TRANSCRIPT: Meeting Six, Session 5

Community Engagement -- Needs, Models and U.S. Actions

Date

August 30, 2011

Location

Washington, DC

Presenters

Carletta Tilousi

Member, Havasupai Tribal Council

Havasupai Tribe

Mitchell Warren

Executive Director, AVAC: Global Advocacy for HIV Prevention

Roger I. Glass, M.D., Ph.D.

Director, Fogarty International Center, Associate Director for International Research , National Institutes of Health

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Transcript

            DR. GUTMANN:  If I could ask everybody to

  please take a seat, we are going to reconvene.

            It is my pleasure now to introduce our panel

  on community engagement.  I will introduce all the

  speakers at the beginning, and then ask each to speak,

  and then we will open it up for questions and comments.

  And I want to thank everybody who has given us comments earlier this morning for really excellent comments.

            Our first speaker will be Carletta Tilousi.

  She is a member of the Havasupai Tribe.  If I pronounce

  that -- would you pronounce it for me?

            MS. TILOUSI:  Havasupai Tribe.

            DR. GUTMANN:  Havasupai Tribe.  And a member

  of the tribal council.  She has been a member of the

  tribal council for the last eight years.  She was the

  lead plaintiff in the Havasupai versus Arizona State

  University case, which we touched on this morning.  She

  holds a bachelor of science degree in justice studies

  from Arizona State University, and she was born and

  raised in the Grand Canyon.

            Welcome, Carletta.

            Mitchell Warren, who will be our second

  speaker, is the executive director of AVAC, which is an

  international non-governmental organization that uses

  education, policy analysis, and advocacy, and a network

  of global collaborations to accelerate the ethical

  development and global delivery of AIDS vaccine, male

  circumcision, microbicides, prep, and other emerging

  HIV prevention options as part of a comprehensive response to the pandemic.  Before joining AVAC he was

  senior director for vaccine preparedness at the

  International AIDS Vaccine Initiative, where he

  directed efforts to increase community understanding

  and national involvement in AIDS vaccine clinical

  trials.

            Welcome, Mitchell.

            Mr. Warren is also a member of the global HIV

  prevention working group convened by the Bill and

  Melinda Gates Foundation and the Kaiser Family

  Foundation.

            Dr. Roger Glass, our third speaker, is the

  director of the Fogarty International Center, and

  associate director for international research at the

  National Institutes of Health.  Prior to his

  appointment at the Fogarty International Center, Dr.

  Glass was the chief of the viral gastroenteritis unit

  at the National Center for Infectious Disease at the

  CDC.  His research interests are in the prevention of

  gastroenteritis from rotoviruses and noroviruses.

  through the application of novel scientific research.

  He has maintained field studies in India, Bangladesh,

  Brazil, Mexico, Israel, Russia, Vietnam, China, and

  elsewhere.  His research has been targeted toward

  epidemiological studies to anticipate the introduction

  of rotovirus vaccines.

            Welcome, Dr. Glass.  We are delighted to have

  you all here.

            And, Carletta, may I ask you to begin?

            MS. TILOUSI:  Good morning.  My name is

  Carletta Tilousi.  Thank you for inviting me here to

  testify on behalf of my community.  I have put together

  a small slide show, so that you can have a visual idea

  of where we are from.

            This is the Grand Canyon.  We are located in

  northern Arizona.  Our population of my people is

  approximately 500-plus members that live in the bottom

  of the Grand Canyon.  We have over about 120 families

  living in Supai Village.

            This is an aerial shot of Supai Village.  It's

  a remote canyon in the side of the Grand Canyon.

  Everything is flown down here through helicopter, mule,

  or hiking down is the only access to the village.  We

  have a high rate of high-school drop-out rate.

  We -- jobs are very limited.  We have government jobs

  down there.  Some of them are for social services,

  health services, and such that is -- provide the

  community.

            We also have approximately five college

  graduates, and I am the third person that has ever

  graduated from college in the history of Havasupai.

  Farming is our main economic source.  We just finished

  our harvest down in the village.  This was our main way

  of surviving down in Supai Canyon.

            A little bit of history.  Our reservation was

  not formed as a formal reservation until 1975, which

  prohibited us from consuming our natural foods, which

  led us to the severe epidemic of diabetes.  The reason

  why I'm here today is to explain a little bit about why

  my people have been plagued with diabetes, due to our

  people being removed from our original lands.  We were

  forced to eat non-familiar foods that caused us to have

  high rates of diabetes in our youth, in our elders.

            Our main economic base is tourism that come

  into Supai Canyon.

            As you see here, a lot of the rock formations

  in the village talk about the history of -- or  Havasupai-- one of the studies that Arizona State

  University did was challenge our existence in

  Havasupai, which was claiming that we were from the

  Bering Straits theory, which contradicted our own

  cultural and religious beliefs.

            Here is the Havasu Waterfalls, which we are

  named after.  Havasu Baaja is the way you say it in our

  language.  In English, lots of people say it,

  "Havasupai People."

            These are other photos of my ancestors who

  have roamed in the Grand Canyon for many years.  This

  type of existence of our indigenous people attracted

  professional scholars from Arizona State University to

  come into our community and seek blood samples.  One of

  the samples that they used was to see where we did come

  from, how we lived for so long in these rugged

  terrains.  And there were many, many publications that

  were published by Arizona State University.

            Here are pictures of two of the professors,

  John Martin and Dr. Theresa Marco.  These are members

  of the Havasupai Tribe who have -- did at this point

  travel to Arizona State University to participate in a

  diabetes study.  Here are our people who have worked in

  the field of food and health.  Some of these ladies are

  clinical health representatives, or working in the

  cafeteria, providing food for the children.

            And one of the collaborative efforts that ASU

  tried to do back then was to provide education of

  diabetes.  This was one of the only things that they

  did that we found documentation on.  I also want to

  note that half of these women in these pictures have

  passed away, due to diabetes complications.

            These are also victims of research.  These are

  the people that found out about how the blood samples

  were transferred from institution across state

  boundaries, and were used for other research, such as

  schizophrenia, the Bering Strait theory, as I mentioned

  earlier, inbreeding amongst the Havasupai.  These are

  very -- studies that were very embarrassing to my

  people, and also to myself.

            I also sit before you as the victim of a

  scientific research.  I also gave blood.  I provided

  blood, and I did not provide any written consent.

            These are our tribal council leaders who also

  stood up against the State of Arizona, and the

  institution and said, "This is not going to happen any

  more to any of -- other indigenous people around the

  world," and took this step forward to bring this issue

  to light.

            One of the main goals of the Arizona State

  University blood case was to bring the blood samples

  back.  We were not going to just fight for monetary

  funds.  We felt that it was very important to bring our

  blood samples back -- of our ancestors back.  Due to

  our religious beliefs, when an individual passes away,

  everything that he or she owns goes with them during

  their burial.  So this really went against our

  religion.

            Here you see in this photo some of the blood

  samples that we retained back.  We only got about

  98 -- approximately 98 samples back.  This is their

  grandfather's blood sample back that they are properly

  reburying back into this person's cemetery.

            Again, this is the -- my ancestors.  The one

  on the right is my great-great-great grandfather.  His

  name is Burro.  That name was given to him because he

  was found roaming around in the Grand Canyon.

            There are many implications that came out of

  this blood case.  I would like to let you know some of

  them.  The reason why I'm here today was a lot of our

  blood samples were misused.  The people's trust in the

  institution was shattered.  Right now, the tribe had

  to -- the tribal council had to no longer allow Arizona

  State University people to come on to the Havasupai

  Reservation.

            One of the main things that we learned now is

  the lack of IRB rules were not being enforced, the lack

  of IRB processes were not being followed.  The lack of

  legal enforcement was also being overlooked.  The only

  thing that happened to these institutions that we found

  out in the end was their funding will be revoked.  And

  the professors currently have not been disciplined.

  They still hold different professorship positions in

  other institutions.

            And it continues.  We are very upset about the

  lack of informed consent that was not even translated

  into my language.  English is my second language.  I

  speak Havasupai 100 percent of the time.  Some of the

  terms that you use here when you're talking in your

  meetings need to be translated to me, you know, so that

  I can properly answer.

            When these folks approached my community, they

  just verbally told these people that were willing to

  find solutions to diabetes -- of course, everybody

  wanted to find some solution to this health epidemic

  that is killing my people.  We just finished burying

  one of my elders who had a stroke, who had been

  fighting diabetes for many years.  We just buried her

  three weeks ago.  So this is something that we face

  every day.

            And if these IRB boards are there to review

  such subjects and such kind of work that is being done

  by these institutions, they need to be enforced, and in

  a way that we understand.  For instance, when the blood

  samples were taken from the Havasupai Reservation, they

  were taken across boundaries.  They were taken to state

  jurisdictions.

            And when we decided to take this case into

  court, the state court said, "We don't have

  jurisdiction."  The federal court said they didn't have

  jurisdiction.  It was just getting tossed around, back

  and forth.  And it was such a high-profile issue, no

  law firm also did not want to take this case, because a

  lot of people worked for Arizona State University, or

  knew people within the institution.

            And then, the other thing is I would also like

  to recommend that our -- when these studies are being

  taken within tribal governments, they need to be

  enforced within tribal court systems.  So, due to these

  other implications, Indian tribes are now reluctant to

  participate -- we, as Havasupai, are reluctant to

  participate -- in any further human subject research

  until we further understand what is the process, until

  we further understand the  translation and implications of

  what needs to be done.

            How do we handle internal review board

  regulations when they are being violated?  Are they

  going to be fined?  Where are they going to be

  enforced?  What happens to these professors when they

  go in and promise solutions to certain epidemics?

            So, those are some of the things that we have

  here.

            We found that there was no written consent by

  any of these professors that were obtained.

  Translation for people.

            And also recognizing the fact that lack of

  education, economy, all those factors need to be

  considered when professors are coming into third world

  conditions.  I come from a community that, any time,

  the water can go out.  Any time the lights can go out.

  Flooding can happen.  Those types of things that we

  face every day.

            We are not against research.  We feel that

  research is needed.  But it needs to be done in a

  proper way.

            So, I thank you for my comments, and I hope

  that we can seek a solution together.

            DR. GUTMANN:  Thank you very much.  Mitchell?

            MR. WARREN:  Thank you.  Let me -- thank you

  very much.  First and foremost, let me thank the

  commission for inviting me.  And, perhaps more

  importantly, thank you for grappling with some of the

  most important and, I would argue, some of the most

  interesting issues of our time.

            We at AVAC, a small policy and advocacy

  organization, have followed your work for some time,

  provided comments back in April, in fact, related to,

  hopefully, the reinstatement at the FDA of focusing on

  the Helsinki Declaration and the highest protection

  provisions.  So we have watched and followed, but that

  is not the purpose of my remarks this morning.

            I am going to talk about the good

  participatory practice guidelines that you heard a bit

  about from Colonel Michael.  I am hopefully going to

  provide some flavor, in a sense of where they came

  from, and, more importantly, where they are going.  It

  is remarkable, what a difference a few years makes.

            Only five or six years ago, when one talked

  about research, looking at what in HIV prevention is

  called pre-exposure prophylaxis, was almost a euphemism

  for unethical research, or at least claims of unethical

  research.  And now we sit four months since results

  have been released that tell us that, in fact, these

  research results provided some of the most

  ground-breaking and important findings in HIV

  prevention research.

            So, how did we traverse those five years from

  research called unethical to research called

  ground-breaking, game-changing, and perhaps epidemic

  ending?  I certainly don't want to pretend that good

  participatory practice was the way in which that

  research transitioned.  But I do want to highlight the

  fact that when those trials first erupted in

  controversy five years ago, a number of us, including

  leadership at UN AIDS led at the time by Peter Piot,

  who I know was part of your international panel and we

  at AVAC, looked at these controversies as an important

  opportunity to reflect on the way research was

  happening.

            Many of the claims that were taking place in

  communities that were engaged in this research, both in

  Asia and in West Africa, as well as communities who

  claimed a right to be engaged in the research

  discourse -- mainly in Europe, and advocates like

  myself sitting in the United States -- were looking at

  the research endeavor taking place and commented on

  several lapses that were perceived to be taking place

  in those trials.  And some of you mentioned those in

  the last session.

            People were concerned about the informed

  consent process, people concerned about the issue of

  language that was used with trial participants, the

  lack of clarity about post-trial access, should these

  interventions prove successful.  And, perhaps most

  challenging, what would happen to someone in one of

  these trials, should they become HIV-infected?  Huge

  issues.

            And we at AVAC wrote a report back in 2005

  that did not seek to blame, did not seek to say this

  research was ethical or not, but sought to really

  understand what was at the heart of the problem.  And

  what we really came to find was that many of the claims

  made were not entirely true, but they were never fully

  answered by research sponsors, research implementers,

  and the trialists.  And I won't try to judge cause and

  effect, but it was very clear that the lack of

  communications between the different stakeholders was

  really at the heart of key problems.

            Coming out of that in 2007, UN AIDS and AVAC

  convened an international panel of researchers,

  ethicists, community activities, to really look at how

  could we do better.  And one of the main

  recommendations coming out of those early discussions

  was that we were missing something critical in the

  research process.  Every clinical trial had good

  clinical practice guidelines that were being followed

  and monitored.  Every product being tested would be

  through a good manufacturing process -- again, a

  process well known, well documented, well monitored.

  Similarly, laboratories under good laboratory practice.

            But in terms of community engagement, in terms

  of participation of multiple stakeholders, there was no

  guideline.  There were lots of idealized visions of

  what community engagement should be.  Sometimes it was

  done very, very well.  Sometimes it was done very, very

  badly.  And most of the time, none of us would know the

  difference.  Not unlike the Supreme Court and

  pornography, we seem to know good community engagement

  when we saw it, but we couldn't actually measure or

  monitor it.  And that put everybody involved in the

  research endeavor, frankly, at risk.

            So, the initial guidelines published finally

  in late 2007 went through the research process, and

  really started at the one area of community engagement

  best known to people, the community advisory board, and

  really articulated a desire that while community

  advisory boards were important, they were not

  sufficient to say that was indeed community engagement.

  And again, if you go back to good clinical practice

  guidelines, the CAB is help up as the way in which

  communities are engaged.

            And instead, the panel that put together the

  initial GPP guidelines went through the research

  process and tried to identify different aspects of the

  research time line where communities could or should be

  engaged.  And you can see in this graphic from the

  latest guidelines that, really, community engagement,

  stakeholder engagement, should take place throughout

  the entire life cycle of the research process.

  Recruitment is recruitment.  Stakeholder engagement,

  community engagement, is not.  And that is often

  missing, I think, in the dialogue.

            So, in beginning the GPP guideline

  development, it was an attempt to try to understand the

  research process, and recognizing that language

  matters.  Even just earlier in this session this

  morning, the discussion of communities -- and it is a

  term that is like Jello in one's hands, it can mean

  many different things to many different people -- and

  you will notice that we transition from good community

  practice ideas to good participatory practice, and we

  transitioned in this second version from talking about

  community engagement to stakeholder engagement,

  recognizing that many different types of stakeholders

  are engaged throughout the research life cycle, and we

  need to ensure that they have mechanisms to engage

  throughout.  And this is just one diagram that shows

  you the many different layers.

            And who gets to decide?  In some of the early

  controversies around the prep research, activists

  outside of the geography of the trials claimed a voice,

  and really were allowed to subvert the research process

  and close clinical trials down for reasons that,

  frankly, boarded on the unethical on the closing them

  down, rather than in the defense of ethical conduct.

  So, different layers of this onion, so to speak, really

  have different voices, different views, and different

  ways to engage.

            Just to differentiate, GCP talks a great deal

  about connecting research teams to trial participants

  through the informed consent process.  In GPP, we tried

  to find a bidirectional approach between a range of

  different stakeholders, and the research teams, not

  only the clinical trialists, but the funders and

  sponsors, as well.

            GPP is divided into three sections.  The first

  identifies the importance of good participatory

  practice.  The second looks at key principles that

  underlie these guidelines.  And the third, then, takes

  a view at each of the clinical trial process points and

  looks at what might be seen as minimal standards,

  minimal ways to really measure and monitor good

  practice.

            This just gives you a little bit more detail

  of what is within each section, really not an attempt

  to test your eyesight or to have you read it, but to

  give you a sense of the depth of these guidelines.

            Again, I do want to focus a bit on the

  different types of advisory mechanisms, because so

  often, if there is a functioning CAB, and if it has

  minutes and notes from its meetings, it is perceived to

  be enough.  And what we've tried to articulate here is

  a range of different types of ways to engage.

            And similarly, here you can see that there are

  many different types of mechanisms, both informal and

  formal.  And they need to be seen in the context in

  which the research is taking place.  This work that I

  am describing took place entirely in the context of HIV

  prevention research, and more particularly, biomedical

  HIV prevention research.

            Can these guidelines be extrapolated to other

  research?  I believe they can.  I think it's the task

  of this commission and many other groups to really

  judge that on its merits.  Can these guidelines be

  distilled to a point where they provide the basics of

  implementation and monitoring?

            And finally, we have gone over the last four

  years from the principles that underlie these

  guidelines, to the guidelines themselves.  And now the

  issue really is how do we implement them, how do we

  monitor them, and how do we evaluate them.  And much of

  this is going to come down to the trial sponsors, much

  as any trial must follow the GCP guidelines.

            I would argue that trial sponsors need to take

  these guidelines just as seriously, if we truly want to

  see communities engaged.  Why does this matter?  Well,

  it matters not just for the conduct of a single trial.

  It matters for the way trials can take place in a

  long-term process with communities over many different

  types of research endeavors.  It really comes down to

  how do we create the trust and respect for the research

  process that researchers and clinicians have, but

  communities often don't, for lack of their input and

  engagement throughout that process.

            So, I would argue that while there are costs

  involved in doing this, as in anything, it is one of

  the best investments we can make in ensuring that the

  research process goes smoothly, and that the answers

  from research can be well implemented into our policies

  and programs, going forward.  Thank you very much.

            DR. GUTMANN:  Thank you very much.  Roger,

  you're on.

            DR. GLASS:  Thanks very much.  And I must say

  I am honored to be here before the commission to speak

  on behalf of our programs at NIH and at Fogarty.  I

  wear two hats at NIH:  I am the director of the Fogarty

  International Center, and I'm also the associated

  director for global health research, which means I

  interact with all of the 27 institutes and centers on

  campus.

            And where our focus at Fogarty has been on

  research and training for global health, our strategic

  plan includes both infectious and non-communicable

  diseases, and we work with all of the institutes and

  centers.  We have an emphasis on implementation, which

  brings us directly into the community involvement that

  Mitch just spoke about.

            Training is a key for our -- training for

  research is key to our mission, and we really have made

  an effort to build partnerships between U.S. and

  foreign academic centers to build up their researchers

  and their academic activities.  And we have over 400

  separate grants, mostly in low and middle income

  countries.

            I want to just start by saying that we see at

  NIH a tremendous growth in clinical trials being

  conducted abroad.  It's a growth industry.  And I work

  in India, where they're anticipating over the next

  decade over $10 billion of clinical research that's

  being taken overseas.  Why is this so, and how do we

  address it?

            Part of the reason for the shift is the harsh

  bureaucratic and regulatory environment in the U.S.,

  and the cost of doing business here, so that many

  companies are subverting these hardships by going

  overseas, which raises a major question of how do we

  deal and provide ethical oversight and training for

  these activities, and the quote here from the New

  England Journal was that we must ensure the ethical and

  scientific integrity of this clinical research

  globally, as you can see.

            Well, where do we go from here?  I wanted to

  bring up Zeke's presentation this morning,

  because -- this is from 2004.  Before this, there was a

  review of ethical principles for research in the United

  States.  And when this moved from the United States to

  the developing countries, this collaborative

  partnership, this community participation, was a key

  change that occurred.  And that is the sphere in which

  we at Fogarty are involved.

            Our mission, then, has been that for the past

  decade, over a decade, we have invested in bioethics

  research.  And much of the research that is conducted

  and support and training in bioethics internationally

  is conducted and supported by the Fogarty International

  Center.  Many of the institutes and centers participate

  in these activities with us, and co-fund.

            But our goal is to build the research ethics

  capacity in low and middle-income countries to

  strengthen local input and participation in questions

  of ethics, to address ethical controversies locally,

  and to promote clinical global health research at NIH.

  We feel it's absolutely imperative that we have a

  framework in place for the protection of human

  subjects.  That's key.

            Well, we do this through our international

  research ethics training programs.  And these have

  developed on creating curricula that are widely used,

  case studies -- and there are two books there that have

  been published by researchers Jim Lowry and Richard

  Cash that are used and are available online -- running

  IRBs and training an IRB in research review, and

  writing guidelines for research.

            Our programs, the yellow dots, are scattered

  throughout the developing world.  And over the past

  decade, we have trained over 500 -- 560 -- master's

  level bioethics trainees through these programs.  We

  have just set up line listings of where these people

  are and what they're doing.  And I amplified a few of

  them, just to see the types of activities that these

  people have become -- these graduates, trainees, have

  become engaged in working on their national ethics

  committees, training and academics and the like.  So,

  these are really key and influential people in their

  own settings.

            Our grantees are from many countries.  And you

  can see Latin America, Africa, Asia.  There are so many

  countries that are not represented, and so this really

  reflects where we have the greatest investment in

  research, but not all the places where research is

  being conducted.

            South Africa and India are on the top of the

  list, and I wanted to just give you a few vignettes of

  what these people are doing.  I would also say that

  these graduates are involved in teaching or

  administration and policy and research, all of these.

  And I think many of you around the table are familiar

  with or have worked with some of these grantees.

            This is Clement Adebamowo, who is from

  Nigeria.  He has been training extensively in Nigeria,

  21 master's university students at Ibadan University.

  But most important, and highlighted with a red arrow,

  he has drafted the Nigerian national code for research

  ethics.  He has been an absolute mover in that country

  for both training and research.  And we could not do

  much of what we do in Nigeria if it hadn't been with

  the help of Clement and his staff and his graduates.

            Another graduate is Nandini Kumar from India.

  She is -- she trained through a Fogarty program in

  bioethics at Toronto.  She set up a bioethics training

  in her own country.  She moved on to the Indian Council

  of Medical Research as deputy director for ethics, so

  she's done the whole range.  And I would say that

  training is a little bit like your retirement fund.

  It's not worth much a year after you've finished your

  training.  But at 10 and 20 years, it really

  accumulates and grows.  And I think that it's growing

  not only her, but all the graduates and the long-term

  trainees in India.

            So, there we have three countries where we've

  been involved.  And last, South Africa -- three

  countries -- Jerome Singh, an absolute academic in

  bioethics.  He's at Caprisa in Durban, University of

  KwaZulu-Natal, where the microbicide trials, the

  circumcision trials, some of the most testy and thorny

  issues of biomedical ethics, and here we have a grantee

  who is trained and is able to address these needs.

            So, how do we go forward with this program?

  These have been terribly effective programs, but

  they've been effective on a small scale.  We haven't

  begun to address the needs that we see with -- if I can

  call it an epidemic of clinical research that will be

  going on in the next decade overseas, and the growing

  trend in that direction.

            We project this huge increase in clinical

  research overseas.  We cannot foresee this happening

  without proper attention to protection of human

  subjects and substantial increases in both the

  infrastructure for bioethics and the capacity-building

  and training that's required.  And this is an area

  where Fogarty, with the other institutes and centers at

  NIH, has played a key role.  And Joe Millum, in the

  audience back here, is our ethicist at Fogarty who

  works closely with Christine Grady's group.  So we

  collaborate even on campus.

            Well, I want to leave you with three

  challenges.  One is that ethics starts at home.  And if

  we go back to that Guatemalan case from yesterday, it

  was really an American investigator who had an American

  chain of command that was all responsible.  We feel

  that protection of human subjects has to begin with the

  training of American medical students and future

  bioresearchers here, so that ethics and understanding

  of the protection of human subjects, of community

  engagement, of equivalent protections, of publication

  of results, of standards of care, those basics, are

  infused in graduates from the very early days, so that

  at least they have a starting point.

            And this -- I hope will be music to your

  ears -- would require more investment in the training

  of biomedical scientists at home in our own

  institutions and academic institutions.  Many of you

  are here because your institutions have strong ethics

  programs.  Those who aren't here are the ones who we

  might well be speaking to, and who could benefit from

  this.

            The second is that we have gone and, over this

  past 60 or 70 years from this case in Guatemala, we've

  gone from parachute research to partnerships.  I think

  the parachute researcher was the person who dropped in

  with his own ethics values, and left with a bunch of

  specimens, exactly what Carletta was talking about.

  And I would say that global health research and local

  research are not extremes, in contrast, but are part of

  a continuum.  And what we do overseas we should be

  doing in our own backyard and our own inner cities.

            So, global health, it's not parachutes, it's

  partnerships.  And to -- and the challenge for you,

  then, is how do we build independent, local bioethics

  capacities, IRBs, and training programs that will be a

  match for what we are doing at home, because we feel

  this is terribly critical, and this is exactly the

  space where Fogarty has been working for the past

  decade or more.

            And finally, sustainability.  What we haven't

  mentioned is training and funding for ethics.  We think

  this is critical, because unless we have a way to

  support the ethics training and the participation of

  ethics into the research agendas into the future, we

  are going to have continuing programs and under-funded

  programs, and we will be liable for the same problems

  from the past.

            So, just to end, this is a picture of our

  recent graduate just last year from Agakhan in ethics.

  And these people will go out with -- to ensure that the

  ethics and the clinical research done in Pakistan meets

  the certain international standards that we all accept

  and would like to see.

            Thank you very much for giving me this

  opportunity to address you with these challenges.

            DR. GUTMANN:  Thank you, Carletta, Mitchell,

  and Roger, for three excellent presentations.  And we

  will have some discussion.

            Before I ask commission members, there is a

  question held over from the last session which is

  appropriate here, and it comes actually from Joe

  Millum.  And, Roger, I think you're -- you may be the

  perfect person to answer this question, and you will

  see why the smile is appropriate.

            What evidence is there that training

  investigators in ethics will improve the conduct of

  research?  Exactly what are the outcomes that could be

  different?

            DR. GLASS:  I would have to throw that back to

  Joe Millum, who is our ethicist, and Christine Grady.

            (Laughter.)

            DR. GUTMANN:  No, no, no --

            DR. GLASS:  I think that certainly -- and in

  my own experience -- the ethical issues -- and I go

  back to Caprisa and the trial -- the ethical issues

  around bringing those trials of microbicides and

  circumcision to the fore had been absolutely

  mind-boggling, because the ethics of how you -- and the

  prep trial.

            I mean these are sophisticated, complicated

  ethical issues that could not have been bridged without

  having a strong ethics program at the University of

  KwaZulu-Natal.  We have been training there extensively

  for over a decade.  And the ethics -- participation of

  the ethicist in those trials has really been critical,

  both to having the trial be conducted properly, and to

  ensure that the funding was consistent, was there.

            DR. GUTMANN:  Yes.

            DR. GLASS:  So I think we could -- but I think

  it's a good question I think we should go back and

  evaluate.  But I can say that we could not be doing

  much of the research in those key countries if we

  didn't have IRBs in place, if we didn't have competent,

  ethically-trained people to speak out and speak locally

  for the local institutions in ethics.

            DR. GUTMANN:  Let me say something on this,

  because it definitely cross-cuts everything this

  commission has been doing in this session and in

  previous sessions.

            When we found moral culpability on the part of

  researchers in Guatemala -- Raju said this, and Nita

  said it, and a number of other people on the commission

  said it -- we were judging, in retrospect, and we

  wanted to be very careful about our judgments about

  culpability of individuals.

            If we don't have ethics education, we cannot

  expect individuals to live up to the ethical standards

  that we impose.  So, we may not know -- and we don't

  have controlled experiments; it would be very hard to

  do them, not impossible -- but we don't know for sure

  what the results of ethics education are.

            What we do know for sure is if we -- and when

  I say "we" here, it's government agencies who are

  responsible for sponsoring research -- if we, if the

  government agencies don't ensure ethical training, then

  they don't have the moral responsibility -- they don't

  have the moral authority to expect people to live up to

  the standards that ethics requires.  And so, I think

  there is something very fundamental here about ethics

  training.

            That leaves open the question of what the most

  effective ethics training is.  Let me just say, then,

  you mentioned several individuals here, and we should

  just say that Nandini Kumar was on the international

  panel, representing an area of -- a very important area

  of the world.  And she, as her fellow colleagues, did a

  fabulous job.  So we thank Fogarty for its ongoing

  contribution to ethics education.

            I am going to open it up for other --

            DR. GLASS:  Let me respond to that.

            DR. GUTMANN:  Go ahead, yes.

            DR. GLASS:  I think also, if you think about

  Nandini and India, much of the growth in trials in the

  next decade will not be NIH-sponsored trials, or just

  Gates-sponsored trials, it will be trials by pharma.

  And if we create an ethical framework for India through

  these, it should permeate or could help permeate, and

  make sure that all trials are conducted with the

  proper --

            DR. GUTMANN:  Yeah.

            DR. GLASS:  -- ethical approval, not just

  those that are government or donor, NGO-sponsored.

            DR. GUTMANN:  And one other part of what you

   -- and I think one of the intents of Joe's question,

  as well, if I may read into it -- is that it's not

  enough just to train individual investigators in

  ethics.  It's also important to train people who are

  going to be responsible for setting up institutions and

  research projects to understand what are the

  institutional requirements for having a good scientific

  and ethical study conducted.

            So, I am going to let other people -- John and

  Nita and Dan, and I will keep the list.  So let's start

  with John.

            DR. ARRAS:  Okay.  This is a question

  addressed to Ms. Tilousi.  Earlier this morning we had

  an interesting exchange with Zeke Emanuel about the

  Havasupai experience.  I was puzzling over this notion

  of a kind of blanket consent for tissue -- you know,

  research on human tissue.  Zeke's response was, well,

  that really will give people the power to decide

  whether they want to participate or not.

            But I am still puzzling over this.  I am still

  puzzling over his position.  Because it seems to me

  that that sort of view puts a lot of pressure on local

  communities, in terms of foresight of, you know, what

  could be done with their samples in the future.  I

  would imagine that most people not trained in medicine

  don't have the foggiest idea what their tissues might

  be used for in the future.

            So I just wanted to ask you whether you were

  listening to that conversation and, if so, what is your

  response to his proposed rule of a kind of open-ended

  blanket consent for tissue acquisition and research?

            MS. TILOUSI:  As I mentioned earlier in the

  presentation, some of us got our blood samples back.  I

  was one that didn't get my blood samples back.  So I

  always question on where it went, what it's been doing.

  You know, there's been several of us that haven't

  received it back.  I would like to know where it went,

  what it's being used for.  If it's for anything good, I

  would like to know.

            I don't think that there should just be a

  blanket full release, you can do whatever you want.  I

  think if it's going to be used for something good, I

  would like to feel good that my body had contributed

  something, something positive to someone's life, or

  some solution to some research.  But I don't -- to me,

  I always still wonder where it went, if it's at the

  University of Southern California, or if it's in the

  University of Arizona, if it still exists, if it's

  damaged.  What is it being used for?  I don't know.

            So that is the question I am going to have to

  live with.  But I don't like the blanket idea.

            DR. GUTMANN:  Nita?

            DR. FARAHANY:  Thank you for all three of

  these presentations, which gives us a lot to think

  about.

            I want to focus on the linkage between

  training and bioethics and community engagement.  And

  as I understand, Roger, the way that you have presented

  it, you know, there is training the leaders in a

  community so that we can set up the institutions and

  the frameworks for ethical research.

            There is the training of the scientists, and

  helping them not just in understanding the rationale,

  but having it be an integral part of the education, so

  it's not just another check-box, but actually part of

  education from day one.  But I wonder if the missing

  link that we have been struggling with and discussing

  is really community engagement, in that for many

  researchers they undergo ethics training already, at

  least domestically somewhat abroad, as well as these

  programs start to become more widespread.

            But understanding the importance and the

  rationale of it, perhaps community engagements and

  being required, encouraged and, from the get-go,

  understanding that participating with and the dialogue

  with the stakeholders would really make the ethics

  requirement real.  Right?  It gives a real face to the

  issues, whether it's at the research population level

  or the broader community.

            So, is community engagement the way in which

  you take the check box of ethical research and make it

  a real experienced issue, such that it's integral, or,

  you know, is that not enough?  And that's directed to,

  really, any of you.

            DR. GUTMANN:  Mitchell, why don't you begin?

            MR. WARREN:  Sure.  It's a fantastic question,

  and I really think it hits to the heart of how research

  gets conducted.  And, you know, because we have created

  the tic box system, and the CAB is really -- and I'm

  exaggerating to make the point, certainly, but CABs are

  often "If I have it, I therefore have done good

  community practice, I have been ethical in my conduct,

  I have engaged community."

            But very often we fail to recognize the

  enormous power imbalance that takes place between trial

  participants, the communities from which those

  participants may come, and the researchers and the

  sponsors.  And while, again, no single document or

  guideline is going to address that power imbalance

  fundamentally, the GPP guidelines are certainly meant

  to provide a bridge to address those imbalances so that

  there is a discourse that can happen.

            You know, if I had to distill the entire

  guideline down to one idea, it's to create a robust

  discussion between the researchers and the communities,

  writ large.  Now, that's a challenge, because robust

  discussion is often not what many trial sponsors want.

  Many of them are quite risk-averse.  And yet, we need

  to move to the point where we recognize it's not just

  about the conduct of one trial.  It's about the way in

  which trials take place over time, particularly as we

  look at the globalization that Roger is describing.

            Many of these communities are engaging in

  dozens of trials at any given time.  So it's not just

  about one trial, it's about how this process engages.

  And I think critical to it is the evidence to show how

  the inputs around the training, on the one hand both of

  ethicists and of researchers, and of community

  stakeholders to be engaged in the discourse is really

  at the heart of it.

            DR. GUTMANN:  Dan?

            DR. SULMASY:  Thanks.  This will probably also

  be mostly for Mr. Mitchell, but -- or for Mr. Warren,

  but could be for others as well.  It's the -- a

  question of who actually represents the community or

  the stakeholders, and whether you have advice within

  your guidelines for who to engage in these robust

  discussions with.  Because people will still be

  helicoptering in, and often engaging new communities,

  and we don't know whether the government or the

  university, or whoever we're talking to, actually

  represents the community.  So, advice about making it

  broad, as well as robust in an engagement.

            MR. WARREN:  That is the trillion-dollar

  question.  Who gets to represent whom?  And very often

  the controversies have erupted when someone not fully

  allowed to or mandated to represent someone decides to

  be that representative.

            What the guidelines do describe is at the very

  outset, before we get to protocol development, to

  informed consent processes, is the kind of formative

  research and community mapping -- and this is

  particular important -- and again, remember, these

  guidelines came out of an HIV prevention research

  world, which is not working in every country and every

  community.

            But certainly much of our research, HIV and

  otherwise, is happening through research centers.  And

  it is not enough to decide in our protocol we want to

  recruit Population X, and therefore we will go to the

  community group that represents that population.  It's

  really important to understand that broader community.

            Who are the people who either validly speak

  for others and with others, and who just might

  parachute in themselves to decide to be that voice?  I

  think it's at our peril to try to define it too

  narrowly.  Because if we do, inevitably we will start a

  trial and we will encounter problems if we don't

  understand that broader universe.  And we may not like

  who is saying, "I represent X or Y," but if we don't

  understand those dynamics, we really are going to find

  ourselves with many more trials mired in controversy

  than in positive results.

            DR. GUTMANN:  Jim, do you want to --

            DR. WAGNER:  Just very quick.  A question.

  Carletta brings up something that we really haven't

  talked about as a commission, and I would be curious to

  know if all three of you agree that it would be

  worthwhile for the commission to spend some time

  thinking about a system of sanctions.

            Carletta seems to express disappointment that,

  having set up the -- not "seems to," she does express

  disappointment that having set up good practices, even

  improving those practices and having education around

  those practices, we will still have violators, and the

  sense that the public, who needs our

  confidence -- particularly as we imagine an increasing

  need for certain kinds of human subjects

  research -- doesn't feel as though we are holding

  ourselves accountable.  Would you recommend that there

  be some conversation about appropriate sanctions?

            DR. GLASS:  Absolutely.  And some trials have

  been closed down because of aberrations of ethical

  review.  Perhaps not enough.  We certainly spend more

  time at the beginning of a trial than in the

  continuity.

            I know, in my own experience, trials we did in

  South Africa with rotovirus vaccine, when we

  interviewed the women who brought their children for a

  vaccination, they had been asked to give a thumbprint

  of their consent.  When I spoke to them about the

  meaning of a thumbprint, the women said, "The only time

  I have ever given a thumbprint was 10 years ago, or 15

  years ago, during apartheid, when that thumbprint, to

  an official, meant that I lost my property."

            And so, for us to ask for a thumbprint for her

  was asking her, potentially, to do something adverse.

  And I think that's one of the reasons why this local

  involvement is key.

            And while training -- we can't train all the

  IRB people and all the medical students.  But by

  training leaders in-country and building their

  departments to be linked to academic departments in the

  U.S. so we get that, we can really have an

  amplification that goes much beyond the small

  investments that we make.

            DR. GUTMANN:  Nelson?

            DR. MICHAEL:  Just very quickly, to comment on

  Roger's colleague's issues about the impact of

  training, when we started working in Nigeria in 2004 in

  a partnership with the Nigerian military medical

  activities, working on HIV/AIDS, we spent about 2 years

  developing initial capacity to roll out the PEPFAR

  program within that community, and then begin to segue

  to do research.

            And we were able to do that fair seamlessly

  because of Clement's West African bioethics activity

  that he had at the University of Abadan which then

  spawned the Nigerian research ethics committee.  So

  exactly at the time we began to segue into science

  activities, the research absorptive capacity had been

  built there by Fogarty, and it allowed that partnership

  to go forward, and was enormously helpful.  That's an

  anecdote, but I think it's a pretty good one, and

  you've put a lot of investment.

            My question really is to Carletta.  Listening

  to what you said was very hard to hear.  And I would

  wonder if 10 years ago, if you had known the gentleman

  sitting next to you, if that sort of thing would have

  happened.  If you had known these two gentlemen, you

  knew about the process of good participatory practices,

  if you had struggled with the issue of other tribal

  community advisory boards or other liaisons to diabetes

  foundations, if you had representation to your state

  and federal congressional members, would this sort of

  thing have been prevented?

            And so, the question really is to the three of

  you.  What can be done that's cross-cutting across

  fields to ensure that people like Carletta know about

  the work that is being done by Fogarty or that's being

  done in an HIV prevention field, that it begins to

  suffuse this process across multiple disciplines?

            DR. GUTMANN:  Let me ask Carletta to answer.

  Would any of this or all of this have helped?

            MS. TILOUSI:  Yes, I think so.  If I had a

  better understanding when they first took my blood and

  explained to me, "This is what it's going to be used

  for.  We're going to come back to you in 30 days and

  tell you if you're going to have diabetes or not, and

  these are the prevention steps that you need to take,"

  I would have been more agreeable.

            At that moment in time, you know, you want to

  know the answer, whether you're going to be diabetic or

  not.

            DR. GUTMANN:  Right, right.

            MS. TILOUSI:  You know, so I think it would

  have been much easier for my community if we all met 10

  years ago.  But we can't go back in time, you know.  We

  need to correct what has happened and move forward.

            DR. GUTMANN:  So, let me ask this question

  that comes from a participant who will actually later

  be a presenter.  But it's a challenging question which

  needs to be asked.  It's from Ruth Macklin, professor

  of bioethics.  We all know Ruth.  Ruth just reminded me

  a few minutes ago of how many decades it was since we

  last met.  But I have followed Ruth's work since then.

  And it is to you, Roger.

            And Ruth writes as follows:  "As a recipient

  of an award from Fogarty for the past 10 years in Latin

  America, I have encountered hostile public response

  from a few people, claiming that the Fogarty program is

  an instance of American ethical 'imperialism' on the

  part of the NIH.  How can we counter this criticism?"

            DR. GLASS:  A good question, Ruth.  And I

  think a part of what we have done at Fogarty is to

  build the partnerships and the training together, so we

  have really tried to avoid exactly that kind of

  criticism.  And I hope we are doing that.  And if we

  are not, I think we have to address that.

            DR. GUTMANN:  Let me ask Mitchell, because

  this is a broader question.  Let me just -- I should

  say the international panel did recommend that the

  training be done not only by Americans, but that other

  countries develop the capacity as, you know -- and it

  was actually Fogarty, while not -- we not mention by

  name -- was an example of what the international panel

  wanted to see more of in their own countries.

  Mitchell?

            MR. WARREN:  Well, I think it's absolutely

  critical.  I mean when I look at the future, it's

  when -- you know, with all due respect to Roger and

  everybody at Fogarty -- it's when Jerome, who I know in

  South Africa and have worked with, when it's Clement,

  when they're the ones sitting at this panel, when

  they're the ones leading the discourse in their

  countries and regionally and internationally, is when

  we will see the real shifts that we need to.  And

  that's not just true of the ethicists at the table.  It

  is going to be true of the researchers at the table.

  Hopefully some day soon a funder is at the table.

            And I think the fourth kind of leg to that

  stool would then be the communities, too.  We often do

  our work, I think, in these siloed approaches, where we

  have the ethicist getting this, and the researchers

  getting this, and the funders doing this.  And

  communities are the nice to haves, but the first to be

  cut out of a budget, or the first issues to be left

  behind.  We will only be successful in that example

  that Ruth gave when communities in those countries are

  engaged and receptive to that work coming, whether it's

  coming from Ruth or from a local investigator.

            So I think we really need to frame this much

  more broadly, and with many more seats at the table,

  and with many different types of representatives in

  those seats.

            DR. GUTMANN:  Factually, we should

  indicate -- because I and my colleagues have been

  involved in this now on the international engagement

  side -- that there are many, many countries in the

  world that have extremely well-developed ethics

  training and groups that are engaged in ethics of

  medical research.  There are many that don't.  But we

  are, as Americans, by no means alone in wanting this to

  move forward.  And the dialogue is very robust between

  our commission and others.

            Yes, Roger?

            DR. GLASS:  Yes, just a comment.  I think we

  are interacting with the DCTP, the Nuffield Center, WHO on these.  We are trying to build the partnerships.  And my own work

  in Bangladesh -- the ethics committee in Bangladesh was

  started by NIH 50 years ago to allow cholera vaccine

  trials to go on in that country.  And now it's a very

  robust organization.  So I think it's building those

  partnerships so that people can participate in this

  dialogue, or the international dialogue, and represent

  themselves, just like Carletta has done here for us

  today.

            DR. GUTMANN:  Thank you, Carletta, Mitchell,

  and Roger.  Very interesting session.

 

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