Dementia: Study Designs, Methodologies and Regulatory Perspectives – One Size Does Not Fit All!
Chairs: Pierre Tariot, MD; Jill Rasmussen, MD
Over the last few years there has been increasing concern about the lack of success of drug candidates in clinical trials in Alzheimer’s dementia and mild cognitive impairment. On a more positive note there has been more interest in conducting trials in other types of dementia as well as moving earlier in the AD process.
It is timely therefore to consider:
► What have we learned from Pharma trials
► What are the similarities and differences when designing clinical trials in various dementia sub-types
► The design of “preclinical” trials (e.g., DIAN, A4, Alzheimer’s Prevention Initiative)
► The value of biomarkers (neuroimaging, CSF etc), genotypes and polymorphisms in identifying relevant patient populations and then enabling a read out in early phase clinical trials
► Regulatory perspectives on:
· Endpoints in early and late phase clinical trials
· Use of biomarkers
· Background medications
· Diagnostic criteria for different dementias
Dementia sub-types, Alzheimer’s disease, vascular, mixed, frontotemporal (FTD), Lewy Body (DLB), and Parkinson’s (PDD) differ in important aspects. For example aetiology and pathophysiology, assessment of background pathology (Parkinson’s disease and parkinsonism in FTD, DLB, PDD), background treatments, choice of scales and primary and secondary endpoints effect size on cognitive endpoints, Inclusion / exclusion criteria, role of neuroimaging and other biomarkers for diagnosis and as an outcome variable and “Regulatory Path”.
From a regulatory perspective the focus of the outcome measures in the first guidelines was on cognition and functioning. More recently we have seen the emergence of guidelines for early dementia and broader thinking around study designs for proof of concept and pivotal studies for drugs with potential to delay progression of the dementias.
This session will explore the lessons learned from experience to date and how that informs, or not, study designs in other dementias and future research. A speaker form the Industry will give a perspective on pathobiological targets or factors not yet addressed in trials in AD dementia. Regulatory agencies from the US and Europe will give their thoughts clinical trial methodology.