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Eric Tchetgen Tchetgen

Publications and source records attributed to Eric Tchetgen Tchetgen.

At least 37 records · Page 2Linked to original sources

Modeling Interference Via Symmetric Treatment Decomposition

Classical causal inference assumes treatments meant for a given unit do not have an effect on other units. This assumption is violated in interference problems, where new types of spillover causal effects arise, and causal inference becomes much more difficult. In addition, interference introduces a unique complication where variables may transmit treatment influences to each other, which is a relationship that has some features of a causal one, but is symmetric. In this paper, we develop a new approach to decomposing the spillover effect into unit-specific components that extends the DAG based treatment decomposition approach to mediation of Robins and Richardson to causal models that admit stable symmetric relationships among variables in a network. We discuss two interpretations of such models: a network structural model interpretation, and an interpretation based on equilibrium of structural equation models discussed in (Lauritzen and Richardson, 2002). We show that both interpretations yield identical identification theory, and give conditions for components of the spillover effect to be identified. We discuss statistical inference for identified components of the spillover effect, including a maximum likelihood estimator, and a doubly robust estimator for the special case of two interacting outcomes. We verify consistency and robustness of our estimators via a simulation study, and illustrate our method by assessing the causal effect of education attainment on depressive symptoms using the data on households from the Wisconsin Longitudinal Study.

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A confounding bridge approach for double negative control inference on causal effects

Unmeasured confounding is a key challenge for causal inference. In this paper, we establish a framework for unmeasured confounding adjustment with negative control variables. A negative control outcome is associated with the confounder but not causally affected by the exposure in view, and a negative control exposure is correlated with the primary exposure or the confounder but does not causally affect the outcome of interest. We introduce an outcome confounding bridge function that depicts the relationship between the confounding effects on the primary outcome and the negative control outcome, and we incorporate a negative control exposure to identify the bridge function and the average causal effect. We also consider the extension to the positive control setting by allowing for nonzero causal effect of the primary exposure on the control outcome. We illustrate our approach with simulations and apply it to a study about the short-term effect of air pollution on mortality. Although a standard analysis shows a significant acute effect of PM2.5 on mortality, our analysis indicates that this effect may be confounded, and after double negative control adjustment, the effect is attenuated toward zero.

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Efficient and Multiply Robust Risk Estimation under General Forms of Dataset Shift

Statistical machine learning methods often face the challenge of limited data available from the population of interest. One remedy is to leverage data from auxiliary source populations, which share some conditional distributions or are linked in other ways with the target domain. Techniques leveraging such \emph{dataset shift} conditions are known as \emph{domain adaptation} or \emph{transfer learning}. Despite extensive literature on dataset shift, limited works address how to efficiently use the auxiliary populations to improve the accuracy of risk evaluation for a given machine learning task in the target population. In this paper, we study the general problem of efficiently estimating target population risk under various dataset shift conditions, leveraging semiparametric efficiency theory. We consider a general class of dataset shift conditions, which includes three popular conditions -- covariate, label and concept shift -- as special cases. We allow for partially non-overlapping support between the source and target populations. We develop efficient and multiply robust estimators along with a straightforward specification test of these dataset shift conditions. We also derive efficiency bounds for two other dataset shift conditions, posterior drift and location-scale shift. Simulation studies support the efficiency gains due to leveraging plausible dataset shift conditions.

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Doubly Robust Proximal Synthetic Controls

To infer the treatment effect for a single treated unit using panel data, synthetic control methods construct a linear combination of control units' outcomes that mimics the treated unit's pre-treatment outcome trajectory. This linear combination is subsequently used to impute the counterfactual outcomes of the treated unit had it not been treated in the post-treatment period, and used to estimate the treatment effect. Existing synthetic control methods rely on correctly modeling certain aspects of the counterfactual outcome generating mechanism and may require near-perfect matching of the pre-treatment trajectory. Inspired by proximal causal inference, we obtain two novel nonparametric identifying formulas for the average treatment effect for the treated unit: one is based on weighting, and the other combines models for the counterfactual outcome and the weighting function. We introduce the concept of covariate shift to synthetic controls to obtain these identification results conditional on the treatment assignment. We also develop two treatment effect estimators based on these two formulas and the generalized method of moments. One new estimator is doubly robust: it is consistent and asymptotically normal if at least one of the outcome and weighting models is correctly specified. We demonstrate the performance of the methods via simulations and apply them to evaluate the effectiveness of a Pneumococcal conjugate vaccine on the risk of all-cause pneumonia in Brazil.

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Single Proxy Control

Negative control variables are sometimes used in non-experimental studies to detect the presence of confounding by hidden factors. A negative control outcome (NCO) is an outcome that is influenced by unobserved confounders of the exposure effects on the outcome in view, but is not causally impacted by the exposure. Tchetgen Tchetgen (2013) introduced the Control Outcome Calibration Approach (COCA) as a formal NCO counterfactual method to detect and correct for residual confounding bias. For identification, COCA treats the NCO as an error-prone proxy of the treatment-free counterfactual outcome of interest, and involves regressing the NCO on the treatment-free counterfactual, together with a rank-preserving structural model which assumes a constant individual-level causal effect. In this work, we establish nonparametric COCA identification for the average causal effect for the treated, without requiring rank-preservation, therefore accommodating unrestricted effect heterogeneity across units. This nonparametric identification result has important practical implications, as it provides single proxy confounding control, in contrast to recently proposed proximal causal inference, which relies for identification on a pair of confounding proxies. For COCA estimation we propose three separate strategies: (i) an extended propensity score approach, (ii) an outcome bridge function approach, and (iii) a doubly-robust approach. Finally, we illustrate the proposed methods in an application evaluating the causal impact of a Zika virus outbreak on birth rate in Brazil.

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Forster-Warmuth Counterfactual Regression: A Unified Learning Approach

Series or orthogonal basis regression is one of the most popular non-parametric regression techniques in practice, obtained by regressing the response on features generated by evaluating the basis functions at observed covariate values. The most routinely used series estimator is based on ordinary least squares fitting, which is known to be minimax rate optimal in various settings, albeit under stringent restrictions on the basis functions and the distribution of covariates. In this work, inspired by the recently developed Forster-Warmuth (FW) learner, we propose an alternative series regression estimator that can attain the minimax estimation rate under strictly weaker conditions imposed on the basis functions and the joint law of covariates, than existing series estimators in the literature. Moreover, a key contribution of this work generalizes the FW-learner to a so-called counterfactual regression problem, in which the response variable of interest may not be directly observed (hence, the name ``counterfactual'') on all sampled units, and therefore needs to be inferred in order to identify and estimate the regression in view from the observed data. Although counterfactual regression is not entirely a new area of inquiry, we propose the first-ever systematic study of this challenging problem from a unified pseudo-outcome perspective. In fact, we provide what appears to be the first generic and constructive approach for generating the pseudo-outcome (to substitute for the unobserved response) which leads to the estimation of the counterfactual regression curve of interest with small bias, namely bias of second order. Several applications are used to illustrate the resulting FW-learner including many nonparametric regression problems in missing data and causal inference literature, for which we establish high-level conditions for minimax rate optimality of the proposed FW-learner.

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GENIUS-MAWII: For Robust Mendelian Randomization with Many Weak Invalid Instruments

Mendelian randomization (MR) has become a popular approach to study causal effects by using genetic variants as instrumental variables. We propose a new MR method, GENIUS-MAWII, which simultaneously addresses the two salient phenomena that adversely affect MR analyses: many weak instruments and widespread horizontal pleiotropy. Similar to MR GENIUS (Tchetgen Tchetgen et al., 2021), we achieve identification of the treatment effect by leveraging heteroscedasticity of the exposure. We then derive the class of influence functions of the treatment effect, based on which, we construct a continuous updating estimator and establish its consistency and asymptotic normality under a many weak invalid instruments asymptotic regime by developing novel semiparametric theory. We also provide a measure of weak identification, an overidentification test, and a graphical diagnostic tool. We demonstrate in simulations that GENIUS-MAWII has clear advantages in the presence of directional or correlated horizontal pleiotropy compared to other methods. We apply our method to study the effect of body mass index on systolic blood pressure using UK Biobank.

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Proximal Causal Inference without Uniqueness Assumptions

We consider identification and inference about a counterfactual outcome mean when there is unmeasured confounding using tools from proximal causal inference (Miao et al. [2018], Tchetgen Tchetgen et al. [2020]). Proximal causal inference requires existence of solutions to at least one of two integral equations. We motivate the existence of solutions to the integral equations from proximal causal inference by demonstrating that, assuming the existence of a solution to one of the integral equations, $\sqrt{n}$-estimability of a linear functional (such as its mean) of that solution requires the existence of a solution to the other integral equation. Solutions to the integral equations may not be unique, which complicates estimation and inference. We construct a consistent estimator for the solution set for one of the integral equations and then adapt the theory of extremum estimators to find from the estimated set a consistent estimator for a uniquely defined solution. A debiased estimator for the counterfactual mean is shown to be root-$n$ consistent, regular, and asymptotically semiparametrically locally efficient under additional regularity conditions.

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Selective machine learning of doubly robust functionals

While model selection is a well-studied topic in parametric and nonparametric regression or density estimation, selection of possibly high-dimensional nuisance parameters in semiparametric problems is far less developed. In this paper, we propose a selective machine learning framework for making inferences about a finite-dimensional functional defined on a semiparametric model, when the latter admits a doubly robust estimating function and several candidate machine learning algorithms are available for estimating the nuisance parameters. We introduce a new selection criterion aimed at bias reduction in estimating the functional of interest based on a novel definition of pseudo-risk inspired by the double robustness property. Intuitively, the proposed criterion selects a pair of learners with the smallest pseudo-risk, so that the estimated functional is least sensitive to perturbations of a nuisance parameter. We establish an oracle property for a multi-fold cross-validation version of the new selection criterion which states that our empirical criterion performs nearly as well as an oracle with a priori knowledge of the pseudo-risk for each pair of candidate learners. Finally, we apply the approach to model selection of a semiparametric estimator of average treatment effect given an ensemble of candidate machine learners to account for confounding in an observational study which we illustrate in simulations and a data application.

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Universal Difference-in-Differences for Causal Inference in Epidemiology

Difference-in-differences is undoubtedly one of the most widely used methods for evaluating the causal effect of an intervention in observational (i.e., nonrandomized) settings. The approach is typically used when pre- and post-exposure outcome measurements are available, and one can reasonably assume that the association of the unobserved confounder with the outcome has the same absolute magnitude in the two exposure arms, and is constant over time; a so-called parallel trends assumption. The parallel trends assumption may not be credible in many practical settings, including if the outcome is binary, a count, or polytomous, as well as when an uncontrolled confounder exhibits non-additive effects on the distribution of the outcome, even if such effects are constant over time. We introduce an alternative approach that replaces the parallel trends assumption with an odds ratio equi-confounding assumption under which an association between treatment and the potential outcome under no-treatment is identified with a well-specified generalized linear model relating the pre-exposure outcome and the exposure. Because the proposed method identifies any causal effect that is conceivably identified in the absence of confounding bias, including nonlinear effects such as quantile treatment effects, the approach is aptly called Universal Difference-in-differences (UDiD). Both fully parametric and more robust semiparametric UDiD estimators are described and illustrated in a real-world application concerning the causal effects of a Zika virus outbreak on birth rate in Brazil.

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Higher Order Estimating Equations for High-dimensional Models

We introduce a new method of estimation of parameters in semiparametric and nonparametric models. The method is based on estimating equations that are $U$-statistics in the observations. The $U$-statistics are based on higher order influence functions that extend ordinary linear influence functions of the parameter of interest, and represent higher derivatives of this parameter. For parameters for which the representation cannot be perfect the method leads to a bias-variance trade-off, and results in estimators that converge at a slower than $\sqrt n$-rate. In a number of examples the resulting rate can be shown to be optimal. We are particularly interested in estimating parameters in models with a nuisance parameter of high dimension or low regularity, where the parameter of interest cannot be estimated at $\sqrt n$-rate, but we also consider efficient $\sqrt n$-estimation using novel nonlinear estimators. The general approach is applied in detail to the example of estimating a mean response when the response is not always observed.

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Prediction Sets Adaptive to Unknown Covariate Shift

Predicting sets of outcomes -- instead of unique outcomes -- is a promising solution to uncertainty quantification in statistical learning. Despite a rich literature on constructing prediction sets with statistical guarantees, adapting to unknown covariate shift -- a prevalent issue in practice -- poses a serious unsolved challenge. In this paper, we show that prediction sets with finite-sample coverage guarantee are uninformative and propose a novel flexible distribution-free method, PredSet-1Step, to efficiently construct prediction sets with an asymptotic coverage guarantee under unknown covariate shift. We formally show that our method is \textit{asymptotically probably approximately correct}, having well-calibrated coverage error with high confidence for large samples. We illustrate that it achieves nominal coverage in a number of experiments and a data set concerning HIV risk prediction in a South African cohort study. Our theory hinges on a new bound for the convergence rate of the coverage of Wald confidence intervals based on general asymptotically linear estimators.

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Double Negative Control Inference in Test-Negative Design Studies of Vaccine Effectiveness

The test-negative design (TND) has become a standard approach to evaluate vaccine effectiveness against the risk of acquiring infectious diseases in real-world settings, such as Influenza, Rotavirus, Dengue fever, and more recently COVID-19. In a TND study, individuals who experience symptoms and seek care are recruited and tested for the infectious disease which defines cases and controls. Despite TND's potential to reduce unobserved differences in healthcare seeking behavior (HSB) between vaccinated and unvaccinated subjects, it remains subject to various potential biases. First, residual confounding may remain due to unobserved HSB, occupation as healthcare worker, or previous infection history. Second, because selection into the TND sample is a common consequence of infection and HSB, collider stratification bias may exist when conditioning the analysis on tested samples, which further induces confounding by latent HSB. In this paper, we present a novel approach to identify and estimate vaccine effectiveness in the target population by carefully leveraging a pair of negative control exposure and outcome variables to account for potential hidden bias in TND studies. We illustrate our proposed method with extensive simulations and an application to study COVID-19 vaccine effectiveness using data from the University of Michigan Health System.

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Semiparametric proximal causal inference

Skepticism about the assumption of no unmeasured confounding, also known as exchangeability, is often warranted in making causal inferences from observational data; because exchangeability hinges on an investigator's ability to accurately measure covariates that capture all potential sources of confounding. In practice, the most one can hope for is that covariate measurements are at best proxies of the true underlying confounding mechanism operating in a given observational study. In this paper, we consider the framework of proximal causal inference introduced by Miao et al. (2018); Tchetgen Tchetgen et al. (2020), which while explicitly acknowledging covariate measurements as imperfect proxies of confounding mechanisms, offers an opportunity to learn about causal effects in settings where exchangeability on the basis of measured covariates fails. We make a number of contributions to proximal inference including (i) an alternative set of conditions for nonparametric proximal identification of the average treatment effect; (ii) general semiparametric theory for proximal estimation of the average treatment effect including efficiency bounds for key semiparametric models of interest; (iii) a characterization of proximal doubly robust and locally efficient estimators of the average treatment effect. Moreover, we provide analogous identification and efficiency results for the average treatment effect on the treated. Our approach is illustrated via simulation studies and a data application on evaluating the effectiveness of right heart catheterization in the intensive care unit of critically ill patients.

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Theory for identification and Inference with Synthetic Controls: A Proximal Causal Inference Framework

Synthetic control (SC) methods are commonly used to estimate the treatment effect on a single treated unit in panel data settings. An SC is a weighted average of control units built to match the treated unit, with weights typically estimated by regressing (summaries of) pre-treatment outcomes and measured covariates of the treated unit to those of the control units. However, it has been established that in the absence of a good fit, such regression estimator will generally perform poorly. In this paper, we introduce a proximal causal inference framework to formalize identification and inference for both the SC and ultimately the treatment effect on the treated, based on the observation that control units not contributing to the construction of an SC can be repurposed as proxies of latent confounders. We view the difference in the post-treatment outcomes between the treated unit and the SC as a time series, which opens the door to various time series methods for treatment effect estimation. The proposed framework can accommodate nonlinear models, which allows for binary and count outcomes that are understudied in the SC literature. We illustrate with simulation studies and an application to evaluation of the 1990 German Reunification.

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Causal Inference with Hidden Mediators

Proximal causal inference was recently proposed as a framework to identify causal effects from observational data in the presence of hidden confounders for which proxies are available. In this paper, we extend the proximal causal inference approach to settings where identification of causal effects hinges upon a set of mediators which are not observed, yet error prone proxies of the hidden mediators are measured. Specifically, (i) We establish causal hidden mediation analysis, which extends classical causal mediation analysis methods for identifying natural direct and indirect effects under no unmeasured confounding to a setting where the mediator of interest is hidden, but proxies of it are available. (ii) We establish hidden front-door criterion, which extends the classical front-door criterion to allow for hidden mediators for which proxies are available. (iii) We show that the identification of a certain causal effect called population intervention indirect effect remains possible with hidden mediators in settings where challenges in (i) and (ii) might co-exist. We view (i)-(iii) as important steps towards the practical application of front-door criteria and mediation analysis as mediators are almost always measured with error and thus, the most one can hope for in practice is that the measurements are at best proxies of mediating mechanisms. We propose identification approaches for the parameters of interest in our considered models. For the estimation aspect, we propose an influence function-based estimation method and provide an analysis for the robustness of the estimators.

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Doubly Robust Calibration of Prediction Sets under Covariate Shift

Conformal prediction has received tremendous attention in recent years and has offered new solutions to problems in missing data and causal inference; yet these advances have not leveraged modern semiparametric efficiency theory for more robust and efficient uncertainty quantification. In this paper, we consider the problem of obtaining distribution-free prediction regions accounting for a shift in the distribution of the covariates between the training and test data. Under an explainable covariate shift assumption analogous to the standard missing at random assumption, we propose three variants of a general framework to construct well-calibrated prediction regions for the unobserved outcome in the test sample. Our approach is based on the efficient influence function for the quantile of the unobserved outcome in the test population combined with an arbitrary machine learning prediction algorithm, without compromising asymptotic coverage. Next, we extend our approach to account for departure from the explainable covariate shift assumption in a semiparametric sensitivity analysis for potential latent covariate shift. In all cases, we establish that the resulting prediction sets eventually attain nominal average coverage in large samples. This guarantee is a consequence of the product bias form of our proposal which implies correct coverage if either the propensity score or the conditional distribution of the response is estimated sufficiently well. Our results also provide a framework for construction of doubly robust prediction sets of individual treatment effects, under both unconfoundedness and allowing for some degree of unmeasured confounding. Finally, we discuss aggregation of prediction sets from different machine learning algorithms for optimal prediction and illustrate the performance of our methods in both synthetic and real data.

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