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On 4 June 2020, after a week of increasing scientific concern and scrutiny, first The Lancet, then the New England Journal of Medicine, retracted studies that were based on inaccessible data. The studies have been extremely damaging to chloroquine and hydroxychloroquine COVID-19 clinical trials around the globe. MORU researchers played a key role in bringing this scandal to light, whose consequences continue to play out.

Major_medical_journals_retract_Covid-19_studies

It has been a wild, rough ride for the COPCOV global prevention study to determine if chloroquine and hydroxychloroquine can prevent Covid-19 in hospital staff working with patients potentially infected with coronavirus.

On 21 May, COPCOV’s UK arm began enrolling participants at two sites, at the Brighton and Sussex University Hospitals and the John Radcliffe Hospital in Oxford, with several more sites slated to come online shortly thereafter.

Then, on 22 May The Lancet published a study by Mehra et al. This paper claimed that hydroxychloroquine significantly increased the risk of death in Covid-19 infected patients.

Immediately following publication of the Lancet article, the UK regulator MHRA ‘paused’ participant enrolment in COPCOV UK. In quick order, the WHO halted the hydroxychloroquine arm of their global SOLIDARITY study, and regulatory authorities in several countries including France asked investigators to pause ongoing randomised controlled clinical trials involving hydroxychloroquine and chloroquine.

Both  the paper in The Lancet and an earlier one in the  New England Journal of Medicine  (NEJM) by three of the same authors as in The Lancet used data provided by the US company Surgisphere – owned by US cardiologist Dr Sapan Desai, the second author in both studies.

MORU researchers thought early on that it seemed likely or even probable that the article was based on flawed data provided by the US company Surgisphere.  James Watson engaged with Columbia University statistician Andrew Gelman and his blog of 40,000 participants. Nick White, Nick Day, Charlie Woodrow, Will Schilling and the COPCOV team worked behind the scenes to closely examine the publication’s data and detail details about Surgisphere and its data. In this ABC Australia interview, James talks about the doubts and what then transpired.

This international effort culminated in an open letter on 28 May signed by over 200  clinicians, medical researchers, statisticians, and ethicists from across the world to the authors and Richard Horton, Editor of the Lancet. Expressing methodological and data integrity concerns, the signatories asked that Surgisphere provide details on data provenance, called for independent validation of the analysis and open access to all data sharing agreements in each jurisdiction cited in the paper to ensure that any mined data was legally and ethically collected.

Weak responses from The Lancet and authors continuing refusal to share the study data by Surgisphere, led to growing examination of Surgisphere and its data by international media and researchers. Many found it surprisingly unlikely that a company of 5 employees could have developed a major global database of confidential hospital records from across the globe, as it claimed.

Attention then turned to a study of coronavirus patients published in the New England Journal of Medicine early May by some of the same authors, including Harvard’s Dr Mandeep R. Mehra. This paper was also based on data from the Surgical Outcomes Collaborative (Surgisphere Corporation, Chicago, IL, USA). This paper had many of same flaws as The Lancet paper. The authors claimed to have electronic patient record data from a high proportion of all hospitalised COVID-19 patients in the countries they are linked with. Yet countries such as UK and Turkey did not have as many hospitalised patients in the entire country as claimed to have been in the Surgisphere linked hospitals at the time of the study.  

On 2 June, James Watson and scientists, researchers, clinical trials experts and statisticians wrote an open letter to the New England Journal and to the authors pointing out the major discrepancies and requesting again that Surgisphere’s data be made public.

The same day, 2 June, the NEJM, followed by The Lancet on 3 June published editorial Expressions of Concern about the two papers.

Pressure continued to increase on the journals and authors. On 4 June, after a review of data, the WHO reversed its decision to halt its global SOLIDARITY hydroxychloroquine trials.

Later that same day, 4 June, after a week of increasing scientific concern and scrutiny, first The Lancet, then a little over an hour later the New England Journal of Medicine, retracted the studies that were based on inaccessible data, provided by the Surgisphere corporation.

Noting that extremely damaging impact of the studies to chloroquine and hydroxychloroquine COVID-19 clinical trials around the globe, MORU made a statement that concluded:

“Many important questions will need to be answered in the coming weeks and months, but we would like to use this unfortunate opportunity to make two relevant recommendations which we believe are in the public interest.

  1. Medical and scientific journals should not accept papers based on inaccessible data
  2. Regulatory authorities and other agencies responding to such reports should satisfy themselves of the veracity and applicability of published data and the correctness of analyses before they act.”

The scandal and its consequences continue to play out. On 8 June, the University of Utah terminated the faculty appointment of Dr Amit Patel, one of the authors of both papers.

As of publication, the MHRA has yet to ‘unpause’ COPCOV UK participant enrolment.

- Nick Day and John Bleho

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