Estimating Effectiveness of Influenza and COVID-19 Vaccines: The “Test-Negative” Design
By
Josh Michaud
Jennifer Kates
April 30, 2026
Clinical Scorecard: Assessing the Efficacy of Influenza and COVID-19 Vaccines Using the 'Test-Negative' Approach
At a Glance
Category Detail
Condition Influenza and COVID-19 Key Mechanisms Vaccine effectiveness (VE) assessed through the test-negative design, comparing vaccination status between cases and controls. Target Population Individuals seeking healthcare with respiratory symptoms. Care Setting Healthcare facilities conducting diagnostic testing.
Key Highlights
Vaccine effectiveness (VE) measures real-world protection against health outcomes. The test-negative design is a prevalent method for studying VE for respiratory vaccines. VE is calculated using odds ratios from cases (positive tests) and controls (negative tests). Statistical techniques control for confounding factors like age and comorbidities. The approach is efficient and reduces bias in healthcare-seeking behavior. Guideline-Based Recommendations
Diagnosis
Use the test-negative design to assess vaccine effectiveness in respiratory diseases. Management
Monitor vaccine effectiveness using observational studies rather than randomized controlled trials. Monitoring & Follow-up
Utilize existing surveillance and diagnostic testing infrastructure in healthcare settings. Risks
Consider potential biases in healthcare-seeking behavior when interpreting results. Patient & Prescribing Data
Patients presenting with respiratory symptoms at healthcare facilities.
Vaccination status should be assessed in conjunction with testing for respiratory pathogens.
Clinical Best Practices
Implement the test-negative design for evaluating vaccine effectiveness. Ensure statistical controls for confounding variables in study designs. Leverage healthcare facility resources for efficient data collection. References
