title: A strategy for dose-finding and safety monitoring based on efficacy and adverse outcomes in phase I/II clinical trials.
abstract: We propose a design strategy for single-arm clinical trials in which the goals are to find a dose of an experimental treatment satisfying both safety and efficacy requirements, treat a sufficiently large number of patients to estimate the rates of these events at the selected dose with a given reliability, and stop the trial early if it is likely that no dose is both safe and efficacious. Patient outcome is characterized by a trinary ordinal variable accounting for both efficacy and toxicity. Like Thall, Simon, and Estey (1995, Statistics in Medicine 14, 357-379), we use Bayesian criteria to generate decision rules while relying on frequentist criteria obtained via simulation to determine a design parameterization with good operating characteristics. The strategy is illustrated by application to a bone marrow transplantation trial for hematologic malignancies and a trial of a biologic agent for malignant melanoma.
authors.affiliation: Department of Biomathematics, M. D. Anderson Cancer Center, University of Texas, Houston 77030, USA. rex@odin.mdacc.tmc.edu
authors.forename: P F
authors.initials: PF
authors.lastname: Thall
authors.forename: K E
authors.initials: KE
authors.lastname: Russell
mesh_terms: D001499:Bayes Theorem; D001699:Biometry; D016026:Bone Marrow Transplantation; D017321:Clinical Trials, Phase I as Topic / Q000379:methods* / Q000706:statistics & numerical data; D017322:Clinical Trials, Phase II as Topic / Q000379:methods* / Q000706:statistics & numerical data; D006086:Graft vs Host Disease; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008545:Melanoma / Q000628:therapy; D012449:Safety; D016896:Treatment Outcome
chemical_list: D018664:Interleukin-12