A Non-parametric Frailty Model for Temporally Clustered Multivariate Failure Times

Abstract A model is introduced here for multivariate failure time data arising from heterogenous populations. In particular, we consider a situation in which the failure times of individual subjects are often temporally clustered, so that many failures occur during a relatively short age interval. The clustering is modelled by assuming that the subjects can be divided into ‘internally homogenous’ latent classes, each such class being then described by a time‐dependent frailty profile function. As an example, we reanalysed the dental caries data presented earlier in Härkänen et al. [Scand. J. Statist. 27 (2000) 577], as it turned out that our earlier model could not adequately describe the observed clustering.     

A Class of Efficient Non-parametric K-sample Tests for Multivariate Counting Processes with Frailties

A K -sample testing problem is studied for multivariate counting processes with time-dependent frailty. Asymptotic distributions and efficiency of a class of non-parametric test statistics are established for certain local alternatives. The concept of efficiency is to show that for every non-parametric test in this class, there is a parametric submodel for which the optimal test has the same asymptotic power as the non-parametric one. The theory is applied to analyse a diabetic retinopathy study data set. A simulation study is also presented to illustrate the theory     

Local composite quantile regression estimation of time-varying parameter vector for multidimensional time-inhomogeneous diffusion models

This paper is dedicated to the study of the composite quantile regression (CQR) estimations of time-varying parameter vectors for multidimensional diffusion models. Based on the local linear fitting for parameter vectors, we propose the local linear CQR estimations of the drift parameter vectors, and verify their asymptotic biases, asymptotic variances and asymptotic normality. Moreover, we discuss the asymptotic relative efficiency (ARE) of the local linear CQR estimations with respect to the local linear least-squares estimations. We obtain that the local estimations that we proposed are much more efficient than the local linear least-squares estimations. Simulation studies are constructed to show the performance of the estimations proposed.     

Graphical representation of survival curves in the presence of time-dependent categorical covariates with application to liver transplantation

Graphical representation of survival curves is often used to illustrate associations between exposures and time-to-event outcomes. However, when exposures are time-dependent, calculation of survival probabilities is not straightforward. Our aim was to develop a method to estimate time-dependent survival probabilities and represent them graphically. Cox models with time-dependent indicators to represent state changes were fitted, and survival probabilities were plotted using pre-specified times of state changes. Time-varying hazard ratios for the state change were also explored. The method was applied to data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Survival curves showing a ‘split’ at a pre-specified time t allow for the qualitative comparison of survival probabilities between patients with similar baseline covariates who do and do not experience a state change at time t. Time since state change interactions can be visually represented to reflect changing hazard ratios over time. A2ALL study results showed differences in survival probabilities among those who did not receive a transplant, received a living donor transplant, and received a deceased donor transplant. These graphical representations of survival curves with time-dependent indicators improve upon previous methods and allow for clinically meaningful interpretation.     

论儒家的生态伦理自然观——“时中”生态智慧与同心圆生态模型

儒家重“时”尚“中”,其生态伦理自然观的精神内核是“时中”。儒家生态伦理自然观具有两重内涵,一是贵人而不惟人的非人类中心主义生态伦理情感立场,二是尽物而亦爱物的待物有别的生态伦理价值选择。在生态文明特别是生态伦理的意义上,两者都遵循着同心圆的生态模型。基于此,儒家的生态伦理自然观对当前的生态文明建设具有非常重要的资源意义和启发作用。     

Penalized spline joint models for longitudinal and time-to-event data

The joint models for longitudinal data and time-to-event data have recently received numerous attention in clinical and epidemiologic studies. Our interest is in modeling the relationship between event time outcomes and internal time-dependent covariates. In practice, the longitudinal responses often show non linear and fluctuated curves. Therefore, the main aim of this paper is to use penalized splines with a truncated polynomial basis to parameterize the non linear longitudinal process. Then, the linear mixed-effects model is applied to subject-specific curves and to control the smoothing. The association between the dropout process and longitudinal outcomes is modeled through a proportional hazard model. Two types of baseline risk functions are considered, namely a Gompertz distribution and a piecewise constant model. The resulting models are referred to as penalized spline joint models; an extension of the standard joint models. The expectation conditional maximization (ECM) algorithm is applied to estimate the parameters in the proposed models. To validate the proposed algorithm, extensive simulation studies were implemented followed by a case study. In summary, the penalized spline joint models provide a new approach for joint models that have improved the existing standard joint models.     

Cancer Risk Assessment with Intermittent Exposure

Applications of methods for carcinogenic risk assessment often focus on estimating lifetime cancer risk. With intermittent or time-dependent exposures, lifetime risk is often approximated on the basis of a lifetime average daily dose (LADD). In this article, we show that there exists a lifetime equivalent constant dose (LECD) which leads to the same lifetime risk as the actual time-dependent exposure pattern. The ratio C = LECD/LADD then provides a measure of accuracy of risk estimates based on the LADD, as well as a basis for correcting such estimates. Theoretical results derived under the classical multistage model and the two-stage birth-death-mutation model suggest that the maximum value of C, which represents the factor by which the LADD may lead to underestimates of risk, will often lie in the range of 2- to 5-fold. The practical application of these results is illustrated in the case of astronauts subjected to relatively short-term exposure to volatile organics in a closed space station environment, and in the case of the ingestion of pesticide residues in food where consumption patterns vary with age.     

A Semi-parametric Bayesian Analysis of Survival Data Based on Lévy-driven Processes

In the presence of covariate information, the proportional hazards model is one of the most popular models. In this paper, in a Bayesian nonparametric framework, we use a Markov (Lévy-driven) process to model the baseline hazard rate. Previous Bayesian nonparametric models have been based on neutral to the right processes, which have a number of drawbacks, such as discreteness of the cumulative hazard function. We allow the covariates to be time dependent functions and develop a full posterior analysis via substitution sampling. A detailed illustration is presented.     

Piecewise proportional hazards models with interval-censored data

We consider the piecewise proportional hazards (PWPH) model with interval-censored (IC) relapse times under the distribution-free set-up. The partial likelihood approach is not applicable for IC data, and the generalized likelihood approach has not been studied in the literature. It turns out that under the PWPH model with IC data, the semi-parametric MLE (SMLE) of the covariate effect under the standard generalized likelihood may not be unique and may not be consistent. In fact, the parameter under the PWPH model with IC data is not identifiable unless the identifiability assumption is imposed. We propose a modification to the likelihood function so that its SMLE is unique. Under the identifiability assumption, our simulation study suggests that the SMLE is consistent. We apply the method to our cancer relapse time data and conclude that the bone marrow micrometastasis does not have a significant prognostic factor.