By Joseph Adetola Adedigba and Sarah Perou Hermans.
Currently, there are no Food and Drug Administration (FDA) approved pharmaceutical treatments for COVID-19, and this has led to speculations concerning the efficacy of various experimental drugs and combinations. Hydroxychloroquine has been promoted as a potential treatment for COVID-19 by United States President Donald J. Trump. On March 19th, 2020, President Trump stated in a press conference that he believed hydroxychloroquine (HCQ) and remdesivir were “game changers” and “essentially approved for prescribed use.”
The FDA commissioner Stephen Hahn then clarified the drugs required further research in a clinical trial prior to approval. President Trump then posted on twitter on March 21st, stating his belief that the combination of hydroxychloroquine and azithromycin “have a real chance to be one of the biggest game changers in the history of medicine.”
Unprecedented circumstances necessitate unprecedented measures. Healthcare professionals across all levels are bound by the Hippocratic oath to utilize any means possible, even at the intersection of what is known and unknown, to save their patients who in this context are the critically ill patients with COVID-19. What is the inflection point to this noble and higher calling of the medical profession? This question can be reflected in one of the most compelling moral, ethical and philosophical dilemmas of today: Should healthcare providers administer hydroxychloroquine to critically ill patients with COVID-19?
Rising fatalities from COVID-19 in certain areas of the world such as the United States and the United Kingdom has led to an increased demand for hydroxychloroquine. The rationale behind this request is understandable, we should save as many lives as possible with any tools or drugs or procedures within our imagination. The reports of COVID-19 patients dying alone and saying goodbye to their loved ones virtually via Facetime is harrowing and creates a context for understanding the increased demand for hydroxychloroquine.
As of April 10th, hydroxychloroquine has still not been approved by the FDA for treatment of COVID-19. However, on March 28th an emergency use authorization was issued, allowing the distribution of hydroxychloroquine that had been donated to the Strategic National Stockpile to patients hospitalized with COVID-19 not eligible for clinical trials. But HCQ is not scientifically proven to treat COVID-19. While Hydroxychloroquine has demonstrated efficacy at inhibiting SARS-COV-2 in vitro, and the rationale exists regarding its anti-inflammatory properties, the clinical evidence has been sparse and questionable.
At the time of President Trump’s press conference, evidence reported was criticized as anecdotal and consisted of 1) a Bioscience Trends letter to the editor discussing a news briefing by the State Council of China reporting the efficacy of hydroxychloroquine but not entailing clinical data 2). A preprint of a non-randomized French clinical trial of hydroxychloroquine and azithromycin in 26 experimental patients with COVID-19 reporting a significant viral load reduction on nasopharyngeal swab at day six.
Since then, two other preprints on March 30th and on April 3rd reported differing results in hydroxychloroquine’s efficacy, both limited by sample size. A study on April 14th of 181 patients concluded that results did not support the use of hydroxychloroquine in COVID-19 patients, and on April 11th a clinical trial in Brazil halted the high dose segment of their hydroxychloroquine trial after 11 patients died.
The complexity of this ethical dilemma can be seen in the non-committal statement by the Director of the Center for Disease Control and Prevention (CDC) on April 10: “We’re not an opinion organization. We’re a science-based, data-driven organization… We’re not recommending it, but we’re not recommending it. We’re recommending for the physician and patient to have that discussion.” While that discussion between the physician and the critically ill COVID-19 patient is challenging, the authors of this blog and the forthcoming publication are of the opinion that hydroxychloroquine should not be used as a shot in the dark in critically ill patients with COVID-19. This assertion is based on a rigorous ethical analysis utilizing the four main principles of bioethics and examining specifics of the pre-approval pathways. These patients cannot give informed consent since the risks and benefits of hydroxychloroquine in COVID-19 patients is not known. Administering hydroxychloroquine to these patients is not an act of beneficence since we have no clinical evidence that the drug works against COVID-19. There is no empirical data to rule out the risk of harm and complications from hydroxychloroquine.
Under distributive justice, prioritizing these patients over patients with malaria and autoimmune conditions, for a scarce resource like hydroxychloroquine will not save the most lives. For example, after President Trump’s press conference, there was an uptick in patients with autoimmune conditions such as Lupus reporting difficulties accessing medication. Without their medication, these patients are in danger of having a lupus flare and are at an increased risk of infections. There is also an important racial context to this issue. Among the patients with lupus in the United States, 40% are black, so actions that could potentially reduce the supply of hydroxychloroquine could exacerbate the reported increased mortality of black patients. This may further the racial inequalities already demonstrated by COVID-19.
This blog post and the extensive analysis in the upcoming publication are meant to facilitate much needed conversations among health professionals, bioethicists, moral philosophers etc. about how to navigate ethical dilemmas in situations where we need to re-interpret our understanding of certain everyday interpretations of morality and ethical principles.
Paper Title: Should Critically Ill Patients with COVID-19 be Treated with Hydroxychloroquine as a Last Resort? A Situational Ethical Analysis
Author(s): Joseph Adetola Adedigba; Sarah Perou Hermans
Affiliations: Tulane University School of Medicine
Competing Interests: None
Social Media Accounts of Post Author(s): @Joseph_Adedigba