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2 Papers About Drug Therapy (hydroxychloroquine)
in COVID-19 Retracted From Prestigious Journals
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JUNE 5, 2020
https://www.idse.net/Covid-19/Article/06-20/2-Papers-About-Drug-Therapy-in-COVID-19-Retracted-From-Prestigious-Journals/58675?sub=747A6C7B288AFFC0C1D9FA943B86C84C2D7CA90D99A344811EAE303450CD21&enl=true&dgid=&utm_source=enl&utm_content=1&utm_campaign=20200605&utm_medium=title
"In the absence of this large registry study of hydroxychloroquine or chloroquine, the jury is still out about whether or not they provide more benefits than harms in people with COVID-19...
it is important that the clinical trials of hydroxychloroquine, and other potential therapies, continue in earnest so that clinicians can have evidence-based treatments as soon as possible," said Dr. White, who recently wrote a review about the use of hydroxychloroquine for COVID-19 (Ann Intern Med 2020 May 27. [Epub Ahead of print])."
By Marie Rosenthal, MS
The recent retraction of two papers that used the Surgical Outcomes Collaborative registry, developed and maintained by Surgisphere Corp., to evaluate the impact of drugs in COVID-19 patients is a cautionary tale, according to C. Michael White, PharmD, FCP, FCCP, who was not involved in both studies but was asked his thoughts about them.
The authors of the two papers, which appeared in The New England Journal of Medicine and the Lancet, retracted the papers after concerns were raised about the data set used in the studies.
The NEJM paper, published online on May 1, reported that underlying cardiovascular disease was associated with an increased risk for death from COVID-19, but that the use of angiotensin-converting enzyme inhibitors and statins were associated with a reduced risk for death from COVID-19.
More consequentially, the Lancet paper, published online on May 22, reported that mortality was higher in people receiving hydroxychloroquine, chloroquine, or either of these drugs with a macrolide antibiotic versus those treated without them. In addition, they reported that those treated with hydroxychloroquine or chloroquine were far more likely to experience ventricular arrhythmias than their counterparts who had not received the drugs.
The Lancet paper prompted the World Health Organization to suspend the hydroxychloroquine arm of a clinical trial for patients with COVID-19, but with the retraction, WHO decided not to modify the study, according to Tedros Adhanom Ghebreyesus, MD, the WHO director-general. "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," he said. So far, more than 3,500 patients have been recruited in 35 countries for this trial.
Earlier this week, concerns were expressed about the veracity of the data supplied by Surgisphere. Therefore, an independent auditor was to review the raw data and the studies, but apparently could not obtain the necessary information from Surgisphere, so the authors withdrew the papers.
"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," wrote Mandeep R. Mehra, MD, of Brigham and Women's Hospital Heart and Vascular Center, in Boston, and lead author of the studies. The retraction for the NEJM study was signed by all four authors, including Sapan S. Desai, MD, PhD, the president and CEO of Surgisphere.
The Lancet retraction, which came about an hour before the NEJM retraction, was not signed by all of the authors. Although longer, it essentially noted the same difficultly in analyzing the raw data. "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. 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," Dr. Mehra; Frank Ruschitzka, MD; and Amit N. Patel, MD, wrote.
"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 wrote.
"We always aspire to perform our research in accordance with the highest ethical and professional guidelines," they wrote, adding that they "no longer vouch for the veracity of the primary data sources."
They said they collaborated in good faith and apologized for the papers.
However, even if the trial data sets were legitimate, there are inherent weaknesses that should be noted, according to Dr. White, the department head and a professor of pharmacy in the Department of Pharmacy Practice at University of Connecticut School of Pharmacy, in Storrs. "By their nature, studies based on claims data or other databases do not provide a high quality of evidence to answer clinical questions, such as the risks versus benefits of a therapy for a condition," he told Infectious Disease Special Edition.
"The big issue is that while you might be able to statistically correct for the impact of some demographic factors, you cannot correct for those factors you do not know at the time are important and you cannot factor in the thought processes of the treating clinicians as they are making treatment choices," Dr. White said.
In the absence of this large registry study of hydroxychloroquine or chloroquine, the jury is still out about whether or not they provide more benefits than harms in people with COVID-19. "Therefore, it is important that the clinical trials of hydroxychloroquine, and other potential therapies, continue in earnest so that clinicians can have evidence-based treatments as soon as possible," said Dr. White, who recently wrote a review about the use of hydroxychloroquine for COVID-19 (Ann Intern Med 2020 May 27. [Epub Ahead of print]).
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