ABSTRACT
This chapter reviews the continual reassessment method (CRM) with multiple toxicity constraints in more detail and describes the quasi-continual reassessment method (quasi-CRM) and the unified approach by Ivanova and Kim. It discusses various methods used for summarizing toxicities into continuous measures and the differences among them. The chapter presents an illustration of a dose-finding clinical trial using the CRM with multiple constraints. It then presents the mathematical framework and the dose-escalation algorithm for the CRM with multiple constraints, the quasi-CRM, and the unified approach by Ivanova and Kim. Before diving into the dose-finding methods for nonbinary outcomes, the chapter discusses the various methods that have been proposed for summarizing toxicity data into a continuous measure, which can then be used with dose-finding methods for continuous outcomes. The time-to-event CRM (TITE-CRM) was proposed to address the shortcomings by allowing for a longer observation window and inclusion of late-onset toxicities.
