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Didier Raoult has complained about the “dictatorship of the methodologists” who insist on randomization and control groups in clinical trials.

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Is France’s president fueling the hype over an unproven coronavirus treatment?

Sciences COVID-19 reporting is supported by the Pulitzer Center.

The highly politicized debate about the use of chloroquine and hydroxychloroquine, two antimalarial drugs, to treat COVID-19 has reached an extreme in France, where two small trials purporting to show potential benefit were done. French physicians have come under enormous pressure from desperate patients to prescribe hydroxychloroquine, despite scant evidence that it works, and 460,000 people have already signed a petition to make it more widely available. Leading the advocacy is a controversial and politically well-connected figure, microbiologist Didier Raoult.

Today his profile rose even higher, as French President Emmanuel Macron traveled to Marseille to meet Raoult, a hospital director and researcher who led the two trials. Macron did not comment after the meeting, but the rendezvous, initiated by Macron, was a clear sign of Raoult’s newfound political clout. Jean-Paul Hamon, president of the Federation of Doctors of France, one of many scientists and doctors critical of the meeting, called it “showbiz politics.”

A survey released by French polling institute IFOP on 6 April revealed that 59% of the French population believes chloroquine is effective against the new coronavirus. Confidence in the drugs is higher on the far right and far left, and reached 80% among sympathizers of the “yellow vest” movement that staged massive protests against Macron’s economic policy in 2018 and 2019. Support is also very high, at 74%, in the Marseille region.

Karine Lacombe, head of infectious diseases at the Saint Antoine Hospital in Paris, has said on French TV that she and her team have received repeated “physical threats” for refusing to prescribe chloroquine; she said she has also seen many falsified prescriptions for the drug. Other doctors have reported similar experiences. The pressure comes on top of the stress caused by shortages of protective equipment, diagnostic tests, and medical staff.

The popular faith in hydroxychloroquine stands in stark contrast to the weakness of the data. Several studies of its efficacy against COVID-19 have delivered an equivocal or negative verdict, and it can have significant side effects, including heart arrhythmias. Raoult’s positive studies have been widely criticized for their limitations and methodological issues. The first included only 42 patients, and Raoult chose who received the drug or a placebo, a no-no in clinical research; the International Society of Antimicrobial Chemotherapy has distanced itself from the paper, published in the society’s International Journal of Antimicrobial Agents. The second study, published as a preprint without peer review, didn’t have a control group at all.

Raoult has dismissed the criticism and complained about the “dictatorship of the methodologists” who insist on randomization and control groups in clinical trials. In his hospital, every patient diagnosed with COVID-19 receives hydroxychloroquine combined with azithromycin, an antibiotic. Raoult claims this has resulted in a very low death rate, which he says he will document soon in a publication.

His advocacy has made him a kind of medical prophet whose work is discussed incessantly in news outlets and on social media. His political connections have amplified his influence. Former conservative industry minister and Nice Mayor Christian Estrosi, a personal friend of Raoult’s, recently appeared on TV after recovering from COVID-19 and told viewers he was “convinced” the combination of hydroxychloroquine and azithromycin cured him.

Raoult has also found some high-level support in the medical world. The online petition in support of hydroxychloroquine was started by cardiologist and former Minister of Health Philippe Douste-Blazy—France’s candidate to lead the World Health Organization in 2017—and Christian Perronne, head of infectious diseases at the renowned Raymond Poincaré University Hospital in Garches, near Paris. Ten other prominent figures from the medical community, including two members of the Academy of Medicine, co-signed the petition, which demands hydroxychloroquine be authorized for mild cases in hospital settings. (Current regulations, which Raoult ignores, allow the drug to be used only for severe cases of COVID-19.)

In the conservative newspaper Le Figaro, three prominent retired oncologists argued that “all patients tested positive for COVID-19 and not included in a clinical trial” should receive the hydroxychloroquine-azithromycin combo.

The French Ministry of Health has been “incredibly rigid” and has “diabolized” hydroxychloroquine, Perronne tells ScienceInsiderHe says there is considerable—though “imperfect and often unpublished”—evidence that the drug has benefits, and he believes its side effects are rare and easy to avoid. Perronne says he has refused to enroll patients in a randomized trial of hydroxychloroquine because a placebo group would be “unethical” for a fatal disease. Instead, he recently decided to give the drug to all patients except the mildest cases.

But many scientists in France are outraged that a potentially harmful drug can be widely used with so little evidence for its efficacy. The fervor also makes it harder to test the drug in a rigorous fashion.

Discovery, a randomized trial launched in at least seven European countries to study the efficacy of hydroxychloroquine and several other treatments, is struggling to recruit participants in France, says Jean-François Bergmann, a former head of infectious disease at the Saint Louis Hospital in Paris. (Macron has met with Discovery’s leaders as well.) “In some hospitals, four out of five patients are declining to take part and refuse any treatment but hydroxychloroquine,” Bergmann says, adding that France is witnessing a form of “medical populism” that is “slowing the emergence of the truth.”

 

Correction, 10 April, 8:10 a.m.: A previous version of this story said the Discovery trial is double-blinded; it is not.