Impact of using time-averaged exposure metrics on binary endpoints in exposure-response analyses.

ABSTRACT: Exposure-response (ER) analyses are routinely performed as part of model-informed drug development to evaluate the risk-to-benefit ratio for dose selection, justification, and confirmation. For logistic regression analyses with binary endpoints, several exposure metrics are investigated, based on pharmacological plausibility, including time-averaged concentration to event (C_avTE). C_avTE is informative because it accounts for dose interruptions, modifications, and reductions and is therefore often compared against ER relationships identified using steady-state exposures. However, its derivation requires consideration in a logistic regression framework for time-invariant ER analysis because it has the potential to introduce bias. This study evaluated different approache

SUBMITTER: Lin YW 

PROVIDER: S-EPMC11780246 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature