Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review.


There was considerable variation in the analytic approach, with 68 unique statistical models identified among the studies.

Harmonization of analytic approaches may improve the potential for pooling VE estimates.

Design features that may affect the validity and comparability of reported estimates were reviewed, including setting, study period, source population, case definition, exposure and outcome ascertainment and statistical model.

Studies were identified from PubMed, reference lists and email updates. Study eligibility: All studies using the test-negative design reporting end-of-season estimates were included.

The test-negative design is a variant of the case-control study being increasingly used to study influenza vaccine effectiveness (VE). In these studies, patients with influenza-like illness are tested for influenza. Vaccine coverage is compared between those testing positive versus those testing negative to estimate VE.

We reviewed features in the design, analysis and reporting of 85 published test-negative studies.

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