Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic
Identifieur interne : 000674 ( Pmc/Corpus ); précédent : 000673; suivant : 000675Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic
Auteurs : 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 LundgrenSource :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America [ 1058-4838 ] ; 2018.
Abstract
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.
We estimated the CFR of medically attended influenza (CFRMA) 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 (CFRAR).
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. CFRMAfor 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 CFRAR to be 0.025%, 16-fold lower than CFRMA.
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.
NCT01056354 and NCT010561.
Url:
DOI: 10.1093/cid/ciy088
PubMed: 29746631
PubMed Central: 6248856
Links to Exploration step
PMC:6248856Le document en format XML
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<author><name sortKey="Simonsen, Lone" sort="Simonsen, Lone" uniqKey="Simonsen L" first="Lone" last="Simonsen">Lone Simonsen</name>
<affiliation><nlm:aff id="AF0001">Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0002">Department of Science and Environment, Roskilde University, Denmark</nlm:aff>
</affiliation>
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<author><name sortKey="Higgs, Elizabeth" sort="Higgs, Elizabeth" uniqKey="Higgs E" first="Elizabeth" last="Higgs">Elizabeth Higgs</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Taylor, Robert J" sort="Taylor, Robert J" uniqKey="Taylor R" first="Robert J" last="Taylor">Robert J. Taylor</name>
<affiliation><nlm:aff id="AF0004">Sage Analytica, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wentworth, Deborah" sort="Wentworth, Deborah" uniqKey="Wentworth D" first="Deborah" last="Wentworth">Deborah Wentworth</name>
<affiliation><nlm:aff id="AF0005">Division of Biostatistics, University of Minnesota, Minneapolis</nlm:aff>
</affiliation>
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<author><name sortKey="Cozzi Lepri, Al" sort="Cozzi Lepri, Al" uniqKey="Cozzi Lepri A" first="Al" last="Cozzi-Lepri">Al Cozzi-Lepri</name>
<affiliation><nlm:aff id="AF0006">University College, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pett, Sarah" sort="Pett, Sarah" uniqKey="Pett S" first="Sarah" last="Pett">Sarah Pett</name>
<affiliation><nlm:aff id="AF0007">Medical Research Council Clinical Trials Unit and Clinical Research Group, University College, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0008">The Kirby Institute, University of New South Wales, Australia</nlm:aff>
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<author><name sortKey="Dwyer, Dominic E" sort="Dwyer, Dominic E" uniqKey="Dwyer D" first="Dominic E" last="Dwyer">Dominic E. Dwyer</name>
<affiliation><nlm:aff id="AF0009">Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research, Westmead Hospital and University of Sydney, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Davey, Richard" sort="Davey, Richard" uniqKey="Davey R" first="Richard" last="Davey">Richard Davey</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
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</author>
<author><name sortKey="Lynfield, Ruth" sort="Lynfield, Ruth" uniqKey="Lynfield R" first="Ruth" last="Lynfield">Ruth Lynfield</name>
<affiliation><nlm:aff id="AF0010">Minnesota Department of Health, St. Paul</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Losso, Marcelo" sort="Losso, Marcelo" uniqKey="Losso M" first="Marcelo" last="Losso">Marcelo Losso</name>
<affiliation><nlm:aff id="AF0011">Hospital J.M. Ramos Mejía, Buenos Aires, Argentina</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Morales, Kathleen" sort="Morales, Kathleen" uniqKey="Morales K" first="Kathleen" last="Morales">Kathleen Morales</name>
<affiliation><nlm:aff id="AF0004">Sage Analytica, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Glesby, Marshall J" sort="Glesby, Marshall J" uniqKey="Glesby M" first="Marshall J" last="Glesby">Marshall J. Glesby</name>
<affiliation><nlm:aff id="AF0012">Weill Cornell Medical College, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Weckx, Jozef" sort="Weckx, Jozef" uniqKey="Weckx J" first="Jozef" last="Weckx">Jozef Weckx</name>
<affiliation><nlm:aff id="AF0013">Testumed Vereniging zonder winstoogmerk, Tessenderlo, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carey, Dianne" sort="Carey, Dianne" uniqKey="Carey D" first="Dianne" last="Carey">Dianne Carey</name>
<affiliation><nlm:aff id="AF0008">The Kirby Institute, University of New South Wales, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lane, Cliff" sort="Lane, Cliff" uniqKey="Lane C" first="Cliff" last="Lane">Cliff Lane</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lundgren, Jens" sort="Lundgren, Jens" uniqKey="Lundgren J" first="Jens" last="Lundgren">Jens Lundgren</name>
<affiliation><nlm:aff id="AF0001">Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark</nlm:aff>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Using Clinical Research Networks to Assess Severity of an Emerging Influenza
Pandemic</title>
<author><name sortKey="Simonsen, Lone" sort="Simonsen, Lone" uniqKey="Simonsen L" first="Lone" last="Simonsen">Lone Simonsen</name>
<affiliation><nlm:aff id="AF0001">Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0002">Department of Science and Environment, Roskilde University, Denmark</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Higgs, Elizabeth" sort="Higgs, Elizabeth" uniqKey="Higgs E" first="Elizabeth" last="Higgs">Elizabeth Higgs</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Taylor, Robert J" sort="Taylor, Robert J" uniqKey="Taylor R" first="Robert J" last="Taylor">Robert J. Taylor</name>
<affiliation><nlm:aff id="AF0004">Sage Analytica, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wentworth, Deborah" sort="Wentworth, Deborah" uniqKey="Wentworth D" first="Deborah" last="Wentworth">Deborah Wentworth</name>
<affiliation><nlm:aff id="AF0005">Division of Biostatistics, University of Minnesota, Minneapolis</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cozzi Lepri, Al" sort="Cozzi Lepri, Al" uniqKey="Cozzi Lepri A" first="Al" last="Cozzi-Lepri">Al Cozzi-Lepri</name>
<affiliation><nlm:aff id="AF0006">University College, London, United Kingdom</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pett, Sarah" sort="Pett, Sarah" uniqKey="Pett S" first="Sarah" last="Pett">Sarah Pett</name>
<affiliation><nlm:aff id="AF0007">Medical Research Council Clinical Trials Unit and Clinical Research Group, University College, London, United Kingdom</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="AF0008">The Kirby Institute, University of New South Wales, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dwyer, Dominic E" sort="Dwyer, Dominic E" uniqKey="Dwyer D" first="Dominic E" last="Dwyer">Dominic E. Dwyer</name>
<affiliation><nlm:aff id="AF0009">Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research, Westmead Hospital and University of Sydney, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Davey, Richard" sort="Davey, Richard" uniqKey="Davey R" first="Richard" last="Davey">Richard Davey</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lynfield, Ruth" sort="Lynfield, Ruth" uniqKey="Lynfield R" first="Ruth" last="Lynfield">Ruth Lynfield</name>
<affiliation><nlm:aff id="AF0010">Minnesota Department of Health, St. Paul</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Losso, Marcelo" sort="Losso, Marcelo" uniqKey="Losso M" first="Marcelo" last="Losso">Marcelo Losso</name>
<affiliation><nlm:aff id="AF0011">Hospital J.M. Ramos Mejía, Buenos Aires, Argentina</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Morales, Kathleen" sort="Morales, Kathleen" uniqKey="Morales K" first="Kathleen" last="Morales">Kathleen Morales</name>
<affiliation><nlm:aff id="AF0004">Sage Analytica, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Glesby, Marshall J" sort="Glesby, Marshall J" uniqKey="Glesby M" first="Marshall J" last="Glesby">Marshall J. Glesby</name>
<affiliation><nlm:aff id="AF0012">Weill Cornell Medical College, New York, New York</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Weckx, Jozef" sort="Weckx, Jozef" uniqKey="Weckx J" first="Jozef" last="Weckx">Jozef Weckx</name>
<affiliation><nlm:aff id="AF0013">Testumed Vereniging zonder winstoogmerk, Tessenderlo, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Carey, Dianne" sort="Carey, Dianne" uniqKey="Carey D" first="Dianne" last="Carey">Dianne Carey</name>
<affiliation><nlm:aff id="AF0008">The Kirby Institute, University of New South Wales, Australia</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lane, Cliff" sort="Lane, Cliff" uniqKey="Lane C" first="Cliff" last="Lane">Cliff Lane</name>
<affiliation><nlm:aff id="AF0003">National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lundgren, Jens" sort="Lundgren, Jens" uniqKey="Lundgren J" first="Jens" last="Lundgren">Jens Lundgren</name>
<affiliation><nlm:aff id="AF0001">Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</title>
<idno type="ISSN">1058-4838</idno>
<idno type="eISSN">1537-6591</idno>
<imprint><date when="2018">2018</date>
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<front><div type="abstract" xml:lang="en"><title>Abstract</title>
<sec id="s1"><title>Background</title>
<p>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.</p>
</sec>
<sec id="s2"><title>Methods</title>
<p>We estimated the CFR of medically attended influenza (CFR<sub>MA</sub>
) 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<sub>AR</sub>
).</p>
</sec>
<sec id="s3"><title>Results</title>
<p>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<sub>MA</sub>
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<sub>AR</sub>
to be 0.025%, 16-fold
lower than CFR<sub>MA</sub>
.</p>
</sec>
<sec id="s4"><title>Conclusions</title>
<p>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.</p>
</sec>
<sec id="s5"><title>Clinical Trials Registration</title>
<p>NCT01056354 and NCT010561.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">Clin. Infect. Dis</journal-id>
<journal-id journal-id-type="publisher-id">cid</journal-id>
<journal-title-group><journal-title>Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</journal-title>
</journal-title-group>
<issn pub-type="ppub">1058-4838</issn>
<issn pub-type="epub">1537-6591</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
<publisher-loc>US</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29746631</article-id>
<article-id pub-id-type="pmc">6248856</article-id>
<article-id pub-id-type="doi">10.1093/cid/ciy088</article-id>
<article-id pub-id-type="publisher-id">ciy088</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Articles and Commentary</subject>
</subj-group>
</article-categories>
<title-group><article-title>Using Clinical Research Networks to Assess Severity of an Emerging Influenza
Pandemic</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Simonsen</surname>
<given-names>Lone</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="corresp" rid="c1"></xref>
<pmc-comment>lsimonsen2@gmail.com </pmc-comment>
</contrib>
<contrib contrib-type="author"><name><surname>Higgs</surname>
<given-names>Elizabeth</given-names>
</name>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taylor</surname>
<given-names>Robert J</given-names>
</name>
<xref ref-type="aff" rid="AF0004">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wentworth</surname>
<given-names>Deborah</given-names>
</name>
<xref ref-type="aff" rid="AF0005">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cozzi-Lepri</surname>
<given-names>Al</given-names>
</name>
<xref ref-type="aff" rid="AF0006">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pett</surname>
<given-names>Sarah</given-names>
</name>
<xref ref-type="aff" rid="AF0007">7</xref>
<xref ref-type="aff" rid="AF0008">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dwyer</surname>
<given-names>Dominic E</given-names>
</name>
<xref ref-type="aff" rid="AF0009">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Davey</surname>
<given-names>Richard</given-names>
</name>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lynfield</surname>
<given-names>Ruth</given-names>
</name>
<xref ref-type="aff" rid="AF0010">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Losso</surname>
<given-names>Marcelo</given-names>
</name>
<xref ref-type="aff" rid="AF0011">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Morales</surname>
<given-names>Kathleen</given-names>
</name>
<xref ref-type="aff" rid="AF0004">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Glesby</surname>
<given-names>Marshall J</given-names>
</name>
<xref ref-type="aff" rid="AF0012">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weckx</surname>
<given-names>Jozef</given-names>
</name>
<xref ref-type="aff" rid="AF0013">13</xref>
<xref ref-type="author-notes" rid="fn0001"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Carey</surname>
<given-names>Dianne</given-names>
</name>
<xref ref-type="aff" rid="AF0008">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lane</surname>
<given-names>Cliff</given-names>
</name>
<xref ref-type="aff" rid="AF0003">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lundgren</surname>
<given-names>Jens</given-names>
</name>
<xref ref-type="aff" rid="AF0001">1</xref>
</contrib>
<contrib contrib-type="author"><collab>INSIGHT FLU002 and FLU003 Study Groups <contrib-group><contrib contrib-type="author"><name><surname>Munroe</surname>
<given-names>David</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Rappoport</surname>
<given-names>Claire</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Schwarze</surname>
<given-names>Siegfried</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Aagaard</surname>
<given-names>Bitten</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Adzic</surname>
<given-names>Dejan</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Grarup</surname>
<given-names>Jesper</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Herrero</surname>
<given-names>Patricia</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Jansson</surname>
<given-names>Per</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Jakobsen</surname>
<given-names>Marie Louise</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Jensen</surname>
<given-names>Birgitte</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Jensen</surname>
<given-names>Karoline B</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Juncher</surname>
<given-names>Heidi</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kjær</surname>
<given-names>Jesper</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Lundgren</surname>
<given-names>Jens</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Lopez</surname>
<given-names>Paco</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mocroft</surname>
<given-names>Amanda</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Pearson</surname>
<given-names>Mary</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Portas</surname>
<given-names>Begoña</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Sabin</surname>
<given-names>Caroline</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Tillmann</surname>
<given-names>Klaus</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Babiker</surname>
<given-names>Abdel</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Braimah</surname>
<given-names>Nafisah</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Collaco-Moraes</surname>
<given-names>Yolanda</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hudson</surname>
<given-names>Fleur</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kummeling</surname>
<given-names>Ischa</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Pacciarini</surname>
<given-names>Filippo</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Paton</surname>
<given-names>Nick</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>George</surname>
<given-names>Michelle</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Harrison</surname>
<given-names>Merrie</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Herman</surname>
<given-names>Kathy</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Krum</surname>
<given-names>Eric</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Larson</surname>
<given-names>Gregg</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Nelson</surname>
<given-names>Ray</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Quan</surname>
<given-names>Kien</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Quan</surname>
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<contrib contrib-type="author"><name><surname>Reilly</surname>
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<given-names>Anchalee</given-names>
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<given-names>Julia A</given-names>
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<contrib contrib-type="author"><name><surname>Lasala</surname>
<given-names>Maria Beatriz</given-names>
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<contrib contrib-type="author"><name><surname>El-Sadr</surname>
<given-names>Wafaa</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Freiberg</surname>
<given-names>Matthew S</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gordin</surname>
<given-names>Fred M</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gulick</surname>
<given-names>Roy</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Gurka</surname>
<given-names>David</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Hodder</surname>
<given-names>Sally</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Markowitz</surname>
<given-names>Norman</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Novak</surname>
<given-names>Richard M</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Paez</surname>
<given-names>Armando</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Patil</surname>
<given-names>Namrata</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Reboli</surname>
<given-names>Annette</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Sands</surname>
<given-names>Michael</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Schooley</surname>
<given-names>Robert</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Simon</surname>
<given-names>Gary L</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Temesgen</surname>
<given-names>Zelalem</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Timpone</surname>
<given-names>Joseph</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Uslan</surname>
<given-names>Daniel Z</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Wade</surname>
<given-names>Barbara Heeter</given-names>
</name>
</contrib>
</contrib-group>
</collab>
</contrib>
</contrib-group>
<aff id="AF0001"><label>1</label>
Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark</aff>
<aff id="AF0002"><label>2</label>
Department of Science and Environment, Roskilde University, Denmark</aff>
<aff id="AF0003"><label>3</label>
National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland</aff>
<aff id="AF0004"><label>4</label>
Sage Analytica, Bethesda, Maryland</aff>
<aff id="AF0005"><label>5</label>
Division of Biostatistics, University of Minnesota, Minneapolis</aff>
<aff id="AF0006"><label>6</label>
University College, London, United Kingdom</aff>
<aff id="AF0007"><label>7</label>
Medical Research Council Clinical Trials Unit and Clinical Research Group, University College, London, United Kingdom</aff>
<aff id="AF0008"><label>8</label>
The Kirby Institute, University of New South Wales, Australia</aff>
<aff id="AF0009"><label>9</label>
Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research, Westmead Hospital and University of Sydney, Australia</aff>
<aff id="AF0010"><label>10</label>
Minnesota Department of Health, St. Paul</aff>
<aff id="AF0011"><label>11</label>
Hospital J.M. Ramos Mejía, Buenos Aires, Argentina</aff>
<aff id="AF0012"><label>12</label>
Weill Cornell Medical College, New York, New York</aff>
<aff id="AF0013"><label>13</label>
Testumed Vereniging zonder winstoogmerk, Tessenderlo, Belgium</aff>
<author-notes><corresp id="c1">Correspondence: L. Simonsen, University of Copenhagen, Universitetsvej 1,
4000 Roskilde, Roskilde, Denmark (<email>lsimonsen2@gmail.com</email>
).</corresp>
<fn id="fn0001"><p>International Network for Strategic Initiatives in Global HIV Trials FLU002 AND FLU003
Study Groups</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>01</day>
<month>8</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub" iso-8601-date="2018-05-08"><day>08</day>
<month>5</month>
<year>2018</year>
</pub-date>
<volume>67</volume>
<issue>3</issue>
<fpage>341</fpage>
<lpage>349</lpage>
<history><date date-type="received"><day>25</day>
<month>8</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>30</day>
<month>4</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>Published by Oxford University Press for the Infectious Diseases
Society of America 2018.</copyright-statement>
<copyright-year>2018</copyright-year>
<license license-type="us-gov"><license-p>This work is written by (a) US Government employee(s) and is in the public
domain in the US.</license-p>
</license>
</permissions>
<self-uri xlink:href="ciy088.pdf"></self-uri>
<abstract><title>Abstract</title>
<sec id="s1"><title>Background</title>
<p>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.</p>
</sec>
<sec id="s2"><title>Methods</title>
<p>We estimated the CFR of medically attended influenza (CFR<sub>MA</sub>
) 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<sub>AR</sub>
).</p>
</sec>
<sec id="s3"><title>Results</title>
<p>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<sub>MA</sub>
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<sub>AR</sub>
to be 0.025%, 16-fold
lower than CFR<sub>MA</sub>
.</p>
</sec>
<sec id="s4"><title>Conclusions</title>
<p>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.</p>
</sec>
<sec id="s5"><title>Clinical Trials Registration</title>
<p>NCT01056354 and NCT010561.</p>
</sec>
</abstract>
<abstract abstract-type="teaser"><p>We demonstrate how to use baseline and prospective data from global clinical research
networks to rapidly assess the severity of an emerging influenza pandemic.</p>
</abstract>
<kwd-group><kwd>severity</kwd>
<kwd>pandemic influenza</kwd>
<kwd>case fatality ratio</kwd>
<kwd>clinical research</kwd>
<kwd>pandemic preparedness</kwd>
</kwd-group>
<counts><page-count count="9"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>
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