Hydroxychloroquine: Wonder-drug, killer, or just your standard antimalarial?

A look at the ambiguous evidence for using hydroxychloroquine in the treatment of COVID-19

Writer: Katie Dale
Editor: Altay Shaw
Artist: Lucie Gourmet

Famously promoted by the US president, the antimalarial drug hydroxychloroquine (sold under the brand name Plaquenil) had become widely considered as a trump card against COVID-19. But on 22nd May, that changed. The Lancet published a study showing an increased risk of mortality in patients treated with hydroxychloroquine, sending shockwaves around the world that shut down clinical trials and left individuals taking the prescription medication in fear.

The study found that hydroxychloroquine use was associated with an 8.7% increase in hospital deaths, and a 5.8% increase in the risk of developing cardiovascular problems. When doing their statistical analysis, the researchers claimed to account for risk factors associated with a worse outcome in COVID-19 patients, including pre-existing lung conditions and diabetes. The scientific community soon took notice, and concerns began to surface about the accuracy and validity of the results. Australian researchers found a worrying discrepancy in the documented number of deaths: the study reported 73 deaths in Australia by 21st April, while official records put the number at 67. 

How can a study published in one of the top 10 medical research journals get such a basic statistic wrong? By classifying data from a particular hospital in Asia as Australian, is how. The patient data for this study was collected and collated into a database by a small healthcare analytics company called Surgisphere, whose CEO Sapan Desai was a co-author of the study in question. When these discrepancies came to light, the other authors not affiliated with Surgisphere commissioned an independent review to investigate the reliability of the database.

The investigation hit a brick wall when Surgisphere refused to make the database available to the reviewers, citing a violation of patient confidentiality and agreements with hospitals involved. As the Lancet was unable to conduct their independent review, they were left with no option but to retract the paper, with the authors unassociated with Surgisphere issuing a letter of apology to the scientific community. Desai refused to comment on the situation and a second paper that used the same database, which he also co-authored, was retracted from the New England Journal of Medicine.

The global impact of this study led to some countries in Europe banning the drug in COVID-19 treatment regimens. The Solidarity Trial led by the World Health Organisation (WHO), which had recruited 3500 patients across 35 countries, temporarily suspended its hydroxychloroquine arm (before resuming it on 4th June). Moreover, this caused a wave of fear to spread among individuals who had started taking hydroxychloroquine, believing it would prevent them from contracting COVID-19. In an age where fake news runs rife on social media, and while the world is gripped by a pandemic, it’s more important than ever that newly published papers are rigorously checked to ensure the results are valid and presented accurately.

Many scientists have raised more general concerns about the huge research output since the COVID-19 crisis began. The critical need to learn more about the virus, develop better treatments, and discover a vaccine has led to a deluge of studies being published. Preprint servers have been overwhelmed with articles, but this research has not passed the peer review process that journals implement to safeguard scientific integrity. The Surgisphere study is a perfect example of a paper slipping through the net, in the rush to beat SARS-CoV-2.

Despite all these studies and clinical trials, it is still not clear whether hydroxychloroquine can or cannot help in the treatment of COVID-19. However, in another recent development, the WHO stopped recruiting patients into the hydroxychloroquine arm of the Solidarity Trial, as they found that hospitalized patients did not benefit. There are many more ongoing trials, but it looks likely that other candidate drugs will have more success in COVID-19 treatment, such as dexamethasone. While the trials roll on, one thing does remain clear: the world must reach a unified stance on hydroxychloroquine use, backed up by reliable and accurate science.  

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