STATISTICS COLLOQUIUM
Brian P. Hobbs, PhD
Associate Staff, Department of Quantitative Health Science in
The Lerner Research Institute
Section Head of Cancer Biostatistics in The Taussig Cancer Institute
Cleveland Clinic
Trial design in the presence of non-exchangeable subpopulations
Abstract
Advances in biology and immunology continue to refine our understanding of cancer pathogenesis, elucidating potential mechanisms of tumor-cell growth, survival, angiogenesis and the systematic suppression of cancer immunity. With FDA approval bestowed on less than 6% of oncology drugs entering human testing between 2006 and 2015, however, the process for translating advances in preclinical knowledge into effective cancer treatment strategies has had limited success historically. Basket trials comprise a class of experimental designs that endeavor to test the effectiveness of a therapeutic strategy among patients defined by the presence of a particular biomarker target (often a molecular feature) rather than a particular cancer type. Acknowledging the potential for differential effectiveness on the basis of traditional criteria for cancer subtyping, evaluations of treatment effectiveness are conducted with respect to the ``baskets'' which collectively represent a partition of the targeted patient population consisting of discrete subtypes. Yet, designs of early basket trials have been criticized for their reliance on basketwise analysis strategies which suffered from limited power in the presence of imbalanced enrollment as well as failed to convey to the clinical community evidentiary measures for consistent effectiveness among the studied clinical subtypes. This presentation is intended to elucidate issues that limit the effectiveness of traditional and “response-adaptive” designs used in precision medicine contexts in oncology. Additionally, I will present a novel class of Bayesian sequential designs based on multi-source exchangeability modeling. The methodology is demonstrated with both analysis and permutation studies based on data reported from a recent basket trial designed to estimate the effectiveness of vemurafenib in BRAF mutant non-melanoma among six clinical sites.
DATE: Wednesday, April 18, 2018
TIME: 4:00 pm
PLACE: Philip E. Austin Bldg., Rm. 108
Coffee will be served at 3:30 pm in the Noether Lounge (AUST 326)
For more information, contact: Tracy Burke at tracy.burke@uconn.edu