| It sounds perfectly reasonable at first blush. Robert F. Kennedy Jr., the US health secretary, is demanding all new vaccines be tested against a placebo before they can win Food and Drug Administration approval. Most vaccines on the market have already undergone that testing. The problem with Kennedy’s directive — for researchers, drug companies and perhaps society at large — is what “new” means. Clinical trials are basically a large-scale way to answer a simple question: Is a new medicine better than whatever we’ve got? When we’ve got nothing, like at the dawn of the Covid-19 pandemic, we want to test new vaccines against placebo. But when there’s already a proven product available, as in the case of HPV, we want to assess new vaccines against the ones whose safety and effectiveness is already established. The scientific reason is pretty direct. Doctors want to know whether they should recommend a new vaccine over an older one, and the only way to make that determination is by looking at head-to-head data. The results of a placebo study would be pretty much irrelevant to their decision. The ethical reason is even clearer. Running a placebo trial would require asking volunteers to willfully forgo an available vaccine for a dangerous disease, putting themselves at risk of infection in order to generate data that may not actually answer key questions. “Why would anyone volunteer for that type of a trial?” says Mansoor Amiji, professor of pharmaceutical sciences at Northeastern University. “Why would I want to be getting a saline solution when a vaccine is already out there?” Even more vexing is the Kennedy directive’s lack of clarity. What we know comes from a terse Health and Human Services Department statement saying that “all new vaccines will undergo safety testing in placebo-controlled trials prior to licensure.” Would “new” include a next-generation HPV vaccine? And what about seasonal flu shots? The virus evolves every year, and the vaccine gets tweaked to target the most worrisome strains. If flu vaccines had to go through the kind of months-long, placebo-controlled trials Kennedy seems to want, they wouldn’t be ready until after the actual flu season, thereby defeating the purpose entirely. “My first reaction is that would be a massive disaster,” says Daina Graybosch, an analyst who covers the pharmaceutical industry for Leerink Partners, about placebo tests for new vaccines. HHS has not responded to follow-up questions. “The vagueness of the announcement is what is concerning to everyone,” Amiji said. “It just doesn’t make any sense.” — Damian Garde | 
