Are the Unvaccinated Unwittingly Enrolled into a Human Challenge Trial?

By Rafael Escandon.

Dr. Walter Reed, between 1900-1901 designed and supervised a Human Challenge Trial (HCT) in Cuba in the search for the causative agent of yellow fever. While the 3 phases of Dr. Reed’s HCT were definitive in their establishment that yellow fever was transmitted via a mosquito-borne vector, ethical questions over the methods, remuneration, effectiveness of treatment offered, and whether participants were adequately informed about the probability of severe illness and death, remain today. Utility of HCTs were discussed early in the SARS COV-2 pandemic, when less was known about transmission, and effectiveness of the vaccines now authorized for emergency use. The current disparity in COVID-19 vaccine coverage between US regions and states, and the recent reports of unfavorable outcomes in the unvaccinated, bears a strong resemblance to a real-world version of a HCT; one without scientific and medical supervision.

A recent analysis of COVID-19 death data from Texas shows that 99.5% of the COVID-19 deaths since February 2021 were in the unvaccinated. Similar data from other states with low vaccine coverage are expected. Therefore, some regions of the USA have, perhaps unwittingly, become reference populations in an HCT studying outcomes in the vaccine hesitant and the vaccine resistant, versus the vaccinated.  For those anchoring their vaccine resistance to an expression of personal liberty, it is frequent that the personal and population risks are falsely under-reported. In that context, to what extent are medical-misinformers, community leaders, politicians and others culpable for influencing these populations to take risks equivalent to enrollment in the placebo group of a clinical trial? And because this is not a formal clinical trial, does the hallmark of bioethics, the principle of respect for persons, not apply?

The 3 COVID-19 vaccines with Emergency Use Authorization (EUA) in the USA have all been studied in large, well-controlled trials, with now more than 340 million doses administered. The estimated proportion of fully covered Americans is just above 53%. While each vaccine demonstrated safety and efficacy in prevention of new SARS-COV2 infections, questions remain about durability of protection and, recently, about protection against SARS-COV2 variants. Questions also remain about the duration of vaccine-mediated protection against severe illness, and risks of hospitalization and death in the vaccinated. Collecting of such real-world evidence holds the promise of generating insight into all of these questions. However, in a country with essentially unlimited vaccine access, further infections and poor outcomes are preventable. Independent Ethics Committees generally have a difficult time approving placebo groups when such effective countermeasures exist.

The criticisms of Walter Reed’s HCT in 1900-01, related largely to adequately reporting information about risks to participants, and overstatement of medicine’s ability to treat and cure yellow fever in 1900-01. In 2021, it must be asked if those who have influenced the unvaccinated; by understating the existence or risks of COVID-19; and/or overstating modern medicine’s ability to treat the condition without sequelae are doing the same as Dr Reed’s team and have some culpability. Have the vaccines’ protections been understated and their risks overstated? Has the concept of personal liberty as an isolated personal choice with no impact on populations been unduly leveraged in the context of such a highly infectious and lethal agent?

If the post-vaccination period in the USA does not qualify as an HCT, then it would seem all unwitting participants at least be entitled to respect and given properly contextualized information on illness and death outcomes in the unvaccinated. And, should those data be convincing, access to an alternative to the placebo arm in which they are currently enrolled.

 

Author: Rafael Escandon

Affiliations: Clinical Research and Development Consultant; Member Pediatric Gene Therapy Medical Ethics Working Group

Competing interests: None

Social media accounts of post author: Twitter: @gernie_blanston

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