title: Development of a multiple sclerosis functional composite as a clinical trial outcome measure.
abstract: The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.
authors.affiliation: AMC Cancer Research Center, Center for Research Methodology and Biometrics, Lakewood, Colarado 80214, USA. cutterg@amc.org
authors.forename: G R
authors.initials: GR
authors.lastname: Cutter
authors.forename: M L
authors.initials: ML
authors.lastname: Baier
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: D L
authors.initials: DL
authors.lastname: Cookfair
authors.forename: J S
authors.initials: JS
authors.lastname: Fischer
authors.forename: J
authors.initials: J
authors.lastname: Petkau
authors.forename: K
authors.initials: K
authors.lastname: Syndulko
authors.forename: B G
authors.initials: BG
authors.lastname: Weinshenker
authors.forename: J P
authors.initials: JP
authors.lastname: Antel
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.forename: G W
authors.initials: GW
authors.lastname: Ellison
authors.forename: F
authors.initials: F
authors.lastname: Lublin
authors.forename: A E
authors.initials: AE
authors.lastname: Miller
authors.forename: S M
authors.initials: SM
authors.lastname: Rao
authors.forename: S
authors.initials: S
authors.lastname: Reingold
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: E
authors.initials: E
authors.lastname: Willoughby
mesh_terms: D002986:Clinical Trials as Topic; D004185:Disability Evaluation; D006801:Humans; D009103:Multiple Sclerosis / Q000628:therapy*; D011379:Prognosis; D015203:Reproducibility of Results; D012494:Sampling Studies; D016896:Treatment Outcome