Dose/exposure-response modeling in dose titration trials: Overcoming the titration paradox.

ABSTRACT: Response-based dose individualization or dose titration is a powerful approach to achieve precision dosing. Yet, titration as an individualization strategy is underused in drug development and therefore not reflected in labeling, possibly partly because of the data analysis challenges associated with assessing dose/exposure-response under dose titration, where there is an inherent risk of selection bias because poor responders would get high doses, whereas good responders would get low doses. In a recent article, this issue of selection bias was termed the "titration paradox." In this study, we demonstrate by means of simulation that the titration paradox may be overcome if longitudinal data from dose titration trials is analyzed using a population approach that accounts for the fact that

SUBMITTER: Kristensen NR 

PROVIDER: S-EPMC9755917 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature