Public health policy makers need annual estimates of influenza vaccine effectiveness as an ongoing evaluation of the United States influenza vaccination program. These estimates must come from observational epidemiologic studies, which are susceptible to numerous sources of bias in study design and analysis. Furthermore, policy makers need information on influenza incidence and on antigenic match between the vaccine and circulating influenza strains to properly interpret vaccine effectiveness estimates. Among members of Group Health Cooperative (GHC), a managed care organization in western Washington State, we propose: (1) To conduct annual test-negative case-control studies of influenza vaccine effectiveness. This design is effective at reducing confounding caused by differences in healthcare-seeking behavior between vaccinated and unvaccinated subjects. We can further reduce confounding by making use of extensive data on our subjects from GHC electronic medical records and administrative databases. We will verify influenza infection by RT-PCR, and will culture influenza viruses from RT-PCR-positive specimens, to be shared with CDC for antigenic characterization. (2) To estimate the burden of influenza in the same population in which we estimate vaccine effectiveness. For estimating incidence, we take advantage of the fact that our case-control subjects are drawn from a defined, enumerated population of GHC enrollees who have few barriers to same-day care for acute illnesses. Over the course of the five year study period our results will give public health policy makers a greater understanding of how influenza vaccine effectiveness fluctuates from year to year and how those fluctuations are related to influenza incidence and antigenic match with the vaccine.

Public Health Relevance

We propose to make yearly estimates of influenza vaccine effectiveness and of the burden of influenza among member of Group Health Cooperative (GHC), a large managed care organization in western Washington State. Within this population we will take advantage of existing GHC systems to efficiently enroll patients with medically attended acute respiratory illness (MAARI), to confirm influenza infection by RT-PCR, to isolate influenza viruses to share with CDC, and to collect detailed information on high-risk medical conditions and other important variables. We will use the collected data to estimate vaccine effectiveness using a test-negative case-control design and to estimate the burden of influenza using a probabilistic multiplier model.

National Institute of Health (NIH)
National Center for Immunication and Respiratory Diseases (NCIRD)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZIP1-GCA (19))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Group Health Cooperative
United States
Zip Code
Jackson, Michael L; Chung, Jessie R; Jackson, Lisa A et al. (2017) Influenza Vaccine Effectiveness in the United States during the 2015-2016 Season. N Engl J Med 377:534-543
Spencer, Sarah; Chung, Jessie; Thompson, Mark et al. (2016) Factors associated with real-time RT-PCR cycle threshold values among medically attended influenza episodes. J Med Virol 88:719-23
Petrie, Joshua G; Cheng, Caroline; Malosh, Ryan E et al. (2016) Illness Severity and Work Productivity Loss Among Working Adults With Medically Attended Acute Respiratory Illnesses: US Influenza Vaccine Effectiveness Network 2012-2013. Clin Infect Dis 62:448-455
Zimmerman, Richard K; Balasubramani, G K; Nowalk, Mary Patricia et al. (2016) Classification and Regression Tree (CART) analysis to predict influenza in primary care patients. BMC Infect Dis 16:503
Thompson, Mark G; Clippard, Jessie; Petrie, Joshua G et al. (2016) Influenza Vaccine Effectiveness for Fully and Partially Vaccinated Children 6 Months to 8 Years Old During 2011-2012 and 2012-2013: The Importance of Two Priming Doses. Pediatr Infect Dis J 35:299-308
Flannery, Brendan; Zimmerman, Richard K; Gubareva, Larisa V et al. (2016) Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015. J Infect Dis 214:1010-9
Chung, Jessie R; Flannery, Brendan; Thompson, Mark G et al. (2016) Seasonal Effectiveness of Live Attenuated and Inactivated Influenza Vaccine. Pediatrics 137:e20153279
Zimmerman, Richard K; Nowalk, Mary Patricia; Chung, Jessie et al. (2016) 2014-2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type. Clin Infect Dis 63:1564-1573
Gaglani, Manjusha; Pruszynski, Jessica; Murthy, Kempapura et al. (2016) Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States. J Infect Dis 213:1546-56
Jackson, Michael L; Rothman, Kenneth J (2015) Effects of imperfect test sensitivity and specificity on observational studies of influenza vaccine effectiveness. Vaccine 33:1313-6

Showing the most recent 10 out of 16 publications