Lancet retracts study flagging hydroxychloroquine trial for coronavirus patients over data concerns
An influential study that raised alarms about the safety of hydroxychloroquine for treating Covid-19 patients — which also led to the World Health Organization (WHO) suspending clinical trial of the drug because of fears of increased deaths from it — has now been retracted by The Lancet that published the paper.
The retraction came at the request of the authors of the study — Hydroxychloroquine or chloroquine with or without a macrolide for treatment of Covid-19: a multinational registry analysis — over concerns about the data used in the paper that came from an international registry. Three of the study's authors said they could no longer vouch for its veracity because Surgisphere, the US-based healthcare firm behind the data, would not allow an independent review of its dataset.
“After the publication of our Lancet article, several concerns were raised with respect to the veracity of the data and analyses conducted by Surgisphere Corporation and its founder and our co-author, Sapan Desai, in our publication. We launched an independent third-party peer review of Surgisphere with the consent of Sapan Desai to evaluate the origination of the database elements, to confirm the completeness of the database, and to replicate the analyses presented in the paper,” said study authors Mandeep R Mehra, Frank Ruschitzka and Amit N Patel in their retraction published by The Lancet.
The authors explained, “Our independent peer reviewers informed us that Surgisphere would not transfer the full dataset, client contracts, and the full ISO audit report to their servers for analysis as such transfer would violate client agreements and confidentiality requirements. 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.”
They said based on this development, they can no longer vouch for the veracity of the primary data sources. “Due to this unfortunate development, the authors request that the paper be retracted. We always aspire to perform our research in accordance with the highest ethical and professional guidelines. We can never forget the responsibility we have as researchers to scrupulously ensure that we rely on data sources that adhere to our high standards,” they said.
The study had concluded that hospitalized Covid-19 patients, treated with hydroxychloroquine and chloroquine, are more likely to die or develop dangerous heart rhythm. It claimed that about one in six patients treated with chloroquine or hydroxychloroquine alone died in the hospital. In contrast, about one in 11 patients in the control group died in the hospital. On June 3, The Lancet had issued an “expression of concern” to alert readers that “important scientific questions” have been raised about data reported in the paper.
The WHO had also resumed the clinical trial to study whether hydroxychloroquine can effectively treat Covid-19. The hydroxychloroquine investigation is just one arm of the agency’s “Solidarity Trial,” which is testing different therapies to determine which are beneficial in the disease caused by the novel coronavirus. “Last week the executive group of the Solidarity Trial decided to implement a temporary pause of the hydroxychloroquine arm of the trial, because of concerns raised about the safety of the drug. This decision was taken as a precaution while the safety data were reviewed. The Data Safety and Monitoring Committee has been reviewing the data. On the basis of the available mortality data, the members of the committee recommended that there are no reasons to modify the trial protocol. The executive group received this recommendation and endorsed the continuation of all arms of the Solidarity Trial, including hydroxychloroquine,” said the WHO on June 3.
In their retraction, the authors say the research team entered this collaboration to contribute “in good faith” and at a time of great need during the Covid-19 pandemic. “We deeply apologize to you, the editors, and the journal readership for any embarrassment or inconvenience that this may have caused,” they said.
Meanwhile, a second paper published in the New England Journal of Medicine (NEJM) that also used patient data from Surgisphere, has been retracted by the journal. The second paper had said that taking certain blood pressure drugs including angiotensin-converting enzyme (ACE) inhibitors did not appear to increase the risk of death among Covid-19 patients, as some researchers had suggested. The NEJM has also issued an expression of concern about the Surgisphere data used in the study.
“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, “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.” We, therefore, request that the article be retracted. We apologize to the editors and to readers of the Journal for the difficulties that this has caused,” said the research team in their retraction published by NEJM.