A bayesian dose-finding design for drug combination trials with delayed toxicities

Abstract

We propose a Bayesian adaptive dose-finding design for drug combina- tion trials with delayed toxicity. We model the dose-toxicity relationship using the Finney model, a model widely used in drug-drug interaction studies. The intu- itive interpretations of the Finney model facilitate incorporating the available prior dose-toxicity information from single-agent trials into combination trials through prior elicitation. We treat unobserved delayed toxicity outcomes as missing data and handle them using Bayesian data augmentation. We conduct extensive sim- ulation studies to examine the operating characteristics of the proposed method under various practical scenarios. Results show that the proposed design is safe and able to select the target dose combinations with high probabilities. © 2013 International Society for Bayesian Analysis.