Transcript Responsibilities of state, community and private - TRT-5

Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
Hugues Fischer, TRT-5 (French Cab), Act Up-Paris, Paris, France
Trials Accelerating Research : Approaches that Work
XVI International Aids Conference
Toronto Canada 13-18 August 2006
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
Issues :
• The early years of the fight against AIDS saw a redefinition of
roles and responsibilities between state, civil society and
private sector on research priorities and research ethics
• Yet, though greatly improved, the resulting compromise system
created for ensuring appropriate protection of research
participants is not perfect
• This poster will explore activities and changes needed to reach
a higher level of protection assurance for clinical research
participants looking back on recent CCR5 antagonist polemic
that opposed the French CAB TRT-5, to 3 pharmaceuticals
companies : Pfizer, Schering-Plough and GSK
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
Naive patients :
generic denomination, but heterogenous situations
Early testing, high CD4
level, moderate viral load
(Stage A)
More advanced patients,
200<CD4<350
VL<100 000
(Stage B)
Late testing, advanced
patients with CD4<200
High viral load
(StageC)
•
Art Cohort Collaboration :
Higher risk of clinical evolution (on a 3 years comparison basis) in patients initiating
validated HAART with CD4<200
•
British Columbia cohort :
Initiation of HAART when VL> 100 000 is correlated with bad prognosis Concording
results were found in other cohorts (MACS, Eurosida, ANRS CO4 / FHDH)
•
CD4 <200 and/or VL > 100 000 : these patients must benefit from both a
validated HAART and a thorough follow up
Responsibilities of state, community and private sector on research ethic
Policy : looking back on recent CCR5 antagonists
Phase II CCR5-antagonist trials in 2005
Dose determination trials
Inclusion criteria limits
Lab and drug
CD4 count
Viral load
Shering Plough
« vicriviroc »
>150 CD4/mm3
no
Pfizer
« maraviroc »
No criteria
no
GSK
« aplaviroc »
>100 CD4/mm3
no
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
Phases II trials :
At this step, what was known
on ARV associations including anti-CCR5 drugs?
KNOWN
•
In vitro data and animal testing
results
•
•
Tolerability in healthy volunteers
Phase I results : drop of viral
load following a 7-10 days antiCCR5 monotherapy (same
order of magnitude as observed
with other ARV) among 60-80
patients with high CD4 (>400)
•
In vitro, evidence of resistance
mutations
UNKNOWN
•
Efficacy and tolerance of antiCCR5 in combination with other
ARV; drug interactions with antiOI medicines
•
Anti-CCR5 efficay and tolerance
on periods longer than 10d
Appropriate doses and
administration schedule
CCR5/CXCR4 switch and
consequences on clinical
evolution
•
•
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
Were there enough data to include
advanced naive patients in Phase II trials?
• Due to the lack of mid-term data concerning association of anti-CCR5
and other ARV, there was a clear risk of sub-optimal treatment
administration in these clinical trails, mainly implying following risks :
• Early failure for naive advanced patients initiating treatment in the
late phase of the disease
• Clinical degradation/ resistance appearance
• Psychological impact following first treatment failure :
• Discouragment and depression
• Loss of confidence in therapy
• Lack of adherence
• Risk of increased Serious Adverse Events (IRS, drug interactions
with OI medicines)
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonists
TRT-5 position
• Evaluation of putative risk/benefit ratio based on
available data suggested that inclusion of naive
advanced patients in these phase II clinical trials
was far too risky.
• Patients’ interest did not favor their participation in
these early trials. More insight should be gained in
stage A patients before inclusion of naive advanced
patients in new class products trials.
Responsibilities of state, community and private sector on research
ethic Policy : looking back on recent CCR5 antagonist
Recommendations
« There is no good science where there is no good ethics »
• In medical research on human, considerations related to the wellbeing of the human subject should take precedence over the
interests of science and society.(Declaration of Helsinki, article 5)…
Although these interests are not necessarily antagonistic.
• There is no contradiction between the TRT-5 position and the fight
of this group for early drug access for experienced patients with
complete therapeutic failure.
• French ethics and expertise in HIV field should promote guidelines
which could be internationally called and used
• Although in this presentation, we focused on entry criteria, there
were many more parameters in these trials which compromised
people security
Meet the TRT5 :
Exibition hall, booth G-471, FRANCE
this afternoon from 2:30 to 4:30