Reliable surrogate outcome measures in multicenter clinical trials of Duchenne muscular dystrophy.
We studied the reliability of a series of endpoints in an evaluation of subjects with Duchenne muscular dystrophy (DMD). The endpoints included quantitative muscle tests (QMTs), timed function tests, forced vital capacity (FVC), and manual muscle tests (MMT). Thirty-one ambulatory subjects with DMD (mean age 8.9 years; range 5-16 years) were evaluated at eight sites by 15 newly trained evaluators as a test of interrater reliability of outcome measures. Both total QMT score [intraclass correlation coefficient (ICC) 0.96] and individual QMT assessments (ICC 0.85-0.96) were highly reliable. Forced vital capacity and all timed function tests were also highly reliable (ICC 0.97-0.99). MMT was the least reliable assessment method (ICC 0.61). These data suggest that primary surrogate outcome measures in large multicenter clinical trials in DMD should use QMT, FVC, or time function tests to obtain maximum power and greatest sensitivity.
Mayhew
Jill E
JE
Research Center for Genetic Medicine, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA.
Florence
Julaine M
JM
Mayhew
Thomas P
TP
Henricson
Erik K
EK
Leshner
Robert T
RT
McCarter
Robert J
RJ
Escolar
Diana M
DM
D000293:Adolescent; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000379:methods*; D004185:Disability Evaluation; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000175:diagnosis / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D009460:Neurologic Examination / Q000379:methods / Q000592:standards; D015588:Observer Variation; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome
D015415:Biomarkers