Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al, 2020)
Lover,
Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an..,
, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis)
Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significant effects from [HCQ+AZ]".
Currently there are
36 HCQ early treatment studies and meta analysis shows:
Lover et al., 10 Apr 2020, preprint, 1 author.
Abstract: medRxiv preprint doi: https://doi.org/10.1101/2020.03.22.20040949; this version posted April 10, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Q UANTIFYING T REATMENT E FFECTS OF
HYDROXYCHLOROQUINE AND AZITHROMYCIN FOR COVID-19:
A SECONDARY ANALYSIS OF AN OPEN LABEL
NON - RANDOMIZED CLINICAL TRIAL
A P REPRINT
Andrew A. Lover∗
Department of Biostatistics and Epidemiology
University of Massachusetts- Amherst
Amherst, MA
alover@umass.edu
April 1, 2020
——————————————————————————————————————————————The author stands by all analytical and statistical aspects of this preprint. However, subsequent to this analysis, further
details of the original study have been released- with major uncertainties in study design, reporting, choice of endpoints,
and most importantly, data integrity [1, 2]. Therefore, all results from the original study should be viewed with
considerable skepticism.
A BSTRACT
Human infections with a novel coronavirus (SARS-CoV-2) were first identified via syndromic
surveillance in December of 2019 in Wuhan China. Since identification, infections (coronavirus
disease-2019; COVID-19) caused by this novel pathogen have spread globally, with more than
250,000 confirmed cases as of March 21, 2020. An open-label clinical trial has just concluded,
suggesting improved resolution of viremia with use of two existing therapies: hydroxychloroquine
(HCQ) as monotherapy, and in combination with azithromycin (HCQ-AZ). [3, 4].
The results of this important trial have major implications for global policy in the rapid scale-up and
response to this pandemic. The authors present results with p-values for differences in proportions
between the study arms, but their analysis is not able to provide effect size estimates.
To address this gap, more modern analytical methods including survival models, have been applied to
these data, and show modest to no impact of HCQ treatment, with more significant effects from the
HCQ-AZ combination, potentially suggesting a role for co-infections in COVID-19 pathogenesis.
The trial of Gautret and colleagues, with consideration of the effect sizes, and p-values from multiple
models, does not provide sufficient evidence to support wide-scale rollout of HCQ monotherapy for
the treatment of COVID-19; larger randomized studies should be considered. These data also suggest
further randomized-controlled studies of HCQ-AZ combination therapy should be undertaken.
Keywords COVID-19 · Emerging pathogens · Pharmaceutical therapies · Clinical trials · Secondary analyses
∗
https://www.umass.edu/sphhs/person/faculty/andrew-lover
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2020.03.22.20040949; this version posted April 10, 2020. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
It is made available under a CC-BY 4.0 International license .
Quantifying Treatment Effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an
open label non-randomized clinical trial
A P REPRINT
Late treatment
is less effective
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