Innovating Clinical Trials for Amyotrophic Lateral Sclerosis: Challenging the Established Order.

ABSTRACT: Development of effective treatments for amyotrophic lateral sclerosis (ALS) has been hampered by disease heterogeneity, a limited understanding of underlying pathophysiology, and methodologic design challenges. We have evaluated 2 major themes in the design of pivotal, phase 3 clinical trials for ALS-(1) patient selection and (2) analytical strategy-and discussed potential solutions with the European Medicines Agency. Several design considerations were assessed using data from 5 placebo-controlled clinical trials (n = 988), 4 population-based cohorts (n = 5,100), and 2,436 placebo-allocated patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The validity of each proposed design modification was confirmed by means of simulation and illustrated for a hypothe

SUBMITTER: van Eijk RPA 

PROVIDER: S-EPMC8456357 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature