Instrumental variable (IV) methods allow us the opportunity to address unmeasured confounding in causal inference. However, most IV methods are only applicable to discrete or continuous outcomes with very few IV methods for censored survival outcomes. In this work we propose nonparametric estimators for the local average treatment effect on survival probabilities under both nonignorable and ignorable censoring. We provide an efficient influence function-based estimator and a simple estimation procedure when the IV is either binary or continuous. The proposed estimators possess double-robustness properties and can easily incorporate nonparametric estimation using machine learning tools. In simulation studies, we demonstrate the flexibility and efficiency of our proposed estimators under various plausible scenarios. We apply our method to the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial for estimating the causal effect of screening on survival probabilities and investigate the causal contrasts between the two interventions under different censoring assumptions.
This article introduces a new instrumental variable approach for estimating unknown population parameters with data having nonrandom missing values. With coarse and discrete instruments, Shao and Wang (2016) proposed a semiparametric method that uses the added information to identify the tilting parameter from the missing data propensity model. A naive application of this idea to continuous instruments through arbitrary discretizations is apt to be inefficient, and maybe questionable in some settings. We propose a nonparametric method not requiring arbitrary discretizations but involves scanni…
Clinical trials involving novel immuno-oncology (IO) therapies frequently exhibit survival profiles which violate the proportional hazards assumption due to a delay in treatment effect, and in such settings, the survival curves in the two treatment arms may have a crossing before the two curves eventually separate. To flexibly model such scenarios, we describe a nonparametric approach for estimating the treatment arm-specific survival functions which constrains these two survival functions to cross at most once without making any additional assumptions about how the survival curves are related…
In randomized clinical trials with survival outcome, there has been an increasing interest in subgroup identification based on baseline genomic, proteomic markers or clinical characteristics. Some of the existing methods identify subgroups that benefit substantially from the experimental treatment by directly modeling outcomes or treatment effect. When the goal is to find an optimal treatment for a given patient rather than finding the right patient for a given treatment, methods under the individualized treatment regime framework estimate an individualized treatment rule that would lead to th…
Instrumental variables (IV) are a useful tool for estimating causal effects in the presence of unmeasured confounding. IV methods are well developed for uncensored outcomes, particularly for structural linear equation models, where simple two-stage estimation schemes are available. The extension of these methods to survival settings is challenging, partly because of the nonlinearity of the popular survival regression models and partly because of the complications associated with right censoring or other survival features. We develop a simple causal hazard ratio estimator in a proportional haza…
This note shows that adding monotonicity or convexity constraints on the regression function does not restore well-posedness in nonparametric instrumental variable regression. The minimum distance problem without regularisation is still locally ill-posed.
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…
The problem of endogeneity in statistics and econometrics is often handled by introducing instrumental variables (IV) which fulfill the mean independence assumption, i.e. the unobservable is mean independent of the instruments. When full independence of IV's and the unobservable is assumed, nonparametric IV regression models and nonparametric demand models lead to nonlinear integral equations with unknown integral kernels. We prove convergence rates for the mean integrated square error of the iteratively regularized Newton method applied to these problems. Compared to related results we derive…
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…
Linear transformation model provides a general framework for analyzing censored survival data with covariates. The proportional hazards and proportional odds models are special cases of the linear transformation model. In biomedical studies, covariates with measurement error may occur in survival data. In this work, we propose a method to obtain estimators of the regression coefficients in the linear transformation model when the covariates are subject to measurement error. In the proposed method, we assume that instrumental variables are available. We develop counting process based estimating…
We suggest two nonparametric approaches, based on kernel methods and orthogonal series to estimating regression functions in the presence of instrumental variables. For the first time in this class of problems, we derive optimal convergence rates, and show that they are attained by particular estimators. In the presence of instrumental variables the relation that identifies the regression function also defines an ill-posed inverse problem, the ``difficulty'' of which depends on eigenvalues of a certain integral operator which is determined by the joint density of endogenous and instrumental va…
We study the problem of nonparametric regression when the regressor is endogenous, which is an important nonparametric instrumental variables (NPIV) regression in econometrics and a difficult ill-posed inverse problem with unknown operator in statistics. We first establish a general upper bound on the sup-norm (uniform) convergence rate of a sieve estimator, allowing for endogenous regressors and weakly dependent data. This result leads to the optimal sup-norm convergence rates for spline and wavelet least squares regression estimators under weakly dependent data and heavy-tailed error terms. …
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…
Arizona State University（亚利桑那州立大学）；Medical College of Wisconsin（威斯康星医学院）
We provide a new flexible framework for inference with the instrumental variable model. Rather than using linear specifications, functions characterizing the effects of instruments and other explanatory variables are estimated using machine learning via Bayesian Additive Regression Trees (BART). Error terms and their distribution are inferred using Dirichlet Process mixtures. Simulated and real examples show that when the true functions are linear, little is lost. But when nonlinearities are present, dramatic improvements are obtained with virtually no manual tuning.
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…
Instrumental variable methods allow for inference about the treatment effect by controlling for unmeasured confounding in randomized experiments with noncompliance. However, many studies do not consider the observed compliance behavior in the testing procedure, which can lead to a loss of power. In this paper, we propose a novel nonparametric likelihood approach, referred to as the binomial likelihood (BL) method, that incorporates information on compliance behavior while overcoming several limitations of previous techniques and utilizing the advantages of likelihood methods. Our proposed meth…
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…
Missing exposure information is a very common feature of many observational studies. Here we study identifiability and efficient estimation of causal effects on vector outcomes, in such cases where treatment is unconfounded but partially missing. We consider a missing at random setting where missingness in treatment can depend not only on complex covariates, but also on post-treatment outcomes. We give a new identifying expression for average treatment effects in this setting, along with the efficient influence function for this parameter in a nonparametric model, which yields a nonparametric …
Towards a Unified Analysis of Neural Networks in Nonparametric Instrumental Variable Regression: Optimization and Generalization
University College London（伦敦大学学院）；Nanyang Technological University（南洋理工大学）；The University of Tokyo（东京大学）；RIKEN Center for Advanced Intelligence Project（理化学研究所革新智能综合研究中心）
The ill-posedness of the inverse problem of recovering a regression function in a nonparametric instrumental variable model leads to estimators that may suffer from a very slow, logarithmic rate of convergence. In this paper, we show that restricting the problem to models with monotone regression functions and monotone instruments significantly weakens the ill-posedness of the problem. In stark contrast to the existing literature, the presence of a monotone instrument implies boundedness of our measure of ill-posedness when restricted to the space of monotone functions. Based on this result we…
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…
Mediation analysis is a strategy for understanding the mechanisms by which treatments or interventions affect later outcomes. Mediation analysis is frequently applied in randomized trial settings, but typically assumes: a) that randomized assignment is the exposure of interest as opposed to actual take-up of the intervention, and b) no unobserved confounding of the mediator-outcome relationship. In contrast to the rich literature on instrumental variable (IV) methods to estimate a total effect of a non-randomized exposure, there has been almost no research into using IV as an identification st…
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 (IV) regression is a strategy for learning causal relationships in observational data. If measurements of input X and output Y are confounded, the causal relationship can nonetheless be identified if an instrumental variable Z is available that influences X directly, but is conditionally independent of Y given X and the unmeasured confounder. The classic two-stage least squares algorithm (2SLS) simplifies the estimation problem by modeling all relationships as linear functions. We propose kernel instrumental variable regression (KIV), a nonparametric generalization of 2SL…
A case-control family study is a study where individuals with a disease of interest (case probands) and individuals without the disease (control probands) are randomly sampled from a well-defined population. Possibly right-censored age at onset and disease status are observed for both probands and their relatives. Correlation among the outcomes within a family is induced by factors such as inherited genetic susceptibility, shared environment, and common behavior patterns. For this setting, we present a nonparametric estimator of the marginal survival function, based on local linear estimation …
The pervasive use of prevalent cohort studies on disease duration, increasingly calls for appropriate methodologies to account for the biases that invariably accompany samples formed by such data. It is well-known, for example, that subjects with shorter lifetime are less likely to be present in such studies. Moreover, certain covariate values could be preferentially selected into the sample, being linked to the long-term survivors. The existing methodology for estimation of the propensity score using data collected on prevalent cases requires the correct conditional survival/hazard function g…
This study extends the Bayesian nonparametric instrumental variable regression model to determine the structural effects of covariates on the conditional quantile of the response variable. The error distribution is nonparametrically modelled using a Dirichlet mixture of bivariate normal distributions. The mean functions include the smooth effects of the covariates represented using the spline functions in an additive manner. The conditional variance of the second-stage error is also modelled using the spline functions such that it varies smoothly with the covariates. Accordingly, the proposed …
Heterogeneous Treatment Effect in Time-to-Event Outcomes: Harnessing Censored Data with Recursively Imputed Trees
Faculty of Data and Decisions Sciences, Technion - Israel Institute of Technology（数据与决策科学学院，技术ion-以色列理工学院）；Department of Statistics and Operations Research, Tel Aviv University（统计与运筹学系，特拉维夫大学）
The use of instrumental variables for estimating the effect of an exposure on an outcome is popular in econometrics, and increasingly so in epidemiology. This increasing popularity may be attributed to the natural occurrence of instrumental variables in observational studies that incorporate elements of randomization, either by design or by nature (e.g., random inheritance of genes). Instrumental variables estimation of exposure effects is well established for continuous outcomes and to some extent for binary outcomes. It is, however, largely lacking for time-to-event outcomes because of compl…
We develop a flexible Erlang mixture model for survival analysis. The model for the survival density is built from a structured mixture of Erlang densities, mixing on the integer shape parameter with a common scale parameter. The mixture weights are constructed through increments of a distribution function on the positive real line, which is assigned a Dirichlet process prior. The model has a relatively simple structure, balancing flexibility with efficient posterior computation. Moreover, it implies a mixture representation for the hazard function that involves time-dependent mixture weights,…
