Findling 2006.

Study characteristics
Methods	3‐week, randomised, double‐blind, parallel trial with 3 arms: IR‐MPH (Ritalin) MR‐MPH (EqXL) placebo
Participants	Number of participants screened: 346 Number of participants randomly assigned: 327 Number of participants included: 318; IR‐MPH 133, MR‐MPH (EqXL) 139, placebo 46 Number of participants followed up: IR‐MPH 120, MR‐MPH (EqXL) 120, placebo 39 (number in each arm is only per protocol population) Number of withdrawals: not stated Diagnosis of ADHD: DSM‐IV (combined (71%), hyperactive‐impulsive (6%), inattentive (23%)) Age: mean 9.5 years (range not reported) IQ: above 80 Sex: 252 boys, 66 girls MPH‐naive: 0% Ethnicity: white (86%), African Caribbean (5.2%), Asian (0.3%), Hispanic (1.6%), other (6.9%) Country: Australia, Canada, USA Setting: outpatient clinic Comorbidity: not stated Comedication: not stated Other sociodemographics: none. No significant differences in baseline demographics were noted between the 2 groups Inclusion criteria Male and female children 6‐12 years of age Stable dose of MPH 3 weeks before screening Diagnosed with ADHD on the basis of DSM‐IV criteria for any subtype and confirmed by administration of the K‐SADS‐PL at screening Attending a school setting in which a single teacher could make morning and afternoon assessments of the child’s behaviour Exclusion criteria Girl who had experienced menarche Comorbid psychiatric disorder requiring medication History of seizure or tic disorder or family history of Tourette’s disorder IQ test score < 80, or functioning at a level of intelligence indicative of an IQ <80 Use of unapproved medication(s) Use of an investigational product within 30 days before trial entry Concurrent chronic or acute illness, disability or medication that might confound the results of rating tests Diagnosed with hyperthyroidism, glaucoma or eating disorder Current substance abuse disorder or living with someone with a current substance abuse disorder Demonstrated lack of response to MPH
Interventions	Participants were randomly assigned to IR‐MPH, ER‐MPH (EqXL) or placebo Mean MPH dosage: not stated Administration schedule: twice daily, morning and lunch Duration of intervention: 3 weeks Titration period: all participants were stable while taking MPH medication before randomisation Treatment compliance: not stated. Children with a previous total daily dose of 10 mg‐20 mg IR‐MPH or 20 mg ER‐MPH were randomly assigned to receive 10 mg IR‐MPH twice daily, 20 mg MR‐MPH (EqXL) once daily or placebo; children given a previous total daily dose of 25 mg‐40 mg IR‐MPH or > 20 mg to < 40 mg ER‐MPH were randomly assigned to receive 20 mg IR‐MPH twice daily, 40 mg MR‐MPH (EqXL) once daily or placebo; children given a previous total daily dose > 40 mg IR‐MPH or < 40 mg ER‐MPH were randomly assigned to receive 20 mg IR‐MPH twice daily, 60 mg MR‐MPH (EqXL) once daily or placebo
Outcomes	ADHD symptoms SNAP‐IV: teacher‐rated at baseline and weekly SNAP‐IV: parent‐rated at baseline and weekly, at the end of the child’s day IOWA CRS (Inattention‐Impulsivity‐Overactivity): teacher and parent Serious AEs Only 1 serious AE (neutropenia) was reported during the trial in MR‐MPH (EqXL) treatment, but the investigator considered it unlikely to be related to the trial medication General behaviour IOWA CRS (oppositional defiance): teacher‐ and parent‐rated, at baseline and weekly (2 h post‐dose and ‐4 h post‐lunch) Non‐serious AEs Barkley Side Effects Rating Scale: parent‐ and teacher‐rated at baseline and weekly AEs, laboratory parameters, vital signs, physical exam, observer‐rated, time point not specified
Notes	Sample calculation: yes Ethics approval: yes; independent ethics committee at each clinical site before trial initiation Key conclusion of trial authors MR‐MPH (EqXL) given once daily was non‐inferior to IR‐MPH given twice daily. Both treatments were superior to placebo in reducing ADHD symptoms Comment from review authors September 2013. Not possible to contact trial authors Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes Any withdrawals due to AEs: yes, 14 placebo, 4 MPH‐IR, 3 Equasym Funding source: provided by Celltech Americas Incorporated, currently part of UCB (Union Chimique Belge)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Randomised" but did not state how
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both MR‐MPH (EqXL) capsules and IR‐MPH tablets were over‐encapsulated in hard gelatin capsules identical to the placebo capsule
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information
Incomplete outcome data (attrition bias) All outcomes	High risk	Stated LOCF but primary efficacy population was the per protocol population, defined as participants who received trial treatment and had ≥ 1 efficacy measurement after the first dose Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol/design was published