The federal agency says it will mandate randomized, controlled clinical trials for vaccination of younger, healthy individuals
It’s been a confusing past few weeks in terms of what the general public’s access to COVID-19 vaccinations will be like in the future.
Public health experts have been verbally jousting with the federal Department of Health and Human Services (HHS) about moves its health officials made recently regarding the vaccines. This could put clinical laboratories on the front lines to help determine whether COVID cases—particularly severe ones—eventually rise as a result.
Food and Drug Administration (FDA) commissioner Martin A. Makary, MD, MPH, and Vinay Prasad, MD, MPH, who leads the agency’s vaccine oversight, announced on May 20 that the agency will require randomized, controlled clinical trials before approving COVID vaccines for healthy individuals under age 65.
“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,” Makary and Prasad wrote in NEJM.
Under the new framework, they noted, the agency expects that it will continue to approve vaccines for adults over 65 as well as younger people with health conditions that put them at high risk of severe outcomes from COVID-19.
The range of diseases is “vast, including obesity and even mental health conditions such as depression,” they wrote. “Estimates suggest that 100 million to 200 million Americans will have access to vaccines in this manner.”
In their NEJM commentary, FDA commissioner Martin Makary, MD (left), and Vinay Prasad, MD (right), wrote, “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.” (Photo copyrights: Wikimedia Commons.)
Former CDC APIC Member Pushes Back
The announcement drew criticism from public health and medical experts.
“The FDA guidance presented in the NEJM was not released in the Federal Register, did not invite comment, and provided only a general outline for COVID-19 vaccine licensure,” wrote pediatrician and vaccinologist Kathryn M. Edwards, MD, in a commentary for STAT. Edwards is a former member of the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP), which makes vaccine recommendations to the agency.
On June 9, in an opinion piece for The Wall Street Journal, HHS Secretary Robert F. Kennedy Jr. announced that he’s removing all 17 current members of ACIP.
“The FDA mandate is to ensure safe and effective vaccines based on the clinical studies performed, but not to develop specific recommendations for their use,” Edwards added. “Providing recommendations on vaccine use for the civilian population is the mandate of the ACIP.”
Edwards contended that extensive data is already available on the safety and effectiveness of COVID-19 vaccines. She stated that “there is no precedent for mandating continued placebo-controlled randomized clinical trials for vaccines that have already been licensed.”
New Policy Announcement Raises Questions
The New York Times notes that many questions remain about the specifics of the new policy and how broadly the vaccines will be available.
A likely scenario, the paper reported, is that health insurers will play a role as “gatekeepers by demanding medical documentation of an underlying condition before agreeing to cover the cost.” Without insurance coverage, people would likely pay approximately $140 per shot out of pocket.
This stands in contrast to European countries, where outreach campaigns target specific populations based on public health recommendations. according to Forbes. However, “in virtually all instances, COVID-19 vaccines can be gotten free of charge across Europe regardless of health or age status,” the article notes.
In their NEJM commentary, Prasad and Makary noted that adoption of the annual COVID-19 booster shot is already low. The CDC reported that 23% of Americans 18 and older received vaccinations in the 2024-2025 season, up slightly from 21.6% in 2023-2024.
Kennedy Steps In
On May 27, Kennedy announced in a video on X that the CDC would remove the COVID-19 vaccine from the recommended immunization schedule for healthy children and healthy pregnant women. Previously, the CDC recommended the vaccine for everyone ages six months and older.
Kennedy was joined in the video by Makary and National Institutes of Health director Jay Bhattacharya MD, PhD.
However, CDC staffers were “blindsided” by the announcement, NPR reported, citing an agency official who requested anonymity.
“Hours after the post on X, CDC staffers received a directive from Secretary Kennedy—dated May 19, but sent May 27—rescinding the department’s 2022 acceptance of the CDC’s recommendations for the use of COVID shots in children and during pregnancy,” NPR reported.
It now appears that HHS has at least partially backtracked on Kennedy’s announcement.
The CDC’s immunization schedule now states that vaccination of healthy children should be a matter of “shared clinical decision-making” between the doctor and parent or patient.
“After confusing, mixed messages from leaders at HHS earlier this week, we are relieved to see today that the CDC updated its schedules for child and adolescent immunizations to allow families to maintain the choice to immunize their children against COVID in consultation with their doctor,” American Academy of Pediatrics president Susan Kressly said in a statement from the organization.
In a June 1 interview with the CBS News program “Face the Nation,” Makary confirmed that the recommendation to vaccinate “should be with the patient and their doctor.”
However, he also criticized ACIP as a “kangaroo court where they just rubber stamp every single vaccine put in front of them.”
Number of patients eligible for genome-driven oncology therapy is increasing, but the percentage who reportedly benefit from the therapy remains at less than 5%
Advances in precision medicine in oncology (precision oncology) are fueling the need for clinical laboratory companion diagnostic tests that help physicians choose the best treatment protocols. In fact, this is a fast-growing area of clinical diagnostics for the nation’s anatomic pathologists. However, some experts in the field of genome-based cancer treatments disagree over whether such treatments offer more hype than hope.
Prasad and his colleagues evaluated 31 US Food and Drug
Administration (FDA) approved drugs, which were “genome-targeted” or
“genome-informed” for 38 indications between 2006 and 2018. The researchers
sought to answer the question, “How many US patients with cancer are eligible
for and benefit annually from genome-targeted therapies approved by the US Food
and Drug Administration?”
They found that in 2018 only 8.33% of 609,640 patients with
metastatic cancer were eligible for genome-targeted therapy—though this was an
increase from 5.09% in 2006.
Even more telling from Prasad’s view, his research team concluded
that only 4.9% had benefited from such treatments. Prasad’s study found the
percentage of patients estimated to have benefited from genome-informed therapy
rose from 1.3% in 2006 to 6.62% in 2018.
“Although the number of patients eligible for genome-driven treatment has increased over time, these drugs have helped a minority of patients with advanced cancer,” the researchers concluded. “To accelerate progress in precision oncology, novel trial designs of genomic therapies should be developed, and broad portfolios of drug development, including immunotherapeutic and cytotoxic approaches, should be pursued.”
The graph above is based on data from a study published in Science titled, “Estimation of the Percentage of US Patients With Cancer Who Benefit from Genome-Driven Oncology,” co-authored by Vinay Prasad, MD, MPH, et al. (Image copyright: Science.)
A Value versus Volume Argument?
Hyman, who leads a team of oncologists that conduct dozens
of clinical trials and molecularly selected “basket studies” each year,
countered Prasad’s assertions by noting the increase in the number of patients
who qualify for precision oncology treatments.
As reported in Science, Hyman said during his AACR
presentation that Sloan Kettering matched 15% of the 25,000 patients’ tumors it
tested with FDA-approved drugs and 10% with drugs in clinical trials.
“I think this is certainly not hype,” he said during the
conference.
Hyman added that another 10% to 15% of patient tumors have a
DNA change that matches a potential drug tested in animals. He expects “basket”
trials to further increase the patient pool by identifying drugs that can work
for multiple tumor types.
The US National Institute of Health (NIH) describes “basket studies” as “a new sort of clinical studies to identify patients with the same kind of mutations and treat them with the same drug, irrespective of their specific cancer type. In basket studies, depending on the mutation types, patients are classified into ‘baskets.’ Targeted therapies that block that mutation are then identified and assigned to baskets where patients are treated accordingly.”
Are Expectations of Precision Medicine Exaggerated?
A profile in MIT Technology Review, titled, “The Skeptic: What Precision Medicine Revolution?,” describes Prasad’s reputation as a “professional scold” noting the 36-year-old professor’s “sharp critiques of contemporary biomedical research, including personalized medicine.” Nevertheless, Prasad is not alone in arguing that precision oncology’s promise is often exaggerated.
“Like most ‘moonshot’ medical research initiatives,
precision medicine is likely to fall short of expectations,” Joyner wrote.
“Medical problems and their underlying biology are not linear engineering
exercises and solving them is more than a matter of vision, money, and will.”
“Although some niche applications have been found for
precision medicine—and gene therapy is now becoming a reality for a few rare
diseases—the effects on public health are miniscule while the costs are astronomical,”
they wrote.
Hope for Precision Medicine Remains High
However, optimism over precision oncology among some industry leaders has not waned. Cindy Perettie, CEO of molecular information company Foundation Medicine of Cambridge, Mass., argues genome-directed treatments have reached an “inflection point.”
“Personalized cancer treatment is a possibility for more patients than ever thanks to the advent of targeted therapies,” she told Genetic Engineering and Biotechnology News. “With a growing number of new treatments—including two pan-tumor approvals—the need for broad molecular diagnostic tools to match patients with these therapies has never been greater. We continue to advance our understanding of cancer as a disease of the genome—one in which treatment decisions can be informed by insight into the genomic changes that contribute to each patient’s unique cancer.”
Prasad acknowledges genome-driven therapies are beneficial for some cancers. However, he told MIT Technology Review the data doesn’t support the “rhetoric that we’re reaching exponential growth, or that is taking off, or there’s an inflection point” signaling rapid new advancements.
“Right now, we are investing heavily in immunotherapy and heavily in genomic therapy, but in other categories of drugs, such as cytotoxic drugs, we have stopped investigating in them,” he told Medscape Medical News. “But it’s foolish to do this—we need to have the vision to look beyond the fads we live by in cancer medicine and do things in a broader way,” he added.
“So, I support broader funding because you have to sustain
efforts even when things are not in vogue if you want to make progress,” Prasad
concluded.
Is precision oncology a fad? Dark Daily has covered the advancements in precision medicine extensively over the past decade, and with the launch of our new Precision Medicine Institute website, we plan to continue reporting on further advancements in personalized medicine.
Time will tell if precision oncology can fulfill its
promise. If it does, anatomic pathologists will play an important role in
pinpointing patients most likely to benefit from genome-driven treatments.
One thing that the debate between proponents of precision
medicine in oncology and their critics makes clear is that more and better
clinical studies are needed to document the true effectiveness of target
therapies for oncology patients. Such evidence will only reinforce the
essential role that anatomic pathologists play in diagnosis, guiding
therapeutic decisions, and monitoring the progress of cancer patients.
