Impact of Length Difference in Risk and Comparison Windows: A Cautionary Note

• Activity Number: 300
• Type: Topic Contributed
• Date/Time: Tuesday, August 11, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Xiaoming Li*
• Companies: Gilead Sciences
• Keywords: Observational study ; Rare event ; Self-comparison

Abstract

Observational safety studies seek to identify potential rare events that may be associated with a licensed product but could not be detected in clinical studies. In vaccine postmarketing safety studies, it is often useful to compare incidence rate in a risk period immediately following vaccination versus a longer self-comparison period for numerous medical events. It is recognized that when the risk and comparison event rates are the same, some of the tests for a difference between the two periods will reach significance by chance alone, and in this case, one would expect the differences reaching significance to be equally likely to be favorable or unfavorable. However, this may not be the case when the risk and comparison periods differ in length and events are rare, even with differential length of follow-up accounted for. An investigation of this phenomenon confirms that unequal comparison periods can affect the direction of chance.