Approximate Bayesian analysis of doubly censored samples from mixture of two Weibull distributions

The purpose of the paper is to estimate the parameters of the two-component mixture of Weibull distribution under doubly censored samples using Bayesian approach. The choice of Weibull distribution is made due to its (i) capability to model failure time data from engineering, medical and biological sciences (ii) added advantages over the well-known lifetime distributions such as exponential, Raleigh, lognormal and gamma distribution in terms of flexibility, increasing and decreasing hazard rate and closed-form distribution function and hazard rate. The proposed two-component mixture of Weibull distribution is even more flexible than its conventional form. However, the estimation of the parameters from the proposed mixture is more complex. Further, we have assumed couple of loss functions under non informative prior for the Bayesian analysis of the parameters from the mixture model. As the resultant Bayes estimators and associated posterior risks cannot be derived in the closed form, we have used the importance sampling and Lindley’s approximation to obtain the approximate estimates for the parameters of the mixture model. The comparison between the performances of approximation techniques has been made on the basis of simulation study and real-life data analysis. The importance sampling is found to be better than Lindley’s approximation as it gives better estimation for shape and mixing parameters of the mixture model and computations under this technique are much easier/shorter than those under Lindley’s approximation.     

Survival functions for the frailty models based on the discrete compound Poisson process

Frailty models are often used to model heterogeneity in survival analysis. The distribution of the frailty is generally assumed to be continuous. In some circumstances, it is appropriate to consider discrete frailty distributions. Having zero frailty can be interpreted as being immune, and population heterogeneity may be analysed using discrete frailty models. In this paper, survival functions are derived for the frailty models based on the discrete compound Poisson process. Maximum likelihood estimation procedures for the parameters are studied. We examine the fit of the models to earthquake and the traffic accidents’ data sets from Turkey.     

Zero-inflated beta distribution for modeling the proportions in quantitative fatty acid signature analysis

Quantitative fatty acid signature analysis (QFASA) produces diet estimates containing the proportion of each species of prey in a predator's diet. Since the diet estimates are compositional, often contain an abundance of zeros (signifying the absence of a species in the diet), and samples sizes are generally small, inference problems require the use of nonstandard statistical methodology. Recently, a mixture distribution involving the multiplicative logistic normal distribution (and its skew-normal extension) was introduced in relation to QFASA to manage the problematic zeros. In this paper, we examine an alternative mixture distribution, namely, the recently proposed zero-inflated beta (ZIB) distribution. A potential advantage of using the ZIB distribution over the previously considered mixture models is that it does not require transformation of the data. To assess the usefulness of the ZIB distribution in QFASA inference problems, a simulation study is first carried out which compares the small sample properties of the maximum likelihood estimators of the means. The fit of the distributions is then examined using ‘pseudo-predators’ generated from a large real-life prey base. Finally, confidence intervals for the true diet based on the ZIB distribution are compared with earlier results through a simulation study and harbor seal data.     

Asymptotic Normality in Mixtures of Power Series Distributions

Abstract.  The problem of estimating the individual probabilities of a discrete distribution is considered. The true distribution of the independent observations is a mixture of a family of power series distributions. First, we ensure identifiability of the mixing distribution assuming mild conditions. Next, the mixing distribution is estimated by non-parametric maximum likelihood and an estimator for individual probabilities is obtained from the corresponding marginal mixture density. We establish asymptotic normality for the estimator of individual probabilities by showing that, under certain conditions, the difference between this estimator and the empirical proportions is asymptotically negligible. Our framework includes Poisson, negative binomial and logarithmic series as well as binomial mixture models. Simulations highlight the benefit in achieving normality when using the proposed marginal mixture density approach instead of the empirical one, especially for small sample sizes and/or when interest is in the tail areas. A real data example is given to illustrate the use of the methodology.     

Optimal collapsing of mixture distributions in robust recursive estimation

Several authors have discussed Kalman filtering procedures using a mixture of normals as a model for the distributions of the noise in the observation and/or the state space equations. Under this model, resulting posteriors involve a mixture of normal distributions, and a “collapsing method” must be found in order to keep the recursive procedure simple. We prove that the Kullback-Leibler distance between the mixture posterior and that of a single normal distribution is minimized when we choose the mean and variance of the single normal distribution to be the mean and variance of the mixture posterior. Hence, “collapsing by moments” is optimal in this sense. We then develop the resulting optimal algorithm for “Kalman filtering” for this situation, and illustrate its performance with an example.     

A Multi-state Piecewise Exponential Model of Hospital Outcomes after Injury

To allow more accurate prediction of hospital length of stay (LOS) after serious injury or illness, a multi-state model is proposed, in which transitions from the hospitalized state to three possible outcome states (home, long-term care, or death) are assumed to follow constant rates for each of a limited number of time periods. This results in a piecewise exponential (PWE) model for each outcome. Transition rates may be affected by time-varying covariates, which can be estimated from a reference database using standard statistical software and Poisson regression. A PWE model combining the three outcomes allows prediction of LOS. Records of 259,941 injured patients from the US Nationwide Inpatient Sample were used to create such a multi-state PWE model with four time periods. Hospital mortality and LOS for patient subgroups were calculated from this model, and time-varying covariate effects were estimated. Early mortality was increased by anatomic injury severity or penetrating mechanism, but these effects diminished with time; age and male sex remained strong predictors of mortality in all time periods. Rates of discharge home decreased steadily with time, while rates of transfer to long-term care peaked at five days. Predicted and observed LOS and mortality were similar for multiple subgroups. Conceptual background and methods of calculation are discussed and demonstrated. Multi-state PWE models may be useful to describe hospital outcomes, especially when many patients are not discharged home.     

On symmetry of finite mixtures of normal distributions

In this note we derive a necessary and sufficient condition for a distribution obtained by taking a finite mixture of multivariate normal distributions to be symmetric about zero. The result derived also holds for mixtures of symmetric stable distributions, including the Cauchy distribution.     

Characterization of a mixture of gamma distributions via conditional finite moments

A necessary and sufficient condition that a continuous, positive random variable follow a gamma distribution is given in terms of any one of its conditional finite moments and an expression involving its failure rate. The results are then used to develop a characterization for a mixture of two gamma distributions. The general results about characterization of a mixture of gamma distributions yield several special cases that have appeared separately in recent literature, including characterization of a single exponential distribution, characterization of a single gamma distribution (in terms of either first or second moments) and a sufficient condition for a mixture of two exponential distributions (in terms of first moments). The condition in this last result is shown to be necessary also. Numerous other cases are possible, using different choices for distribution parameters along with a selection of the mixing parameter, for either individual or mixtures of distributions. Various characterizations can be expressed using higher order moments, too.     

Mode Jumping Proposals in MCMC

Markov chain Monte Carlo algorithms generate samples from a target distribution by simulating a Markov chain. Large flexibility exists in specification of transition matrix of the chain. In practice, however, most algorithms used only allow small changes in the state vector in each iteration. This choice typically causes problems for multi-modal distributions as moves between modes become rare and, in turn, results in slow convergence to the target distribution. In this paper we consider continuous distributions on R ⁿ and specify how optimization for local maxima of the target distribution can be incorporated in the specification of the Markov chain. Thereby, we obtain a chain with frequent jumps between modes. We demonstrate the effectiveness of the approach in three examples. The first considers a simple mixture of bivariate normal distributions, whereas the two last examples consider sampling from posterior distributions based on previously analysed data sets.     

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     

A Bayesian hierarchical mixture model for platelet-derived growth factor receptor phosphorylation to improve estimation of progression-free survival in prostate cancer

Summary.  Advances in understanding the biological underpinnings of many cancers have led increasingly to the use of molecularly targeted anticancer therapies. Because the platelet-derived growth factor receptor (PDGFR) has been implicated in the progression of prostate cancer bone metastases, it is of great interest to examine possible relationships between PDGFR inhibition and therapeutic outcomes. We analyse the association between change in activated PDGFR (phosphorylated PDGFR) and progression-free survival time based on large within-patient samples of cell-specific phosphorylated PDGFR values taken before and after treatment from each of 88 prostate cancer patients. To utilize these paired samples as covariate data in a regression model for progression-free survival time, and be cause the phosphorylated PDGFR distributions are bimodal, we first employ a Bayesian hierarchical mixture model to obtain a deconvolution of the pretreatment and post-treatment within-patient phosphorylated PDGFR distributions. We evaluate fits of the mixture model and a non-mixture model that ignores the bimodality by using a supnorm metric to compare the empirical distribution of each phosphorylated PDGFR data set with the corresponding fitted distribution under each model. Our results show that first using the mixture model to account for the bimodality of the within-patient phosphorylated PDGFR distributions, and then using the posterior within-patient component mean changes in phosphorylated PDGFR so obtained as covariates in the regression model for progression-free survival time, provides an improved estimation.     

Optimal Partitioning for Linear Mixed Effects Models: Applications to Identifying Placebo Responders

A long-standing problem in clinical research is distinguishing drug treated subjects that respond due to specific effects of the drug from those that respond to non-specific (or placebo) effects of the treatment. Linear mixed effect models are commonly used to model longitudinal clinical trial data. In this paper we present a solution to the problem of identifying placebo responders using an optimal partitioning methodology for linear mixed effects models. Since individual outcomes in a longitudinal study correspond to curves, the optimal partitioning methodology produces a set of prototypical outcome profiles. The optimal partitioning methodology can accommodate both continuous and discrete covariates. The proposed partitioning strategy is compared and contrasted with the growth mixture modelling approach. The methodology is applied to a two-phase depression clinical trial where subjects in a first phase were treated openly for 12 weeks with fluoxetine followed by a double blind discontinuation phase where responders to treatment in the first phase were randomized to either stay on fluoxetine or switched to a placebo. The optimal partitioning methodology is applied to the first phase to identify prototypical outcome profiles. Using time to relapse in the second phase of the study, a survival analysis is performed on the partitioned data. The optimal partitioning results identify prototypical profiles that distinguish whether subjects relapse depending on whether or not they stay on the drug or are randomized to a placebo.     

Estimation of prolongation of hospital stay attributable to nosocomial infections: New approaches based on multistate models

Evaluation of the impact of nosocomial infection on duration of hospital stay usually relies on estimates obtained in prospective cohort studies. However, the statistical methods used to estimate the extra length of stay are usually not adequate. A naive comparison of duration of stay in infected and non-infected patients is not adequate to estimate the extra hospitalisation time due to nosocomial infections. Matching for duration of stay prior to infection can compensate in part for the bias of ad hoc methods. New model-based approaches have been developed to estimate the excess length of stay. It will be demonstrated that statistical models based on multivariate counting processes provide an appropriate framework to analyse the occurrence and impact of nosocomial infections. We will propose and investigate new approaches to estimate the extra time spent in hospitals attributable to nosocomial infections based on functionals of the transition probabilities in multistate models. Additionally, within the class of structural nested failure time models an alternative approach to estimate the extra stay due to nosocomial infections is derived. The methods are illustrated using data from a cohort study on 756 patients admitted to intensive care units at the University Hospital in Freiburg.     

Joint modeling of survival time and longitudinal outcomes with flexible random effects

Joint models with shared Gaussian random effects have been conventionally used in analysis of longitudinal outcome and survival endpoint in biomedical or public health research. However, misspecifying the normality assumption of random effects can lead to serious bias in parameter estimation and future prediction. In this paper, we study joint models of general longitudinal outcomes and survival endpoint but allow the underlying distribution of shared random effect to be completely unknown. For inference, we propose to use a mixture of Gaussian distributions as an approximation to this unknown distribution and adopt an Expectation–Maximization (EM) algorithm for computation. Either AIC and BIC criteria are adopted for selecting the number of mixtures. We demonstrate the proposed method via a number of simulation studies. We illustrate our approach with the data from the Carolina Head and Neck Cancer Study (CHANCE).     

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.     

Prediction for generalized linear models

Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.Regression models are often used to make predictions. All the information needed is contained in the predictive distribution. However, this cannot be evaluated explicitly for most generalized linear models. We construct two approximations to this distribution and demonstrate their use on two sets of survival data, corresponding to the outcome of patients admitted to intensive care units and the survival times of leukaemia patients.     

Analysis of a longitudinal ordinal response clinical trial using dynamic models

Summary.  In many areas of pharmaceutical research, there has been increasing use of categorical data and more specifically ordinal responses. In many cases, complex models are required to account for different types of dependences among the responses. The clinical trial that is considered here involved patients who were required to remain in a particular state to enable the doctors to examine their heart. The aim of this trial was to study the relationship between the dose of the drug administered and the time that was spent by the patient in the state permitting examination. The patient's state was measured every second by a continuous Doppler signal which was categorized by the doctors into one of four ordered categories. Hence, the response consisted of repeated ordinal series. These series were of different lengths because the drug effect wore off faster (or slower) on certain patients depending on the drug dose administered and the infusion rate, and therefore the length of drug administration. A general method for generating new ordinal distributions is presented which is sufficiently flexible to handle unbalanced ordinal repeated measurements. It consists of obtaining a cumulative mixture distribution from a Laplace transform and introducing into it the integrated intensity of a binary logistic, continuation ratio or proportional odds model. Then, a multivariate distribution is constructed by a procedure that is similar to the updating process of the Kalman filter. Several types of history dependences are proposed.     

Mixture Distributions Based Methods of Calibration for the Empirical Log-Likelihood Ratio

Empirical likelihood ratio confidence regions based on the chi-square calibration suffer from an undercoverage problem in that their actual coverage levels tend to be lower than the nominal levels. The finite sample distribution of the empirical log-likelihood ratio is recognized to have a mixture structure with a continuous component on [0, + ∞) and a point mass at + ∞. The undercoverage problem of the Chi-square calibration is partly due to its use of the continuous Chi-square distribution to approximate the mixture distribution of the empirical log-likelihood ratio. In this article, we propose two new methods of calibration which will take advantage of the mixture structure; we construct two new mixture distributions by using the F and chi-square distributions and use these to approximate the mixture distributions of the empirical log-likelihood ratio. The new methods of calibration are asymptotically equivalent to the chi-square calibration. But the new methods, in particular the F mixture based method, can be substantially more accurate than the chi-square calibration for small and moderately large sample sizes. The new methods are also as easy to use as the chi-square calibration.     

Modeling Event Times with Multiple Outcomes Using the Wiener Process with Drift

Length of stay in hospital (LOS) is a widely used outcome measure in Health Services research, often acting as a surrogate for resource consumption or as a measure of efficiency. The distribution of LOS is typically highly skewed, with a few large observations. An interesting feature is the presence of multiple outcomes (e.g. healthy discharge, death in hospital, transfer to another institution). Health Services researchers are interested in modeling the dependence of LOS on covariates, often using administrative data collected for other purposes, such as calculating fees for doctors. Even after all available covariates have been included in the model, unexplained heterogeneity usually remains. In this article, we develop a parametric regression model for LOS that addresses these features. The model is based on the time, T, that a Wiener process with drift (representing an unobserved health level process) hits one of two barriers, one representing healthy discharge and the other death in hospital. Our approach to analyzing event times has many parallels with competing risks analysis (Kalbfleisch and Prentice, The Statistical Analysis of Failure Time Data, New York: John Wiley and Sons, 1980)), and can be seen as a way of formalizing a competing risks situation. The density of T is an infinite series, and we outline a proof that the density and its derivatives are absolutely and uniformly convergent, and regularity conditions are satisfied. Expressions for the expected value of T, the conditional expectation of T given outcome, and the probability of each outcome are available in terms of model parameters. The proposed regression model uses an approximation to the density formed by truncating the series, and its parameters are estimated by maximum likelihood. An extension to allow a third outcome (e.g. transfers out of hospital) is discussed, as well as a mixture model that addresses the issue of unexplained heterogeneity. The model is illustrated using administrative data.