Using MRI whole brain atrophy and clinically reported outcomes in combination to assess interim treatment response in multi-arm multi-stage trials in progressive multiple sclerosis

Background: Interim stage outcomes in multi-arm multi-stage trials need not be the same as the final primary outcome, and should be selected with the goal of providing the best chance of continuing with an effective treatment in the study during the early stage where there is also potential to drop an ineffective arm. Jointly considering multiple outcomes can enhance that ability to detect an emerging signal. Methods: The Optimal Clinical Trials Platform for Progressive Multiple Sclerosis (OCTOPUS) study is a randomised, placebo-controlled, double-blind, phase 3, MAMS trial testing treatments for people with progressive multiple sclerosis. The interim analysis was to be based solely on an MR