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

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]