Flexible modelling of simultaneously interval censored and truncated time‐to‐event data

This paper deals with the analysis of data from a HET‐CAM^VT experiment. From a statistical perspective, such data yield many challenges. First of all, the data are typically time‐to‐event like data, which are at the same time interval censored and right truncated. In addition, one has to cope with overdispersion as well as clustering. Traditional analysis approaches ignore overdispersion and clustering and summarize the data into a continuous score that can be analysed using simple linear models. In this paper, a novel combined frailty model is developed that simultaneously captures all of the aforementioned statistical challenges posed by the data. Copyright © 2015 John Wiley & Sons, Ltd.     

Semiparametric mixed-effects models for clustered doubly censored data

The Cox proportional frailty model with a random effect has been proposed for the analysis of right-censored data which consist of a large number of small clusters of correlated failure time observations. For right-censored data, Cai et al. [3] proposed a class of semiparametric mixed-effects models which provides useful alternatives to the Cox model. We demonstrate that the approach of Cai et al. [3] can be used to analyze clustered doubly censored data when both left- and right-censoring variables are always observed. The asymptotic properties of the proposed estimator are derived. A simulation study is conducted to investigate the performance of the proposed estimator.     

Semiparametric Likelihood Estimation in the Clayton–Oakes Failure Time Model

Multivariate failure time data arise when the sample consists of clusters and each cluster contains several possibly dependent failure times. The Clayton–Oakes model (Clayton, 1978; Oakes, 1982) for multivariate failure times characterizes the intracluster dependence parametrically but allows arbitrary specification of the marginal distributions. In this paper, we discuss estimation in the Clayton–Oakes model when the marginal distributions are modeled to follow the Cox (1972) proportional hazards regression model. Parameter estimation is based on an approximate generalized maximum likelihood estimator. We illustrate the model's application with example datasets.     

Shared frailty models with baseline generalized Pareto distribution

Abstract

In this article, we have considered three different shared frailty models under the assumption of generalized Pareto Distribution as baseline distribution. Frailty models have been used in the survival analysis to account for the unobserved heterogeneity in an individual risks to disease and death. These three frailty models are with gamma frailty, inverse Gaussian frailty and positive stable frailty. Then we introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters. We applied these three models to a kidney infection data and find the best fitted model for kidney infection data. We present a simulation study to compare true value of the parameters with the estimated values. Model comparison is made using Bayesian model selection criterion and a well-fitted model is suggested for the kidney infection data.     

Graphical Tests for the Frailty Distribution in the Shared Frailty Model

We extend a diagnostic plot for the frailty distribution in proportional hazards models to the case of shared frailty. The plot is based on a closure property of exponential family failure distributions with canonical statistics z and g(z), namely that the frailty distribution among survivors at time t has the same form, with the same values of the parameters associated with g(z). We extend this property to shared frailty, considering various definitions of a “surviving” cluster at time t. We illustrate the effectiveness of the method in the case where the “death” of the cluster is defined by the first death among its members.     

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.     

Marker processes in survival analysis

In the development of many diseases there are often associated variables which continuously measure the progress of an individual towards the final expression of the disease (failure). Such variables are stochastic processes, here called marker processes, and, at a given point in time, they may provide information about the current hazard and subsequently on the remaining time to failure. Here we consider a simple additive model for the relationship between the hazard function at time t and the history of the marker process up until time t. We develop some basic calculations based on this model. Interest is focused on statistical applications for markers related to estimation of the survival distribution of time to failure, including (i) the use of markers as surrogate responses for failure with censored data, and (ii) the use of markers as predictors of the time elapsed since onset of a survival process in prevalent individuals. Particular attention is directed to potential gains in efficiency incurred by using marker process information.     

Using Frailties in the Accelerated Failure Time Model

The accelerated failuretime (AFT) model is an important alternative to the Cox proportionalhazards model (PHM) in survival analysis. For multivariate failuretime data we propose to use frailties to explicitly account forpossible correlations (and heterogeneity) among failure times.An EM-like algorithm analogous to that in the frailty model forthe Cox model is adapted. Through simulation it is shown thatits performance compares favorably with that of the marginalindependence approach. For illustration we reanalyze a real dataset.     

Statistical inference for the accelerated failure time model under two-stage generalized case–cohort design

Abstract

In this article, we propose a two-stage generalized case–cohort design and develop an efficient inference procedure for the data collected with this design. In the first-stage, we observe the failure time, censoring indicator and covariates which are easy or cheap to measure, and in the second-stage, select a subcohort by simple random sampling and a subset of failures in remaining subjects from the first-stage subjects to observe their exposures which are different or expensive to measure. We derive estimators for regression parameters in the accelerated failure time model under the two-stage generalized case–cohort design through the estimated augmented estimating equation and the kernel function method. The resulting estimators are shown to be consistent and asymptotically normal. The finite sample performance of the proposed method is evaluated through the simulation studies. The proposed method is applied to a real data set from the National Wilm’s Tumor Study Group.     

Semiparametric Global Cross-ratio Models for Bivariate Censored Data

Abstract.  Multivariate correlated failure time data arise in many medical and scientific settings. In the analysis of such data, it is important to use models where the parameters have simple interpretations. In this paper, we formulate a model for bivariate survival data based on the Plackett distribution. The model is an alternative to the Gamma frailty model proposed by Clayton and Oakes. The parameter in this distribution has a very appealing odds ratio interpretation for dependence between the two failure times; in addition, it allows for negative dependence. We develop novel semiparametric estimation and inference procedures for the model. The asymptotic results of the estimator are developed. The performance of the proposed techniques in finite samples is examined using simulation studies; in addition, the proposed methods are applied to data from an observational study in cancer.     

A study of R2 measure under the accelerated failure time models

For right-censored data, the accelerated failure time (AFT) model is an alternative to the commonly used proportional hazards regression model. It is a linear model for the (log-transformed) outcome of interest, and is particularly useful for censored outcomes that are not time-to-event, such as laboratory measurements. We provide a general and easily computable definition of the R² measure of explained variation under the AFT model for right-censored data. We study its behavior under different censoring scenarios and under different error distributions; in particular, we also study its robustness when the parametric error distribution is misspecified. Based on Monte Carlo investigation results, we recommend the log-normal distribution as a robust error distribution to be used in practice for the parametric AFT model, when the R² measure is of interest. We apply our methodology to an alcohol consumption during pregnancy data set from Ukraine.     

An estimating equation for parametric shared frailty models with marginal additive hazards

Summary.  Multivariate failure time data arise when data consist of clusters in which the failure times may be dependent. A popular approach to such data is the marginal proportional hazards model with estimation under the working independence assumption. In some contexts, however, it may be more reasonable to use the marginal additive hazards model. We derive asymptotic properties of the Lin and Ying estimators for the marginal additive hazards model for multivariate failure time data. Furthermore we suggest estimating equations for the regression parameters and association parameters in parametric shared frailty models with marginal additive hazards by using the Lin and Ying estimators. We give the large sample properties of the estimators arising from these estimating equations and investigate their small sample properties by Monte Carlo simulation. A real example is provided for illustration.     

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.     

Estimation in the Positive Stable Shared Frailty Cox Proportional Hazards Model

Shared frailty models are of interest when one has clustered survival data and when focus is on comparing the lifetimes within clusters and further on estimating the correlation between lifetimes from the same cluster. It is well known that the positive stable model should be preferred to the gamma model in situations where the correlated survival data show a decreasing association with time. In this paper, we devise a likelihood based estimation procedure for the positive stable shared frailty Cox model, which is expected to obtain high efficiency. The proposed estimator is provided with large sample properties and also a consistent estimator of standard errors is given. Simulation studies show that the estimation procedure is appropriate for practical use, and that it is much more efficient than a recently suggested procedure. The suggested methodology is applied to a dataset concerning time to blindness for patients with diabetic retinopathy.     

Parametric versus semi-parametric models for the analysis of correlated survival data: A case study in veterinary epidemiology

Correlated survival data arise frequently in biomedical and epidemiologic research, because each patient may experience multiple events or because there exists clustering of patients or subjects, such that failure times within the cluster are correlated. In this paper, we investigate the appropriateness of the semi-parametric Cox regression and of the generalized estimating equations as models for clustered failure time data that arise from an epidemiologic study in veterinary medicine. The semi-parametric approach is compared with a proposed fully parametric frailty model. The frailty component is assumed to follow a gamma distribution. Estimates of the fixed covariates effects were obtained by maximizing the likelihood function, while an estimate of the variance component ( frailty parameter) was obtained from a profile likelihood construction.     

Analysis of Failure Time Data with Mixed-Effects Accelerated Failure Time Model

In randomized clinical trials or observational studies, subjects are recruited at multiple treating sites. Factors that vary across sites may have some influence on outcomes; therefore, they need to be taken into account to get better results. We apply the accelerated failure time (AFT) model with linear mixed effects to analyze failure time data, accounting for correlations between outcomes. Specifically, we use Bayesian approach to fit the data, computing the regression parameters by Gibbs sampler combined with Buckley-James method. This approach is compared with the marginal independence approach and other methods through simulations and an application to a real example.     

The nested joint clustering via Dirichlet process mixture model

This article focuses on the clustering problem based on Dirichlet process (DP) mixtures. To model both time invariant and temporal patterns, different from other existing clustering methods, the proposed semi-parametric model is flexible in that both the common and unique patterns are taken into account simultaneously. Furthermore, by jointly clustering subjects and the associated variables, the intrinsic complex shared patterns among subjects and among variables are expected to be captured. The number of clusters and cluster assignments are directly inferred with the use of DP. Simulation studies illustrate the effectiveness of the proposed method. An application to wheal size data is discussed with an aim of identifying novel temporal patterns among allergens within subject clusters.     

A frailty modeling approach for parental effects in animal breeding

Survival models involving frailties are commonly applied in studies where correlated event time data arise due to natural or artificial clustering. In this paper we present an application of such models in the animal breeding field. Specifically, a mixed survival model with a multivariate correlated frailty term is proposed for the analysis of data from over 3611 Brazilian Nellore cattle. The primary aim is to evaluate parental genetic effects on the trait length in days that their progeny need to gain a commercially specified standard weight gain. This trait is not measured directly but can be estimated from growth data. Results point to the importance of genetic effects and suggest that these models constitute a valuable data analysis tool for beef cattle breeding.     

A Diagnostic for Association in Bivariate Survival Models

We propose exploratory, easily implemented methods for diagnosing the appropriateness of an underlying copula model for bivariate failure time data, allowing censoring in either or both failure times. It is found that the proposed approach effectively distinguishes gamma from positive stable copula models when the sample is moderately large or the association is strong. Data from the Womens Health and Aging Study (WHAS, Guralnik et al., The Womenss Health and Aging Study: Health and Social Characterisitics of Older Women with Disability. National Institute on Aging: Bethesda, Mayland, 1995) are analyzed to demonstrate the proposed diagnostic methodology. The positive stable model gives a better overall fit to these data than the gamma frailty model, but it tends to underestimate association at the later time points. The finding is consistent with recent theory differentiating catastrophic from progressive disability onset in older adults. The proposed methods supply an interpretable quantity for copula diagnosis. We hope that they will usefully inform practitioners as to the reasonableness of their modeling choices.     

Caries on Permanent Teeth: A Non-parametric Bayesian Analysis

Most earlier epidemiological investigations of dental caries have been based on cross-sectional data. Subject-specific information of dental caries in the past, and the duration of exposure of each tooth to the oral environment, are obviously important factors also influencing the presence of dental caries in the future. This has led us to consider multivariate survival models in which the information about the tooth eruption and failure times are combined to assess caries risk. A non-parametric Bayesian intensity model is presented, reflecting, on the one hand, the within subject and between subject sources of variability, and a corresponding split of variability when considering the 28 permanent teeth. We analyse a data set consisting of the dental history of 240 boys, where the observations are based on predetermined dental examinations taking place approximately once every year. Markov chain Monte Carlo integration techniques are applied in the numerical work.