Encouraging adaptive designs in NiHR funded clinical trials

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Transcript 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
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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
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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
• First in man
Phase 1
• Learn
Phase 2
Phase 3
• Confirm
• Evaluate
Pharmaceutical Industry
HTA
To demonstrate superiority, or
To estimate superiority, equivalence, n-i with
equivalence/n-i with better safety profile 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
OPERA
OLDER PEOPLE’S EXERCISE IN RESIDENTIAL ACCOMMODATION
So what is today about
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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?