Local influence of nonlinear mixed effects model based on M-estimation

Abstract

In this work we mainly study the local influence in nonlinear mixed effects model with M-estimation. A robust method to obtain maximum likelihood estimates for parameters is presented, and the local influence of nonlinear mixed models based on robust estimation (M-estimation) by use of the curvature method is systematically discussed. The counting formulas of curvature for case weights perturbation, response variable perturbation and random error covariance perturbation are derived. Simulation studies are carried to access performance of the methods we proposed. We illustrate the diagnostics by an example presented in Davidian and Giltinan, which was analyzed under the non-robust situation.     

A Bayesian random effects model for analyzing mixed negative binomial and continuous longitudinal responses

ABSTRACT

A general Bayesian random effects model for analyzing longitudinal mixed correlated continuous and negative binomial responses with and without missing data is presented. This Bayesian model, given some random effects, uses a normal distribution for the continuous response and a negative binomial distribution for the count response. A Markov Chain Monte Carlo sampling algorithm is described for estimating the posterior distribution of the parameters. This Bayesian model is illustrated by a simulation study. For sensitivity analysis to investigate the change of parameter estimates with respect to the perturbation from missing at random to not missing at random assumption, the use of posterior curvature is proposed. The model is applied to a medical data, obtained from an observational study on women, where the correlated responses are the negative binomial response of joint damage and continuous response of body mass index. The simultaneous effects of some covariates on both responses are also investigated.     

Quantile regression for panel data models with fixed effects under random censoring

Abstract

The locally weighted censored quantile regression approach is proposed for panel data models with fixed effects, which allows for random censoring. The resulting estimators are obtained by employing the fixed effects quantile regression method. The weights are selected either parametrically, semi-parametrically or non-parametrically. The large panel data asymptotics are used in an attempt to cope with the incidental parameter problem. The consistency and limiting distribution of the proposed estimator are also derived. The finite sample performance of the proposed estimators are examined via Monte Carlo simulations.     

Between group variance component interval estimation for the unbalanced heteroscedastic one-way random effects model

The studied topic is motivated by the problem of interlaboratory comparisons. This paper focuses on the confidence interval estimation of the between group variance in the unbalanced heteroscedastic one-way random effects model. Several interval estimators are proposed and compared by means of the simulation study. The most recommended (safest) is the confidence interval based on Bonferroni's inequality.     

A comparison of methods for constructing confidence intervals on contrasts in a three-factor mixed model

This paper compares several methods for constructing a confidence interval on contrasts of fixed effects in a balanced three-factor mixed factorial design with one fixed effect and two random effects. In particular, confidence intervals constructed using PROC MIXED of SAS are compared to other intervals that have been proposed in the literature. Computer simulation is used to compare interval lengths, and determine each method's ability to maintain the stated confidence coefficient.     

Quasi-complete separation in random effects of binary response mixed models

ABSTRACT

Clustered observations such as longitudinal data are often analysed with generalized linear mixed models (GLMM). Approximate Bayesian inference for GLMMs with normally distributed random effects can be done using integrated nested Laplace approximations (INLA), which is in general known to yield accurate results. However, INLA is known to be less accurate for GLMMs with binary response. For longitudinal binary response data it is common that patients do not change their health state during the study period. In this case the grouping covariate perfectly predicts a subset of the response, which implies a monotone likelihood with diverging maximum likelihood (ML) estimates for cluster-specific parameters. This is known as quasi-complete separation. In this paper we demonstrate, based on longitudinal data from a randomized clinical trial and two simulations, that the accuracy of INLA decreases with increasing degree of cluster-specific quasi-complete separation. Comparing parameter estimates by INLA, Markov chain Monte Carlo sampling and ML shows that INLA increasingly deviates from the other methods in such a scenario.     

Testing for random effects and serial correlation in spatial autoregressive models

This paper constructs and evaluates tests for random effects and serial correlation in spatial autoregressive panel data models. In these models, ignoring the presence of random effects not only produces misleading inference but inconsistent estimation of the regression coefficients. Two different estimation methods are considered: maximum likelihood and instrumental variables. For each estimator, optimal tests are constructed: Lagrange multiplier in the first case; Neyman's C(α)$C(\alpha )$ in the second. In addition, locally size-robust tests, for individual hypotheses under local misspecification of the unconsidered parameter, are constructed. Extensive Monte Carlo evidence is presented.     

Joint models for a GLM-type longitudinal response and a time-to-event with smooth random effects

ABSTRACT

Longitudinal studies often entail non-Gaussian primary responses. When dropout occurs, potential non-ignorability of the missingness process may occur, and a joint model for the primary response and a time-to-event may represent an appealing tool to account for dependence between the two processes. As an extension to the GLMJM, recently proposed, and based on Gaussian latent effects, we assume that the random effects follow a smooth, P-spline based density. To estimate model parameters, we adopt a two-step conditional Newton–Raphson algorithm. Since the maximization of the penalized log-likelihood requires numerical integration over the random effect, which is often cumbersome, we opt for a pseudo-adaptive Gaussian quadrature rule to approximate the model likelihood. We discuss the proposed model by analyzing an original dataset on dilated cardiomyopathies and through a simulation study.     

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.     

Diagnostics for repeated measurements in generalized linear mixed effects models

ABSTRACT

As there is an extensive body of research on diagnostics in regression models, various outlier detection methods have been developed. These methods have been extended to mixed effects models and generalized linear models, but there exist intrinsic drawbacks and limitations. This paper presents two-dimensional plots to identify discordant subjects and observations in generalized linear mixed effects models, displaying discordance in two directions. The sTudentized Residual Sum of Squares is not an extension of any regression tools but a new approach designed to efficiently reflect the characteristics of repeated measures. And this noteworthy clustering of outliers is identified in the plot. Applications to real-life examples are presented to illustrate the favorable/beneficial performance of the new tool.     

Diagnostics for repeated measurements in nonlinear mixed effects models

Abstract

This paper introduces a new non-deletion method which identifies discordant subjects in nonlinear mixed effects models under a self-modeling framework. The new method decomposes the population level residuals into two parts and suggests two-dimensional plots to identify discordant subjects. An observation-wise investigation for alleged discordant subjects is also presented. The performances of the new methods are illustrated with simulation data and two real data examples. The new methods successfully identify the intended or important discordant subjects and observations. In a comparison with the local influence method, the new method reaches a consistent conclusion in a simpler and more efficient manner.     

Estimating the Intercept in an Orthogonally Blocked Experiment when the Block Effects are Random

Abstract

For an orthogonally blocked experiment, Khuri [Khuri, A. I. (1992). Response surface models with random block effects. Technometrics 34:26–37] has shown that the ordinary least squares estimator, the generalized least squares estimator and the intra-block estimator of the factor effects in a response surface model with random block effects coincide. The ordinary least squares estimator ignores the blocks, whereas the generalized least squares and the intra-block estimators treat the block effects as random and fixed, respectively. As shown in this paper, the equivalence does not hold for the estimation of the intercept when the block sizes are heterogeneous. Practical examples are given to illustrate the theoretical results.     

Confidence Intervals for the Median of a Finite Population Based on the Sign Test

This article presents methods for constructing confidence intervals for the median of a finite population under simple random sampling without replacement, stratified random sampling, and cluster sampling. The confidence intervals, as well as point estimates and test statistics, are derived from sign estimating functions which are based on the well-known sign test. Therefore, a unified approach for inference about the median of a finite population is given.     

Spherical radial approximation for nested mixed effects models

We consider a likelihood approximation in generalized linear mixed-effects models (GLMM) with multilevel nested random effects. Likelihood evaluation in such models is difficult, hindered by the need for high dimensional integration, where the dimension is proportional to the number of units per level and the number of random effects per unit. Various integration approaches have been proposed, including the penalized quasi-likelihood method, Laplace approximation, quadrature approximation, simulation, and MCMC algorithms. We propose a new quadrature approximation method, which is based on the spherical radial integration approach of Monahan and Genz (J Am Stat Assoc 92:664–674 1997), and at the same time takes advantage of the hierarchical structure of the integration. Our new hierarchical spherical radial method has a time complexity that is linear in the number of units per level and the number of random effects per unit, in contrast to the exponential complexity of the adaptive Gaussian quadrature method of Pinheiro and Chao (J Comput Graph Stat 15:58–81 2006) for the same problem. Using a spline approximation, the generalized additive mixed models (GAMM) are GLMMs with two levels of nested random effects. We apply our method to estimation of GAMMs. We compare it with competing methods through simulations and apply our method to analyze virologic and immunologic responses in an AIDS clinical trial. An R package is written and available at http://?users.?wpi.?edu/?~jgagnon/?software.?html.     

On misspecification of the dispersion matrix in mixed linear models

The general mixed linear model can be written y = Xβ + Zu + e, where β is a vector of fixed effects, u is a vector of random effects and e is a vector of random errors. In this note, we mainly aim at investigating the general necessary and sufficient conditions under which the best linear unbiased estimator for \varvec r(\varvec l, \varvec m) = \varvec l\varvec ￠\varvec b+\varvec m\varvec ￠\varvec u{\varvec \varrho}({\varvec l}, {\varvec m}) = {\varvec l}{\varvec '}{\varvec \beta}+{\varvec m}{\varvec '}{\varvec u} is also optimal under the misspecified model. In addition, we offer approximate conclusions in some special situations including a random regression model.     

Performance of standard imputation methods for missing quality of life data as covariate in survival analysis based on simulations from the International Breast Cancer Study Group Trials VI and VII*

Abstract

Imputation methods for missing data on a time-dependent variable within time-dependent Cox models are investigated in a simulation study. Quality of life (QoL) assessments were removed from the complete simulated datasets, which have a positive relationship between QoL and disease-free survival (DFS) and delayed chemotherapy and DFS, by missing at random and missing not at random (MNAR) mechanisms. Standard imputation methods were applied before analysis. Method performance was influenced by missing data mechanism, with one exception for simple imputation. The greatest bias occurred under MNAR and large effect sizes. It is important to carefully investigate the missing data mechanism.     

A penalized spline estimator for fixed effects panel data models

Estimating nonlinear effects of continuous covariates by penalized splines is well established for regressions with cross-sectional data as well as for panel data regressions with random effects. Penalized splines are particularly advantageous since they enable both the estimation of unknown nonlinear covariate effects and inferential statements about these effects. The latter are based, for example, on simultaneous confidence bands that provide a simultaneous uncertainty assessment for the whole estimated functions. In this paper, we consider fixed effects panel data models instead of random effects specifications and develop a first-difference approach for the inclusion of penalized splines in this case. We take the resulting dependence structure into account and adapt the construction of simultaneous confidence bands accordingly. In addition, the penalized spline estimates as well as the confidence bands are also made available for derivatives of the estimated effects which are of considerable interest in many application areas. As an empirical illustration, we analyze the dynamics of life satisfaction over the life span based on data from the German Socio-Economic Panel. An open-source software implementation of our methods is available in the R package pamfe.     

Analysis of Linear Models with One Factor Having Both Fixed and Random Levels

ABSTRACT

A general theory for a case where a factor has both fixed and random effect levels is developed under one-way treatment structure model. Estimation procedures for the fixed effects and variance components are consider for the model. The testing of fixed effects is considered when the variance–covariance matrix is known and unknown. Confidence intervals for estimable functions and prediction intervals for predictable functions are constructed. The computational procedures are illustrated using data from an on-farm trial.     

Randomized heuristic algorithms for orthogonal projection of a point onto a set

Abstract

The problem of orthogonal projection of a point onto a set is an essential problem of computational geometry. This problem has many practical applications in different areas such as robotics, computer graphics and so on. In the present paper three algorithms for solving this problem are proposed. This algorithms are based on the idea of heuristic random search. Numerical experiments illustrating the work of the proposed methods are presented.     

Composite likelihood for aggregate data from clustered multistate processes under intermittent observation

Abstract

Markov processes offer a useful basis for modeling the progression of organisms through successive stages of their life cycle. When organisms are examined intermittently in developmental studies, likelihoods can be constructed based on the resulting panel data in terms of transition probability functions. In some settings however, organisms cannot be tracked individually due to a difficulty in identifying distinct individuals, and in such cases aggregate counts of the number of organisms in different stages of development are recorded at successive time points. We consider the setting in which such aggregate counts are available for each of a number of tanks in a developmental study. We develop methods which accommodate clustering of the transition rates within tanks using a marginal modeling approach followed by robust variance estimation, and through use of a random effects model. Composite likelihood is proposed as a basis of inference in both settings. An extension which incorporates mortality is also discussed. The proposed methods are shown to perform well in empirical studies and are applied in an illustrative example on the growth of the Arabidopsis thaliana plant.