A competing risks model for correlated data based on the subdistribution hazard

Family-based follow-up study designs are important in epidemiology as they enable investigations of disease aggregation within families. Such studies are subject to methodological complications since data may include multiple endpoints as well as intra-family correlation. The methods herein are developed for the analysis of age of onset with multiple disease types for family-based follow-up studies. The proposed model expresses the marginalized frailty model in terms of the subdistribution hazards (SDH). As with Pipper and Martinussen’s (Scand J Stat 30:509–521, 2003) model, the proposed multivariate SDH model yields marginal interpretations of the regression coefficients while allowing the correlation structure to be specified by a frailty term. Further, the proposed model allows for a direct investigation of the covariate effects on the cumulative incidence function since the SDH is modeled rather than the cause specific hazard. A simulation study suggests that the proposed model generally offers improved performance in terms of bias and efficiency when a sufficient number of events is observed. The proposed model also offers type I error rates close to nominal. The method is applied to a family-based study of breast cancer when death in absence of breast cancer is considered a competing risk.     

Competing risks model with random censoring on the leff

We consider a model involvingk competing risks when the random variables of interest (risks) are censored from the left with the unobservable random variable. The nonparametrical estimators for survival functions of risks are presented and the estimators are strongly approximated with the best rates by appropriate Gaussian processes.     

Flexible simulation of competing risks data following prespecified subdistribution hazards

In recent years different approaches for the analysis of time-to-event data in the presence of competing risks, i.e. when subjects can fail from one of two or more mutually exclusive types of event, were introduced. Different approaches for the analysis of competing risks data, focusing either on cause-specific or subdistribution hazard rates, were presented in statistical literature. Many new approaches use complicated weighting techniques or resampling methods, not allowing an analytical evaluation of these methods. Simulation studies often replace analytical comparisons, since they can be performed more easily and allow investigation of non-standard scenarios. For adequate simulation studies the generation of appropriate random numbers is essential. We present an approach to generate competing risks data following flexible prespecified subdistribution hazards. Event times and types are simulated using possibly time-dependent cause-specific hazards, chosen in a way that the generated data will follow the desired subdistribution hazards or hazard ratios, respectively.     

An additive subdistribution hazard model for competing risks data

The cumulative incidence function plays an important role in assessing its treatment and covariate effects with competing risks data. In this article, we consider an additive hazard model allowing the time-varying covariate effects for the subdistribution and propose the weighted estimating equation under the covariate-dependent censoring by fitting the Cox-type hazard model for the censoring distribution. When there exists some association between the censoring time and the covariates, the proposed coefficients’ estimations are unbiased and the large-sample properties are established. The finite-sample properties of the proposed estimators are examined in the simulation study. The proposed Cox-weighted method is applied to a competing risks dataset from a Hodgkin's disease study.     

Bayesian inference of the fully specified subdistribution model for survival data with competing risks

Competing risks data are routinely encountered in various medical applications due to the fact that patients may die from different causes. Recently, several models have been proposed for fitting such survival data. In this paper, we develop a fully specified subdistribution model for survival data in the presence of competing risks via a subdistribution model for the primary cause of death and conditional distributions for other causes of death. Various properties of this fully specified subdistribution model have been examined. An efficient Gibbs sampling algorithm via latent variables is developed to carry out posterior computations. Deviance information criterion (DIC) and logarithm of the pseudomarginal likelihood (LPML) are used for model comparison. An extensive simulation study is carried out to examine the performance of DIC and LPML in comparing the cause-specific hazards model, the mixture model, and the fully specified subdistribution model. The proposed methodology is applied to analyze a real dataset from a prostate cancer study in detail.     

Semiparametric transformation models with random effects for clustered doubly censored data

For right-censored data, Zeng et al. [Semiparametirc transformation modes with random effects for clustered data. Statist Sin. 2008;18:355–377] proposed a class of semiparametric transformation models with random effects to formulate the effects of possibly time-dependent covariates on clustered failure times. In this article, we demonstrate that the approach of Zeng et al. can be extended to analyse clustered doubly censored data. The asymptotic properties of the nonparametric maximum likelihood estimators of the model parameters are derived. A simulation study is conducted to investigate the performance of the proposed estimators.     

Stratified proportional subdistribution hazards model with covariate-adjusted censoring weight for case-cohort studies

The case-cohort study design is widely used to reduce cost when collecting expensive covariates in large cohort studies with survival or competing risks outcomes. A case-cohort study dataset consists of two parts: (a) a random sample and (b) all cases or failures from a specific cause of interest. Clinicians often assess covariate effects on competing risks outcomes. The proportional subdistribution hazards model directly evaluates the effect of a covariate on the cumulative incidence function under the non-covariate-dependent censoring assumption for the full cohort study. However, the non-covariate-dependent censoring assumption is often violated in many biomedical studies. In this article, we propose a proportional subdistribution hazards model for case-cohort studies with stratified data with covariate-adjusted censoring weight. We further propose an efficient estimator when extra information from the other causes is available under case-cohort studies. The proposed estimators are shown to be consistent and asymptotically normal. Simulation studies show (a) the proposed estimator is unbiased when the censoring distribution depends on covariates and (b) the proposed efficient estimator gains estimation efficiency when using extra information from the other causes. We analyze a bone marrow transplant dataset and a coronary heart disease dataset using the proposed method.     

Proportional hazards model for competing risks data with missing cause of failure

We consider the semiparametric proportional hazards model for the cause-specific hazard function in analysis of competing risks data with missing cause of failure. The inverse probability weighted equation and augmented inverse probability weighted equation are proposed for estimating the regression parameters in the model, and their theoretical properties are established for inference. Simulation studies demonstrate that the augmented inverse probability weighted estimator is doubly robust and the proposed method is appropriate for practical use. The simulations also compare the proposed estimators with the multiple imputation estimator of Lu and Tsiatis (2001). The application of the proposed method is illustrated using data from a bone marrow transplant study.     

Efficient estimation for the proportional hazards model with competing risks and current status data

The proportional hazards model is the most commonly used model in regression analysis of failure time data and has been discussed by many authors under various situations (Kalbfleisch & Prentice, 2002. The Statistical Analysis of Failure Time Data, Wiley, New York). This paper considers the fitting of the model to current status data when there exist competing risks, which often occurs in, for example, medical studies. The maximum likelihood estimates of the unknown parameters are derived and their consistency and convergence rate are established. Also we show that the estimates of regression coefficients are efficient and have asymptotically normal distributions. Simulation studies are conducted to assess the finite sample properties of the estimates and an illustrative example is provided. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

A general joint model for longitudinal measurements and competing risks survival data with heterogeneous random effects

This article studies a general joint model for longitudinal measurements and competing risks survival data. The model consists of a linear mixed effects sub-model for the longitudinal outcome, a proportional cause-specific hazards frailty sub-model for the competing risks survival data, and a regression sub-model for the variance–covariance matrix of the multivariate latent random effects based on a modified Cholesky decomposition. The model provides a useful approach to adjust for non-ignorable missing data due to dropout for the longitudinal outcome, enables analysis of the survival outcome with informative censoring and intermittently measured time-dependent covariates, as well as joint analysis of the longitudinal and survival outcomes. Unlike previously studied joint models, our model allows for heterogeneous random covariance matrices. It also offers a framework to assess the homogeneous covariance assumption of existing joint models. A Bayesian MCMC procedure is developed for parameter estimation and inference. Its performances and frequentist properties are investigated using simulations. A real data example is used to illustrate the usefulness of the approach.     

On the multivariate spatial median for clustered data

The authors consider the multivariate one-sample location problem with clustered data from a nonparametric viewpoint. They propose the spatial median and its affine equivariant version as companion estimators to the affine invariant sign test of Larocque (2003). They extend the asymptotics of the proposed estimators to cluster dependent data and explore the limiting as well as finite-sample efficiencies for multivariate Student distributions. They demonstrate that the efficiency of the spatial median suffers less from intracluster correlation than the mean vector. They use data on the well-being of pupils in Finnish schools to illustrate their work.     

A weighted spatial median for clustered data

A weighted spatial median is proposed for the multivariate one-sample location problem with clustered data. Its limiting distribution is derived under mild conditions (no moment assumptions) and it is shown to be multivariate normal. Asymptotic as well as finite sample efficiencies and breakdown properties are considered, and the theoretical results are supplied with illustrative examples. It turns out that there is a potential for meaningful gains in estimation efficiency: the weighted spatial median has superior efficiency to the unweighted spatial median particularly when the cluster sizes are widely disparate and in the presence of strong intracluster correlation. The unweighted spatial median for clustered data was considered earlier by Nevalainen et al. (Can J Statist, in press, 2007). The proposed weighted estimators provide companion estimates to the weighted affine invariant sign test proposed recently by Larocque et al. (Biometrika, in press, 2007). An affine equivariant weighted spatial median is discussed in parallel.     

A proportional hazards model for the analysis of doubly censored competing risks data

ABSTRACT

Competing risks data are common in medical research in which lifetime of individuals can be classified in terms of causes of failure. In survival or reliability studies, it is common that the patients (objects) are subjected to both left censoring and right censoring, which is refereed as double censoring. The analysis of doubly censored competing risks data in presence of covariates is the objective of this study. We propose a proportional hazards model for the analysis of doubly censored competing risks data, using the hazard rate functions of Gray (1988 Gray, R.J. (1988). A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann. Statist. 16:1141–1154.[Crossref], [Web of Science ®] , [Google Scholar]), while focusing upon one major cause of failure. We derive estimators for regression parameter vector and cumulative baseline cause specific hazard rate function. Asymptotic properties of the estimators are discussed. A simulation study is conducted to assess the finite sample behavior of the proposed estimators. We illustrate the method using a real life doubly censored competing risks data.     

A random‐effects model for clustered circular data

This article considers a circular regression model for clustered data, where both the cluster effects and the regression errors have von Mises distributions. It involves β, a vector of parameters for the fixed effects, and two concentration parameters for the error distribution. A measure of intra‐cluster circular correlation and a predictor for an unobserved cluster random effect are studied. Preliminary estimators for the vector β and the two concentration parameters are proposed, and their performance is compared with that of the maximum likelihood estimators in a simulation study. A numerical example investigating the factors impacting the orientation taken by a sand hopper when released is presented. The Canadian Journal of Statistics 47: 712–728; 2019 © 2019 Statistical Society of Canada     

Competing risks for repairable systems: A data study

We analyze a dataset from the Offshore Reliability Data (OREDA) Database, looking for a model, which can be used to unveil aspects of the quality of the maintenance performed. To do so, we must investigate the mathematical modeling of maintenance and repair of components that can fail due to a variety of failure mechanisms.     

The random partition masking model for interval-censored and masked competing risks data

We study the nonparametric maximum likelihood estimate (NPMLE) of the cdf or sub-distribution functions of the failure time for the failure causes in a series system. The study is motivated by a cancer research data (from the Memorial Sloan-Kettering Cancer Center) with interval-censored time and masked failure cause. The NPMLE based on this data set suggests that the existing masking models are not appropriate. We propose a new model called the random partition masking model, which does not rely on the commonly used symmetry assumption (namely, given the failure cause, the probability of observing the masked failure causes is independent of the failure time; see Flehinger et al. Inference about defects in the presence of masking, Technometrics 38 (1996), pp. 247–255). The RPM model is easier to implement in simulation studies than the existing models. We discuss the algorithms for computing the NPMLE and study its asymptotic properties. Our simulation and data analysis indicate that the NPMLE is feasible for a moderate sample size.     

Survival analysis based on the proportional hazards model and survey data

The authors propose methods based on the stratified Cox proportional hazards model that account for the fact that the data have been collected according to a complex survey design. The methods they propose are based on the theory of estimating equations in conjunction with empirical process theory. The authors also discuss issues concerning ignorable sampling design, and the use of weighted and unweighted procedures. They illustrate their methodology by an analysis of jobless spells in Statistics Canada's Survey of Labour and Income Dynamics. They discuss briefly problems concerning weighting, model checking, and missing or mismeasured data. They also identify areas for further research.     

Nonparametric tests for stratified additive hazards model based on current status data

Stratified regression models are commonly employed when study subjects may come from possibly different strata such as different medical centers, and for the situation, one common question of interest is to test the existence of the stratum effect. To address this, there exists some literature on the testing of the stratum effects under the framework of the proportional hazards model when one observes right-censored data or interval-censored data. In this paper, we consider the situation under the additive hazards model when one faces current status data, for which there does not seem to exist an established test procedure. The asymptotic distributions of the proposed test procedure are provided. Also a simulation study is performed to evaluate the performance of the proposed method and indicates that it works well for practical situations. The approach is applied to a set of real current status data from a tumorigenicity study.     

Model diagnostics for the proportional hazards model with length-biased data

Length-biased data are frequently encountered in prevalent cohort studies. Many statistical methods have been developed to estimate the covariate effects on the survival outcomes arising from such data while properly adjusting for length-biased sampling. Among them, regression methods based on the proportional hazards model have been widely adopted. However, little work has focused on checking the proportional hazards model assumptions with length-biased data, which is essential to ensure the validity of inference. In this article, we propose a statistical tool for testing the assumed functional form of covariates and the proportional hazards assumption graphically and analytically under the setting of length-biased sampling, through a general class of multiparameter stochastic processes. The finite sample performance is examined through simulation studies, and the proposed methods are illustrated with the data from a cohort study of dementia in Canada.