Green 2011.

Study characteristics
Methods	1‐day, randomised, parallel trial with 2 arms: IR‐MPH placebo 6‐month follow‐up of trial participants continuing MPH treatment
Participants	Number of participants screened: not stated Number of participants included: 34 (20 boys, 14 girls) Number of participants followed up: 34 Number of patients continuing MPH treatment beyond the 1‐day trial: 16 Number of participants followed up: 15 Number of withdrawals from extension trial: 1 Patients participating in the 1‐day trial Diagnosis of ADHD: DSM‐IV‐TR (combined (33.3%), hyperactive‐impulsive (not stated), inattentive (50%), not otherwise specified (17.7%)) Age: mean 11.1 years (range 5‐20) IQ: mean: 81.4 MPH‐naive: 61.8% Ethnicity: not stated Country: Israel Setting: hospital/outpatient clinic Comorbidity in total sample: velocardiofacial syndrome (100%), ODD (23.5%), specific phobia (26.5%), generalised anxiety disorder (11.8%), social phobia(11.8%), dysthymic disorder (8.8%) and separation anxiety (5.9%) Comorbidity in MPH group: congenital anomalies of the heart and great vessels (54.5%) Comedication: no other psychotropic medication during the trial Other sociodemographics: none. The 2 groups had similar baseline demographics Inclusion criteria Not stated Exclusion criteria Not stated
Interventions	RCT: participants were randomly assigned to MPH or placebo Number randomised to each group: MPH 22, placebo 12 Mean MPH dosage: 15.7 ± 5.6 mg (0.5 mg/kg) Administration schedule: once Duration of intervention: 1 day Titration period: no mention, none Washout before trial initiation: 3 days Treatment compliance: not stated Follow‐up: some participants continued MPH treatment beyond the RCT Mean MPH dosage: not stated Administration schedule: not stated Duration of treatment: 6 months Treatment compliance: 1 withdrew because of poor compliance
Outcomes	Non‐serious AEs Cardiologic evaluation (ECG, heart rate and BP): immediately before taking the pill (MPH or placebo), and again after 90 min Barkley Side Effects Rating Scale (modified Hebrew Version), parent‐rated: 24 h after MPH administration and at 6‐month follow‐up
Notes	Sample calculation: not stated Ethics approval: trial protocol was approved by the Institutional Review Board of the Rabin Medical Center Comments from trial authors "We found that all participants (100%) with velocardiofacial syndrome treated with MPH exhibited ≥ 1 side effect" "Rate of all side effects immediately observed following initiation of treatment remained similarly high after 6 months of treatment" "According to our findings, it seems that children with velocardiofacial syndrome did not develop tolerance to MPH side effects" None of the children withdrew because of side effects Limitations: short duration of parallel‐group trial and relatively small sample size Key conclusions of trial authors Use of MPH in children with velocardiofacial syndrome appears to be effective and relatively safe Comprehensive cardiovascular evaluation for children with velocardiofacial syndrome before and during stimulant treatment is recommended Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: no Funding source: The Basil O’Connor Starter Scholar Research Award of the March of Dimes, NARSAD (National Alliance for Research in Schizophrenia and Affective Disorders) Young Investigator Award, the Marguerite Stolz Award from the Sackler Faculty of Medicine and the National Institute on Drug Abuse (NIDA) Email correspondence with trial authors: November 2013. We obtained supplemental information regarding ADHD diagnostic criteria from trial authors. Furthermore, we received safety data from the trial sample, excluding participants > 18 years or with IQ < 70 (or both), but we decided not to use these data in our analyses, as data were missing for 60% of the control group.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Participants were randomly assigned to drug or placebo in a 2:1 ratio, according to their order of recruitment
Allocation concealment (selection bias)	High risk	Participants were randomly assigned to drug or placebo in a 2:1 ratio, according to their order of recruitment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and their parents were blinded
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information
Incomplete outcome data (attrition bias) All outcomes	Low risk	No 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. Trial authors have confirmed that planned outcomes for the 1‐day RCT were measured and reported