Stein 2011.

Study characteristics
Methods	8‐week, double‐blind, cross‐over trial comparing the following: ER‐d‐MPH (10 mg, 20 mg, 25‐30 mg) ER‐MAS (10 mg, 20 mg, 25‐30 mg) with a week of randomly assigned placebo within each drug period
Participants	Number of participants screened: 77 Number of participants included: 65 Number of participants followed up: 56 (41 boys, 15 girls) Number of withdrawals: 9 Demographic data on the 56 participants Diagnosis of ADHD: DSM‐IV (combined (67%), hyperactive‐impulsive (0%), inattentive (33%)) Age: mean 11.78 years (range 9‐17) IQ: > 70 MPH‐naive: 35.7% Ethnicity: white (41.0%), African American (41.0%), Asian (2%), Hispanic (7%), bi‐racial/mixed (9%) Country: USA Setting: outpatient clinic Comorbidity: ODD (n = 11, 29.7 %), enuresis (n = 3, 8.1 %), generalised anxiety disorder (n = 1, 2.7 %) and separation anxiety (n = 1, 2.7 %) Comedication: not stated Other sociodemographics: none Inclusion criteria DSM‐IV diagnosis of ADHD, any subtype Signed informed consent and assent CGI‐S‐ADHD rating ≥ 4 Findings on physical exam, laboratory studies, vital signs and ECG are judged to be normal for age Pulse and BP are within 95% of age and sex means Able to complete trial instruments and swallow capsules Willing to commit to the entire visit schedule for the trial, including ≥ 1 visit to university Medical Center Exclusion criteria Intellectual disability, autism, severe mood disorders, Tourette's disorder, seizure disorders or other medical disorders that were contraindications of stimulant treatment that mimic ADHD (e.g. thyroid disorder) Non‐responder to either medication at doses offered in the trial in an adequate trial. Must not have experienced disabling adverse effects with either medication Concomitant psychotropic medications or medications that might have a CNS effect are required Any other medical condition that represents a contraindication for either treatment History of alcohol or drug abuse in the past 3 months, or a positive urinary toxic screen on initial evaluation that is not explained by a time‐limited medical circumstance Girls of childbearing age who are sexually active, do not use acceptable birth control (double protection method) and, after counselling, are unwilling to do so History of allergic reactions to multiple medications History of psychosis Diagnosis of bipolar disorder
Interventions	Participants were randomly assigned to 3 dose conditions of ER‐d‐MPH and ER‐MAS administered sequentially from lowest to highest dose with a randomly assigned week of placebo during each period MPH dosage: 10 mg, 20 mg and 25‐30 mg. Maximum dose was 25 mg in smaller children (i.e. < 35 kg) to minimise potential side effects Administration schedule: once daily Duration of each medication condition: 1 week Washout before trial initiation: 2‐day washout period before beginning of the trial. No washout period between treatment periods Titration period: none Treatment compliance: not stated
Outcomes	ADHD symptoms ADHD Parent Rating Scale, 4th Edition, rated weekly Non‐serious AEs Stimulant Side Effects Rating Scale (Barkley 1990): rated weekly by parents Vital signs (weight, height, BP, pulse and temperature): obtained weekly ECG before and after trial Sleep measured by actigraphy and questionnaires (from abstract)
Notes	Sample calculation: no Ethics approval: approved by the Institutional Review Board of University of Illinois at Chicago Comment from trial authors Short duration of time children were maintained on each dose and fixed dose titration Key conclusions of trial authors Both ER‐d‐MPH and ER‐MAS were associated with significant, dose‐dependent reductions in ADHD symptoms Decreased appetite and insomnia were more common and were seen at higher dose levels for both stimulants Dose level, rather than stimulant class, was strongly related to medication response Although most children responded similarly to both stimulants, 14.3% of total samples were responders to ER‐d‐MPH only, and 12.5% responded only to ER‐MAS Future comparative effectiveness studies with multiple informants and larger samples over longer time periods are necessary to develop a data‐driven, personalised approach to ADHD treatment Comment from review authors Protocol states that an exclusion criterion was "Non‐responder to either medication at the doses offered in the study in an adequate trial". This is not written in the full text of the trial. Asked trial author about this issue, who replied, "Although non response was an exclusion [criterion] a priori, in fact this did not come up and no cases were excluded from participation based upon this". Even though this means that children in the trial were not only responders, we still chose to analyse this trial as part of the studies that included only responders Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; see comments above Any withdrawals due to AEs: yes; 6 Funding source: investigator‐initiated trial sponsored by Novartis Pharmaceuticals, with additional support provided by the University of Illinois at Chicago, Center for Clinical and Translational Science. Email correspondence with trial authors: November and December 2013. We received supplemental data from trial authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Order of drug was randomly assigned so that 50% started with ER‐d‐MPH and 50% started with ER‐MAS; also a randomly assigned week of placebo during each period
Allocation concealment (selection bias)	Low risk	Weekly blister packs containing capsules of trial drug, which were indistinguishable from each other
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participant, caregivers, outcome assessors
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participant, caregivers, outcome assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	All trial participants who received ≥ 2 weeks of trial drug to ensure that all participants had been exposed to ≥ 1 week of active drug were analysed Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Low risk	Outcomes reported according to protocol