Update: On June 4, the study was retracted from The Lancet due to serious concerns over its data. Read our new story about the study’s retraction here.
A massive study that raised serious health concerns about hydroxychloroquine, the malaria drug President Donald Trump has reportedly taken as a coronavirus preventive, is now under scrutiny from more than 180 scientists worldwide who are asking the research team to release its data for outside analysis.
When the study was published last week in the Lancet, a high-profile medical journal, it drew widespread media attention, including from BuzzFeed News. Its massive dataset — consisting of 96,000 hospitalized COVID-19 patients across six continents — seemed to offer the most definitive examination to date of hydroxychloroquine’s inability to fight the coronavirus, and also linked it to a higher risk of death.
But the letter, which went online on Thursday, raises questions about some seemingly inconsistent data in the paper. Among the scientists' 10 concerns are that the average daily doses of hydroxychloroquine were higher than the FDA-recommended amounts and that data reportedly from Australian patients did not seem to match data from the Australian government. This week, the Guardian reported that it could not confirm with several of that country’s health agencies that they provided data to the study.
The study's authors, led by Mandeep Mehra of Harvard Medical School, have repeatedly declined to release their underlying data.
On Friday, the study’s research team corrected some of its data but said its conclusions remained the same.
Not only did the study find no evidence that the malaria drug effectively combats the coronavirus, but it also linked the drug to serious heart problems. Several other studies have previously reached similar conclusions, and the FDA has acknowledged the cardiac risks of this and a related drug, chloroquine, warning that the drugs not be used outside of a hospital setting.
For the first time, the Lancet study also found a link with a higher rate of deaths, finding that hospitalized patients who were given hydroxychloroquine were at least 33% more likely to die than those who did not receive the treatment.
In the wake of the Lancet study, two major hydroxychloroquine clinical trials — one by the World Health Organization, another in the United Kingdom — were put on pause. And the governments of France, Belgium, and Italy banned the drug from being used as a coronavirus treatment.
“Everything points to a drug that has no efficacy,” said Eric Topol, a cardiologist at the Scripps Research Translational Institute, who hasn’t signed the letter but has expressed skepticism publicly about the use of hydroxychloroquine as a treatment. “There’s no sign that it helps anyone. We know it has significant side effects that are worrisome,” including cardiac arrest and a dangerously rapid heart rate called ventricular tachycardia.
Even so, scientists found aspects of the Lancet study that didn’t seem to add up.
One of the biggest concerns of the letter's signatories was that the authors had not released their code or data, even though the Lancet has signed a pledge to share COVID-19–related data.
“Many of us in the scientific community were just very angry at seeing a poorly written and executed study published in The Lancet, given loads of publicity, and then having a hugely negative impact on carefully planned clinical trials around the world,” said James Watson, a Thailand-based statistician with the University of Oxford’s Centre for Tropical Medicine and Global Health, who led the drafting of the letter, in an email to BuzzFeed News.
In response to the correction issued on Friday, Watson said, "The authors have not addressed the other nine points referred to in the letter."
According to the Lancet study, the patient data came from electronic health records, supply chain databases, and financial records. It was collected by Surgisphere, a Chicago-based health data analytics company led by Sapan Desai, one of the study’s coauthors.
Surgisphere says its data use agreements prevent it from sharing individual patient data and the names of its hospital customers, though it can conduct analyses and share aggregate findings. “Our strong privacy standards are a major reason that hospitals trust Surgisphere and we have been able to collect data from over 1,200 institutions across 46 countries,” Desai told BuzzFeed News by email.
But the signatories on the letter say the researchers should at least share aggregated patient data at the hospital level. They are also asking for an independent analysis and for the Lancet to release the peer review comments made about the study prior to publication.
Topol, the cardiologist at Scripps, said he had never heard of Surgisphere before the study. “The main thing they haven’t done is release the data for others to analyze,” he said. “That is important, and I think they should do that.”
In the correction issued Friday, the study’s authors fixed the numbers of participants from Australia and Asia. One hospital tagged as belonging to the Australia region should have instead been assigned to the Asia region, according to the notice. Other corrections were also issued, but the notice stated that none of the changes altered the paper's conclusions.
Lancet spokesperson Jessica Kleyn said the journal will soon publish responses to the study and a response from the authors.
Mehra, the study’s lead author, said he stands by the research. He and his team used Surgisphere’s data “in the absence of a large, robust and publicly available dataset on hydroxychloroquine or chloroquine, and the lack of scientific evidence regarding the safety and benefits of these treatments for hospitalized Covid-19 patients,” said Mehra, medical director of the Brigham and Women’s Hospital Heart and Vascular Center and a professor of medicine at Harvard Medical School, through a spokesperson.
Mehra, Desai, and other researchers also used Surgisphere data in a study published this month in the New England Journal of Medicine about cardiovascular disease in COVID-19 patients. Watson, the researcher organizing the letter, has criticized some of that paper’s supplementary data about age and mortality rates.
Mehra and Desai did not answer questions about this additional study. Jennifer Zeis, a New England Journal of Medicine spokesperson, said that the publication was looking into the questions raised.
The story has been updated to include comments from James Watson about the study's correction.