Ethics Consult: Is a COVID Human Challenge Trial Ethical? MD/JD Bangs Gavel

Welcome to Ethics Consult — an opportunity to discuss, debate (respectfully), and learn together. We select an ethical dilemma in patient care, you vote, and then we present an expert’s judgment.

Last week, you voted on the ethics of a COVID challenge trial. Here are the results from over 1,000 votes:

Assuming that the risks are thoroughly explained in the consent process and all medical care is provided free, can a viral challenge study ethically proceed?

Yes: 59.25%

No: 40.75%

Does the ethics balance change if participants are restricted to those at the lowest risk for severe COVID-19 complications?

Yes: 42.76%

No: 57.24%

And now, bioethicist Jacob M. Appel, MD, JD, weighs in:

The development of vaccines is a slow and painstaking process. In a recent interview, the National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, described hope for a COVID-19 vaccine by the end of 2020 as “aspirational, but … certainly doable.” History suggests otherwise: The fastest vaccine brought to market — that for mumps — took 4 years from the time developer Maurice Hilleman isolated the virus in his own 5-year-old daughter. Other vaccines, such as Jonas Salk’s for polio, took considerably longer to generate. This potential time frame is particularly disturbing in light of the mass casualties caused by the ongoing coronavirus pandemic.

Human challenge trials (HCTs) promise to speed up efficacy assessment by intentionally exposing subjects treated with a candidate vaccine to disease. This approach was famously used by Walter Reed to investigate the transmission of yellow fever and, over the past half-century, has played a crucial role in developing a vaccine for cholera. But HCTs are far from harmless: If the vaccine proves ineffective, participants face the prospect of severe illness or even death.

That is why ethical guidelines from the Council for International Organizations of Medical Sciences prohibit HCTs for diseases “which pose a very high mortality risk due to the absence of effective treatments,” such as anthrax. While some promising treatments for COVID-19 have emerged, it remains a life-threatening condition. At the same time, left unchecked it will likely continue to claim hundreds of thousands, and potentially millions, of lives. The possibility also exists that the disease will be suppressed to the point where incidence rates are temporarily too low to test vaccines in the field without HCTs, while the threat of a second wave of disease remains, making vaccine development fully dependent on this approach.

A strong argument exists for allowing cohorts of young, healthy subjects to participate in HCTs. Mortality rates from COVID-19 among this population are relatively low and possibly comparable to other risks we allow brave volunteers to accept, such as military service, fire fighting, and even space travel. After the Challenger disaster, for example, the National Academy of Sciences estimated that the risk of catastrophic failure on a shuttle flight was 1 in 145. While precise mortality percentages from COVID-19 by age are not yet certain, it appears unlikely that death rates for young, healthy subjects will prove significantly higher than that. So if we are willing to let courageous pioneers explore the solar system, why not let others help save many lives through participation in medical experiments?

The harder ethical challenge comes in selecting the volunteers for HCTs. How should scientists recruit potential subjects? Should the subjects be paid? How much? And should researchers favor including subjects with scientific backgrounds who may be more able to appreciate any risks?

On the one hand, ethical norms might suggest choosing individuals at higher baseline risk of contracting the disease outside of HCTs, whether as a result of geography, occupation, or behavior. On the other hand, many individuals at increased risk of exposure belong to demographic groups (racial, economic) that are at higher risk precisely because of earlier discrimination or structural bias — and one may not wish to compound these risks through HCTs. Of course, subjects in HCTs will get vaccinated ahead of others, so if the vaccine does work, participants may benefit substantially. Refusing to allow someone to participate in an HCT also exposes them to risk: namely, the risk of encountering COVID-19 without the potential benefit of a promising but unproven vaccine.

Jacob M. Appel, MD, JD, is director of ethics education in psychiatry and a member of the institutional review board at Icahn School of Medicine at Mount Sinai in New York City. He holds an MD from Columbia University, a JD from Harvard Law School, and a bioethics MA from Albany Medical College. Appel is the author of the recent book, Who Says You’re Dead? Medical & Ethical Dilemmas for the Curious & Concerned.

And check out some of our past Ethics Consult cases: Ethics of Testing Drugs on Down Syndrome Patients; Let Elderly Woman Visit Husband With COVID? MD/JD Bangs Gavel; Surprise Finding in Organ Donation Match Test