Dozens of scientists have raised concerns over a large-scale study of hydroxychloroquine and chloroquine that led to the World Health Organization suspending clinical trials of the anti-viral drugs as a potential treatment for COVID-19.
Hydroxychloroquine, normally used to treat arthritis, is one of an array of drugs being tested as scientists look for potential treatments for coronavirus patients.
It has also become the most high profile, partly because of comments by US President Donald Trump -- who announced this month he was taking the drug as a preventative measure against coronavirus.
The research, which was published in the Lancet on May 22, looked at records from 96,000 patients across hundreds of hospitals.
It concluded that treatment with hydroxychloroquine and chloroquine, an anti-malarial, showed no benefit and even increased the likelihood of them dying in hospital.
Both drugs can produce potentially serious side effects, particularly heart arrhythmia.
Within days of the research being published the WHO temporarily suspended use of the drugs in its Solidarity trial -- which has seen hundreds of hospitals across several countries enrol patients to test possible treatments for COVID-19.
"This impact has led many researchers around the world to scrutinise in detail the publication in question," said the open letter, signed by a number of prominent scientists.
It added this scrutiny raised "both methodological and data integrity concerns".
The authors list several issues with the study, including a lack of information about the countries and hospitals that contributed to the data, a lack of an ethics review and discrepancies in data for Australia, which did not match published national figures.
"Surgisphere (the data company) have since stated this was an error of classification of one hospital from Asia. This indicates the need for further error checking throughout the database," the letter said.
Among the signatories are clinicians, statisticians and other researchers from around the world, from Harvard to Imperial College London.
- 'Serious doubts' -
Francois Balloux of University College London, said he believed it was his "duty" to add his name to calls for answers to questions about the study and for greater transparency.
"I have serious doubts about the benefit of CQ/HCQ treatment for #COVID19 infection, and cannot wait for the whole drama to be over," he said on Twitter.
"Though, I believe 'research integrity' cannot be invoked only when a paper doesn't support our preconceptions."
The letter was also signed by French researcher Philippe Parola, a colleague of the Marseille-based professor Didier Raoult, whose work has been at the forefront of promoting hydroxychloroquine.
In a statement the Lancet said it had received "several questions" over the study.
"We have referred these questions to the authors and they are working to address the issues that have been raised," it said.
A spokesman for the WHO said a comprehensive review of the drugs was expected to reach a conclusion in mid-June.
"Any decision on the hydroxychloroquine arm of the study must be based in a comprehensive analysis of the available evidence, particularly from concluded and ongoing randomised trials," said Tarik Jasarevic.