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Register a new userEstimation of local treatment under the binary instrumental variable model
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Linbo Wang
Publication date
2020
fields
Mathematical Statistics
and research's language is
English
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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 estimating procedures that improve upon existing proposals in terms of model congeniality, interpretability, robustness or efficiency. Our approach is illustrated via simulation studies and a real data analysis.
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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 estimable from conventional randomized screening trial using instrumental variable type methods. To define the causal effect of interest, we formulate a simplified structural multi-state model for screening trials, based on a hypothetical intervention trial where screening detected individuals would be randomized into early versus delayed treatments. The cancer-specific mortality reductions after screening detection are quantified by a cause-specific hazard ratio. For this, we propose two estimators, based on an estimating equation and a likelihood expression. The methods extend existing instrumental variable methods for time-to-event and competing risks outcomes to time-dependent intermediate variables. Using the multi-state model as the basis of a data generating mechanism, we investigate the performance of the new estimators through simulation studies. In addition, we illustrate the proposed method in the context of CT screening for lung cancer using the US National Lung Screening Trial (NLST) data.
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 zero. Moreover, we derive sharp bounds on the causal effects without additional assumptions. These bounds are informative because they exclude zero. We then consider differential measurement errors, and focus on sensitivity analyses in those settings.
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 $text{argmax}_{mathcal{D}} E[Y_{mathcal{D}(L)}]$ with the aid of a binary instrumental variable, when no unmeasured confounding fails to hold. We also construct novel multiply robust classification-based estimators. Furthermore, we propose to identify and estimate optimal treatment regimes among those who would comply to the assigned treatment under a standard monotonicity assumption. In this latter case, we establish the somewhat surprising result that complier optimal regimes can be consistently estimated without directly collecting compliance information and therefore without the complier average treatment effect itself being identified. Our approach is illustrated via extensive simulation studies and a data application on the effect of child rearing on labor participation.
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 confounding, using instead a time-varying instrumental variable. Our identification conditions require that no unobserved confounder predicts compliance type for the time-varying treatment. We describe a simple weighted estimator and examine its finite-sample properties in a simulation study. We apply the proposed estimator to examine the effect of delivery hospital on neonatal survival probability.
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 hazards model with right censored data. The method exploits a special characterization of IV which enables the use of an intuitive inverse weighting scheme that is generally applicable to more complex survival settings with left truncation, competing risks, or recurrent events. We rigorously establish the asymptotic properties of the estimators, and provide plug-in variance estimators. The proposed method can be implemented in standard software, and is evaluated through extensive simulation studies. We apply the proposed IV method to a data set from the Prostate, Lung, Colorectal and Ovarian cancer screening trial to delineate the causal effect of flexible sigmoidoscopy screening on colorectal cancer survival which may be confounded by informative noncompliance with the assigned screening regimen.
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