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  1. Biologics Post-Market Activities

FDA Sentinel study finds no association between venous thromboembolism and Gardasil vaccination

April 23, 2015

Background

On December 7, 2010, the Food and Drug Administration (FDA) presented a comprehensive postlicensure safety evaluation of Gardasil (Merck Inc. & Co.) to FDA’s Pediatric Advisory Committee (PAC).  In this review, FDA presented safety data from the Vaccine Adverse Event Reporting System (VAERS) [1] and the Centers for Disease Control and Prevention’s Vaccine Safety Datalink (VSD) [2] suggesting that more venous thromboembolism (VTE) cases were being observed than expected after vaccination with Gardasil.  Venous thromboembolism is a condition where blood clots form in the deep veins of the body, especially the lungs and extremities.  Because both the VAERS and VSD data were inconclusive, FDA conducted a follow up study in the Sentinel system.  This FDA update provides a summary of the final analysis, which did not find any evidence of an association between venous thromboembolism and Gardasil vaccination.

Summary of Results
The Sentinel study evaluated the risk of venous thromboembolism in more than 650,000 females aged 9 through 26 years of age, totaling more than 1.4 million doses of Gardasil evaluated.  The study identified only 30 medical record confirmed cases of venous thromboembolism in the 8–9 week observation period after each dose administered in the 3-dose series.  The VTE cases were identified from 5 Sentinel data partners during the time period of 2006–2013.  The study evaluated the risk of VTE 1–28 days after Gardasil vaccination compared to a period approximately one to two months after vaccination.  The study did not identify any evidence of an increased risk of VTE in the 1–28 days after any of the 3 doses of Gardasil vaccination.  The study also scanned the entire 8–9 week observation period and did not find any unusual VTE clusters appearing after Gardasil vaccination, further strengthening the conclusion that there is no increased risk of VTE.

FDA Conclusions
The Sentinel study is the largest study of VTE after Gardasil in the United States to date and builds upon other published studies, including those from Denmark and Sweden that also found no evidence of an increased risk for venous thromboembolism after Gardasil vaccination [3] [4] [5] [6].  FDA is not requesting any changes to Gardasil labeling as a result of this new safety information. 

 

[1] Slade BA, Leidel L, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009 Aug 19;302(7):750-7. doi: 10.1001/jama.2009.1201.

[2] Gee J, Naleway A, Shui I, et al. Monitoring the safety of quadrivalent human papillomavirus vaccine: Findings from the Vaccine Safety Datalink. Vaccine. 2011 Oct 26;29(46):8279-84.

[3] Arnheim-Dahlström L, Pasternak B, Svanstrom H, Sparen P, Hviid A. Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ. 2013 Oct 9;347:f5906. doi: 10.1136/bmj.f5906.

[4] Scheller NM, Pasternak B, Svanström H, Hviid A. Quadrivalent human papillomavirus vaccine and the risk of venous thromboembolism. JAMA. 2014 Jul;312(2):187-8. doi: 10.1001/jama.2014.2198.

[5] Klein NL, Hansen J, et al. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1140-8. doi: 10.1001/archpediatrics.2012.1451.

[6] Naleway A, Crane B, Smith N, Daley M, Donahue J, Gee J, Harrington T, Jackson L, Klein N, Tseng H, Vellozzi C, Weintraub E. Risk of venous thromboembolism following quadrivalent HPV vaccination. 29th International Papillomavirus Conference. Seattle, August 2014.

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