Mixed effects smoothing spline analysis of variance

We propose a general family of nonparametric mixed effects models. Smoothing splines are used to model the fixed effects and are estimated by maximizing the penalized likelihood function. The random effects are generic and are modelled parametrically by assuming that the covariance function depends on a parsimonious set of parameters. These parameters and the smoothing parameter are estimated simultaneously by the generalized maximum likelihood method. We derive a connection between a nonparametric mixed effects model and a linear mixed effects model. This connection suggests a way of fitting a nonparametric mixed effects model by using existing programs. The classical two-way mixed models and growth curve models are used as examples to demonstrate how to use smoothing spline analysis-of-variance decompositions to build nonparametric mixed effects models. Similarly to the classical analysis of variance, components of these nonparametric mixed effects models can be interpreted as main effects and interactions. The penalized likelihood estimates of the fixed effects in a two-way mixed model are extensions of James–Stein shrinkage estimates to correlated observations. In an example three nested nonparametric mixed effects models are fitted to a longitudinal data set.     

ASYMPTOTIC PROPERTIES OF RESTRICTED MAXIMUM LIKELIHOOD (REML) ESTIMATES FOR HIERARCHICAL MIXED LINEAR MODELS

This paper explores the asymptotic distribution of the restricted maximum likelihood estimator of the variance components in a general mixed model. Restricting attention to hierarchical models, central limit theorems are obtained using elementary arguments with only mild conditions on the covariates in the fixed part of the model and without having to assume that the data are either normally or spherically symmetrically distributed. Further, the REML and maximum likelihood estimators are shown to be asymptotically equivalent in this general framework, and the asymptotic distribution of the weighted least squares estimator (based on the REML estimator) of the fixed effect parameters is derived.     

Likelihood-based and Bayesian methods for Tweedie compound Poisson linear mixed models

The Tweedie compound Poisson distribution is a subclass of the exponential dispersion family with a power variance function, in which the value of the power index lies in the interval (1,2). It is well known that the Tweedie compound Poisson density function is not analytically tractable, and numerical procedures that allow the density to be accurately and fast evaluated did not appear until fairly recently. Unsurprisingly, there has been little statistical literature devoted to full maximum likelihood inference for Tweedie compound Poisson mixed models. To date, the focus has been on estimation methods in the quasi-likelihood framework. Further, Tweedie compound Poisson mixed models involve an unknown variance function, which has a significant impact on hypothesis tests and predictive uncertainty measures. The estimation of the unknown variance function is thus of independent interest in many applications. However, quasi-likelihood-based methods are not well suited to this task. This paper presents several likelihood-based inferential methods for the Tweedie compound Poisson mixed model that enable estimation of the variance function from the data. These algorithms include the likelihood approximation method, in which both the integral over the random effects and the compound Poisson density function are evaluated numerically; and the latent variable approach, in which maximum likelihood estimation is carried out via the Monte Carlo EM algorithm, without the need for approximating the density function. In addition, we derive the corresponding Markov Chain Monte Carlo algorithm for a Bayesian formulation of the mixed model. We demonstrate the use of the various methods through a numerical example, and conduct an array of simulation studies to evaluate the statistical properties of the proposed estimators.     

A note on model selection using information criteria for general linear models estimated using REML

It is common practice to compare the fit of non‐nested models using the Akaike (AIC) or Bayesian (BIC) information criteria. The basis of these criteria is the log‐likelihood evaluated at the maximum likelihood estimates of the unknown parameters. For the general linear model (and the linear mixed model, which is a special case), estimation is usually carried out using residual or restricted maximum likelihood (REML). However, for models with different fixed effects, the residual likelihoods are not comparable and hence information criteria based on the residual likelihood cannot be used. For model selection, it is often suggested that the models are refitted using maximum likelihood to enable the criteria to be used. The first aim of this paper is to highlight that both the AIC and BIC can be used for the general linear model by using the full log‐likelihood evaluated at the REML estimates. The second aim is to provide a derivation of the criteria under REML estimation. This aim is achieved by noting that the full likelihood can be decomposed into a marginal (residual) and conditional likelihood and this decomposition then incorporates aspects of both the fixed effects and variance parameters. Using this decomposition, the appropriate information criteria for model selection of models which differ in their fixed effects specification can be derived. An example is presented to illustrate the results and code is available for analyses using the ASReml‐R package.     

Editorial collaborators

A simulation study of the binomial-logit model with correlated random effects is carried out based on the generalized linear mixed model (GLMM) methodology. Simulated data with various numbers of regression parameters and different values of the variance component are considered. The performance of approximate maximum likelihood (ML) and residual maximum likelihood (REML) estimators is evaluated. For a range of true parameter values, we report the average biases of estimators, the standard error of the average bias and the standard error of estimates over the simulations. In general, in terms of bias, the two methods do not show significant differences in estimating regression parameters. The REML estimation method is slightly better in reducing the bias of variance component estimates.     

Likelihood inference for small variance components

The authors explore likelihood‐based methods for making inferences about the components of variance in a general normal mixed linear model. In particular, they use local asymptotic approximations to construct confidence intervals for the components of variance when the components are close to the boundary of the parameter space. In the process, they explore the question of how to profile the restricted likelihood (REML). Also, they show that general REML estimates are less likely to fall on the boundary of the parameter space than maximum‐likelihood estimates and that the likelihood‐ratio test based on the local asymptotic approximation has higher power than the likelihood‐ratio test based on the usual chi‐squared approximation. They examine the finite‐sample properties of the proposed intervals by means of a simulation study.     

Approximate composite marginal likelihood inference in spatial generalized linear mixed models

Non-Gaussian spatial responses are usually modeled using spatial generalized linear mixed model with spatial random effects. The likelihood function of this model cannot usually be given in a closed form, thus the maximum likelihood approach is very challenging. There are numerical ways to maximize the likelihood function, such as Monte Carlo Expectation Maximization and Quadrature Pairwise Expectation Maximization algorithms. They can be applied but may in such cases be computationally very slow or even prohibitive. Gauss–Hermite quadrature approximation only suitable for low-dimensional latent variables and its accuracy depends on the number of quadrature points. Here, we propose a new approximate pairwise maximum likelihood method to the inference of the spatial generalized linear mixed model. This approximate method is fast and deterministic, using no sampling-based strategies. The performance of the proposed method is illustrated through two simulation examples and practical aspects are investigated through a case study on a rainfall data set.     

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.     

Logistic regression analyses for indirect data

The article’s topic is logistic regression for direct data on the covariates, but indirect data on the endogenous variable. The indirect data may result from a privacy-protecting survey procedure for sensitive characteristics or from statistical disclosure control. Various procedures to generate the indirect data exist. However, we show that it is possible to develop a general approach for logistic regression analyses with indirect data that covers many procedures. We first derive a general algorithm for the maximum likelihood estimation and a general procedure for variance estimation. Subsequently, lots of examples demonstrate the broad applicability of our general framework.     

Variance least squares estimators for multivariate linear mixed model

Non-iterative, distribution-free, and unbiased estimators of variance components by least squares method are derived for multivariate linear mixed model. A general inter-cluster variance matrix, a same-member only general inter-response variance matrix, and an uncorrelated intra-cluster error structure for each response are assumed. Projection method is suggested when unbiased estimators of variance components are not nonnegative definite matrices. A simulation study is conducted to investigate the properties of the proposed estimators in terms of bias and mean square error with comparison to the Gaussian (restricted) maximum likelihood estimators. The proposed estimators are illustrated by an application of gene expression familial study.     

Reml estimation for repeated measures analysis

Models for repeated measures or growth curves consist of a mean response plus error and the errors are usually correlated. Both maximum likelihood and residual maximum likelihood (REML) estimators of a regression model with dependent errors are derived for cases in which the variance matrix of the error model admits a convenient Cholesky factorisation. This factorisation may be linked to methods for producing recursive estimates of the regression parameters and recursive residuals to provide a convenient computational method. The method is used to develop a general approach to repeated measures analysis.     

Estimation of parameters in DNA mixture analysis

In [7], a Bayesian network for analysis of mixed traces of DNA was presented using gamma distributions for modelling peak sizes in the electropherogram. It was demonstrated that the analysis was sensitive to the choice of a variance factor and hence this should be adapted to any new trace analysed. In this paper, we discuss how the variance parameter can be estimated by maximum likelihood to achieve this. The unknown proportions of DNA from each contributor can similarly be estimated by maximum likelihood jointly with the variance parameter. Furthermore, we discuss how to incorporate prior knowledge about the parameters in a Bayesian analysis. The proposed estimation methods are illustrated through a few examples of applications for calculating evidential value in casework and for mixture deconvolution.     

The robustness of the quasilikelihood estimator

The quasilikelihood estimator is widely used in data analysis where a likelihood is not available. We illustrate that with a given variance function it is not only conservative, in minimizing a maximum risk, but also robust against a possible misspecification of either the likelihood or cumulants of the model. In examples it is compared with estimators based on maximum likelihood and quadratic estimating functions.     

Two-stage hierarchical modeling for analysis of subpopulations in conditional distributions

In this work, we develop modeling and estimation approach for the analysis of cross-sectional clustered data with multimodal conditional distributions where the main interest is in analysis of subpopulations. It is proposed to model such data in a hierarchical model with conditional distributions viewed as finite mixtures of normal components. With a large number of observations in the lowest level clusters, a two-stage estimation approach is used. In the first stage, the normal mixture parameters in each lowest level cluster are estimated using robust methods. Robust alternatives to the maximum likelihood estimation are used to provide stable results even for data with conditional distributions such that their components may not quite meet normality assumptions. Then the lowest level cluster-specific means and standard deviations are modeled in a mixed effects model in the second stage. A small simulation study was conducted to compare performance of finite normal mixture population parameter estimates based on robust and maximum likelihood estimation in stage 1. The proposed modeling approach is illustrated through the analysis of mice tendon fibril diameters data. Analyses results address genotype differences between corresponding components in the mixtures and demonstrate advantages of robust estimation in stage 1.     

Fast EM-type implementations for mixed effects models

The mixed effects model, in its various forms, is a common model in applied statistics. A useful strategy for fitting this model implements EM-type algorithms by treating the random effects as missing data. Such implementations, however, can be painfully slow when the variances of the random effects are small relative to the residual variance. In this paper, we apply the 'working parameter' approach to derive alternative EM-type implementations for fitting mixed effects models, which we show empirically can be hundreds of times faster than the common EM-type implementations. In our limited simulations, they also compare well with the routines in S-PLUS® and Stata® in terms of both speed and reliability. The central idea of the working parameter approach is to search for efficient data augmentation schemes for implementing the EM algorithm by minimizing the augmented information over the working parameter, and in the mixed effects setting this leads to a transfer of the mixed effects variances into the regression slope parameters. We also describe a variation for computing the restricted maximum likelihood estimate and an adaptive algorithm that takes advantage of both the standard and the alternative EM-type implementations.     

Local maximum likelihood estimation and inference

Local maximum likelihood estimation is a nonparametric counterpart of the widely used parametric maximum likelihood technique. It extends the scope of the parametric maximum likelihood method to a much wider class of parametric spaces. Associated with this nonparametric estimation scheme is the issue of bandwidth selection and bias and variance assessment. This paper provides a unified approach to selecting a bandwidth and constructing confidence intervals in local maximum likelihood estimation. The approach is then applied to least squares nonparametric regression and to nonparametric logistic regression. Our experiences in these two settings show that the general idea outlined here is powerful and encouraging.     

Estimating the variance for heterogeneity in arm‐based network meta‐analysis

Network meta‐analysis can be implemented by using arm‐based or contrast‐based models. Here we focus on arm‐based models and fit them using generalized linear mixed model procedures. Full maximum likelihood (ML) estimation leads to biased trial‐by‐treatment interaction variance estimates for heterogeneity. Thus, our objective is to investigate alternative approaches to variance estimation that reduce bias compared with full ML. Specifically, we use penalized quasi‐likelihood/pseudo‐likelihood and hierarchical (h) likelihood approaches. In addition, we consider a novel model modification that yields estimators akin to the residual maximum likelihood estimator for linear mixed models. The proposed methods are compared by simulation, and 2 real datasets are used for illustration. Simulations show that penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood reduce bias and yield satisfactory coverage rates. Sum‐to‐zero restriction and baseline contrasts for random trial‐by‐treatment interaction effects, as well as a residual ML‐like adjustment, also reduce bias compared with an unconstrained model when ML is used, but coverage rates are not quite as good. Penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood are therefore recommended.     

Variance components estimation for the balanced random effects model under mixed prior distributions

For the balanced random effects models, when the variance components are correlated either naturally or through common prior structures, by assuming a mixed prior distribution for the variance components, we propose some new Bayesian estimators. To contrast and compare the new estimators with the minimum variance unbiased (MVUE) and restricted maximum likelihood estimators (RMLE), some simulation studies are also carried out. It turns out that the proposed estimators have smaller mean squared errors than the MVUE and RMLE.     

A semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data

We propose a flexible semiparametric stochastic mixed effects model for bivariate cyclic longitudinal data. The model can handle either single cycle or, more generally, multiple consecutive cycle data. The approach models the mean of responses by parametric fixed effects and a smooth nonparametric function for the underlying time effects, and the relationship across the bivariate responses by a bivariate Gaussian random field and a joint distribution of random effects. The proposed model not only can model complicated individual profiles, but also allows for more flexible within-subject and between-response correlations. The fixed effects regression coefficients and the nonparametric time functions are estimated using maximum penalized likelihood, where the resulting estimator for the nonparametric time function is a cubic smoothing spline. The smoothing parameters and variance components are estimated simultaneously using restricted maximum likelihood. Simulation results show that the parameter estimates are close to the true values. The fit of the proposed model on a real bivariate longitudinal dataset of pre-menopausal women also performs well, both for a single cycle analysis and for a multiple consecutive cycle analysis. The Canadian Journal of Statistics 48: 471–498; 2020 © 2020 Statistical Society of Canada     

Functional variance estimation using penalized splines with principal component analysis

In many fields of empirical research one is faced with observations arising from a functional process. If so, classical multivariate methods are often not feasible or appropriate to explore the data at hand and functional data analysis is prevailing. In this paper we present a method for joint modeling of mean and variance in longitudinal data using penalized splines. Unlike previous approaches we model both components simultaneously via rich spline bases. Estimation as well as smoothing parameter selection is carried out using a mixed model framework. The resulting smooth covariance structures are then used to perform principal component analysis. We illustrate our approach by several simulations and an application to financial interest data.