Impossible Standards for Vaccine Testing

The top vaccine regulator at the Food and Drug Administration (FDA) wants to impose vague but sweeping new standards on vaccine testing that, health experts say, would impede the development of new immunizations and likely curtail access to life-saving shots, according to a memo sent to staff on November 28.

Vinay Prasad, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research (CBER), proposed the "path forward" in an internal memo in which he claimed—but provided no evidence—that COVID-19 vaccines caused the death of 10 children.

Many infectious disease experts say Prasad should share the evidence on which he based his argument. Linking a vaccine to an adverse event requires a high level of evidence, including autopsy results and medical records that rule out other causes of death and show whether the affected person was infected with the coronavirus itself, said Paul Offit, MD, an infectious disease specialist at Children’s Hospital of Philadelphia and co-inventor of a rotavirus vaccine.

Prasad is "making a fairly fantastic statement," Offit said. "He should provide extraordinary evidence that that's clear, and he didn't, which is incredibly irresponsible and unprofessional to do."

In the memo, Prasad wrote that the FDA's current vaccine approval process falls short.

In the future, the FDA will "demand pre-market randomized trials assessing clinical endpoints for most new products," including vaccines, Prasad wrote. He noted that COVID-19 vaccines have not been tested in randomized controlled trials (RCTs) in pregnant women. Such trials are the most rigorous type of study, but they can cost millions of dollars and take years to produce results.

"We will not be granting marketing authorization to vaccines in pregnant women" without such evidence, Prasad wrote. The memo's contents were first reported by a PBS News correspondent in a series of posts on X, the social media platform.

Asking for the impossible
Demanding an RCT would prevent pregnant women from receiving most vaccines, said Jake Scott, MD, a clinical associate professor of infectious disease and geographic medicine at Stanford University School of Medicine.

That's because pregnant women are almost never included in RCTs of vaccines or other drugs due to potential risks to the fetus, Scott said. Instead, the FDA does careful safety monitoring and measures antibody levels in women's blood, which can show whether the vaccine is generating an immune response.

In his memo, Prasad also wrote that "pneumonia vaccine makers will have to show their products reduce pneumonia," at least after they're licensed, rather than provide indirect evidence of protection, such as antibody levels.

Prasad appears to refer to a childhood pneumonia vaccine that blocks infections with pneumococcus bacteria, which has been updated and improved several times over the years, said Dorit Reiss, PhD, a law professor at the University of California Law, San Francisco. Although the first version of the vaccine protected children from seven bacterial strains, the latest iteration protects against 20 strains.

Pneumococcal vaccines on the market today are approved based on antibody levels that correlate with protection and have been validated over decades, Scott said.

Proving that childhood vaccines prevent cases of pneumonia would be difficult, Scott said, because so many pathogens can cause pneumonia, including the flu, COVID-19 and respiratory syncytial virus (RSV).

It would be unethical to use placebos and let people get pneumococcal pneumonia.
Requiring manufacturers to conduct additional clinical trials every time they want to add additional viral or bacterial strains would delay updates by several years, all the while leaving people vulnerable to the bacteria, Reiss said. Some companies may decide that conducting such trials is too expensive.

"You'd need massive, expensive trials that many companies won't pursue," Scott said.

Conducting RCTs of proven vaccines could also be unethical, said Jesse Goodman, MD, who previously filled Prasad's role at the FDA and now directs Georgetown University's Center on Medical Product Access, Safety and Stewardship.

"It would be unethical to use placebos and let people get pneumococcal pneumonia," Goodman said.

The Department of Health and Human Services, which oversees the FDA, did not respond to a request for comment.

Flu vaccines also in crosshairs
Prasad's memo was also extremely critical of flu vaccine testing.

But performing large clinical trials on each year's influenza vaccines before the start of flu season would be impossible, Scott said. Although vaccines are made the same way every year, the viral strains used to produce them typically change each year, based on the viruses in circulating. Scientists make their best guess about which strains to include in Northern Hemisphere vaccines in February or March, because manufacturing them takes six months.

Requiring any additional testing could prevent the vaccines from being ready for the flu season, which begins in the fall in the Northern Hemisphere.

Although new vaccines are extensively tested before their initial approval, Reiss said Prasad is correct when he says that updated flu shots undergo minimal testing from year to year.

"But it's minimal testing for a reason," she said. "If you're demanding more, you're making it almost impossible to approve an annual vaccine. He didn't tell us exactly in detail what the FDA is going to say, but this is going to demand a large clinical trial every year. That's just not going to happen."

Conducting an RCT of each season's flu vaccine would be impossible, Scott said, given that these studies typically take several years.

If the FDA requires RCTs for annual flu shots, the results would not be ready until years later, rendering the vaccines worthless, Scott said.

Prasad issued his memo just days before a two-day meeting of the Center for Disease Control and Prevention's (CDC's) influential vaccine committee, which is scheduled to be held Thursday and Friday. The Advisory Committee on Immunization Practices recommends which vaccines Americans should receive, and its decisions influence which vaccines are covered by insurance or federal programs.

Many researchers told CIDRAP News they fear that the committee could use Prasad's memo to justify further restrictions on vaccines.

"Even if vaccines remain technically available," Scott said, "without CDC recommendations or insurance coverage, access disappears. It's a de facto ban disguised as higher standards."

"The [influenza] virus has proven far more dangerous to children than any documented vaccine risk," Scott said.

https://www.cidrap.umn.edu/childhood-vaccines/fda-official-proposes-impossible-standards-vaccine-testing-could-curtail-access

Impossible Standards for Vaccine Testing

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