ObjectiveTo describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size.DesignSystematic review.Data sourcesMedline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019.Eligibility criteriaProspective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention.Results3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%–10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3–1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size.ConclusionAbsolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.
Background: Medication reconciliation reduces potential medication discrepancies and adverse drug events. The role of pharmacy technicians in obtaining best possible medication histories (BPMHs) and performing reconciliation at the admission and transfer interfaces of care for pediatric patients has not been described. Objectives: To compare the completeness and accuracy of BPMHs and reconciliation conducted by a pharmacy technician (pilot study) and by nurses and/or pharmacists (baseline). The severity of identified unintentional discrepancies was rated to determine their clinical importance. Methods: This prospective cohort comparison study involved patients up to 18 years of age admitted to and/or transferred between the Cardiology ward and the Cardiac Critical Care Unit of a pediatric tertiary care teaching hospital. A pharmacy resident conducted two 3-week audits: the first to assess the completeness and accuracy of BPMHs and reconciliation performed by nurses and/or pharmacists and the second to assess the completeness and accuracy of BPMHs and reconciliation performed by a pharmacy technician. Results: The total number of patients was 38 in the baseline phase and 46 in the pilot period. There were no statistically significant differences between the baseline and pilot audits in terms of completion of BPMH (82% [28/34]
A regimen of gentamicin 6 mg/kg IV every 24 hours for Pediatric Intensive Care Unit/Cardiac Critical Care Unit patients at SickKids weighing ≥5 kg with SCr <20% above age-specific upper normal limit before initiation of gentamicin is proposed.
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