FEDERAL OVERSIGHT OF RESEARCH INVOLVING HUMAN SUBJECTS
     (Slide.)
     MR. CAPRON:  Am I on?
     DR. SHAPIRO:  You are on.  
     MR. CAPRON:  Is this picking up for you?  Okay.
     I hope you can all see the screen since we have gone to such
lengths to make it project.  
     One of our basic subjects is the federal oversight of
research involving human subjects and we are looking today at a
particular aspect of it.  Our mandate and the initial focus we
took was on the system established by federal agencies that
conduct or sponsor research and we recognize that although this
part of the report, which is the one that we have seen drafts of
so far, is an important and essential and, indeed, we thought
without cloning we were going to finish it in the first year.  We
did not.  The so-called federal agencies report.       But there
are two subsidiary issues which we are not fully addressing now
but which are essential.
     (Slide.)
     The first is how well are IRB's actually following the rules
that are set forth.  The second is how well are subjects being
protected.  Now those are not the same thing obviously.  The
IRB's can be doing a great job of following the rules and
subjects could still not be well protected if the rules were not
effective in protecting them.  We recognize both of these as
topics we want to address but we have not yet fully developed a
plan of how we are going to go about that. 
     (Slide.)
     In looking at the federal agency report so far we have seen
certain problems.  First, there has been an uneven execution of
the responsibility to protect subjects among agencies.  Second,
there is a variation in the amount of attention that agencies
give.  Third, there has been wide variation in the application of
the rules.  Indeed, in even understanding questions like what is
research, what is exempt.  Some of the agencies have looked at
things that seemed to us to be research and said, "No, they are
not research.  We do not have to have IRB's review them."
     (Slide.)
     At the moment I think it is too soon to reach conclusions
and we need to hear from each of the agencies about their own
response.  Some of the problems are obvious ones but there is one
which stands out and that is the lack of an authoritative office
to deal with these issues in the federal government.  
     (Slide.)
     So the question that we determined to look at as a whole
commission is the one is there a need to have a government-wide
human subjects office.  We sought advice on this from Charles
McCarthy, who is the former director of OPRR, and John Fletcher,
who was the first in-house ethicist at the Clinical Center and
then went on to be professor at the University of Virginia where
he has now recently become emeritus.  
     We also received additional expert advice from Joan Porter,
who reported at our last subcommittee meeting and who is here
today again.  And from Tina Gonsalus, whose views we have not
actually heard yet, who was looking at the additional question
that was raised by David Cox, which is whether this opportunity
ought to be seized if we are talking about a government-wide
effort to say it should also encompass the research which is not
federally funded.
     (Slide.)
     Now it seems to me from the papers that we have received
from McCarthy and Fletcher that it is very obvious that the
history has very much shaped the present approach to human
subjects regulations.  In particular, from the 1950's as NIH grew
by leaps and bounds the Intramural Research Program was the major
focus.  
     Disregard spelling errors, please. 
     And within that program normal volunteers did receive an
informed consent process and a prior review by disinterested
scientists, not by outsiders but at least by scientists who were
not directly involved in the research.   But patient subjects
were not federally protected because, in effect, the studies they
were in were regarded as therapy.  Beginning in the mid 1960's
extramural research grew more rapidly and the process of
overseeing the protections was handled by the institutional
relations branch in the Division of Research Grants.  That was
done centrally for all the institutes.  That was true of all the
negotiations that went on with the institution since research is
institution and not investigator based.
     (Slide.)
     In 1966 Surgeon General Stewart at the time that certain
revelations were coming out about problems with human subjects
research issued a policy on the protection of research subjects
and made this a responsibility of that Institutional Relations
Branch at the DRG.  And that office simply followed the pattern
that it had already followed in handling the financial and other
administrative arrangements in that it entered into assurances
with institutions about the way they would carry out their
federally funded research and that is where the model of the
assurances comes from. 
     (Slide.)
     The DRG put emphasis, as Charles McCarthy reminded us, on
education, not sanctions.  And, indeed, up until the time of the
Tuskegee study there were no sanctions ever issued for any
violation by any research institution.  
     (Slide.)
     Dr. McCarthy is a little more sanguine about the extent to
which research institutions prior to 1974 actually had some form
of internal mechanism and other researchers like Bernard Barber
writing at the time showed that many institutions had not yet
advanced to the point of advanced prior review of research
involving people other than the research community.  
     (Slide.)
     In 1971 the policy that had been established for NIH was
extended to the whole of the Public Health Service and this
begins part of the history of the discomfort in this area because
the moving force remained the NIH and the IRB/DRG.  
     (Slide.)
     In 1972 Robert Marston, who was Director of the National
Institutes of Health, faced with the emerging scandal of the
Tuskegee study, which had been a PHS study and not an NIH study
but was focusing on the government's involvement in research and
with Senate hearings going into a wide range of other
questionable research, changed the Institutional Relations Branch
into the -- that aspect of their work into the Office for
Protection of Research Risks, which he lodged in the Office of
the Director. 
     (Slide.)
     At this time there were some in Congress who favored
enacting legislation with sanctions for violations of human
subjects rights but this was steadfastly opposed by the National
Institutes of Health and eventually an agreement was worked out
and the DHEW relented on the notion that it should not have any
regulations as such.  There previously had been a policy, not
regulations.  They should not have regulations.  They agreed they
would have regulations and the Senate backed off of the notion of
legislating this.  So the provisions of the 1974 Research Act
were limited.  
     It, of course, established the National Commission to study
this area but beyond that it established the firm requirement
that regulations would be issued that would have informed consent
and prior review through an Institutional Review Board and it
also made clear that the department had the responsibility to
provide consultation and education on the subject. 
     (Slide.)
     The National Commission recommendations which were all
forthcoming by 1978 were largely adopted.  Of course, children
and the mentally infirmed, institutionalized and mentally
infirmed were not accepted.   The children were later and much
more recently adopted.   These became the basis for the 1981
regulations which are really the framework that we still have.
     The President's Commission recommended the Common Rule on
Human Subjects for protection from all the 20 plus agencies that
support such research and that occurred in 1981.  A decade later
for reasons that Joan Porter nicely surveyed for us that Common
Rule was finally published in the Federal Register and one of the
things we are still studying is the difficulty in having it truly
be a common rule in application.
     (Slide.)
     The Office for Protection from Research Risk sometimes found
itself subject to direct interference within NIH.  In 1992 or
thereabouts there was an attempt by the Director to intervene and
be involved in some fashion with the Gallo investigation that was
then going on for research that had gone on, on the AIDS virus in
Africa involving also a French collaborator.  This was declined
by Dr. McCarthy but there was that kind of pressure that existed. 

     Moreover, the NIH Intramural Program dragged its feet in
cooperating with OPRR on a number of occasions until it was
threatened with a disclosure of its failure to have complied with
its own federal policy and the threat included the notion that
revelation would be made that a subject had died in a sleep study
at NIMH.  The death was apparently actually not connected to the
researchers it later turned out but that threat was sufficient to
get NIH to sign on to its assurance. 
     (Slide.)
     OPRR is, however, by the description of Dr. McCarthy and Dr.
Fletcher dependent on whistleblowers and the press because it
does not really have any institutional examinations.  The Food
and Drug Administration by contrast does go out and at least go
through a paper trail at institutions.  The OPRR, NIH and the
other agencies do not.
     OPRR has a large case load and depends on outside expertise
to -- for most of the scientific evaluation of the cases that are
brought to its attention and it has difficulty carrying out major
investigations.  Dr. McCarthy talked not only about the backlog
in investigations but also the impediments that it has to act
like an investigatory office.  
     (Slide.)
     To sum up then, the problems revealed by history are first
that the Department of HEW and the other agencies or HHS now that
sponsors science see research as the primary mission and address
human subjects protection only when pushed, usually following a
crisis of some sort.
     Secondly, that no federal agency holds the position of an
authority to ensure the adequacy and uniformity of human subjects
protection.  Indeed, no one knows how much human subjects
research is now ongoing with federal sponsorship much less beyond
federal sponsorship.
     The Office for Protection from Research Risks that NIH has
the informal role of first among equals among the offices and the
different agencies, it has by far the largest number of projects,
but it does not have staff or authority to exercise actual power
over the other agencies.
     (Slide.)
     Third, the oversight of protecting human subjects is
delegated to research institutions because of that history of the
assurance process and those institutions themselves obviously
have conflicts of interest in wanting to see research go ahead
rather than being overly concerned about human subjects
protection. 
     The assurance process has by now become routinized and you
can see why.  A relatively small office has responsibility for
almost 450 multi-project five-year renewable assurances, 3,000
special projects, single project assurances, and 1,500
cooperative research projects.  And as a result fewer resources
are available today for its traditional educational function.
     (Slide.)
     Sixth, despite some differences, and I think this was
interesting because we were looking for people with contrasting
perspectives, despite some differences and emphasis both McCarthy
and Fletcher agreed NIH and the rest of the Public Health Service
has not strongly supported formal processes for human subjects
protection. 
     (Slide.)
     When asked, they refused to provide material support for the
process of developing the Common Rule, which eventually ended up
in the Office of Science and Technology Policy, and it has been
slow to comply with OPRR findings and the terms of its own
multiple project assurance.
     (Slide.)
     So looking at the recommendations we got from our two
principal experts, first McCarthy recommended the creation of an
Office of Research Ethics within the Office of the Secretary of
Health and Human Services to have three divisions.  One concerned
with human subjects protection, which is our focus.  And then
another with animal, laboratory animal, protection.  And a final
one of Scientific Integrity, another issue which has engaged the
scientific community and the National Academy of Sciences and so
forth in recent years.  
     (Slide.)
          He also said that the Human Subjects Protection
Division should have at least two branches.  The first an
education branch and the second a compliance branch.  And that
the office should make an annual report to the Congress which
would include a report on the performance of not only all the
agencies within the Department of Health and Human Services but
all other federal departments and agencies.  It would, therefore,
have government-wide authority even though it was lodged in the
Office of the Secretary of HHS. 
     (Slide.)
     And that the Director of the Office of Research Ethics would
submit his or her own statement of personnel and budget needs to
Congress independent of the HHS submission.  
     (Slide.)
     John Fletcher recommends the creation of a National Office
of Human Subjects Research advised by a national advisory
committee on human subjects research made up of 11 to 13 people
from outside government.  This is in line with the recommendation
made by Jay Katz a number of years ago actually when this
commission was being empaneled when he said, "You do not need the
National Bioethics Advisory Commission, what we need now is a
group that would actually have continuing oversight of the
administration of these rules."  
     (Slide.)
     Fletcher also said that the National Office of Human
Subjects Research would have government-wide authority and made
analogies to the Nuclear Regulatory Commission and the Office of
Governmental Ethics.  And the Congress would appropriate funds
directly for the NOHSR and the Senate would confirm the Director
nominated by the President.   The office would have authority to
sanction violations of the regulations.
     (Slide.)
     And then going beyond the type of the office to oversee
government sponsored research Fletcher recommended,in line with
David's suggestion and something we are going to hear more about
from Tina, I guess, is the extension of the oversight of the
office to all human subjects at least as to the basic provision
of IRB review and informed voluntary consent.  
     (Slide.)
     Now we need to look at these recommendations and say what
are their strengths and weaknesses.  For the McCarthy
recommendation the strengths seem to be that lodging this in the
office of a major department of the government gives it
protection because the Secretary is a powerful figure in the
United States Government and the office, therefore, is not
standing alone but has the protection of the Secretary.  And it
would also make absolutely clear that sitting at the head of HHS
that office has authority over all divisions of the Public Health
Service, which ORR struggles to exercise today.
     The weakness is that it does not fully remove the conflict
of interest because it leaves the office within a department
which is the major sponsor of research by the government and it
compromises the independence of that person because being a part
of the Office of the Secretary, whatever independence one may
have, is somewhat dependent on the forbearance of the Secretary
who may not be happy with everything the office is suggesting.
     It creates the problem of a department having an office
which then has oversight over sister departments and agencies.  
     (Slide.)
     Looking at the Fletcher recommendations, the strength is
that clearly this office would be independent of the research
sponsors and it would benefit from an outside board which would
bring not only expertise but visibility to the subject.  It would
not be just a group of government employees.  They would be
responding to and seek the advice of outsiders who would have the
ability to raise the issue publicly under the Federal Advisory
Committees Act.
     The weaknesses are that, you know, we clearly need White
House and/or -- probably and as well as or -- real sponsorship. 
If the White House is not interested in protecting this office
and if a committee of Congress or certain members of the
committee do not regard it as an important function that they
want to protect and ensure its independence, a small office like
this will not have independence.  The press alone cannot ensure
the independence of an office like this. 
     Furthermore, absent some current human subjects scandal it
may be difficult to create a new agency in our present smaller
government era.  
     (Slide.)
     Having said this I also want to suggest for our discussion
that there is certain things we can focus on and other things
that we can exclude.  The central objective I hope we could agree
on would be to create a body with authority and ability to get
the job done.  Although OPRR is the major human subjects
protection body today, its performance need not be the focus of
any report.  Indeed, I would suggest it would be inappropriate to
focus in on OPRR.  The concern is with structural problems, some
of which affect OPRR's operations, some effect its location, and
likewise the location of comparable offices in either
departments.  The concern is with all federal agencies and just
looking at OPRR would wrongly focus us on NIH.  
     (Slide.)
     Also, our present mode of operation, and all the concerns
that have been raised about the assurance process and the
adequacy of IRB's, need not figure as a topic for us in this
report.  We have committed ourselves to the notion that that is a
topic that needs to be studied.  Were there to be such an office,
either at the secretarial level or as an independent agency,
certainly it would be appropriate for that office then to take on
this responsibility and maybe continue the present format and
maybe modify it.  
     But our satisfaction with or questions about, or our
dissatisfaction with the current method of assurances, and the
use of IRB's is not something we have to determine and I think
should not really be a subject of debate while we are deciding do
we need a government-wide agency and/or any of these models the
ones that we should follow.  I think that would be a distraction.
     (Slide.)
     Likewise, if we believe that the office should have
government-wide jurisdiction we might -- and yet we are unable to
see or unable to develop private enthusiasm for bringing their
research under such an office we might say, "Let's see if it
works on the government-wide basis and then as a later issue that
office could go to the Congress, assuming that Glenn bill does
not already pass, and say there really are issues with privately
funded research and the best way to ensure that is conducted in
an appropriate way is to bring it under this office.
     Finally, one point I did not put up here but I think is
obvious, when one talks about this office I think it is best not
to use the elocution that we used occasionally at first, which
was "elevating OPRR to." 
     Both for the reason I do not think we should solely focus on
OPRR but it is very likely that just as the departments have
their own ethics offices now to deal with the conflict of
interest and so forth administratively within their office or
agency, and yet there is a government-wide office of governmental
ethics it is very likely that we need a governmental-wide policy
setting, rule interpreting and maybe investigating body, and an
agency by agency ability to work with their own grantees and
their own researchers to get how the rules apply and the process
of giving the grants and so forth.  All that remains. 
     It very well may mean that only a small part of what is now
done in any of the agency's own office for protection of research
subjects would be transferred over.  Those offices really have
ongoing responsibilities but the overall educational,
interpretive and public visibility issues would really be handled
by this other office.
     I was struck not only by the very high quality of the papers
that we have gotten but also by their very surprisingly large
congruence.  I think that it would be useful for us to focus on
some of the almost political issues that arise in one approach
rather than another if we can first agree on the overall
objectives. 
     Thank you.  
     DR. SHAPIRO:  Thank you very much for that very helpful
presentation.
     I would like now to turn immediately rather than go to -- I
hope you will forgive us, Alex -- rather than turning directly to
discussion to some of the issues you have raised I would really
like to turn to our guests and see what comments they would like
to offer.
     I know Professor Fletcher has to leave shortly so I would
like to turn to him first and see what further comments and/or
advice he might have for us at this time.
                            * * * * *


                   E V E N I N G  S E S S I O N
     DR. FLETCHER:  Thank you, Mr. Chairman.  
     I was very impressed with Alex's laying out of the issues. 
I did not disagree with any of it.  I was struck with how much
Charles McCarthy and I did agree on since we do have different
perspectives but I think our main difference is one of political
philosophy, if you will, that he wants and expects the success of
the body that he envisions, which essentially is the same body
that I envision except with the outside advisory committee.  His
does not have that. 
     He feels that in the real political world a government-wide
body with these responsibilities could not succeed without the
protection of a powerful secretarial member of the cabinet.  
     I agree with the point that Alex made in his comment on the
weakness of the McCarthy proposal is that it does not remove the
conflict of interest.
     I think that the degree of the weakness of the present
system, the weakness of the present system that we have, in
protection of human subjects is influenced -- I want to choose
the right word -- somewhere between moderately and heavily
because obviously OPRR's position in the whole scheme of things
is not the only problem.  IRB's are the problem.  The lack of
available resources within institutions, federal agencies,
universities, of persons with expertise to lead this effort is a
problem.  
     But I do think that it is -- the conflict of interest and
the conflict of missions is a kind of persistent weakness that
demoralizes the whole system.  I have been aware of it all of my
adult life from the time that the solution was invented in the
early '70s to have NIH effectively regulating itself.  And if you
have that kind of central conflict of missions and conflict of
interest it is the kind of national commentary on evading the
problem.  
     So I would say even in an era of smaller government that
leaders in Congress and the American people are interested in
better government, to have smaller and better, and there is not
an enormous new amount of appropriations to be made in creating a
new body and going about doing this right.  
     So I would say that the McCarthy plan is a good one except
that it lacks the national advisory committee feature but it is
in the wrong location.  The location still begs the question and
if it is put there it will continue into the next era, the kind
of demoralizing effect that has produced such lack of respect,
particularly from within the federal sector, in looking down on
our present body, the OPRR.  
     I think that the commission should take a strong position
and my recommendation would be to take a strong position in
overcoming this conflict of missions, structural conflict, as a
violation of -- it is a violation of the principle that Congress
used in adopting the legislation of the National Research Act,
which was to put the interest of research subjects first.  And
the basic problem is that the location of OPRR in government or
of the McCarthy plan in government still evades the deeper
ethical principle on which the whole system rests.     If you
have a contradiction at that basic level that is not really an
acceptable ethical solution to the problem that we are in.  
     DR. SHAPIRO:  Thank you very much.  Thank you for those
remarks.
     Let me turn to our other guests again before turning to
members of the commission.  
     We have got someone who has traveled all the way from the
middle part of the country, Illinois, so let me turn to you, Ms.
Gonsalus.
     MS. GONSALUS:  Thank you.  It is a pleasure to be here. 
Since you do not have anything in writing from me I will take a
few minutes to lay out --
     MR. CAPRON:  You have to get on top of these microphones. 
     MS. GONSALUS:  Okay.  How about now?  Have I done it yet?  
     (Simultaneous discussion.)  
     MS. GONSALUS:  Since you do not have anything in writing
from me I thought I would take probably four or five minutes to
lay out the path that I have followed and the kind of advice I am
going to submit to you.  I would welcome your reactions to it. 
     By way of self-disclosure I think it is important to tell
you two or three things about what brings me to this place and
who I am and what I do.  I am a parasite on the research system. 
I am a university administrator and a lawyer.  I am pure
overhead.  That is one of the most important things. 
     In that capacity what kind of work do I do?  The kind of
work that I do -- in my university I am known as the Department
of Yucky Problems.  I got a promotion last year and now I am
Department of Yucky Problems and Streamlining.  
     The kind of yucky problems that I do --
     DR. DUMAS:  What kind of problems?
     MS. GONSALUS:  Yucky problems. 
     DR. CASSELL:  Yucky.  
     MS. GONSALUS:  Yucky problems. 
     DR. DUMAS:  Oh.
     DR. CASSELL:  Hold it in your hand.  
     MS. GONSALUS:  Okay.  We will keep working on this.  
     Yucky problems.  
     DR. DUMAS:  Yes. 
     MS. GONSALUS:  Which means that I come from what I call the
train wreck school of professional ethics.  There is a problem, a
train wreck, there is bodies, there is blood, there is people
screaming and crying, there is mess on the ground, and that is my
job.  I go and deal with it.  That means that I have had a
variety of internal compliance related responsibilities, problem
response.  
     My major professional interest is in how do you conduct
effective and credible internal investigations inside an
institution when you have a number of conflicts of interest built
into the system.  How do you go about doing an effective and
credible job of self-regulation, professional self-regulation? 
So that is where my major interests lay.
     I look at the problems.  I try to solve them as best I can
and then we try to go on, and then we try to look at and review
and improve, if possible, both the policies and the structure
that were in place when the train wreck occurred to try to
prevent future such events.  So that is my professional interest
and how I come to be here. 
     I also served on the United States Commission on Research
Integrity, which also informs my view on perhaps some of the
actions that you should take or not take, and I will come back to
that at the very end of my remarks. 
     I was asked to look at the possible unified government's
federal and private human subject research under an OPRR-like
structure.  Let me just discuss some of the issues of the OPRR-like structure.  I understand that you as a commission
unanimously passed a resolution in May that no person should be
enrolled in research without the protections of informed consent
and an independent review of the risks and benefits of that
research. 
     I understand that you have had a form of Presidential
endorsement of that concept by saying that no American should be
an unwitting guinea pig in experimentations putting them at risk. 
     Conceptually, therefore, I think that where I started in
this task was to say if you take our current definition of
research and apply it globally to all research involving human
subjects what happens.  I remind you that given the kind of work
that I do I bring a relentlessly practical perspective to these
issues.  I am not very good at the concept.  I start with the
immediate problem.  
     So instantly practical problems began to intrude into my
examination of these issues.  The current definition of research
is quite properly, I think, very broad.  "Systematic
investigation designed to develop or contribute to generalized
knowledge where you obtain data through intervention or
interaction with subjects."
     Global applicability of that definition could sweep many
activities into its scope that encompass very little risk, little
or no risk.  And so one of the questions is how remote must the
risk of serious harm be in order to encompass an activity within
the definition of research and, therefore, the regulation of it
and, therefore, a system that requires paper, and people, and
oversight, and costs, and benefits.  How do you balance those
issues?
     So very early on there would have to be an effort to design
exemptions.  We right now have six exemptions for things that
require prior review.  There would be very serious work involved,
I believe, in designing appropriate exemptions.  If you think
about the definition broadly applied to all activities the
current definition of research you could arguably -- you would
encompass many activities of polling organizations, market
research, arguably some forms of journalism, as well as the
things that are obviously considered research.  The kinds of
things that are of the most concern.  For example, some of the in
vitro fertilization clinics and diet clinics.  Some of the things
that you immediately think of when you think of as unregulated
research, health services research, internal evaluation research,
corporations that are looking at how do their employees like one
thing or another about the company.  There are a whole variety of
things that could be encompassed under the current definition.  
     So examining carefully the prospect of serious harm, how
small is it, is it small, versus the cost of regulation is I
think the most pressing important issue.  I think that one could
design appropriate exemptions with appropriate work but that
raises a second category of practical problems which I have to
tell you is really hanging me up.
     Who determines the applicability of the exemptions?  Clearly
in terms of a basic principle you do not want the person who is
performing the research, him or herself, to be deciding that the
research is exempt so there has to be some level of review.  Who
does the review?  How much paperwork?  Do you need to assist
them?  Do you build in an incentive for a much larger system of
for profit IRB's?  Do you build an incentive for a system where
you have pristine paperwork and you have lots of people
completing paperwork and reviewing things and filling out forms? 
And the very serious ethical issues sort of get lost in shuffle
because you have diluted the effort so much.  
     Do you have this -- I mean, I could imagine developing an
immaculate extensive system of paperwork that had no meaningful
ethical review in it.  I have seen IRB's function that were very,
very good at the paperwork but spent no time talking about what I
think are the issues that an IRB ought to grapple with. 
     So the question is would expansion divert valuable resources
and valuable energy and how do you avoid that outcome?  The
danger is creating a burdensome possibly profit driven rubber
stamping system diluting attention to the serious ethical issues. 

     I could go on about the problems that I ran into but having
sort of come to that point I decided to stop and go at it from a
different perspective, which is rather than making it global with
the current definition, to take a better system of encompassing
all federal agency research, which I believe is addressed in some
of the reports that you have had, and then adding in on a list
basis -- I am not fond as a principle of laundry lists and I have
strenuously opposed the laundry list approach to definition of
research misconduct.  But I did explore taking -- just listing
known areas of research that put human beings at risk and adding
those whether conducted privately or publicly to the scope of
federal oversight.
     Gary Ellis has defined seven areas in some of the letters
that he has written and he wrote me a letter and he sent some
copies of these.  He made a presentation at the PRIMER meeting
recently where he defined seven areas that are beyond the
boundaries of existing regulations that are places that questions
have arisen and where there are people potentially at risk. 
     Colleges and universities not receiving federal research
funds, some in vitro fertilization clinics, some weight loss or
diet clinics, some physician offices, dentist offices, and
psychotherapists offices.  
     One of the examples is the dentist who decides to take out
of the next number of patients that he has the fillings on the
theory that he is conducting a form of research.  Does he know it
is research?  Maybe and maybe not.  
     Some legal services clinics.  On my campus we have some very
interesting examinations going on in our clinic at our law school
about when are you actually conducting research.  When you are
taking students, you videotape them, you teach them how to
interview clients, the clients give their consent for the
interview, but then you go on, you train other students with it,
and then you start doing research on how do you generalize this
knowledge about this sort of interviewing and how do you use
these.  Pretty interesting questions that they are exploring.  
     Some corporate and industrial health safety and fitness
programs and some developers of genetic tests.  
     So my current thinking is that rather than taking the global
approach with all the practical problems that entails it would be
superior to start with the known problems, add them in, take a
cautious incremental approach where you can document the
cost/benefit ratio, that official cost/benefit ratio of adding in
some regulatory system rather than taking a sweeping approach. 
     I think that you have to focus on the goals of protecting
subjects from risk, the unwitting participation aspects, and
again on the focus of informed consent an independent review
where you know that there is a danger of risk.  
     So then the question is how do you reach that within the
available resources consistent with reality.  The paradigm that I
think is applicable that I use in thinking about a lot of the
problems that I deal with is one that was first introduced --
actually I heard Bud Relman give a presentation probably 15 years
ago and he used the term "low incidence, high severity problem." 
     The serious problems do not occur very often.  When they do
occur they are very, very serious.  
     So what is the low incidence, high severity problem of this
nature?  What sort of response does it suggest?
     To my thinking of low incidence, high severity problem the
most sensible approach is that you put almost all of your
resources into education.  Most people most of the time want to
do the right thing and you have to make sure you know what it is. 
We do not have adequate resources in our system for that right
now. 
     The second thing you have to do after education is that when
you have problems you have to respond to them.  We have very
serious problems in the research community and in the academic
research community with designing appropriate responses to
problems.  It is a fundamental problem of professional self-regulation.  We have -- it manifests itself both in how the
universities respond and also how the federal government
responds.  
     Inside universities -- I was at a conference a couple of
years ago where an IRB executive secretary was talking about a
system they designed on their campus for tracking the
publications of researchers on their campuses and then trying to
correlate them with IRB approved protocols, which raised a
firestorm of protest on campus at the big brother concept.
     In the arena of research misconduct any time we talk about
government regulatory mechanisms and government oversight we can
invoke the specter of the science police.  The science police are
going to try to destroy research as we know it. 
     There is serious resistance to any kind of inspection
system.  Now it is widely accepted that we could have an
inspection system for animal sites but the concept of having
inspection for human sits is anathema.  
     And the third issue -- and the third thing -- is you have
education, you have response to problems, and the third thing you
need, I think, for a low incidence, high severity problem, is to
have penalties for violation because I assure you that many, many
people are busy.  They have lots to do.  And no matter how well
meaning they are and no matter how much they believe in theory in
the ethical issues if it is demonstrated time and again that
there is no penalty for a serious violation people have better
ways to spend their time than to fuss with this nonsense.  
     So that is the three things I say.
     This leads to two issues and I have brought my conclusions. 
There are resource issues that someone is going to have to
grapple with because the current structure does not have enough
staff and not enough money, and probably not enough power to
engage in either any of the education response to problems and
penalties for violation that does not exist presently.  
     And then we have the structural problems and there are, I
think, disabling existing structural problems that must not be
perpetuated as we move forward into doing better.  
     The first is the structural conflicts of interest identified
by Dr. Fletcher and Dr. McCarthy.
     The second is the insufficient resources issue that there
are not enough resources for the current mission in terms of
IRB's that do not work well.  You have earnest people engaged in
an inadequate and insufficient review process.  You do not have
adequate education of PI's.  You have research that just flat out
has not been submitted for review because somebody does not
conceive that he or she is conducting research.  And then you
have review systems that do not work very well.  The behavioral
sciences I think are a perfect example. 
     The third disabling structural -- existing structural
problem is the uneven application and the uneven jurisdiction
both within federal agencies and then beyond to universities.  
     I think the most likely answer is a different governmental
status and structure in budget, single standard, single office,
but a single office with some kind of decentralized or
distributed system where you have a single standard, a single
office, but it works in a distributed way within the agencies
along the model that was just discussed.  
     I think there are some very fine models to explore.  The
Office of Governmental Ethics I think is the prime model worth
exploration.  
     Gratuitously I am going to add a final note, which is that I
think that it is your job, in fact, to explore and to try to
solve the structural problem and to make a very explicit
recommendation about what the structure should be and I hope you
will retain really solid experts who understand the political
realities to give you advice on this to help you devise a
structure that will work, to find the proper niche, to find the
proper reach, authority, jurisdiction, the proper budgetary
protection, the right clout to get action when needed.
     I will tell you that from my experience on the Commission on
Research Integrity, which I would call mixed, I would say that as
you work it is extraordinarily important to think about to whom
your report is submitted.  Who receives your report and how
exactly will it get implemented?   What will be done with it?  
     If you make sort of a generic recommendation somebody should
think about this and improve the structure you could be looking
another two, four, five, six, ten years, never for actually
making a difference in how this works.  I cannot believe that
this number of really busy, really expert people should put in
that kind of effort for that kind of result.
     Thank you. 
     DR. SHAPIRO:  Thank you very much.  
     Ms. Porter, is there anything you would like to add to what
you told us last time, which was extremely helpful to all of us?
     MS. PORTER:  I think I would like to address a little bit
different focus that might help in making some decisions on where
the best locus for a federal office to oversee and to regulate
human subjects protections would be.
     I actually have a handout and some overheads that are very
brief, mercifully and uncharacteristically, but I think they
help.
     DR. SHAPIRO:  Please. 
     MS. PORTER:  We did not collaborate before we came together
today, the various presenters, but I think you will be struck by
the amount of compatibility there is amongst the presentations
even though the approach is somewhat different. 
     (Slide.)
     I thought that it might be helpful to the commissioners to
try to decide on what the goal of a federal office would be and
then use those goals to inform the best location for the
accomplishment of those goals.  
     I have put together two sets of goals.  Goals that a human
participant in research would expect the federal office for
protection of human subjects to carry out and then the second
overhead will give a list of goals that I think any entity
regulated by a federal office for protection of human subjects
would carry out.  I did not address animal welfare issues in this
particular presentation. 
     (Slide.)
     First of all, what should a human participant in research or
any other member of the public for that matter expect from a
federal regulatory office for protection of participants in
research?  I think, first of all, and maybe these are not in my
priority order, these are based on my values, there is
considerable overlap between what an individual would expect and
what an institution or an entity would expect from a federal
office.  Maybe you would choose to put different goals on here or
take some of these goals off but I think it is the starting
place. 
     First of all, an individual participant in research would
expect easy access to information on rights and welfare as
research participants and some support in exercise of those
rights.  I think the person would expect adequate and timely
information to and education for those entities regulated
concerning protection of human subjects in research.  They would
expect that the organizations carrying out the research had been
informed about what they were supposed to do and guided in what
they were supposed to do.  
     I think the individual would expect adequate and consistent
-- at least minimal protections in research regardless of the
source of funding or support.  Obviously we see that this is a
major issue.  How far is this office going to regulate?  As far
as it does now or is it going to take on all research regardless
of resources, or support, or funding?
     I think we have to start thinking in this direction.  I
think in this day and age it is not appropriate to ask
individuals to try to sort out is it federally funded research or
is it under a state law or is someone looking after my rights and
welfare, or is it one of those seven categories which were
alluded to that simply fall between the cracks.
     I also think that the individual would expect timely and
consistent investigations of allegations of noncompliance with
human subjects protections by both regulated entities and the
investigators.  And then, of course, responsible follow-up --
follow-through on findings of noncompliance with human subject
protections by regulated entities and investigators. 
     Then I would believe that the individual would want an
office that was there to carry out actions that would be
consistent with promoting protection of human participants in
research in an as political a manner as possible.  That is an
office that would stand as a champion of human subjects rights
and welfare above other goals that might be competing and that
were inconsistent with that goal.
     For example, we heard this morning a discussion of the use
of tissue samples and the idea that, oh, it would be a tragedy to
lose this important invaluable research but it may also be a
tragedy to collect information or use information that
represented a violation of the rights and welfare of individuals. 
So there has to be some office that is a champion for human
subjects protection in the milieu of larger competing issues or
different competing issues, or resource demands. 
     (Slide.)
     Likewise, I think, what would an entity that was regulated
by a federal central office expect?  I think they would expect
many of the same things, of course.  They would want adequate and
timely information and education concerning protection of human
participants in research.  They would want guidance and help in
knowing what they were supposed to and how to carry it out. 
     I think the regulated entities would want to have an office
that was able to ensure well developed, broadly open and
proactive policy development and regulatory interpretations and
modifications.  Somebody that was really well connected with what
was going on in the world in terms of new technologies,
development of new data collection systems, and certainly it is
going to be more than just federally conducted research.  
     Someone -- some office that understood the health care
delivery system very well because much of our research will be
coming from our health care delivery system as we move towards
more managed care systems and consolidated systems of health care
delivery. 
     The regulated entity, I would expect, would want the federal
office to have the ability to coordinate the federal
organizations supporting or conducting research under the Common
Rule.  They would want some kind of ability to ensure appropriate
consistency so that all of the federal entities were not going
off in their own direction.  
     They would certainly want fair and consistent enforcement of
the regulatory compliance authorities.  I have added here, but
you probably cannot read it, including feedback to the regulated
entities on the pitfalls to be avoided.  If entities are in
noncompliance we owe them and other entities an explanation of
why that is the case and try to put in some corrective measures. 
     And then I think another goal would be to have actions again
consistent with promoting protection of human participants in an
as a political a manner as possible.  Try to keep it shielded
from politics and other goals that divert us from really
protecting people who are involved in research. 
     Lastly, I think the regulated entities would have some
expectation of minimization of paperwork and other administrative
burdens consistent with the accomplishment of protection goals. 
I also think an important goal to preserve is decentralization
and having decisions made at the local level and the benefit of
understanding the local milieu so that there was not a big
centralized group that would dictate but that would have an open
system that would ebb and flow and collect information and
develop policies and procedures that could be applicable but
would help from the local perspective.
     All of this, of course, would require adequate numbers and
quality of staff.  Other adequate resources, creativity,
credibility, visibility, openness, compassion, energy, and
sufficient independence and authority to effect these
expectations.  
     I think if you would take these goals or others that you
might come up with and crosswalk them with different
organizational options it might become more clear what was the
preferable locus for a federal office for oversight.  
     We do not have to be gurus at public administration to
understand that there is a formal organization and an informal
organization.  In some of the most irrational organizational
locations effectiveness can happen, productivity can happen, and
even at some of the most ideally placed organizational levels
apparently sometimes things do not get done because there are so
many unanticipated consequences.  
     There are perturbations from the environment that we do not
expect and so something that looks ideal on paper might not work
either.  But I think our goal is to try to come up with the best
place to maximize what needs to be done and part of that is
deciding what needs to be done and coming to some consensus on
that and then moving on.
     I think Dr. McCarthy's suggestions, I think Dr. Fletcher's
suggestions, both have pros and cons.  Some of these goals would
be better addressed in the organization that Dr. Fletcher
proposes.  Some would be better addressed in what Dr. McCarthy
has proposed.  But there may be other permutations and
alternatives too that could be laid on the table.