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Register a new userQuantile Regression Modeling of Recurrent Event Risk
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Huijuan Ma
Publication date
2018
fields
Mathematical Statistics
and research's language is
English
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Progression of chronic disease is often manifested by repeated occurrences of disease-related events over time. Delineating the heterogeneity in the risk of such recurrent events can provide valuable scientific insight for guiding customized disease management. In this paper, we present a new modeling framework for recurrent event data, which renders a flexible and robust characterization of individual multiplicative risk of recurrent event through quantile regression that accommodates both observed covariates and unobservable frailty. The proposed modeling requires no distributional specification of the unobservable frailty, while permitting the exploration of dynamic covariate effects. We develop estimation and inference procedures for the proposed model through a novel adaptation of the principle of conditional score. The asymptotic properties of the proposed estimator, including the uniform consistency and weak convergence, are established. Extensive simulation studies demonstrate satisfactory finite-sample performance of the proposed method. We illustrate the practical utility of the new method via an application to a diabetes clinical trial that explores the risk patterns of hypoglycemia in Type 2 diabetes patients.
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In ordinary quantile regression, quantiles of different order are estimated one at a time. An alternative approach, which is referred to as quantile regression coefficients modeling (QRCM), is to model quantile regression coefficients as parametric functions of the order of the quantile. In this paper, we describe how the QRCM paradigm can be applied to longitudinal data. We introduce a two-level quantile function, in which two different quantile regression models are used to describe the (conditional) distribution of the within-subject response and that of the individual effects. We propose a novel type of penalized fixed-effects estimator, and discuss its advantages over standard methods based on $ell_1$ and $ell_2$ penalization. We provide model identifiability conditions, derive asymptotic properties, describe goodness-of-fit measures and model selection criteria, present simulation results, and discuss an application. The proposed method has been implemented in the R package qrcm.
Radiomics involves the study of tumor images to identify quantitative markers explaining cancer heterogeneity. The predominant approach is to extract hundreds to thousands of image features, including histogram features comprised of summaries of the marginal distribution of pixel intensities, which leads to multiple testing problems and can miss out on insights not contained in the selected features. In this paper, we present methods to model the entire marginal distribution of pixel intensities via the quantile function as functional data, regressed on a set of demographic, clinical, and genetic predictors. We call this approach quantile functional regression, regressing subject-specific marginal distributions across repeated measurements on a set of covariates, allowing us to assess which covariates are associated with the distribution in a global sense, as well as to identify distributional features characterizing these differences, including mean, variance, skewness, and various upper and lower quantiles. To account for smoothness in the quantile functions, we introduce custom basis functions we call quantlets that are sparse, regularized, near-lossless, and empirically defined, adapting to the features of a given data set. We fit this model using a Bayesian framework that uses nonlinear shrinkage of quantlet coefficients to regularize the functional regression coefficients and provides fully Bayesian inference after fitting a Markov chain Monte Carlo. We demonstrate the benefit of the basis space modeling through simulation studies, and apply the method to Magnetic resonance imaging (MRI) based radiomic dataset from Glioblastoma Multiforme to relate imaging-based quantile functions to demographic, clinical, and genetic predictors, finding specific differences in tumor pixel intensity distribution between males and females and between tumors with and without DDIT3 mutations.
In this paper, we develop a quantile functional regression modeling framework that models the distribution of a set of common repeated observations from a subject through the quantile function, which is regressed on a set of covariates to determine how these factors affect various aspects of the underlying subject-specific distribution. To account for smoothness in the quantile functions, we introduce custom basis functions we call textit{quantlets} that are sparse, regularized, near-lossless, and empirically defined, adapting to the features of a given data set and containing a Gaussian subspace so {non-Gaussianness} can be assessed. While these quantlets could be used within various functional regression frameworks, we build a Bayesian framework that uses nonlinear shrinkage of quantlet coefficients to regularize the functional regression coefficients and allows fully Bayesian inferences after fitting a Markov chain Monte Carlo. Specifically, we apply global tests to assess which covariates have any effect on the distribution at all, followed by local tests to identify at which specific quantiles the differences lie while adjusting for multiple testing, and to assess whether the covariate affects certain major aspects of the distribution, including location, scale, skewness, Gaussianness, or tails. If the difference lies in these commonly-used summaries, our approach can still detect them, but our systematic modeling strategy can also detect effects on other aspects of the distribution that might be missed if one restricted attention to pre-chosen summaries. We demonstrate the benefit of the basis space modeling through simulation studies, and illustrate the method using a biomedical imaging data set in which we relate the distribution of pixel intensities from a tumor image to various demographic, clinical, and genetic characteristics.
As a competitive alternative to least squares regression, quantile regression is popular in analyzing heterogenous data. For quantile regression model specified for one single quantile level $tau$, major difficulties of semiparametric efficient estimation are the unavailability of a parametric efficient score and the conditional density estimation. In this paper, with the help of the least favorable submodel technique, we first derive the semiparametric efficient scores for linear quantile regression models that are assumed for a single quantile level, multiple quantile levels and all the quantile levels in $(0,1)$ respectively. Our main discovery is a one-step (nearly) semiparametric efficient estimation for the regression coefficients of the quantile regression models assumed for multiple quantile levels, which has several advantages: it could be regarded as an optimal way to pool information across multiple/other quantiles for efficiency gain; it is computationally feasible and easy to implement, as the initial estimator is easily available; due to the nature of quantile regression models under investigation, the conditional density estimation is straightforward by plugging in an initial estimator. The resulting estimator is proved to achieve the corresponding semiparametric efficiency lower bound under regularity conditions. Numerical studies including simulations and an example of birth weight of children confirms that the proposed estimator leads to higher efficiency compared with the Koenker-Bassett quantile regression estimator for all quantiles of interest.
In this paper, we develop a new censored quantile instrumental variable (CQIV) estimator and describe its properties and computation. The CQIV estimator combines Powell (1986) censored quantile regression (CQR) to deal with censoring, with a control variable approach to incorporate endogenous regressors. The CQIV estimator is obtained in two stages that are non-additive in the unobservables. The first stage estimates a non-additive model with infinite dimensional parameters for the control variable, such as a quantile or distribution regression model. The second stage estimates a non-additive censored quantile regression model for the response variable of interest, including the estimated control variable to deal with endogeneity. For computation, we extend the algorithm for CQR developed by Chernozhukov and Hong (2002) to incorporate the estimation of the control variable. We give generic regularity conditions for asymptotic normality of the CQIV estimator and for the validity of resampling methods to approximate its asymptotic distribution. We verify these conditions for quantile and distribution regression estimation of the control variable. Our analysis covers two-stage (uncensored) quantile regression with non-additive first stage as an important special case. We illustrate the computation and applicability of the CQIV estimator with a Monte-Carlo numerical example and an empirical application on estimation of Engel curves for alcohol.
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