Brams 2012.
Study characteristics | ||
Methods | Randomised, double‐blind, 3‐period × 3‐treatment cross‐over trial in a 12‐h laboratory classroom setting with 3 interventions
Each period lasted 7 days |
|
Participants | Number of participants screened: not stated Number of participants included: 165 (57% boys, 43% girls) Number of participants followed up: 157 Number of withdrawals: 8 Diagnosis of ADHD: DSM‐IV (combined or predominantly hyperactive‐impulsive subtype) Age: mean 9.6 years (range 9.3 to 10.0) IQ: above normal MPH‐naive: 0% Ethnicity: white (38.2%), African American (31.5%), Hispanic (22.4%), other (7.9%) Country: USA Setting: outpatient clinic (laboratory classroom) Comorbidity: no significant medical illness Comedication: not stated Other sociodemographics: none Inclusion criteria
Exclusion criteria
|
|
Interventions | Participants were randomly assigned to 1 of 6 possible drug condition orders of 20 mg ER‐d‐MPH, 30 mg ER‐d‐MPH and placebo Administration schedule: once daily, morning Duration of each medication condition: 7 days Washout before trial initiation: 1 week Medication‐free period between interventions: no Titration period: none (fixed doses) Treatment compliance: no information |
|
Outcomes |
ADHD symptoms
Serious AEs
1 participant experienced 2 serious AEs (peritonsillar abscess and oral bullae) while receiving 20 mg ER‐d‐MPH and was hospitalised for 6 days for the peritonsillar abscess. Serious AEs were considered not related to trial drug. Participant discontinued the trial for missed trial drug during hospitalisation Non‐serious AEs
|
|
Notes | Sample calculation: no Ethics approval: yes Comments from trial authors
Key conclusions of trial authors
Exclusion of MPH non‐responders/children who have previously experienced AEs while taking MPH before randomisation: yes; children with a poor prior response, or known sensitivity, to all MPH or d‐MPH products based on medical history were excluded Withdrawals due to AEs: no Funding source: Novartis Pharmaceuticals Corporation Email correspondence with trial authors: September 2013. Not possible to contact trial authors |
|
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Participants were randomly assigned to 1 of 6 treatment sequences. All participants were given the lowest available number from the randomisation numbers provided at each site. A randomisation list was produced by using a validated system that automated the random assignment of treatment sequences to randomisation numbers in the specified ratio |
Allocation concealment (selection bias) | Low risk | Randomisation data were kept strictly confidential until the time of unblinding |
Blinding of participants and personnel (performance bias) All outcomes | Low risk | All trial medications and packaging were identical in appearance for blinding purposes. Participants, parents, trial centre personnel and those who assessed outcomes were blinded to trial treatment |
Blinding of outcome assessment (detection bias) All outcomes | Low risk | All trial medications and packaging were identical in appearance for blinding purposes. Participants, parents, trial centre personnel and those who assessed outcomes were blinded to trial treatment |
Incomplete outcome data (attrition bias) All outcomes | Low risk | 8 dropouts from the MPH group. The ITT population included all randomly assigned participants who took ≥ 1 dose of trial medication and had ≥ 1 post‐dose efficacy measurement. The safety population consisted of all participants who took ≥ 1 dose of trial medication Selection bias (e.g. titration after randomisation → exclusion): no |
Selective reporting (reporting bias) | Unclear risk | No published protocol |