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
Gerlovin et al.,
Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with..,
American Journal of Epidemiology, doi:10.1093/aje/kwab183
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
risk of death, 22.0% higher, HR 1.22, p = 0.18, treatment 90 of 429 (21.0%), control 141 of 770 (18.3%), adjusted per study, HCQ+AZ.
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risk of death, 21.0% higher, HR 1.21, p = 0.33, treatment 49 of 228 (21.5%), control 141 of 770 (18.3%), adjusted per study, HCQ.
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risk of mechanical ventilation, 55.0% higher, HR 1.55, p = 0.02, treatment 64 of 429 (14.9%), control 69 of 770 (9.0%), adjusted per study, HCQ+AZ.
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risk of mechanical ventilation, 33.0% higher, HR 1.33, p = 0.25, treatment 32 of 228 (14.0%), control 69 of 770 (9.0%), adjusted per study, HCQ.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Gerlovin et al., 24 Jun 2021, retrospective, USA, peer-reviewed, 21 authors.
Abstract: American Journal of Epidemiology
Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021.
This work is written by (a) US Government employee(s) and is in the public domain in the US.
Vol. 190, No. 11
https://doi.org/10.1093/aje/kwab183
Advance Access publication:
June 24, 2021
Original Contribution
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
∗ Correspondence to Dr. Hanna Gerlovin, VA Boston Healthcare System, 150 South Huntington Avenue (151-MAV), Boston, MA
02130 (e-mail: Hanna.Gerlovin@va.gov).
Initially submitted December 15, 2020; accepted for publication June 17, 2021.
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 conf licting
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.
COVID-19; gradient boosting; hydroxychloroquine; pharmacoepidemiology; propensity score; survival analysis;
treatment outcome
Abbreviations: CI, confidence interval; GBM, gradient boosting machine; HCQ, hydroxychloroquine; HR, hazard ratio; SARSCoV-2, severe acute respiratory syndrome coronavirus 2; VA, Veterans Affairs.
In the swell of the coronavirus disease 2019 (COVID-19)
pandemic, the world rushed to find therapies and prophylactic treatments, and hydroxychloroquine (HCQ) became an
early front-runner (1, 2). HCQ is a common antimalarial and
antirheumatologic drug with immunosuppressive functions.
Results of early in vitro studies suggested HCQ might be
repurposed to treat infections with a strong immune component (1, 3, 4), such as COVID-19. This was appealing,
considering its low cost and widespread availability. The US
Food and Drug Administration issued an emergency use
authorization for HCQ on March 28, 2020 (5), prior to the com
pletion of a randomized controlled trial, only to revoke it less
than 3 months later, following concerns about HCQ-associated adverse events reported from observational studies (6, 7).
At about the..
Late treatment
is less effective
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