A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease.

ABSTRACT: One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period. We conducted simulations to identify the optimal noninferiority testing procedure to ensure the method was robust across scenarios and assumptions, and to evaluate the appropriate mo

SUBMITTER: Liu-Seifert H 

PROVIDER: S-EPMC4363486 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature