McBride 1988a.

Study characteristics
Methods	Individual, double‐blind, cross‐over trial for 4 weeks with 2 interventions: MPH placebo
Participants	Number of participants screened: not stated Number of participants included: 73 Number of participants followed up: 70 (53 boys, 17 girls) Number of withdrawals: 3 Diagnosis of ADHD: DSM‐III (77% met the criteria for ADD‐H) Mean age: MPH responders 8.5 (SD not stated), MPH non‐responders 9.5 (SD not stated). Range 6‐17 years Mean IQ: MPH responders 102 (SD 21), MPH non‐responders 89 (SD 23) MPH‐naive: 71 (97%) Ethnicity: not stated Country: USA Setting: outpatient clinic Comorbidity: not stated Comedication: carbamazepine or phenytoin or valproic acid or mephobarbital (6.4 receiving a combination of these drugs). Clonidine (n = 1) Sociodemographics: no information Inclusion criteria Referred because the child’s academic performance was below that expected on the basis of his abilities, as documented by psychological testing, or because his behavioural dysfunction was interfering with self‐image and socialisation, or for both reasons 6‐17 years of age No child was excluded from the trial on the basis of low intelligence, history of seizures or concurrent medication Exclusion criteria Not stated
Interventions	Participants were randomly assigned to 1 of 2 possible drug condition orders of 0.3 mg/kg MPH and placebo. MPH was rounded to the nearest 1.25 mg Mean MPH dosage: no information, but mean dose during follow‐up was 0.36 mg/kg/dose Administration schedule: morning and 4 h later Duration of each medication condition: 2 weeks Washout before trial initiation: none Medication‐free period between interventions: none Titration period: none Treatment compliance: no information
Outcomes	ADHD symptoms Abbreviated Conners' Teacher and Parent Questionnaire Parent Questionnaires was rated at the end of each weekend and at the end of each school week. Teacher Questionnaires were filled out at the end of the week Serious AEs No serious side effects during the trial Non‐serious AEs No information about how data on side effects were obtained None of the parents of responders who had experienced side effects during the trial thought the effects were significant enough that they should not treat their child with MPH, and no side effects other than appetite suppression continued during regular therapy after the trial Follow‐up 6 months after: n = 33. 15 had no change in weight curves. 1 gained 7 kg beyond his original percentile
Notes	Sample calculation: no information Ethics approval: no information Comments from trial authors Participants in this study were not a randomly selected group of children with ADD but, rather, a referral population already screened by their school psychologists and primary care physicians Individual children with differing absorption, metabolism or underlying neurochemical abnormality may have different response thresholds, and potential responders may have been overlooked because they did not consistently try a higher dose 15% of children with ADD in this study were adopted The finding that non‐responders were older may reflect the development of secondary characteristics such as decreased motivation and poor study habits in long‐term ADD ‐symptoms not easily reversed during a short trial A problem inherent in this trial, as in an open trial, is dependence on the observations of teachers and parents who have variable observational skills, variable tolerance for symptoms of ADD and different perspectives on medication Lower Conners' scores may be explained by the fact that many characteristics rated on Conners' questionnaires reflect hyperactivity, and some of these children were more inattentive than hyperactive Key conclusions of trial authors 51 (of 70) children showed improvement during 1 of the 2‐week periods, and that period corresponded with MPH therapy in 48 6 of the 22 who did not respond to MPH experienced worsening of function while taking the drug. No serious side effects were reported during the trial 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: not declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	The pharmacist labelled the 2 sets of capsules as “Medicine A” and “Medicine B” in either order by coin flip for the first 22 trials, and then by using a random numbers table
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The manner of labelling was sealed by the pharmacist in an envelope that was not opened until the trial had ended and findings had been discussed with the parents
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Objectivity was lessened for a few parents because the decreased appetite associated with MPH led them to suspect which capsules contained the drug
Incomplete outcome data (attrition bias) All outcomes	Low risk	In the few trials for which 1‐3 of 10 items on Conners' questionnaire had not been scores, the score was prorated based on 30 points maximum 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 selective reporting