Development of an Ordinal Scale Treatment Endpoint for Adults Hospitalized With Influenza. (17th June 2020)

• Record Type: Journal Article
• Authors: Lee, Nelson; Smith, Stephanie W; Hui, David S C; Ye, Ming; Zelyas, Nathan; Chan, Paul K S; Drews, Steven J; Zapernick, Lori; Wong, Rity; Labib, Mary; Shokoples, Sandy; Eurich, Dean T
• Is Part Of: Clinical infectious diseases. Volume 73:Number 11(2021)
• Page Start: e4369
• Page End: e4374
• Publication Date: 2020-06-17
• Subjects: influenza -- treatment endpoint -- ordinal scale -- antiviral -- neuraminidase inhibitors; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa777
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients' diverse clinical trajectories and low event rates. Methods: A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts' datasets (2015/2016−2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. Results: Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ± SD, 4.3 ± 0.6 vs 3.5 ± 0.6, P < .001). Improved outcomes with NAI treatment within 5 days were indicated by significantly lower clinical status scores over time (unadjusted odds ratio [OR], 0.53; 95% confidence interval [CI], .41−.69; P < .001; adjusted OR, 0.62; 95% CI, .50−.77; P < .001, for baseline score, age, and within-patient correlations). In subanalysis, influenza vaccination was also associated with lower scores (adjusted OR, 0.67; 95% CI, .50−.90; P = .007). Analyses of binary endpoints showed insignificant results. Conclusions: The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development. Abstract : Using data from a multicenter hospital cohort (n = 1226), we showed that treatment-related clinical improvement and outcomes could be indicated by ordinal scale score changes over time. Further evaluation of ordinal scale as a treatment endpoint is warranted.