Findling 2014.

Study characteristics
Methods	Parallel trial of aripiprazole versus placebo
Participants	Inclusion criteria Male or female children or adolescents with a mental age of at least 24 months 6‐17 years of age, inclusive, at the time of the baseline visit Meets current diagnostic criteria of the DSM 4‐TR for autistic disorder Displays behaviors such as tantrums, aggression, self‐injurious behaviour, or a combination of these problems. An ABC subscale score ≥ 18 AND a CGI‐S score ≥ 4 at the screening and baseline visits Exclusion criteria Previous treatment with aripiprazole for at least 3 weeks' duration at an adequate daily dose, without demonstrating a clinically meaningful response Lifetime diagnosis of psychiatric disorder such as bipolar disorder, psychosis, or schizophrenia, or a current diagnosis of PDD‐NOS, Asperger's syndrome, Rett's syndrome, childhood disintegrative disorder, or Fragile X syndrome At significant risk for suicide Unstable epilepsy or history of severe head trauma or stroke Other unstable medical conditions Location/setting: child and adolescent psychiatry, Johns Hopkins Hospital, USA Sample size: 85 (41 aripiprazole, 44 placebo) Number of withdrawals/dropouts: 19 dropouts in aripiprazole group due to: withdrawal (5), LTFU (1), lack of efficacy (13); 25 dropouts in placebo group due to: adverse event (1), lack of efficacy (23), noncompliance (1) Mean age: aripiprazole 10.1 years, placebo 10.8 years IQ: mental age of at least 24 months Gender: aripiprazole male 30/41; placebo 38/44 male Baseline ABC‐I or other BoC: not reported (only change from baseline) Concurrent medications: "allowed antipsychotics apart from aripiprazole include antidepressants, benzodiazepines (for procedures only), stimulants, alpha‐agonists, mood stabilizers, and atomoxetine. Diphenhydramine for sleep or serious behaviur problems, nonbenzodiazepine sleep aids for insomnia, and melotonin for insomnai were permitted". History of previous medications: not reported
Interventions	Intervention (aripiprazole): "Phase 1 (single blind): Participants received an initial dose of aripiprazole 2 mg daily, titered up to 5, 10, or 15 mg once daily to optimize clinical benefit, for a maximum of 26 weeks. Phase 2 (randomised): Aripiprazole was continued at the (fixed) dose prescribed at the end of Phase 1, once daily for 16 weeks. The dose (within the range of 2‐15 mg/day) could have been adjusted based on efficacy and tolerability". Comparator (placebo): equivalent placebo for 16 weeks
Outcomes	Primary outcomes: irritability (change from baseline), measured using the ABC‐Irritability subscale (Aman 1985); AEs Secondary outcomes: QoL, measured with the PedsQL Timing of outcome assessment: ABC‐I and AEs were assessed every 2 weeks and PedsQL every 4 weeks
Notes	Study start date: March 2011 Study end date: June 2012 Source of funding: Bristol‐Myers Squibb Conflicts of interest: "Dr Findling receives or has received research support from, acted as a consultant to, received royalties from, and/or served on a speaker’s bureau for Abbott, Addrenex, Alexza, American Psychiatric Press, AstraZeneca, Biovail, Bracket, Bristol‐Myers Squibb, Dainippon Sumitomo Pharma, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, National Institutes of Health, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Sanofi‐Aventis, Schering‐Plough, Seaside Therapeutics, Sepracore, Shionogi, Shire, Solvay, Stanley Medical Research Institute, Sunovion, Supernus, Transcept, Validus, WebMD and Wyeth".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided about sequence generation
Allocation concealment (selection bias)	Unclear risk	Details not provided about allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided about blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details not provided about blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	Paper mentions the PedQoL and Caregiver Strain Questionnaire that were administered every 4 weeks in the double‐blind phase. Neither outcome was reported in the paper. LTFU: aripiprazole 19/39 did not complete the trial (withdrawal (5); LTFU (1); Lack of efficacy (13)) Placebo: 25/43 did not complete the trial (adverse event (1), poor/noncompliance (1), lack of efficacy (23))
Selective reporting (reporting bias)	High risk	Quote: "Safety assessments were made every 2 weeks in the double blind phase". Relatively few AEs reported for double‐blind phase suggesting reporting bias.
Other bias	High risk	There is an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed".