Over a 20-year period, United States Food and Drug Administration (FDA)-approved vaccines were found to be remarkably safe, according to data published in the Annals of Internal Medicine. Although existing postmarketing surveillance programs identified a large proportion of safety issues, these were of limited clinical significance.

To investigate postmarketing safety modifications in FDA-approved vaccines, the initial and subsequent labels of all 57 vaccines that were approved during the study period (January 1996-December 2015) were included in a descriptive analysis of the prevalence and characteristics of post approval, safety-related label changes.

Randomized controlled trials supported the initial approval for 93% of the vaccines, with a median cohort size of 4161 participants (interquartile range [IQR] 2204-8634 participants). Investigators identified 58 post-approval, safety-related label modifications associated with 25 vaccines. These included 49 warnings and precautions, 8 contraindications, and 1 safety-related withdrawal. The characteristics of initial approval trials were similar in vaccines with and without postmarketing, safety-related label modifications. Expansion of population restrictions (n=21) was the most common safety issue triggering label modifications, followed by allergies (n=13); and post marketing surveillance was the most common source of safety data (n=28 of 58).

Investigators reported several study limitations including that the initial signal triggering safety-related label changes may not necessarily represent the sources of other safety data received and processed by the FDA. Investigators also chose to focus on a single source of initial safety signal despite the fact that some safety issues were supported by data from several sources of varying importance as this would have complicated the analysis; a different method may have resulted in different findings. It is also possible that wording in drug labels about the triggering data sources may be inaccurate or incomplete. Inferential analysis was also limited by the small number of safety modifications and by heterogeneity of the included vaccines.

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 “A review of all safety-related label modifications…found that vaccines were remarkably safe,” said investigators. A large proportion of safety issues were quickly identified via current postmarketing surveillance programs, which led to the withdrawal of only a single vaccine. “These data highlight the robustness of the vaccine approval and postmarketing surveillance processes and confirm population vaccination as a major public health strategy.”


Tau N, Yahav D, Shepshelovich D. Postmarketing safety of vaccines approved by the U.S. Food and Drug Administration: A cohort study. [published online July 28, 2020]. Ann Intern Med. doi:10.7326/M20-2726