Journals retract two major Covid studies
Two of the world’s leading medical journals have retracted major studies on the coronavirus disease, including one that raised safety concerns about the experimental use of anti-malarial drugs for treatment of Covid-19 amid scientific scrutiny of dubious data sets used for the analysis.
Both studies, which were published in The Lancet and the New England Journal of Medicine (NEJM), used data from a little-known Chicago-based health analytics company called Surgisphere, which has been consistently opaque about its data sources.
The study published in The Lancet retrospectively analysed around 96,000 patient records to conclude that the anti-malaria drugs hydroxychloroquine and chloroquine offered no benefits in treating Covid-19 and even raised the risk of irregular heart rhythm (arrhythmia) and death.
Following the study, the World Health Organization (WHO) suspended the hydroxychloroquine and chloroquine arm of its multi-country Solidarity Trail to validate four experimental Covid-19 treatments, but announced this week that it was resuming the trials.
In the absence of a treatment or vaccine, hydoxychloroquine and chloroquine are among several approved drugs being repurposed to treat Covid-19. Among its champions is US President Donald Trump, who has announced that he has been taking hydroxychloroquine as a prophylaxis to prevent infection.
The drug has been used to treat people for malaria, rheumatoid arthritis, and lupus, against which it has been shown to offer benefits, experts stress.
Following Surgisphere’s refusal to share its data and methodology after at least 120 scientists and clinicians called for an independent audit of the data it claimed were sourced from 671 hospitals across six continents, three of the four authors of the hydroxychloroquine and chloroquine paper not affiliated with Surgisphere retracted the study.
The retraction came two days after The Lancet issued an “Expression of Concern to alert readers to the fact that serious scientific questions have been brought to our attention” on Wednesday.
“We can no longer vouch for the veracity of the primary data sources,” Mandeep Mehra of Brigham and Women’s Hospital in Boston, Frank Ruschitzka of University Hospital Zurich, and Amit Patel of University of Utah said in a statement issued by The Lancet. The fourth study author, Dr Sapan Desai, a vascular surgeon and Surgisphere’s chief executive, did not join the retraction.
“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,” the researchers wrote.
Late on Thursday, the NEJM also retracted a study using data from the same company that found that blood pressure medications were safe for people with Covid-19.
“Rapid review is actually causing problems because the reviewers are being chosen in haste and they don’t have adequate time to look at the data properly. They feel the pressure of time to respond quickly, and may not notice some of the problems with the data. Secondly, you may not get the best combination of reviewers given the deluge of studies out there. When the publication speed is high, study authors and reviewers don’t notice the traffic signals,” said Dr Srinath Reddy, president, Public Health Foundation of India, who is an independent expert on the executive group of the steering committee of Solidarity Trial.
“I think that what happened just highlights the self-correcting nature of scientific process. The only lesson I can state is an obvious one. If the conclusions are important to your work, read the paper carefully and judge its merit independently. Do not assume quality from the names or affiliations of the authors, or the name of the journal. The publication process is as prone to human fallibility as anything else,” said Dr Anurag Agrawal, director of the Delhi-based Institute of Genomics and Integrative Biology,.
Agrawal is among the top scientists in India to have written to WHO chief scientist Soumya Swaminathan questioning the health agency’s decision to suspend the hydroxychloroquine and chloroquine part of Solidarity Trial following The Lancet study. The letter said the WHO’s decision to pause the trial is “knee-jerk” because the database is flawed and the malaria drugs were given to the sickest patients.
India is the world’s biggest producer of hydroxychloroquine, which is approved for use as a prophylaxis and has been given to asymptomatic health workers and contacts of Covid-19 patients since March 23. This was expanded to include frontline workers from May 22.
A study from India found that having four or more doses of hydroxychloroquine lowers the odds of getting infected by Sars-CoV-2, the virus that causes the coronavirus disease. The study, published in the Indian Journal of Respiratory Research earlier this week, said the anti-malaria drug lowered the risk of infection by 80% if taken as recommended. The National Task Force for the coronavirus in India recommended a once-a-week maintenance dose for seven weeks -- 400 mg once every week, following the loading dose of 400 mg.
Hydroxychloroquine does not prevent disease when given as a post-exposure prophylaxis within four days after high-risk or moderate-risk exposure to Covid-19, reported the first gold-standard clinical trial of hydroxycholoroquine in Covid-19 published in NEJM on Wednesday, Other clinical trials, including some looking at the drugs as treatments, are under way.