The use of statistical MUNE in a multicenter clinical trial.
Techniques to estimate motor unit number (MUNE) measure the number of functioning motor units in a muscle. In diseases characterized by progressive motor unit loss, such as amyotrophic lateral sclerosis (ALS), MUNE may be useful to monitor disease progression or beneficial response to treatment. As part of a multicenter, placebo-controlled, randomized, double-blind clinical trial testing the efficacy of creatine in patients with ALS, statistical MUNE was measured in 104 patients tested monthly for 6 months. The objective was to determine whether MUNE was a reliable and sensitive outcome measure in the context of a multicenter trial. Formal training and reliability testing was required for all MUNE evaluators. Testing of normal controls showed a high degree of test-retest reliability. All patient data were combined as the experimental treatment showed no efficacy. There was a 23% decline in MUNE over 6 months. The technique as employed in this trial overemphasized the presence of small motor units; this problem was partially addressed by poststudy data monitoring and censuring. Thus, MUNE can be used reliably as an outcome measure in multicenter clinical trials; specific remedies are suggested for the difficulties encountered in this study.
Shefner
J M
JM
Department of Neurology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, New York 13210, USA. shefner@upstate.edu
Cudkowicz
M E
ME
Zhang
H
H
Schoenfeld
D
D
Jillapalli
D
D
D000200:Action Potentials / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology*; D002452:Cell Count; D003401:Creatine / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D004568:Electrodiagnosis; D004594:Electrophysiology; D006801:Humans; D009046:Motor Neurons / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D015588:Observer Variation; D011786:Quality Control; D015203:Reproducibility of Results; D012107:Research Design; D016896:Treatment Outcome
D003401:Creatine