Hale 2011.

Study characteristics
Methods	Cross‐over trial with 2 interventions: MPH placebo Phases: baseline, placebo, LD‐MPH and HD‐MPH for 4 weeks per medication phase
Participants	Number of participants screened: 65 Number of participants included: 56 (39 boys, 17 girls) Number of participants followed up: not stated Number of withdrawals: not stated Diagnosis of ADHD: DSM‐IV‐TR (combined (58.9%), hyperactive‐impulsive (7.1%), inattentive (33.9%)) Age: mean 120.84 months (approximately 10.1 years) (SD 30.85 months, range 6‐16 years) IQ: mean 99.56 (SD 6.84, n = 41) MPH‐naive: number not stated ("All participants were either medication‐naive or received an appropriate wash‐out period") Ethnicity: European American (82%), African American (18%) Country: USA Setting: outpatient clinic Comorbidity: specific learning disability (n = 13), ODD/CD (n = 11), anxiety/depression (n = 6) Comedication: not stated Other sociodemographics: middle class (n = 44), lower class (n = 12); urban (n = 36), suburban (n = 13), rural (n = 7) Inclusion criteria Diagnosis based on DSM‐IV‐TR criteria by referring physician ‐ independent confirmation by licensed and/or certified psychologist Demonstrated significant attention, hyperactivity and/or impulse control problems interfering with major life function in both home and school settings ≥ 1.5 SD above the mean on ≥ 1 of the attention problems on the CBCL, Teacher Report Form; Inattention and/or Hyperactive‐Impulsive subscales of the CPRS ‐ Revised and Long; or CTRS ‐ Revised Exclusion criteria ≥ 1 comorbid secondary diagnosis History of mental disability Seizure disorder ‐ brain injury Other medical condition affecting cognitive or neuropsychological performance ‐ missing or different instruments for measuring MPH response (i.e. missing data)
Interventions	Participants were randomly assigned to 1 of 6 possible drug condition orders of MPH (0.15 mg/kg, 0.30 mg/kg) and placebo Mean MPH dosage: not stated Administration schedule: twice daily Duration of each medication condition: 4 weeks Washout before trial initiation: 2 days Medication‐free period between interventions: no Titration period: none Treatment compliance: not stated
Outcomes	ADHD symptoms CTRS ‐ Revised and Long: teacher‐rated at baseline and at treatment follow‐up General behaviour Schools Situation Questionnaire ‐ Revised: teacher‐rated at baseline and at treatment follow‐up Non‐serious AEs Side Effects Rating Scale, unclear who rated: at baseline and at treatment follow‐up
Notes	Sample calculation: no Ethics approval: not stated Comment from trial authors Several trial limitations are worth noting. First. age limitations. Second, neuropsychological tests that were not counterbalanced and analysed for order effects. Third, inter‐rater reliability during MPH trials. 4th, intelligence/cognitive screening Key conclusion of trial authors "Robust cognitive and behavioural MPH response was achieved for children with significant baseline executive working memory/self regulation (EWM/SR) impairment, yet response was poor for those with adequate EWM/SR baseline performance. Even for strong MPH responders, the best dose for neuropsychological functioning was typically lower than the best dose for behaviour. Findings offer 1 possible explanation for why long‐term academic MPH treatment gains in ADHD have not been realised" Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: not stated Funding source: research part funded by the Neuropsychiatric Research Institute, Fargo, North Dakota, USA Email correspondence with trial authors: June‐August 2014. Emailed trial authors twice to request additional information but have not received a reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	All medications and placebos were prepared by the trial pharmacist, who randomly assigned children to 1 of 6 trial orders in placebo (P), low‐dose (L) and high‐dose (H) conditions (P‐L‐H, P‐H‐L, L‐P‐H, L‐H‐P, H‐L‐P, H‐P‐L)
Allocation concealment (selection bias)	Low risk	Research assistants, teacher, parents and participants were blinded to the order of conditions. Ground MPH tablet was placed in lactose‐filled opaque capsules for active drug conditions, with lactose included only for the placebo condition, and was administered twice per day
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Research assistants, teacher, parents and participants were blinded to the order of conditions. All medications and placebos were prepared by the trial pharmacist. Ground MPH tablet was placed in lactose‐filled opaque capsules for the active drug condition, with lactose included only for the placebo condition
Blinding of outcome assessment (detection bias) All outcomes	Low risk	After results were analysed, the order of conditions was revealed
Incomplete outcome data (attrition bias) All outcomes	High risk	Participants for whom data were missing or different instruments were used for MPH response were excluded 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