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Fast inference for robust nonlinear mixed-effects models. (English) Zbl 07716692

Summary: The interest for nonlinear mixed-effects models comes from application areas as pharmacokinetics, growth curves and HIV viral dynamics. However, the modeling procedure usually leads to many difficulties, as the inclusion of random effects, the estimation process and the model sensitivity to atypical or nonnormal data. The scale mixture of normal distributions include heavy-tailed models, as the Student-\(t\), slash and contaminated normal distributions, and provide competitive alternatives to the usual models, enabling the obtention of robust estimates against outlying observations. Our proposal is to compare two estimation methods in nonlinear mixed-effects models where the random components follow a multivariate scale mixture of normal distributions. For this purpose, a Monte Carlo expectation-maximization algorithm (MCEM) and an efficient likelihood-based approximate method are developed. Results show that the approximate method is much faster and enables a fairly efficient likelihood maximization, although a slightly larger bias may be produced, especially for the fixed-effects parameters. A discussion on the robustness aspects of the proposed models are also provided. Two real nonlinear applications are discussed and a brief simulation study is presented.

MSC:

62-XX Statistics

Software:

Ox; tlmec; MEMSS; R; S-PLUS
Full Text: DOI

References:

[1] Andrews, D. R.; Mallows, C. L., Scale mixtures of normal distributions, J. R. Stat. Soc., 36, 99-102 (1974) · Zbl 0282.62017
[2] Davidian, M.; Giltinan, D. M., Nonlinear Models for Repeated Measurement Data (1995), Chapman and Hall: Chapman and Hall, London
[3] Dempster, A. P.; Laird, N. M.; Rubin, D. B., Maximun likelihood from incomplete data via the em algorithm (with discussion), J. R. Stat. Soc. B, 39, 1-38 (1977) · Zbl 0364.62022
[4] Doornik, J.A., An object-oriented matrix programming language ox 6, 2009.
[5] Gelfand, A.; Hills, S.; Racine-Poon, A.; Smith, A., Illustration of Bayesian inference in normal data models using Gibbs sampling, J. Am. Stat. Assoc., 85, 972-985 (1990)
[6] Gelman, A.; Rubin, D. B., Inference from iterative simulation using multiple sequences, Stat. Sci., 7, 457-472 (1992) · Zbl 1386.65060
[7] Gilks, W. R.; Richardson, S.; Spiegelhalter, D. J., Markov Chain Monte Carlo In Practice (1996), Chapman and Hall: Chapman and Hall, London · Zbl 0832.00018
[8] Kuhn, E.; Lavielle, M., Maximum likelihood estimation in nonlinear mixed effects models, Comput. Stat. Data Anal., 49, 1020-1038 (2005) · Zbl 1429.62279
[9] Lachos, V. H.; Bandyopadhyay, D.; Dey, D. K., Linear and nonlinear mixed-effects models for censored HIV viral loads using normal/independent distributions, Biometrics, 67, 1594-1604 (2011) · Zbl 1274.62806
[10] Lange, K.; Sinsheimer, J. S., Normal/independent distributions and their applications in robust regression, J. Comput. Graph. Stat., 2, 175-198 (1993)
[11] Lee, S. Y.; Xu, L., Influence analyses of nonlinear mixed-effects models, Comput. Stat. Data Anal., 45, 321-341 (2004) · Zbl 1429.62280
[12] Lindstrom, M. J.; Bates, D. M., Nonlinear mixed effects models for repeated measures data, Biometrics, 46, 673-687 (1990)
[13] Louis, T. A., Finding the observed information matrix when using the em algorithm, J. R. Stat. Soc B (Methodol.), 44, 226-233 (1982) · Zbl 0488.62018
[14] Lucas, A., Robustness of the student-t based m-estimator, Commun. Stat. - Theory Methods, 26, 1165-1182 (1997) · Zbl 0920.62041
[15] Matos, L. A.; Prates, M. O.; Chen, M. H.; Lachos, V. H., Likelihood-based inference for mixed-effects models with censored response using the multivariate-t distribution, Stat. Sin., 23, 1323-1342 (2013) · Zbl 1534.62143
[16] Meza, C.; Osorio, F.; De la Cruz, R., Estimation in nonlinear mixed-effects models using heavy-tailed distributions, Stat. Comput., 22, 121-139 (2012) · Zbl 1322.62030
[17] Osorio, F.; Paula, G. A.; Galea, M., Assessment of local influence in elliptical linear models with longitudinal structure, Comput. Stat. Data Anal., 51, 4354-4368 (2007) · Zbl 1162.62367
[18] Paula, G. A.; Medeiros, M.; Vilca-Labra, F. E., Influence diagnostics for linear models with first-order autoregressive elliptical errors, Stat. Probab. Lett., 79, 339-346 (2009) · Zbl 1155.62052
[19] Pinheiro, J. C.; Bates, D. M., Mixed-Effects Models in S and S-Plus (2000), Springer · Zbl 0953.62065
[20] R Core Team, R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing, Vienna, Austria, 2014. Available at http://www.R-project.org/.
[21] Russo, C. M.; Aoki, R.; Paula, G. A., Assessment of variance components in nonlinear mixed-effects elliptical models, TEST (Madrid), 21, 519-545 (2012) · Zbl 1284.62134
[22] Russo, C. M.; Paula, G. A.; Aoki, R., Influence diagnostics in nonlinear mixed-effects elliptical models, Comput. Stat. Data Anal., 53, 4143-4156 (2009) · Zbl 1417.62327
[23] Savalli, C.; Paula, G. A.; Cysneiros, F. J.A., Assessment of variance components in elliptical linear mixed models, Stat. Modell., 6, 59-76 (2006) · Zbl 07257125
[24] Schumacher, F. L.; Dey, D. K.; Lachos, V. H., Approximate inferences for nonlinear mixed effects models with scale mixtures of skew-normal distributions, J. Stat. Theory Pract., 15, 1-26 (2021) · Zbl 1477.62319 · doi:10.1007/s42519-021-00172-5
[25] Tan, M.; Tian, G. L.; Fang, H. B., An efficient MCEM algorithm for fitting generalized linear mixed models for correlated binary data, J. Stat. Comput. Simul., 77, 929-943 (2007) · Zbl 1131.62065
[26] Verbeke, G.; Molenberghs, G., Linear Mixed Models for Longitudinal Data (2000), Springer · Zbl 0956.62055
[27] Walker, S., An EM algorithm for nonlinear random effects models, Biometrics, 52, 934-944 (1996) · Zbl 0868.62058
[28] Wei, G. C.G.; Tanner, M. A., A monte carlo implementation of the em algorithm and the poor man’s data augmentation algorithm, J. Am. Stat. Assoc., 85, 699-704 (1990)
[29] Wolfinger, R., Laplace’s approximation for nonlinear mixed models, Biometrika, 80, 791-795 (1993) · Zbl 0800.62351
[30] Wu, L., Exact and approximate inferences for nonlinear mixed-effects models with missing covariates, J. Am. Stat. Assoc., 99, 700-709 (2004) · Zbl 1117.62446
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