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

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24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)703-722
Number of pages20
JournalBayesian Analysis
Volume8
Issue number3
DOIs
StatePublished - 2013

Keywords

  • Adaptive design
  • Combining drugs
  • Late-onset toxicity
  • Maximum tolerated dose
  • Missing data
  • Phase I trial

ASJC Scopus subject areas

  • Statistics and Probability
  • Applied Mathematics

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