Practical designs for Phase I combination studies in oncology

J Biopharm Stat. 2016;26(1):150-66. doi: 10.1080/10543406.2015.1092029.


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.

Keywords: Continual reassessment method; Phase I trials; dose finding; drug combination; partial ordering.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials, Phase I as Topic / methods*
  • Dose-Response Relationship, Drug
  • Humans
  • Medical Oncology / methods*
  • Neoplasms / drug therapy*
  • Research Design