Challenges to clinical trials in multiple sclerosis: outcome measures in the era of disease-modifying drugs

Abstract

This review summarizes standard and evolving outcome measures in multiple sclerosis (MS) clinical trials. Progress in the development of MS treatments has led to an increasing number of clinical trials and a need for sensitive, timely, and clinically relevant outcome measures. Relapse rate and the Expanded Disability Status Scale remain the standard clinical outcome measures, but the MS Functional Composite continues to gain additional validation as a meaningful outcome measure. The uncertain relationship between MRI outcome measures and clinical disability has been a persistent challenge in MS clinical trials, but there is increasing evidence supporting a correlation between MRI changes and disability in relapsing-remitting MS patients. Additionally, new imaging techniques are being developed to further increase the sensitivity of MRI as a tool in MS clinical trials. Optical coherence tomography is another outcome measure gaining influence in clinical trials. Some of the greatest challenges remain in the subset of primary progressive MS clinical trials in which brain atrophy appears to be the most promising imaging outcome measure, but the optimal clinical measures and study durations are still uncertain. Progress in MS clinical trials requires critical evaluation of existing and future outcome measures and their relationships to one another.