Transcript HIVNAT The HIV Netherlands Australia Thailand Research Collaboration Ethical considerations of HIV research in Thailand: the HIV-NAT as a case study Praphan Phanuphak, M.D., Ph.D. Faculty of.

HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Ethical considerations of HIV
research in Thailand: the HIV-NAT as a
case study
Praphan Phanuphak, M.D., Ph.D.
Faculty of Medicine, Chulalongkorn University
&
The Thai Red Cross AIDS Research Centre
Bangkok, Thailand
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
HIV-NAT
The HIV Netherlands Australia Thailand
Research Collaboration
104 Rajdumri Road
Pathumwan
Bangkok 10330 Thailand
Tel: +66 2 255 7334/5 Fax: +66 2 252 5779
www.hivnat.org
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HIVNAT
Collaborating organizations
The HIV Netherlands Australia Thailand Research
Collaboration
Thai Red Cross AIDS Research Centre (TRC ARC)
Bangkok, Thailand
Prof. Praphan Phanuphak
National Centre in HIV Epidemiology and Clinical Research
(NCHECR)
University of New South Wales, Sydney, Australia
Prof. David A. Cooper
International AIDS Therapy Evaluation Centre (IATEC)
University of Amsterdam, The Netherlands
Prof. Joep. M.A. Lange
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Mission and Objectives
Conduct multi-centre HIV-related clinical studies according to good clinical
practice (GCP) and good laboratory practice (GLP) guidelines in Thailand
and the region
Provide access to antiretroviral therapy for HIV-infected people in Thailand
Educate healthcare workers in Thailand and the region on GCP, GLP and
HIV medicine
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Milestones
1995
HIV-NAT concept
1996
start of operations
first patients enrolled on study
1997
first presentations at international meetings
1998
Bangkok symposium in HIV medicine
UNAIDS collaborating centre
1999
UNAIDS Best Practice
2000
first pK study of NLV in newborn
2003
approximately 1,500 patients on studies
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009*
D4T ER
HIV-NAT STUDY
TIMELINES
HIVNAT
ESPRIT
Decadurabolin
2NN
BMS PI
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The HIV Netherlands Australia Thailand Research
Collaboration
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Mid 1996
004 IL-2 Vanguard
003.2
003.1
003
002.2 extension
002.2
001.4*
002.1
001.3
002
001.2
001.1
001
1997
1998
* 2 new studies
started June
1999
20002001 2001
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HIVNAT
Ethical considerations
The HIV Netherlands Australia Thailand Research
Collaboration
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Biased ethical approval: authoritative or political
Unethical conduct or deviation of the approved
protocol without 3rd party supervision
Ineffective consent process or not telling the whole
true story
Subjects do not have much choice
What to offer to those who cannot enroll or fail the
inclusion criteria?
End of trial medications
Research colonialism
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HIVNAT
Ethics
The HIV Netherlands Australia Thailand Research
Collaboration
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Ethical approval, protocols and consent form are just
arbitrary processes.
Integrity of researchers is most crucial. It is inherent
within individuals but can be shaped up if they know
that someone is looking after them.
Research watchdog is useful to guarantee
international standards but sometimes can be a
stumble block.
Voice of the local affected people should be listened.
We need to help them to get the best possible
options.
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Quantitative studies of the quality of
the informed consent given by the
Thai researchers in the ESPRIT
study
Christine Pace, Ezekiel J. Emanuel, et
al
Department of Clinical Bioethics
NIH
HIVNAT
ESPRIT
The HIV Netherlands Australia Thailand Research
Collaboration
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A phase III international study of SC IL-2
4000 subjects worldwide, 368 from Thailand
Randomized 1:1 with ARV alone, a 5-year study
141 patients immediately after signing the informed
consent to join ESPRIT were invited to participate in
in-person interview before learning of their
randomization assignments
The survey was administered by Thai personnel
trained by NORC who had no affiliation with ESPRIT
ESPRIT staff had no access to the completed Q&A
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HIVNAT
The informed consent process
The HIV Netherlands Australia Thailand Research
Collaboration
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Initial information given by M.D. or VCT counselor
Group discussion of the protocol led by a nurse
coordinator (20-30 min)
Thai version of the informed consent document
provided with 20 minutes to read
Q & A session before signing the 2600 words long
standard NIH informed consent
The survey used a 67-question questionnaires,
developed by NORC, Univ. Chicago, with an average
of 33 minutes long in-person interview
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HIVNAT
Main findings of the survey
The HIV Netherlands Australia Thailand Research
Collaboration
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High level of knowledge about the study (over 93%
vs 28% in US study) including the side-effects
21% felt that the discussion was more useful than the
written materials
None had pressure from the ESPRIT research team
to join the study
30% had pressure from their health-related
circumstances to join
Understanding treatment randomization was a
problem, only 31%
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Conclusion
The results challenge the claim that research
participants in developing countries cannot
give voluntary and fully informed consent.
However, independent monitoring such as
this is essential.
Of note: 48% of the subjects had completed college
or graduate schools.
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HIVNAT
End of trial medications: strategies of
HIV-NAT
The HIV Netherlands Australia Thailand Research
Collaboration
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Try to negotiate for at least 2 years of ARV supply or
life-long if possible
If patients do not yet need ARV, for example, in a pK
study, 2 years guarantee of ARV when ARV is
needed in the future. Grant is given for future ARV.
Request ARV support from the MOPH, some success
Roll-over protocols
HIV-NAT Drug Fund
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HIVNAT
HIV-NAT 001 series
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The HIV Netherlands Australia Thailand Research
Collaboration
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001 : Half-dose vs. full-dose ZDV/ddC
001.1: d4T/ddI/SQV-SGC vs. ZDV/3TC/SQV-SGC (1400
mg bid)
001.2: 001.1 +/- itraconazole 100 or 200 mg OD to look
for SQV plasma level
001.3: SQV-SGC 1600 mg + RTV 100 mg OD (for
undetectable VL) vs. SQV-SGC 1400 mg bid (for
detectable VL)
001.4: Continuous OD SQV/RTV vs. week on-week off
vs. CD4-guided (STI)
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
HIV-NAT drug fund
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Initiated in November 2001
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Subsidize antiretroviral drugs based on “a Co-Pay
and a Sliding Scale System” for post-trial patients
and patients in trials with intolerance or resistance
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Rule: patient pays at least 1500 Baht and HIVNAT at
most 5000 Baht
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Funding of 2 million baht (first year) and 1 million
baht (subsequent years)
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Progress report (End of year 2002)
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868 in-trial, 278 post-trial
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83 patients requested assistance
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62 patients received assistance
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Budget used: 413,321 Baht
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Number of patients who requested drug fund assistance
83
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Post-trial
76
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In-trial but had intolerance or resistance to ARV provided by 7
the trial
Number of patients who received subsidization from HIV-NAT
62
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Mean monthly amount in USD1 patient has to pay
44 (0 to 209)
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Mean monthly amount in USD HIV-NAT subsidizes
41 (1 to 120)
Number of patients who did not receive subsidization
21
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Number of patients who can afford the total drug cost2
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Number of patients whose requests were denied3
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HIVNAT
The HIV Netherlands Australia Thailand Research
Collaboration
Future plans
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Re-evaluate patients’ financial status every 12
months
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Patient questionnaire to assess
– Benefits
– Problems
– Suggestions for improvement
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HIVNAT
Summary
The HIV Netherlands Australia Thailand Research
Collaboration
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Ethics in performing HIV research is a real concern in
Thailand but can be improved.
Good and ethical HIV research can be done but it
should be closely monitored.
Ethical standardization is ideal but should not be a
barrier for doing research in developing countries and
should be tailored to fit each country, taking into the
consideration of all stakeholders in the country, not
only from the North or the funding agencies.
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