SDS Seminar Series – Dr. William Rosenberger

The Spring 2024 SDS Seminar Series continues on April 19th from 2:00 p.m. to 3:00 p.m. with Dr. William Rosenberger (Statistics and Computing, George Mason University). This event is in-person.    

Title: Design and Inference for Enrichment Trials with a Continuous Biomarker

Abstract: We describe the philosophical approaches to two-stage enrichment designs, in which a benefitting subpopulation is targeted in a second stage, after a first stage identifies the threshold of a predictive, continuous biomarker. The design issue we address is sample size estimation for the first and second stages, and the consequences of poorly estimating the threshold. These design issues are established based on an approach where the two stages are conducted and analyzed separately, and stage two is considered a confirmatory trial. Another approach is to combine the data from the two stages, and we demonstrate how to do that by testing two hypotheses simultaneously with test statistics that (we show) have an asymptotic normal distribution. While a bivariate normal model is used to give insights into the predictive nature of the biomarker, and to visualize some closed-form solutions, in principle other models can certainly be used (but perhaps yield fewer insights.) As in many ongoing, long-term research projects, our work probably raises more questions than it answers!

Joint work with Nancy Flournoy, Rosamarie Frieri, and Zhantao Lin