Would riluzole be efficacious in the new ALS trial design?

摘要

Aggarwal and colleagues report the results of a double-blind, placebo-controlled trial of lithium in patients with amyotrophic lateral sclerosis (ALS). Only one drug-riluzole-has proved effective in extending the lifespan of patients with ALS, and it does so by only 3-6 months. After the publication of a pilot study from Italy, which showed a favourable effect of lithium in a transgenic mouse model of ALS and in an open-label study in 44 patients, Aggarwal and colleagues undertook their larger trial in Canada and the USA. This trial was designed to detect an effect of similar size to that in the pilot study, in which a 40% decrease in the rate of neurological decline was reported. Criteria for early stopping in the study by Aggarwal and colleagues were defined on the basis of this effect size and, indeed, the first interim analysis met the criterion for futility and the trial was stopped. This design has more advantages than the classic trial design, especially in the possibility for increased speed of drug screening; however, we have a few concerns.