A Review of Clinical Trial Designs in Amyotrophic Lateral Sclerosis

SUMMARY Amyotrophic lateral sclerosis is a serious disease characterized by a rapid decline in the ability to carry out daily activities, which leads to death within 2–5 years of diagnosis. Numerous agents for slowing disease progression have been tested but only one (riluzole) has proven to be moderately successful. Here we review clinical trial designs with a focus on novel Phase II designs developed since 2005, that attempt to speed up the process of testing new agents. The review is organized by four features that are critical in defining a clinical trial: the comparison group, the end point, the method of analysis and the type of trial. We note continuing trends over the past 5 years toward more efficient designs with shorter duration trials, increased interest in biomarkers and use of well-characterized historical controls.