Statistical analysis
TUBERCULOSIS PLEURISY, EVENT, RECRUITMENT, TUBERCULOSIS, ADVERSE REACTION
In our original sample size calculations, 12 clusters per group and a harmonic mean of 125 patients per cluster gave 85% power to detect a 40% risk reduction in the primary composite outcome at the 5% level, assuming an 18% risk of the primary composite outcome in the control group, 5% loss to follow-up, and a coefficient of variation of outcome of 0·3. In recalculation after two clusters were combined, a harmonic mean of 108 patients per cluster (due to slower than expected recruitment), allowing for 10% loss to follow-up, gave 83% power to detect a 40% risk reduction in the primary composite outcome. Sample size calculations were conducted using the Stata command clustersampsi.The intention-to-treat population was defined as participants enrolled into the trial, excluding those who met a post-enrolment exclusion criterion (participants who stopped taking the fixed-dose combination treatment within the first month due to an adverse reaction; permanently stopped their treatment within the first month because of travel or hospitalisation; had their treatment extended due to updated diagnosis of tuberculosis pleurisy, or tracheal or bronchial tuberculosis; or had diagnosis of drug resistance due to non-rifampicin drug resistance), and participants with a change of diagnosis confirmed by the endpoint review committee. The per-protocol population further excluded participants who withdrew early from use of the medication event reminder monitor, regardless of the reason given.All analyses were done in Stata (version 15), using the clan command. Our primary estimand was a risk ratio (RR), calculated using the logarithm of the cluster proportions: this estimates the ratio of geometric means of the cluster-level risks in each group, so all percentages reported are geometric means. The primary analysis was adjusted for age, sex, occupation, migrant status, distance to clinic, education level, household expenditure, and smear result at treatment initiation, using the two stage approach.For the primary outcome, the primary analysis was based on multiple imputation in the intention-to-treat population. Multiple imputation due to missing composite outcome was applied with 25 imputations (This trial is registered with ISRCTN, 35812455.