The Ethics of Human Challenge Trials in COVID-19 Era – Part 1

The modern history of immunizations goes back to Dr. Edward Jenner.

On May 14, 1796, Jenner took samples from the lesions of a dairymaid who was infected with cowpox and attempted to inoculate an 8-year-old boy.

The boy suffered mild fever and body aches. Nine days later, the boy felt cold and lost his appetite only to feel fine the next day.

Jenner then waited several weeks before exposing the boy to smallpox. The cowpox inoculation proved successful, and the boy never developed smallpox.

This marked the beginning of the eradication of smallpox and the development of human challenge trials.

A human challenge trial is the intentional exposure of a human subject to a parasite, bacteria or virus for the purpose of testing a potential vaccine or prophylactic treatment.

They are regularly conducted all over the world. Most notably, they are used to test new malaria drugs and the annual influenza vaccinations.

These trials are rarely discussed in the media and when covered, the reporting is specious, equating them to the horrors of Nazi research.

As these trials could aid in rapidly getting a COVID-19 vaccine to market, we need to do two things:

• We need to understand how human challenge trials are conducted.
• We need to reflect upon the ethical implications of these studies.

In the case of viral vaccines, the developmental stage is very time consuming. The process often exceeds 18 months, beginning with concept development, moving to animal trials and later enacting early human trials before ultimately conducting double-blind studies leading to FDA approval.

By taking what is a relatively safe vaccine like the annual flu vaccine, researchers can cut months of development off the process by inoculating a subject with the new vaccine and then exposing them to the live virus.

This is done with healthy patients who are not at risk for serious complications and in a controlled clinical study. While serious complications can and have occurred, they are extremely rare.

Modern human challenge trials are different from the reckless experiment of Dr. Jenner or the cruel inhuman research of Nazi Germany.

These studies are governed by the rules of the Nuremberg Code, which was developed following World War II in order to have guidelines for evaluating how medical research is conducted upon human beings.

Of the 10 principles in the code, the most important are that human research subjects need to give voluntary consent, unnecessary harm to human subjects should be avoided, and the risk to subjects should never exceed the potential humanitarian good.

Modern human challenge trials require the subject to be informed about the process and nature of the experiment just like regular drug trials.

Researchers go to great lengths to minimize risk to the subjects and possible exposure of others outside the trial.

In addition, trials and medical experiments receiving federal funding are required to gain approval from an ethics committee or independent review board.

The majority of new research studies or trails published in medical journals have a clinical ethicist listed as one of the authors.

Even with the above safeguards, one still needs to consider potential moral problems.

The concern of most ethicists falls into two categories.

1. The protection of vulnerable populations.

Unfortunately, some in the 20th century did conduct research upon non-voluntary patients. Among these were the development of a syphilis treatment protocol with Guatemalan prisoners in the 1940s and the research done upon mentally handicapped children at Willow Brook School.

The tendency to compensate research subjects in Western countries also opens the doors for poor communities to be preyed upon by unscrupulous researchers.

This was seen in the middle of the last century when studies were conducted in underdeveloped countries.

2. Risk mediation.

Human challenge trials that have studied malaria, influenza or cholera have done so with decades of scientific data.

Either these diseases have a very low mortality rate or there are well-established treatment protocols.

In the event that the challenge trial becomes dangerous for the subject, researchers can step in and treat the patient with already established drugs and procedures.

As there is no standardized treatment for COVID-19, this safety net is not available to protect trial participants.

This process works well with known diseases. It might not work well with a new virus like COVID-19.

Physicians and researchers are well aware of the progression of malaria and influenza. We are only just now developing a knowledge base for the novel coronavirus.

For example, we are still confused as to why it attacks some and not others. By and large, younger populations do better with COVID-19 but some young people do not.

Without additional knowledge, researchers will not be able to responsibly select subjects in order to mediate risks.

While the development of COVID-19 vaccinations and treatments are exciting, ethicists and health care workers need to be reminded that all clinical trials must focus upon the protection of their subjects.

We cannot have advanced health care without human research, but we must not lose our humanity in the process of preventing illness.

As the World Health Organization stated in their 2016 regulatory considerations for human challenge trials: “It is essential that challenge studies be conducted within an ethical framework in which truly informed consent is given. When conducted, human challenge studies should be undertaken with abundant forethought, caution and oversight. The value of the information to be gained should clearly justify the risks to human subjects. Information to be gained should clearly justify the risks.”

Therefore, whether a drug trial or a human challenge trail, the moral community needs to ask a lot of questions in order to ensure the protection of the brave men and women who volunteer to participate in medical research.

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