All human research, including COVID-19 vaccine trials, should be guided by the four ethical principles of autonomy, beneficence, nonmaleficence, and justice. When researchers, data safety monitoring boards, or the Food and Drug Administration (FDA) decide to stop a clinical trial or expedite approval or use of an investigational product, these principles still apply, says Alison Bateman-House, MPH, PhD, assistant professor in the division of medical ethics at NYU Grossman School of Medicine in New York City.
“When we’re talking about approving a new medical product, there is the possibility of benefit to those who are helped by that product and who really needs that product to be approved,” Bateman-House says. “There is also a risk of harm if something is approved prematurely.”
Americans are particularly enamored with the idea of autonomy, she notes. “There already are ideas from people that we should just allow the public to get access to these drugs, even if they’re not approved,” Bateman-House says.
The attitude is “I know it’s not approved, but I want it anyway.”
“If people want this product, is it the role of the government to protect them from themselves?” she asks.
It could be argued COVID-19 investigational therapeutics and vaccines are beneficial because of the potential of curing the disease or preventing it. But investigational drugs also can cause adverse events and harm. The fourth ethical principle of justice applies to how equitably the clinical trial investigators are enrolling subjects. If they are enrolling disproportionately fewer minorities, it could be argued the trials are not meeting the standard of justice.
Justice also applies to how quickly investigational products are made available to the public. “On the grounds of justice, we could push this product out quickly,” Bateman-House explains. “Do we have a justice-based obligation to get these products out of trials and to individuals through compassionate use programs or approving the product as soon as possible?”
All these ethical claims are reasonable, but they also can compete when the research community, public health officials, and governmental agencies debate policy during a pandemic. “I think this is the debate happening right now,” Bateman-House says. “You can’t have four competing claims at once.”
Some have put forth the idea that people should decide the risks for themselves when potential cures and vaccines are under investigation, she notes. “Other people say individual risk tolerance has no place in public health interventions when a population intervention is at stake.”
In the United States, the general reckoning on ethical principles has been in favor of the gold-standard clinical trial process with limited exceptions in which seriously ill or terminally ill people might obtain an investigational treatment through expanded access, Bateman-House says.
“We don’t do this for healthy people,” she says. “The precedent for a vaccine is we wouldn’t release it before it’s fully approved by the FDA, but these are not normal times.”
What is imperative is that any decision made about emergency use authorizations, compassionate use access, and early approval of a COVID-19 therapeutic or vaccine be made based on science, not with any political influence, Bateman-House says.
“That accounts for the anger and revulsion that has been evinced toward the idea of partisan politics influencing FDA decision-making,” she adds.
Bateman-House suggests IRBs take these actions when reviewing clinical trials, particularly when they are related to COVID-19:
• Ask more questions. “When you see a protocol for a COVID vaccine or for any therapeutic or intervention, I would encourage you to look at who the recruited population is and ask, ‘Why?’” Bateman-House says.
“Typically speaking, IRBs are looking to make sure vulnerable subjects are protected and there is no undue inducement of people,” she adds. “In terms of justice and equity, they also need to know who is and is not recruited for this trial, and whether there is a rational reason for that.”
For instance, if investigators only recruit men, are there evidence-based reasons for excluding women? “I would go back to the investigator to make sure there’s a really good reason for that and not just go along with it,” Bateman-House says.
• Check and update policies. One difference between research before and after COVID-19 is that investigators are experimenting with study design, sometimes in ways that might go against IRBs and institutional policies. For example, researchers in Boston are performing self-experimentation, vaccinating themselves with a potential COVID-19 vaccine candidate.1
“This gets back to the autonomy question,” Bateman-House says. “The attitude is ‘If I want to and I’m a highly educated scientist and I understand the risks and benefits, let me make a decision.’”
But this type of situation might break institutional rules. They also could sow further distrust in the research community, she notes.
“Any sort of deviation from the norm is worthy of concern because people may misconstrue it,” Bateman-House says.
It could contribute to society fracturing in its response to an eventual coronavirus vaccine, she adds.
- Regalado A. Some scientists are taking a DIY coronavirus vaccine, and nobody knows if it’s legal or if it works. MIT Technology Review, July 29, 2020. https://www.technologyreview.com/2020/07/29/1005720/george-church-diy-coronavirus-vaccine/