With the staggering number of over 7 million confirmed COVID-19 cases worldwide, scientists are trying to speed up the research for a cure. Hydroxychloroquine, an anti-malaria drug, is being scrutinised as a viable treatment. However, studies on its efficacy show contrasting data, slowing down the progress towards a standardised therapeutic approach.
At this point in time, the only drug that has passed clinical trials is remdesivir. Although it has shown promise to treat COVID-19, it must be administered intravenously at the hospital over the course of a few days and is now in short supply. Because of the difficulties encountered in its application and acquisition, researchers were hopeful hydroxychloroquine could be a valid substitute.
Hydroxychloroquine is cheap and highly available. Early studies showed how the medicament, identically to the similar medicine chloroquine, interfered with the replication of the virus. Politicians, such as U.S. President Donald Trump, endorsed the drug even though the evidence of its action to defeat COVID-19 is slim and inconsistent. The President declared he used hydroxychloroquine as a prophylactic measure, confusing the public’s thoughts on the drug. Doctors worry that the amount of misinformation circulating around the effectiveness of hydroxychloroquine will skew the public opinion on the medicament.
The Lancet, a peer-reviewed general medical journal, published a study from cardiologist Mandeep Mehra, whose data highlighted how the fatality rate for COVID-19 increased from 9% to 18% in patients treated with hydroxychloroquine. Although the research was based on observational studies and not on a clinical trial, the WHO has halted the use of the medicament in the treatment group of the Solidarity trial, a joint effort of 35 countries to find a cure to the pandemic. Individual countries have also paused clinical trials and prescription of hydroxychloroquine to COVID-19 patients. Dr Mehra defends his studies, affirming he does not support the WHO stopping the clinical trials. While the effects of these observational studies might only be transient, research on hydroxychloroquine has been suspended, pending review of The Lancet’s publication.
The safety measures adopted because of the studies are also threatening the continuity of the trials. One example is rheumatologist Jon Giles’ prevention research, which focused on the use of the medicine in preventing infection in households where a member had been diagnosed with COVID-19. The U.S. Food and Drug Administration (FDA) issued a cautionary notice about the effects of hydroxychloroquine on the heart, making it compulsory for patients to have an electrocardiogram (ECG) taken before participating to the trial. Dr Giles concluded his research, as he did not think sending patients to the Doctor’s office during a pandemic was safe.
The negative publicity around hydroxychloroquine may now affect the number of patients enrolling in clinical trials, although the medicament has been successfully used to treat several illnesses in the past 60 years. The antagonistic advertising, combined with a decreased pool of potential candidates, threatens the advances in the research for a cure.
In the meantime, researchers have highlighted skews in The Lancet‘s data publication. They reported an almost equal number of smokers and obese individuals around the world, making the statistics difficult to analyse. One other problem the observational studies have is they did not provide scientists with the raw numbers, but only with a model extrapolation made by Dr Mehra. On his defence, Dr Mehra tracked down the mistakes and prompted The Lancet to correct them, asserting the errors do not affect the quality of his findings.
Researchers are still doubtful about Dr Mehra’s results and believe the reason hydroxychloroquine is deemed to increase the mortality rate is based on the real-world bias of observational studies. Daniel Freilich of Basset Medical Centre in Copperstown, New York, concludes that patients given hydroxychloroquine were often sicker than those who were treated differently. This is because of the doctors’ predisposition to administer the drug to those sufferers already in critical conditions, thus skewing the collected data and contributing to the alleged higher mortality rate.
Dr Mehra keeps defending his research, stating his team considered the differences between the patients’ conditions, still finding a higher mortality rate. However, he partially recanted his findings, saying the study only underlined the correlation between hydroxychloroquine and higher death rates, but this does not mean the results were not determined by other factors that may have added up to the mortality difference. The effects of Dr Mehra’s paper highlight the importance of peer-review and correct spreading of information, especially in the current pandemic.