Modeling the Impacts of Clinical Influenza Testing on Influenza Vaccine Effectiveness Estimates

Abstract

Background Test-negative design studies for evaluating influenza vaccine effectiveness (VE) enroll patients with acute respiratory infection. Enrollment typically occurs before influenza status is determined, resulting in over-enrollment of influenza-negative patients. With availability of rapid and accurate molecular clinical testing, influenza status could be ascertained prior to enrollment, thus improving study efficiency. We estimate potential biases in VE when using clinical testing. Methods We simulate data assuming 60% vaccinated, 25% of those vaccinated are influenza positive, and VE of 50%. We show the effect on VE in five scenarios. Results VE is affected only when clinical testing preferentially targets patients based on both vaccination and influenza status. VE is overestimated by 10% if non-testing occurs in 39% of vaccinated influenza-positive patients and 24% of others; and if non-testing occurs in 8% of unvaccinated influenza-positive patients and 27% of others. VE is underestimated by 10% if non-testing occurs in 32% of unvaccinated influenza-negative patients and 18% of others. Conclusions Although differential clinical testing by vaccine receipt and influenza positivity may produce errors in estimated VE, bias in testing would have to be substantial and overall proportion of patients tested would have to be small to result in a meaningful difference in VE.

Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccines for Preventing Coronavirus Disease 2019 Hospitalizations in the United States

“…Detailed eligibility criteria are shown in Supplementary Appendix B. Covid-19 cases included patients hospitalized with a clinical syndrome consistent with acute Covid-19 (≥1 of the following: fever; cough; shortness of breath; loss of taste; loss of smell; use of respiratory support for the acute illness; or new pulmonary findings on chest A c c e p t e d M a n u s c r i p t 8 imaging consistent with pneumonia) and a positive test for SARS-CoV-2 within 10 days following symptom onset. [13][14][15] Test-negative controls were hospitalized with a clinical syndrome consistent with acute Covid-19 and tested negative for SARS-CoV-2. Syndrome-negative controls were hospitalized without a clinical syndrome consistent with Covid-19 and tested negative for SARS-CoV-2.…”

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era

“…In addition, the PCR method is not routinely available in outpatient clinics. A second limitation is the possible fluctuation of the estimation of the VE in case-control design in clinical settings [50] , [51] , Another limitation is that we combined the seasonal data. However, we always adjusted the data by season.…”