title: Practical designs for Phase I combination studies in oncology.
abstract: Phase I trials evaluating the safety of multidrug combinations are becoming more common in oncology. Despite the emergence of novel methodology in the area, it is rare that innovative approaches are used in practice. In this article, we review three methods for Phase I combination studies that are easy to understand and straightforward to implement. We demonstrate the operating characteristics of the designs through illustration in a single trial, as well as through extensive simulation studies, with the aim of increasing the use of novel approaches in Phase I combination studies. Design specifications and software capabilities are also discussed.
authors.affiliation: a Division of Translational Research & Applied Statistics, Department of Public Health Sciences , University of Virginia , Charlottesville , Virginia , USA.
authors.forename: Nolan A
authors.initials: NA
authors.lastname: Wages
authors.affiliation: b Department of Biostatistics , The University of North Carolina at Chapel Hill , Chapel Hill , North Carolina , USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.affiliation: c Quantitative Decision Strategies and Analytics, Advisory Services, Quintiles Inc. , Durham , North Carolina , USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Marchenko
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008495:Medical Oncology / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D012107:Research Design
keywords: Continual reassessment method; Phase I trials; dose finding; drug combination; partial ordering