Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/164556
Title: Evaluating primary endpoints for COVID-19 therapeutic trials to assess recovery
Authors: Douin, David J.
Siegel, Lianne
Grandits, Greg
Phillips, Andrew
Aggarwal, Neil R.
Baker, Jason
Brown, Samuel M.
Chang, Christina C.
Goodman, Anna L.
Grund, Birgit
Higgs, Elizabeth S.
Hough, Catherine L.
Murray, Daniel D.
Paredes, Roger
Parmar, Mahesh
Pett, Sarah
Polizzotto, Mark N.
Sandkovsky, Uriel
Self, Wesley H.
Young, Barnaby Edward
Babiker, Abdel G.
Davey, Victoria J.
Kan, Virginia
Gelijns, Annetine C.
Matthews, Gail
Thompson, B. Taylor
Lane, H. Clifford
Neaton, James D.
Lundgren, Jens D.
Ginde, Adit A.
Keywords: Science::Medicine
Issue Date: 2022
Source: Douin, D. J., Siegel, L., Grandits, G., Phillips, A., Aggarwal, N. R., Baker, J., Brown, S. M., Chang, C. C., Goodman, A. L., Grund, B., Higgs, E. S., Hough, C. L., Murray, D. D., Paredes, R., Parmar, M., Pett, S., Polizzotto, M. N., Sandkovsky, U., Self, W. H., ...Ginde, A. A. (2022). Evaluating primary endpoints for COVID-19 therapeutic trials to assess recovery. American Journal of Respiratory and Critical Care Medicine, 206(6), 730-739. https://dx.doi.org/10.1164/rccm.202112-2836OC
Journal: American Journal of Respiratory and Critical Care Medicine 
Abstract: Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.
URI: https://hdl.handle.net/10356/164556
ISSN: 1073-449X
DOI: 10.1164/rccm.202112-2836OC
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Tan Tock Seng Hospital
National Centre for Infectious Diseases, Singapore
Rights: © 2022 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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