Innovative statistical methodologies to subgroup analysis in clinical trials

FDA PA 19?306 Bierer, Barbara E., M.D. Innovative statistical methodologies to subgroup analysis in clinical trialsProject SummaryThe Multi?Regional Clinical Trial (MRCT) Center of Brigham and Women's Hospital and Harvard (MRCTCenter) is a research and policy center created to address the conduct, oversight, ethics and regulatoryenvironment of clinical trials, with a focus on multinational trials. To do the work, we function as aindependent convener to engage diverse stakeholders from industry, CROs, academia, patients andpatient advocacy groups, non?profit organizations, and global regulatory agencies to address problemsin rigor and integrity of trials. In this proposal, we propose to convene a public conference ofstatisticians, clinical trialists, regulators, and patient/patient advocates to discuss innovative statisticalmethodologies to subgroup analysis in clinical trials. This conference is highly relevant to the FDA'sefforts to promote inclusion of individuals of diverse backgrounds and characteristics in clinical trials andto considerations of regional differences in multi?national trials. Different subgroups appear tonecessitate different approaches. That is, continuous (e.g. age), categorical (e.g. sex) , and overlapping(e.g. co?morbidity, polypharmacy) variables differ, and each may command different statistical analyses.The conference will address traditional approaches, Bayesian methods, and other innovative models andexplore the advantages and limitations of each. Further, the role of visualization and graphicalrepresentation will be discussed. Not all subgroup analyses must be performed at the level of theindividual clinical trial; analyses of post?approval observational data may illuminate importantdifferences across subgroups that were not discoverable during product development. For the clinicianand for the patient, the important factor is not the average treatment effect, but rather whether thebenefit of the product or intervention will outweigh the risks for the individual likely to take the product.