Luby 2006.

Study characteristics
Methods	Parallel trial of risperidone versus placebo
Participants	Inclusion criteria: aged 2.5‐6.0 years previously diagnosed with DSM‐4 criteria for autism or PDD‐NOS (American Psychiatric Association 1994) Exclusions: other known significant central nervous system (CNS) disorders significant medical problems or other psychiatric disorders requiring pharmacotherapy Location/setting: "psychiatric outpatient clinic at Washington University School of Medicine", USA Sample size: 23 (11 risperidone, 12 placebo) Number of withdrawals/dropouts: 1 exclusion from risperidone group as the "child did not meet the threshold for an ASD on the CARS or GARS [Gilliam Autism Rating Scale] at baseline, despite having been referred with a clinical diagnosis, and was excluded from analyses". 1 dropout from placebo group due to parent report of severe hyperactivity Gender: risperidone 9/11 male, placebo 8/12 male Mean age: risperidone 4.1 years, placebo 4 years IQ: not reported Baseline ABC‐I or other BoC: not an outcome Concomitant medications: not reported History of previous medications: not reported.
Interventions	Intervention (risperidone) for 6 months: the majority of participants started risperidone at 0.5 mg once daily; mean starting dose was 0.03 mg/kg/day. 81.8% of risperidone participants took 1 mg (0.5 mg twice daily) after 4 weeks; 27.3% of risperidone participants were dispensed total daily doses of 1.5 mg after 8 weeks, whereas all others received total daily doses of 1 mg. The final risperidone mean dose was 0.05 mg/kg/day and mean daily final dose was 1.14 mg (SD 0.32). Comparator (placebo) for 6 months: placebo participants were dispensed 0.5 mg daily doses. Mean final daily dose was 1.38 mg (0.57), which was comparable to risperidone.
Outcomes	Primary outcomes: AEs Secondary outcomes: none reported Timing of outcome assessments: at baseline visit, weekly visits during the 1st study month, biweekly visits during the 2nd month, followed by monthly visits for months 3–6
Notes	Study start date: November 1999 Study end date: November 2002 Source of funding: "this study was funded by Janssen Pharmaceutica as an investigator initiated project to Dr. Luby". Conflicts of interest: none disclosed Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Patients were consecutively assigned by an unblinded child psychiatrist (J.L) to risperidone or placebo treatment using a randomisation table obtained from the WUSM pharmacy and derived using a standard software package
Allocation concealment (selection bias)	High risk	Quote: "Patients were consecutively assigned by an unblinded child psychiatrist"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Parents and raters who conducted all standardized assessments were blind to treatment group"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Parents and raters who conducted all standardized assessments were blind to treatment group"
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants, apart from one who did not meet the required baseline threshold for ASD on the CARS or Gilliam Autism Rating Scale, were included in the analysis. LTFU: 1 participant withdrew from placebo group due to staring spells. No other LTFU reported
Selective reporting (reporting bias)	High risk	All children were previously diagnosed and referred by a clinician. "the treating psychiatrist (J.L) was unblinded and conducted regular clinical assessments over the 6‐month period". The unblinded child psychiatrist was also the lead investigator.
Other bias	High risk	All children were previously diagnosed and referred by a clinician. "the treating psychiatrist (J.L) was unblinded and conducted regular clinical assessments over the 6‐month period". The unblinded child psychiatrist was also the lead investigator.