1887
  1. Home
  2. Eurosurveillance
  3. Volume 26, Issue 36, 09/Sep/2021
  4. Article
Research Open Access
Like 0
Download

Abstract

Background

Cohort studies on vaccine effectiveness are prone to confounding bias if the distribution of risk factors is unbalanced between vaccinated and unvaccinated study subjects.

Aim

We aimed to estimate influenza vaccine effectiveness in the elderly population in Finland by controlling for a sufficient set of confounders based on routinely available register data.

Methods

For each of the eight consecutive influenza seasons from 2012/13 through 2019/20, we conducted a cohort study comparing the hazards of laboratory-confirmed influenza in vaccinated and unvaccinated people aged 65–100 years using individual-level medical and demographic data. Vaccine effectiveness was estimated as 1 minus the hazard ratio adjusted for the confounders age, sex, vaccination history, nights hospitalised in the past and presence of underlying chronic conditions. To assess the adequacy of the selected set of confounders, we estimated hazard ratios of off-season hospitalisation for acute respiratory infection as a negative control outcome.

Results

Each analysed cohort comprised around 1 million subjects, of whom 37% to 49% were vaccinated. Vaccine effectiveness against laboratory-confirmed influenza ranged from 16% (95% confidence interval (CI): 12–19) to 48% (95% CI: 41–54). More than 80% of the laboratory-confirmed cases were hospitalised. The adjusted off-season hazard ratio estimates varied between 1.00 (95% CI: 0.94–1.05) and 1.08 (95% CI: 1.01–1.15), indicating that residual confounding was absent or negligible.

Conclusion

Seasonal influenza vaccination reduces the hazard of severe influenza disease in vaccinated elderly people. Data about age, sex, vaccination history and utilisation of hospital care proved sufficient to control confounding.

© 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.2021.26.36.2100054
2021-09-09
2024-12-21
/content/10.2807/1560-7917.ES.2021.26.36.2100054
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/26/36/eurosurv-26-36-3.html?itemId=/content/10.2807/1560-7917.ES.2021.26.36.2100054&mimeType=html&fmt=ahah

References

  1. Baum U, Sundman J, Jääskeläinen S, Nohynek H, Puumalainen T, Jokinen J. Establishing and maintaining the National Vaccination Register in Finland. Euro Surveill. 2017;22(17):30520.  https://doi.org/10.2807/1560-7917.ES.2017.22.17.30520  PMID: 28488994 
  2. Smith PG, Rodrigues LC, Fine PE. Assessment of the protective efficacy of vaccines against common diseases using case-control and cohort studies. Int J Epidemiol. 1984;13(1):87-93.  https://doi.org/10.1093/ije/13.1.87  PMID: 6698708 
  3. Halloran ME, Longini IM Jr, Struchiner CJ. Estimability and interpretation of vaccine efficacy using frailty mixing models. Am J Epidemiol. 1996;144(1):83-97.  https://doi.org/10.1093/oxfordjournals.aje.a008858  PMID: 8659489 
  4. Baum U, Auranen K, Kulathinal S, Syrjänen R, Nohynek H, Jokinen J. Cohort study design for estimating the effectiveness of seasonal influenza vaccines in real time based on register data: The Finnish example. Scand J Public Health. 2020;48(3):316-22.  https://doi.org/10.1177/1403494818808635  PMID: 30387371 
  5. Remschmidt C, Wichmann O, Harder T. Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: a systematic review. BMC Infect Dis. 2015;15(1):429.  https://doi.org/10.1186/s12879-015-1154-y  PMID: 26474974 
  6. World Health Organization (WHO). Influenza (seasonal). Geneva: WHO; 2018. Available from: https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)
  7. Hellfritzsch M, Thomsen RW, Baggesen LM, Larsen FB, Sørensen HT, Christiansen CF. Lifestyle, socioeconomic characteristics, and medical history of elderly persons who receive seasonal influenza vaccination in a tax-supported healthcare system. Vaccine. 2017;35(18):2396-403.  https://doi.org/10.1016/j.vaccine.2017.03.040  PMID: 28343782 
  8. Foppa IM, Ferdinands JM, Chung J, Flannery B, Fry AM. Vaccination history as a confounder of studies of influenza vaccine effectiveness. Vaccine X. 2019;1:100008.  https://doi.org/10.1016/j.jvacx.2019.100008  PMID: 31384730 
  9. Han L, Ran J, Mak YW, Suen LK, Lee PH, Peiris JSM, et al. Smoking and influenza-associated morbidity and mortality: a systematic review and meta-analysis. Epidemiology. 2019;30(3):405-17.  https://doi.org/10.1097/EDE.0000000000000984  PMID: 30789425 
  10. World Health Organization (WHO). ICD-10: international statistical classification of diseases and related health problems: tenth revision, 2nd ed. Geneva: WHO; ‎2004‎. Available from: https://apps.who.int/iris/handle/10665/4298015
  11. Kalbfleisch J, Prentice RL. The statistical analysis of failure time data. 2nd ed. Hoboken: John Wiley and Sons; 2002.
  12. 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 
  13. Rondy M, El Omeiri N, Thompson MG, Levêque A, Moren A, Sullivan SG. Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies. J Infect. 2017;75(5):381-94.  https://doi.org/10.1016/j.jinf.2017.09.010  PMID: 28935236 
  14. Rondy M, Gherasim A, Casado I, Launay O, Rizzo C, Pitigoi D, et al. Low 2016/17 season vaccine effectiveness against hospitalised influenza A(H3N2) among elderly: awareness warranted for 2017/18 season. Euro Surveill. 2017;22(41).  https://doi.org/10.2807/1560-7917.ES.2017.22.41.17-00645  PMID: 29043961 
  15. Örtqvist Å, Brytting M, Leval A, Hergens MP. Impact of repeated influenza vaccinations in persons over 65 years of age: A large population-based cohort study of severe influenza over six consecutive seasons, 2011/12-2016/17. Vaccine. 2018;36(37):5556-64.  https://doi.org/10.1016/j.vaccine.2018.07.052  PMID: 30076104 
  16. Rose AMC, Kissling E, Gherasim A, Casado I, Bella A, Launay O, et al. Vaccine effectiveness against influenza A(H3N2) and B among laboratory-confirmed, hospitalised older adults, Europe, 2017-18: A season of B lineage mismatched to the trivalent vaccine. Influenza Other Respir Viruses. 2020;14(3):302-10.  https://doi.org/10.1111/irv.12714  PMID: 32022450 
  17. Stuurman AL, Bollaerts K, Alexandridou M, Biccler J, Díez Domingo J, Nohynek H, et al. Vaccine effectiveness against laboratory-confirmed influenza in Europe - Results from the DRIVE network during season 2018/19. Vaccine. 2020;38(41):6455-63.  https://doi.org/10.1016/j.vaccine.2020.07.063  PMID: 32778474 
  18. Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010;59(33):1057-62. PMID: 20798667 
  19. Rose A, Kissling E, Emborg HD, Larrauri A, McMenamin J, Pozo F, et al. Interim 2019/20 influenza vaccine effectiveness: six European studies, September 2019 to January 2020. Euro Surveill. 2020;25(10):2000153.  https://doi.org/10.2807/1560-7917.ES.2020.25.10.2000153  PMID: 32183932 
  20. Belongia EA, Skowronski DM, McLean HQ, Chambers C, Sundaram ME, De Serres G. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence. Expert Rev Vaccines. 2017;16(7):1-14.  https://doi.org/10.1080/14760584.2017.1334554  PMID: 28562111 
  21. Valenciano M, Kissling E, Larrauri A, Nunes B, Pitigoi D, O’Donnell J, et al. Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I-MOVE multicentre test-negative case-control study, 2011/2012-2016/2017. Influenza Other Respir Viruses. 2018;12(5):567-81.  https://doi.org/10.1111/irv.12562  PMID: 29659149 
  22. Jackson LA, Jackson ML, Nelson JC, Neuzil KM, Weiss NS. Evidence of bias in estimates of influenza vaccine effectiveness in seniors. Int J Epidemiol. 2006;35(2):337-44.  https://doi.org/10.1093/ije/dyi274  PMID: 16368725 
  23. Zhang HT, McGrath LJ, Ellis AR, Wyss R, Lund JL, Stürmer T. Restriction of pharmacoepidemiologic cohorts to initiators of medications in unrelated preventive drug classes to reduce confounding by frailty in older adults. Am J Epidemiol. 2019;188(7):1371-82.  https://doi.org/10.1093/aje/kwz083  PMID: 30927359 
  24. Nation ML, Moss R, Spittal MJ, Kotsimbos T, Kelly PM, Cheng AC. Influenza vaccine effectiveness against influenza-related mortality in Australian hospitalized patients: a propensity score analysis. Clin Infect Dis. 2021;72(1):99-107. PMID: 31903487 
  25. Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology. 2009;20(4):512-22.  https://doi.org/10.1097/EDE.0b013e3181a663cc  PMID: 19487948 
  26. Stürmer T, Joshi M, Glynn RJ, Avorn J, Rothman KJ, Schneeweiss S. A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods. J Clin Epidemiol. 2006;59(5):437-47.  https://doi.org/10.1016/j.jclinepi.2005.07.004  PMID: 16632131 
  27. Elze MC, Gregson J, Baber U, Williamson E, Sartori S, Mehran R, et al. Comparison of propensity score methods and covariate adjustment: evaluation in 4 cardiovascular studies. J Am Coll Cardiol. 2017;69(3):345-57.  https://doi.org/10.1016/j.jacc.2016.10.060  PMID: 28104076 
  28. Jackson ML, Nelson JC, Jackson LA. Why do covariates defined by International Classification of Diseases codes fail to remove confounding in pharmacoepidemiologic studies among seniors? Pharmacoepidemiol Drug Saf. 2011;20(8):858-65.  https://doi.org/10.1002/pds.2160  PMID: 21671442 
  29. Tokars JI, Patel MM, Foppa IM, Reed C, Fry AM, Ferdinands JM. Waning of measured influenza vaccine effectiveness over time: the potential contribution of leaky vaccine effect. Clin Infect Dis. 2020;71(10):e633-41.  https://doi.org/10.1093/cid/ciaa340  PMID: 32227109 
  30. Baum U, Kulathinal S, Auranen K. Mitigation of biases in estimating hazard ratios under non-sensitive and non-specific observation of outcomes-applications to influenza vaccine effectiveness. Emerg Themes Epidemiol. 2021;18(1):1-10.  https://doi.org/10.1186/s12982-020-00091-z  PMID: 33446220 
Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes, Finland, 2012/13 to 2019/20
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Ulrike+Baum&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Baum Ulrike</a>, <a href="/search?value1=Sangita+Kulathinal&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kulathinal Sangita</a>, <a href="/search?value1=Kari+Auranen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Auranen Kari</a></span>. Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes, Finland, 2012/13 to 2019/20. <a href="/content/ecdc">Euro Surveill.</a> 2021;26(36):pii=2100054. <a href="https://doi.org/10.2807/1560-7917.ES.2021.26.36.2100054" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2021.26.36.2100054</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 12 Jan 2021;&nbsp;&nbsp; <span class="generated">Accepted</span>: 24 Jun 2021 </span> </p>
/content/10.2807/1560-7917.ES.2021.26.36.2100054
/content/10.2807/1560-7917.ES.2021.26.36.2100054
Loading

Data & Media loading...

Supplementary data

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