title: A dose-finding approach based on shrunken predictive probability for combinations of two agents in phase I trials.
abstract: 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.
authors: Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Aichi, 466-8560, Japan.
authors: Akihiro
authors: A
authors: Hirakawa
authors: Chikuma
authors: C
authors: Hamada
authors: Shigeyuki
authors: S
authors: Matsui
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003198:Computer Simulation; D006801:Humans; D020714:Maximum Tolerated Dose; D015233:Models, Statistical
keywords: combination; dose-finding studies; phase I trial; prediction; shrinkage