On topic of the thread. More at the link that gets into the study design recommendations and other considerations.
https://www.nejm.org/doi/full/10.1056/NEJMsb2506929#f1
An Evidence-Based Approach to Covid-19 Vaccination
Authors: Vinay Prasad, M.D., M.P.H., and Martin A. Makary, M.D., M.P.H.Author Info & Affiliations
Published May 20, 2025
Over the past 5 years, the United States has moved toward an annual Covid-19 booster program. Each fall, Covid-19 booster shots are developed, alongside seasonal influenza vaccines, and are recommended for every American. As compared with vaccination policies in all European nations, the U.S. policy has been the most aggressive (see Figure 1).1 While all other high-income nations confine vaccine recommendations to older adults (typically those older than 65 years of age), or those at high risk for severe Covid-19, the United States has adopted a one-size-fits-all regulatory framework and has granted broad marketing authorization to all Americans over the age of 6 months.1 The U.S. policy has sometimes been justified by arguing that the American people are not sophisticated enough to understand age- and risk-based recommendations.2 We reject this view.
Although the rapid development of multiple Covid-19 vaccines in 2020 represents a major scientific, medical, and regulatory accomplishment,3 the benefit of repeat dosing — particularly among low-risk persons who may have previously received multiple doses of Covid-19 vaccines, had multiple Covid-19 infections, or both — is uncertain. The American people, along with many health care providers, remain unconvinced.
Over the past two seasons, uptake of the annual Covid-19 booster has been poor, according to the Centers for Disease Control and Prevention (CDC). Less than 25% of Americans received boosters each year, ranging from less than 10% of children younger than 12 years of age in the 2024–2025 season to 50% of adults over 75 years old.4 Even health care workers remain hesitant, with less than one third participating in the 2023–2024 fall booster program.5 There may even be a ripple effect: public trust in vaccination in general has declined,6 resulting in a reluctance to vaccinate that is affecting even vital immunization programs such as that for measles–mumps–rubella (MMR) vaccination, which has been clearly established as safe and highly effective. In recent years, reduced MMR vaccination rates have been a growing concern and have contributed to serious illness and deaths from measles. Against this context, the Food and Drug Administration (FDA) seeks to provide guidance and foster evidence generation.
Moving forward, the FDA will adopt the following Covid-19 vaccination regulatory framework: On the basis of immunogenicity — proof that a vaccine can generate antibody titers in people — the FDA anticipates that it will be able to make favorable benefit–risk findings for adults over the age of 65 years and for all persons above the age of 6 months with one or more risk factors that put them at high risk for severe Covid-19 outcomes, as described by the CDC (Figure 2). For all healthy persons — those with no risk factors for severe Covid-19 — between the ages of 6 months and 64 years, the FDA anticipates the need for randomized, controlled trial data evaluating clinical outcomes before Biologics License Applications can be granted. Insofar as possible, when approving a Covid-19 vaccine for high-risk groups, the FDA will encourage manufacturers to conduct randomized, controlled trials in the population of healthy adults as part of their postmarketing commitment.