Ethical Challenges in HIV Research in Thailand Krittaecho Siripassorn Bamrasnaradura Infectious Diseases Institute, Thailand November 2013
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Ethical Challenges in HIV Research in Thailand
Krittaecho Siripassorn Bamrasnaradura Infectious Diseases Institute, Thailand
November 2013
Outline
• Challenge in Vulnerability
• Challenge in ICF documents
• Challenge in the SAE reports
Outline
• Challenge in Vulnerability
• Challenge in ICF documents
• Challenge in the SAE reports
Vulnerability in Research
Vulnerable person
– Those who are relatively (or absolutely)
incapable of protecting their own interests
– Examples: racial minorities, very sick,
institutionalized, IVDU, prisoner, HIV etc.
Vulnerability in Research
Group-based approach Analytic approach
Examples: racial minorities,
very sick, institutionalized,
IVDU, prisoner, HIV etc.
Easier to identify person as
vulnerable and enforce
protection
Some circumstances may be
redundant, overlook individual
variations
Cognitive/communicative
vulnerability
Institutional vulnerability
Deferential vulnerability
Medical vulnerability
Economic vulnerability
Social vulnerability
Bankert EA & Amdur RJ, Institutional Review Board Management and Function, 2nd ed.
Clinical researches in BIDI
Title Design Phase Subjects
BIDI-MONO RCT 2 HIV, Adult, already on ARV with good response
START RCT 4 HIV, Adult, CD4 >500, naïve
AI467003 RCT 2b HIV, Adult, CD >200, naïve
PREDICT cohort Cohort NA HIV, Children, previously enrolled in PREDICT study
HIV-NAT 113 Cohort NA HIV, Children, failure to secondline ARV treatment
Informed consent Title Vulnerability Invited Signed consent
BIDI-MONO Chronic stable dis, already received ARV and treatment result is good
188 71
START Did not received any ARV before 8 8
AI467003 Did not received any ARV before
25
25
PREDICT cohort
Already receive ARV and participate in another study
16 16
HIV-NAT 113 Failure to previous treatment 6 6
Vulnerability in HIV Research
• In general, vulnerability of participant with
HIV infection should be addressed
– However, the vulnerability should be
addressed within the context of a specific
population
– HIV-infected patients who already received a
successful ARV may be less vulnerable than who were naïve to ARV
Outline
• Changes in Vulnerability
• Challenge in ICF documents
• Challenge in the SAE reports
HIV & Stigma
• AIDS stigma exist worldwide, although they
manifest themselves differently across countries,
communities, and individuals
• Stigma can result in people with HIV being
insulted, rejected, gossiped about and excluded
from social activities
• Fear of this happening can lead to people with
HIV being nervous about telling others that they have HIV or avoiding contact with other people
www.unaids.org
Clinical researches in BIDI
Title Design Phase Subjects
BIDI-MONO RCT 2 HIV, Adult, already on ARV with good response
START RCT 4 HIV, Adult, CD4 >500, naïve
AI467003 RCT 2b HIV, Adult, CD >200, naïve
PREDICT cohort Cohort NA HIV, Children, previously enrolled in PREDICT study
HIV-NAT 113 Cohort NA HIV, Children, failure to secondline ARV treatment
There were 71 subjects signed ICF, however none of them kept the ICF with them
The title of the HIV protocol may stigmatize participants in the study
Consent Form
Title: Prevalence and factors associated to
metabolic syndrome in HIV-infected patients who
receive antiviral treatment in Bamrasnaradura Infectious Diseases Institute
Questionnaire research done by pharmaceutical students
Consent Form
Title: Prevalence and factors associated to
metabolic syndrome in patients who receive
medical care in Bamrasnaradura Infectious Diseases Institute
Only 10 (7%) from 140 subjects kept their consent documents with them
The word “HIV” was deleted from the protocol title before EC approval
Delete protocol title from consent document
may protect the HIV-infected participants from stigmatization
Please kindly invite me to present data next year because enrollment will start about Jan 2014
Outline
• Changes in Vulnerability
• Challenge in ICF documents
• Challenge in the SAE reports
ICH-GCP
“All SAEs should be reported immediately to the
sponsor except for those SAEs that the protocol or
other document (e.g., Investigator's Brochure)
identifies as not needing immediate reporting.”
ICH-GCP 4.11 (1)
WHO: Standards and Operational Guidance for Ethics Review of Health Related Research with Human Participants, 2011
“All serious, unexpected adverse
events related to the conduct
of the study/study product or
unanticipated problems involving
risks of harm to the participants or
others are promptly reported
to the REC and/or other relevant
authorities, as required by REC
policies and applicable laws”
Immune Reconstitution Syndrome in HIV-Infected Patients Taking Antiretroviral Therapy
• Observational study
• Objective:
– to investigate what factors may lead to the
development of immune reconstitution syndrome
(IRIS) in HIV-infected patients and what the outcome
is after IRIS
• Subjects:
– Adult, HIV+ve, CD<100, naïve to antiretroviral
– N: Thailand 100, Kenya 200, US 300
ClinicalTrials.gov Identifier:NCT00286767
HIV patient CD4 <100
Receive ARV
as standard practice
4 years follow-up
Risks that were not related to study procedure
ARV toxictiy (estimated 2-5%)
IRIS (generally about 20-37%) Opportunistic infection
Study procedure: Blood samples, CT scan, aphreresis
N = 100 (Thai)
Risks that were related to study procedure
Related to study procedure Confidentiality issue
On-site SAE reports in IRIS study
• 80 subjects enrolled since
Sep 2012
On-site SAE reports
(Sep 2012-Oct 2013)
• Total N = 45 (3.5/months)
• Initial/ Follow up (n) = 30/15
• Death N = 8
The risk of this study is higher than normal practice?
Death rate in the IRIS study
Death rate
This Study 10% (8/80)
Cohort study: HIV CD<100 during
2002-2004 (death rate during 1st year)
20%
1 Breaux K. AIDS Care 2010
Initial report of IRIS study
• Drug toxicity (n = 5)
• IRIS (n = 22)
• Others
– Brain tumor (n = 1)
– Renal calculi (n = 1)
– Appendicitis (n = 1)
• No SAE due to protocol procedures
HIV patient CD4 <100
Receive ARV
as standard practice
4 years follow-up
Risks that were not related to study procedure
ARV toxictiy (n = 5)
IRIS (n = 22)
Study procedure: Blood samples, CT scan, aphreresis
N = 100 (Thai)
Risks that were related to study procedure
Related to study procedure Confidentiality issue
These types of
SAE reports
were expected and anticipated
These types of
SAE reports were
unexpected or unanticipated
WHO: Standards and Operational Guidance for Ethics Review of Health Related Research with Human Participants, 2011
“All serious, unexpected adverse
events related to the conduct
of the study/study product or
unanticipated problems involving
risks of harm to the participants or
others are promptly reported
to the REC and/or other relevant
authorities, as required by REC
policies and applicable laws”
ICH-GCP
“All SAEs should be reported immediately to the
sponsor except for those SAEs that the protocol or
other document (e.g., Investigator's Brochure)
identifies as not needing immediate reporting.”
ICH-GCP 4.11 (1)
Challenge in the IRIS study
• The justification of exemption of SAE
report in the observational study that was
expected and anticipated should be
concerned
• This issue might be addressed in the
protocol
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