Register-Based Cohort Studies Optimal for Estimates of Influenza Vaccine Effectiveness

elderly man receiving vaccine, injection, influenza
Researchers evaluated 3 different study designs to determine their accuracy in measuring influenza vaccine effectiveness among older patients.

The register-based cohort study design produced the most precise estimates of influenza vaccine effectiveness (IVE), proving it as the optimal method for annual IVE surveillance. These findings were published in Vaccine.

Researchers evaluated 3 study designs, including an active test-negative design, a register-based cohort design, and a register-based case-control design, to compare their weaknesses and strengths in estimating IVE against influenza A virus infection in patients aged 65 years and older. The studies assessed 3 influenza seasons, comprising periods from December 2015 to May 2016 (season 1), November 2016 to April 2017 (season 2), and December 2017 to May 2018 (season 3).

For the active test-negative design trial, adjusted IVE estimates for seasons 1 through 3 were 82% (95% CI, 26-96), 21% (95% CI, -179 to 77), and 15% (95% CI, -113 to 66), respectively.

For the register-based case-control study design, crude and adjusted IVE estimates ranged from 47% to 52% in season 1, 10% to 29% in season 3, and -27% to 1% in season 3.

For the register-based cohort study design, adjusted IVE estimates for each of the 3 seasons were 48% (95% CI, -9 to 75), 29% (95% CI, 1-49), and 13% (95% CI, -21 to 37), respectively.

The researchers found that IVE estimates varied more based on influenza seasons than on study design. Although the results of the 3 studies were similar, the register-based cohort study produced results closest to the active test-negative design study, and the register-based case-control study was not as precise.

Study limitations included the lack of generalizability to younger age groups, insufficient statistical power to provide precise IVE estimates, and potential inaccuracy of the sourced data.

“This study further supports the use of register-based cohort design… [for the]  routine estimation of IVE, since it requires a lot less effort… and gives IVE estimates that are comparable to those observed in an active [test-negative design] study,” the researchers concluded.

Disclosure: This research was supported by the Finnish Institute for Health and Welfare which receives funding from Sanofi Inc, Pfizer Inc, and GlaxoSmithKline Biologicals SA. Please see the original reference for a full list of disclosures.


Halme J, Syrjänen RK, Baum U, Palmu AA. Effectiveness of trivalent influenza vaccines against hospitalizations due to laboratory-confirmed influenza a in the elderly: comparison of test-negative design with register-based designs. Vaccine. 2022;40(31):4242-4252. doi:10.1016/j.vaccine.2022.05.080