Bayesian dose-finding in phase I/II clinical trials using toxicity and efficacy odds ratios

Biometrics. 2006 Sep;62(3):777-84. doi: 10.1111/j.1541-0420.2006.00534.x.


A Bayesian adaptive design is proposed for dose-finding in phase I/II clinical trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new treatment. Without specifying any parametric functional form for the drug dose-response curve, we jointly model the bivariate binary data to account for the correlation between toxicity and efficacy. After observing all the responses of each cohort of patients, the dosage for the next cohort is escalated, deescalated, or unchanged according to the proposed odds ratio criteria constructed from the posterior toxicity and efficacy probabilities. A novel class of prior distributions is proposed through logit transformations which implicitly imposes a monotonic constraint on dose toxicity probabilities and correlates the probabilities of the bivariate outcomes. We conduct simulation studies to evaluate the operating characteristics of the proposed method. Under various scenarios, the new Bayesian design based on the toxicity-efficacy odds ratio trade-offs exhibits good properties and treats most patients at the desirable dose levels. The method is illustrated with a real trial design for a breast medical oncology study.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bayes Theorem*
  • Biometry
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / secondary
  • Clinical Trials, Phase I as Topic / statistics & numerical data*
  • Clinical Trials, Phase II as Topic / statistics & numerical data*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Likelihood Functions
  • Logistic Models
  • Models, Statistical
  • Odds Ratio
  • Toxicology / statistics & numerical data