tetano
Editor, Senior Moderator
Open Forum Infect Dis. 2019 Mar 14;6(4)
fz137. doi: 10.1093/ofid/ofz137. eCollection 2019 Apr.
[h=1]Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.[/h] King JC[SUP]1[/SUP], Beigel JH[SUP]2[/SUP], Ison MG[SUP]3[/SUP], Rothman RE[SUP]4[/SUP], Uyeki TM[SUP]5[/SUP], Walker RE[SUP]1[/SUP], Neaton JD[SUP]6[/SUP], Tegeris JS[SUP]1[/SUP], Zhou JA[SUP]1[/SUP], Armstrong KL[SUP]1[/SUP], Carter W[SUP]7[/SUP], Miele PS[SUP]7[/SUP], Willis MS[SUP]1[/SUP], Dugas AF[SUP]8[/SUP], Tracy LA[SUP]7[/SUP], Vock DM[SUP]6[/SUP], Bright RA[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] 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.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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.
[h=4]Conclusions:[/h] 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.
[h=4]KEYWORDS:[/h] antivirals; clinical site recruitment; enrollment criteria; influenza; therapeutic trial endpoints
PMID: 31037242 PMCID: PMC6479095 DOI: 10.1093/ofid/ofz137
Free PMC Article
fz137. doi: 10.1093/ofid/ofz137. eCollection 2019 Apr.[h=1]Clinical Development of Therapeutic Agents for Hospitalized Patients With Influenza: Challenges and Innovations.[/h] King JC[SUP]1[/SUP], Beigel JH[SUP]2[/SUP], Ison MG[SUP]3[/SUP], Rothman RE[SUP]4[/SUP], Uyeki TM[SUP]5[/SUP], Walker RE[SUP]1[/SUP], Neaton JD[SUP]6[/SUP], Tegeris JS[SUP]1[/SUP], Zhou JA[SUP]1[/SUP], Armstrong KL[SUP]1[/SUP], Carter W[SUP]7[/SUP], Miele PS[SUP]7[/SUP], Willis MS[SUP]1[/SUP], Dugas AF[SUP]8[/SUP], Tracy LA[SUP]7[/SUP], Vock DM[SUP]6[/SUP], Bright RA[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] 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.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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.
[h=4]Conclusions:[/h] 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.
[h=4]KEYWORDS:[/h] antivirals; clinical site recruitment; enrollment criteria; influenza; therapeutic trial endpoints
PMID: 31037242 PMCID: PMC6479095 DOI: 10.1093/ofid/ofz137
Free PMC Article