Interplay of priors and skeletons in two-stage 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...

The flexible bivariate continual reassessment method

An Application of Continual Reassessment Method Using SAS System

The Bayesian technique, Continual Reassessment Method (CRM), introduced by O’Quigley et al. (1990) is a new design for phase I trials in cancer. The goal of this design is to reduce the number of patients who receive lower doses, which are not expected to be effective, and to obtain a more accurate estimate of the maximum tolerated dose (MTD). The CRM has a couple of attractive characters, whic...

Robust EM Continual Reassessment Method in Oncology Dose Finding.

The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To over...

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 ...