tackling ivermectin .
https://www.francesoir.fr/opinions-tribunes/quand-le-monde-deconnde
Author (s): Enzo Lolo, for FranceSoir
TRIBUNE - Dr Maudrux: "I had started to do it, he did it, I could not have done better, I am delivering it to you."
Article by Enzo Lolo, initially published on his blog Médiapart , then taken up by Dr Gérard Maudrux on his blog .
An article in “ Décodeurs ” tackles ivermectin . By disguising the arguments of those who consider the treatment effective, by using scientifically contested arguments and by seeking to politicize the molecule. We answer them. The “Décodeurs” du Monde published on April 13 an article claiming to shed light on the debate on ivermectin, by asking a fundamental question: “ Is this a proven treatment in the face of the epidemic due to SARS-CoV- 2 or a false hope? "Such a question, on which the lives of thousands of patients in France and millions around the world may depend, deserved rigorous treatment from" Décodeurs ". Unfortunately, the quantity of scientific elements that the “Decoders” have not seen, or at least not mentioned, is considerable, and the article only manages to generate confusion, which we will detail here.
Are there any scientific arguments in favor of ivermectin?
One paragraph of the article in Le Monde , in particular, is astounding, titled:
"What are they relying on to defend ivermectin?" ".
He achieves the feat of citing arguments on which no one leans, and of silencing almost all of the arguments used by the " defenders " of ivermectin. This paragraph cites in all and for all 4 scientific sources, which are therefore presented as “ the justifications ” put forward to support the use of ivermectin against Covid-19:
1) The Australian in vitro study conducted by Caly et al. and published in June 2020 in Antiviral Research.
Today, no voice evokes this study as a justification for ivermectin treatments. Certainly, this study had an important role in paving a way, and in leading researchers around the world to conduct clinical studies to evaluate the effectiveness of ivermectin in patients . But it is not on an in vitro study , carried out in Petri dishes or test tubes that one thinks of relying to confirm the effectiveness of a treatment.
2) The article by Bernigaud et al. , published in December 2020 in the Annales de Dermatologie et de Vénérologie .
It is true that this article is sometimes mentioned by the defenders of ivermectin, because of its spectacular nature (zero cases of severe Covid and zero deaths in a nursing home affected by Covid-19 in March 2020), but the “ defenders »Of ivermectin are aware that this article has limits: this is not a trial conducted on ivermectin, but a case of serendipity - the title of the article makes it clear from the outset - , where ivermectin appears to have had unexpected effects on Covid-19 when administered against scabies. Charlotte Bernigaud and her colleagues had not planned to conduct a study, and therefore did not set up a dedicated protocol. In particular, no control group is formed, either prospectively or retrospectively. This study was likely to warrant research, such as that by Caly et al . and it may be a clue , but it is not used as "proof" of the efficacy of ivermectin.
3) A study conducted by Dias de Malho et al. on hamsters.
If this study can shed light on certain mechanisms of action of ivermectin, no one thinks of evoking it as proof of its effectiveness for the treatment of human patients .
4) The study by Rajter et al. , uploaded in October 2020 and published in Chest.
This is the only one of the 4 studies cited by the “ Décodeurs ” which actually corresponds to the type of studies on which the “defenders” of ivermectin are based. But Le Monde cites only that one (" We can also cite a study conducted in the United States (...) ") forgetting that there were 49 other trials carried out on humans, the results of which are available online , and on which the “defenders” of ivermectin rely. Worse still, the “ Decoders ” seem to close the debate: “(…) [the study] shows that treatment with ivermectin is associated with lower mortality, but points out that “Randomized trials are needed to confirm these results ” . " This sentence deserves a rebuttal end product itself alone!
First, it is customary to conclude a scientific article by conceding that other work must come to corroborate what one thinks to have found, and this type of formula is not to be taken at face value, and even less to be interpreted as " underlined ", as the " Decoders". But above all, between the posting of this conclusion online by Rajter and his colleagues on October 13, 2020, and the publication on April 13, 2021 of the “Decoders” article, 6 months elapsed, during which 22 results of Randomized Controlled Trials Have Been Made Public! Have the Decoders noticed?
And that's all ?
Obviously, the " Decoders " did not interview any of the "advocates" of ivermectin before releasing an imaginary version and their arguments. Indeed, none of their serious arguments are mentioned:
- nor the 49 clinical trials (including 26 randomized controlled trials) conducted on ivermectin in addition to that of Rajter et al . A priori exhaustive directory of studies available online can be found here .
- nor the meta-analyzes carried out from these 50 trials, according to different methodologies, all agreeing to show a drop in mortality in patients treated with ivermectin, a drop of between 68 and 83%. Among the meta-anlyses used as arguments in favor of treatments including ivermectin, we find those of:
Kory et al. (peer reviewed twice, first by Frontiers of Pharmacology , which however refused to publish it , then by the International Journal of Therapeutics )
Hill et al. (preprint)
Lawrie et al. (preprint)
Bryant et al. (preprint, study conducted according to the strict “Cochrane” methodology)
Nardelli et al. (peer reviewed, published in Signa Vitae )
- nor systematic reviews, in which researchers assess the studies already available:
Cobos-Campos et al. (preprint)
Kalfas et al. (preprint)
McCullough et al. (peer reviewed, published in Reviews of Cardiovascular Medicine )
Guillausseau published in Horizons & Thérapies
Yagisawa et al. (peer reviewed, published in the Japanese Journal of Antibiotics )
- nor the epidemiological studies carried out on countries or regions which have favored the use of ivermectin:
Study by Hellwig and Maia comparing the impact of Covid-19 in African countries depending on the existence or not of a policy massive use of ivermectin to prevent parasitic diseases;
Study by Tanioka et al. , quite close to the previous one, comparing the African countries organizing the prevention of onchorcerciasis by treatment with ivermectin and those which do not;
Study by Juan Chamie on the cases of Peru, Chiapas in Mexico, Uttar Pradesh in India, several regions of Argentina, Alto Parana in Paraguay, and several cities in Brazil having adopted ivermectin against to Covid-19;
Study by Emmerich comparing two Brazilian states, Pará and Amazonas, published in Int. Journal of Environmental Researh and Public Healt h , and summarized here .
- nor the assessment of the benefit / risk balance, taking into account the fact that ivermectin is an extremely safe drug , without serious side effects, even in the event of an overdose . With a dose of humor, Dr. Maudrux - that "Decoders" mention, but they apparently did not read the blog , and they clearly do not interviewed - proposed on 1 st April this year that the we replace the famous "Stay at home with doliprane" by a " Stay at home with ivermectin», Since, even if it is useless, ivermectin is at least more harmless than paracetamol. Joking aside, with practically no risk and dozens of clinical studies and observations in real population accumulating signs of significant efficacy, the "defenders" of ivermectin stress that the benefit / risk balance is clearly favorable. .
- nor the Law: in France, the National Medicines Safety Agency (ANSM) does not have to wait for the “ proof ” of efficacy of a medicine to issue a Temporary Recommendation for Use (RTU). Indeed, according to article R5121-76-6 of the Public Health Code, created by decree n ° 2012-742 of May 9, 2012, a presumption of effectiveness is sufficient: “(…) the agency proceeds to the evaluation of the presumed efficacy and safety of the medicinal product in the indication or the conditions of use considered. If this assessment makes it possible to presume that the ratio between the expected benefit and the adverse effects incurred is favorable, it draws up a draft temporary recommendation for use.. ” As we have just seen, this presumption of favorable benefit / risk balance is, according to the “defenders” of ivermectin, widely established. Much better established, they say, than for a series of drugs (Remdesivir, Bamlanivimab…) which have recently received a Temporary Authorization for Use. However, an ATU must nevertheless be based, according to article R5121-68 , on a " strong presumption", with more stringent conditions, insofar as the ATU concerns medicinal products which have not yet received an ATU. Marketing Authorization for other diseases, which are therefore less well known.)
Considerations remote from science.
The article in Le Monde does not only use scientific arguments to assess the efficacy of ivermectin: in the paragraph entitled " who are its defenders?" "The" Decoders "take the party to first quote three personalities of the extreme right. How can such a politicization of the molecule shed light on the effectiveness of the treatment? It is only in a second step that the article mentions that scientists and practitioners also “ support ” ivermectin, as does the 2015 Nobel Prize for Medicine Satoshi Omura. To read the " Decoders ", One might think that these scientists waited for the French far-right to tell them what to think about it ... It is moreover on another very little scientifically founded amalgam that the article opens: ivermectin has points in common with hydroxychloroquine and would have become " the new obsession of those who formerly defended the protocol of Professor Didier Raoult ". Is this a rigorous way to shed light on the question of the effectiveness of the molecule?
An untransformed essay.
The " Decoders " border on serious work when they indicate that several countries have used ivermectin against Covid-19. But each time they miss important information, not even wondering what effect it could have had on the health of the inhabitants ...
- They cite Slovakia, which officially validated ivermectin in January, giving as a reference an article from January 28, 2021 from TrialSiteNews, but they do not dig, and do not relay this other article from TrialSiteNews which, on April 11, 2021 , takes stock of what has been happening in Slovakia since the official authorization of ivermectin: shortages until March, increase in the price of the drug imposed by Austrian suppliers, efficacy reported by doctors, campaign to denigrate the treatment in part of the media, and recent drop in the number of cases detected… They cite the Czech Republic, Bolivia, Guatemala and Honduras, but without further details. They cite " certain states of Mexico », Giving as a source an article which does not speak at all about the states of Mexico but about the IMSS (Social Security for Mexican employees in the private sector), which effectively began in December 2020 to distribute treatment kits including ivermectin to all patients who test positive in the centers it manages in the country. (The case of Mexico has been discussed here and here .) They cite Bolivia, where 350,000 doses of ivermectin had been distributed, and Peru, for saying that the country recently removed ivermectin from the list of recommended treatments. Why ? With what effects? The readers of Le Monde will not know.
What arguments against ivermectin?
Finally, the " Decoders " give the floor to "experts" to denigrate ivermectin, but without innovating: the arguments have not changed for months, despite the release of new studies and the production of meta-analyzes. The arguments provided are:
- Prescrire's article of February 11. - the "Detox Channel" published by Inserm on January 26 - the interview with D. Costagliola (from Inserm) in the Conversation on March 10 - A press release from the French Society of Pharmacology and Therapeutics (SFPT) - the criticisms of M. Molimard (of the SFPT), similar to those he delivered to 20 Minutes on December 20, 2020 - the article by Lopez-Medina et al. published in JAMA
The " Decoders " do not mention any of the detailed rebuttals that, for example, Dr Maudrux opposes point by point to the arguments of Prescrire, Inserm and D. Costagliola, and which will be found here and there . It should be noted that some of the criticisms of D. Costagliola or M. Molimard, taken up by Le Monde, go beyond logic or scientific approach:
- “ D. Costaglila deplored the few published essays. "
At a time when the world put this article online, 50 trials were published. Did D. Costagliola's remark deserve to be repeated?
- “ The studies cited by the advocates of ivermectin are, for the most part, preprints , preprints which must be submitted to scientific expertise . »
Does the fact that a" majority "of studies have not yet been validated have the slightest influence on those which have already been validated by peers (peer-reviewed)? Surprisingly, D. Costagliola does not mention any of the latter; surprisingly, the world did not realize that as of April 13, 27 of the trials on ivermectin had already been peer-reviewed (1) Admittedly, these studies are not all of good quality and some have significant biases. But this is not the case for all, and researchers who have carried out meta-analyzes, and part of the work of which is to assess the impact of bias, have been able to conclude that ivermectin is effective.
- “ The doses of ivermectin used in certain trials are sometimes much higher than those authorized in humans . "
Many things are implied in this criticism: the trials in which doses of ivermectin are" normal "would be irrelevant? This is not the case: regardless of the doses used, ivermectin has indicated a beneficial effect. Exceeding the dose currently authorized in humans would be dangerous? This is not the case, as a study by Guzzo et al. published in 2013.
Finally, the study by Lopez-Molina et al. published in JAMA is the most widely used scientific argument against ivermectin: it is on this study that the WHO, EMA and ANSM have relied to publish recommendations not to use ivermectin. This study is however the subject of fundamental scientific criticisms, and of questioning at the same time on its method, on its errors, on its biases, and on the discrepancy between its conclusions and its results. On the study page , reading the comments (under the "Comment" button) is uplifting, and an open letter to JAMA from 100 US physicians, titled " The JAMA Ivermectin Study Is Irreparably Flawed." », Condenses in one page of severe scientific and ethical criticisms. One of their criticisms is to recall that just because the results of the study are statistically insignificant does not imply the ineffectiveness of the treatment, as the authors write in their conclusion. A recent post aimed precisely to shed light on this reasoning.
Conclusions
The last part of the “Decoders” article simply reminds us that the health authorities (WHO, European Medicines Agency and ANSM) have taken a stand against the use of ivermectin. This is factually correct, but we could have expected from Le Monde a more incisive journalistic work, aiming for example to compare the scientific arguments retained to authorize the Remdesivir, the monoclonal antibodies (Bamlanivimab) or the vaccines, with the existing scientific arguments. in favor of ivemrectin. In conclusion, the article of "Décodeurs" du Monde masks the existence of numerous scientific arguments in favor of the use of ivermectin, reports disconnected from the news and scientifically contested arguments in an attempt to discredit the molecule, and resorts to processes remote from science, by politicizing treatment and by presenting the problem as a question opposing "defenders" suffering from an "obsession" to scientists (epidemiologist, pharmacologist ...), forgetting that the main stake of an effective treatment is to save lives, to to relieve hospitals and intensive care units, to reduce general fear and anxiety and to allow life to resume a less impeded and less supervised course.
Peer-reviewed studies on ivermectin published before April 13:
Chowdhury et al., Eurasian Journal of Medicine and Oncology doi: 10.14744 / ejmo.2021.16263
Rahman et al, J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi: 10.3329 / jbcps.v38i0
Alam et al. , Journal of Bangladesh College of Physicians and Surgeons, doi: 10.3329 / jbcps.v38i0.47512
Bhattacharya et al. , Int. J. Scientific Research, doi: 10.36106 / ijsr / 7232245
Espitia-Hernandez et al. , Biomedical Research, 31: 5
Shouman et al. , Journal of Clinical and Diagnostic Research, doi: 10.7860 / JCDR / 2020 / 46795.0000
Kishoria et al. , Paripex - Indian Journal of Research, doi: 10.36106 / paripex
Podder et al. , IMC J. Med. Science, 14: 2, July 2020
Chachar et al. , International Journal of Sciences, 9: 31-35, doi: 10.18483 / ijSci.2378
Rajter et al. , Chest, doi: 10.1016 / j.chest.2020.10.009
Chaccour et al. , Scientific Reports, doi: 10.1038 / s41598-020-74084-y
Guerrero et al ., Colombia Médica, doi: 10.25100 / cm.v51i4.4613
Behera et al. , PLOS ONE, doi: 10.1371 / journal.pone.0247163
Morgenstern et al., J. Clinical Trials
Camprubí et al ., PLoS ONE, 15:11, doi: 10.1371 / journal.pone.0242184
Spoorthi et al ., IAIM, 2020, 7:10, 177-182
Carvallo et al ., Journal of Biomedical Research and Clinical Investigation, doi: 10.31546 / 2633-8653.1007
Bernigaud et al ., Annals of Dermatology and Venereology, doi: 10.1016 / j.annder.2020.09.231
Ahmed et al. , International Journal of Infectious Diseases, doi: 10.1016 / j.ijid.2020.11.191
Chaccour et al ., EClinicalMedicine, doi: 10.1016 / j.eclinm.2020.100720
Hussain et al ., International Journal of Molecular and Immuno Oncology, doi: 10.25259 / IJMIO_30_2020
Alam et al ., European Journal ofMedical and Health Sciences, doi: 10.24018 / ejmed.2020.2.6.599
Procter et al ., Reviews in Cardiovascular Medicine, doi: 10.31083 / j.rcm.2020.04.260
Wijaya et al ., Cermin Dunia Kedokteran, 47: 7
Hirsch et al ., Microbiology & Infectious Diseases
Babalola et al ., QJM: An International Journal of Medicine, doi: 10.1093 / qjmed / hcab035
Lima-Morales et al , International Journal of Infectious Diseases, doi: 10.1016 / j.ijid.2021.02.014
Elalfy et al. , J. Med. Virol., Doi: 10.1002 / jmv.26880
López-Medina et al ., JAMA, doi: 10.1001 / jama.2021.3071
Galan et al ., Pathogens and Global Health, doi: 10.1080 / 20477724.2021.1890887
Pott-Junior et al ., Toxicology Reports, doi: 10.1016 / j.toxrep.2021.03.003
Del Franco et al ., Journal of Biomedical Research and Clinical Investigation, doi: 10.31546 / 2633-8653.1008
Mourya et al. , Int. J. Health and Clinical Research Recommend (7)
And another article from another friend, on the same subject: https: //www.agoravox.fr/actualites/medias/article/fausses-nouvelles-et-m ...
Author (s): Enzo Lolo, for FranceSoir