Vaccine safety monitoring in the US is a multilayered process that combines passive and active functions, as well as expert analyses of specific safety questions. Side effects are passively reported from databases while illness rates are actively surveilled.

Vaccine safety continues to be monitored well after the shots are FDA cleared and become available to the public. But what is involved in each step, who monitors vaccines, and for how long are discussed by experts below.

What key criteria inform vaccine safety decisions and approval by the FDA?

Prior to a vaccine’s approval, the FDA evaluates safety across all three required phases of clinical trials, and safety monitoring continues in a fourth, postmarketing phase, said Robert H. Hopkins, Jr, MD, medical director of the National Foundation for Infectious Diseases, and professor of internal medicine and pediatrics at the College of Medicine, University of Arkansas Medical Sciences, Little Rock, Arkansas, in an interview.

“During clinical trials, both solicited adverse events specifically identified by trial designers and unsolicited adverse events are systematically collected and analyzed,” said Hopkins.

“The final stage of clinical trials for a new vaccine typically includes tens of thousands of participants and is designed to detect common safety concerns,” said Hopkins. After approval, postmarketing surveillance continues to monitor for less common adverse events that may not have been identified during clinical trials, he added.

What are the steps in the vaccine safety monitoring process?

The Vaccine Adverse Event Reporting System (VAERS) is operated jointly by the CDC and the FDA. The passive monitoring program allows healthcare providers, drug companies, and the public to report possible side effects from vaccines. VAERS serves as an early warning system that can identify unusual patterns or events in response to vaccination, such as allergic reactions, but does not prove causality.

At the next level, several systems exist for active surveillance of vaccines in use. The Vaccine Safety Datalink (VSD) is a partnership between the CDC and healthcare organizations to review electronic health records and compare rates of illness in vaccinated vs unvaccinated groups.

V-safe, a smartphone-based tool, allows individuals to self-report side effects following vaccination and allows real-time data collection.

Finally, the Clinical Immunization Safety Assessment (CISA) project, established by the CDC in 2001, provides consultations to healthcare providers on vaccine safety questions and conducts research to address specific vaccine safety concerns.

“Vaccine safety experts in the United States frequently collaborate with counterparts in other countries to broaden the net even further to evaluate the safety of a new vaccine,” said Hopkins. “The newest safety system, V-safe, was launched with COVID-19 vaccines and has since been expanded to assess RSV [respiratory syncytial virus] vaccines,” he added.

How do passive and active monitoring work together?

“VAERS serves as a broad early warning system where anyone can report any problem after a vaccine is administered,” said Shirin Mazumder, MD, infectious diseases specialist and associate professor at The University of Tennessee Health Science Center, Memphis, Tennessee, in an interview.

Data analysis and expert review follow a VAERS report, as the next level of safety monitoring checkpoints, she said.

If VAERS identifies a potential vaccine safety issue, the CDC and FDA use data from the VSD and CISA to determine how often the adverse event occurs. Experts conduct controlled studies to determine the frequency of an adverse event, whether it was caused by the vaccine, and risk factors. Based on the results of this research, public health officials may update vaccine information or adjust recommendations.

“Since VAERS reports may not always indicate a causal link, other surveillance methods such as VSD and CISA are in place to help determine causality,” Mazumder said. “All of the surveillance systems together help to create a multilayered system to ensure vaccine safety and benefit public health,” Mazumder emphasized.

Despite limitations and inevitable adverse events/side effects, how does the current system continue to support the benefits of vaccination over the risks? What additional work is needed?

Vaccine safety monitoring in the US is quite robust but requires financial support, scientific and epidemiologic expertise, and human resources to continue to operate, Hopkins said. “Expanded monitoring using more electronic medical record systems, ongoing development of consensus definitions for potential adverse events, expansion of V-Safe like projects, and broader international collaborations could all deepen the ability to assess and monitor vaccine safety,” he noted. The current system is well prepared to assess vaccine safety longitudinally and has resulted in hundreds of published studies supporting the safety and effectiveness of current vaccines, Hopkins said. “We, as a society, need to continue to support these systems and the experts who operate them to ensure the ongoing safe use of vaccines,” he emphasized.

How should clinicians advise patients about vaccine safety?

“Vaccines are among the most closely monitored medical products in use today, with safety assessed before approval and continuously evaluated afterward using multiple, complementary surveillance systems,” Hopkins told Medscape Medical News. “The evidence remains clear: Vaccines help prevent severe disease, and undermining confidence in their safety risks increasing illness, disability, and deaths that vaccination can help prevent,” he said.

VAERS limitations include the possibility of both overreporting and underreporting of vaccine-related issues, and it is possible that rare events may be missed, Mazumder told Medscape Medical News. “The VSD relies on data from electronic health record systems from integrated health systems, which may not accurately represent all populations and can be limited in diversity depending on the available data,” she noted.

However, the combination of passive and active systems for vaccine safety monitoring in the US allows for reliable capture and analysis of potential adverse events, said Mazumder. The current system has been in place for decades and has a history of successfully identifying vaccine safety issues, she added. “The current system allows for a thorough investigation of safety concerns to ensure the benefits of vaccines in preventing life-threatening infections outweigh the possibility of rare adverse events,” she said.

Hopkins and Mazumder disclosed having no relevant financial relationships.