Clinical Study Design to Assess Both Short- and Long-term Efficacy in Addition to Group Sequential Test on Safety.

Abstract

In clinical studies for disorders such as rheumatoid arthritis, type 2 diabetes mellitus, multiple sclerosis, osteoporosis, etc, sometimes the developers need to address safety concerns (eg, cardiovascular risk) in the phase III development, so that a large long-term safety study is needed before registration. This article does not contain any studies with human or animal subjects performed by any of the authors. Aiming for potential regulatory approval with a single confirmatory study, the authors suggest a design that assesses short-term efficacy (eg, signs or symptoms) and long-term efficacy (eg, structure or imaging), as well as safety (eg, major adverse cardiac events), for which a group sequential test is performed applying an alpha spending function. A graphical testing procedure is suggested for the data analysis. The testing procedure controls the family-wise type I error rate. The study may reach all or part of short-term efficacy, long-term efficacy, and/or safety objectives. It is possible to get market approval with a single confirmatory study that assesses short-term efficacy, long-term efficacy, and safety.