Characterization of the likelihood continual reassessment method

Xiaoyu Jia, Shing M. Lee, Ying Kuen Cheung

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

This paper deals with the design of the likelihood continual reassessment method, which is an increasingly widely used model-based method for dose-finding studies. It is common to implement the method in a two-stage approach, whereby the model-based stage is activated after an initial sequence of patients has been treated. While this two-stage approach is practically appealing, it lacks a theoretical framework, and it is often unclear how the design components should be specified. This paper develops a general framework based on the coherence principle, from which we derive a design calibration process. A real clinical-trial example is used to demonstrate that the proposed process can be implemented in a timely and reproducible manner, while offering competitive operating characteristics. We explore the operating characteristics of different models within this framework and show the performance to be insensitive to the choice of dose-toxicity model.

Original languageEnglish
Pages (from-to)599-612
Number of pages14
JournalBiometrika
Volume101
Issue number3
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • Adaptive design
  • Clinical trial
  • Coherence
  • Dose finding
  • Indifference interval

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