Vaccine Safety Datalink (VSD)

The Vaccine Safety Datalink (VSD) is a collaborative project between CDC’s Immunization Safety Office, integrated healthcare organizations, and networks across the United States. The VSD started in 1990 and continues today to monitor the safety of vaccines and conduct studies about rare and serious adverse events following immunization. As of September 28, 2022, there are 13 VSD sites that provide clinical, methodological, and data expertise; 11 currently are data-providing sites and the remaining sites provide subject matter expertise.

The VSD uses electronic health data from participating sites to monitor and assess the safety of vaccines. The VSD collects information about the kind of vaccine given to each patient, the date of vaccination, and other vaccinations given on the same day. This vaccine safety system also uses information about medical illnesses that have been diagnosed at doctors’ offices, urgent care visits, emergency department visits, and hospital stays to help monitor the safety of vaccines. The VSD conducts vaccine safety studies based on questions or concerns raised from the medical literature and reports to the Vaccine Adverse Event Reporting System (VAERS) and other vaccine safety systems. When there are new vaccines that have been recommended for use in the United States, or if there are changes in how a vaccine is recommended, the VSD will monitor the safety of these vaccines.

The VSD has a long history of monitoring and evaluating the safety of vaccines.  Since 1990, investigators from the VSD have published numerous studies to address vaccine safety concerns.  Listed below are examples of how VSD has monitored or evaluated the safety of vaccines:

• White Paper on Studying the Safety of the Childhood Immunization Schedule [PDF – 64 pages]
• Are vaccines that contain additives or preservatives safe for children?
• Are rotavirus vaccines safe for infants?
• Do vaccines cause febrile seizures?
• Are there safety concerns following Human Papillomavirus (HPV) Vaccine?
• Are the COVID-19 vaccines safe for children?

Participating VSD Healthcare Organizations

Sites that do not provide data are denoted with an asterisk(*).

• Acumen (Burlingame, CA)
• Denver Health, Denver, Colorado
• Harvard Pilgrim Health Care Institute, Boston, Massachusetts
• HealthPartners Institute, Minneapolis, Minnesota
• Indiana University (Indianapolis, IN)*
• Kaiser Permanente Colorado, Denver, Colorado
• Kaiser Permanente Mid-Atlantic States (Rockville, MD)
• Kaiser Permanente Northern California, Oakland, California
• Kaiser Permanente Northwest, Portland, Oregon
• Kaiser Permanente Southern California, Los Angeles, California
• Kaiser Permanente Washington, Seattle, Washington
• Marshfield Clinic Research Institute, Marshfield, Wisconsin
• OCHIN (Portland, OR)*

VSD aims to:

• Conduct research on important vaccine safety questions in large populations
• Conduct vaccine safety studies that come from questions or concerns in the medical literature or from other vaccine safety systems, like VAERS
• Monitor possible adverse events when new vaccines are licensed or when there are new vaccine recommendations
• Provide information to committees who make vaccine safety recommendations for the nation

Rapid Cycle Analysis

Rapid Cycle Analysis (RCA) allows VSD to detect adverse events following vaccination in near real time so the public can be informed quickly of possible safety concerns.

Weekly, the VSD analyzes their data to determine if the rates of predefined adverse events of special interest (AESI) following a specific vaccine is higher than the rates of AESI in a comparison group. If this occurs, this signals CDC that there may be a health problem occurring after administration of this vaccine and additional follow-up analyses are needed. If the rate of adverse events among vaccinated people is higher than among the comparison group beyond a certain limit, the vaccine may be associated with an adverse event. VSD has used RCA to publish important safety information about many vaccines, some of which are listed below:

• COVID-19 vaccine
  • Guillain-Barré Syndrome (GBS) after COVID-19 vaccination
  • Myocarditis and pericarditis following mRNA COVID-19 vaccination
• Gardasil (human papillomavirus vaccine)
  • Quadrivalent HPV Vaccine
  • 9-Valent HPV Vaccine
• Influenza
  • Seasonal
  • 2009 H1N1
• Kinrix (DTaP-IPV)  (DTaP and polio)
• Measles, mumps, rubella, and varicella (MMRV)
• Meningococcal
• Pentacel (DTaP-IPV/Hib) (diphtheria, tetanus, pertussis [DTap], HiB, and polio)
• Rotavirus
• Shingrix
• Tetanus, Diphtheria, Pertussis (Tdap)

Evaluating Safety of Vaccines in Pregnancy

Vaccination protects people who are pregnant and unborn babies from several preventable diseases and complications of those diseases. Evaluating the safety of vaccines given to people who are pregnant [PDF – 2 pages] is a high priority for the VSD.

Using an electronic health record to determine a person’s stage in their pregnancy is complicated. The VSD has developed algorithms to identify people who are pregnant and determine the start and end dates of the pregnancy. VSD is also able to use data to study the health of children born to people who were vaccinated during pregnancy. VSD has published multiple studies related to pregnancy and vaccination during pregnancy and continues to study the safety of Tdap vaccination, inadvertent HPV vaccination, influenza vaccination, and COVID-19 vaccination during pregnancy. Any major findings related to vaccines are studied and published as needed.

Research Methods to Study Vaccine Safety

VSD investigators have pioneered the development of statistical methods to conduct valid, accurate vaccine safety studies. Methods developed by the VSD in the past have been adopted by other researchers using large-linked databases, and VSD investigators continue to develop and refine statistical approaches for vaccine safety research. Some of the methods developed by the VSD are listed below:

• Maximized sequential probability ratio test (MaxSPRT [PDF – 22 pages] ) (CMaxSPRT)
• Group sequential analysis
• Case-centered analysis
• Sequential concurrent comparator analysis
• Tree-scan analysis

These methods allow VSD to conduct timely and reliable vaccine safety monitoring and evaluations.

How Can I Access VSD Data?

From time to time, scientists (from outside CDC and outside the VSD network) want to analyze VSD data. Depending on the request, interested researchers may be able to access VSD data and data from VSD publications through public use datasets, the VSD data sharing program, and collaboration with current VSD investigators.