Postmarketing Safety of Vaccines Approved by the U.S. Food and Drug Administration : A Cohort Study

Ann Intern Med. 2020 Sep 15;173(6):445-449. doi: 10.7326/M20-2726. Epub 2020 Jul 28.


Background: Vaccines are one of the greatest achievements in public health. Prevalence and clinical significance of emerging postapproval, vaccine-related safety issues have not been systematically studied.

Objective: To explore postmarketing safety modifications in U.S. Food and Drug Administration (FDA)-approved vaccine labels.

Design: Retrospective cohort study.

Setting: United States.

Participants: Initial and subsequent labels of all vaccines that were FDA-approved between 1 January 1996 and 31 December 2015.

Measurements: The primary aim was a descriptive analysis of the prevalence and characteristics of postapproval, safety-related label changes. The secondary aim was to describe the distribution of data sources triggering these modifications.

Results: The study cohort comprised 57 FDA-approved vaccines. Initial approval for 53 (93%) of the vaccines was supported by randomized controlled trials, with a median cohort size of 4161 participants (interquartile range, 2204 to 8634 participants). There were 58 postapproval, safety-related label modifications associated with 25 vaccines (49 warnings and precautions, 8 contraindications, and 1 safety-related withdrawal). The initial approval trial characteristics were similar in vaccines with and without postmarketing, safety-related label modifications. The most common safety issue triggering label modifications was expansion of population restrictions (n = 21 [36%]), followed by allergies (n = 13 [22%]). The most common source of safety data was postmarketing surveillance (n = 28 of 58 [48%]).

Limitation: The data source of the initial signal triggering safety-related label changes may not necessarily represent all safety data received and processed by the FDA.

Conclusion: Over a 20-year period, vaccines were found to be remarkably safe. A large proportion of safety issues were identified through existing postmarketing surveillance programs and were of limited clinical significance. These findings confirm the robustness of the vaccine approval system and postmarketing surveillance.

Primary funding source: None.

MeSH terms

  • Drug Labeling* / methods
  • Drug Labeling* / standards
  • Drug Labeling* / statistics & numerical data
  • Humans
  • Product Surveillance, Postmarketing* / methods
  • Retrospective Studies
  • United States
  • United States Food and Drug Administration*
  • Vaccines / adverse effects*
  • Vaccines / therapeutic use


  • Vaccines