Monika Berezowska1, Isaac Hayden1, Andrew Brandon2, Arsenii Zats1,4, Mehzabin Patel1, Tadao Tamura1,4, Shelby Barnett2, Kayode Ogungbenro3, Gareth Veal2, Alaric Taylor-roffey, Jugal Suthar1,4
1Vesynta, 2Translational and Clinical Research Institute, Newcastle University Centre for Cancer, 3Division of Pharmacy & Optometry, School of Health Sciences, University of Manchester, 4UCL
Background: Current drug dosing strategies, based on fixed dosing or a single scaling factor (e.g. body surface area), often fail to consider between patient variability, leading to suboptimal outcomes. Model-Informed Precision Dosing (MIPD), supported by population pharmacokinetic (popPK) models, aims to personalise therapy by accounting for demographic characteristics, organ function, and drug-specific pharmacokinetic properties. Despite its potential, MIPD and specifically, PK-informed precision dosing, remains underutilised in clinical practice due to challenges in model development, validation, and integration with clinical workflows. Objectives: This review [1] aims to deliver detailed recommendations for integrating popPK models into MIPD software to optimise therapeutic outcomes. The focus is on addressing key implementation barriers and providing a comprehensive, end-to-end framework for incorporating MIPD tools into healthcare systems, bringing us a step closer to making dose individualisation standard-of-care. Methods: A comprehensive literature review was conducted, focusing on the best practices for the development and validation of popPK models. The manuscript also assessed the guidelines from regulatory and advisory bodies to ensure model quality and robustness when incorporated into MIPD software. Additionally, technical requirements for integrating MIPD tools into clinical workflows and electronic health records (EHRs) were explored. The potential use of machine learning was evaluated for its potential in enhancing popPK model accuracy, dose recommendations and applicability in healthcare settings. Results: We identified fundamental process steps in developing and integrating popPK models into MIPD software, and provided best practice recommendations for each stage: ?Data considerations: highlighted the importance of standardised data collection, formatting, exploration, and cleaning to ensure regulatory compliance, reproducibility, and accuracy. ?Model building: summarised the process of planning, selecting appropriate software, and developing nonlinear mixed-effects models, including structural, statistical, and covariate models, along with validation techniques. ?Adaptation of literature models: Provided guidelines for sourcing, transcribing, verifying, and evaluating published models to ensure they are fit for clinical application. ?Application in healthcare: discussed strategies for model selection, a priori and a posteriori predictions, uncertainty quantification, treatment regimen optimisation, and continuous integration of patient data. ?Software integration: emphasised the need for interoperability with electronic health records, adherence to regulatory standards, and quality control measures for clinical deployment. Conclusion: This review takes a multifaceted consideration to integrate popPK models into precision dosing software, with recommended approaches consolidated into standardised guidelines covering the entire workflow from data handling to clinical application. Enhancing interoperability with electronic health records and fostering communication among stakeholders are crucial for the widespread adoption of MIPD tools. By establishing best practices and clear implementation pathways, we can leverage the clinical utility of MIPD for dose optimisation and ultimately enhance patient care.
[1] Berezowska M, Hayden IS, Brandon AM, et al. Recommended approaches for integration of population pharmacokinetic modelling with precision dosing in clinical practice. Br J Clin Pharmacol. 2024; 1-16. doi:10.1111/bcp.16335
Reference: PAGE 33 (2025) Abstr 11697 [www.page-meeting.org/?abstract=11697]
Poster: Methodology - Other topics