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.     

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.     

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.     

Estimating percentile-specific treatment effects in counterfactual models: a case-study of micronutrient supplementation, birth weight and infant mortality

Summary.  Clinical trials of micronutrient supplementation are aimed at reducing the risk of infant mortality by increasing birth weight. Because infant mortality is greatest among the low birth weight (LBW) infants (2500 g or under), an effective intervention increases the birth weight among the smallest babies. The paper defines population and counterfactual parameters for estimating the treatment effects on birth weight and on survival as functions of the percentiles of the birth weight distribution. We use a Bayesian approach with data augmentation to approximate the posterior distributions of the parameters, taking into account uncertainty that is associated with the imputation of the counterfactuals. This approach is particularly suitable for exploring the sensitivity of the results to unverifiable modelling assumptions and other prior beliefs. We estimate that the average causal effect of the treatment on birth weight is 72 g (95% posterior regions 33–110 g) and that this causal effect is largest among the LBW infants. Posterior inferences about average causal effects of the treatment on birth weight are robust to modelling assumptions. However, inferences about causal effects for babies at the tails of the birth weight distribution can be highly sensitive to the unverifiable assumption about the correl-ation between the observed and the counterfactuals birth weights. Among the LBW infants who have a large causal effect of the treatment on birth weight, we estimate that a baby receiving the treatment has 5% less chance of death than if the same baby had received the control. Among the LBW infants, we found weak evidence supporting an additional beneficial effect of the treatment on mortality independent of birth weight.     

Grouped poisson regression models: theory and an application to public house visit frequency

In this paper we extend the Poisson regression model to deal with the situation in which the event count is observed le in “grouped” form, By this we mean that for some observations, all that is known about the count is that it falls within a certain range of integers, and the actual value is unknown, A typical likelihood contribution for this extended model is the sum of a set of consecutive Poisson probabilities, The log-likelihood function is derived for a general grouping rule, using a logarithmic link for the Poisson mean, This log-likelihood function is shown to be globally concave. The model is applied to grouped count data on the frequency of trips to pubs made over a one-week period by a sample of Norfolk young persons.     

Estimation of variance components in the mixed effects models: A comparison between analysis of variance and spectral decomposition

The mixed effects models with two variance components are often used to analyze longitudinal data. For these models, we compare two approaches to estimating the variance components, the analysis of variance approach and the spectral decomposition approach. We establish a necessary and sufficient condition for the two approaches to yield identical estimates, and some sufficient conditions for the superiority of one approach over the other, under the mean squared error criterion. Applications of the methods to circular models and longitudinal data are discussed. Furthermore, simulation results indicate that better estimates of variance components do not necessarily imply higher power of the tests or shorter confidence intervals.