Placebo effects and participant heterogeneity in clinical trials of autism spectrum disorder

Abstract

In The Lancet Psychiatry, Suma Jacob and colleagues report the largest randomised controlled trial so far published of pharmacological treatment for autistic adults. 1 Jacob S Veenstra-Vander Weele J Murphy D et al. Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trial. Lancet Psychiatry. 2022; (published online Feb 10.)https://doi.org/10.1016/S2215-0366(21)00429-6 Google Scholar This phase 3 multicentre trial (V1aduct) tested the efficacy and safety of balovaptan, a selective brain-penetrant receptor antagonist of the vasopressin 1a (V1a) receptor, on social adaptive behaviour, as measured by the Vineland-II two-domain composite (2DC) score, a composite of the Vineland-II socialisation and communication domains. The trial was discontinued following futility analyses after 50% of participants completed the week 24 follow-up visit, which found least-squares mean changes in Vineland-II 2DC scores of 2·91 (SE 1·52) in the balovaptan group (n=79) and 4·75 (1·60) in the placebo group (n=71), with an estimated treatment difference of −1·84 (95% CI −5·15 to 1·48). Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trialBalovaptan did not improve social communication in autistic adults. This study provides insights into challenges facing autism spectrum disorder trials, including the considerable placebo response and the selection of appropriate outcome measures. Full-Text PDF