Operating Characteristics for Continual Reassessment Method Using a Surrogate Endpoint

A trivariate continual reassessment method for phase I/II trials of toxicity, efficacy, and surrogate efficacy.

Recently, many Bayesian methods have been developed for dose finding when simultaneously modeling both toxicity and efficacy outcomes in a blended phase I/II fashion. A further challenge arises when all the true efficacy data cannot be obtained quickly after the treatment so that surrogate markers are instead used (e.g., in cancer trials). We propose a framework to jointly model the probabiliti...

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...

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

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 ...