Multistage Designs for Vaccine Safety Studies

Abstract

In a placebo-controlled vaccine safety trial, the primary interest is to demonstrate that the vaccine is sufficiently safe, rejecting the null hypothesis that the relative risk of an adverse event attributable to the vaccine is above a prespecified value, greater than one. We develop sequential as well as multistage designs for such trials where the interim analyses are conducted not after a given number of subjects but rather after a given number of events observed. We show that these designs achieve significant improvement over single-stage conditional test in terms of both the required number of events to be observed and the required number of subjects to be enrolled.

Key Words:

• Conditional test
• Consumer risk
• Curtailed procedure
• Fully sequential test
• Multistage designs
• Poisson approximation
• Producer risk
• Sequential designs
• Vaccine efficacy
• Vaccine safety

ACKNOWLEDGMENT

The authors thank the reviewers for providing valuable suggestions and insights, which contributed to a substantial improvement of the paper.