Sample-Size Evaluation in Group-Sequential Designs for Clinical Trials with Two Continuous Endpoints as Co-Primary Contrasts

• Activity Number: 534
• Type: Contributed
• Date/Time: Wednesday, August 7, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Koko Asakura*+ and Kenichi Hayashi and Tomoyuki Sugimoto and Takashi Sozu and Toshimitsu Hamasaki
• Companies: Osaka University Graduate School of Medicine and Osaka University Graduate School of Medicine and Hirosaki University Graduate School of Science and Technology and Kyoto University School of Public Health and Osaka University Graduate School of Medicine
• Keywords: Correlated endpoints ; Interim analysis ; Power ; Sample size reestimation ; Two-arm design

Abstract

In many recent clinical trials, two or more endpoints may be investigated as co-primary, with the aim of providing a comprehensive picture of the intervention's benefits. In such clinical trials, while no adjustment is necessary for Type I error control, the sample size is increased as the number of endpoints to be considered is increased. One way of reducing the sample size is to incorporate the correlations among the endpoints into the sample size estimation. However, a major concern is how and when the correlations may be incorporated appropriately into the sample size estimation, as the correlations are usually unknown. We consider this issue within group sequential designs for two-arm trials with two continuous endpoints as the co-primary contrasts. In this presentation, we outline the calculation of power and sample size estimation, where sample size reestimation may be considered at the interim of the trial, using CHW statistics (Cui et al., Biometrics 1999; 55: 853-857). We also evaluate how power and sample size behave with the correlation between endpoints. Finally, we discuss whether the correlation should be incorporated at sample size estimation.