2023 FDA Science Forum
Statistical Challenges in Evaluating Safety of Response-guided Dose-titrated Drugs
- Authors:
- Center:
-
Contributing OfficeCenter for Drug Evaluation and Research
Abstract
In some therapeutic settings, drug dose is titrated to optimize the benefit-risk tradeoffs of treatment. Response-guided titration is based on individual patient’s therapeutic response, as measured by an objective clinical parameter of interest. However, safety assessment of response-guided dose-titrated drugs in clinical trials can be complicated, due to: i) the inter- and intra-individual variability in exposure, and ii) potential for confounding if the adverse event of interest is associated with the clinical marker used to guide the dose-titration regimen. In this study, we discuss statistical challenges in evaluating safety of response-guided dose-titrated drugs in clinical trials and illustrate the use of a sensitivity analysis to examine the magnitude of potential confounding.
