Estimating Influenza Vaccine Effectiveness with the Test-Negative Design Using Alternative Control Groups: A Systematic Review and Meta-Analysis

Abstract

One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011-2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VE FLU-; 2) patients who tested positive for other/another respiratory virus (ORV), VE ORV+; and 3) patients who tested negative for all viruses in the panel (PAN), VE PAN-. These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VE FLU- estimates, 62 VE ORV+ estimates, and 33 VE PAN- estimates were extracted. Pooled estimates of the difference in VE ("VE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group. Show more