Identifying a maximum tolerated contour in two‐dimensional dose finding. (22nd February 2016)

• Record Type: Journal Article
• Authors: Wages, Nolan A.
• Other Names: Cheung Ken guestEditor.; Iasonos Alexia guestEditor.; Jaki Thomas guestEditor.; O'Quigley John guestEditor.
• Is Part Of: Statistics in medicine. Volume 36:Number 2(2017)
• Page Start: 242
• Page End: 253
• Publication Date: 2016-02-22
• Subjects: phase I -- dose finding -- drug combination -- equivalence contour; Medical statistics -- Periodicals; Statistique médicale -- Périodiques; Statistiques médicales -- Périodiques; 610.727
• DOI: 10.1002/sim.6918
• Languages: English
• ISSNs: 0277-6715

Abstract

Abstract : The majority of phase I methods for multi‐agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDCs for further testing for efficacy in a phase II setting. In this paper, we present a new dose‐finding method that extends the continual reassessment method to account for the location of multiple MTDCs. Operating characteristics are demonstrated through simulation studies and are compared with existing methodology. Some brief discussion of implementation and available software is also provided. Copyright © 2016 John Wiley & Sons, Ltd.