Veenstra‐VanderWeele 2017.

Study characteristics
Methods	12‐week parallel trial of arbaclofen versus placebo
Participants	Inclusion criteria: current diagnosis of ASD CGI‐S score of moderate or higher at time of screening and baseline before randomisation stable medications for at least 4 weeks prior to the study seizure‐free for at least 6 months and be on anticonvulsants or seizure‐free for three years without taking anticonvulsants any non‐pharmacological interventions must have been continuing for at least 2 months prior to the study. Exclusion criteria: participants with other conditions including drug or alcohol abuse plan to change interventions during the study have taken other investigational drugs in the past 30 days unable to take oral medications an allergy or intolerance to arbaclofen Location/setting: 25 sites across USA Sample size: 150 were randomised, arbaclofen 76, placebo 74 Mean age: 11.6 years (range 5‐21 years) Mean IQ: IQ > 70 in approximately 50% of participants Gender: arbaclofen 63% were male; placebo 61% were male Baseline ABC‐I scores: arbaclofen group 17.2; placebo 15.6 Reasons for dropouts: arbaclofen 15 discontinued (LTFU (1), AEs (8), protocol violation (1), withdrew consent (4), other (1)). Placebo 5 discontinued (AE (2), withdrew consent (2), other (1)) Concomitant medications: arbaclofen 14 were on concomitant psychoactive medication; placebo: 12 were on concomitant psychoactive medication Previous medications: details not provided
Interventions	Intervention (arbaclofen) for 12 weeks: starting dose of arbaclofen was 5 mg twice daily increasing to 10 mg twice daily up to a maximum dose of 10 mg 3 times daily for children < 12 years. Children ≥ 12 years could have 15 mg 3 times daily Comparator (placebo) for 12 weeks: matching placebo tablets
Outcomes	Primary outcomes: ABC‐I (change from baseline) (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: baseline and week 12 (endpoint)
Notes	Study start date: May 2011 Study end date: September 2012 Funding: Seaside Therapeutics (pharmaceutical company) Conflicts of interest: various study authors received funding from and consulted with pharmaceutical companies. Trial registry: NCT01288716
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised 1: 1 to either arbaclofen or placebo according to a centrally generated randomisation list, with stratification by age (5–11 or 12–21 years) and concomitant use of psychoactive medication.
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Blinding was maintained by utilizing identical tablets containing either STX209 or placebo"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Apart from "Double‐blinded" details were not provided.
Incomplete outcome data (attrition bias) All outcomes	High risk	Large dropout (20%) with many dropping out in treatment group due to AEs
Selective reporting (reporting bias)	Low risk	Same primary outcome on trial reg
Other bias	High risk	Funded by Seaside Therapeutics and the team has interests in a range of pharma companies