Szobot 2004.

Study characteristics
Methods	4‐day, double‐blind, placebo‐controlled, randomised parallel‐group trial: fixed dose‐escalating of MPH placebo
Participants	Number of participants screened: not stated Number of participants included: 36 (all boys) Number of participants followed up: 36 (MPH 19, placebo 17) Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV, combined (MPH 84.6%, placebo 76.5%) Age: mean 11.6 years IQ: mean 94.7 MPH‐naive: not stated. But no psychiatric medication for the past 6 months Ethnicity: European‐Brazilian (89%) Country: Brazil Setting: outpatient clinic Comorbidity: CD and ODD (MPH 58.8%, placebo 68.4%), depressive disorder (MPH 5.2%, placebo 5.9%), multiple anxiety disorder (MPH 5.2%, placebo 0%), tic disorder (MPH 0%, placebo 5.9%) Comedication: not stated Other sociodemographics: low‐ to middle‐income families Inclusion criteria Diagnosis of ADHD according to DSM‐IV criteria (American Psychiatric Association, 1994) Between 8 and 17 years old Male sex Exclusion criteria Presence of any neurological or significant clinical disease Presence of bipolar disorder or any substance abuse/dependence disorder Use of any psychiatric medication in the previous 6 months Estimated IQ < 70
Interventions	Participants were randomly assigned to MPH or placebo Number of participants randomised to each group: MPH 19, placebo 17 Mean MPH dosage: 0.72 mg/kg/d Administration schedule: twice/d: morning and lunchtime Duration of intervention: 4 days Titration period: first day 0.35 mg/kg Treatment compliance: good
Outcomes	ADHD symptoms Conners' Abbreviated Rating Scale (ABRS) Quality of life Children’s Global Assessment Scale (CGAS). CGAS was scored by a child psychiatrist Non‐serious AEs A research assistant called each family to check side effects. No participants had to interrupt the protocol because of side effects
Notes	Sample calculation: no Ethics approval: approved by the Ethical Committee of the HCPA (approved as an IRB by the Office for Human Research Protections, USA) Comments from trial authors "Our results extend the efficacy of MPH for ADHD core symptoms as extensively demonstrated in clinical trials with samples from developed countries to samples from developing countries, for whom a diverse culture may modulate clinical presentation of the disorder" "This study’s rate of robust response with methylphenidate might reflect the short duration (4 days) of the clinical trial" "Results may not generalise to other different sociocultural groups or to patients from the community" "Side effects were not objectively registered" Key conclusion of trial authors "MPH group had a significantly greater decrease in ABRS scores and a significantly greater increase in CGAS scores when compared with the placebo group (P value < 0.01)" 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: research funds from Hospital de Clínicas de Porto Alegre, FAPERGS and NOVARTIS Email correspondence with trial authors: October 2013. We received from the trial authors supplemental information regarding blinding and allocation concealment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomly assigned on the basis of a computer‐derived algorithm (EPIINFO6)
Allocation concealment (selection bias)	Low risk	Only the doctor performing the randomisation knew the allocation, and he had nothing to do with data collection
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind: participants, parents and all research team members who had contact with participants. Both MPH and placebo pills were manufactured by a single pharmaceutical company; they had the same format and colour and were given to participants in 4 different blisters
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All research team members who had contact with participants
Incomplete outcome data (attrition bias) All outcomes	Low risk	None Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo‐responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol identified