The Impact of Unmeasured Confounding in Observational Studies: a Plasmode Simulation Study of Targeted Maximum Likelihood Estimation

Abstract

Unmeasured confounding can cause considerable problems in observational studies and may threaten the validity of the estimates of causal treatment effects. There has been discussion on the amount of bias in treatment effect estimates that can occur due to unmeasured confounding. We investigate the robustness of a relatively new causal inference technique, targeted maximum likelihood estimation (TMLE), in terms of its robustness to the impact of unmeasured confounders. We benchmark TMLE’s performance with the inverse probability of treatment weighting (IPW) method. We utilize a plasmode-like simulation based on variables and parameters from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). We evaluated the accuracy and precision of the estimated treatment effects. Though TMLE performed better in most of the scenarios considered, our simulation study results suggest that both methods performed reasonably well in estimating the marginal odds ratio, in the presence of unmeasured confounding. Nonetheless, the only remedy to unobserved confounding is controlling for as many as available covariates in an observational study, because not even TMLE can provide safeguard against bias from unmeasured confounders.

Implementing TMLE in the presence of a continuous outcome

“…3 TMLE has been shown to outperform inverse probability of treatment weighting (IPTW) and G-computation methods (discussed later), particularly when model misspecification is likely. [3][4][5][6][7][8] Despite its gaining recognition in the statistical sciences, there is a shortage of resources accessible to practitioners who could benefit from using TMLE in real-world scenarios. In particular, though Luque-Fernandez et al provide a well-written guide to TMLE for a binary outcome, 5 such a tutorial for Gruber and van der Laan's method for a continuous outcome has yet to be published.…”