The Causal Roadmap and simulation studies to inform the Statistical Analysis Plan for real-data applications

The Causal Roadmap outlines a systematic approach to our research endeavors: define quantity of interest, evaluate needed assumptions, conduct statistical estimation, and carefully interpret of results. At the estimation step, it is essential that the estimation algorithm be chosen thoughtfully for its theoretical properties and expected performance. Simulations can help researchers gain a better understanding of an estimator's statistical performance under conditions unique to the real-data application. This in turn can inform the rigorous pre-specification of a Statistical Analysis Plan (SAP), not only stating the estimand (e.g., G-computation formula), the estimator (e.g., targeted minimum loss-based estimation [TMLE]), and adjustment variables, but also the implementation of the estimator -- including nuisance parameter estimation and approach for variance estimation. Doing so helps ensure valid inference (e.g., 95% confidence intervals with appropriate coverage). Failing to pre-specify estimation can lead to data dredging and inflated Type-I error rates.