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A comparative study of adaptive dose‐finding designs for phase I oncology trials of combination therapies
Author(s) -
Hirakawa Akihiro,
Wages Nolan A.,
Sato Hiroyuki,
Matsui Shigeyuki
Publication year - 2015
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.6533
Subject(s) - maximum tolerated dose , medicine , phase (matter) , oncology , mathematics , computer science , clinical trial , statistics , chemistry , organic chemistry
Little is known about the relative performance of competing model‐based dose‐finding methods for combination phase I trials. In this study, we focused on five model‐based dose‐finding methods that have been recently developed. We compared the recommendation rates for true maximum‐tolerated dose combinations (MTDCs) and over‐dose combinations among these methods under 16 scenarios for 3 × 3, 4 × 4, 2 × 4, and 3 × 5 dose combination matrices. We found that performance of the model‐based dose‐finding methods varied depending on (1) whether the dose combination matrix is square or not; (2) whether the true MTDCs exist within the same group along the diagonals of the dose combination matrix; and (3) the number of true MTDCs. We discuss the details of the operating characteristics and the advantages and disadvantages of the five methods compared. Copyright © 2015 John Wiley & Sons, Ltd.