Quantile regression based on a weighted approach under semi-competing risks data

In this article, we investigate the quantile regression analysis for semi-competing risks data in which a non-terminal event may be dependently censored by a terminal event. Due to the dependent censoring, the estimation of quantile regression coefficients on the non-terminal event becomes difficult. In order to handle this problem, we assume Archimedean Copula to specify the dependence of the non-terminal event and the terminal event. Portnoy [Censored regression quantiles. J Amer Statist Assoc. 2003;98:1001–1012] considered the quantile regression model under right-censoring data. We extend his approach to construct a weight function, and then impose the weight function to estimate the quantile regression parameter for the non-terminal event under semi-competing risks data. We also prove the consistency and asymptotic properties for the proposed estimator. According to the simulation studies, the performance of our proposed method is good. We also apply our suggested approach to analyse a real data.     

A general quantile residual life model for length‐biased right‐censored data

The quantile residual lifetime function provides comprehensive quantitative measures for residual life, especially when the distribution of the latter is skewed or heavy‐tailed and/or when the data contain outliers. In this paper, we propose a general class of semiparametric quantile residual life models for length‐biased right‐censored data. We use the inverse probability weighted method to correct the bias due to length‐biased sampling and informative censoring. Two estimating equations corresponding to the quantile regressions are constructed in two separate steps to obtain an efficient estimator. Consistency and asymptotic normality of the estimator are established. The main difficulty in implementing our proposed method is that the estimating equations associated with the quantiles are nondifferentiable, and we apply the majorize–minimize algorithm and estimate the asymptotic covariance using an efficient resampling method. We use simulation studies to evaluate the proposed method and illustrate its application by a real‐data example.     

Regression analysis based on conditional likelihood approach under semi-competing risks data

Medical studies often involve semi-competing risks data, which consist of two types of events, namely terminal event and non-terminal event. Because the non-terminal event may be dependently censored by the terminal event, it is not possible to make inference on the non-terminal event without extra assumptions. Therefore, this study assumes that the dependence structure on the non-terminal event and the terminal event follows a copula model, and lets the marginal regression models of the non-terminal event and the terminal event both follow time-varying effect models. This study uses a conditional likelihood approach to estimate the time-varying coefficient of the non-terminal event, and proves the large sample properties of the proposed estimator. Simulation studies show that the proposed estimator performs well. This study also uses the proposed method to analyze AIDS Clinical Trial Group (ACTG 320).     

Joint modeling approach for semicompeting risks data with missing nonterminal event status

Semicompeting risks data, where a subject may experience sequential non-terminal and terminal events, and the terminal event may censor the non-terminal event but not vice versa, are widely available in many biomedical studies. We consider the situation when a proportion of subjects’ non-terminal events is missing, such that the observed data become a mixture of “true” semicompeting risks data and partially observed terminal event only data. An illness–death multistate model with proportional hazards assumptions is proposed to study the relationship between non-terminal and terminal events, and provide covariate-specific global and local association measures. Maximum likelihood estimation based on semiparametric regression analysis is used for statistical inference, and asymptotic properties of proposed estimators are studied using empirical process and martingale arguments. We illustrate the proposed method with simulation studies and data analysis of a follicular cell lymphoma study.     

Quantile Regression For Longitudinal Biomarker Data Subject to Left Censoring and Dropouts

Quantile regression is increasingly used in biomarker analysis to handle nonnormal or heteroscedastic data. However, in some biomedical studies, the biomarker data can be censored by detection limits of the bioassay or missing when the subjects drop out from the study. Inappropriate handling of these two issues leads to biased estimation results. We consider the censored quantile regression approach to account for the censoring data and apply the inverse weighting technique to adjust for dropouts. In particular, we develop a weighted estimating equation for censored quantile regression, where an individual’s contribution is weighted by the inverse probability of dropout at the given occasion. We conduct simulation studies to evaluate the properties of the proposed estimators and demonstrate our method with a real data set from Genetic and Inflammatory Marker of Sepsis (GenIMS) study.     

Marginal Regression Analysis for Semi-Competing Risks Data Under Dependent Censoring

Abstract.  Multiple events data are commonly seen in medical applications. There are two types of events, namely terminal and non-terminal. Statistical analysis for non-terminal events is complicated due to dependent censoring. Consequently, joint modelling and inference are often needed to avoid the problem of non-identifiability. This article considers regression analysis for multiple events data with major interest in a non-terminal event such as disease progression. We generalize the technique of artificial censoring, which is a popular way to handle dependent censoring, under flexible model assumptions on the two types of events. The proposed method is applied to analyse a data set of bone marrow transplantation.     

Quantile regression methods for left-truncated and right-censored data

Left-truncated and right-censored (LTRC) data are encountered frequently due to a prevalent cohort sampling in follow-up studies. Because of the skewness of the distribution of survival time, quantile regression is a useful alternative to the Cox's proportional hazards model and the accelerated failure time model for survival analysis. In this paper, we apply the quantile regression model to LTRC data and develops an unbiased estimating equation for regression coefficients. The proposed estimation methods use the inverse probabilities of truncation and censoring weighting technique. The resulting estimator is uniformly consistent and asymptotically normal. The finite-sample performance of the proposed estimation methods is also evaluated using extensive simulation studies. Finally, analysis of real data is presented to illustrate our proposed estimation methods.     

Power-transformed linear regression on quantile residual life for censored competing risks data

ABSTRACT

This paper proposes a power-transformed linear quantile regression model for the residual lifetime of competing risks data. The proposed model can describe the association between any quantile of a time-to-event distribution among survivors beyond a specific time point and the covariates. Under covariate-dependent censoring, we develop an estimation procedure with two steps, including an unbiased monotone estimating equation for regression parameters and cumulative sum processes for the Box–Cox transformation parameter. The asymptotic properties of the estimators are also derived. We employ an efficient bootstrap method for the estimation of the variance–covariance matrix. The finite-sample performance of the proposed approaches are evaluated through simulation studies and a real example.     

Maximum likelihood analysis of semicompeting risks data with semiparametric regression models

The “semicompeting risks” include a terminal event and a non-terminal event. The terminal event may censor the non-terminal event but not vice versa. Because times to the two events are usually correlated, the non-terminal event is subject to dependent/informative censoring by the terminal event. We seek to conduct marginal regressions and joint association analyses for the two event times under semicompeting risks. The proposed method is based on the modeling setup where the semiparametric transformation models are assumed for marginal regressions, and a copula model is assumed for the joint distribution. We propose a nonparametric maximum likelihood approach for inferences, which provides a martingale representation for the score function and an analytical expression for the information matrix. Direct theoretical developments and computational implementation are allowed for the proposed approach. Simulations and a real data application demonstrate the utility of the proposed methodology.     

Improving estimation efficiency for semi-competing risks data with partially observed terminal event

Semi-competing risks data arise when two types of events, non-terminal and terminal, may be observed. When the terminal event occurs first, it censors the non-terminal event. Otherwise the terminal event is observable after the occurrence of the non-terminal event. In practice, it can be hard to ascertain all terminal event information after the non-terminal event. Yu and Yiannoutsos [(2015), ‘Marginal and Conditional Distribution Estimation from Double-Sampled Semi-Competing Risks Data’, Scandinavian Journal of Statistics, 42, 87–103] considered a setting when the terminal event is ascertained via double sampling from only a subset of patients who experienced the non-terminal event. They discussed estimation for marginal and conditional distributions under this double sampled semi-competing risk data framework. We propose a more efficient estimation method in the same setting by fully utilising the non-terminal event information. The efficiency gain can be substantial as observed in our simulation study.     

Empirical likelihood weighted composite quantile regression with partially missing covariates

This paper develops a novel weighted composite quantile regression (CQR) method for estimation of a linear model when some covariates are missing at random and the probability for missingness mechanism can be modelled parametrically. By incorporating the unbiased estimating equations of incomplete data into empirical likelihood (EL), we obtain the EL-based weights, and then re-adjust the inverse probability weighted CQR for estimating the vector of regression coefficients. Theoretical results show that the proposed method can achieve semiparametric efficiency if the selection probability function is correctly specified, therefore the EL weighted CQR is more efficient than the inverse probability weighted CQR. Besides, our algorithm is computationally simple and easy to implement. Simulation studies are conducted to examine the finite sample performance of the proposed procedures. Finally, we apply the new method to analyse the US news College data.     

Quantile Regression Methods for Longitudinal Data with Drop-outs: Application to CD4 Cell Counts of Patients Infected with the Human Immunodeficiency Virus

Patients infected with the human immunodeficiency virus (HIV) generally experience a decline in their CD4 cell count (a count of certain white blood cells). We describe the use of quantile regression methods to analyse longitudinal data on CD4 cell counts from 1300 patients who participated in clinical trials that compared two therapeutic treatments: zidovudine and didanosine. It is of scientific interest to determine any treatment differences in the CD4 cell counts over a short treatment period. However, the analysis of the CD4 data is complicated by drop-outs: patients with lower CD4 cell counts at the base-line appear more likely to drop out at later measurement occasions. Motivated by this example, we describe the use of `weighted' estimating equations in quantile regression models for longitudinal data with drop-outs. In particular, the conventional estimating equations for the quantile regression parameters are weighted inversely proportionally to the probability of drop-out. This approach requires the process generating the missing data to be estimable but makes no assumptions about the distribution of the responses other than those imposed by the quantile regression model. This method yields consistent estimates of the quantile regression parameters provided that the model for drop-out has been correctly specified. The methodology proposed is applied to the CD4 cell count data and the results are compared with those obtained from an `unweighted' analysis. These results demonstrate how an analysis that fails to account for drop-outs can mislead.     

NEW EFFICIENT ESTIMATION AND VARIABLE SELECTION METHODS FOR SEMIPARAMETRIC VARYING-COEFFICIENT PARTIALLY LINEAR MODELS

The complexity of semiparametric models poses new challenges to statistical inference and model selection that frequently arise from real applications. In this work, we propose new estimation and variable selection procedures for the semiparametric varying-coefficient partially linear model. We first study quantile regression estimates for the nonparametric varying-coefficient functions and the parametric regression coefficients. To achieve nice efficiency properties, we further develop a semiparametric composite quantile regression procedure. We establish the asymptotic normality of proposed estimators for both the parametric and nonparametric parts and show that the estimators achieve the best convergence rate. Moreover, we show that the proposed method is much more efficient than the least-squares-based method for many non-normal errors and that it only loses a small amount of efficiency for normal errors. In addition, it is shown that the loss in efficiency is at most 11.1% for estimating varying coefficient functions and is no greater than 13.6% for estimating parametric components. To achieve sparsity with high-dimensional covariates, we propose adaptive penalization methods for variable selection in the semiparametric varying-coefficient partially linear model and prove that the methods possess the oracle property. Extensive Monte Carlo simulation studies are conducted to examine the finite-sample performance of the proposed procedures. Finally, we apply the new methods to analyze the plasma beta-carotene level data.     

Bayesian variable selection and estimation in maximum entropy quantile regression

Quantile regression has gained increasing popularity as it provides richer information than the regular mean regression, and variable selection plays an important role in the quantile regression model building process, as it improves the prediction accuracy by choosing an appropriate subset of regression predictors. Unlike the traditional quantile regression, we consider the quantile as an unknown parameter and estimate it jointly with other regression coefficients. In particular, we adopt the Bayesian adaptive Lasso for the maximum entropy quantile regression. A flat prior is chosen for the quantile parameter due to the lack of information on it. The proposed method not only addresses the problem about which quantile would be the most probable one among all the candidates, but also reflects the inner relationship of the data through the estimated quantile. We develop an efficient Gibbs sampler algorithm and show that the performance of our proposed method is superior than the Bayesian adaptive Lasso and Bayesian Lasso through simulation studies and a real data analysis.     

Analyzing panel count data with a dependent observation process and a terminal event

Panel count data occur in many fields and a number of approaches have been developed. However, most of these approaches are for situations where there is no terminal event and the observation process is independent of the underlying recurrent event process unconditionally or conditional on the covariates. In this paper, we discuss a more general situation where the observation process is informative and there exists a terminal event which precludes further occurrence of the recurrent events of interest. For the analysis, a semiparametric transformation model is presented for the mean function of the underlying recurrent event process among survivors. To estimate the regression parameters, an estimating equation approach is proposed in which an inverse survival probability weighting technique is used. The asymptotic distribution of the proposed estimates is provided. Simulation studies are conducted and suggest that the proposed approach works well for practical situations. An illustrative example is provided. The Canadian Journal of Statistics 41: 174–191; 2013 © 2012 Statistical Society of Canada     

Buckley–James-type estimation of quantile regression with recurrent gap time data

In longitudinal studies, an individual may potentially undergo a series of repeated recurrence events. The gap times, which are referred to as the times between successive recurrent events, are typically the outcome variables of interest. Various regression models have been developed in order to evaluate covariate effects on gap times based on recurrence event data. The proportional hazards model, additive hazards model, and the accelerated failure time model are all notable examples. Quantile regression is a useful alternative to the aforementioned models for survival analysis since it can provide great flexibility to assess covariate effects on the entire distribution of the gap time. In order to analyze recurrence gap time data, we must overcome the problem of the last gap time subjected to induced dependent censoring, when numbers of recurrent events exceed one time. In this paper, we adopt the Buckley–James-type estimation method in order to construct a weighted estimation equation for regression coefficients under the quantile model, and develop an iterative procedure to obtain the estimates. We use extensive simulation studies to evaluate the finite-sample performance of the proposed estimator. Finally, analysis of bladder cancer data is presented as an illustration of our proposed methodology.     

A generalized Q–Q plot for longitudinal data

Most biomedical research is carried out using longitudinal studies. The method of generalized estimating equations (GEEs) introduced by Liang and Zeger [Longitudinal data analysis using generalized linear models, Biometrika 73 (1986), pp. 13–22] and Zeger and Liang [Longitudinal data analysis for discrete and continuous outcomes, Biometrics 42 (1986), pp. 121–130] has become a standard method for analyzing non-normal longitudinal data. Since then, a large variety of GEEs have been proposed. However, the model diagnostic problem has not been explored intensively. Oh et al. [Modeldiagnostic plots for repeated measures data using the generalized estimating equations approach, Comput. Statist. Data Anal. 53 (2008), pp. 222–232] proposed residual plots based on the quantile–quantile (Q–Q) plots of the χ²-distribution for repeated-measures data using the GEE methodology. They considered the Pearson, Anscombe and deviance residuals. In this work, we propose to extend this graphical diagnostic using a generalized residual. A simulation study is presented as well as two examples illustrating the proposed generalized Q–Q plots.     

Quantile regression in heteroscedastic varying coefficient models

Varying coefficient models are flexible models to describe the dynamic structure in longitudinal data. Quantile regression, more than mean regression, gives partial information on the conditional distribution of the response given the covariates. In the literature, the focus has been so far mostly on homoscedastic quantile regression models, whereas there is an interest in looking into heteroscedastic modelling. This paper contributes to the area by modelling the heteroscedastic structure and estimating it from the data, together with estimating the quantile functions. The use of the proposed methods is illustrated on real-data applications. The finite-sample behaviour of the methods is investigated via a simulation study, which includes a comparison with an existing method.     

Modeling of semi-competing risks by means of first passage times of a stochastic process

In semi-competing risks one considers a terminal event, such as death of a person, and a non-terminal event, such as disease recurrence. We present a model where the time to the terminal event is the first passage time to a fixed level c in a stochastic process, while the time to the non-terminal event is represented by the first passage time of the same process to a stochastic threshold S, assumed to be independent of the stochastic process. In order to be explicit, we let the stochastic process be a gamma process, but other processes with independent increments may alternatively be used. For semi-competing risks this appears to be a new modeling approach, being an alternative to traditional approaches based on illness-death models and copula models. In this paper we consider a fully parametric approach. The likelihood function is derived and statistical inference in the model is illustrated on both simulated and real data.