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Two‐stage design for dose‐finding that accounts for both efficacy and safety
Author(s) -
Dragalin Vladimir,
Fedorov Valerii V.,
Wu Yuehui
Publication year - 2008
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.3356
Subject(s) - bivariate analysis , estimator , context (archaeology) , maximum tolerated dose , variance (accounting) , computer science , mathematics , econometrics , point estimation , probit model , statistics , medicine , toxicity , economics , paleontology , accounting , biology
We introduce a two‐stage design for dose‐finding in the context of Phase I/II studies, where two binary correlated endpoints are available, for instance, one for efficacy and one for toxicity. The bivariate probit model is used as a working model for the dose–response relationship. Given a ‘desirable point’ for the marginal probabilities of efficacy and toxicity, the goal is to find the target dose that is ‘closest’ to the desirable point. The criterion of optimality (objective function) is the variance of the estimator for that dose. Optimal experimental design methodology is used to construct efficient dose allocation procedures that treat patients in the study at doses that are both safe and efficacious. Copyright © 2008 John Wiley & Sons, Ltd.