Ruling Out a Safety Margin

• Activity Number: 44
• Type: Contributed
• Date/Time: Sunday, August 9, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kunthel By* and Thomas Ly and John Yap and Jessica Kim
• Companies: and FDA and FDA and FDA
• Keywords: rule-out ; rare events ; non-inferiority ; safety margin

Abstract

Post-market safety outcome studies to evaluate risk are often conducted as a condition of approval (PMR/PMC) or after a post-market signal has been elicited. Often, these studies are designed to detect a pre-specified relative risk under the alternative hypothesis. We discuss challenges associated with interpretation of results under this type of hypothesis testing in the setting of safety studies. We consider a ruling-out approach as an alternative hypothesis testing paradigm that may address some of these challenges. Difficulties associated with conducting rule-out studies such as sample size and margin selection will also be discussed.