Newcorn 2008.

Study characteristics
Methods	20‐site, randomised, placebo‐controlled, double‐blind, 6‐week, parallel trial with 3 arms: ER‐MPH placebo atomoxetine (not used in this review)
Participants	Number of participants screened: 635 Number of participants included: 294 (211 boys, 83 girls) randomised to the arms used in this review (516 including the atomoxetine arm, not used in this review) Number of participants followed‐up: 237 (MPH 180, placebo 57) Number of withdrawals: 57 (MPH 40, placebo 17) DSM‐IV diagnosis of ADHD (combined (67%), hyperactive‐impulsive (1%), inattentive (32%)) Age: MPH mean 10.2, placebo mean 10.1 (range 6‐16) IQ: not stated MPH‐naive: 41%/121 Ethnicity: not stated Country: USA Setting: outpatient clinic Comorbidity: ODD (36%) Comedication: not stated Other sociodemographics: no significant differences in baseline demographics were noted between the 2 groups Inclusion criteria Children 6‐16 years of age Meeting DSM‐IV criteria for ADHD, any subtype Symptom severity at entry was required to be ≥ 1.5 SD above USA age and sex norms, as assessed by the ADHD‐RS‐IV ‐ Parent Version ADHD as the primary diagnosis Exclusion criteria Seizures, bipolar disorder, psychotic illness or pervasive developmental disorder Taking concomitant psychoactive medications Anxiety or tic disorders or both Previously treated with an adequate trial of MPH or amphetamine and either did not experience at least some improvement in ADHD signs and symptoms (non‐responders) or did experience intolerable AEs
Interventions	Participants were randomly assigned to OROS‐MPH or placebo Number of participants randomised: MPH 220, placebo 74 Mean MPH dosage: 39.9 mg/d (SD 14.6) or 1.26 mg/kg/d (SD 0.55) Administration schedule: single morning dose Duration of intervention: 6 weeks Titration period: none Treatment compliance: not stated. Participants were required to discontinue any psychoactive medication for ≥ 5 days before entering the trial
Outcomes	ADHD symptoms ADHD‐RS: observer‐rated at baseline and at weeks 1, 3 and 6 CPRS, ADHD Index: rated at baseline and at weeks 1, 3 and 6 General behaviour Quality of life Child Health Questionnaire: parent/teacher/observer‐rated at baseline and at weeks 3 and 6 Serious AEs Non‐serious AEs Open‐ended questioning for AEs and vital signs: observer‐rated at baseline and at weeks 1, 3 and 6 No differences were observed in mean change in SBP between placebo and MPH Weight loss was significantly greater with MPH than with placebo
Notes	Sample calculation: no Ethics approval: yes; approved by each site’s ethical review board Comments from trial authors It is likely that the MPH dose was suboptimal for some adolescent participants Restricting the dose of MPH to 54 mg could also have limited response in some younger participants, as OROS‐MPH sometimes is prescribed at doses higher than the FDA‐recommended maximum for children Key conclusion of trial authors Both treatments produced robust improvement, with a statistically significant difference in response favouring OROS‐MPH Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes Any withdrawals due to AEs: yes. 12 in assessment 1, and 3 in assessment 2 Funding source: Eli Lilly and Company Email correspondence with trial authors: November 2013 and January 2014. We requested additional data from trial authors but never received them
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Trial drugs were administered according to a double‐dummy design. Identically appearing capsules were used
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Trial drugs were administered according to a double‐dummy design. Identically appearing capsules were used
Incomplete outcome data (attrition bias) All outcomes	Low risk	NNTB was calculated for each treatment in relation to placebo and for atomoxetine in relation to MPH. The number of participants was chosen to have 90% power to declare non‐inferiority on the basis of a comparison of response rates, with a non‐inferiority margin of 15% Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Low risk	No indication of selective reporting