Restricted maximum likelihood (REML) is now well established as a method for estimating the parameters of the general Gaussian linear model with a structured covariance matrix, in particular for mixed linear models. Conventionally, estimates of precision and inference for fixed effects are based on their asymptotic distribution, which is known to be inadequate for some small-sample problems. In this paper, we present a scaled Wald statistic, together with an F approximation to its sampling distribution, that is shown to perform well in a range of small sample settings. The statistic uses an adjusted estimator of the covariance matrix that has reduced small sample bias. This approach has the advantage that it reproduces both the statistics and F distributions in those settings where the latter is exact, namely for Hotelling T2 type statistics and for analysis of variance F-ratios. The performance of the modified statistics is assessed through simulation studies of four different REML analyses and the methods are illustrated using three examples.

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Small Sample Inference for Fixed Effects from Restricted Maximum Likelihood

We propose a general, nonlinear mixed effects model for repeated measures data and define estimators for its parameters. The proposed estimators are a natural combination of least squares estimators for nonlinear fixed effects models and maximum likelihood (or restricted maximum likelihood) estimators for linear mixed effects models. We implement Newton-Raphson estimation using previously developed computational methods for nonlinear fixed effects models and for linear mixed effects models. Two examples are presented and the connections between this work and recent work on generalized linear mixed effects models are discussed.

https://www.jstor.org/stable/pdfplus/2532087.pdf

Nonlinear Mixed Effects Models for Repeated Measures Data

INTRODUCTION What Are Linear Mixed Models (LMMs)? A Brief History of Linear Mixed Models LINEAR MIXED MODELS: AN OVERVIEW Introduction Specification of LMMs The Marginal Linear Model Estimation in LMMs Computational Issues Tools for Model Selection Model-Building Strategies Checking Model Assumptions (Diagnostics) Other Aspects of LMMs Power Analysis for Linear Mixed Models Chapter Summary TWO-LEVEL MODELS FOR CLUSTERED DATA: THE RAT PUP EXAMPLE Introduction The Rat Pup Study Overview of the Rat Pup Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model Estimating the Intraclass Correlation Coefficients (ICCs) Calculating Predicted Values Diagnostics for the Final Model Software Notes and Recommendations THREE-LEVEL MODELS FOR CLUSTERED DATA THE CLASSROOM EXAMPLE Introduction The Classroom Study Overview of the Classroom Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model Estimating the Intraclass Correlation Coefficients (ICCs) Calculating Predicted Values Diagnostics for the Final Model Software Notes Recommendations MODELS FOR REPEATED-MEASURES DATA: THE RAT BRAIN EXAMPLE Introduction The Rat Brain Study Overview of the Rat Brain Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model The Implied Marginal Variance-Covariance Matrix for the Final Model Diagnostics for the Final Model Software Notes Other Analytic Approaches Recommendations RANDOM COEFFICIENT MODELS FOR LONGITUDINAL DATA: THE AUTISM EXAMPLE Introduction The Autism Study Overview of the Autism Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model Calculating Predicted Values Diagnostics for the Final Model Software Note: Computational Problems with the D Matrix An Alternative Approach: Fitting the Marginal Model with an Unstructured Covariance Matrix MODELS FOR CLUSTERED LONGITUDINAL DATA: THE DENTAL VENEER EXAMPLE Introduction The Dental Veneer Study Overview of the Dental Veneer Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model The Implied Marginal Variance-Covariance Matrix for the Final Model Diagnostics for the Final Model Software Notes and Recommendations Other Analytic Approaches MODELS FOR DATA WITH CROSSED RANDOM FACTORS: THE SAT SCORE EXAMPLE Introduction The SAT Score Study Overview of the SAT Score Data Analysis Analysis Steps in the Software Procedures Results of Hypothesis Tests Comparing Results across the Software Procedures Interpreting Parameter Estimates in the Final Model The Implied Marginal Variance-Covariance Matrix for the Final Model Recommended Diagnostics for the Final Model Software Notes and Additional Recommendations APPENDIX A: STATISTICAL SOFTWARE RESOURCES APPENDIX B: CALCULATION OF THE MARGINAL VARIANCE-COVARIANCE MATRIX APPENDIX C: ACRONYMS/ABBREVIATIONS BIBLIOGRAPHY INDEX

Linear Mixed Models: A Practical Guide Using Statistical Software

The neurobiology and control of anxious states

Random-effects regression models have become increasingly popular for analysis of longitudinal data. A key advantage of the random-effects approach is that it can be applied when subjects are not measured at the same number of timepoints. In this article we describe use of random-effects pattern-mixture models to further handle and describe the influence of missing data in longitudinal studies. For this approach, subjects are first divided into groups depending on their missing-data pattern and then variables based on these groups are used as model covariates. In this way, researchers are able to examine the effect of missing-data patterns on the outcome (or outcomes) of interest. Furthermore, overall estimates can be obtained by averaging over the missing-data patterns. A psychiatric clinical trials data set is used to illustrate the random-effects pattern-mixture approach to longitudinal data analysis with missing data. Longitudinal studies occupy an important role in psychological and psychiatric research. In these studies the same individuals are repeatedly measured on a number of important variables over a series of timepoints. As an example, a longitudinal design is often used to determine whether a particular therapeutic agent can produce changes in clinical status over the course of an illness. Another application for the longitudinal study is to assess potential indicators of a change, in the subject's clinical status; for example, the assessment of whether drug plasma level measurements indicate clinical outcome. Even in well-controlled situations, missing data invariably occur in longitudinal studies. Subjects can be

/pdf/application-of-random-effects-pattern-mixture-models-for-4sb84l14l6.pdf

Application of Random-Effects Pattern-Mixture Models for Missing Data in Longitudinal Studies

For longitudinal data on several individuals, linear models that contain both random effects across individuals and autocorrelation in the within-individual errors are studied. A score test for autocorrelation in the within-individual errors for the “conditional independence” random effects model is first developed. An explicit maximum likelihood estimation procedure using the scoring method for the model with random effects and (autoregressive) AR(1) errors is then derived. Empirical Bayes estimation of the random effects and prediction of future responses of an individual based on this random effects with AR(1) errors model are also considered. A numerical example is presented to illustrate these methods.

Models for Longitudinal Data with Random Effects and AR(1) Errors

NMDA receptor complex antagonists have potential anxiolytic effects as measured with separation-induced ultrasonic vocalizations.

For cross-over designs, we show that one can recover information on direct and/or residual treatment effects from an inter-block (patients as blocks) analysis as is done in an incomplete block design.1 By combining the intra- and inter-block estimates, we obtain the generalized least squares estimate. In analysing cross-over trials, we recommended this approach provided the between-patient variance component can be estimated efficiently.

Recovery of inter‐block information in cross‐over trials

Asymptotic properties of the score test for autocorrelation in a random effects with AR(1) errors model

For longitudinal data on several individuals, linear models that contain both random effects across individuals and autocorrelation in the within-individual errors are studied. A score test for aut...

Eric M. Chi

Papers

Models for Longitudinal Data with Random Effects and AR(1) Errors

NMDA receptor complex antagonists have potential anxiolytic effects as measured with separation-induced ultrasonic vocalizations.

Recovery of inter‐block information in cross‐over trials

Asymptotic properties of the score test for autocorrelation in a random effects with AR(1) errors model

Analysis of Longitudinal Data by Models with Random Effects and Ar(1) Errors