Stochastic comparisons in frailty models

The frailty model in survival analysis accounts for unobserved heterogeneity between individuals by assuming that the hazard rate of an individual is the product of an individual specific quantity, called “frailty” and a baseline hazard rate. It is well known that the choice of the frailty distribution strongly affects the nonparametric estimate of the baseline hazard as well as that of the conditional probabilities. This paper reviews the basic concepts of a frailty model, presents various probability inequalities and other monotonicity results which may prove useful in choosing among alternative specifications. More specifically, our main result lies in seeing how well known stochastic orderings between distributions of two frailities translate into orderings between the corresponding survival functions. Some probabilistic aspects and implications of the models resulting from competing choices of the distributions of frailty or the baseline are compared.     

Frailty models and copulas: similarities and differences

Copulas and frailty models are important tools to model bivariate survival data. Equivalence between Archimedean copula models and shared frailty models, e.g. between the Clayton-Oakes copula model and the shared gamma frailty model, has often been claimed in the literature. In this note we show that, in both the models, there is indeed a well-known equivalence between the copula functions; the modeling of the marginal survival functions, however, is quite different. The latter fact leads to different joint survival functions.     

On comparisons of population and subpopulations in frailty models

Abstract

This paper studies stochastic comparisons between a population and subpopulations in both multiplicative and additive frailty models. The comparisons between a population and its baseline in stochastic ordering are conducted as a special case. We build equivalent characterizations of some common stochastic orders between a population and a subpopulation, in terms of the frailty of the subpopulation and the first two moments of frailty variable. Some examples and applications are discussed as well.     

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.     

Conditional and marginal estimates in case-control family data – extensions and sensitivity analyses

This work considers two specific estimation techniques for the family-specific proportional hazards model and for the population-averaged proportional hazards model. So far, these two estimation procedures were presented and studied under the gamma frailty distribution mainly because of its simple interpretation and mathematical tractability. Modifications of both procedures for other frailty distributions, such as the inverse Gaussian, positive stable and a specific case of discrete distribution, are presented. By extensive simulations, it is shown that under the family-specific proportional hazards model, the gamma frailty model appears to be robust to frailty distribution mis-specification in both bias and efficiency loss in the marginal parameters. The population-averaged proportional hazards model, is found to be robust under the gamma frailty model mis-specification only under moderate or weak dependency within cluster members.     

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.     

Modelling survival data using mixtures of frailties

Frailty models are often used to describe the extra heterogeneity in survival data by introducing an individual random, unobserved effect. The frailty term is usually assumed to act multiplicatively on a baseline hazard function common to all individuals. In order to apply the frailty model, a specific frailty distribution has to be assumed. If at least one of the latent variables is continuous, the frailty must follow a continuous distribution. In this paper, a finite mixture of continuous frailty distributions is used in order to describe situations in which one (or more) of the latent variables separates the population in study into two (or more) subpopulations. Closure properties of the unobserved quantity are given along with the maximum-likelihood estimates under the most common choices of frailty distributions. The model is illustrated on a set of lifetime data.     

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.     

A covariance-based test for shared frailty in multivariate lifetime data

We decompose the score statistic for testing for shared finite variance frailty in multivariate lifetime data into marginal and covariance-based terms. The null properties of the covariance-based statistic are derived in the context of parametric lifetime models. Its non-null properties are estimated using simulation and compared with those of the score test and two likelihood ratio tests when the underlying lifetime distribution is Weibull. Some examples are used to illustrate the covariance-based test. A case is made for using the covariance-based statistic as a simple diagnostic procedure for shared frailty in a parametric exploratory analysis of multivariate lifetime data and a link to the bivariate Clayton–Oakes copula model is shown.     

Shared frailty models based on reversed hazard rate for modified inverse Weibull distribution as baseline distribution

The unknown or unobservable risk factors in the survival analysis cause heterogeneity between individuals. Frailty models are used in the survival analysis to account for the unobserved heterogeneity in individual risks to disease and death. To analyze the bivariate data on related survival times, the shared frailty models were suggested. The most common shared frailty model is a model in which frailty act multiplicatively on the hazard function. In this paper, we introduce the shared gamma frailty model and the inverse Gaussian frailty model with the reversed hazard rate. We introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in the model. We present a simulation study to compare the true values of the parameters with the estimated values. We also apply the proposed models to the Australian twin data set and a better model is suggested.     

Estimation of the cumulative baseline hazard function for dependently right-censored failure time data

In this paper, we study the properties of a special class of frailty models when the frailty is common to several failure times. The models are closely linked to Archimedean copula models. We establish a useful formula for cumulative baseline hazard functions and develop a new estimator for cumulative baseline hazard functions in bivariate frailty regression models. Based on our proposed estimator, we present a graphical model checking procedure. We fit a leukemia data set using our model and end our paper with some discussions.     

A Distribution for Multivariate Frailty Based on the Compound Poisson Distribution with Random Scale

Frailty models are often used to model heterogeneity in survival analysis. The most common frailty model has an individual intensity which is a product of a random factor and a basic intensity common to all individuals. This paper uses the compound Poisson distribution as the random factor. It allows some individuals to be non-susceptible, which can be useful in many settings. In some diseases, one may suppose that a number of families have an increased susceptibility due to genetic circumstances. Then, it is logical to use a frailty model where the individuals within each family have some shared factor, while individuals between families have different factors. This can be attained by randomizing the Poisson parameter in the compound Poisson distribution. To our knowledge, this is a new distribution. The power variance function distributions are used for the Poisson parameter. The subsequent appearing distributions are studied in some detail, both regarding appearance and various statistical properties. An application to infant mortality data from the Medical Birth Registry of Norway is included, where the model is compared to more traditional shared frailty models.     

Impact of misspecified residual correlation structure on the parameter estimates in a shared spatial frailty model

In practice, survival data are often collected over geographical regions. Shared spatial frailty models have been used to model spatial variation in survival times, which are often implemented using the Bayesian Markov chain Monte Carlo method. However, this method comes at the price of slow mixing rates and heavy computational cost, which may render it impractical for data-intensive application. Alternatively, a frailty model assuming an independent and identically distributed (iid) random effect can be easily and efficiently implemented. Therefore, we used simulations to assess the bias and efficiency loss in the estimated parameters, if residual spatial correlation is present but using an iid random effect. Our simulations indicate that a shared frailty model with an iid random effect can estimate the regression coefficients reasonably well, even with residual spatial correlation present, when the percentage of censoring is not too high and the number of clusters and cluster size are not too low. Therefore, if the primary goal is to assess the covariate effects, one may choose the frailty model with an iid random effect; whereas if the goal is to predict the hazard, additional care needs to be given due to the efficiency loss in the parameter(s) for the baseline hazard.     

On some generalized orderings: In the spirit of relative ageing

ABSTRACT

We introduce some new generalized stochastic orderings (in the spirit of relative ageing) which compare probability distributions with the exponential distribution. These orderings are useful to understand the phenomenon of positive ageing classes and also helpful to guide the practitioners when there are crossing hazard rates and/or crossing mean residual lives. We study some characterizations of these orderings. Inter-relations among these orderings have also been discussed.     

A STOCHASTIC ORDERING FOR RANDOM VARIABLES WITH APPLICATIONS

A new univariate stochastic ordering is introduced. Some characterization results for such an ordering are stated. It is proved that the ordering is an integral stochastic ordering, obtaining a maximal generator. By means of this generator, the main properties of the ordering are deduced. A method for introducing univariate stochastic orderings, suggested by the new ordering, is analysed. Relationships with other stochastic orderings are also developed. To conclude, an example of an application of the new ordering to the field of medicine is proposed.     

A Weibull Regression Model with Gamma Frailties for Multivariate Survival Data

Frequently in the analysis of survival data, survival times within the same group are correlated due to unobserved co-variates. One way these co-variates can be included in the model is as frailties. These frailty random block effects generate dependency between the survival times of the individuals which are conditionally independent given the frailty. Using a conditional proportional hazards model, in conjunction with the frailty, a whole new family of models is introduced. By considering a gamma frailty model, often the issue is to find an appropriate model for the baseline hazard function. In this paper a flexible baseline hazard model based on a correlated prior process is proposed and is compared with a standard Weibull model. Several model diagnostics methods are developed and model comparison is made using recently developed Bayesian model selection criteria. The above methodologies are applied to the McGilchrist and Aisbett (1991) kidney infection data and the analysis is performed using Markov Chain Monte Carlo methods. This revised version was published online in July 2006 with corrections to the Cover Date.     

Characterizations and ordering properties based on log-odds functions

In this paper, we obtain some general results on characterizations of probability distributions from relationships between conditional moment, failure rate, and log-odds rate functions. We also study stochastic orders and classes based on the log-odds rate function and some relationships with usual stochastic orderings and classes. Some characterizations and ordering properties are obtained by using weighted distributions.     

Ascertainment-Adjusted Maximum Likelihood Estimation for the Additive Genetic Gamma Frailty Model

The additive genetic gamma frailty model has been proposed for genetic linkage analysis for complex diseases to account for variable age of onset and possible covariates effects. To avoid ascertainment biases in parameter estimates, retrospective likelihood ratio tests are often used, which may result in loss of efficiency due to conditioning. This paper considers when the sibships are ascertained by having at least two affected sibs with the disease before a given age and provides two approaches for estimating the parameters in the additive gamma frailty model. One approach is based on the likelihood function conditioning on the ascertainment event, the other is based on maximizing a full ascertainment-adjusted likelihood. Explicit forms for these likelihood functions are derived. Simulation studies indicate that when the baseline hazard function can be correctly pre-specified, both approaches give accurate estimates of the model parameters. However, when the baseline hazard function has to be estimated simultaneously, only the ascertainment-adjusted likelihood method gives an unbiased estimate of the parameters. These results imply that the ascertainment-adjusted likelihood ratio test in the context of the additive genetic gamma frailty may be used for genetic linkage analysis.     

Gamma shared frailty model based on reversed hazard rate

Abstract

Frailty models are used in survival analysis to account for unobserved heterogeneity in individual risks to disease and death. To analyze bivariate data on related survival times (e.g., matched pairs experiments, twin, or family data), shared frailty models were suggested. Shared frailty models are frequently used to model heterogeneity in survival analysis. The most common shared frailty model is a model in which hazard function is a product of random factor(frailty) and baseline hazard function which is common to all individuals. There are certain assumptions about the baseline distribution and distribution of frailty. In this paper, we introduce shared gamma frailty models with reversed hazard rate. We introduce Bayesian estimation procedure using Markov Chain Monte Carlo (MCMC) technique to estimate the parameters involved in the model. We present a simulation study to compare the true values of the parameters with the estimated values. Also, we apply the proposed model to the Australian twin data set.     

Non-mixture cure correlated frailty models in Bayesian approach

In this article, we develop a Bayesian approach for the estimation of two cure correlated frailty models that have been extended to the cure frailty models introduced by Yin [34]. We used the two different type of frailty with bivariate log-normal distribution instead of gamma distribution. A likelihood function was constructed based on a piecewise exponential distribution function. The model parameters were estimated by the Markov chain Monte Carlo method. The comparison of models is based on the Cox correlated frailty model with log-normal distribution. A real data set of bilateral corneal graft rejection was used to compare these models. The results of this data, based on deviance information criteria, showed the advantage of the proposed models.