Using clinical research networks to assess severity of an emerging influenza pandemic

Lone Simonsen, Elizabeth Higgs, Robert J. Taylor, Deborah Wentworth, Al Cozzi-Lepri, Sarah Pett, Dominic E. Dwyer, Richard Davey, Ruth Lynfield, Marcelo Losso, Kathleen Morales, Marshall J. Glesby, Jozef Weckx, Dianne Carey, Cliff Lane, Jens Lundgren

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4 Scopus citations


Background Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. Methods We estimated the CFR of medically attended influenza (CFR MA) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009-2011) and post-pandemic (2012-2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFR AR). Results During the pandemic period, 5.0% (3.1%-6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%-12.6%) died. CFR MA for pH1N1 was 0.4% (0.2%-0.6%) in the pandemic period 2009-2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012-2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFR AR to be 0.025%, 16-fold lower than CFR MA. Conclusions Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. Clinical Trials Registration NCT01056354 and NCT010561.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalClinical Infectious Diseases
Issue number3
StatePublished - Jul 18 2018



  • case fatality ratio
  • clinical research
  • pandemic influenza
  • pandemic preparedness
  • severity

Cite this

Simonsen, L., Higgs, E., Taylor, R. J., Wentworth, D., Cozzi-Lepri, A., Pett, S., Dwyer, D. E., Davey, R., Lynfield, R., Losso, M., Morales, K., Glesby, M. J., Weckx, J., Carey, D., Lane, C., & Lundgren, J. (2018). Using clinical research networks to assess severity of an emerging influenza pandemic. Clinical Infectious Diseases, 67(3), 341-349.