Effectiveness of the AS03-Adjuvanted Vaccine against Pandemic Influenza Virus A/(H1N1) 2009 – A Comparison of Two Methods; Germany, 2009/10

Abstract

During the autumn wave of the pandemic influenza virus A/(H1N1) 2009 (pIV) the German population was offered an AS03-adjuvanted vaccine. The authors compared results of two methods calculating the effectiveness of the vaccine (VE). The test-negative case-control method used data from virologic surveillance including influenza-positive and negative patients. An innovative case-series methodology explored data from all nationally reported laboratory-confirmed influenza cases. The proportion of reported cases occurring in vaccinees during an assumed unprotected phase after vaccination was compared with that occurring in vaccinees during their assumed protected phase. The test-negative case-control method included 1,749 pIV cases and 2,087 influenza test-negative individuals of whom 6 (0.3%) and 36 (1.7%), respectively, were vaccinated. The case series method included data from 73,280 cases. VE in the two methods was 79% (95% confidence interval (CI) = 35–93%; P = 0.007) and 87% (95% CI = 78–92%; P<0.001) for individuals less than 14 years of age and 70% (95% CI = −45%–94%, P = 0.13) and 74% (95% CI = 64–82%; P<0.001) for individuals above the age of 14. Both methods yielded similar VE in both age groups; and VE for the younger age group seemed to be higher.

Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review

“…Thus, classification of patients presenting within 2 weeks of vaccination as vaccinated may represent a source of exposure misclassification. In most analyses (n=67), patients were classified as vaccinated if 14 or more days had elapsed between vaccination and either symptom onset or presentation – four of these actually used 13 days [31, 37, 68, 92], and one used 15 days [66]. Seventeen papers did not apply any restriction or did not specify that they did.…”

“…Age is accepted as a confounder of VE estimates because vaccine coverage and the risk of illness caused by influenza virus infection can both vary substantially by age. Five studies did not include some kind of adjustment for age either because they used a stepwise model building approach [36, 40, 62, 92] or restricted the age group studied [72]. Age was usually specified as a categorical variable (n=67), the choices of which varied considerably, but was also used as a linear term (n=9 [12, 29, 47, 59, 80, 81, 108, 87, 88, 95]), cubic spline (n=2 [60, 97]), a matching variable (n=3 [14, 64]) and in one instance as a quadratic term [26].…”

Effectiveness of MF59™ Adjuvanted Influenza A(H1N1)pdm09 Vaccine in Risk Groups in the Netherlands

“…Several studies evaluated the effectiveness of ASO3-adjuvanted influenza A(H1N1)pdm09 vaccine against laboratory confirmed H1N1 in the general population [14], [15], [16], [17], [18], [19], reporting VE estimates between 60% and 95%. The effectiveness of AS03-adjuvanted influenza A(H1N1)pdm09 vaccine was found to be lower in an at risk population under 65 in Denmark (49% against laboratory confirmed ILI, 44% against hospitalisation) [18].…”

Does outpatient laboratory testing represent influenza burden and distribution in a rural state?

“…While there have been studies evaluating methods for selecting control groups and attempts to assess the magnitude of biases due to control group selection, these have been limited for influenza and have largely been focused on biases in influenza vaccine efficacy estimates derived from case–control studies 4, 19, 20. Specifically, it has been noted that biases in case–control studies tend to underestimate true vaccine effectiveness 19, 20. There are implications for the lack of representativeness of outpatient laboratory‐confirmed groups for either surveillance or control group purposes.…”