Modeling Exposure-Driven Adverse Event Time Courses in Oncology Exemplified by Afatinib.

ABSTRACT: Models were developed to characterize the relationship between afatinib exposure and diarrhea and rash/acne adverse event (AE) trajectories, and their predictive ability was assessed. Based on pooled data from seven phase II/III clinical studies including 998 patients, mixed-effects models for ordered categorical data were applied to describe daily AE severity. Clinical trial simulation aided by trial execution models was used for internal and external model evaluation. The final exposure-safety model consisted of longitudinal logistic regression models with first-order Markov elements for both AEs. Drug exposure was included as daily area under the concentration-time curve (AUC), and drug effects on the AEs were correlated. Clinical trial simulation allowed adequate prediction of maximum

SUBMITTER: Niebecker R 

PROVIDER: S-EPMC6482278 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature