PK/PD translational modeling for dose selection in clinical trial design

Mentors:
Leads: Angelean Hendrix (Amadore Biosciences) and Mette Olufsen (Mathematics, NCSU)

Intellectual merit and significance:
Pharmaceutical development is a highly interdisciplinary process that requires sophisticated quantitative skills [1]. Regulatory agencies are increasingly requiring modeling and simulation of animal data to justify the safety and efficacy of compounds before human trials [2]. In this project, we take simulated animal data from 2 species and use mathematical and statistical methods to predict human exposures and responses in a First in Human trial.

Objectives:
Students will learn the basics of drug development and translational modeling methods. Students will use NonMem to construct necessary data sets, model 2 species of animal data, and apply allometric scaling to predict human exposure and efficacy.

Outcomes:
Pharmacomatricians with industry-specific skills are in high demand. This project will help expose students to a possible career in industry using their applied mathematics and statistical skills and expose them to the challenges of drug development.

References:
1. Mager D, Jusko W. Development of translational pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther. 2008 Jun;83:909-912.
2. Lave’ T, Caruso A, Parrot N, Walz A. Translational PK/PD modeling to increase probability of success in drug discovery and early development. Drug Discov Today Technol 2016;21-22:27-34.