Max-Combo Test for Time-to-Event Endpoints Under Nonproportional Hazards

• Activity Number: 238 - Addressing Nonproportional Hazards Issues in Oncology Clinical Trial Design
• Type: Topic-Contributed
• Date/Time: Wednesday, August 11, 2021 : 10:00 AM to 11:50 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Ray Lin*
• Companies: Genentech
• Keywords: Weighted log-rank test; Non-Proportional Hazards; Cox model; Survival Analysis

Abstract

Non-proportional hazards have been observed in clinical trials with time to event endpoints, such as the delayed treatment effect observed in cancer immunotherapies and the diminishing effect caused by the confounding due to follow-up therapies. The log-rank test loses power and the standard Cox model usually produces biased estimates under such conditions. These statistical impacts may lead to false-negative studies; in addition, they may also provide misleading clinical interpretation of the results. The Non-Proportional Hazards Cross-Pharma Working Group was formed in 2016 with more than 15 companies across the pharmaceutical industry and have been conducting research to evaluate alternative analysis methods under non-proportional hazards. The findings and the recommendations of the Working Group will be presented and discussed.