Unmeasured confounding is a threat to causal inference and individualized decision making. Similar to Cui and Tchetgen Tchetgen (2020); Qiu et al. (2020); Han (2020a), we consider the problem of identification of optimal individualized treatment regimes with a valid instrumental variable. Han (2020a) provided an alternative identifying condition of optimal treatment regimes using the conditional Wald estimand of Cui and Tchetgen Tchetgen (2020); Qiu et al. (2020) when treatment assignment is subject to endogeneity and a valid binary instrumental variable is available. In this note, we provide a necessary and sufficient condition for identification of optimal treatment regimes using the conditional Wald estimand. Our novel condition is necessarily implied by those of Cui and Tchetgen Tchetgen (2020); Qiu et al. (2020); Han (2020a) and may continue to hold in a variety of potential settings not covered by prior results.
The instrumental variable method consistently estimates the effect of a treatment when there is unmeasured confounding and a valid instrumental variable. A valid instrumental variable is a variable that is independent of unmeasured confounders and affects the treatment but does not have a direct effect on the outcome beyond its effect on the treatment. Two commonly used estimators for using an instrumental variable to estimate a treatment effect are the two stage least squares estimator and the control function estimator. For linear causal effect models, these two estimators are equivalent, bu…
In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment switching might substantially bias the evaluation of treatment efficacy or safety. To account for treatment switching, instrumental variable (IV) methods by leveraging the initial randomized assignment as an IV serve as natural adjustment methods because they allow dependent treatment switching possibly due to underlying prognoses. However, the ``exclusion restric…
There is a fast-growing literature on estimating optimal treatment regimes based on randomized trials or observational studies under a key identifying condition of no unmeasured confounding. Because confounding by unmeasured factors cannot generally be ruled out with certainty in observational studies or randomized trials subject to noncompliance, we propose a general instrumental variable approach to learning optimal treatment regimes under endogeneity. Specifically, we establish identification of both value function $E[Y_{\mathcal{D}(L)}]$ for a given regime $\mathcal{D}$ and optimal regimes…
Consider the problem of estimating the local average treatment effect with an instrument variable, where the instrument unconfoundedness holds after adjusting for a set of measured covariates. Several unknown functions of the covariates need to be estimated through regression models, such as instrument propensity score and treatment and outcome regression models. We develop a computationally tractable method in high-dimensional settings where the numbers of regression terms are close to or larger than the sample size. Our method exploits regularized calibrated estimation, which involves Lasso …
The method of instrumental variables provides a fundamental and practical tool for causal inference in many empirical studies where unmeasured confounding between the treatments and the outcome is present. Modern data such as the genetical genomics data from these studies are often high-dimensional. The high-dimensional linear instrumental-variables regression has been considered in the literature due to its simplicity albeit a true nonlinear relationship may exist. We propose a more data-driven approach by considering the nonparametric additive models between the instruments and the treatment…
Instrumental variable (IV) methods are widely used to adjust for the bias in estimating treatment effects caused by unmeasured confounders in observational studies. In this manuscript, we provide empirical and theoretical evidence that the IV methods may result in biased treatment effects if applied on a data set in which subjects are preselected based on their received treatments. We frame this as a selection bias problem and propose a procedure that identifies the treatment effect of interest as a function of a vector of sensitivity parameters. We also list assumptions under which analyzing …
Instrumental variables are widely used to deal with unmeasured confounding in observational studies and imperfect randomized controlled trials. In these studies, researchers often target the so-called local average treatment effect as it is identifiable under mild conditions. In this paper, we consider estimation of the local average treatment effect under the binary instrumental variable model. We discuss the challenges for causal estimation with a binary outcome, and show that surprisingly, it can be more difficult than the case with a continuous outcome. We propose novel modeling and estima…
We propose the instrumental variable regime (IVR) method to estimate the causal effects of multiple sequential treatments. This method serves to address the problem of endogenous selections of sequential treatments. An IVR is a sequence of instrumental variables in which each IV instruments for an endogenous treatment variable. Our proposed method generalizes the LATE model in Imbens and Angrist (1994) from a single treatment to many treatments applied sequentially. More precisely, with the IVR this model allows for estimating the local average treatment regime effects (LATRE), possibly condit…
This paper considers the instrumental variable quantile regression model (Chernozhukov and Hansen, 2005, 2013) with a binary endogenous treatment. It offers two identification results when the treatment status is not directly observed. The first result is that, remarkably, the reduced-form quantile regression of the outcome variable on the instrumental variable provides a lower bound on the structural quantile treatment effect under the stochastic monotonicity condition (Small and Tan, 2007; DiNardo and Lee, 2011). This result is relevant, not only when the treatment variable is subject to mis…
In observational studies, treatments are typically not randomized and therefore estimated treatment effects may be subject to confounding bias. The instrumental variable (IV) design plays the role of a quasi-experimental handle since the IV is associated with the treatment and only affects the outcome through the treatment. In this paper, we present a novel framework for identification and inference using an IV for the marginal average treatment effect amongst the treated (ETT) in the presence of unmeasured confounding. For inference, we propose three different semiparametric approaches: (i) i…
Robins 1997 introduced marginal structural models (MSMs), a general class of counterfactual models for the joint effects of time-varying treatment regimes in complex longitudinal studies subject to time-varying confounding. In his work, identification of MSM parameters is established under a sequential randomization assumption (SRA), which rules out unmeasured confounding of treatment assignment over time. We consider sufficient conditions for identification of the parameters of a subclass, Marginal Structural Mean Models (MSMMs), when sequential randomization fails to hold due to unmeasured c…
This paper discusses endogenous treatment models with duration outcomes, competing risks and random right censoring. The endogeneity issue is solved using a discrete instrumental variable. We show that the competing risks model generates a non-parametric quantile instrumental regression problem. The cause-specific cumulative incidence, the cause-specific hazard and the subdistribution hazard can be recovered from the regression function. A distinguishing feature of the model is that censoring and competing risks prevent identification at some quantiles. We characterize the set of quantiles for…
This paper considers identification and estimation of the causal effect of the time Z until a subject is treated on a survival outcome T. The treatment is not randomly assigned, T is randomly right censored by a random variable C and the time to treatment Z is right censored by min(T,C). The endogeneity issue is treated using an instrumental variable explaining Z and independent of the error term of the model. We study identification in a fully nonparametric framework. We show that our specification generates an integral equation, of which the regression function of interest is a solution. We …
Estimating the causal effect of a treatment or exposure for a subpopulation is of great interest in many biomedical and economical studies. Expected shortfall, also referred to as the super-quantile, is an attractive effect-size measure that can accommodate data heterogeneity and aggregate local information of effect over a certain region of interest of the outcome distribution. In this article, we propose the ComplieR Expected Shortfall Treatment Effect (CRESTE) model under an instrumental variable framework to quantity the CRESTE for a binary endogenous treatment variable. By utilizing the s…
Instrumental variables (IV) estimation suffers selection bias when the analysis conditions on the treatment. Judea Pearl's early graphical definition of instrumental variables explicitly prohibited conditioning on the treatment. Nonetheless, the practice remains common. In this paper, we derive exact analytic expressions for IV selection bias across a range of data-generating models, and for various selection-inducing procedures. We present four sets of results for linear models. First, IV selection bias depends on the conditioning procedure (covariate adjustment vs. sample truncation). Second…
Instrumental variable is an essential tool for addressing unmeasured confounding in observational studies. Two stage predictor substitution (2SPS) estimator and two stage residual inclusion(2SRI) are two commonly used approaches in applying instrumental variables. Recently 2SPS was studied under the additive hazards model in the presence of competing risks of time-to-events data, where linearity was assumed for the relationship between the treatment and the instrument variable. This assumption may not be the most appropriate when we have binary treatments. In this paper, we consider the 2SRI e…
IV regression in the context of a re-sampling is considered in the work. Comparatively, the contribution in the development is a structural identification in the IV model. The work also contains a multiplier-bootstrap justification.
Suppose one is interested in estimating causal effects in the presence of potentially unmeasured confounding with the aid of a valid instrumental variable. This paper investigates the problem of making inferences about the average treatment effect when data are fused from two separate sources, one of which contains information on the treatment and the other contains information on the outcome, while values for the instrument and a vector of baseline covariates are recorded in both. We provide a general set of sufficient conditions under which the average treatment effect is nonparametrically i…
Instrumental variable methods can identify causal effects even when the treatment and outcome are confounded. We study the problem of imperfect measurements of the binary instrumental variable, treatment or outcome. We first consider non-differential measurement errors, that is, the mis-measured variable does not depend on other variables given its true value. We show that the measurement error of the instrumental variable does not bias the estimate, the measurement error of the treatment biases the estimate away from zero, and the measurement error of the outcome biases the estimate toward ze…
Efficient semiparametric estimation of marginal treatment effects with genetic instrumental variables
MRC Biostatistics Unit, University of Cambridge（剑桥大学 MRC 生物统计单元）；Department of Economics, University of Oxford（牛津大学经济系）；Cardiovascular Epidemiology Unit, University of Cambridge（剑桥大学心血管流行病学单元）
This paper analyzes the effect of a discrete treatment Z on a duration T. The treatment is not randomly assigned. The confounding issue is treated using a discrete instrumental variable explaining the treatment and independent of the error term of the model. Our framework is nonparametric and allows for random right censoring. This specification generates a nonlinear inverse problem and the average treatment effect is derived from its solution. We provide local and global identification properties that rely on a nonlinear system of equations. We propose an estimation procedure to solve this sy…
Measurement error is ubiquitous in many variables - from blood pressure recordings in physiology to intelligence measures in psychology. Structural equation models (SEMs) account for the process of measurement by explicitly distinguishing between latent variables and their measurement indicators. Users often fit entire SEMs to data, but this can fail if some model parameters are not identified. The model-implied instrumental variables (MIIVs) approach is a more flexible alternative that can estimate subsets of model parameters in identified equations. Numerous methods to identify individual pa…
Instrumental variables are commonly used to estimate effects of a treatment afflicted by unmeasured confounding, and in practice instruments are often continuous (e.g., measures of distance, or treatment preference). However, available methods for continuous instruments have important limitations: they either require restrictive parametric assumptions for identification, or else rely on modeling both the outcome and treatment process well (and require modeling effect modification by all adjustment covariates). In this work we develop the first semiparametric doubly robust estimators of the loc…
Zhejiang University（浙江大学）；Emory University（埃默里大学）；Tsinghua University（清华大学）；Shanghai AI Laboratory（上海人工智能实验室）；Shanghai Institute for Advanced Study of Zhejiang University（浙江大学上海高等研究院）
The advent of the big data era brought new opportunities and challenges to draw treatment effect in data fusion, that is, a mixed dataset collected from multiple sources (each source with an independent treatment assignment mechanism). Due to possibly omitted source labels and unmeasured confounders, traditional methods cannot estimate individual treatment assignment probability and infer treatment effect effectively. Therefore, we propose to reconstruct the source label and model it as a Group Instrumental Variable (GIV) to implement IV-based Regression for treatment effect estimation. In thi…
One of the most common mistakes made when performing data analysis is attributing causal meaning to regression coefficients. Formally, a causal effect can only be computed if it is identifiable from a combination of observational data and structural knowledge about the domain under investigation (Pearl, 2000, Ch. 5). Building on the literature of instrumental variables (IVs), a plethora of methods has been developed to identify causal effects in linear systems. Almost invariably, however, the most powerful such methods rely on exponential-time procedures. In this paper, we investigate graphica…
University of Pennsylvania（宾夕法尼亚大学）；University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；Washington University in St. Louis（圣路易斯华盛顿大学）；Harvard T.H. Chan School of Public Health（哈佛大学陈曾熙公共卫生学院）
Instrumental variables (IVs) are widely used for estimating causal effects in the presence of unmeasured confounding. Under the standard IV model, however, the average treatment effect (ATE) is only partially identifiable. To address this, we propose novel assumptions that allow for identification of the ATE. Our identification assumptions are clearly separated from model assumptions needed for estimation, so that researchers are not required to commit to a specific observed data model in establishing identification. We then construct multiple estimators that are consistent under three differe…
Individualized treatment rules (ITRs) are considered a promising recipe to deliver better policy interventions. One key ingredient in optimal ITR estimation problems is to estimate the average treatment effect conditional on a subject's covariate information, which is often challenging in observational studies due to the universal concern of unmeasured confounding. Instrumental variables (IVs) are widely-used tools to infer the treatment effect when there is unmeasured confounding between the treatment and outcome. In this work, we propose a general framework of approaching the optimal ITR est…
The primary analysis of randomized screening trials for cancer typically adheres to the intention-to-screen principle, measuring cancer-specific mortality reductions between screening and control arms. These mortality reductions result from a combination of the screening regimen, screening technology and the effect of the early, screening-induced, treatment. This motivates addressing these different aspects separately. Here we are interested in the causal effect of early versus delayed treatments on cancer mortality among the screening-detectable subgroup, which under certain assumptions is es…
This paper studies the identifying power of an instrumental variable in the nonparametric heterogeneous treatment effect framework when a binary treatment is mismeasured and endogenous. Using a binary instrumental variable, I characterize the sharp identified set for the local average treatment effect under the exclusion restriction of an instrument and the deterministic monotonicity of the true treatment in the instrument. Even allowing for general measurement error (e.g., the measurement error is endogenous), it is still possible to obtain finite bounds on the local average treatment effect.…
In randomized trials, researchers are often interested in mediation analysis to understand how a treatment works, in particular how much of a treatment's effect is mediated by an intermediated variable and how much the treatment directly affects the outcome not through the mediator. The standard regression approach to mediation analysis assumes sequential ignorability of the mediator, that is that the mediator is effectively randomly assigned given baseline covariates and the randomized treatment. Since the experiment does not randomize the mediator, sequential ignorability is often not plausi…
Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjus…
We propose a generalization of the recently developed system identification method called Sign-Perturbed Sums (SPS). The proposed construction is based on the instrumental variables estimate and, unlike the original SPS, it can construct non-asymptotic confidence regions for linear regression models where the regressors contain past values of the output. Hence, it is applicable to ARX systems, as well as systems with feedback. We show that this approach provides regions with exact confidence under weak assumptions, i.e., the true parameter is included in the regions with a (user-chosen) exact …
Instrumental variable methods are often used for parameter estimation in the presence of confounding. They can also be applied in stochastic processes. Instrumental variable analysis exploits moment equations to obtain estimators for causal parameters. We show that in stochastic processes one can find such moment equations using an integrated covariance matrix. This provides new instrumental variable methods, instrumental variable methods in a class of continuous-time processes as well as a unified treatment of discrete- and continuous-time processes.
Robins (1998) introduced marginal structural models (MSMs), a general class of counterfactual models for the joint effects of time-varying treatment regimes in complex longitudinal studies subject to time-varying confounding. He established identification of MSM parameters under a sequential randomization assumption (SRA), which essentially rules out unmeasured confounding of treatment assignment over time. In this technical report, we consider sufficient conditions for identification of MSM parameters with the aid of a time-varying instrumental variable, when sequential randomization fails to…
Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement messages that increase t…
Instrumental variable methods have been widely used to identify causal effects in the presence of unmeasured confounding. A key identification condition known as the exclusion restriction states that the instrument cannot have a direct effect on the outcome which is not mediated by the exposure in view. In the health and social sciences, such an assumption is often not credible. To address this concern, we consider identification conditions of the population average treatment effect with an invalid instrumental variable which does not satisfy the exclusion restriction, and derive the efficient…
Nonparametric Inference with an Instrumental Variable under a Separable Binary Treatment Choice Model
Department of Statistics, University of Illinois Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校统计学系）；Department of Statistics and Data Science, University of Pennsylvania（宾夕法尼亚大学统计与数据科学系）
Point processes are probabilistic tools for modeling event data. While there exists a fast-growing literature studying the relationships between point processes, it remains unexplored how such relationships connect to causal effects. In the presence of unmeasured confounders, parameters from point process models do not necessarily have causal interpretations. We propose an instrumental variable method for causal inference with point process treatment and outcome. We define causal quantities based on potential outcomes and establish nonparametric identification results with a binary instrumenta…
University of California, Irvine（加州大学欧文分校）；George Washington University（乔治华盛顿大学）；University of Michigan at Ann Arbor（密歇根大学安娜堡分校）；Duke University（杜克大学）
Pricing based on individual customer characteristics is widely used to maximize sellers' revenues. This work studies offline personalized pricing under endogeneity using an instrumental variable approach. Standard instrumental variable methods in causal inference/econometrics either focus on a discrete treatment space or require the exclusion restriction of instruments from having a direct effect on the outcome, which limits their applicability in personalized pricing. In this paper, we propose a new policy learning method for Personalized pRicing using Invalid iNsTrumental variables (PRINT) f…
There is an increasing interest in estimating heterogeneity in causal effects in randomized and observational studies. However, little research has been conducted to understand heterogeneity in an instrumental variables study. In this work, we present a method to estimate heterogeneous causal effects using an instrumental variable approach. The method has two parts. The first part uses subject-matter knowledge and interpretable machine learning techniques, such as classification and regression trees, to discover potential effect modifiers. The second part uses closed testing to test for the st…
University College London（伦敦大学学院）；University of Oxford（牛津大学）；The Alan Turing Institute（艾伦·图灵研究所）
We propose a kernel-based nonparametric estimator for the causal effect when the cause is corrupted by error. We do so by generalizing estimation in the instrumental variable setting. Despite significant work on regression with measurement error, additionally handling unobserved confounding in the continuous setting is non-trivial: we have seen little prior work. As a by-product of our investigation, we clarify a connection between mean embeddings and characteristic functions, and how learning one simultaneously allows one to learn the other. This opens the way for kernel method research to le…
