Connor 2000.

Study characteristics
Methods	3‐month, randomised, blind, parallel‐group trial with 3 arms: MPH and clonidine clonidine monotherapy (clonidine + placebo) MPH monotherapy (MPH + placebo)
Participants	Number of participants screened: 24 Number of participants included: 24 (MPH + clonidine 8 boys, 0 girls; clonidine + placebo 8 boys, 0 girls; MPH + placebo 8 boys, 0 girls) Number of participants randomly assigned: MPH + clonidine 8, placebo + clonidine 8, placebo + MPH 8 Number of participants followed up: MPH + clonidine 8, placebo + clonidine 6, placebo + MPH 7 Number of withdrawals: MPH + clonidine 0, placebo + clonidine 2, placebo + MPH 1 Diagnosis of ADHD: DSM‐III‐R (combined (100%)) Mean age: MPH + clonidine 10.1 years, placebo + clonidine 9.3 years, placebo + MPH 8.9 years IQ: > 70 MPH‐naive: 54% Ethnicity: white (11%), African American (1%), Asian (0%), Hispanic (0%), other (0%) Country: USA Setting: outpatient clinic Comorbidity: ODD or CD (100%) Comedication: not stated Other sociodemographics: no significant differences in baseline demographics were noted between groups   Inclusion criteria DSM‐III‐R for ADHD DSM‐III‐R for ODD or CD, score of 1.5 SD above the mean for age and sex on the Parent CBCL, Attention problems scale (T score > 65) and a score on the Teacher Child Attention Problem Rating Scale of ≥ 93rd percentile Score 1.5 SD above the mean for age and sex on the Parent or Teacher CBCL, Delinquency or Aggression problems scale Normal findings from general physical examination by family physician within 6 months before trial entry Exclusion criteria Medical history that contraindicated use of stimulants or clonidine
Interventions	Participants were randomly assigned to MPH + clonidine or placebo + clonidine MPH dose: 35.0 (5.67) mg/d Administration schedule: twice/d Duration of intervention: 12 weeks Titration period: 4 weeks after randomisation Treatment compliance: “All subjects were acceptably compliant with the protocol”
Outcomes	General behaviour Disruptive Behavior Disorders Rating Scale: parent‐ and teacher‐rated monthly Home Situations Questionnaire: parent‐rated monthly School Situations Questionnaire: teacher‐rated monthly Non‐serious AEs Possible side effects of MPH and clonidine: combined Stimulant/Clonidine Side Effects Rating Scale, parent‐ and teacher‐rated monthly Pulse and BP obtained monthly. ECG measured after first month. Height and weight obtained monthly
Notes	Intervention groups used: MPH + clonidine; control group: placebo + clonidine Ethics approval: yes Sample calculation: no Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: no Any withdrawals due to AEs: no (1 in the MPH‐only group, not included here) Funding source: supported by a UMMS (University of Massachusetts Medical School) Small Grants Project Award Email correspondence with trial authors: June 2013. We obtained additional information from trial authors, but it was not possible to receive supplemental data. We could not perform a meta‐analysis on any of the outcomes, as we did not have relevant data and transformation was not possible.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	8 participants were randomly assigned to each group. 3 participants were previous MPH treatment failures and refused randomisation to the MPH‐alone trial arm. These 3 participants were partially randomly assigned to MPH and clonidine or to clonidine alone. All other children were fully randomly assigned
Allocation concealment (selection bias)	Low risk	After trial completion, the medication blind was broken. All medication capsules and placebo capsules were prepared by the UMMS (University of Massachusetts Medical School) Pharmacy in identical capsules to disguise taste and smell. All participants in all trial groups received an equal number of capsules per day.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All teachers, school nurses, parents, children and research assistants completing dependent measures were blinded to the child's treatment group for the trial duration. Completion of ECGs for only 2 clonidine treatment groups may have broken blinding for parent raters and for the child (but not for teacher raters nor for research assistants administering the Gordon Diagnostic System (GDS), who remained blinded as to whether the child had received an ECG). This is not relevant to us, as we are using data only on the 2 groups completing ECGs
Blinding of outcome assessment (detection bias) All outcomes	Low risk	As stated above
Incomplete outcome data (attrition bias) All outcomes	Low risk	LOCF Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Low risk	Reply from trial author on our request for the protocol: protocol described in the trial