Abstract: Clinical Microbiology and Infection 27 (2021) 6e8
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Clinical Microbiology and Infection
journal homepage: www.clinicalmicrobiologyandinfection.com
Commentary
Rational for meta-analysis and randomized treatment: the COVID-19
example
Didier Raoult 1, 2, *
1)
2)
MEPHI, IRD, Aix Marseille Univ, AP-HM, Marseille, France
IHU-M
editerran
ee Infection, Marseille, France
a r t i c l e i n f o
Article history:
Received 21 September 2020
Received in revised form
9 October 2020
Accepted 13 October 2020
Available online 21 October 2020
Editor: L. Leibovici
My opinion is that hydroxychloroquine has become the symbol
of a struggle between practising physicians and methodologists [1],
and the Western world against the rest of the world [2]. This leads
to great confusion in the literature between, on the one hand, the
advocates of an empirical approach based on the sensitivity of
bacteria, viruses or parasites to anti-infectious agents in vitro and
the rational use of these anti-infectious agents in patients, and, on
the other hand, the analysts who, taking up the various studies, are
more specifically interested in the form of the studies to determine
the existence of biases. Recently, hydroxychloroquine, from my
point of view, became a paradigm of such conflict.
For example, when testing hydroxychloroquine, exclusion of
patients without confirmed diagnosis is for us a major issue. In
contrast, several studies do not consider this parameter to be
essential [3,4], including a large study testing the efficacy of
hydroxychloroquine prophylaxis [5]. This inclusion criterion is
mandatory for me. In addition, there are considerable differences in
dosing regimens as there is no standard dosing regimen: the Recovery Trial gave a theoretically toxic dosage at baseline (2.4 g),
others use 200 mg daily, while we prescribe, in my institute, 600
mg daily, as in Q fever or Whipple's disease [6]. Also, it is important
to compare the duration of treatment. Entering hospital data with a
hydroxychloroquine yes/no answer does not tell much about the
DOI of original article: https://doi.org/10.1016/j.cmi.2020.08.022.
dite
ranne
e Infection, Aix Marseille Universite
, Marseille, France.
* IHU Me
E-mail address: didier.raoult@gmail.com.
treatment. These are major problems with the inclusion criteria in
big data studies.
The stage of the disease at which treatment is given is critical.
Two reviews explain that there are four stages in the disease [6,7].
There is a first virological stage, when the antiviral drugs can be
effective, a second viro-immunological stage, when the immunological reaction aggravates the patient's condition and is associated
with abnormal coagulation phenomena including antiphospholipid antibodies [8], a third stage that is exclusively or
almost exclusively immune, also called the cytokine storm, and
finally a fourth stage, resulting from multiple pulmonary and
visceral injuries. Thus, each stage probably corresponds to different
therapeutic strategies. Finally, evaluation of the therapeutic efficiency in all infections of the lung is usually performed after 3 days
of treatment. Mixing patients of different stages, with different
doses and durations of treatment, may result in a false result known
as “Simpson's paradox” [9]: studying separate groups of patients
from the same study may result in opposite conclusions. Some
French studies exclude patients who are treated while they have
already been..
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