- The British scientific journal published an expression of concern on Tuesday, raising doubts about the reliability of the chloroquine study published on May 22 in its pages.
- Doubts shared by another benchmark scientific journal and which inflate the concerns raised by many scientists, who questioned the methodology used.
- After having suspended its ongoing trials on hydroxychloroquine the day after the publication of the study in The Lancet , the WHO announces their resumption this Wednesday.
"Expression of concern". Or "expression of concern" in French. It was with this formal warning, used by scientific journals to signify that a study is potentially problematic, that The Lancet decided Tuesday evening to "alert readers to the fact that serious scientific questions have been raised to (its ) be careful ”about the study on hydroxychloroquine and Covid-19 published in its pages on May 22. A study according to which the hydroxychloroquine did not prove its effectiveness on the patients of the Covid-19 hospitalized and would be even harmful, inducing a high risk of mortality.
The World Health Organization (WHO) and France had decided soon after to suspend all ongoing clinical trials on hydroxychloroquine and its derivatives. Defender of this molecule since the first hour to the point of taking it himself as a preventive measure, Donald Trump had meanwhile declared that he had stopped his daily intake on discovering the publication. But today, are the results of this study to be thrown away?
"Concerns related to methodology and data integrity"
The large observational study published in The Lancet covers data from 96,000 patients hospitalized between December 2019 and April 2020 in 671 hospitals worldwide, and compares the state of those who received treatment with hydroxychloroquine and azithromycin compared to that of patients who have not received it.
Since its publication, many researchers have expressed their doubts, starting with Professor Didier Raout, who had described it as "messy" and led by "nickel-plated feet". "The house of cards is collapsing," he tweeted on Wednesday. Under the hashtag #LancetGate, the defenders of hydroxychloroquine had quickly expressed their feelings on social networks from May 22. Even scientists skeptical about the value of this treatment have expressed doubts about the methodology used by the authors of this study.
In an open letter published on May 28, dozens of scientists around the world noted that the scrutiny of the Lancet study raises "both methodological and data integrity concerns". They draw up a long list of problematic points, from inconsistencies in the doses administered in certain countries to ethical questions on the collection of information, including the refusal of the authors to give access to raw data.
Doubts about Surgisphere society
These data were collected by Surgisphere, which presents itself as a health data analysis company based in the United States. In its press release published on Tuesday, The Lancet recalls that an "independent audit on the source and validity of the data has been requested by the authors not affiliated with Surgisphere and is in progress, with results expected very soon".
“There are doubts about the integrity of the Lancet study. In retrospect, it seems that policy makers have relied too much on this paper, "commented Professor Stephen Evans, of the London School of Hygiene and Tropical Medicine. Additional problem: another benchmark medical journal, the New England Journal of Medicine (NEJM), published this Tuesday an "expression of concern" about a study by the same team, carried out with the databases of Surgisphere. "Recently, fundamental concerns have been raised about the quality of the information contained in this database", wrote in this expression of concern the editor of the NEJM, Eric Rubin.
The authors, Dr. Mandeep Mehra and his colleagues, defend themselves. "We are proud to contribute to the work on the Covid-19" in this period of "uncertainty", declared on May 29 one of them, Sapan Desai, owner of Surgisphere. According to The Lancet , the Surgisphere database notably contains the data of more than 63,000 Covid-19 patients admitted to 559 hospitals in North America as of April 14. The CEO and founder of Surgisphere, Sapan Desai, however, refused to disclose the names of the hospitals concerned, citing confidentiality agreements. However, The Scientist magazine conducted the investigation and was unable to find any hospitals that participated in this data collection. Many establishments contacted even assured that they had not provided data. The same goes for The Guardian, which contacted the main hospitals in Sydney and Melbourne in Australia - the study advances data on Australian patients - but all indicated that they had not provided data to Surgisphere.
The efficacy of chloroquine not yet demonstrated to date
But this distance taken by the Lancet does not change the fact that to date, "we still have no evidence of the effectiveness of treatment with chloroquine / Azithromycin", the treatment acclaimed by Professor Didier Raoult, underlines on Twitter Pr Gibert Deray, head of the nephrology department at the Pitié-Salpêtrière hospital in Paris. And if this controversial study on hydroxychloroquine probably has methodological biases, the conclusions based on a toxicity of this treatment could however be exact. Before the controversy over this study, other work carried out on a smaller scale reached the same conclusions, without any methodological bias being raised.
“Taking hydroxychloroquine and azithromycin is associated with a risk of increased cardiovascular toxicity. They should not be administered outside of clinical trials and require close monitoring, "said Dr. Mariell Jessup, Scientific Director of the American Heart Association. Inserm recalls that "hydroxychloroquine and azithromycin can have a deleterious impact on the cardiovascular system and constitute a potentially fatal combination, according to a large analysis of a WHO database on adverse drug reactions , published in Circulation ”. This study, which is not related to Covid-19 research, is a retrospective and observational analysis of a WHO database including more than 21 million reports of adverse event cases, all classes of drugs combined, from more than 130 countries, between November 14, 1967 and March 1, 2020. Or almost exclusively before the COVID-19 pandemic.
And after ?
After this umpteenth turnaround, what will happen now? It was on the basis of the publication of this work in the British journal that the World Health Organization decided to suspend all of its clinical trials on hydroxychloroquine. Just like in France with the Discovery clinical trial. The researchers therefore decided not to recruit new patients in the research arm for this drug. And the decree authorizing the prescription of chloroquine in compassionate use at the hospital for severe cases of Covid-19 was repealed on May 27.
On Wednesday, WHO announced the resumption of clinical trials on hydroxychloroquine. After analysis of "available data on mortality", the members of the Safety and Monitoring Committee considered "that there is no reason to modify the protocol" of clinical trials, announced the Director-General of WHO , Tedros Adhanom Ghebreyesus, during a virtual press conference.
For his part, the Minister of Health Olivier Véran contacted The Lancet to obtain details on the methodology of this study, said government spokesman Sibeth Ndiaye on Wednesday after the Council of Ministers. She also assured that the suspension of the use of chloroquine in France on Covid-19 patients was not based solely on this controversial study. For the time being, the government has not communicated on a possible resumption of tests and treatments based on chloroquine on Covid-19 patients.
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Coronavirus: Scientists doubt The Lancet study on chloroquine
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Coronavirus: WHO suspends clinical trials with hydroxychloroquine for safety
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