MEETING OF THE GENETICS SUBCOMMITTEE OF THE NATIONAL BIOETHICS ADVISORY COMMISSION

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MEETING OF THE GENETICS SUBCOMMITTEE OF THE
NATIONAL BIOETHICS ADVISORY COMMISSION
Friday, January 10, 1997
8:13 a.m.
The Madison Hotel
Washington, D.C.
EBERLIN REPORTING SERVICE
14208 Piccadilly Road
Silver Spring, Maryland
20906
(301) 460-8369
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I N D E X
JOINING THE SUBCOMMITTEE IN ITS DISCUSSION:
DEBRA SASLOW, OFFICE ON WOMEN'S HEALTH, DEPARTMENT OF
HEALTH AND HUMAN SERVICES
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DAVID KORN, AMERICAN ASSOCIATION OF MEDICAL COLLEGES
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MARK GUYER, NATIONAL CENTER FOR HUMAN GENOMIC RESEARCH
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P R O C E E D I N G S
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DR. SHAPIRO:
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brief announcements.
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the other.
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Colleagues, there are just two
One of a more personal nature than
Let me get to the regular announcement first.
We are as I mentioned yesterday, I may have
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mentioned yesterday, I cannot remember now, considering
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meeting elsewhere, that is elsewhere than Washington,
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D.C. area, for our July meeting.
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Bill to look at various possibilities.
I am going to be asking
We have received
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various invitations from particular locations who would
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like to have us meet there and I think it is a good idea
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for us to meet outside of Washington to be able to at the
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very least to get public comment and so on from people
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who are not directly in this area.
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As Bill reviews these, of course, a key
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aspect is going to be what kind of support we can get
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from the location to support our meeting and so on.
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will be a key aspect of it.
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let you know that I am going to have Bill investigating
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the various possibilities.
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or want to find out about this or want to suggest places,
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please contact Bill.
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That
In any case I just wanted to
Any of you who are interested
Now for the personal announcement before we
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get down to the business.
If any of you see a stray
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black Lands End briefcase, I am missing one.
So I
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thought I walked in here this morning with it but in any
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case if you see one --
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DR.
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DR. SHAPIRO:
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:
DR.
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DR. SHAPIRO:
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I do not believe so.
That has
the --
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Is this it?
you.
:
Are you "HTS"?
That sounds like it.
Thank
I knew this would be a help.
(Simultaneous discussion.)
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DR. SHAPIRO:
Do not auction it off, please.
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Tom, thank you very much for the few minutes.
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DR. DOMMEL:
Before Tom gets underway the
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seating arrangement is, I am sure you figured out by now,
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for the members of the public this is a meeting of the
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Subcommittee on Genetics of the National Bioethics
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Advisory Commission.
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committee members, subcommittee members of the Genetics
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Committee or the invited speakers to join in, in that
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subcommittee's work or staffers.
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the table commission members or staff will be seated
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without the name plates.
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So where the name plates are, are
And then elsewhere at
So any commission member who would like to
sit at the table who is not please come up and join us.
DR. MURRAY:
Welcome to the second meeting of
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the Genetics Subcommittee of the National Bioethics
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Advisory Commission.
I am glad we started on such a high
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note.
We already made a discovery.
I refer to my
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briefcase as my life support system.
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less calm about it if I had lost mine.
I would be much
We have until 10:00 o'clock at which point we
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will adjourn.
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then the Human Subjects Subcommittee will meet from 10:30
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until 12:30.
As we had hoped yesterday the full commission
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There will be a half an hour break and
gave its assent to our desire to press ahead with the
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first report on the issue of stored tissue samples.
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was a subject that we had picked as one that was
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appropriate for our intensive work in the first year even
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as we begin work also on at least two other issues with
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which we have interest, that is genetic discrimination
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and privacy on the one hand and gene patenting on the
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other.
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on the issue of stored tissue samples.
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This
But we are going to focus this morning's meeting
We have asked three guests specifically to
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join us and make brief comments, about five minutes each,
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coming from different perspectives.
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Korn and I will ask each of them to introduce themselves
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in a minute.
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Debbie Saslow.
We have Dr. David
Dr. David Korn, Dr. Mark Guyer and Dr.
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We also have two people, at least two people
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in the audience, who also have a great deal -- who know a
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great deal about this issue and whom we may feel free to
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call upon and they should feel free to add to our
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conversations.
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yourselves.
Let me begin by asking you to introduce
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Would you do that, Dan and Elizabeth?
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DR. DRELL:
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I am Dan Drell with the
Department of Energy, Human Genome Program.
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DR. MURRAY:
Elizabeth?
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DR. THOMPSON:
I am Elizabeth Thompson and I
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am the assistant director for Clinical Genetics Research
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in the ELSI program at the NCHGR and currently on detail
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to the director's office in the Office of Policy
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Coordination.
DR. MURRAY:
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Thank you very much.
You should
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feel free also to be a resource for us if you have
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anything that you think would contribute to our
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conversation.
Debra, may I ask you to introduce yourself
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and to begin by telling us about your work with the
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National Action Plan on Breast Cancer and particularly
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the focus group study?
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DR. SASLOW:
Can you hear me?
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DR. MURRAY:
Move it very close.
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DR. SASLOW:
I am Debbie Saslow and I work at
DR. MURRAY:
Actually would you mind sitting
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the --
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here?
That is at the request of other commission
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members.
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DEBRA SASLOW, OFFICE ON WOMEN'S HEALTH,
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
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DR. SASLOW:
I am Debra Saslow.
I work at
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the Office on Women's Health and am on the National
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Action Plan on Breast Cancer which is coordinated by the
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Office on Women's Health.
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one of which has been dealing with tissue banking issues
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and has spent most of its time on ethical issues and
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We have six working groups,
developing a model informed consent form.
I believe you all have a copy of our focus
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group report which explains some background and history
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about the project and provides the draft form that was
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focus group tested.
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just a few relevant points specifically about the
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genetics issue which I think is what you are most
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interested in.
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I am going to limit my comments to
First of all, one of the premises for this --
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one of the early decisions made by the committee that
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developed this form was that they were only going to
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address prospective studies.
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the issue for now of retrospective studies.
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came up yesterday.
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tissue that would be collected from this point on.
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They were going to ignore
I know that
So it is developing a form for any
They recognize that a lot of genetic research
is not different than general clinical scientific
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research, however there are some types of genetic
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research that are different and that do need to be
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handled differently.
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plan the example dear to their hearts is the Tay-Sachs
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samples that were used to identify BRCA mutations that
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are more prevalent in the Ashkenazi Jewish population and
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that that research has the potential to be used to
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discriminate not only against individuals but against a
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group of people.
Given that this is a breast cancer
What they decided to do to address that was
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to specifically mention genetic research in their
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informed consent form which other than that deals with
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cancer research in general using breast cancer as a
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model.
They start -- this was a long process.
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I
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would be happy to answer specific questions about how
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long it took and who is on the committee.
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with a much longer form and gradually got whittled down.
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We also worked with a low literacy translator and
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genetics.
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because that is a difficult topic to explain to the
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general public on a low reading level.
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But it started
That was an obstacle for dealing with genetics
They started with several questions on the
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consent form.
Actually they started with four and ended
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up with three and may decrease that further.
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fourth question that was deleted was:
But the
"Do you give your
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consent for your tissue to be used for genetic research?"
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And the reason they deleted that was for practical
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reasons.
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tissue can be used for cancer research but not cancer
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research that deals with genetics.
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that some mention of genetic research needed to be
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mentioned in the form itself and that consent for cancer
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research would include research that involved genetic
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research.
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They did not think they could track.
This
But they did feel
That sentence that was left or sentence or
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two did raise some confusion for the focus groups.
The
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committee that developed the form will be addressing the
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results of the focus groups in the next couple of weeks.
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They meet by conference call and they are leaning towards
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developing a question and answer form that would
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accompany the informed consent and that this consent form
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would be given to patients a week or two before they
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needed to sign it so that they could take it home, think
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about it and discuss it with their families.
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Those patients who want more information, who
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want to know more about genetic research and other issues
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such as -- the second question was:
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consent for research other than cancer?"
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medical research.
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some consumers might object to their tissue being used
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for such things as behavioral research which is another
"Do you give your
So general
And that question came about because
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topic that came up yesterday.
So this Q&A form would address -- would
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explain genetic research and why some people might object
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to it as well as some of the other issues that came up as
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confusing to these focus groups or that some people might
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want more information about such as what are these other
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types of medical research and why should I be concerned
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about them.
Those are my main points about the genetics
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issue.
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working group that has been very active dealing with
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hereditary susceptibility issues.
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banking group has used breast cancer as a model for
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cancer, the genetics group has used breast cancer as a
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model for genetics.
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have done might be of interest or might be able to
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provide resources to this committee.
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I would like to mention that we have another
Whereas the tissue
I think that a lot of the work they
We have done a lot of work on genetic
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discrimination.
We have addressed health insurance,
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employment issues.
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by state of legislation.
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in the coming months.
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groups, of just a lot of different information that I
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think might be of interest.
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trials susceptibility working group.
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that came up yesterday.
We have thick notebooks going state
We will be addressing privacy
We have address lists of consumer
We also have a clinical
That is an issue
A consumer involvement group.
So I would be happy to continue to provide
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any information I can.
DR. MURRAY:
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Thank you.
This is the first
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time we will have met as a subcommittee with other
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members of the commission present and it seems to me to
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be quite artificial to say that to invite questions or
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comments from only members of the subcommittee.
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not going to do that.
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sense of other commissioners who are here but not members
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Please ask your questions if you have any
questions of Dr. Saslow at this point.
MS. KRAMER:
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Bette?
Debra, you mentioned that they
used the Tay-Sachs material.
DR. SASLOW:
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I mean I will rely on the common
of the subcommittee.
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So I am
Not the action plan but
researchers.
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MS. KRAMER:
That material has been used.
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DR. SASLOW:
To my understanding that is
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blood samples.
MS. KRAMER:
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Sachs.
I mean other than for the Tay-
They have gone back subsequently and used it.
DR. SASLOW:
Right.
It is my understanding
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that individuals who are Jewish and, therefore, gave
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blood samples to be tested for whether or not they are a
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carrier for Tay-Sachs, that those stored samples were
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then used by researchers and that those samples were used
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in research that identified BRCA-1 mutations that are
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prevalent in the Jewish community.
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MS. KRAMER:
Now did they go back to the
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donors of that blood to get an informed consent for that?
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They did not?
DR. SASLOW:
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No.
And that also brings me to
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the third question in our consent form which is "Do you
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give your consent to be reconsented if we want to use
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your samples for something that is not in the original
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consent form?"
We tried to make the consent form as
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inclusive as possible but left that as an opening.
MS. KRAMER:
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I was just curious and maybe you
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know the answer to this or maybe Tom or David:
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went back and used the samples that were taken for Tay-
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Sachs had that -- was that anonymous?
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DR. SASLOW:
I believe so.
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MS. KRAMER:
It was?
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DR.
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MS. KRAMER:
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MR. HOLTZMAN:
:
It was.
It was.
Were they anonymous or
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anonymized?
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back to those people or was it impossible?
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I mean, was it theoretically possible to go
DR.
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When they
:
That I do not know the
answer to.
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DR. THOMPSON:
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DR. MURRAY:
I do.
Elizabeth?
DR. THOMPSON:
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Dr. Collins was involved in
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that research and he after much deliberation, they made
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the meticulously -- I mean, they anonymized them but
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there was no possibility of linking them back, none, by
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anybody.
DR. MURRAY:
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Zeke?
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DR. EMANUEL:
At some point early on you talked about the
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fact that for some tests you were worried because it
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might be used to stigmatize a group and discriminate and
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you were in that context referring to the Tay-Sachs and
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Ashkenazi Jews.
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apply broadly to genetic tests that might -- we do not
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know before we start -- track with different racial
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ethnic groups.
I did not understand why that does not
DR. SASLOW:
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It does.
I think my point is
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that there is also other types of research.
You know,
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genetic research can be defined pretty widely and if you
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are studying just DNA and not looking at genetic
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predisposition or genetic disease some people would
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consider that genetic research.
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probably be addressing more of that.
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example.
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there are also examples of research that might not have
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any potential harm or raise concerns to the consumer.
I think Dr. Korn will
That was one
There are many other potential examples but
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DR. MURRAY:
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DR. MIIKE:
Larry?
Let me get clear about the
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process that you are in, in revising the form.
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now asked an additional question about reconsent after
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the initial with the objective being that once they sign
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this one they are reconsented for any subsequent use?
DR. SASLOW:
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No.
You have
We are giving them the
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option to be notified, to be contacted in this case by a
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middle person in the process of anonymizing samples and
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not by the actual researcher, but by this tissue banking
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middle group to recontact somebody to ask them if their
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tissue may be used for some purpose that turns out not to
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be covered in the original consent form.
DR. MIIKE:
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Just let me ask on that specific
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point then.
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answer when just a simple statement within the consent
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form informs them that they may be recontacted?
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it seems kind of weird to me that you ask them a yes or
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no question, that they sign on that says you may contact
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them when you could simply just ask them or just in the
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informed consent process tell them that something like
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that may happen.
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Why do you ask a question for a yes or no
Anyway,
But maybe I am not articulating what I am
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trying to say and I am trying to put forth.
But the
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process that you are going through now you found certain
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things that need to be improved so you may have added an
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additional question and then you are going back, at the
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current time back into the explanatory part of the
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document to try to make a better connect between the
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explanation and the question?
DR. SASLOW:
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The genetics question was
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deleted prior to the focus group testing just based on
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the committee discussion.
DR. MIIKE:
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whole revision process.
DR. SASLOW:
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I am just looking in terms of the
Right.
There was a lot of
revision prior to focus group testing just within
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committee and the committee -- the focus group report was
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only recently received by the committee.
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address the concerns raised by the focus groups although
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based on some preliminary results that were communicated
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to them during the process we already have some ideas of
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the direction they will be going to finalize this one.
DR. MIIKE:
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They will now
Is the group also sort of
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standing back and seeing that at the end of the process
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can you really get informed consent about this at all?
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It seems like it sets -- it starts to get into such a
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wide open consent kind of an arrangement that you just
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sort of -- I begin to feel that it sort of -- I do not
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want to use the word -- I guess I better not.
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just seems like it is a -- it is trying to establish a
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process for something that is almost a disconnect in
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terms of a real consent.
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get at?
But it
Do you see what I am trying to
I mean, it is a consent to such a broadly open -
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-
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DR. EMANUEL:
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DR. MIIKE:
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DR. EMANUEL:
It is overly broad.
Yes.
Maybe I can amplify it.
When I
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read the statement -- one of the -- we are always
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balancing things.
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it so that people do consent and on the other hand you do
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not want them to consent something to so vague that it
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applies to almost anything.
Are you getting -- you want to make
I guess one of the questions
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is whether number two, the second question, is just so
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open that in fact you are not really getting consent.
It looks -- I mean, it smells like consent,
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it is a signed piece of paper, but people have no idea
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what they are saying yes to when you ask them in that
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form.
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protect people and give them a chance to understand what
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their tissue is being used for, in fact it is really
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robbing them of consent when it is so overly broad.
So that -- while informed consent is meant to
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I think that --
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DR. MIIKE:
Yes.
Do I have it right, Larry?
I guess it is a -- I am not
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following anybody, but I guess it is a deficiency of an
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informed process that boils it down to a written
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statement that one signs.
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that.
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look at.
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through and end up with a piece of paper, but the whole -
I guess that we are stuck with
That is an issue I really want the commission to
Not the procedure that one currently goes
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- the whole process about can we actually get some
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reasonable way of true informed consent in the whole
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process.
It just -- what I am getting at is that since
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you are sort of bound by the current way of getting
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informed consent which is an ultimate piece of paper, it
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seems -- especially when you get into these kinds of
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areas that I do not really -- I see it as sort of an
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impossible task to get truly informed consent this way.
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DR. MURRAY:
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DR. COX:
David?
I have a comment and then a
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question to Debra.
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a way of trying to protect research subjects in this kind
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of a setting against unwanted recontact, and in fact -- I
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will just make a pretty dogmatic statement that something
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through good wishes paternalism cannot necessarily be
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good.
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for things that I have no interest in because I am on
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mailing lists and I have a very simple solution to that.
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I hang up the phone.
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The comment is a perception, again in
I know that I am contacted by people constantly
So I think that this is something that goes
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on in our society on a regular basis and if people are
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recontacted simply because they happen to be on this
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particular mailing list, i.e. they were on one research
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thing, then in that specific situation they have a very
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specific way of saying that they have no interest at all.
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Does that really infringe upon their rights as an
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individual or their privacy?
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issue I would like to explore a little bit and it is
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along the same things you are talking about, Larry.
I think that is the kind of
The question I had for you, Debra, was if
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there was a specific reason why your group chose not to
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deal with retrospective samples because this commission
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is talking about dealing with retrospective samples and
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one reason could be it is because you think it is a
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nonproblem.
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a problem.
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reason was.
The other reason could be it is like too big
So whatever -- I am interested in what the
DR. SASLOW:
13
I think the reason was that it
14
is a separate problem and that they would have to deal
15
with them not together and they decided to take one piece
16
of it.
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mention the reason for the question is to protect people
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who do not want to be contacted but also another piece of
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this project is principles that they have developed that
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are geared towards IRBs and that would set out rules for
21
recontact so that you would not be contacted 25 times.
22
There would be some kind of priority and limitation of
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how many times you could recontact.
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big piece of the project of dealing with informed consent
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and ethical issues.
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As far as the reconsent I would just like to
DR. COX:
So this is just one
Can I do a follow up, Tom?
So
1
then, Larry, in regards to you that this piece in many
2
ways really perhaps is not an informed consent but it is
3
a separate thing in between that is basically dealing
4
with protecting people against recontact and not to --
5
those sound to me like two very different things in terms
6
of consent for -- broad consent for another study as
7
opposed to consent for recontact.
DR. EMANUEL:
8
9
are not about recontact.
DR. COX:
10
No.
Yes, but questions one and two
They are about using tissue.
So I am not specifically
11
talking about one and two here specifically but in terms
12
of recontact per se.
13
DR. MURRAY:
14
MR. HOLTZMAN:
Steve?
Let me address one and two and
15
Zeke's question of whether it is done in a written form
16
or some better kind of form, the whole notion of is it
17
possible to get consent for something, a genuine consent
18
when you cannot describe what it is you are going to do
19
because your question goes to that and whether that is
20
possible?
21
do a genetic study trying to identify the genetic basis
22
of say asthma.
23
of that because people -- we take a blood pressure
24
reading and so consequently if you are also doing a
25
hypertension study it might be useful for example if you
26
find the polymorphism to go back and do an association
So some real life experience.
We go out and
As part of the clinical characterization
1
study back into that cohort that you found in the asthma
2
study.
3
it?
It could be very useful.
So how do you handle
What I see modeled there at least as the way
4
5
we have adopted it is you ask for the consent of the
6
person for the use in the particular study that you can
7
describe.
8
have familial say asthma that they could have an
9
intrinsic interest in that disease so that you get
The next level is to recognize that if they
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consent for additional studies within that disease.
11
then the last is getting the consent for a broader more
12
wide open consent for use in future research.
13
And
So in that way you are trying to give people
14
the ability to say how far they want to go.
15
are raising the question is that last request valid?
16
DR. COX:
17
MR. HOLTZMAN:
I think you
Right.
And it seems the position at
18
least we have taken in our work is that there are people
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who by giving the people those different levels of the
20
ability to discriminate it recognizes that someone can
21
say, sure, I am quite happy that my sample can be used in
22
any way to help medical research.
23
DR. EMANUEL:
Well, I think it is in the
24
anyway that requires a certain imaginative capacity on
25
the person who is giving the consent as well as an
26
ability to predict what science is going to hold in five,
1
2
ten, twenty years.
That is very difficult.
Now, you know, when I wear two hats, one hat
3
as a researcher myself, I understand why I want that.
4
is a big problem trying to track everyone down, you know,
5
maybe ten or twenty years later, and we could get
6
extremely valuable information.
7
It
I do not deny it.
On the other hand, you know, I want to say
8
did someone really consent in the way we mean consent
9
when they signed this for something that is going to
10
happen ten, five years down the line in a completely
11
different area.
12
stretching the notion of consent there a little far and
13
we may say that is stretched for a good reason and we are
14
going to accept it.
15
what we are balancing.
I think, you know, again we are
But I think we have to recognize
16
DR. MURRAY:
17
DR. DUMAS:
Rhetaugh?
It seems to me that the issue to
18
me is informed consent and the farther removed the person
19
is from the initial intent of the transaction the less
20
informed they are going to be.
21
the issue is whether or not in getting some a priori
22
consent far ahead of time you are, indeed, getting
23
informed consent.
I propose that you are not.
24
DR. MURRAY:
25
DR. GREIDER:
26
So I think that for me
Carol?
That was exactly my point.
signing this one is giving consent but not informed
In
1
consent for exactly the reason that Zeke just said.
MR. HOLTZMAN:
2
I guess I wanted to challenge
3
that.
4
and saying I want to use this sample and I am going to
5
use it in ways in which I cannot imagine this medical
6
practice changes medical research changes.
7
that.
8
basis for making a decision as to whether or not I want
9
to consent or to qualify that assent in various ways such
10
I mean, I can imagine someone coming to me, right,
I feel fully informed.
I understand
I feel like I have the
as that is fine as long as it is anonymized.
DR. GREIDER:
11
All right.
But you are not the average
12
consumer.
You can imagine what some of these things
13
might be down the road in terms of medical research.
MR. HOLTZMAN:
14
Not necessarily, Carol.
All
15
right.
Maybe what I am saying to myself is if there is
16
no harm that can come to me, for example, if it is
17
anonymized, all right, but I am quite happy it is used in
18
any way.
19
here really of whether you are going to go paternalistic
20
in trying to make a decision about what constitutes the
21
ability of one to be informed or whether you are going to
22
say can we structure it in such a way that people can
23
exercise an autonomy right to make a decision, whether
24
they have a sufficient ground.
DR. DUMAS:
25
26
It does not matter to me.
community.
So it is a question
Think about potential harm to
Raise the issue of what might be perceived as
1
potential harm to a community who use the samples to show
2
for example some inherent problem in a particular class
3
of people.
4
community.
5
That could be conceived as potential harm to
MR. HOLTZMAN:
I think that is a very valid
6
point, Rhetaugh, and that is what is interesting about
7
going back to the samples from Tay-Sachs is that even
8
anonymized, having removed the individual identifiers --
9
10
11
DR. DUMAS:
Right.
MR. HOLTZMAN:
characterization of the sample -- the group of samples.
12
DR. DUMAS:
13
MR. HOLTZMAN:
14
15
-- nevertheless you had a
Right.
I think that is a valid issue
that one needs to think about.
DR. COX:
Steve, it seems to me that your
16
argument -- okay, if I got it right -- was that sure this
17
is fine because it will not do any harm because things
18
are anonymized.
19
anonymized so you did not even know the group that they
20
came from too, then like totally anonymized, then I could
21
see your argument.
22
anonymized then we know that there is -- whatever the
23
probability --
In fact, if they were completely
But otherwise if they are not
24
(Technical difficulties.)
25
DR. MURRAY:
We have lost sound.
26
DR. SASLOW:
I just wanted to mention --
DR. MURRAY:
We have lost sound.
3
DR.
:
4
DR. MURRAY:
We have sound.
5
DR. SASLOW:
I wanted to mention that members
1
2
Can you
hear me?
Yes.
Go ahead, Debra.
6
of this committee included consumers, that those
7
consumers in this case just happened to be Jewish as well
8
as breast cancer survivors and that they were looking at
9
from the perspective of, you know, when I got my breast
10
tissue removed, this is how I feel the community issue
11
was discussed.
12
DR. MURRAY:
13
DR. MIIKE:
Thank you.
Larry?
Having started off the way I did
14
now let me change tracks a bit.
15
are -- faced with the dilemma that you are faced which we
16
just discussed, it seems that what the group is trying to
17
do is to say there may be times in the future where it
18
will be used for things unknown and we are asking you for
19
broad consent to recontact you.
20
if there is a recontact process and if at that time those
21
are initial consent were then provided enough information
22
to then make a subsequent independent decision about
23
their reuse.
24
this revision of the consent form.
25
26
It seems that what you
I would feel comfortable
That I assume is what is being attempted in
What you just said is they are just giving
permission to be recontacted.
It is not a blanket
1
provision to be -- to use their tissue in anyway.
2
that correct?
DR. SASLOW:
3
Is
I think the second question
4
deals with other medical issues that we can understand
5
now and that would be addressed in a separate, not in the
6
actual consent form, but in a separate like Q&A or
7
brochure for those who want the information which goes
8
back to the broader issue of the informed consent.
9
of these focus group participants do not want all the
A lot
10
information and that has been a difficult thing for us to
11
deal with.
12
that is a start for either IRBs or this group or some
13
other group to take off and come up with rules about
14
reconsent.
15
As far as the reconsent again that is a piece
But the idea is that there may be something
16
in this consent form that is not covered and something
17
that researchers want to do with the tissue and they
18
should not automatically be able to call up somebody and
19
say, hey, can I use your tissue for something else.
20
if that is okay with the person then they can give the
21
consent to be recontacted again with the -- under certain
22
rules that are yet to be generated about -- but that
23
would not be a call every other night from any researcher
24
for any purpose.
25
26
DR. MIIKE:
But with the intent that when
they are recontacted they are then given another
But
1
explanation of the specific use of them?
DR. SASLOW:
2
Right.
There would be a whole
3
another consent form for whatever, you know, would be
4
appropriate at that time.
DR. EMANUEL:
5
May I?
We have been talking
6
about anonymizing the tissue samples and all.
7
read this consent that is not part of it, right?
8
part of the whole point of this consent is to keep all
9
the medical history that goes along with that tissue
10
sample so you have the richest pool of research data
11
possible.
DR. SASLOW:
12
But as I
I mean,
Without the person's name and
13
keeping in mind that this is cancer research where they
14
would want to know, for example, with breast cancer was a
15
person estrogen positive or negative, did they relapse,
16
et cetera.
DR. EMANUEL:
17
I have to say I still do find
18
number two -- I think it needs more thought.
I mean that
19
is just my reaction here.
20
absolutely understand why one wants to have this and I
21
can see that it is hugely important and it makes things
22
efficient.
23
conditions might it be permissible and do you need more
24
information in this kind of consent before -- about how
25
it is going to be handled, et cetera, before that consent
26
can be considered informed and legitimate.
And again as a researcher I
But I think we need to think about under what
1
DR. MURRAY:
2
DR. GREIDER:
Carol?
I guess I also have a question
3
between question two and question three.
4
reads, "I agree that my tissue may be kept for research
5
about other medical questions."
6
agree that someone may contact me in the future to ask me
7
to take part in more research."
8
number two, why would they even need number three?
9
10
11
DR. EMANUEL:
Question two
And question three, "I
If somebody signs yes to
They might need a different
tissue for example.
DR. MURRAY:
I would like to make a
12
distinction that goes to why we invited you here.
13
have been focused, I think appropriately we have been
14
focused on whether or not this kind of particular form
15
would be satisfactory, that is whether it would, in fact,
16
as a -- you know, given informed judgments by people
17
sophisticated about this kind of research and about the
18
ethics of human subjects research, whether this
19
particular form and process would be adequate.
20
We
We also though invited you here not so much
21
to judge the form and process, and I just have to note
22
for the record as far as I know most consent forms are
23
not developed with this kind of care.
24
if we can raise these kinds of complaints about one that
25
has been developed with excruciatingly detail and care
26
heaven help the rest of them.
So if this is --
We also invited you here though to find out
1
2
what it all means to the people who are asked to sign the
3
forms.
4
this tissue -- that there are tissue banks and at least
5
one of the comments indicated that, you know, the banks -
6
- people make money in banks and there are lots and lots
7
of interesting interpretations that your respondents made
8
in these focused groups.
What do they understand when they are told that
It goes -- there are comments about the
9
10
motivations.
Why people would agree.
There was
11
interesting information about the question of -- we had
12
the question yesterday whether individuals as sort of
13
isolated, atomistic persons who just make these decisions
14
in the full glory of their autonomy, or whether in fact
15
they see themselves as situated in families and they want
16
to talk to their families, and you have information that
17
pertains to them.
18
to go talk to their families for the most part.
19
not see themselves as making these decisions entirely in
20
isolation.
My gloss on it is that yes they want
They do
Is there anything you want to stress to us
21
22
about how they understand genetics and how they
23
understand what it means to give -- to provide tissues
24
for research or should we just -- the data can speak for
25
itself.
26
I would like to give you that opportunity and then we are
But if you would like to say anything more to us
1
going to take you off the hot seat.
DR. SASLOW:
2
Okay.
I think as far as
3
genetics there is not good understanding about what the
4
concern is so even if they understand genetics they might
5
not understand the implications.
6
lot of people who do not want to know, who just want to
7
sign it and do what you want and there are others who
8
want a lot more information, and so again our response
9
will most likely be here is separate information outside
I think that there is a
10
that consent form.
11
practical issue, we foresee the informed consent form
12
being delivered and presented to the consumer by a
13
doctor.
14
If you want it, it is here.
Again a
We wanted a doctor.
Presumably their surgeon with some
15
explanation, with some conversation, do you have any
16
questions, do you want to discuss this, here are the
17
things that, you know, commonly come up. But also with
18
the understanding that a lot of doctors do not take the
19
time to do that and just hand it to people as they are
20
being wheeled into surgery.
21
information but with the hope that there will be more.
22
So we are providing the
I also want to underscore that one of the
23
biggest goals of this project was for the consent to be
24
informed and not to develop a consent form, but for the
25
consent process to be informed.
26
lot of this and I think the report speaks for what the
And that was behind a
1
public is responding.
DR. MURRAY:
2
I see Bette wants to say
3
something and David wants to say something, and then I
4
think we are going to -- we want you still here but maybe
5
sitting there and we will invite Dr. Korn to come up and
6
speak next.
7
Bette?
8
MS. KRAMER:
9
Debra, when we spoke a few weeks
ago I think you told me that your group was developing an
10
informational video.
Has that -- do you intend to use
11
that along with this or -DR. SASLOW:
12
That video is on genetic testing
13
for breast cancer.
It is done by the different working
14
groups.
It deals with the hereditary susceptibility
15
issues.
The informed consent deals strictly with
16
donating tissue for research.
So there is overlap --
MS. KRAMER:
So it did not pertain to this
19
DR. MURRAY:
David?
20
DR. COX:
17
18
issue.
Since this commission as Tom -- at
21
least the subcommittee in particular is very interested
22
in finding out what the public's perception to stored
23
tissue banks is I found it very interesting in the focus
24
groups that one of the conclusions was that the
25
participants were suspicious about the motivations behind
26
tissue bank research.
So what were they suspicious of?
1
2
Because the
-- I would be interested in that.
DR. SASLOW:
3
We were told by experts that
4
conduct focus groups that we should give as little as
5
information at the outset as possible who we are
6
sponsoring.
7
there.
8
African American community was very suspicious about, you
9
know, the whole -- you know what those researchers like
So I think that there was a lot of suspicion
Again there were cultural differences.
The
10
to do with our tissue and they will take -- all the
11
groups, but particularly on some of the Baltimore African
12
Americans were very suspicious about profit and about
13
using tissue for unethical reasons.
14
lot of misunderstanding or a lack of information about
15
what research is and how it works.
16
DR. MURRAY:
17
Dr. Korn, would you be willing to join us at
18
Thank you very much, Debra.
the front of the table for a bit?
DR. KORN:
19
20
I think there is a
It does not seem to improve the
quality of the sound system I am sure.
DR. MURRAY:
21
Let me just switch the cards
22
around.
23
are usually in California but you are at the Association
24
of American Medical Colleges now as a distinguished
25
research scholar if I recall correctly.
26
Dr. Korn has consented to join us.
I gather you
DAVID KORN, AMERICAN ASSOCIATION OF MEDICAL COLLEGES
DR. KORN:
1
Yes.
Well, thank you very much
2
for allowing me to be with you today and feed you some
3
fuel for your debate.
4
faculty member at Stanford for 29 years.
5
the Department of Pathology for 17 and vice-president of
6
the university and medical school for 12 -- 11.
7
sabbatical now with the Association of American Medical
8
Colleges undergoing rest and rehabilitation, and it has
9
been very successful.
I will just say that I have been a
I was chair of
I am on
Let me try to give you a somewhat different
10
11
perspective on this issue of tissue issue.
12
about --
13
(Technical difficulties.)
14
DR. KORN:
I will talk
-- although it is not just
15
generally recognized by the public, and we can argue and
16
apologize for that forever but it is a fact, our nation's
17
hospitals and especially the academic medical centers
18
collectively contain an enormous archive of human tissue
19
samples that represent a unique resource that reflects
20
the prevalence and protein expressions of human disease
21
over time.
22
that goes back to the time that these materials began to
23
be collected over a 100 years ago.
24
It is a document of human disease over time
The specimens were all removed for medical
25
reasons under sparing general broad consent language that
26
usually provided a proviso for research and educational
1
uses and were submitted to the path lab for diagnostic
2
evaluation.
3
to pathology.
That is why they were removed and submitted
Although they were not collected specifically
4
5
for research purposes these specimens have, in fact,
6
served as a rich source of materials for clinical
7
pathological investigations that again as a fact have
8
provided most of the vocabulary and much of the
9
foundation of modern medicine.
10
That is what modern
medicine has evolved from.
The results of the studies because of the
11
12
technologies available have historically been of public
13
benefit, not private.
14
consequence to individual patients from whom the tissues
15
have been derived.
16
practice and standard of informed consent for this vast
17
body of research, vast body of research, has been minimal
18
and I would say in the context of present understanding
19
inadequate.
20
And thus of little immediate
Accordingly and admittedly the
What has changed of course has been the
21
introduction of dramatic new technologies like monoclonal
22
antibodies and polymerase chain reaction which allows
23
investigators to go back to these fixed paraffin imbedded
24
section tissues and examine genetic abnormalities either
25
in gene structure or expression and infer whether these
26
changes are as they commonly are of somatic origin and
1
therefore not inheritable or on occasion of germ line
2
origin and therefore inheritable.
The power of these approaches provides unique
3
4
insights into the mechanisms of human diseases.
For
5
example, neoplasms is as evident from just reading the
6
contemporary medical literature that I believe cannot be
7
obtained by other means and they offer enormous promise
8
of advancements and diagnosis and prognosis and therapy,
9
and even prevention.
At the same time, however, by their
10
nature the results may be construed to have major
11
predictive consequences for individual patient sources
12
and their families and this fact has rested the entire
13
topic of research on human tissue from a historic state
14
of peaceful repose to sharp prominence in the public
15
consciousness.
Now a lot of the committees and groups have
16
17
been wrestling with these issues.
18
sponsorship of the ELSI program and a number of proposals
19
have been circulated or published in the last couple of
20
years.
21
strongly that these efforts have suffered from a lack of
22
broad based scientific input.
23
in the proposals which many of my scientific colleagues
24
and I find to be disappointing and unduly threatening to
25
an entire class of promising research.
26
Many of them under the
I think that these efforts -- I think very
I think this is reflected
I would like to make four general
1
observations about these processes which are personal and
2
then offer some specific recommendations that I realize
3
will be controversial.
4
First I think that the deliberations have
5
failed to distinguish between two different issues.
One
6
of them is genetic testing which I think should be
7
defined narrowly and which raises considerations of
8
definition and appropriate informed consent.
9
is genetic information that can be obtained or inferred
The other
10
from a myriad of clinical and research sources and which
11
raises concerns of privacy and of the protection of the
12
confidentiality.
13
readily accepted.
14
unique and different in kind from all other private,
15
sensitive, often predictive, often stigmatizing
16
information that can exist in a medical record.
17
I think secondly it has been too
In my case the genetic information is
I argue that the difference is not so much
18
qualitative, it is one of degree, and I think the
19
distinction is important in devising appropriate and
20
workable, and I underline workable mechanisms for
21
protecting confidentiality.
22
Third, I think it is disappointing then in
23
attempting to deal with issues that heavily center on
24
preventing the misuse of genetic information obtained
25
through research so much effort has been expended not in
26
trying to strengthen the protection of the information
1
but in burdening the conduct of genetic inquiry and
2
erecting barriers to the ongoing creation of the
3
knowledge base.
4
I think the proposals thus far have a very
5
commendable input of bioethical and legal perspective but
6
an inadequate input of scientific perspective.
7
they come down too heavily on the side of private
8
interest at the expense of public benefit and thereby
9
destroy the delicate equipoise that must always be
10
respected in research involving human subjects.
11
me make a couple of specific suggestions.
12
discussion if you will.
13
I think
So let
Fuel for
First of all, I think that much more
14
attention has to be paid to the definition of terms in
15
order to achieve precision and avoid confusion and
16
adverse unintended consequences.
17
contemporary molecular biology terms like genetic
18
research, genetic sample and even genetic tests
19
colloquially used are exceedingly broad and so inclusive
20
and imprecise that it is inadvisable to attempt to use
21
them as the basis for new research guidelines or
22
regulations.
23
In the context of
I would respectfully suggest that an example
24
of the semantic contortions that one gets into in not
25
dealing with these definitional issues is beautifully
26
illustrated in the scholarly commentary to the genetic
1
privacy act by George Annas and his associates.
2
commend it to your attention.
I
Secondly, I would argue that genetic testing
3
4
appropriately defined should unarguably meet a high
5
standard of informed consent.
6
proposed are too broad and overreaching and I think they
7
should be narrowed to focus on the purpose of the study
8
rather than on the kinds of research methodologies that
9
are used.
But again the definitions
For example, I make no pretense of being a
10
geneticist as David Cox knows, I would suggest that such
11
a test might be one that is carried out on individuals to
12
determine the presence of particular inheritable risk
13
factors of established predictor significance for
14
purposes of genetic counseling and/or medical management
15
or on populations for epidemiologic purposes.
I think the research studies on human tissues
16
17
removed for medical reasons ordinarily should not be
18
construed as genetic tests even if they involve
19
examination of gene structure and function.
20
of such studies should not be considered diagnostic,
21
should not be entered into the medical record ever and
22
should not be communicated to the source of the tissue
23
ever.
24
The results
There appears to be general agreement.
Third, that the informed consent protocols
25
used for research on human tissue specimens must be
26
strengthened and that different stringencies of informed
1
consent perhaps should apply depending on whether samples
2
are anonymous or linkable to patient sources.
3
point out that research on samples that are coded but
4
linkable to patient sources -- I would argue, excuse me,
5
that research on samples that are coded but linkable to
6
patient sources should continue to be eligible for
7
approval under a general informed consent mechanism under
8
specific circumstances that I will address in a second.
9
But I also would suggest in any new consent protocols
I would
10
developed for use in the clinical setting must be clear
11
and simple, and provide the patient with a clear yes/no
12
option.
I do not know how many people in this room
13
14
have been in surgery.
15
facing surgery on the instant of the anesthesia you are
16
in no mood to get into a elaborate dialectics over
17
potential future uses of your scraps of tissue.
18
simply are not.
19
care what the language says.
20
consent.
21
I have.
And I will tell you that
That is not informed consent.
You
I do not
That is not informed
I would argue that the language should be
22
crafted in conformity with the principle of general
23
informed consent.
24
should be based upon the premise that the national tissue
25
archive has always been and should remain a public
26
resource dedicated to the public good.
I know that is controversial.
And not a
That it
1
depository like a savings bank of private property.
I know fourth that efforts are underway in
2
3
the Congress and many states legislatively to strengthen
4
the protection of clinical genetic information and
5
prohibit its misuse in discriminatory fashion.
6
that many of these initiatives are hasty, ill considered
7
and inadvertently over reaching even at the same time
8
that they contain substantial loop holes that undermine
9
their intended purposes.
I believe
Much more thoughtful effort
10
must continue in this arena and similar efforts must be
11
initiated to secure genetic information created in
12
research.
13
Now elsewhere I have suggested and I am not
14
sure it is a good suggestion that a mechanism like the
15
certificate of confidentiality mechanism or some new
16
mechanism from statute might be developed to protect as a
17
class all genetic information created in research and
18
that such protection could be conferred on research
19
institutions through an assurance mechanism that required
20
those institutions to have in force an institutional
21
confidentiality policy that met specific requirements
22
including the provision of severe sanctions against
23
violations of that confidentiality rule.
24
Finally I would urge the subcommittee to
25
broaden participation in this important debate by
26
reaching out to the scientific community and especially
1
to those who are increasingly employing the tools of
2
contemporary molecular biology and molecular genetics to
3
tissue samples of human origin to gain unique insights
4
into human diseases that are major burdens to our
5
society, both in terms of human suffering and resource
6
consumption.
7
I think I will stop there.
I have a handout
8
which you have and I would just point out to you again
9
for a fuel for your discussions that there is a model
10
consent language that I tacked on to the end of this
11
statement just to give you an idea of the other extreme
12
if you like from some of the proposals that have been
13
attempted or circulated by other groups.
14
I would like to just point out to you that
15
when you think of the tissue archive there is no way as
16
some of the people on this side of the table have already
17
said to predict the kinds of research applicability that
18
might be -- that might arise months, years or decades
19
later than the collection of that tissue.
20
So if you really believe in informed consent
21
where every potential use of this material could be
22
presented honestly and completely to a patient in
23
advance, it is impossible.
24
other alternative that you would have then is to go back
25
to each patient or their next of kin on every single
26
specimen that might be identified as interesting for some
It is impossible.
The only
1
study of the disease in question or whatever else might
2
be useful for those tissues.
3
used longitudinally to study the diseases for which they
4
were removed.
5
them.
Most of those tissues are
In general that is what happens to most of
That is how our knowledge of disease is
6
7
developed.
It is the mechanism by which the knowledge of
8
disease and its manifestations, its classifications,
9
subsets of disease and how they respond to different
10
therapies or do not respond is accumulated into the
11
medical literature.
12
That is how it happens.
This resource is an irreplaceable, invaluable
13
resource that has to be maintained with maximum
14
accessibility for the public.
15
that point in mind as you get into these very, very
16
difficult issues that you are wrestling with.
17
luck with your deliberations.
18
19
20
DR. MURRAY:
I urge you to try to keep
I wish you
Thanks.
Thanks.
Let me invite questions
or comments.
DR. COX:
Dr. Korn, as one of the members of
21
the scientific community that does use this information I
22
would like to say that I really think that your analysis
23
of the historical present of this versus the present time
24
is a very apt and interesting one and that is where I
25
would like to come into this discussion.
26
If I heard you right you said that
1
historically that this information really was used -- it
2
did not have applicability to individuals and that what
3
is different if I heard you right is that with the new
4
technology now there is a perception that the new
5
technology will have applicability to individual.
It strikes me that that is where the
6
7
discussion and where the turf is divided up really lies
8
because if, in fact, we are in a new time where
9
information does have important consequences to
10
individuals then this distinction of information as being
11
research versus practice becomes a blurred one.
It again strikes me that that is really where
12
13
the discussion lies in terms of whether we even need to
14
have a different view of dealing with stored tissue
15
samples.
16
that particular point because if we are in a new time
17
where the historical tissue archives now have different
18
implications for individuals, first are we in that kind
19
of a time and, if so, then how do we deal with that?
20
So I would very much like to hear your views on
DR. KORN:
Okay.
Fair enough.
First of all,
21
implications I think -- would you agree that implications
22
are particularly relevant to the discussion if you are
23
picking up something that is germ line?
24
DR. COX:
I would like to go even broader
25
than that just in terms of implications to the individual
26
whether they are germ line or not.
I think that the
1
specific -- it is, is it information that the individual
2
could or should use for making personal decisions?
DR. KORN:
3
Well, it is my -- again, I want to
4
emphasize that being in the jobs I have had, and I have
5
gotten deliciously distant from some of the front lines
6
on this, so if I misspeak I hope you will correct me.
7
But I do not really believe that the study of somatic
8
changes in tumors, for example, has very much in general
9
particular interest to the patient sources.
I think that
10
information is much more pertinent to developing an
11
understanding of the progressive changes that lead to the
12
transformation of the normal cell to a malignant cell.
It is of interest I think that as far as I
13
14
can recall not a single proposal except the one that came
15
out of Dr. Holtzman's genetic testing task force, not
16
you, the Johns Hopkins Holtzman, even mention the
17
difference between somatic and germ line mutations.
18
is never mentioned in any of the documents and proposals
19
that have been circulated, including George Annas'
20
compendium.
21
It
Now, yes, if you are doing research on
22
tissues and you pick up a germ line mutation, yes, you
23
definitely could argue that this has significance for the
24
person and probably the family of the individual who has
25
submitted that tissue.
26
guess the way I come down on this is that I want to keep
But I think that in order -- I
1
access and use of the research of the tissue archive as
2
unencumbered and unburdened as we can.
I am willing to trade off on certain
3
4
conditions in order to accomplish that and one of the
5
conditions that I personally would be willing to trade
6
off on and again I am sure that this can be debated is
7
that this material, this information is never diagnostic,
8
it is never entered into a chart, and it is never
9
communicated, and nothing needs to be identified with a
10
particular individual.
Most researchers as far as I know who are
11
12
using tissue for these kinds of studies have no interest
13
whatever in the name, address and social security number
14
of a patient.
15
a lot of this data is very -- of very limited value
16
unless, for example, you can go back to the clinical
17
record and find out it is what the biological correlates
18
are.
19
a tissue repository mechanism where the investigator need
20
never have access to the chart but would go through a
21
secure linkage point or request through a secure linkage
22
point the information.
23
There does have to be linkability because
That can be done through a protected mechanism like
Now I do not know whether everybody in the
24
room understands what I am talking about but let me give
25
you a very simple example.
26
modern medicine is the inability of clinicians and
One of the vexing problems in
1
pathologists who receive a minimal breast lesion detected
2
by mammography let's say to know whether or not that
3
lesion is going to be a problem to the woman from whom it
4
has been removed.
In many, many cases removal of that minimal
5
6
lesion is a cure.
But there are other cases in which it
7
will not be a cure and those patients need aggressive
8
chemo and/or irradiation therapy, and maybe tamoxifen,
9
and all kinds of other interesting things.
We cannot
10
really tell which of those minimal lesions.
The same
11
thing is with prostate in males for example.
If we could
12
find particular genetic markers that would reliably
13
predict benign behavior or aggressive behavior in these
14
now confusing lesions which are so abundant it would be
15
an enormous public benefit and an enormous benefit to
16
patients.
17
think we do not want to hinder.
18
it.
19
20
That is a kind of genetic research that I
DR. COX:
We do not want to hinder
David, I completely understand that
and that is in the --
21
DR. KORN:
22
DR. COX:
Yes, I know you do.
-- sort of historical model.
But
23
in the context of where information can be used by the
24
individual to make decisions then it is difficult.
25
would just say with respect to somatic mutation, and I am
26
not an oncologist, we have an oncologist here, but I
I
1
think that there are clinical decisions made based on the
2
distribution of somatic mutations in terms of what your
3
therapy is right now and medical practice now that has
4
direct implications to a specific individual in terms of
5
what their somatic mutations are.
So I am not saying this is easy and I
6
7
certainly understand the paradigm that you are talking
8
about which has been, as you very eloquently state, has
9
been the historical basis of all of modern medicine.
But
10
I think that if we are in this modern time which I did
11
not hear from you whether you think we are or not, where
12
things are different, then we have to deal with -- then
13
do we have to deal with those differences?
14
offs that you spoke about which you are willing to give
15
up to be able to maintain the historical way of doing
16
things.
17
into is should we be -- how do we adjudicate those trade
18
offs.
I think that is what this commission is looking
DR. KORN:
19
The trade
I respect your point, David, and I
20
do not really disagree with it.
I do not believe the
21
current standard of informed consent is adequate.
22
said that and I will say it again.
23
strengthened.
24
goes about doing this I think is critical and I think
25
there are two very serious issues -- three serious issues
26
here.
I have
I think it has to be
But how it is strengthened and how one
One, the emotional state of most people who
1
2
are going to be asked to do that consent.
They are not
3
going to be sitting around a desk having an intellectual
4
discussion about genetics.
5
to death about what this thing is in their body that
6
needs to be removed.
They are going to be scared
Two, it is impossible to predict what kinds
7
8
of applications, technologies and questions might be
9
benefited from using that tissue over a long stretch of
10
the future.
Three, I think that how you ask questions, as
11
12
many of you know better than I, has a very, very big
13
impact on what kind of answers you get.
14
something magical about the word "genetic" right now.
15
reminds me, a senior citizen, very much of the furor in
16
the early '70s when recombinant DNA came along and there
17
were enormous -- there was enormous hysteria about the
18
threat to the ecosystem that was going to be offered by
19
recombinant DNA.
20
banning of research in the City of Cambridge and other
21
places.
22
fan that kind of hysteria.
23
end whatever.
24
There is
It
There were mass meetings and the
I mean this is a kind of -- we do not want to
DR. EMANUEL:
I think that leads to no good
I -- you have said twice now
25
that you think the standard of informed consent that we
26
had used is inadequate.
As I understand it there is --
1
when you come into a hospital there is generally among
2
the papers, certainly in academic hospitals a statement
3
that your medical record and other related information
4
could be used for research, and that is usually the carte
5
blanch on which we have done a lot of this medical
6
records and related work.
7
Why is that inadequate in your view?
8
DR. KORN:
I think it is fair to say that
9
what happens with tissue is that buried in the operative
10
consent form which most people do not read is a sentence
11
or two that says any tissue not required for diagnosis
12
may be used for educational research purposes.
13
not think that is informed consent.
14
I just do
I think that that -- I mean, I am not saying
15
you should adopt this thing that I tacked on to the
16
statement, but some separate statement that says that
17
these kinds of tissues have been used very importantly in
18
developing medical information and progress.
19
would like to be able to use your tissues for such
20
studies now and in the future years, and I think it is
21
important to deal with this issue of property interests.
22
That we
I do not believe that people have property
23
interests in their scraps of tissue.
I know that is also
24
debatable but that is how I feel about it.
25
is only one really good case to my knowledge that has
26
adjudicated this which is the Moore case out in
I know there
1
California.
But I do not think that people should have
2
ownership of their scraps.
3
DR. MURRAY:
4
MR. HOLTZMAN:
Steve Holtzman had a question.
Not so much a question as a
5
comment.
First I would like to thank you for your
6
presentation.
7
here is in some ways the beginning of a conceptual road
8
map of all the kinds of distinctions we could profitably
9
draw and clarify.
I think what we as a committee are getting
So, for example, genetic tests.
10
Somatic mutation looking at that or changes in
11
transcriptional profiles of genes is very different than
12
looking for inheritable mutation.
13
paradigm.
14
different than if what you are talking about is looking
15
at anonymous samples for transcriptional markers.
16
The latter is your
The kinds of concerns you have are very
The kind of question David raised is has the
17
technology changed the nature of the relevance of the
18
investigations of the individuals.
19
For example, the idea of doing longitudinal studies
20
looking at morphological changes which has classically
21
been done in terms of pathology studies.
22
something that says if I see that change it is relevant
23
to the individual.
24
I am not sure, David.
You could find
Another aspect is, is there a difference when
25
the collection of the sample is in the context of a
26
research study, which at least is my paradigm with doing
1
genetic studies and you can go through this consenting
2
process, versus when it is in the context of the
3
pathology getting the scrap of tissue.
4
that there may be important differences.
5
pathology departments right now also, as we deal with
6
them as a commercial firm, they do not know what to do.
7
They find themselves looking for guidance.
I know that the
Does it matter that it is the investigator
8
9
It seems to me
down the hall who wants to look for a molecular marker
10
versus it is a commercial firm that wants to look for a
11
molecular marker?
12
other hand the investigator down the hall finds the
13
molecular marker and that institution turns around and
14
licenses it to a commercial firm.
15
problem.
On the
That does not seem a
So I think -- again we need to get into these
16
17
Does that make a difference?
distinctions and try to get some clarity.
DR. MURRAY:
18
Steve, do I recall correctly
19
that you were trained as a philosopher before you went
20
into --
21
(Laughter.)
22
DR. GREIDER:
23
DR. MURRAY:
24
25
26
I just wanted to -- good philosophical work
there.
DR. GREIDER:
I just wanted to address the
practical issue that has been raised a couple of times
1
between the difference between a somatic change and a
2
germ line change.
3
useful distinction to make because we do not want is
4
going to happen in the future in research.
I do not think that that would be a
For instance, there are examples where you
5
6
might want to cross a somatic change and then later
7
experimentally discover that somatic change is due to a
8
germ line mutation.
For instance, mutated phenotypes and
9
other such things.
So I do not think that we could, you
10
know, prospectively say that we know that a somatic
11
change has no implication on the germ line.
DR. KORN:
12
I would like to make just one
13
other clarification of what David Cox asked me before.
14
believe that if a particular genetic marker is identified
15
as and accepted as a valuable diagnostic indicator in a
16
particular disease it moves rapidly out of the research
17
setting into the diagnostic -- armamentarium diagnostic
18
work up.
19
marker in a prostate lesion had important prognostic or
20
therapeutic interest then the path lab would begin doing
21
that test as part of the diagnostic work up of the
22
specimen submitted to it by the surgeon.
23
I
In other words, if one knew that a particular
Now I would call to your attention that
24
because of the semantic problems, the definitional
25
problems, if you read literally and in good faith, a
26
number of the proposals that are out there to date, they
1
would require not only informed consent for any
2
particular or potential use of research -- in research of
3
the tissue, but it would require informed consent of a
4
whole host of diagnostic tests that become part of the
5
routine evaluation of specimens.
6
In fact, unless the surgeon or the clinician
7
knew in advance exactly which of those tests were going
8
to be necessary for that particular specimen, which
9
usually does not happen until the first pathology look is
10
made, you would have to keep going back and forth to the
11
patient and say, well, now we have got to do another test
12
and we are going to have to look at another gene, and let
13
me explain all this to you.
14
I mean it is cumbersome and I do not think
15
that is what was intended by any of the working groups.
16
They were not trying to get into the diagnostic process.
17
The language has a way of seeping into very unexpected
18
corners when you are using very broad and vague terms.
19
think that is a problem.
20
DR. MURRAY:
I
David, you framed things
21
usefully, even starkly when you said that this is -- one
22
could understand this debate as an effort to strike a
23
balance between private interests, the protection of
24
private interests and public benefit.
25
legitimate way of framing it.
26
only way but it is certainly a useful way.
That is a
I am not sure it is the
So I have been thinking about what are the
1
2
sorts of private interests, or to put it another way, the
3
concerns of subjects that might be at issue here and let
4
me just -- in the spirit of Steve's comments let me try
5
to list what strikes me as a few as I recall them from
6
reading the various statements in the literature that I
7
have read.
8
9
One is discrimination not just for self but
also potentially against family.
A second is privacy
10
which is not again subsumed under discrimination but also
11
concerns about information about me but also about my
12
family again.
13
that I would disapprove for whatever reason because it
14
involves research into group differences because it
15
involves research into behavior.
16
let your imagination run on this.
A third is the possible uses in research
You know, on can just
That is a possibility.
17
A fourth is commercialization which David Cox
18
keeps reminding us is an issue that people have concerns
19
about and that can take different colorations.
20
be not getting my share although the evidence I saw from
21
the work that Debra Saslow has presented to us indicates
22
that not everyone is concerned with so much getting it
23
for me but there would be some reasonable use which again
24
was sort of second cut on commercialization might be a
25
kind of unjust enrichment without appropriate return to
26
the people -- the categories of people or to the public.
It could
1
You get unjust private enrichment rather than public
2
enrichment.
3
large category.
So commercialization is for me the fourth
And then the fifth which you framed as a kind
4
5
of generalized property interest, people maintain
6
property interest in bits of their tissue.
I am not arguing that all five of those are
7
8
legitimate or that they are widely held, but they strike
9
me as at least five different and I would invite other
10
members of the commission if they had other thoughts if
11
they wanted to extend there.
12
of -- I am sure we can generate a laundry list and we can
13
look critically at each of those kinds of concerns or
14
interest.
15
legitimate.
16
that might appropriately be sacrificed in the furtherance
17
of the larger public interest of research.
Some of them might strike us being much more
Others as well.
MR. HOLTZMAN:
18
That seems to be the kind
Maybe the sorts of things
Well, one of the things that
19
Alta raised yesterday is that how people feel about all
20
those things might -- it also might make the difference
21
which tissue is at stake.
22
tissue.
23
you know, it is pretty odd when you think about it that
24
organs you can only donate, blood you donate, blood is
25
fractionated and the plasma is sold.
26
hand is purchased when you go to a plasma phoresis
All right.
The reproductive
But if you then look at our societal practices,
Plasma on the other
1
center.
Urine, which is also used to find markers and
2
whatnot, people do not seem to have the same relationship
3
related to their urine in quite the way they are related
4
to their blood and to organs.
When we just jump into as our paradigm highly
5
6
charged areas like breast tissue and cancer I think we
7
get ourselves confused and in the most well meaning way
8
we start to lay down paradigms of how this should be
9
handled then it is problematic.
We really need to lay
10
open all of the different relationships and look at the
11
historical -- how we do things with all these different
12
kinds of tissues, the different circumstances under which
13
we as a society collect them and use them.
PROF. BACKLAR:
14
I am interested that the only
15
talk about the negative aspects.
16
negative.
17
future generations.
18
and information that they may wish.
19
people I believe who might want to be linked to their
20
tissue.
21
the issue just as we have explored the negative.
22
Your list is all
There are no positives.
I have concerns about
My obligation to future generations
There are many
I think we should start to explore that side of
DR. EMANUEL:
Can I amplify that?
I mean, it
23
seems to me that certainly when I wear my clinical hat
24
one of the things almost all patients who come in want to
25
know is if there is going to be research on their tissue
26
if they might benefit.
The idea that this research is
1
only negative, and I cannot talk about it in terms of
2
generalizable for people who are not sick, but certainly
3
when they are sick they are very concerned about the
4
latest potential advance that might be to their benefit
5
and whether their tissue might contribute in that way.
So part of what I was going to follow up on
6
7
the idea of putting it as individual interest versus
8
public good may not fully capture it because many people
9
as individuals have an interest in the public good being
10
advanced.
11
interest.
12
13
14
A personal interest as well as a general
PROF. BACKLAR:
This is Eric's -- the
individual in a context.
DR. EMANUEL:
So I think I would -- well, it
15
seems to me that this might be an area where we should
16
urgently and promptly commission a paper to think through
17
these balances and interests because it might help us.
18
mean, if in fact what we are going to end up doing is
19
balancing individual interests, community interests,
20
researcher interest, having those spelled out in the way
21
you have done and talking about their strength and
22
saliency may help clarify in all of our minds rather than
23
just each of us doing it on one foot in five minutes.
24
25
26
DR. MURRAY:
I agree completely, Steve.
Larry and Alta?
DR. MIIKE:
Actually this is the genetic
I
Yes.
1
subcommittee part of the day but this is most useful to
2
me for one of the two areas where I wanted the Human
3
Research Committee to look at.
4
informed consent thing, it seems to me that it is sort of
5
like trying to fit my shoe and my foot in my baby's shoe.
6
In a sense that -- you know, I mean we talked
Getting back to the
7
yesterday about the change in the paradigm of research
8
and yet we are still stuck in all modes.
9
coming to my mind here is that I do not think there is
This is what is
10
any -- we are not even satisfied with informed consent in
11
the traditional way because as you say the way it is
12
applied is you never get really informed consent.
So it seems to me that from this standpoint
13
14
here we need to look at two things.
15
regardless of what the legal system now says we are
16
required to do, I do not think we should be restrained by
17
that in terms of the informed consent process because I
18
think part of our mission is to look for some major
19
change in the way that even the legal system looks at
20
things.
21
One is whether --
We talked about that in the patent area.
But I think the side that we need to look
22
into in this base is what are we trying to prevent, what
23
kinds of harm are we trying to prevent, and how we can do
24
that without just sort of being stuck in the informed
25
consent process?
26
issues to me it is too narrow a way to look at it if we
So when we get into these kinds of
1
just sort of limit ourselves to the current requirements
2
that we must go through in order to try to fit this
3
unfittable thing into a legal type of situation.
4
DR. MURRAY:
5
PROF. CHARO:
Thanks, Larry.
Thanks.
Alta?
First an apology
6
because I may something that somebody else said.
7
spending half my time scribbling to the chair of my own
8
subcommittee.
9
I was
I had the good fortune of spending a fair
10
amount of time with Gail Geller last spring who works on
11
the breast cancer stuff and although we have not actually
12
written it up we found ourselves talking a lot about a
13
phenomenon we called inflicted insight.
14
she thought McFadden might have coined in which people
15
are given information that actually causes harm by virtue
16
of having been given the information.
17
A phrase that
It arose in the context of breast cancer
18
because there particularly information about your genetic
19
predispositions tended to be coupled with complete
20
confusion or absence of information about what one ought
21
to do with that information.
22
to provoke anxiety without any real constructive purpose
23
to which it could be put, at least one that was
24
confidently known.
So its overall result was
25
And it strikes me that this is the thing that
26
might distinguish genetic information from other kinds of
1
information, Dr. Korn, if only because the amount of
2
information that is available through tissue samples
3
through genetic testing as opposed to the other kinds of
4
testing traditionally done is greater and the uncertainty
5
about what that information means is greater at this time
6
in history.
7
So I find on your list of things to concern
8
yourself with, Tom, particularly in light of the
9
difficulty of informed consent when you do not know what
10
you are consenting to, which is particularly true in this
11
area, that perhaps an additional thing to float through
12
your subcommittee would be to take into consideration the
13
degree to which we are talking about obtaining consent
14
from people in a process that in and of itself, to the
15
extent that it tells people we have information that may
16
or may not be a value in disease identification or
17
predisposition identification might itself constitute
18
this kind of inflicted insight problem.
19
suggest you should not tell people because I understand
20
if they turn out to be valuable in the end they may come
21
back and say why did not you tell me.
22
That is not to
We ran into specifically this problem at
23
Wisconsin with regard to samples that were stored in a
24
research context and they were sampled and tested and
25
then years later better test developed, earlier on
26
presymptomatic but for a disease for which there was no
1
presymptomatic therapy that had any proven value in
2
preventing or ameliorating onset, and we were totally
3
stuck as to what to do.
4
answers.
So I am not suggesting any
I am only adding something to your list.
5
DR. MURRAY:
6
DR. KORN:
David, do you have a comment?
Yes.
There is another phrase that
7
I would urge you to keep in mind that I was told about by
8
an epidemiologist called "uninformed denial."
9
think that is -- you know, you have got informed consent,
10
inflicted anxiety and now uninformed denial, what you are
11
trying to do is steer a path that is not going to get on
12
any of those reefs and I think it is a tough problem.
13
14
Well, I really appreciate the opportunity and
very much respect the challenge that you have got.
15
DR. MURRAY:
16
Mark Guyer to join us.
17
18
And I
Thank you very much.
Let me ask
MARK GUYER, NATIONAL CENTER FOR HUMAN GENOMIC RESEARCH
DR. GUYER:
I am Mark Guyer and I am with the
19
National Center for Human Genomic Research and my title
20
is assistant director for scientific coordination.
21
22
23
24
25
26
DR. MURRAY:
Were you planning a coup, a
demotion or what?
DR. GUYER:
No, it just -- it is a historical
statement, not a predictive one.
Tom asked me to come here today and talk
about the experience we have had in dealing with some
1
human subjects issues in relation to collecting material
2
for the Human Genome Project for determining the human
3
DNA sequence, large scale DNA sequencing.
4
specifically I want to talk a little bit about what led
5
us to developing a policy which we promulgated last
6
summer and then some of the reaction to it without
7
talking about the policy itself which I understand you
8
have all seen and I am assuming that you have read.
9
And
The background is that as the Human Genome
10
Project began and was conducted for the first several
11
years before the stage where we had to really consider
12
producing sequence I think it had been all along assumed,
13
it was clear that it had been assumed all along that the
14
sources for the material which was eventually going to be
15
sequenced were going to be numerous and that -- and
16
anonymous, unlinked at least to the individuals who
17
donated the materials to make the cell lines or the clone
18
banks, or so forth.
19
And so with that assumption in mind we did
20
not really focus on some of the questions that would be
21
raised by having large amounts of information about
22
individuals in the public domain.
23
similarities in what we are doing to some of the
24
questions that have been raised this morning and some
25
differences.
26
is important to remember that what we were doing is
I think there are some
I think in listening to what I am saying it
1
specifically collecting samples to develop a resource, a
2
research resource that is going to be widely used, widely
3
distributed, and presumably will be used in ways that are
4
now unanticipated.
5
came up earlier today I think are entirely relevant to
6
this.
And so some of the questions that
7
When we -- about -- just about two years ago
8
now the Genome Project started to move into a phase where
9
we were developing the capacity for doing DNA sequencing
10
on a large scale and testing ways that would eventually
11
bring us to the point where we could really go into
12
production on developing this first human reference
13
sequence and we called for grant applications.
14
Again assuming probably without thinking too
15
deeply about it that we were going to get proposals that
16
involved a lot of different resources, a lot of different
17
sources rather.
18
the case and when the applications came in, and there
19
were almost a couple dozen applications, most of them
20
involved a very limited number of DNA sources because as
21
it turned out that is really all there were.
22
technology for doing DNA sequencing had come to focus on
23
a new kind of vector system and there were really very
24
few clone libraries that had been made using that vector
25
system.
26
readily available to the people who were proposing to do
And then as it turned out that was not
The
Probably only two or three really that were
1
this research.
And so all of a sudden a year or so ago we
2
3
realized that some of the assumptions we were making
4
about how the source issue was going to be handled were
5
not correct.
6
very much stimulated by the need to try and understand
7
the issues that would be raised by having the human DNA
8
sequence, the first reference sequence, come from a very
9
limited number of individuals and as it turned out in
So the policy that we then developed was
10
some cases even made from -- developed from clone banks
11
that had not been collected even with appropriate
12
informed consent.
13
The policy that we eventually developed, and
14
this is -- make sure that everybody understands it, this
15
was a policy developed jointly by the NCHGR and the
16
Department of Energy Genome Programs, but only in the
17
U.S.
18
internationally even though the sequencing program is an
19
international program.
20
This was not a policy that had its development
The policy that we came up with was based on
21
our conclusion that, in fact, given what DNA sequence
22
information is and that DNA sequence information is
23
uniquely identifiable with an individual that some of the
24
standard approaches for human subjects protection
25
involving anonymity did not pertain in this case, that
26
ultimately with DNA sequence information, maybe not now,
1
but sometime in the not too distant future, individuals
2
could be identified and that in -- even in the reference
3
sequence if it had been derived from just a couple of
4
individuals there were clearly going to be ultimately
5
genes carried by those one or two individuals identified
6
which had mutations and raised many of the questions that
7
we have all been discussing about implications for health
8
status and so forth.
So the policy that was developed really had a
9
10
two pronged approach to the problem.
11
the number of clone sources that would be used for
12
sequencing so that ultimately this -- that we would
13
return to the model that we had assumed in the first
14
place.
15
developing would actually be a mosaic that would be
16
comprised of DNA from as many individuals as possible
17
therefore limiting the information that theoretically
18
could be derived about any one of them to as minimal as
19
possible.
20
One was to increase
The reference sequence the Genome Project was
The second was that with every attempt to
21
keep those individuals identity confidential on top of
22
everything else but realizing that we could not guarantee
23
anonymity, to really focus on trying to -- on the
24
informed consent of getting the donors of this material
25
to indicate and to provide them with as much information
26
as possible about what they were donating and the project
1
that they were donating for, and what the potential risks
2
were including this issue of unanticipated use and
3
therefore unanticipated risk.
So the guidance and the policy that I presume
4
5
you have seen tried to incorporate that.
6
publicly last summer.
7
not even know how I was going to fill up the five minutes
8
of time.
9
It was issued
In terms of reaction to it I did
There has been very little reaction.
There were a couple of articles in the press
10
about it, a piece in Science, a two page piece in
11
Science, that generated two published letters in Science
12
and that is basically the extent of the public reaction.
13
We have not had calls, as far as I know the
14
DOE has not had calls.
Francis Collins tells me that
15
nobody has come up to him in private and said anything.
16
There have been -- there were some concerns originally on
17
the part of the people who were involved in the DNA
18
sequencing, a concern that whatever we might do would
19
slow down the research.
20
were willing to take.
21
have been a particularly significant problem because we
22
addressed that by not prohibiting the use of the existing
23
libraries until the point at which the new libraries
24
could be made available.
25
did require that those people who had been involved in
26
constructing the existing libraries go back to the donors
I think that was a risk that we
But even that does not seem to
The existing libraries.
But we
1
and obtain what we called consent for continuing use
2
basically as a stop gap until new libraries that were
3
made under more acceptable conditions could be developed.
The only other element in terms of reaction
4
5
that I can think of is on the part of the people who are
6
going to go out and make the new libraries.
7
-- there are only a couple.
8
laboratories in the U.S. that I know of that are involved
9
in making the new libraries.
There really
Maybe three or four.
Three
They have actually been
10
very responsive to this policy.
11
with their IRBs locally and with us in terms of
12
developing the consent forms and protocols for collecting
13
specimens for making DNA libraries in ways that we have
14
found acceptable.
DR. MURRAY:
15
They have both worked
Thanks, Mark.
I am pleased to
16
hear about the reaction, your sense of the reaction of
17
the scientific community.
18
assailed by a very distinguished and well known scientist
19
for what he described -- he used fairly flowery language
20
to criticize this document and others.
21
has been -- which -- it was interesting since I had
22
nothing to do with the preparation of any of them and had
23
not read them at that point.
24
ago.
25
26
DR. GUYER:
I am surprised because I was
And I guess he
This was several months
Whatever your response was it
must have been very effective.
DR. MURRAY:
1
2
effective, I guess.
Yes.
3
(Laughter.)
4
DR.
5
(Laughter.)
6
PROF. CAPRON:
7
(Laughter.)
8
DR. MURRAY:
9
down.
It must have been very
Well, I hit him is what I did.
:
And he is now dead.
But we have used his tissues.
I got his consent on the way
Yes.
10
(Laughter.)
11
DR. MURRAY:
12
We have a little time for questions or
Thanks very much, Mark.
13
comments with Mark, a little dialogue with Mark.
Here is
14
my plan:
15
I would like us to take the last ten minutes and I am
16
going to let us -- I am going to count that from 9:55 to
17
10:05 since we did start about ten minutes late.
18
do not want to encroach too much on the break or
19
certainly not on the next subcommittee.
20
at 10:05.
21
briefly begin a conversation about future subcommittee
22
meetings.
23
the products, beginning the process of having what sort
24
of products we want to commission through the NBAC staff.
25
So we will start that at 9:55 so we have like seven
26
minutes to talk with Mark.
Two hours was not very much time to begin with.
But I
So we will end
I would like to give us ten minutes just to
We will make a recommendation.
And also about
1
DR. COX:
I just wanted to make a comment,
2
Mark, is that with respect to the Genome Project at the
3
very beginning for years the press have been asking whose
4
genome is going to be sequenced and the scientific
5
community, myself included, blew that off pretty easily
6
because it was obvious to me we were not going to be
7
sequencing one person's genome.
8
me to realize that we actually were sequencing that
9
person's genome.
It was quite a shock to
So perhaps the scientific community can
10
-- in broadening their context and looking at what the
11
public concerns are can sometimes head things off at the
12
pass and this was an interesting lesson that I have
13
chalked up on that science personally.
14
DR. MURRAY:
15
DR. SHAPIRO:
Harold?
I have really some simple
16
comments and reaction.
17
Korn for that wonderful phrase "repose and obscurity"
18
which is in your paper which I think is a kind of
19
wonderful phrase and it can be used in many situations.
20
But that is a part of the sentence which talks about
21
research that cannot be accomplished by any other means
22
as I recall that testimony.
23
First of all I want to thank Dr.
That is an important sentence and I just want
24
to observe that that is not well understood.
I mean it
25
is well understood by scientists.
26
that scientists do not understand it but it is simply not
I am not trying to say
1
well understood and therefore in balancing the costs and
2
benefits to whatever solutions are reached I think, Tom,
3
we need to do something in the educational role of our
4
commission to make sure that people can understand just
5
what the importance of this is.
6
examples.
7
but I think it is something we have not attended to very
8
well just in that area and I hope that I can do something
9
about it going ahead and going forward.
10
I think there are many
I do not want to take time now to go into that
The second issue which I would perhaps ask
11
any of the people who have presented today to respond to
12
is in all these issues of trying to balance the costs and
13
benefits and interests of various kinds here even if one
14
assumes that in an initial situation that you have the
15
appropriate informed consent, that people think the
16
benefit is worth the cost for providing their tissue
17
under whatever circumstances.
18
We are always faced with the issue as a
19
number of our speakers have indicated this morning that
20
there are unanticipated costs and benefits out there.
21
That is since we do not know what the progress of science
22
is going to be and we are accumulating this archive there
23
is by definition a stream of unanticipated benefits and
24
unanticipated costs.
25
Now no one is going to worry very much about
26
the unanticipated benefits because it is only a benefit.
1
If that happens that is great.
There is no controversy.
2
It is the unanticipated costs that attract people's
3
attention and can be responsible for what Dr. Korn talked
4
about as a kind of scare situation.
5
early 1970's with the recombinant DNA scare.
6
have to be very cautious about that because there is no
7
end to the long list of unanticipated costs one can
8
imagine.
You looked at the
I think we
9
There is any kind of scenario you can develop
10
in this without limit and I think -- I just hope as we go
11
ahead that while we have to be conscious that that
12
possibility exists of course that we have to be careful
13
not to over emphasize or inappropriate -- I do not want
14
to say over emphasize, inappropriately focus on that as
15
we go ahead.
DR. MURRAY:
16
17
Thank you.
Any other comments
or questions of Mark in particular?
Thank you.
18
Should we have another -- when
19
should we have the next subcommittee meeting?
I have not
20
really spoken with you about this but let me make a --
21
float a proposal.
22
March.
23
and we would try to coordinate it with the other
24
subcommittee, have them back to back if at all possible,
25
in April?
26
February is next month and scheduling with damnably
The next full commission meeting is
What would you think about a subcommittee meeting
Why April and not February?
Well, because
1
difficult.
2
Number two, I would like to have us have some
3
products to look at before the next subcommittee meeting
4
and I wonder if you think -- I mean, my sense is we ought
5
to be able to commission at least a couple of the
6
conceptual papers and have them in the commissioner's
7
hands by at least last March so that we have a couple of
8
weeks to look at them and think about them before we got
9
together again in April.
That is my proposal.
10
11
Please tell me what you
think.
DR. COX: I quite agree getting some things in
12
13
our hands now is very important.
I was struck by what we
14
have seen already in the context of focus groups and with
15
the public views with respect to the stored tissue
16
samples, but rather than providing answers that to me can
17
provide even more of an impetus to have such focus groups
18
specifically with respect to our own interest in this
19
subject.
20
pronto.
So I would really like to see that go forward
21
DR. MURRAY:
22
DR. COX:
No.
More focused report.
Focus group addressing the
23
public perception of stored tissue samples in banks and I
24
think that what that is going to require just as what we
25
have seen from -- in the breast cancer case are
26
thoughtful questions and professionals organizing focus
1
groups that provide open ended questions so that we can
2
get a better feel of how the public perceives this issue.
DR. EMANUEL:
3
Can I ask in that light, Dr.
4
Saslow, were you or your office intending any more
5
generalizable -- beyond focus groups usually you go to
6
surveys of particular groups on some of the issues
7
raised?
DR. SASLOW:
8
9
No.
Our next step is to after
we revise this to pilot test and then actually we will
10
not be doing it.
11
process.
We are hoping through the NIH grant
12
DR. MURRAY:
13
DR. SHAPIRO:
Harold?
I have two comments.
One is
14
the April time frame seems fine, but if that is what the
15
subcommittee decides to do I think it might be helpful to
16
consider that when you commission a paper from an
17
individual that they may, in fact, report to us in some
18
kind of initial way in March when we are all here so that
19
we can have some impact, we meaning the subcommittee, I
20
apologize, can have some impact and some interaction with
21
whoever it is the paper is commissioned from.
22
In some cases that may not be possible but
23
where it is possible, we will leave it to the chair to
24
decide that, that might be very helpful in getting the
25
work so when the product arrives in April it will be well
26
understood by the subcommittee members.
That is one
1
2
comment.
The second comment is that in deciding
3
eventually just what papers or projects we ought to
4
commission there will have to be some kind of iterative
5
process where we know something about the time it will
6
take to do something, whether that has got to be a long-
7
term project or a shorter term project.
8
sitting here right now, I do not know how long you have
9
spent on these focus groups, how long it took you to
As I am just
10
mobilize it and do it, that would lead you to do it
11
faster the second time, most of us would.
12
But that may -- we are going to have to
13
reiterate around a bit as we look at the portfolio
14
possibilities and look at just what we can do in the
15
various time frames we have laid out.
16
17
DR. MURRAY:
One of the things we will need
to do, I believe, is draw up a kind of work plan.
18
DR. SHAPIRO:
19
DR. MURRAY:
Right.
And, you know, start from next
20
October when we will have a report and figure out what we
21
need to have each month or so however to reach that goal.
22
My -- having -- you know, I write conceptual papers and
23
not empirical papers myself, it may still take time for
24
whatever reason.
25
26
DR. COX:
Tom, in Harold's point, I mean I
guess there is professional groups that do these focus
1
studies and they can make it very simple.
2
DR. MURRAY:
3
DR. COX:
Absolutely.
They call one up and they say it is
4
going to take us two years.
5
like to know.
6
months and how much money?
But that is what I would
Is it going to take us two years or three
7
DR. MURRAY:
8
DR.
9
DR. MURRAY:
I agree.
:
Three months is the -Three months.
Part of the work
10
plan is figuring out what each of the proponents
11
realistically is going to take to get a product and where
12
optimally it would fit in our own deliberations and
13
report drafting, et cetera.
14
PROF. CHARO:
15
DR. MURRAY:
16
PROF. CHARO:
Excuse me, Tom.
Alta?
I think this is my staffer
17
background coming out again but I recall lots of very
18
complicated rules about financial limits above which you
19
were not allowed to single source something so you have
20
to put it out for bid which would drag the process on
21
further.
22
remember what those numbers are, but depending on what it
23
is you are planning to do you may not be allowed to just
24
single source and that might make the whole time frame
25
particularly complex.
26
So I am not sure I understand -- I do not
DR. MURRAY:
Steve?
1
DR. EMANUEL:
As I recall it is $25,000 and
2
probably for these focus groups depending upon how
3
elaborate you want to get them you should be able to get
4
in well under that.
5
DR. MURRAY:
It will be hard to find an
6
ethicist to write a paper for less than that I imagine
7
but we will just have to --
8
PROF. CAPRON:
9
DR. MURRAY:
10
13
14
We will have to scrape the
bottom of the barrel but we will manage.
MR. HOLTZMAN:
11
12
Especially a conceptual paper.
DR. DOMMEL:
Tom?
And time for the IRB review and
approval of the project with the focus group.
MR. HOLTZMAN:
A question, Tom, it seems to
15
me we said we were going to start by looking at the issue
16
of retrospective samples knowing full well that we would
17
draw morals from that in terms of processing such as
18
consent and use for future samples.
19
maybe we start with a conceptual paper.
20
You have suggested
I am almost inclined to say where I would
21
like to start is by learning out about what are the
22
samples we are talking about?
23
collections?
24
with respect to consent and other aspects?
25
now being reused under what understanding about how they
26
may be reused?
What are these different
Under what conditions were they collected
How are they
Because clearly the pathologists have a very
1
2
different understanding than the public health
3
authorities who are in possession of the blood spots from
4
infants.
5
people who have the serums from the Framingham study.
6
Under a very different understanding of for profit
7
clinical pathology lab or genetics testing lab.
8
think that would be a good place to start, is to know
9
what it is we are talking about here.
A very different understanding than say the
DR. MURRAY:
10
So I
By conceptual I just meant
11
conceptual as opposed to going out and gathering original
12
data and running subjects like focus groups.
13
descriptive paper, that would have been a more accurate
14
description on my part.
15
commission very rapidly.
So a
I think that also we could
I would like to see that.
16
Let me just -- we did this yesterday and then
17
we had some good feedback about extensions, refinements,
18
additions.
19
minutes and I think this can only be the beginning of our
20
conversation which will have to continue via e-mail,
21
telephone calls and other things.
22
It is 10:00 o'clock so we have just a few
That is fine.
But let me see if I have -- I have at least
23
this list of the sorts of things we would like to see
24
done in order for our own work to continue.
25
one or more descriptions of what these tissue collections
26
are like, what uses are made of these tissues.
One are --
This is
1
something we would like to have done quickly I note and
2
also that we should attend both to sort of public
3
collections and also private collections.
4
suggested that.
5
with maybe more than one subpart.
Someone had
So that is one -- at least one component
A second component would be this analytical
6
7
paper about cultural, ethnic and religious views and how
8
they might differ in the U.S. about the use of stored
9
tissue.
10
A third thing would be the focus groups which
11
thanks to the work that Debra Saslow has reported we can
12
focus primarily on public perceptions of tissue banks,
13
uses of stored tissue, et cetera.
14
component.
That is a third
A fourth component is called a conceptual
15
16
paper.
17
based in part on the position papers that we have seen
18
but also would try to raise the list of concerns that
19
people might have, the private interest versus public
20
benefit and not limited only to objections on the private
21
side but also to, you know, people's interest and
22
positive views about having their tissue stored.
23
suspect would be one paper but maybe not.
24
It is a kind of normative analysis that would be
That I
We want to have some kind of international
25
perspective, that is a collection and review of
26
international statements and the dates going on in at
1
least a few other places about stored tissue samples.
2
that is the comparative international piece.
So
We may or may not want someone to sort of
3
4
take this together and give us a sort of policy analysis
5
of what the reasonable options seem to be, at least to
6
deliver to the commission for the commission's own
7
deliberations.
Those are the pieces I had.
We did originally have in mind from the
8
9
That is it.
subcommittee meeting the possibility of an opinion, a
10
public opinion poll, up to ten questions.
11
a lot of enthusiasm for that yesterday.
12
but we did not do an all things considered view of it.
Now let me --
Are there members of the subcommittee who
13
14
I did not hear
would like to see some public opinion poll data on this?
15
Bette?
16
MS. KRAMER:
Tom, I would like to suggest
17
that you question some professional person who can give
18
you some feedback as to the relative value of focus
19
groups versus public opinion.
20
want both but I think you want to try and find out which
21
one is going to be more productive for us in this
22
instance.
23
DR. MURRAY:
Yes.
Obviously you would not
I left one thing out which
24
is it was -- I guess it started with Alta's suggestion
25
that if we wanted to find out what -- sort of a sampling
26
of what the public felt about this in a more opinion poll
1
rather than focus group fashion, rather than just asking
2
the general public we might look to groups of people who
3
have, in fact, had stored tissue and who have been sort
4
of -- who have had occasion to think about it.
5
remains a possibility.
6
Zeke and David?
7
DR. EMANUEL:
Yes.
That
When we think about the
8
public opinion survey there are a variety of ways of
9
doing it. One is our own survey.
One is tacking on
10
questions to an already existing survey which is
11
incredibly cheap actually and many of these big survey
12
groups are going to particular populations.
So if we are very interested in certain
13
14
subpopulations they are doing these kinds of surveys for
15
all sorts of other governmental, et cetera, reasons and
16
we may be able to get good minority looks or looks at
17
what minority groups think of it for example.
I think that there may be some groups already
18
19
looking at certain specific populations, maybe not in
20
relation to tissue samples but in relation to genetic
21
testing, et cetera, that we may again be able to tack on
22
some questions either to their surveys or to their focus
23
groups.
24
DR. MURRAY:
At least one of the major
25
national opinion pollsters does offer this sort of
26
service where you can do it.
You can pay for questions.
1
DR. EMANUEL:
2
DR. MURRAY:
Exactly.
But for us the question would be
3
are there -- this is getting to be the question, the
4
third question, the third use of the concept question.
5
Do we have a question or a set of questions that we want
6
to ask to the general public?
7
not a lot of -- not a certainty that we have those
8
questions.
9
possibility for us and maybe that should be something
10
What I heard yesterday was
I would like to leave that as an open
that we continue to dialogue on.
11
Steve and David?
12
MR. HOLTZMAN:
What I would like to suggest
13
is the one danger with saying what you are going to do is
14
follow up Alta's suggestion and go and talk to groups
15
about their experience thinking about the question of
16
stored tissue samples is typically the groups you will
17
have will be people who have the kinds of diseases that
18
are highly charged.
19
broad sample here.
20
What we are talking about are a
We need to -- so I do not have a problem with
21
going to those groups and maybe what you need to do --
22
but then you start -- you have to cast the net much wider
23
because the kinds of samples Dr. Korn is describing come
24
from all different kinds of patients and under all
25
different kinds of situations.
26
Again it is much like when one talks about
1
what is a genetic disease if your paradigm is a highly
2
penetrative disorder which you cannot do anything about
3
with a single gene, it is very different than if you
4
start to talk about the more kinds of common diseases
5
that are polygenic.
6
themselves in terms of a genetic disease versus those
7
with these others you get very different impressions.
DR. MURRAY:
8
9
And if you ask people to identify
Steve.
Yes, that is a good reminder,
You are going to have, except for my closing
10
comment, you are going to have the last word out of
11
fairness to the next subcommittee.
12
Yes?
13
DR. COX:
I hope it is worth it.
I agree
14
with what Steve just said and with respect to Bette's
15
comment I really do think we need professional input
16
about what the best way to get information broadly from
17
the public is and not just from specific interest groups.
18
But I will say I
19
group already and I think we should always build on what
20
already exists.
21
learned something from Debra's focus
What I saw from your focus group is that
22
people were suspicious because they did not what stored
23
tissue banks were about and it is pretty hard to get
24
public opinion polls from people asking about things if
25
they do not know.
26
So in my own view I think I would like to see
1
the commission work with whatever professionals we have
2
to come up with scenarios with which we could not direct
3
what the answers are going to be but at least have
4
scenarios that encompass some of the things that we would
5
like to get answers back about.
6
7
8
9
DR. MURRAY:
Thank you very much.
We will
try to -- Jim?
DR. CHILDRESS:
Just a question since this
concerns both the subcommittees.
We have not talked
10
about whether to try to have a meeting prior -- of our
11
subcommittees back to back prior to the next meeting, at
12
least I have been in and out of discussion this morning
13
so I am not sure that has been discussed.
14
It seems to me that might be useful to do
15
while we have virtually everyone present if the staff
16
does not object, is to see whether we could find some
17
dates and actually move forward because if we are
18
expected to make some kind of report at the March
19
meeting, only about eight weeks away, we really do need
20
to have a meeting of the subcommittees prior to that.
21
least that is my view.
22
DR. MURRAY:
At
What I had proposed, I guess you
23
were out of the room, Jim, what I had proposed was that
24
we not -- our subcommittee not try to meet in February,
25
but the time would be better spent for us reviewing
26
materials and commissioning various products which we
1
would have at least preliminary reports on at the March
2
full commission meeting, but then a chance for the
3
subcommittee to have more polished versions of for an
4
extended meeting in April.
DR. CHILDRESS:
5
6
All right.
We will raise it
with the next subcommittee too and see what it says.
DR. MURRAY:
7
I do not have a strong feeling
8
about that.
9
use of our time and give us a reasonable amount of time
10
It just struck me that might be a sensible
to get report -- initial reports in.
Bill hands me a note and also from Margaret
11
12
Quinlan to consider some dates.
I do not think we should
13
try to schedule at this time but just keep these in mind.
14
The third and fourth of April, the 17th and 18th of
15
April, and I have to tell you I am probably teaching
16
those weeks.
Our semester ends in mid-April.
So we might also -- if you would be willing
17
18
to accommodate me think about towards the end of April or
19
the beginning of May.
20
many of us or even in May.
21
dates.
22
fill out their calendars.
23
That would be a possibility for
But we should not try to set
We should get that -- each and everybody should
What I am going to propose to do is with the
24
help of NBAC staff prepare a kind of just brief
25
description of these components, these products, and when
26
we would like to try to get them in, and get it
1
disseminated to all members of the commission, get your
2
feedback on it rapidly so that we can then go -- you
3
know, if you approve or if you want to modify them we can
4
commission them.
Thank you very much.
5
I want to particularly
6
thank Debra Saslow, David Korn and Mark Guyer for coming
7
and spending the morning with us, and all the members of
8
the commission, particularly the subcommittee.
We will reconvene at 10:30.
9
(Whereupon, the proceedings were adjourned at
10
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10:11 a.m.)
* * * * *
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46
MEETING OF THE HUMAN SUBJECTS SUBCOMMITTEE OF THE
NATIONAL BIOETHICS ADVISORY COMMISSION
Friday, January 10, 1997
10:35 a.m.
The Madison Hotel
Washington, D.C.
EBERLIN REPORTING SERVICE
14208 Piccadilly Road
Silver Spring, Maryland
20906
(301) 460-8369
1
2
3
4
5
6
7
8
9
10
11
12
13
I N D E X
JOINING THE SUBCOMMITTEE IN ITS DISCUSSION:
ROBERT J. LEVINE, YALE UNIVERSITY SCHOOL OF MEDICINE
REBECCA DRESSER, CENTER FOR BIOMEDICAL ETHICS,
CASE WESTERN RESERVE UNIVERSITY
4
16
1
P R O C E E D I N G S
1
DR. CHILDRESS:
2
In order to use the full two
3
hours most efficiently I think we ought to go ahead and
4
get started even if we have to interrupt it at some point
5
to talk just for a few minutes about additional
6
scheduling.
This is scheduled to end at 12:30 and since
7
8
people have travel plans to meet we will certainly try to
9
do that.
10
I should also mention that Bill Dommel will
11
be out for the next little while and Margaret Quinlan
12
will be handling everything from the staff's standpoint.
13
14
Harold Shapiro, anything you would like to
say before we get started?
15
DR. SHAPIRO:
No.
16
DR. CHILDRESS:
17
Well, you will recall from our discussion
Okay.
18
yesterday the Human Subjects Subcommittee is interested
19
in working on different levels, one considering general
20
perspectives, principles and concepts, and the other
21
looking at specific areas of concern particularly for
22
policy development.
23
most important has to do with cognitively impaired
24
research subjects because of the gaps in federal
25
regulations and guidelines for this particular area.
And in the specific areas one of the
2
There is a consensus not only in the Human
1
2
Subjects Subcommittee but also in NBAC and also in the
3
literature that this is one gap that ought to be closed
4
if possible.
I quote from two 1996 publications:
5
"The new
6
National Bioethics Advisory Commission should act
7
promptly to develop more precise principles and
8
procedures to guide future research on mentally disabled
9
subjects."
The second one:
10
"There should be a federal
11
policy for the ethical conduct of research on persons who
12
by reason of mental or behavioral disorders are
13
vulnerable and that they are not capable of giving
14
adequate informed consent.
15
by a national advisory group modeled after the National
16
Commission for the Protection of Human Subjects."
The policy should be formed
Well, those two 1996 challenges to the
17
18
National Bioethics Advisory Commission came from our two
19
panelists.
20
from Robert Levine.
21
join us today despite adverse travel conditions and
22
complicated schedules, and share with us some of their
23
reflections about the issues involved in thinking about
24
cognitively impaired subjects and the kinds of policies
25
and guidelines that might be developed to more adequately
26
protect them.
The first from Rebecca Dresser and the second
We are delighted that they could
3
Let me say a word about each of our
1
2
panelists.
Rebecca Dresser holds the John Deaver Drinko
3
Baker and Hostler (?) chair in the School of Law at Case
4
Western Reserve University.
5
the Center for Biomedical Ethics, School of Medicine, at
6
Case Western.
7
area over the last 15 years and is the author of numerous
8
articles in medical journals as well as co-author of a
9
Case book, Law and Bioethics.
She is also a professor in
She has taught in the law and bioethics
10
Robert J. Levine is professor of medicine and
11
lecturer of pharmacology at the Yale University School of
12
Medicine and chairperson of the Institutional Review
13
Board at the Yale Newhaven medical center.
14
former editor of Clinical Research and the current editor
15
of IRB, Review of Human Subjects Research, and has been
16
involved as a consultant in several and international
17
agencies involved in the development of policy in this
18
area.
He is a
I mentioned in my memo that his book, Ethics
19
20
and Regulation of Clinical Research from 1986 is one of
21
the most important works in this area.
So we are delighted that they could be with
22
23
us today.
24
Our procedure is the following:
25
We start with Bob who as a staff member of
26
the National Commission for the Protection of Human
4
1
Subjects was deeply involved in the discussions and
2
deliberations surrounding the whole range of issues
3
covered by the National Commission, but including for our
4
purposes today the institutionalized mentally infirmed
5
subjects.
6
And as soon as he finishes his eight to ten
7
minute set of remarks we will ask -- give everyone to
8
raise a few questions for clarification and then before
9
proceeding into substantive discussion we will ask
10
Rebecca Dresser to present her remarks and then have an
11
opportunity for a few questions for clarification, and
12
then have both of them involved together in our
13
substantive discussion because both of them have really
14
focused in this area in important ways that can
15
illuminate what we are about.
16
17
18
So, Bob, we will start with you and then we
will turn to Rebecca.
ROBERT J. LEVINE, YALE UNIVERSITY SCHOOL OF MEDICINE
19
DR. LEVINE:
Well, thank you very much, Jim.
20
It is a pleasure to be here with you.
I take
21
it as a great privilege to be invited to participate in
22
your important project.
23
here was not half the fun.
If I may so, though, getting
24
Jim tells me that you probably all have read
25
the various readings that were sent to you to prepare for
26
this meeting.
That then frees me up of any
5
1
responsibility for giving you details.
I am going to
2
instead try to provide an overview of the big picture.
Understand that this consideration of dealing
3
4
with people with cognitive incapacity or suspected
5
cognitive incapacity has two purposes.
6
to be part of a larger project to consider the meaning of
7
vulnerable as it applied to prospective research subject
8
populations.
Firstly it seems
Secondly, it is an important consideration in
9
10
its own right, it being the only field of individuals
11
that the old DHEW regulations defined as those with
12
limited capacities for consent.
13
does not have any federal regulations guiding the conduct
14
of research in them.
The only category that
15
The reason that these people were identified
16
or the reasons in general that people or populations are
17
identified as vulnerable is that in general there is some
18
reason to suspect that they lack the capacity to give
19
informed consent.
20
the National Commission as those institutionalized as
21
mentally infirmed there were two elements of this
22
capacity that at least had to be suspected of being
23
absent.
24
In the case of the category defined by
The first is that for many of them they lack
25
the cognitive capacity to be properly informed to reach
26
what the Nuremberg code calls an understanding or an
6
1
enlightened consent.
The second feature is that they are
2
in positions of dependency so they lack what the
3
Nuremberg code calls the capacity to provide a voluntary
4
consent.
In particular, as the commission was
5
6
addressing not all people with competent disability but
7
only those who were institutions.
8
consideration that simply living in an institution for a
9
long period of time made one quite dependent regardless
There is a
10
of one's cognitive ability.
11
recommendations that were made by the National
12
Commission.
13
So that influences the
Now dependency is also extended in some of
14
the international documents but not in the American
15
regulations to cover people who are subordinates in a
16
hierarchical structure.
17
Walter Reed invited buck privates to be bitten by yellow
18
fever mosquitoes this was considered potentially coercive
19
in that buck privates in those days rarely would resist
20
any recommendation made by a major.
21
So, for example, when Major
The same would go -- similar considerations
22
are applied to students.
You probably have already heard
23
about the problems of psychology departments in
24
universities requiring in some cases requiring
25
undergraduate students to serve as research subjects and
26
giving them course credit for doing this.
7
1
So to leave the general issue of
2
vulnerability and to focus more specifically on those
3
institutionalized as mentally infirmed I want to first
4
call attention to the fact that the Congress asked the
5
commission to deliberate about those institutionalized as
6
mentally infirmed.
7
The commission introduced the word "as" to
8
show its skepticism.
It was their belief and it was
9
probably correct that there are a goodly number of people
10
who are institutionalized as mentally infirmed even
11
though they do not have mental infirmity.
12
if empirical work in the 1990's would support that vision
13
but it did in the 1970's.
I do not know
14
The structure of the recommendations and what
15
became the proposed regulations is characteristic of the
16
National Commission's approach to dealing with vulnerable
17
populations.
18
They first defined one category of research
19
in which all of the procedures taken together present no
20
more than minimal risk.
21
definition, I trust you are familiar with the definition
22
of minimal risk.
23
this concept and find it very unsatisfying.
24
a nondefinition but it is the one we are stuck with.
25
26
You are all familiar with the
Many of my colleagues have analyzed
It really is
Now once you get beyond minimal risk then the
National Commission recommends that regulations be
8
1
developed as they did for their earlier recommendations
2
for research involving children.
3
categorize the research -- or no, not categorize the
4
research but categorize the components, the procedures,
5
the interventions that are going to be performed in terms
6
of whether they hold out the prospect of direct benefit
7
for the individual subject.
8
therapeutic research or nontherapeutic research.
But you should
They do not refer to
I was troubled to see that most of the
9
10
documents circulated to this group today rely on that
11
distinction and I can give you many, many examples of how
12
this distinction leads you into conceptual snares.
13
American College of Physicians Statement, for example,
14
which relies on this distinction finds it impossible to
15
give advice on how you would treat cognitively impaired
16
subjects who are being enrolled in a placebo controlled
17
trial.
18
The
You might argue that the drug, the active
19
drug arm would be therapeutic or would hold out the
20
prospect of direct benefit.
21
support applying the same standards to the placebo arm.
22
This is the sort of conceptual ambivalence that confronts
23
you every time you use this distinction.
But this could certainly not
24
Alex Capron has heard me say that before.
25
We have discussed it in print.
26
Now if the procedure that presents more than
9
1
minimal risk holds out the prospect of direct benefit
2
then according to the National Commission recommendation
3
and also according to the children’s regulations the
4
justification of imposing this risk is just like it is in
5
medical practice.
6
You have got to find that the procedure
7
itself offers consequences or the expected benefit is at
8
least as good as anything else out there in the practice
9
of medicine and that nothing superior is being withheld.
10
Aside from that justification there are no additional
11
procedural protections apart from what is necessary for
12
all minimal risk research.
13
Now the other category is when the
14
intervention or procedure does not hold out the prospect
15
of direct benefit.
16
more stringent standards to the justification.
17
have to find that the information being sought is of
18
vital importance to the solution of the problem and,
19
secondly, in the case of children they said that the
20
procedure would present experiences that were
21
commensurate with what the children subjects would
22
experience by virtue of their situation, their disease,
23
for example.
In that case you have got to apply
First you
I can give you more detail if you like.
24
Now also when you are dealing with procedures
25
that do not hold out the prospect of direct benefit there
26
are additionally stringent requirements for committee
10
1
review, for checking with the treating physician to see
2
that the participation in research will not interfere
3
with the course of therapy, and various other things that
4
you could read about.
There is also a requirement that the
5
6
increment above minimal risk must be something that can
7
be characterized as a minor increase.
8
a minor increase then it has to be removed by the Ethics
9
Advisory Board, parenthetically I trust you know that
If it is more than
10
there has been no such board since 1980 when its money
11
was given to the President's Commission.
Now I think that they should have found the
12
13
same amount of money for the President's Commission but
14
they also should have kept the Ethics Advisory Board.
Now are these recommendations relevant in
15
16
1997?
I think they provide a good structure, a good
17
logical system for thinking about the problems.
18
some changes are necessary for two reasons.
19
reason is that the commission was focusing on people
20
having two problems and one of them was
21
institutionalization.
However,
The first
22
My recommendation is that you come up with a
23
set of standards that would apply to all people who might
24
have incapacity by virtue of cognitive disability or
25
suspected cognitive disability and for that reason the
26
recommendations would have to be revised to accommodate
11
1
those who were living out in the world and not in
2
institutions.
A second reason for revising some of these
3
4
recommendations without departing from the conceptual
5
structure is that in the 1970's we were living with this
6
attitude of protectionism.
7
presumption that research was dangerous, that you know
8
you could get hurt.
9
of the Nazi war criminals and many people writing at the
There was a prevailing
We were still living in the shadow
10
time thought that what the Nazi research physicians did
11
was typical of research.
Subsequently we have gone through a great
12
13
revision in our perception of research.
14
often it is portrayed as being totally benign and
15
beneficial.
16
I think the current attitude is just as wrong headed as
17
the old attitude was.
18
Now all too
As I have written and perhaps you have read,
It is not only dangerous and exploitive and
19
it is only benign and beneficial, but good can come of it
20
for individuals as well as populations.
21
forward with it while maintaining our vigilance to see to
22
it that any potential exploitation or injury, any
23
potential for exploitation or injury is minimized.
24
One closing remark:
We should go
I think the greatest
25
problem presented in the field of doing research on
26
people who have disorders that can produce cognitive
12
1
disability is the problem of what has come to be called
2
drug free research.
3
Placebo controlled clinical trials, placebo
4
washout periods, and one additional thing would be the
5
so-called probe studies where drugs are given in order to
6
explore the pathogenesis of these serious disorders such
7
as schizophrenia where drugs are given to see whether or
8
not they will exacerbate the condition, to see whether
9
they will bring about a transient increase in symptoms.
10
These studies are very valuable but they are
11
also very frightening to deliberately induce symptoms in
12
people who may have questionable capacities to understand
13
and in case you induce the symptoms you might have a
14
problem with assuring the subject's freedom to withdraw
15
at any time, you know, as is required by all ethical
16
codes and regulations.
17
If you like I am going to talk more later
18
during the discussion period about this drug free
19
research business but I believe I have occupied a little
20
bit more than my time line.
21
Thank you.
22
DR. CHILDRESS:
23
As I mentioned at the outset let's just take
24
a few questions for clarification only, not to engage in
25
a substantive discussion yet.
26
in the substantive discussion as well.
Thank you very much, Bob.
We want to involve Rebecca
So if there are
13
1
any questions for clarification since Bob had to cover a
2
lot of things in a short period of time?
3
MS. FLYNN:
I am not sure it is appropriate
4
at this moment but I wanted to ask you for just a little
5
bit more information about your statement that the
6
current structure provides in your view an adequate
7
framework for us to then move in whatever additional
8
directions that we may see fit.
9
terms of the way in which we have characterized and
Are you speaking in
10
classified the vulnerability or the way in which we have
11
characterized and classified the risk itself?
12
just enlighten me a little bit more as to why you are
13
feeling that the current framework is, in fact, strong
14
enough and adequate to build on?
15
DR. LEVINE:
Can you
Well, thank you very much for
16
the question.
17
referring to the conceptual structure.
18
sense when dealing with vulnerable populations to
19
categorize research as minimal risk and then to recognize
20
that there is a second category of research in which some
21
of the procedures or components could hold out -- could
22
present more than minimal risk.
23
When I refer to the framework I am
I think it makes
I think that it is a good idea within that
24
category to analyze the specific procedure intervention
25
that is presenting more than minimal risk and if it has a
26
reasonable prospect of providing therapeutic, diagnostic,
14
1
prophylactic benefit then the proper method of analysis
2
or justification of this risk is very close to the method
3
of justification in the practice of medicine that it is
4
bringing to this individual advantages that are on a par
5
at least with the best known alternative.
If on the other hand the procedure presents
6
7
that more than minimal risk is not beneficial, not
8
therapeutic, then I would impose stringent restrictions
9
on who can do it.
I will give you an example of an actual
10
11
clinical trial which was analyzed as therapeutic
12
research.
13
That is thrombolysis and myocardial infarction using
14
enzymes to dissolve clots in the coronary arteries.
15
Clearly therapeutic.
16
the placebo controlled arm was to insert a catheter into
17
the coronary artery for purposes of infusing placebo.
It was one of the early phase TIMI trials.
However, one of the components in
In a study of that sort if you are analyzing
18
19
things according to therapeutic research you get what I
20
call the fallacy of the package deal.
21
thing is therapeutic you cannot justify everything in the
22
same way.
23
Just because one
Now to get to the other component of your
24
question, no, I am not claiming that we now have an
25
adequate definition of vulnerability.
26
to include the things that are in the CIOMS World Health
I would expand it
15
1
Organization document recognizing that members of
2
hierarchical -- subordinate members of hierarchical
3
structures, and you can read all this stuff.
4
not recommending that the term "minimal risk" is in its
5
present form useful.
I am also
I tried to write an alternative term in 1976
6
7
and failed seriously.
8
to advise you.
So you better call on someone else
DR. CHILDRESS:
9
Since not everyone may recall
10
the definition, you just mentioned it in passing but did
11
not -- go ahead and state what it is at this point, the
12
definition of minimal risk that has been used and is
13
problematic.
DR. LEVINE:
14
There is no such thing as "the"
15
definition of minimal risk.
The National Commission
16
wrote definitions of minimal risk that were peculiarly
17
relevant to each category of subjects.
18
of them were adequate.
19
HEW regulation writers did was homogenize them all so
20
that they could put one definition in the mainstream of
21
the regulations.
In my view none
But what the HHS or in those days
What it does is it says that minimal risk is
22
23
the degree of risk that is -- I am paraphrasing -- on a
24
par with that expected in a routine medical,
25
psychological or dental examination covering all the
26
basis.
And that one should also take into account the
16
1
circumstances of the individuals expected or accustomed
2
life experience.
3
problematic.
4
for linebackers, you know, and for violinists if you take
5
into account the circumstances of their life.
Both components of that are
You would have a different standard than
When you say the risk is on a par with what
6
7
one encounters in a routine medical examination the
8
problem you were discussing in the first half of this
9
morning, genetics, where you are developing very private
10
information about people, one could argue, well, that is
11
what doctors do when they take a history.
12
minimal risk why didn't you start your meeting at 8:30?
13
And these are the sorts of problems you have to contend
14
with.
DR. CHILDRESS:
15
16
So genetics is
Any other question for
clarification only?
Okay.
17
Thanks again, Bob, and we will have
18
the subcommittee discussion in a moment.
19
Rebecca, welcome.
20
REBECCA DRESSER, CENTER FOR BIOMEDICAL ETHICS,
21
CASE WESTERN RESERVE UNIVERSITY
DR. DRESSER:
22
23
Thank you.
I am very honored
to be here with you.
24
Just in light of what we were just discussing
25
I have here the actual definition in the regs of minimal
26
risk.
It is the probability and magnitude of harm or
17
1
discomfort anticipated are not greater in and of
2
themselves than those ordinarily encountered in daily
3
life or during the performance of routine physical or
4
psychological examinations or tests.
5
to just, you know, walking outside, driving the car, that
6
kind of thing.
Okay.
7
So it also refers
Again I am going to assume that you
8
have read my article so I am not just going to review it.
9
I wanted to highlight a few points and then add some
10
things that I was -- I thought of just trying to be a
11
little bit creative about these problems.
I think one central problem here is the
12
13
varied nature of the people that we are talking about.
14
Not only do individuals in the different groups that we
15
are talking about vary substantially such as people with
16
dementia, I mean there is just such a range of capacities
17
and situations, certainly people with psychiatric
18
disorders.
19
example, with dementia you have a condition that is
20
eventually going to end in death, progressive.
21
not have that in the other major groups with
22
developmental disability and mental disorder.
23
a difference.
24
Also the groups themselves vary.
For
You do
So that is
The fluctuating capacity that people -- that
25
many people with psychiatric disorder have going.
26
point they are capable and at others they are not.
At one
That
18
1
is also the case with people in earlier stages of
2
dementia.
3
disability.
Not so often the case with developmental
But it is just such a complex group.
I think we have to accept that policy
4
5
probably cannot address all the specific problems of
6
these different groups.
7
principles but there is also always going to have to be a
8
lot of supplementation.
9
try to do is prepare some of the supplementary material
We can try to get some general
Perhaps what this group ought to
10
to enrich some of the specific issues that are only going
11
to arise with certain kinds of research in this area.
12
Also, you know, inevitably I think we have to
13
rely on the good faith of IRBs and investigators at some
14
level.
15
but there is the fine grain nature of these issues that
16
is going to make us have to rely on individual
17
examination of studies and subjects, and so forth.
We want to try to provide them a lot of guidance
Now I want to mention seven substantive
18
19
points.
20
representatives.
21
here.
22
disclosure have to be individualized to each subject.
23
And the other basic problem is that you want to select a
24
subject representative who is appropriate for the subject
25
who is incapable.
26
First, capacity, assessment and subject
There are a couple of basic problems
One is that capacity assessment and information
I think it might be possible to address both
19
1
those problems with a mechanism that requires somebody
2
who is independent otherwise of the research project to
3
be involved in this.
4
the subject is capable of understanding and can make a
5
voluntary choice, whether the subject understands the
6
information, the actual disclosure process, the substance
7
of the disclosure, being involved in that process, and
8
also then being involved in that process when a subject
9
representative is involved.
First in terms of assessing whether
The current federal policy requires or says
10
11
that incapable subjects may be involved in research with
12
the informed permission and consent of a subject -- a
13
legally authorized representative, and then it does not
14
define that.
15
do not address this at all.
It leaves it up to state law.
Most states
So who is that?
So one issue is should this be a legal
16
17
guardian?
Even as a lawyer I do not really think that
18
that is such a great mechanism to use.
19
guardianship is fairly general.
20
decisions to make people guardians.
21
people could have legal guardians and they would have
22
been appointed without any discussion of research
23
involvement certainly a specific project that might be
24
proposed.
25
expense and costs are probably unnecessary in terms of
26
protecting subjects.
Legal
Probate judges make
It is typically
I just think it is way over broad and then the
20
Again I think if you have the involvement of
1
2
an independent person who is speaking with the subject
3
representative, giving the information, assessing
4
understanding and assessing the ability of the subject
5
representative to follow the standards that that
6
representative ought to follow which is making decisions
7
based on whether they think the subject would agree to
8
participate if the subject were competent or
9
alternatively doing things that are in the subject's best
10
11
interest.
I think education, working with the
12
individual subject representative is a better way to
13
protect subjects than to just say, oh, well, everybody
14
has to be a legal guardian.
15
addresses the problem adequately.
16
I just do not think that
I would say with both of these areas this
17
therapeutic misconception is a major, major problem and
18
really requires a lot of attention.
19
subjects research there is a tendency for people to
20
confuse being in research and being in treatment, and
21
thinking that people who are doing things to them for
22
research are doing what is best for them.
23
so important to be very clear with people that even in
24
research that offers perspective direct benefit there
25
will not be the individualized attention typically say to
26
a dosage to catering the intervention to the individual
In all human
And it is just
21
1
person that that person would get in the clinical
2
situation.
I almost think that when research projects
3
4
are proposed, even potentially beneficial research
5
projects, people should put on a different color coat.
6
They should take off their white coat and put on a red
7
coat or something, or something that really reduces this
8
possibility of confusion between this is my doctor who is
9
there to do what is best for me and this is a researcher
10
who certainly is concerned about me but the overall goal
11
is to produce knowledge that will benefit others.
Okay.
12
Second area, advanced directives for
13
research.
14
lot of reservations about it.
15
choosing -- just designating a future surrogate decision
16
maker is not as problematic as asking somebody to issue
17
specific instructions about research participation.
18
the language of advanced directives that is the proxy
19
directive is not as problematic as the instruction
20
directive.
21
Now this is attracting some support.
I have a
I do not -- I think that
In
Problems with the instruction directive are
22
limited subject ability to be informed ahead of time of
23
all the information that is necessary to make an informed
24
decision about research participation.
25
the regulations there are all these requirements that
26
people have to understand before they make an informed
If you look at
22
1
decision to enter research.
The longer the time lapse
2
between the person's competency when the person is asked,
3
well, would you like to participate in this project, and
4
the time when the person becomes incompetent, and the
5
advance directive takes effect, the more likelihood new
6
information would have arisen about the study, about the
7
subject's condition, about lots of things that the
8
subject would not have been aware of at the time the
9
consent was elicited.
So I just think this adequate information is
10
11
a problem and then somebody is going to have to then
12
represent the subject once the subject becomes incapable
13
and then it just kicks into the usual situation where you
14
have an incapable subject and a representative.
The other thing is research is a -- research
15
16
participation is a process.
17
consent at one point is not enough.
18
continuing consent all during the project.
19
to have the ability to change their minds once they are
20
in the middle of it and saying, wait a minute, I do not
21
think this is for me.
22
have a subject representative to do that for an incapable
23
subject.
24
It is not an event.
Giving
There has to be
Everybody has
So again you are going to have to
For somebody to give binding consent to
25
participate in a future research project we would not
26
accept that for a competent or I do not think we should
23
1
2
accept it for somebody who later becomes incapable.
Now an interesting issue here is whether --
3
if we are going to set limits on the risks to which
4
incapable people can be exposed, should it be appropriate
5
to allow people who make an advanced directive saying I
6
am willing to be -- I am very concerned about dementia.
7
I am in the early stages.
8
I am willing to expose myself to moderate or high risks
9
in the future because it is so important to me to find a
I have seen it in my family.
10
cure for this or whatever.
11
imposed on somebody like that than we would on somebody
12
who never makes a directive like that and is entered into
13
a dementia study.
14
And allow greater risk to be
I have real problems with that although I
15
know there are different views of this.
16
the conflict between honoring the competent person's
17
autonomy to consent to future severe risks versus our
18
duty to protect people who are incapable at the time
19
those risks or burdens are imposed.
20
It really raises
I would say when we are talking about
21
research my preference would be to err on the side of
22
protection but maybe we will talk about that here.
23
also think it is important as a practical matter to
24
realize few people will make these kinds of directives.
25
I mean we know that very few people or relatively few
26
people make advanced treatment directives.
I
24
If we are talking about advanced research
1
2
directives where people are consenting in advance to
3
accepting significant risks when they have dementia or
4
perhaps when they are incapable because of a psychiatric
5
disorder, I do not know that that many people will be
6
interested.
7
attention and time on that.
8
to be a very small group of people.
9
getting enough subjects for research I just do not see
10
So I hope that we do not spend too much
I think it is always going
In terms of
that that would be a workable way.
11
I know I am going on too long.
12
Assent and experiential assessment for
13
incapable subjects.
I think it is really important to
14
remember that once people become incapable they do not
15
lose the ability to express their preferences.
16
they can show us in a number of ways physical resistance,
17
just evasion, avoidance, as well as linguistic ways.
18
they do not want to be involved in a research project.
That is
but
Now this issue of whether we should ever
19
20
impose interventions, because a lot of these things such
21
as shots, being physically restrained for a limited
22
period of time could be quite upsetting to somebody who
23
has dementia or a mental disorder, or a developmental
24
disability.
25
26
I think we should have a low tolerance for
forcing research interventions on research -- incapable
25
1
research subjects who indicate any kind of resistance.
2
Maybe a short term giving somebody a shot is one thing,
3
particularly if it is in a project that offers them
4
direct benefit.
5
conservative on this.
6
liberal in interpreting their communication that they do
7
not want to be involved in a project.
8
9
But I would prefer to be very
Also on the other hand very
Research burden expected benefit assessment
for incapable subjects.
This is a big issue for you all.
10
I think one thing we really need here again is a monitor,
11
a research auditor in the words of Jessica Berg.
12
because these things are so individualistic.
13
incapable subjects being -- getting a shot, being
14
restrained will not be upsetting.
15
Somebody has to be there watching to see how the
16
individual experiences it.
17
place for an otherwise independent person.
18
Again
For some
For others it will be.
So again this might be a
I was thinking we now have this mechanism of
19
the clinical ethics consultant who is there to kind of
20
back up the hospital ethics committee and to go on site
21
and to observe individual cases.
22
develop something like that for the IRB, that is an
23
individual who is very trained in these issues who could
24
either go between the actual research process, the
25
disclosure process and so forth, and then going back to
26
the IRB and reporting.
Perhaps we could
26
Risk limits, again if you do decide to adopt
1
2
risk classifications and limits I hope that this
3
definition of minimal risk and minor increase over
4
minimal risk can be enriched.
5
thing.
It is a very slippery
I am not surprised that you were not successful.
One thing that I think might be helpful is to
6
7
develop some case examples that IRBs and investigators
8
could look at.
9
where we think it is minimal risk.
Just giving examples, here is a situation
Here is a situation
10
where for this subject it seems like greater than minimal
11
risk.
12
increase over minimal risk.
Here is a situation where it is beyond a minor
Again because of the complex nature of these
13
14
individual situations I think perhaps stories, case
15
examples, narratives are going to give better guidance
16
than trying to put things into conceptual definitions.
Finally, I would just encourage -- oh, an
17
18
examination when we are looking at potential benefits to
19
incapable subjects that again we think about, well, what
20
are we -- what is the exact benefit?
21
questions:
22
subject to a potentially lethal risk if the research
23
offers a prospective direct benefit in terms of improved
24
cognitive function?
25
dementia drugs.
26
Here is some
Is it acceptable to expose an incapable
That might be the case with say some
Is it acceptable to expose such subjects to a
27
1
risk of a physically disabling injury in research that
2
offers the subject possible improved functioning or
3
extended life?
4
To what extent is extended biological life a
5
benefit for somebody who has moderate or severe dementia?
6
I think we have to think about that.
There is the big danger I think of being too
7
8
liberal about accepting risks in research that offers
9
subjects direct benefit and we really need to scrutinize
10
what the value of the potential direct benefit is to the
11
individual subject and not just take it at face value.
Then finally I would just encourage
12
13
developing some mechanisms for greater consumer
14
involvement in the planning and the carrying out of this
15
research.
16
the problems of these populations are going to be aware
17
of issues that even bioethicists will not.
18
very valuable to avoid problems to have their input.
I just think that people who are in touch with
It is just
Then finally this individualized model of
19
20
decision making that we have had.
That is somebody goes
21
in and gets the information and makes the decision, goes
22
forward.
23
actual real life decision making.
24
capable tend to have family members they may want to
25
involve.
26
subject representative.
I just think that is really not suited to
Even people who are
Incapable subjects may have more than one
28
I think it would be good if we could
1
2
incorporate that even though I know it is very messy and
3
could be practically very difficult.
4
reflects the messiness of actual human decision making
5
and we ought to be at least open to it.
6
Thank you.
7
DR. MURRAY:
8
I just think it
Thank you, Rebecca.
Any
questions for clarification only at this point?
Alex?
9
PROF. CAPRON:
10
I wanted to know whether you
11
were saying in describing the state law situation about
12
legally authorized representative whether the
13
uncertainties you were identifying were if who is the
14
representative or who is an appropriate representative,
15
or this question of the authority of such a person to
16
consent for research which involved anything more than
17
minimal risk for the subject?
DR. DRESSER:
18
Well, I guess there is both.
19
mean, you know, a lot of states now authorize family
20
members to make treatment decisions as surrogates.
21
PROF. CAPRON:
22
DR. DRESSER:
Right.
But what does that -- what
23
implication does that have for research which is so
24
different?
25
PROF. CAPRON:
26
DR. DRESSER:
I
Having looked at the state -Yes.
Actually --
29
PROF. CAPRON:
1
-- law as well as statutory
2
law, do you think most states have not addressed it or
3
they have addressed it and they have left you with
4
answers that are unsatisfactory?
5
were saying.
DR. DRESSER:
6
I was not sure what you
I do not think most states have
7
addressed it at all.
If they have addressed it, it has
8
only been in the clinical situation and not the research
9
situation.
DR. CHILDRESS:
10
And let me also say we
11
welcome Alex officially to the Human Subjects
12
Subcommittee.
13
floater but we have him now so we are delighted.
People have wondered about Alex as the
14
(Laughter.)
15
DR. CHILDRESS:
This discussion is open to
16
everyone obviously and not simply to the Human Subjects
17
Subcommittee, but any other questions for clarification
18
only before we move into the substantive discussion
19
involving both our panelists?
MS. FLYNN:
20
Just follow up a moment on Alex's
21
issue.
Do we -- are you aware of any information as to
22
how well the advanced directives for treatment for
23
cognitively impaired patients are actually working?
24
they?
25
something that is being viewed as useful?
Is it, in
26
fact, being implemented in large measure?
How is it
Is this something that is growing?
Is this
Are
30
1
playing out in the real world?
DR. DRESSER:
2
Well, I think one of your
3
colleagues has a lot of information on that.
4
Backlar who has written on that.
5
to answer that question.
PROF. BACKLAR:
6
Trish
So I would defer to her
I am embarrassed to say that,
7
Laurie, you are going to have to repeat your question.
8
only heard about advanced directives and I did not know
9
if we were talking about the psychiatric treatment or for
10
research.
I
I am presuming it is for research.
11
MS. FLYNN:
Actually I was asking the
12
question that her comment raised.
13
how well and to what extent advanced directives for
14
psychiatric treatment are actually being implemented?
15
have certainly anecdotally heard a variety of experiences
16
but I wonder if this is something that is moving along
17
and becoming accepted, and being increasingly utilized,
18
and being adhered to or honored in the actual situation
19
or not?
DR. BACKLAR:
20
What do we know about
Well, I actually have an
21
article that came out in Psychiatric Services in
22
December.
23
DR. CHILDRESS:
24
DR. BACKLAR:
I
Could you share that with us?
On a survey, a preliminary
25
survey that we did in Oregon.
There are a number of
26
states that have -- we start to describe what the
31
1
situation is with advanced directives for psychiatric
2
care.
3
list them for you but there are not very many that
4
actually have legislated approval for an advanced
5
directive for psychiatric care treatment.
There are a number of states and I am unable to
There are a number of states that incorporate
6
7
within their advanced directives for health care
8
generally the possibility of one choosing psychiatric
9
treatment.
In Oregon we are one of the first states that
10
did pass legislature and our document was passed in '93
11
and came out in January of '94.
12
for two years.
13
We have had it in place
This preliminary survey told us that very few
14
people know about it, point one, that most of providers
15
know very little.
16
used a number of times for people when they were in
17
crisis and in those times when it was used when they were
18
in crisis, I am talking not in quotation marks, their
19
wishes were honored.
20
But we did find out that it had been
Our document provides for a proxy or
21
surrogate decision maker and we were interested to find
22
that only in the documents that we were able to find out
23
that had been made out, not just used, less than one-
24
third appointed a surrogate decision maker, which was of
25
some interest to us.
26
simply did not know what we were talking about.
Most families reported that they
They
32
1
found the document quite confusing and they thought that
2
perhaps it meant they needed an attorney.
I think that there are a number of issues
3
4
about advanced directives generally.
But I think there
5
are many advantages for an advanced directive for
6
psychiatric treatment which we have not begun to
7
understand.
8
advanced directive for end of life care and I was talking
9
to Rebecca before when we were coming into the hall.
One is they are very different from an
10
Advanced directives for end of life care is -- you
11
prepare something for you do not know what is going to
12
happen.
13
do not know what is going to be our end of life issue.
It is unknown until it occurs pretty much.
We
But an advanced directive for psychiatric
14
15
treatment, in fact, should be only for somebody who has
16
had an experience of a decompensation or psychotic
17
period, and it might be a great advantage for them to be
18
able to say that this is what works for me, this does not
19
work for me, and to make sure that that is going to
20
occur.
21
do with privacy, confidentiality.
22
go into a hospital somewhere out of your state or even in
23
your state, how are people going to know about it?
24
are lots of issues to do with this that have not been
25
well looked out for.
26
On the other hand you are going to have issues to
How do people if you
There
The other big advantage is that certainly if
33
1
one works well with one's health care provider and your
2
family member or surrogate decision maker, there is a
3
wonderful opportunity for really truly informed consent
4
in terms of medication, understanding one's illness,
5
becoming involved in one's "recovery."
Laurie, I know you know what I mean by
6
7
recovery in terms of mental disorders.
DR. CHILDRESS:
8
9
Well, let's view this as the
first substantive area for discussion now that it has
10
been put out on the table and let's talk a bit more about
11
advanced directives, their role, their ethical and
12
practical problems, what kinds of different views we have
13
on that and then we will move into other topics as
14
members of the subcommittee and NBAC wish.
Rebecca, Bob, anything else you would like to
15
16
say about advanced directives?
17
DR. DRESSER:
18
DR. CHILDRESS:
19
DR. DRESSER:
20
DR. CHILDRESS:
21
22
add?
I think I used my time.
Oh, no, this is for our -Yes.
Anything else you want to
Bob?
DR. LEVINSON:
I think that it is a good idea
23
to encourage advanced directives.
Rebecca mentioned that
24
you would not want to allow people to make binding
25
commitments, even people with mental, full cognitive
26
capacity, but I do want to point out that in psychiatric
34
1
practice and to a limited extent in research we do
2
acknowledge the validity of what has been called Ulysses
3
contrast.
The contrast is taken from the -- you know,
4
5
from the myth where Ulysses or Odysseus as you prefer
6
wanted to sail past the place where there was this
7
irresistible lure of the sirens and so on, and what he
8
asked is that his crew bind him to the mast of the ship
9
and leave his ears unplugged so he could hear this
10
without being lured into this and he had the crew cover
11
their ears.
12
where people who have intermittent psychotic disorders
13
can sign a paper, a Ulysses contract, saying next time
14
this happens put me in the hospital for my own good.
15
bypasses the necessity for formal commitment proceedings
16
and things of this sort.
This has been used in psychiatric practice
It
In research it has been used more in doing
17
18
research on such things as alcoholism where people when
19
they are sober sign a contract saying next time I get
20
really roaring drunk it is okay if you draw my blood to
21
do some research.
22
really heavy considerations.
I have not seen it get into any of the
The point that has had long experience with
23
24
advanced directives for research is the clinical center
25
at NIH.
26
that they drafted the first -- what I call -- research
I think it is correct if my memory is correct
35
1
living will.
2
early 1980's and they have been using it ever since.
3
applies not only to the people with mental disturbance,
4
Alzheimer's, but also to people who will lose capacity
5
because they have septicemia, a bacterial infection that
6
is overwhelming and things of that sort.
DR. CHILDRESS:
7
8
That is not what they call it.
Back in the
It
Other points about advanced
directives?
DR. DRESSER:
9
Just for those of you who might
10
be interested, the International Journal of Law and
11
Psychiatry in '96, I did not write down the exact volume,
12
there is a really thorough analysis of research advanced
13
directives for people with mental impairment.
14
give it a qualified endorsement that say that it should
15
be limited to minimal risk research and it is very
16
thorough and it kind of goes through a lot of the pros
17
and cons.
18
And they
You know, I just think it is very important
19
to remember advanced directives in treatment are people
20
issuing instructions about their future care, what is in
21
their best interest in the future.
22
about research we are talking about doing things for the
23
benefit of others and these authors express some concern
24
and I think it is legitimate that once -- if we put a lot
25
of weight in this mechanism, will there be pressure put
26
on subjects in these groups to sign these directives?
When we are talking
36
1
Will they be, you know, highly encouraged?
2
of things.
3
is people will be deemed capable of making these
4
directives because there is an incentive to get them into
5
the research.
Will capacity judgments be compromised?
That
So I think those are all legitimate
6
7
Those kinds
questions.
DR. FLYNN:
8
Does the NIH experience that Dr.
9
Levine referenced -- does the NIH experience with a form
10
of this kind of advanced directive for research shed any
11
light on what the actual practice has been?
12
hear your reluctant, Rebecca, to seeing this as a useful
13
tool and if I am hearing Dr. Levine correctly he is
14
saying that there has been considerable experience at NIH
15
with this kind of approach.
DR. LEVINE:
16
Because I
I wish somebody from the NIH
17
Clinical Center Bioethics Office was here.
18
suggest that for updating on this you might contact --
19
well, Ezekial Emanuel, where is he?
20
DR. CHILDRESS:
21
DR. LEVINE:
So let me
He just left.
All right.
Well, when he comes
22
back ask him about it.
Although he has not been there
23
enough, but several like Evan Duranso would --
24
DR. CHILDRESS:
25
DR. LEVINE:
26
thing.
Gary Ellis might.
But Gary is in a whole different
Gary, do you know about that?
37
DR. ELLIS:
1
2
Dr. Allison Wickman would be the
one --
3
DR. CHILDRESS:
4
DR. ELLIS:
Dr. Levine is quite correct in
5
parsing out the bureaucracy.
6
DR. CHILDRESS:
7
8
Dr. Allison Wickman would -
You are near a mike but you
are not using it.
DR. ELLIS:
9
10
Allison is not here today.
Dr. Allison Wickman would
probably be able to answer that question.
11
DR. CHILDRESS:
12
DR. LEVINE:
Thank you, Gary.
While you are waiting for more
13
complete information there is quite a number of
14
safeguards built into this.
15
is played by the -- an individual designated in their
16
policy as the Clinical Center Bioethicist and when in
17
doubt you clear things through this individual.
18
could be Allison Wickman or some of the others in that
19
office.
Curiously the pivotal role
This
I think that as you are weighing the
20
21
safeguards -- what I have heard so far today and what I
22
am accustomed to hearing when these matters are discussed
23
is primarily focused on getting the best possible
24
assurances of the autonomy of the individual research
25
subject.
26
of that sort of thing you can look at the regulations for
I think if you want to read an extreme example
38
1
what was then called those institutionalized as mentally
2
disabled that were proposed by DHEW in 1978.
These evoked a massive outpouring of protest
3
4
from what was loosely called the public.
You have got to
5
calculate the costs.
6
doing research on some categories of subjects.
7
have to get the go ahead from seven separate agents and
8
agencies.
9
know.
The way they have it set up is for
You would
And the researchers simply said too much, you
We will ignore those with mental incapacity
10
because it is so much easier and less expensive and less
11
time consuming to do research elsewhere or with other
12
people.
13
So I would caution you about excessive focus
14
simply on autonomy of the subjects and try to balance the
15
considerations.
16
the United States of developing what came to be called
17
the therapeutic orphan phenomenon which was applied to
18
children.
19
this population too.
We have been through the experience in
But subsequently it has applied to women and
20
DR. CHILDRESS:
21
PROF. CHARO:
22
directives.
Alta and then Alex?
This is not about advanced
Is yours, Alex?
23
DR. CHILDRESS:
24
PROF. CAPRON:
Okay.
Thanks.
My question is to Rebecca.
25
You have expressed in other contents very eloquently your
26
skepticism about the concept of advanced directives
39
1
because of the nonidentity of the individuals to whom
2
they will apply once incapacitated with the individual
3
who is expressing these now.
4
reflection on that as it applies to this context.
5
I would like to have your
I would also like your further reflection on
6
the comment you were making about the problem in the
7
research context with the choice that is being expressed
8
which is the choice to say I am willing to give to others
9
in the future and I am willing to take some risk on
10
behalf of the greater good because it seems to me that in
11
a certain way one could say that that choice is the sort
12
of thing where it makes more sense to use an advanced
13
directive than about any particularity.
14
I mean, you did express and I would agree
15
with you a preference for proxy directive and instructive
16
directives on the argument that particular instructions
17
that one will give is going to be so contingent on the
18
actual conditions as they develop and it is better to
19
have a proxy who is there, who is situated and can see
20
what has happened.
21
But as to this basic fundamental choice which
22
is either I am a person who is willing to have some risks
23
-- to take some risks for the benefit of others so that
24
others can learn from my condition, something which a
25
competent patient is understood to be able to do and of
26
course is at risk of being exploited and being pushed
40
1
2
into.
But what we see in some ways as a chance for
3
ennoblement and gaining meaning from a serious illness
4
that one cannot defeat, at least I can allow this to help
5
others, you know, in a way is a person who is facing the
6
prospect of a mental incapacity because of Alzheimer's or
7
some other deteriorating condition.
8
to being able to make that choice and isn't that the kind
9
of choice which it does make sense to say you either want
Not really entitled
10
to put yourself in category A or B.
11
circles back to the question is it fair to allow me now
12
to choose for my future self.
13
relationship between them.
14
DR. DRESSER:
But then again that
So you see the
Well, you know, I think you
15
articulate the values conflict here.
16
it is good for people to be altruistic.
17
the policy question is do we think that that is so good
18
and do we think that the rewards that competent people
19
could gain from volunteering themselves for future
20
harmful research balance the harms that would be imposed
21
on the person as an incapable subject who no longer
22
appreciates those earlier values of altruism.
23
is just experiencing something very negative and harmful.
24
Certainly we think
I guess for me
That is,
You know, I think as a society that is the
25
choice we have to make and it is one balance when you are
26
talking about treatment, and I have some of the same
41
1
concerns there.
But when you are talking about research
2
where these people are being imposed on to advance the
3
needs of others, as well as to advance their former
4
values, I just think it gets even more -- of more
5
concern.
DR. FLYNN: Is your objections to this
6
7
specific to the cognitively impaired?
8
you would not hold this concern for individuals who are -
9
- have other disorders but are not necessarily
10
cognitively impaired?
PROF. CAPRON:
11
12
In other words,
They do not need advanced
directives.
13
DR. FLYNN:
14
DR. DRESSER:
I understand.
Yes.
See they can always --
15
no, I think that competent people should -- I mean, of
16
course the regulations require IRBs to only approve
17
research where the risks are reasonable in relation to
18
the anticipated benefits to the subject and/or society.
19
So there is even a view that people with full autonomy
20
should not be exposed to extreme research risks unless
21
there is a good reason.
22
here.
23
greater examination when you are talking about imposing
24
risks on people who do not really understand why they are
25
in the project now.
26
Certainly that should apply
But I also think that there should be perhaps a
I mean they just -- it is -- if you are
42
1
talking about a psychiatric disorder, I think it is a
2
little bit less troubling because if somebody who has
3
been through decompensation, been through the research
4
experience, and has fluctuating competency I guess I
5
would have less problems with that person saying, okay,
6
well, I am willing to go through that again in the future
7
when I am incapable because that person is familiar with
8
what it is going to be like.
I still am not totally convinced that that
9
10
would be the best outcome.
11
dementia where this, you know, the person who has the
12
mild dementia or has dementia in the family has no idea
13
really except based perhaps on observation of some other
14
--
15
DR. FLYNN:
But if you are talking about
Well, you have made the
16
distinction that I was interested in because I think that
17
is an important distinction that people with psychiatric
18
disorders fluctuate as you said earlier in their ability,
19
capacity and autonomy.
20
-- as you pointed out, in the course that we see for
21
people with dementia.
22
your view of the potential utility of these approaches.
23
24
25
26
That is quite different than the
I wondered whether that affected
DR. CHILDRESS:
Bob wants to respond and then
we will shift gears to a different topic with Alta.
DR. LEVINE:
Point of question, when you
asked will you apply these considerations only to those
43
1
who are cognitively impaired, there is all too common a
2
problem of thinking about the cognitively impaired as
3
those who have been labeled with psychiatric diagnoses.
4
During the last few months of life many people are
5
cognitively impaired.
I also -- I am not going to elaborate that
6
7
but I am going to say that there is a set of studies done
8
by Barbara Stanley and her colleagues where they
9
evaluated the capacity to consent to research in
10
voluntarily committed patients in a locked ward and
11
compared it with the patients in the general medical ward
12
of the same hospital.
13
hospital.
14
better for whatever that is worth.
And the involuntarily committed uniformly did
DR. CHILDRESS:
15
16
I believe it was Bellevue
Alta?
Did you want to tie
into this?
17
DR. CASSELL:
18
DR. CHILDRESS:
19
DR. CASSELL:
Let me wait until Alta is
21
PROF. CHARO:
Are you sure?
22
DR. CASSELL:
Yes, I am sure.
23
DR. CHILDRESS:
24
DR. CASSELL:
20
25
26
Well, on that topic.
Okay.
finished.
Really?
Altruism?
No.
I want to extend a comment
and I do not want her jumping up and down.
DR. CHILDRESS:
All right.
44
1
PROF. CHARO:
No, I am calm.
2
DR. CASSELL:
No.
3
PROF. CHARO:
I would like to shift gears if
4
I might because although this has clearly not been mine
5
completely and there were a number of other substantive
6
issues that are of great interest, I am personally very
7
interested in the notions of benefit and what in the
8
world direct means as well as issues of risk.
9
In order to focus my mind on the constructive
10
possibilities in the commission setting I would really
11
love to get the benefit of kind of a road map of the
12
obstacles, whether they were political within the
13
government, political within the research community,
14
within the patient community, all three, or if there was
15
indeed a single or two substantive issues that truly
16
prevent a consensus that have prevented any movement on
17
this issue since the time of the National and President's
18
Commission and now in order to just -- because there is a
19
tremendous wealth of literature on all of the issues we
20
are talking about that has been developing and improving
21
over the years.
22
focus on most intensely I would love to get a road map of
23
what the problem has been in moving forward.
24
25
26
But in order to figure out which one to
I know you wrote a little bit about the
beginning of it but since then.
DR. LEVINE:
I think you have an excellent
45
1
resource on the history of obstacles in Alex Capron.
2
exchange of letters between the President's Commission
3
and the Secretary of Health and Human Services I think
4
highlighted the problems.
5
just a bit.
PROF. CAPRON:
6
The
I will go back before that
Could I say those are
7
published letters in the President's Commission's reports
8
on research ethics and it really is I think going to be a
9
necessity, Bill, for this subcommittee to have copies of
10
the report on compensating research subjects and the two
11
biannual reports.
PROF. CHARO:
12
13
And if I may before -- Bob,
before you begin, see you are doing what I do.
14
DR. LEVINE:
15
PROF. CHARO:
I am going to jump up and down.
Right.
And without stopping
16
from summarizing it you present in the piece that was
17
distributed a nice summary of the initial problems that
18
took place before the National Commission and DHEW and
19
these letters then take us up through the time of the
20
President's Commission.
21
I mean, like that is still 15 years of history and these
22
proposals have been out there, the literature has been
23
out there.
24
desperately curious to get, especially for now, current
25
feelings.
26
want to also -- what is holding this thing up?
But that is still more than a --
The model drafts have been out there and I am
Although I know what the history is but you
46
1
DR. LEVINE:
Well, let me venture an opinion.
2
One, this is not the only area where individuals or
3
groups of individuals have lobbied the federal government
4
for improving the regulations in substantial ways.
5
have the repeated eloquent arguments by John Fletcher
6
about why we really need that Ethics Advisory Board back
7
and that has -- I do not know if it has fallen on deaf
8
ears but it has not elicited any action.
9
I think in the field that we are discussing
10
here there is inaction because there has not been a
11
powerful movement insisting that the regulations be
12
rewritten or written.
13
commission can be the powerful force that will cause
14
something to be done.
15
We
And I am hoping that this
But what we have seen since the President's
16
Commission adjourned finally in 1983 is that there have
17
been occasional individuals or small groups calling for
18
regulations in the field and what they are calling for
19
are very different things, some want this, some want
20
that, but it is not like -- we saw regulation writers
21
mobilized a couple of years ago when a lot of different
22
groups formed a coalition insisting that there be some
23
accommodation in the informed consent regulations that
24
would enable research in emergency circumstances and the
25
-- you know, you must know the history of this.
26
is what I am trying to say.
But that
It is a coalition of people.
47
And then what happened was the writing of an
1
2
amendment to the regulations, public comment and so on,
3
and now it is a final regulation, and this continuing
4
unhappiness on the part of some participants in the
5
discussion.
6
But at least something happened.
PROF. CHARO:
But, Bob, to be really specific
7
if I am hearing you correctly what you are saying is that
8
more than anything else since the initial set of
9
difficulties we are faced with a situation of inertia,
10
not positive active opposition on the part of any part of
11
the government but simply inertia, and a lack of
12
consensus among interested people that would form a
13
single force that would push.
14
around which specific issues in those regulations the
15
lack of consensus can be attributed to.
16
DR. LEVINE:
I would then like to know
The lack of -- I think those who
17
have been pushing hardest for developing regulations in
18
this field have been more or less in agreement.
19
judgment they have generally erred on the side of calling
20
for what I consider excessive oversight and I would not
21
have people monitor research on people with incapacity
22
which presents minimal risk.
In my
23
The arguments I have seen published generally
24
do not distinguish minimal risk from other categories and
25
generally do not distinguish the reasonable expectations
26
of a procedure that would present more than minimal risk.
48
1
They all too often say, well, for therapeutic research do
2
this and nontherapeutic do that.
So there are people talking about it.
3
4
think that is all I can say about it.
PROF. CHARO:
5
So there is resistance on some
6
parts for the excessive protectionism of others as
7
perceived?
8
DR. LEVINE:
9
PROF. CHARO:
10
I do not think -- you know, I -I just do not understand what
the -DR. LEVINE:
11
12
You are asking me to read the
mind of regulation writers.
13
PROF. CHARO:
14
DR. CHILDRESS:
15
16
I
Okay.
All right.
Laurie wants to get in on
this.
DR. FLYNN:
Again at the risk of being
17
inappropriate, I think there are a couple of things that
18
have gone on in this arena.
19
many of the cognitively impaired with individuals who are
20
disadvantaged not only by virtue of cognitive impairment
21
but are often quite impoverished, Medicaid and Medicare
22
recipients often living in circumstances where the kinds
23
of organized advocacies that have gathered around other
24
disorders has not been so easy to create.
25
26
We are dealing at least with
It has -- I think then an issue that my own
organization of families largely and consumers who have
49
1
these disorders has come to over the past several years
2
because of the kinds of issues that have come up through
3
the media.
4
regarded in the psychiatric community as an avid research
5
advocate and truly a believer and participant in research
6
that I have been astonished at how threatened and
7
resistant much of the research establishment has been by
8
the notion of examining and perhaps extending protections
9
in this arena.
10
And I will tell you as someone who is widely
When I press on it they raise two issues.
11
They raise the one that you did and quite properly
12
because some of the proposals out there really are
13
burdensome and excessive, and I think restigmatize in
14
some ways the whole enterprise.
15
concerned about the fragility of the research enterprise
16
around these disorders, that these are difficult to
17
engage subjects, very difficult to understand disorders.
18
The protocols are often complex and there are many very
19
controversial issues particularly with respect to those
20
that have the most severe incapacity and disorders,
21
compounded by the sometimes fluctuating nature of that
22
lack of cognitive awareness.
23
They are also very
So it is a difficult field and a field that
24
is in some ways at some breakthrough points in terms of
25
basic understandings of the disorders and some real
26
advances in clinical treatments.
Folks are very afraid
50
1
to have anything upset that.
But unfortunately the way it has been
2
3
perceived often by people like myself is that there is an
4
arrogance in that community about, you know, what is
5
best.
6
folks who have not had organized advocates.
7
bad people.
8
described in the '70s.
9
are just kind of getting somewhere and asking these
We have been used to being in charge of these
We are not
We are a long way away from the climate you
Why are you coming now when we
10
questions of us?
So it has been surprising to me the
11
depth of that resistance in the research community
12
itself.
DR. LEVINE:
13
Let me agree but add one thing.
14
And that is a constituency that is impoverished does not
15
have much of a voice.
16
area that we have seen a dramatic research, research in
17
emergency situations, there is no constituency of
18
research subjects.
19
subjects of this are people who will get hit by a truck
20
and have head trauma.
21
in advance.
22
resuscitation.
23
But the constituency in the one
I mean, the people who will be the
We cannot round up this population
But people who will need cardiopulmonary
So one of the things that dramatizes the fact
24
that there is no constituency is that FDA put into this
25
regulation that you can only use this emergency exception
26
if you consult with the community.
Well, where is that
51
1
community to consult with?
2
up the maneuver, the procedures for community
3
consultation, I never had this in mind.
4
community that you could find.
5
6
7
DR. CHILDRESS:
As the person who first wrote
I had in mind a
Rebecca, do you respond
before we -DR. DRESSER:
8
Laurie largely.
9
such a complex area.
I was just going to agree with
I think that part of it is because it is
For example, what Bob just said
10
about not having an independent person monitoring
11
research that is minimal risk, in this population
12
research that maybe prospectively looks like -- first of
13
all, we have all agreed that the definition of minimal
14
risk gets pretty vague so what is it.
15
defined it, in this population something that you think
16
would be minimal risk to an individual subject might turn
17
into greater risk, that is it might become more
18
experientially burdensome than you thought it would be.
19
And even if you
So it is more difficult I think to make
20
prospective judgments about how subjects are going to
21
experience these things as individuals.
22
example why there is a lack of consensus I think because
23
it is so complex.
24
DR. LEVINE:
25
DR. CHILDRESS:
26
DR. LEVINE:
That is just one
I have to respond.
A brief response.
You said what we need is case
52
1
histories to exemplify what we mean.
And I would suggest
2
that a typical research project on somebody with severe
3
cognitive impairment might impose the burden of having
4
the blood drawn once or twice a day.
5
can be experientially burdensome to a small subset of
6
this population.
I agree that this
However, as experiential burdens go it pales
7
8
into insignificance with the other experiential burdens
9
they have every day like maybe getting someone to bring
10
them a toothbrush or getting someone to wheel them into
11
the room where they can get their breakfast.
12
blood is trivial in comparison to what these people go
13
through lobbying for rights that most of us never even
14
think about.
DR. DRESSER:
15
Drawing
Well, I guess I just think that
16
substandard conditions should not be a justification for
17
rationalizing research risks.
18
should -DR. CHILDRESS:
19
20
21
22
important.
But I do not think that we
This is interesting and
Let's get some more comments.
DR. CASSELL:
Well, I have to leave shortly.
I did not have to leave shortly when I had my hand up.
23
(Laughter.)
24
PROF. CHARO:
I am sorry.
25
DR. CASSELL:
But I think that there is never
26
a lack for people to write regulations.
So if you see an
53
1
error in which effective regulations have not been
2
written it is not for lack of regulation writers.
3
are some things that -- there are some things where the
4
difficulty posed by the problem is just unresolvable and
5
the basic problem that is posed here is shifting
6
cognitive capacity.
7
for somebody tomorrow who today was one thing and
8
tomorrow is another?
9
will be tomorrow if my cognitive capacity shifts, and I
10
There
And who, in fact, can be responsible
Am I the same person today as I
promise you it will little by little?
But, in fact, everybody who is sick is in
11
12
that situation but we have not the knowledge about that.
13
As Bob pointed out there is a piece of work done on sick
14
people in an ordinary medical world.
15
that shows that there is impairment in people's thinking
16
with all serious illness.
17
and that somebody who is well now and signs a consent is
18
not the same person one day post operatively as they were
19
when they signed that consent.
I have done work
And that somebody who is --
They simply are not.
On the other hand they are not a different
20
21
person.
22
different.
23
philosophical argument of how do we know whether they
24
were the same or not.
25
26
There is something about them that is not at all
I do not want to get into that old
But what we come to here is realizing that
the person cannot be their own spokesperson, that there
54
1
are circumstances in which the person cannot be their own
2
spokesperson.
3
a monitor in we find out that if you get a monitor into
4
enough situations you cannot do the work.
5
-- there is no way for the person's cognitive impairment
6
to be accounted for on a day-to-day basis.
7
way to have somebody supervising other people's work and
8
then what do we do in the absence of that because the
9
research has to be done for the very people who are
10
On the other hand, when we attempt to get
So now we have
There is no
cognitively impaired I mean in other words.
And Laurie says she is an advocate for the
11
12
research.
She is not an advocate for research just
13
because she loves research but because she knows the
14
nature of the problem of the persons who are sick.
So then we begin to see that -- something we
15
16
have already discussed in the subcommittee.
We begin to
17
see a changing relationship and the need to make happen,
18
not to wish into existence, but to make happen a changing
19
relationship between investigator and subject that has
20
more benefit for the subject than any monitor will.
Now I would like to say that all research,
21
22
all human endeavors for that matter, depend on a degree
23
of trust.
24
will do what they say do, that they will be responsible
25
for sick persons.
26
In fact, persons are good and true, that they
Rebecca brings up another very important
55
1
point when she points out the inherent conflict of
2
interest between the investigator as the seeker for
3
knowledge and the investigator as a caregiver.
4
an inherent conflict of interest.
5
otherwise.
6
is to say, well, we have to solve that in some way.
There is
It cannot be
It must not be otherwise.
On the other hand
If we will just accept for the moment that
7
8
this mind bending problem has to be solved and cannot be
9
solved in the way we have done it in the past, that is to
10
try and figure out another way of writing the regulations
11
that will somehow change the cognitive shifts that go on
12
in the human mind if we will just accept that that is not
13
going to be our solution.
14
a chance of moving forward.
Then I think we actually have
15
Just as an anecdote years and years ago when
16
I was in the air pollution business everybody was trying
17
to get, you know, what number of amount of sulfur oxide
18
in the air could we write that would make everybody
19
protected if it was below that.
20
epidemiologic research on air pollution.
21
about that?
22
was no number.
23
number.
24
will be process.
25
26
What number?
And in those days I did
I bent my head
Well, finally the conclusion
Give up the idea that there will be a
The idea, in fact, it will not be numbers, it
Here I think we are going to come to much of
the same kind of conclusion.
If you say when I am
56
1
finished speaking with reason, well but that is a vague -
2
- you do not have to have a solution when you start out.
3
You have to have a direction.
4
PROF. CHARO:
Eric, I am not going to dispute
5
a word you said about the kind of core substantive issues
6
that applies to many of these people.
7
respectfully differ with your underlying premise.
8
there are lots of regulation writers.
9
writing the regulation is a major pain in the neck and
But I do
Yes,
But actually
10
nobody wants to do it unless they are forced to.
I mean,
11
the routine to get it through is just nightmarish.
12
It strikes me that where the regulation came
13
down is because, in fact, in essence there was no patient
14
group at the table.
15
as potential subjects because they could not recognize
16
that in themselves, kind of thing you were describing
17
with the emergency stuff, or the patient groups would
18
dismiss out of hand.
19
Either people did not see themselves
The prisoners, well, they are a very
20
identifiable group, they confide in one another, they
21
know they are going to be targeted, but nobody is going
22
to pay attention to what they say anyway.
23
they are not even allowed to vote if they are felons.
And, in fact,
24
Pregnant women routinely dismissed because as
25
the Researcher announced yesterday they are physiological
26
sound to be absent minded and basically cognitively
57
1
impaired.
I loved that announcement.
As a result I think that in some ways the
2
3
problem here as weird as it is to say, you know, the
4
morning news is wonderful, the problem is as weird as it
5
is to say is that there is a patient group, it does not
6
know how to find itself, it does not know how to identify
7
itself, but in this case because of the very substantive
8
problems that have been identified, the variability of
9
the patients, et cetera, they have a voice through their
10
allies, their families, but the voices are not uniform.
11
They are conflicting.
So there is not a consensus that can allow
12
13
that patient group to sit at the table and so you do not
14
get anywhere.
15
but elites and that is the French bioethics model and it
16
works beautifully.
17
do.
18
Without the patient groups we have nothing
They make much more progress than we
DR. CASSELL:
Alta, you cannot have a patient
19
group where the people who will be uninjured the day
20
after tomorrow.
21
PROF. CHARO:
Right.
But that is an
22
advantage in many ways because it allows just the elite,
23
the researchers and the lawyers, and the regulators to
24
sit down and make progress and do it without the fuss and
25
muss of the public.
26
DR. CASSELL:
Is that what you are
58
1
suggesting?
2
PROF. CHARO:
No, it is not.
3
DR. CASSELL:
I would be slightly surprised
4
if that is the conclusion you came to.
PROF. CHARO:
5
What I am asking, though, is if
6
we do not want to cut the public out, that we do
7
recognize the lack of consensus from them at the table is
8
going towards your efforts to regulate I would be really
9
interested if there is some way to splice this public and
10
find the core group that do have a consensus on certain
11
kinds of subjects and kinds of settings, and work on
12
those things where regulation probably could be adopted,
13
and then continue to work on the areas that are not yet
14
easily regulated because there is genuine difference of
15
opinion.
16
So, for example, you made a big distinction
17
and everybody else has about people who are experienced
18
with various forms of cognitive impairment or emotional
19
impairment, and now are currently competent and might go
20
forward, et cetera, et cetera, as opposed to those who
21
are unfamiliar with the experience, it is going to be a
22
long-term experience, a permanent experience and they are
23
going to be incompetent to the point where even things
24
like assent are unrealistic.
25
26
It strikes me that in those more severe cases
actually there might be some consensus around an
59
1
extremely protectionist attitude.
2
debates are circling around the more problematic cases of
3
partial competencies, sporadic competency, degrees of
4
risk, et cetera.
5
populations and find the ones where there is a consensus
6
within the patients and patient allies, have them work
7
with the researchers and the regulators, and move forward
8
with some portion of the puzzle.
Maybe it is possible to split off
DR. CASSELL:
9
And that the real
Alta, if you go and solve the
10
problem of changing competency in all the other groups
11
where competency has been taken for granted up until now
12
all you do is protect a small group.
13
PROF. CHARO:
Yes.
14
DR. CASSELL:
If you stay in the same model,
15
the same model that was there before, not as you rightly
16
pointed out, if it is impossible to find it, let's go get
17
where there is a group and do that.
18
PROF. CHARO:
Yes.
19
DR. CASSELL:
That is the only problem with
20
it.
It may, in fact, be necessary for certain groups
21
where no matter what solution you find that works for
22
everybody else will not work for patients -PROF. CHARO:
23
I agree.
It is a classic
24
dilemma, democracy is a messy business.
25
American President at the movies, "Democracy is hard
26
work.
America is hard work."
You heard the
And the question is
60
1
whether you want some short term gains while you do the
2
rest of the hard work or that the short term gains are
3
not working.
DR. CASSELL:
4
Well, but in the past what
5
happens in this is what people have done in a conclusion
6
like that is take the small group, write regulations for
7
the small group and leave the basic problem untouched.
DR. CHILDRESS:
8
9
time.
We have a scarce resource of
We have only about 15 more minutes before -- Tom,
10
will you be around until the end?
11
some of the questions we talked about over break about
12
the future.
13
our substantive discussion.
14
into this particular part?
15
We will need to pursue
So we will have about 15 more minutes for
DR. FLYNN:
Laurie, do you want to tie
I just want to endorse the point
16
of view that Eric is espousing both in earlier comments
17
about the -- I think based on the discussions we have had
18
and the interactions we had yesterday, looking at some
19
new ways to deal with these issues that engage the
20
broader community in creative ways that further the
21
dialogue and ultimately create a messier, if you will,
22
process that may, indeed, help us get to some of the most
23
difficult solutions that have alluded us so far.
24
I would be worried about -- as much as I see
25
advantages in trying to move forward on those areas where
26
there would be agreement because I think the bigger
61
1
problems are the ones that are plaguing us now are the
2
ones that are affecting large numbers of individuals and
3
where we can no longer afford to be silent.
4
wrestle through this and I think Eric is pointing in a
5
direction that would be very helpful to us as we attempt
6
it.
7
DR. CHILDRESS:
8
DR. COX:
9
We have to
Yes?
At the risk of being repetitive
this really hits a key with me, too, and the -- an easy
10
way to deal with research is to make it very separate
11
from medical practice.
12
-- I understand why you did it, Rebecca -- of saying, in
13
fact, you know, let's have the researchers wear red coats
14
and let practitioners wear white coats.
15
basically keeping this irreconcilable conflict from
16
having to be considered.
17
I was really struck by something
That is a way of
But I really think that this is where the
18
action is, is because it is not so clean, and we have to
19
be willing to deal with the mess of this because it is
20
adjudicating a new relationship between research and
21
medical practice, whether it is for, you know,
22
particularly vulnerability groups or not.
23
looking forward to the mess but I really do completely
24
agree with Eric and other spokespeople in this, but that
25
is almost certainly where the solution is.
26
PROF. CHARO:
I am not
There probably should be some
62
1
pink colored ones too for the nurses.
2
DR. CHILDRESS:
3
DR. SHAPIRO:
Harold and then Trish.
I was just going to make a
4
remark that given American history red coat is not a very
5
good idea.
6
(Laughter.)
7
DR. SHAPIRO:
8
DR. CHILDRESS:
9
10
All right.
Try some other color.
All right.
Trish?
Okay.
In the last 15 minutes what are some of the
issues from people we have not heard.
11
Alex?
12
PROF. CAPRON:
Just to pursue this question,
13
putting aside the color of the coat, do you have thoughts
14
about what kind of separation that would need to be
15
between a person in a professional role who plays the
16
evaluative and to a certain extent representative
17
function with the incapacitated patient in terms of
18
making sure that the incapacity really is not correctable
19
in the near future so that the patients could give
20
consent making evaluating the risk/benefit and so forth
21
from the patient's point of view, how you would set up a
22
relationship in terms of who appoints this person, who
23
funds the person's efforts and so forth that would make
24
them sufficiently separate from the research enterprise
25
that they would not be kind of captive of that
26
enterprise?
63
1
For example, in the transplant area some
2
people worry about the doctors who are making
3
determinations that death has occurred are too closely
4
related to the transplant team and the law tried to
5
specify, no, they should be completely disconnected from
6
it and so forth.
7
for that effort by the transplant team and so forth.
8
mean, those kinds of things can arise.
9
In the end they are likely to be paid
I
So have you given thought in this context of
10
how that would be done?
11
funding mechanism, separate appointment mechanism, et
12
cetera, et cetera, and would it be possible to have a
13
person playing that professional role and yet a separate
14
person playing the surrogate role, the proxy role for the
15
patient who is not a professional but is either the
16
relative or the court appointed person who, in effect,
17
would turn to this expert for advice but the expert would
18
not be the decision maker.
19
20
21
22
23
Would one need a separate
That is really two sets of questions about
their role and their independence.
DR. CHILDRESS:
Rebecca, do you want to
respond first?
DR. DRESSER:
Sure.
This is a tough one.
I
24
think some of the things Eric was saying were suggesting
25
that it would be possible for some members of research
26
teams to adequately fulfill this role of accurate
64
1
disclosure and assessment of capacity and, you know, just
2
the decision making process.
3
true.
4
on the other hand I think that having somebody
5
independent of the research project is not a guarantee
6
that that person will adequately do this.
I think that is certainly
I think that some researchers could do this.
And
7
So it is just a question, I think, for policy
8
purposes of if you create this separate role are you more
9
likely to get what you are interested in than if you
10
tried to assign it to one of the members of the research
11
team?
12
can figure out how to think about that as well as I can.
13
In terms of funding, I mean it is sort of the
That is the question and, you know, I think you
14
same issue we have with hospital ethics consultants.
15
mean right now coming out of general funds there is some
16
concern about, you know, should this be factored into
17
patient fees and all these questions.
18
going to come from?
19
written into a research proposal as a cost?
20
investigators are not going to be thrilled with that idea
21
but that is one avenue.
Where is the money
I guess there really -- should it be
Obviously
I do not know if there could be a creation of
22
23
I
a separate fund, you know, for issues.
DR. LEVINE:
24
I am glad, Alex, that you are
25
attentive to the problems created by so-called unfunded
26
mandates.
There has been an extensive literature
65
1
developed on having third parties superimposed on the
2
research process where there is an expectation that there
3
could be a conflict of interest.
4
first wrote about it at length was Harry Beecher who
5
recommended in the process of getting informed consent
6
that he would have consent discussed by somebody other
7
than the investigator.
8
the role of physician and investigator.
I think the person who
He also talked about separating
9
This then provoked me to review what had been
10
written about it and there is a passage in my book where
11
on review of all of this I come to the conclusion that if
12
you assume that the researcher and that the treating
13
physician have differing motivations, irreconcilably
14
different to the extent that you separate the roles, then
15
you want to be awfully sure that the investigator is
16
never left alone with the subject.
I mean, after consent is done they are the
17
18
investigators on his or own to savagely abuse the
19
subject.
20
to assure that there is a physician around every time the
21
investigators can contact the subject is to have them
22
both and have it the same body.
23
My conclusion was and remains that the only way
DR. BRITO:
From personal experience I would
24
say that even when they inhabit the same body there can
25
be a conflict.
26
DR. LEVINE:
Of course.
But if you want to
66
1
find any human beings that have unambiguous univocal
2
approaches in problem solving then we really are going to
3
have an unfunded mandate.
DR. BRITO:
4
I have a general question about
5
regulations, et cetera.
One of the main problems I have
6
with informed consent, this goes along lines of informed
7
consents not just for cognitively impaired but just in
8
any situation, is that -- and I brought this up before,
9
it seems like we always put the onus of the
10
responsibility on the person signing the informed
11
consent, and it just seems something very basic that if
12
we put more of that responsibility on the investigator by
13
having he or she sign an informed consent that applies to
14
that specific research project it would make rather sense
15
there.
16
requires --
17
Does that -- is there any legislation that
DR. LEVINE:
Albert Reese, a sociologist,
18
wrote an elegant paper showing how the consent form was
19
an instrument designed to protect the institution against
20
the subject.
21
the subject comes back some day and says you did not get
22
informed consent from me,
23
information, you can say, "Oh, yes, I did and I have got
24
a signed receipt for that."
25
26
Basically what it is, is a receipt so if
you can give me the
If we really saw these instruments as
something designed to serve the subject's interest we
67
1
would do it more like a product warranty.
2
a piece of paper that the investigator signed and hand it
3
over to the subject so the subject would have the
4
receipt.
5
I do not see informed consent as being such a large
6
justification for research.
7
that is most often discussed.
We are still stuck with that to this day.
But
It tends to be the thing
I think some of the international documents
8
9
We would have
have a better perspective saying first look at scientific
10
design; second look at the confidence of the
11
investigators; third look at the balance of risks and
12
benefits; and after you are done with that then you
13
decide -- then you -- if you pass those three tests now
14
it is time to discuss the informed consent.
15
with the informed consent.
DR. CHILDRESS:
16
17
18
We begin
I have Laurie and then
Rhetaugh.
DR. FLYNN:
I think we could profit just
19
parenthetically from a whole session with you folks on
20
the issues of informed consent that we have identified.
21
I want to move to a slightly different issue and it may
22
be addressing in some of your writings, which I confess
23
have yet the experience of really delving into and I am
24
very eager to read your book.
25
26
What is your view or what is your assessment
of the -- some of the concerns that we have just
68
1
articulated around the vulnerability again and special
2
needs of your population as we look at the variability of
3
IRBs and your experience in dealing with these kinds of
4
protocols, in the wide range of training and knowledge
5
that may be available and the make up of these IRBs, a
6
variety of ideas float around, everything from there
7
should be some super perhaps national IRB or special
8
regionally designated IRBs that specialize in certain of
9
these areas so that there is a growing capacity to make
10
11
those distinctions.
My own organization has a great interest in
12
seeing IRBs that do substantial work in psychiatric
13
research recruit and significantly involve members of the
14
community of concern, family members, advocates, patients
15
who have recovered and live in the community to be direct
16
participants in some of that.
17
What is your view of how we might -- given
18
what we have all identified as the very difficult issues
19
here, how might the IRB system or structure, or
20
mechanisms perhaps help us address this?
21
DR. DRESSER:
A lot of what was -- what has
22
just been discussed, I keep thinking about this UCLA
23
schizophrenia study where, you know, one of the problems
24
that the federal officials investigating saw was that the
25
researchers were the care givers and that was not
26
explicitly dealt with as it should have been.
But, you
69
1
know, I believe that one of their -- I do not recall
2
whether it was a requirement or a recommendation but it
3
was that the UCLA IRB include someone who was a consumer
4
representative or community representative.
I really support that.
5
I think that
6
community involvement on IRBs -- to do it effectively it
7
is difficult.
8
lay members are often very intimidated and it takes a
9
while to -- I would say a year or two to get the hang of
Any people who have been on IRBs know that
10
it and, you know, sometimes it works and sometimes it
11
does not.
12
support that that person gets from the other people.
13
it is not a panacea but it can be helpful.
14
It depends on the person.
DR. FLYNN:
It depends on the
So
Dr. Levine, did you have a view
15
on specializing IRBs?
16
of becoming a regional or national repository for this
17
kind of research that falls in the area of perhaps most
18
impaired, greater than minimal risk might be reviewed?
19
DR. LEVINE:
In other words, certain IRBs sort
I think that the National
20
Commission put together a very sophisticated analysis of
21
why have these sort of general practitioner IRBs located
22
right in the institution where the research will be done.
23
Part of it has to do with you cannot write it all in
24
regulations.
25
to know which members of your staff need watching more
26
than the others.
You have got to be right there on the scene
Although you do not see that written
70
1
about very often I think most people on IRBs know that
2
they have to individualize that sort of oversight too.
3
Let me get back to an earlier --
4
PROF. CAPRON:
Bob, could you stop right
5
there.
Do we have -- you say it is not written about
6
very much and people are nodding their heads that it is a
7
sensible idea.
8
say that has proven to be an important mechanism because
9
certainly the notion of centralized and localized review
10
is greatly buttressed by the notion that there are these
11
intangible benefits.
Do we have any basis on which we could
The kinds of manifestations of that in terms
12
13
of individuals -- IRBs refusing to allow its center to
14
participate in a multicenter trial because the
15
investigator at that center, the oncologist, happens to
16
be not reliable whereas at another institution he or she
17
is.
18
people.
Or consent monitors being widely prescribed for
I mean how would one get tangible evidence
19
20
that IRBs have done this or is it simply a matter that
21
they read the protocols?
22
about it?
I mean, has anybody written
You edit IRB --
23
(Simultaneous discussion.)
24
DR. CHILDRESS:
25
26
We have one more question and
we have to get on before we -PROF. CAPRON:
I am just very concerned with
71
1
this kind of -- I am really desperate for information or
2
for something that -DR. LEVINE:
3
There are no data.
What there
4
is, is the armchair anthropology of people like me and a
5
couple of others.
6
having monitors, what we have within the institution
7
where the IRB has established itself as a credible unit
8
we have a system of informal monitoring that would be
9
vastly experience to purchase.
What we talk about is instead of
We get medical students, nurses, professors
10
11
walking in and saying I think there is something funny
12
going on over there, would you take a look at it.
13
respond to all of this.
14
of behavior that would confound sociologists who are
15
obsessed with power imbalances.
You
This is not -- this is the sort
One thing we had a couple of years ago was a
16
17
medical resident came in to say that he thought that
18
there was coercion of an elderly woman, female, research
19
subject in a protocol where the principal investigator
20
was an associate dean.
21
it turned out the PI did not even know what his fellows
22
were doing.
23
hurry.
As it turned out there was and as
But we got it straightened out in a real
I am seeing George Caspara (?) sitting there
24
25
and it makes me wonder if we are going to get inspected
26
for this.
72
DR. CHILDRESS:
1
2
end now.
3
be the last one.
I have to get Rhetaugh's question and that will
4
Rhetaugh?
5
DR. DUMAS:
6
DR. CHILDRESS:
7
DR. DUMAS:
8
DR. CHILDRESS:
9
10
Unfortunately, we are at the
I do not want a question.
Or comment.
I had a comment on another -Could you make your comment
and this will be our final word and then we will need to
talk just a bit about procedure.
DR. DUMAS:
11
I do not even really -- I do not
12
think it is appropriate at this point.
13
beyond it.
DR. CHILDRESS:
14
15
16
17
Okay.
We have gone
All right.
Thanks
very much.
Please join me in thanking our two commenters
for such a --
18
(Applause.)
19
DR. CHILDRESS:
We hope we can call on you
20
again for written contributions or other contributions.
21
This has been a most helpful session.
22
identified several areas where we need a lot more
23
information.
24
We, unfortunately,
Several of us have talked a bit about the
25
future in passing.
One of the things we might consider
26
for our subcommittee is -- given what we have heard
73
1
today, if we have another session, I am now making this
2
more specific, for them to get some of the people,
3
perhaps Jonathan Marino from the University of
4
Pennsylvania, Center for Bioethics, study of informed
5
consent which is also moving in the direction of trying
6
to talk about guidelines for the cognitively impaired.
7
And the possible Maryland legislation and Dr. Schwartz
8
and others have been involved in.
These would be two more specific versions
9
10
that would take what we have heard and try to focus on
11
things more generally in a more specific concrete
12
direction.
If that is something that the subcommittee
13
14
would find appropriate we might try to schedule at least
15
an hour or so on that, perhaps two hours, at a subsequent
16
session.
PROF. CHARO:
17
18
21
Can we add to your task list
over time?
DR. CHILDRESS:
19
20
Is that, subcommittee, appropriate?
Oh, sure.
Yes.
We will
need to.
The second thing that some of us have talked
22
about in passing is what kinds of papers to try to
23
commission if we could.
24
in the discussions.
25
could identify the right sort of person or persons for
26
the discussion about vulnerability.
These are some that have come up
One would be to get something if we
74
1
A second would obviously be to focus on
2
issues surrounding community and how taking that kind of
3
perspective might lead us to rethink some ways to
4
reinterpret the Belmont principles.
5
A third, obviously something that would be
6
another possibility too would be to make it feed into a
7
report would be to get -- maybe we have enough in the
8
literature from the contributors we have heard from today
9
and I think Harold Levine and others have contributed in
10
this area, to talk about the shift in paradigms or the
11
changing context, the nature of research, but that might
12
be another possibility.
13
could think about and there may well be others as well.
14
Those are at least some that we
PROF. CHARO:
I would like to add just two
15
things that I think are really concrete that might be
16
quite do-able.
17
commitment to get a copy of the agency reports within X
18
number of days, X whatever, and a commitment among
19
subcommittee members to read it and be ready to discuss
20
an evaluation of it while other work is proceeding in
21
parallel so that we have the possibility of doing
22
something with those.
23
First can we get some -- can we get a
That is A.
And, B, in light of today's discussion, and I
24
was nodding, Alex, because I recognize the situation
25
because I thought it was a good idea, could we through e-
26
mail perhaps accumulate a list of pieces of information
75
1
about the actual operation of IRBs that we have all
2
noticed and then send a letter to the institutions that
3
have multiple assurances at IRBs that we do know about
4
and invite their chairs to submit written comments of any
5
sort that they wish but notifying them that these are
6
already areas we have identified in which we really lack
7
information.
8
9
And so to the extent that those are things
they would like to talk about it would be particularly
10
appreciated.
11
targeted invitation for written input that might provide
12
some of the stuff that we cannot get from commissioned
13
papers because we do not have the time or money.
14
This is not a survey.
DR. CHILDRESS:
Right.
This is a very
That would be useful
15
and also I will get the National Reference Center for
16
Bioethics Literature to give us as much as they can in
17
this area as well.
18
DR. DRESSER:
One thing you might think
19
about, we did not talk about the New York Appellate
20
decision today.
21
DR. CHILDRESS:
22
DR. DRESSER:
Right.
Even though that did not apply
23
to federally funded research in the federal regs I think
24
it raises a lot of issues about the regs and it might be
25
worth it for somebody to go through that very carefully
26
and point to the issues.
76
DR. CHILDRESS:
1
2
5
Good.
Thank you.
And everybody has that packet of material.
Okay.
3
4
Right.
Any response to Alta's suggestion and
the others?
PROF. CAPRON:
Yes.
I would like to say
6
publicly what I said to you privately and then you can
7
get feedback either now or otherwise from other
8
subcommittee members.
9
we are going to have useful meetings to -- and be able to
I think there is great urgency if
10
produce a report -- to commission papers very soon and
11
the experience of the National Commission which was
12
operating on a very short deadline as to its first report
13
on fetal research is an experience which is now 20 years
14
old and the world has changed, and the people who you
15
turn to are busier than they were then.
16
less going on.
But there was
17
But for an important presidentially appointed
18
body that is mandated to look at a subject I think it is
19
possible to get good people to do work on a short
20
schedule even if what they present to you first is a
21
brief written outline and then an oral presentation of
22
their issues.
23
effect of asking Rebecca and Bob to do that for us today
24
but they are not commissioned to then write reports.
25
have got to have that kind of fodder.
26
staff and others are going to be able to turn out reports
You know, we have had the benefit in
We
Frankly, if the
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you need that kind of work and we need it in March and we
2
need it in June whenever we are meeting.
3
I just want to say I am very, very hopeful
4
that once whatever funding commitments are necessary for
5
Bill and others to get the secretary to sign the contract
6
that those people be already identified and contacts be
7
made with them and that we get the four, or five, or six
8
papers that you just described under way so that they are
9
there when we need them.
10
DR. CHILDRESS:
11
PROF. CAPRON:
And also -And that those reports -- I am
12
talking about something that will not just come back to
13
our subcommittee but would be someone coming to talk to
14
the whole commission that we would have arranged that we
15
have a substantive discussion with people who can really
16
take us deeply inside some of these issues.
17
PROF. CHARO:
Alex, but no matter how fast
18
you make it, it is already getting late.
19
own analytical staff until we have one?
20
DR. CHILDRESS:
Can't we be our
I do not think they are
21
mutually exclusive.
I would propose we pursue both
22
simultaneously if the subcommittee agrees.
23
those topics we have heard, those -- what changes or
24
alterations would you want to make in those and I will
25
depend on you e-mail and otherwise for getting names and
26
suggestions?
Are those --
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1
DR. DUMAS:
I am concerned about what we are
2
planning to do by March and I do not know what Alta has
3
suggested is intended to be part of that March report.
4
thought I saw the IRB issues on the lower end of the list
5
of priorities.
6
we are going to meet again and (2) what are we going to
7
do between now and then.
8
I
So I need some orientation about (1) when
DR. CHILDRESS:
Well, I think in terms of the
9
IRBs appearing low on the list of priorities mainly that
10
was for purposes of being able to complete a project but
11
several of these things overlap and we will be pursuing
12
along the way.
13
approaching the priorities that there is so much of a
14
need in the area of informed consent and IRBs that we are
15
probably not going to be in a good position to have a
16
strong recommendation by October.
17
carrying that process forward.
18
overlap substantially, the informed consent language,
19
that was the area we talked about today.
20
know, does that help?
21
22
23
24
25
26
It was my impression of the way we are
DR. SCOTT-JONES:
But we need to be
Obviously those two
So I do not
This is on a different
topic so you can go ahead.
DR. CHILDRESS:
those lines.
Okay.
Anything else along
Is that --
PROF. CHARO:
Can we -- we could commit for
the day before the March meeting if we wanted to try to
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1
convene a subcommittee.
We could commit to having
2
reviewed the agency reports and come back to discuss
3
them, and if there is a consensus about an evaluation,
4
find that consensus.
5
language of the consensus if one exists about the need
6
for universal coverage of protections from research
7
regardless of the mechanism that is chosen and to submit
8
that for the March meeting for the full committee.
And, second, to discuss the
DR. CHILDRESS:
9
We need to do that.
I quite
10
agree.
11
that Tom and I have had some passing conversations about.
12
There are several possibilities.
13
14
Regarding another meeting, this was something
DR. SCOTT-JONES:
If you are ending I would
like to just go ahead and say what I was going to say.
15
DR. CHILDRESS:
16
DR. SCOTT-JONES:
Please.
I am sorry.
Well, first of all, I agree
17
with Alta that we need to move towards products and I
18
just wanted to say that the three topics that I have
19
noted that you have said, Jim, would be good for
20
commission papers, vulnerability, community, and shifting
21
research paradigms.
22
I think that because we have discussed those
23
at length and we were not quite in complete agreement on
24
them, but if we were to commission papers that we
25
probably should try to develop a paragraph or two on each
26
one of those ourselves and circulated them and make sure
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1
that we are all agreeing and asking for the same thing.
2
I would be especially interested in working on the --
3
well, any of those three as far as developing a paragraph
4
that would say what we really need and what we would
5
really be asking for.
DR. CHILDRESS:
6
That is very important
7
because that has to be done obviously before we can get
8
someone to sign on.
9
trying to have them -- if all this could be arranged,
And then the other part would be
10
trying to have them available for a March meeting or a
11
late February meeting, or whatever, at which time we
12
could -- I am not talking about the large meeting, but a
13
separate -- at which time we could work with them in
14
further refining the direction of the project.
15
to say the paragraph will be important to get them
16
started, but then as they get into it we need to interact
17
with them in that direction.
That is
Does that make sense?
So do others want to take -- you will take
18
19
primary responsibility for getting a first draft started
20
on -DR. SCOTT-JONES:
21
22
23
24
25
26
Are we trying to assign
that now?
DR. CHILDRESS:
I thought you were ready to
volunteer for one of those.
DR. SCOTT-JONES:
No.
I mean, I would be
happy to work with Arturo on vulnerability.
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1
DR. CHILDRESS:
2
DR. SCOTT-JONES:
3
DR. CHILDRESS:
5
DR. SCOTT-JONES:
6
DR. CHILDRESS:
Okay.
-- whatever -Any other?
Okay.
start the first draft then on the third topic.
DR. BRITO:
8
9
I would be happy to work on
the --
4
7
Oh, good, okay.
So did we decide on the meeting
DR. CHILDRESS:
No.
That is something we
11
have to do but make sure we cover this first.
12
else on the three papers?
Okay.
13
Anything
Now, Tom, what thoughts have you had
about the meeting matter?
DR. MURRAY:
15
16
Okay.
and --
10
14
I will
About whether to have a meeting
before March?
17
DR. CHILDRESS:
18
DR. MURRAY:
Yes.
We had as some of you heard a
19
brief conversation at the end of the first session this
20
morning about whether to have one and there had seemed to
21
be a consensus, which was really apparent and not real,
22
not to have one before the March meeting of the full
23
commission.
24
Zeke Emanuel came up to me afterwards and
25
expressed a view that he thought it might be useful to
26
get together even if we just got together for half a day
82
1
or a day to sort of -- as he put it a schmooz meeting to
2
sort of schmooz about what the various topics were.
3
said, "Well, what if we actually could have the
4
contractors who are writing papers identified and have
5
them be present for part of that conversation."
6
"Yes, that sounds like a good idea."
I
He said,
7
So I am quite willing to try to see a meeting
8
occur as you say perhaps in mid to late February where we
9
bring at least two or three of our potential paper
10
writers, contractors in to sort of think aloud about what
11
ought to be in their papers.
12
sort of very crude outline at that point.
13
respond to that and raise our own consensus.
14
happy to see that happen if it is something that could be
15
put together and if other members of the subcommittee
16
thought that it would be a good thing.
They might have an initial
We could
I would be
17
I see some nods of affirmation on that.
18
DR. CHILDRESS:
19
Subcommittee?
20
direction sound useful?
21
what people think.
What about the Human Subjects
What is your rule on that?
Does that
Let's get some feedback and see
22
DR. SHAPIRO:
23
DR. CHILDRESS:
24
DR. SHAPIRO:
Jim, can I -Please.
A number of very critical
25
things have to happen in both subcommittees in the next
26
week or ten days.
Just to name the most obvious, it is
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1
mobilizing our own intellectual capital in some kind of
2
effective way so that every member of every subcommittee
3
can be expected -- can be asked by the chairman to do
4
something and to harness their own intellectual capital.
5
Individuals have to be identified for those areas which
6
the subcommittee chairs feel that we have to identify
7
papers as Alex used the unfortunate word of fodder for
8
our thought, but in any case certainly to help us think
9
more clearly through some of these things.
10
Within now and a week from now or ten days
11
from now I believe it will be true that both Tom and Jim
12
will have a much clearer notion of what can be available
13
for useful discussion at what time.
14
is, Jim, for both of these subcommittees, is that we
15
spend this next week or ten days in e-mail, telephone and
16
other kinds of contact so that you can better feel your
17
way as to how useful another meeting would be either
18
before or after the March meeting.
19
So my own suggestion
If we are fortunate we can meet before the
20
March meeting in which case the March meeting will be all
21
that much more effective.
22
setting the agenda for the March meeting is to be in
23
contact with people, see where you are going to be if you
24
are going to meet before or after because that will
25
impact the agenda of the March meeting itself.
26
What I would wait to do before
So my thought is that we cannot easily settle
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1
all of these things here today but that we take that as
2
high priority must item to do in the next week or ten
3
days at the most to settle these issues and to try to
4
schedule something which is convenient for the various
5
subcommittee members.
6
time now if we are going to meet our October aspirations.
It is an extraordinarily important
So my thought is if you and Tom would agree
7
8
that we could leave it that way, that puts a lot of
9
responsibility on my shoulders, yours and Tom's shoulders
10
over the next ten days, but I do not know any other way
11
to get a conclusion here.
12
DR. CHILDRESS:
13
Is that satisfactory from the
members of the subcommittee standpoint?
DR. MURRAY:
14
One thing could we do, could we
15
ask the staff to do right away is to resurvey the group
16
just to see about availability in late February?
17
DR. SHAPIRO:
18
DR. MURRAY:
19
Yes.
Because we could start that
right now.
20
DR. CHILDRESS:
21
DR. MIIKE:
Larry?
Until Harold mentioned the March
22
meeting I was going to say that we need to know what we
23
were going to talk about the March meeting.
24
putting in these interim meetings post the March meeting
25
without any discussion about what the March meeting is.
26
I think we are coming fairly rapidly to an artificial
We are
85
1
distinction between our regularly scheduled meetings and
2
ad hoc meetings.
3
meeting as just another one of the meetings around these
4
overall issues and not reserve it for any particular --
So I would rather look at the March
DR. SHAPIRO:
5
Larry, it may, in fact, work
6
out that way.
It may, in fact, work out that what the
7
March meeting comes to be is something for us to work on
8
these issues.
9
possibility for the March agenda, at least for part of
But there is at least one other
10
the March agenda, which I expressed yesterday, but if it
11
turns out it could be postponed for another meeting, and
12
that is I do want to give an opportunity to certain
13
groups to address the committee regarding issues that we
14
are addressing that have not for one reason or another
15
taken advantage of the public comment session and that
16
reach out to invite them to come and speak to us.
Now it would not have to be the March
17
18
meeting.
So that is just one of the other items which we
19
have room in the March meeting we will try to accomplish.
DR. CHILDRESS:
20
And as we discussed there
21
might be ways to focus some of those contributions to
22
some of the areas we talked about this time.
23
absolutely.
Yes,
24
DR. MIIKE:
One last comment is that we need
25
to build in some redundancy here.
26
kinds of things before one cannot depend on commission
Having done these
86
1
papers and expect that they are going to be valuable.
2
I think that -- I see Alta nodding her head over there.
3
So we have had a whole bunch of --
4
5
6
PROF. CHARO:
So
As both author and the
requester of such papers.
DR. MIIKE:
So I think that in our planning
7
we should be prepared that a certain number of these are
8
not going to be useful.
9
DR. CHILDRESS:
I think you are quite right
10
and I would hope that this interactive process that we
11
are talking about of providing direction and selecting
12
the right sort of people we hope and then giving them
13
feedback and process as well as having them give us
14
feedback might well produce a better product because
15
quite often these papers are commissioned with just a
16
brief statement and then the author is sent off to
17
prepare the paper.
18
At least what we have been talking about,
19
Tom, I think it is correct to say would be a much more
20
interactive process if we could do it, which I think
21
would be mutually beneficial.
22
Bill, Harold, anything you folks want to say?
23
DR. SHAPIRO:
24
DR. DOMMEL:
No.
We will resurvey all the
25
commission members and -- we will resurvey all of the
26
commission members as to their availability for meetings
87
1
in February and March, April, May.
2
take the lead on seeing that everyone gets the federal
3
agency responses by mail and you receive those by
4
Wednesday.
Except for Alta, I have hers right here.
5
(Laughter.)
6
PROF. CHARO:
7
DR. CHILDRESS:
8
And it is full.
Harold, do you want a final
word?
DR. SHAPIRO:
9
DR. CHILDRESS:
10
11
I will ask Emily to
Thank you very much.
Thank you very much this
morning and again, Rebecca and Bob, thank you for --
12
DR. DRESSER:
13
(Whereupon, the proceedings were concluded at
14
15
16
17
18
19
20
21
22
23
24
25
26
Thank you.
12:41 p.m.)
* * * * *
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2
3
4