Interval estimation of parameters in an unbalanced mixed two-fold nested classification-the last-stage uniformity case

A procedure for the construction of exact simultaneous confidence intervals on functions of the fixed-effects parameters and on functions of variance components in an unbalanced, mixed, two-fold nested classification is introduced. The type of model considered in this paper enables the construction of such intervals to be based on the corresponding ANOVA table using its mean square ratios.     

Umvu estimators for the population mean and variance based on random effects models for lognormal data

Cross-classified data are often obtained in controlled experimental situations and in epidemiologic studies. As an example of the latter, occupational health studies sometimes require personal exposure measurements on a random sample of workers from one or more job groups, in one or more plant locations, on several different sampling dates. Because the marginal distributions of exposure data from such studies are generally right-skewed and well-approximated as lognormal, researchers in this area often consider the use of ANOVA models after a logarithmic transformation. While it is then of interest to estimate original-scale population parameters (e.g., the overall mean and variance), standard candidates such as maximum likelihood estimators (MLEs) can be unstable and highly biased. Uniformly minimum variance unbiased (UMVU) cstiniators offer a viable alternative, and are adaptable to sampling schemes that are typiral of experimental or epidemiologic studies. In this paper, we provide UMVU estimators for the mean and variance under two random effects ANOVA models for logtransformed data. We illustrate substantial mean squared error gains relative to the MLE when estimating the mean under a one-way classification. We illustrate that the results can readily be extended to encompass a useful class of purely random effects models, provided that the study data are balanced.     

Unbiasedness of two-stage estimation and prediction procedures for mixed linear models

The traditional method for estimating or predicting linear combinations of the fixed effects and realized values of the random effects in mixed linear models is first to estimate the variance components and then to proceed as if the estimated values of the variance components were the true values. This two-stage procedure gives unbiased estimators or predictors of the linear combinations provided the data vector is symmetrically distributed about its expected value and provided the variance component estimators are translation-invariant and are even functions of the data vector. The standard procedures for estimating the variance components yield even, translation-invariant estimators.     

Applying skovgaard's modified directed likelihood statistic to mixed linear models

The introduction of software to calculate maximum likelihood estimates for mixed linear models has made likelihood estimation a practical alternative to methods based on sums of squares. Likelihood based tests and confidence intervals, however, may be misleading in problems with small sample sizes. This paper discusses an adjusted version of the directed log-likelihood statistic for mixed models that is highly accurate for testing one parameter hypotheses. Indroduced by Skovgaard (1996, Journal of the Bernoulli Society,2,145-165), we show in mixed models that the statistic has a simple conpact from that may be obtained from standard software. Simulation studies indicate that this statistic is more accurate than many of the specialized procedure that have been advocated.     

Counterexamples to a result of broemeling on simultaneous inferences for variance ratios of some mixed linear models

In a recent paper5 Broemeling (1978) extended his earlier work on one-sided confidence regions for the variance ratios of balanced random-effects models to the two-sided case. The extension depends on a probability Inequality which was claimed to be tru We show here that it is false, hence the proof of the main result given in Ms parer is in error W also show Lhat the ntatement of his result remains true in certain special cases.     

Harmonic mean approach to unbalanced mixed effects models under heteroscedastic variances

In this paper we consider unbalanced mixed models (Scheffe's model) under heteroscedastic variances. By using the harmonic mean approach, It is shown that the problems appear to be anologous to those problems from balanced mixed models under homoscedastic variance. Thus, by using harmonic mean approach, statistical inferences about fixed effects and variance components are derived by using those from balanced models under homoscedastic variance. Laguerre polynomial expansion is used Lo approximate sampling distributions of relevant statistics.     

Harmonic mean approach to uunbalanced random effects models under heteroscedasticity

In this paper we consider unbalanced random effects models under heteroscedastic variances. By using' the harmonic mean approach, it is shown that the problems are analogous to those from balanced random effects models under horaoscedastic variances. Thus, by using the harmonic mean approach, statistical inferences about variance components are derived by using procedures from balanced models under homoscedastic variances. Laguerre polynomial expansion is used to approximate the sampling distributions of relevant statistics.     

A revisit to two-way factorial ANOVA with mixed effects and interactions

Abstract

Two mixed models exist in analysis of two-way factorial ANOVA with mixed effects and interactions: the constrained and unconstrained models. The constrained model is unfavored because there is no convincing rationale for the enforced constraints on its random interactions and a lack of clear interpretation about its variance components. The purpose of this study is to further explore the relationship between these two models. We reveal some nice features of the constrained model on partition of the responsive variance. An alternative formulation of ANOVA that follows from this exploration is also presented.     

The effects of missing serial effects and/or heteroscedastic errors on mixed models using repeated growth data

When a two-level multilevel model (MLM) is used for repeated growth data, the individuals constitute level 2 and the successive measurements constitute level 1, which is nested within the individuals that make up level 2. The heterogeneity among individuals is represented by either the random-intercept or random-coefficient (slope) model. The variance components at level 1 involve serial effects and measurement errors under constant variance or heteroscedasticity. This study hypothesizes that missing serial effects or/and heteroscedasticity may bias the results obtained from two-level models. To illustrate this effect, we conducted two simulation studies, where the simulated data were based on the characteristics of an empirical mouse tumour data set. The results suggest that for repeated growth data with constant variance (measurement error) and misspecified serial effects (ρ > 0.3), the proportion of level-2 variation (intra-class correlation coefficient) increases with ρ and the two-level random-coefficient model is the minimum AIC (or AIC_c) model when compared with the fixed model, heteroscedasticity model, and random-intercept model. In addition, the serial effect (ρ > 0.1) and heteroscedasticity are both misspecified, implying that the two-level random-coefficient model is the minimum AIC (or AIC_c) model when compared with the fixed model and random-intercept model. This study demonstrates that missing serial effects and/or heteroscedasticity may indicate heterogeneity among individuals in repeated growth data (mixed or two-level MLM). This issue is critical in biomedical research.     

Testing random effects in linear mixed models: another look at the F‐test (with discussion)

This article re‐examines the F‐test based on linear combinations of the responses, or FLC test, for testing random effects in linear mixed models. In current statistical practice, the FLC test is underused and we argue that it should be reconsidered as a valuable method for use with linear mixed models. We present a new, more general derivation of the FLC test which applies to a broad class of linear mixed models where the random effects can be correlated. We highlight three advantages of the FLC test that are often overlooked in modern applications of linear mixed models, namely its computation speed, its generality, and its exactness as a test. Empirical studies provide new insight into the finite sample performance of the FLC test, identifying cases where it is competitive or even outperforms modern methods in terms of power, as well as settings in which it performs worse than simulation‐based methods for testing random effects. In all circumstances, the FLC test is faster to compute.     

An evaluation of ridge estimator in linear mixed models: an example from kidney failure data

This paper is concerned with the ridge estimation of fixed and random effects in the context of Henderson's mixed model equations in the linear mixed model. For this purpose, a penalized likelihood method is proposed. A linear combination of ridge estimator for fixed and random effects is compared to a linear combination of best linear unbiased estimator for fixed and random effects under the mean-square error (MSE) matrix criterion. Additionally, for choosing the biasing parameter, a method of MSE under the ridge estimator is given. A real data analysis is provided to illustrate the theoretical results and a simulation study is conducted to characterize the performance of ridge and best linear unbiased estimators approach in the linear mixed model.     

Approximate one-sided tolerance limits in random effects model and in some mixed models and comparisons

An approximate closed-form one-sided tolerance limit (TL) in a general mixed model is proposed. One-sided TLs for the distribution of observable random variable and for the distribution of unobservable random variable in one-way random model are obtained as special cases from the one for the general mixed model. Applications to a two-way nested random model are also given. The merits of the TLs are evaluated using Monte Carlo simulation and compared with the existing ones. Our comparison studies indicate that the approximate TLs are quite satisfactory for all parameter and sample size configurations, and better than the existing ones in some cases. Approximate confidence intervals for exceedance probabilities in one-way random effects model are also proposed. The procedures are illustrated using three examples.     

Weibull and generalised exponential overdispersion models with an application to ozone air pollution

We consider the problem of estimating the mean and variance of the time between occurrences of an event of interest (inter-occurrences times) where some forms of dependence between two consecutive time intervals are allowed. Two basic density functions are taken into account. They are the Weibull and the generalised exponential density functions. In order to capture the dependence between two consecutive inter-occurrences times, we assume that either the shape and/or the scale parameters of the two density functions are given by auto-regressive models. The expressions for the mean and variance of the inter-occurrences times are presented. The models are applied to the ozone data from two regions of Mexico City. The estimation of the parameters is performed using a Bayesian point of view via Markov chain Monte Carlo (MCMC) methods.     

GMM Estimation with persistent panel data: an application to production functions

This paper considers the estimation of Cobb-Douglas production functions using panel data covering a large sample of companies observed for a small number of time periods. GMM estimatorshave been found to produce large finite-sample biases when using the standard first-differenced estimator. These biases can be dramatically reduced by exploiting reasonable stationarity restrictions on the initial conditions process. Using data for a panel of R&Dperforming US manufacturing companies we find that the additional instruments used in our extended GMM estimator yield much more reasonable parameter estimates.     

A Bayesian approach for generalized linear models with explanatory biomarker measurement variables subject to detection limit: an application to acute lung injury

Biomarkers have the potential to improve our understanding of disease diagnosis and prognosis. Biomarker levels that fall below the assay detection limits (DLs), however, compromise the application of biomarkers in research and practice. Most existing methods to handle non-detects focus on a scenario in which the response variable is subject to the DL; only a few methods consider explanatory variables when dealing with DLs. We propose a Bayesian approach for generalized linear models with explanatory variables subject to lower, upper, or interval DLs. In simulation studies, we compared the proposed Bayesian approach to four commonly used methods in a logistic regression model with explanatory variable measurements subject to the DL. We also applied the Bayesian approach and other four methods in a real study, in which a panel of cytokine biomarkers was studied for their association with acute lung injury (ALI). We found that IL8 was associated with a moderate increase in risk for ALI in the model based on the proposed Bayesian approach.     

A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.