Clinical outcome measures in multiple sclerosis.

Clinical outcome measures are indispensable when studying the natural course of multiple sclerosis (MS) and critical for determining the effect of an intervention. For these purposes clinical outcome measures should be valid, reliable, and responsive. Moreover they should assess clinically relevant aspects of the disease. Given the nature of the disease, outcome measures in MS should be able to capture multiple clinical dimensions. Long-term disability-free survival is the ultimate goal of MS treatment. Since the observation period in clinical trials is too short to get a final answer on that outcome, clinicians and researchers rely on extrapolation of the results beyond the treatment period. Yet the long-term predictive value of most outcome measures (e.g., relapse rate) used for short-term responses has not yet been determined. The expanded disability status scale (EDSS) is the outcome measure that is most often included in MS studies. The EDSS appeals to most neurologists as it is the result of a standardized neurologic examination and neurologists know it well. However, when considered critically, the EDSS has serious weaknesses from a clinimetric point of view that limit its value as an outcome measure in MS. The search for an alternative outcome measure that can fulfill all essential requirements and will be accepted by the scientific community, clinicians, and regulatory agencies is a huge challenge.