A multicentre double-blind placebo-controlled randomised trial of SerTRaline for AnxieTy in adults with Autism (STRATA)

Aims: i) to determine the effectiveness of the Selective Serotonin Reuptake Inhibitor (SSRI) sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and quantify its adverse effects; ii) to determine its cost effectiveness; iii) to explore patients' views and experiences of taking study medication and identify reasons for completing/not completing the study. Methods: Design: Two parallel group multi-centre pragmatic randomised placebo-controlled trial with internal pilot and an embedded QuinteT Recruitment Intervention. Allocation will be at the level of the individual. Setting: Autism services in 5 centres in the UK and Western Australia, with further recruitment from cohorts/registries and other sources. Target population: Adults with an autism diagnosis (including those with a mild intellectual disability) made by a specialist and anxiety as measured by GAD-7 score>=10. Health technology: Sertraline, recommended as the first-choice SSRI for anxiety disorders. Primary Outcome: GAD-7 scores at 16 weeks post randomisation (continuous outcome). Secondary Outcomes: Adverse effects (Toronto side effects scale, suicidality, open ended questions); Response (50% reduction in GAD-7 score); Other anxiety constructs: Liebowitz Social Anxiety Scale; Obsessive compulsive symptoms (OCI-R); Intolerance of uncertainty (IUS-12); Repetitive behaviours (RBQ-2A); depressive symptoms (PHQ-9); work and social adjustment (WSAS); quality of life (WHOQOL-BREF with ASQOL); utility (EQ-5D-5L); adherence to medication, and carer burden (caregiver burden scale). Data will be collected face-to-face or if participants prefer, by skype, phone or web at 16, 24- and 52-weeks post-randomisation, with brief contact at 2 and 8 weeks. Economic evaluation: the incremental cost per quality-adjusted life year (QALY) calculated from a health and social care payer perspective, and a societal perspective. Resource-use will be measured at 24 and 52 weeks. Qualitative study: semi-structured interviews will take place at various times during the study. Sample size: Based on ADEPT data, a sample of 306 participants, estimating 20% attrition at 16 weeks and a correlation of 0.37 between the baseline and 16-week GAD-7 scores will give us 90% power (alpha 0.05) to detect a mean difference of 2.2 points (0.39 SD) in GAD-7 scores between groups. Statistical analysis: Intention-to-treat analysis (ITT) using linear regression to estimate mean difference in GAD-7 scores at 16-weeks post-randomisation between groups, adjusted for baseline score and stratification/minimisation variables (primary analysis). A Complier Average Causal Effect analysis to examine the efficacy of sertraline based on treatment compliance status for comparison with the ITT estimate and a repeated measures analysis to examine the effect of the intervention over 52 weeks. Timelines: Preparation 6 months. Internal pilot with recruitment progression criteria 9 months. Further 15 months recruitment all sites. Follow-up 12 months. Analysis/Reporting 6 months. Total 48 months. Impact/dissemination: The results will contribute to guidelines on managing anxiety in adults with a diagnosis of autism. We will publish findings in high impact journals in open access format, present them at relevant conferences, and develop accessible summaries. We will also disseminate results widely through news and social media, newsletters, blogs, and policy briefs.