Causal Effects of Time‐Varying Treatments: The G‐Formula
The g formula is a cornerstone method for estimating causal effects of time-varying treatments using longitudinal observational data in the presence of time-varying confounders that are affected by prior treatment. Standard regression techniques often fail in this setting because adjustment for such covariates can distort the very effects under study. The g-formula addresses this problem by expressing the mean potential outcome under specified static or dynamic treatment regimes as a function of the joint distribution of covariates, treatments and outcomes, which can be approximated via parametric or semi-parametric models and simulation. This review presents the g-formula, emphasizing intuitive explanations. After outlining the causal framework and the core identification assumptions-consistency, sequential exchangeability and positivity-the article describes practical parametric g-formula: model specification for covariate and outcome processes, implementation via forward simulation, and the interpretation of marginal causal contrasts between clinically relevant regimes. The g-formula is then situated within the family of g-methods alongside inverse probability weighting and targeted maximum likelihood estimation, highlighting complementary strengths and limitations. A dedicated section discusses concrete applications, including analyses of highly active antiretroviral therapy and AIDS or death, dynamic 'when to start' antiretroviral strategies in HIV and electronic health record-based evaluations of blood pressure treatment targets. Practical guidance on modelling choices, diagnostics and transparent reporting is provided to support applied researchers considering g-formula in clinical and epidemiological investigations.
Authors
- Carmine Zoccali (ORCID: https://orcid.org/0000-0002-6616-1996)
- Giovanni Tripepi
Institutions
- Istituto di Fisiologia Clinica (IT)
- Biogem (IT)
- Renal Research Institute (US)
- Czech Academy of Sciences, Institute of Physiology (CZ)
Publication Details
- Journal
- European Journal of Clinical Investigation
- Published
- 2026-06-30
- DOI
- https://doi.org/10.1111/eci.70239
- Primary Topic
- Advanced Causal Inference Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00