FDA Exploring Evidence-Based Approach for Evaluating Vaccine Coadministration Safety

FDA Exploring Evidence-Based Approach for Evaluating Vaccine Coadministration Safety

Back in August, the Food and Drug Administration (FDA) announced the restricted approval of Pfizer-BioNTech’s COMIRNATY COVID-19 vaccine, citing terms and restrictions that suggest more robust proof of vaccine effectiveness must be provided before the agency gives the thumbs-up for new products.

This particular approval, issued by the Center for Biologics Evaluation and Research (CBER), was limited to use only in adults 65 years and older and individuals 5-64 years with at least one high-risk condition for severe COVID-19 outcomes, rather than broadly for all ages. The memo indicates this decision was based on declining rates of severe COVID in healthy populations, insufficient evidence of benefit for healthy individuals, and known risks such as myocarditis.

The agency also asserted no high-quality data shows that vaccination reduces long COVID, transmission, or days missed from school or work in any age group…so these factors will no longer form the basis of approval claims. The FDA will also require three postmarketing studies, including randomized trials for middle-age adults without high-risk conditions, to better determine risk-benefits in a larger population.

However, that was only the first set of new flaming hoops for vaccine manufacturers. Center for Biologics Evaluation and
Research (CBER) Director Vinay Prasad plans to light up even more, as explained in his August memo.

The FDA will now require randomized controlled trials (RCTs) to substantiate claims about the safety and effectiveness of administering COVID-19 and influenza vaccines together. Prasad expressed concern that, without such trials, the FDA cannot confirm that concurrent vaccine administration is both safe and effective, disputing previous reliance on antibody measurements alone to support this practice.

CBER OCD [Office of the Center Director] will require pragmatic, randomized controlled trials, randomizing persons eligible for multiple vaccines to concomitantly administer them in a single session, or to administer some sequence of the vaccines. The trial could be performed with a hierarchical statistical design, testing first noninferiority and then superiority. The primary endpoint would be clinical, for instance: symptomatic RSV, COVID-19, and influenza. Secondary endpoints would be severe disease, and adverse events.

Such a trial could be initially designed for noninferiority of clinical events, but, because of increased  compliance, and attrition in the sequential group, the trial could have a hierarchical superiority analysis.  It is possible, but not certain, that concurrent administration will lead to superior outcomes. Finally,  because this trial would be powered for clinical endpoints, there would be sufficient sample size to adjudicate important safety questions. Does the concurrent administration increase the rate of Bell’s  palsy by, for instance, 5, 10 or 20%? Such a trial may be able to ascertain even unexpected increases in  safety signals.

In the absence of such studies, FDA cannot affirm that concurrent administration is both safe and effective.

Big Pharma is bracing for the changes, requiring actual data on results and adverse effects before approvals are granted.

Although the new requirement was laid out in communications on Pfizer’s coronavirus vaccine Comirnaty, it will likely affect any company manufacturing vaccines for COVID-19, influenza or respiratory syncytial virus.

Apparently reading the writing on the wall, Pfizer last month sent a letter to healthcare providers warning that certain lots of its 2025-26 COVID vaccine “contain unapproved prescribing information inside the cartons.”

That language related to “concomitant administration of Pfizer-BioNTech COVID-19 vaccine, bivalent with a respiratory syncytial virus (RSV) vaccine or with an RSV vaccine and an influenza vaccine in individuals 65 years of age and older,” according to the letter, which the FDA has posted on its Comirnaty information page.

FDA’s Vinay Prasad floats controlled trial requirements for vaccine coadministration claims.
https://t.co/I93IU2GUWp

— Lennox Bennett (@LebenTech) September 5, 2025

Frankly, the pharmaceutical firms  should embrace Prasad’s reasonable requests. Hot Air’s David Strom explains why, as the new demands are a direct result of how they and their minions in the government botched the handling of the covid vaccine:

I never used to question the safety or effectiveness of vaccines–I didn’t expect them to be risk-free or to be 100% effective, but I trusted the people who approved them that the risks were worth the benefits.

Now, frankly, I don’t. Because I know that these people are perfectly willing to lie. They act like cult leaders, and I treat them as such. Not everything a cult leader says is a lie, but I have plenty of reason to doubt them and their motives.

Prasad does not have a history of hostility to vaccines or most medical treatments; he does have a history of demanding solid evidence.

That’s comforting to me, and his approach will ensure that the first step to restoring trust in public health is being taken.

It is going to take the FDA, the pharmaceutical industry, and public health officials a very long time to recover the trust they squandered. I wish Prasad a great deal of luck and success when dealing with the covid cultists still remaining in our bureaucracy.

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