Statistical methods for primary and secondary outcomes {20a}
death
EVENTS
We will draft a statistical analysis plan (SAP) for use by the Data Monitoring Committee (DMC) during their ongoing review. The SAP will be finalised before the trial database is locked for the final analysis.The primary analysis comparing IM and IV tranexamic acid will be a per-protocol analysis. The analysis comparing tranexamic acid to placebo will be an intention-to-treat analysis. We will analyse the data and present statistics by randomised group. We will tabulate demographic and other baseline characteristics. Descriptive statistics for continuous variables will include the mean, standard deviation, median, range, and the number of observations. We will present categorical variables as numbers and percentages. Effect measures will be relative risk. Precision will be quantified using 95% confidence intervals. We will use the composite strategy to account for intercurrent events that may preclude the measurement of key efficacy and safety outcomes (e.g. early death, surgical interventions, discharge, or transfer to another hospital).To compare the IV and IM routes of administration, we need to prespecify a non-inferiority margin—a predetermined margin of difference that is clinically acceptable. Women often experience treatment delays while waiting for a doctor or travelling to the hospital. Because tranexamic acid’s effectiveness falls by about 10% for every 15-min delay, a 1-h treatment delay corresponds to a 40% reduction in effectiveness. If IM administration preserves 60% of the benefit achieved with IV administration, IM tranexamic acid would be equivalent to an IV injection with a 1-h delay. An effect of this size from a more accessible route of administration with potentially fewer side effects would be clinically relevant. A 60% preservation fraction corresponds to a relative risk between IM and IV tranexamic acid of 1.13. If the upper limit of the two-sided 95% confidence interval for IM versus IV tranexamic acid is less than 1.13, then evidence of non-inferiority will have been provided.