Design and implementation of a replication study: The Music for Autism (M4A) binational assessor-blinded randomised crossover trial

Abstract Many autistic children suffer from social communication problems, reduced participation, and mental health issues. Music therapy has beneficial but heterogeneous effects; its mechanisms are incompletely understood. The Music for Autism (M4A) trial aims to replicate and expand a previous trial examining brain mechanisms and clinical outcomes of music versus play-based therapy for autistic children. This paper presents M4A’s design and implementation; we examine feasibility of this replication trial based on the first wave of recruitment. M4A is a crossover randomised controlled trial currently conducted at two sites (Bergen, Norway; Vienna, Austria). Children aged 6-12 years diagnosed with autism spectrum disorder will be randomised to a sequence of weekly individual music and play-based therapy (3 months for each intervention; 3-month washout period). Outcomes assessed before and after each intervention period include communication (blinded, assessed by teachers); functional brain connectivity (from functional magnetic resonance imaging, fMRI); and further behavioural and biological outcomes. The planned total sample size of 80 will ensure adequate power. Recruitment in the first wave (14 randomised) was below expectations. Baseline characteristics were similar to the previous study, but some variables (severity, functioning) were difficult to assess and compare. A range of functioning levels were included. Interventions were well accepted; fidelity was adequate. Timing of interventions and assessments was challenging when blinded assessors were hard to reach. Blinding was successful. Movement in fMRI was an issue in some children, but we developed preparation strategies to help also low-functioning children to successfully complete the scans. No study-related adverse events occurred. M4A has a strong design, appears feasible, and promises important new insights into the mechanisms and outcomes of music therapy for ASD. Multinational replicability of controlled trials of complex psychosocial interventions in ASD combining clinical and brain imaging outcomes can be challenging and requires careful planning. Trial registration: Clinicaltrials.gov NCT04936048 * AGr and MR contributed equally to this work and share first authorship. CG, GS, and KS contributed equally to this work and share last authorship.