Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples.
In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA.
L A
LA
Renfro
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA.
D J
DJ
Sargent
D024221:Antineoplastic Protocols; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
D014408:Biomarkers, Tumor