Blum 2011.

Study characteristics
Methods	This double‐blind, placebo‐controlled, cross‐over trial with the child's clinically most effective dose as identified by a systematic open‐label titration procedure investigated whether components of attention and executive functioning improve when children with ADHD are treated with OROS‐MPH 2‐week, cross‐over trial with 2 interventions: OROS‐MPH placebo
Participants	Number of participants screened: 41 Number of participants included: 34 Number of participants followed up: 30 (24 boys, 6 girls) Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV‐TR (combined (100%)) Age: mean 8 years 6 months (range 6 years 5 months‐12 years 6 months) IQ: mean 97.8 (range 77‐132) MPH‐naive: number not stated Ethnicity: white (80%), African American (13.3%), other (6.7%) Country: USA Setting: outpatient clinic Comorbidity type: ODD (40%), specific learning difficulty (33.3%), anxiety (6.67%), dysthymia (3.3%) Comedication: not stated Other sociodemographics: none Inclusion criteria Children 6‐12 years of age, in first grade or higher DSM‐IV‐TR diagnosis of ADHD combined type Parent and teacher ratings on the ADHD‐RS‐IV, of at least the 85th centile for hyperactivity/impulsivity and inattention, or both (if the child was not taking medication at enrolment) IQ > 75 on the WASI Exclusion criteria Children with a past or current diagnosis of a chronic tic disorder, a pervasive developmental disorder, cerebral palsy, bipolar disorder, major depression, head injury requiring hospitalisation, psychotic disorder, glaucoma, cardiovascular disease, epilepsy, OCD serious enough to warrant separate treatment or suicidal or homicidal behaviour or ideation History of side effects with MPH requiring discontinuation of the medication Children were also excluded if they were known to be unable to swallow a tablet Use within 14 days of MAOI Long‐term treatment with coumarin, clonidine or tricyclic antidepressants
Interventions	Participants were randomly assigned to OROS‐MPH and placebo in random order MPH dosage: 9 children treated with 18 mg, 13 with 36 mg and 8 with 54 mg of OROS‐MPH Administration schedule: not stated Duration of each medication condition: 1 week Washout before trial initiation: not stated Medication‐free period between interventions: not stated Titration period: 2‐ to 3‐week open‐label, multi‐dose‐titration protocol to determine the child’s optimal dose as recommended by practice guidelines Treatment compliance: 30 children completed the trial; however, compliance regarding trial medication is not stated
Outcomes	ADHD symptoms ADHD‐RS‐IV, both parent‐ and teacher‐rated at the end of each week of the different medication trial Non‐serious AEs Stimulant Drug Side Effects Rating Scale, parent‐rated at the end of each week of the different medication trial. These data are not reported in the article
Notes	Sample calculation: not stated Ethics approval: yes; approved by the Committee for the Protection of Human Subjects at The Children’s Hospital of Philadelphia Comment from trial authors "In conducting analyses for the cross‐over trial, our team examined the effects of crossing participants from the first treatment condition to the second treatment condition (i.e. the carry‐over effect).(.....) Because no statistically significant sequence effects were noted, data from both periods were combined, and final analyses were reduced to paired comparisons" Key conclusion of trial authors When OROS‐MPH was used to treat children with ADHD at the clinically most effective dose, general improvement was noted on tasks requiring response inhibition; response to treatment in other domains was variable or was not demonstrated. Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes Withdrawals due to AEs: 0 Funding source: supported by an investigator‐initiated grant from Ortho McNeil Janssen Scientific Affairs Email correspondence with trial authors: January 2014: emailed trial authors twice to request additional information but received no response
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomly assigned and counterbalanced across participants
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Referred to as double‐blind but no information provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Referred to as double‐blind but no information provided
Incomplete outcome data (attrition bias) All outcomes	High risk	Completer analysis reported Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	Clinical trial ID: NCT00530257, no indication of selective reporting