McGough 2006.

Study characteristics
Methods	Phase II, randomised, double‐blind, placebo‐controlled, laboratory‐classroom, cross‐over trial with a lead‐in open‐label dose‐optimisation phase: MPH transdermal system placebo
Participants	Number of participants screened: 93 entered the open‐label dose‐optimisation phase Number of participants included: 80 (from ITT: 57 boys (72%), 22 girls (28%)) Number of participants followed up: 79 Number of withdrawals: 1 participant discontinued because of "protocol violation" Diagnosis of ADHD: DSM‐IV‐R (combined 62 (79%), hyperactive‐impulsive 4 (5%), inattentive 13 (17%)) Age: mean 9.1 years (SD 1.7, range 6‐12) IQ: > 70 MPH‐naive: 37% Ethnicity: white 55 (70%), African American 8 (10%), Asian 2 (3%), other 14 (18%) Country: USA Setting: outpatient clinic Comorbidity: not stated Comedication: no Other sociodemographics: none   Inclusion criteria 6 to‐12 years of age inclusive ADHD DSM‐IV diagnosis using Kiddie Schedule for Affective Disorders and Schizophrenia and psychiatric assessment ADHD‐RS score ≥ 26 at baseline/unmedicated Normal laboratory parameters and vital signs including ECG Either known to be responsive to stimulants or‐naive to stimulant treatment Exclusion criteria Comorbid psychiatric diagnosis (apart from ODD) History of seizures History of tic disorders Intellectual disability Any illness or skin disorder that might jeopardise safety or compromise trial assessments No clonidine, atomoxetine, antidepressants, investigational medications, hepatic P450 enzyme‐altering agents, medications with CNS effects, sedatives, anxiolytics or antipsychotics within the 30 days before screening
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of MPH and placebo Number randomised to each group: cross‐over, 42 MPH/placebo, 38 placebo/MPH Mean MPH dosage: "At the end of the dose optimization phase of the study, the majority of patients (78%) were optimized to either the 16 mg or 20 mg dosage strengths" Administration schedule: once daily Duration of each medication condition: 1 week Washout before trial initiation: "up to 28 days" Medication‐free period between interventions: 4:00 pm to 7:00 am the next day (15 h) Titration period: 5‐week dose‐optimisation phase before randomisation Treatment compliance: "During the laboratory classroom period, 97% and 96% of participants were compliant with [methylphenidate transdermal system] MTS and placebo treatments respectively"
Outcomes	ADHD symptoms Primary outcome SKAMP at multiple time points: pre‐dose and 2, 3, 4, 5, 6, 7.5, 9. 10.5 and 12 h post‐dose ADHD‐RS‐IV (administered at each visit) CPRS‐R‐S (Conners 1997a). Completed at 11:00 am and 3:00 pm on the Sunday before the first visit and subsequently, before each visit to the centre "The mean values of the CPRS‐R over the 11:00 am and 3:00 pm time points were used in the analysis" Non‐serious adverse outcomes Vital signs, BP, pulse, oral temperature, respiratory rate, height, weight, laboratory measures, physical examination, dermal evaluation
Notes	Sample calculation: yes Ethics approval: yes Key conclusions of trial authors Treatment with MPH transdermal system resulted in statistically significant improvement in all efficacy measures Time course and therapeutic effects of MPH transdermal system suggest that this novel MPH delivery system provides efficacious once‐daily treatment for ADHD Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; "Participants were either known to be responsive to stimulants or‐naive to stimulant treatment". Participants were only randomised after the open‐label phase if they reached acceptable efficacy without unacceptable AEs. Any withdrawals due to AEs: no Funding source: Shire US Inc Email correspondence with trial authors: June 2014. We obtained supplemental information regarding risk of bias. Additional data were not available (Ramstad 2013a [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Participants were randomized into either 1 week of [methylphenidate transdermal system] MTS or 1 week of [placebo transdermal system] PTS (in their individually optimized dose) and were crossed over to the opposite treatment the following week" From correspondence: "Participants were randomized centrally for each of the study conditions. Randomization codes were not available to site study staffs, but were provided to research pharmacies at each site which corresponded to a particular dose pack" (Ramstad 2014 [pers comm])
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Phase‐II randomized, double‐blind, placebo‐controlled laboratory classroom, crossover study with a lead‐in open‐label dose optimization phase" From correspondence: "Active and inactive patches were identical in appearance" (Ramstad 2014 [pers comm])
Blinding of outcome assessment (detection bias) All outcomes	Low risk	See above
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 1 participant excluded due to protocol violation Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Low risk	Trial protocol identified (NCT00466791), all outcomes reported