Hawk 2018.

Study characteristics
Methods	A 3‐day cross‐over‐trial with 3 arms 1 day LD‐MPH 1 day HD‐MPH 1 day of placebo Phases: 2 (1 day baseline day, then cross‐over‐trial)
Participants	Number of participants screened: not stated Number of participants included: 84 Number of participants followed‐up: 82 (74% boys, 26% girls). Trial authors provided data for 80 participants Number of withdrawals: 2 (AE: moderate motor ticks at the 0.3 mg/kg dose, which led to exclusion) Diagnosis of ADHD: DSM‐IV (subtype not stated) Age: mean 10.8 years (SD 1.1, range 9‐12) IQ: 103 (SD 14) MPH‐naive: 21% Ethnicity: white (81%), black (12%) other (7%) Country: USA Setting: outpatient clinic Comorbidity: ODD (44%), CD (27%) Comedication: no psychotropic medication Additional sociodemographics: none Inclusion criteria DSM‐IV diagnosis of ADHD 9‐12 years of age Exclusion criteria Full‐scale IQ < 80 History of seizures, neurological disorders and other medical problems Contraindicating psychostimulant treatment Current use of non‐ADHD psychotropic medications History or concurrent diagnosis of pervasive developmental disorder or psychosis, and sensory problems that would make it difficult to complete the task
Interventions	Participants were randomly assigned to 1 of 6 possible drug condition orders different orders of LA‐MPH in 2 different doses (OROS‐MPH; Concerta) and placebo, receiving each drug for a single day. 1 (LD) provided equivalent effects to 3 times/d IR‐MPH at 0.3 mg/kg dose, producing a total daily dose of 0.9 mg/kg The other (HD) was equivalent to 3 times/d IR‐MPH 0.6 mg/kg dose, producing a total daily dose of 1.8 mg/kg Number randomised to each group: dosing order was counterbalanced among participants Mean medication dosage: doses ranged from 27‐90 mg (dose was capped at 90 mg for safety reasons). Mean low and high doses were 1.06 mg/kg (SD 0.12) and 2.02 mg/kg (SD 0.23), respectively Administration schedule: once daily, morning, 90 min before trial Duration of each medication: 1 day Washout before trial initiation: 24 h Medication‐free period between interventions: none Treatment compliance: not stated
Outcomes	ADHD symptoms Teacher ratings of Inattention/Overactivity on the Modified‐IOWA Scale. No information on timing of outcome assessment for this outcome available Serious AEs None reported Non‐serious AEs Daily assessments of BP and heart rate
Notes	Sample calculation: no Ethics approval: yes; all procedures were approved by the University at Buffalo Children and Youth Institutional Review Board Comments from trial authors "The majority of children had a history of well‐tolerated treatment with stimulant medication, and the trial was not adequately powered to evaluate the possible moderating role of treatment history." "Data were collected in a summer research camp with clinical outcomes focusing on an analogue classroom. This permitted strong experimental control but does not reflect the environments in which children’s behaviour is most problematic." "We examined a narrow range of clinical outcomes, which limits generalisability." "It is critical to determine whether our findings for acute intervention (one day per treatment condition) generalise to more ecologically valid treatment durations, as well as varying combinations of medication and behavioral intervention." Key conclusion of trial authors "Building upon decades of largely independent literatures demonstrating the clinical and cognitive effects of stimulants among children with ADHD, the present work provides the first evidence that stimulant effects on specific cognitive processes (namely working memory and inhibitory control) actually account for, or partially mediate, individual differences in clinical response to stimulants." Comments from review authors The 24 stimulant‐naïve children, as well as an unnumbered amount of children who usually took a low dose of MPH were always allocated to receive 1 day LD‐MPH before HD. While trial authors were able to supply us with additional information regarding risk of bias and teacher rated ADHD symptom data, side‐effects data were unfortunately not available. Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH: no Any withdrawals due to AEs: yes, 2 Funding source: supported by grants from the NIMH and from the National Institute on Drug Abuse (NIDA) Email correspondence with trial authors: August and October 2021. Trial authors supplied us with information regarding risk of bias and teacher ratings of inattention on the modified IOWA scale through personal email in August and October 2021 (Storm 2021c [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Nothing stated
Allocation concealment (selection bias)	Low risk	Meds were dispensed by a pharmacist who was otherwise uninvolved with trial procedures
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Medication and placebo were administered in identical opaque capsules by trial staff upon arrival to camp
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Ratings were made blind to treatment condition and were aggregated across classes within condition
Incomplete outcome data (attrition bias) All outcomes	High risk	Data were reported for the 80 participants who were not withdrawn due to AEs. Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): yes, the high medication dose was withheld from 2 participants who experienced AE's at the low dose. These 2 participants were excluded from the analysis.
Selective reporting (reporting bias)	High risk	No trial protocol available While the Pittsburgh Side Effect Rating Scale, which inquires about common side effects seen with stimulants (rated none to severe) was used during the trial, no side effect data are available.