A Bayesian dose-finding design for outcomes evaluated with uncertainty

Matthew J. Schipper, Ying Yuan, Jeremy M.G. Taylor, Randall K. Ten Haken, Christina Tsien, Theodore S. Lawrence

Research output: Contribution to journalArticlepeer-review


Introduction: In some phase I trial settings, there is uncertainty in assessing whether a given patient meets the criteria for dose-limiting toxicity. Methods: We present a design which accommodates dose-limiting toxicity outcomes that are assessed with uncertainty for some patients. Our approach could be utilized in many available phase I trial designs, but we focus on the continual reassessment method due to its popularity. We assume that for some patients, instead of the usual binary dose-limiting toxicity outcome, we observe a physician-assessed probability of dose-limiting toxicity specific to a given patient. Data augmentation is used to estimate the posterior probabilities of dose-limiting toxicity at each dose level based on both the fully observed and partially observed patient outcomes. A simulation study is used to assess the performance of the design relative to using the continual reassessment method on the true dose-limiting toxicity outcomes (available in simulation setting only) and relative to simple thresholding approaches. Results: Among the designs utilizing the partially observed outcomes, our proposed design has the best overall performance in terms of probability of selecting correct maximum tolerated dose and number of patients treated at the maximum tolerated dose. Conclusion: Incorporating uncertainty in dose-limiting toxicity assessment can improve the performance of the continual reassessment method design.

Original languageEnglish (US)
Pages (from-to)279-285
Number of pages7
JournalClinical Trials
Issue number3
StatePublished - Jun 2021


  • Phase I
  • continual reassessment method
  • data augmentation
  • maximum tolerated dose

ASJC Scopus subject areas

  • Pharmacology


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