0001
 1          DEPARTMENT OF HEALTH AND HUMAN SERVICES
 2                         + + + + +
 3             SECRETARY'S ADVISORY COMMITTEE ON
 4                 HUMAN RESEARCH PROTECTION
 5                         + + + + +
 6                          MEETING
 7                         + + + + +
 8   
                           THURSDAY
 9                     DECEMBER 11, 2003
10                         + + + + +
11               The Advisory Committee met in the Franklin
12   Room in the Sheraton Four Points Hotel, 1201 K Street,
     N.W., Washington, D.C., at 8:30 a.m., Ernest Prentice,
13   Ph.D., Chairman, presiding.
14   PRESENT
15   ERNEST D. PRENTICE, Ph.D., Chair
     BERNARD A SCHWETZ, D.V.M, Ph.D., Acting Executive
16   
                           Secretary
17   CATHERINE SLATINSHEK, M.A., Executive Director
     THOMAS L. ADAMS, CAE, Member
18   MARK BARNES, J.D., L.L.M., Member
     CELIA B. FISHER, Ph.D., Member
19   E. NIGEL HARRIS, M. Phil., M.D., D.M., Member
     ROBERT G. HAUSER, M.D., Member
20   
     NANCY L. JONES, Ph.D., Member
21   FELIX A. KHIN-MUANG-GYI, Pharm. D., Member
     SUSAN KORNETSKY, M.P.H, Member
22   MARY L. POLAN, M.D., Ph.D., M.P.H., Member
     SUSAN L. WEINER, Ph.D., Member
0002
 1   
 2   
 3   
 4   
 5   
 6   Ex Officio Members
 7   
 8   HOWARD L. BRADLEY     Social Security Administration
 9   KATHRYN LYNN CATES    U.S. Department of Veterans
10                         Affairs
11   
12   FRANCIS D. CHESLEY, M.D., Agency for Healthcare
13                         Research and Quality
14   ROGER CORTESI         U.S. Environmental Protection
15                         Agency
16   PATTY DECOT           U.S. Department of Defense
17   ANITA EISENSTADT      National Science Foundation
18   DAVID LePAY, M.D., Ph.D., Food and Drug Administration
19   
20   DEBORAH A. PRICE      U.S. Department of Education
21   SUSAN ROSE            U.S. Department of Energy
22   DAVID SHORE           National Institutes of Health
0003
 1   
 2                      C-O-N-T-E-N-T-S
 3   
 4   AGENDA ITEM                                  PAGE
 5   
 6   Welcome:Opening Remarks                         4
 7   
 8   
 9   Report on Issues                                6
10   
11   Overview of Charges to Subcommittees           11
12   
13   Subpart D Subcommittee                         18
14   
15   
16   Subpart C Subcommittee                         87
17   
18   HRPP Accreditation Subcommittee               156
19   
20   Public Comment                                192
21   
22   Summary of Day's Activities                   238
0004
 1                   P-R-O-C-E-E-D-I-N-G-S
 2                                            (8:39 a.m.)
 3               CHAIRMAN PRENTICE:  Okay, everybody, I
 4   think we're going to get started.  Good morning.  My
 5   name is Ernie Prentice.  I am the Chair of SACHRP.  I
 6   was in Philadelphia yesterday and someone told me
 7   that, you know the name SACHRP, the acronym SACHRP,
 8   sounds angelic.  And looking at my SACHRP members, I
 9   think that the ladies might qualify.  I'm not so sure
10   about you gentlemen, however.  
11               I'd like to welcome everybody and in
12   particular I would like to welcome members of the
13   public to this second meeting of this year.  We have
14   three more scheduled for next year.  We have an
15   ambitious agenda over the next two days so I would
16   like to kind of give you an overview of what we're
17   going to do today.  
18               This slide contains the charter for
19   SACHRP.  As you can see, the focus of our committee is
20   on vulnerable subject populations, in particular,
21   neonates, children, prisoners, the decisionally
22   impaired, pregnant women, embryos, fetuses and I think
0005
 1   you will find that that, indeed, has been our focus
 2   initially. 
 3               We're also going to look at other areas
 4   pertaining to protection of human subjects although we
 5   have not really gotten into these areas yet.  And we
 6   will discuss future activities of the committee some
 7   time today and tomorrow.  This is a quote from
 8   Secretary Thompson, which I think is very appropriate
 9   for all of us to remember.  We must make sure we allow
10   science and medical research to advance for the good
11   of all Americans, but not at the expense of the people
12   who participate in clinical trials.  You're obviously
13   all familiar with a number of events that have led to
14   skepticism, a mistrust on the part of the American
15   public concerning whether or not they will be
16   protected if they enroll in clinical research.
17               So part of the focus of this committee is
18   going to try to instill public trust in clinical
19   research.  These are the members of SACHRP and I know
20   that those of you in the audience cannot see the
21   nameplates on the table as it's arranged, so what I'd
22   like to is I will go through the names of the
0006
 1   committee members and if you would please raise your
 2   hands so that the audience will know who you are, that
 3   will be helpful.  Beginning with Tom Adams, Celia
 4   Fisher, Nigel Harris, Nancy Jones, Mary Lake Polan,
 5   Mark Barnes is not here yet, oh, there he is.  Felix
 6   Gyi, Robert Hauser, Susan Kornetsky, Susan Weiner. 
 7   The Executive Secretary of SACHRP is Dr. Bern Schwetz. 
 8   The Executive Director of SACHRP is Cathy Slatinshek.
 9               We have a number of ex officio members of
10   SACHRP.  I know that they are not all here, so I'm not
11   going to really go through all of the names of these
12   individuals.  We will eventually identify them as we
13   interact with them, but I would really like to thank
14   ex officio members for being part of our committee. I
15   think it's very, very important.  
16               The next item on our agenda is to have Dr.
17   Schwetz report on issues, so Dr. Schwetz, would you,
18   please take over?
19               DR. SCHWETZ:  May I do it from here,
20   Ernie?
21               CHAIRMAN PRENTICE:  Yes, you may.
22               DR. SCHWETZ:  Okay.  Well, let me extend
0007
 1   my welcome to all of you as well and thanks to the
 2   SACHRP members, to the ex officio members and in
 3   addition this time is the subcommittee members who are
 4   also here who have done a huge amount of work in the
 5   intervening time since the last meeting.  
 6               I'm going to talk first just for a minute
 7   about the PRIM&R meeting, first to thank, Susan
 8   Kornetsky for helping to co-chair, co-organize what I
 9   think was a wonderful meeting.  That many people in
10   the room attended and I think it was a great meeting
11   and thank you.  I was looking for things related to
12   SACHRP in the PRIM&R meeting and it turns out SACHRP
13   was quite prominent in the meeting and I think
14   appropriately so, prominent in a very positive way. 
15   Also the discussions and the session topics that were
16   part of the whole PRIM&R and arena meeting, I think,
17   reinforced the priorities that SACHRP is working on,
18   so it's good to see that reinforcement that the issues
19   that you're working on are ones that were topics of a
20   lot of discussion at the main meeting of our IRB
21   colleagues in the country.
22               The reality is, though, after three or
0008
 1   four days last weekend here and now another two days
 2   here, we realize the amount of time that represents,
 3   so, again, thank you for being here for a couple of
 4   more days.  We'll try not to have this meeting go over
 5   into the weekend.  I said last time that I was going
 6   to start meetings with the ex officio members outside
 7   of SACHRP meetings and we had a meeting some weeks ago
 8   and what I was hoping is that I would engage them in
 9   the topics of discussion of SACHRP and things to
10   anticipate for new priorities and that maybe we would
11   meet, you know, before every SACHRP meeting or at
12   least between them some time.  
13               Well, it turns out they were so
14   enthusiastic about meeting that they want to meet on
15   a monthly basis.  And I was very pleased to see that
16   level of enthusiasm but what they also voiced was the
17   desire on the part of the ex officios to work on
18   things so that they wouldn't have to become an issue
19   for SACHRP.  Now, that doesn't mean you're not going
20   to have anything to do, but nonetheless, I am glad to
21   see the attitude among the rest of the federal agency
22   representatives under the common rule that there are
0009
 1   a lot of issues that we should be talking about and
 2   taking care of on our own without having to be
 3   reminded by other groups of experts.  
 4               When we talked about accreditation, one
 5   thing that the ex officios pointed out was that
 6   something that the Government could be doing in that
 7   area is to help with the process of tracking the
 8   information that it will take to decide what is the
 9   impact of accreditation some years down the road and
10   perhaps there is a role for the Government to help in
11   that process, not necessarily to do it, but to be
12   involved in how it is that we track the impact of
13   accreditation. 
14               And the meeting that we had ended with a
15   decision that we -- and volunteering by NIH that let's
16   take on the issue as ex officios of adverse events and
17   have a meeting now early in January to begin to work
18   across agencies expanding from the NIH, FDA experience
19   and working with FDA and OHRP and the other agencies,
20   to begin to build a process for dealing with what a
21   lot of us see as a high priority dealing with adverse
22   events. 
0010
 1               So that's part of what you're going to
 2   hear tomorrow from Amy Patterson and from others in
 3   that discussion with the adverse events situation
 4   tomorrow.  I also mentioned last time that I was going
 5   to be meeting with all the representatives of the
 6   Common Rule and FDA to try to get a list of high
 7   priority items from them.  Well, I'm pretty much
 8   through.  We have a couple of them to talk with yet
 9   but I -- there was no problem to generate a list from
10   the ones that I talked to and it's everything from
11   application of the Common Rule to social and
12   behavioral research as an issue for a number of
13   agencies.  Adverse event reporting was clearly one
14   that was mentioned frequently.  Policy on classified
15   research, which was moved a certain distance some time
16   ago and needs to be picked up again.  
17               The new human subject protection resource
18   manual which we are working on and there's an endless
19   list of better guidance that was requested as we
20   talked to people, everything from how to deal with
21   exemptions, expedited review, continuing review, a
22   generic decision tree of when do you have to go to an
0011
 1   IRB and particularly perhaps with behavioral and
 2   social research, equivalent protections, definition of
 3   research, that seems to come back every time we give
 4   people an opportunity to talk about priorities, that's
 5   there.  Data banks, tissue banks, survey research in
 6   foreign countries, selection of community members for
 7   IRB's.  This is just kind of a taste of the longer
 8   list of priorities.  So my plan for now is to continue
 9   to discuss this list of priorities, to organize it and
10   to discuss it with the ex officios and with the other
11   agency representatives so that we can identify highest
12   priority items either for us to work on or Ernie, that
13   I would discuss with you with the prospect of bringing
14   it back to SACHRP and have discussions here on some of
15   these.  
16               So Ernie, I'll leave it at that.  Again,
17   thanks to all of you for being here.  
18               CHAIRMAN PRENTICE:  Thanks, Bernie.  At
19   the last meeting we established a work plan and I
20   would like to briefly describe that work plan.  We're
21   going to meet two to three times per year and at the
22   moment we have three SACHRP subcommittees composed of
0012
 1   eight to 12 members each.  The number of subcommittees
 2   is more or less dictated by workload and the
 3   availability of OHRP support for the subcommittees. 
 4   The subcommittees will meet in person or by tele-
 5   conference as necessary.  Each subcommittee does have
 6   a designated OHRP liaison who provides both expertise
 7   and staff support for the work of the subcommittee.  
 8               Reports are going to be provided to SACHRP
 9   for discussion and we will have reports today from the
10   three subcommittees established which I'll describe in
11   a moment and obviously, the objective is to formulate
12   recommendations and guidance which will be given to
13   HHS and OHRP for consideration.  This is the
14   SACHRP/OHRP implementation of the work plan.  Now, I
15   think it's important to recognize that this is a joint
16   effort.  This is not just a SACHRP effort or an OHRP
17   effort.  It's a partnership between SACHRP and OHRP
18   and I think that's very, very important.
19               We have three subcommittees.  The first
20   one is the Subpart D Subcommittee dealing with
21   additional protections for children involved as
22   research subjects.  Celia Fisher and Susan Kornetsky
0013
 1   are the co-chairs.  The OHRP staff support, the
 2   liaisons have been Leslie Ball, who has moved onto
 3   FDA, and Michael Carome, who has assumed
 4   responsibility to be our liaison for this particular
 5   subcommittee.  
 6               The Subpart C Subcommittee deals with
 7   research involving prisoners.  The co-chairs are Mark
 8   Barnes and Nancy Dubler.  Staff support is Karena
 9   Cooper, who will be moving onto other responsibilities
10   and Julia Gorey.  We have the third Subcommittee, the
11   HRPP accreditation subcommittee.  HRPP means Human
12   Research Protection Program.  The co-chairs are Thomas
13   Adams and Felix Gyi.  OHRP liaison is Yvonne Higgins. 
14   Now, there is some other general staff support, Dr.
15   Irene Stith-Coleman and Keisha Johnson-Modlin.  She is
16   actually the individual who makes sure that we
17   actually arrive here.  She takes care of all our plane
18   reservations, our hotel reservations, everything, so
19   we wouldn't be here if it were not for her.
20               And I would not be here if it were not for
21   Jodie Hume, who is the UNMC staff support for me, so
22   she kind of keeps me on track, so thank you for that,
0014
 1   Jody.  So what are the charges to these three
 2   subcommittees?  Well, this is the committee charge for
 3   the Subpart D Subcommittee; provide recommendations
 4   for possible adoption by SACHRP and OHRP on elements
 5   of a Subpart D 407 Panel Review process that will
 6   best, best achieve the goals of transparency, public
 7   input, expert input, timeliness, clarity,
 8   harmonization, meaning harmonization between OHRP and
 9   FDA who have -- also have a Subpart D, and if
10   possible, consensus.  And you will understand why this
11   is in quotes when Dr. Fisher issues her report,
12   because depending upon the model that we ultimately
13   select, we may or may not be able to reach consensus
14   because of FACA requirements.
15               Now, perhaps you're wondering what this is
16   all about here.  I'm sure that some of you recognize
17   that this is a picture of Baby Faye.  Baby Faye was
18   the youngest person in the world to ever receive a
19   xenotransplantation.  October 26th, 1984, Baby Faye
20   received the heart of a baboon.  She was suffering
21   from hypoplastic left heart syndrome, she had days to
22   live.  There were apparently no pediatric human hearts
0015
 1   available and the decision was made by Dr. Leonard
 2   Bailey at Loma Linda University to perform this
 3   historic transplant.  Now, the additional protections
 4   for children became effective in 1983.  So they were
 5   in effect at the time of this transplant.  
 6               However, this research was not covered by
 7   Subpart D because it was not federally funded.  So
 8   consequently, there was no requirement that Loma Linda
 9   submit this protocol, assuming that there was time to
10   begin with, this protocol for a 407 panel review.  And
11   a 407 panel review is designed to have an additional
12   level of ethical, scientific, medical and regulatory
13   review at the level of HHS for protocols involving
14   children that are highly problematic, that have
15   national interest.  I would suggest that had this
16   research protocol been funded by HHS back in 1984, it
17   certainly would have gone up for a review at the 407
18   level prior to its initiation.
19               So this is the initial charge of the
20   Subpart D subcommittee, to look at this 407 panel
21   review process, which, as I said, is a process in
22   place where an IRB cannot approve the protocol under
0016
 1   lesser categories of pediatric research; therefore,
 2   they've got to ask for review at the federal level for
 3   federally funded research.
 4               The second subcommittee is the Subpart C 
 5   Subcommittee additional protections for prisoners. 
 6   The charge to this subcommittee is to provide
 7   recommendations for possible adoption by SACHRP and
 8   OHRP on the current Subpart C, which by the way is
 9   about 25 years old with consideration of whether or
10   not Subpart C is adequate.  If not, provide
11   recommendations on how Subpart C should be revised. 
12   Now, perhaps you're wondering what this slide is all
13   about.  Well, this is a slide of a prisoner involved
14   in research at Stateville Prison in Illinois.  These
15   are jars containing malaria infected mosquitoes.  
16               I think we need to remember that the penal
17   system as it existed 25 years ago compared to today is
18   like night and day.  The problems that prisoners face
19   these days, infection with Hepatitis C, it's epidemic,
20   HIV, the conditions that are incarcerated.  It's a
21   different environment and we really need to take a
22   look at whether or not we are adequately addressing
0017
 1   the principle of justice in consideration of these
 2   additional requirements of Subpart C.  So we're going
 3   to have a report from the Subpart C Subcommittee a
 4   little bit later on this morning.
 5               The third Subcommittee's charge is the
 6   HRPP Subcommittee charge and to consider certification
 7   of HRPP accreditation organizations and there are only
 8   two of them currently, AAHRPP and PHRP, incentives
 9   that could or should be in place to motivate
10   organizations to achieve accreditation and what is the
11   potential impact of accreditation.  So we'll have a
12   report from that subcommittee to discuss as well
13   today.
14               This is the rest of the agenda for today. 
15   We're almost up to -- well, actually, we're about one
16   minute past 9:00 o'clock, so we're just about on time. 
17   Between 9:00 and 10:30 we will have the Subpart D
18   Subcommittee Report.  We're going to take a short
19   break. Then between 10:45 and 12:15, the Subpart C
20   Subcommittee Report.  There will be lunch.   Lunch is
21   on your own.  There's a restaurant in the hotel here
22   and I trust there are restaurants somewhere around
0018
 1   here as well.  Then we will have the report from the
 2   HRPP Accreditation Subcommittee.  We will have a
 3   public comment period between 2:30 and 3:30.  The
 4   comments at the moment are going to be limited to five
 5   minutes per person.  There will be a sign-up sheet at
 6   the back if you would care to address SACHRP, and we
 7   invite you to do so.
 8               We'll take a short break and then we'll
 9   kind of summarize the discussion that's occurred over
10   the course of the day.  So that will be the agenda for
11   today.  Okay, now I would like to invite Celia Fisher
12   and Susan Kornetsky to come up and give us the report
13   on the Subpart D Subcommittee.
14               DR. FISHER:  Okay, so Susan Kornetsky, who
15   just had to make a call, and I are the chairs of the
16   Subpart D Subcommittee.  We had a -- we've had a
17   wonderful subcommittee, as you can see.  We have
18   terrific members on our subcommittee and we have -- as
19   Ernie said, we have worked in partnership with --
20   we've worked in partnership with OHRP to really come
21   up with, I think, some very specific issues that need
22   to be addressed in the 407 process.  
0019
 1               The goals of the meeting, as Ernie had
 2   talked about, was to develop recommendations for the
 3   revision of the 45 CRF 46.407 process for SACHRP
 4   consideration and for possible OHRP adoption and just
 5   to remind all of you, 407 is research otherwise not
 6   approvable which presents an opportunity to
 7   understand, prevent or alleviate a serious problem
 8   effecting the help or welfare of children and by
 9   otherwise not approvable, we're talking about not
10   fitting into 4.04, .05 and .06 which would be either
11   minimal risk with no direct benefit, above minimal
12   risk with the potential of direct benefit and above
13   minimal risk without the potential of direct benefit.
14   And when a protocol does not fit any of those three,
15   an IRB has to make a decision about whether or not to
16   submit it for a 407 review.
17               Now, the first thing that the subcommittee
18   decided to talk about was whether or not we endorse in
19   principle the 407 process and why is it important and
20   we were unanimous in being supportive of this process
21   because we felt that it supports both pediatric
22   research, which is important to the welfare of
0020
 1   children, as well as it has sufficient protections for
 2   children involved in this research.  It does so by
 3   providing a national perspective for which other types
 4   of research does not have because other types of
 5   research are local in their review which is
 6   appropriate for the 404 to 406, but when IRB's judge
 7   a protocol to be worthy both from a human subjects
 8   position as well as from a scientific validity
 9   position, the 407 provides a vehicle for national
10   review of these issues.
11               The other part that we italicized is, is
12   that it's important to note that the IRB plays a
13   critical role in the 407 process because it does not
14   get to OHRP or to the federal level unless an IRB
15   makes a determination that it's worthy to be reviewed. 
16   So some people have looked at the 407 as in some sense
17   taking away decision power but actually, there is
18   incredible decision power that goes on with the 407 at
19   the IRB level.  
20               I wanted to quickly review what the
21   current process is.  In the current process, the IRB
22   forwards a protocol for review if it doesn't meet the
0021
 1   404 to 406 criteria but presents a reasonable
 2   opportunity to further understanding prevention or
 3   alleviation of a serious problem effecting the health
 4   and welfare of children.  Then there is a period of
 5   public review and comment and experts write individual 
 6   recommendations.  And I'll talk about the various
 7   options for that type of process.  
 8               OHRP then submits a recommendation to the
 9   Secretary and the Secretary determines whether the
10   protocol meets either 404 or 406 or presents a
11   reasonable opportunity to address a serious social
12   problem that the human subjects protections procedures
13   are appropriate and that therefore, it should be
14   approved or approved with stipulation as a 407.
15               One of the other first things that our
16   committee decided to do was to say before we make a
17   recommendation about potential processes for the 407
18   or how to enhance them, we need to figure out what the
19   goals are that an enhanced 407 process should meet and
20   those goals were the six that we outline here;
21   enhanced transparency, how do we get adequate public
22   input, how do we get adequate expert input, timeliness
0022
 1   of the process, the three C's, clarity, consistency
 2   and consensus and how do we help to maximize -- oh, it
 3   should be OHRP/FDA harmonization.  Is that wrong?  Oh,
 4   yes, sorry.  Okay.  We didn't catch that.
 5               Okay, so the first -- so what I've done
 6   here in the slides is to try to articulate what we
 7   thought the goals were and then some of the
 8   recommendations we might have to enhance the process
 9   and then get to the very specific processes
10   themselves.  So in terms of transparency, one of the
11   first issues to address was to whom must this process
12   be transparent and so stakeholders, among others, are
13   IRB's need to understand that process, the public in
14   general, disease specific populations and their
15   advocates as well as investigators who will be
16   designing these studies.
17               Second, the process needs to be
18   transparent and how is the expert panel selected, who
19   is the expert panel for each protocol, how is the
20   agenda for the discussion -- I'm sorry, how is the
21   discussion for the agenda determined.  What
22   information will be available to the public and what
0023
 1   is the role of the IRB's?  What kind of information
 2   needs to be transparent, the individual expert or the
 3   general summaries, recommendations to the Secretary
 4   from individuals, a consensus panel that occurs and
 5   from OHRP, and the Secretary's decision and rationale.
 6               One of the most important reasons for
 7   transparency is educative.  That this is a process
 8   that is fairly unique, there hasn't been a lot of
 9   407's and therefore, the public IRB's investigators 
10   do not really need to be education and one of the
11   things that we thought of was that transparency helps
12   with a body of cases that will increase consistency
13   and clarity over time.
14               To enhance transparency, we need to
15   facilitate direct communication between OHRP and IRB's
16   at the initiation of the process, so that if there are
17   questions that need to be asked, OHRP has the ability,
18   time, and guidelines to be able to assist in this
19   process.  In addition, using the Federal Register and
20   the OHRP website more than it's used now to post
21   materials so that the public can comment, so that
22   expert opinions are available, so that OHRP and
0024
 1   Secretary's recommendations are available.  And to
 2   provide detailed OHRP and Secretary rationales, once
 3   again, to provide feedback and an educational purpose. 
 4   Public input is very important and we talked about how
 5   to enhance that.  Right now the regulations call for
 6   but do not specify the mechanism for public review and
 7   comment and our subcommittee along with OHRP,
 8   recommended that it's very important that materials
 9   under review be available to the public for input and
10   so by posting them on the web, that could very easily
11   facilitate that.  That experts need to have access to
12   public comment prior to making their decision and so
13   that would create an issue with respect to time -- the
14   time frame that the public would be asked for input
15   and the expert panel would either meet or make their
16   recommendations.  And finally, that at least part of
17   an expert panel meeting should be open to the public.
18               How do you enhance expert input?  The
19   regulation calls for expertise in science, medicine,
20   education, ethics and law.  And OHRP has found that
21   although it's easier to get ethics advice, it's much
22   more difficult to identify for each protocol the
0025
 1   unique scientific and child pediatric expertise that
 2   is necessary.  So one of the things we thought might
 3   be helpful was to have what's called a blended panel
 4   and that would be that there would be a standing pool
 5   of scientists, ethicists, legal advice, advocates,
 6   that OHRP could select from but also then to get the
 7   specific expertise, that unique expertise would be
 8   blended for each particular protocol.  
 9               Now, the challenge of that is that many
10   scientists or expert advocates may not be familiar
11   with the 407 process as the bioethicists or IRB or
12   legal members are and so we recommended that there
13   would be an orientation process beforehand, let's say
14   an hour before the meeting, in addition to materials
15   to familiarize those new members or members unique to
16   the specific protocol.  And then to make sure that the
17   expert child advocate is present and is not simply a
18   member of the community which is undefined, but
19   actually has some expertise and familiarity with the
20   condition or issue, social issue under investigation.
21               In terms of timeliness, prior to
22   submission to the 407 process, a protocol has to
0026
 1   undergo months of IRB review and that means that
 2   sometimes it's out of sync with the funding cycle. 
 3   One of the things that delays means in addition,
 4   sometimes 407 is only one part of a protocol, so the
 5   IRB has approved the other part of the protocol, and
 6   so the study is underway already before it's gotten to
 7   a 407 review.  
 8               And so some of the things that will also
 9   effect timeliness is whether or not OHRP can do prior
10   screening before it gets to a panel, the number of
11   protocols, which is uncertain at the moment.  They've
12   been varied.  They're increasing over time but we
13   don't know what they're going to be.  Panel selection,
14   whether we use the blended model and whether the panel
15   has or has not autonomy and we'll talk about that when
16   we get to the two most feasible models, and the time
17   to gather public input.  
18               In addition, there are many problems that
19   occur for multi-site studies which I'll just mention
20   but our subcommittee did not have time to review and
21   which we're interested in reviewing at our next
22   meeting.  To enhance the timeliness, it's very
0027
 1   important that IRB's have sufficient information. 
 2   Right now, they may be submitting protocols that are
 3   not really appropriate for 407 reviews, so
 4   transparency and all the other things we've been
 5   talking about is very important and therefore, they
 6   have a role in only submitting appropriate protocols
 7   and in providing sufficient information so that even
 8   if it is appropriate for 407 and it doesn't have to go
 9   back and say, "You forgot to give us this and that",
10   and I'll detail that later.
11               That if possible, to have some kind of
12   consistent submission and review time frame that is
13   compatible with OHRP's many other responsibilities but
14   that investigators and IRB's can have some sense of
15   regularity.  In addition, to save time to have OHRP
16   review 407's and be able to send back for either a re-
17   review or for further information those types of
18   protocols that would not be -- it would not be
19   efficient for the panel to review, the blended panel
20   model and then the use of the web and electronic
21   format and one of the goals would be to have all
22   submissions be submitted through the web at some
0028
 1   point, so that it could be easily transmitted to
 2   panels, et cetera.
 3               Clarity, consistency and consensus,
 4   clearly as I've been talking about transparency as an
 5   educative tool, there needs to be unambiguous
 6   definitions of certain terms of Subpart D, which we
 7   did not deal with at present.  The Institute of
 8   Medicine is coming out with a report making
 9   recommendations, NHRPAC has made a report.  We hope
10   our subcommittee will address some of these issues. 
11   For example, definition of minimal risk, definition of
12   condition, definition of minor increment over minimal
13   risk, all of those go into the 404 to 406 definition
14   and in order for there to be consistency in what is or
15   is not a 407 review, those definitions need to have
16   some type of clarity and consensus in our community.
17               There needs to be clear expectations of
18   the role of stakeholders.  What is the role of the
19   investigator in giving information to the IRB?  What
20   is the role of the IRB in giving information to OHRP,
21   OHRP's responsibility to give sufficient information,
22   both public input to the panel and then their
0029
 1   obligation to submit it to the Secretary and the
 2   Secretary at his discretion, to provide sufficient
 3   information to build cases.  
 4               Another problem is, is that to date there
 5   has not been consistency in whether or not panel
 6   members actually meet together and the subcommittee
 7   felt it was critically important that there be face-to
 8   face contact among panel members and a sharing of
 9   ideas.  Whether or not a group consensus would be met
10   depends upon the model, but clearly the sharing of
11   ideas.  When we were going over some of the previous
12   protocols for 407, it was very interesting to note
13   that there was some information that some panel
14   members had that others didn't based on their
15   expertise and so that, if, in fact, the other panel
16   members had that information, they might have made a
17   different recommendation.
18               And in addition, we thought that all panel
19   members, even though they were coming from expertise
20   of ethics or scientific or children or advocacy needed
21   to be -- needed to make recommendations for the entire
22   protocol and so that's another reason why, because if
0030
 1   they're only taking responsibility for their one part,
 2   there may lack a consensus -- not a consensus but a
 3   consistent type of review.  And we also felt that it
 4   was important to have multi-year staggered panel terms
 5   so that you had some ongoing expertise.
 6               The final issue was the importance of OHRP
 7   and FDA harmonization.  Currently the regulations are
 8   quite similar when it comes to a 407 type review
 9   except for the fact that OHRP but not the FDA has a
10   standard that permits a waiver of parental permission
11   under some circumstances.  And that's something we
12   won't deal with in this meeting, but something for
13   future consideration.  Harmonization should reflect
14   the goals and missions of both agencies and
15   transparency when there are independent agency reviews
16   is very important because once again, it builds a case
17   to allow for certain types of consistency.  There has
18   been at least one joint 407 review with FDA and OHRP
19   and we anticipate that there will be more in the
20   future.
21               So what are the four models of 407 review? 
22   Now, just to define, a federal advisory committee has
0031
 1   certain responsibilities and privileges.  One of the
 2   privileges is to meet and to achieve a consensus
 3   opinion.  Right now 407's are non-FAC, non-F-A-C,
 4   bodies and therefore, they are not permitted to
 5   achieve a consensus statement.  And so that's an
 6   important area for SACHRP's discussion.
 7               The four models is the -- all of them are
 8   non-FAC except for the SACHRP Subcommittee model. 
 9   First is a non-FAC closed panel meeting that is not
10   open to the public but the panel member meet face-to-
11   face.  A second one is also non-FAC but the experts
12   never meet and they are sent the materials and then
13   they provide an independent written recommendation. 
14   The third would be a subcommittee of SACHRP which, as
15   a subcommittee, could achieve a consensus because
16   SACHRP is a FAC and the final one is a non-FAC open
17   panel to which the public could come, they would meet
18   face-to-face, but there would be no consensus
19   document.  They would still write individual reports.
20               We did not consider a fifth model which
21   was the creation of a new separate 407 FAC panel
22   because it was felt that this was not feasible at this
0032
 1   time to do.  That it would not be approved and it
 2   would take a long time for that kind of an approval. 
 3   So, the subcommittee determined that the only models
 4   were -- that could meet the goals, those six goals
 5   that I just reviewed, was either the SACHRP
 6   subcommittee model or the non-FAC open panel, and so 
 7   I want to discuss now -- many of our recommendations
 8   are common to both models, so I'm going to go over the
 9   recommendations, the detailed recommendations for
10   process that are common to both in a non-FAC open
11   panel model and a SACHRP subcommittee model and then
12   present what would be different.
13               So the steps that we recommended is that
14   number one, OHRP provide clear guidelines and SACHRP
15   recommendations are going to be helpful to OHRP in
16   doing that in terms of the 407 process once we all
17   come to some consensus about what it should be.  IRB's
18   only submit appropriate protocol with minutes for
19   their rationale.  They need to state explicitly when
20   the protocol failed to meet the 404, 405 and 406. 
21   They need to demonstrate that even though it did not
22   meet those, that is it scientifically valid and also
0033
 1   has adequate human subject protections.  One of the
 2   things that people involved in the 407 process has
 3   been concerned about is, is that the 407 should not be
 4   a waste paper basket for difficult protocols that the
 5   OHRP -- I'm sorry, that the IRB just doesn't really
 6   want to deal with but rather they really need to meet
 7   the criteria for a 407.  
 8               That the OHRP screens all applications and
 9   can have a dialogue with an IRB about whether or not
10   it's readily apparent that this is not a 407-type of
11   application or that they have not provided sufficient
12   information for a panel review.  So -- and in speaking
13   with OHRP, that screening process, there would be a de
14   facto assumption that a 407 would be sent to the panel
15   but this really provides an issue of timeliness and
16   education so that it's really grossly apparent that it
17   doesn't fit, that the panel is not wasting its time.
18               Then there would be a Federal Register
19   notice and materials would be posted on the OHRP
20   website.  Then we would have this blended panel where
21   there would be a standing pool and protocol specific
22   experts selected.  They would receive all materials
0034
 1   and public comment prior to their meeting.  They would
 2   then meet face-to-face.  There would be an orientation
 3   meeting for experts who were not familiar with the
 4   process.  All panel members, whether or not it was a
 5   FAC subcommittee or non-FAC, would express their
 6   opinions to each other, review all materials and
 7   listen to public comment.  We thought in both models,
 8   it was very important for the public to be present at
 9   least partially at the meeting.
10               Then and between seven and eight where
11   there are differences, which I don't want to discuss
12   yet, so what would also be in common is that once OHRP
13   received either the individual recommendations or a
14   consensus and then SACHRP review, OHRP develops its
15   own recommendation based upon all materials and
16   forwards this recommendation to the Secretary.  The
17   Secretary approves or disapproves the 407 request. 
18   The OHRP directly notifies an institution in writing
19   of the Secretary's decision.  At the Secretary's
20   discretion the decision, a detailed rationale and
21   supporting materials are posted on the OHRP website
22   for the educational value.  If the Secretary approves
0035
 1   with stipulation, the investigator then modifies the
 2   protocol, submits it again for the IRB approval.  The
 3   IRB makes a decision about whether or not it should be
 4   approved and if it should be approved, then submits it
 5   to the OHRP for final approval.  So that's what we're
 6   recommending irrespective -- that's kind of a defining
 7   new process, irrespective of which kind of panel model
 8   is used.
 9               Now, for the two models we thought were
10   feasible, the non-FAC model has an advantage of
11   timeliness.  As you can see, there's only two things
12   that occur.  After the panel is convened and discusses
13   the materials that there's public comment, that all
14   the experts provide their views.  Each panel member
15   writes an independent recommendation and then the
16   individual reports are posted on the OHRP website for
17   information but not for comment and then OHRP proceeds
18   to do everything in steps 8 through whatever.
19               The SACHRP subcommittee does not have an
20   advantage of timeliness because it needs to be decided
21   by the SACHRP committee and then go to SACHRP. 
22   However, the advantage is that the subcommittee can
0036
 1   write a consensus report and reach consensus.  For the
 2   SACHRP subcommittee model, at least one member of
 3   SACHRP must be on the subcommittee.  That person could
 4   be chair, it could be a co-chair with a non-SACHRP
 5   member, could be a member him or herself, or it could
 6   be a standing member or we could do a rotation in
 7   terms of SACHRP members.  That might not be -- the
 8   rotation might be ideal from a time perspective, might
 9   not be ideal because it would mean there was not
10   continuity of expertise.
11               The subcommittee then creates a consensus
12   report with specific recommendation, rationale and a
13   minority report if appropriate.  The -- this is an
14   advantage over what's gone on in the past because in
15   the past you have these disconnected independent
16   reviews.  The subcommittee report is posted on the
17   OHRP website.  Any additional public comment is
18   received and is then forwarded to SACHRP when it
19   meets.  A portion of the SACHRP meeting would be
20   devoted to review subcommittee -- a subcommittee
21   representative is present and the meeting is open to
22   the public and SACHRP rules on the report and forwards
0037
 1   it to OHRP and it starts with number 8 and continues. 
 2   One of the problems was that in order for the
 3   subcommittee SACHRP model to work, you don't want
 4   SACHRP kind of reinventing the wheel and spending as
 5   much time on every particle as the subcommittee did,
 6   because then there's really no purpose of the
 7   subcommittee.  And so the question was, what kind of
 8   criteria might SACHRP adopt for itself in terms of how
 9   it would handle a subcommittee recommendation in a way
10   that was timely, transparent but also would not take
11   up all of SACHRP's time and not be redundant.  So this
12   is what the subcommittee recommended.
13               One is, is that SACHRP could just simply
14   accept the report as written.  This would be -- these
15   would be four steps that would be unique to each
16   protocol.  It could accept the report and write its
17   own brief comment.  It could return to the
18   subcommittee for further consideration if there was a
19   significant gap in the rationale or new information
20   that was very significant came to SACHRP after the
21   panel, the subcommittee had met.  
22               The key here is that SACHRP would have to
0038
 1   really make a decision that there were critical
 2   differences in its opinion or critical gaps,
 3   significant errors in the subcommittee report to
 4   either -- to send it back.  If, in fact, it sends back
 5   the report, and it still -- SACHRP still believes that
 6   the report needs to be rejected once again, for
 7   significant -- either the SACHRP committee is in
 8   opposition to the recommendation or they feel there's
 9   been a significant gap in what was recommended, then
10   we recommend that they would either refer their report
11   back again, ask OHRP to constitute a new subcommittee
12   or submit a report to OHRP with a dissent.  
13               So I know this is a lot to think about but
14   the issue here was if SACHRP decided to use the
15   subcommittee model, how one could make it practical
16   and not redundant, not time-consuming and the other
17   problem with the SACHRP subcommittee model is that
18   although the advantage of having a subcommittee is
19   consensus, if, in fact, SACHRP doesn't agree with the
20   subcommittee, then it's not providing that advantage
21   of consensus.  So basically, the subcommittee did not
22   make a recommendation for one or the other.  We
0039
 1   thought that SACHRP should be considering this
 2   information, discuss it and then we could bring it
 3   back in terms of what we think are the two most
 4   feasible models.  
 5               Just to very quickly move with additional
 6   considerations, is that once we decide on a process,
 7   we think it's very important to have this process be
 8   adopted not simply by those protocols that are funded
 9   by appropriate federal agencies but in some way -- and
10   that's something we'll address in our next
11   subcommittee meeting.  In addition, the subcommittee
12   felt that whatever model was accepted by SACHRP that
13   the subcommittee should be working hand in hand with
14   OHRP to be monitoring whether or not the process works
15   and to be making recommendations if necessary for a
16   re-review. 
17               In addition, as you recall, there was an
18   algorithm that was presented to SACHRP at our last
19   meeting and SACHRP asked the subcommittee to review
20   it.  The subcommittee did review it.  It basically
21   simply specifies or details in a schematic form
22   exactly what is in the regulations.  OHRP feels that
0040
 1   it will be helpful to IRBs and to the public to be
 2   able to use this schemata, so the subcommittee
 3   recommended that it would be adopted.  We also wanted
 4   to stipulate that it is not a panacea because until
 5   definitions of condition, minimal risk and those other
 6   very important definitions that need to be part of
 7   whether or not something is a 407, that it's still
 8   going to be somewhat difficult, but that it is a
 9   useful algorythm that we feel should be adopted
10   because it does not say anything more than what the
11   regulations currently say.  
12               We also are asking SACHRP to allow us to
13   have a subcommittee name change because we realized as
14   we were working on the federal regulations that the
15   decisions we have to make are involved with Subpart A
16   for example, and will be in some of the other
17   subparts, so we'd like to be called the SACHRP
18   Subcommittee for Research Involving Children, and our
19   next steps would be after -- number one, take the
20   feedback from today's meeting back to the subcommittee
21   to come up with a model that SACHRP asks us to
22   consider, to recommend the guidelines for definitions,
0041
 1   to identify the characteristics of when we say public
 2   or advocates what do we mean, who are they, how they
 3   best represent the groups that are going to be
 4   involved in the research and to address the 407 multi-
 5   site problem which is certainly very complicated.  
 6               So that's our presentation and discussion,
 7   questions?  You all have this so it's -- you all have
 8   this printed out so you can look at the different
 9   steps and I can put them on here.  And Susan is also
10   here to answer questions.  Susan, maybe you want to
11   come up here.  
12               MR. BARNES:  I would like to know what Dr.
13   Schwetz thinks of these two alternatives, the open
14   committee model versus the SACHRP subcommittee model.
15               CHAIRMAN PRENTICE:  Unfortunately, Dr.
16   Schwetz is not here at the moment, so --
17               DR. FISHER:  Can we ask, Mike, would you
18   want to respond to that, but your opinion, obviously.
19               DR. CAROME:  Either model would be
20   acceptable and feasible from OHRP's perspective.
21               MS. KORNETSKY:  It was made very clear to
22   us that they didn't have any preconceived idea of
0042
 1   which would be the better model.  It was made very
 2   clear to the committee.
 3               DR. FISHER:  Tom.
 4               MR. ADAMS:  When you were looking at the
 5   different models, you indicated that you didn't
 6   believe that a separate 407 panel would be feasible
 7   and I just wondered the why of that.
 8               DR. FISHER:  Bern, would you mind speaking
 9   to that in terms of why a new fact panel would not be
10   feasible at the moment?
11               DR. SCHWETZ:  Well, the only reason it
12   isn't feasible is because about the only way you can
13   get a new federal advisory committee today is to
14   disband another one.  And since OHRP doesn't have any
15   one to give up, and I wouldn't want to recommend that
16   SACHRP be given up to create another FACA committee,
17   it's just not a viable option at this point.
18               MR. BRADLEY:  My understanding is that
19   under the existing 407 there was not an opportunity
20   for experts to share opinions and therefore, the best
21   decision may not have been reached as a result.  With
22   the non-SACHRP option, clearly you have an opportunity
0043
 1   for the experts to share opinion and to have a
 2   discussion.  The one drawback is that they will then
 3   not produce a consensus document.  Do you see, either
 4   of you see a high value in that consensus document? 
 5   Will that serve the purpose for the individual
 6   investigation or will it advance our ability to
 7   provide better protection for children?
 8               MS. KORNETSKY:  Ernie, did you want us to
 9   take a pause?
10               CHAIRMAN PRENTICE:  Yes, I beg your
11   indulgence, okay.
12               MS. KORNETSKY:  Well, get back to that.
13               CHAIRMAN PRENTICE:  It's my pleasure to
14   introduce to you Rear Admiral Christie Beato, who is
15   the acting Assistant Secretary for Health at the U.S.
16   Department of Health and Human Services.  I've got a
17   rather lengthy bio here.  I won't read it all but I do
18   want to at least tell you a little bit about Christie. 
19   Her responsibilities within the Department are focused
20   on leading the Department's efforts to reduce health
21   disparities and combat HIV/AIDS, encourage prevention
22   strategies to reduce chronic diseases and advance
0044
 1   women's health.  
 2               Prior to joining the Department, Dr. Beato
 3   was at the University of New Mexico, School of
 4   Medicine.  She was the Medical Director of several
 5   clinics and then in 1999 she became the school's
 6   Associate Dean for Clinic Affairs and was quickly
 7   promoted to Chief Medical Officer of the UNM Hospital
 8   System which by the way, I had the pleasure of going
 9   there and reviewing their HRPP program some time back.
10               She was the first woman to serve in that
11   position.  She was responsible for 1,000 physicians,
12   five hospitals, a budget of more than 500 million and
13   the integration of academic affairs, clinical research
14   and patient care, you know, quite a job.  So we're
15   absolutely delighted that you can find time in your
16   busy schedule to come to this meeting and talk to our
17   committee.
18               DR. BEATO:  Thank you so much.  Good
19   morning.  Thank you all for having me and thank you
20   most of all for serving in the capacity that you all
21   are to really give advice to the Secretary and the
22   President.
0045
 1               I really want to take the time out to come
 2   here today because I think that I want to bring the
 3   emphasis to the -- and appreciation to the work that
 4   you're doing here in terms of human research subject
 5   protection, which is a very, very important job, not
 6   only as we see the science and technology moving
 7   forward but also with the whole genetic and geno
 8   component.  The issue of bio-ethics has to be and must
 9   continue to be paramount.  
10               I really want to thank your committee and
11   I want to thank specifically the subcommittee members
12   for their help.  The thoughtfulness that you have
13   described in your subsections are really incredible
14   and we sincerely appreciate that and it will be put to
15   good use, trust me.  It is my understanding from Dr.
16   Prentice that a lot has happened since your first
17   meeting in July and that you have been a very
18   productive group and my sincere thanks for that.
19               Regarding the subcommittees of the SACHRP
20   and Subparts C and D, the charge from the Secretary is
21   to advise in matters pertaining to spacial populations
22   and that will continue to remain one of the highest
0046
 1   priorities of our department, specifically Subpart D,
 2   which is research involving children for process
 3   conducting 407 panel expert reviews.  What we really,
 4   really want to see is implementation of a process
 5   that's transparent and timely for protocols that come
 6   to the Secretary's office for final approval, so I
 7   want to sincerely thank you for that.
 8               Subpart C, as we know it, not much as been
 9   done since 1978, that's research involving prisoners. 
10   And the question that I would pose you is, for an
11   adequate framework for review and approval of these
12   protocols, do we need to make changes?  If so, what
13   they are and if not, then how do we consider today's
14   situation with prisons and prisoners?  There seems to
15   -- in my opinion, still exist some confusion in the
16   research community about research involving prisoners
17   and perhaps one of the focuses ought to be increased
18   education in that community of researchers. 
19               It's like, you know, we haven't looked at
20   some things since 1978.  We always should be reviewing
21   and seeing how we can improve our process rather than
22   the same old thing moving forward.  In terms of
0047
 1   regarding the subcommittee on accreditation of
 2   institution, our Department remains supportive of the
 3   accreditation and the fact that it should be voluntary
 4   and a non-government process.  Now that that process
 5   is moving to many of them sort of voluntarily becoming
 6   accredited, what I would like to pose to the committee
 7   is what do you believe the role of the Federal
 8   Government should be at this point, specifically in
 9   the Department?  Should it be one of oversight? 
10   Should we look at other mechanisms for oversight?  But
11   the ultimate out goal that I would like to see is what
12   outcome evaluation process can be put in place to
13   insure that the intent of these voluntary
14   accreditations are truly followed and that we have an
15   accountability system that we can track to insure
16   that.  
17               Anyway that's really basically in a
18   nutshell where I wanted to basically really thank the
19   subcommittee and the committee as a whole but I know
20   that the work horses have been the subcommittee and my
21   deep appreciation goes to you for that.  I wanted to
22   take time out, because like I said when I first was
0048
 1   asked to join this Administration, I was asked to
 2   really focus on where my priorities would be if I were
 3   to come in a leadership role.  This was December of
 4   2000 and I basically, in my letter to the President
 5   outlining three items.  My first item was recruitment
 6   and retention.  I don't believe that we can have a
 7   sustainable viable medical research or delivery system
 8   in our nation without a real diverse, vibrant pool of
 9   highly qualified individuals in all aspects of that
10   field.  
11               And I'm very concerned with the lack of
12   not just diversity but numbers of kids really enthused
13   and going into the science and technology and medicine
14   and health care delivery system.  The second one was
15   bioethics, coming from academical medical centers and
16   a state that has many challenges in diversity and
17   wonderful things but how do we keep the research
18   momentum moving into new frontiers, keeping the
19   paramount of human dignity and human protection always
20   first and foremost and the third one was bioterrorism,
21   understanding how quickly some ill people might use
22   our modern technology and genetic reverse
0049
 1   transcription and mutation and things like that, and
 2   coming from a nuclear state, also you don't need much
 3   to do a lot of harm.  So before 9/11 even was on the
 4   horizon, those were the three things that I was the
 5   most concerned about and I am very honored and humbled
 6   to serve this country and actually have a role in all
 7   three, so I want to thank you for your role.  You're
 8   like my number 2 thing that I was very concerned about
 9   and I really want to see strengthen and protected as
10   we move forward leading the world, really, in research
11   and human subject protection, so thank you.
12               (Applause)
13               CHAIRMAN PRENTICE:  Thank you very much,
14   Dr. Beato.  
15               MS. KORNETSKY:  We can go back to the
16   question that was raised about the value of consensus. 
17   First of all, although I have not been involved
18   actually in the 407 process, I think the say it's been
19   handled before, there has been an opportunity -- there
20   have been different ways that it's been handled, so
21   there has been an opportunity for individual experts
22   to meet as a group and discuss.  It has -- there have
0050
 1   been one or two examples where people just wrote
 2   independent opinions and sent them in.  So I think in
 3   both models we can have the commonality of dependent
 4   people meeting and discussing things.  I think, as
 5   Celia pointed out and what your question is asking is
 6   about the value of, you know, consensus and what we
 7   feel about that.  
 8               My own sense in thinking about that is
 9   eventually a -- OHRP needs to give some guidance to
10   the Secretary and I think it's a matter of looking at
11   whether there's a consensus document or whether they
12   are going to have 12 different independent decisions
13   to work with.  And if you go out to the website and
14   look at some of the independent letters, there -- they
15   may be the same point, but two individual decisions
16   made, one they feel falls into one category or the
17   other.  And sometimes the opinions are very, very
18   different.  
19               So -- and I guess I would, you know, ask 
20   the value of consensus for OHRP as well, whether they
21   feel that that's something that's important.  Mary?
22               DR. POLAN:  Thank you.  In reading the
0051
 1   example that was given in the briefing book, clearly
 2   meeting together and talking about it is critically
 3   important.  And what came out, which I think is
 4   probably true, is that if you ask five different
 5   doctors the same question, you'll get five different
 6   answers.  So producing a consensus is always a
 7   challenge.  
 8               If the option for the subcommittee, SACHRP
 9   subcommittee, which certainly would be there, is for
10   a majority opinion with a potential minority opinion
11   or dissenting opinion or whatever you want to call it,
12   it seems to me that OHRP would be the ones to
13   rationalize those two so that simply by having a
14   subcommittee doesn't mean you're going to have a
15   consensus.  It just means that you would have maybe
16   two opinions rather than 12 and those two opinions
17   could have lots of different ideas in them.  So it
18   seems to me the major rationalization project is going 
19   to be in OHRP's corner to then send it forward and I
20   was impressed with the potential for back alleyways
21   and you know, circuitous routes if you have a
22   subcommittee of SACHRP to send it back and not agree.
0052
 1   And since timeliness is a major issue, and as I look
 2   through the dates of the prior 407 applications, none
 3   of them were reviewed and approved within less than a
 4   year and a year was really lightening speed.  I think
 5   that's a major consideration.
 6               DR. FISHER:  I agree.  One of the things,
 7   I put this slide back up because I think what we have
 8   to think about is, is that we are making
 9   recommendations that will improve -- if we continue to
10   use a non-FAC panel, it will be used in a very
11   different way.  And just as, you know, we're talking
12   and I think our opinions have gone, you know, both
13   ways, but given -- it may be wise to see how these
14   processes work in a non-FAC panel to see whether --
15   because you're absolutely right.  
16               OHRP needs to make a decision irrespective
17   of whether it's a non-FAC or a subcommittee panel and
18   the critical issue is timeliness and whether or not
19   the expert opinions are helpful to OHRP in the long
20   run and so it may be wise to start with the non-FAC
21   panel because that's the easiest option to implement
22   and continue to work with OHRP to see -- to monitor
0053
 1   and see whether or not that meets the improvements
 2   that we've articulated as goals.
 3               MS. KORNETSKY:  One of the major
 4   differences and I think Celia is right, that either
 5   model there will be improvements and recommendations
 6   and one of the things from people who have served on
 7   407's who have had some concerns, I think, is the idea
 8   of sort of public input and how to open that up and
 9   either way, there's a recommendation that part of the
10   meeting be open to the public even if it is just a
11   group of experts, you know, getting together, that
12   part of that meeting will be opened up so that they
13   can get that input.  So there are definitely
14   improvements in the model.
15               DR. GYI:  A couple of questions; first,
16   did your group consider what happens to the
17   subcommittee after SACHRP is disbanded?
18               DR. FISHER:  Well, exactly.  I mean, one
19   of our -- one of the major concerns is that tying this
20   to SACHRP in addition to taking up a lot of SACHRP
21   time, potentially having problems with consensus, is
22   that your -- we don't know how often or when or if
0054
 1   SACHRP would be renewed and so it is placing in
 2   jeopardy a process that OHRP has put a lot of effort
 3   into that may or may not exist after SACHRP is or is
 4   not renewed.
 5               DR. GYI:  I wonder if I might extend that
 6   question to you, Dr. Schwetz, if we were to go down
 7   that path, what options exist for the continuation of
 8   the 407 subcommittee or 407 panel?
 9               DR. SCHWETZ:  If you're saying that the
10   benefit of having a subcommittee of SACHRP being that
11   it is a FACA meeting, SACHRP expires and isn't
12   renewed, it isn't a given that we would have access to
13   that slot for a continuing FACA because that advisory
14   committee would go back into the Department and they
15   would use it for the highest priority.  And it may not
16   be this at that time, so it's not a guarantee.  
17               What that means then is that we would
18   revert by default back to the process that we've had -
19   - either that you're going to recommend as an
20   alternate to the subcommittee of SACHRP or to another
21   mechanism, so we wouldn't stop doing it but we'd
22   revert back to Plan B.
0055
 1               DR. GYI:  Another question.
 2               DR. FISHER:  Felix and then Mark, yes.
 3               DR. GYI:  A follow-up question is, you
 4   know, we appreciate the fact that your subcommittee
 5   addressed this from the perspective of advising OHRP
 6   with our priority determination that there would be
 7   some harmonization between FDA and OHRP, in your list
 8   of stakeholders, you -- I didn't see sponsor
 9   organizations as an example to be educated regarding
10   the process as well as to help with the dissemination
11   of information and implementation of the process that
12   you are starting.  I wonder if we might want to also
13   think about the fact that education has to occur at
14   the point in time when pen hits the paper, the design
15   of the protocol, which would eliminate a number of
16   different issues that the 407 panels might have to
17   address if the designers and the writers of the
18   protocol understood what the issues are up front.
19               MS. KORNETSKY:  I definitely agree with
20   that and as we talk about multi-center studies, that
21   very frequently are by -- you know, by corporate
22   sponsors that's even going to become more important
0056
 1   but the point is very well taken.
 2               DR. FISHER:  And our committee's
 3   recommendation was that this process in some way be
 4   generalized or adopted by non-federal funded projects
 5   but it is something that we will make as a formal
 6   recommendation probably next time or we can make it
 7   now, but I think we need to know what the process is
 8   before we make that recommendation.  Mark and then
 9   Ernie, I'm sorry.
10               CHAIRMAN PRENTICE:  Go ahead, Mark.
11               MR. BARNES:  I used to be a state and
12   local government official and it was -- and as a
13   government official, I think if I were in Dr.
14   Schwetz's place or Mike Carome's place or somebody
15   else, I think I would -- if I thought that I could get
16   consensus from a blue ribbon panel, I think I would
17   prefer that because frankly, it's something that I
18   could then take a decision on with a greater degree of
19   certainty.  But with that said, I think Mary Polan
20   makes a good point and so my factual question really
21   is, among the 407 applications that you guys looked at
22   and considered as examples, I mean, how often was it
0057
 1   that there were bitter divisions or there were two
 2   kind of opposite points of view and I think that's an
 3   important kind of factual question because I know
 4   that, you know, those of us who serve on IRBs most of
 5   the time the way that most of us, I think, try to work
 6   even in IRBs that might have differing opinions about
 7   things is to try to reach consensus and I think in
 8   about, you know, 90 percent of the cases at least in
 9   my experience sitting on a few IRBs, in about 90
10   percent of the cases we always avoid votes because
11   there really is unanimity of opinion.
12               So I guess my question really with all
13   that said, is sort of how many opinions are there that
14   you've seen in these areas?
15               DR. FISHER:  Susan, do you want to comment
16   or maybe Ernie, who has -- 
17               MS. KORNETSKY:  I was going to ask Ernie
18   if he wanted to -- I mean, I've read the reports and
19   sometimes they're major and sometimes they're minor,
20   but I don't have a sense of sort of overall if there's
21   a pattern to it.
22               CHAIRMAN PRENTICE:  I'm not so sure
0058
 1   there's really a pattern, Mark.  We've had protocols
 2   that were highly problematic from an ethical viewpoint
 3   as well as a scientific medical viewpoint that we had
 4   great debate on and very little agreement.  And on the
 5   other hand, we've had other protocols where people
 6   pretty much agreed rather quickly that this was
 7   something that was either potentially approvable under
 8   407 or, in fact, it was really not a 407 category
 9   protocol, it really is a 405, in which case we
10   recommended it be considered as such.  
11               I know that I would have appreciated the
12   opportunity to reach some kind of a consensus on the
13   407 panels that I sat on.  When I wrote my independent
14   reports as did everybody else and then eventually I
15   had an opportunity to look at some of those reports,
16   quite frankly, I was surprised at some of the content
17   of the reports of my colleagues.  I thought they were
18   going in one direction during our discussion but when
19   I read the reports, they went in a different
20   direction.  So that kind of took me back.
21               So I think there's definitely value in
22   reaching, you know, consensus, but the only model that
0059
 1   will permit the panel to reach consensus is the SACHRP
 2   model and that's certainly got some significant
 3   disadvantages in terms of timeliness and other factors
 4   related to workload.  
 5               I looked at -- I guess I kind of looked at
 6   the 407 reviews as sort of like an IRB meeting, where
 7   you've got a protocol and you all sit down and you
 8   bring to bear your collective wisdom and experience
 9   and indeed, your values, and you decide, you know,
10   whether or not this is a protocol that really ought to
11   be conducted.  So clearly from an ethical viewpoint,
12   my bias would be a consensus is the best way to go but
13   it may not be practical to go in that direction.
14               DR. FISHER:  I think, just some other
15   points that were raised by the subcommittee about the
16   SACHRP model was the extent to which SACHRP members
17   had -- the selection of SACHRP is not protocol
18   specific in terms of the type of ethic, scientific or
19   advocate type of expertise and so one of the issues,
20   as I said, there's a tension between consensus that
21   might be able to be reached by the subcommittee and
22   the danger of a lack of consensus and lake of
0060
 1   timeliness by a SACHRP review.  Now it might -- we
 2   tried to address that by the criteria and maybe we
 3   could come up with -- maybe SACHRP could make
 4   recommendations and the subcommittee could fine tune
 5   recommendations for how we facilitate the process, a
 6   consensus panel process, once it reached SACHRP, but
 7   I think unless we do that in a way that's efficient
 8   and practical, we've not solved the consensus problem
 9   with the subcommittee.  Tom, I mean -- yeah, Tom.
10               MR. ADAMS:  It's obvious that the
11   subcommittee spent a lot of time looking at process
12   and I'm curious as to whether you also developed
13   timelines as to how the processes would move. 
14   Currently it's taking a year or in excess of a year to
15   move through the 407 process.  Does the subcommittee
16   report envision speeding that timeline up or would it
17   stretch it out?
18               MS. KORNETSKY:  I think we would -- I
19   mean, the goal is to speed it up and I think the
20   desire of OHRP is also to speed it up.  I think that's
21   been one of, you know, the problems.  But you also
22   have to sort of look at the realities of when these
0061
 1   things come forward, public comment periods, and then
 2   how often we meet.  So, you know, we have not -- we
 3   have not gone you know, detail by detail by time, but
 4   I think that's one of the goals and --
 5               DR. FISHER:  I think the process will be
 6   facilitated by some of our recommendations and one of
 7   the problems that we can't address is we do not know
 8   how many 407s are going to be submitted each year, it
 9   could be two, it could be 12.  We did discuss
10   potentially there might be two meetings a year, but if
11   you look at -- if we implement a screening process
12   that OHRP can do, if the guidelines and clarity of
13   what the responsibilities of investigators in ORBs is
14   or are, whichever is plurals.  If we have the standing
15   pool of individuals, all of those steps will make the
16   process more timely irrespective of which model would
17   be used. 
18               In fact, the SACHRP model extends the
19   process because not only does the subcommittee have to
20   meet, if it met once or twice a year, but then it has
21   to wait, it has to meet in a timely fashion prior to
22   SACHRP, so that all the materials can be put in. 
0062
 1   SACHRP has to make a decision, but I think that by
 2   definition if these steps are adopted, we will see a
 3   shortening of the process.  And also with the website,
 4   once the website really gets up and materials are
 5   submitted through the website, that's also another
 6   step.  Nigel.
 7               DR. HARRIS:  The other comment was with
 8   respect to the subcommittee and their recommendation,
 9   their report to SACHRP, how complete is the
10   information that will come to SACHRP so that they can
11   make a study judgment because in truth, if, in fact,
12   R01 gets its consensus report and a minority report,
13   you still have lost a lot of the discussion and
14   information that one may need for a study decision.
15               MS. KORNETSKY:  If we chose that model, it
16   would certainly be up to this group to, you know, say
17   what they felt they needed in order to make the
18   determination.  I mean, we really work very hard, and
19   I think the processes and actions that we could take
20   is that I mean, we all wanted to avoid this group
21   being looked at as just, you know, passing it on and
22   stamping it.  So you bring up a very good point.
0063
 1               DR. FISHER:  Yes, Mary.
 2               DR. POLAN:  I just have another issue that
 3   I wanted to bring up when this one is done.  I don't
 4   know if this one is finished.
 5               DR. FISHER:  About 407?
 6               DR. POLAN:  About 407, yeah, another point
 7   that you all made.  
 8               DR. FISHER:  Felix?
 9               DR. GYI:  It seems to me that we -- if we
10   had to bring the decision making to a SACHRP committee
11   level, we're duplicating the discussions that had
12   already gone on and to have the expertise repeated
13   again for the digestion of this particular committee. 
14   I just don't see how we would be able to replicate
15   that level of understanding without devoting a
16   significant amount of time to it.
17               MR. BARNES:  I wonder if based on what
18   Felix says, I think there's a lot of truth in that but
19   did you guys consider the possibility instead of
20   bringing it -- bringing the judgment to the full
21   committee, instead having a committee, a subcommittee
22   of this group actually be that committee?
0064
 1               MS. KORNETSKY:  I'm not sure we would be
 2   permitted to do that.  Dr. Schwetz is shaking his
 3   head.
 4               DR. SCHWETZ:  That's not really an option
 5   because the subcommittee of a FACA committee is not a
 6   free-standing FACA committee.  It can only make
 7   recommendations to the parent FACA committee for them
 8   to decide whether or not a report is accepted or not. 
 9   So the subcommittees can't bypass the committee.
10               DR. FISHER:  Yes.
11               DR. JONES:  Is there something you could
12   do that would be a little bit in the middle, have the
13   non-FACA meeting, make the decisions and maybe on a
14   bi-annual process have a subcommittee review and
15   review the cases that came up and clarify the
16   definitions, make a consensus at that point?
17               DR. FISHER:  That wouldn't be able to be
18   done in the way you've just articulated.  However, I
19   think to have the Subpart D committee, or
20   subcommittee, whatever we're called, monitoring the
21   process and reporting to SACHRP, not making decisions
22   on individual protocols --
0065
 1               DR. JONES:  Right, but then getting
 2   broader guidance.
 3               DR. FISHER:  Right, and working with OHRP 
 4   to say is this working, is there any other
 5   recommendations that we should have, I think that's an
 6   excellent idea.  We really wouldn't know at least for
 7   a year or 18 months in terms of being able to monitor
 8   in a way because it really depends on the number, but
 9   I think that if that's what SACHRP wanted, that kind
10   of report based on dialogue between the subcommittee
11   and OHRP and perhaps, comment from those IRBs who went
12   through the process, would be very helpful.  Yes,
13   Robert.
14               DR. HAUSER:  You know, it seems to me that
15   the essential question is what process is in the best
16   interest of the human subject, in this case, a child. 
17   And my sense is that the SACHRP approach is probably
18   going to lead to the best decision and that we ought
19   to go that route and figure out how to make it work. 
20   Nothing is ever cast in stone forever.  We could do it
21   for a year.  We could do it for two years and try to
22   work out the issues.  But my belief is that that would
0066
 1   be in the best interest of the human subject.  
 2               DR. FISHER:  Ernie and then Susan.
 3               CHAIRMAN PRENTICE:  Yeah, I'd like to
 4   pursue the issue of consensus a little bit further and
 5   ask OHRP to comment on their view of how important it
 6   is or not important to reach consensus.  Bern, would
 7   you comment on that?
 8               DR. SCHWETZ:  Well, obviously, there have
 9   been a dozen or more reviews without a consensus
10   process.  So the absence of a new process that didn't
11   -- the presence of a new process that didn't reach a
12   consensus, wouldn't cause this to fail.  A consensus
13   would be helpful but it isn't absolutely essential. 
14   Even if we had a consensus document from a panel
15   review as we present the issue to the Department for
16   the Secretary's decision, we would tease it apart and
17   present all of the major opinions that were
18   accumulated from the public and from the experts.  So
19   the fact that a consensus had been reached would be
20   part of that report to the Department but we wouldn't
21   just say that the experts reached a consensus and
22   here's the recommendation.  So what's more important
0067
 1   to us is to have well articulated expert opinions that
 2   we can use to lay out the range of thinking and then
 3   add to that whether or not there appeared to have been
 4   a wide range of agreement.
 5               The couple of panels that I've been on, it
 6   wasn't a matter so much that the panels were really
 7   divided in their opinions about whether we would
 8   recommend approval or not if we moved this to a
 9   consensus decision.  It was more so a situation where
10   people coming from different areas of expertise had
11   recommendations about whether or not there should be
12   changed to the protocol recommended to the author of
13   the protocol rather than whether or not this should
14   ever be approved.  So there was kind of a feeling that
15   if, in fact, the decision is to approve this, here's
16   what it would take to do it right.  People said there
17   are fatal flaws here and that would be, you know, the
18   substance of my opinion that this is fatally flawed. 
19               So you don't -- we haven't taken these to
20   that consensus but what's really more important is
21   that we get the range of thinking so that we can
22   construct the document to the Office of the Secretary
0068
 1   that represents that range.
 2               DR. FISHER:  Yes, Susan.
 3               DR. WEINER:  It's not clear to me that
 4   having the 407 process be a subcommittee of SACHRP is
 5   more protective at all.  I mean, we're really talking
 6   about trying -- under those circumstances trying to
 7   achieve three levels of consensus beyond initial IRB
 8   consideration, and I think that time is also in the
 9   interest of protecting children with conditions that
10   need more rapid progress to treat and deal with them.
11   So I think that, you know, the subcommittee -- the
12   SACHRP subcommittee recommendation adds additional
13   layers of review without necessarily adding value.
14               DR. FISHER:  Tom?
15               MR. ADAMS:  Just one last concern to
16   mention and that is regarding the role of SACHRP
17   itself.  When you look at the charge, the advisory
18   committee appears to be set up to advise on relatively
19   broad policy issues and to begin to do the 407 reviews
20   would, in fact, move the committee to some degree away
21   from broad policy issues and into the implementation
22   to some extent albeit still advisory business.  And I
0069
 1   do worry that it might take away from the overall --
 2   the overall role of the advisory committee.  
 3               DR. FISHER:  Mary, you had a -- Mary, do
 4   you have your point or is that about the process or
 5   did we --
 6               DR. POLAN:  No, I had a completely
 7   different point.
 8               DR. FISHER:  Okay, let me ask then, if the
 9   SACHRP members would think about what guidance, what
10   kind of feedback do you want to direct our
11   subcommittee to consider?  Do you have a priority in
12   terms of those two models to flesh out and are there
13   specific problems with those two models that yet need
14   to be addressed and is there a priority on one of
15   those models?  Nigel, did you want to say something?
16               DR. HARRIS:  Do you have any idea about
17   how many of these protocols, as far as protocols might
18   be coming through at a time?
19               DR. SCHWETZ:  The answer is no, but we can
20   guess.  If history says anything, we might expect a
21   couple a year but there are other activities that have
22   gone on in this area that have encouraged additional,
0070
 1   you know, more studies to be done in children which we
 2   certainly want to help facilitate.  So that suggests,
 3   as somebody said earlier that, you know, instead of
 4   one or two per year it could be 10 or 12, but I would
 5   be surprised if it moves in that direction very
 6   quickly.  So I would anticipate that we're looking at
 7   a continuing work load of maybe two, three or four per
 8   year.  I'd be surprised if to got up to a dozen.
 9               DR. FISHER:  I thought maybe we could just
10   ask Dave LePay if he sees -- if he wants to say
11   anything from an FDA perspective or whether you have
12   another sense of anything that's coming down the pike
13   that might be joint reviews in terms of numbers and
14   then I think Ernie wants to say something.
15               DR. LePAY:  I would probably just comment,
16   you know, at this point, of course, we have achieved
17   just in the past week or week or so pediatric
18   legislation.  We're certainly going to be evaluating
19   that in terms of its implications for pediatric
20   research for trials as well as for our own operations
21   in this area.  So it's very difficult for me to
22   comment until we've actually had a chance to evaluate
0071
 1   that a bit further.  Of course, our experience with
 2   Subpart D is much shorter than OHRP's.  Our regulation
 3   has only been in place well, certainly for, what a
 4   couple of years now perhaps and we've seen a
 5   relatively small number of protocols so far.  It's
 6   very difficult again, to guess whether any of these
 7   changes that are coming forward will have impact to
 8   there.  
 9               At the moment, we certainly are not seeing
10   that but that's -- you know, this is just -- we're all
11   in the stage of educated guesses at this point and
12   obviously, we're committed to working with OHRP to
13   make sure that the panel process works as far as for
14   both of us jointly and I think that's probably as far
15   as I can comment at this stage.
16               DR. FISHER:  Thank you.  Ernie?
17               MS. KORNETSKY:  Can I just --
18               DR. FISHER:  Oh, sure.
19               MS. KORNETSKY:  From sort of an
20   institutional perspective since I've been involved in
21   pediatric research for about 20 years, I think, you
22   know, my sense is we are beginning to see things that
0072
 1   are coming closer to -- I mean, to it and I don't know
 2   whether they're institutions but we're -- years ago,
 3   I don't think there was anything that came close to
 4   407.  We're beginning to hear things that are sort of
 5   borderline, so my sense is that we may see, you know,
 6   some and I think perhaps maybe some in the past were
 7   not submitted because the process was not good, so we
 8   think we're seeing better education of what needs to
 9   come before 407 and the new initiatives to do more
10   pediatric research there may be some but I agree with
11   Dr. Schwetz, I don't think it's going to be lots of
12   them, but I think we may see a couple a year.
13               DR. FISHER:  Ernie -- oh, okay.  Ernie and
14   then Nigel.
15               CHAIRMAN PRENTICE:  I think we need to
16   recognize that the number of 407 applications may be
17   dependent upon how the regulations are interpreted. 
18   We don't have any concrete interpretations we all
19   agree upon right now and that determines how you
20   categorize the research in the first place.  So the
21   IOM report is going to give us some guidance.  SACHRP
22   is certainly going to have to look at the IOM report
0073
 1   and try to formulate recommendations for
 2   interpretation of Subpart D and that's going to
 3   dictate how many protocols we might ultimately get. 
 4   I mean, how do you determine what's a minor increase
 5   over minimal risk?  
 6               Well, if you utilize an irrelative
 7   standard that has wide latitude, then you can probably
 8   categorize protocols under 406 but if you have a
 9   rather narrow threshold, then it might kick it up to
10   407.  So that would be the first point I would like to
11   make.
12               The second point is, it's been my -- you
13   know, my perspective over the years that IRB's right
14   now don't really understand Subpart D as it exists. 
15   And there are probably quite a few protocols that
16   could have gone up to 407 panel review that did not go
17   because they didn't really understand the regulations
18   as we currently sort of interpret them as a common IRB
19   community.  The third point is that if you extend the
20   407 review process to non-federally funded research at
21   institutions that have FWAs, theoretically you're
22   going to increase the workload quite significantly, so
0074
 1   I think we need to recognize that.  
 2               The fourth point I want to make is we have
 3   15 minutes left and I'm sure that we could continue
 4   discussing this all day, so there are some things that
 5   I want to accomplish in the next 15 minutes.  Now, the
 6   one thing I want to accomplish is the name change,
 7   which should be relatively simple to achieve.  The
 8   second thing is the algorithm which we discussed last
 9   time but we've not really touched upon it this time. 
10   I would like to get that out of the way.  The third
11   thing is to continue getting direction to the
12   subcommittee from SACHRP as to what they're expecting
13   you to do next because you have a meeting coming up in
14   January, is that not correct?
15               DR. FISHER:  January 9th.
16               CHAIRMAN PRENTICE:  And we're going to
17   expect another report arising out of that meeting for
18   our consideration at the next SACHRP meeting.  So we
19   need to try to get this done in 15 minutes.  If we
20   can't do it all in 15 minutes, there is some
21   flexibility later on during the day, so I just want to
22   make you aware of the time constraints here.
0075
 1               DR. FISHER:  Then let me ask whether there
 2   is guidance.  Do we have any -- I don't know what our
 3   process should be for determining this but you know,
 4   whether there's a ranking of the two models for our
 5   subcommittee to consider because I do want to go back.
 6   You know, otherwise, if we don't have a ranking we're
 7   really just going back and doing what we just did and
 8   so I'd really prefer -- I think Susan and I would just
 9   really prefer some type of ranking and I know that --
10   Bob and then Mark.
11               DR. HAUSER:  I think there are two
12   questions.  One is the process.  The other is do we
13   believe in consensus?  And I would like to know how
14   important we feel consensus is around this issue.
15               DR. FISHER:  Mark?
16               MR. BARNES:  Just to get something out of
17   the way, can I make a motion that we change the name
18   of the committee as proposed and we adopt the
19   algorithm that has been recommended by the
20   subcommittee.
21               DR. POLAN:  Second.
22               CHAIRMAN PRENTICE:  Second, all right,
0076
 1   I'll take over at this particular point because this
 2   is now SACHRP business.  There's been a motion
 3   forwarded, there's been a second.  Is there any
 4   further discussion?  Let's get a vote.  All those
 5   signify by raising your hands.
 6               Any opposed, any abstentions?  Motion
 7   carries so we now have two things done.
 8               MS. KORNETSKY:  Thank you, Mark.
 9               DR. FISHER:  Thank you, Mark.  Okay, back
10   to Robert's question, how important is consensus and
11   whether or not there's an advantage?  Does one model
12   have a consensus advantage and I think Robert's other
13   point was, is there a distinction in the level of
14   human subjects' protections between the two models. 
15   Yes, Susan.
16               DR. WEINER:  I often work in a community
17   that operates by consensus and once the consensus is
18   achieved, it's not re-reviewed and essentially what
19   we've got here is two additional levels of review
20   after some consensus is achieved.  So the initial
21   consensus is not really a consensus, it's a
22   recommendation.  So I'm not really sure how valid that
0077
 1   concept is in this context.
 2               DR. FISHER:  Yes, Felix?
 3               DR. GYI:  I just wanted to raise a point
 4   relating to what Susan had said before and a slide
 5   that Ernie had put up there when he addressed --
 6   introduced this topic.  You know, the question of
 7   whether Baby Fay's procedure might have been
 8   considered research or not is still debatable.  I
 9   think that even today if we had such a procedure that
10   needed to be conducted, going through a process like
11   this of the nature that we're talking about would have
12   obviated the delivery of the type of surgical care
13   that that child would have needed. 
14               CHAIRMAN PRENTICE:  It was clearly
15   research, it was an IRB review at Loma Linda.
16               DR. GYI:  All right, if we assume that to
17   be true, how can we subject that -- this process to
18   that procedure?
19               MS. KORNETSKY:  That's a good point.
20               DR. FISHER:  And I think your point raises
21   two issues. One was what Ernie was talking about
22   before, I think or Bern, in the sense that definitions
0078
 1   of research really need to be addressed and that might
 2   become a priority of our committee for many subparts
 3   and the second is, you're addressing the issue of
 4   timeliness and I think that was Susan's issue as well. 
 5   Mary.
 6               DR. POLAN:  It actually bears on the thing
 7   that I wanted to bring up, which if we've only got 15
 8   minutes, I'll say it really fast.  I heard two
 9   different things in terms of broadening the groups of
10   research that need to come under 407 review, and I'd
11   like to know which is really -- what you're really
12   talking about.   One in the slide was it should apply
13   to all research projects coming through, you know,
14   people who get NIH money, whether or not NIH or
15   government monies sponsor it. 
16               The next thing I heard was it should apply
17   to all children's research.  So those are two
18   different concepts and I'd like to know what you think
19   because monitoring and enforcing that is really
20   difficult. 
21               DR. FISHER:  I think that that's not
22   something we're recommending now.  I think that will
0079
 1   be our next subcommittee meeting because it is very
 2   complex.  And so getting back to the question at hand,
 3   is there -- let me ask it this way; are there specific
 4   improvements to the common process that SACHRP wants,
 5   you know, those numbers 1 through 12 that I
 6   highlighted?  Were those -- okay.
 7               Then the second question is, are there
 8   aspects of the non-FAC open panel, non-consensus as a
 9   panel model but face-to-face that the committee would
10   -- that we haven't raised that the committee thinks
11   needs to be considered that could make that model more
12   greatly improved?
13               MR. BARNES:  I'm not sure that this will
14   make it improved but I just think it's worthwhile
15   noting like there is an institutional burden that
16   differs between the two models that the subcommittee
17   has put forth.  In one there may be a panoply of
18   experts who have sharp disagreements, perhaps about
19   something in which case the institutional burden
20   really falls on the staff of OHRP to reconcile those.
21   Okay, and so that's where the institutional burden
22   lies.
0080
 1               And the other model that you've proposed,
 2   the institutional burden would lie on this committee
 3   to reconcile those things.  I mean, ultimately we give
 4   a recommendation to OHRP but the -- you know, the
 5   brunt of the responsibility or at least half of it is
 6   going to rest here.  That is different.  I'm not sure
 7   which one is preferable but that is a different
 8   result.
 9               And the final thing I would say that
10   personally I agree with Bob Hauser.  I mean, I think
11   that consensus is a good thing when you discuss risky
12   protocols because it goes together and it tends to
13   even out the rough edges and satisfy legitimate
14   concerns on all sides.  So I think -- personally, I
15   think that's a great benefit.  However, I think that
16   the timing point is also critical.  So it would be
17   nice, I mean, in terms of what my personal preference
18   would be to be able to have a consensus model that
19   satisfied, you know, the -- or ameliorated the timing
20   problems so that these things could be expedited.
21               DR. FISHER:  So it seems to me one of the
22   things that you might want our subcommittee to do
0081
 1   would be to number one, explore the consensus issue in
 2   both of those models in terms of the pros and cons,
 3   but number two, it seems as if we need a non-
 4   cumbersome model to be able to accept -- if SACHRP
 5   adopted the subcommittee model, we really need to fine
 6   tune something to which we're not taking up more time,
 7   we have explicit criteria, we could accept the
 8   subcommittee recommendation and you know, I'm
 9   wondering, we gave you our best at this point.  Are
10   there recommendations for that and is that a priority.
11               CHAIRMAN PRENTICE:  Let me throw something
12   out.  There are 407 reviews and there are 407 reviews. 
13   They're not all alike, even though they do get kicked
14   upstairs for review.  What about the possibility of
15   thinking about triaging 407 reviews up to the level of
16   SACHRP under exceptional circumstances where you want
17   a consensus model.  You think it's absolutely vitally
18   important considering the nature of the research
19   protocol; whereas for other 407 reviews, they do
20   qualify for a 407 review but they're not as
21   problemmatic and certainly I know that there are a lot
22   of protocols that I looked at where I don't think it's
0082
 1   necessary for it to go through two layers of consensus
 2   review.  Whereas, there is probably one or two
 3   protocols that I looked at where I would be feeling
 4   pretty comfortable if it did.  So perhaps that's
 5   something that your subcommittee could consider.  I
 6   don't know, Bern, is it possible to have two different
 7   kinds of 407 reviews within the federal bureaucracy?
 8               DR. SCHWETZ:  Well, if I understood your
 9   recommendation correctly, the review by a non-FACA
10   panel would be common to all reviews and some of them
11   would be referred back -- would be referred to SACHRP
12   for additional consensus consideration.
13               CHAIRMAN PRENTICE:  Correct.
14               DR. SCHWETZ:  So then you don't really
15   have two models. You have one and you have an expert -
16   - or you have another opportunity for consultation
17   beyond the standard model; is that correct?
18               CHAIRMAN PRENTICE:  Yes.
19               DR. FISHER:  Is that possible?
20               DR. SCHWETZ:  Yeah, I think it is but it
21   would be -- it won't be easy to define what's the
22   trigger for coming to SACHRP.
0083
 1               MS. KORNETSKY:  My concern about that is
 2   if it's so controversial with the group of experts who
 3   really know in detail the issue, I'm not so sure that
 4   I'm going to have the expertise and with all due
 5   respect to my colleagues here, that they're going to
 6   have the expertise to resolve those differences as
 7   consensus.
 8               CHAIRMAN PRENTICE:  Then if that is,
 9   indeed, true, then why are we talking about having a
10   consensus model at all at the level of SACHRP? 
11   Correct?
12               DR. FISHER:  Exactly.  
13               MR. BARNES:  It seems to me -- I mean, the
14   reason that we're thinking about consensus at the
15   level of SACHRP is because like an IRB where everyone
16   that is on the IRB doesn't have expertise in every
17   protocol that comes up, it's because the questions
18   that tend to be the most difficult are after the
19   science and the medicine has been defined and then the
20   question is really one of ethics.  I mean, that's the
21   reason that you want, I think, consensus.
22               DR. FISHER:  Susan.
0084
 1               DR. WEINER:  But then the consensus is at
 2   the level of the subcommittee.  Then at the level of
 3   SACHRP, under reconsideration, then essentially at the
 4   level of OHRP to make its recommendation -- to take
 5   under advisement whatever the opinions were.  The
 6   consensus also allows the opportunity for alternative
 7   opinion without -- to be expressed without standing in
 8   the way and hopefully whatever, you know -- if we go
 9   this route there would be that opportunity.  
10               But to get back to my original point, you
11   know, once consensus is arrived it's not really
12   because it has to be re-reviewed.
13               MS. KORNETSKY:  I would also like to
14   address a point that Mark made and that consensus
15   either at a subcommittee or SACHRP level is not a
16   panacea for OHRP because they have to make their own
17   independent decision anyway.  So I just -- you know,
18   that was something I hadn't realized until we had our
19   subcommittee meeting and so I think that you know,
20   that's important to take into account.  
21               Does anybody want to make a recommendation
22   for where our subcommittee should go with this?  I
0085
 1   think it's important -- we can go a number of ways. 
 2   One is you can advise the subcommittee to address the
 3   issue of consensus and timeliness.  We can tell the
 4   subcommittee that you've approved the other steps that
 5   are not involved and who that panel is and how it
 6   worked.  
 7               And do you want the subcommittee to come
 8   up with a specific -- to rank for you the models at
 9   their next meeting?
10               CHAIRMAN PRENTICE:  Can I make a
11   suggestion here?  We've had a lot of discussion about
12   the different models, the advantages and disadvantages
13   and I understand that people need to think more about
14   it, but I would be interested in knowing what they're
15   thinking right now, which way are they leaning.  I
16   think that would be helpful to your subcommittee when
17   you go back to discuss these issues, so perhaps you
18   might consider kind of taking sort of like a poll here
19   of the two models and how people -- you know, are you
20   inclined to go with one or the other?
21               DR. FISHER:  As Chair, would you like to
22   do that?
0086
 1               CHAIRMAN PRENTICE:  All right.  So we have
 2   two models here.  We've got the non-FACA model with
 3   the enhancements to produce greater transparency,
 4   public input, et cetera, you know, to improve the
 5   entire process.  We've talked about how that can be
 6   done and I think we all agree on that.  And then we
 7   have the FACA model which has to be a subcommittee of
 8   SACHRP.  Then we talked about this other sort of
 9   hybrid thing, but let's put that on the shelf for the
10   time being.  
11               So I'm going to ask for sort of like a
12   straw vote here of how many people are in favor of the
13   FACA SACHRP subcommittee model, raise your hands.
14               DR. FISHER:  And Susan and I are
15   abstaining, by the way.
16               CHAIRMAN PRENTICE:  Yes.
17               DR. FISHER:  Don't look at us.
18               CHAIRMAN PRENTICE:  Raise your hands. 
19   Okay, nobody.  How many are in favor of the non-FACA
20   model with the enhancements, raise your hands?  How
21   many people are abstaining?  Okay, so there are a
22   couple of -- okay, so clearly that gives you an
0087
 1   indication of the leaning of the committee.
 2               DR. FISHER:  Okay.
 3               CHAIRMAN PRENTICE:  In the next two
 4   minutes, is there any final directions you want to
 5   give to the Subpart D Subcommittee?  All right, so
 6   what we're going to expect is further consideration of
 7   these issues and a recommendation from the
 8   subcommittee for one model and the reasons why, okay? 
 9               All right, we're going to now take a 15-
10   minute break.  We're about three minutes behind, so
11   we'll reconvene at -- right about -- a little bit
12   before 20 of or 10 of.  
13               (A brief recess was taken.)
14               CHAIRMAN PRENTICE:  The next item on our
15   agenda is a report from the co-chair of the Subpart C
16   Subcommittee dealing with additional protections for
17   prisoners who are involved in research as subjects and
18   Mark Barnes is going to deliver that particular
19   report.  So Mark, would you take over?
20               MR. BARNES:  Thanks, Ernie, and thank you
21   for the time to present on behalf of the subcommittee
22   today.  Nancy Dubler, who is a Professor of Social
0088
 1   Medicine at Montefiore Medical Center  in New York and
 2   I were asked by -- actually by NHRPAC first, the
 3   predecessor committee to this one, to chair a -- to
 4   co-chair a subcommittee or working group on looking at
 5   the problems, the interpretation and application that
 6   seemed to lurk in Subpart C governing federally funded
 7   research, federally supported research involving
 8   prisoners or people in correctional custody and that
 9   committee was constituted for about a week and then
10   NHRPAC was disbanded and, of course, now we're with
11   SACHRP and Nancy Dubler and I were asked by Ernie
12   Prentice to co-chair this working group.  
13               It was actually a nice coincidence because
14   Ernie had first asked me to co-chair the group and
15   asked whom I would recommend to co-chair the group and
16   he and I had come to the same conclusion without his
17   even knowing that Nancy, in fact, had been the co-
18   chair of the previous NHRPAC working group.  
19               Nancy is not here today and I'm giving the
20   report for both Nancy and myself and the other members
21   of the subcommittee but she has a deep experience in
22   correctional issues since Montefiore Hospital for many
0089
 1   years had the contract with the New York City
 2   Correctional System to run the Rikers Island
 3   Correctional Facility in New York which actually is
 4   the largest penal colony in the world with
 5   approximately 20,000 people at any one time on one
 6   island and with multiple health needs, everything from
 7   tuberculosis to HIV to diabetes and many, many other
 8   chronic conditions facing people who are incarcerated
 9   there.  
10               We put together, with Ernie's direction or
11   under Ernie's direction, a subcommittee consisting of
12   people who -- I guess about 10 or 12 members, and the
13   roster is in your package today under one of the tabs
14   and I won't go through the membership but suffice it
15   to say that it includes many people with deep
16   experience in correctional health care and also in
17   corrections administration both of which are truly
18   important to areas of expertise to this process.  
19               We met for a full day on a cold day in
20   December.  We were hosted, actually, at the OHRP
21   headquarters and we are deeply grateful to Cathy and
22   also to Karena Cooper, who's sitting back here, who
0090
 1   has run some of the Secretarial Consultation Panels or
 2   all of them in recent memory in regard to these
 3   protocols that require Secretarial review and the
 4   committee met in person and we discussed a whole
 5   variety of issues but we were primarily directed by
 6   the initial charge to the committee to the NHRPAC
 7   Committee that had been authored by Greg Koski, when
 8   he was Bernie's predecessor as Director of OHRP and
 9   then there was some additional guidance that was given
10   by OHRP and the current administration of OHRP.  Both
11   of these are also tabs in the binder.
12               We went through both Greg Koski's original
13   charge.  We went through the additional questions that
14   were asked or posed to the committee, the subcommittee
15   by OHRP and we had really what I think was a full and
16   a rich day of discussion about the issues.  The
17   problem with Subpart C is -- I mean, there are a
18   number of problems and I'll sort of try to illustrate
19   them briefly today and talk about some of the major
20   topics that we discussed and where we're going in our
21   analysis and in our proposed schedule for
22   recommendations to SACHRP, but there are a number of
0091
 1   problems that lurk.  This set of regulations, the
 2   Subpart C regs, were, as was said before by the
 3   Assistant Secretary, they were drafted and adopted in
 4   1978.  They actually -- unlike some of the other
 5   sections, especially of course, Subpart A, these regs
 6   in Subpart C basically have been adopted only by three
 7   federal agencies.  They've been adopted by HHS. 
 8   They've been adopted by the Social Security
 9   Administration and they've been adopted by the Central
10   Intelligence Agency, believe it or not.  The -- so the
11   other agencies are left out of this.
12               One of the original items that emerged and
13   something that has been -- has really demanded
14   clarification for a long time and I think that the
15   subcommittee has been grateful, especially to the OHRP
16   staff and to General Counsel's office at HHS for
17   answering these questions, relate to the questions of
18   what exactly the jurisdiction of Subpart C is and
19   exactly what studies actually are required to go
20   through what steps under Subpart C.  There's a --
21   suffice it to say, there's a lot of confusion out
22   there among IRB's as to exactly what Subpart C covers
0092
 1   and what it ought to cover and what they ought to do
 2   with protocols that involve people in correctional
 3   custody.  Now, what we did and the way that I'm going
 4   to organize the presentation today is that we, through
 5   a whole series of discussions that day, we tried to
 6   take things thematically and we tried to take things
 7   in clusters of issues, and after a full day's
 8   discussion, we basically were able to group the
 9   questions under Subpart C, the areas of ambiguity, the
10   areas that we thought merited sustained attention by
11   the Subcommittee, into about eight groups of issues.
12               And those eight groups of issues, we then
13   assigned members of the subcommittee in teams of
14   either two or three to work on these issues and just
15   to make the -- so you understand the process, what
16   we've asked these teams to do and I will go through
17   the list of issues with you and describe some of them,
18   we asked the teams to have a -- to consider among
19   themselves, among the two or three members of the team
20   or working group, the constellation of issues that
21   have been -- that had been assigned to them and then
22   to report back in a very substantive way with a full
0093
 1   discussion of the issues or a fuller discussion we had
 2   had on that one day in December as well as with
 3   recommendations to the full committee when we have our
 4   next meeting, full day meeting in January.  We asked
 5   them to do that and then we would have a sort of round
 6   table discussion in more depth than we were able to
 7   have in December about the issues and hopefully reach
 8   some at least initial conclusions or recommendations
 9   about the issues in January with an additional two-
10   month process after the January meeting of writing up
11   the recommendations and trying to come up with a draft
12   report.  
13               Those people who are assigned to the teams
14   presumably would write those portions of the report
15   that would fall under the issues that were assigned to
16   them.  So basically what we're looking at just in
17   terms of schedule, Ernie, is we're looking at an
18   additional meeting, a full-day meeting in January. 
19   We're looking at write-ups and drafts that go forward
20   in February and March and we're looking for an
21   additional meeting in March with a report back to this
22   committee either at its next meeting or -- when is the
0094
 1   next meeting of this committee actually?  Is it in
 2   March or -- when in March is the -- 
 3               A VOICE:  It's the first Monday and
 4   Tuesday in March.
 5               MR. BARNES:  I have a feeling we will have
 6   a draft for you before that meeting actually.  And it
 7   will be a draft, obviously, and it will be -- we can
 8   give a presentation.  Nancy and I can give a
 9   presentation then with time, not only during the
10   meeting but afterwards for this committee as a whole
11   to comment on the draft.  So that's the process.
12               Now, let me go through the groups of
13   issues that we -- to which we've assigned these teams
14   of subcommittee members.  First of all, and Karena, if
15   I misspeak about anything, you are truly the world's
16   expert on Subpart C so if I misspeak, then please, you
17   are not going to offend me by interrupting me.  
18               The first thing is, as I had mentioned,
19   the issue of the jurisdiction of Subpart C and exactly
20   what it covers.  Subpart C actually, and some of us
21   learned this for the first time, and I won't say that
22   I learned the whole thing for the first time, but I
0095
 1   certain learned pieces of this for the first time in
 2   our meeting in December.  Subpart C really is meant to
 3   cover only research that is funded or supported by HHS
 4   itself.  That's really all it covers.  And the
 5   processes that are demanded both for certification to
 6   the Secretary that certain standards have been met and
 7   also that -- including a certification that the
 8   research falls into one of four categories in Subpart
 9   C, and only those categories may be -- or constitute
10   research that may be conducted among prisoners, those
11   kinds of steps are required strictly speaking, only
12   for research that is supported or funded by HHS.
13               The other thing that may not be
14   immediately apparent and there's been a lot of
15   confusion out there is that just because an
16   institution signs an FWA, does not mean that the
17   institution must actually agree to Subpart C.  In
18   fact, and we had some figures bandied about, but a
19   sizeable proportion of those institutions that sign
20   federal-wide assurances in fact ascribe only to
21   Subpart A or perhaps to Subpart A and D but they do
22   not subscribe in large measure to the protections of
0096
 1   Subpart C.  When they do ascribe to them and incur
 2   voluntarily the obligations of Subpart C of meeting
 3   those standards, then they acquire some responsibility
 4   to have -- to internally, have an internal process
 5   that essentially replicates what is done for HHS
 6   funded studies at the federal level, that is a
 7   certification that the studies meet the seven
 8   requirements or seven criteria for research conducted
 9   among prisoner, but they essentially -- it's an
10   internal process with internal record keeping that may
11   be reviewed by OHRP in an audit, a site visit or audit
12   or driven by a complaint but only if, again, that
13   institution actually voluntarily has ascribed to --
14   has subscribed to the requirements of Subpart C in its
15   federal-wide assurance which again, is not required
16   except for federally funded -- for HHS funded or
17   supported research.
18               The other piece of that which is part of
19   the -- of a definition that we think needs some
20   clarification in looking at and there was some --
21   there clearly was some ambiguity in answers that we
22   received from a very well-intentioned and well-meaning
0097
 1   and I'm sure very hard-working attorney within the
 2   General Counsel's office at HHS, who may actually be
 3   here for all I know, and that is what is meant by
 4   federally funded or federally supported.  
 5               Now, clearly if a grant is actually -- a
 6   research grant from NIH, from CDC and it has as its
 7   targeted population or as part of its targeted
 8   population those who are in correctional custody, then
 9   that would be research that would be supported by HHS
10   or PHS, therefore HHS.  But there are additional
11   situations, for example, when the GCRCs give
12   infrastructure funding, when the NIH has salary
13   support for an investigator, not dedicated to a
14   particular study but general salary support for an
15   investigator and research on prisoners is conducted by
16   that investigator with salary support from HHS, is
17   that research that is supported by federal HHS
18   funding?  And there are some ambiguities there and I
19   think that we got the answer that we received from
20   counsel's office at HHS is that all of those
21   ambiguities have, in fact, not been worked out.
22               The bottom line is that although the --
0098
 1   really is this in terms of the jurisdiction.  In the
 2   process of adopting the Common Rule Subpart A and also
 3   adopting -- making these recommendations when the
 4   National Commission was meeting in the `70's, making
 5   these recommendations about the need for additional
 6   protections for research, human subjects research
 7   conducted among persons who are in correctional
 8   custody, there was a policy decision made that those
 9   persons in general are deserving of a greater level or
10   higher level of scrutiny of research projects in which
11   they might be enrolled or would be offered enrollment.
12               The background of that, of course, is that
13   in many cases especially in the 1960's and before,
14   Phase 1 studies were widely conducted on prisoners
15   really kind of with or without their consent.  They
16   were just -- prisoners were told, "You're going to be
17   enrolled in a Phase 1 study", and they would all be
18   given Phase 1 drugs and the adverse effects or absence
19   of adverse effects would be monitored. 
20               There was other research that was
21   ethically highly questionable, one study of which
22   Ernie talked about this morning regarding deliberate
0099
 1   exposure of prisoners, state prisoners to malaria that
 2   were conducted and that were highly questionable and
 3   also highly questioned in the National Commission's
 4   research on the subject and its review.  
 5               Actually, the National Commission report
 6   is in the materials today and I really recommend it
 7   for your reading.  It's a very interesting historical
 8   document.  It talks -- and it will tell you actually
 9   how much the debate has changed or the terms of the
10   debate, because at that point, when the Commission met
11   and was discussing these issues, a log of hat it was
12   talking about was really protecting prisoners from
13   research, whereas a lot of the things that Nancy and
14   I and other members of the committee -- of the
15   Subcommittee had heard was kind of on the opposite end
16   of the spectrum of prisoners wanting access at this
17   point, to protocols because they feel like there would
18   be better healthcare that would accompany those
19   protocols which has its own ethical issues, but
20   there's certainly a difference in emphasis of the
21   debate and discourse at this point.
22               So despite the fact that there was this
0100
 1   general kind of consensus reached by the National
 2   Commission that prisoner because of the special
 3   circumstances in which they find themselves, the
 4   possibility of coercion, the possibility of really of
 5   there not being any kind of voluntary informed
 6   consent, the possibility that the full research
 7   apparatus with the reporting of adverse events and IRB
 8   review and frankness in disclosures to IRB might not
 9   be met because of the larger context in which the
10   research might take place, all of these things were
11   pointed out by the National Commission in its report
12   but what eventuated was a statute, Subpart C, that is
13   only applied voluntarily to non-HHS funded research.
14               So there is a wide variety of research
15   going on out there that involves prisoners that is
16   done even by researchers who are at institutions that
17   signed FWAs but if the research is not supported by
18   HHS, if it's not funded by HHS, and if the -- and/or
19   if the institution has not voluntarily submitted
20   itself to the jurisdiction of Subpart C, that research
21   does not have to comply with the Subpart C standards
22   or with any of the special protections that are
0101
 1   offered in Subpart C.
 2               So in regard to the first question of
 3   jurisdiction, the committee asked a couple of people
 4   and actually those people are sitting at the table,
 5   Ernie Prentice and myself, to look at the issue of the
 6   jurisdictional definitions and whether it would be --
 7   whether it should be a broader jurisdiction for
 8   Subpart C, whether the jurisdiction for Subpart C,
 9   even if the wording of Subpart C were not changed,
10   could be broadened through interpretations or expanded
11   in certain ways through interpretations that would be
12   legally viable but nevertheless would offer people in
13   correctional custody some additional protection or
14   higher level of scrutiny for research.
15               So that is one working group is just
16   looking at the question of jurisdiction.  Karena, did
17   misspeak on anything or did I get it right?  Okay,
18   thank you.  
19               The second working group is looking at
20   what is kind of a jurisdictional issue in and of
21   itself, and that is who is a prisoner.  Certainly
22   people who are in state or federal or local
0102
 1   correctional custody in a county jail or a city jail
 2   or a state prison or federal prison, those people
 3   would by anybody's estimation be in correctional
 4   custody but what about people -- and by the way there
 5   is some OHRP guidance on this but the committee -- the
 6   subcommittee thought that even the guidance deserves
 7   some scrutiny to see whether we would agree with the
 8   decisions made at this point, but what about people
 9   who are involuntarily committed to mental health
10   facilities because they are criminally insane.  
11               What about people -- and there is an
12   emerging group of people like this, who actually serve
13   prison sentences under state laws because of sexual
14   abuse of minors but then they are not released even
15   after their sentence ends because they are
16   involuntarily mentally committed, involuntarily
17   committed in a kind of quasi-criminal proceeding based
18   on their propensity or alleged propensity to commit
19   future crimes and recommit the crimes for which
20   they've been originally incarcerated, what about those
21   people in that sort of after they've served their
22   sentence but before they've actually been released
0103
 1   from some kind of involuntary confinement?  
 2               And then of course, there's the range of
 3   people who are on parole, probation, halfway houses,
 4   et cetera.  There is guidance about this and I won't
 5   go into all of it but there are areas of ambiguity. 
 6   In addition to that, in regard to who is a prisoner,
 7   one of the difficulties that researchers have found in
 8   regard to dealing with Subpart C when they have to
 9   deal with Subpart C is that when one has a study and
10   the study was never intended really to encompass
11   incarcerated populations or prisoners within the
12   subject population, but all of a sudden in the middle
13   of the study one person becomes incarcerated, then
14   oddly enough even if the person was voluntarily
15   enrolled in the study years before in a longitudinal
16   study, he or she was incarcerated, once they go into
17   correctional custody, Subpart C may apply.  
18               And at that point the individual
19   investigator would -- assuming the study was federally
20   funded or the study was conducted under the
21   jurisdiction of an IRB, that had signed an FWA, that
22   voluntarily submitted the institution and the IRB to
0104
 1   Subpart C, would have to file an application under
 2   Subpart C to meet all the criteria of Subpart C even
 3   for one person who had gone into correctional custody
 4   during one point in the study.  And this has been a
 5   kind of nightmare, I think it's safe to say, that at
 6   least we heard from some of the subcommittee members
 7   in regard to attempted compliance with Subpart C.
 8               There is, by the way, one exception under
 9   OHRP interpretation, which is that when a person is in
10   an interventional clinical trial and the person goes
11   into correctional custody and the researcher or
12   principal investigator deems that it is essential that
13   the person continue to receive the medication or
14   treatment, essential for his or her own health, they
15   can do that for a short period of time pending IRB
16   review and approval under a full Subpart C
17   application.
18               But I think it's fair to say is that
19   really deterring research among populations that may
20   be at risk for incarceration, is it an unneeded burden
21   on existing research and so that is -- those are among
22   the questions that are going to be looked at by that
0105
 1   working -- but that sub-working group.  
 2               The third working group or third team, is
 3   looking at the question of the role of the mandated
 4   prisoner representative on an IRB that considers
 5   studies that fall under Subpart C.  There is a
 6   requirement that there be a prisoner or prisoner
 7   representative who is on the IRB that will consider
 8   the studies but the empirical question that we want to
 9   ask and at least gather antidotal evidence on would be
10   what -- who actually is selected to be the prisoner
11   representative, what are they supposed to do or what
12   perspective are they really supposed to bring to bear,
13   are they doing it successfully and what -- how does
14   the requirement work out in regard to multi-site
15   studies because in multi-site studies actually what
16   the  regulation of Subpart C allows you to do, allows
17   the researchers to do is actually have a prisoner
18   representative only on one of the IRBs in a multi-site
19   study where the other sites actually have IRBs that
20   are approving the study that have no prisoner reps on 
21   them.  That is entirely allowed by the existing
22   regulations and the question is, is that really -- is
0106
 1   that good enough to achieve the objectives of Subpart
 2   C.
 3               And then an addition question is how can
 4   we -- what should be the criteria, if it's not going
 5   to be a person who is formerly in correctional custody
 6   or even if it is, if it's simply going to be a
 7   prisoner representative or someone who has empathy for
 8   the population or an affiliation with the population
 9   because for example, they have been a health provider
10   to the population, because they had family in
11   correctional custody, what kind of criteria should be
12   applied to a person who would actually qualify as a
13   prisoner representative under that requirement?  So
14   that is the -- that's the third set of issues.
15               The fourth set of issues is in regard to
16   terminating studies and one of -- it's quite odd
17   actually, maybe not odd, maybe there's a reason for
18   it, but one of the criteria among the seven criteria
19   for the approval of studies under Subpart C is a kind
20   of follow-up requirement that is not present in any of
21   the other subparts and that is the final, the seventh
22   requirement in regard to the IRB approval of the study
0107
 1   that falls under Subpart C is that the Board -- where
 2   the Board finds -- the IRB finds that there may be a
 3   need for follow-up exam or care of participants after
 4   the end of the participation, the IRB must assure
 5   itself that adequate provision has been made for such
 6   examination or care or -- I'm sorry, taking into
 7   account the varying lengths of individual prisoner's
 8   sentences and for informing participants of the fact.
 9               So there's kind of a requirement for
10   follow-up care that you may see guidance about in the
11   Declaration of Helsinki and the different kind of
12   adumbrations of the Declaration that have been added
13   to recently, but you don't see it in the common rule
14   and you don't see it in the other subparts.  So our
15   question is, how is that working?  Is it wise, should
16   it be strengthened?  What does it mean?  How are IRBs
17   interpreting it?  
18               And then finally under that, should there
19   be other issues that explicitly ought to be referenced
20   either in Subsection 7, that seventh criterion, or in
21   OHRP guidance on the seventh criterion in regard to
22   what should happen when these studies end.  And
0108
 1   obviously, I mean, not to beat around the bush, the
 2   issue here is if an inmate in correctional custody
 3   gets better healthcare because they're enrolled in a
 4   study than he or she would if they were not enrolled
 5   in a study, then what should the provision be, what
 6   should the ethical standard be for what's going to
 7   happen when the researcher and the research team
 8   leaves the correctional facility?  So that's the
 9   fourth set of questions. 
10               The fifth set of questions really focuses
11   on the fact that for studies for research that falls
12   under Subpart C, there -- and this is under one of the
13   tabs, the actually regulation for Subpart C is under
14   one of the tabs in the binder that the committee
15   members have, there actually are only four categories
16   of research that may be approved.  If a study does not
17   fall under one of the four categories of research,
18   then it may not be approved at all by the IRB or by
19   OHRP if it goes up to the OHRP level and those -- and
20   two of the four set of categories actually embrace a
21   minimal risk standard which I'll get to in a second,
22   which is different than the minimal risk standard that
0109
 1   we all know and either love or don't love in the
 2   Common Rule in Subpart A.  But the question here, and
 3   this is one of the -- perhaps that largest kind of
 4   task for one of our working groups, is to ask whether
 5   these four categories make sense?  Are they too
 6   restrictive?  We doubt that they're too broad but are
 7   they too restrictive?  One of the -- one of the kinds
 8   of reports that we got, kind of antidotal report from
 9   Karena and the OHRP staff, is that a lot of what
10   happens here is that individuals, in order --
11   individual researchers, in order to fit their study
12   within the four categories actually may kind of
13   contort the studies to make sure they do fit in one of
14   the four categories when strictly speaking, in terms
15   of the original research intent, it may be very valid
16   and beneficial, beneficent research intent.  It may
17   comport with notions of justice and fairness and
18   everything else, but it may actually