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Project

Master protocol methodological pharmacometrics research

Background and rationale: Pharmacometrics (mixed effects) modelling and simulation is increasingly used to characterise, understand, and predict the dose-exposure-response relationships of drugs. Consequently, model-informed drug development (MIDD) has become an established business value, facilitating a cost-efficient drug development process. Population-level dosing is the preferred dosage strategy, followed by group-level dosing (e.g., adjusting for body weight, or interacting drugs) when one dose does not fit all real-word patients. If not possible to achieve safe and effective group-level dosing, individual-level dosing is the sole remaining option. Individual-level dosing can be done relying on individual patient data gathered through therapeutic drug monitoring (TDM), biomarker monitoring, response monitoring, etc. Bayesian forecasting model-informed precision dosing (MIPD) software tools have been proposed for guiding individual-level dosing. 

The pharmacometrics toolkit involves theoretical, mathematical/statistical modelling and simulation constructs to facilitate MIDD and MIPD. While pharmacometrics method development staggers and the toolkit may seem saturated, not all pharmacometrics research questions have been answered. 

Objective: To perform exploratory methodological pharmacometrics research, aiming to expand the pharmacometrics toolkit with model building/evaluation/simulation options, thereby providing a basis for continued growth of pharmacometrics modelling and simulation approaches to address currently unanswered questions regarding safety and efficacy, dosage strategy, and study design and interpretation. 

Research hypothesis: A flexible toolkit for developing pharmacometrics models with adequate descriptive and predictive performance will facilitate more efficient drug dosing. 

Trial design: This master protocol spans a continuously changing battery of exploratory, methodological (application-oriented) pharmacometrics studies. The protocol serves as a common ‘screening platform’ for pharmacometrics methodology. Since pharmacometrics is data-driven (top-down), the availability of a large, heterogeneous library of clinical and nonclinical data is a basic requirement to facilitate the methodological research. Therefore, data are a means, whilst method development is the goal. Data will be retrospectively collected from other studies. 

Study procedures: This is an exploratory, monocentre study at KU Leuven.

Data handling: Data will be coded prior to sharing for exploratory methodological pharmacometrics analyses. Data files will be stored in the KU Leuven’s secure servers with a copy on a local computer.

Date:1 Oct 2021 →  Today
Keywords:Pharmacometrics
Disciplines:Clinical pharmacy