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Updated: Apr 21, 2026

An Optimized Hemagglutination Inhibition HI Assay to Quantify Influenza-specific Antibody Titers
Published on: December 1, 2017
Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review
Sheena G Sullivan1, Shuo Feng, Benjamin J Cowling
1WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity , 792 Elizabeth St, Melbourne VIC 3000 , Australia.
Background:
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.
Objectives:
We reviewed features in the design, analysis and reporting of 85 published test-negative studies.
Data Sources:
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.
Study Appraisal:
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.
Results:
There was considerable variation in the analytic approach, with 68 unique statistical models identified among the studies.
Conclusion:
Harmonization of analytic approaches may improve the potential for pooling VE estimates.
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