The Multiple Sclerosis Functional Composite: a new clinical outcome measure for multiple sclerosis trials

• Published in: Multiple sclerosis Vol. 8; no. 5; pp. 359 - 365
• Main Authors: Rudick, R A, Cutter, G, Reingold, S
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01-10-2002; Arnold; Sage Publications Ltd
• Subjects: Biological and medical sciences; Clinical outcomes; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; clinical trials; multiple sclerosis functional composite; outcome measures; multiple sclerosis; EDSS; Short term; Clinical test; Nervous system diseases; Drug combination; Multiple sclerosis; Prognosis; Nuclear magnetic resonance imaging; Inflammatory disease; Quality of life; Atrophy; Case study; Walking; Central nervous system disease; Medical imagery; Evolution; Combined treatment; Ambulatory; Brain (vertebrata)
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1191/1352458502ms845oa

With the advent and widespread use of partially effective disease modifying drug therapies for multiple sclerosis (MS), future clinical trials will undoubtedly test experimental interventions against standard therapy, or will test combinations of drugs against standard therapy. In either case, incremental progress in slowing disability progression in future MS clinical trials will require much larger sample sizes, more sensitive outcome measures, or a combination of the two. Because improved clinical outcome methods would likely accelerate progress in MS therapeutics, the National Multiple Sclerosis Society (NMSS) convened an international task force in 1994 to recommend improved clinical outcome measures. As the result of a two-year process of discussion and data analysis, the task force recommended the Multiple Sclerosis Functional Composite (MSFC) as a new clinical outcome measure for future MS trials. MSFC consists of timed tests of walking, arm function, and cognitive function, expressed as a single score along a continuous scale. The task force recommended that MSFC be included in future MS trials, and recommended a series of validation studies. Subsequent studies have provided evidence that MSFC correlates moderately with Expanded Disability Status Scale (EDSS), and that correlation is driven by strong correlations with the ambulatory function component; arm function and cognitive function correlate at lower levels with EDSS. The MSFC correlates better than EDSS with magnetic resonance imaging (MRI) variables, including brain atrophy, and shows significant correlation with patient-reported disease-related quality of life (QOL). MSFC and short-term change in MSFC correlate with future clinical and MRI status, and the strength of the correlations compares favorably with well-known cardiovascular risk factors. The studies in aggregate indicate that MSFC and MSFC change are clinically meaningful, and that MSFC has substantial advantages over alternative clinical outcome measures for MS clinical trials.