Variable screening for ultrahigh dimensional censored quantile regression

Quantile regression is a flexible approach to assessing covariate effects on failure time, which has attracted considerable interest in survival analysis. When the dimension of covariates is much larger than the sample size, feature screening and variable selection become extremely important and indispensable. In this article, we introduce a new feature screening method for ultrahigh dimensional censored quantile regression. The proposed method can work for a general class of survival models, allow for heterogeneity of data and enjoy desirable properties including the sure screening property and the ranking consistency property. Moreover, an iterative version of screening algorithm has also been proposed to accommodate more complex situations. Monte Carlo simulation studies are designed to evaluate the finite sample performance under different model settings. We also illustrate the proposed methods through an empirical analysis.     

Identification of longitudinal biomarkers for survival by a score test derived from a joint model of longitudinal and competing risks data

In this paper, we consider joint modelling of repeated measurements and competing risks failure time data. For competing risks time data, a semiparametric mixture model in which proportional hazards model are specified for failure time models conditional on cause and a multinomial model for the marginal distribution of cause conditional on covariates. We also derive a score test based on joint modelling of repeated measurements and competing risks failure time data to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data.     

Quantile-adaptive variable screening in ultra-high dimensional varying coefficient models

The varying-coefficient model is an important nonparametric statistical model since it allows appreciable flexibility on the structure of fitted model. For ultra-high dimensional heterogeneous data it is very necessary to examine how the effects of covariates vary with exposure variables at different quantile level of interest. In this paper, we extended the marginal screening methods to examine and select variables by ranking a measure of nonparametric marginal contributions of each covariate given the exposure variable. Spline approximations are employed to model marginal effects and select the set of active variables in quantile-adaptive framework. This ensures the sure screening property in quantile-adaptive varying-coefficient model. Numerical studies demonstrate that the proposed procedure works well for heteroscedastic data.     

Model-free conditional feature screening for ultra-high dimensional right censored data

This paper is concerned with the conditional feature screening for ultra-high dimensional right censored data with some previously identified important predictors. A new model-free conditional feature screening approach, conditional correlation rank sure independence screening, has been proposed and investigated theoretically. The suggested conditional screening procedure has several desirable merits. First, it is model free, and thus robust to model misspecification. Second, it has the advantage of robustness of heavy-tailed distributions of the response and the presence of potential outliers in response. Third, it is naturally applicable to complete data when there is no censoring. Through simulation studies, we demonstrate that the proposed approach outperforms the CoxCS of Hong et al. under some circumstances. A real dataset is used to illustrate the usefulness of the proposed conditional screening method.     

Planning and analyzing clinical trials with competing risks: Recommendations for choosing appropriate statistical methodology

In the analysis of time‐to‐event data, competing risks occur when multiple event types are possible, and the occurrence of a competing event precludes the occurrence of the event of interest. In this situation, statistical methods that ignore competing risks can result in biased inference regarding the event of interest. We review the mechanisms that lead to bias and describe several statistical methods that have been proposed to avoid bias by formally accounting for competing risks in the analyses of the event of interest. Through simulation, we illustrate that Gray's test should be used in lieu of the logrank test for nonparametric hypothesis testing. We also compare the two most popular models for semiparametric modelling: the cause‐specific hazards (CSH) model and Fine‐Gray (F‐G) model. We explain how to interpret estimates obtained from each model and identify conditions under which the estimates of the hazard ratio and subhazard ratio differ numerically. Finally, we evaluate several model diagnostic methods with respect to their sensitivity to detect lack of fit when the CSH model holds, but the F‐G model is misspecified and vice versa. Our results illustrate that adequacy of model fit can strongly impact the validity of statistical inference. We recommend analysts incorporate a model diagnostic procedure and contingency to explore other appropriate models when designing trials in which competing risks are anticipated.     

Modelling and analysis of recall-based competing risks data

In this paper we consider the analysis of recall-based competing risks data. The chance of an individual recalling the exact time to event depends on the time of occurrence of the event and time of observation of the individual. In particular, it is assumed that the probability of recall depends on the time elapsed since the occurrence of an event. In this study we consider the likelihood-based inference for the analysis of recall-based competing risks data. The likelihood function is constructed by incorporating the information about the probability of recall. We consider the maximum likelihood estimation of parameters. Simulation studies are carried out to examine the performance of the estimators. The proposed estimation procedure is applied to a real life data set.     

Identification of Longitudinal Biomarkers in Survival Analysis for Competing Risks Data

In recent years, joint analysis of longitudinal measurements and survival data has received much attention. However, previous work has primarily focused on a single failure type for the event time. In this article, we consider joint modeling of repeated measurements and competing risks failure time data to allow for more than one distinct failure type in the survival endpoint so we fit a cause-specific hazards sub-model to allow for competing risks, with a separate latent association between longitudinal measurements and each cause of failure. Besides, previous work does not focus on the hypothesis to test a separate latent association between longitudinal measurements and each cause of failure. In this article, we derive a score test to identify longitudinal biomarkers or surrogates for a time to event outcome in competing risks data. With a carefully chosen definition of complete data, the maximum likelihood estimation of the cause-specific hazard functions is performed via an EM algorithm. We extend this work and allow random effects to be present in both the longitudinal biomarker and underlying survival function. The random effects in the biomarker are introduced via an explicit term while the random effect in the underlying survival function is introduced by the inclusion of frailty into the model.

We use simulations to explore how the number of individuals, the number of time points per individual and the functional form of the random effects from the longitudinal biomarkers considering heterogeneous baseline hazards in individuals influence the power to detect the association of a longitudinal biomarker and the survival time.     

A Method for Analyzing Disease-Specific Mortality with Missing Cause of Death Information

In this paper, we examine a method for analyzing competing risks data where the failure type of interest is missing or incomplete, but where there is an intermediate event, and only patients who experience the intermediate event can die of the cause of interest. In some applications, a method called “log-rank subtraction” has been applied to these problems. There has been no systematic study of this methodology, though. We investigate the statistical properties of the method and further propose a modified method by including a weight function in the construction of the test statistic to correct for potential biases. A class of tests is then proposed for comparing the disease-specific mortality in the two groups. The tests are based on comparing the difference of weighted log-rank scores for the failure type of interest. We derive the asymptotic properties for the modified test procedure. Simulation studies indicate that the tests are unbiased and have reasonable power. The results are also illustrated with data from a breast cancer study.     

How to Make Model‐free Feature Screening Approaches for Full Data Applicable to the Case of Missing Response?

It is quite a challenge to develop model‐free feature screening approaches for missing response problems because the existing standard missing data analysis methods cannot be applied directly to high dimensional case. This paper develops some novel methods by borrowing information of missingness indicators such that any feature screening procedures for ultrahigh‐dimensional covariates with full data can be applied to missing response case. The first method is the so‐called missing indicator imputation screening, which is developed by proving that the set of the active predictors of interest for the response is a subset of the active predictors for the product of the response and missingness indicator under some mild conditions. As an alternative, another method called Venn diagram‐based approach is also developed. The sure screening property is proven for both methods. It is shown that the complete case analysis can also keep the sure screening property of any feature screening approach with sure screening property.     

Accelerated failure time models for the analysis of competing risks

Competing risks are common in clinical cancer research, as patients are subject to multiple potential failure outcomes, such as death from the cancer itself or from complications arising from the disease. In the analysis of competing risks, several regression methods are available for the evaluation of the relationship between covariates and cause-specific failures, many of which are based on Cox’s proportional hazards model. Although a great deal of research has been conducted on estimating competing risks, less attention has been devoted to linear regression modeling, which is often referred to as the accelerated failure time (AFT) model in survival literature. In this article, we address the use and interpretation of linear regression analysis with regard to the competing risks problem. We introduce two types of AFT modeling framework, where the influence of a covariate can be evaluated in relation to either a cause-specific hazard function, referred to as cause-specific AFT (CS-AFT) modeling in this study, or the cumulative incidence function of a particular failure type, referred to as crude-risk AFT (CR-AFT) modeling. Simulation studies illustrate that, as in hazard-based competing risks analysis, these two models can produce substantially different effects, depending on the relationship between the covariates and both the failure type of principal interest and competing failure types. We apply the AFT methods to data from non-Hodgkin lymphoma patients, where the dataset is characterized by two competing events, disease relapse and death without relapse, and non-proportionality. We demonstrate how the data can be analyzed and interpreted, using linear competing risks regression models.     

Applying competing risks regression models: an overview

In many clinical research applications the time to occurrence of one event of interest, that may be obscured by another??so called competing??event, is investigated. Specific interventions can only have an effect on the endpoint they address or research questions might focus on risk factors for a certain outcome. Different approaches for the analysis of time-to-event data in the presence of competing risks were introduced in the last decades including some new methodologies, which are not yet frequently used in the analysis of competing risks data. Cause-specific hazard regression, subdistribution hazard regression, mixture models, vertical modelling and the analysis of time-to-event data based on pseudo-observations are described in this article and are applied to a dataset of a cohort study intended to establish risk stratification for cardiac death after myocardial infarction. Data analysts are encouraged to use the appropriate methods for their specific research questions by comparing different regression approaches in the competing risks setting regarding assumptions, methodology and interpretation of the results. Notes on application of the mentioned methods using the statistical software R are presented and extensions to the presented standard methods proposed in statistical literature are mentioned.     

A sure independence screening procedure for ultra-high dimensional partially linear additive models

We introduce a two-step procedure, in the context of ultra-high dimensional additive models, which aims to reduce the size of covariates vector and distinguish linear and nonlinear effects among nonzero components. Our proposed screening procedure, in the first step, is constructed based on the concept of cumulative distribution function and conditional expectation of response in the framework of marginal correlation. B-splines and empirical distribution functions are used to estimate the two above measures. The sure screening property of this procedure is also established. In the second step, a double penalization based procedure is applied to identify nonzero and linear components, simultaneously. The performance of the designed method is examined by several test functions to show its capabilities against competitor methods when the distribution of errors is varied. Simulation studies imply that the proposed screening procedure can be applied to the ultra-high dimensional data and well detect the influential covariates. It also demonstrate the superiority in comparison with the existing methods. This method is also applied to identify most influential genes for overexpression of a G protein-coupled receptor in mice.     

Statistical methods for dependent competing risks

Many biological and medical studies have as a response of interest the time to occurrence of some event,X, such as the occurrence of cessation of smoking, conception, a particular symptom or disease, remission, relapse, death due to some specific disease, or simply death. Often it is impossible to measureX due to the occurrence of some other competing event, usually termed a competing risk. This competing event may be the withdrawal of the subject from the study (for whatever reason), death from some cause other than the one of interest, or any eventuality that precludes the main event of interest from occurring. Usually the assumption is made that all such censoring times and lifetimes are independent. In this case one uses either the Kaplan-Meier estimator or the Nelson-Aalen estimator to estimate the survival function. However, if the competing risk or censoring times are not independent ofX, then there is no generally acceptable way to estimate the survival function. There has been considerable work devoted to this problem of dependent competing risks scattered throughout the statistical literature in the past several years and this paper presents a survey of such work.     

Power and sample size considerations in clinical trials with competing risk endpoints

In clinical trials with a time-to-event endpoint, subjects are often at risk for events other than the one of interest. When the occurrence of one type of event precludes observation of any later events or alters the probably of subsequent events, the situation is one of competing risks. During the planning stage of a clinical trial with competing risks, it is important to take all possible events into account. This paper gives expressions for the power and sample size for competing risks based on a flexible parametric Weibull model. Nonuniform accrual to the study is considered and an allocation ratio other than one may be used. Results are also provided for the case where two or more of the competing risks are of primary interest.     

A New lifetime model for multivariate survival data with a surviving fraction

In this paper we propose a new lifetime model for multivariate survival data with a surviving fraction. We develop this model assuming that there are m types of unobservable competing risks, where each risk is related to a time of the occurrence of an event of interest. We explore the use of Markov chain Monte Carlo methods to develop a Bayesian analysis for the proposed model. We also perform a simulation study in order to analyse the frequentist coverage probabilities of credible interval derived from posteriors. Our modelling is illustrated through a real data set.     

Analysis of Competing Risks by Using Bayesian Smoothing

We consider the competing risks set-up. In many practical situations, the conditional probability of the cause of failure given the failure time is of direct interest. We propose to model the competing risks by the overall hazard rate and the conditional probabilities rather than the cause-specific hazards. We adopt a Bayesian smoothing approach for both quantities of interest. Illustrations are given at the end.     

Testing dependence between the failure time and failure modes: An application of enlarged filtration

The model of independent competing risks provides no information for the assessment of competing failure modes if the failure mechanisms underlying these modes are coupled. Models for dependent competing risks in the literature can be distinguished on the basis of the functional behaviour of the conditional probability of failure due to a particular failure mode given that the failure time exceeds a fixed time, as a function of time. There is an interesting link between monotonicity of such conditional probability and dependence between failure time and failure mode, via crude hazard rates. In this paper, we propose tests for testing the dependence between failure time and failure mode using the crude hazards and using the conditional probabilities mentioned above. We establish the equivalence between the two approaches and provide an asymptotically efficient weight function under a sequence of local alternatives. The tests are applied to simulated data and to mortality follow-up data.     

Semiparametric analysis of mixture regression models with competing risks data

In the analysis of competing risks data, cumulative incidence function is a useful summary of the overall crude risk for a failure type of interest. Mixture regression modeling has served as a natural approach to performing covariate analysis based on this quantity. However, existing mixture regression methods with competing risks data either impose parametric assumptions on the conditional risks or require stringent censoring assumptions. In this article, we propose a new semiparametric regression approach for competing risks data under the usual conditional independent censoring mechanism. We establish the consistency and asymptotic normality of the resulting estimators. A simple resampling method is proposed to approximate the distribution of the estimated parameters and that of the predicted cumulative incidence functions. Simulation studies and an analysis of a breast cancer dataset demonstrate that our method performs well with realistic sample sizes and is appropriate for practical use.     

Analysis of interval censored competing risk data with missing causes of failure using pseudo values approach

Competing risks often occur when subjects may fail from one of several mutually exclusive causes. For example, when a patient suffering a cancer may die from other cause, we are interested in the effect of a certain covariate on the probability of dying of cancer at a certain time. Several approaches have been suggested to analyse competing risk data in the presence of complete information of failure cause. In this paper, our interest is to consider the occurrence of missing causes as well as interval censored failure time. There exist no method to discuss this problem. We applied a Klein–Andersen's pseudo-value approach [Klein, JP Andersen PK. Regression modeling of competing risks data based on pseudovalues of the cumulative incidence function. Biometrics. 2005;61:223–229] based on the estimated cumulative incidence function and a regression coefficient is estimated through a multiple imputation. We evaluate the suggested method by comparing with a complete case analysis in several simulation settings.     

Nonparametric inference for panel count data with competing risks

In survival and reliability studies, panel count data arise when we investigate a recurrent event process and each study subject is observed only at discrete time points. If recurrent events of several types are possible, we obtain panel count data with competing risks. Such data arise frequently from transversal studies on recurrent events in demography, epidemiology and reliability experiments where the individuals cannot be observed continuously. In the present paper, we propose an isotonic regression estimator for the cause specific mean function of the underlying recurrent event process of a competing risks panel count data. Further, a nonparametric test is proposed to compare the cause specific mean functions of the panel count competing risks data. Asymptotic properties of the proposed estimator and test statistic are studied. A simulation study is conducted to assess the finite sample behaviour of the proposed estimator and test statistic. Finally, the procedures developed are applied to a real data arising from skin cancer chemo prevention trial.