Hollander 2020b.

Study characteristics
Methods	24‐week parallel trial of balovaptan versus placebo
Participants	Inclusion criteria: boys and girls aged 5‐17 years who are fluent in English, meet the DSM‐5 criteria for ASD, CGI score of at least 4 at screening, an IQ of at least 70 "Language, hearing, and vision compatible with the study measurements as judged by the Investigator" a parent or guardian who can accompany the participant to study visits and who is willing to provide consent for the participant female participants cannot be breast‐feeding during the trial and must have a negative pregnancy test, and must use a contraceptive method from screening until 28 days following the trial Exclusion criteria Start or change in psychosocial intervention (including investigational) within 4 weeks prior to screening Unstable or uncontrolled psychiatric and/or neurological disorder including uncontrolled epilepsy (defined as a seizure within the past 6 months) unstable cardiovascular disease, history of alcohol or substance abuse/dependence, or abnormality on ECG at screening Concomitant medical conditions that affect the pulmonary, gastrointestinal, hepatic, renal, metabolic, or immune systems Medications such as anticonvulsants were requred to be at a stable dose for at least 4 weeks prior to screening for the trial. Location/setting: 44 sites across the USA Sample size: 134 Number of withdrawals/dropouts: placebo, 26 dropped out (AEs (3); lack of efficacy (1); LTFU (3); physician decision (1); withdrawal by participant (18)). Balovaptan, unclear, groups are not clearly defined. Gender: 83% and 84% were male in the intervention and placebo groups respectively. Mean age: approximately 12 years in both groups IQ: not reported Baseline ABC‐I scores or other BoC: not reported Concomitant medications: not reported History of previous medications: not reported
Interventions	Intervention (balovaptan) for 24 weeks: participants received age‐adjusted total daily oral dose approximately equivalent to the adult dose of 10 mg/day of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enroled in the open‐label extension). Comparator: participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Outcomes	Primary outcomes: none reported Secondary outcomes: QoL (change from baseline) measured using the PedsQL (Varni 2001). Higher scores suggest a higher QoL Timing of outcome assessments: baseline, weeks 12 and 24 (endpoint)
Notes	Study start date: 2016 Study end date: 2020 Source of funding: F. Hoffmann‐La Roche Ltd (pharmaceutical company) Conflicts of interest: various grants and other support from pharmaceutical companies
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided apart from "randomised study"
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided apart from "Masking: Double (Participant, Investigator)"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details not provided apart from "Masking: Double (Participant, Investigator)"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Difficult to understand participant flow
Selective reporting (reporting bias)	High risk	The paper/presentation mentions the ABC‐Irritability however, it wasn't reported and was not listed on the trial registry. Also, the study was "Terminated (The 24‐week analysis indicated no clinical or statistical benefit for the primary endpoint for the overall study population. No new safety concerns identified.)"
Other bias	High risk	List of disclosures included payment by pharma company, for many of the study authors