Ongoing safety monitoring requirements for approved vaccines.
Pre-licensure clinical trials are essential but limited: they typically enroll tens of thousands of participants and last months to a few years. Some adverse events are too rare, too delayed, or too specific to certain populations to appear during trials. Post-market surveillance systems exist to detect these signals after a vaccine reaches millions of people in real-world conditions.
No single system can do this alone. The United States and other countries operate layered monitoring programs — some designed to cast a wide net for any potential signal, others designed to rigorously verify whether a signal represents a genuine safety concern.
The Vaccine Adverse Event Reporting System is the broadest signal detector in the U.S. safety monitoring infrastructure. Co-managed by the CDC and FDA, VAERS accepts reports from anyone — healthcare providers, manufacturers, and the public. Its strength is scope: it can detect unexpected patterns across millions of doses. Its limitation is that reports alone do not establish causation; they identify signals that require further investigation. For detailed information, see our VAERS page.
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) operates the Yellow Card Scheme, which serves a similar function to VAERS. Healthcare professionals and the public can submit reports of suspected adverse reactions. The MHRA analyzes reports for emerging safety signals.
Passive systems rely on voluntary reporting. This means they are subject to both underreporting (not all events are reported) and reporting bias (media attention can increase reports for specific conditions). These limitations are well-documented and are precisely why passive systems are paired with active verification systems.
The VSD is a collaboration between the CDC and nine integrated healthcare organizations covering approximately 12 million people. Unlike VAERS, the VSD uses electronic health records to actively monitor vaccinated populations. It can compare rates of health events in vaccinated vs. unvaccinated groups, providing the statistical power to confirm or rule out safety signals detected by passive systems.
The FDA's BEST system uses large-scale health insurance claims data and electronic health records to conduct rapid safety studies. BEST was significantly expanded during the COVID-19 vaccine rollout and can analyze data from tens of millions of individuals.
Active systems do not wait for reports. They continuously analyze health data from defined populations, comparing expected vs. observed rates of specific conditions after vaccination. This design allows them to establish whether an association is statistically significant and to estimate actual risk levels.
The relationship between passive and active systems forms a detection-to-verification pipeline:
Step 1 — Signal Detection: VAERS or international passive systems identify an unexpected pattern (e.g., an unusual number of reports of a specific condition following vaccination).
Step 2 — Signal Verification: VSD, BEST, or international active systems conduct controlled studies to determine whether the signal represents a genuine increased risk or is consistent with background rates.
Step 3 — Regulatory Action: If active surveillance confirms a genuine safety concern, regulatory agencies can update vaccine labeling, issue safety communications, modify recommendations, or in rare cases suspend or revoke authorization.
This pipeline has produced concrete results. For example, the detection of myocarditis following mRNA COVID-19 vaccines followed this exact sequence: VAERS reports triggered investigation, VSD and BEST studies confirmed an elevated risk in specific age groups, and regulatory agencies updated guidance accordingly.
Transparency advocates have called for increased public access to underlying surveillance records and analytical methodologies, arguing that open data strengthens public confidence in the monitoring process.
The European Medicines Agency operates EudraVigilance, a centralized system for reporting and analyzing suspected adverse reactions to medicines authorized in the European Economic Area. EudraVigilance combines passive reporting with signal detection algorithms.
The World Health Organization coordinates international pharmacovigilance through the Uppsala Monitoring Centre and the VigiBase database, which aggregates adverse event reports from over 170 countries. This global scope allows detection of signals that may be too rare to appear in any single national system.
For detailed information on international reporting systems, see our Global Reporting Systems hub.