A Two-Stage, Phase II Clinical Trial Design with Nested Criteria for Early Stopping and Efficacy: Expected Trial Duration and Tools for Planning

• Activity Number: 540 - SPEED: Clinical Trial Design, Longitudinal Analysis, and Other Topics in Biopharmaceutical Statistics
• Type: Contributed
• Date/Time: Wednesday, August 1, 2018 : 11:35 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Michelle DeVeaux* and Michael John Kane and Daniel Zelterman
• Companies: Regeneron Pharmaceuticals and Yale University and Yale University
• Keywords: curtailed sampling; expected sample size; expected trial duration; minimax design

Abstract

Often, the endpoint chosen to evaluate the treatment efficacy in an early phase clinical trial requires a lengthy follow-up time on each patient. We propose a two-stage design for a clinical trial with an early stopping rule for safety. This design employs different criteria to assess early stopping and efficacy. The early stopping rule is based on a criteria that can be determined more quickly than efficacy. These separate criteria are also nested in the sense that efficacy is a special case of, but usually not identical to, the early stopping criteria. This method is illustrated with a Phase II design comparing patients treated for lung cancer with a novel drug combination to a historical control. In this example, the early stopping rule is based on the number of patients who exhibit progression-free survival (PFS) at 2 months post treatment follow-up. Efficacy is judged by the number of patients who have PFS at 6 months. We demonstrate our design has sample size and power comparable to the Simon two-stage design, but exhibits shorter expected duration. We are developing an R package and Shiny web application that allow for easy planning of this design under curtailed sampling.