METAANALYSIS OF THE PLACEBO-TREATED GROUPS IN CLINICAL-TRIALS OF PROGRESSIVE MS

The behavior of the control groups can substantially affect the power and outcome of a clinical trial. We report a meta-analysis of the cont rol groups of four large, double-blind, placebo-controlled clinical tr ials of immunosuppressive treatment of progressive MS to address the s ensitivity of five hypothetical definitions of treatment failure (TF). The rate of TF in the aggregate control groups (n = 427) was 31% when a confirmed increase of 1.0 expanded disability status scale (EDSS) p oint was required at the end of the trial; it was 51% when confirmatio n was not required and TF was allowed at the first point where the cri teria for TF were met. The rate of confirmed TF was 45% when the TF cr iteria were indexed to baseline EDSS, accounting for the observed diff erences in staying times at different EDSS levels. We developed models predicting TF in progressive MS. In addition to baseline EDSS, the py ramidal functional score and, for one definition, brainstem functional score were associated with probability of TF.