Pharmacoepidemiology, Machine Learning, and COVID-19: An Intent-to-Treat Analysis of Hydroxychloroquine, With or Without Azithromycin, and COVID-19 Outcomes Among Hospitalized US Veterans

Hanna Gerlovin, Daniel C. Posner, Yuk Lam Ho, Christopher T. Rentsch, Janet P. Tate, Joseph T. King, Katherine E. Kurgansky, Ioana Danciu, Lauren Costa, Franciel A. Linares, Ian D. Goethert, Daniel A. Jacobson, Matthew S. Freiberg, Edmon Begoli, Sumitra Muralidhar, Rachel B. Ramoni, Georgia Tourassi, J. Michael Gaziano, Amy C. Justice, David R. GagnonKelly Cho

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 among patients hospitalized with COVID-19. We examined the effects of HCQ alone and in combination with azithromycin in a hospitalized population of US veterans with COVID-19, using a propensity score-adjusted survival analysis with imputation of missing data. According to electronic health record data from the US Department of Veterans Affairs health care system, 64,055 US Veterans were tested for the virus that causes COVID-19 between March 1, 2020 and April 30, 2020. Of the 7,193 veterans who tested positive, 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 there was an increased risk of intubation when HCQ was used in combination with azithromycin (hazard ratio = 1.55; 95% confidence interval: 1.07, 2.24). In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treatment of 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.

Original languageEnglish
Pages (from-to)2405-2419
Number of pages15
JournalAmerican Journal of Epidemiology
Volume190
Issue number11
DOIs
StatePublished - Nov 1 2021

Bibliographical note

Publisher Copyright:
© 2021 Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Keywords

  • COVID-19
  • gradient boosting
  • hydroxychloroquine
  • pharmacoepidemiology
  • propensity score
  • survival analysis
  • treatment outcome

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