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Clinical Trial
. 2022 Nov;11(16):1161-1172.
doi: 10.2217/cer-2022-0069. Epub 2022 Sep 23.

Evaluating real-world COVID-19 vaccine effectiveness using a test-negative case-control design

Matthew W Reynolds  1 , Alex Secora  1 , Alice Joules  1 , Lisa Albert  1 , Emma Brinkley  1 , Tom Kwon  1 , Christina Mack  1 , Stephen Toovey  2 , Nancy A Dreyer  1
Affiliations
Clinical Trial

Evaluating real-world COVID-19 vaccine effectiveness using a test-negative case-control design

Matthew W Reynolds et al. J Comp Eff Res. 2022 Nov.

Abstract

Aim: It is important to assess if clinical trial efficacy translates into real-world effectiveness for COVID-19 vaccines. Materials & methods: We conducted a modified test-negative design (TND) to evaluate the real-world effectiveness of three COVID-19 vaccines. We defined cases in two ways: self-reported COVID-19-positive tests, and self-reported positive tests with ≥1 moderate/severe COVID-19 symptom. Results: Any vaccination was associated with a 95% reduction in subsequently reporting a positive COVID-19 test, and a 71% reduction in reporting a positive test and ≥1 moderate/severe symptom. Conclusion: We observed high effectiveness across all three marketed vaccines, both for self-reported positive COVID-19 tests and moderate/severe COVID-19 symptoms. This innovative TND approach can be implemented in future COVID-19 vaccine and treatment real-world effectiveness studies. Clinicaltrials.gov identifier: NCT04368065.

Keywords: COVID-19; SARS-CoV-2; patient-reported outcomes; person-generated health data; symptoms; test-negative design; vaccines.

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Figures

Figure 1.
Figure 1.. Vaccination status determination at time of COVID-19 testing for single-dose and two-dose vaccines.
Figure 2.
Figure 2.. Vaccine effectiveness of preventing cases of COVID-19 among those with at least one vaccination versus unvaccinated, overall and by manufacturer (primary analysis based on COVID-19 test results).
Figure 3.
Figure 3.. Vaccine effectiveness of preventing cases of COVID-19 among those with at least one vaccination versus unvaccinated, overall and by manufacturer (secondary analysis based on test results and requiring at least one moderate to severe symptom).
See this image and copyright information in PMC

References

    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. 384(5), 403–416 (2021). - PMC - PubMed
    1. Polack FP, Thomas SJ, Kitchin N et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 383(27), 2603–2615 (2020). - 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. 384(23), 2187–2201 (2021). - PMC - PubMed
    1. Patel MM, Jackson ML, Ferdinands J. Postlicensure evaluation of COVID-19 vaccines. JAMA 324(19), 1939–1940 (2020). - PubMed

    2. • Peer-reviewed publication of post-licensure evaluation of COVID-19 vaccines using test-negative design. Findings show that “the test-negative design is popular because it offers 2 advantages: simplified logistics, because controls are already identified when identifying cases, and reduced confounding due to similar health care use patterns between cases and controls, similar to a nested case–control study”.

    1. Chua H, Feng S, Lewnard JA et al. The use of test-negative controls to monitor vaccine effectiveness: a systematic review of methodology. Epidemiology 31(1), 43–64 (2020). - PMC - PubMed

    2. • Peer-reviewed publication of methodology of using test-negative design. Findings show that “The test-negative design has been increasingly used as an efficient study design to estimate vaccine effectiveness for a range of vaccines and pathogens”.

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