With the lack of public trust and confidence the biggest barrier to SARS-CoV-2 vaccines in the U.S., the risk of granting an emergency use authorization (EUA) to a vaccine with safety issues or questionable efficacy could destroy confidence in future FDA-approved products.

That message was drummed home throughout the Oct. 22 meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee, even though the meeting was convened to shine light on the FDA’s commitment to the scientific process and the many checks being built into the review process and monitoring programs for the vaccines.

Authorizing a weak vaccine would do more harm than good, Doran Fink, deputy director of the Division of Vaccines and Related Products Applications at the FDA’s Center for Biologics Evaluation and Research, told the committee. It could create a false sense of safety, deter development of more effective vaccines and lead to biologic creep. That’s why the FDA has set stringent standards for an EUA for a vaccine, Fink explained.

Those standards, detailed in a guidance issued earlier this month, are similar to what’s required for full licensure, including 50% efficacy. However, the six candidates being developed through the U.S.’ Operation Warp Speed (OWS) initiative will have to demonstrate at least 60% efficacy, Hilary Marston, medical officer and policy adviser for pandemic preparedness at the National Institute of Allergies and Infectious Diseases, told the panel.

When asked about the difference, she said OWS set the efficacy bar higher due to the urgency of the pandemic and to ensure the greatest impact possible against COVID-19.

While the vaccine candidates will have to reach a higher efficacy bar, the median two-month follow-up required for an EUA is only a third of the six months required for full licensure, Fink said, adding that most adverse effects with vaccines occur within six weeks of administration. He also stressed that an EUA would allow use only in the populations for which the data support.

The shorter follow-up and the other standards laid out in the FDA’s guidance haven’t quieted public concerns. As a result, vaccine hesitancy and lack of confidence dominated testimony during the adcom’s public hearing session, with many speakers calling for longer premarket follow-up. Speakers also pressed for standardized endpoints in the trials and strong data to show how a vaccine worked in various groups. In addition, a few said the FDA should have to follow the adcom’s recommendation on granting a vaccine EUA.

While the agency has said it will convene the panel to consider each EUA request, it generally considers the committee’s vote as advisory.

Vaccine hesitancy concerns weren’t limited to the public hearing, as they permeated much of the testimony of experts from the FDA, NIH and other government agencies who described how they were working to build trust and confidence in a vaccine.

What’s being said

Some of the most telling testimony came from Susan Winckler, CEO of the Reagan-Udall Foundation, as she described the COVID-19 Vaccine Confidence project the foundation has undertaken. As part of the project, the foundation is holding listening sessions with frontline workers and traditionally underrepresented groups. Winckler said six major themes have emerged in the eight listening sessions held so far:

  • The first is concern about the speed at which the vaccine development has progressed. While people appreciated the urgency of the pandemic, they struggled with the validity of a vaccine developed in less than a year when previous vaccines were years in development. One person in a listening session said trying to develop a COVID-19 vaccine in a year is “pretty absurd.”
  • The second theme is the growing distrust of government and government agencies. Mixed messages from various agencies and early missteps at the CDC have helped erode trust, according to comments made at the listening sessions. Some participants said the FDA couldn’t be trusted to keep Americans safe.
  • The distrust isn’t limited to government. For many participants, it extended to doctors and the medical establishment. Individuals in underrepresented communities said they get different treatment than others. There also was a strong belief that various organizations have been bought off by big pharma.
  • A fourth theme is a concern that political and economic factors will be prioritized over science and public health in approving a vaccine.
  • Listening sessions with underrepresented groups produced concerns that the vaccines aren’t being adequately tested in those groups, so there won’t be adequate data to show whether a vaccine will be effective or safe for them. For instance, one person noted that Native Americans are particularly vulnerable, but there is no clear definition of who is a Native American for clinical trial purposes.
  • The final theme plays into the distrust of the government by questioning how the vaccines are being developed and how they’ll be used in a nation with such racial disparities. Some people said they felt that the trials were another Tuskegee study, referencing the government’s 40-year natural history study of untreated syphilis in African American men who were told they were receiving free health care. Another person noted that Alaskan natives are at the highest risk of death from COVID-19, but they’re being used as guinea pigs for the rich. “The more they study me, the more they’ll know how to get rid of me,” one person said in a listening session.

A different kind of vaccine hesitancy was revealed at focus groups the CDC conducted a few months ago, said Janell Routh, medical officer and program lead for the Division of Viral Diseases at the CDC’s National Center for Influenza and National Respiratory Diseases. While most of the people in those groups were open to getting a COVID-19 vaccine, they wanted to wait a few months after one became available to see how effective it was, she said.

Panelist Michael Kurilla, director of the Division of Clinical Innovation at the NIH’s National Center for Advancing Translation Sciences, said the reports vaccine sponsors continue to put out about the progress of their clinical trials could add to that kind of hesitancy, as they could set up a situation in which people may wait for what may be a “better vaccine.”

That is an issue, Routh agreed. For instance, some people may want to wait for a one-dose vaccine instead of one that requires two doses.

As part of its efforts to build confidence in a vaccine, the CDC has created a communications framework to address the public’s concerns, and it’s working with community partners to reach people at increased risk of severe disease, Routh said. Meanwhile, it’s continuing to collect data to get insight into what’s driving vaccine hesitancy.