Cox 2006.

Study characteristics
Methods	Randomised, double‐blind, placebo‐controlled, cross‐over trial of adolescent drivers with ADHD who were assessed on a driving simulator after taking: 72 mg of OROS‐MPH 30 mg of ER‐MAS placebo Phases: 3 (2 relevant phases)
Participants	Number of participants screened: not stated Number of participants included: 35 (19 boys, 16 girls) Number of participants followed up: 35 Number of withdrawals: 2 Diagnosis of ADHD: DSM‐IV (combined 21 (60%), hyperactive‐impulsive 2 (6%), inattentive 12 (34%)) Age: mean 17.8 years (range 16‐19) IQ: not stated MPH‐naive: not stated Ethnicity: not stated Country: USA Setting: outpatient clinic Comorbidity: agoraphobia (2.9%), CD and marijuana abuse (2.9%), OCD (2.9%), OCD and hypomania (2.9%), nicotine dependence (5.7%) Comedication: 2 were taking no medication, 21 were taking MPH and 12 were taking amphetamine formulations at the start of the trial Other sociodemographics: none Inclusion criteria Adolescent drivers 16‐19 years of age ADHD according to DSM‐IV. To meet inclusion criteria for a diagnosis of ADHD, adolescents first needed to surpass clinical cut‐offs for ADHD on a commonly used parent rating scale, the ADHD‐RS‐IV Psychiatrist confirmed ADHD diagnosis with the Standardized Interview for Adult ADHD (DSM‐IV) Positive history of stimulant responsiveness, as disclosed by adolescents and by parent reports; current licence to drive and reported daily driving activity Exclusion criteria Adolescents were excluded when they had a history of tics or any adverse reaction to stimulant medication History of substance abuse disclosed by patient or parent Co‐existing medical condition or medication usage known to interfere with safe administration of stimulant medications
Interventions	Participants were randomly assigned to 1 of 2 relevant drug condition orders of MPH and placebo Mean MPH dosage: 72 mg/d Administration schedule: 2 overlaid capsules/tablets in blister packs each day on awakening Duration of each medication condition: 17 days Washout before trial initiation: not stated Medication‐free period between interventions: 4‐21 days between OROS‐MPH and MAS Titration period: half dose (36 mg/d OROS‐MPH) days 1‐5, full dose (72 mg/d OROS‐MPH) days 6‐17 initiated after randomisation Treatment compliance: not stated. Pill counts were completed at each trial visit
Outcomes	Non‐serious AEs Throughout the trial, only 1 AE was reported ‐ urinary difficulty. This AE occurred during treatment with 36 mg of OROS‐MPH and was resolved after 2 days without discontinuation of the medicine Self‐Reported Stimulant Drug Side Effects Rating Scale on days 5 and 10
Notes	Sample calculation: no Ethics approval: yes Comments from trial authors Automobile accidents are the leading cause of death among adolescents, and collisions are 2‐4 times more likely to occur among adolescents with ADHD Studies have demonstrated that stimulants improve driving performance Results provide evidence supporting most literature on children with short‐acting stimulants; longer‐acting stimulants appear equally effective for female and male post‐pubertal adolescents with ADHD Limitation of this trial is that few participants with hyperactive subtype were included, limiting extrapolation of results to this subgroup Key conclusions of trial authors This trial validates the use of stimulants to improve driving performance in adolescents with ADHD In this trial, OROS‐MPH promoted significantly improved driving performance compared with placebo and ER‐MAS Comments from review authors Effects of MPH were also measured, but not in comparison with placebo. Therefore, we could not use these data in the review Some participants are > 18 years. However, as mean age is > 19 years, this trial is still included but was tested by sensitivity analyses Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; excluded if any history of AEs to stimulant medications Any withdrawals due to AEs: no Funding source: supported by funding from McNeil Pediatrics, a division of McNeil‐PPC Incorporated Email correspondence with trial authors: February 2014. We received additional information from trial authors. Data from the Self‐Reported Stimulant Drug Side Effects Rating Scale are no longer available (Krogh 2013b [pers comm]).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Using a random‐numbers table, each participant was assigned"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Treatments were provided in different forms: "Participants took 2 overlaid capsules/tablets in blister packs each day on awakening". Participants and research assistants were blinded to medication conditions
Blinding of outcome assessment (detection bias) All outcomes	High risk	"Participants were either tested on placebo or were not required to come in for testing". Participants and research assistants were blinded to medication condition
Incomplete outcome data (attrition bias) All outcomes	Low risk	Email correspondence with trial author: no dropouts and all were followed up (Krogh 2013b [pers comm]) Selection bias (e.g. titration after randomisation → exclusion): none described
Selective reporting (reporting bias)	Low risk	Email correspondence with trial author, who stated that all planned outcome measures and analyses are described in the papers (Krogh 2013b [pers comm])