title: Comparing the ability of various compositive outcomes to discriminate treatment effects in MS clinical trials. The Multiple Sclerosis Collaborative Research Group (MSCRG).
abstract: We compared the ability of the Kurtzke Expanded Disability Status Scale (EDSS) and a composite outcome of non-physician-based measures of time to ambulate 25 feet (TA) and manual dexterity (the Box and Block Test [BBT], and 9-Hole Peg Test [9HPT]) to discriminate treatment effects in the Phase III study of interferon beta-1a. A log-rank comparison of Kaplan-Meier curves by treatment group showed the non-physician-based composite of BBT, 9HPT, and TA was of comparable sensitivity (P = 0.013) in discriminating sustained treatment failure as the EDSS alone (P = 0.029). The composite of BBT, 9HPT, TA, and EDSS was more sensitive (P = 0.009) in discriminating sustained treatment failure than the EDSS alone. Compositive outcomes of the EDSS and non-physician-based measures of manual dexterity and timed ambulation provide an appealing strategy to reduce the number of patients required to discriminate treatment effects in MS clinical trials.
authors.affiliation: UCSF/MT Zion Multiple Sclerosis Center, University of California at San Francisco, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Goodkin
authors.forename: R L
authors.initials: RL
authors.lastname: Priore
authors.forename: K E
authors.initials: KE
authors.lastname: Wende
authors.forename: M
authors.initials: M
authors.lastname: Campion
authors.forename: D N
authors.initials: DN
authors.lastname: Bourdette
authors.forename: R M
authors.initials: RM
authors.lastname: Herndon
authors.forename: J S
authors.initials: JS
authors.lastname: Fischer
authors.forename: L D
authors.initials: LD
authors.lastname: Jacobs
authors.forename: D L
authors.initials: DL
authors.lastname: Cookfair
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: J R
authors.initials: JR
authors.lastname: Richert
authors.forename: A M
authors.initials: AM
authors.lastname: Salazar
authors.forename: C V
authors.initials: CV
authors.lastname: Granger
authors.forename: J H
authors.initials: JH
authors.lastname: Simon
authors.forename: J J
authors.initials: JJ
authors.lastname: Alam
authors.forename: D M
authors.initials: DM
authors.lastname: Bartoszak
authors.forename: J
authors.initials: J
authors.lastname: Braiman
authors.forename: C M
authors.initials: CM
authors.lastname: Brownscheidle
authors.forename: M E
authors.initials: ME
authors.lastname: Coats
authors.forename: S L
authors.initials: SL
authors.lastname: Cohan
authors.forename: D S
authors.initials: DS
authors.lastname: Dougherty
authors.forename: R P
authors.initials: RP
authors.lastname: Kinkel
authors.forename: M K
authors.initials: MK
authors.lastname: Mass
authors.forename: F E
authors.initials: FE
authors.lastname: Munschauer
authors.forename: R H
authors.initials: RH
authors.lastname: Whitham
mesh_terms: D002986:Clinical Trials as Topic; D004185:Disability Evaluation; D006225:Hand / Q000503:physiopathology; D006801:Humans; D008722:Methods; D009048:Motor Skills / Q000502:physiology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D011597:Psychomotor Performance; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology