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A dose‐finding approach based on shrunken predictive probability for combinations of two agents in phase I trials
Author(s) -
Hirakawa Akihiro,
Hamada Chikuma,
Matsui Shigeyuki
Publication year - 2013
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.5843
Subject(s) - logistic regression , monotonic function , toxicity , computer science , basis (linear algebra) , shrinkage , maximum tolerated dose , statistics , econometrics , mathematics , medicine , mathematical analysis , geometry
We develop a novel dose‐finding method for two‐agent combination phase I trials on the basis of the shrunken predictive probability of toxicity. In this method, a shrinkage logistic regression model that allows distinct shrinkage multipliers for the coefficients of the main effects of two agents and their interaction on the probability of toxicity constructs the toxicity outcome. We also propose dose‐escalation/de‐escalation decision rules on the basis of the shrunken predictive probability of toxicity. Simulation studies under various patterns of monotonic dose‐response relationships for combinations of two agents demonstrated that the proposed method performed no worse than the existing two dose‐finding methods we selected. Copyright © 2013 John Wiley & Sons, Ltd.