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Register a new userModel-Assisted Inference for Covariate-Specific Treatment Effects with High-dimensional Data
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Peng Wu
Publication date
2021
fields
Mathematical Statistics
and research's language is
English
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Covariate-specific treatment effects (CSTEs) represent heterogeneous treatment effects across subpopulations defined by certain selected covariates. In this article, we consider marginal structural models where CSTEs are linearly represented using a set of basis functions of the selected covariates. We develop a new approach in high-dimensional settings to obtain not only doubly robust point estimators of CSTEs, but also model-assisted confidence intervals, which are valid when a propensity score model is correctly specified but an outcome regression model may be misspecified. With a linear outcome model and subpopulations defined by discrete covariates, both point estimators and confidence intervals are doubly robust for CSTEs. In contrast, confidence intervals from existing high-dimensional methods are valid only when both the propensity score and outcome models are correctly specified. We establish asymptotic properties of the proposed point estimators and the associated confidence intervals. We present simulation studies and empirical applications which demonstrate the advantages of the proposed method compared with competing ones.
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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 penalties but carefully chosen loss functions for estimating coefficient vectors in these regression models, and then employs a doubly robust estimator for the treatment parameter through augmented inverse probability weighting. We provide rigorous theoretical analysis to show that the resulting Wald confidence intervals are valid for the treatment parameter under suitable sparsity conditions if the instrument propensity score model is correctly specified, but the treatment and outcome regression models may be misspecified. For existing high-dimensional methods, valid confidence intervals are obtained for the treatment parameter if all three models are correctly specified. We evaluate the proposed methods via extensive simulation studies and an empirical application to estimate the returns to education.
With a large number of baseline covariates, we propose a new semi-parametric modeling strategy for heterogeneous treatment effect estimation and individualized treatment selection, which are two major goals in personalized medicine. We achieve the first goal through estimating a covariate-specific treatment effect (CSTE) curve modeled as an unknown function of a weighted linear combination of all baseline covariates. The weight or the coefficient for each covariate is estimated by fitting a sparse semi-parametric logistic single-index coefficient model. The CSTE curve is estimated by a spline-backfitted kernel procedure, which enables us to further construct a simultaneous confidence band (SCB) for the CSTE curve under a desired confidence level. Based on the SCB, we find the subgroups of patients that benefit from each treatment, so that we can make individualized treatment selection. The innovations of the proposed method are three-fold. First, the proposed method can quantify variability associated with the estimated optimal individualized treatment rule with high-dimensional covariates. Second, the proposed method is very flexible to depict both local and global associations between the treatment and baseline covariates in the presence of high-dimensional covariates, and thus it enjoys flexibility while achieving dimensionality reduction. Third, the SCB achieves the nominal confidence level asymptotically, and it provides a uniform inferential tool in making individualized treatment decisions.
In this paper, we study the estimation and inference of the quantile treatment effect under covariate-adaptive randomization. We propose two estimation methods: (1) the simple quantile regression and (2) the inverse propensity score weighted quantile regression. For the two estimators, we derive their asymptotic distributions uniformly over a compact set of quantile indexes, and show that, when the treatment assignment rule does not achieve strong balance, the inverse propensity score weighted estimator has a smaller asymptotic variance than the simple quantile regression estimator. For the inference of method (1), we show that the Wald test using a weighted bootstrap standard error under-rejects. But for method (2), its asymptotic size equals the nominal level. We also show that, for both methods, the asymptotic size of the Wald test using a covariate-adaptive bootstrap standard error equals the nominal level. We illustrate the finite sample performance of the new estimation and inference methods using both simulated and real datasets.
This paper develops new tools to quantify uncertainty in optimal decision making and to gain insight into which variables one should collect information about given the potential cost of measuring a large number of variables. We investigate simultaneous inference to determine if a group of variables is relevant for estimating an optimal decision rule in a high-dimensional semiparametric framework. The unknown link function permits flexible modeling of the interactions between the treatment and the covariates, but leads to nonconvex estimation in high dimension and imposes significant challenges for inference. We first establish that a local restricted strong convexity condition holds with high probability and that any feasible local sparse solution of the estimation problem can achieve the near-oracle estimation error bound. We further rigorously verify that a wild bootstrap procedure based on a debiased version of the local solution can provide asymptotically honest uniform inference for the effect of a group of variables on optimal decision making. The advantage of honest inference is that it does not require the initial estimator to achieve perfect model selection and does not require the zero and nonzero effects to be well-separated. We also propose an efficient algorithm for estimation. Our simulations suggest satisfactory performance. An example from a diabetes study illustrates the real application.
Differences between biological networks corresponding to disease conditions can help delineate the underlying disease mechanisms. Existing methods for differential network analysis do not account for dependence of networks on covariates. As a result, these approaches may detect spurious differential connections induced by the effect of the covariates on both the disease condition and the network. To address this issue, we propose a general covariate-adjusted test for differential network analysis. Our method assesses differential network connectivity by testing the null hypothesis that the network is the same for individuals who have identical covariates and only differ in disease status. We show empirically in a simulation study that the covariate-adjusted test exhibits improved type-I error control compared with naive hypothesis testing procedures that do not account for covariates. We additionally show that there are settings in which our proposed methodology provides improved power to detect differential connections. We illustrate our method by applying it to detect differences in breast cancer gene co-expression networks by subtype.
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