Döpfner 2004.

Study characteristics
Methods	Randomised, double‐dummy, double‐blind, cross‐over, multi‐centre trial with 3 interventions: IR‐MPH 10 mg‐40 mg ER‐MPH 10 mg‐40 mg placebo Phases: trial was subdivided into 5 stages: pre‐screening, run‐in phase (duration: 1 workday), trial phases 1 and 2 (duration in each case: 4 workdays plus weekend) and trial phase 3 (duration: 4 workdays). Participants also received a behavioural therapy intervention and social skills training at school.
Participants	Number of participants screened: not stated Number of participants included: 82 Number of participants followed up: 79 (71 boys, 8 girls) Number of withdrawals: 3   Participants followed up Diagnosis of ADHD: DSM‐IV or ICD‐10 (combined (92.4%), hyperactive‐impulsive (0%), inattentive (7.6%)) Age: mean 10 years (range 6 to 16) IQ: 103 ± 10.4 MPH‐naive: 0% Ethnicity: not stated Country: Germany Setting: outpatient clinic Comorbidity: ODD/CD (44%) Comedication: not stated Other sociodemographics: none Inclusion criteria Meeting criteria for an ICD‐10 diagnosis of Hyperkinetic disorder (F90) or for a DSM‐IV diagnosis of ADHD 8‐15 years of age MPH responders on the basis of clinical assessment and after careful titration All patients had to be treated with IR‐MPH at least twice daily or once daily with a retard preparation During previous month, MPH dosage had to be unchanged. Daily MPH dosage was ≥ 10 mg IQ ≥ 85 Body weight > 20 kg Written informed consent of parents and participants to join the trial Exclusion criteria Patients attending schools for mentally handicapped, sensory handicapped or physically handicapped children Patients who, during the past 4 weeks, were treated with other medication because of ADHD, apart from MPH Diagnosis of a severe developmental disorder or psychosis Previous convulsive disorder; EEG indicated susceptibility to convulsions Case history of pathological changes in liver function or liver disease Severe depressive disorder (CBCL, teacher‐rated, > 70 on the Anxiety‐depression scale) or a severe anxiety disorder according to clinical diagnosis
Interventions	Participants were randomly assigned to different orders of IR‐MPH, ER‐MPH and placebo Mean MPH dosage: 22 mg ± 6 mg. Dosage was identical in MPH groups but did not exceed 1 mg/kg body weight. Thus, 9 (11%) participants received a daily dose of 10 mg, 54 (68%) received 20 mg, 14 (17%) received 30 mg and 2 (3 %) received 40 mg Administration schedule: 9:00 am and 1:00 pm Duration of each medication condition: 4 days, and for trial phase 1 + 2 (also weekends) Washout before trial initiation: none Medication‐free period between interventions: none Titration period: had to be oriented to the optimum individual dosage previously determined in clinical treatment trials initiated before randomisation Treatment compliance: not stated
Outcomes	ADHD symptoms SKAMP: rated by clinic personnel/caregiver staff for each child at 9:00 am, 11:00 am, 12:30 pm, 3:00 pm and 4.15 pm Fremdbeurteilungsbogen für Hyperkinetische Störungen (3rd party assessment form for hyperkinetic disorders): staff/personnel‐rated, at 1:00 pm and 4:45 pm Non‐serious AEs Questionnaire on side effects (Side Effects Rating Scale)
Notes	Sample calculation: not stated Ethics approval: approved by local university ethics committees Comment from trial authors "Althogh the analogue classroom attempts to mimic many aspects of a regular school classroom, it represents a unique setting that may influence behaviour. Analogue assessments included only ADHD participants; no control or normal participants were available for comparison" Carry‐over effect: as no evidence for possible carry‐over effects was noted, no secondary analyses for carry‐over effects were performed Key conclusions of trial authors These data provide support for the benefit of this novel, once‐daily MPH preparation for the treatment of ADHD On all measures analysed, both twice/d IR‐MPH and ER‐MPH produced significant improvement relative to placebo. Moreover, ER‐MPH was not significantly different from twice/d, IR‐MPH, even longer than 7 h after dosing Longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in‐school administration Comments from review authors For the article in German (Döpfner 2003 in Döpfner 2004), only 1 review author who knew German extracted the data. All other articles were assessed for data by 2 review authors. We received Döpfner 2003 (Döpfner 2004) from HB Pharma 18 participants in the sample from Clinic for Neuropediatrics, University of Kiel, received response cost token‐based behaviour training (RCT) (Gerber 2012 in Döpfner 2004) Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH: yes; included only MPH responders Any withdrawals due to AEs: no Funding source: conducted and sponsored by MEDICE Arzneimittel Pütter GmbH & Co. KG as part of the drug approval process for Medikinet‐Retard Email correspondence with trial authors. We received some data from trial authors in July 2013. We sent 2 additional emails to different trial authors to request data in July 2014 but received no answer.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Order in which participants were allocated to respective treatment arms was randomly assigned
Allocation concealment (selection bias)	Unclear risk	Order in which participants were allocated to respective treatment arms was randomly assigned
Blinding of participants and personnel (performance bias) All outcomes	Low risk	To guarantee a double‐blind trial, the double‐dummy method was used (i.e. participants took the capsule once/d and the tablets twice daily). Only 1 of the 2 galenical forms contained the active substance; the other form contained placebo. In the placebo group, participants took both placebo capsules and placebo tablets
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not stated
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not stated Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol obtained