Testing a Primary and a Secondary Endpoint in a Group Sequential Design

• Activity Number: 226
• Type: Topic Contributed
• Date/Time: Monday, August 2, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Ajit C. Tamhane*+ and Cyrus R. Mehta and Lingyun Liu
• Companies: Northwestern University and Cytel Inc. and Cytel Inc.
• Keywords: Gatekeeping procedures ; Multiple endpoints ; O'Brien-Fleming boundary ; Pocock boundary ; Primary power ; Secondary power

Abstract

We consider a clinical trial where the primary endpoint is a gatekeeper for the secondary endpoint. A two-stage group sequential test is used. The FWER of false significance on either endpoint is to be controlled at level a. The type I error rate for the primary endpoint is controlled by choosing any a-level boundary, e.g., the O'Brien-Fleming (OF) or the Pocock (PO) boundary. Given any a-level boundary for the primary endpoint, the boundary for the secondary endpoint to control the FWER is determined. We show that the FWER is maximized when the correlation coefficient ? between the two endpoints equals 1. The critical constants required to control the FWER are computed for different combinations of OF and PO boundaries and for different ?. When ? is unknown, the upper confidence limit on ? from the first stage data is used to compute boundaries. A clinical trial example is provided.