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Table 1 Conceptual framework: Indicators and conclusions for presence of confounding by indication and healthy vaccinee bias in influenza vaccine effectiveness studies

From: Frequency and impact of confounding by indication and healthy vaccinee bias in observational studies assessing influenza vaccine effectiveness: a systematic review

Indicator Conclusion References
Vaccinated study participants have a higher proportion of comorbidities than unvaccinated study participants, as indicated by baseline characteristics High risk of confounding by indication in the unadjusted data set [6, 38]
Vaccinated study participants have a lower proportion of comorbidities than unvaccinated study participants, as indicated by baseline characteristics High risk of healthy vaccinee bias in the unadjusted data set [35, 36]
Inclusion of comorbidities in the regression model increases vaccine effectiveness Confounding by indication has led to underestimation of vaccine effectiveness in the unadjusted data set [7]
Inclusion of comorbidities in the regression model decreases vaccine effectiveness Healthy vaccinee bias has led to overestimation of vaccine effectiveness in the unadjusted data set [7]
Significant effects of influenza vaccination appear outside the influenza season (“off-season estimates”), despite adjustment for comorbidities Residual confounding by healthy vaccinee bias [3, 11, 36]