Vaccines, Blood & Biologics

Two FDA CBER Mini-Sentinel Studies Completed on the Safety of Gardasil and Rotavirus Vaccines

Mini-Sentinel is a pilot project to inform the development of an active surveillance system, the Sentinel System, for monitoring the safety of FDA-regulated medical products. FDA’s Center for Biologics Evaluation and Research (CBER) has evaluated three different vaccines (RotaTeq, Rotarix and Gardasil) using the Mini-Sentinel system. ( These evaluations were conducted to provide better information to help clarify potential safety concerns that had been reported by other surveillance systems and enable FDA to better assess any potential risk.  Both studies are now complete and their final study reports are available online.

  1. Intussusception after rotavirus vaccination. Intussusception is the most common form of bowel obstruction in infancy and has been closely monitored since the voluntary withdrawal of the first rotavirus vaccine: Rotashield. FDA carefully assessed the risk for intussusception in large clinical trials in more than 60,000 children prior to licensure for both of the currently available rotavirus vaccines (RotaTeq and Rotarix).  No increased risk for intussusception was observed in these trials for either vaccine. However, several postmarketing studies [1],[2] from other countries subsequently suggested a potential increased risk. ( FDA conducted this Mini-Sentinel safety assessment because intussusception is a very rare event and prior studies had not been large enough to sufficiently evaluate this risk among children in the United States. Mini-Sentinel has the largest general population cohort for vaccine safety surveillance in the United States and FDA conducted this investigation to better quantify the potential risk of intussusception among US children.  See below for the final study results.
  2. Venous thromboembolism (VTE) after human papillomavirus vaccine. Venous thromboembolism is a condition that involves blood clots that form in the deep veins of the body (deep vein thrombosis) or in the lungs (pulmonary embolism). VTE can result from a combination of hereditary and acquired risk factors, including hormonal contraception.  FDA approved Gardasil in 2006 based on studies involving more than 21,000 males and females. No increased risk for VTE was identified in these studies. Postlicensure surveillance in the Vaccine Safety Datalink identified no safety risks among eight health outcomes which were evaluated, but a non-statistically significant increased rate of VTE after Gardasil was reported.[4] However, all of the confirmed cases of VTE in this study had other risk factors present that might explain their blood clots. FDA conducted this Mini-Sentinel safety assessment to evaluate VTE with improved control for these other risk factors.  See below for the final study results.

[1] Patel MM, López-Collada VR, Bulhões MM, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med. 2011 Jun 16;364(24):2283-92.
[2] Buttery JP, Danchin MH, Lee KJ, et al. Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia. Vaccine. 2011 Apr 5;29(16):3061-6.
[3] Yih KW, Lieu TA, et al. Intussusception Risk after Rotavirus Vaccination in U.S. Infants. N Engl J Med 2014 Feb 6; 370:503-512. DOI: 10.1056/NEJMoa1303164
[4] 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.

Page Last Updated: 04/24/2015
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