Andreas Lindauer, Nicolas Luyckx, Erno van Schaick, Emilie Hénin, Stéphanie Blaizot, Sajid Ali Shah, Pierre-Alexandre Noguine, Christian Laveille
Calvagone SAS, France
Introduction: Campsis (www.campsis.org) is a suite of R packages designed to facilitate the setup and execution of PK/PD simulations in a user-friendly way. The two core packages, campsismod[1] and campsis[2], are open-source and freely available on CRAN and GitHub since 2022. Campsismod is dedicated to the manipulation of the pharmacometric model, while campsis executes the simulation using rxode2 or mrgsolve.
e-Campsis[3] is an online application that assists users in setting up and running simulations, visualizing and post-processing results, and exploring scenarios in an intuitive and interactive way. The complete simulation code can be downloaded and reproduced or further adapted offline in R. This mini-tutorial provides an overview of the campsis building blocks and their functionality.
Methods: The tutorial begins with an introduction to the two main packages, campsis and campsismod, and their interaction. Campsimod contains functions for loading, editing, and expanding a model and its parameters in a scripted way. Using a model from the library, the structure of the model code (parameters, differential equations, initial conditions, etc.) will be demonstrated. Key functions like add(), replace(), and delete() will be introduced to highlight the possibilities of adapting the model code in a scripted way to preserve reproducibility and allow automation. Thanks to campsismod, it is straightforward to combine multiple models into a single model code for PK/PD simulations or simulations of multiple compounds/formulations, avoiding manual editing and copy-pasting.
Next, the focus shifts to campsis, showcasing the functions used to define the dosing regimen, observation schedule, and covariates in treatment arms. Special functions for time-varying covariates, inter-occasion variability, bootstrapping, and dose adaptation will also be briefly discussed. The convenience of using the scenario() function to explore how changes to parameter values or other model components affect the results will be demonstrated.
The key function simulate() will be presented, which handles the actual (parallel) execution of the simulation using the R packages rxode2[4] or mrgsolve[5] based on the user’s choice.
In the third part of the tutorial, the freely accessible web application e-Campsis will be presented. e-Campsis is a graphical user interface that facilitates the configuration of models, setting up of a study design, exploration of scenarios, and visualization of results while running campsis functions in the background. This allows individuals knowledgeable in M&S but not versed in R-coding to run population PK/PD simulations themselves. Hands-on pharmacometricians in contrast will find it useful to have a visual tool available that allows adapting and exploring simulations in real-time in team meetings and running ad-hoc scenarios on the spot. Moreover, the R code that is automatically generated by e-Campsis can be downloaded and further adapted if desired.
Additional convenience features, like automatic translation of NONMEM models to campsis, post-processing of simulation results, generation of sensitivity analysis and forest plots, are available in a professional version of e-Campsis.
Results: As a result, the audience will gain insight into the inner workings of the campsis suite. After the tutorial they will be able to select a PK model from the library, understand the building blocks of the model code, set up a study design, and execute the simulation in e-Campsis. Those in the audience who are familiar with R can download the simulation code and will be able to understand its structure. The interested (hands-on) user will find the self-explanatory function names easy to remember and, with the help of the documentation, will quickly be able to make full use of campsis and campsismod to run even complex simulations themselves.
Conclusions: The campsis suite aims to be a robust tool for both hands-on pharmacometricians and non-coding experts. Its versatility allows it to manage complex simulation settings, such as response-triggered dose adaptation. For simpler, yet often more impactful simulations, e-Campsis is set to revolutionize the way simulations are used in communication. It moves away from the traditional approach of using pre-prepared static slides, and instead, promotes an interactive and highly educational method of conveying information. This shift not only enhances understanding but also ensures the message is effectively communicated.
References:
[1] https://cran.r-project.org/web/packages/campsismod/index.html
[2] https://cran.r-project.org/web/packages/campsis/index.html
[3] www.e-campsis.com
[4] https://github.com/nlmixr2/rxode2
[5] https://github.com/metrumresearchgroup/mrgsolve
Reference: PAGE 32 (2024) Abstr 10804 [www.page-meeting.org/?abstract=10804]
Poster: Methodology - New Modelling Approaches
PDF poster / presentation (click to open)
Video: Video (click to open)