Silva 2006.

Study characteristics
Methods	Cross‐over trial with 2 interventions: d‐MPH‐ER 20 mg once daily placebo Phases: 2 cross‐over phases
Participants	Number of participants screened: not stated Number of participants included: 54 (38 boys, 16 girls) Number of participants followed up: 53 Number of withdrawals: 1 Diagnosis of ADHD: DSM‐IV (combined (90.7%), hyperactive‐impulsive (0%), inattentive (9.3%)) Age: mean 9.4 years (range 6‐12) IQ: not stated MPH‐naive: none Ethnicity: predominantly white Country: USA Setting: laboratory classroom Comorbidity: not stated Comedication: not stated Other sociodemographics: none Inclusion criteria Boys and girls Age 6‐12 years Diagnosed with ADHD Must have been stabilised on MPH 20 mg/d to 40 mg/d for ≥ 1 month For girls: pre‐menarchal, sexually abstinent or using reliable contraceptive and have negative urine pregnancy test Exclusion criteria Investigator deemed IQ below average or evidence of IQ < 80; home‐schooled Tourette's syndrome Tic disorder Significant medical illness Significant psychiatric illness (schizophrenia, bipolar disorder, autism) Parents or guardians unable to understand or follow instructions Taking antidepressants Initiated psychotherapy 3 months before screening Positive urine drug screening Poor response to MPH Currently taking other medications for ADHD Taking or planning to take another investigational drug within 30 days of trial start; previously participated in ER‐d‐MPH trial
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of 20 mg/d d‐MPH‐ER and placebo Mean MPH dosage: 20 mg/d Administration schedule: once daily; morning Duration of each medication condition: 1 week Washout before trial initiation: 1 day Medication‐free period between interventions: 1 day Titration period: none Treatment compliance: 100% in laboratory classroom sessions
Outcomes	ADHD symptoms SKAMP: once weekly, observer‐rated Non‐serious AEs Recorded AEs described by parents and children, as well as in laboratory school setting, 1 day each week
Notes	Sample calculation: yes Ethics approval: not stated Comments from trial authors "One of the inclusion criteria in this study was that participants were known to be currently stable on another MPH preparation" "We listed all side effects, irrespective of whether they were reported by parent or child. These were gathered both during the week preceding laboratory observation days and during the laboratory classroom day" "We did not systematically analyse compliance data during the week preceding the laboratory classroom." Key conclusion of trial authors "In this study, once‐daily d‐MPH‐ER 20 mg was a safe and effective treatment for paediatric participants with ADHD symptoms" Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes Any withdrawals due to AEs: yes; 1 (during placebo) Funding source: Novartis Email correspondence with trial authors: June 2014. Sent twice to trial author to ask for additional information but have not received a reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned by computerised random number assignment
Allocation concealment (selection bias)	Low risk	Trial medication comprised 1 bottle of 5 capsules of blinded trial medication or 1 bottle of 5 matching placebo capsules
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind. Trial medication comprised 1 bottle of 5 capsules of blinded trial medication or 1 bottle of 5 matching placebo capsules
Blinding of outcome assessment (detection bias) All outcomes	Low risk	3 independent blinded raters
Incomplete outcome data (attrition bias) All outcomes	Low risk	Safety population consisted of all participants who received ≥ 1 dose of trial medication. Efficacy population comprised all randomly assigned participants who provided valid efficacy measurements for both treatment periods Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol identified