Journal finally retracts the discredited hydroxychloroquine paper Premium

French study on hydroxychloroquine for COVID-19 retracted due to ethical concerns after global attention and FDA approval.

More than four-and-a-half years after the highly questionable “study” by a French researcher Didier Raoult and others claiming that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin was “significantly associated with viral load reduction/disappearance in COVID-19 patients” was published on March 20, 2020, the paper was finally retracted on December 17 this year. The paper published in the International Journal of Antimicrobial Agents was withdrawn because of concerns about the ethical approval for the research. The paper that was submitted to the journal on March 16, 2020 was accepted for publication the very next day.

Three days after the paper was published, ICMR approved the use of hydroxychloroquine as a prophylaxis by healthcare workers and those caring for COVID-19 patients. The drug was also granted an emergency use authorisation by the U.S. FDA on March 28, 2020, which was revoked about once-a-half months later. The publication of the paper and the FDA approval raised a lot of attention globally and contributed to a demand for the drug despite appropriate evidence of its benefit. The drug was also strongly backed by the then U.S. President Donald Trump.

On April 3, a fortnight after the paper was published, the journal publisher — the International Society of Antimicrobial Chemotherapy (ISAC) — which co-owns the journal with Elsevier, expressed concerns saying that the “article does not meet the Society’s expected standard”. An independent review commissioned by the journal also concluded that the trial had “several major methodological issues, including the design, outcome measure and the statistical analyses”. Yet, the journal did not retract the paper until a few days ago.

Addressing the concerns about the peer-reviewing process, the ISAC statement said that despite being the Editor-in-Chief of the journal and an author of the paper, “Jean-Marc Rolain had no involvement in the peer review of the manuscript and has no access to information regarding its peer review”.

The paper came under investigation again a few months ago when three authors of the paper contacted the journal saying that they had “concerns regarding the presentation and interpretation of results” and no longer wanted to be associated with the article, as per documents seen by Retraction Watch. Responding to Retraction Watch, a spokesperson for the journal said that the “journal was re-opening the previously closed investigation after receiving the authors’ requests”. 

Ethical approval for the study was granted on March 6 and as per the paper, the follow-up of the participants was supposed to last for 14 days. But with a “submission date of March 16, the timeline becomes seemingly impossible”, Elisabeth M Bik, an independent research integrity researcher wrote on PubPeer in March 2020. In the retracted notice, the journal addresses this concern saying: “The journal has not been able to establish whether all patients could have entered into the study in time for the data to have been analysed and included in the manuscript prior to its submission on the 20th March 2020, nor whether all patients were enrolled in the study upon admission as opposed to having been hospitalised for some time before starting the treatment described in the article.” 

As per the details available in the EU clinical trials register, the secondary objective of the trial was to evaluate the “clinical effectiveness of treatment on time to apyrexia, normalization of respiratory rate, and average length of hospital stay and mortality”. Results of the secondary objective are not available in the paper. While the primary objective of the study was to shorten the period of virus carrying and thus contagion, the secondary endpoint is “very important for determining whether patients may have clinical benefit and not only a reduced risk of infecting others”, a researcher wrote on PubPeer.