tetano
Editor, Senior Moderator
The Journal of Infectious Diseases 2010;201:1654?1662
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20111-0008$15.00
DOI: 10.1086/652498
PERSPECTIVE
End Points for Testing Influenza Antiviral Treatments for Patients at High Risk of Severe and Life‐Threatening Disease
Michael G. Ison,1
Menno D. de Jong,6
Kevin J. Gilligan,2
Elizabeth S. Higgs,3
Andrew T. Pavia,4
Jerome Pierson,3 and
Frederick G. Hayden5.7
1Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 2Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC; 3Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 4Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City, Utah; 5Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia; 6Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and 7International Activities, Wellcome Trust, London, United Kingdom
Influenza infection results in substantial morbidity and mortality in hospitalized patients, including those who are immunocompromised or pregnant. Antiviral therapy likely provides considerable benefit to these patients, but few studies have been successfully conducted in these high‐risk populations, and no drugs are specifically licensed for treating these subgroups. One of the key challenges facing novel antiviral drug development for influenza is determining the appropriate efficacy end points that would enable rapid regulatory approval for drug use in seriously ill patients, for whom risk‐benefit assessments differ from those with uncomplicated illness. All available antiviral drugs currently affect viral replication, and respiratory tract viral titers correlate with both symptoms and measures of host inflammatory responses, including cytokine and chemokine expression that are likely responsible for many of the clinical symptoms. Consequently, we outline the evidence to support the use of primary virological end points in studies of antiviral agents involving patients who are hospitalized with severe influenza or those who are at high risk of severe and life‐threatening disease.
Received 20 October 2009; accepted 21 December 2009; electronically published 27 April 2010.
http://www.journals.uchicago.edu/doi/abs/10.1086/652498
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20111-0008$15.00
DOI: 10.1086/652498
PERSPECTIVE
End Points for Testing Influenza Antiviral Treatments for Patients at High Risk of Severe and Life‐Threatening Disease
Michael G. Ison,1
Menno D. de Jong,6
Kevin J. Gilligan,2
Elizabeth S. Higgs,3
Andrew T. Pavia,4
Jerome Pierson,3 and
Frederick G. Hayden5.7
1Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 2Biomedical Advanced Research and Development Authority, US Department of Health and Human Services, Washington, DC; 3Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 4Division of Pediatric Infectious Diseases, University of Utah, Salt Lake City, Utah; 5Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia; 6Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and 7International Activities, Wellcome Trust, London, United Kingdom
Influenza infection results in substantial morbidity and mortality in hospitalized patients, including those who are immunocompromised or pregnant. Antiviral therapy likely provides considerable benefit to these patients, but few studies have been successfully conducted in these high‐risk populations, and no drugs are specifically licensed for treating these subgroups. One of the key challenges facing novel antiviral drug development for influenza is determining the appropriate efficacy end points that would enable rapid regulatory approval for drug use in seriously ill patients, for whom risk‐benefit assessments differ from those with uncomplicated illness. All available antiviral drugs currently affect viral replication, and respiratory tract viral titers correlate with both symptoms and measures of host inflammatory responses, including cytokine and chemokine expression that are likely responsible for many of the clinical symptoms. Consequently, we outline the evidence to support the use of primary virological end points in studies of antiviral agents involving patients who are hospitalized with severe influenza or those who are at high risk of severe and life‐threatening disease.
Received 20 October 2009; accepted 21 December 2009; electronically published 27 April 2010.
http://www.journals.uchicago.edu/doi/abs/10.1086/652498