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Am J Epidemiol . Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromyc

tetano

Editor, Senior Moderator
Am J Epidemiol


. 2021 Jun 24;kwab183.
doi: 10.1093/aje/kwab183. Online ahead of print.
Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans


Hanna Gerlovin[SUP] 1 [/SUP], Daniel C Posner[SUP] 1 [/SUP], Yuk-Lam Ho[SUP] 1 [/SUP], Christopher T Rentsch[SUP] 2 3 [/SUP], Janet P Tate[SUP] 2 4 [/SUP], Joseph T King Jr[SUP] 2 5 [/SUP], Katherine E Kurgansky[SUP] 1 [/SUP], Ioana Danciu[SUP] 6 [/SUP], Lauren Costa[SUP] 1 [/SUP], Franciel A Linares[SUP] 6 [/SUP], Ian D Goethert[SUP] 6 [/SUP], Daniel A Jacobson[SUP] 6 7 8 [/SUP], Matthew S Freiberg[SUP] 9 10 [/SUP], Edmon Begoli[SUP] 6 [/SUP], Sumitra Muralidhar[SUP] 11 [/SUP], Rachel B Ramoni[SUP] 11 [/SUP], Georgia Tourassi[SUP] 6 [/SUP], J Michael Gaziano[SUP] 1 12 13 [/SUP], Amy C Justice[SUP] 2 4 14 [/SUP], David R Gagnon[SUP] 1 15 [/SUP], Kelly Cho[SUP] 1 12 13 [/SUP]



Affiliations

Abstract

Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. We examined the effects of HCQ alone, and in combination with azithromycin, in a hospitalized COVID-19 positive, United States (US) Veteran population using a propensity score adjusted survival analysis with imputation of missing data. From March 1, 2020 through April 30, 2020, 64,055 US Veterans were tested for COVID-19 based on Veteran Affairs Healthcare Administration electronic health record data. Of the 7,193 positive cases, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and an increased risk of intubation when used in combination with azithromycin [Hazard Ratio (95% Confidence Interval): 1.55 (1.07, 2.24)]. In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treating patients hospitalized with COVID-19 using a national sample of the US Veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.

Keywords: covid-19; gradient boosting; hydroxychloroquine; pharmacoepidemiology; propensity score; survival analysis; treatment outcome.
 
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