Observational data are increasingly used to study and draw causal inferences about the effects of treatments. Target trial emulation (TTE) is a framework for mitigating biases in causal investigations through specification of an observational study, targeting a specific causal research question, based on a real or hypothetical randomised controlled trial. Investigations into the effects of treatment discontinuation are of growing interest and particularly relevant in cystic fibrosis (CF), where treatment burden is high and new transformative therapies are becoming widespread. We aim to use the TTE framework to investigate the effect of discontinuation of inhaled corticosteroids (ICS) on clinical outcomes in people with CF. Our observational emulation will be based on the CF WISE (Withdrawal of Inhaled Steroids Evaluation) trial (PMID:16556691).

Two study designs proposed for investigating treatment effects using observational data are the prevalent new-user design and the sequential trials design. Each design uses different but related methods to address similar causal questions; however, the comparability between them remains uncertain. We will conduct a population-based cohort study using data from the UK CF Registry between January 2016 and June 2018 and apply these designs. We will specify the target trial protocol for each study design. Estimates for the causal effects of discontinuing ICS will be obtained and compared with those from the CF-WISE trial.

This study has received approval from the UK CF Registry Research Committee for both the research and access to data. Ethical approval has also been granted by the LSHTM Ethics Committee. The UK CF Registry has NHS Research Ethics Committee approval (REC reference: 24/EE/0012). The findings from this project will be submitted to peer-reviewed journals and presented at academic conferences.