Group-Sequential Strategies When Considering Multiple Binary Outcomes as Co-Primary Endpoints

• Activity Number: 128
• Type: Contributed
• Date/Time: Monday, August 4, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Toshimitsu Hamasaki*+ and Koko Asakura and Scott R. Evans
• Companies: Osaka University Graduate School of Medicine and Osaka University and Harvard School of Public Health
• Keywords: Group-sequential designs ; Co-primary endpoints ; equal/unequal information time ; Power ; Sample size relaculation ; Type I error rate

Abstract

Recent clinical trials are often conducted with the objective of comparing a test intervention with that of a control intervention based on several binary outcomes as co-primary. "Co-primary" in this setting means that the trial is designed to evaluate if the test intervention is superior to the control on all endpoints, thus evaluating the intervention's multidimensional effects. In this presentation, we discuss group-sequential strategies with multiple binary endpoints as co-primary. We derive the power and required sample size within two decision-making frameworks: (1) to evaluate if superiority of a test intervention relative to control has been demonstrated for all endpoints at the same interim timepoint of the trial, and (2) to evaluate if superiority has been shown for all endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the utility of the method in practice using Monte-Carlo simulation and investigate the behavior of the sample sizes with varying design characteristics. We provide a real example to illustrate the methodology. We also discuss sample size recalculation based on observed interim data.