The hydroxychloroquine debate was thought to be buried.
And yet the molecule defended by Professor Didier Raoult to treat cases of Covid-19 is resurfacing in the scientific community.
The reason?
The professor and his team of researchers from the Institut hospitalo-universitaire (IHU) Méditerranée Infection in Marseille published a letter on the National Center for Biotechnology Information (NCBI) website, reviewing their first non-randomized clinical trial carried out in March 2020 This publication is supposed to counter the many criticisms which have been made, in particular on the methodology of their essay.
As a reminder, the study involved a small sample, i.e. 42 patients divided into three groups: a first (18 people) who did not receive treatment, a second (16 people) who was administered hydroxychloroquine. and a third (8 people) who received a treatment combining hydroxychloroquine and azithromycin, an antibiotic.
What this letter says
Far from satisfying everyone, the letter made many scientists react.
One sentence particularly caught the attention, causing since last weekend a salvo of reactions on social networks.
In the first paragraph of the letter, Didier Raoult and his team stress that “the needs for oxygen therapy, resuscitation transfers and deaths have not varied significantly from one group to another”.
In other words, hydroxychloroquine would not reduce the mortality of Covid patients.
Some believed to see behind this observation, a first retreat of the professor who did not stop defending the molecule, in spite of the recurring criticisms of his colleagues.
However, the IHU team in Marseille does not seem to mention the ineffectiveness of its treatment in any way, since it adds in its letter: “The length of stay in hospital and viral persistence were significantly shorter in the group. of patients treated ”.
The treatment would therefore be in their eyes, always effective, at least on the viral load of Covid-19.
What the IHU responds to
"There is obviously no change of position," protested against Parisian Yanis Roussel, doctoral student and spokesperson for the IHU in Marseille.
“To say that we are going backwards and absolutely grotesque.
These criticisms do not come from scientists but from dishonest people or activists who instrumentalize our remarks, ”judges this close to Didier Raoult.
No admission of failure therefore, but confusion on the part of the scientific world which "would mix several studies", defends Yanis Roussel.
“The first IHU study dating from March 2020 never drew a conclusion on mortality but on the viral load, which drops thanks to the treatment of hydroxychloroquine and azithromycin.
The object of this essay was simply not mortality!
Because we would not have been able to show a significant difference clinically with such a small sample ”, assures the doctoral student.
And to add: "The IHU made several other studies on mortality in 2020, also showing its effectiveness and we do not take a line out!
".
Are these details convincing?
If Didier Raoult's team continues to defend the effectiveness of the molecule on viral load, the data it shares in its latest publication does not support its arguments, however, believes Thibault Fiolet, doctoral student in public health epidemiology at Inserm.
“The main problem is that we do not have all the figures to judge the effectiveness of the molecule or not.
We only have data for the first seven days of treatment.
However, according to the European protocol, patient data must be collected up to the fourteenth day.
This leads us to believe that there is indeed a selection of results, ”notes the specialist.
For its part, the IHU sweeps away the criticisms, ensuring that the results were not communicated beyond that because "100% of the patients treated then no longer had a viral load".
But fragmented data does not seem to be the only flaw in the clinical trial.
By noting the details provided in the letter of January 2021, a difference in the methodology appears: in 2020, the trial had 36 patients ... while they are finally 42 in the document of 2021.
In addition to the problems of methodology, the interpretation of the results also raises questions.
Regarding viral load, the differences between the three groups of patients are not obvious, believes Thibault Fiolet.
To realize this, we must refer to the “p-value”, a statistical indicator which will compare the proportion of negative people to the PCR test between the groups treated with hydroxychloroquine and the others.
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"If the p-value is less than 0.05, we say that there is a significant difference between the groups and therefore a significant effect of the drug", specifies the epidemiologist.
This effect is clearly visible on the fifth and sixth day when a p-value of 0.003 and 0.001 is observed.
“On the sixth day we see a significant difference in terms of cure between the groups in favor of hydroxychloroquine.
In other words, the molecule seems to reduce the viral load of the virus.
However, this difference is not found either on the fourth day or on the seventh day with p-values of 0.07 and 0.051 ”, analyzes the scientist.
Study data from 42 patients from the first non-randomized clinical trial in March 2020 by the Marseille IHU / National Center for Biotechnology Information (NCBI)
The data then remain fragile to draw a conclusion: "These inconsistencies and the non-publication of the data until the fourteenth day suggest that the results are due to chance or to bias given the very small number", concludes Thibault Fiolet. .
In summary
Despite what has been understood by some, Professor Didier Raoult and his teams absolutely do not give up hydroxychloroquine.
"To say that we are going backwards and absolutely grotesque", we are assured on the side of the IHU.
The molecule is still struggling to convince the scientific world.
As a reminder, the National Agency for the Safety of Medicines and Health Products (ANSM) rejected last October the IHU's request to use the antimalarial even in an exceptional way to treat patients with Covid-19 , in view of the “data available, very heterogeneous and unequal”.