Inferring the causal effect of a treatment on an outcome in an observational study requires adjusting for observed baseline confounders to avoid bias. However, adjusting for all observed baseline covariates, when only a subset are confounders of the effect of interest, is known to yield potentially inefficient and unstable estimators of the treatment effect. Furthermore, it raises the risk of finite-sample bias and bias due to model misspecification. For these stated reasons, confounder (or covariate) selection is commonly used to determine a subset of the available covariates that is sufficient for confounding adjustment. In this article, we propose a confounder selection strategy that focuses on stable estimation of the treatment effect. In particular, when the propensity score model already includes covariates that are sufficient to adjust for confounding, then the addition of covariates that are associated with either treatment or outcome alone, but not both, should not systematically change the effect estimator. The proposal, therefore, entails first prioritizing covariates for inclusion in the propensity score model, then using a change-in-estimate approach to select the smallest adjustment set that yields a stable effect estimate. The ability of the proposal to correctly select confounders, and to ensure valid inference of the treatment effect following data-driven covariate selection, is assessed empirically and compared with existing methods using simulation studies. We demonstrate the procedure using three different publicly available datasets commonly used for causal inference.
It is important to draw causal inference from observational studies, which, however, becomes challenging if the confounders have missing values. Generally, causal effects are not identifiable if the confounders are missing not at random. We propose a novel framework to nonparametrically identify causal effects with confounders subject to an outcome-independent missingness, that is, the missing data mechanism is independent of the outcome, given the treatment and possibly missing confounders. We then propose a nonparametric two-stage least squares estimator and a parametric estimator for causal…
Mediation analysis is appealing for its ability to improve understanding of the mechanistic drivers of causal effects, but real-world data complexities challenge its successful implementation, including: 1) the existence of post-exposure variables that also affect mediators and outcomes (thus, confounding the mediator-outcome relationship), that may also be 2) multivariate, and 3) the existence of multivariate mediators. Interventional direct and indirect effects (IDE/IIE) accommodate post-exposure variables that confound the mediator-outcome relationship, but currently, no estimator for IDE/I…
Interventional effects for mediation analysis were proposed as a solution to the lack of identifiability of natural (in)direct effects in the presence of a mediator-outcome confounder affected by exposure. We present a theoretical and computational study of the properties of the interventional (in)direct effect estimands based on the efficient influence fucntion (EIF) in the non-parametric statistical model. We use the EIF to develop two asymptotically optimal, non-parametric estimators that leverage data-adaptive regression for estimation of the nuisance parameters: a one-step estimator and a…
The era of big data has witnessed an increasing availability of multiple data sources for statistical analyses. We consider estimation of causal effects combining big main data with unmeasured confounders and smaller validation data with supplementary information on these confounders. Under the unconfoundedness assumption with completely observed confounders, the smaller validation data allow for constructing consistent estimators for causal effects, but the big main data can only give error-prone estimators in general. However, by leveraging the information in the big main data in a principle…
Causal inference in observational studies can be challenging when confounders are subject to missingness. Generally, the identification of causal effects is not guaranteed even under restrictive parametric model assumptions when confounders are missing not at random. To address this, We propose a general framework to establish the identification of causal effects when confounders are subject to treatment-independent missingness, which means that the missing data mechanism is independent of the treatment, given the outcome and possibly missing confounders. We give special consideration to commo…
Interventional effects have been proposed as a solution to the unidentifiability of natural (in)direct effects under mediator-outcome confounders affected by the exposure. Such confounders are an intrinsic characteristic of studies with time-varying exposures and mediators, yet the generalization of the interventional effect framework to the time-varying case has received little attention in the literature. We present an identification result for interventional effects in a general longitudinal data structure that allows flexibility in the specification of treatment-outcome, treatment-mediator…
Given a causal graph, the do-calculus can express treatment effects as functionals of the observational joint distribution that can be estimated empirically. Sometimes the do-calculus identifies multiple valid formulae, prompting us to compare the statistical properties of the corresponding estimators. For example, the backdoor formula applies when all confounders are observed and the frontdoor formula applies when an observed mediator transmits the causal effect. In this paper, we investigate the over-identified scenario where both confounders and mediators are observed, rendering both estima…
Unlike parametric regression, machine learning (ML) methods do not generally require precise knowledge of the true data generating mechanisms. As such, numerous authors have advocated for ML methods to estimate causal effects. Unfortunately, ML algorithms can perform worse than parametric regression. We demonstrate the performance of ML-based single- and double-robust estimators. We use 100 Monte Carlo samples with sample sizes of 200, 1200, and 5000 to investigate bias and confidence interval coverage under several scenarios. In a simple confounding scenario, confounders were related to the t…
Propensity score weighting is a tool for causal inference to adjust for measured confounders. Survey data are often collected under complex sampling designs such as multistage cluster sampling, which presents challenges for propensity score modeling and estimation. In addition, for clustered data, there may also be unobserved cluster effects related to both the treatment and the outcome. When such unmeasured confounders exist and are omitted in the propensity score model, the subsequent propensity score adjustment will be biased. We propose a calibrated propensity score weighting adjustment fo…
Multiple imputation is widely used to handle missing data. Although Rubin's combining rule is simple, it is not clear whether or not the standard multiple imputation inference is consistent when coupled with the commonly-used full sample estimators. This article establishes a unified martingale representation of multiple imputation for a wide class of asymptotically linear full sample estimators. This representation invokes the wild bootstrap inference to provide consistent variance estimation under the correct specification of the imputation models. As a motivating application, we illustrate …
Efficient Nonparametric Inference for Mediation Analysis with Nonignorable Missing Confounders
Institute of Statistics and Big Data, Renmin University of China（中国人民大学统计与大数据研究院）；Center for Applied Statistics and School of Statistics, Renmin University of China（中国人民大学应用统计中心及统计学院）；School of Management and Economics, The Chinese University of Hong Kong, Shenzhen（香港中文大学（深圳）经管学院）
There has been increasing interest in recent years in the development of approaches to estimate causal effects when the number of potential confounders is prohibitively large. This growth in interest has led to a number of potential estimators one could use in this setting. Each of these estimators has different operating characteristics, and it is unlikely that one estimator will outperform all others across all possible scenarios. Coupling this with the fact that an analyst can never know which approach is best for their particular data, we propose a synthetic estimator that averages over a …
Doubly robust estimators of causal effects are a popular means of estimating causal effects. Such estimators combine an estimate of the conditional mean of the outcome given treatment and confounders (the so-called outcome regression) with an estimate of the conditional probability of treatment given confounders (the propensity score) to generate an estimate of the effect of interest. In addition to enjoying the double-robustness property, these estimators have additional benefits. First, flexible regression tools, such as those developed in the field of machine learning, can be utilized to es…
The Doubly Robust (DR) estimation of ATE can be carried out in 2 steps, where in the first step, the treatment and outcome are modeled, and in the second step the predictions are inserted into the DR estimator. The model misspecification in the first step has led researchers to utilize Machine Learning algorithms instead of parametric algorithms. However, existence of strong confounders and/or Instrumental Variables (IVs) can lead the complex ML algorithms to provide perfect predictions for the treatment model which can violate the positivity assumption and elevate the variance of DR estimator…
Propensity score methods are an important tool to help reduce confounding in non-experimental studies. Most propensity score methods assume that covariates are measured without error. However, covariates are often measured with error, which leads to biased causal effect estimates if the true underlying covariates are the actual confounders. Although some studies have investigated the impact of a single mismeasured covariate on estimating a causal effect and proposed methods for handling the measurement error, almost no work exists investigating the case where multiple covariates are mismeasure…
The problem of missingness in observational data is ubiquitous. When the confounders are missing at random, multiple imputation is commonly used; however, the method requires congeniality conditions for valid inferences, which may not be satisfied when estimating average causal treatment effects. Alternatively, fractional imputation, proposed by Kim 2011, has been implemented to handling missing values in regression context. In this article, we develop fractional imputation methods for estimating the average treatment effects with confounders missing at random. We show that the fractional impu…
Causal mediation analysis can improve understanding of the mechanisms underlying epidemiologic associations. However, the utility of natural direct and indirect effect estimation has been limited by the assumption of no confounder of the mediator-outcome relationship that is affected by prior exposure---an assumption frequently violated in practice. We build on recent work that identified alternative estimands that do not require this assumption and propose a flexible and double robust semiparametric targeted minimum loss-based estimator for data-dependent stochastic direct and indirect effect…
We study nonparametric estimation for the partially conditional average treatment effect, defined as the treatment effect function over an interested subset of confounders. We propose a hybrid kernel weighting estimator where the weights aim to control the balancing error of any function of the confounders from a reproducing kernel Hilbert space after kernel smoothing over the subset of interested variables. In addition, we present an augmented version of our estimator which can incorporate estimations of outcome mean functions. Based on the representer theorem, gradient-based algorithms can b…
For observational studies, we study the sensitivity of causal inference when treatment assignments may depend on unobserved confounders. We develop a loss minimization approach for estimating bounds on the conditional average treatment effect (CATE) when unobserved confounders have a bounded effect on the odds ratio of treatment selection. Our approach is scalable and allows flexible use of model classes in estimation, including nonparametric and black-box machine learning methods. Based on these bounds for the CATE, we propose a sensitivity analysis for the average treatment effect (ATE). Our…
Inverse probability of treatment weighting (IPTW) is a popular propensity score (PS)-based approach to estimate causal effects in observational studies at risk of confounding bias. A major issue when estimating the PS is the presence of partially observed covariates. Multiple imputation (MI) is a natural approach to handle missing data on covariates, but its use in the PS context raises three important questions: (i) should we apply Rubin's rules to the IPTW treatment effect estimates or to the PS estimates themselves? (ii) does the outcome have to be included in the imputation model? (iii) ho…
We revisit the classical causal inference problem of estimating the average treatment effect in the presence of fully observed confounding variables using two-stage semiparametric methods. In existing theoretical studies of methods such as G-computation, inverse propensity weighting (IPW), and two common doubly robust estimators -- augmented IPW (AIPW) and targeted maximum likelihood estimation (TMLE) -- they are either bias-dominated, or have similar asymptotic statistical properties. However, when applied to real datasets, they often appear to have notably different variance. We compare thes…
Causal inference has been increasingly reliant on observational studies with rich covariate information. To build tractable causal procedures, such as the doubly robust estimators, it is imperative to first extract important features from high or even ultra-high dimensional data. In this paper, we propose causal ball screening for confounder selection from modern ultra-high dimensional data sets. Unlike the familiar task of variable selection for prediction modeling, our confounder selection procedure aims to control for confounding while improving efficiency in the resulting causal effect est…
New York University（纽约大学）；Columbia University（哥伦比亚大学）
Causal inference from observational data requires assumptions. These assumptions range from measuring confounders to identifying instruments. Traditionally, causal inference assumptions have focused on estimation of effects for a single treatment. In this work, we construct techniques for estimation with multiple treatments in the presence of unobserved confounding. We develop two assumptions based on shared confounding between treatments and independence of treatments given the confounder. Together, these assumptions lead to a confounder estimator regularized by mutual information. For this e…
This paper studies the confounding effects from the unmeasured confounders and the imbalance of observed confounders in IV regression and aims at unbiased causal effect estimation. Recently, nonlinear IV estimators were proposed to allow for nonlinear model in both stages. However, the observed confounders may be imbalanced in stage 2, which could still lead to biased treatment effect estimation in certain cases. To this end, we propose a Confounder Balanced IV Regression (CB-IV) algorithm to jointly remove the bias from the unmeasured confounders and the imbalance of observed confounders. The…
Relationship between two popular modeling frameworks of causal inference from observational data, namely, causal graphical model and potential outcome causal model is discussed. How some popular causal effect estimators found in applications of the potential outcome causal model, such as inverse probability of treatment weighted estimator and doubly robust estimator can be obtained by using the causal graphical model is shown. We confine to the simple case of binary outcome and treatment variables with discrete confounders and it is shown how to generalize results to cases of continuous variab…
Proximal Mediation Analysis with Unmeasured Treatment-Induced Confounding
Center for Applied Statistics and School of Statistics, Renmin University of China（中国人民大学统计学院与应用统计中心）；Department of Biostatistics & Medical Informatics, University of Wisconsin-Madison（威斯康星大学麦迪逊分校生物统计与医学信息学系）
We study the problem of learning conditional average treatment effects (CATE) from observational data with unobserved confounders. The CATE function maps baseline covariates to individual causal effect predictions and is key for personalized assessments. Recent work has focused on how to learn CATE under unconfoundedness, i.e., when there are no unobserved confounders. Since CATE may not be identified when unconfoundedness is violated, we develop a functional interval estimator that predicts bounds on the individual causal effects under realistic violations of unconfoundedness. Our estimator t…
National University of Singapore（新加坡国立大学）；London School of Economics and Political Science（伦敦政治经济学院）
This work extends causal inference with stochastic confounders. We propose a new approach to variational estimation for causal inference based on a representer theorem with a random input space. We estimate causal effects involving latent confounders that may be interdependent and time-varying from sequential, repeated measurements in an observational study. Our approach extends current work that assumes independent, non-temporal latent confounders, with potentially biased estimators. We introduce a simple yet elegant algorithm without parametric specification on model components. Our method a…
Instrumental variable (IV) methods are widely used for estimating average treatment effects in the presence of unmeasured confounders. However, the capability of existing IV procedures, and most notably the two-stage residual inclusion (2SRI) procedure recommended for use in nonlinear contexts, to account for unmeasured confounders in the Cox proportional hazard model is unclear. We show that instrumenting an endogenous treatment induces an unmeasured covariate, referred to as an individual frailty in survival analysis parlance, which if not accounted for leads to bias. We propose a new proced…
High-dimensional data can be useful for causal inference by providing many confounders that may bolster the plausibility of the ignorability assumption. Propensity score methods are powerful tools for causal inference, are popular in health care research, and are particularly useful for high-dimensional data. Recent interest has surrounded a Bayesian formulation of these methods in order to flexibly estimate propensity scores and summarize posterior quantities while incorporating variance from the (potentially high-dimensional) treatment model. We discuss methods for Bayesian propensity score …
Propensity score weighting is a tool for causal inference to adjust for measured confounders in observational studies. In practice, data often present complex structures, such as clustering, which make propensity score modeling and estimation challenging. In addition, for clustered data, there may be unmeasured cluster-specific variables that are related to both the treatment assignment and the outcome. When such unmeasured cluster-specific confounders exist and are omitted in the propensity score model, the subsequent propensity score adjustment may be biased. In this article, we propose a ca…
Estimating average causal effect (ACE) is useful whenever we want to know the effect of an intervention on a given outcome. In the absence of a randomized experiment, many methods such as stratification and inverse propensity weighting have been proposed to estimate ACE. However, it is hard to know which method is optimal for a given dataset or which hyperparameters to use for a chosen method. To this end, we provide a framework to characterize the loss of a causal inference method against the true ACE, by framing causal inference as a representation learning problem. We show that many popular…
We consider the problem of constructing bounds on the average treatment effect (ATE) when unmeasured confounders exist but have bounded influence. Specifically, we assume that omitted confounders could not change the odds of treatment for any unit by more than a fixed factor. We derive the sharp partial identification bounds implied by this assumption by leveraging distributionally robust optimization, and we propose estimators of these bounds with several novel robustness properties. The first is double sharpness: our estimators consistently estimate the sharp ATE bounds when one of two nuisa…
Assessing treatment effects in observational data with missing confounders: A comparative study of practical doubly-robust and traditional missing data methods
Kaiser Permanente Washington Health Research Institute（凯撒永久华盛顿健康研究所）；University of Washington（华盛顿大学）；TL Revolution, LLC（TL革命有限责任公司）；Vanderbilt University（范德堡大学）；University of California at Berkeley（加州大学伯克利分校）；University of Auckland（奥克兰大学）；US Food and Drug Administration（美国食品药品监督管理局）
