The natural history of multiple sclerosis: implications for trial design

The understanding of the natural history of multiple sclerosis has many imp lications for the design and interpretation of randomized controlled trials . Selection criteria, patient stratification, outcome measurements, and def initions of treatment failure can influence randomized controlled trial res ults and limit comparisons among trials. The focus of future studies should shift from short-term determinations of efficacy to definitive evaluations of long-term effectiveness. This will require novel investigative strategi es such as the use of historic controls derived from natural history studie s. (C) 1999 Lippincott Williams & Wilkins.