Analysis of cure rate survival data under proportional odds model

Due to significant progress in cancer treatments and management in survival studies involving time to relapse (or death), we often need survival models with cured fraction to account for the subjects enjoying prolonged survival. Our article presents a new proportional odds survival models with a cured fraction using a special hierarchical structure of the latent factors activating cure. This new model has same important differences with classical proportional odds survival models and existing cure-rate survival models. We demonstrate the implementation of Bayesian data analysis using our model with data from the SEER (Surveillance Epidemiology and End Results) database of the National Cancer Institute. Particularly aimed at survival data with cured fraction, we present a novel Bayes method for model comparisons and assessments, and demonstrate our new tool’s superior performance and advantages over competing tools.     

The use of auxiliary variables in capture-recapture modelling: An overview

I review the use of auxiliary variables in capture-recapture models for estimation of demographic parameters (e.g. capture probability, population size, survival probability, and recruitment, emigration and immigration numbers). I focus on what has been done in current research and what still needs to be done. Typically in the literature, covariate modelling has made capture and survival probabilities functions of covariates, but there are good reasons also to make other parameters functions of covariates as well. The types of covariates considered include environmental covariates that may vary by occasion but are constant over animals, and individual animal covariates that are usually assumed constant over time. I also discuss the difficulties of using time-dependent individual animal covariates and some possible solutions. Covariates are usually assumed to be measured without error, and that may not be realistic. For closed populations, one approach to modelling heterogeneity in capture probabilities uses observable individual covariates and is thus related to the primary purpose of this paper. The now standard Huggins-Alho approach conditions on the captured animals and then uses a generalized Horvitz-Thompson estimator to estimate population size. This approach has the advantage of simplicity in that one does not have to specify a distribution for the covariates, and the disadvantage is that it does not use the full likelihood to estimate population size. Alternately one could specify a distribution for the covariates and implement a full likelihood approach to inference to estimate the capture function, the covariate probability distribution, and the population size. The general Jolly-Seber open model enables one to estimate capture probability, population sizes, survival rates, and birth numbers. Much of the focus on modelling covariates in program MARK has been for survival and capture probability in the Cormack-Jolly-Seber model and its generalizations (including tag-return models). These models condition on the number of animals marked and released. A related, but distinct, topic is radio telemetry survival modelling that typically uses a modified Kaplan-Meier method and Cox proportional hazards model for auxiliary variables. Recently there has been an emphasis on integration of recruitment in the likelihood, and research on how to implement covariate modelling for recruitment and perhaps population size is needed. The combined open and closed 'robust' design model can also benefit from covariate modelling and some important options have already been implemented into MARK. Many models are usually fitted to one data set. This has necessitated development of model selection criteria based on the AIC (Akaike Information Criteria) and the alternative of averaging over reasonable models. The special problems of estimating over-dispersion when covariates are included in the model and then adjusting for over-dispersion in model selection could benefit from further research.     

Generalized accelerated failure time spatial frailty model for arbitrarily censored data

Flexible incorporation of both geographical patterning and risk effects in cancer survival models is becoming increasingly important, due in part to the recent availability of large cancer registries. Most spatial survival models stochastically order survival curves from different subpopulations. However, it is common for survival curves from two subpopulations to cross in epidemiological cancer studies and thus interpretable standard survival models can not be used without some modification. Common fixes are the inclusion of time-varying regression effects in the proportional hazards model or fully nonparametric modeling, either of which destroys any easy interpretability from the fitted model. To address this issue, we develop a generalized accelerated failure time model which allows stratification on continuous or categorical covariates, as well as providing per-variable tests for whether stratification is necessary via novel approximate Bayes factors. The model is interpretable in terms of how median survival changes and is able to capture crossing survival curves in the presence of spatial correlation. A detailed Markov chain Monte Carlo algorithm is presented for posterior inference and a freely available function frailtyGAFT is provided to fit the model in the R package spBayesSurv. We apply our approach to a subset of the prostate cancer data gathered for Louisiana by the surveillance, epidemiology, and end results program of the National Cancer Institute.     

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.     

The use of auxiliary variables in capture-recapture modelling: an overview

I review the use of auxiliary variables in capture-recapture models for estimation of demographic parameters (e.g. capture probability, population size, survival probability, and recruitment, emigration and immigration numbers). I focus on what has been done in current research and what still needs to be done. Typically in the literature, covariate modelling has made capture and survival probabilities functions of covariates, but there are good reasons also to make other parameters functions of covariates as well. The types of covariates considered include environmental covariates that may vary by occasion but are constant over animals, and individual animal covariates that are usually assumed constant over time. I also discuss the difficulties of using time-dependent individual animal covariates and some possible solutions. Covariates are usually assumed to be measured without error, and that may not be realistic. For closed populations, one approach to modelling heterogeneity in capture probabilities uses observable individual covariates and is thus related to the primary purpose of this paper. The now standard Huggins-Alho approach conditions on the captured animals and then uses a generalized Horvitz-Thompson estimator to estimate population size. This approach has the advantage of simplicity in that one does not have to specify a distribution for the covariates, and the disadvantage is that it does not use the full likelihood to estimate population size. Alternately one could specify a distribution for the covariates and implement a full likelihood approach to inference to estimate the capture function, the covariate probability distribution, and the population size. The general Jolly-Seber open model enables one to estimate capture probability, population sizes, survival rates, and birth numbers. Much of the focus on modelling covariates in program MARK has been for survival and capture probability in the Cormack-Jolly-Seber model and its generalizations (including tag-return models). These models condition on the number of animals marked and released. A related, but distinct, topic is radio telemetry survival modelling that typically uses a modified Kaplan-Meier method and Cox proportional hazards model for auxiliary variables. Recently there has been an emphasis on integration of recruitment in the likelihood, and research on how to implement covariate modelling for recruitment and perhaps population size is needed. The combined open and closed 'robust' design model can also benefit from covariate modelling and some important options have already been implemented into MARK. Many models are usually fitted to one data set. This has necessitated development of model selection criteria based on the AIC (Akaike Information Criteria) and the alternative of averaging over reasonable models. The special problems of estimating over-dispersion when covariates are included in the model and then adjusting for over-dispersion in model selection could benefit from further research.     

Predictive comparison of joint longitudinal-survival modeling: a case study illustrating competing approaches

The joint modeling of longitudinal and survival data has received extraordinary attention in the statistics literature recently, with models and methods becoming increasingly more complex. Most of these approaches pair a proportional hazards survival with longitudinal trajectory modeling through parametric or nonparametric specifications. In this paper we closely examine one data set previously analyzed using a two parameter parametric model for Mediterranean fruit fly (medfly) egg-laying trajectories paired with accelerated failure time and proportional hazards survival models. We consider parametric and nonparametric versions of these two models, as well as a proportional odds rate model paired with a wide variety of longitudinal trajectory assumptions reflecting the types of analyses seen in the literature. In addition to developing novel nonparametric Bayesian methods for joint models, we emphasize the importance of model selection from among joint and non joint models. The default in the literature is to omit at the outset non joint models from consideration. For the medfly data, a predictive diagnostic criterion suggests that both the choice of survival model and longitudinal assumptions can grossly affect model adequacy and prediction. Specifically for these data, the simple joint model used in by Tseng et al. (Biometrika 92:587–603, 2005) and models with much more flexibility in their longitudinal components are predictively outperformed by simpler analyses. This case study underscores the need for data analysts to compare on the basis of predictive performance different joint models and to include non joint models in the pool of candidates under consideration.     

Automatic model selection for high-dimensional survival analysis

Many different models for the analysis of high-dimensional survival data have been developed over the past years. While some of the models and implementations come with an internal parameter tuning automatism, others require the user to accurately adjust defaults, which often feels like a guessing game. Exhaustively trying out all model and parameter combinations will quickly become tedious or infeasible in computationally intensive settings, even if parallelization is employed. Therefore, we propose to use modern algorithm configuration techniques, e.g. iterated F-racing, to efficiently move through the model hypothesis space and to simultaneously configure algorithm classes and their respective hyperparameters. In our application we study four lung cancer microarray data sets. For these we configure a predictor based on five survival analysis algorithms in combination with eight feature selection filters. We parallelize the optimization and all comparison experiments with the BatchJobs and BatchExperiments R packages.     

A Quantile Survival Model for Censored Data

In this paper we propose a quantile survival model to analyze censored data. This approach provides a very effective way to construct a proper model for the survival time conditional on some covariates. Once a quantile survival model for the censored data is established, the survival density, survival or hazard functions of the survival time can be obtained easily. For illustration purposes, we focus on a model that is based on the generalized lambda distribution (GLD). The GLD and many other quantile function models are defined only through their quantile functions, no closed‐form expressions are available for other equivalent functions. We also develop a Bayesian Markov Chain Monte Carlo (MCMC) method for parameter estimation. Extensive simulation studies have been conducted. Both simulation study and application results show that the proposed quantile survival models can be very useful in practice.     

A model with long-term survivors: negative binomial Birnbaum-Saunders

Abstract

We propose a cure rate survival model by assuming that the number of competing causes of the event of interest follows the negative binomial distribution and the time to the event of interest has the Birnbaum-Saunders distribution. Further, the new model includes as special cases some well-known cure rate models published recently. We consider a frequentist analysis for parameter estimation of the negative binomial Birnbaum-Saunders model with cure rate. Then, we derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We illustrate the usefulness of the proposed model in the analysis of a real data set from the medical area.     

A dependent Dirichlet process model for survival data with competing risks

In this paper, we first propose a dependent Dirichlet process (DDP) model using a mixture of Weibull models with each mixture component resembling a Cox model for survival data. We then build a Dirichlet process mixture model for competing risks data without regression covariates. Next we extend this model to a DDP model for competing risks regression data by using a multiplicative covariate effect on subdistribution hazards in the mixture components. Though built on proportional hazards (or subdistribution hazards) models, the proposed nonparametric Bayesian regression models do not require the assumption of constant hazard (or subdistribution hazard) ratio. An external time-dependent covariate is also considered in the survival model. After describing the model, we discuss how both cause-specific and subdistribution hazard ratios can be estimated from the same nonparametric Bayesian model for competing risks regression. For use with the regression models proposed, we introduce an omnibus prior that is suitable when little external information is available about covariate effects. Finally we compare the models’ performance with existing methods through simulations. We also illustrate the proposed competing risks regression model with data from a breast cancer study. An R package “DPWeibull” implementing all of the proposed methods is available at CRAN.

     

Bayesian nonparametric survival analysis using mixture of Burr XII distributions

ABSTRACT

Recently, the Bayesian nonparametric approaches in survival studies attract much more attentions. Because of multimodality in survival data, the mixture models are very common. We introduce a Bayesian nonparametric mixture model with Burr distribution (Burr type XII) as the kernel. Since the Burr distribution shares good properties of common distributions on survival analysis, it has more flexibility than other distributions. By applying this model to simulated and real failure time datasets, we show the preference of this model and compare it with Dirichlet process mixture models with different kernels. The Markov chain Monte Carlo (MCMC) simulation methods to calculate the posterior distribution are used.     

Model selection for two-sample problems with right-censored data: An application of Cox model

For investigating differences between two treatment groups in medical science, selecting a suitable model to capture the underlying survival function for each group with some covariates is an important issue. Many methods, such as stratified Cox model and unstratified Cox model, have been proposed for investigating the problem. However, different models generally perform differently under different circumstances and none dominates the others. In this article, we focus on two sample problems with right-censored data and propose a model selection criterion based on an approximately unbiased estimator of Kullback-Leibler loss, which accounts for estimation uncertainty in estimated survival functions obtained by various candidate models. The effectiveness of the proposed method is justified by some simulation studies and it also applied to an HIV+ data set for illustration.     

An extension of the gamma distribution

ABSTRACT

The gamma distribution has been widely used in many research areas such as engineering and survival analysis. We present an extension of this distribution, called the Kummer beta gamma distribution, having greater flexibility to model scenarios involving skewed data. We derive analytical expressions for some mathematical quantities. The estimation of parameters is approached by the maximum likelihood method and Bayesian analysis. The likelihood ratio and formal goodness-of-fit tests are used to compare the presented distribution with some of its sub-models and non nested models. A real data set is used to illustrate the importance of the distribution.     

Competing risks model for clustered data based on the subdistribution hazards with spatial random effects

In some applications, the clustered survival data are arranged spatially such as clinical centers or geographical regions. Incorporating spatial variation in these data not only can improve the accuracy and efficiency of the parameter estimation, but it also investigates the spatial patterns of survivorship for identifying high-risk areas. Competing risks in survival data concern a situation where there is more than one cause of failure, but only the occurrence of the first one is observable. In this paper, we considered Bayesian subdistribution hazard regression models with spatial random effects for the clustered HIV/AIDS data. An intrinsic conditional autoregressive (ICAR) distribution was employed to model the areal spatial random effects. Comparison among competing models was performed by the deviance information criterion. We illustrated the gains of our model through application to the HIV/AIDS data and the simulation studies.KEYWORDS: Competing risks, subdistribution hazard, cumulative incidence function, spatial random effect, Markov chain Monte Carlo     

On estimation and influence diagnostics for log-Birnbaum–Saunders Student-t regression models: Full Bayesian analysis

The purpose of this paper is to develop a Bayesian approach for log-Birnbaum–Saunders Student-t regression models under right-censored survival data. Markov chain Monte Carlo (MCMC) methods are used to develop a Bayesian procedure for the considered model. In order to attenuate the influence of the outlying observations on the parameter estimates, we present in this paper Birnbaum–Saunders models in which a Student-t distribution is assumed to explain the cumulative damage. Also, some discussions on the model selection to compare the fitted models are given and case deletion influence diagnostics are developed for the joint posterior distribution based on the Kullback–Leibler divergence. The developed procedures are illustrated with a real data set.     

COM–Poisson cure rate survival models and an application to a cutaneous melanoma data

In this paper, we develop a flexible cure rate survival model by assuming the number of competing causes of the event of interest to follow the Conway–Maxwell Poisson distribution. This model includes as special cases some of the well-known cure rate models discussed in the literature. Next, we discuss the maximum likelihood estimation of the parameters of this cure rate survival model. Finally, we illustrate the usefulness of this model by applying it to a real cutaneous melanoma data.     

A log-linear regression model for the odd Weibull distribution with censored data

We introduce the log-odd Weibull regression model based on the odd Weibull distribution (Cooray, 2006). We derive some mathematical properties of the log-transformed distribution. The new regression model represents a parametric family of models that includes as sub-models some widely known regression models that can be applied to censored survival data. We employ a frequentist analysis and a parametric bootstrap for the parameters of the proposed model. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes and present some ways to assess global influence. Further, for different parameter settings, sample sizes and censoring percentages, some simulations are performed. In addition, the empirical distribution of some modified residuals are given and compared with the standard normal distribution. These studies suggest that the residual analysis usually performed in normal linear regression models can be extended to a modified deviance residual in the proposed regression model applied to censored data. We define martingale and deviance residuals to check the model assumptions. The extended regression model is very useful for the analysis of real data.     

Semi-parametric survival analysis via Dirichlet process mixtures of the First Hitting Time model

Time-to-event data often violate the proportional hazards assumption inherent in the popular Cox regression model. Such violations are especially common in the sphere of biological and medical data where latent heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed in the literature which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the First Hitting Time (FHT) paradigm which assumes that a subject’s event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of the FHT model have also been proposed which allow for better modeling of data with unmeasured covariates. While often appropriate, these methods often display limited flexibility due to their inability to model a wide range of heterogeneities. To address this issue, we propose a Bayesian model which loosens assumptions on the mixing distribution inherent in the random effects FHT models currently in use. We demonstrate via simulation study that the proposed model greatly improves both survival and parameter estimation in the presence of latent heterogeneity. We also apply the proposed methodology to data from a toxicology/carcinogenicity study which exhibits nonproportional hazards and contrast the results with both the Cox model and two popular FHT models.

     

A proportional-hazards model for survival analysis and long-term survivors modeling: application to amyotrophic lateral sclerosis data

The majority of survival data are affected by explanatory variables. We develop a new regression model for survival data analysis. As an alternative to standard mixture models, another model is proposed to describe the eventual presence of a surviving fraction. The proposed models are based on the Marshall–Olkin extended generalized Gompertz distribution. A maximum-likelihood inference is presented in the presence of covariates and a censorship phenomenon. Explanatory variables are incorporated into the model through proportional-hazards to evaluate the effect of risk factors on overall survival under different assumptions. Parametric, semi-parametric, and non-parametric methods are applied to survival analysis of patients treated for amyotrophic lateral sclerosis. Interesting results about riluzole use and other treatment effects on patients'' survival have been obtained.