Aim: The aim of this project is to describe a causal (counterfactual) approach for analyzing when to start statin treatment to prevent cardiovascular disease using real-world evidence. Methods: We use directed acyclic graphs to operationalize and visualize the causal research question considering selection bias, potential time-independent and time-dependent confounding. We provide a study protocol following the 'target trial' approach and describe the data structure needed for the causal assessment. Conclusion: The study protocol can be applied to real-world data, in general. However, the structure and quality of the database play an essential role for the validity of the results, and database-specific potential for bias needs to be explicitly considered.
Keywords: big data; cardiovascular disease; causal inference; inverse probability of censoring weighting (IPCW); observational study; real-world evidence; statin; study design; target trial; time-dependent confounding.