Method of Balanced Adjustment in Testing Coprimary Endpoints

• Activity Number: 226
• Type: Topic Contributed
• Date/Time: Monday, August 2, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): George Kordzakhia*+
• Companies: FDA
• Keywords: co-primary endpoints ; type I error rate

Abstract

In a clinical trial with multiple co-primary endpoints, the type II error could increase depending on the correlation among the endpoints. Patel (1991) proposed an approach that adjusts the significance levels for testing each co-primary endpoint based on the idea of restricting the null space. In the scenario that statistical significance of each individual hypothesis is not required, we introduce a testing approach in which the significance level for a co-primary endpoint is adjusted upward only if the treatment shows high significance in one (or more than one) of the remaining co-primary endpoints. The method is applicable for the scenario where the null space is restricted. Our testing approach controls maximum joint false positive rate over the restricted null space, but it does not assure that each individual hypothesis is statistically significant.