A protocol for emulating a published randomised controlled trial using registry data: effects of azithromycin in young adults with cystic fibrosis

Target trial emulation can be used to evaluate the effects of treatments using observational data. The trial emulation approach involves specifying key elements of a protocol for a target trial (a randomised controlled trial designed to address the question of interest) and then describing how best to emulate the trial using observational data. Recent years have seen an uptake of target trial emulation in several disease areas, although there are limited examples in cystic fibrosis. This protocol describes a study which aims to assess the applicability of target trial emulation in cystic fibrosis (CF). We aim to emulate an existing trial in CF and assess to what extent the results from the trial can be replicated using registry data. We aim to emulate a published trial (i.e., the target trial) which found evidence for beneficial effects of azithromycin use on lung function in young adults with cystic fibrosis. Two emulated trials are planned: one using data from the UK CF Registry and one using data from the US CF Registry. The inclusion and exclusion criteria, treatment and outcome definitions, follow-up period, and estimand of interest are all designed to match the published trial as closely as possible. Inverse-probability-of-treatment weighting will be used in the emulated trials to account for confounding bias. Results obtained in the emulated trials using registry data will be compared to the results obtained in the published randomised controlled trial.