Loebel 2016.

Study characteristics
Methods	6‐week, double‐blind RCT, parallel trial of lurasidone (20 mg/day or 60 mg/day) versus placebo
Participants	Inclusion criteria: children 6‐17 years who met the DSM‐4‐TR criteria for a diagnosis of AS a score of ≥ 18 on the ABC‐I subscale and a score of ≥ 4 (moderate‐or‐greater severity) on the CGI‐S Exclusion criteria: a current diagnosis of bipolar disorder, schizophrenia, major depressive disorder, Fragile‐X syndrome, or childhood disintegrative disorder confirmed genetic disorder associated with cognitive and/or behavioural disturbance or profound intellectual disability a history of seizures (unless seizure‐free and off medication for 6 months or more) use of any psychotropic medications Location/setting: not reported Sample size: 148 (lurasidone 60 mg/day 51, 20 mg/day lurasidone 48, placebo 49) Number of withdrawals/dropouts: placebo: lack of efficacy (1), AEs (4), lost to follow‐up (1), withdrew consent (4); lurasidone 60 mg/day: lack of efficacy (1), AEs (2), miscellaneous (1); lurasidone 20 mg/day: AEs (2), lack of efficacy (1), lost to follow‐up (2), withdrawal by participant (1) Gender: placebo 40/49 male, lurasidone 60 mg/day 43/51 male, lurasidone 20 mg/day 38/48 male Mean age: placebo 11 years, lurasidone 20 mg/day 10.5 years, lurasidone 60 mg/day 10.5 years IQ: not reported Baseline ABC‐I or other BoC: irritability, placebo 29.0, lurasidone 60 mg/day 27.0 Concurrent medications: not reported History of previous medications: any antipsychotic: placebo 19/49, lurasidone 20 mg/day 17/48, lurasidone 60 mg/day 16/51. Any psychostimulant: placebo 18/49, lurasidone 20 mg/day 11/48, lurasidone 60 mg/day 16/51. Any antidepressant: placebo 6/49, lurasidone 60 mg/day 5/51
Interventions	Intervention 1 (lurasidone 60 mg/day) for 6 weeks: study participants randomised to the 60 mg/day arm received lurasidone 20 mg/day from days 1–3, 40 mg/day from days 4–6, and 60 mg/day from day 7 to week 6. If the participant was not able to tolerate the 60 mg/day dose, a one‐time dose reduction to 40 mg/day was permitted (between days 8 and 29); the 40 mg/day dose was then maintained for the remainder of the study. Intervention 2 (lurasidone 20 mg/day) for 6 weeks: mean of 0.476 mg/kg/day Comparator (placebo) for 6 weeks: matching placebo
Outcomes	Primary outcomes: irritability, measured with the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: none reported Timing of outcome assessments: weekly
Notes	Study start date: August 2013 Study end date: November 2014 Source of funding: researchers were employed by Sunovion Pharmaceuticals. Conflicts of interest: "Drs Loebel, Goldman, Silva, Hernandez, Mankoski, and Deng are employees of Sunovion Pharmaceuticals Inc. Dr Brams has been a speaker, consultant, and served on advisory boards for Novartis Pharmaceuticals Corp and Shire; and has received grant‐research support from Novartis Pharmaceuticals Corp, Shire, and Eli Lilly. Dr Findling receives or has received research support, acted as a consultant and/or served on a speaker’s bureau for Alcobra, American Academy of Child & Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, AstraZeneca, Bracket, Bristol‐Myers Squibb, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, Elsevier, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press Johnson and Johnson, Jubilant Clinsys, KemPharm, Lilly, Lundbeck, Merck, NIH, Neurim, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Purdue, Rhodes Pharmaceuticals, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD". Trial registry: NCT01911442
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised via an interactive voice/web response system
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blinding although details not explicitly provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blinding although details not explicitly provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	The ITT population consisted of randomised study participants who received at least 1 dose of study medication and had at least 1 postbaseline efficacy assessment.
Selective reporting (reporting bias)	Low risk	The trial was registered on clinicaltrials.gov and all outcomes were reported.
Other bias	High risk	"The sponsor was involved in the design, collection, and analysis of the data." "Drs. Loebel, Goldman, Silva, Hernandez, Mankoski, and Deng are employees of Sunovion Pharmaceuticals Inc."