Symbolic neural networks for automated covariate modeling in a mixed-effects framework
(2024) 12th IFAC Symposium on Biological and Medical Systems (BMS) In IFAC-PapersOnLine- Abstract
- Mixed-effects models are used to describe the inter-patient variability in drugs. Modeling of these variabilities include both fixed and random effects. Fixed effects relate covariates such as age and weight to compartment volumes and clearances, whereas random effects account for unexplained variability. Traditionally, the development of fixed effects models is an inefficient process where covariate relationships are evaluated in a step-wise manner. In this study, we implemented a symbolic neural network (SNN) to automate the development of a fixed effects model and used it to develop a population pharmacokinetic model for propofol. With the SNN, we can find covariate relationships that are traditionally not evaluated. Then, we apply... (More)
- Mixed-effects models are used to describe the inter-patient variability in drugs. Modeling of these variabilities include both fixed and random effects. Fixed effects relate covariates such as age and weight to compartment volumes and clearances, whereas random effects account for unexplained variability. Traditionally, the development of fixed effects models is an inefficient process where covariate relationships are evaluated in a step-wise manner. In this study, we implemented a symbolic neural network (SNN) to automate the development of a fixed effects model and used it to develop a population pharmacokinetic model for propofol. With the SNN, we can find covariate relationships that are traditionally not evaluated. Then, we apply random effects and estimate parameters in the standard mixed-effects modeling framework. Our final model shows comparable predictive performance to a published model for propofol, despite having fewer covariates and model parameters. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/28d9cd55-798f-4f21-a111-7bddacb03bad
- author
- Sundell, Jesper LU ; Wahlquist, Ylva LU and Soltesz, Kristian LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- in press
- subject
- in
- IFAC-PapersOnLine
- publisher
- IFAC Secretariat
- conference name
- 12th IFAC Symposium on Biological and Medical Systems (BMS)
- conference location
- Villingen-Schwenningen, Germany
- conference dates
- 2024-09-11 - 2024-09-13
- ISSN
- 2405-8963
- project
- Learning pharmacometric model structures from data
- language
- English
- LU publication?
- yes
- additional info
- © 2024.. This work has been accepted to IFAC for publication under a Creative Commons Licence CC-BY-NC-ND
- id
- 28d9cd55-798f-4f21-a111-7bddacb03bad
- date added to LUP
- 2024-04-12 11:50:57
- date last changed
- 2024-04-16 11:16:21
@article{28d9cd55-798f-4f21-a111-7bddacb03bad, abstract = {{Mixed-effects models are used to describe the inter-patient variability in drugs. Modeling of these variabilities include both fixed and random effects. Fixed effects relate covariates such as age and weight to compartment volumes and clearances, whereas random effects account for unexplained variability. Traditionally, the development of fixed effects models is an inefficient process where covariate relationships are evaluated in a step-wise manner. In this study, we implemented a symbolic neural network (SNN) to automate the development of a fixed effects model and used it to develop a population pharmacokinetic model for propofol. With the SNN, we can find covariate relationships that are traditionally not evaluated. Then, we apply random effects and estimate parameters in the standard mixed-effects modeling framework. Our final model shows comparable predictive performance to a published model for propofol, despite having fewer covariates and model parameters.}}, author = {{Sundell, Jesper and Wahlquist, Ylva and Soltesz, Kristian}}, issn = {{2405-8963}}, language = {{eng}}, publisher = {{IFAC Secretariat}}, series = {{IFAC-PapersOnLine}}, title = {{Symbolic neural networks for automated covariate modeling in a mixed-effects framework}}, url = {{https://lup.lub.lu.se/search/files/180133628/covariate_model_random_effects.pdf}}, year = {{2024}}, }