Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.

Autor: King JC; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Beigel JH; National Institutes of Health, Division of Microbiology and Infectious Diseases, Bethesda, Maryland., Ison MG; Divisions of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois., Rothman RE; Department of Emergency Medicine, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, Maryland; for the ED Influenza Research Consortium., Uyeki TM; Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia., Walker RE; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Neaton JD; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis., Tegeris JS; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Zhou JA; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Armstrong KL; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Carter W; US Food and Drug Administration, Division of Antiviral Products, Silver Spring, Maryland., Miele PS; US Food and Drug Administration, Division of Antiviral Products, Silver Spring, Maryland., Willis MS; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia., Dugas AF; Shady Grove Medical Center, Rockville, Maryland., Tracy LA; US Food and Drug Administration, Division of Antiviral Products, Silver Spring, Maryland., Vock DM; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis., Bright RA; US Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Washington, District of Columbia.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2019 Mar 14; Vol. 6 (4), pp. ofz137. Date of Electronic Publication: 2019 Mar 14 (Print Publication: 2019).
DOI: 10.1093/ofid/ofz137
Abstrakt: Background: Since 1999, the US Food and Drug Administration approved neuraminidase and endonuclease inhibitors to treat uncomplicated outpatient influenza but not severe hospitalized influenza. After the 2009 pandemic, several influenza hospital-based clinical therapeutic trials were unsuccessful, possibly due to certain study factors. Therefore, in 2014, the US Health and Human Services agencies formed a Working Group (WG) to address related clinical challenges.
Methods: Starting in 2014, the WG obtained retrospective data from failed hospital-based influenza therapeutic trials and nontherapeutic hospital-based influenza studies. These data allowed the WG to identify factors that might improve hospital-based therapeutic trials. These included primary clinical endpoints, increased clinical site enrollment, and appropriate baseline enrollment criteria.
Results: During 2018, the WG received retrospective data from a National Institutes of Health hospital-based influenza therapeutic trial that demonstrated time to resolution of respiratory status, which was not a satisfactory primary endpoint. The WG statisticians examined these data and believed that ordinal outcomes might be a more powerful primary endpoint. Johns Hopkins' researchers provided WG data from an emergency-department (ED) triage study to identify patients with confirmed influenza using molecular testing. During the 2013-2014 influenza season, 4 EDs identified 1074 influenza-patients, which suggested that triage testing should increase enrollment by hospital-based clinical trial sites. In 2017, the WG received data from Northwestern Memorial Hospital researchers regarding 703 influenza inpatients over 5 seasons. The WG applied National Early Warning Score (NEWS) at patient baseline to identify appropriate criteria to enroll patients into hospital-based therapeutic trials.
Conclusions: Data received by the WG indicated that hospital-based influenza therapeutic trials could use ordinal outcome analyses, ED triage to identify influenza patients, and NEWS for enrollment criteria.
Databáze: MEDLINE
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