Modified Continual Reassessment Method in Phase I Clinical Trials of Categorical and Numerical Response Models

• Activity Number: 414
• Type: Contributed
• Date/Time: Tuesday, August 5, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Section on Bayesian Statistical Science
• Author(s): Ying Ji*+ and Xiaobin Yang and Keying Ye
• Companies: University of Texas at San Antonio and Analytic Focus and University of Texas at San Antonio
• Keywords: Continual reassessment method ; Dose finding ; Clinical trails

Abstract

Phase I clinical trials represent the first application of a new drug or treatment to human subjects. The primary goal of Phase I clinical trial is to establish the maximum tolerated dose (MTD) for phase II trials. In 1990, O'Quigley et al proposed a model-based clinical trial design, called Continual Reassessment Method (CRM). Its various modi?ed versions have improved the performance in ?nding MTD adaptively in the case of dichotomous toxicity responses in phase I clinical trials. We introduce the concept of the overall maximum tolerated dose which makes it possible to study both dichotomous and polychotomous response models under a uni?ed framework. Furthermore, categorical (such as dichotomous and polychotomous) and numerical (such as continuous) toxicity responses are presented under the unified model. Some simulation results based on categorical and numerical toxicity response are provided in this study. As an example of the continuous toxicity response, the normal toxicity response is studied along with a family of the target toxicity probabilities.