Kortekaas‐Rijlaarsdam 2017.

Study characteristics
Methods	A 2 ‐week cross‐over trial with 2 arms: 1 week of ER‐MPH (Equasym XL®) 1 week of placebo Phases: 1
Participants	Number of participants screened: 78 Number of participants included: 65 Number of participants followed‐up: 63/61 (43 boys, 20 girls) Number of withdrawals: 4 Diagnosis of ADHD: DSM‐IV (subtype not stated) Age: mean 10.49 years (SD 1.24, range 8‐13) IQ: 97.68 (SD 13.82) MPH‐naive: if participants were MPH‐naive, they had to go through a medication titration at their treating physician and be at a stable dose for at least 3 weeks. Ethnicity: not stated Country: the Netherlands Setting: outpatient Comorbidity: not stated Comedication: not stated Additional sociodemographics: socioeconomic status: mean 5.24 (SD 0.86) Inclusion criteria Aged 8‐13 years A clinical diagnosis of ADHD confirmed by the DISC‐4, Parent version A score > 90th percentile on the Inattentive and/or Hyperactive/Impulsive scale of both parent and teacher version of the Disruptive Behavior Disorder Rating Scale An estimated full‐scale IQ of at least 70 Treatment with MPH or indication for treatment with MPH At least 1 year of Dutch primary school education to ensure full understanding of test instructions Exclusion criteria Neurological or psychiatric disorder other than ODD, CD, learning disorder, dyslexia, anxiety disorder
Interventions	Participants were randomly assigned to 1 of 2 different medication orders of MPH and placebo Number randomised to each group: 33 received MPH‐placebo, 32 received placebo‐MPH Mean medication dosage: daily doses varied between 10 and 40 mg, with 27% of the children receiving 10 mg, 44% receiving 20 mg, 24% receiving 30 mg, and 5% receiving 40 mg Administration schedule: not stated Duration of each medication: 1 week Washout before trial initiation: 48 h Medication‐free period between interventions: 48 h Titration period: mean treatment before trial initiation: 30.7 months (SD 19.1) Treatment compliance: not stated
Outcomes	ADHD symptoms SWAN, assessed on the last day of each treatment week
Notes	Sample calculation: yes, 63 Ethics approval: the current trial has been carried out in accordance with the Declaration of Helsinki and was approved by the local ethics committee. Key conclusion of trial authors "Efficacy of the MPH intervention compared with placebo was confirmed by robust parent‐ and teacher‐rated behavioral improvements with medium to large effect sizes, in line with previous studies." "For academic accuracy and productivity, effects of MPH were small‐ to medium‐sized and were limited to those academic subjects for which children with ADHD underperformed in comparison to TD [typically developing] children." Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH: yes Any withdrawals due to AEs: 3 (2 not related to intervention) Funding source: unclear, but Shire was a collaborator Email correspondence with the trial authors: August and November 2021. We contacted the trial authors for information regarding risk of bias and first period data through personal email in August and November 2021, but no answer was received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Our academic pharmacist, who was not in contact with any participants, was responsible for randomisation using predefined randomisation blocks to determine medication or placebo sequence"
Allocation concealment (selection bias)	Unclear risk	Nothing stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both active MPH and placebo capsules were inserted in other capsules to ensure visual equality
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Researchers, children, parents, and teachers were blinded to the intervention
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT on 63 of 65 participants Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	All outcomes from protocol reported