Bootstrap tests for variance components in generalized linear mixed models

In many applications of generalized linear mixed models to clustered correlated or longitudinal data, often we are interested in testing whether a random effects variance component is zero. The usual asymptotic mixture of chi‐square distributions of the score statistic for testing constrained variance components does not necessarily hold. In this article, the author proposes and explores a parametric bootstrap test that appears to be valid based on its estimated level of significance under the null hypothesis. Results from a simulation study indicate that the bootstrap test has a level much closer to the nominal one while the asymptotic test is conservative, and is more powerful than the usual asymptotic score test based on a mixture of chi‐squares. The proposed bootstrap test is illustrated using two sets of real‐life data obtained from clinical trials. The Canadian Journal of Statistics © 2009 Statistical Society of Canada     

Likelihood ratio tests in linear mixed models with one variance component

Summary.  We consider the problem of testing null hypotheses that include restrictions on the variance component in a linear mixed model with one variance component and we derive the finite sample and asymptotic distribution of the likelihood ratio test and the restricted likelihood ratio test. The spectral representations of the likelihood ratio test and the restricted likelihood ratio test statistics are used as the basis of efficient simulation algorithms of their null distributions. The large sample χ ² mixture approximations using the usual asymptotic theory for a null hypothesis on the boundary of the parameter space have been shown to be poor in simulation studies. Our asymptotic calculations explain these empirical results. The theory of Self and Liang applies only to linear mixed models for which the data vector can be partitioned into a large number of independent and identically distributed subvectors. One-way analysis of variance and penalized splines models illustrate the results.     

Testing variance components in balanced linear growth curve models

It is well known that the testing of zero variance components is a non-standard problem since the null hypothesis is on the boundary of the parameter space. The usual asymptotic chi-square distribution of the likelihood ratio and score statistics under the null does not necessarily hold because of this null hypothesis. To circumvent this difficulty in balanced linear growth curve models, we introduce an appropriate test statistic and suggest a permutation procedure to approximate its finite-sample distribution. The proposed test alleviates the necessity of any distributional assumptions for the random effects and errors and can easily be applied for testing multiple variance components. Our simulation studies show that the proposed test has Type I error rate close to the nominal level. The power of the proposed test is also compared with the likelihood ratio test in the simulations. An application on data from an orthodontic study is presented and discussed.     

Robust Poisson likelihood estimation for frailty Cox models: A simulation study

Frailty models can be fit as mixed-effects Poisson models after transforming time-to-event data to the Poisson model framework. We assess, through simulations, the robustness of Poisson likelihood estimation for Cox proportional hazards models with log-normal frailties under misspecified frailty distribution. The log-gamma and Laplace distributions were used as true distributions for frailties on a natural log scale. Factors such as the magnitude of heterogeneity, censoring rate, number and sizes of groups were explored. In the simulations, the Poisson modeling approach that assumes log-normally distributed frailties provided accurate estimates of within- and between-group fixed effects even under a misspecified frailty distribution. Non-robust estimation of variance components was observed in the situations of substantial heterogeneity, large event rates, or high data dimensions.     

Smooth Semi‐nonparametric Analysis for Mixture Cure Models and Its Application to Breast Cancer

Mixture cure models are widely used when a proportion of patients are cured. The proportional hazards mixture cure model and the accelerated failure time mixture cure model are the most popular models in practice. Usually the expectation–maximisation (EM) algorithm is applied to both models for parameter estimation. Bootstrap methods are used for variance estimation. In this paper we propose a smooth semi‐nonparametric (SNP) approach in which maximum likelihood is applied directly to mixture cure models for parameter estimation. The variance can be estimated by the inverse of the second derivative of the SNP likelihood. A comprehensive simulation study indicates good performance of the proposed method. We investigate stage effects in breast cancer by applying the proposed method to breast cancer data from the South Carolina Cancer Registry.     

Confidence intervals and tests on the variance ratio in random models with two variance components

The LM test is modified to test any value of the ratio of two variance components in a mixed effects linear model with two variance components. The test is exact, so it can be used to construct exact confidence intervals on this ratio.Exact Neyman-Pearson (NP) tests on the variance ratio are described.Their powers provide attainable upper bounds on powers of tests on the variance ratio.Efficiencies of LM tests, which include ANOVA tests, and NP tests are compared for unbalanced, random, one-way ANOVA models.Confidence intervals corresponding to LM tests and NP tests are described.     

Estimation in Semiparametric Marginal Shared Gamma Frailty Models

The semiparametric marginal shared frailty models in survival analysis have the non–parametric hazard functions multiplied by a random frailty in each cluster, and the survival times conditional on frailties are assumed to be independent. In addition, the marginal hazard functions have the same form as in the usual Cox proportional hazard models. In this paper, an approach based on maximum likelihood and expectation–maximization is applied to semiparametric marginal shared gamma frailty models, where the frailties are assumed to be gamma distributed with mean 1 and variance θ. The estimates of the fixed–effect parameters and their standard errors obtained using this approach are compared in terms of both bias and efficiency with those obtained using the extended marginal approach. Similarly, the standard errors of our frailty variance estimates are found to compare favourably with those obtained using other methods. The asymptotic distribution of the frailty variance estimates is shown to be a 50–50 mixture of a point mass at zero and a truncated normal random variable on the positive axis for θ₀ = 0. Simulations demonstrate that, for θ₀ < 0, it is approximately an x −(100 − x )%, 0 ≤ x ≤ 50, mixture between a point mass at zero and a truncated normal random variable on the positive axis for small samples and small values of θ₀; otherwise, it is approximately normal.     

Analysis of means approach for random factor analysis

Analysis of means (ANOM) is a powerful tool for comparing means and variances in fixed-effects models. The graphical exhibit of ANOM is considered as a great advantage because of its interpretability and its ability to evaluate the practical significance of the mean effects. However, the presence of random factors may be problematic for the ANOM method. In this paper, we propose an ANOM approach that can be applied to test random effects in many different balanced statistical models including fixed-, random- and mixed-effects models. The proposed approach utilizes the range of the treatment averages for identifying the dispersions of the underlying populations. The power performance of the proposed procedure is compared to the analysis of variance (ANOVA) approach in a wide range of situations via a Monte Carlo simulation study. Illustrative examples are used to demonstrate the usefulness of the proposed approach and its graphical exhibits, provide meaningful interpretations, and discuss the statistical and practical significance of factor effects.     

Physically meaningful covariates

The difficulty of detecting cloud seeding effects increases with the scale of the area being treated. Complex numerical models have been constructed for predicting seeding effects but remain largely untested. Their variables can, however, be used as a basis for selecting covariates for the evaluation of seeding results. A conceptual model of the physical factors for an orographic cloud are presented and key parameters (covariates) that can be derived from upwind rawinsonde sounding data are discussed. Multiple regression equations relating 6-hourly snowfall in the San Juan Mountains of Colorado to sounding-derived co-variates accounted for about half of the variance. When this approach is applied to seeded and not seeded samples separately it is found that the differences depend heavily upon 2nd order terms. The physical bases for this are discussed.

In the case of cumulus clouds, whether isolated or embedded in an orographic cloud, the situation is more complex and the use of co-variates has, thus far, been less rewarding.     

A Hybrid Approximation Bayesian Test of Variance Components for Longitudinal Data

The test of variance components of possibly correlated random effects in generalized linear mixed models (GLMMs) can be used to examine if there exists heterogeneous effects. The Bayesian test with Bayes factors offers a flexible method. In this article, we focus on the performance of Bayesian tests under three reference priors and a conjugate prior: an approximate uniform shrinkage prior, modified approximate Jeffreys' prior, half-normal unit information prior and Wishart prior. To compute Bayes factors, we propose a hybrid approximation approach combining a simulated version of Laplace's method and importance sampling techniques to test the variance components in GLMMs.     

Box–Cox t random intercept model for estimating usual nutrient intake distributions

The issue of estimating usual nutrient intake distributions and prevalence of inadequate nutrient intakes is of interest in nutrition studies. Box–Cox transformations coupled with the normal distribution are usually employed for modeling nutrient intake data. When the data present highly asymmetric distribution or include outliers, this approach may lead to implausible estimates. Additionally, it does not allow interpretation of the parameters in terms of characteristics of the original data and requires back transformation of the transformed data to the original scale. This paper proposes an alternative approach for estimating usual nutrient intake distributions and prevalence of inadequate nutrient intakes through a Box–Cox t model with random intercept. The proposed model is flexible enough for modeling highly asymmetric data even when outliers are present. Unlike the usual approach, the proposed model does not require a transformation of the data. A simulation study suggests that the Box–Cox t model with random intercept estimates the usual intake distribution satisfactorily, and that it should be preferable to the usual approach particularly in cases of highly asymmetric heavy-tailed data. In applications to data sets on intake of 19 micronutrients, the Box–Cox t models provided better fit than its competitors in most of the cases.     

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.     

Graphical technique for comparing designs for random models

Methods for comparing designs for a random (or mixed) linear model have focused primarily on criteria based on single-valued functions. In general, these functions are difficult to use, because of their complex forms, in addition to their dependence on the model's unknown variance components. In this paper, a graphical approach is presented for comparing designs for random models. The one-way model is used for illustration. The proposed approach is based on using quantiles of an estimator of a function of the variance components. The dependence of these quantiles on the true values of the variance components is depicted by plotting the so-called quantile dispersion graphs (QDGs), which provide a comprehensive picture of the quality of estimation obtained with a given design. The QDGs can therefore be used to compare several candidate designs. Two methods of estimation of variance components are considered, namely analysis of variance and maximum-likelihood estimation.     

Bivariate zero-inflated negative binomial regression model with applications

Count data often display excessive number of zero outcomes than are expected in the Poisson regression model. The zero-inflated Poisson regression model has been suggested to handle zero-inflated data, whereas the zero-inflated negative binomial (ZINB) regression model has been fitted for zero-inflated data with additional overdispersion. For bivariate and zero-inflated cases, several regression models such as the bivariate zero-inflated Poisson (BZIP) and bivariate zero-inflated negative binomial (BZINB) have been considered. This paper introduces several forms of nested BZINB regression model which can be fitted to bivariate and zero-inflated count data. The mean–variance approach is used for comparing the BZIP and our forms of BZINB regression model in this study. A similar approach was also used by past researchers for defining several negative binomial and zero-inflated negative binomial regression models based on the appearance of linear and quadratic terms of the variance function. The nested BZINB regression models proposed in this study have several advantages; the likelihood ratio tests can be performed for choosing the best model, the models have flexible forms of marginal mean–variance relationship, the models can be fitted to bivariate zero-inflated count data with positive or negative correlations, and the models allow additional overdispersion of the two dependent variables.     

ASYMPTOTIC NORMALITY OF GOODNESS-OF-FIT STATISTICS FOR SPARSE POISSON DATA

Goodness-of-fit tests for discrete data and models with parameters to be estimated are usually based on Pearson's χ2 or the Likelihood Ratio Statistic. Both are included in the family of Power-Divergence Statistics SDλ which are asymptotically χ2 distributed for the usual sampling schemes. We derive a limiting standard normal distribution for a standardization Tλ of SDλ under Poisson sampling by considering an approach with an increasing number of cells. In contrast to the χ2 asymptotics we do not require an increase of all expected values and thus meet the situation when data are sparse. Our limit result is useful even if a bootstrap test is used, because it implies that the statistic Tλ should be bootstrapped and not the sum SDλ. The peculiarity of our approach is that the models under test only specify associations. Hence we have to deal with an infinite number of nuisance parameters. We illustrate our approach with an application.     

Adaptive Inference for Multi-Stage Survey Data

Multi-level models can be used to account for clustering in data from multi-stage surveys. In some cases, the intraclass correlation may be close to zero, so that it may seem reasonable to ignore clustering and fit a single-level model. This article proposes several adaptive strategies for allowing for clustering in regression analysis of multi-stage survey data. The approach is based on testing whether the PSU-level variance component is zero. If this hypothesis is retained, then variance estimates are calculated ignoring clustering; otherwise, clustering is reflected in variance estimation. A simple simulation study is used to evaluate the various procedures.     

The influence of a single observation on some standard test statistics

The ideas of influence are now well known, and influence functions have been investigated widely, especially in the contexts of regression analysis and multivariate analysis. However, there seems to be no published account of the influence of single observations on simple one-sample tests for means and variance. The usual test statistics, based on normality assumptions, for a mean when the variance is known, and for the variance, display an obvious behaviour when an extra observation is added to a data set. However, the t-test for a single mean has a more interesting, and less predictable, pattern of behaviour. The t-statistic also demonstrates how the theoretical influence function can sometimes be misleading when used to estimate the effect of inserting or deleting a single observation.     

Modification of GEE1 and linear mixed-effects models for heteroscedastic longitudinal Gaussian data

A characterization of GLMs is given. Modification of the Gaussian GEE1, modified GEE1, was applied to heteroscedastic longitudinal data, to which linear mixed-effects models are usually applied. The modified GEE1 models scale multivariate data to homoscedastic data maintaining the correlation structure and apply usual GEE1 to homoscedastic data, which needs no-diagnostics for diagonal variances. Relationships among multivariate linear regression methods, ordinary/generalized LS, naïve/modified GEE1, and linear mixed-effects models were discussed. An application showed modified GEE1 gave most efficient parameter estimation. Correct specification of the main diagonals of heteroscedastic data variance appears to be more important for efficient mean parameter estimation.     

Testing for separability of spatial–temporal covariance functions

Most applications in spatial statistics involve modeling of complex spatial–temporal dependency structures, and many of the problems of space and time modeling can be overcome by using separable processes. This subclass of spatial–temporal processes has several advantages, including rapid fitting and simple extensions of many techniques developed and successfully used in time series and classical geostatistics. In particular, a major advantage of these processes is that the covariance matrix for a realization can be expressed as the Kronecker product of two smaller matrices that arise separately from the temporal and purely spatial processes, and hence its determinant and inverse are easily determinable. However, these separable models are not always realistic, and there are no formal tests for separability of general spatial–temporal processes. We present here a formal method to test for separability. Our approach can be also used to test for lack of stationarity of the process. The beauty of our approach is that by using spectral methods the mechanics of the test can be reduced to a simple two-factor analysis of variance (ANOVA) procedure. The approach we propose is based on only one realization of the spatial–temporal process.We apply the statistical methods proposed here to test for separability and stationarity of spatial–temporal ozone fields using data provided by the US Environmental Protection Agency (EPA).