Clinical development of therapeutic agents for hospitalized patients with influenza: Challenges and innovations

James C. King*, John H. Beigel, Michael G. Ison, Richard E. Rothman, Timothy M. Uyeki, Robert E. Walker, James D. Neaton, John S. Tegeris, James A. Zhou, Kimberly L. Armstrong, Wendy Carter, Peter S. Miele, Melissa S. Willis, Andrea F. Dugas, La Ree A. Tracy, David M. Vock, Rick A. Bright

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalOpen Forum Infectious Diseases
Volume6
Issue number4
DOIs
StatePublished - Apr 2019

Fingerprint

Proxy
Human Influenza
Triage
Therapeutics
Hospital Emergency Service
Research Personnel
Clinical Trials
Endonucleases
National Institutes of Health (U.S.)
Neuraminidase
Pandemics
United States Food and Drug Administration
Health Services
Inpatients
Outpatients

Keywords

  • Antivirals
  • Cinical site recruitment
  • Enrollment criteria
  • Influenza
  • Therapeutic trial endpoints

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

King, James C. ; Beigel, John H. ; Ison, Michael G. ; Rothman, Richard E. ; Uyeki, Timothy M. ; Walker, Robert E. ; Neaton, James D. ; Tegeris, John S. ; Zhou, James A. ; Armstrong, Kimberly L. ; Carter, Wendy ; Miele, Peter S. ; Willis, Melissa S. ; Dugas, Andrea F. ; Tracy, La Ree A. ; Vock, David M. ; Bright, Rick A. / Clinical development of therapeutic agents for hospitalized patients with influenza : Challenges and innovations. In: Open Forum Infectious Diseases. 2019 ; Vol. 6, No. 4.
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title = "Clinical development of therapeutic agents for hospitalized patients with influenza: Challenges and innovations",
abstract = "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.",
keywords = "Antivirals, Cinical site recruitment, Enrollment criteria, Influenza, Therapeutic trial endpoints",
author = "King, {James C.} and Beigel, {John H.} and Ison, {Michael G.} and Rothman, {Richard E.} and Uyeki, {Timothy M.} and Walker, {Robert E.} and Neaton, {James D.} and Tegeris, {John S.} and Zhou, {James A.} and Armstrong, {Kimberly L.} and Wendy Carter and Miele, {Peter S.} and Willis, {Melissa S.} and Dugas, {Andrea F.} and Tracy, {La Ree A.} and Vock, {David M.} and Bright, {Rick A.}",
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King, JC, Beigel, JH, Ison, MG, Rothman, RE, Uyeki, TM, Walker, RE, Neaton, JD, Tegeris, JS, Zhou, JA, Armstrong, KL, Carter, W, Miele, PS, Willis, MS, Dugas, AF, Tracy, LRA, Vock, DM & Bright, RA 2019, 'Clinical development of therapeutic agents for hospitalized patients with influenza: Challenges and innovations', Open Forum Infectious Diseases, vol. 6, no. 4. https://doi.org/10.1093/ofid/ofz137

Clinical development of therapeutic agents for hospitalized patients with influenza : Challenges and innovations. / King, James C.; Beigel, John H.; Ison, Michael G.; Rothman, Richard E.; Uyeki, Timothy M.; Walker, Robert E.; Neaton, James D.; Tegeris, John S.; Zhou, James A.; Armstrong, Kimberly L.; Carter, Wendy; Miele, Peter S.; Willis, Melissa S.; Dugas, Andrea F.; Tracy, La Ree A.; Vock, David M.; Bright, Rick A.

In: Open Forum Infectious Diseases, Vol. 6, No. 4, 04.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical development of therapeutic agents for hospitalized patients with influenza

T2 - Challenges and innovations

AU - King, James C.

AU - Beigel, John H.

AU - Ison, Michael G.

AU - Rothman, Richard E.

AU - Uyeki, Timothy M.

AU - Walker, Robert E.

AU - Neaton, James D.

AU - Tegeris, John S.

AU - Zhou, James A.

AU - Armstrong, Kimberly L.

AU - Carter, Wendy

AU - Miele, Peter S.

AU - Willis, Melissa S.

AU - Dugas, Andrea F.

AU - Tracy, La Ree A.

AU - Vock, David M.

AU - Bright, Rick A.

PY - 2019/4

Y1 - 2019/4

N2 - 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.

AB - 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.

KW - Antivirals

KW - Cinical site recruitment

KW - Enrollment criteria

KW - Influenza

KW - Therapeutic trial endpoints

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U2 - 10.1093/ofid/ofz137

DO - 10.1093/ofid/ofz137

M3 - Article

C2 - 31037242

AN - SCOPUS:85066394737

VL - 6

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

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ER -