Schachar 2008.

Study characteristics
Methods	Single‐centre, randomised, double‐blind, 3‐way cross‐over trial with 2 interventions: MPH (IR or ER) Placebo Phases: IR‐and multi‐layer (ER)‐release
Participants	Number of participants screened: not stated Number of participants included: 18 Number of participants followed up: 17 (15 boys, 2 girls) Number of withdrawals: 1 Diagnosis of ADHD: DSM‐IV diagnosis of ADHD (combined (100%)) Age: mean 11.3 years (range 6.8‐15.3) IQ: ≥ 85 MPH‐naive: 5 (29.4) Ethnicity: not stated Country: USA Setting: outpatient clinic, laboratory classroom setting Comorbidity: no Comedication: not stated Other sociodemographics: none Inclusion criteria 6‐15 years of age IQ ≥ 85 within previous 12 months Mentally and physically competent to provide written informed consent Ability to read, speak and understand English Otherwise able to comply with trial protocol Exclusion criteria Allergic to MPH or amphetamines, or had a history of serious adverse reactions to MPH or lack of response to MPH Serious or unstable medical illness, comorbid psychiatric illness of sufficient severity to require treatment or currently receiving psychotropic medications or herbal treatments Disorders of the sensory organs (particularly deafness), autism, psychosis or any unstable psychiatric conditions
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of IR‐MPH and ER‐MPH and placebo Mean MPH dosage: 31.2 mg/d (SD 11.7 mg/d; range 20‐60 mg/d), 1.2 mg/kg Administration schedule: twice daily, in the morning and at noon (4 h apart) Duration of each medication condition: 6 days Washout before trial initiation: 1 day Titration period: none. Participants who were receiving MPH at the time of trial entry received the dose of MPH that they were taking before entry into the trial Treatment compliance: not stated
Outcomes	ADHD symptoms IOWA: parent‐rated weekly (8 times in 1 day) Conners' Continous Performance Task: rated weekly (8 times in 1 day) Non‐serious AEs Clinical Assessment of Side Effects Scale: parents and teachers separately, rated weekly 1 day before other assessments Spontaneously reported AEs: investigator, collected weekly
Notes	Sample calculation: no Ethics approval: yes Key conclusion of trial authors Both ER‐MPH and IR‐MPH compared with placebo demonstrated significant improvement on IOWA‐CRS average total score, with onset of action observable by 1 h Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes Any withdrawals due to AEs: no Funding source: Purdue Pharma (Canada) Email correspondence with trial authors: May 2014. Emailed trial authors to ask for supplementary information but have not received a reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly assigned to a treatment sequence according to a Latin square
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind; not further described
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind; not further described
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 1 withdrawal due to inability to swallow capsules, all other participants were included in efficacy analyses. All participants were included in safety analyses. Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol was published