Tannock 1995a.

Study characteristics
Methods	4‐day, randomised, double‐blind, placebo‐controlled, cross‐over trial with: 3 doses of MPH (0.3 mg/kg, 0.6 mg/kg and 0.9 mg/kg) placebo With initial 1‐day open‐label trial
Participants	Number of participants screened: 28 Number of participants included: 28 (25 boys, 3 girls) Number of participants followed up: 28 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐III‐R (subtype not stated) Age: mean 8.9 years (range 7‐11) IQ: mean 106.5 (15.6) MPH‐naive: 80% Ethnicity: white (90%), other (10%) Country: Canada Setting: outpatient clinic Comorbidity: ODD or CD (35%), learning disabilities (39%) Comedication: not stated Other sociodemographics: none Inclusion criteria ADHD, DSM‐III‐R Exclusion criteria IQ: WISC‐R: score < 80 Anxiety disorder (DSM‐III‐R) Major neurological, physical or sensory impairment
Interventions	Participants were randomly assigned to 3 doses of MPH (0.3 mg/kg, 0.6 mg/kg, 0.9 mg/kg) and placebo Mean MPH dosage: not stated Administration schedule: once daily Duration of each medication condition: 1 day Washout before trial initiation: for children receiving MPH before trial, washout period ≥ 48 h before trial, with no washout between periods Titration period: no, but all children participated in an initial 1‐day open trial with a 0.3 mg/kg dose of MPH to ascertain tolerance, before proceeding with the double‐blind, placebo‐controlled trial Treatment compliance: not stated
Outcomes	Non‐serious AEs Cardiovascular function (heart rate). Radial pulse, taken for 1 min with the child seated, was measured 3 times during each session: immediately before medication (time 0) and again at 1 h (time 1) and 2 h (time 2) following administration of the oral dose. From time 0 to time 1, children were seated at a table, colouring or playing quietly with puzzles or board games: children completed the cognitive task from time 1 to time 2
Notes	Sample calculation: yes Ethics approval: yes; Institutional Research Ethics Board Key conclusions of trial authors "Results indicate that MPH enhanced cognitive flexibility, although the high dose was less effective than lower doses in enhancing response inhibition" "Dissociations of dose effects on cognitive function and behaviour were demonstrated: dose‐response functions for changes in behaviour were linear, whereas the function for response inhibition was U‐shaped" Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; 1‐day open‐label trial to ascertain tolerance towards medication, but all participants were analysed Any withdrawals due to AEs: no Funding source: Medical Research Council of Canada and Health and Welfare Canada Email correspondence with trial authors: August 2013. We received from the first trial authors supplemental information regarding dropouts, screening and ethics approval
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised
Allocation concealment (selection bias)	Low risk	All medication was prepared by the hospital pharmacy and was packaged in opaque gelatin capsules to avoid detection of dose and taste
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Children, parents, teachers and research staff were all blinded to medication conditions
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Children, parents, teachers and research staff were all blinded to medication conditions
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data from all 28 participants were analysed Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Low risk	No indication of selective reporting