Tucker 2009.

Study characteristics
Methods	Multi‐centre, open‐label RCT including behaviour treatment as co‐intervention with 2 arms ER‐MPH and behavioural treatment Behavioural treatment
Participants	Number of participants screened: 142 Number of participants included: 109 Number of participants followed up: 104 (66 boys, 38 girls) Number of withdrawals: 5 Diagnosis of ADHD: DSM‐IV (subtypes not described) Age: mean 8.4 years (range 6‐12) IQ: not stated; all age‐appropriate cognitive functioning MPH‐naive: 100% Ethnicity: white (73.1%), African American (24.0%), other (2.9%) Country: USA Setting: outpatient clinic Comorbidity: none Comedication: no Other sociodemographics: none Inclusion criteria DSM‐IV diagnosis of ADHD Age‐appropriate cognitive functioning Exclusion criteria Previous exposure to MPH or any amphetamine‐based medication Positive urine drug screen Clinically significant abnormality in the screening assessment (physical exam, vital signs, laboratory tests) Cardiac abnormality History of seizures or schizophrenia; current diagnosis of mood disorder or anxiety disorder
Interventions	Participants were randomly assigned to ER‐MPH plus behavioural treatment or to behavioural treatment alone. We considered this as ER‐MPH versus no intervention. Mean MPH dosage: not stated Administration schedule: once daily Duration of intervention: 3 months Titration period: initiated after randomisation. MPH was started at 10 mg/d and could be increased weekly in intervals of 10 mg/d to a maximum of 60 mg/d. MPH was administered to achieve the desired clinical effect with minimum or no side effects Treatment compliance: not stated
Outcomes	ADHD symptoms Conners' ADHD/DSM‐IV Scales for Parents: measured at baseline and at end of treatment Non‐serious AEs Investigating for potential genotoxic effects: no significant differences were found Chromosomal aberrations (CAs), including micronuclei (MN) and sister chromatid exchanges (SCEs), in cultured peripheral blood lymphocytes. Blood samples were obtained from all participating patients for evaluation of cytogenetic status at baseline and after 3 months of treatment. These data are not used in the review
Notes	Sample calculation: yes Ethics approval: yes; approved by the ethics committees for all 17 trial centres Key conclusion of trial authors These findings support the notion that MPH does not induce chromosomal alterations nor other types of genetic damage in children treated for ADHD Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no; all participants were MPH‐naive Any withdrawals due to AEs: no Funding source: Novartis Pharmaceuticals Corporation Email correspondence with trial authors: December 2013 and January 2014. Not able to contact trial authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised; no further description
Allocation concealment (selection bias)	Unclear risk	Randomisation was stratified by age group (6‐8 years and 9‐12 years) and by centre
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not stated
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Evaluation of cytogenetic damage by blinded slide readers
Incomplete outcome data (attrition bias) All outcomes	High risk	Outcome data reported for 68 of 109 randomly assigned participants Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol identified