Considerations in Vaccine Lot Consistency Trials

• Activity Number: 513
• Type: Contributed
• Date/Time: Wednesday, August 4, 2010 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Xiao Sun*+ and Joshua Chen
• Companies: Merck Research Laboratories and Merck Research Laboratories
• Keywords: vaccine trial ; lot consistency ; power

Abstract

Demonstration of lot consistency in randomized clinical trials using three consecutively manufactured lots is generally required prior to licensure of an experimental vaccine. Lot consistency is declared if the 95% CI of the ratios of geometric mean of titers for each of the three pairs of lots is contained within a prespecified margin. In many cases, lot consistency study is designed as a substudy embedded in a larger clinical trial with objectives other than lot consistency, for example, to show noninferior immune response between two age groups, with one age group within the lot consistency substudy and the other outside the substudy. In this presentation, we will discuss some statistical considerations for such a trial. In particular, we will discuss the impact of between-lot variability on the power of showing lot consistency and the appropriate strategy for the noninferiority test.