1887
  1. Home
  2. Eurosurveillance
  3. Volume 29, Issue 7, 15/Feb/2024
  4. Article
Perspective Open Access
Like 0
Download

Educational

Abstract

Many vaccine effectiveness (VE) analyses of severe disease outcomes such as hospitalisation and death include ‘false’ cases that are not actually caused by the infection or disease under study. While the inclusion of such false cases inflate outcome rates in both vaccinated and unvaccinated populations, it is less obvious how they affect estimates of VE. Illustrating the main points through simple examples, this article shows how VE is underestimated when false cases are included as outcomes. Depending how the outcome indicator is defined, estimates of VE against severe disease outcomes, whose definition allows for the inclusion of false cases, will be biased downwards and may in certain circumstances approximate the same level as the VE against infection. The bias is particularly pronounced for vaccines that offer high levels of protection against severe disease outcomes but poor protection against infection. Analysing outcomes that are measured with low sensitivity generally does not cause bias in VE studies; defining outcome indicators that minimise the number of false cases rather than the number of missed cases is preferable in VE studies.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2024.29.7.2300259
2024-02-15
2024-04-27
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2024.29.7.2300259
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/29/7/eurosurv-29-7-5.html?itemId=/content/10.2807/1560-7917.ES.2024.29.7.2300259&mimeType=html&fmt=ahah

References

  1. World Health Organization (WHO). Classification of omicron (B.1.1.529): SARS-CoV-2 variant of concern. Geneva: WHO: 2021. Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern
  2. Bálint G, Vörös-Horváth B, Széchenyi A. Omicron: increased transmissibility and decreased pathogenicity. Signal Transduct Target Ther. 2022;7(1):151.  https://doi.org/10.1038/s41392-022-01009-8  PMID: 35525870 
  3. Bager P, Wohlfahrt J, Bhatt S, Stegger M, Legarth R, Møller CH, et al. , Omicron-Delta study group. Risk of hospitalisation associated with infection with SARS-CoV-2 omicron variant versus delta variant in Denmark: an observational cohort study. Lancet Infect Dis. 2022;22(7):967-76.  https://doi.org/10.1016/S1473-3099(22)00154-2  PMID: 35468331 
  4. Nyberg T, Ferguson NM, Nash SG, Webster HH, Flaxman S, Andrews N, et al. , COVID-19 Genomics UK (COG-UK) consortium. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022;399(10332):1303-12.  https://doi.org/10.1016/S0140-6736(22)00462-7  PMID: 35305296 
  5. Voor In ’t Holt AF, Haanappel CP, Rahamat-Langendoen J, Molenkamp R, van Nood E, van den Toorn LM, et al. Admissions to a large tertiary care hospital and Omicron BA.1 and BA.2 SARS-CoV-2 polymerase chain reaction positivity: primary, contributing, or incidental COVID-19. Int J Infect Dis. 2022;122(2):665-8.  https://doi.org/10.1016/j.ijid.2022.07.030  PMID: 35842214 
  6. Stowe J, Andrews N, Kirsebom F, Ramsay M, Bernal JL. Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study. Nat Commun. 2022;13(1):5736.  https://doi.org/10.1038/s41467-022-33378-7  PMID: 36180428 
  7. Price AM, Flannery B, Talbot HK, Grijalva CG, Wernli KJ, Phillips CH, et al. Influenza vaccine effectiveness against influenza A(H3N2)-related illness in the United States during the 2021-2022 influenza season. Clin Infect Dis. 2023;76(8):1358-63.  https://doi.org/10.1093/cid/ciac941  PMID: 36504336 
  8. Poland GA, Kennedy RB, Tosh PK. Prevention of monkeypox with vaccines: a rapid review. Lancet Infect Dis. 2022;22(12):e349-58.  https://doi.org/10.1016/S1473-3099(22)00574-6  PMID: 36116460 
  9. Deputy NP, Deckert J, Chard AN, Sandberg N, Moulia DL, Barkley E, et al. Vaccine effectiveness of JYNNEOS against mpox disease in the United States. N Engl J Med. 2023;388(26):2434-43.  https://doi.org/10.1056/NEJMoa2215201  PMID: 37199451 
  10. Gram MA, Emborg H-D, Schelde AB, Friis NU, Nielsen KF, Moustsen-Helms IR, et al. Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study. PLoS Med. 2022;19(9):e1003992.  https://doi.org/10.1371/journal.pmed.1003992  PMID: 36048766 
  11. Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, et al. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med. 2022;386(16):1532-46.  https://doi.org/10.1056/NEJMoa2119451  PMID: 35249272 
  12. Jackson ML, Rothman KJ. Effects of imperfect test sensitivity and specificity on observational studies of influenza vaccine effectiveness. Vaccine. 2015;33(11):1313-6.  https://doi.org/10.1016/j.vaccine.2015.01.069  PMID: 25659280 
  13. Field trials of health interventions: a toolbox. Smith PG, Morrow RH, Ross DA. 3rd edition. Oxford: Oxford University Press; 2015. pp. 211-212.  PMID: 26225404 
  14. Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology. 2010;21(3):383-8.  https://doi.org/10.1097/EDE.0b013e3181d61eeb  PMID: 20335814 
  15. Hansen CH, Moustsen-Helms IR, Rasmussen M, Søborg B, Ullum H, Valentiner-Branth P. Short-term effectiveness of the XBB.1.5 updated COVID-19 vaccine against hospitalisation in Denmark: a national cohort study. Lancet Infect Dis. 2024;24(2):e73-4.  https://doi.org/10.1016/S1473-3099(23)00746-6  PMID: 38190834 
  16. Chung H, Austin PC, Brown KA, Buchan SA, Fell DB, Fong C, et al. Effectiveness of COVID-19 vaccines over time prior to omicron emergence in Ontario, Canada: test-negative design study. Open Forum Infect Dis. 2022;9(9):ofac449.  https://doi.org/10.1093/ofid/ofac449  PMID: 36147595 
  17. World Health Organization (WHO). Evaluation of COVID-19 vaccine effectiveness: Interim guidance. Geneva: WHO; 2021. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-vaccine_effectiveness-measurement-2021.1
Bias in vaccine effectiveness studies of clinically severe outcomes that are measured with low specificity: the example of COVID-19-related hospitalisation
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Christian+Holm+Hansen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hansen Christian Holm</a></span>. Bias in vaccine effectiveness studies of clinically severe outcomes that are measured with low specificity: the example of COVID-19-related hospitalisation. <a href="/content/ecdc">Euro Surveill.</a> 2024;29(7):pii=2300259. <a href="https://doi.org/10.2807/1560-7917.ES.2024.29.7.2300259" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2024.29.7.2300259</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 17 May 2023;&nbsp;&nbsp; <span class="generated">Accepted</span>: 07 Nov 2023 </span> </p>
/content/10.2807/1560-7917.ES.2024.29.7.2300259
/content/10.2807/1560-7917.ES.2024.29.7.2300259
Loading

Data & Media loading...

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error