G-formula for causal inference via multiple imputation

Abstract: G-formula is a popular approach for estimating treatment or exposure effects from longitudinal data that are subject to time-varying confounding. G-formula estimation is typically performed by Monte-Carlo simulation, with non-parametric bootstrapping used for inference. We show that G-formula can be implemented by exploiting existing methods for multiple imputation (MI) for synthetic data. This involves using an existing modified version of Rubin's variance estimator. In practice missing data is ubiquitous in longitudinal datasets. We show that such missing data can be readily accommodated as part of the MI procedure when using G-formula, and describe how MI software can be used to implement the approach. We explore its performance using a simulation study and an application from cystic fibrosis.