Presented at the 2018 Meeting of the European Network to Cure ALS (ENCALS), on June 21, 2018.
Background: We previously developed regression models for total ALSFRS-R score, ALSFRS-R subscores, vital capacity (VC), and percent expected VC, and time-to-event models for loss of speech, use of wheelchair, gastrostomy, use of NIV (using time to 50% expected VC as a surrogate) and survival.
Methods: The models were utilized to create drug development applications, including for use in randomization/covariate adjustment, enrichment, virtual controls and to select subgroups within a larger trial that demonstrate a treatment effect.
Conclusions: The virtual control, enrichment, detectable effect cluster (DEC) and randomization/covariate tools provide an objective measure of efficacy in early clinical trials, decrease trial heterogeneity, find “hot spots” of patients with demonstrable benefit and lower sample size/increase power for drug development trials in ALS. These applications represent a significant paradigm shift with broad implications for the conduct of trials in ALS in particular and can be extended to a range of neurodegenerative diseases.
Authors: Danielle Beaulieu, Albert A. Taylor, Andrew Conklin, David L. Ennist