s Integration of Pharmacogenomics and Pharmacometrics to Support Drug Development, Regulatory and Therapeutic Decisions

Pharmacogenomics as a science aims at individualizing the treatment based on the genetic makeup, to mitigate the chances of adverse drug events and/or to maximize the efficacy in a sub-population. Pharmacometrics is the science of quantifying disease, drug and trial characteristics with the goal to influence key drug development, regulatory and therapeutic decisions. Pharmacometric analysis as a tool has revolutionized the way dose/dosing regimens or clinical trials are being designed prospectively to answer key drug development questions. Exposure-response relationships established in adult patients have made it possible to make dosing recommendations in special populations (pediatrics and organ function impaired patients), leading to approval of doses/dosing regimen that were not studied in registration trials. Until now, pharmacogenomics is predominantly used retrospectively to understand the between subject variability of drug’s pharmacokinetic and pharmacodynamic properties. In this article we discuss how the advent of advanced pharmacometric tools can leverage prior pharmacogenomic information to prospectively design late stage clinical trials. In addition, selected case studies are presented that demonstrates the application of modeling and simulation in supporting dose selection in patients with allelic variants across different therapeutic areas.