Encouraging adaptive designs in NiHR funded clinical trials
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Transcript of Encouraging adaptive designs in NiHR funded clinical trials
Encouraging adaptive designs in NiHR funded clinical trials
Professor Sallie Lamb
Chair, CET Board
Welcome and Housekeeping
• Bathroom facilities
• Break-out areas
• Coffee and lunch
• Fire alarm and drill
• Travel expenses
• Queries
Adaptive designs
• Most discussion has arisen from drug development and approval trials
• Most guidance is provided within this context
• Most methodological development has also been within this context
• Fit for purpose for NiHR trials (HTA) ?
• When indicated ?
• How facilitated ?
Adaptive designs
• Covers many different types of adaptation
• Futility and early stopping
• Treatment selection
• Dose response
• Sub-group refinement
• Interim sample size re-estimation
Adaptive designs
• Some applications not well understood
• Many myths – around speed, cost and method
• Widely accepted that operational issues are as important as statistical issues
NiHR funded research is different
• NiHR HTA programme – largest funder of academic clinical trials in the UK – pragmatic, phase III
• Commissioned and responsive mode
• NiHR EME programme – phase II/mechanistic
• NiHR programme grants
• NiHR fellowship applications
Trial phases
Pharmaceutical Industry HTA
To demonstrate superiority, or equivalence/n-i with better safety profile
To estimate superiority, equivalence, n-i with better safety profile
Risk of accepting null hypothesis to be minimised or eliminated prior to Phase III
Usually no risk to accepting null hypothesis - value of information remains high and investment worthwhile*
Drug trials for regulatory approval Few trials to support regulatory approval
Main driver of design – companies/regulator
Main driver of design – academics/funder
Outcomes - disease specific as primary
Various layers of outcome – disease specific, generic HQoL, cost
Comparators – placebo and/or active control
Comparators – usual care/ best current practice
Maximise effect prior to Phase III (a) Evaluate effect in everyday settings
O P E R A
OLDER PEOPLE’S EXERCISE IN RESIDENTIAL ACCOMMODATION
So what is today about
• Identify the issues• Methodological• Logistical – recruitment, ethics• Logistical - funding arrangements*• Talks – stats, trialist, and economics• Discussion – stick-its, group work• Workshops• Dissemination
Workshops
• What are the (applied) methodological questions that need to be addressed?
• What are the practical/organisational implications of using adaptive designs?
• What guide can we give for when adaptive designs should be considered?
• How should we encourage the greater use of adaptive designs in NiHR research?