Transcript New types of trials: Smaller, faster, cheaper etc.

Traditional vs novel trial
designing
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Giuseppe M.C. Rosano, MD, PhD
Why should we do it faster?
From 2000 to 20010, the top 10 pharma companies started 􏰂more than 1700 new
projects/year
Loscalzo J (2012) Circulation 125:638-645.
Why should we do it faster?
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Time
Costs
Efficiency
Innovation
25 Years life-cycle of a drug
New chemical entity approval and cost
of R&D
1.3B$/Drug
From bench to bedside
Reasons for termination of clinical
development program on NCEs
C. K. Atterwill; M. G. Wing Molecular and Cellular Approaches to Lead Optimization in Pharmaceutical Development
Definitions of stages of clinical trials
2B studies in selected indications
Traditional controlled clinical trial
TARGET POPULATION
RANDOM
TREATMENT A
TREATMENT B
OUTCOME
OUTCOME
STATISTICAL COMPARISON
Traditional trial designs
Traditional trial designs
Traditional trial designs
Scheme for a prototypical n-of-1 trial
modified from Zucker et al. 2006
Animal models and human PK/PD
1. More than 25% of drug entering CTs fail because of “poor
pharmacology”
2. Animal data are useless to indicate the effective dose in
humans (1/100th of the therapeutic dose in animals)
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Animal models are only required to test safety. Efficacy should
be either tested in big animals or should be directly tested in
humans
3. Animal studies
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Kill promising drugs (may work at therapeutic concentrations)
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Promote drugs that are ineffective
Can we skip earlier phases of
clinical drug development?
• Aloperidol
• LCZ696
Adaptive trial designs
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A decision-oriented, sequential learning process
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At any stage, the data may be analysed and next stages
redesigned taking into account all available data from the trial,
or even from outside, based on predefined rules
1. Allocation Rule: how new patients will be assigned to available
treatments
2. Sampling Rule: how many subjects will be sampled at the next
stage
3. Stopping Rule: when to stop the trial
4. Decision Rule: allows for change in hypothesis, primary endpoint, statistical method or patient population design
Adaptive trial designs
Drop-Loser Adaptive Study Design
Learning phase
Confirmatory phase
Adaptive Licensing: the way forward
Basic principle
Make innovative drug access easier through an
early approval and acknowledgement of
uncertainty of data...
…but not of the risk!
(a) Current scenario
(b) AL scenario
Eichler et al. Clin Pharmacol Ther. 2012 Mar
How to streamline clinical trials
• Duration
• Costs
Study design
Sample size
• It is not efficient
• It is unnecessarily complicated
PI
• Too many people Involved
CROs
Patient recruitment/retention
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Pre-trial registries
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Consortiums
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Use of social media (twitter/facebook)
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New software
3.
Patients' organizations – double-edge sword