tetano
Editor, Senior Moderator
Int J Epidemiol
. 2025 Jun 11;54(4):dyaf089.
doi: 10.1093/ije/dyaf089. Bias in control selection associated with the use of rapid tests in influenza vaccine effectiveness studies
Eero Poukka[SUP] 1 2 [/SUP], Caitriona Murphy[SUP] 3 [/SUP], Loretta Mak[SUP] 3 [/SUP], Samuel M S Cheng[SUP] 3 [/SUP], Malik Peiris[SUP] 3 4 [/SUP], Tim K Tsang[SUP] 3 5 [/SUP], Sheena G Sullivan[SUP] 6 7 [/SUP], Benjamin J Cowling[SUP] 3 5 [/SUP]
Affiliations
Background: In test-negative design (TND) studies that use rapid tests to estimate influenza vaccine effectiveness (VE), a common concern is case-control misclassification due to imperfect diagnostic accuracy. An imperfect test can also fail to exclude from the control group people infected with other influenza types or other vaccine-preventable respiratory viruses. We investigated these biases while evaluating VE for the 2023/24 seasonal influenza vaccination.
Methods: A TND study was conducted among outpatients aged ≥6 months of age who visited an outpatient clinic in Hong Kong between 15 December 2023 and 13 August 2024. VE was estimated for polymerase chain reaction (PCR)- and rapid-test-confirmed influenza A and B with exclusions of other types of influenza and SARS-CoV-2 based on either PCR or rapid test. Alternatively, for the exclusion of SARS-CoV-2, we adjusted the analysis with COVID-19 vaccination. VE was estimated by using logistic regression adjusted for confounders.
Results: In a study population of 1691 participants, VE against influenza A by PCR was 49% [95% confidence interval (CI) 26%-65%] after the exclusion of PCR-confirmed influenza B and SARS-CoV-2 controls. The corresponding VE against influenza B was 65% (95% CI 35%-81%). VE estimated by adjusting for COVID-19 vaccination status yielded similar estimates to these. When case-control status and exclusions from test-negative controls were determined by using the rapid test, VE was reduced by 5%age-15%age points.
Conclusion: In TND studies using rapid tests, reduced sensitivity affects both case-control classification and control group exclusions, potentially causing bias. New methods for these biases could help to adapt participatory cohorts for the monitoring of VE for influenza, COVID-19, and respiratory syncytial virus.
Keywords: PCR test; bias; influenza; rapid test; test-negative design; vaccine effectiveness.
. 2025 Jun 11;54(4):dyaf089.
doi: 10.1093/ije/dyaf089. Bias in control selection associated with the use of rapid tests in influenza vaccine effectiveness studies
Eero Poukka[SUP] 1 2 [/SUP], Caitriona Murphy[SUP] 3 [/SUP], Loretta Mak[SUP] 3 [/SUP], Samuel M S Cheng[SUP] 3 [/SUP], Malik Peiris[SUP] 3 4 [/SUP], Tim K Tsang[SUP] 3 5 [/SUP], Sheena G Sullivan[SUP] 6 7 [/SUP], Benjamin J Cowling[SUP] 3 5 [/SUP]
Affiliations
- PMID: 40574484
- DOI: 10.1093/ije/dyaf089
Background: In test-negative design (TND) studies that use rapid tests to estimate influenza vaccine effectiveness (VE), a common concern is case-control misclassification due to imperfect diagnostic accuracy. An imperfect test can also fail to exclude from the control group people infected with other influenza types or other vaccine-preventable respiratory viruses. We investigated these biases while evaluating VE for the 2023/24 seasonal influenza vaccination.
Methods: A TND study was conducted among outpatients aged ≥6 months of age who visited an outpatient clinic in Hong Kong between 15 December 2023 and 13 August 2024. VE was estimated for polymerase chain reaction (PCR)- and rapid-test-confirmed influenza A and B with exclusions of other types of influenza and SARS-CoV-2 based on either PCR or rapid test. Alternatively, for the exclusion of SARS-CoV-2, we adjusted the analysis with COVID-19 vaccination. VE was estimated by using logistic regression adjusted for confounders.
Results: In a study population of 1691 participants, VE against influenza A by PCR was 49% [95% confidence interval (CI) 26%-65%] after the exclusion of PCR-confirmed influenza B and SARS-CoV-2 controls. The corresponding VE against influenza B was 65% (95% CI 35%-81%). VE estimated by adjusting for COVID-19 vaccination status yielded similar estimates to these. When case-control status and exclusions from test-negative controls were determined by using the rapid test, VE was reduced by 5%age-15%age points.
Conclusion: In TND studies using rapid tests, reduced sensitivity affects both case-control classification and control group exclusions, potentially causing bias. New methods for these biases could help to adapt participatory cohorts for the monitoring of VE for influenza, COVID-19, and respiratory syncytial virus.
Keywords: PCR test; bias; influenza; rapid test; test-negative design; vaccine effectiveness.