Parametric Proportional Odds Frailty Models

We define a parametric proportional odds frailty model to describe lifetime data incorporating heterogeneity between individuals. An unobserved individual random effect, called frailty, acts multiplicatively on the odds of failure by time t. We investigate fitting by maximum likelihood and by least squares. For the latter, the parametric survivor function is fitted to the nonparametric Kaplan–Meier estimate at the observed failure times. Bootstrap standard errors and confidence intervals are obtained for the least squares estimates. The models are applied successfully to simulated data and to two real data sets. Least squares estimates appear to have smaller bias than maximum likelihood.     

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.     

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.     

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.     

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.     

Shared frailty model based on reversed hazard rate for left censored data

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in the individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin or family data), the shared frailty models were suggested. In this article, we introduce the shared gamma frailty models with the reversed hazard rate. We develop the Bayesian estimation procedure using the 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 apply the model to a real life bivariate survival dataset.     

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.     

Testing Heterogeneity for Frailty Distribution in Shared Frailty Model

Abstract

The frailties, representing extra variations due to unobserved measurements, are often assumed to be iid in shared frailty models. In medical applications, however, a speculation can arise that a data set might violate the iid assumption. In this paper we investigate this conjecture through an analysis of the kidney infection data in McGilchrist and Aisbett (McGilchrist, C. A., Aisbett, C. W. (1991). Regression with frailty in survival analysis. Biometrics 47:461–466). As a test procedure, we consider the cusum of squares test which is frequently used for monitoring a variance change in statistical models. Our result strongly sustains the heterogeneity of the frailty distribution.     

Correlated gamma frailty models for bivariate survival data

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 (e.g., matched pairs experiments, twin or family data) the shared frailty models were suggested. Shared frailty models are used despite their limitations. To overcome their disadvantages correlated frailty models may be used. In this article, we introduce the gamma correlated frailty models with two different baseline distributions namely, the generalized log logistic, and the generalized Weibull. We introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in these models. We present a simulation study to compare the true values of the parameters with the estimated values. Also we apply these models to a real life bivariate survival dataset related to the kidney infection data and a better model is suggested for the data.     

Nonparametric Panel Estimation of Labor Supply

In this article, we estimate structural labor supply with piecewise-linear budgets and nonseparable endogenous unobserved heterogeneity. We propose a two-stage method to address the endogeneity issue that comes from the correlation between the covariates and unobserved heterogeneity. In the first stage, Evdokimov’s nonparametric de-convolution method serves to identify the conditional distribution of unobserved heterogeneity from the quasi-reduced model that uses panel data. In the second stage, the conditional distribution is plugged into the original structural model to estimate labor supply. We apply this methodology to estimate the labor supply of U.S. married men in 2004 and 2005. Our empirical work demonstrates that ignoring the correlation between the covariates and unobserved heterogeneity will bias the estimates of wage elasticities upward. The labor elasticity estimated from a fixed effects model is less than half of that obtained from a random effects model.     

Diagnostic Plots for Assessing the Frailty Distribution in Multivariate Survival Data

In biomedical studies, frailty models arecommonly used in analyzing multivariate survival data, wherethe objective of the study is to estimate both the covariateeffect and the dependence between the multivariate survival times.However, inference based on these models are dependent on thedistributional assumption of frailty. We propose a diagnosticplot for assessing the frailty assumption. The proposed methodis based on the cross-ratio function and the diagnostic plotsuggested by Oakes (1989). We use kernel regression smoothingwith bandwidth choice by cross-validation, to obtain the proposedplot. The resulting plot is capable of differentiating betweenthe gamma and positive stable frailty models when strong associationis present. We illustrate the feasibility of our method usingsimulation studies under known frailty distributions. The approachis applied to data on blindness for each eye of diabetic patientswith adult onset diabetes and a reasonable fit to the gamma frailtymodel is found.     

Frailty models for survival data

A frailty model is a random effects model for time variables, where the random effect (the frailty) has a multiplicative effect on the hazard. It can be used for univariate (independent) failure times, i.e. to describe the influence of unobserved covariates in a proportional hazards model. More interesting, however, is to consider multivariate (dependent) failure times generated as conditionally independent times given the frailty. This approach can be used both for survival times for individuals, like twins or family members, and for repeated events for the same individual. The standard assumption is to use a gamma distribution for the frailty, but this is a restriction that implies that the dependence is most important for late events. More generally, the distribution can be stable, inverse Gaussian, or follow a power variance function exponential family. Theoretically, large differences are seen between the choices. In practice, using the largest model makes it possible to allow for more general dependence structures, without making the formulas too complicated.This paper is a revised version of a review, which together with ten papers by the author made up a thesis for a Doctor of Science degree at the University of Copenhagen.     

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 a convergent stochastic estimation algorithm for frailty models

A maximum likelihood estimation procedure is presented for the frailty model. The procedure is based on a stochastic Expectation Maximization algorithm which converges quickly to the maximum likelihood estimate. The usual expectation step is replaced by a stochastic approximation of the complete log-likelihood using simulated values of unobserved frailties whereas the maximization step follows the same lines as those of the Expectation Maximization algorithm. The procedure allows to obtain at the same time estimations of the marginal likelihood and of the observed Fisher information matrix. Moreover, this stochastic Expectation Maximization algorithm requires less computation time. A wide variety of multivariate frailty models without any assumption on the covariance structure can be studied. To illustrate this procedure, a Gaussian frailty model with two frailty terms is introduced. The numerical results based on simulated data and on real bladder cancer data are more accurate than those obtained by using the Expectation Maximization Laplace algorithm and the Monte-Carlo Expectation Maximization one. Finally, since frailty models are used in many fields such as ecology, biology, economy, …, the proposed algorithm has a wide spectrum of applications.     

Validation of prognostic indices using the frailty model

A major issue when proposing a new prognostic index is its generalisibility to daily clinical practice. Validation is therefore required. Most validation techniques assess whether “on average” the results obtained by the prognostic index in classifying patients in a new sample of patients are similar to the results obtained in the construction set. We introduce a new important aspect of the generalisibility of a prognostic index: the heterogeneity of the prognostic index risk group hazard ratios over different centers. If substantial variability between centers exists, the prognostic index may have no discriminatory capability in some of the centers. To model such heterogeneity, we use a frailty model including a random center effect and a random prognostic index by center interaction. Statistical inference is based on a Bayesian approach using a Laplacian approximation for the marginal posterior distribution of the variances of the random effects. We investigate different ways to summarize the information available from this marginal posterior distribution. Our approach is applied to a real bladder cancer database for which we demonstrate how to investigate and interpret heterogeneity in prognostic index effect over centers.     

Asymptotic Properties of Adaptive Likelihood Weights by Cross-Validation

For clinical trials on neurodegenerative diseases such as Parkinson's or Alzheimer's, the distributions of psychometric measures for both placebo and treatment groups are generally skewed because of the characteristics of the diseases. Through an analytical, but computationally intensive, algorithm, we specifically compare power curves between 3- and 7-category ordinal logistic regression models in terms of the probability of detecting the treatment effect, assuming a symmetric distribution or skewed distributions for the placebo group. The proportional odds assumption under the ordinal logistic regression model plays an important role in these comparisons. The results indicate that there is no significant difference in the power curves between 3-category and 7-category response models where a symmetric distribution is assumed for the placebo group. However, when the skewness becomes more extreme for the placebo group, the loss of power can be substantial.     

Defective models induced by gamma frailty term for survival data with cured fraction

In this paper, we propose a defective model induced by a frailty term for modeling the proportion of cured. Unlike most of the cure rate models, defective models have advantage of modeling the cure rate without adding any extra parameter in model. The introduction of an unobserved heterogeneity among individuals has bring advantages for the estimated model. The influence of unobserved covariates is incorporated using a proportional hazard model. The frailty term assumed to follow a gamma distribution is introduced on the hazard rate to control the unobservable heterogeneity of the patients. We assume that the baseline distribution follows a Gompertz and inverse Gaussian defective distributions. Thus we propose and discuss two defective distributions: the defective gamma-Gompertz and gamma-inverse Gaussian regression models. Simulation studies are performed to verify the asymptotic properties of the maximum likelihood estimator. Lastly, in order to illustrate the proposed model, we present three applications in real data sets, in which one of them we are using for the first time, related to a study about breast cancer in the A.C.Camargo Cancer Center, São Paulo, Brazil.     

贝叶斯隐马尔科夫异质面板模型及应用研究

针对不可观测异质性非时变假设导致的删失变量偏差及推断无效问题,构建贝叶斯隐马尔科夫异质面板模型,刻画截面个体间的动态时变不可观测异质性,诊断经济系统环境中可能存在的隐性变点,设计相应的马尔科夫链蒙特卡洛抽样算法估计模型参数,并对中国各地区的金融发展与城乡收入差距关系进行实证分析,捕捉到金融发展与城乡收入差距间长期稳定关系的隐性变化,发现了区域个体不可观测异质性存在的动态时变特征。研究结果表明各参数的迭代轨迹收敛且估计误差非常小,验证了贝叶斯隐马尔科夫异质面板模型的有效性。     

Count data and treatment heterogeneity in 2×2 crossover trials

Count data are routinely assumed to have a Poisson distribution, especially when there are no straightforward diagnostic procedures for checking this assumption. We reanalyse two data sets from crossover trials of treatments for angina pectoris , in which the outcomes are counts of anginal attacks. Standard analyses focus on treatment effects, averaged over subjects; we are also interested in the dispersion of these effects (treatment heterogeneity). We set up a log-Poisson model with random coefficients to estimate the distribution of the treatment effects and show that the analysis is very sensitive to the distributional assumption; the population variance of the treatment effects is confounded with the (variance) function that relates the conditional variance of the outcomes, given the subject's rate of attacks, to the conditional mean. Diagnostic model checks based on resampling from the fitted distribution indicate that the default choice of the Poisson distribution for the analysed data sets is poorly supported. We propose to augment the data sets with observations of the counts, made possibly outside the clinical setting, so that the conditional distribution of the counts could be established.     

The determinants of price in online auctions: more evidence from unbalanced panel data

This study provides an alternative approach that takes account of the unobserved effects of each seller under a sample selection framework while using online auction data. We use data collected from Yahoo! Kimo Auction (Taiwan) to demonstrate that earlier empirical results of online auction studies may be biased due to violating the assumption of independence of the error terms between sample observations. Empirical findings show that seller reputation is no longer as the most important factor for buyers to bid on items, while the sample data confirm the unobserved heterogeneity of sellers and sample selection problem.