Statistical analysis
depression, PTSD, TEAEs
DISEASE, SECONDARY, DISORDERS, DISORDER
SAS version 9.4 (SAS Institute) was used for analyses. Sample size was calculated to achieve a power of 90% at an alpha of 0.0499.Efficacy was tested using an MMRM analysis comparing the change from baseline to 18 weeks after baseline in CAPS-5 and SDS scores between treatment groups in two-sided tests with alpha set at 0.0499. The alpha was adjusted to account for an administrative interim analysis for sample size re-estimation conducted after all participants were enrolled and 60% of primary endpoint data had been collected. Fixed effects were treatment, visit, treatment group by visit interaction and dissociative subtype; baseline CAPS-5 score was a covariate. Primary and secondary efficacy analyses used a de jure (related to initially randomized treatment) estimand and a supportive de facto (treatment policy) estimand of the modified intention-to-treat population, which required exposure to MDMA or placebo and at least one follow-up CAPS-5 assessment, as in MAPP1 (ref. In additional exploratory analyses, 13 covariates were assessed in the model, with alpha set at 0.0499: age, sex (self-reported), prior use of selective SSRIs, work disability, disease severity, PTSD duration, dissociative subtype, overnight site stay, site ID, moderate depression (as measured by the BDI-II), severe adverse childhood experiences and moderate alcohol and substance use disorder risk (as measured by the Drug Use Disorders Identification Test and the Alcohol Use Disorders Identification Test). Analyses of primary or secondary outcomes by gender were not planned a priori; some exploratory analyses included sex as a covariate (Safety analysis evaluated TEAEs at the participant level, including all participants who received MDMA or placebo. Causal association with MDMA was determined based on relative incidence of TEAEs with at least a two-fold difference between groups.