Principled Methods for Estimating Conditional and Marginal Efficacy Measures in Time-to-Event Outcomes Using Web-Interactive Shiny Apps

Music City Center 

As a continuation of the first presentation, we focus on time-to-event outcomes using Hazard Ratios (HR) and Time Ratios (TR) as efficacy measures in a heterogeneous patient population with differential treatment efficacy across different biomarker subgroups. We present interactive web-based Shiny applications that implement principled methods to estimate conditional and marginal efficacy measures under the proportional hazards model (for HR) and the accelerated failure time model (for TR).

To illustrate these methods, we analyze data from two cancer clinical trials. The first dataset comes from the OAK study, a randomized, open-label, phase 3 trial evaluating the efficacy of atezolizumab, a humanized anti-PD-L1 treatment, versus docetaxel in previously treated patients with non-small-cell lung cancer. The biomarker of interest is PD-L1 expression (≥1% vs. <1% on tumor cells or tumor-infiltrating immune cells). The second dataset is from Genentech's randomized phase II trial investigating onartuzumab combined with erlotinib vs erlotinib alone in patients with advanced non-small-cell lung cancer, where the biomarker is MET status determined by immunohistochemistry (IHC). Both studies use overall survival as the time-to-event outcome.