Sequential and Adaptive RCT Designs with Time-to-Event Endpoints

• Activity Number: 443
• Type: Topic Contributed
• Date/Time: Wednesday, August 6, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Scott Emerson*+
• Companies: University of Washington
• Keywords: Survival analysis ; censored data

Abstract

A great many confirmatory phase 3 clinical trials have as their primary endpoint a comparison of the distribution of time to some event (e.g., time to death or progression free survival). The most common statistical analysis models include the logrank test and/or the proportional hazards regression model. Just as commonly, the true distributions do not satisfy the proportional hazards assumption. Providing users are aware of the nuances of those methods, such departures need not preclude the use of those analytic techniques any more than violations of the location shift hypothesis precludes the use of the t test. In this talk I discuss some aspects of the analysis of censored time to event data that must be carefully considered in sequential and adaptive sampling. In particular, I discuss the how the changing censoring distribution during a sequential trial affects the analysis of distributions with crossing hazards and crossing survival curves.