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arXiv · 2404.11406

Pharmacokinetic Measurements in Dose Finding Model Guided by Escalation with Overdose Control

Arnab Kumar Maity·Satrajit Roy Chowdhury·Ray Li·Lada Markovtsova·Roberto Bugarini
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Abstract

Oncology drug development starts with a dose escalation phase to find the maximal tolerable dose (MTD). Dose limiting toxicity (DLT) is the primary endpoint for dose escalation phase. Traditionally, model-based dose escalation trial designs recommend a dose for escalation based on an assumed dose-DLT relationship. Pharmacokinetic (PK) data are often available but are currently only used by clinical teams in a subjective manner to aid decision making. Formal incorporation of PK data in dose-escalation models can make the decision process more efficient and lead to an increase in precision. In this talk we present a Bayesian joint modeling framework for incorporating PK data in Oncology dose escalation trials. This framework explores the dose-PK and PK-DLT relationships jointly for better model informed dose escalation decisions. Utility of the proposed model is demonstrated through a real-life case study along with simulation.

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Arnab Kumar Maity, Satrajit Roy Chowdhury, Ray Li, Lada Markovtsova, Roberto Bugarini. 2024-04-17. Pharmacokinetic Measurements in Dose Finding Model Guided by Escalation with Overdose Control. https://arxiv.org/abs/2404.11406

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