Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 29;12(1):10946.
doi: 10.1038/s41598-022-13809-7.

Comparability of clinical trials and spontaneous reporting data regarding COVID-19 vaccine safety

Chongliang Luo  1   2 , Jingcheng Du  3 , Adam Cuker  4 , Ebbing Lautenbach  5   6 , David A Asch  7   8 , Gregory A Poland  9 , Cui Tao  3 , Yong Chen  10   11
Affiliations

Comparability of clinical trials and spontaneous reporting data regarding COVID-19 vaccine safety

Chongliang Luo et al. Sci Rep. .

Abstract

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines ("Pfizer" vaccine dose 1 and 2, "Moderna" vaccine dose 1 and 2, and "Janssen" vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.

PubMed Disclaimer

Conflict of interest statement

Dr. Cuker has served as a consultant for Synergy; has received authorship royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, Spark, and Takeda. Dr. Asch is partner and part owner of VAL Health. Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland provides consultative advice on vaccine development to Merck & Co., Medicago, GlaxoSmithKline, Sanofi Pasteur, Johnson & Johnson/Janssen Global Services LLC, Emergent Biosolutions, Dynavax, Genentech, Eli Lilly and Company, Kentucky Bioprocessing, Bavarian Nordic, AstraZeneca, Exelixis, Regeneron, Janssen, Vyriad, Moderna, and Genevant Sciences, Inc. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Dr. Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. Poland has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. The rest of the authors report no conflicts of interest.

Figures

Figure 1
Figure 1
The reporting risks of AEs after COVID-19 vaccines reported in VAERS from 12/14/2020 to 09/17/2021. The denominators (numbers of VAERS reports on particular vaccine doses) are 83,877, 57,431, 101,383, 54,386 and 29,877 for Pfizer dose 1 and 2, Moderna dose 1 and 2, and Janssen vaccines respectively.
Figure 2
Figure 2
COVID-19 vaccine safety study from three randomized controlled trials– (RCTs) and the CDC vaccine adverse event reporting system (VAERS). Five groups are compared, i.e. Pfizer-1st (P1), Pfizer-2nd (P2), Moderna-1st (M1), Moderna-2nd (M2) and Janssen (J). Rank consistency is shown between RCTs and VAERS regarding local and systemic adverse events (AEs), including pain, erythema, swelling, headache, fever, chill, fatigue, nausea/vomiting, arthralgia and myalgia. The evidence is extended to study the other severe and rare AEs including shingles, hearing impairment, thrombosis, facial paralysis, anaphylaxis, pulmonary embolism, myocarditis, and GBS using VAERS. aFollow up 7 days for solicited local and systemic AEs, and 1 month for unsolicited AEs; bage 16 + for the Pfizer trial, and no exclusion of participants with history of COVID-19 infection for the Janssen trial; csample size N = 9839, 9839, 15,168, 14,677 and 3356 for P1, P2, M1, M2 and J, respectively; dreported to VAERS from Dec. 2020 to Sep. 2021; eN = 83,877, 57,431, 101,383, 54,386 and 29,877 for P1, P2, M1, M2 and J respectively; fGBS Guillain–Barré syndrome.
See this image and copyright information in PMC

References

    1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577. - DOI - PMC - PubMed
    1. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021;384(5):403–416. doi: 10.1056/NEJMoa2035389. - DOI - PMC - PubMed
    1. Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N. Engl. J. Med. 2021;384(23):2187–2201. doi: 10.1056/NEJMoa2101544. - DOI - PMC - PubMed
    1. Thomas SJ, Moreira ED, Jr, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months. N. Engl. J. Med. 2021;385(19):1761–1773. doi: 10.1056/NEJMoa2110345. - DOI - PMC - PubMed
    1. See I, Su JR, Lale A, et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021;325:2448–2456. doi: 10.1001/jama.2021.7517. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances