Arcane arguments made by vaccine critics — many false or misleading — about how some vaccines are tested could end up having significant implications if one of their own becomes the nation's top health official.

Why it matters: Robert F. Kennedy Jr., President-elect Trump's choice to lead HHS, has said he isn't going to take away vaccines from anyone, although he'll be able to use the bully pulpit to sow fear if he so chooses.

• But changes to vaccine approval requirements that align with vaccine critics' arguments or the removal of some vaccines from federal recommendation lists could disrupt or deter efforts to combat infectious diseases at a time when the U.S. is increasingly vulnerable to them.

Why it matters II: In today's world, a perfectly normal response to hearing alarming new information is to further investigate it.

• That means that mainstream health experts — and journalists — should probably be prepared to respond to critics' most prominent arguments.
• "These questions are amplified, they're now out there on social media, and I think it is important to not say, 'This is just dumb,' but to say 'Ok, [I] understand what the question is and here's what we think the answer is and why,'" said Jesse Goodman, a Georgetown professor who was previously the FDA's chief scientist.

State of play: Vaccine testing protocols recently became part of the national narrative after the New York Times reported that Aaron Siri, a close Kennedy ally, brought lawsuits on behalf of an anti-vaccine client that sought to revoke the FDA's approval of some vaccines, including a polio immunization.

• "The goal is simply to ensure that vaccines are subject to proper testing for safety and efficacy," Siri wrote in a WSJ op-ed responding to the article.
• He argued that the polio vaccine in question "was licensed based on a clinical trial with no control group and only three days of safety review after injection."
• Kennedy himself said in a Stat News interview in 2017 that he'd like to see steps taken to "reform the process so that vaccines are subject to the same kind of safety scrutiny and safety testing that other drugs are subject to. We need to, prior to licensing vaccines, we need to do gold standard safety testing, like every other drug approval requires."

Between the lines: Misinformation is most persuasive when it has some tie to the truth. In this case, that tie is that some vaccines aren't required to undergo traditional trials in which one large group of people receives the vaccine while another receives a placebo.

• That's because in those select cases, running a placebo arm of the trial would create big ethical or practical concerns. But there are other ways to vigorously test such vaccine candidates for safety and efficacy, including after they've been deployed in the real world.
• And those cases are the exception, not the rule.
• "In the modern era, almost all of the trials have had placebo controls," Goodman said. "If anything, vaccines are usually subjected to a higher level of scrutiny and larger clinical trials and more monitoring because they are given to healthy people, usually."

Reality check: Where vaccine critics' arguments completely fall apart is in their assertions about safety issues, and the idea that any vaccines are untested, unmonitored drugs with overall negative health impacts.

• "Vaccines are subjected to greater scrutiny than drugs," wrote Paul Offit, a pediatrician specializing in infectious diseases at the Children's Hospital of Philadelphia, in response to Kennedy's 2017 interview, also in Stat. The CDC runs the Vaccine Safety Datalink, and "[n]othing like this exists on the drug side."
• Offit also serves on the FDA's vaccine advisory committee.

This post-marketing scrutiny is designed to, in part, pick up on any rare adverse effects that didn't show up in clinical trials.

• That's how scientists picked up on the COVID-19 vaccines' tie to myocarditis, for example.
• But that monitoring system can still be improved, Goodman said, potentially with the help of technological advancements.
• "We could try to move toward a much wider capture of the data on these vaccines as they're used, and that would enable detection of rare events and also answering questions about things that come up," he said.

Sometimes, testing a new vaccine against a placebo is impractical or unethical.

Case in point: When testing a vaccine against a disease for which an effective immunization already exists, there would be huge ethical problems with withholding that older vaccine from a group of people in order to test a new one.

• This was the case with the polio vaccine that Siri's lawsuit contests, the Children's Hospital of Philadelphia's Offit recently wrote on his Substack.
• That vaccine is made the same way as the original polio vaccine, he writes, which was tested in hundreds of thousands of children.
• "No academic institution could ethically perform the study that the lawyer requested," Offit wrote. "A study that included a placebo group would place those children at unnecessary risk of a preventable infection."

In some cases like this, the appropriate control is the existing vaccine, not a placebo, Georgetown's Goodman said.

• "They're not saying because there's an existing vaccine we're not going to study safety," he added. "It may not be in a placebo-controlled trial, but they are going to require extensive safety data on that vaccine."

Yes, but: Part of vaccine critics' argument comes down to quibbling over the definition of "placebo," Johns Hopkins professor William Moss said.

• "When they say placebo, I think in some circumstances they are taking a very narrow definition of placebo, meaning basically water or salt water. And that is too narrow a view," he said.

As another example, the annual flu shot is put on the market each year without the updated version being tested again in a placebo-controlled trial, although it is still tested using surrogate measures.

• That shot is updated based on the virus strain predicted to circulate that year. But even if scientists wanted to do a placebo-controlled trial for every update for the sake of total thoroughness, that wouldn't work: They'd have to wait for the strain in question to begin circulating among people, and by the time the results were in, it would be too late.
• Requiring placebo-controlled trials for flu shot updates "would make vaccines more out of date," said David Kessler, a former FDA commissioner.

And in still other scenarios, using a control group of unvaccinated clinical trial participants to test a new vaccine would just be impossible.

• That would be the case in testing vaccines against diseases that have already been eliminated in the U.S., like rubella.
• A "limitation of a randomized control trial is that it needs to be done in a situation where a large enough number of people are being exposed to the virus so that you can actually measure efficacy," Moss said.

This would also be true for any new vaccine developed for the sake of future preparedness — say, as a precaution against the bird flu circulating among livestock currently.

• Having the most effective possible vaccine on hand would be incredibly useful should the virus eventually be able to spread between people. But testing a new vaccine candidate in a large-scale, placebo-controlled clinical trial ahead of time would also be impossible.
• "You'd still want to evaluate the effectiveness. But if we had an emergent outbreak and we wanted to vaccinate people quickly, you could do immunogenicity studies, and you'd have to make the inference that antibody levels" would be effective against the virus, Moss said.

The bottom line: Suppression of vaccine misinformation is becoming less and less of an option, and that could lead to wider vaccine hesitancy in the U.S.

• And if critics' arguments were actually translated into vaccine policy, that could have further real-world implications.
• "If you create a lot of uncertainty around requirements, that could really make it difficult to develop products and potentially affect innovation and the innovation economy," Goodman said.