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

• Published in: American journal of epidemiology Vol. 190; no. 11; pp. 2405 - 2419
• Main Authors: Gerlovin, Hanna, Posner, Daniel C, Ho, Yuk-Lam, Rentsch, Christopher T, Tate, Janet P, King, Joseph T, Kurgansky, Katherine E, Danciu, Ioana, Costa, Lauren, Linares, Franciel A, Goethert, Ian D, Jacobson, Daniel A, Freiberg, Matthew S, Begoli, Edmon, Muralidhar, Sumitra, Ramoni, Rachel B, Tourassi, Georgia, Gaziano, J Michael, Justice, Amy C, Gagnon, David R, Cho, Kelly
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 02.11.2021; Oxford Publishing Limited (England)
• Subjects: Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibiotics; Azithromycin; Azithromycin - adverse effects; Azithromycin - therapeutic use; Clinical trials; Coronaviruses; COVID-19; COVID-19 - drug therapy; COVID-19 - mortality; Drug Therapy, Combination; Electronic health records; Electronic medical records; Female; Health services; Hospitalization; Hospitalization - statistics & numerical data; Humans; Hydroxychloroquine; Hydroxychloroquine - adverse effects; Hydroxychloroquine - therapeutic use; In vivo methods and tests; Intention to Treat Analysis; Machine Learning; Male; Middle Aged; Missing data; Observational studies; Patients; Pharmacoepidemiology; Population studies; Retrospective Studies; SARS-CoV-2; Survival; Survival analysis; Treatment Outcome; United States - epidemiology; Veterans; Veterans - statistics & numerical data; Viral diseases; Viruses; United States; United States > US; COVID-19; gradient boosting; hydroxychloroquine; survival analysis; treatment outcome; pharmacoepidemiology; propensity score
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwab183

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.