Chacko 2005.

Study characteristics
Methods	6‐week within‐participant, randomised, placebo‐controlled, double‐blind, daily cross‐over trial with 3 interventions: MPH at 0.3 mg/kg given at 7:45 am and 11:45 am MPH at 0.6 mg/kg given at 7:45 am and 11:45 am Placebo given at 7:45 am and 11:45 am Phases: daily cross‐over between medication conditions. 2 weeks of baseline and adjustment period before 6‐week medication trial. Data from this paper pertain to 5‐ and 6‐year‐old children attending a summer treatment programme between 1987 and 1997 (Pelham 1996)
Participants	Number of participants screened: not stated Number of participants included: 36 (32 boys, 4 girls) Number of participants followed up: 36 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐III‐R (n = 35, subtype not stated); DSM‐IV (n = 1, combined type) Age: mean 6.13 years (range 5‐6) IQ: mean 102 (SD 15.50) MPH‐naive: not reported Ethnicity: white (86%), other (14%) Country: USA Setting: outpatient clinic (summer treatment programme) Comorbidity: ODD (50%), CD (27.7%) Comedication: not stated Other sociodemographics: none Inclusion criteria Diagnosis of ADHD according to DSM Between 5 and 6 years of age Parental consent Exclusion criteria None stated
Interventions	Participants were randomly assigned, daily, to 1 of 3 possible interventions: 0.3 mg/kg MPH, 0.6 mg/kg MPH and placebo Mean MPH dosage: not stated Administration schedule: twice/d 7:45 am and 11:45 am from Monday through Thursday Duration of each medication condition: daily shifted Washout before trial initiation: not stated Medication‐free period between interventions: maximum 18‐h gap between doses (11:45 am to 7:45 am the following day) and no medication Thursday to Sunday Titration period: before the 6‐week trial began, participants underwent a 2‐week baseline and adjustment period Treatment compliance: not stated
Outcomes	Serious AEs None reported Non‐serious AEs "Classroom teachers, counselors, and parents completed daily ratings of the presence and severity of common stimulant side effects" Side effects are reported as occurring: "none" (i.e. symptom was assessed and was found absent), "mild" (i.e. symptom was present but was not sufficient to cause concern among child, peers or adults), "moderate" (i.e. symptom caused impairment of functioning or social embarrassment to the degree that benefits of medication must be considerable to justify risks of continuing medication) or "severe" (i.e. symptom caused significant impairment of functioning or social embarrassment to the degree that the child should not continue to receive medication). Rating of "moderate" or "severe" signifies clinically significant side effects. Side effects are based on staff/parent subjective report on severity of the side effect. Children were considered to have significant side effects in a particular area if clinically significant side effects were reported within that area for ≥ 50% of observations in a given condition
Notes	Sample calculation: no information Ethics approval: no information Comments from trial authors Trial limitations. Most participants were white males, limiting the generalisability of findings to females and ethnic minorities Furthermore, the sample size did not allow statistical analyses of ADHD subtype or comorbidity Key conclusion of trial authors Stimulant medication is an effective treatment for young children diagnosed with ADHD; however, multiple domains of functioning must be assessed for the most effective dose for young children with ADHD to be determined Comments from review authors Participants in this trial were attending a summer treatment programme between 1987 and 1997 (Pelham 1996) Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: unclear; 2 weeks of adjustment period before the medication condition ‐ no information on how many were screened and how many participated during baseline weeks Withdrawals due to AEs: none Funding source: during the conduct of this research, Dr. Pelham was supported by grants from the NIMH (MH48157, MH47390, MH45576, MH50467, MH53554, MH62946), NIAAA (AA06267, AA11873), National Institute on Drug Abuse (NIDA) (DA05605, DA12414), National Institute of Neurological Disorders and Stroke (NINDS) (NS39087), National Institute for Environmental Studies (NIES) (ES05015) and National Institute of Child Health and Human Development (NICHHD) (HD42080) Email correspondence with trial authors: December 2013. We emailed trial authors to request additional information about trial sample and side effects. Trial authors replied to say that the data are no longer available. Data from this trial could not be used in meta‐analyses
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Active medication and placebo were disguised in opaque capsules and were dispensed in daily pill reminders. Each condition occurred one or two times per week, with the order of the conditions randomized on a daily basis. Data were averaged across days within conditions for each child"
Allocation concealment (selection bias)	Unclear risk	“Each condition occurred one or two times per week, with the order of the conditions randomized on a daily basis”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“Active medication and placebo were disguised in opaque capsules and were dispensed in daily pill reminders” Double‐blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Double‐blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts Side effects were measured for 30 participants Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	High risk	Unclear how the population sample was selected from the group of attendees at these programmes over a 10‐year period