By Melinda Young
The COVID-19 pandemic has created more uncertainty in human research protections in 2021. IRBs will see more non-coronavirus studies come their way, but they also will have to navigate the many COVID-19 trials that continue to be a big part of the research picture.
One issue IRBs will face is whether the benefits continue to outweigh the risks for people who enroll in COVID-19 vaccine studies. Now that highly effective vaccines have received emergency use authorizations (EUAs), is it ethical for people to enroll in vaccine trials in which they could be assigned to the control/placebo arm?
The authors of a new paper from the National Institutes of Health (NIH) asked these two questions:
- “First, if a vaccine candidate is found to be safe and efficacious in a placebo-controlled trial, should the researchers continue that trial as designed?”
- “Second, should researchers continue to test other vaccine candidates using placebo-controlled trials?”1
“The primary ethical considerations are to ensure that the trials continue to have sufficient social value and do not expose participants to excessive risks,” says David Wendler, PhD, senior researcher and head of the section on research ethics in the department of bioethics at the NIH Clinical Center. Wendler is the principal author of the COVID-19 vaccine trial ethics paper.
“With respect to social value, the question is whether or not a placebo arm continues to be needed to collect valuable information that could not otherwise be obtained,” Wendler says.
IRBs also might face a third question: Is it ethical to continue to enroll people in COVID-19 vaccine trials when highly effective and safe vaccines could be available to them within months?
“The important question is to evaluate the risks to the participants in comparison to what would happen to them otherwise,” he adds. “If an individual is a candidate for obtaining the vaccine outside of research, then it would be important to assess how the risks and potential benefits of being in the trial compare to receiving the vaccine.”
IRBs and researchers might consider the feasibility of completing a placebo-controlled trial once an efficacious vaccine is available outside of research.
“This will depend on how individuals react to the possibility of getting the vaccine outside of the study, to the extent it’s feasible, and also to their willingness to continue to participate in research,” Wendler explains. “Because these factors are unknown to a certain extent, it requires predictions of how individuals will react in order to figure out what is the best approach.”
Researchers need to develop plans for how new information about vaccine clinical trials is conveyed to participants. “The plan will need to be approved by the review committees overseeing the study,” he adds.
“Rapid evaluation of vaccine therapy has allowed manufacturers to move toward EUAs. If they show a modicum of success, we’d like to end those trials so people can avail themselves of those therapies,” said Jonathan Seltzer, MD, MBA, MA, FACC, chief scientific officer at WIRB-Copernicus Group (WCG) ACI Clinical. Seltzer spoke at a WCG webinar on Dec. 2, 2020.
A concern about the COVID-19 vaccines that receive EUAs is there would be a push to give the vaccine to the placebo wing so there no longer would be a controlled trial, says Herschel S. Nachlis, PhD, research assistant professor of government and policy fellow in the Rockefeller Center for Public Policy and Social Sciences at Dartmouth College.
“The problem with the EUA is that even if the short-term evidence is good, it would undermine the large-scale, Phase III trial,” Nachlis says.
The Pfizer/BioNTech and Moderna vaccines received the first COVID-19 vaccine EUAs in the United States, with a 95% success rate. The evidence was so compelling that it appeared to alleviate many of the public concerns about a fast-tracked vaccine.
“The results on the mRNA vaccines were 95% efficacy against any disease and 100% efficacy against severe disease,” said Kathleen M. Neuzil, MD, MPH, FIDSA, fellow with the Infectious Diseases Society of America (IDSA) and director of the Center for Vaccine Development and Global Health and Myron M. Levine professor in vaccinology at the University of Maryland School of Medicine. She spoke at IDSA’s virtual COVID-19 vaccine briefing on Dec. 3, 2020.2
“If we can get enough vaccine out there, we could have an impact on this pandemic very, very quickly,” Neuzil said. “We can save lives. We can keep people out of the hospital and get people back to work, and children back to school.”
Most of the vaccine side effects are short-term, and oversight will continue as the EUA vaccines are released. “The CDC and FDA already have robust systems in place to continue to monitor these vaccines,” Neuzil added.
However, when the first vaccine doses were rolled out nationwide to healthcare professionals, on-the-ground reactions and uptake of the vaccines suggested the public was unconvinced the vaccines were safe. In December 2020, one in four Americans surveyed by the Kaiser Family Foundation COVID-19 Vaccine Monitor said they would not take the vaccine.3
IRBs can ask COVID-19 clinical trial sponsors to increase their transparency, which is essential to building trust in these new treatments and vaccines. For example, some sponsors are releasing details about how their clinical trials operate.
“I think it’s been good they have released the protocols for these trials to a degree of transparency that isn’t usually achieved,” Nachlis says.
The Biden administration likely will start federal efforts to improve the vaccine rollout and increase public trust in the science behind the vaccines.
“I think one thing we’ll see is something more closely approximating the standard of very deliberate, rigorous, politically insulated, and the almost obscure regulatory process that we’re used to,” Nachlis says. “We’ll return to some sense of normalcy.”
The public health crisis will continue, but it will not be fed by election-year pressures, he adds.
- Wendler D, Ochoa J, Millum J, et al. COVID-19 vaccine trial ethics once we have efficacious vaccines. Science 2020;370:1277-1279.
- Infectious Diseases Society of America. IDSA media briefing: COVID-19 vaccine progress report. Dec. 3, 2020. https://www.idsociety.org/multimedia/videos/idsa-media-briefing-COVID-19-Vaccine-Progress-Report/
- Hamel L, Kirzinger A, Munana C, et al. KFF COVID-19 Vaccine Monitor: December 2020. Kaiser Family Foundation. Dec. 15, 2020. https://www.kff.org/coronavirus-covid-19/report/kff-covid-19-vaccine-monitor-december-2020/