Rational Discourse Is Hard at Work at the FDA

In June 2025, the U.S. Food and Drug Administration instituted what is formally known as a class Safety Labeling Change to the prescribing information of mRNA COVID‑19 vaccines, requiring updated warnings about the risks of myocarditis and pericarditis following administration of these products. In conjunction with manufacturers, the FDA directed that safety labeling for the Pfizer‑BioNTech and Moderna mRNA vaccines be revised to convey new safety information about the estimated risk of heart‑related inflammatory conditions observed following vaccination, including unadjusted incidence estimates and clinical findings from post‑approval studies. This expanded warning explicitly noted that the highest estimated incidence occurred in younger males, particularly in the 12‑ to 24‑year age range, based on data collected in mid‑2025 during insurance claims analyses and safety monitoring data. This regulatory action marked a significant evolution in how the agency communicates and manages emerging safety signals associated with widely used vaccines.

This labeling change was not an isolated press release buried in a technical docket. Leaders within the agency, including Vinay Prasad, MD, MPH and Martin A. Makary, MD, MPH, published a peer‑reviewed Viewpoint in Journal of the American Medical Association (JAMA; July 2025) outlining the rationale and significance of the FDA’s safety labeling update. They explained that the “class Safety Labeling Change” was intentionally pursued and communicated through scientific literature in addition to regulatory outlets to underscore its scientific basis.

In early 2026, Prasad and Makary responded to a letter to the editor defending this shift by articulating regulatory epistemology: the FDA’s obligation to grant marketing authorization for medical products only when there is substantial certainty that the benefits outweigh the risks, and to admit when evidence is insufficient to support generalized use of additional vaccine doses in certain populations.

In their reply, they posed the rhetorical question of whether a healthy seven‑year‑old child would receive meaningful benefit from repeated mRNA boosters if she has already experienced multiple SARS‑CoV‑2 infections and pointedly acknowledged that physicians do not know with certainty the benefits in such scenarios. They invoked the FDA’s own regulatory framework, the limits of available evidence, and the practice of stratifying authorization by age and risk categories.

Subscribe now

The essence of their argument was that scientific regulators must explicitly weigh benefits against risks and refuse authorization when benefit is uncertain or unmeasured. This is not a rhetorical flourish. The legal and scientific standards governing FDA decisions require that benefits outweigh risks with substantial certainty before a product is authorized or its indications are expanded. When evidence is incomplete, wishing for benefit, averaging outcomes across heterogeneous populations, or deferring to external pressure cannot substitute for demonstrable, compelling data on net benefit. What Prasad and Makary encoded in that letter is not simply agency talking points but an articulation of prior probability thresholds that, in principle, govern rational decision‑making under uncertainty.

As of late 2025, the U.S. Centers for Disease Control and Prevention continues to state that cases of myocarditis and pericarditis have been rarely observed following receipt of COVID-19 vaccines used in the United States. In the agency’s Clinical Considerations for COVID-19 Vaccination, CDC notes that when these inflammatory cardiac events do occur after vaccination, they have been reported most frequently in adolescent and young adult males within about 7 days after receipt of a second dose of an mRNA COVID-19 vaccine, while also acknowledging that cases have occurred in females, other age groups, and in association with other doses.

CDC’s guidance further explains that most patients with myocarditis after mRNA COVID-19 vaccination have experienced resolution of symptoms by the time of hospital discharge, and it continues to counsel that clinicians should consider myocarditis or pericarditis in persons presenting with acute chest pain, shortness of breath, or palpitations after vaccination, noting that in younger children symptoms may be less specific. On its Safety Considerations for COVID-19 Vaccines page, CDC explicitly advises that counseling should include awareness of these symptoms and the need to seek care if they develop, particularly during the week following vaccination. CDC’s clinical recommendations still direct healthcare providers to report suspected cases to vaccine safety monitoring systems such as VAERS.

It is also accurate to state that studies specifically designed to evaluate long-term health consequences of COVID-19 vaccine–associated myocarditis and pericarditis have not been conducted. Neither CDC nor peer-reviewed literature to date (as reflected in major systematic reviews and regulatory surveillance reports) has published prospective, longitudinal cohort studies with substantial follow-up that quantify the incidence or nature of longer-term sequelae after myocarditis or pericarditis following COVID-19 vaccination. The available safety data instead consist primarily of adverse event reporting system signals, case series, short-term follow-up in post-approval studies, and clinical experience up to hospital discharge or brief outpatient follow-up. This gap in long-term outcome data is consistent with CDC’s emphasis on acute clinical management and early symptom recognition rather than on chronic prognosis, and it underscores the broader issue that longitudinal outcome studies in vaccine safety signals are lacking in the COVID-19 vaccine safety literature.

The labeling change and the JAMA discussions occurred against a backdrop of broader policy reorientation at federal health agencies. Independent reporting has documented that the June 2025 labeling update expanded the age groups and specificity of warnings to reflect new empirical incidence estimates and post‑approval study observations. In parallel, leadership changes at the CDC and FDA, influenced by new appointees under Health Secretary Robert F. Kennedy Jr., have prompted debates about vaccine strategy and advisory panel composition. Some news reporting suggests the FDA may consider additional regulatory adaptations such as expanded boxed warnings or expanded safety scrutiny for vaccines, including historical evidence reviews and stricter evidentiary standards for approval. These developments have attracted criticism from public health experts who argue that established vaccine safety frameworks already balance benefit and risk effectively, even for rare adverse events.

Crucially, the data supporting myocarditis as a genuine but rare phenomenon associated with mRNA vaccines are not controversial among clinical researchers. Independent reviews and systematic assessments have concluded that there is a causal relationship between mRNA vaccines and myocarditis, particularly in younger males, based on epidemiological and mechanistic evidence, even as the absolute frequency of events remains low. Such causal assessments are consistent with labeling changes and reinforce the need for regulators to transparently communicate both the evidence and its limitations.

Viewed together, the FDA’s actions and the scientific discourse around them illustrate what happens when a regulatory agency confronts uncertainty with explicit reasoning. The agency did not retreat into policy slogans. Instead, its leaders placed their interpretations and internal judgments before the scientific community in a public forum, acknowledged uncertainty where it exists, and tied authorization decisions to clearly articulated benefit–risk reasoning. This is not how regulatory decision‑making has often been communicated in recent years. For much of the COVID‑19 pandemic and its aftermath, public health messaging tended to emphasize uniformity of approach and the predominance of benefit narratives, sometimes at the expense of candid disclosure of uncertainty or differential risk by subgroup. The labeling change and the associated peer‑reviewed discourse represent a break from that pattern—a break toward a model of rational, transparent, evidence‑anchored regulatory discourse.

Whether the broader medical establishment will internalize and adopt this model is an open question. Journals, guideline committees, and professional societies have grown accustomed to policy narratives constructed on broad consensus rather than granular uncertainty. What the FDA’s recent engagement demonstrates, however, is that regulatory science can and should be conducted—and communicated—on the basis of explicit thresholds, open acknowledgment of knowledge gaps, and disciplined evaluation of benefits and risks.

If medicine at large is to become more rational and less reactive, it will have to learn from this example.

Subscribe now

Share this content

Subscribe to SciPublHealth

Comments

Leave a ReplyCancel reply