Integration of Time‐Varying Pharmacometric Modeling With Cox Regression for Time‐to‐Event Analysis in NONMEM

Although time-varying Cox regression modeling approaches have been developed, exposure-response analyses for time-to-event (TTE) endpoints often rely on static exposure covariates and may overlook the real-world dosing variability and drug concentration fluctuations over time. To better characterize pharmacokinetic (PK) or pharmacodynamic (PD) effects on TTE endpoints, a methodology was proposed to integrate time-varying pharmacometric models with Cox regression in the non-linear mixed effects m