PBPK and Population Modeling Seamlessly Linked to Clinical Trial Simulation in an Open-Source Software Platform

该项目的目标是为生物等效性（BE）开发一个全面的开源软件平台。

The goal of this project is to develop a comprehensive, open-source software platform for bioequivalence (BE) study design. Components of the platform will implement a framework for population modeling based on physiological- ly-based pharmacokinetic (PBPK) models integrated with a trial simulator. The framework will consist of: 1) Model structures appropriate for a wide range of compounds and routes of administration; 2) Diverse and robust parametric and nonparametric methods for population modeling to update prior PBPK model parameter value distributions with individual data; 3) Simulation of a variety of BE trial designs with standard and novel optimal sampling strategies; 4) Software implementation of an integrated workflow. To build the framework, the project will focus on the following aims that align with the workflow. Aim 1: Add inhalational and dermal penetration routes to existing intravenous and oral routes in the Open Systems Pharmacology (OSP) Suite and an in vitro-in vivo formulation/dissolution correlation module. Aim 2: Integrate a variety of parametric and nonparametric population algorithms based in part upon the Pmet- rics package for R to update PBPK models when individual data are available. Aim 3: Develop a BE trial simulator by re- purposing existing capabilities within OSP and Pmetrics to simulate output for a wide range of BE trial designs, incorpo- rating standard and novel optimal sampling algorithms and existing R modules for sample size calculations and analysis of predicted trial outcomes. Aim 4: Implement a seamlessly integrated software workflow of model building, updating and simulating, hosted on the OSP platform, and using state of the art engineering to create a freely available, open- source product.