Assessing relapses in treatment trials of relapsing and remitting multiplesclerosis: can we do better?

Published Phase III immunomodulatory treatment trials in relapsing and remi tting multiple sclerosis have demonstrated a modest decline in attack rates , but only a minor effect on disability. As genuine disability progression is difficult to ascertain in relatively short studies with the conventional rating scales available, the acquisition and analysis of relapse data ore critical. However, there ore as yet unresolved questions related to the let ter. We will first discuss the problems associated with relapse definitions by trial investigators, the paucity of the data collected (especially on t he magnitude and duration of exacerbations) and statistical issues in their analysis. We will then suggest practical points for obtaining more accurat e information on relapses and evaluating them meaningfully. While there is still general consensus among neurologists that primary endpoints for thera peutic trials should be clinical, improvements for future protocols ore ess ential.