Pelham 2014.

Study characteristics
Methods	3‐week, randomised, controlled, cross‐over trial with 2 factors ‐ medication and behavioural intervention ‐ with daily medication changes: MPH placebo behavioural treatment
Participants	Number of participants screened: not stated Number of participants included: 48 (44 boys, 4 girls) Number of participants followed up: 47 Number of withdrawals: 1 Diagnosis of ADHD: DSM‐IV (subtypes not stated) Age: mean 9.35 years (range 5‐12) IQ: mean 106.33 (SD 14.61; range not stated) MPH‐naive: not stated Ethnicity: white (79%), African American (12.5%) Country: USA Setting: outpatient, Summer Treatment Program Comorbidity: not stated Comedication: not stated Other sociodemographics: none Inclusion criteria DSM‐IV ADHD IQ ≥ 80 No documented adverse response to, or medical conditions that would contraindicate use of, MPH Exclusion criteria Not stated
Interventions	Participants were randomly assigned to 1 of 3 possible drug condition orders of 0.15 mg/kg/dose MPH 3 times/d; 0.3 mg/kg/dose MPH 3 times/d; 0.6 mg/kg/dose MPH 3 times/d and placebo Mean MPH dosage: not clearly stated: "average doses were 5.4 mg (range 2.5‐10), 11 mg (range 6.25‐20), and 21 mg (range 11.25‐30), respectively" Administration schedule: 3 time points Duration of each medication condition: 0.15 mg dose for 4 days, 0.30 mg dose for 4 days and 0.6 mg dose for 3 days, switched daily Washout before trial initiation: not stated Medication‐free period between interventions: not stated Titration period: not stated Treatment compliance: "One child’s parents withdrew from the study after 2 days because of their concerns about possible side effects of the medication"
Outcomes	ADHD symptoms IOWA CRS: rated by counsellors, daily General behaviour IOWA CRS O/D: rated by counsellors, daily Non‐serious AEs Counsellors completed the Pittsburgh Side Effects Rating Scale, daily Trial staff monitored ratings for clinically significant AEs, daily
Notes	Sample calculation: no Ethics approval: yes Comments from trial authors "The prototypic child with ADHD could be treated with the equivalent of 0.15 mg/kg MPH (5 mg per dose in the current sample) twice daily—a dose lower than that used in studies of stimulant treatment in the past 30 years—if he or she is receiving moderate‐ to high‐intensity behavioural treatment" "Our data show that stimulant doses can be reduced dramatically if a child is treated with behaviour modification" Key conclusion of trial authors "Results illustrate the importance of taking dosage/intensity into account when evaluating combined treatments; there were no benefits of combined treatments when the dosage of either treatment was high but combination of the low‐dose treatments produced substantial incremental improvement over unimodal treatment" Comment from review authors Very difficult to understand the real effect of medication because of daily oscillation of the dose Inclusion of MPH responders only/exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; only participants not having any documented adverse response to MPH were included Any withdrawals due to AEs: yes (n = 1) Funding source: grant from the NIMH (MH62946). Dr. Pelham was funded by grants from the NIH (MH62946, MH69614, MH53554, MH69434, MH65899, MH78051, MH062946, NS39087, AA11873, DA12414, HD42080) and the Institute of Education Sciences (L03000665A). Dr. Fabiano was supported in part by a Ruth S. Kirschstein National Research Service Award Predoctoral Fellowship (1F31MH064243‐01A1) and by the Department of Education, Institute of Education Sciences (R324J06024, R324B06045) Email correspondence with trial authors: April 2015. We emailed trial authors to request supplemental information but have not received a response
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomised
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	High risk	"The children, their parents, and clinical staff members were uninformed of medication condition and only the research coordinator, pharmacist and medical director had access to the medication order. The medical director could reveal medication conditions in cases of severe side‐effect reports"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Observers were independent staff members who were not involved in the children’s treatment"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only one participant withdrew from the trial. Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No access to protocol. No description in clinicaltrials.gov