Clinical trials in ALS: a review of the role of clinical and neurophysiological measurements.
We have reviewed all the published clinical trials of ALS and, from those considered sufficiently large, and containing a control group, we have evaluated their methodology with regard to statistical power. This implies a critical analysis of the endpoint measurements. We have concluded that clinical endpoints used in clinical trials of ALS have frequently been insufficiently sensitive, non-linear, or even not intuitively highly relevant to the disease. We suggest that the ALS-FRS, perhaps also MUNE and the Neurophysiological Index, may be the best measures currently available. These techniques have complementary characteristics that allow them to be used to address different aspects of the disease and its treatment in various trials designs. In the past some trials may have failed to demonstrate a treatment effect because the chosen endpoint measures and the trial design were inappropriate.
de Carvalho
Mamede
M
Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal. mswash@btinternet.com
Costa
João
J
Swash
Michael
M
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D006801:Humans; D009482:Neurophysiology; D011786:Quality Control; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D015996:Survival Rate; D016896:Treatment Outcome