Methodological problems in evaluating efficacy of a treatment in multiple sclerosis

Multiple sclerosis is currently an incurable disease and there is much interest in developing new disease-modifying treatments and testing them in clinical trials. Because therapies are essentially partially effective, neurologists have to develop ways to assess whether the medication they test slows down the course of the disease. Promising treatments selected for Phase III clinical trials are first tested in Phase I/II studies, where preliminary evidence of efficacy is demonstrated in the absence of severe adverse events. Phase III clinical trials are designed to detect significant differences between responses to active therapies and a placebo or a marketed drug. The selection and usage of instruments to detect changes in patients is probably the most important issue in their design. The purpose of this paper is to discuss methodological problems of evaluating drug efficacy in phase III MS trials, including the characteristics of the ideal instrument to measure progression of the disease, the strengths and limitations of existing clinical, radiologic and laboratory outcome measures.