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Cited by 510Influenza Virus Research StudiesStatistical Methods in EpidemiologyVaccine Coverage and Hesitancy

The test-negative design for estimating influenza vaccine effectiveness

Jackson, Michael L., Nelson, Jennifer C.·2013·Vaccine
DOI 10.1016/j.vaccine.2013.02.053
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Abstract

Objective The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed.Methods In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative.Results With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time.Conclusions The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata.

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  • Vaccine effectiveness was estimated using the test-negative, case-control study design.

    “Vaccine effectiveness was estimated using the test-negative, case–control study design11,12, applying methodology that was developed earlier to assess duration of protection of the BNT162b213 and mRNA-127314 vaccines in the same population during pre-Omicron SARS-CoV-2 infection waves (Methods).”

    From Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar (2022) · cites this paper as [11]

  • Vaccine effectiveness against symptomatic SARS-CoV-2 Omicron infection during the Omicron wave in Qatar was estimated using the test-negative, case-control study design, a standard design for assessing vaccine effectiveness.

    “Vaccine effectiveness against symptomatic SARS-CoV-2 Omicron (B.1.1.529)1 infection during the large Omicron wave in Qatar, between December 23, 2021 and February 28, 2022, was estimated using the test-negative, case–control study design, a standard design for assessing vaccine effectiveness11,12,36,40.”

    From Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar (2022) · cites this paper as [11]

  • The cohort study design applied earlier to the same population of Qatar yielded findings similar to those of the test-negative case-control design, supporting the validity of this standard approach in assessing vaccine effectiveness.

    “However, the cohort study design applied earlier to the same population of Qatar yielded findings similar to those of the test-negative case–control design36,38,39, supporting the validity of this standard approach in assessing vaccine effectiveness11,12,36,40.”

    From Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar (2022) · cites this paper as [11]

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Authors
Jackson, M. L., & Nelson, J. C.
Affiliations
Kaiser Permanente Washington Health Research Institute (US)
Corresponding author
Jackson, Michael L.
ORCID
Venue
Vaccine
Publisher
Elsevier BV
Published
2013-04
Volume
31
Issue
17
Pages
2165-2168
ISSN
0264-410X (ISSN-L)
DOI
10.1016/j.vaccine.2013.02.053
OpenAlex
W2010123683
Cited by
510
References
17
Citations by year
2026: 32 · 2025: 46 · 2024: 45 · 2023: 42 · 2022: 54 · 2021: 42 · 2020: 33 · 2019: 39 · 2018: 30 · 2017: 34 · 2016: 38 · 2015: 25 · 2014: 36 · 2013: 14
FWCI
27.50
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Vaccine (publishedVersion)
  • PubMed (publishedVersion)
Funders
Centers for Disease Control and Prevention (U01IP000466)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
  • Social Sciences › Health › Vaccine Coverage and Hesitancy
Keywords
test-negative design, influenza vaccine effectiveness, acute respiratory illness, health-seeking behavior, confounding, observational study design
MeSH terms
Adolescent, Adult, Humans, Influenza, Human, Influenza Vaccines, Patient Acceptance of Health Care, Research Design, Time Factors, Vaccination, Bias, Incidence, Treatment Outcome

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