Optimal Designs with Interim Analyzes for Phase II Studies with Long-Term Time-Specific Endpoints

• Activity Number: 410
• Type: Topic Contributed
• Date/Time: Tuesday, August 5, 2014 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Bo Huang*+ and Neal Thomas
• Companies: Pfizer and Pfizer
• Keywords: Optimal design ; Long-term time-specific endpoint ; Time-to-event ; Oncology

Abstract

With the advent of novel cancer therapies targeting molecular pathways or the immune system, time-to-event variables evaluated at longer times (e.g., 6 or 12 months) are increasingly used as the primary endpoint in Phase II trials. Two-stage Simon designs (1989) have often been used in single-arm phase II oncology trials to reduce the expected sample size under the null hypothesis. Accurate implementation of the Simon design can be difficult, and the difficulty increases with a longer-term endpoint, because it requires complete information from each accrued patient. Earlier work of Case and Morgan (2003) generalized the Simon design so it can be implemented without an accrual pause for a single-arm 2-stage trial. We develop optimal 2-stage and 3-stage single-arm or randomized 2-arm designs with analogous optimality criteria. The proposed optimal designs allow a brief pre-planned pause (>=0) in accrual before interim analyses to more efficiently utilize data from the accrued patients, and to allow focused data collection before the interim analyses. We provide software (R package OptInterim) that creates the optimal designs and also simulates their properties to check asymptotic