TRANSCRIPT: Meeting Six, Session 4

International Research Panel Results and Discussion

Date

August 30, 2011

Location

Washington, DC

Presenters

Nelson Michael, M.D., Ph.D.

Commission Member

Christine Grady, R.N., Ph.D.

Commission Member

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Transcript

DR. WAGNER:  In our -- thank you, Zeke.  In

  our next section we get to hear from a couple of our

  commission members, Christine Grady and Nelson Michael.

  They served along with our chair, Amy Gutmann, and John

  Arras, on the international search panel, which, as

  Amy noted before, was set up as a subcommittee of this

  commission.  On behalf of the entire commission, thanks

  to the four of you for being engaged in that.

 

            Now, Christine and Nelson will report to us on

  the findings and recommendations of the subcommittee

  that were drafted at the conclusion of your third

  meeting, I believe, in July.

            And according to the terms of reference for

  the international research panel, their task was to

  advise the commission in the following areas,

  commissioners, and that is:  the dominant norms and

  competing alternatives driving ethics of medical

  research and different -- in different global regions

  that are outside the United States; two, conflicts, if

  any, between U.S. norms and international standards,

  something that Zeke was just talking about; three,

  challenges facing researchers conducting U.S.-funded

  research in global settings; and four, possible

  strategies to address differences in regional norms for

  medical research.

            So, with that, which of the two of

  you -- Nelson, you're going to begin?  Welcome, and

  thanks for doing this.

            DR. MICHAEL:  Thank you, Dr. Wagner.  So, I

  thank the commission for allowing Christine and I to

  speak to you today about, I think, a very, very rich

  process that both of us, along with John Arras and our

  committee chair, Amy Gutmann, were really privileged to

  spend time with a large international group of

  colleagues.  And I found it unbelievably informative.

  This is coming from the background of somebody who has

  been doing international research all my professional

  life.  And I learned a lot from these colleagues, and I

  found them both professionally very engaging and

  helpful on this topic, and I think I've made a number

  of lifelong friends, as have we all, on that commission

  subcommittee.  It was a very well-selected group.

            So, the way this is going to occur, I am going

  to talk about the first two recommendations that have

  come out of the report that has been described earlier

  today, and Christine will then take over from me, and

  will describe the next three of the total of five

  recommendations.

            So, I don't want to do much reading, so -- but

  I will just have you look at this, and I will read the

  top line sentence.  So, the first recommendation was

  that researchers must demonstrate respect for human

  subjects and their communities in all phases of

  clinical trial design and implementation.

            Recognizing other cultural standards and

  practices through community engagement -- and that is

  the buzz word -- is one concrete means of showing

  respect.  And here you see two sub-topics that I will

  talk about briefly at the very end of my remarks, in

  terms of increasing ongoing international dialogue

  between U.S. and international bodies as being a

  critical part to protecting human subjects, and also

  touching briefly on equivalent protections, which I

  think you are going to see as a theme multiple times

  here today.

            So, what is community engagement?  That is a

  very large catch term.  And I think that one thing I am

  hoping in the next session to get from some of the

  presenters is their view on some of the more specific

  aspects of what we mean by community engagement.  So

  this isn't just high-minded talk, it can be distilled

  to implementation and meaningful evaluation to see if

  this process truly does increase protection for

  research volunteers, and isn't simply a salve.

            So, I see this, and the panel saw this, as a

  process that was additive to all of the top-down

  normative body and regulatory processes that are

  already in place, to -- and by that I mean scientific

  review, the institutional review board, or ethical

  review committee process.  This is something that is

  additive to what is already in place.  This is a

  bottom-up process to strengthen the transparency of

  research activities.

            In that sense, it's a microphone.  This

  process is a microphone from the community from which

  subjects are embedded to the research activities and to

  the researchers themselves, but also to the related

  communities in which all of us exist.  This would

  include -- and tangible examples of what community

  engagement could be, and manifestations of those would

  be -- community advisory boards, open meetings to

  discuss research activities that are forming and are

  ongoing, what their implications are.  These would

  include invitations for community representation on

  study teams and to bring liaisons from the community to

  normative bodies and non-governmental organizations.

            An essential distillation of this process of

  community engagement, which would be research is

  continuously viewed and struggled with -- and I use

  that term pointedly -- it's struggled with -- by the

  broader number and type of partners that are engaged in

  scientific and clinical research activities to ensure

  that subjects and communities continue to endorse

  benefit outweighing risk.

            So, this addresses and respects international

  diversity and ethics and practices.  However, I think

  it's very, very important to say, and we spent some

  time talking about this as a deliberative body, that

  community engagement is necessary, but it is not

  sufficient, in and of itself, to strengthen bioethical

  standards, and potentially one could expose

  circumstances where community approaches in specific

  cases are actually contrary to overall views of

  bioethics or intrinsic rights that the majority of

  individuals living on this planet would endorse.

            And, therefore, this process may, in fact,

  expose information that would lead research teams to

  actually decide not to do science, not to do research

  in that particular time and place, and could modify

  that science, or even stop the process, all together.

            So, in terms of specifics about community

  engagement, the World Health Organization, UN AIDS, and

  the AIDS Vaccine Advisory Coalition -- and we're very

  honored today to have, in the next session, to have a

  representative from AVAC, the executive director,

  Mitchell Warren, who I'm sure will be talking a little

  bit about good participatory practices.  But this has

  been -- they just released a second version of this

  approach, so there is some granularity to, again, the

  high-minded comments that I am making now.  I think

  there is a process in place to guide us to how one

  would actually implement and actually evaluate this

  process, and I will let -- I'm sure Mitchell will be

  talking about that to some degree.

            Let me just end by pointing to these two

  points that are clarified here, under the first

  recommendation.  There needs to be an increased

  dialogue between U.S. bioethical conversations and

  those which occur in the international arena.  And this

  is, I think, most notably demonstrated by the second

  point -- and this was discussed during Zeke's

  conversation with us, as well, about equivalent

  protections.

            I think we need to embrace the protection of

  subjects over the embrace of compliance with

  regulations.  And in that sense, I think the system

  needs a little more sanity so that we can concentrate

  on that which may be very well and good in an

  international norm -- an example that's given in the

  report is the differential application of annual

  continuing review processes, which are different, as an

  example, between the United States and the United

  Kingdom -- and I think that we need to be reflective on

  how U.S. standards and compliance to those standards

  may, in fact, not truly be enhancing research

  protections.  And there needs to be a dialogue and a

  give-and-take in that sense, so that, ultimately, the

  best thing is done for research participants, either

  here in the United States, or overseas.

            So, let me stop there and go on to the second

  recommendation.  And this is one I don't think I need

  to say much about, because we discussed a lot of this,

  as it worked out, just in the past few minutes.

            So the second recommendation was that funders

  of human subjects research should support ethics

  training for investigators and others, to include IRB

  members.

            Now, this is not as counterculture to

  discussions that we just had emphasizing protection

  over compliance, because part of the discussions

  involve the fact that, yes, we thought it was important

  for researchers to understand that training in

  bioethics isn't just a box-checking exercise, it isn't

  just a requirement.  It needs to be something that

  truly is embraced, so that the scientific process can

  be completely integrated, and not seen as just simply

  an adjunct or a hurdle, in the worst case, to get over

  before science can be done.

            Because experienced investigators will

  understand that even a single episode in their careers

  of lapses in ethical execution of science has very dire

  consequences, not just for individuals, but for

  institutions and their -- and potentially, even the

  entire field in which they are involved in.  So this is

  something that needs to be done in a way that is seen

  as meaningful by researchers, and not simply a burden.

            In that sense, ethical training needs to be

  balanced, in terms of cultural differences that may

  exist between what is done in one's home country and

  what is done overseas, and the sense this research

  needs to be done in a context where ethical training

  isn't simply an onerous online series of endless

  training that is seen as pro forma.

            But that said, as I am a person that is

  subject to a lot of that online endless box-checking

  exercises, I find very little in the current training

  that really has helped me to be an international

  researcher, and I think that that is something that,

  clearly, would be an important strengthening of ethical

  training as we go on, to focus on the implications and

  the differences of doing research, both in the United

  States as well as overseas.

            So, in that sense, I think that would be a

  recommendation that we would have, that that kind of

  training be more focused and have a better rationale

  for the implications for doing the research overseas.

            Let me just close by saying that ethical

  training -- and this is something I think that probably

  Dr. Glass will resonate with and maybe discuss -- I

  haven't seen your slides yet, but this is something I

  think that you will feel strongly about -- is I think

  that we need to strengthen ethical review committees

  and strengthen IRBs overseas.

            When we talk about IRB training, we're not

  simply talking about box-checking exercises for

  individual scientists.  We're talking about a way to

  ensure that, as we, the world community, begins to do

  research in more and more countries, that there is

  equivalent strength of IRBs.

            And I will tell you that, in my own

  experience, the Fogarty International Center, the

  European EDCDP, the WHO, and some of the WHO-associated

  activities, like the African AIDS vaccine program, is

  very interested in spending their resources on ethical

  strengthening of ERCs and IRBs overseas.

            And, importantly, that process is linked to

  normative bodies and oversight by groups like the World

  Health Organization so that, at the end of the day, it

  isn't just a researcher talking to their IRB, their

  institution, saying, "Yes, I sent a team that was

  funded by the Fogarty, it went overseas, it trained

  this IRB, everything is fine, everything is fine now."

  It's never good enough for a researcher to say

  everything is fine.  Others need to look into that

  process.

            So, let me stop there and hand the control

  over to my colleague.

            DR. GRADY:  Okay.  So I want to echo what

  Nelson said, that it was an honor to be part of the

  international panel.  It was a remarkably committed,

  engaged, and thoughtful group of people from around the

  world.  And under Amy's very capable leadership, and

  the staff's indefatigable efforts, we began our work

  right away and in three short days, I think,

  accomplished a lot.

            I am going to talk about the three

  recommendations that are left.  But I wanted to say

  that the recommendations reflect the discussions of the

  panel, and are presented to the commission now for

  consideration.  They are not, like, "finalized," I

  guess, is the way I would think about it.

            And also, that they were based on a set of

  findings that the report also begins to describe, and I

  just wanted to comment on a couple of those findings,

  because I think they're relevant to understand the

  recommendations.

            One of those is that the panel noted that in

  the decades since the Guatemala experiments, there has

  been a number of rules, standards, and principles that

  have been developed for protecting human subjects, both

  in the United States and across the world, and that

  many of these rules and standards actually agree on

  some fundamental principles that do protect human

  subjects.

            Despite that agreement, there is some

  variation.  There are some conflicts.  And there are

  differences in implementation and interpretation that

  sometimes do create challenges, especially in

  multi-national research.

            We also, of course, noted the increase in

  international research, which comes with both benefits

  and potential problems, in the sense that it's very

  important for finding ways to benefit the health of

  people around the world, and understanding differences,

  but it also is true that different places have

  different levels of experience with protecting human

  subjects, and sometimes there are ways to find routes

  around protections.

            So, to focus on the three recommendations,

  this is the third one that the panel came up with:

  Greater efforts are needed to enhance transparency,

  monitor ongoing research, and hold researchers and

  institutions responsible and accountable for violations

  of applicable rules, standards, and practices.  To

  enhance transparency and accountability, governments

  should consider requiring all greater-than-minimal risk

  research to be registered, and results reported.

            I think -- I don't think anyone would disagree

  with transparency, or the notion of transparency.  We

  have heard about that throughout lots of our meetings.

  And we discussed yesterday the role of lack of

  transparency as a factor in the Guatemala experiments.

  Certainly shining a light on research makes it

  difficult to ignore the ethics, and allows people to

  comment on the ethics.

            Similarly, accountability.  One of the members

  of the panel in particular, I think, frequently said,

  "It's not the fact that we lack standards and rules,

  but we lack or we don't have enough enforcement of

  them."

            And I think he also included, in addition to

  enforcement, knowledge, that the -- as Nelson talked

  about, training and education of investigators and

  IRBs.  Investigators and institutions can only be held

  accountable for things that they know about.  The rules

  have to extend -- they have to be available to them,

  they have to know how to apply them, and they have to

  know what the consequences are of not adhering to them.

  And there are a number of consequences that we could

  talk about.

            The specific recommendation here is about

  registration.  And certainly it is one way of

  increasing transparency.  I think it's notable that in

  the last decade or so there have been a lot of efforts

  to have clinical trials registered around the world.

  Certainly the Declaration of Helsinki says every

  clinical trial must be registered in a

  publicly-accessible database.  The WHO says

  registration of clinical trials is a scientific and

  ethical responsibility.

            Our current U.S. law, as found in the Food and

  Drug Administration Amendments Act of 2007, requires

  advance registration in a public database,

  clinicaltrials.gov, of applicable clinical trials,

  which include mostly intervention studies that are

  under FDA regulation, and does not include a bunch of

  studies that one might question whether or not they

  should be in there.  Phase one studies, for example,

  observational, epidemiological, and some others.

            I think, interestingly, by the current

  definitions of clinicaltrials.gov, what is applicable

   -- most of the studies that were done in Guatemala, if

  they were being done today, would not be registered in

  the clinicaltrials.gov.

            It's also interesting that many other

  jurisdictions around the world have similar public

  registries.  The European Medicines Agency has an

  online registry that it's had for several years.  Many

  countries have established national registration

  requirements.  Brazil has one that's been in effect for

  a long time, India, China.

            The International Council of Medical Journal

  Editors require, as a condition of consideration for

  publication, registration in a public registry.  So

  there is a lot of efforts already in place.

            So, I found myself thinking, as I was

  preparing for today:  What could the commission do that

  would advance this particular area of transparency,

  especially through registration?  Certainly we could

  endorse the policies of the Declaration of Helsinki or

  the ICGAME -- JME, (sic) or FDA, or the European

  Directive, et cetera.  We could think about expanding

  the requirements for registration, to include more

  clinical trials that are -- or more clinical research

  that is not currently covered, and we could also talk

  about maybe other options for encouraging or enforcing

  accountability and transparency beyond registration.

            So, going on to --

            DR. GUTMANN:  Could I just quickly --

            DR. GRADY:  Yes?

            DR. GUTMANN:  You mentioned FDA, but you

  didn't mention NIH, which sponsors an awful lot of

  clinical trials.

            DR. GRADY:  Yes.  So all clinical trials that

  are interventional are required to be published in

  clinicaltrials.gov if they're NIH trials.

            The next recommendation from the panel was the

  United States should implement a system to compensate

  research subjects for research-related injuries.  And

  we talked about one model, which I will get to in a

  second.

            I think everyone knows that, in the United

  States, neither sponsors nor institutions are required

  to provide compensation for research injuries, or free

  medical care for injuries.  They are only required by

  regulation to inform participants who are in

  greater-than-minimal risk research what will happen to

  them if they are injured.  And there is a lot of debate

  about how that language should be phrased in consent

  forms and a lot of time spent on that.

            Many European countries -- again, as many

  people know -- do mandate clinical trials insurance.

  And we also know that research carries risk, some

  serious risk -- although serious risk and death seems

  to be relatively rare.  We heard from Zeke and from

  others that we don't have data, we don't' really know

  what the level of risk is in research.

            There was an interesting study done a few

  years ago by the Lewin Group which looked at 102

  academic medical centers in the United States to see

  what kind of policies they had for treating -- for

  offering medical care for research-related injuries to

  participants in their research.  And well more than

  half offered none.  They charged for treatment for

  injuries in the usual way, through insurance companies

  or directly to the participants, if they didn't have

  insurance.  None offered compensation for anything

  beyond medical care, like lost wages or of pain and

  suffering, or anything like that.

            Again, everybody knows in the U.S. the way to

  get compensation for research injury is through the

  tort system.  And I think what's really interesting is

  if when you go back in to look at the history, decades

  of discussion have ensued about the need for a system

  of compensation for research injury.  And national

  commissions, one after the other for 30, 40 years, have

  recommended a no-fault system of some sort for

  compensation for research injuries.

            And interestingly, although commissions have

  recommended it, and lots of moral justification has

  been written about it, no such system has been

  established.  There are lots of interesting obstacles

  that we could talk about.

            Again, I think it's interesting to see what's

  happened in the last decade.  Many countries around the

  world and some U.S. research institutions have actually

  moved forward and developed compensation systems.  I

  think there is some interesting -- I had some examples

  of problems that could occur, but I want to say more

  about what the commission's -- I mean the -- sorry, the

  panel's recommendation points to.

            It points to the possibility of examining the

  vaccine injury compensation program, which is a

  U.S.-based no-fault alternative to the traditional tort

  system for compensating people who are injured from

  compulsory childhood vaccines.  And this is a system

  that is funded by a surcharge on vaccines that are

  pooled and available for damages.  There is a list of

  eligible side-effects, acceptable time frame, and it

  covers a lot of different kinds of injuries.

            There are other options for no-fault

  mechanisms that might be worth exploring.  And I think

  it's really maybe important for the commission to think

  about what the other options are, as well as to find

  out more about the vaccine injury compensation system.

            So, again, I thought about what should the

  commission do.  I think, certainly, we can call for

  no-fault insurance, like many previous commissions

  have.  We might be able to dig deeper and propose some

  tangible structures for no-fault compensation systems.

  Again, there are others that have been written about

  and proposed besides the model based on Vaccine Injury

  Compensation Act.

            And the fifth recommendation from the panel

  was continued efforts to harmonize and guide

  interpretation of rules should be made a priority over

  creating new rules.

            As you know, we just heard about the proposed

  rule-making from the government, in terms of changing

  the Common Rule, which suggests that there is a need to

  revise and continue to update rules, even if there is

  not a need for more rules.  But interestingly, as I was

  thinking about this, if I talk about registration and

  compensation for injury, if we were to attend to both

  of those, both of those might end up necessitating new

  rules.

            I think that the panel was really in

  agreement -- in heated agreement, actually -- that new

  rules are not necessarily better.  We don't need new

  rules.  But we need sound, clear, streamlined rules

  that can make efficiencies and promote quality, in

  terms of research.

            I also think it's interesting that we

  have -- we continue to talk about harmonization.

  Again, nobody, I think, disagrees with the need for

  harmonization.  Of note, Ruth Macklin, in one of the

  papers that we had received, opined that harmonization

  is probably not feasible, and part of the reason is

  because there are radically different interests that

  the stakeholders have, in terms of research needs.

            I think it's interesting to think about what

  kinds of harmonization we could promote, whether we

  should, as a commission, endorse streamlining,

  revision, harmonization, evidence-based protection, the

  promotion of a culture of responsibility using the

  rules that do exist.  I mean there are lots of possible

  ways to go forward.  But I think the goal is

  efficiency, protection, and harmonization.

            And that is all I was going to say.

            DR. WAGNER:  Christine, thank you.  And

  Nelson -- and Nita has a question.

            DR. FARAHANY:  First, thank you both.  This

  was incredibly informative.  And thank you, all of you,

  for participating in what sounds like an incredibly

  productive process.

            I wanted to focus, Christine, on

  recommendation number four about the no-fault, or

  strict liability system.  And you know, it strikes me

  as a challenging one, particularly given the number of

  past commissions that have recommended it, but also as

  a person who teaches tort law, and is somewhat

  committed to the tort system, it seems at odds with the

  National Vaccine Act approach.

            So, the National Vaccine Act is actually a

  compulsory process, versus an assumption of the risk

  that people undertake with engaging in human subjects

  research.  And so, it seems, theoretically, at least,

  different to me, if you choose to engage in research.

            And it seems like it dovetails with another

  discussion that we have been having, which is what are

  the benefits of research to individuals and to the

  community.  And thinking about how you balance the

  benefits of research versus the risks of research that

  might pose to an individual, this might be one of those

  areas of benefits of research that we would think

  about, which is what is the compensation for the risk,

  or how do you overcome the risk.

            It might be different, though, as well, right?

  We might think the benefits of engaging in research,

  both to the community and the individual, are

  sufficient such that a strict liability system weighs

  heavily against the researchers, and more in favor of

  the individual.  So it seems like this is a delicate

  and difficult area.

            So, I was hoping you could elaborate a little

  bit about the rationale for a strict liability system,

  and for thinking about, given that this is an

  assumption of the risk -- and one of the things, of

  course, that we promote is informed consent and the

  need for informed consent -- how those work together.

            DR. GRADY:  I probably can't, but I can say a

  few things that I think are maybe relevant to that

  question, Nita.

            I think the panel, for example, talked very

  briefly about the vaccine injury compensation program.

  There has been, however, some literature that has

  addressed this as a possible model for research-related

  injury.

            And I think, you know, there are lots of

  reasons that it works okay in the vaccine world and

  might not work so well in the research world.  One of

  them is that the -- you know, there are a limited list

  of vaccines that are predictable, to some extent, in

  terms of what their side-effects are.  And they are

  compulsory, as you suggested, in a certain way,

  although some would argue with that.

            The other is that, you know, research is -- I

  mean we do have this system where we ask people to

  accept the risks of research, and they have the choice

  to not accept those risks.  And some people have

  argued, once you have done that, you don't need to

  offer them the benefit of care for their

  research-related injuries, that, you know, that's part

  of what they bargained for, so to speak.  But that

  seems -- I don't -- that doesn't seem right to me.  I

  mean I have to say I think --

            DR. GUTMANN:  One thing.  The international

  panel felt strongly that it was wrong and a mistake

  that the United States was an outlier in not specifying

  any system for compensation for research subjects,

  other than you get a lawyer and sue.  And most research

  subjects just -- it's just too difficult to do it.

  It's much more difficult than in the case of a -- you

  know, somebody hits you with a car and you -- there are

  lawyers who come and, you know -- what are called

  ambulance chasers, and you can do it.

            The -- where -- the U.S. is an outlier here.

  What -- and it doesn't mean that there aren't arguments

  to be made, but the panel felt very strongly it was an

  outlier on the wrong side.

            What the panel did not feel strongly about is

  what the right mechanism would be.  It used the vaccine

  example as an example of something that works in its

  area and is available, but it did not specify.  And in

  some future meeting we will explore possibilities.  But

  the strong point of the panel was not to have rules

  about compensation for certain kinds of injury is a bad

  thing.

            DR. FARAHANY:  And just to clear up that, so

  the strong recommendation is not that it be a strict

  liability scheme, just that some scheme be developed?

            DR. GUTMANN:  Absolutely right.  There is not

  a strong recommendation about what the scheme should

  be.  There is a very strong recommendation that there

  ought to be some understanding of having a scheme for

   -- a system for compensation.

            And there was also a sense that, although

  previous commissions have recommended this, they have

  recommended it among one among, in some cases, dozens

  of recommendations, and have not highlighted this, and

  have not gone into any depth, which is what the panel

  is asking us to do, on what such a scheme might look

  like.

            So the panel is asking us to make this a

  priority among the things we look at, and look at it in

  some depth.

            DR. WAGNER:  But, Nita, you're suggesting it

  as the commission -- is we incorporate this in our

  recommendations going forward, we should consider

  recommending against strict liability system?

            DR. FARAHANY:  I want to think about it more

  carefully.  I mean this is -- but I -- my intuition

  would be that a pure strict liability scheme in a

  system like this one would probably not be the

  appropriate one.

            But I am open to that being something --

            DR. WAGNER:  It's a conversation the committee

  should --

            DR. FARAHANY:  It's a conversation we should

  have, yeah.

            DR. ARRAS:  As a fortunate member of this

  team, I just want to make a comment about the framing

  of this report, okay, because this report leaves out a

  number of really hot-button issues in the world of

  international research; issues that have drawn a lot of

  heated discussion.  For example, the standard of care

  and the use of placebos in trials, the provision of

  post-trial access to drugs, and what that should look

  like, or the provision of ancillary care during a

  vaccine trial.

            So these are all very contentious, contested

  issues, and I just think it's important to note, for

  the commission and for the broader public, that, given

  the limited time frame that our group was facing, we

  decided to bracket those questions and focus

  exclusively in our report on issues closer to the bone

  of protecting subjects from risk and harm and offenses

  to dignity.  Right?

            But, with any luck and more time, the larger

  commission will hopefully address some of those other

  issues, which I think are extremely important, and we

  could shed light on.  Thanks.

            DR. WAGNER:  Roger, got you.  But this might

  be a place to insert Joseph Millum's question.  He is

  at NIH, where he is a bioethicist.  But he recalls

  that, with regard to equivalent protections -- and I

  don't know which one of you to go to on this, or anyone

  from that group -- that in 2003 there was a working

  group that reported a proposed method for

  deliberating -- excuse me, for determining whether

  foreign regulations offered equivalent protections.

            And the question is are we aware of that, and

  why has it not gone forward, if we are aware of it?

            DR. MICHAEL:  Let me defer to Christine,

  because this is something that's very close to her.

            DR. GRADY:  Well, we are aware of that, Joe.

            (Laughter.)

            DR. GRADY:  It hasn't been adopted by the

  regulators.  And, therefore, either it needs to be

  adopted or revisited, and maybe more detail needs to be

  put into place.

            But I think Zeke's point also is very

  important.  You know, a lot of people over the years

  have agreed that equivalent protections ought to

  be -- that quote, that possibility in the regulations

  ought to be utilized, but it has never been fleshed out

  sufficiently to allow it to be utilized.

            DR. WAGNER:  So it has to be further --

            DR. GRADY:  Well, I think that that report

  that Joe referred to, if we're going to pursue

  equivalent protections, we would look at that report in

  some detail and say, "What, from that report, can we

  salvage and say, 'This ought to be done now,' and what

  needs to be changed, since now we're in 2011, besides

   -- from 2003" --

            DR. GUTMANN:  Could I ask a specific question

  about equivalent protections?  So we were given, on the

  panel -- and, mind you, everything we did on the panel

  we said was going to be a prologue to what the

  commission did in some more -- in some cases, in some

  more depth.

            So, we were given one example of what an

  equivalent protection would be, which is in the United

  Kingdom the reporting is less frequent than the

  reporting requirement in this country.  But otherwise,

  there is no substantive difference.  And that should be

  seen as an equivalent set of protections.  They agree

  on informed consent, on all the other important things

  on equivalent protections.

            Is there any other example?  Because we need

  to -- if we're going to go down the road of equivalent

  protections, we ought to -- we've got to start by

  cases.

            DR. GRADY:  Right.

            DR. GUTMANN:  Of where, intuitively at least,

  you would say, "Sure, that's equivalent."

            DR. GRADY:  Yeah.

            DR. GUTMANN:  Is there another example, or is

  that it?

            DR. GRADY:  Well, I think I probably provided

  that example.  It was annual review, the need for

  annual review.  But I'm sure there are other examples.

  I'm not sure I can come up with one right now, but I'm

  sure there are other --

            DR. GUTMANN:  So one of the things we should

  do as a commission is ask those who have come before to

  provide us with at least a short list of equivalent

  protections, and we should look at them and see whether

  they strike us as equivalent.  And if they do, then we

  may have a recommendation to be made.  But if they

  don't, this may -- there may not be equivalent -- I

  don't know.

            DR. WAGNER:  Essentially, an --

            DR. GUTMANN:  I am totally agnostic, because

  that's the only example that I have actually been

  given.

            I mean another example -- no, one other

  example are different ways of obtaining informed

  consent, different forms for informed consent, which

  are basically the same, but just are different forms.

            DR. WAGNER:  Formatting.

            DR. GUTMANN:  Yeah.

            DR. GRADY:  I think one of the debates has

  been to what extent do procedures need to be

  equivalent, the procedures for review, approval,

  consent, et cetera.

            DR. WAGNER:  As opposed to purposes.

            DR. GRADY:  As opposed to principles or any

  more substantive requirements.

            DR. GUTMANN:  Yeah, yeah.  So we need -- we

  just need some of the examples.

            DR. WAGNER:  Raju?

            DR. KUCHERLAPATI:  Thanks, Jim.

            I have, actually, questions about many of the

  recommendations.  So maybe I would focus first on the

  first two recommendations, Nelson.  And the first

  recommendation is about community engagement, and the

  second recommendation is about training.

            The way the recommendations are, you know,

  worded right now seem to suggest that, you know, such

  community engagement doesn't exist today and,

  similarly, that -- it also suggests that training, you

  know, the IRBs and the investigators, about -- you

  know, doesn't exist.  And I wanted to make sure that

  that wasn't the intention.  Or -- I'm not sure

  that -- I would imagine that there are, indeed -- there

  is community engagement today.  It may not be adequate,

  I don't know what the recommendation is.  Can you

  clarify that?

            DR. MICHAEL:  No, I think that's very helpful.

  And I find -- you know, it's provocative that you would

  read it that way.  That certainly was not the intent.

  So I think that's an important thing to hear, that you

  would see it as -- in that light.

            Certainly training exists, and certainly

  community engagement exists, but it's differentially

  applied, and it's differentially effective.  And I

  think that is -- really was the point, to emphasize in

  both of those arenas, that community engagement,

  honestly, is something that I think 10 years ago people

  just shrugged their shoulders about.  You know, Father

  knows best.  The research pushes down community

  engagement as a megaphone from researchers to the

  communities that tell them what researchers or health

  ministries want to do.  And I think the historical

  record may suggest some of those activities 60 years

  ago.

            This is not to say that these activities don't

  exist today, but they need to be strengthened and made

  more transparent and more pervasive.  And I think that

  probably Mitchell and others maybe in the next session

  will provide a little more granularity about what we

  actually mean by community engagement.

            But I will tell you that in my organization,

  it's been a real uphill process to get hard-core

  clinical investigators to want to talk about things

  that sound, frankly, fuzzy and soft, but understanding

  that there are significant liabilities, I would say, to

  do research overseas in the absence of really embracing

  the substance of both of those issues.

            DR. WAGNER:  We have a comment.  Is it Carla

  Saenz?  Is that the proper pronunciation in the --

            DR. GUTMANN:  Carlos, could you stand up?

            DR. WAGNER:  Carla.

            DR. GUTMANN:  Oh, Carla.

            DR. WAGNER:  Carla, yeah.

            DR. GUTMANN:  Carla.

            DR. WAGNER:  From the Pan American Health

  Organization, who offers this comment, which I think is

  an important comment to take into consideration, that

  their organization welcomes the recommendation to

  increase training in research ethics.

            They want, however, to point out that what is

  needed is training that is effective -- that is, that

  targets the real needs, and also in the context of the

  region, even though the broad needs are the same

  throughout the world -- and also training that is

  efficient, that is coordinated with all other national,

  international initiatives.  Often, training -- her

  experience is that training in Latin America is

  neither.

            So, we may want to incorporate these kinds of

  thoughts in a recommendation going forward, not

  that -- just that training exist, but are there some

  ways to gauge how it is both effective and efficient,

  in doing so.

            We are actually probably at a good place for a

  break.  We ran a little long because we ran long in the

  early session.  It would be great to get back here at

  quarter of, so we could start again.  Thanks, Nelson

  and Christine, for your presentation.

            (Applause.)

 

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