Adaptive prior variance calibration in the Bayesian continual reassessment method

Bayesian Model Averaging Continual Reassessment Method BMA-CRM

This document provides the statistical background for the Bayesian model averaging continual reassessment method (BMA-CRM). The BMA-CRM is a Bayesian model-based phase I clinical trial design. The primary goal of the BMA-CRM is to identify the maximum tolerated dose (MTD) of a new drug, which is typically defined as the dose with a doselimiting toxicity (DLT) probability that is closest to the ...

The flexible bivariate continual reassessment method

Continual reassessment method with multiple toxicity constraints.

This paper addresses the dose-finding problem in cancer trials in which we are concerned with the gradation of severe toxicities that are considered dose limiting. In order to differentiate the tolerance for different toxicity types and grades, we propose a novel extension of the continual reassessment method that explicitly accounts for multiple toxicity constraints. We apply the proposed meth...

Adaptive design improvements in the continual reassessment method for phase I studies.

The continual reassessment method (CRM) enables full and efficient use of all data and prior information available in a phase I study. However, despite a number of recent enhancements to the method, its acceptance in actual clinical practice has been hampered by several practical difficulties. In this paper, we consider several further refinements in the context of phase I oncology trials. In p...

The continual reassessment method and its applications: a Bayesian methodology for phase I cancer clinical trials.

We discuss the continual reassessment method (CRM) and its extension with practical applications in phase I and I/II cancer clinical trials. The CRM has been proposed as an alternative design of a traditional cohort design and its essential features are the sequential (continual) selection of a dose level for the next patients based on the dose-toxicity relationship and the updating of the rela...