Robust transformation mixed‐effects models for longitudinal continuous proportional data

The authors propose a robust transformation linear mixed‐effects model for longitudinal continuous proportional data when some of the subjects exhibit outlying trajectories over time. It becomes troublesome when including or excluding such subjects in the data analysis results in different statistical conclusions. To robustify the longitudinal analysis using the mixed‐effects model, they utilize the multivariate t distribution for random effects or/and error terms. Estimation and inference in the proposed model are established and illustrated by a real data example from an ophthalmology study. Simulation studies show a substantial robustness gain by the proposed model in comparison to the mixed‐effects model based on Aitchison's logit‐normal approach. As a result, the data analysis benefits from the robustness of making consistent conclusions in the presence of influential outliers. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

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.     

A new REML (parameter expanded) EM algorithm for linear mixed models

Linear mixed models are regularly applied to animal and plant breeding data to evaluate genetic potential. Residual maximum likelihood (REML) is the preferred method for estimating variance parameters associated with this type of model. Typically an iterative algorithm is required for the estimation of variance parameters. Two algorithms which can be used for this purpose are the expectation‐maximisation (EM) algorithm and the parameter expanded EM (PX‐EM) algorithm. Both, particularly the EM algorithm, can be slow to converge when compared to a Newton‐Raphson type scheme such as the average information (AI) algorithm. The EM and PX‐EM algorithms require specification of the complete data, including the incomplete and missing data. We consider a new incomplete data specification based on a conditional derivation of REML. We illustrate the use of the resulting new algorithm through two examples: a sire model for lamb weight data and a balanced incomplete block soybean variety trial. In the cases where the AI algorithm failed, a REML PX‐EM based on the new incomplete data specification converged in 28% to 30% fewer iterations than the alternative REML PX‐EM specification. For the soybean example a REML EM algorithm using the new specification converged in fewer iterations than the current standard specification of a REML PX‐EM algorithm. The new specification integrates linear mixed models, Henderson's mixed model equations, REML and the REML EM algorithm into a cohesive framework.     

ASYMPTOTIC LIKELIHOOD APPROXIMATIONS USING A PARTIAL LAPLACE APPROXIMATION

Elimination of a nuisance variable is often non‐trivial and may involve the evaluation of an intractable integral. One approach to evaluate these integrals is to use the Laplace approximation. This paper concentrates on a new approximation, called the partial Laplace approximation, that is useful when the integrand can be partitioned into two multiplicative disjoint functions. The technique is applied to the linear mixed model and shows that the approximate likelihood obtained can be partitioned to provide a conditional likelihood for the location parameters and a marginal likelihood for the scale parameters equivalent to restricted maximum likelihood (REML). Similarly, the partial Laplace approximation is applied to the t‐distribution to obtain an approximate REML for the scale parameter. A simulation study reveals that, in comparison to maximum likelihood, the scale parameter estimates of the t‐distribution obtained from the approximate REML show reduced bias.     

Fast and Accurate Inference for the Smoothing Parameter in Semiparametric Models

A fast and accurate method of confidence interval construction for the smoothing parameter in penalised spline and partially linear models is proposed. The method is akin to a parametric percentile bootstrap where Monte Carlo simulation is replaced by saddlepoint approximation, and can therefore be viewed as an approximate bootstrap. It is applicable in a quite general setting, requiring only that the underlying estimator be the root of an estimating equation that is a quadratic form in normal random variables. This is the case under a variety of optimality criteria such as those commonly denoted by maximum likelihood (ML), restricted ML (REML), generalized cross validation (GCV) and Akaike's information criteria (AIC). Simulation studies reveal that under the ML and REML criteria, the method delivers a near‐exact performance with computational speeds that are an order of magnitude faster than existing exact methods, and two orders of magnitude faster than a classical bootstrap. Perhaps most importantly, the proposed method also offers a computationally feasible alternative when no known exact or asymptotic methods exist, e.g. GCV and AIC. An application is illustrated by applying the methodology to well‐known fossil data. Giving a range of plausible smoothed values in this instance can help answer questions about the statistical significance of apparent features in the data.     

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.     

A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed‐effects models

A version of the nonparametric bootstrap, which resamples the entire subjects from original data, called the case bootstrap, has been increasingly used for estimating uncertainty of parameters in mixed‐effects models. It is usually applied to obtain more robust estimates of the parameters and more realistic confidence intervals (CIs). Alternative bootstrap methods, such as residual bootstrap and parametric bootstrap that resample both random effects and residuals, have been proposed to better take into account the hierarchical structure of multi‐level and longitudinal data. However, few studies have been performed to compare these different approaches. In this study, we used simulation to evaluate bootstrap methods proposed for linear mixed‐effect models. We also compared the results obtained by maximum likelihood (ML) and restricted maximum likelihood (REML). Our simulation studies evidenced the good performance of the case bootstrap as well as the bootstraps of both random effects and residuals. On the other hand, the bootstrap methods that resample only the residuals and the bootstraps combining case and residuals performed poorly. REML and ML provided similar bootstrap estimates of uncertainty, but there was slightly more bias and poorer coverage rate for variance parameters with ML in the sparse design. We applied the proposed methods to a real dataset from a study investigating the natural evolution of Parkinson's disease and were able to confirm that the methods provide plausible estimates of uncertainty. Given that most real‐life datasets tend to exhibit heterogeneity in sampling schedules, the residual bootstraps would be expected to perform better than the case bootstrap. Copyright © 2013 John Wiley & Sons, Ltd.     

Penalized Empirical Likelihood via Bridge Estimator in Cox's Proportional Hazard Model

We propose the penalized empirical likelihood method via bridge estimator in Cox's proportional hazard model for parameter estimation and variable selection. Under reasonable conditions, we show that penalized empirical likelihood in Cox's proportional hazard model has oracle property. A penalized empirical likelihood ratio for the vector of regression coefficients is defined and its limiting distribution is a chi-square distributions. The advantage of penalized empirical likelihood as a nonparametric likelihood approach is illustrated in testing hypothesis and constructing confidence sets. The method is illustrated by extensive simulation studies and a real example.     

Likelihood-based approaches for multivariate linear models under inequality constraints for incomplete data

In this paper, we consider a multivariate linear model with complete/incomplete data, where the regression coefficients are subject to a set of linear inequality restrictions. We first develop an expectation/conditional maximization (ECM) algorithm for calculating restricted maximum likelihood estimates of parameters of interest. We then establish the corresponding convergence properties for the proposed ECM algorithm. Applications to growth curve models and linear mixed models are presented. Confidence interval construction via the double-bootstrap method is provided. Some simulation studies are performed and a real example is used to illustrate the proposed methods.     

A class of partially linear single‐index survival models

The authors define a class of “partially linear single‐index” survival models that are more flexible than the classical proportional hazards regression models in their treatment of covariates. The latter enter the proposed model either via a parametric linear form or a nonparametric single‐index form. It is then possible to model both linear and functional effects of covariates on the logarithm of the hazard function and if necessary, to reduce the dimensionality of multiple covariates via the single‐index component. The partially linear hazards model and the single‐index hazards model are special cases of the proposed model. The authors develop a likelihood‐based inference to estimate the model components via an iterative algorithm. They establish an asymptotic distribution theory for the proposed estimators, examine their finite‐sample behaviour through simulation, and use a set of real data to illustrate their approach.     

Using Adjacent-category Logits Procedure for Estimating Receiver Operating Characteristic Surface

This article presents a semiparametric method for estimating receiver operating characteristic surface under density ratio model. The construction of the proposed method is based on the adjacent-category logit model and the empirical likelihood approach. A bootstrap approach for the VUS estimator inference is presented. In a simulation study, the proposed estimator is compared with the existing parametric and nonparametric estimators in terms of bias, standard error, and mean square error. Finally, a real data example and some discussions on the proposed method are provided.     

Likelihood‐based Inference with Missing Data Under Missing‐at‐Random

Likelihood‐based inference with missing data is challenging because the observed log likelihood is often an (intractable) integration over the missing data distribution, which also depends on the unknown parameter. Approximating the integral by Monte Carlo sampling does not necessarily lead to a valid likelihood over the entire parameter space because the Monte Carlo samples are generated from a distribution with a fixed parameter value. We consider approximating the observed log likelihood based on importance sampling. In the proposed method, the dependency of the integral on the parameter is properly reflected through fractional weights. We discuss constructing a confidence interval using the profile likelihood ratio test. A Newton–Raphson algorithm is employed to find the interval end points. Two limited simulation studies show the advantage of the Wilks inference over the Wald inference in terms of power, parameter space conformity and computational efficiency. A real data example on salamander mating shows that our method also works well with high‐dimensional missing data.     

Bias‐reduced marginal Akaike information criteria based on a Monte Carlo method for linear mixed‐effects models

In linear mixed‐effects (LME) models, if a fitted model has more random‐effect terms than the true model, a regularity condition required in the asymptotic theory may not hold. In such cases, the marginal Akaike information criterion (AIC) is positively biased for (?2) times the expected log‐likelihood. The asymptotic bias of the maximum log‐likelihood as an estimator of the expected log‐likelihood is evaluated for LME models with balanced design in the context of parameter‐constrained models. Moreover, bias‐reduced marginal AICs for LME models based on a Monte Carlo method are proposed. The performance of the proposed criteria is compared with existing criteria by using example data and by a simulation study. It was found that the bias of the proposed criteria was smaller than that of the existing marginal AIC when a larger model was fitted and that the probability of choosing a smaller model incorrectly was decreased.     

Confidence intervals for variance components in unbalanced one-way random effects model using non-normal distributions

In scenarios where the variance of a response variable can be attributed to two sources of variation, a confidence interval for a ratio of variance components gives information about the relative importance of the two sources. For example, if measurements taken from different laboratories are nine times more variable than the measurements taken from within the laboratories, then 90% of the variance in the responses is due to the variability amongst the laboratories and 10% of the variance in the responses is due to the variability within the laboratories. Assuming normally distributed sources of variation, confidence intervals for variance components are readily available. In this paper, however, simulation studies are conducted to evaluate the performance of confidence intervals under non-normal distribution assumptions. Confidence intervals based on the pivotal quantity method, fiducial inference, and the large-sample properties of the restricted maximum likelihood (REML) estimator are considered. Simulation results and an empirical example suggest that the REML-based confidence interval is favored over the other two procedures in unbalanced one-way random effects model.     

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.     

Generalized empirical likelihood inference in partial linear regression model for longitudinal data

In this paper, empirical likelihood inference for longitudinal data within the framework of partial linear regression models are investigated. The proposed procedures take into consideration the correlation within groups without involving direct estimation of nuisance parameters in the correlation matrix. The empirical likelihood method is used to estimate the regression coefficients and the baseline function, and to construct confidence intervals. A nonparametric version of Wilk's theorem for the limiting distribution of the empirical likelihood ratio is derived. Compared with methods based on normal approximations, the empirical likelihood does not require consistent estimators for the asymptotic variance and bias. The finite sample behaviour of the proposed method is evaluated with simulation and illustrated with an AIDS clinical trial data set.     

Maximum likelihood estimation for the proportional odds model with mixed interval-censored failure time data

This article discusses regression analysis of mixed interval-censored failure time data. Such data frequently occur across a variety of settings, including clinical trials, epidemiologic investigations, and many other biomedical studies with a follow-up component. For example, mixed failure times are commonly found in the two largest studies of long-term survivorship after childhood cancer, the datasets that motivated this work. However, most existing methods for failure time data consider only right-censored or only interval-censored failure times, not the more general case where times may be mixed. Additionally, among regression models developed for mixed interval-censored failure times, the proportional hazards formulation is generally assumed. It is well-known that the proportional hazards model may be inappropriate in certain situations, and alternatives are needed to analyze mixed failure time data in such cases. To fill this need, we develop a maximum likelihood estimation procedure for the proportional odds regression model with mixed interval-censored data. We show that the resulting estimators are consistent and asymptotically Gaussian. An extensive simulation study is performed to assess the finite-sample properties of the method, and this investigation indicates that the proposed method works well for many practical situations. We then apply our approach to examine the impact of age at cranial radiation therapy on risk of growth hormone deficiency in long-term survivors of childhood cancer.     

Likelihood Inference for Unions of Interacting Discs

Abstract. This is probably the first paper which discusses likelihood inference for a random set using a germ‐grain model, where the individual grains are unobservable, edge effects occur and other complications appear. We consider the case where the grains form a disc process modelled by a marked point process, where the germs are the centres and the marks are the associated radii of the discs. We propose to use a recent parametric class of interacting disc process models, where the minimal sufficient statistic depends on various geometric properties of the random set, and the density is specified with respect to a given marked Poisson model (i.e. a Boolean model). We show how edge effects and other complications can be handled by considering a certain conditional likelihood. Our methodology is illustrated by analysing Peter Diggle's heather data set, where we discuss the results of simulation‐based maximum likelihood inference and the effect of specifying different reference Poisson models.     

Empirical Likelihood for the Additive Hazards Model with Current Status Data

We investigate empirical likelihood for the additive hazards model with current status data. An empirical log-likelihood ratio for a vector or subvector of regression parameters is defined and its limiting distribution is shown to be a standard chi-squared distribution. The proposed inference procedure enables us to make empirical likelihood-based inference for the regression parameters. Finite sample performance of the proposed method is assessed in simulation studies to compare with that of a normal approximation method, it shows that the empirical likelihood method provides more accurate inference than the normal approximation method. A real data example is used for illustration.     

Covariate Decomposition Methods for Longitudinal Missing‐at‐Random Data and Predictors Associated with Subject‐Specific Effects

Investigators often gather longitudinal data to assess changes in responses over time within subjects and to relate these changes to within‐subject changes in predictors. Missing data are common in such studies and predictors can be correlated with subject‐specific effects. Maximum likelihood methods for generalized linear mixed models provide consistent estimates when the data are ‘missing at random’ (MAR) but can produce inconsistent estimates in settings where the random effects are correlated with one of the predictors. On the other hand, conditional maximum likelihood methods (and closely related maximum likelihood methods that partition covariates into between‐ and within‐cluster components) provide consistent estimation when random effects are correlated with predictors but can produce inconsistent covariate effect estimates when data are MAR. Using theory, simulation studies, and fits to example data this paper shows that decomposition methods using complete covariate information produce consistent estimates. In some practical cases these methods, that ostensibly require complete covariate information, actually only involve the observed covariates. These results offer an easy‐to‐use approach to simultaneously protect against bias from both cluster‐level confounding and MAR missingness in assessments of change.