Corkum 2020.

Study characteristics
Methods	A 4‐week cross‐over‐trial with 2 arms: 2 weeks of ER‐MPH 2 weeks of placebo Phases: 2 (baseline followed by 4‐week, double‐blind trial)
Participants	Number of participants screened: 32 Number of participants included: 26 (23 boys, 3 girls) Number of participants followed up: 26 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV‐TR (combined type: 17 (65.4%), inattentive type: 9 (34.6%)) Age: mean 8 years and 8 months (SD 24.5 months, range 6‐12 years) IQ: 95.6 (SD 31.6) MPH‐naive: 100% Ethnicity: white (n = 23), Latin American (n = 2), Aboriginal (n = 1) Country: Canada Setting: outpatient and sleep laboratory Comorbidity: learning disorder (n = 8, 30.8%) Comedication: not stated Additional sociodemographics: socioeconomic status was calculated using the Boyd‐NP scale and was in the average range (M 68.7, SD 23.2). Mean household annual income fell in the bracket of CAD 51,000 to CAD 60,000. Inclusion criteria Medication‐naïve 6‐12 years old DSM‐IV‐TR diagnosis of ADHD Exclusion criteria Full scale IQ falling > 1 SD below the mean according to the WISC‐IV Known neurological, genetic, metabolic, or seizure disorder Previous diagnosis of a primary sleep disorder Undergoing behavioural or pharmacological treatment for sleep problems A diagnosis of another primary mental health disorder based on the clinical diagnostic procedures (excluding comorbid diagnoses of learning disabilities Pubertal development beyond Tanner Stage 2 Currently taking or had previously taken psychotropic medication PolySomnography evidence indicative of a sleep breathing problem
Interventions	Participants were randomly assigned to 1 of 2 possible orders of placebo for 2 weeks and MPH (Biphentin) for 2 weeks. Children weighing < 20 kg received a 20 mg daily dose, children weighing 20‐30 kg were given 30 mg, and children weighing > 30 kg were given 40 mg. Number randomised to each group: not stated Mean medication dosage: not stated Administration schedule: once daily within 1 h of waking Duration of each medication: 2 weeks (data related to sleep and daytime behaviour were collected during the 1st and 3rd weeks of this trial (i.e. after the 1st week of each condition). The 2nd and 4th weeks were used in situations in which the first week of a condition was not considered typical by the parent, e.g. child was ill) Washout before trial initiation: not necessary as all participants were medication‐naive Medication‐free period between interventions: none Titration period: none Treatment compliance: not measured. Parents reported informally to the paediatrician that the children had been adherent
Outcomes	ADHD symptoms CPRS‐Revised: Long Version assessed at week 1 and 3 CTRS‐Revised: Long Version assessed at week 1 and 3 Non‐serious AEs Sleep parameters assessed by polysomnography and actigraphy sleep onset latency, sleep efficiency, and total sleep time (also reported as sleep duration) assessed at week 1 and 3
Notes	Sample calculation: yes; "with an effect size (Cohen’s f) of 0.18 and power set at 0.95 and an alpha of 0.05, 26 participants were determined to be the minimal sample size needed” Ethics approval: yes Comments from trial authors "It is likely that the inconsistencies in results between actigraphy and polysomnography are due to the fact that polysomnography is collected in a novel and controlled environment for one night compared to actigraphy that is collected at home over a number of nights." "Our trial also had an unequal sex distribution, but this is consistent with known differences in ADHD diagnoses in boys versus girls. Moreover, research indicates that there are no sex differences in terms of sleep problems in pre‐pubertal children." Key conclusion of trial authors The main finding of this trial was that based on actigraphy, MPH had a negative impact on total sleep time due to a 30‐min increase in sleep onset latency. Increased sleep onset latency resulting in reduced total sleep time, which has been linked to poorer daytime functioning, is a potential AE of stimulant medication, which may require management to optimise outcome. Comment from review authors It is not clear if another article is going to report on the full population of the trial or if Corkum 2020 is the main article, as there are some small discrepancies in the participant information between the 3 included articles. Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH: no Any withdrawals due to AEs: no Funding source: Canadian Institutes of Health Research Email correspondence with trial authors: August and September 2021. Trial authors were contacted for information regarding main article, risk of bias and first‐period data through personal email in August and Semptember 2021, but no answer was received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was conducted using blocking on an online calculator (randomised in blocks of 10)
Allocation concealment (selection bias)	Low risk	The randomisation schedule was conducted through a third‐party
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The pharmacists prepared the medication and placebo by placing these in identical gelatin capsules so that children and parents could not identify whether capsules contained medication or the placebo
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The randomisation schedule was conducted through a third‐party, and the child, family, teachers, and trial staff were all blind to medication condition; only the trial paediatricians and pharmacists were aware of the medication status of the participants
Incomplete outcome data (attrition bias) All outcomes	Low risk	No withdrawals Selection bias (e.g. titration after randomisation → exclusion): no
Selective reporting (reporting bias)	Unclear risk	No protocol available