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FDA expert advisors wonder: Why did the FDA approve a second booster before consulting us?

AP Photo/Damian Dovarganes

It’s pretty sketchy.

Especially for an agency that had bent over backward in the past to assure the public that everything was being done above board with the vaccines. When scientists detected a few cases of blood clotting in recipients of the Johnson & Johnson vaccine last year, that product was briefly yanked from the market while experts investigated. The FDA did so in order to show good faith and give Americans confidence that the feds wouldn’t try to cover up an unexpected side effect of a vaccine if one was detected.

It ended up backfiring. After J&J’s temporary suspension, the upward trend in vaccine uptake in the U.S. immediately reversed. But the point stands — normally the FDA goes by the book with COVID vaccine approvals so that it can’t be accused of sleight of hand.

When it comes to approving new doses, “by the book” is supposed to be a two-step process. First, the FDA’s outside panel of experts (VRBPAC) meets to discuss the data for and against that dose and ultimately votes on whether to recommend it or not. Then the FDA itself issues a decision on whether to recommend it, almost always following VRBPAC’s advice. In the case of the recently approved second COVID booster, though, the two steps were reversed. Last week the FDA issued its ruling, recommending a fourth dose for everyone 65 and over and authorizing it as an option for everyone 50 and over. Then, yesterday, VRBPAC met to discuss the wisdom of that decision and other matters.

“That’s like having lawyers present arguments to a judge who’s already issued a verdict,” wrote Dr. Marty Makary recently.

Even stranger, neither Pfizer nor Moderna asked the FDA to authorize fourth doses for everyone 50 and over. They were aiming purely for senior citizens. The FDA took it upon itself to issue a broader than requested authorization.

What’s going on here? I have a theory, but VRBPAC’s own members sound mystified.

Dr. Paul Offit, a co-inventor of the rotavirus vaccine and member of VRBPAC, said he couldn’t explain why the FDA didn’t present its data to the committee first before moving ahead with authorization: “The way it’s working here is that the government basically just declares that this is what they’re going to do.”…

Dr. Cody Meissner is a childhood vaccination expert at Tufts University who also sits on VRBPAC. He similarly couldn’t explain why his insight, along with the other committee members, wasn’t sought out before authorizing Pfizer’s fourth dose…

The rush to get fourth doses could have downsides, experts told the Daily Caller. Both Offit and Gandhi independently raised the issue of original antigenic sin — a phenomenon in which the immune system continually produces an immune response targeted at the first encounter with a pathogen, rather than updated strains or variants. It’s possible that this process could render variant-specific vaccine doses or boosters ineffective, because the body bases its immune response on the original vaccine dose.

“I think to have this decision made in-house behind closed doors without having the transparency of a full debate that a regularly called ACIP meeting would have provided – I think that’s unfortunate,” said Dr. William Schaffner to CNBC. Offitt agreed, adding that a public open discussion of how vaccine decisions are being made might encourage Americans who aren’t up to date on their shots to go out and get vaxxed.

VRBPAC’s members confronted Dr. Peter Marks, the head of the FDA’s vaccine division, at yesterday’s after-the-fact meeting and asked why their input hadn’t been solicited. “We consider that as not a major expansion or a major change, but something that we looked over the data and felt was reasonable to do at the time,” said Marks about authorizing a fourth dose. But numerous experts, including Offitt, have raised questions about the Israeli study on which the decision to authorize the dose was based, particularly the fact that it wasn’t a randomized clinical trial. Instead it compared Israelis who’d chosen to get a fourth shot to those who’d opted against it, introducing the possibility of behavioral differences between those two groups into the mix. (People who are more likely to choose vaccination may also be more likely to wear masks and social-distance, reducing their risk of infection.)

My guess is that the FDA did what it did to overcorrect for the slow pace with which the feds approved the first booster last year. Remember that fiasco? Biden got ahead of the science early last fall, promising that boosters for all adults would soon be approved. Then the FDA and CDC told him to hold his horses since the data wasn’t solid yet on whether all adults would benefit. Later in September, boosters were finally approved, but only for certain vulnerable people. It wasn’t until mid-November, about the time that Omicron was emerging in Africa, that boosters were approved for all adults. If the feds had authorized boosters for all early last fall and then pushed hard to encourage people to get them, many more Americans might have been boosted by the time Omicron ran wild through the country in January. Who knows how many deaths might have been averted.

Having erred before on the side of caution with the data, it seems that the FDA is now erring on the side of approval. BA.2 is ravaging the Far East and has driven case counts to their highest level yet in England; it seems a matter of time before we experience a major wave here too. (It may have already begun in Washington.) Solution: Approve a fourth booster lickety split, before even hearing from VRBPAC, in order to head BA.2 off at the pass and hope that that decision saves the lives of a few grandmas and grandpas.

If that’s not the explanation for the rushed approval, what is?

Anyway, instead of talking about a fourth dose, yesterday’s VRBPAC meeting was spent discussing the thorny issue of whether to change the vaccines’ formula before fall in order to target Omicron. Right now the formula is based on the spike protein of the original Wuhan virus, which has held up well in protecting recipients from severe illness but not from infection. A new vaccine tailored to Omicron’s spike protein should increase the protection from severe illness further and might even reduce the risk of catching COVID. But changing the formula is a major, major risk: If a dangerous new variant emerges that’s descended from the original Wuhan strain rather than the strange Omicron offshoot of that strain, the new vaccine might be ineffective against it.

Essentially, vaccine developers have to gamble on whether they believe future variants are likely to be variants of Omicron or some earlier strain. “Expert after expert at the meeting described how much guesswork is involved in that effort,” the Times said of yesterday’s session. “No one knows which variant of the virus will dominate in the fall, when federal officials consider a new surge highly likely. There is some chance that before then, another variant like Omicron will emerge and redraw the coronavirus picture in a wholly unexpected way.” How lucky do you feel?

I think they’re going to end up changing the formula. If Omicron/BA.2 are effectively the only games in town anymore with COVID, with all other strains at near-extinction, it makes sense to focus vaccine efforts on them.

Exit quotation from Marks: “What keeps me up at night is the knowledge that we can’t keep boosting. We’re going to have vaccine exhaustion, and I’m not talking about immune exhaustion but physical exhaustion from people who won’t get boosted.”