The International Indian Statistical Association (IISA) presents a webinar on "Is Inadequate Risk Stratification Diluting Hazard Ratio Estimates in Randomized Clinical Trials?"
6/13/2024 | 12:00 - 1:00 PM (Eastern) / 9:00 - 10:00 AM (Pacific)
Registration (free but required):
https://weillcornell.zoom.us/webinar/register/WN_gCetBjNPQCKJDb6Bi7_RtA
Abstract: In randomized clinical trials, survival analyses without risk stratification, or with stratification based on pre-selected factors revealed at the end of the trial to be at most weakly associated with risk, are quite common. We caution that such analyses are likely delivering hazard ratio estimates that dilute the evidence of benefit for the test relative to the control treatment. To make our case, first we use a hypothetical scenario to contrast risk-unstratified and risk-stratified hazard ratios. Thereafter, we draw attention to the 5-STAR methodology in which a pre-specified treatment-blinded algorithm is applied to survival times from the trial to partition patients into well-separated risk strata using baseline covariates determined to be jointly strongly prognostic for event risk. After treatment unblinding, a treatment comparison is done within each risk stratum and stratum-level results are averaged for overall inference. We illustrate the utility of 5-STAR based on a reanalysis of data for the primary and key secondary endpoints from three large cardiovascular outcomes trials. An R package to implement 5-STAR is available at https://github.com/rmarceauwest/fiveSTAR. (This is joint research with Rachel Marceau West at Merck.)
Speaker Bio: Devan V. Mehrotra, PhD, is Vice President of Biostatistics at Merck Research Laboratories (MRL), the R&D Division of Merck & Co., Inc. He has made significant contributions towards the research, development and regulatory approval of medical drugs and vaccines across a broad spectrum of therapeutic areas. He was awarded an MRL Presidential Fellowship in 2012. Dr. Mehrotra is also an adjunct Professor of Biostatistics at the University of Pennsylvania and an elected Fellow of the American Statistical Association. He has served as a subject matter expert for the Bill and Melinda Gates Foundation (for HIV vaccine development), the US National Academy of Sciences (for missing data issues in clinical trials), the Coalition for Epidemic Preparedness Innovations (for COVID-19 vaccine development), and the International Council on Harmonization (for ICH E9/R1 on estimands and sensitivity analyses).
A flyer is attached to this post, and available for download at this link: https://www.dropbox.com/scl/fi/iy2lpbc5e1nobe0f6pqln/IISA-Flyer-June-2024.pdf?rlkey=ncu30o50iapn5jj3kudizg4rx&e=1&dl=0
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Himel Mallick, PhD, FASA
Principal Investigator (Tenure-track Faculty)
Cornell University
New York, New York 10065
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