Smith 1998.

Study characteristics
Methods	Main trial: 8‐week intensive Summer Treatment Program, including a 6‐week, double‐blind, cross‐over trial with 4 interventions: 3 different doses of MPH Placebo Follow‐up trial: retrospective follow‐up trial of 16 individuals who completed double‐blind, placebo‐controlled, cross‐over studies during 2 separate Summer Treatment Programs
Participants	Main trial Number of participants screened: not stated Number of participants included: 49 Number of participants followed up: 46 (41 boys, 5 girls) Number of withdrawals: 3 Diagnosis of ADHD: DSM‐III‐R (subtype not stated) Age: mean 13.8 years (range 12‐17) IQ: mean 101 (range 65‐129) MPH‐naive: 28% Ethnicity: white (85%), African American (15%) Country: USA Setting: outpatient clinic (summer treatment program) Comorbidity: ODD (50%), CD (15%) Comedication: no Other sociodemographics: median family income USD 38,500 Inclusion criteria Meeting DSM‐III‐R diagnostic criteria for ADHD 12th birthday before the protocol began Verbal IQ > 80 No conditions that precluded a trial of stimulant medication or full participation in Summer Treatment Program academic and athletic activities Exclusion criteria No information Follow‐up trial (Not used in this review) Number of participants included: 16 (all boys) Number of participants followed up: 16 Number of withdrawals: none Diagnosis of ADHD: DSM‐III‐R Age: mean (children) 10.2 years (range 8‐11); mean (adolescents) 12.7 years (range 12‐14.5) IQ: mean (children) 109; mean (adolescents) 107 MPH‐naive: 4 (25%) Ethnicity: white (100%) Country: USA Comorbidity: not stated Comedication: not stated Sociodemographics: family income (children USD 37,943; adolescents USD 49,650)
Interventions	Main trial Participants were randomly assigned to 1 of the possible drug condition orders of 25 mg/d, 50 mg/d or 75 mg/d MPH and placebo Mean MPH dosage: 0.17 mg/kg Administration schedule: 3 times/d: 7:45 am, 11:45 am, 3:45 pm Duration of each medication condition: 6 days Washout before trial initiation: 2 weeks Medication‐free period between interventions: 16 h Titration period: none Treatment compliance: not stated Follow‐up trial (Not used in this review) Participants were randomly assigned to 1 of the possible drug condition orders of 0.3 mg/kg MPH and placebo Mean MPH dosage: 0.3 mg/kg Administration schedule: twice/d: 8:00 am and 12:00 pm Duration of each medication condition: 1 day Washout before trial initiation: 2 weeks Medication‐free period between interventions: 20 h Titration period: none Treatment compliance: not stated. Adolescents were evaluated on a protocol that included placebo and 3 doses of MPH. To facilitate comparison, doses for adolescents were converted to milligrams per kilogram, and the dose closest to 0.3 mg/kg was used in this trial
Outcomes	ADHD symptoms IOWA CRS (subscale: Inattention/Overactivity): completed every day by counsellors and classroom teachers General behaviour IOWA CRS (subscale: Oppositional Defiant): completed every day by counsellors and classroom teachers Non‐serious AEs Smith 1998: "side effects rating form (rating 12 potential side effects associated with stimulant medication on a 4‐point scale. A side effect rating of 3 (severe) was defined as troubling enough to contraindicate that dose of medication): completed every day by counsellors and parents during medication assessment" Evans 1997 (secondary reference under Smith 1998): "ratings on major side effects associated with MPH: completed each day by classroom teachers"
Notes	Sample calculation: no Ethics approval: not stated Comments from trial authors Main trial One participant had a full‐scale IQ of 65 but was judged to be sufficiently intelligent to understand the behavioural contingencies, activity rules and social skills training provided in the programme Comment on high response rate in this study compared with other studies of adolescents with ADHD Higher response rate in this study may be due to greater statistical and methodological power to detect medication effects compared with previous studies, including (1) a larger sample, (2) a broader range of doses, (3) measurement in a well‐controlled, naturalistic setting, (4) repeated replications of medication conditions and (5) a statistical cutoff of 0.5 to define a positive response to medication Follow‐up trial For data compared in this study, randomisation and medication administration procedures were identical for children and adolescents, except that adolescents were evaluated on a protocol that included placebo and 3 doses of MPH. To facilitate comparison, doses for adolescents were converted to milligrams per kilogram, and the dose closest to 0.3 mg/kg was used in this study Sample included only white males Only one third of participants in the adolescent programme had completed the summer treatment programme for children Students exhibited a much higher than expected positive response to stimulant medication Key conclusions of trial authors Main trial Results show that the shape of the dose‐response curve is influenced by the measurement method; most adolescents exhibited improved social behaviour when treated with MPH, most positive effects of MPH were achieved at the lowest dose and diminishing positive effects and increasing risk of negative effects were noted with successively higher doses Follow‐up trial Stimulant medication is equally effective with children and adolescents with ADHD who are engaged in similar activities Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: no Funding source: grants from the National Institute on Drug Abuse, the NIMH, the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Child Health and Human Development Email correspondence with trial authors: September 2014. We contacted trial authors twice to ask for supplemental information/data but have received no response
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Medication conditions were randomly assigned daily, with each condition occurring once a week. Thus, adolescents received a mode of 6 replications of each medication condition
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blind; no further information
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blind; no further information
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"Some missing data was caused by holidays or absences from the program" Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol