The importance of endpoint selection: How effective does a drug need to be for success in a clinical trial of a possible Alzheimer ’s disease treatment?

AbstractTo date, Alzheimer ’s disease (AD) clinical trials have been largely unsuccessful. Failures have been attributed to a number of factors including ineffective drugs, inadequate targets, and poor trial design, of which the choice of endpoint is crucial. Using data from the Alzheimer’s Disease Neuroimaging Initiative , we have calculated the minimum detectable effect size (MDES) in change from baseline of a range of measures over time, and in different diagnostic groups along the AD development trajectory. The Functional Activities Questionnaire score had the smallest MDES for a single endpoint where an effect o f 27% could be detected within 3 years in participants with Late Mild Cognitive Impairment (LMCI) at baseline, closely followed by the Clinical Dementia Rating Sum of Boxes (CDRSB) score at 28% after 2 years in the same group. Composite measures were even more successful than single endpoints with an MDES of 21% in 3 years. Using alternative cognitive, imaging, functional, or composite endpoints, and recruiting patients that have LMCI could improve the success rate of AD clinical trials.

Source: European Journal of Epidemiology - March 23, 2018 Category: Epidemiology Source Type: research