Medics who edit the prestigious journal The Lancet have “expressed concern” over the safety of a drug Donald Trump takes to ward off the coronavirus.
The president announced in May he had been taking the malaria medication hydroxychloroquine for a week and a half.
He has also described fellow-malaria drug chloroquine as “something really incredible”.
First-time prescription rates and online searches for the treatments soared after Trump’s endorsements.
This is despite safety concerns, with a chloroquine study in Brazil having to be cut short when patients developed an irregular heart rate and a hydroxychloroquine trial in the US being linked to higher death rates.
The Lancet editors have issued an “Expression of Concern to alert readers to the fact that serious scientific questions have been brought to our attention”, citing a damning Harvard study into the treatments.
This has been met with a mixed response, with some experts questioning the validity of the Harvard research.
Early research suggests the coronavirus is mild in four out of five cases, however, it can trigger a respiratory disease called COVID-19.
Drugs may increase COVID-19 death risk
The Lancet editors put the statement out after a study of more than 96,000 patients hospitalised with the coronavirus raised alarm bells.
The Harvard scientists found those given hydroxychloroquine were 33% more likely to die than patients in the control group, who received other forms of care.
This rose to a 44% higher risk when hydroxychloroquine was combined with the antibiotic macrolide.
“Hydroxychloroquine or chloroquine, often in combination with a macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit”, the scientists wrote in their Lancet paper.
Chloroquine, both alone and with macrolide, was found to raise a patient’s death risk by 36%.
All these drug regimens also increased the odds of de-novo ventricular arrhythmia, the sudden onset of abnormal beating in the lower chambers of the heart.
This can cause the heart to beat too fast, preventing oxygen-rich blood from reaching the brain and triggering a cardiac arrest.
The patients on hydroxychloroquine with macrolide were over five times more likely to develop the arrhythmia than those in the control group.
“We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19,” concluded the Harvard scientists.
“Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.”
Following concerns about the data the Harvard study used, which came from the private company Surgisphere, an independent audit is being carried out.
The Lancet editors said they will update their stance accordingly.
Stopping drug trials ‘completely unjustified’
Experts have had mixed reactions to the Lancet editors’ Expression of Concern, noting the Harvard study’s drawbacks.
The research was said to have a “profound impact” on the World Health Organization’s decision to stop testing the treatments in its trials, as well as it no longer recommending they be prescribed “off-label”.
Other clinical trials investigating the drugs have also been halted.
“This is completely unjustified,” said Professor Peter Horby from the University of Oxford.
“Even if the [Harvard] results were correct, observational data such as this, with its inherent weaknesses, should not be used to stop trials which will provide definitive and actionable answers.”
The Harvard study used Australian patient data via Surgisphere.
“The number of COVID cases that were supposed to be from a subset of Australian hospitals was actually greater than the sum total of cases in Australia reported at the time”, said Professor Babak Javid from Cambridge University Hospitals.
“Several other inconsistencies have also emerged. The raw data have not been made available for general scrutiny.”
Professor Javid worries studies like this may put patients off being enrolled in clinical trials.
Other experts echoed his concerns.
“Doubts regarding data integrity severely undermine the peer review process and pose a fundamental threat to the advancement of scientific and clinical understanding amidst this devastating pandemic,” said Dr Stephen Griffin from the University of Leeds.
“Second, the withdrawal of these drugs from various clinical settings based upon what may be dubious mortality data could deprive COVID patients of a potentially effective therapy.
“Lastly, we must ask is it feasible, or indeed fair, for individual peer reviewers to assess such studies, as they necessarily depend upon intrinsic trust and cannot logistically validate such enormous data sets.”
Despite his concerns, Dr Griffin added the increase in mortality among patients in the Harvard study was “unexpected”, with previous studies also suggesting the drugs may have “no therapeutic benefit”.
“It will require placebo-controlled RCTs [randomised controlled trials] to finally establish both the safety and effectiveness of these drugs”, he said.
“Until these data are available and the outcomes of [independent] investigations are known, the true clinical usefulness of these repurposed drugs remains unknown.
“It is therefore prudent they remain assessed only within the context of RCTs and that their off-label use is restricted.”
RCTs are considered the “gold standard” of research. They involve patients being randomly allocated to a treatment group.
Professor Evans from The London School of Hygiene and Tropical Medicine agreed these trials are important, but added they may be difficult to recruit for as officials get more of a handle on the coronavirus outbreak.
“With the current falls in the numbers of cases of COVID-19 and deaths from it in many countries the full answers could still be delayed”, he said.
Speaking of hydroxychloroquine, Professor Martin Landray from the University of Oxford added: “This is a drug that is very widely used for a disease that kills hundreds of thousands of people, but on the basis of no good evidence.
“The sooner we get answers from randomised controlled trials the better.
“If it turns out hydroxychloroquine is effective for COVID-19, then let’s use it; if not, let’s abandon it. But this is not a time for speculation”.
What is the coronavirus?
Since the coronavirus outbreak was identified at the end of 2019, more than 6.4 million cases have been confirmed worldwide, according to Johns Hopkins University.
Of these cases, over 2.7 million are known to have recovered.
Globally, the death toll has exceeded 381,000.
The coronavirus mainly spreads face to face via infected droplets expelled in a cough or sneeze.
Symptoms include fever, cough and a loss of taste or smell.
The coronavirus has no “set” treatment, with most patients naturally fighting off the infection.
Those requiring hospitalisation are given “supportive care”, like ventilation, while their immune system gets to work.
Officials urge people ward off infection by washing their hands regularly and maintaining social distancing.
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