Effectiveness of Seasonal Influenza Vaccine against Pandemic (H1N1) 2009 Virus. Discussion – Part 2
When stratified by age, estimates of vaccine effectiveness for working-age adults were higher and more precise than those for children. We previously demonstrated that the sentinel practitioner surveillance program in Victoria is well suited for estimating vaccine effectiveness among working-age adults, who account for most of the surveillance population, and the 2010 results were consistent with this observation. The relatively few participants in the young (childhood) age groups meant the study had insufficient power to produce defined or significant estimates of vaccine effectiveness. At the other end of the age spectrum, 2% of study participants (5 controls and 0 case-patients) in 2010 were >65 years of age compared with an average of 7% in this age group during 2003–07. Although the absence of pandemic (H1N1) 2009 case-patients >65 years of age is not surprising, given that older adults have been shown to have relatively higher levels of cross-reactive antibodies to pandemic (H1N1) 2009 virus, the reason for the low proportion of controls in this age group remains unclear. Among the several explanations are a true lower rate of ILI in older persons during 2010, a lower rate of visits to practitioners for ILI by persons in this age group (or treatment at other health services such as hospitals), or preferential sampling of younger persons by practitioners (and perhaps awareness that pandemic [H1N1] 2009 was the predominant circulating influenza virus subtype).
In addition to having a sample size large enough to provide vaccine effectiveness estimates by age group and influenza type, several other considerations with regard to design of case–control studies of influenza vaccine effectiveness have been proposed: 1) whether the control group best represents the vaccination coverage of the source population and 2) whether collection and confounding variables have been adjusted for, particularly underlying chronic conditions for which vaccine is recommended and previous influenza vaccination history. A 2010 survey of pandemic vaccination suggests that monovalent vaccine coverage in the control group was generally consistent with that in the general population and that use of monovalent vaccine was ≈17% among those from Victoria, compared with 13% among controls. No equivalent survey of 2010 seasonal vaccine usage was available for comparison.
Data about concurrent conditions of study participants that would indicate need for influenza vaccination were not collected during the 2010 influenza season; thus, adjustment of the vaccine effectiveness estimates for this potentially confounding variable could not be conducted. Such confounding by indication (or negative confounding), in which persons at higher risk for influenza are more likely to be vaccinated, underestimates effectiveness of influenza vaccine but may be counteracted by healthy vaccinee bias (or positive confounding), which overestimates effectiveness. The extent to which these biases occur is likely to vary and may explain the positive and negative variation of crude influenza vaccine effectiveness estimates after adjustment for chronic conditions in several similar test-negative case–control studies. Speculation about the relative effects of these biases on how many received monovalent vaccine is also difficult; vaccination was funded for the entire population of Australia, but at the end of February 2010, only 18% had been vaccinated.