By Yves Saint James Aquino and Nicolo Cabrera

The controversy surrounding the off-label use of hydroxychloroquine (HCQ) for COVID-19 highlights the inherent inequality of disease conditions. In this brief ethics explainer, we argue that we need to make explicit the clinical and non-clinical factors that determine the inequality of diseases. The varying appraisals of disease inequality, in turn, reveal the values that govern the contrasting prioritisation among health care institutions.

The uses of HCQ approved by the US Food and Drug Administration (FDA) are in the prophylaxis and treatment of malaria and the treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis. Just recently the US FDA has also issued limited emergency use authorization, though not approval, for the treatment of COVID-19. The role of HCQ in treating COVID-19 has been suggested by demonstrations of in vitro activity against SARS-CoV-2, anecdotal reports and a small non-randomized study conducted in France. It is widely accepted that the use of HCQ should be evaluated with randomized controlled trials (RCTs) before being deemed proven therapy.

Since the suggestion that HCQ could be used to prevent or treat COVID-19, various health care organizations in the US have responded differently. Some authorities across the US at the state or healthcare organization levels have taken steps to regulate or restrict its use to preserve the supply for proven indications. On the other hand, some plan to reallocate HCQ exclusively for COVID-19 patients. For example, in California, Kaiser Permanente allegedly sent a patient a letter saying their prescription for chloroquine, a drug related to HCQ, will not be refilled because of high demand for COVID-19 patients. Somewhere in the middle are institutions undertaking clinical trials to investigate the benefit of HCQ for COVID-19.

Some infectious disease clinicians do not support the use of HCQ for COVID-19 outside of a clinical trial setting due to concerns about its safety and a lack of clarity about whether the risk of adverse events outweigh benefit. In addition, the case against using HCQ for COVID-19 is at least partially based on its threat to the supply for conditions for which the drug was approved (i.e., malaria) or proven to work in RCTs (i.e., SLE).

It appears, however, that the varying ethical permissibility of prioritising the use of HCQ for one disease over another reflects how clinicians and health care institutions view the inequality between the two. Diseases are unequal by virtue of importance based on several clinical and non-clinical factors.

First, contagiousness is a key factor that causes one disease to be deemed far more important than others. Unlike in malaria and lupus, contagiousness in COVID-19 entails a sense of larger scale, more sense of urgency, and greater threat. Several medical institutions in the US have stockpiled HCQ for COVID-19 despite the uncertain benefit, and even before the recent FDA emergency authorisation. The Lupus Foundation of America has raised concerns that increased demand could potentially divert access away from people with lupus.

Second, clinical features of illness determine the inequality of diseases. This refers to the acuity of presenting symptoms, course of illness and mortality rate, among others. SLE is incurable. Current use of HCQ for SLE is to alleviate flares and prevent organ damage. COVID-19 is a viral disease, and based on current data, a substantial number of patients recover from the condition. A case could be made that SLE requires lifetime access to the drug and, thus, should take priority over COVID-19 cases.

Third, public profile is another factor that informs the inequality of disease conditions. Unlike the first two, public profile of a disease is a non-clinical factor. Public profile is best exemplified by two conditions in two extremes of perceived popularity: breast cancer and (any type of) orphan disease. Breast cancer has become so popular that people have written about the backlash of awareness campaigns on patients with the condition, as well as the allegedly ensuing neglect of other types of cancers. On the other extreme are orphan diseases, so called because drug companies are not inclined to adopt them to develop treatments.

In the current scenario, lupus (and to some extent malaria) are closer to the orphan disease side of the spectrum, and COVID-19 in the other extreme. Unlike breast cancer, the popularity of COVID-19 is not due to any corporatized awareness campaign. The popularity of COVID-19 is due to the 24/7 coverage, the grim picture in countries like Italy and Iran, the daily updates on incidence and fatality rates and the social interventions (e.g., lockdowns), among others. Public profile of a disease can drive prioritisation on the part of clinicians, professional regulators, and politicians. Consequently, efforts to respond to the outbreak may come at the expense of other medical conditions, such as lupus.

Given the rapid progression of the pandemic, we acknowledge the need for quick clinical and policy responses. Although we do not advocate for a particular manner of allocating medications, we wish to highlight the need for ethical evaluation to make explicit the values based on disease inequalities. We need to strike a balance between matters of urgency and matters of equity, with some medical conditions becoming vulnerable to neglect as all resources are diverted towards COVID-19.

Authors: Yves Saint James Aquino¹, Nicolo Cabrera²

Affiliations:

¹ Department of Philosophy, Macquarie University, Sydney, Australia

² Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, United States

Competing interests: None