Planning for Pharmacovigilance in Phase III Vaccine Trials

• Activity Number: 663
• Type: Contributed
• Date/Time: Thursday, August 2, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Zhen Jiang*+ and Estelle Russek-Cohen and Michael Nguyen
• Companies: FDA/CBER and FDA/CBER and FDA/CBER
• Keywords: Vaccine ; safety assessment ; premarket

Abstract

Vaccines are routinely administrated to healthy infants and adults in U.S., which make the safety of vaccines a critical element in the evaluation of a new vaccine. While we recognize that phase III vaccine trials are often sized for efficacy or in the context of vaccines that may not be first of a kind, possibly an immunogenicity endpoint, they may not have sufficient power to detect rare but serious adverse events. This poster provides comparison of several statistical methods for inference on risk difference and relative risk when assessing rare adverse events in large clinical trials, considering confidence intervals and power. Finally, we also identify reasonable practices in developing protocols that consider safety assessments, which includes standardized data collection, minimizing missing data, aggregated safety assessment, subgroup analysis etc., recognizing that rarer or unanticipated safety issues will never be fully addressed prior to the postmarket phase. We illustrate our findings using the results of an influenza trial.