Effect of Sample Size Re-Estimation in Adaptive Clinical Trials for Alzheimer's Disease and MCL

• Activity Number: 605
• Type: Contributed
• Date/Time: Thursday, August 7, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Guoqiao Wang*+ and Richard Kennedy and Lon Schneider and Gary Cutter
• Companies: University of Alabama at Birmingham and University of Alabama at Birmingham and University of Southern California Keck School of Medicine and University of Alabama at Birmingham
• Keywords: Alzheimer's disease ; Adaptive design ; Sampe Size Re-estimation ; Longitudinal trial design

Abstract

Purpose: Clinical trials of drugs to modify disease progression and longer-term trials in AD have not shown efficacy, and adaptive trial designs that prospectively allow for modifications in design after the start of the trial have been proposed as a potential remedy.

Methods: Based on a metadata base of 18 ADCS studies and ADNI, we simulated different clinical trials and conducted a single sample size re-estimation (SSR) at 6 months or 12 months to investigate the utility of SSR in AD. SSR in longitudinal trial design was also investigated, and the decision to increase the number of recruiters or the number of longitudinal measures was compared.

Results: SSR yielded variable increase in power and sample size. SSR based on 12-month data shower greater gain in power than 6-month data. The gain in power diminished over larger initial sample sizes.

Conclusion: Variability in individual outcomes in AD trials may limit the utility of adaptive trials designs using SSR and particularly for smaller trials and trials using SSR based on 6- and 12-month data. More work on SSR in longitudinal trial design is needed to effectively implement this strategy in AD clinical trials.