Use of the Multiple Sclerosis Functional Composite as an outcome measure in a phase 3 clinical trial

Background: The Multiple Sclerosis Functional Composite (MSFC) is a multidi mensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), a nd cognitive function (Paced Auditory Serial Addition Test). The MSFC is th e primary outcome measure in the ongoing multinational phase 3 trial of int erferon beta-1a (Avonex) in patients with secondary progressive MS. Objective: To assess the practice effects, reliability, and validity of the MSFC clinical outcome measure. Design: Examining technicians underwent formal training using standardized materials. The MSFC was performed according to a standardized protocol. The 436 patients enrolled in the international Multiple Sclerosis Secondary Pr ogressive Avonex Controlled Trial underwent 3 prebaseline MSFC testing sess ions before randomization. Results: Practice effects were evident initially for the MSFC but stabilize d by the fourth administration. The Paced Auditory Serial Addition Test dem onstrated the most prominent practice effects. The reliability of the MSFC was excellent, with an intraclass correlation coefficient for session 3 (fi nal prebaseline session) vs session 4 (baseline) of 0.90. The MSFC at basel ine correlated moderately strongly with the Kurtzke Expanded Disability Sta tus Scale. Among the MSFC components, the Timed 25-Foot Walk correlated mos t closely. Correlations among the 3 MSFC components were weak, suggesting t hey assess distinct aspects of neurologic function in patients with MS. Conclusions: The MSFC demonstrated excellent intrarater reliability in this multinational phase 3 trial. Three prebaseline testing sessions were suffi cient to compensate for practice effects. The pattern of correlations among the MSFC, its components, and the Kurtzke Expanded Disability Status Scale supported the validity of the MSFC.