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MULTIPLY ROBUST ESTIMATORS OF CAUSAL EFFECTS FOR SURVIVAL OUTCOMES.

ABSTRACT: Multiply robust estimators of the longitudinal g-formula have recently been proposed to protect against model misspecification better than the standard augmented inverse probability weighted estimator (Rotnitzky et al., 2017; Luedtke et al., 2018). These multiply robust estimators ensure consistency if one of the models for the treatment process or outcome process is correctly specified at each time point. We study the multiply robust estimators of Rotnitzky et al. (2017) in the context of a survival outcome. Specifically, we compare various estimators of the g-formula for survival outcomes in order to 1) understand how the estimators may be related to one another, 2) understand each estimator's robustness to model misspecification, and 3) construct estimators that can be more efficient than others in certain model misspecification scenarios. We propose a modification of the multiply robust estimators to gain efficiency under misspecification of the outcome model by using calibrated propensity scores over non-calibrated propensity scores at each time point. Theoretical results are confirmed via simulation studies, and a practical comparison of these estimators is conducted through an application to the US Veterans Aging Cohort Study.

SUBMITTER: Wen L

PROVIDER: S-EPMC9401091 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

MULTIPLY ROBUST ESTIMATORS OF CAUSAL EFFECTS FOR SURVIVAL OUTCOMES.

Wen Lan L Hernán Miguel A MA Robins James M JM

Scandinavian journal of statistics, theory and applications 20211111 3

Multiply robust estimators of the longitudinal g-formula have recently been proposed to protect against model misspecification better than the standard augmented inverse probability weighted estimator (Rotnitzky et al., 2017; Luedtke et al., 2018). These multiply robust estimators ensure consistency if one of the models for the treatment process or outcome process is correctly specified at each time point. We study the multiply robust estimators of Rotnitzky et al. (2017) in the context of a sur ...[more]

PMID: 36033967

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Project description:BackgroundWhen estimating the causal effect on survival outcomes in observational studies, it is necessary to adjust confounding factors due to unbalanced covariates between treatment and control groups. There is no study on multiple robust method for estimating the difference in survival functions. In this study, we propose a multiply robust (MR) estimator, allowing multiple propensity score models and outcome regression models, to provide multiple protection.MethodBased on the previous MR estimator (Han 2014) and pseudo-observation approach, we proposed a new MR estimator for estimating the difference in survival functions. The proposed MR estimator based on the pseudo-observation approach has several advantages. First, the proposed estimator has a small bias when any PS and OR models were correctly specified. Second, the proposed estimator considers the advantage pf the pseudo-observation approach, which avoids proportional hazards assumption. A Monte Carlo simulation study was performed to evaluate the performance of the proposed estimator. And the proposed estimator was used to estimate the effect of chemotherapy on triple-negative breast cancer (TNBC) in real data.ResultsThe simulation studies showed that the bias of the proposed estimator was small, and the coverage rate was close to 95% when any model for propensity score or outcome regression is correctly specified regardless of whether the proportional hazard assumption holds, finite sample size and censoring rate. And the simulation results also showed that even though the propensity score models are misspecified, the bias of the proposed estimator was still small when there is a correct model in candidate outcome regression models. And we applied the proposed estimator in real data, finding that chemotherapy could improve the prognosis of TNBC.ConclusionsThe proposed estimator, allowing multiple propensity score and outcome regression models, provides multiple protection for estimating the difference in survival functions. The proposed estimator provided a new choice when researchers have a "difficult time" choosing only one model for their studies.

Project description:Commonly used semiparametric estimators of causal effects specify parametric models for the propensity score (PS) and the conditional outcome. An example is an augmented inverse probability weighting (IPW) estimator, frequently referred to as a doubly robust estimator, because it is consistent if at least one of the two models is correctly specified. However, in many observational studies, the role of the parametric models is often not to provide a representation of the data-generating process but rather to facilitate the adjustment for confounding, making the assumption of at least one true model unlikely to hold. In this paper, we propose a crude analytical approach to study the large-sample bias of estimators when the models are assumed to be approximations of the data-generating process, namely, when all models are misspecified. We apply our approach to three prototypical estimators of the average causal effect, two IPW estimators, using a misspecified PS model, and an augmented IPW (AIPW) estimator, using misspecified models for the outcome regression (OR) and the PS. For the two IPW estimators, we show that normalization, in addition to having a smaller variance, also offers some protection against bias due to model misspecification. To analyze the question of when the use of two misspecified models is better than one we derive necessary and sufficient conditions for when the AIPW estimator has a smaller bias than a simple IPW estimator and when it has a smaller bias than an IPW estimator with normalized weights. If the misspecification of the outcome model is moderate, the comparisons of the biases of the IPW and AIPW estimators show that the AIPW estimator has a smaller bias than the IPW estimators. However, all biases include a scaling with the PS-model error and we suggest caution in modeling the PS whenever such a model is involved. For numerical and finite sample illustrations, we include three simulation studies and corresponding approximations of the large-sample biases. In a dataset from the National Health and Nutrition Examination Survey, we estimate the effect of smoking on blood lead levels.

Dataset Information

MULTIPLY ROBUST ESTIMATORS OF CAUSAL EFFECTS FOR SURVIVAL OUTCOMES.

Publications

MULTIPLY ROBUST ESTIMATORS OF CAUSAL EFFECTS FOR SURVIVAL OUTCOMES.

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