Download Ethics in a new era

Ethics in a new era
Microbicides 2012 Preconference
Bridget Haire
Ethical issues in research
• Balance of risks of benefits
• Fairness
• Consent
– Voluntary
– Sufficient understanding
– No coercion
• Promote justice, avoid exploitation
– Reasonable likelihood that the trial community
will eventually derive benefit
– Risks not disproportionate or unreasonable
Community role in ethical research
process
• Make the research better
• Get the best deal possible for participants*
and the local community (risk/benefit
balance, fairness, consent, no exploitation)
• Communicate effectively with research team
about issues that affect the research process,
outcomes and participants
• Communicate with and listen to the wider
community about the research
What’s the new era?
• Positive trial results: can we still use placebos?
• Adherence as critical: supporting it, measuring
it, communicating honestly about it
• ‘Futility’ results (FemPrEP, Voice)
– Stopping rules: when should a trial be stopped for
futility?
– Are IIB trials still useful?
New biomedical intervention strategies
Effect size
(CI)
Study
Prime-boost HIV
Vaccine (Thai RV144)
1% tenofovir gel
1% tenofovir
(Caprisa
004, Karim etgel
al.)
(Caprisa 004,oral-PrEP
Karim et al.) in MSM
TDF/FTC
31% (1, 51)
39% (6, 60)
44% (15, 63)
(iPrEx, Grant et al 2010)
Medical male circumcision
(MMC) (Orange Farm, Rakai, Kisumu)
TDF/FTC oral-PrEP in
heterosexuals (TDF2, CDC)
TDF oral-PrEP in serodiscordant
57% (42, 68)
63% (22, 83)*
62% (34, 78)*
Partner (Partners PrEP)
73% (49, 85)*
TDF/FTC oral-PrEP in serodiscordant
Partner (Partners PrEP)
96% (82, 99)*
Immediate ART for positive
Partners (HPTN052)
0% 10
Slide: Robin Shattock IAS Plenary Rome 2011
20
30
40
50
60
70
80
90 100%
Efficacy
When should new interventions be
added to prevention package?
• If the method been recommended by
international bodies or adopted nationally
• But also if:
– the evidence is strong AND
– the intervention has shown efficacy in the relevant
population; AND
– if provision is feasible.
If the evidence is strong…
• Statistically significant (P = <0.05)
• Effect size is substantial (lowest end of the
confidence interval needs to big enough to
have an impact)
• More than one trial, or one trial with a very
strong result
• Not entirely black and white, and subject to
arguments about specific situations
Relevant populations
• Route of exposure (vagina/penis, rectum,
intravenous)
• Might extrapolation be reasonable in some
instances?
Is provision feasible?
• What are the barriers – regulatory, costassociated, manufacturing issues?
• Cost associated issues might be resolvable
through drug donations
• Regulatory issues may be resolvable through
advocacy (or maybe not)
• Manufacturing issues may be impossible to
solve short-term
When should a new intervention not
be added?
• When there are safety issues regarding drugdrug interactions
• When the addition of a new intervention
would compromise the ability of the trial to
answer the relevant question
• (Is the trial addressing a relevant question?)
Grey areas
• Ipergay- French trial of PrEP in gay men
comparing intermittent PrEP with placebo
• Issues
– Continuous PrEP shown modestly effective in
iPrEX (44%, but higher in good adherers)
– Proof-of-concept in Partners PrEP and TNF2
(Botswana), though with penile exposure
– BUT not approved for prevention (yet) anywhere
ASPIRE – more grey
• Vaginal ring that delivers the ARV dapivrine
• Ph III trial of 3476 randomised to active ring or
ring with placebo
• Positive trial results that should be considered
HPTN052 (early treatment of positive partner),
CAPRISA 004 (tenofovir gel) Partners PrEP, TNF 2
(PrEP)
• Negative results FemPrEP, VOICE
Vaginal rings
Issue in ASPIRE
• PrEP could not be added to both arms, due to
potential drug/drug interactions
• Head-to-head against PrEP or tenofovir gel?
• Early treatment offer for HIV positive partners
of participants (applying HPTN052 lessons)?
IIB Trials/Stopping rules
• Both FemPrEP and VOICE were designed so
that if a product was ineffective at certain
time points, that arm of the trial was stopped
• Is this useful?
• Smaller trials have less power to give an
answer
• Should trials be stopped for futility?
Ethics sessions at M2012
• Standard of Prevention – Monday 11am
• Social and ethical issue in HIV Prevention –
Monday 2 pm
• Beyond the Trial: ethical and operational
challenges for post-trial access– Wednesday
11am