Harfterkamp 2014.

Study characteristics
Methods	Parallel trial of atomoxetine versus placebo
Participants	Inclusion criteria: 6‐17 years of age IQ of at least 60 dual diagnosis of ASD (based on DSM‐4) and ADHD Exclusion criteria: weight of < 20 kg presence of psychosis, bipolar disorder, or substance abuse a serious medical illness history of seizures ongoing use of psychoactive medications other than the study drug intended start of a structured psychotherapy or inpatient treatment Location/setting: 9 Dutch child and adolescent psychiatry centres, 6 university centres, (Amsterdam, Groningen, Leiden, Maastricht, Nijmegen, and Utrecht), and 3 non‐university centres (The Hague, Hoorn, an Oosterhout). Sample size: 48 in atomoxetine group, 49 in placebo group Number of withdrawals/dropouts: placebo group: protocol violation (2), physician decision (1). Atomoxetine group: AE (1), protocol violation (2), lack of efficacy (1), parent/ caregiver decision (1) Gender: atomoxetine 42/48 male, placebo 41/49 Mean age: atomoxetine 9.9 years, placebo 10.0 years IQ: atomoxetine 91, placebo 94.6 Baseline ABC‐I or other BoC: atomoxetine ABC‐I 17.3, placebo ABC‐I 16.2 Concomitant medications: participants were not permitted to be using psychoactive medications prior to study on an ongoing basis History of previous medications: atomoxetine 18/48 and placebo 18/49 had not received any prior psychopharmacological treatment
Interventions	Intervention (atomoxetine) for 8 weeks: maximum of 1.2 mg/kg/day daily dose. First week 0.5 mg/kg/day; 2nd week 0.8 mg/kg/day; 1.2 mg/kg/day for 6 weeks Comparator (placebo) for 8 weeks: maximum of 1.2 mg/kg/day daily dose. First week 0.5 mg/kg/day; 2nd week 0.8 mg/kg/day; 1.2 mg/kg/day for 6 weeks
Outcomes	Primary outcomes: irritability, measured using the ABC‐I subscale (Aman 1985) AEs Secondary outcomes: tolerability Timing of outcome assessments: baseline and 8 weeks (endpoint)
Notes	Study start date: October 2006 Study end date: March 2008 Source of funding: funded by Eli Lilly and company. "Myriam Harfterkamp has accepted invitations for congress travels from Eli Lilly and Eurocept. Ruud B. Minderaa was advisor for Eli Lilly. Jan K. Buitelaar has been a consultant to/member of advisory board of, and/or speaker for Bristol‐Myer Squibb, Eli Lilly, Janssen Cilag BV, Medice, Organon/Shering Plough, Servier, Shire, and Union Chimique Belge (UCB). Gigi van de LooNeus has received honoraria for a presentation from Eli Lilly and wasmember oftheadvisory boardforUCBPharma B.V. andShire. Rutger‐Jan van der Gaag has no financial disclosures. Pieter J. Hoekstra has received honoraria for presentations or advice from Desitin, Eli Lilly, and Shire". Conflicts of interest: none declared Trial registry: NCT00380692
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Details not provided
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Details not provided
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Details were not provided
Incomplete outcome data (attrition bias) All outcomes	Low risk	An ITT analysis was used and all participants who received at least 1 dose of the drugs were included in the analysis
Selective reporting (reporting bias)	Low risk	Results reported on clinicaltrials.gov (NCT00380692)
Other bias	High risk	Sponsor: Eli Lilly and Company Information provided by: Eli Lilly and Company