Optimum Designs for Clinical Trials to Test Disease-Modifying Agents on Alzheimer's Disease

• Activity Number: 158
• Type: Topic Contributed
• Date/Time: Monday, August 1, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Chengjie Xiong*+
• Companies: Washington University
• Keywords: disease-modifying trials ; optimum design ; linear mixed models ; intersection-union test

Abstract

Therapeutic trials of disease-modifying agents on Alzheimer's disease (AD) differ from the symptomatic trials because the former require novel designs and analyses involving switch of treatments for at least a portion of subjects enrolled. Randomized start and randomized withdrawal designs are two examples. Crucial design parameters such as sample size allocations and treatment switch time are important to understand in designing such clinical trials. A general linear mixed effects model is proposed to formulate the appropriate hypothesis for the test of disease-modifying efficacy of novel therapeutic agents on AD. This model incorporates the potential correlation on the rate of cognitive or biomarker change before and after the treatment switch. Optimum sample size allocations and treatment switch time of such trials are determined according to the model. An intersection-union test through an optimally chosen test statistic is used for the test of treatment efficacy. Using reported data on symptomatic trials on AD, the proposed methodology is applied to design future disease-modifying trials on AD.