Postapproval Vaccine Safety Surveillance for COVID-19 Vaccines in the US

Since January 2020, more than 7.8 million cases of coronavirus disease 2019 (COVID-19) and 215 000 deaths have occurred in the US. In response to the pandemic, vaccine development has been moving at record speed through strong public or private partnerships, with nearly 200 vaccine candidates in development or in trials. In the US, 8 vaccine candidates have received federal support under Operation Warp Speed, and 4—from Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, and Janssen—have entered phase 3 trials. Vaccines will be critical for the prevention and control of COVID-19 in the US and worldwide, yet these efforts cannot succeed without public confidence in a vaccination program. Demonstrating vaccine efficacy and safety during clinical trials and implementing a robust postlicensure vaccine safety monitoring system as the vaccine is deployed in larger, more diverse populations is central to public confidence and enabling timely and accurate policy decisions for population-level use. In response to the 2009 H1N1 pandemic and informed by prior experience during the 1976 swine flu vaccination program, the US government assembled a coordinated response to monitor the safety of H1N1 vaccines by convening a Federal Immunization Safety Task Force, composed of numerous federal agencies.1 Led by the National Vaccine Program Office, a harmonized national plan was developed for monitoring vaccine safety that involved a public-private partnership.2 The H1N1 Vaccine Safety Risk Assessment Working Group (VSRAWG) was established as an independent body to review vaccine safety–related data on the 2009 H1N1 vaccine as it became available.1 Importantly, VSRAWG provided transparent and timely communication about vaccine safety as data accumulated and vaccines were broadly distributed in the population. The Advisory Committee on Immunization Practices (ACIP) initially convened the COVID-19 Vaccine Safety Technical (VaST) Working Group in June 2020 to advise the ACIP COVID-19 Vaccine Workgroup and the full ACIP on the safety of COVID-19 vaccines in development and postapproval. The group includes scientific expertise in coronavirus immunology, clinical trials, postmarket vaccine safety surveillance, risk communication, public health, and clinical medicine, as well as federal partners (Centers for Disease Control and Prevention [CDC], US Food and Drug Administration [FDA], Department of Defense [DoD], Veterans Administration [VA], Indian Health Service [IHS]) with long-standing experience in vaccine safety surveillance. The objectives of the VaST Working Group are to review and interpret preapproval and postapproval COVID-19 vaccine candidate safety data and provide guidance on presenting safety data to ACIP and the general public. More specifically, VaST is reviewing the capabilities and protocols of existing and novel vaccine safety surveillance systems that will be engaged in COVID-19 vaccine safety. A brief overview of key considerations for postauthorization/ postlicensure safety surveillance is outlined below, as a starting point for public discussions about plans for COVID-19 vaccine safety monitoring. In addition to phase 4 studies to monitor safety and effectiveness, passive and active safety surveillance systems serve critical functions in ensuring vaccine safety and maintaining vaccine confidence (eTable in the Supplement). The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that relies on reporting by patients or family members, health care professionals, or manufacturers to capture temporally associated, potential adverse events after vaccination.3 VAERS is comanaged by the FDA and CDC and serves as an early warning system for potential safety signals that may be temporally related to vaccines. The rapid identification of an intussusception signal after widespread use of rotavirus vaccines in infants exemplifies the essential role of passive surveillance in the US.4 To rapidly evaluate safety signals, however, active vaccine safety surveillance systems are essential. The Vaccine Safety Datalink is a 30-year collaboration between the CDC and 9 health systems that use health care encounter data and electronic medical records to capture data on vaccines and potential outcomes of interest in a well-defined population of approximately 11.3 million insured patients, with near real-time capabilities for signal detection, signal refinement, and signal evaluation. Similarly, the VA has well-established capabilities to track and monitor vaccine adverse events using an active surveillance system that can detect safety signals in near real time and conduct signal refinement and signal evaluation activities through electronic medical record review in approximately 6.4 million veterans. In addition, the FDA-Centers for Medicare & Medicaid Services (CMS) active surveillance program, established in 2008, is currently enabled for near real-time safety surveillance of CMS claims data for more than 50 million beneficiaries older than 65 years, including approximately 650 000 nursing home residents. These wellestablished active safety surveillance systems form the foundation of monitoring COVID-19 vaccine safety. Novel approaches to complement existing safety surveillance systems are also being explored. Given the need for real-time visibility and to maximize efficiency, several large systems are developing capabilities for enhanced passive surveillance. This approach will leverage systems designed to track COVID-19 vaccine administration and pair them with standardized reporting mechanisms for potential adverse events, such as VIEWPOINT