Calibration of prior variance in the Bayesian continual reassessment method

Stat Med. 2011 Jul 30;30(17):2081-9. doi: 10.1002/sim.4139. Epub 2011 Mar 17.


The continual reassessment method (CRM) is an adaptive model-based design used to estimate the maximum tolerated dose in phase I clinical trials. Asymptotically, the method has been shown to select the correct dose given that certain conditions are satisfied. When sample size is small, specifying a reasonable model is important. While an algorithm has been proposed for the calibration of the initial guesses of the probabilities of toxicity, the calibration of the prior distribution of the parameter for the Bayesian CRM has not been addressed. In this paper, we introduce the concept of least informative prior variance for a normal prior distribution. We also propose two systematic approaches to jointly calibrate the prior variance and the initial guesses of the probability of toxicity at each dose. The proposed calibration approaches are compared with existing approaches in the context of two examples via simulations. The new approaches and the previously proposed methods yield very similar results since the latter used appropriate vague priors. However, the new approaches yield a smaller interval of toxicity probabilities in which a neighboring dose may be selected.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Bayes Theorem*
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Bortezomib
  • Clinical Trials, Phase I as Topic / methods*
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Humans
  • Lymphoma, B-Cell / drug therapy
  • Maximum Tolerated Dose*
  • Models, Statistical*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects


  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib