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
. 2013 Apr 19;31(17):2165-8.
doi: 10.1016/j.vaccine.2013.02.053. Epub 2013 Mar 13.

The test-negative design for estimating influenza vaccine effectiveness

Michael L Jackson  1 , Jennifer C Nelson
Affiliations

The test-negative design for estimating influenza vaccine effectiveness

Michael L Jackson et al. Vaccine. .

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Substances

LinkOut - more resources