title: The current design of oncology phase I clinical trials: progressing from algorithms to statistical models.
abstract: In this article we examine how phase I trial designs for anti-cancer agents have developed over the past few decades. We review the use of algorithmic, relatively non- statistical designs, and then describe nonparametric and parametric statistically-driven designs that have better operating characteristics than algorithmic designs. We then follow with a description of how the original parametric design, known as the continual reassessment method (CRM), has been generalized and expanded to create designs for many complex settings that occur in early-phase oncology trials. We conclude with a discussion of outstanding issues and controversies that continue to exist with phase I trial designs.
authors.affiliation: University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USA. tombraun@umich.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
keywords: Dose-finding; dose-limiting toxicity (DLT); maximum tolerated dose (MTD)