“There’s Only One Chance To Get This Right”: FDA Panel Fights COVID-19 Vaccine Problems | Sciences

Sciences‘s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Concerns raised yesterday by an advisory group to the US Food and Drug Administration (FDA) may again put the brakes on Operation Warp Speed, the US government’s push of $ 10.8. billion to rapidly move COVID-19 candidate vaccines from concept to communities.

As new cases of pandemic coronavirus in the US set a daily high of more than 75,000, the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) held a 9-hour virtual meeting to discuss a regulatory pathway that could allow large-scale use of a COVID-19 that has only minimal evidence of safety and efficacy. A so-called emergency use authorization (EUA) could use preliminary data from the vaccine’s efficacy trials now underway to cut many months off the standard approval process, and the FDA wanted VRBPAC to weigh on the wisdom of taking this shortcut. The audience, streamed live on YouTube, drew huge interest, and some of the committee members – a mix of academics, consumer representatives, and government scientists – sent a disturbing but clear message to the FDA: Keep your horses.

Several members of the VRBPAC were concerned that an EUA could contribute to the growing public hesitancy toward COVID-19 vaccines by fueling the perception that the FDA was compromising its famously high standards. Sheldon Toubman, an attorney for the committee representing consumers, strongly urged the FDA not to issue an EUA for a COVID-19 vaccine, arguing that the agency should stick to the traditional approval process. “There’s only one chance to get this right,” Toubman said. “And if we do it wrong, then we will finish, it will be years. Because there is already a serious problem with lack of trust, and [lack of] trust will become so severe at that point that we won’t be able to get out of it. “

The committee also discussed the possibility that an early authorization of a vaccine could disrupt many of the ongoing COVID-19 vaccine efficacy trials, derailing attempts to obtain the strongest and most convincing safety and efficacy data. . And several members were concerned that the latest FDA guidance for vaccine companies that might seek a USA does not yet have strict enough safety criteria.

Four candidate vaccines selected by Operation Warp Speed ​​are now in efficacy trials, comparing the incidence of COVID-19 disease in at least 30,000 participants blindly receiving a vaccine or placebo. They are designed to end when they have about 150 cases of symptomatic disease, but independent monitoring boards will tell researchers if a vaccine appears to be working in 50 cases and again in 100 cases. FDA guidance issued in June says the agency will consider issuing an EUA for a vaccine if it shows at least 50% efficacy in any of these tests.

The FDA has agreed to seek VRBPAC’s comments if a COVID-19 vaccine company applies for an EUA. Doran Fink, deputy director of the FDA’s vaccine division, warned the committee that allowing the use of a weakly effective COVID-19 vaccine could do more harm than good, and not just because of its impact on the trials of other candidates. “It could do so by providing a false sense of security that interferes with measures to reduce [COVID-19] transmission, ”Fink warned, citing effective non-medical interventions such as wearing masks and social distancing.

Researchers from the Reagan-Udall Foundation, a nonprofit organization established by Congress to “advance the mission of the FDA,” told the committee about the sobering results of its COVID-19 Vaccine Confidence Project, that underscored the misgivings of people in underrepresented communities and “frontline workers” in service, retail, and healthcare settings. Some interviewees “would want to wait months, or even years, before opting for a vaccine” due to mistrust widespread toward the government and the healthcare system itself, the foundation’s researchers noted. The country’s racial and ethnic disparities also played a role, especially given the infamous Tuskegee experiment in which black men were denied treatment. of syphilis so researchers could better understand the disease. “The more they study me, the more they know how to get rid of me,” said an en interviewed researchers.

President Donald Trump repeatedly lobbied for a US COVID-19 vaccine ahead of the Nov. 3 election, but the FDA effectively eliminated that possibility earlier this month when it issued a second guidance that added a safety stipulation: Two must have passed. months after at least half the people in the trial have received all doses of the vaccine, in order to see if side effects appear over time. However, several committee members and public commenters argued that 2 months was not enough, and urged the FDA to extend this to at least 6 months.

Committee member Paul Offit, a vaccine researcher at the Children’s Hospital of Philadelphia, noted that the US already issued for COVID-19 treatments has created confusion about how early approval could be given to a vaccine. Under pressure from the Trump administration, the FDA issued USAs for hydroxychloroquine and convalescent plasma based on the standard that “may be effective,” a “very low bar” that did not require convincing efficacy data from a randomized controlled trial. . Neither treatment really works, Offit said, adding that those USEs tainted the validity of the process. “I think we have a language problem,” said Offit, who advocated changing the name of the process. A US vaccine, by contrast, requires evidence of efficacy and at least some guarantees of safety, which is much closer to the full approval process.

The FDA explicitly asked the committee for guidance on what the meeting’s chair, epidemiologist Arnold Monto of the University of Michigan School of Public Health, referred to as “a very thorny issue”: whether a USA for a COVID-19 vaccine 19 could undermine efforts to evaluate the safety and efficacy of that product and other candidates as well. Before the meeting, Pfizer, which has one of the most advanced candidates in efficacy trials, put the dilemma in sharp focus in a letter it sent to the FDA.

If the FDA granted the company an EUA, wrote a senior vice president of the company, Pfizer would want FDA approval to give its vaccine to those in the placebo arm, a step that would later compromise the capacity of the 2-year study. to continue collecting comparative data on the safety and efficacy of the vaccine and placebo. A representative from Moderna, who also has a candidate who is well ahead of efficacy trials, told the committee that “participants are beginning to ask when they will know whether they will receive the study vaccine or a placebo.”

“Once a decision is made to unmask an ongoing placebo-controlled trial, that decision cannot be reversed,” Fink noted, emphasizing that future data from the control arm “is lost forever.”

FDA representatives suggested a way out of the dilemma: Instead of receiving an EUA, a vaccine could be approved for “expanded access”, limiting its use to select populations at high risk for COVID-19. This pathway is generally reserved to allow the use of experimental treatments in patients who have life-threatening conditions, but it has been used before for vaccines, such as one for meningitis B in college students. Since access to the vaccine would be limited, the approach has the advantage of allowing efficacy trials to continue.

Offit suggested after the meeting that to continue collecting vital data on vaccine efficacy from trials, the FDA may need to use a mechanism such as expanded access, or create a new one, that sits somewhere in between a US and full approval. “They just don’t have a lot of headroom right now,” Offit said.