Fine 1993.

Study characteristics
Methods	3‐week double‐blind, cross‐over trial with 2 interventions: MPH twice/d (2 doses: 0.3 mg/kg and 0.6 mg/kg) placebo twice/d Phases: medical trial or typical clinical procedure, concluded with recommendation for treatment, follow‐up (6 weeks and 3 months)
Participants	Number of participants screened: 24 who were randomly assigned: 12 "typical clinical procedure", 12 "medical trial" Number of participants included: 12 (sex not stated). Participants in the medical trial group were randomly assigned to different possible drug condition orders Number of participants followed up: 12 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐III‐R (subtype not stated) Age: mean 101.58 months (approximately 8.5 years) (range 6‐10 years) IQ: not stated MPH‐naive: 12 Ethnicity: not stated Country: Canada Setting: outpatient clinic Comorbidity: not stated Comedication: not stated Other sociodemographics: (socioeconomic status calculated using Blishen Index; lower score indicates higher socioeconomic status): medical trial: mean 3.42 (SD 0.90); typical clinical procedure: mean 3.50 (SD 1.88) Inclusion criteria ADHD diagnosis. Parent interview with psychiatrist, several parent (mother and father) and teacher ratings. Included if any positive Exclusion criteria Physical or mental disability Tic disorders
Interventions	Participants in the medical trial group were randomly assigned to different possible drug condition orders of 0.3 mg/kg and 0.6 mg/kg MPH and placebo Mean MPH dosage: not stated Administration schedule: twice/d Duration of each medication condition: "the different interventions were randomly assigned across days" Washout before trial initiation: not stated Medication‐free period between interventions: not stated Titration period: not stated Treatment compliance: missed pills mean 1.92 (SD 1.44). Furthermore, compliance was assessed by urine test. By 6‐week follow‐up, parent‐reported compliance was 83%; by 3 months, it was 73%
Outcomes	ADHD symptoms Abbreviated CRS: rated on weekdays by teachers and on weekends by parents SNAP: rated daily, but not stated by whom Non‐serious AEs Side effects questionnaire: rated weekly by parents ("Across the 12 children, ratings were available from an average of 2.58 placebo days, 1.33 LD‐MPH days and 1.75 high‐dose MPH days")
Notes	Sample calculation: not stated Ethics approval: not stated Comments from trial authors Small sample size Rely on parent ratings to assess side effects Key conclusions of trial authors Fine 1993: "Our analyses revealed that several side‐effects appeared equally often on placebo as on active medication and the parents’ reports of side effects are significantly related to reports of ADHD symptomatology" (p 28) Johnston 1993 (in Fine 1993): "In summary, this study finds mixed support for the prediction that medication trials would enhance acceptability, satisfaction, and compliance associated with MPH" (p 728) Comments from review authors This trial aims to examine differences in attitudes of parents whose children participate in a medical trial or are subjected to "typical clinical procedure" Only the medical trial group represents a cross‐over design Fine 1993 deals only with the medical trial group, and Johnston 1993 (in Fine 1993) deals with both 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: CIBA‐GEIGY Canada Email correspondence with trial authors: June 2014. Emailed trial authors for supplemental information and received the following response: "I did look at the questions, but unfortunately, given how long ago the study was conducted, I do not still have the data necessary to answer" (Krogh 2014b [pers comm])
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	24 children were matched in pairs on sex and age and then were randomly assigned to the medication trial or to the typical clinical procedure. Higher and lower doses of MPH and placebo were randomly assigned across days by the hospital pharmacy
Allocation concealment (selection bias)	Low risk	Higher and lower doses of MPH and placebo were randomly assigned across days by the hospital pharmacy. Active medication and placebo were packaged in capsule form to disguise taste and visual differences, and were dispensed in envelopes for daily use
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Parents, teacher, child and resident were blinded to the daily medication status of the child. "Active medication and placebo were packaged in capsule form to disguise taste and visual differences, and were dispensed in envelopes for daily use". All evaluations were conducted by psychiatric residents blinded to the hypotheses of the trial
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Parents, teacher, child and resident were blinded to the daily medication status of the child. All evaluations were conducted by psychiatric residents blinded to the hypotheses of the trial
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Across 12 children, ratings were available for an average of 2.58 placebo days, 1.33 LD‐MPH days and 1.75 HD‐MPH days. Ratings for each child were averaged across each of the 3 treatment conditions. Data for all participants were available for measures of missed pills and appointments. 1 participant was missing on measures of parent‐reported compliance at 6‐week follow‐up, and 2 participants at 3‐month follow‐up. 3 participants lacked data for the number of missing envelopes. 4 participants did not provide urine for analysis, and 4 were missing physician reports of compliance (6‐week and 3‐month follow‐ups). As the result of intervening school holidays, teacher reports of compliance are available for only 16 children (8 in each condition) at each follow‐up. MPH non‐responders were not excluded. Did not state the method used to account for missing outcome data Selection bias (e.g. titration after randomisation → exclusion of MPH non‐responders or placebo responders): no
Selective reporting (reporting bias)	Unclear risk	No protocol was identified