Quinn 2004.

Study characteristics
Methods	Cross‐over trial with 3 interventions: d,l‐MPH d‐MPH placebo
Participants	Number of participants screened: not stated Number of participants included: 32 Number of participants followed up: 31 (all boys) Number of withdrawals: 1 Diagnosis of ADHD: DSM‐IV (combined (87.1%), hyperactive‐impulsive (9.7%), inattentive (3.2%)) Age: not stated (range 9‐12 years) IQ: > 80 MPH‐naive: 0% Ethnicity: not stated Country: USA and Canada Setting: outpatient clinic Comorbidity: (0%) Comedication: 0% for other medications for ADHD Other sociodemographics: none Inclusion criteria Male, between 9 and 12 years of age Meet DSM‐IV criteria for ADHD, as confirmed by the DISC Clinical history of positive response to treatment with ≥ 20 mg/d of d,l‐MPH for ≥ 1 month Rating > 90th percentile on Parent and Teacher Versions of the SNAP ADHD‐RS IQ ≥ 80 as assessed by a validated intelligence test Exclusion criteria Any associated CNS, cardiovascular, renal or respiratory disorder Known sensitivity to MPH or receiving other medication for ADHD Comorbid clinical disorders reported during clinical interview or identified during administration of the DISC
Interventions	Participants were randomly assigned to 1 of the possible drug condition orders of d‐MPH, d,I‐MPH and placebo. Both the order of drugs and the dose sequence were randomly assigned Mean MPH dosage: d‐MPH 2.5 mg, 5 mg or 10 mg; d,l‐MPH 5 mg, 10 mg or 20 mg Administration schedule: once at 8.30 am Duration of each medication condition: 1 day. Interventions were separated by ≥ 6 days Washout before trial initiation: 24 h Medication‐free period between interventions: ≥ 24 h Titration period: none Treatment compliance: administered at the laboratory
Outcomes	ADHD symptoms CLAM Scale: teacher‐rated, at 2 h, 3.5 h and 6 h (CLAM aggressive/defiant, CLAM inattention/overactivity) Conners’ Hyperactivity Index: teacher‐rated, at 2 h, 3.5 h and 6 h Non‐serious AEs AEs Average pulse rate also measured
Notes	Sample calculation: no Ethics approval: approved by each centre’s institutional review board Comments from trial authors (limitations) Trial was conducted in a laboratory school setting (no healthy participants, high level of staffing, short and repetitive classroom period compared with a regular classroom setting) Relatively small sample size Narrow age range Key conclusions of trial authors Efficacy of MPH resides in the d‐isomer. Elimination of the i‐isomer does not diminish the efficacy of an acute dose of MPH This trial demonstrates that single low (2.5 mg), medium (5 mg) and high (10 mg) doses of d‐MPH match the efficacy of equimolar single low (5 mg), medium (10 mg) and high (20 mg) doses of d,l‐MPH over a 6‐h period, based on repeated measurements of a surrogate measure of academic performance Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; included only children stable on MPH Any withdrawals due to AEs: no Funding source: Celgene Email correspondence with trial authors: July ‐August 2014. We contacted trial authors to obtain safety data and supplemental information regarding randomisation, allocation concealment, blinding, handling of incomplete outcome data and outcomes, but we were not successful
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised. Both the order of drugs and the dose sequence were randomly assigned
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Except for first practice day, on which only participants were blinded, administration of doses was double‐blinded throughout the trial
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind. Blinded observers rated behaviour
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Trial authors report only 1 respondent LTFU, not related to side effects Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	All outcomes reported. No protocol available