Posey 2005.

Study characteristics
Methods	Cross‐over trial of methylphenidate versus placebo
Participants	Inclusion criteria: children aged 5‐14 years diagnosis of autistic disorder, Asperger disorder, or PDD‐NOS based on the criteria in the DSM‐4 interfering symptoms of hyperactivity and/or impulsiveness present for at least 6 months and commenced prior to 7 years of age mental age of at least 18 months Exclusion criteria: concurrent psychotropic medications other neuropsychiatric disorders that might require alternative medical management significant medical conditions such as heart or liver disease seizures in the past 6 months hypertension treatment with methylphenidate hydrochloride within the past 2 years history of severe adverse response to methylphenidate Location/setting: 5 centres, Indiana University (Indianapolis), the Kennedy Krieger Institute at John Hokins University (Baltimore), The Ohio State University (Columbus), the University of California (Los Angeles), Yale University (New Haven), USA Sample size: 66 Number of withdrawals/dropouts: 8 exited cross‐over phase, 7 due to AEs (3 from high dose, 3 medium dose and 1 low dose), 1 due to other reasons, withdrawing consent prior to receiving treatment. Gender: 59/66 male Mean age: 7.5 years IQ: mental age of at least 18 months Baseline ABC‐I or other BoC: ABC‐I 16.5 Concomitant medications: no concurrent psychotropic medications for at least 1‐3 weeks (1 week for stimulants and clonidine hydrochloride; 2 weeks for antidepressants except fluoxetine and citalopram hydrobromide; 3 weeks for fluoxetine, citalopram hydrobromide, or antipsychotics) prior to baseline visit. History of previous medications: not described
Interventions	Intervention (methylphenidate) for 4 weeks: dosage levels were varied depending on the weight of the child. The low‐dosage level approximate 0.125 mg/kg per dose. The medium‐dosage level approximate 0.250 mg/kg per dose. The high‐dosage level approximate 0.500 mg/kg per dose. Each participant received 1 week placebo and 1 week each of 3 different doses in random order (except high dose never followed placebo). Each dose was received 3 times daily (8 am, 12 pm, 4 pm). Comparator (placebo) for 4 weeks: equivalent placebo
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale; however, only baseline scores reported AEs Secondary outcomes: none reported Timing of outcome assessments: details not provided
Notes	Study start date: November 2001 Study end date: September 2003 Source of funding: research supported by authors' contracts with National Institute of Mental Health, and grants with various universities, the General Clinical Research Centers, National Center for Research Resources, National Institutes of Health, Bethesda, and by the Korczak Foundation, Amsterdam Conflicts of interest: none declared Trial registry: NCT00025779
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation lists were generated centrally and were held by an investigational pharmacist at each site.
Allocation concealment (selection bias)	Unclear risk	Details not provided
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Clinicians, the patient, and the caregiver were blind to treatment assignment during this phase.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The rating clinician was also kept blinded to any information about AEs or changes in vital signs or weight.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Consistent with ITT principles, all of the data from participants receiving 2 medium doses (owing to the inability to tolerate a high dose) were analysed. No significant differences were found between these 2 weeks of receiving the medium dose, so the data were combined. LTFU unclear as they did not report for intervention and placebo groups.
Selective reporting (reporting bias)	High risk	ABC‐I was reported in baseline scores however it was not reported in the endpoint scores (only ABC hyperactivity).
Other bias	Low risk	None identified