The Lancet, one of the world’s top medical journals, on Thursday retracted an influential study that raised alarms about the safety of the experimental Covid-19 treatments chloroquine and hydroxychloroquine amid scrutiny of the data underlying the paper.

Just over an hour later, the New England Journal of Medicine retracted a separate study, focused on blood pressure medications in Covid-19, that relied on data from the same company.

The retractions came at the request of the authors of the studies, published last month, who were not directly involved with the data collection and sources, the journals said.

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“We can no longer vouch for the veracity of the primary data sources,” Mandeep Mehra of Brigham and Women’s Hospital, Frank Ruschitzka of University Hospital Zurich, and Amit Patel of University of Utah said in a statement issued by the Lancet. “Due to this unfortunate development, the authors request that the paper be retracted.”

The retraction of the Lancet paper is sure to add fuel to contentious arguments about the potential of chloroquine and hydroxychloroquine, two old malaria drugs, in Covid-19, the disease caused by the novel coronavirus. President Trump has touted them as valuable treatments, despite a lack of rigorous data showing they have a benefit.

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Meanwhile, on Wednesday, researchers reported the results of the first gold-standard clinical trial of hydroxycholoroquine in Covid-19, concluding that it did not prevent infections any better than placebo. Other clinical trials, including some looking at the drugs as treatments, are ongoing.

The Lancet study gained so much attention because it went further than other observational studies that had similarly found the drugs were not associated with improved outcomes for patients. The study, which was purportedly based on patient data from 671 hospitals on six continents, reported the drugs also corresponded to higher mortality.

The findings led to the pause of some global clinical trials studying hydroxychloroquine so researchers could check for any safety concerns. Outside experts, however, quickly raised concerns after noticing inconsistencies in the data. They asked the company that compiled and analyzed the data, Surgisphere, to explain how it sourced its data.

As scrutiny grew, the authors on the paper not affiliated with Surgisphere called for an independent audit. In their Lancet statement Thursday, they said that Surgisphere was not cooperating with the independent reviewers and would not provide the data.

“As such, our reviewers were not able to conduct an independent and private peer review and therefore notified us of their withdrawal from the peer-review process,” the researchers wrote.

Outside experts raised similar concerns about the New England Journal study, which found that the blood pressure medications were safe to take for people with Covid-19. It was also based on data from Surgisphere.

In the New England Journal retraction statement, the study authors wrote, “Because all the authors were not granted access to the raw data and the raw data could not be made available to a third-party auditor, we are unable to validate the primary data sources underlying our article.” They apologized “for the difficulties that this has caused.”

Concerns about the health risks of chloroquine and hydroxychloroquine were based on evidence beyond the Lancet paper. Earlier, the Food and Drug Administration warned the drugs should not be used in Covid-19 outside a clinical trial or beyond hospitalized patients because of the risks to heart health.

The drugs are safe for people to take for malaria, rheumatoid arthritis, and lupus, for whom they are shown to have benefits, experts stress.

  • Thanks to researchers and the general reporter. Your painstaking efforts to safeguard the health of humanity is appreciated.

  • So what research did the Food and Drug Adm. do or what study did they use to arrive at their conclusions about hydroxychloroquine?

    • None -they simply summarized the evidence from the literature. In this case the evidence was based on the fraudulent ‘studies’ published in Lancet and NEJM.

    • The FDA based their statement on standard practice. They have studies on the efficacy of these drugs for treating specific disease. They have none for treatment of COVID-19. They are very conservative in their approach – they only approve a drug for use when there is actual proof its benefits outweigh its risks. They don’t have that proof for treatment of COVID-19. And, the FDA statement was from before these studies were published and hasn’t changed.

    • Of course not. FDA does not base conclusions on one (or even two) studies that have just been published. Hydroxychloroquine has been used for decades, by thousands if not millions of people, for malaria, rheumatoid arthritis, systemic lupus erythematosus, and other conditions. There is extensive information about its effects, including its sometimes life-threatening side effects. FDA bases conclusions on extensive reviews of primary data, not on articles published in medical journals, newspapers, or Fox News.

      These two articles are not the only ones to show that these drugs have not benefited patients with coronavirus disease, they are just the only ones that have been retracted. They were not retracted because their conclusions were found to be wrong, but because an effort to investigate the source of the data was unable to confirm its validity. The retraction of these articles tells us nothing about the safety or effectiveness of these drugs, only about the uselessness of the studies. We know about the side effects of hydroxychloroquine from decades of scientific research and clinical experience. Many other studies have been and are being done on the effects of hydroxychloroquine on patients with Covid-19. So far, it has found to be of no benefit. (Here are links to two more: https://doi.org/10.1001/jama.2020.8630 and https://doi.org/10.1056/NEJMoa2012410.) Some people have suggested that it might be of benefit in certain circumstances that haven’t been studied, such as when given in combination with other agents or when given earlier in the disease or even as prevention. Until there is evidence about its use in these circumstances, however, we don’t know whether it is beneficial, harmful, or neither. We do know that it can have severe side effects.

      Government malfeasance happens. Often. Government corruption happens. Often. People are dishonest. Often. But that doesn’t mean that everything every person does is dishonest, and it doesn’t mean that everything anyone in government does is corrupt. It is prudent to suspect malfeasance in any government action (which is why Inspectors General investigating government misconduct should not be fired for doing so, by the people they are investigating). It is not prudent to conclude that any action taken by any part of the government is corrupt just because you suspect it could be or you disagree with it.

  • A recent study out of India indicates that HCQ can help prevent COVID-19 if taken before getting the virus. Of course, you won’t see this mentioned, or the retraction of Surgisphere’s fraudulent papers, in the popular media.

    See: https://indianexpress.com/article/india/preventive-use-of-hcq-in-frontline-healthcare-workers-icmr-study-6442948/

    “A new study by the Indian Council of Medical research (ICMR), which examined the prophylactic role of Hydroxychloroquine (HCQ) to prevent SARS-nCOV2, found that the risk of healthcare workers (HCWs) contracting the infection was much lower if a sustained dose was taken along with use of personal protective equipment (PPE).

    “Biologically, it appears plausible that HCQ prophylaxis, before onset of infection, may inhibit the virus from gaining a foothold,” stated ‘Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19’, a study published recently in the Indian Journal of Medical Research.”

  • Informed professionals know this is patently untrue. “The Lancet” represents a plurality of findings in diverse medical fields. If anything, Dr. Horton is tolerant to a fault, as evidenced by his problematic reluctance to retract Dr. Wakefield’s work.

    Dear STAT: please moderate your comments section for false, inflammatory remarks.

  • It is pretty sad that Lancet had to retract the paper.
    I know people who really don’t believe much in science, and after this kind of retraction, they are even more skeptical abou science. Mainly because people say Lancet is a very important scientifical journal.
    So, if they fail, how come they will continue putting trust in science and their results?
    Not really related but, this can help fuel anti-vaccers for example.
    But I still believe in science and good science. There are a lot of groups working hard to prove or even disprove things around.
    https://www.realgramas.com.br/

    • This is not sad for science.This shows it is working.Good science is a picky bastard and will call out bad method.People who hang their hat on bad critical thinking,have a problem in method that must be addressed before they can be reasoned with.

    • The thing about science is that a single paper rarely ever establishes anything with certainty. The media like to hype new studies they report on, because their job is to tell you what’s new, and they want you to feel that it’s important and valuable and be glad you heard about it. They don’t tell you about the hundred previous studies and how this one fits in with what other studies have found. The fact is that nothing is established until many studies have confirmed it, in different places, by different people, using different methods, investigating different aspects of it, possible explanations of it, ways it may be used to solve problems, and finding out how, when, and why it is true. If it turns out not to be true, most often people lose interest in it and move on to something more likely to yield important new information. In rare cases, it turns out a paper is fraudulent, and when that happens it’s generally because it made a major splash, and many other people started to research it further, and found they couldn’t confirm what the original paper claimed to have found. In this case, the data didn’t turn out to be fraudulent, but the people who came up with the data weren’t able (or willing) to provide details about how and where they collected the data to show that they had done it legitimately and properly, so the authors who had analyzed the data and written it up retracted the paper because they realized they couldn’t back up the validity of their findings. But it is commonplace, almost universal in science for different studies to show conflicting results, because they’ve used different methods, made different assumptions, or did the work differently. When the media report studies they may give the impression that one study settles something. It doesn’t. When many studies find the same thing, it becomes accepted. When they don’t, more work has to be done to figure out why they found different things. It’s usually because most things are complicated, so, looking at it from different perspectives, you see different things (kind of like relationships 😉). That doesn’t mean a mistake was made, it just means things are complicated, and multiple studies provide a fuller picture than just one. But journalists don’t always take the trouble to explain this. In some cases, though, papers turn out to be based on shoddy or even fraudulent work. In this case, it looks like the study should never have been published in the first place. The authors should have made certain they could trust the data they were using before they did their study and submitted the paper for publication. The authors and the journal were undoubtedly racing to get the information out to minimize the damage being done, because disturbingly large numbers of people were already starting to take the drugs, which put them at risk of serious side effects, for no benefit, and kept people who needed the drugs from being able to get them. (And, yes, probably also to increase their own fame.) Rushing often does result in mistakes being made. And of course there might also have been some dishonesty involved; we don’t know. (Sometimes when people rush they take shortcuts and don’t do all the careful checking they should; in my view that’s kind of midway between honest error and dishonesty.) But in this case the retraction actually happened remarkably quickly after the papers were published. So that’s an example of science being unusually swift in correcting its mistakes. Mistakes happen in every human activity (as does dishonesty); we all make mistakes. Science is no different. I hope this helps.

    • Journal reputation is a poor proxy for reliability. Retrospective cohort studies, especially in this pandemic, are plagued with statistical issues that modelling cannot completely remove, regardless of the journal they are published in. Even with verifiable data and peer review, the conclusions drawn from such studies need to be considered with large spoons of salt.

    • We are all in harms way. And doctors can and will also act sometimes irrationally so have compassion and sympathy for these unfornate doctors that involved in this mess, that in hindsigth looks to good to be true. But this is also how peer-reveiw are meant to work, it will be judged/evaluated by your peers. And in this case it was a open and closed cased quite. While a unfortunate and tragic detour for the well meaning and good doctors that where fooled to think this was treasuretrove, I only suspect there was one scam artist at the heart of this. While we should and always will expect the very best from NEJM, Lancet and Harvard.

      It is also like the laws of physical, when you go fast, its difficult to go deep. So this is a bit like a pilot trying to do emergency landing fast but your instruments do not work or they give you the wrong info, and you do not have the luxury of double checking it.

      So while Surgisphere was a almost comical set-up, it should not be impossible for high tech companies like Microsoft, Google, Amazon and/or Facebook to provide this infrastructure to provide accurate/verified global but anonymized data for our common good while complying with data protection etc. I.e. if you take a data collection that WHO and CDC collected, it fails to ask to collect and ask for these vital questions like risk factors, current medications, emergency measures etc. So one would think that in 2020 we would know even more detail, to figth this and any future threat with hard data and science. So if these information systems could be harnessed to collect these type of data in real time and not in the same stoneage before with paper and pen by snail mail, we could have this kind of treasure throve for our mutual benefit. It is mystery why also we do not have such system, it should not be just a fantasy, its something that can be done.

      But remember doctors are trained to fix and heal fast, but faced with an enemy that has outsmart every government and scientists so far, the quest and pressure to find a solution and cure can be so distracting that what seems like common sense is goes out the window. Also trust between doctors are high, so something can wrong/fake and accepted at “facevalue”.

      But this is peer reveiw in action. And while unfortunately there is collateral damage for those involved and lessons to be learned. And time lost.

      But remember that the good doctors and journals fooled in this scam is now also hurting and show them compassion as well, so they can be put back to good use as this scam seems to be a one man show.

      And kudos to journalist in Guardian and bloggers that helped spot the scam.

      But watch out for doing justice or being a vigilante online.

      “schadenfreude” is a zero sum game.

      “-pleasure derived by someone from another person’s misfortune.
      pleasure derived by someone from another person’s misfortune.”

      By design and default every human is imperfect, bound to fail sometimes. Even the very best and the top. Its the great equalizer.

    • It’s particularly unfortunate that The Lancet retracted the publication, given that they were the journal that arguably started the whole anti-vax movement by publishing an outright fraudulent article. Yes, they retracted it, but the damage was done and the repercussions continue to increase exponentially. Polio is now starting to become a disease of significance again, after decades of negligible significance. The pharmacist at my local chemist shop, who even lived a couple of blocks from me, was a very vocal anti-vaxxer. No amount of discussion and mention of actual facts would change his mind, and eventually he was fired for forcing his views on customers.
      So it’s no wonder that people who managed to never learn any science in school (and there’s a LOT of them) are perplexed by what appears to be significant cracks in the wall of infallibility of the scientific method. And when the President of the United States starts promoting his own strange ideas, the line between common sense and political belief gets even more blurred. He means well, but the CDC now reports over 1/3 of Americans have tried experiments with gargling or drinking bleach and similar insane behaviours. At least chloroquine requires a prescription, but there doesn’t appear to be any shortage of physicians who are ready to use political beliefs in place of the system they were trained to follow.

  • The problem here is that journals are literally being flooded with COVID-19 articles and reviews are being rushed to get results out to healthcare providers. 3rd-tier journals especially are cranking out a flood of COVID-19-related articles. What this story points out is that even top-tier journals are vulnerable. Sadly, the press does not put retractions in perspective for readers by pointing out that quality published trials might still sustain the conclusions of the retracted papers.

  • Why did the authors not seek to validate their primary data sources BEFORE rushing to publish? This is shoddy science, and the authors deserve academic condemnation. Compounding the problem is that the same authors were involved in BOTH retracted papers. Trusting a shady service like Surgisphere without verifying the primary data is likewise shameful.

    • Indeed. It seems the authors relied on third-party data, which is not new. This incident confirms the critical importance of checking both the accuracy and completeness of source data. The fact Surgisphere would not provide the entire data sets is troubling. More important is how these shenanigans corrode public trust in science and medicine. The Lancet’s retraction will be used to validate the anti-science, antivaxx suspicions that flourish in the general population.

    • The use of third-party data is not uncommon in pharma studies with large sample sizes. It’s not a problem in and of itself, but study management (in this case: the authors) and regulatory authorities should be more vigilant, especially when dealing with opportunistic newcomers to the field.

      Industry watchdogs warned that easing regulatory standards (such as accelerating COVID-19 study authorizations and clinical site initiations) would have deleterious effects on data quality. They have unfortunately been proven right.

  • That both The Lancet and New England Journal of Medicine have now retracted two recent, highly publicised papers purporting to show negative results with hydroxychloroquine is a stain on both their venerable escutcheons

    Editors of both journals are perceived to have leftish viewpoints in regard to politics, at least affecting medical policies

    It would be good for this paper – to which I subscribe and which does otherwise excellent service – whose analysts also commented on the purported, likely fraudulent findings with some apparent relish, also retract their analyses …

    In so far as hydroxychloroquine is concerned then, with many early reports of some utility – especially given early and with zinc – the final say is still in the offing ie the jury is still out

    Here are some pertinent references for further reading on the question of HCQ plus zinc plus either doxycycline ( my preferred choice because it isn’t associated with further cardiac risk) or azithromycin

    https://aapsonline.org/hcq-90-percent-chance/

    https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1

    https://www.preprints.org/manuscript/202005.0057/v1

    https://www.evms.edu/media/evms_public/departments/internal_medicine/Marik-Covid-Protocol-Summary.pdf?fbclid=IwAR1dRzQGq6_HyQYC4IMNrUFztw9LiI1pHJcz64hBfZ6ifB99gaCUqUVDzx4

    https://pjmedia.com/news-and-politics/stacey-lennox/2020/05/14/new-hydroxychloroquine-trial-could-be-destined-to-fail-n392407

    https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3

    https://www.medrxiv.org/content/10.1101/2020.04.27.20073379v1

    https://www.middleeasteye.net/news/hydroxychloroquine-coronavirus-turkey-lancet-study-who-trial

    • This Pandemic as been very revealing. I’ve been a nurse for 30 years in many different areas of nursing. I became an Infection Preventionist 2 yrs ago for a LTC facility. In early February, before the outbreak of Covid-19 in the U.S. I looked to our own national health organizations such as the NIH, CDC and NIH for guidance. I could not understand why there was virtually NO information on this virus up to this point. I also searched the WHO website to little avail. I’ve done a lot of my own research on this virus and if Hydroxycholoquine was a viable treatment. Listened to front line DR’s, of which there were many using it to treat very ill patients in the hospital with good results. I’ve come to the sad conclusion that these health organizations mentioned here have become more about politics than medicine. The WHO being the worst offender.

  • Standard Fake News M.O.
    Have a study or report created that pushes a false narrative, usually against Trump or his voters, publish it and have the entire leftist media echo chamber run the story with circular corroboration. When it’s finally discovered to be total hokum, bury it, cover the tracks and leave the false impression as “fact” to be used in tag lines and talking points ad infinitum. Mission Accomplished.

    • Of course, just ignore this part of the article: “Meanwhile, on Wednesday, researchers reported the results of the first gold-standard clinical trial of hydroxycholoroquine in Covid-19, concluding that it did not prevent infections any better than placebo. “

    • Right you are Ken. Researchers always seem to verify the position of the person/company paying for the study. For years, researchers verified that smoking didn’t cause cancer. These people are responsible for millions of deaths but at least they were paid well to provide cover for the cigarette companies.

    • I guess what you are suggesting is that you should believe whatever you want to, because all science is suspect.

    • @Rob
      You said “Of course, just ignore this part of the article:…” Once it’s a main topic on CNN or NBC or FOX or any of the others, then your comment will be relevant.

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