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

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.