Strong Consistency of MLE in Nonlinear Mixed-effects Models with Large Cluster Size

The search for conditions for the consistency of maximum likelihood estimators in nonlinear mixed effects models is difficult due to the fact that, in general, the likelihood can only be expressed as an integral over the random effects. For repeated measurements or clustered data, we focus on asymptotic theory for the maximum likelihood estimator for the case where the cluster sizes go to infinity, which is a minimum assumption required to validate most of the available methods of inference in nonlinear mixed-effects models. In particular, we establish sufficient conditions for the (strong) consistency of the maximum likelihood estimator of the fixed effects. Our results extend the results of Jennrich (1969) and Wu (1981) for nonlinear fixed-effects models to nonlinear mixed-effects models. Running title: consistency of MLE.

[1]  Ralph A. Bradley,et al.  The asymptotic properties of ML estimators when sampling from associated populations , 1962 .

[2]  D. Bates,et al.  Approximations to the Log-Likelihood Function in the Nonlinear Mixed-Effects Model , 1995 .

[3]  Changbao Wu,et al.  Asymptotic Theory of Nonlinear Least Squares Estimation , 1981 .

[4]  D. Majumdar,et al.  Bacterial redox protein azurin, tumor suppressor protein p53, and regression of cancer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  J. Streibig,et al.  Nonlinear Mixed-Model Regression to Analyze Herbicide Dose–Response Relationships1 , 2004, Weed Technology.

[6]  L. Nie,et al.  Strong Consistency of the Maximum Likelihood Estimator in Generalized Linear and Nonlinear Mixed-Effects Models , 2006 .

[7]  Dibyen Majumdar,et al.  Conditional Second-Order Generalized Estimating Equations for Generalized Linear and Nonlinear Mixed-Effects Models , 2002 .

[8]  A. Wald Note on the Consistency of the Maximum Likelihood Estimate , 1949 .

[9]  D. Bates,et al.  Nonlinear mixed effects models for repeated measures data. , 1990, Biometrics.

[10]  B. Hoadley Asymptotic Properties of Maximum Likelihood Estimators for the Independent Not Identically Distributed Case , 1971 .

[11]  E. Vonesh,et al.  A note on the use of Laplace's approximation for nonlinear mixed-effects models , 1996 .

[12]  Eric R. Ziegel,et al.  Multivariate Statistical Modelling Based on Generalized Linear Models , 2002, Technometrics.

[13]  D J Roe Comparison of population pharmacokinetic modeling methods using simulated data: results from the Population Modeling Workgroup. , 1997, Statistics in medicine.

[14]  R. Gomeni,et al.  A two-step iterative algorithm for estimation in nonlinear mixed-effect models with an evaluation in population pharmacokinetics. , 1995, Journal of biopharmaceutical statistics.

[15]  Marie Davidian,et al.  Nonlinear Models for Repeated Measurement Data , 1995 .

[16]  E. Vonesh,et al.  Linear and Nonlinear Models for the Analysis of Repeated Measurements , 1996 .

[17]  Jiming Jiang Wald consistency and the method of sieves in REML estimation , 1997 .

[18]  R. Jennrich Asymptotic Properties of Non-Linear Least Squares Estimators , 1969 .

[19]  M Davidian,et al.  Some general estimation methods for nonlinear mixed-effects models. , 1993, Journal of biopharmaceutical statistics.

[20]  Russell D. Wolfinger,et al.  Two Taylor-series approximation methods for nonlinear mixed models , 1997 .

[21]  A REDUCTION THEOREM FOR CERTAIN SEQUENTIAL EXPERIMENTS. , 1979 .

[22]  H. Cramér Mathematical methods of statistics , 1947 .

[23]  N. Breslow,et al.  Approximate inference in generalized linear mixed models , 1993 .

[24]  Kai Lai Chung,et al.  A Course in Probability Theory , 1949 .