Postmarketing Vaccine Safety Assessments

Abstract

After the initial randomized clinical trials and emergency use authorization of the COVID-19 vaccines by the US Food and Drug Administration (FDA) during the COVID-19 pandemic, the US Centers for Disease Control and Prevention (CDC) and the FDA undertook extensive postmarketing vaccine safety surveillance activities in the US, with close monitoring by an independent safety committee. 1 Analysis of surveillance data identified several important adverse events associated with receipt of the COVID-19 vaccines.When evolving data provided evidence for a potential causal relationship between vaccine receipt and a specific adverse event, the potential risk associated with the vaccine was quantified, other risk factors for the specific adverse event were identified (eg, age, sex), and the risks vs benefits were assessed. 1 On January 13, 2023, the FDA and the CDC issued a joint public communication 2 about the identification of a preliminary safety signal within the Vaccine Safety Datalink surveillance system for ischemic stroke within 21 days after receipt of a COVID-19 bivalent mRNA vaccine for individuals 65 years of age and older. This public communication 2 also specified that the safety signal indicating a potential increased risk of stroke appeared greater when the COVID-19 bivalent mRNA vaccines (also called boosters) were given concomitantly with either a high-dose or adjuvanted influenza vaccine than when given alone.To further investigate this safety signal, the FDA conducted an analysis and Lu et al 3 report the results in this issue of JAMA. The analysis used data from Medicare beneficiaries aged 65 years or older and assessed the risk of stroke after receipt of either brand of COVID-19 bivalent mRNA vaccine alone or when given concomitantly with a high-dose or adjuvanted influenza vaccine. Lu et al 3 used a self-controlled case series design in which individuals act as their own controls. The temporal association between a transient exposure and an event is evaluated and all time-invariant confounding is eliminated. 4 Among more than 5 million recipients of either brand of COVID-19 bivalent mRNA vaccine, the study identified 11 001 (0.20%) with a cerebrovascular outcome (nonhemorrhagic stroke, transient ischemic attack, or hemorrhagic stroke). The study found no increased stroke risk associated with either brand of COVID-19 bivalent mRNA vaccine when administered alone. The results from this large cohort are reassuring and are consistent with those reported from France 5 and Israel. 6 In addition, no safety signal has been issued by the European Medicines Agency. 7 Even though these studies provide reassurance of no increased stroke risk associated with either brand of COVID-19 19. Global Vaccine Data Network. Genomics of COVID-19 vaccine-related adverse events. Accessed February 13, 2024. https://www. globalvaccinedatanetwork.org/genomics-covid-19vaccine-induced-adverse-events 20. US Food and Drug Administration. Vaccines. Accessed February 13, 2024. https://www.fda.gov/ vaccines-blood-biologics/vaccines