The case test-negative design for studies of the effectiveness of influenza vaccine in inpatient settings

摘要: Background The test-negative design (TND) to evaluate influenza vaccine effectiveness is based on patients seeking care for acute respiratory infection, with those who test positive as cases and the test-negatives serving controls. This has not been validated inpatient setting where selection bias might be different from an outpatient setting. Methods We derived mathematical expressions (VE) against laboratory-confirmed hospitalizations used numerical simulations verify theoretical results exploring expected biases under various scenarios. explored meaningful interpretations of VE estimates TND studies. Results studies capture vaccine-mediated protection source population hospitalizations. If vaccination does modify disease severity, these are equivalent virus infection. chronic cardiopulmonary individuals enrolled because non-infectious exacerbation, biased (too high) will result. status adjusted accurately, unbiased. illness cannot adequately characterized, excluding may provide unbiased estimates. Conclusions offers logistic advantages can valid VE. highly vaccinated exacerbation conditions eligible study inclusion, result unless this group well characterized analysis adjust it. Otherwise, such groups subjects should excluded analysis.