Near real-time surveillance for influenza vaccine safety: proof-of-concept in the Vaccine Safety Datalink Project

Abstract

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06-2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillain-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

Figure 1.

Risk and control periods for an example potential adverse event proximal to vaccination in the 2007/08 influenza season. The cumulative number of events occurring during each period, summed across previous seasons, is represented by a and b. The number of events occurring during the current season is represented by c and d. A) In the self-controlled case series approach, d is compared with c. B) In the difference-in-difference approach, d is compared with c, adjusting for the comparison of b with a.

Figure 2.

Weekly sequential analysis results for seizures among trivalent inactivated influenza vaccine recipients aged ≥18 years in the 2007/08 influenza season, Vaccine Safety Datalink Project. A) Self-controlled case series approach; B) difference-in-difference approach.