What should we think ?

Chloroquine, this antimalarial treatment, is causing a lot of debate on social networks even among scientists. What should we think of this substance in the fight against Covid-19?

The following article does not judge medical practice in the field in times of health crisis. You have to be aware of the difficulty and the need to be pragmatic against this epidemic. Likewise, when navigating in the unknown in an unprecedented situation, the measures taken are necessarily unprecedented. BUT. Because yes, there is a "but".

To introduce the objective of this article, let us quote Gandhi: Error does not become truth because it propagates and multiplies; truth does not become error because no one sees it. " If this famous and elegant speech can be used to justify everything and its opposite, we will try to honor it here.

The aim will then be to identify and assess the body of evidence that we have at the time of writing, in order to know whether the chloroquine is (or is not, you have to know how to put your hope aside) an adequate treatment (that is to say having a specific effect greater than placebo and a positive risk-benefit balance) against the new Covid-19 disease induced by SARS-CoV-2 infection.

Brief feedback on chloroquine

Chloroquine is a preventive antimalarial and curative. It is also used against autoimmune diseases such as lupus. Most of the time, its chemical derivative is prescribed: hydroxychloroquine (that is to say, with a group alcohol OH more on the molecule). As for the drug, it door the trade name of Plaquenil for hydroxychloroquine and Nivaquine for chloroquine.

Following the media outburst concerning this molecule which we will talk about below, a comment was published in the scientific literature by two researchers (Franck Touret and Xavier de Lamballerie) fromEmerging Virus Unit from the University of Aix-Marseille. Here is what we can learn about chloroquine and its history in the treatment of respiratory viral diseases:

  • Experiences in vitro (on cells, therefore) suggest that chloroquine inhibits replication of SARS-CoV-2.

  • Chloroquine has shown its potential in the past in vitro against a lot of virus different but has always failed in testing in vivo (on living organisms, therefore) on animal models.

  • Chloroquine has often been proposed in the management of human respiratory viral disease. Without success.

  • The Chinese consensus, Which attests to its effectiveness, does not mention any raw data. However, the process of peer review, independent evaluations of the method and results, as well as replication of studies are essential to judge the potential benefits (but also risks) for patients.

Here is a measured, nuanced comment, up to date with the data currently known. Unfortunately, not all researchers are so cautious.

Media excitement

With such cases, the media are having a great time. In these moments, one can only regret the general ignorance of what the scientific method is. However, they are not alone. Indeed, Didier raoult, infectiologist and professor of microbiology at the Institut-hospitalo-universitaire (IHU) Méditerranée at the Timone hospital in Marseille is making a lot of talk about him at the moment. This great teacher (which we do not try in this article, we do not judge the man or his great career but many data) seems to be the source of this excitement, with a published ehealth February 25, 2020, initially titled " Coronavirus : game over ! " (based on the consensus of Chinese experts already cited) then renamed some time later “Coronavirus: Towards a way out of the crisis? " Since then, he has intervened a lot in the media, with little care, to talk about chloroquine. He is particularly active on the ehealth platform Youtube also, which is quite curious for a scientist, especially when it is to present works that have not been read by his peers.

If it is not a question of judging a doctor on the ground, especially in times of crisis, one can wonder where has passed the caution in the communication of the results, essential quality of the scientist? Before a treatment is accepted and approved it normally takes a long time. A time that we do not necessarily have at the moment, in medical practice. Is. This is easily understood. However, this also requires rigor. This rigor is essential if we want to learn something. Otherwise, we don't learn, strictly speaking, nothing.

The role of the science journalist has not changed. To use the words of a colleague, Florian Gouthière – who has just written a very enlightening article on the subject – on his blog curiologie.com, the role of a science journalist would be rather " to inform about the uncertain, in an uncertain world. To do this, we need to make the general public understand that uncertainty is consubstantial with the progress of scientific knowledge, and that a public announcement – as exciting as it is – must still stand the Review of time. "

Therefore, we understand that the media runaway can be harmful. Be careful, if you are hospitalized, trust your doctor.

Simply, like science of which the scientific journalist reports, he informs about the description. The normative then belongs to everyone. Informing about the description then amounts, as initially specified, to seizing the large body of available evidence and judging a given hypothesis or assertion more or less likely. It can change over time and prove us right – or wrong. Whatever happens, an honest science journalist will take the side of hard data. But before time goes by and clinical tests quality are made, impossible to know. Neither we, nor eminent teachers, have the capacity to predict the future.

Authority is not an argument

In this story, it is important to return to this basic principle of the skeptical approach. The authority, the diploma or the celebrity of a person are not arguments. Of course, our judgment heuristics make us believe our doctor when he talks to us about medicine. And it's legitimate. Nevertheless, our doctor remains a biased human being who can make mistakes, especially if he gets carried away, as was the case with Professor Raoult, when he titled his ehealth " Coronavirus: end of game! " on the sole basis of a consensus of experts without raw data. The game is, unfortunately, far from over. You just have to look at the curves of contamination current whose evolution is exponential. Also, the number of deceased people is increasing (that of people also cured, fortunately).

In addition, this professor is illustrated by his numerous publications, which gives him even more confidence in his field. However, when you dig slightly, you realize that a certain number (not all, of course) are published in newspapers where the editors are sometimes part of its research team. Some are also accepted with insane speed that leaves no time for the peer review process. It is neither more nor less a short circuit sporadic of the scientific approach.

Unfortunately, this kind of practice is more and more common and can be explained in part by the weather in which evolves the world of science and research currently. The goal is to be talked about, to publish a lot of innovative research, to make a name for yourself. All this in order to obtain funding which is sorely lacking. Sometimes it goes through a amputation clear of the rules of scientific art.

Professor Raoult's study: a nest with “bias”

For a hypothesis to be scientifically validated, it takes a lot rigorous studies, Similarly reproduced around the world and independently. Studies are underway to assess the one we are talking about today, namely: " is chloroquine effective in the treatment of Covid-19 ? " Professor Raoult's study has just been sent, accepted and published in record time (which is not a good sign.) What can we draw as a conclusion from this study to validate or invalidate the initial hypothesis? Well not much! Let us list point by point the methodological biases of this paper (for even more details, you can consult the page PubPeer dedicated to this study, where criticism and questions are coming from the scientific community).

  • The study is carried out in open-label, that is to say without a blindness procedure (the patient and the doctor know who is in which group, which exposes to major bias) and without randomization (which means that the potential confounding factors are probably not not excluded).

  • The objectives of the study are much more moderate than Professor Raoult's interventions in the media. We can then read there "We are assessing the role of hydroxychloroquine on viral loads respiratory ", the goal being to lower them. However, an article appeared in the newspaper Nature concerning the study of respiratory diseases such as those induced by SARS-CoV-1 or MERS-CoV concluded in 2016 that the most serious forms were associated with a decrease in viremia. This pushes us to be extra careful when we hear Professor Raoult exclaim on Youtube " if you no longer have the virus, you are saved ”, even though, as we will see below, the clinical condition of the patients is not described in his essay.

  • The team had set as a secondary objective monitoring changes in parameters such as apyrexia, normalization of frequency respiratory, the duration mean hospitalization and mortality. This ghost data is completely absent from the paper.

  • Patients were treated with either hydroxychloroquine alone or with a antibiotic (azithromycin) with hydroxychloroquine, or they were not treated (control group). No placebo treatment, therefore. From the outset, we know that all that can be learned from this experience is a comparison between two treatments and a non-treatment, not between a treatment and a sham, which is essential to know the effect. clean of what you think is a "medicine". In addition, the control group was not on the same site as the treated group.

  • The sample is small with 26 patients initially (only 20 at the end of the study), which is too small to obtain robust results contrary to what Professor Raoult claims. The laws of probability don't change, even in times of pandemic.

  • Neither the clinical status nor the initial viral load of patients is known. The clinical condition also remains unknown at the end of the study. In addition, viral load tests give variable results depending on the day (a positive stroke, a negative stroke and then positive again). We can therefore legitimately question the current reliability of these tests.

  • The follow-up was to last 14 days, but the results presented only go until 6e day, which is clearly not normal.

  • Certain exclusion criteria (such as not integrating children under the age of 12) are not respected.

  • Some patients were considered "lost to follow-up". This usually happens, but here it is the authors who have chosen to exclude them. We then discover that all these patients were part of the chloroquine group. Three were transferred to intensive care, one died, one patient may not have been ill, and one patient wanted to stop treatment because of side effects. It is surprising that the three intensive care patients were not followed up.

  • His paper does not respect the ethical bases of a scientific publication. The study is published in a newspaper where the chief editor works under the orders of Professor Raoult, in the same institute. Also, note that the document was received on March 16, accepted on March 17 and published on March 20.

The Zhejiang University School of Medicine (China) has also just published a Covid-19 prevention and treatment manual where it can be read on page 40 that the data concerning chloroquine are insufficient to consider it as a treatment and where the combination of hydroxychloroquine and azithromycin is strongly discouraged. The World Health Organization (WHO) also spoke yesterday and state this “Small observational, non-randomized studies won't give us the answers we need. Using an untested pill without the right evidence could raise false hopes and even do more harm than good and lead to a shortage of the essential pill needed to treat other illnesses ”.

A new chinese study (with a protocol also imperfect but still a little more serious than that of the Marseillaise study) recently concluded that hydroxychloroquine alone was ineffective compared to no treatment on a small sample. His conclusion is this: "The prognosis of current COVID-19 patients is good. A larger sample size study is needed to investigate the effects of hydroxychloroquine in the treatment of COVID-19. Further research should determine a better endpoint and take full account of the feasibility of experiments such as the sample size. " But a single study proves nothing. As this study concludes, we need more research.

Finally, the Minister of Health, Olivier Véran, answered questions about chloroquine and Professor Raoult's study, not lacking in temperance regarding the results obtained.

The importance of informing with nuance

This article wishes, in addition to informing you about the interest (or non-interest) currently known of chloroquine in the treatment of Covid-19, to make you understand the importance of nuanced information. The media excitement does not serve any legitimate cause if not in the best of cases reassure the population for reasons which will prove good, in the worst give them false hopes, which will not fail to discredit you completely. Likewise, if this treatment is effective, we will certainly have lost a little time to save lives. On the other hand, if it turns out that it does not work, or even that it worsens the situation, we will have saved it. Treating is not always better than doing nothing. For example, in these early days, thehomeopathy ((which is nothing but a placebo) was more beneficial to patients than bloodletting. Doing nothing was the best way to save lives. You have to keep that in mind.

In addition, the consequences of this type of communication are difficult to predict, except perhaps for those who know human behavior well. On the other side of the Atlantic, Donald Trump captured these results with the same enthusiasm than Professor Raoult. He is currently doing pressure on the Food and Drug Administration ((FDA) for chloroquine to be expressly authorized. With us, pharmacies are currently facing an unusual request of chloroquine. Note that Professor Raoult has never spoken or advised of self-medication.

Any argument other than rigorous and documented data is not an argument. They can “serve” on the media or political level, but when we try to make understand (and not impose) a fact on an audience or on a readership, we must necessarily go through an argument concrete. However, we have seen, for the moment, the body of evidence concerning the assertion " chloroquine is effective in the treatment of Covid-19 " is too thin to judge it as likely. There is a difference between what doctors do in a crisis situation and the construction and the diffusion of what we commonly call knowledge.

Doctors are currently fighting to save lives. Chloroquine is part of the latest therapeutic arsenal (because of its low level of evidence) recommended by different learned societies (two molecules, Remdesivir and the Lopinavir / ritonavir combination are offered first) in the management of intensive care patients infected with SARS-CoV-2. The defamatory speeches which suppose that in hospitals, one does not treat because one does not give chloroquine is a lie and a lack of respect for the medical teams.

The Minister of Health said that studies were underway on a larger scale. Large clinical trials have just been launched to evaluate several potential treatments (including hydroxychloroquine), the French part of which will be carried out by the National Institute of Science and Medical Research (Inserm). We will have to wait for the results of these experiments to be able to update our remarks. Finally, like everyone else, we strongly hope that time proves our epistemic prudence to face this new disease.

Already visible consequences

Two days after writing this article, this media-scientific excitement is already showing its harmful consequences. According to Banner Health Hospital in the United States, a 60-year-old man died (and his wife is in a state of concern) after ingesting too high doses of chloroquine phosphate. In France, shortages are noted according to an article in the Parisian and Lupus patients, for whom treatment is necessary, find it difficult to find it. The Sanofi group, a major player in the pharmaceutical industry, ensures that stocks arrive.

Because of this shambles, The National Agency for the Safety of Medicines (ANSM) expressly requests in a press release this thursday march 26 "pharmacists to dispense these drugs (hydroxychloroquine and lopinavir / ritonavir) only on medical prescription in their usual indications, this in order to secure their access to patients who benefit from them for their chronic treatment". The agency "calls for the responsibility of each actor in the chain of care in order to guarantee the supply of treatments allowing the care of patients who have or will need it."

To note :

To complete this article, the editorial staff advises you the excellent and brief analysis of Nicolas Martin sure France Culture concerning chloroquine as well as the very complete article by Florian Gouthière on the same subject: Covid-19 & chloroquine: about a very fragile study, and a dangerous media and political excitement "

To learn more about the evolution of the coronavirus or Covid-19 Chloroquine and Covid-19: caution is advised with the anti-malaria drug How to make your own homemade hydroalcoholic gel? US to study treatment for coronavirus

Covid-19 symptoms: diabetes and hypertension as aggravating factorsThis is what Wuhan coronavirus looks like

This will also interest you

SARS-COV-2 pandemic: should you be worried? Health measures are being taken by all European governments to limit the spread of the virus. Should we be worried about the current pandemic?

Did you like this article ? Don't hesitate to share it with your friends and help us to promote ABSMARTHEALTH :)! The editorial team thanks you.

The post What should we think ? appeared first on Smart Be Well.