR. CAPRON:  -- this is more or less something to submit to
you and Jonathan if people have some creativity.  
     DR. CHILDRESS:  And Diane was -- because a part of this grew
out of our discussion in early December at the conference which
used this particular title and part of it is an effort to get at
how the subject is first sort of confronted.  What do we see? 
Questions are raised about the person's capacity to consent.  
     However, your point is well taken.  
     Diane, do you want to respond?
     DR. SCOTT-JONES:  We did spend a lot of time discussing this
issue, Alex, and I agree with you.  It is not really an elegant
or a precise term to use but if you use other terms such as
uncertain, uncertain connotes lacking self-confidence or
something like that so it is not the best term either.  What we
were using before, decisionally impaired, became awkward in its
use throughout the text.  
     I think part of the problem is that we are lumping together
and calling a population be referred to persons who lack decision
making capacity as a population when, in fact, there are many
different groups who are being lumped under this rubric and a
better choice -- I do not think we can practically do it but a
better choice would be to talk about persons with various
disorders separately and call them by some more descriptive term. 
I think we are going to have this problem as long as we are
lumping together disparate groups of people and that is where the
problem lies. 
     DR. CHILDRESS:  But we are interested, in part, in what they
share and it is how we described what level used for what they
share that becomes critical for the report. 
     DR. SCOTT-JAMES:  But what they share is not really always
shared because some of the persons covered under this chapter
would be incapacitated almost all the time.  Some others would be
rarely incapacitated.  We even put children in here and we tried
to fix that a bit by referring to younger children but we even
put children in here who are developmentally appropriate in their
decision making.  So it is just --
     MR. CAPRON:  That is one of the reasons we dropped
impairment.
     DR. SCOTT-JONES:  Right.  
     DR. CHILDRESS:  Zeke -- oh, sorry, I missed the comment. 
     MR. CAPRON:  Well, that is one of the reasons we dropped
impairment because a child of seven who does not have an adult's
decision making capacity is not impaired, it is a normal child,
but they do not have full decision making capacity. 
     In some ways the question that Laurie was raising before
about people who are born with disorders which make them always
unable to participate in decisions are not even covered by this
report as it is now entitled.  They are not of questionable
decision making capacity.  They lack decision making capacity.  
     I mean one escape is to say this report narrowly addresses
the category of people who go in and out of decision making
capacity and where you have to make certain in any circumstance
where they are when you are engaging them in the consent process. 
     DR. CHILDRESS:  Zeke has a creative solution.
     DR. EMANUEL:  No, no, no.  I am struck as I was struck
actually this morning by the fact that we seem to all be in the
grip of a different kind of picture as to who these -- fit into
each of these boxes.  
     It may be that what is in your mind, Alex, is a certain kind
of experiment that really stuck out -- stuck with you and I may
have a different kind of experiment as the sort of paradigm that
I am thinking these rules ought to apply to.  Part of the reasons
we are at loggerheads is because we have not made these
distinctions. 
     I think Laurie hinted at some of the kinds of distinctions
we should make.  I think -- and this, I think, applies equally to
this morning's session -- it might be helpful if we had some
paradogmatic cases to see if we could agree on them and
understand them.  You know, are we talking about sending someone
into the PET scanner with an A-Line is?  Is that the kind of case
that we are really talking about as greater than minimal risk
with no potential benefit for them?  Or is it something else?  A
more invasive procedure than just an A-line but we are talking
about a -- you know, I do not know -- bronchial or, you know,
something else?     So I find this -- we are talking in the
abstract sometimes and I think having some cases might be
helpful.       
     The second thing I would like to raise is a tension that I
think I hear between research and clinical care.  A long standing
relationship between the researcher and the research population
has certain advantages for the prospective consent to get into a
study.  It also has the problem, which I have confronted in
oncology, of confusing very easily in the mind of the patient
whether this is research or whether this is really clinical care. 

     No matter how many times you say it "no benefit to you, no
benefit, you will not benefit, it is simply a toxicity study,"
they understand something completely different.  I fear that if
you do have one of the tensions of these long-standing
relationships might get better understanding between the patient
and the doctor but they have the other fact that you slide, and
that the consent then -- the patient understands something
different no matter how many times the words are said and how
competent they really ought to be. 
     MR. CAPRON:  Right.  The longstanding relationship does not
have to be with the researcher.  I mean, the -- if a researcher
in an institution says to her colleagues who have patients in X,
Y, Z condition over time, "I would like you to consider exploring
with your patients participation in research," obviously you -- I
expect you to explore it with them during periods when they are
able to comprehend but I recognize that they may be in other
periods when they cannot, and those may be the periods when I am
interested in studying them.  
     And after you have determined in this process that they are
willing to participate I will then come into the picture, tell
them that the research -- and I am not their treater.  I am
coming in to ask them to be in research but you have got the
ongoing relationship with them and you will be the one who is in
a position to say they are able to understand the kinds of things
I would be raising or not understanding it. 
     I do not think we have to anticipate the -- but you are
absolutely right.  The notion of a therapeutic misconception or
therapeutic confusion that arises is pervasive in human subjects
research and it is probably particularly an issue with long-term
relationships and particularly in relationships where there are
difficulties in mental processes. 
     DR. CHILDRESS:  Diane gets the last word and then we will
turn it over to Harold.  We might even get in a three or four
minute break here.  
     DR. SCOTT-JONES:  I just wanted to point out that on page
nine and ten of the report there is a pretty good discussion of -- I am sorry.  There is a good discussion of varieties in
decision making impairment.  I think the problem is that when we
get to recommendations we lose this complexity and we make the
population homogeneous again.  But here the various elements that
are important, including the situation itself, the particular
decisions to be made, all of that is laid out here pretty well. 
What we need to do is to find some way to incorporate this into
the recommendation and not lose these distinctions. 
     DR. CHILDRESS:  Okay.  Arturo wants to stick in one quick
work. 
     DR. BRITO:  I had been raising my hand here but you could
not see me. 
     I was going to make reference to the same page, page nine,
but even there the terminology is tough because I think varieties
itself has a lot of implementations.  A suggestion that I was
going to bring up tomorrow actually because I thought it was more
detailed but since we are on the topic, to refer to this section
as different or differing levels of decision making ability, and
then within that Jonathan, I thought, did a good job talking
about the fluctuating ability and the prospective incapacity. 
But there is one missing here and that is progressive incapacity
and progressive prospective incapacity.  You refer to Alzheimer's
as a perspective but it is really a progressively prospective.  
     He does discuss under the first paragraph of chapter X where
it becomes more complicated because someone put along the two or
more of the categories.  So I thought it was already addressed
and just changing a few of the words around.  But you are right,
at the end we need to readdress it. 
     DR. CHILDRESS:  Good.  We will work on this some tomorrow. 
People who cannot be here tomorrow, whether they are on the
subcommittee or on the full commission, please give us any
suggestions you have.  We focused really on one part of the
report.  We paid most of the attention to that.  A very important
one and very critical to what we are doing but there is a lot
more there and we hope that you will give us suggestions so that
we can move forward with the draft.
     Jonathan?
     DR. MORENO:  Can I just say two things?  
     I have lots of things I would like to say but I have
exercised remarkable restraint, I think, over the last hour.
     It does seem to me that with respect to research advance
directives or whatever you want to call them that this analogy
with regard to end of life in a clinical setting is important. 
Nobody has mentioned one that the investigator has an incentive
to sign up subjects and use whatever device is available, which
is not the case, although I have tried to convince my physician
colleagues it is in their best interest to get their patients
signing advance directives in New York I have not succeeded but I
think investigators have an inherent incentive to use devices
such as this.       Whether that will make much of a difference
at all belong in the big picture and I think the stable question
that Zeke raised is a very important one and it is an empirical
question.  
     I also want to say that on page 145 the current text does
come close to a default position that Laurie and others called
for, for family members.  It is not in the -- my inadequate chart
but is on page 145 and under 5.  Perhaps that should be stricken. 

     DR. SHAPIRO:  Okay.  Thank you. 
     I think we are going to have to call an end to this
discussion.  
     Jim, thank you very much.  I know your committee is meeting
tomorrow and will make use of a good deal of this -- some of the
comments that have come up here today. 
     We are going to take a five minute break because we have to
set up the projector and so on, and we will move on to the last
two items on our agenda. 
     Thank you very much.  
     (Whereupon, a brief recess was taken from 3:11 p.m. until
3:26 p.m.)
     DR. SHAPIRO:  First of all, let me make a logistical
announcement.  For those of you that have any marked up copies of
the genetics report, the one that began with the overview and had
some outlines of the rest of the chapters and so on, and had the
section on religious attitudes done up and so on, would you
please make sure to give those to Kathy Hanna before you leave. 
So if you have any marked copies please give them to Kathy or one
of the members of the staff before you leave. 
     Now we are just slightly delayed by a technological glitch
in the projector here.  We hope that will be finished in the next
few minutes.  That means we may or may not get to our last item,
which is processes in changing regulations.  We may take that up
next time.  But I want to wait and try to get this done because I
know Professor Fletcher and others have to go and I want to get
to that as soon as we can.  So I will just ask you for your
patience for another few moments. 
     Order, please.  Colleagues?  
     Trish, are you ready? 
     I want to turn to Alex in a second to lead us through this
discussion.  Also we have a number of guests who are here to help
us with this discussion.  
     One last change in the agenda.  We will with thanks to
Rachel's tolerance postpone the discussion of processes in
changing regulations until next time.  
     So this will be the last item of our discussion today so let
me turn to Alex.
     Alex?
     MR. CAPRON:  I am getting wired. 
     DR. SHAPIRO:  Alex is getting wired.  It is not enough that
the world is wired, he has to be wired as well.
     (Simultaneous discussion.)