Leora R Feldstein, Jill M Ferdinands, Wesley H Self, Adrienne G Randolph, Michael Aboodi, Adrienne H Baughman, Samuel M Brown, Matthew C Exline, D Clark Files, Kevin Gibbs, Adit A Ginde, Michelle N Gong, Carlos G Grijalva, Natasha Halasa, Akram Khan, Christopher J Lindsell, Margaret Newhams, Ithan D Peltan, Matthew E Prekker, Todd W Rice, Nathan I Shapiro, Jay Steingrub, H Keipp Talbot, M Elizabeth Halloran, Manish Patel
Journal of Infectious Diseases
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.