Simone Cassani: No financial relationships to disclose
Objectives: Many questions throughout the drug development stages can be answered using simulations of a modified pharmacometric model. NMsim automates the simulation of Nonmem models and provides a concise interface for modifying the control stream integrated into the simulation command. We aim to showcase these features through some examples that are highly relevant in pharmacometrics.
Methods: A standard popPK model estimated on a publicly available data set was used. The NMsim R package was shown to address questions like the following with simple R code: • How will the concentration-time profile be affected if switching formulation and reducing absorption rate by a range of fold-values? • How will a dose delay of different amounts of time affect the predicted concentration-time profile? • What is the expected concentration-time profile in patients with a certain DDI effect on clearance and bioavailability? • How does log-likelihood depend on different assumed values of absorption rate?
The seamless workflow of NMsim allows the codes to be readily applicable to most Nonmem popPK models.
Results: NMsim provides a flexible and concise interface for modifying control streams prior to simulation or estimation. Model-agnostic code examples were provided and results shown illustrated how simply a model-based approach to some questions common to drug development can be performed.
Conclusions: Although the examples provided in this work address selected questions related to certain parameters of a popPK model, we hope to inspire the audience to see that these features provide a powerful tool to easily explore the implications of various properties of a pharmacometric model. All software, code, and data used are freely available for the audience to modify to their own needs.
Citations: [1] 2024. NMsim: An R package that can simulate Nonmem models. https://philipdelff.github.io/NMsim [2] 2024. NMsim: Seamless ‘Nonmem’ Simulation Platform. https://cran.r-project.org/web/packages/NMsim
