r-vis - cefic-lricefic-lri.org/wp-content/uploads/2019/12/9.-george...2019/12/09 · aims and...

George Loizou, Alex Hogg and Kevin McNally

HSE Science and Research Centre

R-Vis

An Open Access PBPK Modelling Platform

Aims and Objectives

• Further develop R-Vis, a prototype application for the analysis of structure and performance of physiologically based pharmacokinetic

(PBPK), and other models, written in the free, open source syntax, R

• Provide a common, transparent and independently auditable, free-to-use platform

• Provide a labour-saving application that also shifts emphasis away from mathematics and programming to mechanistic toxicology

LRI – R-Vis: An Open Access PBPK Modelling Platform

A PBPK Model

R Syntax Viewed in RStudio


Home Page

Import Model

LRI – – R-Vis: An Open Access PBPK Modelling Platform

Plotter

Select Parameters and Outputs


Parameters (constants)• Anatomical

• Physiological

• Metabolic

• Physicochemical

Outputs (calculated values)• Rates of uptake

• Dermal, oral, inhalation

• Concentrations:

• Venous, arterial, plasma, red blood cells

• Organs and tissues

• Urinary excretion

• exhalation

Plotter


Plotter

Plot Output


Plotter

Multiple Outputs


Evidence

Importing Data


Evidence

Tweaking Parameters


Evidence

Tweaking Parameters Using Ranges


Good Modelling Practice

Model Structure and Biological Plausibility

22/11/2019LRI – PRESENTATION TITLE

Evaluating Variability and Uncertainty


Morris Test – Elementary Parameter Screening

Sensitivity Analysis


Extended Fourier Amplitude Sensitivity Test - eFAST

Global Sensitivity Analysis


LRI – PRESENTATION TITLE

Parameter configurations available to all modules

Shared State


Markov Chain Monte Carlo Sampling

Parameter Estimation – Reverse Dosimetry


Bayesian Inference – Prior Knowledge

LRI – PRESENTATION TITLE

Probabilistic Modelling

Monte Carlo Sampling


Incorporating Inter-Individual Differences


Incorporating Inter-Individual Differences: Organs/Tissue Distributions



Generating Virtual Humans

Settings – User Preferences

Appearance


Acknowledgements

• Alex Hogg – Programmer

• Kevin McNally – Statistical/Mathematical Modeller

• Cefic-LRI


-

Tel +32 2 436 9415 – [email protected]

www. cefic-lri.org

-

European Chemical Industry Council (Cefic)

Rue Belliard 40

1040 Brussels

Tel +32 2 436 93 00

www.cefic-lri.org

LRI SECRETARIAT

THE VOICE OF THE CHEMICAL INDUSTRY IN EUROPE

r-vis - cefic-lricefic-lri.org/wp-content/uploads/2019/12/9.-george...2019/12/09 · aims and...

Documents