Comparing the ability of various compositive outcomes to discriminate treatment effects in MS clinical trials. The Multiple Sclerosis Collaborative Research Group (MSCRG).
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.
Goodkin
D E
DE
UCSF/MT Zion Multiple Sclerosis Center, University of California at San Francisco, USA.
Priore
R L
RL
Wende
K E
KE
Campion
M
M
Bourdette
D N
DN
Herndon
R M
RM
Fischer
J S
JS
Jacobs
L D
LD
Cookfair
D L
DL
Rudick
R A
RA
Richert
J R
JR
Salazar
A M
AM
Granger
C V
CV
Simon
J H
JH
Alam
J J
JJ
Bartoszak
D M
DM
Braiman
J
J
Brownscheidle
C M
CM
Coats
M E
ME
Cohan
S L
SL
Dougherty
D S
DS
Kinkel
R P
RP
Mass
M K
MK
Munschauer
F E
FE
Whitham
R H
RH
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