Evaluating Biomarkers for Prognostic Enrichment of Clinical Trials

• Activity Number: 643 - Biomarkers and Clinical Trials
• Type: Invited
• Date/Time: Thursday, August 2, 2018 : 10:30 AM to 12:20 PM
• Sponsor: WNAR
• Author(s): Kathleen F. Kerr* and Jeremy Roth and Kehao Zhu and Heather Thiessen-Philbrook and Allison Meisner and Francis Perry Wilson and Steven Coca and Chirag Parikh
• Companies: University of Washington and University of Washington and Axio Research and Yale University and Johns Hopkins University and Yale University and Icahn School of Medicine at Mount Sinai and Yale University
• Keywords: biomarker; clinical trial; prognostic enrichment; sample size

Abstract

For an intervention intended to reduce the occurrence of an unwanted clinical event, a prognostically enriched clinical trial enrolls only patients at relatively higher risk of the event. A study population with a higher event rate requires a smaller sample size for an adequately powered trial. Thus a potential role for biomarkers is for clinical trial prognostic enrichment. However, while there is broad agreement that biomarkers should be evaluated with respect to their intended use, little has been written about how to evaluate a biomarker for prognostic enrichment of clinical trials. We identify key considerations when evaluating a biomarker and a screening threshold, and methods for assessing their utility for prognostic enrichment. We also provide methods for an approximate evaluation based on a biomarker's AUC. Results show that modestly performing biomarkers can sometimes be useful for prognostic enrichment. Methods are available in an R package, BioPET, and a webtool at www.prognosticenrichment.com.