title: Flexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control.
abstract: We examine a large class of prior distributions to model the dose-response relationship in cancer phase I clinical trials. We parameterize the dose-toxicity model in terms of the maximum tolerated dose (MTD) gamma and the probability of dose limiting toxicity (DLT) at the initial dose rho(0). The MTD is estimated using the EWOC (escalation with overdose control) method of Babb et al. We show through simulations that a candidate joint prior for (rho0,gamma) with negative a priori correlation structure results in a safer trial than the one that assumes independent priors for these two parameters while keeping the efficiency of the estimate of the MTD essentially unchanged.
authors.affiliation: Department of Biostatistics and Winship Cancer Institute, Emory University, 1518 Clifton Road, NE, Atlanta, GA 30322, USA. mourad_tighiouart@emory.org
authors.forename: Mourad
authors.initials: M
authors.lastname: Tighiouart
authors.forename: André
authors.initials: A
authors.lastname: Rogatko
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil