Influence diagnostics for random effect survival models: Application to a recurrent infection study for kidney patients on portable dialysis

In modeling multivariate failure time data, a class of survival model with random effects is applicable. It incorporates the random effect terms in the linear predictor and includes various random effect survival models as special cases, such as the random effect model assuming Cox's proportional hazards, with Weibull baseline hazards and with power family of transformation in the relative risk function. Residual maximum likelihood (REML) estimation of parameters is achieved by adopting the generalised linear mixed models (GLMM) approach. Accordingly, influence diagnostics are developed as sensitivity measures for the REML estimation of model parameters. A data set of recurrent infections of kidney patients on portable dialysis illustrates the usefulness of the influence diagnostics. A simulation study is carried out to examine the performance of the proposed influence diagnostics.     

Multilevel cumulative logistic regression model with random effects: Application to British social attitudes panel survey data

A multilevel model for ordinal data in generalized linear mixed models (GLMM) framework is developed to account for the inherent dependencies among observations within clusters. Motivated by a data set from the British Social Attitudes Panel Survey (BSAPS), the random district effects and respondent effects are incorporated into the linear predictor to accommodate the nested clusterings. The fixed (random) effects are estimated (predicted) by maximizing the penalized quasi likelihood (PQL) function, whereas the variance component parameters are obtained via the restricted maximum likelihood (REML) estimation method. The model is employed to analyze the BSAPS data. Simulation studies are conducted to assess the performance of estimators.     

Robust diagnostics for the heteroscedastic regression model

The assumption of equal variance in the normal regression model is not always appropriate. Cook and Weisberg (1983) provide a score test to detect heteroscedasticity, while Patterson and Thompson (1971) propose the residual maximum likelihood (REML) estimation to estimate variance components in the context of an unbalanced incomplete-block design. REML is often preferred to the maximum likelihood estimation as a method of estimating covariance parameters in a linear model. However, outliers may have some effect on the estimate of the variance function. This paper incorporates the maximum trimming likelihood estimation ( [Hadi and Luce?o, 1997] and [Vandev and Neykov, 1998]) in REML to obtain a robust estimation of modelling variance heterogeneity. Both the forward search algorithm of Atkinson (1994) and the fast algorithm of Neykov et al. (2007) are employed to find the resulting estimator. Simulation and real data examples are used to illustrate the performance of the proposed approach.     

Random effects in promotion time cure rate models

In this paper, a survival model with long-term survivors and random effects, based on the promotion time cure rate model formulation for models with a surviving fraction is investigated. We present Bayesian and classical estimation approaches. The Bayesian approach is implemented using a Markov chain Monte Carlo (MCMC) based on the Metropolis-Hastings algorithms. For the second one, we use restricted maximum likelihood (REML) estimators. A simulation study is performed to evaluate the accuracy of the applied techniques for the estimates and their standard deviations. An example on an oropharynx cancer study is used to illustrate the model and the estimation approaches considered in the study.     

Stacked Laplace-EM algorithm for duration models with time-varying and random effects

An extension of the Cox proportional hazards model for clustered survival data is proposed. This allows both general random effects (frailties) and time-varying regression coefficients, the latter being smooth functions of time. The model is fitted using a mixed-model representation of penalized spline smoothing which offers a unified framework for estimation of the baseline hazard, the smooth effects and the random effects. The estimator is computed using a stacked laplace-EM (SLaEM) algorithm. More specifically, the smoothing parameters are integrated out in the log likelihood via a Laplace approximation. The approximation itself involves an integrated log-likelihood over the random cluster effects, for which the EM algorithm is used. A marginal Akaike information criterion is developed for selection among possible candidate models. The time-varying and mixed effects model is applied to unemployment data taken from the German Socio-Economic Panel. The duration of unemployment is modeled in a flexible way including smooth covariate effects and individual random effects.     

Semiparametric estimation of a nested random effects model for the analysis of multi-level clustered failure time data

Multi-level clustered failure time data arise when the clustering of data occurs at more than one level. It is of interest to estimate the relative risks of covariates and clustering effect of failure times at each level. We consider a nested random effect proportional hazards model, where a subcluster-specific frailty operates multiplicatively on the conditional hazard model, and its distribution function depends on a cluster-specific random frailty. Under this model, we propose a Monte-Carlo EM-based semiparametric estimation procedure to estimate regression coefficients, nonparametric baseline cumulative hazard and the association parameters. In addition, we derive a covariance matrix of the parameter estimates. We illustrate the proposed method using clustered survival data collected from a vitamin A supplementation trial in Nepal, where it is of scientific interest to assess the clustering effect of mortality within households and within villages. We use simulations to study the performance of the proposed estimation procedure.     

Hierarchical-likelihood approach for nonlinear mixed-effects models

The restricted maximum likelihood (REML) procedure is useful for inferences about variance components in linear mixed models (LMMs). However, its extension to nonlinear mixed models (NLMMs) is often hampered by analytically intractable integrals. For NLMMs various estimation methods have been suggested, but they have suffered from unsatisfactory biases. In this paper we propose a statistically and computationally efficient REML procedure, based upon hierarchical likelihood. Numerical studies show that the proposed method reduces the biases in the existing methods that we studied. We also study how the current REML procedure for LMMs can be modified to compute the proposed estimators.     

Likelihood approach for count data in longitudinal experiments

In many cancer studies and clinical research, repeated observations of response variables are taken over time on each individual in one or more treatment groups. In such cases the repeated observations of each vector response are likely to be correlated and the autocorrelation structure for the repeated data plays a significant role in the estimation of regression parameters. A random intercept model for count data is developed using exact maximum-likelihood estimation via numerical integration. A simulation study is performed to compare the proposed methodology with the traditional generalized linear mixed model (GLMM) approach and with the GLMM when penalized quasi-likelihood method is used to perform maximum-likelihood estimation. The methodology is illustrated by analyzing data sets containing longitudinal measures of number of tumors in an experiment of carcinogenesis to study the influence of lipids in the development of cancer.     

Likelihood approach for count data in longitudinal experiments

In many cancer studies and clinical research, repeated observations of response variables are taken over time on each individual in one or more treatment groups. In such cases the repeated observations of each vector response are likely to be correlated and the autocorrelation structure for the repeated data plays a significant role in the estimation of regression parameters. A random intercept model for count data is developed using exact maximum-likelihood estimation via numerical integration. A simulation study is performed to compare the proposed methodology with the traditional generalized linear mixed model (GLMM) approach and with the GLMM when penalized quasi-likelihood method is used to perform maximum-likelihood estimation. The methodology is illustrated by analyzing data sets containing longitudinal measures of number of tumors in an experiment of carcinogenesis to study the influence of lipids in the development of cancer.     

Estimation in the probit normal model for binary outcomes using the SAEM algorithm

Generalized linear mixed models (GLMM) form a very general class of random effects models for discrete and continuous responses in the exponential family. They are useful in a variety of applications. The traditional likelihood approach for GLMM usually involves high dimensional integrations which are computationally intensive. In this work, we investigate the case of binary outcomes analyzed under a two stage probit normal model with random effects. First, it is shown how ML estimates of the fixed effects and variance components can be computed using a stochastic approximation of the EM algorithm (SAEM). The SAEM algorithm can be applied directly, or in conjunction with a parameter expansion version of EM to speed up the convergence. A procedure is also proposed to obtain REML estimates of variance components and REML-based estimates of fixed effects. Finally an application to a real data set involving a clinical trial is presented, in which these techniques are compared to other procedures (penalized quasi-likelihood, maximum likelihood, Bayesian inference) already available in classical softwares (SAS Glimmix, SAS Nlmixed, WinBUGS), as well as to a Monte Carlo EM (MCEM) algorithm.     

RE-EM trees: a data mining approach for longitudinal and clustered data

Longitudinal data refer to the situation where repeated observations are available for each sampled object. Clustered data, where observations are nested in a hierarchical structure within objects (without time necessarily being involved) represent a similar type of situation. Methodologies that take this structure into account allow for the possibilities of systematic differences between objects that are not related to attributes and autocorrelation within objects across time periods. A standard methodology in the statistics literature for this type of data is the mixed effects model, where these differences between objects are represented by so-called “random effects” that are estimated from the data (population-level relationships are termed “fixed effects,” together resulting in a mixed effects model). This paper presents a methodology that combines the structure of mixed effects models for longitudinal and clustered data with the flexibility of tree-based estimation methods. We apply the resulting estimation method, called the RE-EM tree, to pricing in online transactions, showing that the RE-EM tree is less sensitive to parametric assumptions and provides improved predictive power compared to linear models with random effects and regression trees without random effects. We also apply it to a smaller data set examining accident fatalities, and show that the RE-EM tree strongly outperforms a tree without random effects while performing comparably to a linear model with random effects. We also perform extensive simulation experiments to show that the estimator improves predictive performance relative to regression trees without random effects and is comparable or superior to using linear models with random effects in more general situations.     

Parameter learning for the nonlinear system described by Hammerstein model with output disturbance

A novel parameter learning scheme using multi-signal processing is developed that aims at estimating parameters of the Hammerstein nonlinear model with output disturbance in this paper. The Hammerstein nonlinear model consists of a static nonlinear block and a dynamic linear block, and the multi-signals are devised to estimate separately the nonlinear block parameters and the linear block parameters; the parameter estimation procedure is greatly simplified. Firstly, in view of the input–output data of separable signals, the linear block parameters are computed through correlation analysis method, thereby the influence of output noise is effectively handled. In addition, model error probability density function technology is employed to estimate the nonlinear block parameters with the help of measurable input–output data of random signals, which not only controls the space state distribution of model error but also makes error distribution tends to normal distribution. The simulation results demonstrate that the developed approach obtains high learning accuracy and small modeling error, which verifies the effectiveness of the developed approach.     

Influence diagnostics for generalized linear mixed models: applications to clustered data

The Cook's distance for generalized linear mixed models is investigated, with applications to clustered data. In particular, first-order approximations are derived for the best linear unbiased predictor of the parameters due to cluster deletion. A small-scale simulation study shows that the method provides an efficient way to identify influential clusters. The notion of joint and conditional influence is also considered to address the masking effects of cluster-wise deletion. A data set on maternity length of hospital stay illustrates the usefulness of the proposed diagnostics.     

Optimal linear granulometric estimation for random sets

This paper addresses two pattern-recognition problems in the context of random sets. For the first, the random set law is known and the task is to estimate the observed pattern from a feature set calculated from the observation. For the second, the law is unknown and we wish to estimate the parameters of the law. Estimation is accomplished by an optimal linear system whose inputs are features based on morphological granulometries. In the first case these features are granulometric moments; in the second they are moments of the granulometric moments. For the latter, estimation is placed in a Bayesian context by assuming that there exists a prior distribution for the parameters determining the law. A disjoint random grain model is assumed and the optimal linear estimator is determined by using asymptotic expressions for the moments of the granulometric moments. In both cases, the linear approach serves as a practical alternative to previously proposed nonlinear methods. Granulometric pattern estimation has previously been accomplished by a nonlinear method using full distributional knowledge of the random variables determining the pattern and granulometric features. Granulometric estimation of the law of a random grain model has previously been accomplished by solving a system of nonlinear equations resulting from the granulometric asymptotic mixing theorem. Both methods are limited in application owing to the necessity of performing a nonlinear optimization. The new linear method avoids this. It makes estimation possible for more complex models.     

Flexible modelling of random effects in linear mixed models—A Bayesian approach

Flexible modelling of random effects in linear mixed models has attracted some attention recently. In this paper, we propose the use of finite Gaussian mixtures as in Verbeke and Lesaffre [A linear mixed model with heterogeneity in the random-effects population, J. Amu. Statist. Assoc. 91, 217-221]. We adopt a fully Bayesian hierarchical framework that allows simultaneous estimation of the number of mixture components together with other model parameters. The technique employed is the Reversible Jump MCMC algorithm (Richardson and Green [On Bayesian Analysis of Mixtures with an Unknown Number of Components (with discussion). J. Roy. Statist. Soc. Ser. B 59, 731-792]). This approach has the advantage of producing a direct comparison of different mixture models through posterior probabilities from a single run of the MCMC algorithm. Moreover, the Bayesian setting allows us to integrate over different mixture models to obtain a more robust density estimate of the random effects. We focus on linear mixed models with a random intercept and a random slope. Numerical results on simulated data sets and a real data set are provided to demonstrate the usefulness of the proposed method.     

Score tests for zero-inflated generalized Poisson mixed regression models

Zero-inflated Poisson (ZIP) regression model is a popular approach to the analysis of count data with excess zeros. For correlated count data where the observations are either repeated or clustered outcomes from individual subjects, ZIP mixed regression model may be appropriate. However, ZIP model may often fail to fit such data either because of over-dispersion or because of under-dispersion in relation to the Poisson distribution. In this paper, we extend the ZIP mixed regression model to zero-inflated generalized Poisson (ZIGP) mixed regression model, where the base-line discrete distribution is generalized Poisson (GP) distribution, which is a natural extension of standard Poisson distribution. Furthermore, the random effects are considered in both zero-inflated and GP components throughout the paper. An EM algorithm for estimating parameters is proposed based on the best linear unbiased prediction-type (BLUP) log-likelihood and the residual maximum likelihood (REML). Meanwhile, several score tests are presented for testing the ZIP mixed regression model against the ZIGP mixed regression model, and for testing the significance of regression coefficients in zero-inflation and generalized Poisson portion. A numerical example is given to illustrate our methodology and the properties of score test statistics are investigated through Monte Carlo simulations.     

Semiparametric analysis of clustered interval-censored survival data with a cure fraction

A generalization of the semiparametric Cox’s proportional hazards model by means of a random effect or frailty approach to accommodate clustered survival data with a cure fraction is considered. The frailty serves as a quantification of the health condition of the subjects under study and may depend on some observed covariates like age. One single individual-specific frailty that acts on the hazard function is adopted to determine the cure status of an individual and the heterogeneity on the time to event if the individual is not cured. Under this formulation, an individual who has a high propensity to be cured would tend to have a longer time to event if he is not cured. Within a cluster, both the cure statuses and the times to event of the individuals would be correlated. In contrast to some models proposed in the literature, the model accommodates the correlations among the observations in a more natural way. A multiple imputation estimation method is proposed for both right-censored and interval-censored data. Simulation studies show that the performance of the proposed estimation method is highly satisfactory. The proposed model and method are applied to the National Aeronautics and Space Administration’s hypobaric decompression sickness data to investigate the factors associated with the occurrence and the time to onset of grade IV venous gas emboli under hypobaric environments.     

On empirical Bayes penalized quasi-likelihood inference in GLMMs and in Bayesian disease mapping and ecological modeling

Penalized quasi-likelihood(PQL) procedure for statistical inference in generalized linear mixed models (GLMMs) and in Bayesian disease mapping and ecological modeling are revisited. In GLMM framework, empirical Bayes PQL (EBPQL) procedure is discussed in the context of approximating posterior point and interval prediction of random effects. An in-depth Monte Carlo assessment on EBPQL point and interval estimation of random effects, fixed effects, and prior parameters in univariate and bivariate (shared component) disease mapping and ecological models is presented, with illustrative examples including spatial and ecological modeling of infant mortality rates (relative uncommon events), suicide hospitalization rates (rare events) and suicide mortality rates (extremely rare events), and associated ecological risk factors in local health areas in British Columbia Canada. In particular, EBPQL interval prediction of random effects is explored by prediction uncertainty attributions with respect to uncertainties associated with estimation of random effects, fixed effects, and prior parameters. Estimation of percent attributions of EBPQL random effects prediction errors to prior uncertainty is developed in the context of GLMMs and explored in Bayesian disease mapping and ecological models, suggesting evidence that uncertainty about prior parameter(s) may have minor and negligible influence on EBPQL interval prediction of random effects in Bayesian hierarchical disease mapping and ecological modeling of moderate Poisson observations. The EBPQL inference procedure may be judiciously and profitably utilized in Bayesian disease mapping and ecological model development.     

Asymptotic normality analysis of the estimation error of steady-state models for industrial processes: SISO case

The asymptotic normality of the estimation error of steady-state models for industrial processes is investigated under quite mild conditions. The estimate is formed from the estimated parameters of an approximate linear model which is strongly consistent with the steady-state gain of slow time-varying linear SISO systems. In the parameter estimation, the weighted least-squares method is employed. The input signal (the system set point) is the usual step change din the optimization procedure. The rate of convergence is given. The stationarity and the distribution of the stochastic process are not demanded. It is also worth mentioning that, under some acceptable conditions, robustness to the structure of the approximate linear model is achieved. A simulation study shows that, for limited length of the sampled data, the best choice for the structure of approximate models as regards estimation precision is dependent upon the realization of the stochastic noise.     

Parameters of the diffusion leaky integrate-and-fire neuronal model for a slowly fluctuating signal

Stochastic leaky integrate-and-fire (LIF) neuronal models are common theoretical tools for studying properties of real neuronal systems. Experimental data of frequently sampled membrane potential measurements between spikes show that the assumption of constant parameter values is not realistic and that some (random) fluctuations are occurring. In this letter, we extend the stochastic LIF model, allowing a noise source determining slow fluctuations in the signal. This is achieved by adding a random variable to one of the parameters characterizing the neuronal input, considering each interspike interval (ISI) as an independent experimental unit with a different realization of this random variable. In this way, the variation of the neuronal input is split into fast (within-interval) and slow (between-intervals) components. A parameter estimation method is proposed, allowing the parameters to be estimated simultaneously over the entire data set. This increases the statistical power, and the average estimate over all ISIs will be improved in the sense of decreased variance of the estimator compared to previous approaches, where the estimation has been conducted on each individual ISI. The results obtained on real data show good agreement with classical regression methods.