NEWS 29 MAY 2020 Safety fears over drug hyped to treat the coronavirus spark global confusion A study that suggested using hydroxychloroquine — a malaria drug — to treat people with COVID-19 could be dangerous has slowed clinical trials, but the study itself has also been questioned. PDF version Hydroxychloroquine has had a controversial history during the coronavirus pandemic.Credit: George Frey/AFP/Getty A study suggesting that the malaria drug hydroxychloroquine is dangerous to people with severe cases of COVID-19 is sowing confusion among researchers — and halting clinical trials that are crucial to finding out whether the medication is effective at treating people infected with the novel coronavirus. In light of the study, this week, the World Health Organization (WHO) has paused enrolment in its trial of the drug as a treatment for COVID-19, as have regulators in the United Kingdom, France and Australia, where similar trials are under way. But the picture isn’t clear-cut: on 28 May, 120 researchers signed a letter to The Lancet, which published the study1, highlighting concerns about the quality of the data and its analysis. Hydroxychloroquine has had a controversial history during the pandemic, with politicians such as US president Donald Trump endorsing the medication, which is cheap and easy to administer, as a treatment despite scant evidence that it works. Researchers have been eagerly awaiting results from clinical trials to yield a clear answer. But now they fear that the Lancet study, and the negative press coverage that followed, might dissuade patients from joining the trials, which would make it even harder to determine whether the drug works against COVID-19. “There’s so much swirling around it, people won’t want to enter those trials,” says David Smith, an infectious-disease specialist at the University of California in San Diego. “In which case, it will be an open question that won’t get answered.” [paste:font size="6"]Coronavirus and COVID-19: Keep up to date There is currently only one treatment that has shown promise against COVID-19 in a rigorous clinical trial and that drug, remdesivir, is in short supply and must be administered intravenously over several days, typically in a hospital. In the early days of the pandemic, which has now killed more than 350,000 people, many were hopeful that hydroxychloroquine, a relatively cheap and widely available drug, might offer some benefits. Early laboratory studies suggested that the drug, as well as a similar medicine named chloroquine, might interfere with replication of the coronavirus, but trials in humans have been inconclusive so far. In the meantime, advocacy by politicians such as Trump — who has not only endorsed hydroxychloroquine’s use but said that he has taken it prophylactically — has muddied public perception of the drug. “Some people come in and say, ‘The president takes it, I need to take it,’” says Smith. “And others say, ‘The president’s taking it, I’m definitely not taking it.’” Safety concerns Researchers have been waiting for results from a number of randomized, controlled clinical trials testing hydroxychloroquine as a COVID-19 treatment. The Lancet study was not based on such trials. Instead, it was an observational study cataloguing the effects of hydroxychloroquine in about 96,000 patients hospitalized with COVID-19 around the world. The study found the drug had no benefit, and instead found a worryingly higher mortality rate among those who received it: 18%, compared with 9% in those who did not. Data from observational studies can be useful to get a sense of how a drug performs outside the confines of a clinical trial, in which patients are often more carefully selected for treatment and monitored than in the real world. But observational studies can also be prone to real-world bias: one concern, for example, is that physicians might be more likely to give a drug to patients who are sicker and more likely to die. Nevertheless, the results have led regulators and clinical-trial sponsors to take action. The WHO has paused enrolment in the hydroxychloroquine treatment group of its large Solidarity trial, an effort in 35 countries to test potential COVID-19 therapies that is also testing three other potential COVID-19 treatments. The UK Medicines and Healthcare Regulatory Agency (MHRA) has similarly paused most of the country’s hydroxychloroquine trials for COVID-19, pending further safety assessments. And in France, where clinical-trial enrolment has been halted, doctors have been forbidden to prescribe the drug outside of clinical trials to people with COVID-19.
