A two-dimensional search algorithm for dose-finding trials of two agents.
Existing algorithms for identifying the maximum tolerated combination in dose-finding trials of two agents are mostly one-dimensional. Moreover, these algorithms use only the frequency of observed dose-limiting toxicities as the basis for dose escalations and deescalations. In this article, we propose a two-dimensional algorithm that uses not only the frequency but also the source of dose-limiting toxicities to direct dose escalations and deescalations. In addition, when the doses of both agents are escalated simultaneously, a more conservative design replaces a default aggressive design to evaluate the resulting dose combination. Our method aims to increase in-trial patient safety without unnecessary increase in sample size.
Department of Mathematics, San José State University, San José, CA 95192, USA. beeleng.lee@sjsu.edu
Bee Leng
BL
Lee
Shenghua Kelly
SK
Fan
D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols; D017321:Clinical Trials, Phase I as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy*; D061214:Patient Safety; D018401:Sample Size