Advancing personalized treatment of Alzheimer's disease: a call for the N-of-1 trial design

Abstract

There has not been a new treatment for Alzheimer's disease (AD) for over a decade, with a large number of Phase II/III randomized clinical trials failing. Randomized clinical trials examine group effects that may be difficult to extrapolate to the individual patient given the multifactorial pathogenic processes associated with AD, and are increasingly long in duration, expensive to run, requiring large sample sizes that are difficult to recruit. An alternative approach is to consider N-of-1 trial designs. The N-of-1 trial is ideal to evaluate effectiveness of interventions for chronic conditions combining the rigor of a randomized trial with the tailoring of therapy to an individual. This review examines the N-of-1 design, its benefits and limitations, and how it could be implemented to investigate new therapies for AD.