Transcript Change in Perceptions Associated with More Effective Therapies

International Research Ethics:
Issues in Prevention Trials
Steve Morin, Ph.D.
AIDS Policy Research Center
AIDS Research Institute
University of California, San Francisco
http://ari.ucsf.edu/policy/policy.htm
NIH Funding for International AIDS
Research, FY 1996-2004
Source: Fauci, NIAID, 2003
The Community-Based VCT
Prevention Trial

HPTN 043: A Phase IIB Randomized Trial to
Evaluate the Efficacy of Community-Based HIV
Voluntary Counseling and Testing to Reduce HIV
Seroincidence (funded by NIMH).

32 communities in Africa (Tanzania, Zimbabwe,
and South Africa) and 14 communities in Thailand
will be randomized to either a community-based
HIV voluntary counseling and testing (CBVCT)
intervention or clinic-based standard VCT (SVCT).
Background

Most HIV infections are in sub-Saharan Africa, yet
only a small fraction of Africans know their HIV
status.

Voluntary HIV Counseling and Testing (VCT) is an
effective method of promoting behavior change,
but utilization of VCT is still low in African
communities with a high prevalence of HIV.
Harare
Zimbabwe
~25% of sexually active Zimbabwean
adults are infected with HIV, yet a small
percentage know their HIV status
Community-Based VCT

Intervention has three major strategies:
 to make VCT more available in community settings
 to engage the community through outreach; and
 to provide post-test support.

These three strategies are designed to change
community norms and reduce risk for HIV infection
among all community members, irrespective of whether
they participated directly in the intervention.
The road to market in Epworth
Mobile VCT Pilot Study

Offered free, anonymous VCT from a mobile
caravan

Rotated once a week to 6 sites in Epworth

Rapid tests were performed (15 minutes)

Testers were offered the option to wait for results
outside the caravan or return on another day
“Plan for Tomorrow -- Get HIV Tested Today”
Setting up the caravan for VCT at the Solani Marketplace in Epworth
Counselors and outreach worker ready for action
What’s different about international
research?

Vast disparities in wealth between
sponsor and host countries

Limited resources in host country

History of exploitation
Anticipating
Ethical Issues
What are the ethical issues?

Research questions and priorities

Interventions for control group

Post-trial access to interventions

Informed consent

IRB review
Research questions and priorities

Helsinki
 “a reasonable likelihood that [study
populations] stand to benefit from the results”

NBAC
 “limited to those studies that are responsive to
the health needs of the host country”
Response

The CBVCT question emerged from prior
research in Tanzania and Kenya.

Issue is considered important to key
stakeholders in revising the National AIDS
Control Plan.

It addresses both an important behavioral
science question and a need of the host
country.
Interventions for control group

Helsinki
 “Best current prophylactic, diagnostic, and
therapeutic methods”
 Rejected “highest attainable and sustainable”
standard

NBAC
 Effective treatment preferred, but current (no)
care may be justified to meet host country
health needs
Response

The standard of care (SOC) for VCT as a
prevention intervention was established in
the Tanzania and Kenya trial.

In the control arm of this trial, we establish
the same clinic-based VCT as SOC.

SOC was chosen over “available care” for
scientific as well as ethical reasons.
Post-trial access to interventions

Helsinki
 Subjects “should be assured of access to the best
proven prophylactic, diagnostic, and therapeutic
methods identified by the study

NBAC
 “Reasonable, good faith efforts” to provide access
to participants
 Address access issues in planning
 Negotiate agreements in advance
Response

Representative from the Zimbabwe Ministry
of Health National AIDS Control Program
serves as an investigator.

USAID involved in planning and primary
VCT contractor serves as technical advisor.

CDC involved in planning and developing
laboratory measures for assessing primary
endpoint.
Informed Consent

Communicate information
 on multiple levels (community, family, individual)
 in multiple formats (oral, written)
 over time

Assess participant’s understanding
Response

Involved local researchers in developing the
informed consent documents.

Developed Community Advisory Board that
reviewed consent documents and process.

Modified US approaches to be reduce
miscommunication.

Integrated concepts of informed consent
into pre-test counseling.
Where does HIV
Prevention
Research Fit in
the Big Picture?
Coverage of Antiretroviral Therapy in
Developing Countries, 2002
(Adults by Region)
Source: Fauci, NIAID, 2003
Total Federal HIV/AIDS Spending by Category
FY 2002
Source: Kaiser Family Foundation, 2003
Total Federal HIV/AIDS Spending by
Department of Agency
FY 2002
Source: Kaiser Family Foundation, 2003
The President’s Emergency Plan for
AIDS Relief
Source: Fauci, NIAID, 2003
The International Mother and Child
Prevention Initiative
Source: Fauci, NIAID, 2003
President’s Emergency Plan for AIDS
Relief: Funding Breakdown
Source: Fauci, NIAID, 2003
NIH Mission
1) Foster fundamental creative discoveries, innovative
research strategies, and their applications as a basis to
advance significantly the Nation’s capacity to protect and
improve health;
2) Develop, maintain, and renew scientific human and
physical resources that will assure the Nation’s capability to
prevent disease;
3) Expand the knowledge base in medical and associated
sciences in order to enhance the Nation’s economic wellbeing and ensure a continued high return on the public
investment in research; and
4) Exemplify and promote the highest level of scientific
integrity, public accountability, and social responsibility in
the conduct of science.
Planning for
Unanticipated
Ethical
Challenges
Community Advisory Boards

Represent community -- bridge, link, go-between,
liaison -- make suggestions about protocols

Safeguard/protect the community -- clearinghouse
for ethical issues -- promote respect for
participants

Legitimize research in communities -- respond to
misinformation, provide access
Community leaders play an important role, as they facilitate
access to the local community, as well as understanding and
acceptance of research.
“That is why you saw us coming to look in, when
the caravan came … people could see that I
was also involved in this project and that
they should not try anything because I am
here and we are the ones who have brought
this project.
We were giving ourselves accolades...you thought
you had the accolades but we were the ones
who had them!
We want to tell you … we were telling people
we brought the project so that they could
embrace it, there was no problem my
children (referring to staff).”
Barbara Mangwende, Chair
of the Epworth CAB
Bread

Challenge: Many participants coming for
pilot study were weak from hunger.
Nurse raised issue of whether we can
feed them bread?

Should the research study feed them?
Response

Extensive discussion in counseling supervision
session and consultation with other projects.

Determined that offering food would be coercive
under the circumstances; referral to food
programs would be more appropriate.

Providing food (incentive) would also change the
study -- would no longer be testing whether
changing community norms leads to increased
awareness of status and decreased new
infections.
Antiretroviral Therapy

Challenge: HIV drugs are not generally available.
Referral options are limited. Treatment advocates,
some developing country researchers, and some
at NIH have suggested it is “unethical” to conduct
HIV testing if the researchers do not provide
treatment.

What should the researchers do?
Response

Conducted focused discussion of the issue with
local CAB.

Consensus was that VCT was of benefit to
participants and community even in absence of
treatment.

Providing treatment would also change the study - would no longer be testing whether changing
community norms leads to increased awareness
of status and decreased new infections.
HPTN Guidance

Prevention trials should make “practically
achievable” effective prevention methods
“reasonably available” to all people screened or
enrolled -- VCT & condom availability.

In conducting research in settings where
standards of HIV care are poor, consider
opportunities to contribute to the local
infrastructure.
What should investigators do?

Raise and address issues
 Expect close scrutiny and harsh criticism
 Justify design proactively
 Plan for potential criticisms

Make good-faith, reasonable efforts
 Involve host country scientists, community leaders,
political leaders

Seek US and host country review and consider
community consultation
Acknowledgements





National Institute of Mental Health (NIMH) and Office of
AIDS Research (OAR)
Leslie Wolf, JD & Bernard Lo, MD, UCSF Program in
Medical Ethics and CAPS Policy & Ethics Core
Epworth Community Advisory Board and Epworth
Local Board
Community Working Group & Ethics Working Group,
HIV Prevention Trials Network
Zimbabwe Investigators: Gertrude KhumaloSakutukwa, Katherine Fritz, Tinofa Mutevedzi, Taurai
Vaki and Owen Mapfumo