A platform trial approach to proof-of-concept (POC) studies in autism spectrum disorder: Autism spectrum POC initiative (ASPI)

Contemp Clin Trials Commun. 2023 Jan 16:32:101061. doi: 10.1016/j.conctc.2023.101061. eCollection 2023 Apr.

Abstract

Background: Over the past decade, autism spectrum disorder (ASD) research has blossomed, and multiple clinical trials have tested potential interventions, with varying results and no clear demonstration of efficacy. Lack of clarity concerning appropriate biological mechanisms to target and lack of sensitive, objective tools to identify subgroups and measure symptom changes have hampered the efforts to develop treatments. A platform trial for proof-of-concept studies in ASD could help address these issues. A major goal of a platform trial is to find the best treatment in the most expeditious manner, by simultaneously investigating multiple treatments, using specialized statistical tools for allocation and analysis. We describe the setup of a platform trial and perform simulations to evaluate the operating characteristics under several scenarios. We use the Autism Behavior Inventory (ABI), a psychometrically validated web-based rating scale to measure the change in ASD core and associated symptoms.

Methods: Detailed description of the setup, conduct, and decision-making rules of a platform trial are explained. Simulations of a virtual platform trial for several scenarios are performed to compare operating characteristics. The success and futility criteria for treatments are based on a Bayesian posterior probability model.

Results: Overall, simulation results show the potential gain in terms of statistical properties especially for improved decision-making ability, while careful planning is needed due to the complexities of a platform trial.

Conclusions: Autism research, shaped particularly by its heterogeneity, may benefit from the platform trial approach for POC clinical studies.