Nonparametric Bayesian survival analysis using mixtures of Weibull distributions

Bayesian nonparametric methods have been applied to survival analysis problems since the emergence of the area of Bayesian nonparametrics. However, the use of the flexible class of Dirichlet process mixture models has been rather limited in this context. This is, arguably, to a large extent, due to the standard way of fitting such models that precludes full posterior inference for many functionals of interest in survival analysis applications. To overcome this difficulty, we provide a computational approach to obtain the posterior distribution of general functionals of a Dirichlet process mixture. We model the survival distribution employing a flexible Dirichlet process mixture, with a Weibull kernel, that yields rich inference for several important functionals. In the process, a method for hazard function estimation emerges. Methods for simulation-based model fitting, in the presence of censoring, and for prior specification are provided. We illustrate the modeling approach with simulated and real data.     

A Bayesian approach to mixture cure models with spatial frailties for population‐based cancer relative survival data

As the treatments of cancer progress, a certain number of cancers are curable if diagnosed early. In population‐based cancer survival studies, cure is said to occur when mortality rate of the cancer patients returns to the same level as that expected for the general cancer‐free population. The estimates of cure fraction are of interest to both cancer patients and health policy makers. Mixture cure models have been widely used because the model is easy to interpret by separating the patients into two distinct groups. Usually parametric models are assumed for the latent distribution for the uncured patients. The estimation of cure fraction from the mixture cure model may be sensitive to misspecification of latent distribution. We propose a Bayesian approach to mixture cure model for population‐based cancer survival data, which can be extended to county‐level cancer survival data. Instead of modeling the latent distribution by a fixed parametric distribution, we use a finite mixture of the union of the lognormal, loglogistic, and Weibull distributions. The parameters are estimated using the Markov chain Monte Carlo method. Simulation study shows that the Bayesian method using a finite mixture latent distribution provides robust inference of parameter estimates. The proposed Bayesian method is applied to relative survival data for colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the cure fractions. The Canadian Journal of Statistics 40: 40–54; 2012 © 2012 Statistical Society of Canada     

Joint model-based clustering of nonlinear longitudinal trajectories and associated time-to-event data analysis,linked by latent class membership: with application to AIDS clinical studies

Longitudinal and time-to-event data are often observed together. Finite mixture models are currently used to analyze nonlinear heterogeneous longitudinal data, which, by releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, can cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, and be associated with clinically important time-to-event data. This article develops a joint modeling approach to a finite mixture of NLME models for longitudinal data and proportional hazard Cox model for time-to-event data, linked by individual latent class indicators, under a Bayesian framework. The proposed joint models and method are applied to a real AIDS clinical trial data set, followed by simulation studies to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and Cox model are fitted separately.     

Testing for the Presence of a Cure Fraction in Clustered Interval‐Censored Survival Data

Clustered interval‐censored survival data are often encountered in clinical and epidemiological studies due to geographic exposures and periodic visits of patients. When a nonnegligible cured proportion exists in the population, several authors in recent years have proposed to use mixture cure models incorporating random effects or frailties to analyze such complex data. However, the implementation of the mixture cure modeling approaches may be cumbersome. Interest then lies in determining whether or not it is necessary to adjust the cured proportion prior to the mixture cure analysis. This paper mainly focuses on the development of a score for testing the presence of cured subjects in clustered and interval‐censored survival data. Through simulation, we evaluate the sampling distribution and power behaviour of the score test. A bootstrap approach is further developed, leading to more accurate significance levels and greater power in small sample situations. We illustrate applications of the test using data sets from a smoking cessation study and a retrospective study of early breast cancer patients.     

Estimating Cure Rates From Survival Data: An Alternative to Two-Component Mixture Models

This article considers the utility of the bounded cumulative hazard model in cure rate estimation, which is an appealing alternative to the widely used two-component mixture model. This approach has the following distinct advantages: (1) It allows for a natural way to extend the proportional hazards regression model, leading to a wide class of extended hazard regression models. (2) In some settings the model can be interpreted in terms of biologically meaningful parameters. (3) The model structure is particularly suitable for semiparametric and Bayesian methods of statistical inference. Notwithstanding the fact that the model has been around for less than a decade, a large body of theoretical results and applications has been reported to date. This review article is intended to give a big picture of these modeling techniques and associated statistical problems. These issues are discussed in the context of survival data in cancer.     

Latent mixture modeling for clustered data

Statistics and Computing - This article proposes a mixture modeling approach to estimating cluster-wise conditional distributions in clustered (grouped) data. We adapt the mixture-of-experts model...     

The inverse power Lindley distribution

Several probability distributions have been proposed in the literature, especially with the aim of obtaining models that are more flexible relative to the behaviors of the density and hazard rate functions. Recently, two generalizations of the Lindley distribution were proposed in the literature: the power Lindley distribution and the inverse Lindley distribution. In this article, a distribution is obtained from these two generalizations and named as inverse power Lindley distribution. Some properties of this distribution and study of the behavior of maximum likelihood estimators are presented and discussed. It is also applied considering two real datasets and compared with the fits obtained for already-known distributions. When applied, the inverse power Lindley distribution was found to be a good alternative for modeling survival data.     

Bayesian Kernel Mixtures for Counts

Although Bayesian nonparametric mixture models for continuous data are well developed, there is a limited literature on related approaches for count data. A common strategy is to use a mixture of Poissons, which unfortunately is quite restrictive in not accounting for distributions having variance less than the mean. Other approaches include mixing multinomials, which requires finite support, and using a Dirichlet process prior with a Poisson base measure, which does not allow smooth deviations from the Poisson. As a broad class of alternative models, we propose to use nonparametric mixtures of rounded continuous kernels. An efficient Gibbs sampler is developed for posterior computation, and a simulation study is performed to assess performance. Focusing on the rounded Gaussian case, we generalize the modeling framework to account for multivariate count data, joint modeling with continuous and categorical variables, and other complications. The methods are illustrated through applications to a developmental toxicity study and marketing data. This article has supplementary material online.     

Modelling heterogeneity of survival in band-recovery data using mixtures

Finite mixture methods are applied to bird band-recovery studies to allow for heterogeneity of survival. Birds are assumed to belong to one of finitely many groups, each of which has its own survival rate (or set of survival rates varying by time and/or age). The group to which a specific animal belongs is not known, so its survival probability is a random variable from a finite mixture. Heterogeneity is thus modelled as a latent effect. This gives a wide selection of likelihood-based models, which may be compared using likelihood ratio tests. These models are discussed with reference to real and simulated data, and compared with previous models.     

Modelling heterogeneity of survival in band-recovery data using mixtures

Finite mixture methods are applied to bird band-recovery studies to allow for heterogeneity of survival. Birds are assumed to belong to one of finitely many groups, each of which has its own survival rate (or set of survival rates varying by time and/or age). The group to which a specific animal belongs is not known, so its survival probability is a random variable from a finite mixture. Heterogeneity is thus modelled as a latent effect. This gives a wide selection of likelihood-based models, which may be compared using likelihood ratio tests. These models are discussed with reference to real and simulated data, and compared with previous models.     

Mean and cell-mean imputation resulting in the use of a semicontinuous distribution and a mixture of semicontinuous distributions

Zero-inflated models are commonly used for modeling count and continuous data with extra zeros. Inflations at one point or two points apart from zero for modeling continuous data have been discussed less than that of zero inflation. In this article, inflation at an arbitrary point α as a semicontinuous distribution is presented and the mean imputation for a continuous response is discussed as a cause of having semicontinuous data. Also, inflation at two points and generally at k arbitrary points and their relation to cell-mean imputation in the mixture of continuous distributions are studied. To analyze the imputed data, a mixture of semicontinuous distributions is used. The effects of covariates on the dependent variable in a mixture of k semicontinuous distributions with inflation at k points are also investigated. In order to find the parameter estimates, the method of expectation–maximization (EM) algorithm is used. In a real data of Iranian Households Income and Expenditure Survey (IHIES), it is shown how to obtain a proper estimate of the population variance when continuous missing at random responses are mean imputed.     

Nonparametric and semiparametric regression estimation for length-biased survival data

For the past several decades, nonparametric and semiparametric modeling for conventional right-censored survival data has been investigated intensively under a noninformative censoring mechanism. However, these methods may not be applicable for analyzing right-censored survival data that arise from prevalent cohorts when the failure times are subject to length-biased sampling. This review article is intended to provide a summary of some newly developed methods as well as established methods for analyzing length-biased data.     

Additive mixed models with approximate Dirichlet process mixtures: the EM approach

We consider additive mixed models for longitudinal data with a nonlinear time trend. As random effects distribution an approximate Dirichlet process mixture is proposed that is based on the truncated version of the stick breaking presentation of the Dirichlet process and provides a Gaussian mixture with a data driven choice of the number of mixture components. The main advantage of the specification is its ability to identify clusters of subjects with a similar random effects structure. For the estimation of the trend curve the mixed model representation of penalized splines is used. An Expectation-Maximization algorithm is given that solves the estimation problem and that exhibits advantages over Markov chain Monte Carlo approaches, which are typically used when modeling with Dirichlet processes. The method is evaluated in a simulation study and applied to theophylline data and to body mass index profiles of children.     

Robust mixture modeling using the skew <Emphasis Type="Italic">t</Emphasis> distribution

A finite mixture model using the Student's t distribution has been recognized as a robust extension of normal mixtures. Recently, a mixture of skew normal distributions has been found to be effective in the treatment of heterogeneous data involving asymmetric behaviors across subclasses. In this article, we propose a robust mixture framework based on the skew t distribution to efficiently deal with heavy-tailedness, extra skewness and multimodality in a wide range of settings. Statistical mixture modeling based on normal, Student's t and skew normal distributions can be viewed as special cases of the skew t mixture model. We present analytically simple EM-type algorithms for iteratively computing maximum likelihood estimates. The proposed methodology is illustrated by analyzing a real data example.     

Testing the Homogeneity of Two Survival Functions Against a Mixture Alternative Based on Censored Data

When the survival distribution in a treatment group is a mixture of two distributions of the same family, traditional parametric methods that ignore the existence of mixture components or the nonparametric methods may not be very powerful. We develop a modified likelihood ratio test (MLRT) for testing homogeneity in a two sample problem with censored data and compare the actual type I error and power of the MLRT with that nonparametric log-rank test and parametric test through Monte-Carlo simulations. The proposed test is also applied to analyze data from a clinical trial on early breast cancer.     

Heterogeneous data modeling with two-component Weibull–Poisson distribution

The mixture distribution models are more useful than pure distributions in modeling of heterogeneous data sets. The aim of this paper is to propose mixture of Weibull–Poisson (WP) distributions to model heterogeneous data sets for the first time. So, a powerful alternative mixture distribution is created for modeling of the heterogeneous data sets. In the study, many features of the proposed mixture of WP distributions are examined. Also, the expectation maximization (EM) algorithm is used to determine the maximum-likelihood estimates of the parameters, and the simulation study is conducted for evaluating the performance of the proposed EM scheme. Applications for two real heterogeneous data sets are given to show the flexibility and potentiality of the new mixture distribution.     

An Extended Mixture Distribution Survival Tree for Patient Pathway Prognostication

Mixture distribution survival trees are constructed by approximating different nodes in the tree by distinct types of mixture distributions to improve within node homogeneity. Previously, we proposed a mixture distribution survival tree-based method for determining clinically meaningful patient groups from a given dataset of patients’ length of stay. This article extends this approach to examine the interrelationship between length of stay in hospital, outcome measures, and other covariates. We describe an application of this approach to patient pathway and examine the relationship between length of stay in hospital and/or treatment outcome using five-years’ retrospective data of stroke patients.     

Modeling Data with Flat Densities

In this article, a simple probability distribution for modeling data with flat densities is introduced and used to model real world assessment data. The new distribution is a mixture of three distributions, two truncated normals, and a uniform. The parameters are estimated by using the sample percentiles because the likelihood and the method of moment approaches result in complicated forms. The proposed method is mainly based on the shape of the empirical density. The proposed method looks promising for modeling flat densities that are similar to the one used in the study.     

Analysis of mixed correlated semi-continuous and β-inflated Poisson responses

ABSTRACT

In this article, inflation at an arbitrary point β of a member of power series exponential family and mean-inflation as a cause of having semi-continuous distribution are discussed. Also, a joint modeling of such a semi-continuous response and β-inflated Poisson response is presented. Simultaneous effects of covariates on both responses, which have two-component mixture distributions, are investigated. To find the parameter estimates, the maximum likelihood approach is used. The proposed model is illustrated on some simulation studies and applied to a real survey dataset.     

Vertical modeling: analysis of competing risks data with a cure fraction

In this paper, we extend the vertical modeling approach for the analysis of survival data with competing risks to incorporate a cure fraction in the population, that is, a proportion of the population for which none of the competing events can occur. The proposed method has three components: the proportion of cure, the risk of failure, irrespective of the cause, and the relative risk of a certain cause of failure, given a failure occurred. Covariates may affect each of these components. An appealing aspect of the method is that it is a natural extension to competing risks of the semi-parametric mixture cure model in ordinary survival analysis; thus, causes of failure are assigned only if a failure occurs. This contrasts with the existing mixture cure model for competing risks of Larson and Dinse, which conditions at the onset on the future status presumably attained. Regression parameter estimates are obtained using an EM-algorithm. The performance of the estimators is evaluated in a simulation study. The method is illustrated using a melanoma cancer data set.