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An Interactive MIDD Framework for Evaluation and Comparison of PBPK Model Performance

Modeling and simulation are becoming indispensable elements in drug development. Mechanistic modeling is susceptible to impacting several drug development and regulatory decisions through extrapolations beyond clinically researched scenarios by using its capacity to incorporate diverse data to provide a detailed and comprehensive understanding of a physiological and biological system. Physiologically based pharmacokinetic (PBPK) modeling is the fastest-growing Model-informed drug development subfield, and regulatory authorities currently demand or advocate its usage for specific applications. Shiny is based on the open-source software R, which is widely used in the statistics and data science communities, including finance, medicine, and pharmaceuticals. Shiny conveys complex models to non-technical audiences via interactive graphics and sensitivity analysis. The Shiny R package is a crucial development that opens up PBPK models developed in R to a wider audience. This project's main goal is to create a framework and, a user-friendly tool for PBPK model evaluations and performance comparisons during model development, customized for the Open System Pharmacology Suite. To develop the PBPK framework, a PBPK model was retrieved from the open system pharmacology repository on GitHub, and based on the model and parameter identification inputs, the shiny framework was coded in R.Principal diagnostic techniques such as visual predictive checks to match and correlate model-simulated concentration-time profiles with clinical data, the goodness of fit (GOF) analysis (e.g., residuals over time, residuals against predictions, etc.), and extensive precision and bias measures were used to assess and validate the performance robustness of the model. Various quantitative metrics such as root mean square error, mean absolute error, and concordance correlation coefficient were used to assess and evaluate the model performance. The PBPK-QSP shiny framework was developed, allowing users to do the model evaluation with minimal effort. Using frameworks such as Shiny can expedite and automate the PBPK procedure, saving a significant amount of money and time in the evaluation of model performance.

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-487963
Date January 2022
CreatorsGaramani, Dylan
PublisherUppsala universitet, Institutionen för farmaci
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeStudent thesis, info:eu-repo/semantics/bachelorThesis, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess

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