Flapper 2008.

Study characteristics
Methods	4‐week, double‐blind, randomised, placebo‐controlled, cross‐over trial of MPH and placebo with weekly switches of 4 dosage levels; capsules of: 0.5 mg/kg 0.75 mg/kg 1 mg/kg placebo MPH‐sensitive children continued in an open‐label trial for 4 weeks
Participants	Number of participants screened: 80 Number of participants included: 30 (22 boys, 8 girls) Number of participants followed up: 30 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV (combined (37%), hyperactive‐impulsive (7%), inattentive (57%)) Age: mean 105.2 months (approximately 8.8 years) (SD 25.1, range 7‐12 years) IQ: > 70 MPH‐naive: 100% Ethnicity: not stated Country: the Netherlands Setting: outpatient clinic Comorbidity: developmental co‐ordination disorder (100%) Comedication: not stated Other sociodemographics: none Inclusion criteria ADHD, DSM‐IV Developmental co‐ordination disorder, DSM‐IV ADHD symptoms had to be severe for ≥ 6 items on the DSM‐IV ADHD‐RS, Parent Version, investigator administered and scored Total score on the Movement Assessment Battery for Children below the 5th centile Exclusion criteria Comorbid disorders (including pervasive developmental disorder) Not medication‐naive IQ score below normal range (< 70), as assessed by the WISC–R (Dutch Edition)
Interventions	Participants were randomly assigned to possible drug orders of the 3 daily doses of MPH (0.5 mg/kg, 0.75 mg/kg, 1 mg/kg) and placebo Mean optimal dosage: 0.66 mg/kg/d (SD 0.22) Administration schedule: twice/d Duration of each medication condition: 1 week Washout before trial initiation: none. All were medication‐naive Medication‐free period between interventions: none Titration period: none Treatment compliance: not stated
Outcomes	ADHD symptoms 18‐Item ADHD‐RS‐IV: rated weekly (each Friday) by parents and teachers
Notes	Sample calculation: yes Ethics approval: procedures were performed in accordance with the ethical standards of the University Medical Centre, University of Groningen Comment from trial authors One aim of the trial was to investigate the effectiveness of MPH in improving the fine motor performance of children with ADHD and developmental co‐ordination disorder (DCD). To prevent confounding by fluctuations in ADHD symptoms, these had to be reduced by selecting MPH‐sensitive children Key conclusions of trial authors Children with ADHD/DCD and their parents rated overall quality of life as poorer than for healthy controls, manifested in domains of motor and autonomic functioning, as well as cognitive and psychosocial functioning "In our trial, significant improvements in health‐related quality of life were noted after treatment with MPH, as was improvement in symptoms of ADHD and motor functioning" Fine motor performance in children with ADHD‐DCD was poorer before use of MPH than afterwards Impairment in manual dexterity and poor quality of handwriting and drawing improved after MPH use, but performance remained poorer than in the control group Comment from review authors Only data from the 4‐week cross‐over trial are useful for the review; therefore all data extracted were derived from the cross‐over period Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: no Funding source: none (no funding was available). This double‐blind placebo‐controlled trial of MPH was performed as a clinical treatment program as best clinical practice to determine the effects of MPH and optimal dose compared with placebo Email correspondence with trial authors: August 2013‐January 2014. We obtained supplemental information regarding participant demographics and efficacy data
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random order by pharmacist
Allocation concealment (selection bias)	Low risk	Medication codes were broken at time 2 (endpoint)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Parents, teachers, children and paediatrician were kept blinded to the child’s drug condition and dosage level
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Parents, teachers, children and paediatrician were kept blinded to the child’s drug condition and dosage level
Incomplete outcome data (attrition bias) All outcomes	Low risk	No participant withdrew; no ITT was needed. 7 children whose ADHD symptoms were not sensitive enough to MPH (effect < 25%) were excluded from the 4‐week open‐label period. However, as we are using in this review only data from the preceding cross‐over period, exclusion of these children does not cause high risk of bias Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	No indication of reporting bias