Negative variance components for non-negative hierarchical data with correlation,over-, and/or underdispersion

The concept of negative variance components in linear mixed-effects models, while confusing at first sight, has received considerable attention in the literature, for well over half a century, following the early work of Chernoff [7 H. Chernoff, On the distribution of the likelihood ratio, Ann. Math. Statist. 25 (1954), pp. 573–578.[Crossref] , [Google Scholar]] and Nelder [21 J.A. Nelder, The interpretation of negative components of variance, Biometrika 41 (1954), pp. 544–548.[Crossref], [Web of Science ®] , [Google Scholar]]. Broadly, negative variance components in linear mixed models are allowable if inferences are restricted to the implied marginal model. When a hierarchical view-point is adopted, in the sense that outcomes are specified conditionally upon random effects, the variance–covariance matrix of the random effects must be positive-definite (positive-semi-definite is also possible, but raises issues of degenerate distributions). Many contemporary software packages allow for this distinction. Less work has been done for generalized linear mixed models. Here, we study such models, with extension to allow for overdispersion, for non-negative outcomes (counts). Using a study of trichomes counts on tomato plants, it is illustrated how such negative variance components play a natural role in modeling both the correlation between repeated measures on the same experimental unit and over- or underdispersion.     

Bayesian variable selection for proportional hazards models

The authors consider the problem of Bayesian variable selection for proportional hazards regression models with right censored data. They propose a semi-parametric approach in which a nonparametric prior is specified for the baseline hazard rate and a fully parametric prior is specified for the regression coefficients. For the baseline hazard, they use a discrete gamma process prior, and for the regression coefficients and the model space, they propose a semi-automatic parametric informative prior specification that focuses on the observables rather than the parameters. To implement the methodology, they propose a Markov chain Monte Carlo method to compute the posterior model probabilities. Examples using simulated and real data are given to demonstrate the methodology.     

Effects of unstratified and centre‐stratified randomization in multi‐centre clinical trials

This paper deals with the analysis of randomization effects in multi‐centre clinical trials. The two randomization schemes most often used in clinical trials are considered: unstratified and centre‐stratified block‐permuted randomization. The prediction of the number of patients randomized to different treatment arms in different regions during the recruitment period accounting for the stochastic nature of the recruitment and effects of multiple centres is investigated. A new analytic approach using a Poisson‐gamma patient recruitment model (patients arrive at different centres according to Poisson processes with rates sampled from a gamma distributed population) and its further extensions is proposed. Closed‐form expressions for corresponding distributions of the predicted number of the patients randomized in different regions are derived. In the case of two treatments, the properties of the total imbalance in the number of patients on treatment arms caused by using centre‐stratified randomization are investigated and for a large number of centres a normal approximation of imbalance is proved. The impact of imbalance on the power of the study is considered. It is shown that the loss of statistical power is practically negligible and can be compensated by a minor increase in sample size. The influence of patient dropout is also investigated. The impact of randomization on predicted drug supply overage is discussed. Copyright © 2010 John Wiley & Sons, Ltd.     

Empirical Bayes models of Poisson clinical trials and sample size determination

Bayesian methods are often used to reduce the sample sizes and/or increase the power of clinical trials. The right choice of the prior distribution is a critical step in Bayesian modeling. If the prior not completely specified, historical data may be used to estimate it. In the empirical Bayesian analysis, the resulting prior can be used to produce the posterior distribution. In this paper, we describe a Bayesian Poisson model with a conjugate Gamma prior. The parameters of Gamma distribution are estimated in the empirical Bayesian framework under two estimation schemes. The straightforward numerical search for the maximum likelihood (ML) solution using the marginal negative binomial distribution is unfeasible occasionally. We propose a simplification to the maximization procedure. The Markov Chain Monte Carlo method is used to create a set of Poisson parameters from the historical count data. These Poisson parameters are used to uniquely define the Gamma likelihood function. Easily computable approximation formulae may be used to find the ML estimations for the parameters of gamma distribution. For the sample size calculations, the ML solution is replaced by its upper confidence limit to reflect an incomplete exchangeability of historical trials as opposed to current studies. The exchangeability is measured by the confidence interval for the historical rate of the events. With this prior, the formula for the sample size calculation is completely defined. Published in 2009 by John Wiley & Sons, Ltd.     

Bayesian weighted inference from surveys

Data from large surveys are often supplemented with sampling weights that are designed to reflect unequal probabilities of response and selection inherent in complex survey sampling methods. We propose two methods for Bayesian estimation of parametric models in a setting where the survey data and the weights are available, but where information on how the weights were constructed is unavailable. The first approach is to simply replace the likelihood with the pseudo likelihood in the formulation of Bayes theorem. This is proven to lead to a consistent estimator but also leads to credible intervals that suffer from systematic undercoverage. Our second approach involves using the weights to generate a representative sample which is integrated into a Markov chain Monte Carlo (MCMC) or other simulation algorithms designed to estimate the parameters of the model. In the extensive simulation studies, the latter methodology is shown to achieve performance comparable to the standard frequentist solution of pseudo maximum likelihood, with the added advantage of being applicable to models that require inference via MCMC. The methodology is demonstrated further by fitting a mixture of gamma densities to a sample of Australian household income.     

Methods for combining ancillary data in stochastic compartment models of cancer mortality: Generalization of heterogeneity models∗

In analyzing mortality data there may be available information from survey and other sources that describe the marginal distribution of risk factors. We present a mortality model where nationally representative survey data on risk factor distributions are combined with data on cohort mortality rates to increase information, i.e., a fixed marginal risk factor distribution is combined with a cohort model representing unobserved individual risk heterogeneity. The model is applied to lung cancer mortality in nine U.S. white male cohorts aged 30 to 70 in 1950 and followed 38 years. Estimates of the cohort specific proportions of smokers were made from the National Health Interview Survey. Comparisons are made for models with different patterns of changes with age of individual heterogeneity.     

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.     

Joint analysis of longitudinal measurements and survival times with a cure fraction based on partly linear mixed and semiparametric cure models

In a joint analysis of longitudinal quality of life (QoL) scores and relapse-free survival (RFS) times from a clinical trial on early breast cancer conducted by the Canadian Cancer Trials Group, we observed a complicated trajectory of QoL scores and existence of long-term survivors. Motivated by this observation, we proposed in this paper a flexible joint model for the longitudinal measurements and survival times. A partly linear mixed effect model is used to capture the complicated but smooth trajectory of longitudinal measurements and approximated by B-splines and a semiparametric mixture cure model with the B-spline baseline hazard to model survival times with a cure fraction. These two models are linked by shared random effects to explore the dependence between longitudinal measurements and survival times. A semiparametric inference procedure with an EM algorithm is proposed to estimate the parameters in the joint model. The performance of proposed procedures are evaluated by simulation studies and through the application to the analysis of data from the clinical trial which motivated this research.