090 Clinical trials in amyotrophic lateral sclerosis: a systematic review

Abstract

BackgroundAmyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disease. Despite decades of clinical trials, there remains a pressing unmet need for effective treatments. We reviewed past and present ALS clinical trials to understand the methodological challenges in trial design and delivery.MethodsTrial registry databases including clinicaltrials. gov, International Clinical Trials Registry Platform, European Union Clinical Trials Register, and PubMed were systematically searched to identify Phase II, Phase II/III and Phase III Clinical Trials of Investigational Medicinal Products (CTIMPs) assessing potential disease modifying treatments in ALS. Trials registered, completed or published during 2008–2019 were included.Results125 CTIMPs, evaluating 76 drugs, involving 15647 people with ALS (pwALS) were reviewed. Ten drugs were tested in three or more trials. Trials employed predominantly traditional two-arm designs; only 12 used novel designs. Median number of participants was 86. 40% of trials had an attrition rate ≥ 20%. There was a wide variation of primary outcome measures and primary endpoints used.ConclusionHistorically, limited participation of pwALS in trials, resources and outcome measures hindered definitive and timely evaluation of drugs in two-arm trials. We propose that future trials will need to be more flexible, scalable and acceptable to all stakeholders.charis.wong@ed.ac.uk