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. Author manuscript; available in PMC: 2023 Jul 22.
Published in final edited form as: Stat Med. 2022 Feb 16;41(12):2132–2165. doi: 10.1002/sim.9348

TABLE 1.

Overview of literature on comparison of TMLE and other estimators

Authors Title Year Description of results Pro/Con
Chatton, et al20 G-computation, propensity score-based methods, and targeted maximum likelihood estimator for causal inference with different covariates sets: a comparative simulation study 2020 Article compares different semiparametic approaches, including TMLE and matching, but finds G-computation performs relatively best. Given their simulation, this was predictable because they simulated from a parametric model and used the same model for estimating the regression, thus showing the superiority of maximum likelihood estimation in parametric models. This is not a realistic setting. Con
Talbot and Beaudoin21 A generalized double robust Bayesian model averaging approach to causal effect estimation with application to the study of osteoporotic fractures 2020 Proposed a generalized Bayesian causal effect estimation (GBCEE), which outperformed double robust alternatives(including C-TMLE). Also showed “target” A-IPTW is superior than C-TMLE in a nonrealistic setting(only using true confounders). Con
Zivich and Breskin16 Machine learning for causal inference: on the use of cross-fit estimators 2020 A simulation study assessing the performance of G-computation, IPW, AIPW, TMLE, doubly robust cross-fit (DC) AIPW and DC-TMLE. With correctly specified parametric models, all of the estimators performed well. When used with machine learning, the DC estimators outperformed other estimators. Neutral
Ju, et al22 Scalable collaborative targeted learning for high-dimensional data 2019 Results from simulations suggested superior performance of C-TMLE relative to both A-IPTW and noncollaborative (“standard”) TMLE estimators. Pro
Ju, et al23 On adaptive propensity score truncation in causal inference 2019 By adaptively truncating the estimated propensity score with a more targeted objective function, the Positivity-C-TMLE estimator achieves the best performance for both point estimation and confidence interval coverage among all estimators considered. Pro
Bahamyirou, et al24 Understanding and diagnosing the potential for bias when using machine learning methods with doubly robust causal estimators 2019 Simulation results showed superior performance of C-TMLE and TMLE relative to IPTW. Pro
Wei, et al25 A data-adaptive targeted learning approach of evaluating viscoelastic assay driven trauma treatment protocols 2019 C-TMLE outperformed the other doubly robust estimators (IPTW, A-IPTW, stabilized IPTW, TMLE) in the simulation study. Pro
Rudolph, et al.26 Complier stochastic direct effects: identification and Robust Estimation 2019 Showed that the EE and TMLE estimators have advantages over the IPTW estimator in terms of efficiency and reduced reliance on correct parametric model specification. Pro
Pirracchio, et al.18 Collaborative targeted maximum likelihood estimation for variable importance measure: illustration for functional outcome prediction in mild traumatic brain injuries 2018 Showed much more robust performance of C-TMLE relative to TMLE using the same type of realistic parametric bootstrap as used in this paper. This was under severe near-positivity violations. Pro
Luque-Fernandez, et al.27 Targeted maximum likelihood estimation for a binary treatment: A tutorial 2018 Showed relatively superior performance of TMLE when compared with A-IPTW estimator in terms of bias. Pro
Levy, et al28 A fundamental measure of treatment effect heterogeneity 2018 Showed the advantage of CV-TMLE over TMLE in that TMLE was affected by overfitting while CV-TMLE appeared unaffected. Pro
Schuler and Rose29 Targeted maximum likelihood estimation for causal inference in observational studies 2017 Showed superior performance of TMLE relative to misspecified parametric models. Pro
Pang, et al30 Effect estimation in point-exposure studies with binary outcomes and high-dimensional covariate data—a comparison of targeted maximum likelihood estimation and inverse probability of treatment weighting 2016 Showed relatively superior performance for the TMLE to IPTW, which showed greater instability when positivity violations occurred. Pro
Schnitzer, et al31 Variable selection for confounder control, flexible modeling and collaborative targeted minimum loss-based estimation in causal inference 2016 Using IPTW with flexible prediction for the propensity score can result in inferior estimation, while TMLE and C-TMLE may benefit from flexible prediction and remain robust to the presence of variables that are highly correlated with treatment. Pro
Zheng, et al32 Doubly robust and efficient estimation of marginal structural models for the hazard function 2016 Showed that the TMLE for marginal structual model (MSM) for a hazard function has relatively superior performance. The bias reduction over a misspecified IPTW or Gcomp estimator is clear in the simulation studies even for a moderate sample size. Pro
Schnitzer, et al33 Double robust and efficient estimation of a prognostic model for events in the presence of dependent censoring 2016 This study demonstrated that even when the analyst is ignorant of the true data generating form, TMLE with super learner can perform about as well as IPTW or TMLE with correct parametric model specification. Pro
Kreif, et al34 Evaluating treatment effectiveness under model misspecification: A comparison of targeted maximum likelihood estimation with bias-corrected matching 2014 Examined the relative performance of TMLE, EE, and matching estimators showing superior performance of TMLE when the outcome regression is misspecified. Pro
Schnitzer, et al35 Effect of breastfeeding on gastrointestinal infection in infants: A targeted maximum likelihood approach for clustered longitudinal data 2014 Compared TMLE with IPTW and G-computation, under the plausible scenario of being given transformed versions of the confounders. Only TMLE with super learner was able to unbiasedly estimate the parameter of interest. Pro
Gruber and van der Laan36 An application of targeted maximum likelihood estimation to the meta-analysis of safety data 2013 Reported superiority of both TMLE and A-IPTW to misspecified parametric models, but the data-generating distributions used resulted in little difference between the semiparametric approaches. Neutral
Lendle, et al37 Targeted maximum likelihood estimation in safety analysis 2013 Showed superior performance of TMLE and C-TMLE relative to A-IPTW estimators in the context of positivity violations. Pro
Díaz and van der Laan38 Targeted data adaptive estimation of the causal dose response curve 2013 Showed relatively superior performance of CV-TMLE relative to CV-A-IPTW estimators, especially in the presence of empirical violations of the positivity assumption. Pro
Schnitzer, et al39 Targeted maximum likelihood estimation for marginal time-dependent treatment effects under density misspecification 2013 In the simulation study, TMLE did not produce a reduction in finite-sample bias or variance for correctly specified densities compared with the G-computation estimator, but it had much better performance than G-computation when the outcome model was misspecified. Neutral
Petersen, et al17 Diagnosing and responding to violations in the positivity assumption 2012 Showed superior performance of TMLE relative to misspecified parametric models, in comparison with A-IPTW, IPTW and G-computation. Pro
van der Laan and Gruber40 Targeted minimum loss based estimation of causal effects of multiple time point interventions 2012 In the setting of multiple time point interventions, showed TMLE outperformed IPTW and MLE estimators. Pro
Porter, et al.41 The relative performance of targeted maximum likelihood estimators 2011 Showed relatively superior performance of C-TMLE relative to A-IPTW estimators particularly when there are covariates that are strongly associated with the missingness, while being weakly or not at all associated with the outcome. Pro
Wang, et al42 Finding quantitative trait loci genes with collaborative targeted maximum likelihood learning 2011 Based on actual genetic data, results suggested greater robustness of findings using C-TMLE relative to parametric approaches for high throughput genetic data. Pro
Díaz and van der Laan43 Population intervention causal effects based on stochastic interventions 2011 Paper focused on new estimators for stochastic (eg, shift) interventions relevant to estimating causal effects of continuous interventions. In their simulation, they did not observe significant differences between the TMLE and the A-IPTW. Neutral
Gruber and van der Laan44 An application of collaborative targeted maximum likelihood estimation in causal inference and genomics 2010 Showed more robust performance in high-dimensional simulations comparing TMLE to estimating equation approaches (A-IPTW). Pro
Stitelman and van der Laan45 Collaborative Targeted Maximum Likelihood for Time to Event Data 2010 The results show that, compared with TMLE, IPTW, and A-IPTW, the C-TMLE method does at least as well as the best estimator under every scenario and, in many of the more realistic scenarios, behaves much better than the next best estimator in terms of both bias and variance. Pro
Moore and van der Laan46 Covariate adjustment in randomized trials with binary outcomes: targeted maximum likelihood estimation 2009 Demonstrated how the use of covariate information in randomized clinical trials could use the TMLE framework, which results in improved performance, without bias, relative to standard methods. Pro
Rose and van der Laan47 Simple optimal weighting of cases and controls in case-control studies 2008 IPTW method for causal parameter estimation was outperformed in conditions similar to a practical setting by the new case-control weighted TMLE methodology. Pro

Note: The Pro/Con column refers to a simple binary classification of the relative performance of the TMLE estimators reported in the paper, “Pro” indicating that the TMLE performed superior to other competing estimators.