Authors retract influential Lancet article that found hydroxychloroquine risks

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Authors retract influential Lancet article that found hydroxychloroquine risks

Michael Erman

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Reuters•June 4, 2020

 

 

 

 

 

 

 

 

 

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By Michael Erman

NEW YORK (Reuters) - An influential medical journal article that found hydroxychloroquine increased the risk of death in COVID-19 patients was retracted on Thursday, adding to the controversy around a drug championed by U.S. President Donald Trump.

Three of the authors of the article retracted it, citing concerns about the quality and veracity of data in the study.

The anti-malarial drug has been controversial in part due to support from Trump, as well as implications of the study published in British medical journal the Lancet last month, which led several COVID-19 studies to be halted.

The three authors said Surgisphere, the company that provided the data, would not transfer the dataset for an independent review and that they "can no longer vouch for the veracity of the primary data sources."

The fourth author of the study, Dr. Sapan Desai, the chief executive of Surgisphere, declined to comment on the retraction.

"When you have reputable journals that put this kind of work out and are retracted 10 days later, it just increases mistrust," said Dr. Walid Gellad, a professor at University of Pittsburgh's medical school. "It just adds fuel to the fire of this controversy around hydroxychloroquine ... It's the last thing we needed with this particular drug."

Another study published in the New England Journal of Medicine that relied on Surgisphere data and shared the same lead author, Harvard Medical School Professor Mandeep Mehra, was also retracted for the same reason.

The observational study published in the Lancet on May 22 said it looked at 96,000 hospitalized COVID-19 patients, some treated with the decades-old malaria drug. It claimed that those treated with hydroxychloroquine or the related chloroquine had higher risk of death and heart rhythm problems than patients who were not given the medicines.

The World Health Organization, which paused hydroxychloroquine trials after The Lancet study was released, said on Wednesday it was ready to resume trials, and dozens of other trials have resumed or are in process.

"I did not do enough to ensure that the data source was appropriate for this use," the study's lead author, Harvard Medical School Professor Mandeep Mehra, said in a statement. "For that, and for all the disruptions – both directly and indirectly – I am truly sorry."

Many scientists voiced concern about the study, which had already been corrected last week to reflect that some of the location data was wrong. Nearly 150 doctors signed an open letter to the Lancet calling the article's conclusions into question and asking to make public the peer review comments that preceded publication.

 

(Reporting by Michael Erman and Peter Henderson; Editing by Leslie Adler and Tom Brown)

Edited June 6, 2020 by XCR1250

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Surgisphere: governments and WHO changed Covid-19 policy based on suspect data from tiny US company

Surgisphere, whose employees appear to include a sci-fi writer and adult content model, provided database behind Lancet and New England Journal of Medicine hydroxychloroquine studies

Melissa Davey in Melbourne and Stephanie Kirchgaessner in Washington and Sarah Boseley in London

 

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  A tiny US company, Surgisphere, is behind flawed data which led to governments and the world health organisation changing health policy Photograph: Anthony Brown/Alamy Stock Photo

The World Health Organization and a number of national governments have changed their Covid-19 policies and treatments on the basis of flawed data from a little-known US healthcare analytics company, also calling into question the integrity of key studies published in some of the world’s most prestigious medical journals.

A Guardian investigation can reveal the US-based company Surgisphere, whose handful of employees appear to include a science fiction writer and an adult-content model, has provided data for multiple studies on Covid-19 co-authored by its chief executive, but has so far failed to adequately explain its data or methodology.

Data it claims to have legitimately obtained from more than a thousand hospitals worldwide formed the basis of scientific articles that have led to changes in Covid-19 treatment policies in Latin American countries. It was also behind a decision by the WHO and research institutes around the world to halt trials of the controversial drug hydroxychloroquine. On Wednesday, the WHO announced those trials would now resume.

Two of the world’s leading medical journals – the Lancet and the New England Journal of Medicine – published studies based on Surgisphere data. The studies were co-authored by the firm’s chief executive, Sapan Desai.

Late on Tuesday, after being approached by the Guardian, the Lancet released an “expression of concern” about its published study. The New England Journal of Medicine has also issued a similar notice.

An independent audit of the provenance and validity of the data has now been commissioned by the authors not affiliated with Surgisphere because of “concerns that have been raised about the reliability of the database”.

Questions raised over hydroxychloroquine study which caused WHO to halt trials for Covid-19

 

 

 

The Guardian’s investigation has found:

• A search of publicly available material suggests several of Surgisphere’s employees have little or no data or scientific background. An employee listed as a science editor appears to be a science fiction author and fantasy artist whose professional profile suggests writing is her fulltime job. Another employee listed as a marketing executive is an adult model and events hostess, who also acts in videos for organisations.

• The company’s LinkedIn page has fewer than 100 followers and last week listed just six employees. This was changed to three employees as of Wednesday.

• While Surgisphere claims to run one of the largest and fastest hospital databases in the world, it has almost no online presence. Its Twitter handle has fewer than 170 followers, with no posts between October 2017 and March 2020.

• Until Monday, the “get in touch” link on Surgisphere’s homepage redirected to a WordPress template for a cryptocurrency website, raising questions about how hospitals could easily contact the company to join its database.

• Desai has been named in three medical malpractice suits, unrelated to the Surgisphere database. In an interview with the Scientist, Desai previously described the allegations as “unfounded”.

• In 2008, Desai launched a crowdfunding campaign on the website Indiegogo promoting a wearable “next generation human augmentation device that can help you achieve what you never thought was possible”. The device never came to fruition.

• Desai’s Wikipedia page has been deleted following questions about Surgisphere and his history, first raised in 2010.

 

 

 Sapan Desai, the chief executive of Surgisphere. Photograph: Gore Medical

At a press conference on Wednesday, the WHO announced it would resume its global trial of hydroxychloroquine, after its data safety monitoring committee found there was no increased risk of death for Covid patients taking it.

 

 

 

 

The WHO director general, Dr Tedros Adhanom Ghebreyesus, said that all parts of the Solidarity trial, which is investigating a number of potential drug treatments, would go ahead. So far, more than 3,500 patients have been recruited to the trial in 35 countries.

“On the basis of the available mortality data, the members of the committee recommended that there are no reasons to modify the trial protocol,” said Tedros. “The executive group received this recommendation and endorsed continuation of all arms of the Solidarity trial, including hydroxychloroquine.”

Doubts over Lancet study

Questions surrounding Surgisphere have been growing in the medical community for the past few weeks.

On 22 May the Lancet published a blockbuster peer-reviewed study which found the antimalarial drug hydroxychloroquine, which has been promoted by Donald Trump, was associated with a higher mortality rate in Covid-19 patients and increased heart problems.

Trump, much to the dismay of the scientific community, had publicly touted hydroxychloroquine as a “wonder drug” despite no evidence of its efficacy for treating Covid-19.

The Lancet study, which listed Desai as one of the co-authors, claimed to have analysed Surgisphere data collected from nearly 96,000 patients with Covid-19, admitted to 671 hospitals from their database of 1,200 hospitals around the world, who received hydroxychloroquine alone or in combination with antibiotics.

The negative findings made global news and prompted the WHO to halt the hydroxychloroquine arm of its global trials.

 

We trust that this review ... will tell us more about the status of the findings

Editor of the Lancet, Richard Horton

But only days later Guardian Australia revealed glaring errors in the Australian data included in the study. The study said researchers gained access to data through Surgisphere from five hospitals, recording 600 Australian Covid-19 patients and 73 Australian deaths as of 21 April.

But data from Johns Hopkins University shows only 67 deaths from Covid-19 had been recorded in Australia by 21 April. The number did not rise to 73 until 23 April. Desai said one Asian hospital had accidentally been included in the Australian data, leading to an overestimate of cases there. The Lancet published a small retraction related to the Australian findings after the Guardian’s story, its only amendment to the study so far.

The Guardian has since contacted five hospitals in Melbourne and two in Sydney, whose cooperation would have been essential for the Australian patient numbers in the database to be reached. All denied any role in such a database, and said they had never heard of Surgisphere. Desai did not respond to requests to comment on their statements.

Another study using the Surgisphere database, again co-authored by Desai, found the anti-parasite drug ivermectin reduced death rates in severely ill Covid-19 patients. It was published online in the Social Science Research Network e-library, before peer-review or publication in a medical journal, and prompted the Peruvian government to add ivermectin to its national Covid-19 therapeutic guidelines.

 

 

 Richard Horton, the editor of the Lancet. Photograph: Richard Saker/The Observer

The New England Journal of Medicine also published a peer-reviewed Desai study based on Surgisphere data, which included data from Covid-19 patients from 169 hospitals in 11 countries in Asia, Europe and North America. It found common heart medications known as angiotensin-converting–enzyme inhibitors and angiotensin-receptor blockers were not associated with a higher risk of harm in Covid-19 patients.

On Wednesday, the NEJM and the Lancet published an expression of concern about the hydroxychloroquine study, which listed respected cardiologist Mandeep Mehra as the lead author and Desai as co-author.

Lancet editor Richard Horton told the Guardian: “Given the questions raised about the reliability of the data gathered by Surgisphere, we have today issued an Expression of Concern, pending further investigation.

“An independent data audit is currently underway and we trust that this review, which should be completed within the next week, will tell us more about the status of the findings reported in the paper by Mandeep Mehra and colleagues.”

Surgisphere ‘came out of nowhere’

One of the questions that has most baffled the scientific community is how Surgisphere, established by Desai in 2008 as a medical education company that published textbooks, became the owner of a powerful international database. That database, despite only being announced by Surgisphere recently, boasts access to data from 96,000 patients in 1,200 hospitals around the world.

 

It doesn’t make sense. It would require many more researchers than it claims to have

Dr James Todaro, MedecineUncensored

When contacted by the Guardian, Desai said his company employed just 11 people. The employees listed on LinkedIn were recorded on the site as having joined Surgisphere only two months ago. Several did not appear to have a scientific or statistical background, but mention expertise in strategy, copywriting, leadership and acquisition.

Dr James Todaro, who runs MedicineUncensored, a website that publishes the results of hydroxychloroquine studies, said: “Surgisphere came out of nowhere to conduct perhaps the most influential global study in this pandemic in the matter of a few weeks.

“It doesn’t make sense,” he said. “It would require many more researchers than it claims to have for this expedient and of multinational study to be possible.”

Desai told the Guardian: “Surgisphere has been in business since 2008. Our healthcare data analytics services started about the same time and have continued to grow since that time. We use a great deal of artificial intelligence and machine learning to automate this process as much as possible, which is the only way a task like this is even possible.”

It is not clear from the methodology in the studies that used Surgisphere data, or from the Surgisphere website itself, how the company was able to put in place data-sharing agreements from so many hospitals worldwide, including those with limited technology, and to reconcile different languages and coding systems, all while staying within the regulatory, data-protection and ethical rules of each country.

Desai said Surgisphere and its QuartzClinical content management system was part of a research collaboration initiated “several years ago”, though he did not specify when.

Trump says he’s taking hydroxychloroquine against Covid-19 despite FDA warnings

 

 

 

“Surgisphere serves as a data aggregator and performs data analysis on this data,” he said. “We are not responsible for the source data, thus the labor intensive task required for exporting the data from an Electronic Health Records, converting it into the format required by our data dictionary, and fully deidentifying the data is done by the healthcare partner.”

This appears to contradict the claim on the QuartzClinical website that it does all the work, and “successfully integrates your electronic health record, financial system, supply chain, and quality programs into one platform”. Desai did not explain this apparent contradiction when the Guardian put it to him.

Desai said the way Surgisphere obtained data was “always done in compliance with local laws and regulations. We never receive any protected health information or individually identifiable information.”

Peter Ellis, the chief data scientist of Nous Group, an international management consultancy that does data integration projects for government departments, expressed concern that Surgisphere database was “almost certainly a scam”.

“It is not something that any hospital could realistically do,” he said. “De-identifying is not just a matter of knocking off the patients’ names, it is a big and difficult process. I doubt hospitals even have capability to do it appropriately. It is the sort of thing national statistics agencies have whole teams working on, for years.”

“There’s no evidence online of [Surgisphere] having any analytical software earlier than a year ago. It takes months to get people to even look into joining these databases, it involves network review boards, security people, and management. It just doesn’t happen with a sign-up form and a conversation.”

 

There continues to be a fundamental misunderstanding about what our system is and how it works

Sapan Desai

None of the information from Desai’s database has yet been made public, including the names of any of the hospitals, despite the Lancet being among the many signatories to a statement on data-sharing for Covid-19 studies. The Lancet study is now disputed by 120 doctors.

When the Guardian put a detailed list of concerns to Desai about the database, the study findings and his background, he responded: “There continues to be a fundamental misunderstanding about what our system is and how it works”.

“There are also a number of inaccuracies and unrelated connections that you are trying to make with a clear bias toward attempting to discredit who we are and what we do,” he said. “We do not agree with your premise or the nature of what you have put together, and I am sad to see that what should have been a scientific discussion has been denigrated into this sort of discussion.”

‘The peak of human evolution’

An examination of Desai’s background found that the vascular surgeon has been named in three medical malpractice suits in the US, two of them filed in November 2019. In one case, a lawsuit filed by a patient, Joseph Vitagliano, accused Desai and Northwest Community Hospital in Illinois, where he worked until recently, of being “careless and negligent”, leading to permanent damage following surgery. 

Northwest Community Hospital confirmed that Desai had been employed there since June 2016 but had voluntarily resigned on 10 February 2020 “for personal reasons”.

“Dr Desai’s clinical privileges with NCH were not suspended, revoked or otherwise limited by NCH,” a spokeswoman said. The hospital declined to comment on the malpractice suits. Desai said in the interview with the Scientist that he deemed any lawsuit against him to be “unfounded”.

 

 

 

 

Brigham and Women’s Hospital, the institution affiliated with the hydroxychloroquine study and its lead author, Mandeep Mehra, said in a statement: “Independent of Surgisphere, the remaining co-authors of the recent studies published in The Lancet and the New England Journal of Medicine have initiated independent reviews of the data used in both papers after learning of the concerns that have been raised about the reliability of the database”. 

Mehra said he had routinely underscored the importance and value of randomised, clinical trials and that such trials were necessary before any conclusions could be reached. “I eagerly await word from the independent audits, the results of which will inform any further action,” he said.

Desai’s now-deleted Wikipedia page said he held a doctorate in law and a PhD in anatomy and cell biology, as well as his medical qualifications. A biography of Desai on a brochure for an international medical conference says he has held multiple physician leadership roles in clinical practice, and that he is “a certified lean six sigma master black belt”.

It is not the first time Desai has launched projects with ambitious claims. In 2008, he launched a crowdfunding campaign on the website indiegogo promoting a “next generation human augmentation device” called Neurodynamics Flow, which he said “can help you achieve what you never thought was possible”.

“With its sophisticated programming, optimal neural induction points, and tried and true results, Neurodynamics Flow allows you to rise to the peak of human evolution,” the description said. The device raised a few hundred dollars, and never eventuated.

Ellis, the chief data scientist of Nous Group, said it was unclear why Desai made such bold claims about his products given how likely it was that the global research community would scrutinise them.

“My first reaction is it was to draw attention to his firm, Ellis said. “But it seems really obvious that this would backfire.”

Today Prof Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, said: “I welcome the statement from the Lancet, which follows a similar statement by the NEJM regarding a study by the same group on cardiovascular drugs and COVID-19. 

“The very serious concerns being raised about the validity of the papers by Mehra et al need to be recognised and actioned urgently, and ought to bring about serious reflection on whether the quality of editorial and peer review during the pandemic has been adequate. Scientific publication must above all be rigorous and honest. In an emergency, these values are needed more