Epstein 2011.

Study characteristics
Methods	Cross‐over trial with 2 interventions 3 preliminary phases to determine optimal dose followed by 2‐phase trial of the following: optimal dose of MPH placebo
Participants	Number of participants screened: not stated Number of participants included: not clear Number of participants followed up: 93 (numbers of boys and girls: not stated) Number of withdrawals: not clear Diagnosis of ADHD: DSM‐IV (combined (n = 45), hyperactive‐impulsive (n = 48), inattentive (n = 0)) Age: mean 8.1 years (range 7‐11) IQ: mean 105.58 MPH‐naive: 100% Ethnicity: white (75%), African American (22%), other (3%) Country: USA Setting: outpatient clinic Comorbidity: ODD (n = 34), CD (n = 4), anxiety disorders (n = 31), mood disorders (n = 2) Comedication: not stated Other sociodemographics: none Inclusion criteria Children 7‐11 years of age who met the diagnostic criteria for ADHD, plus 6 non‐overlapping symptoms in a symptom domain on the Diagnostic Interview for Children ‐ Parent Report and Vanderbilt Teacher Rating Scale; both parents and teachers reported ≥ 4 symptoms in that domain Exclusion criteria Children with an IQ below 80 (on the WASI) or a score < 80 on the Reading or Numerical operations subtests of the Wechsler Individual Achievement Test or possible organic brain injury
Interventions	Participants were randomly assigned to an optimal dose of MPH and placebo Mean MPH dosage: 1.13 mg/kg Administration schedule: testing 1‐4 h after medication ingestion Duration of each medication condition: 1 week Washout before trial initiation: no apparent washout Titration period: each of the 3 doses was trialled for 1 week before random assignment to identify an optimal dose Treatment compliance: not reported
Outcomes	ADHD symptoms Vanderbilt ADHD‐RS: completed by parents and teachers at the end of 1 week Non‐serious AEs Referred to the Pittsburgh Side Effects Rating Scale: completed by parents and teachers at the end of each week, but data were not reported
Notes	Sample calculation: not stated Ethics approval: not stated Comments from trial authors "Although we used a placebo‐controlled, double‐blind titration trial to determine optimal dosage, the highest dosage used in this trial was 54 mg for children ≥ 25 kg and 36 mg for children < 25 kg" "Also, a significant minority of children (24%) exited the titration trial, with the placebo dosage as their optimal dosage, which is comparable with the stimulant response rate in other studies. The fact that 19% of children in the optimal dose condition received the same stimulant dosage (i.e. placebo) as was received by the placebo control group may have affected the ability of this trial to detect between‐group differences for some trial outcomes (e.g. accuracy)" Key conclusion of trial authors None regarding our outcomes of interest Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: not stated Funding source: NIH and NIMH Email correspondence with trial authors: April 2014. We were able to obtain supplemental information regarding data (Storebø 2015b).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Double‐blind"; capsules were "identical" (p 2, p 1063)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Double‐blind", capsules were "identical" (p 2, p 1063)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not clear whether any participants were LTFU Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	No indication of selective reporting