Modeling longitudinal count data with dropouts

This paper explores the utility of different approaches for modeling longitudinal count data with dropouts arising from a clinical study for the treatment of actinic keratosis lesions on the face and balding scalp. A feature of these data is that as the disease for subjects on the active arm improves their data show larger dispersion compared with those on the vehicle, exhibiting an over‐dispersion relative to the Poisson distribution. After fitting the marginal (or population averaged) model using the generalized estimating equation (GEE), we note that inferences from such a model might be biased as dropouts are treatment related. Then, we consider using a weighted GEE (WGEE) where each subject's contribution to the analysis is weighted inversely by the subject's probability of dropout. Based on the model findings, we argue that the WGEE might not address the concerns about the impact of dropouts on the efficacy findings when dropouts are treatment related. As an alternative, we consider likelihood‐based inference where random effects are added to the model to allow for heterogeneity across subjects. Finally, we consider a transition model where, unlike the previous approaches that model the log‐link function of the mean response, we model the subject's actual lesion counts. This model is an extension of the Poisson autoregressive model of order 1, where the autoregressive parameter is taken to be a function of treatment as well as other covariates to induce different dispersions and correlations for the two treatment arms. We conclude with a discussion about model selection. Published in 2009 by John Wiley & Sons, Ltd.     

Generalised quasi‐likelihood inference in a semi‐parametric binary dynamic mixed logit model

There exists a recent study where dynamic mixed‐effects regression models for count data have been extended to a semi‐parametric context. However, when one deals with other discrete data such as binary responses, the results based on count data models are not directly applicable. In this paper, we therefore begin with existing binary dynamic mixed models and generalise them to the semi‐parametric context. For inference, we use a new semi‐parametric conditional quasi‐likelihood (SCQL) approach for the estimation of the non‐parametric function involved in the semi‐parametric model, and a semi‐parametric generalised quasi‐likelihood (SGQL) approach for the estimation of the main regression, dynamic dependence and random effects variance parameters. A semi‐parametric maximum likelihood (SML) approach is also used as a comparison to the SGQL approach. The properties of the estimators are examined both asymptotically and empirically. More specifically, the consistency of the estimators is established and finite sample performances of the estimators are examined through an intensive simulation study.     

Modern Statistics for Spatial Point Processes*

Abstract. We summarize and discuss the current state of spatial point process theory and directions for future research, making an analogy with generalized linear models and random effect models, and illustrating the theory with various examples of applications. In particular, we consider Poisson, Gibbs and Cox process models, diagnostic tools and model checking, Markov chain Monte Carlo algorithms, computational methods for likelihood-based inference, and quick non-likelihood approaches to inference.     

Conditional Akaike Information Criteria for a Class of Poisson Mixture Models with Random Effects

Focusing on the model selection problems in the family of Poisson mixture models (including the Poisson mixture regression model with random effects and zero‐inflated Poisson regression model with random effects), the current paper derives two conditional Akaike information criteria. The criteria are the unbiased estimators of the conditional Akaike information based on the conditional log‐likelihood and the conditional Akaike information based on the joint log‐likelihood, respectively. The derivation is free from the specific parametric assumptions about the conditional mean of the true data‐generating model and applies to different types of estimation methods. Additionally, the derivation is not based on the asymptotic argument. Simulations show that the proposed criteria have promising estimation accuracy. In addition, it is found that the criterion based on the conditional log‐likelihood demonstrates good model selection performance under different scenarios. Two sets of real data are used to illustrate the proposed method.     

Estimation of the Intensity Parameter of the Germ‐Grain Quermass‐Interaction Model when the Number of Germs is not Observed

The Quermass‐interaction model allows to generalize the classical germ‐grain Boolean model in adding a morphological interaction between the grains. It enables to model random structures with specific morphologies, which are unlikely to be generated from a Boolean model. The Quermass‐interaction model depends in particular on an intensity parameter, which is impossible to estimate from classical likelihood or pseudo‐likelihood approaches because the number of points is not observable from a germ‐grain set. In this paper, we present a procedure based on the Takacs–Fiksel method, which is able to estimate all parameters of the Quermass‐interaction model, including the intensity. An intensive simulation study is conducted to assess the efficiency of the procedure and to provide practical recommendations. It also illustrates that the estimation of the intensity parameter is crucial in order to identify the model. The Quermass‐interaction model is finally fitted by our method to P. Diggle's heather data set.     

Simplex Mixed‐Effects Models for Longitudinal Proportional Data

Abstract. Continuous proportional outcomes are collected from many practical studies, where responses are confined within the unit interval (0,1). Utilizing Barndorff‐Nielsen and Jørgensen's simplex distribution, we propose a new type of generalized linear mixed‐effects model for longitudinal proportional data, where the expected value of proportion is directly modelled through a logit function of fixed and random effects. We establish statistical inference along the lines of Breslow and Clayton's penalized quasi‐likelihood (PQL) and restricted maximum likelihood (REML) in the proposed model. We derive the PQL/REML using the high‐order multivariate Laplace approximation, which gives satisfactory estimation of the model parameters. The proposed model and inference are illustrated by simulation studies and a data example. The simulation studies conclude that the fourth order approximate PQL/REML performs satisfactorily. The data example shows that Aitchison's technique of the normal linear mixed model for logit‐transformed proportional outcomes is not robust against outliers.     

A compound Poisson model for word occurrences in DNA sequences

Summary. We present a compound Poisson model describing the occurrence process of a set of words in a random sequence of letters. The model takes into account the frequency of the words and their overlapping structure. The model is compared with a Markov chain model in terms of fit and parsimony. Special attention is given to the detection of poor or rich regions. Several applications of the model are presented and a combination of the Markov and compound Poisson models is proposed.     

Rubbery Polya Tree

Abstract. Polya trees (PT) are random probability measures which can assign probability 1 to the set of continuous distributions for certain specifications of the hyperparameters. This feature distinguishes the PT from the popular Dirichlet process (DP) model which assigns probability 1 to the set of discrete distributions. However, the PT is not nearly as widely used as the DP prior. Probably the main reason is an awkward dependence of posterior inference on the choice of the partitioning subsets in the definition of the PT. We propose a generalization of the PT prior that mitigates this undesirable dependence on the partition structure, by allowing the branching probabilities to be dependent within the same level. The proposed new process is not a PT anymore. However, it is still a tail‐free process and many of the prior properties remain the same as those for the PT.     

Impact of missing data on type 1 error rates in non‐inferiority trials

In this paper, a simulation study is conducted to systematically investigate the impact of different types of missing data on six different statistical analyses: four different likelihood‐based linear mixed effects models and analysis of covariance (ANCOVA) using two different data sets, in non‐inferiority trial settings for the analysis of longitudinal continuous data. ANCOVA is valid when the missing data are completely at random. Likelihood‐based linear mixed effects model approaches are valid when the missing data are at random. Pattern‐mixture model (PMM) was developed to incorporate non‐random missing mechanism. Our simulations suggest that two linear mixed effects models using unstructured covariance matrix for within‐subject correlation with no random effects or first‐order autoregressive covariance matrix for within‐subject correlation with random coefficient effects provide well control of type 1 error (T1E) rate when the missing data are completely at random or at random. ANCOVA using last observation carried forward imputed data set is the worst method in terms of bias and T1E rate. PMM does not show much improvement on controlling T1E rate compared with other linear mixed effects models when the missing data are not at random but is markedly inferior when the missing data are at random. Copyright © 2009 John Wiley & Sons, Ltd.     

Variational Bayes for estimating the parameters of a hidden Potts model

Hidden Markov random field models provide an appealing representation of images and other spatial problems. The drawback is that inference is not straightforward for these models as the normalisation constant for the likelihood is generally intractable except for very small observation sets. Variational methods are an emerging tool for Bayesian inference and they have already been successfully applied in other contexts. Focusing on the particular case of a hidden Potts model with Gaussian noise, we show how variational Bayesian methods can be applied to hidden Markov random field inference. To tackle the obstacle of the intractable normalising constant for the likelihood, we explore alternative estimation approaches for incorporation into the variational Bayes algorithm. We consider a pseudo-likelihood approach as well as the more recent reduced dependence approximation of the normalisation constant. To illustrate the effectiveness of these approaches we present empirical results from the analysis of simulated datasets. We also analyse a real dataset and compare results with those of previous analyses as well as those obtained from the recently developed auxiliary variable MCMC method and the recursive MCMC method. Our results show that the variational Bayesian analyses can be carried out much faster than the MCMC analyses and produce good estimates of model parameters. We also found that the reduced dependence approximation of the normalisation constant outperformed the pseudo-likelihood approximation in our analysis of real and synthetic datasets.     

What is the effective sample size of a spatial point process?

Point process models are a natural approach for modelling data that arise as point events. In the case of Poisson counts, these may be fitted easily as a weighted Poisson regression. Point processes lack the notion of sample size. This is problematic for model selection, because various classical criteria such as the Bayesian information criterion (BIC) are a function of the sample size, n, and are derived in an asymptotic framework where n tends to infinity. In this paper, we develop an asymptotic result for Poisson point process models in which the observed number of point events, m, plays the role that sample size does in the classical regression context. Following from this result, we derive a version of BIC for point process models, and when fitted via penalised likelihood, conditions for the LASSO penalty that ensure consistency in estimation and the oracle property. We discuss challenges extending these results to the wider class of Gibbs models, of which the Poisson point process model is a special case.     

A Mixed Model Approach for Geoadditive Hazard Regression

Abstract.  Mixed model based approaches for semiparametric regression have gained much interest in recent years, both in theory and application. They provide a unified and modular framework for penalized likelihood and closely related empirical Bayes inference. In this article, we develop mixed model methodology for a broad class of Cox-type hazard regression models where the usual linear predictor is generalized to a geoadditive predictor incorporating non-parametric terms for the (log-)baseline hazard rate, time-varying coefficients and non-linear effects of continuous covariates, a spatial component, and additional cluster-specific frailties. Non-linear and time-varying effects are modelled through penalized splines, while spatial components are treated as correlated random effects following either a Markov random field or a stationary Gaussian random field prior. Generalizing existing mixed model methodology, inference is derived using penalized likelihood for regression coefficients and (approximate) marginal likelihood for smoothing parameters. In a simulation we study the performance of the proposed method, in particular comparing it with its fully Bayesian counterpart using Markov chain Monte Carlo methodology, and complement the results by some asymptotic considerations. As an application, we analyse leukaemia survival data from northwest England.     

Forward Simulation Markov Chain Monte Carlo with Applications to Stochastic Epidemic Models

For many stochastic models, it is difficult to make inference about the model parameters because it is impossible to write down a tractable likelihood given the observed data. A common solution is data augmentation in a Markov chain Monte Carlo (MCMC) framework. However, there are statistical problems where this approach has proved infeasible but where simulation from the model is straightforward leading to the popularity of the approximate Bayesian computation algorithm. We introduce a forward simulation MCMC (fsMCMC) algorithm, which is primarily based upon simulation from the model. The fsMCMC algorithm formulates the simulation of the process explicitly as a data augmentation problem. By exploiting non‐centred parameterizations, an efficient MCMC updating schema for the parameters and augmented data is introduced, whilst maintaining straightforward simulation from the model. The fsMCMC algorithm is successfully applied to two distinct epidemic models including a birth–death–mutation model that has only previously been analysed using approximate Bayesian computation methods.     

On Bayesian analyses and finite mixtures for proportions

When the results of biological experiments are tested for a possible difference between treatment and control groups, the inference is only valid if based upon a model that fits the experimental results satisfactorily. In dominant-lethal testing, foetal death has previously been assumed to follow a variety of models, including a Poisson, Binomial, Beta-binomial and various mixture models. However, discriminating between models has always been a particularly difficult problem. In this paper, we consider the data from 6 separate dominant-lethal assay experiments and discriminate between the competing models which could be used to describe them. We adopt a Bayesian approach and illustrate how a variety of different models may be considered, using Markov chain Monte Carlo (MCMC) simulation techniques and comparing the results with the corresponding maximum likelihood analyses. We present an auxiliary variable method for determining the probability that any particular data cell is assigned to a given component in a mixture and we illustrate the value of this approach. Finally, we show how the Bayesian approach provides a natural and unique perspective on the model selection problem via reversible jump MCMC and illustrate how probabilities associated with each of the different models may be calculated for each data set. In terms of estimation we show how, by averaging over the different models, we obtain reliable and robust inference for any statistic of interest.     

Multivariate Poisson regression with covariance structure

In recent years the applications of multivariate Poisson models have increased, mainly because of the gradual increase in computer performance. The multivariate Poisson model used in practice is based on a common covariance term for all the pairs of variables. This is rather restrictive and does not allow for modelling the covariance structure of the data in a flexible way. In this paper we propose inference for a multivariate Poisson model with larger structure, i.e. different covariance for each pair of variables. Maximum likelihood estimation, as well as Bayesian estimation methods are proposed. Both are based on a data augmentation scheme that reflects the multivariate reduction derivation of the joint probability function. In order to enlarge the applicability of the model we allow for covariates in the specification of both the mean and the covariance parameters. Extension to models with complete structure with many multi-way covariance terms is discussed. The method is demonstrated by analyzing a real life data set.     

MODELLING TRUNCATED AND CLUSTERED COUNT DATA

Count response data often exhibit departures from the assumptions of standard Poisson generalized linear models. In particular, cluster level correlation of the data and truncation at zero are two common characteristics of such data. This paper describes a random components truncated Poisson model that can be applied to clustered and zero‐truncated count data. Residual maximum likelihood method estimators for the parameters of this model are developed and their use is illustrated using a dataset of non‐zero counts of sheets with edge‐strain defects in iron sheets produced by the Mobarekeh Steel Complex, Iran. The paper also reports on a small‐scale simulation study that supports the estimation procedure.     

A Method for Bayesian Monotonic Multiple Regression

Abstract. When applicable, an assumed monotonicity property of the regression function w.r.t. covariates has a strong stabilizing effect on the estimates. Because of this, other parametric or structural assumptions may not be needed at all. Although monotonic regression in one dimension is well studied, the question remains whether one can find computationally feasible generalizations to multiple dimensions. Here, we propose a non‐parametric monotonic regression model for one or more covariates and a Bayesian estimation procedure. The monotonic construction is based on marked point processes, where the random point locations and the associated marks (function levels) together form piecewise constant realizations of the regression surfaces. The actual inference is based on model‐averaged results over the realizations. The monotonicity of the construction is enforced by partial ordering constraints, which allows it to asymptotically, with increasing density of support points, approximate the family of all monotonic bounded continuous functions.     

Bayesian inference for non-Gaussian Ornstein–Uhlenbeck stochastic volatility processes

Summary.  We develop Markov chain Monte Carlo methodology for Bayesian inference for non-Gaussian Ornstein–Uhlenbeck stochastic volatility processes. The approach introduced involves expressing the unobserved stochastic volatility process in terms of a suitable marked Poisson process. We introduce two specific classes of Metropolis–Hastings algorithms which correspond to different ways of jointly parameterizing the marked point process and the model parameters. The performance of the methods is investigated for different types of simulated data. The approach is extended to consider the case where the volatility process is expressed as a superposition of Ornstein–Uhlenbeck processes. We apply our methodology to the US dollar–Deutschmark exchange rate.     

Estimated estimating equations: semiparametric inference for clustered and longitudinal data

Summary.  We introduce a flexible marginal modelling approach for statistical inference for clustered and longitudinal data under minimal assumptions. This estimated estimating equations approach is semiparametric and the proposed models are fitted by quasi-likelihood regression, where the unknown marginal means are a function of the fixed effects linear predictor with unknown smooth link, and variance–covariance is an unknown smooth function of the marginal means. We propose to estimate the nonparametric link and variance–covariance functions via smoothing methods, whereas the regression parameters are obtained via the estimated estimating equations. These are score equations that contain nonparametric function estimates. The proposed estimated estimating equations approach is motivated by its flexibility and easy implementation. Moreover, if data follow a generalized linear mixed model, with either a specified or an unspecified distribution of random effects and link function, the model proposed emerges as the corresponding marginal (population-average) version and can be used to obtain inference for the fixed effects in the underlying generalized linear mixed model, without the need to specify any other components of this generalized linear mixed model. Among marginal models, the estimated estimating equations approach provides a flexible alternative to modelling with generalized estimating equations. Applications of estimated estimating equations include diagnostics and link selection. The asymptotic distribution of the proposed estimators for the model parameters is derived, enabling statistical inference. Practical illustrations include Poisson modelling of repeated epileptic seizure counts and simulations for clustered binomial responses.     

Optimal Estimator for Logistic Model with Distribution‐free Random Intercept

Logistic models with a random intercept are prevalent in medical and social research where clustered and longitudinal data are often collected. Traditionally, the random intercept in these models is assumed to follow some parametric distribution such as the normal distribution. However, such an assumption inevitably raises concerns about model misspecification and misleading inference conclusions, especially when there is dependence between the random intercept and model covariates. To protect against such issues, we use a semiparametric approach to develop a computationally simple and consistent estimator where the random intercept is distribution‐free. The estimator is revealed to be optimal and achieve the efficiency bound without the need to postulate or estimate any latent variable distributions. We further characterize other general mixed models where such an optimal estimator exists.