This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rudick, R A Articles by Reingold, S Search for Related Content PubMed PubMed Citation Articles by Rudick, R A Articles by Reingold, S Social Bookmarking                   What's this?

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

Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research (Area U10), The Cleveland Clinic Foundation, Cleveland, Ohio, USA, rudickr{at}ccf.org

G Cutter

Center for Research Methodology and Biometrics, AMC Cancer Research Center, 1600 Pierce St., Lakewood, Colorado 80214, USA

S Reingold

Research Programs Department, National Multiple Sclerosis Society, 733 Third Avenue, New York, New York 10017, USA

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.

Key Words: EDSS • clinical trials • multiple sclerosis • multiple sclerosis functional composite • outcome measures

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R.A. Marrie and M. Goldman Validity of performance scales for disability assessment in multiple sclerosis Multiple Sclerosis, November 1, 2007; 13(9): 1176 - 1182. [Abstract] [PDF]

				O. Khan Can clinical outcomes be used to detect neuroprotection in multiple sclerosis? Neurology, May 29, 2007; 68(22_suppl_3): S64 - S71. [Abstract] [Full Text] [PDF]

				J. A. Bobholz, S. M. Rao, L. Lobeck, C. Elsinger, A. Gleason, J. Kanz, S. Durgerian, and E. Maas fMRI study of episodic memory in relapsing-remitting MS: correlation with T2 lesion volume. Neurology, November 14, 2006; 67(9): 1640 - 1645. [Abstract] [Full Text] [PDF]

				M M Nieuwenhuis, H Van Tongeren, P S Sorensen, and M Ravnborg The Six Spot Step Test: a new measurement for walking ability in multiple sclerosis Multiple Sclerosis, August 1, 2006; 12(4): 495 - 500. [Abstract] [PDF]

				M. P. Sanfilipo, R. H.B. Benedict, B. Weinstock-Guttman, and R. Bakshi Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis Neurology, March 14, 2006; 66(5): 685 - 692. [Abstract] [Full Text] [PDF]

				S L Minden, D Frankel, L Hadden, J Perloff, K P Srinath, and D C Hoaglin The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics Multiple Sclerosis, February 1, 2006; 12(1): 24 - 38. [Abstract] [PDF]

				R. Bakshi, G. J. Hutton, J. R. Miller, and E.-W. Radue The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis Neurology, December 14, 2004; 63(11_suppl_5): S3 - S11. [Abstract] [Full Text]

				L Nicholl, J Hobart, L Dunwoody, F Cramp, and A Lowe-Strong Measuring disability in multiple sclerosis: is the Community Dependency Index an improvement on the Barthel Index? Multiple Sclerosis, August 1, 2004; 10(4): 447 - 450. [Abstract] [PDF]

				L. Kappos Effect of drugs in secondary disease progression in patients with multiple sclerosis Multiple Sclerosis, May 1, 2004; 10(3_suppl): S46 - S55. [Abstract] [PDF]

				A. J Thompson Developing clinical outcome measures in multiple sclerosis: an evolving process Multiple Sclerosis, October 1, 2002; 8(5): 357 - 358. [PDF]