Principles
This prospective analysis will be carried out on studies conducted in multiple countries, which increases effect size estimates across different conditions as well as the external validity of the results. We plan a prospective analysis of individual de-identified patient-level data. Common variables from all datasets will be combined to conduct the analysis.
If consent for participation is withdrawn or consent to continue is not given, the data will not be used unless consent to do so is obtained, including for all mortality time points. Analyses will be performed by intention-to-treat according to the participants’ randomly allocated group, regardless of treatment compliance. These analyses will include participants for whom consent to continue is refused but the use of data already collected is allowed, including the primary outcome, and will exclude patients who do not fulfil the study entry criteria.[29]
Missing data will not be imputed. The multilevel models described in the analysis are able to handle missing data due to loss to follow-up. Where there are missing observations, the number of observations used will be reported. Two-sided hypothesis testing at a significance level of 0.05 will be used. No adjustment for multiple tests will be made, with the interpretation of the significance of the tests being appropriate for the primary or secondary nature of the outcome. Analyses will be conducted using the Statistical Package for the Social Sciences (SPSS) Research Engine, Version 24.0 IBM SPSS Statistics or later, and “R” version 3.5.0 or later.