Evaluation of Some Alternative Designs for Phase 2 Multiple Sclerosis Trials—A Simulation Study

Abstract

The typical pivotal experimental therapeutic study design in multiple sclerosis (MS) is a randomized, double-blind, placebo-controlled clinical trial with clinical primary outcomes. In earlier phase studies, primary endpoints are often not clinical and typically include changes in magnetic resonance imaging (MRI) parameters, such as the cumulative number of new gadolinium-enhanced lesions over six months of treatment. In this article, we compare two trial designs—a group sequential method and an adaptive method—with respect to differences in power level and required sample size to those of a classical one-stage study design without interim analysis. The results of a simulation study based on pooled MRI data from a large number of clinical MS trials show that using a group-sequential design provides a significant reduction in required sample size compared with the classical one-stage design. If the observed treatment effect on study is smaller than the assumed one, the power of the adaptive method is larger than in the classical approach.