Transcript Ethical Issues in International Clinical Trials

Ethical issues in international
clinical trials
Bernard Lo, M.D.
University of California San Francisco
May 28, 2009
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HIV prevention in Cambodia
 RCT of daily tenofovir as pre-exposure
prophylaxis (PrEP)
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PrEP protests
 Should receive standard interventions

Prevention services
• Needle exchange, methadone for IDUs
Dialysis for renal failure
 ART for seroconverters

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PrEP protests
 Access to drug after trial
Manufacturer offered to sell at cost
 Still unaffordable

 Lack of informed consent
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Questions for audience
 State of art prevention services?
 Access to study drug after trial?
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Need research in developing
countries
 Some conditions primarily in South
 Uncertainty over best Rx

Optimal therapies not feasible
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Drug company interest in
developing countries
 Trials cheaper and quicker

Many “naive” patients
 Simultaneous licensing in many
countries
 Most clinical trials now offshore
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Tenofovir study
 Trials halted, delayed
 Results expected 2009
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Issues to discuss
1. Interventions for control group

Placebo controls
2. Informed consent
3. Benefits to participants and
communities
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Fundamental ethical principles
1. Beneficence


Acceptable risk/benefit balance
Withholding beneficial interventions criticized as
unethical
2. Respect for participants

Informed and voluntary consent
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Fundamental ethical principles
3. Justice

Criticized for exploitation, double standard
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1. Interventions for control group
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Interventions for control group:
Helsinki #29 (2000)
 Interventions must be tested against
“best current prophylactic, diagnostic,
and therapeutic methods”
 Rejected “highest attainable and
sustainable”
www.wma.net
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Interventions for control group:
NBAC report (2001)
 Studies must address priorities of host
country
 Pertinent research question may be: is
a limited intervention better than
current (no) care?
http://bioethics.georgetown.edu/nbac/
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Interventions for control group:
Helsinki (2008)
 Placebo necessary to determine safety
and efficacy
 Compelling and scientifically sound
methodological reasons
 No serious and irreversible harm
www.wma.net
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2. Informed consent
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RCT of prenatal folate
 Prevent birth defects?
 Unethical to useplacebo control in U.S.
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Prenatal folate trial in China
 Subjects illiterate women in rural areas
One child policy
 Misinformation about trial
 Concerns that birth defects ascribed to drug
 Seek permission from mother-in-law

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What is culturally appropriate?
 Respect for persons is universal
 Tailor consent procedures and
documentation to particular situation
Not longer consent form
 Participant may seek permission from third
party

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Innovations in informed consent
 Consult with community
representatives
What are participants’ concerns about
study?
 What will be difficult to understand?
 How best to explain study?

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Innovations in informed consent
 Assess participant comprehension

Disclosing information is necessary but not
sufficient

Shift emphasis away from consent form
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3. Benefits to participants and
communities
 In return for helping researchers and
sponsors, what benefits should
participants and communities receive?
 Should not take unfair advantage
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Benefitsto participants during trial
 Physical exam, laboratory tests
 Short-term medical care
 Clinical significance?
If no care for diagnosed problems
 If no ongoing care for chronic condition

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Post-trial access
 “Reasonable” availability of study drug

Few positive pivotal trials
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Fair benefits
 To community where trial carried out,
not just participants
 Education, training
 Volunteer clinical care
 Equipment after trial
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Summary
 Ethical issues in any clinical trial
 Particularly complex in global setting
 Adverse publicity from allegations of
unethical behavior
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