Ethical Considerations When Prescribing Unproven Therapies for COVID-19

The COVID-19 pandemic has uncovered a recurring and particular ethical problem in medicine.  In the face of serious illnesses for which no cure exists or pharmacologic treatment options are limited, many patients will demand better and faster access to unproven treatments while many scientists and physicians  contend that more rigorous research is needed to establish safe, effective treatments. These lines are obviously arbitrary – not all patients and physicians fit neatly into these categories – but the ethical tension remains. Bringing an urgently needed effective medication to the public quickly and safely during a pandemic involves difficult tradeoffs.

This tension surfaced during the AIDS epidemic, when patients and activists pushed the US government to accelerate research and expand access to potential but uncertain HIV treatments.  A similar scenario unfolded again during the COVID-19 pandemic as arguments surfaced for wider access to potentially beneficial treatments at the same time as others cautioned against exuberance for unproven treatments. 

For physicians who were faced with choices earlier this year about whether to prescribe unproven treatments for COVID-19 like hydroxychloroquine (HQ), there were generally 2 options available. The first was the FDA emergency use authorization (EUA) which provided not approval, but temporary authorization due to the public health emergency on the basis that the medication may be effective and that the benefits outweighed the risks. The second option was to prescribe HQ “off-label,” that is, based on a physician’s authority to prescribe FDA-approved medications for an unapproved use as part of their broader authority to practice medicine.  Because HQ was already FDA approved for use in malaria prophylaxis and lupus among other indications, physicians had the legal authority to prescribe it for both COVID-19 treatment and prophylaxis if they believed it was medially indicated.  As clinical practice guidelines were being developed, individual physicians and hospital guideline committees were beset with figuring how and when they would prescribe HQ for appropriate patients. 

The medical literature is now replete with HQ’s significant limitations and risks, particularly its lack of beneficial effect on hospitalizations, intubation, and mortality. However, an ethics perspective may have provided some guidance for thinking rigorously and constructively about how to prescribe this medication during a public health emergency. Central to this process is to identify and then assess the known and unknown risks, benefits, and alternatives available at the time. Once those are acknowledged, weighed, and clearly communicated, clinicians can more easily justify an ethically strong position.

Many of the risks of HQ were well-established from its prior FDA approval for indicated conditions. Patients with lupus, rheumatoid arthritis, and malaria had been prescribed this medication sometimes for years, and the risks were well known and understood. Others in the medical community asserted this, and thus the potential for benefit during a public health emergency, even if unknown, was central to saving lives. However, a counterpoint to this assertion is that this claim suffers from an inadequate appreciation of risk. 

First, if patients relied on an unproven medical treatment like HQ, it might reduce their likelihood of engaging in effective preventive behavioral interventions like physical distancing, hand washing, and masking, which are all known to reduce COVID-19 transmission. Second, although the risks of HQ were understood for FDA approved medical conditions, its risks in acute COVID-19 illness were unknown. Third, off-label prescribing was credited with reducing the number of eligible patients for ongoing COVID-19 treatment research studies. Although the effect on research wasn’t a risk to the individual patient, it had important public health risks, as an absence of research on HQ in well-designed studies was needed to identify how best to treat all patients with COVID-19. This last point highlights the ongoing ethical tension between the needs of individual patients and those of the community, and how a pandemic can shape those challenges. For clinicians, the primary responsibility is to the care and treatment of the patient in front of them, not to the public. Patients depend on and expect this from their physicians because it is central to building the trust needed for high-quality patient care. But this duty is not without limits and may be harder to justify when there is a disproportionately large benefit to the community compared to individual patients during a pandemic.

Finally, both patients and physicians are prone to the cognitive error of commission bias, that is, the belief that doing nothing is always worse than doing something. It is the misconception that an action like prescribing medication could only reliably produce benefit, not harm. It’s unknown if this bias interfered with clinical reasoning about HQ, which may have been heightened during the pandemic. 

Enhancing access to untested treatments while providing them safely and effectively is an ongoing challenge, one we hope will get better at over time. Thoughtful attention to the known and unknown risks and benefits with attention to our own biases can be a helpful start to making more progress.

David J. Alfandre MD, MSPH, is a healthcare ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the NCEHC or the VA.

This article originally appeared on Renal and Urology News