The Ethics of Human Challenge Trials in COVID-19 Era – Part 2

Thirty-five members of the U.S. House of Representatives sent a letter to the Food and Drug Administration (FDA) on April 20 requesting that the FDA streamline the approval process for the development of COVID-19 vaccines.

“We write to assure you that Congress understands that a more risk-tolerant development process is likely appropriate in the case of a COVID-19 vaccine,” the letter states. “In the case of accelerated human trials, justifiable risks may be taken by parallel testing of multiple dose levels, advancing more rapidly from phase to phase and potentially by challenge trials that involve deliberately infecting volunteers.”

In light of the growing number of coronavirus cases, it is understandable that many would call for an expedited approval process.

The letter calls for the use of “challenge trials,” yet few in the public are aware of these trials.

A human challenge trial is an experimental study where a healthy subject is given a vaccine or preventative medication and then exposed to a virus, insect or pathogen, as I explained in yesterday’s article.

The practice of human challenge trials brings up some thorny ethics questions. Most notably are research subject vulnerability and the mediation of risk.

Researchers do point out that, in spite of potential risk, there is great potential benefit for society. While this resonates with a utilitarian audience, not all moral thinkers are in agreement. Some look to more value based (or deontological) systems for guidance.

One such approach often used in health care is called the “Doctrine of Double Effect,” which goes back to Thomas Aquinas and is at the heart of Catholic moral theory.

The doctrine acknowledges that often when we seek good outcomes, negative consequences can and do occur. It sets forth four principles for weighing moral permissibility in such cases.

1. The Rule of Intentionality.

This is the most well-known rule, which considers questions such as: “Why am I doing this?” and “What are my intentions?”

A palliative care physician can give morphine to a dying patient for the purpose of pain control but not to speed up the dying process, for instance. If the patient needs an excessive amount of drugs for pain management but those drugs also slow respiration, then it can be morally permissible because the intention is to make the patient comfortable, not to hasten death.

In the case of human challenge trials, researchers would argue that infecting the subject is for research and not to make the patient sick. While this statement is true, it also reveals the problem: the research study takes precedence over the subject.

In the course of human challenge trials, the knowledge gained from the trial only applies to the research subject indirectly. The primary action and intention is the infection of the subject. Good may come from the study but not necessarily good for the research subject.

However one looks at human challenge trials, it must be acknowledged that researchers are intentionally giving potentially life threatening contagion to healthy subjects. For many this seems wrong on an intrinsic level. It violates the “do no harm” maxim.

2. The Rule of Permissibility.

Often overlooked in the Doctrine of Double Effect is that the act in question must be morally good or at least morally neutral. The rule of permissibility argues that if an act is immoral then it is always immoral.

Going back to the case of providing pain relief at the end of life, relieving pain is seen as morally permissible, or even an obligatory action.

By contrast, human challenge trials have to reconcile the process of infecting an otherwise healthy patient. This act itself is not a treatment with side effects like chemotherapy. It is an act of harm or at best potential harm.

3. The Rule of Proportionality.

This rule insists that the good effect of an action must considerably outweigh the negative effects.

Therefore, in the case of chemotherapy, oncologists must believe that the benefit of the drug outweighs its side effects.

This can be argued for human challenge trials. Unfortunately, unlike other types of clinical trials, the good from human challenge trials is primarily for society at large and only secondarily for the subject.

Herein lies the problem: For whom is the benefit of the trial?

4. The Rule of Ends and Means.

Considerations of proportionality lead directly to a consideration of ends and means. One should not use a bad approach to achieve good results.

While human challenge trials avoid this direct line of thought, it is this “means-end” equation that leads to the challenge that researchers are using their subjects as a means to an end.

The “means-end” principle has run through Christian and western thought from the Middle Ages through the Enlightenment and Immanuel Kant right up to today.

While no one would consider a human challenge trial without voluntary subjects, the moral community needs to ask if those brave individuals have now become a means to an end for society’s battle against COVID-19.

The fact that they volunteered does not remove society’s obligation to protect them from becoming a means to an end.

What makes human challenge trials different from a lot of drug trials is not the risk of harm to a subject or a patient; it is the process of infecting a healthy subject with a contagion.

In the case of drug trials, an unhealthy patient is given a trial dosage of a chemical that has the hope of treating their already existing illness. In this manner, there is direct benefit to the research subject.

Human challenge trials, on the other hand, expose a healthy subject to a risky contagion and the bulk of the benefit goes to society.

While the doctrine of double effect may not be the ultimate standard for evaluating the use of human challenge trials, this time-honored moral framework raises significant questions that should force the moral community, bioethicists and lawmakers to step back and seriously think about these trials.

These concerns call us to step up to the moral obligation that society has to the men and women who volunteer for human challenge trials. They do us a great service, but we must not let society take advantage of them

Editor’s note: This is the second of a two-part series. Part one is available here.