Lopez 2003.

Study characteristics
Methods	Cross‐over trial with 3 interventions: IR‐MPH (Ritalin) ER‐MPH (Concerta) placebo Phases: 4 Placebo ER‐MPH (Concerta) 18 mg ER‐MPH (Concerta) 38 mg IR‐MPH (Ritalin) 20 mg Evaluated on day 0, randomly assigned to drug condition on days 7, 14, 21 and 28. 1 practice visit for a trial duration of 5 weeks in total
Participants	Number of participants screened: not stated Number of participants included: 36 (29 boys, 7 girls) Number of participants followed up: 36 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV (subtype not stated) Age: mean 9 years (range 6‐12) IQ: not stated MPH‐naive: no Ethnicity: white (36%), African American (27%), Hispanic or other (36%) Country: USA Setting: outpatient clinic, laboratory classroom setting Co‐morbidity: not stated Co‐medication: not stated Other sociodemographics: none Inclusion criteria Met ADHD criteria based on DISC Parents consented to participation Exclusion criteria Concurrent significant medical or psychiatric illness or substance use disorder
Interventions	Participants were randomly assigned to 1 of 24 (4 × 3 × 2 × 1) possible drug condition orders of IR‐MPH (Ritalin) 20 mg, ER‐MPH 18 mg (Concerta), ER‐MPH 36 mg (Concerta) and placebo Mean MPH dosage: not stated Administration schedule: not stated Duration of each medication condition: 1 day Washout before trial initiation: not stated Medication‐free period between interventions: on the morning following each trial period, participants resumed their regularly prescribed medication up to Thursday evening before the next trial period day on Saturday Titration period: all participants had been stabilised on an equivalent dose of 10 mg twice daily of MPH before trial entry Treatment compliance: no participants discontinued the trial prematurely
Outcomes	ADHD symptoms SKAMP: observer, during each trial period Non‐serious AEs Physical exam, vital signs, haematology, blood chemistries, urinalysis ‐ screening AEs: self‐reported, each trial period Vital signs: observer, measured every 2 h at each trial period AEs did occur in < 3% of participants exposed to each agent and dose, and 1 participant from each treatment group experienced a single mild AE that included abdominal pain, nausea and dyspnoea
Notes	Sample calculation: yes Ethics approval: yes Comment from trial authors "Although single blinding of raters added to the objectivity of the observations, lack of medication blinding had both negative and positive implications. On the negative side, participants may have noticed the difference in the appearance of agents administered to them, thus producing bias …[...]... another issue to contemplate is that all participants in the study had previously been stabilised on MPH and, irrespective of blinding, may well have been able to identify when they were receiving placebo" Key conclusion of trial authors Although both IR‐MPH (Ritalin) and ER‐MPH (Concerta) were shown to be effective, the different release profile for each formulation can result in distinct differences between effects on measures of attention and deportment Comment from review authors Not able to use reported data Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes, all participants were stabilised previously on MPH Any withdrawals due to AEs: no Funding source: Novartis Email correspondence with trial authors: April 2014. We received supplemental information from trial authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Order of medication assignment was determined by random assignment by a computer programme
Allocation concealment (selection bias)	Unclear risk	Participants were randomly assigned to 4 treatment periods. For purposes of this trial, with the exception of the medicating nurse, all trial personnel were blinded to the medication administered to the child
Blinding of participants and personnel (performance bias) All outcomes	High risk	Single‐blind. For purposes of this trial, with the exception of the medicating nurse, all trial personnel were blinded to the medication administered to the child
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information
Incomplete outcome data (attrition bias) All outcomes	Low risk	None reported. No participants discontinued the trial prematurely. Selection bias: no
Selective reporting (reporting bias)	Unclear risk	Protocol not identified