Vaccine 30 (2012) 2024–2031 Contents lists available at SciVerse ScienceDirect Vaccine j ourna l ho me pag e: www.elsevier.com/locate/vaccine Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010–2011 Alison Tse a,∗ , Hung Fu Tseng b , Sharon K. Greene a , Claudia Vellozzi c , Grace M. Lee a,d , On behalf of the VSD Rapid Cycle Analysis Influenza Working Group 1 a Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, United States b Department of Research and Evaluation, Southern California Kaiser Permanente, Pasadena, CA, United States c Immunization Safety Office, Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, GA, United States d Division of Infectious Diseases & Department of Laboratory Medicine, Children’s Hospital Boston, Boston, MA, United States a r t i c l e i n f o Article history: Received 3 October 2011 Received in revised form 12 December 2011 Accepted 6 January 2012 Keywords: Trivalent inactivated influenza vaccine Vaccine safety Vaccine Safety Datalink Project Febrile seizures a b s t r a c t In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010–2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0–1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0–1 days vs. 14–20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6–59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit–risk framework to ensure that population health benefits are maximized. © 2012 Elsevier Ltd. All rights reserved. DOIs of original articles: 10.1016/j.vaccine.2011.12.040, 10.1016/j.vaccine.2011.12.042 ∗ Corresponding author at: Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, 6th floor, Boston, MA 02215, United States. Tel.: +1 617 509 9978; fax: +1 617 859 8112. 1 VSD Rapid Cycle Analysis Influenza Working Group (Group authors)—Centers for Disease Control and Prevention: Eric Weintraub, Natalie McCarthy, Jerome Tokars, Frank DeStefano, Karen Broder; Group Health Cooperative: Lisa Jackson, Jennifer Nelson; Harvard Pilgrim Health Care Instiute: Martin Kulldorff, Melisa Rett, Tracy Lieu, Lingling Li; HealthPartners Research Foundation: James D. Nordin; Kaiser Permanente Colorado: Jason Glanz, Simon Hambidge, Matthew F. Daley; Marshfield Clinic Research Foundation: Edward A. Belongia, Stephanie Irving; Kaiser Permanente Northern California: Nicola Klein, Roger Baxter; Kaiser Permanente Northwest: Allison Naleway; Southern California Kaiser Permanente: S. Michael Marcy, Steven J. Jacobsen. 0264-410X/$ – see front matter © 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2012.01.027