Bayesian Estimation in NONMEM

Overview

Journal CPT Pharmacometrics Syst Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2023 Nov 29

PMID 38017712

Authors

Curtis K Johnston

Timothy Waterhouse

Matthew Wiens

John Mondick

Jonathan French

William R Gillespie

Affiliations

Soon will be listed here.

Abstract

Bayesian estimation is a powerful but underutilized tool for answering drug development questions. In this tutorial, the principles of Bayesian model development, assessment, and prior selection will be outlined. An example pharmacokinetic (PK) model will be used to demonstrate the implementation of Bayesian modeling using the nonlinear mixed-effects modeling software NONMEM.

Citing Articles

Bayesian Population Pharmacokinetic Modeling of Ondansetron for Neonatal Opioid Withdrawal Syndrome.

Lam K, Mondick J, Peltz G, Wu M, Kraft W Clin Transl Sci. 2025; 18(2):e70147.

PMID: 39930952 PMC: 11811511. DOI: 10.1111/cts.70147.

Implementing a Bayesian approach using Stan with Torsten: Population pharmacokinetics analysis of somatrogon.

Wang Y, Pei X, Niu T, Korth-Bradley J, Fostvedt L CPT Pharmacometrics Syst Pharmacol. 2024; 14(2):351-364.

PMID: 39652456 PMC: 11812939. DOI: 10.1002/psp4.13279.

Semi-mechanistic population pharmacokinetic modeling of DZIF-10c, a neutralizing antibody against SARS-Cov-2: predicting systemic and lung exposure following inhaled and intravenous administration.

Kurup S, Velez de Mendizabal N, Becker S, Bolella E, De Sousa D, Fatkenheuer G J Pharmacokinet Pharmacodyn. 2024; 52(1):3.

PMID: 39636474 PMC: 11621205. DOI: 10.1007/s10928-024-09947-2.

Within-chain parallelization-Giving Stan Jet Fuel for population modeling in pharmacometrics.

Davis C, Vaddady P CPT Pharmacometrics Syst Pharmacol. 2024; 14(1):52-67.

PMID: 39465998 PMC: 11706427. DOI: 10.1002/psp4.13238.

Bayesian estimation in NONMEM.

Johnston C, Waterhouse T, Wiens M, Mondick J, French J, Gillespie W CPT Pharmacometrics Syst Pharmacol. 2023; 13(2):192-207.

PMID: 38017712 PMC: 10864934. DOI: 10.1002/psp4.13088.

References

Wang W, Hallow K, James D . A Tutorial on RxODE: Simulating Differential Equation Pharmacometric Models in R. CPT Pharmacometrics Syst Pharmacol. 2016; 5(1):3-10. PMC: 4728294. DOI: 10.1002/psp4.12052. View

Aoki Y, Nordgren R, Hooker A . Preconditioning of Nonlinear Mixed Effects Models for Stabilisation of Variance-Covariance Matrix Computations. AAPS J. 2016; 18(2):505-18. PMC: 4779107. DOI: 10.1208/s12248-016-9866-5. View

Knebel W, Gastonguay M, Malhotra B, El-Tahtawy A, Jen F, Gandelman K . Population pharmacokinetics of atorvastatin and its active metabolites in children and adolescents with heterozygous familial hypercholesterolemia: selective use of informative prior distributions from adults. J Clin Pharmacol. 2013; 53(5):505-16. DOI: 10.1002/jcph.66. View

Gisleskog P, Karlsson M, Beal S . Use of prior information to stabilize a population data analysis. J Pharmacokinet Pharmacodyn. 2003; 29(5-6):473-505. DOI: 10.1023/a:1022972420004. View

Broeker A, Wicha S . Assessing parameter uncertainty in small-n pharmacometric analyses: value of the log-likelihood profiling-based sampling importance resampling (LLP-SIR) technique. J Pharmacokinet Pharmacodyn. 2020; 47(3):219-228. PMC: 7289778. DOI: 10.1007/s10928-020-09682-4. View

Chan Kwong A, Calvier E, Fabre D, Gattacceca F, Khier S . Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine. J Pharmacokinet Pharmacodyn. 2020; 47(5):431-446. PMC: 7520416. DOI: 10.1007/s10928-020-09695-z. View

Guede D, Reigner B, Vandenhende F, Derks M, Beyer U, Jordan P . Bayesian adaptive designs in single ascending dose trials in healthy volunteers. Br J Clin Pharmacol. 2014; 78(2):393-400. PMC: 4137831. DOI: 10.1111/bcp.12344. View

Carpenter B, Gelman A, Hoffman M, Lee D, Goodrich B, Betancourt M . Stan: A Probabilistic Programming Language. J Stat Softw. 2022; 76. PMC: 9788645. DOI: 10.18637/jss.v076.i01. View

Qiu J, Martinez M, Tiwari R . Evaluating In Vivo-In Vitro Correlation Using a Bayesian Approach. AAPS J. 2016; 18(3):619-34. PMC: 5256600. DOI: 10.1208/s12248-016-9880-7. View

10.

Riglet F, Mentre F, Veyrat-Follet C, Bertrand J . Bayesian Individual Dynamic Predictions with Uncertainty of Longitudinal Biomarkers and Risks of Survival Events in a Joint Modelling Framework: a Comparison Between Stan, Monolix, and NONMEM. AAPS J. 2020; 22(2):50. DOI: 10.1208/s12248-019-0388-9. View

11.

Langdon G, Gueorguieva I, Aarons L, Karlsson M . Linking preclinical and clinical whole-body physiologically based pharmacokinetic models with prior distributions in NONMEM. Eur J Clin Pharmacol. 2007; 63(5):485-98. DOI: 10.1007/s00228-007-0264-x. View

12.

Johnston C, Waterhouse T, Wiens M, Mondick J, French J, Gillespie W . Bayesian estimation in NONMEM. CPT Pharmacometrics Syst Pharmacol. 2023; 13(2):192-207. PMC: 10864934. DOI: 10.1002/psp4.13088. View

13.

Nguyen T, Mouksassi M, Holford N, Al-Huniti N, Freedman I, Hooker A . Model Evaluation of Continuous Data Pharmacometric Models: Metrics and Graphics. CPT Pharmacometrics Syst Pharmacol. 2016; 6(2):87-109. PMC: 5321813. DOI: 10.1002/psp4.12161. View

14.

Bauer R . NONMEM Tutorial Part II: Estimation Methods and Advanced Examples. CPT Pharmacometrics Syst Pharmacol. 2019; 8(8):538-556. PMC: 6709422. DOI: 10.1002/psp4.12422. View

15.

Cella M, Gorter de Vries F, Burger D, Danhof M, Pasqua O . A model-based approach to dose selection in early pediatric development. Clin Pharmacol Ther. 2010; 87(3):294-302. DOI: 10.1038/clpt.2009.234. View

16.

Krishnan S, Friberg L . Bayesian forecasting of tumor size metrics and overall survival. CPT Pharmacometrics Syst Pharmacol. 2022; 11(12):1604-1613. PMC: 9755925. DOI: 10.1002/psp4.12869. View

17.

Wade J, Kelman A, Howie C, Whiting B . Effect of misspecification of the absorption process on subsequent parameter estimation in population analysis. J Pharmacokinet Biopharm. 1993; 21(2):209-22. DOI: 10.1007/BF01059771. View

18.

Bauer R, Guzy S, Ng C . A survey of population analysis methods and software for complex pharmacokinetic and pharmacodynamic models with examples. AAPS J. 2007; 9(1):E60-83. PMC: 2751305. DOI: 10.1208/aapsj0901007. View

19.

Bauer R . NONMEM Tutorial Part I: Description of Commands and Options, With Simple Examples of Population Analysis. CPT Pharmacometrics Syst Pharmacol. 2019; 8(8):525-537. PMC: 6709426. DOI: 10.1002/psp4.12404. View

20.

Wang Y . Derivation of various NONMEM estimation methods. J Pharmacokinet Pharmacodyn. 2007; 34(5):575-93. DOI: 10.1007/s10928-007-9060-6. View