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GDUFA IV Statement of Dr. Diana Zuckerman, President of CPTF

Policy, Testimony & Briefings

July 11, 2025

I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  I appreciate the opportunity to speak today.

My perspective is based on my 35 years of working on issues pertaining to the safety and effectiveness of medical products. I have post-doctoral training in epidemiology and public health, and was a faculty member and researcher at Vassar, Yale, and Harvard before moving to Washington to work as a Congressional investigator on FDA issues in the U.S. Congress. Prior to my current position, I also worked at HHS and the White House. Our research center is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products or have any financial interest in our work.

I am one of the FDA’s biggest fans, because I fully appreciate the agency’s importance.  As a founding Board member of the Alliance for a Stronger FDA, I work with nonprofits and industry to increase appropriations for the FDA. We all know that our healthcare system relies on generic drugs and frankly would collapse without them. I wish appropriations would be sufficient to support all of FDA’s essential work, but we know that the FDA needs user fees to ensure getting safe and effective medical products to market in a timely manner. However, speed is not the most important part of that equation.

There have been many inspiring statements in the FDA this year about transparency and about the need for the FDA to regulate industry, rather than be influenced by unduly cozy relationships with industry. An important first step would be for user fee negotiations to include patient, consumer, and public health advocates, instead of only industry and the FDA negotiating behind closed doors. Unfortunately, all user fee negotiations have focused on what industry wants and needs and what they are willing to pay for, and not on what patients and consumers want and need.

On a personal note, my life has depended on generic drugs, which I’ve taken for cancer treatment and for high blood pressure. Like most patients, we trust that generic medications work but we don’t always know for sure. We all depend on generic drugs and understand their importance, so all of us in this room are in this together, and we need to work together.

Trust in generic drugs is essential to help to make healthcare more affordable. Trust in the FDA and in generic drugs has eroded in recent years, and that’s why GDUFA needs to explicitly show that user fees will focus on ensuring that generic drugs are truly equivalent to brand name treatments in all the ways that matter to patients. Speed should be secondary, because when patients realize that some generic drugs are ineffective or unsafe, it harms patients but also harms companies whose products are safe and effective.

Let’s talk about Performance Goals in GDUFA. Up until now, too few have been focused on safety or effectiveness. We are glad that metrics have included the number of inspections and timeliness of inspections and follow-up warning letters, import alerts, and regulatory meetings, and those metrics should included. However, they are not sufficient.

Last summer, the FDA determined that Synapse (a company in India) “faked and forged” data submitted to the FDA. FDA withdrew the bioequivalency rating of 400 of their drugs, but they are still on the market. Neither patients nor pharmacists have access to the names of those drugs. Why is that? That is terribly unfair to patients, but it is also unfair to companies whose safe and effective generic medications are competing with those 400 drugs. And it is also unfair to generic companies that make excellent medications when patients don’t know which generic drugs they can trust.

Valisure has also conducted research showing a sizable number of generic drugs are substandard, with doses that are too high, too low, or drugs that are contaminated or have other problems.

These are just some examples of why post-market surveillance, inspections, and re-inspections are so important and why GDUFA should include funding for those purposes and include those types of metrics in the Commitment Letter.

GDUFA should include metrics showing that these problems are being addressed and generic drugs are truly safe and equivalent to brand name drugs. That’s the promise that GDUFA and the FDA have made to patients and it needs to be kept.

Here is an important list of the kinds of metrics that are missing from previous GDUFA Commitment Letters and should be included in FDA monitoring under GDUFA IV. They are the exact same list that the FDA states are criteria for all generic drugs. They must be:

• Pharmaceutically equivalent
• Capable of making the drug correctly
• Capable of making the drug consistently
• The active ingredient is the same as the name brand and the
same amount gets in the body
• Inactive ingredients are safe
• Drug does not break down over time

We’ve heard about the progress that has been made at the FDA thanks to GDUFA. That progress is wonderful, but to regain trust, improvements should be measurable and included as metrics in GDUFA IV.

Thank you for the opportunity to share my views with you today.

MIT Technology Review

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Meet Jim O’Neill, the longevity enthusiast who is now RFK Jr.’s right-hand man

By Jessica Hamzelou, July 1, 2025

June 30, 2025

When Jim O’Neill was nominated to be the second in command at the US Department of Health and Human Services, Dylan Livingston was excited. As founder and CEO of the lobbying group Alliance for Longevity Initiatives (A4LI), Livingston is a member of a community that seeks to extend human lifespan. O’Neill is “kind of one of us,” he told me shortly before O’Neill was sworn in as deputy secretary on June 9. “And now [he’s] in a position of great influence.”

As Robert F. Kennedy Jr.’s new right-hand man, O’Neill is expected to wield authority at health agencies that fund biomedical research and oversee the regulation of new drugs. And while O’Neill doesn’t subscribe to Kennedy’s most contentious beliefs—and supports existing vaccine schedules—he may still steer the agencies in controversial new directions.

Although much less of a public figure than his new boss, O’Neill is quite well-known in the increasingly well-funded and tight-knit longevity community. His acquaintances include the prominent longevity influencer Bryan Johnson, who describes him as “a soft-spoken, thoughtful, methodical guy,” and the billionaire tech entrepreneur Peter Thiel.

In speaking with more than 20 people who work in the longevity field and are familiar with O’Neill, it’s clear that they share a genuine optimism about his leadership. And while no one can predict exactly what O’Neill will do, many in the community believe that he could help bring attention and resources to their cause and make it easier for them to experiment with potential anti-aging drugs.

This idea is bolstered not just by his personal and professional relationships but also by his past statements and history working at aging-focused organizations—all of which suggest he indeed believes scientists should be working on ways to extend human lifespan beyond its current limits and thinks unproven therapies should be easier to access. He has also supported the libertarian idea of creating new geographic zones, possibly at sea, in which residents can live by their own rules (including, notably, permissive regulatory regimes for new drugs and therapies).

[….]

Not everyone working in health is as enthusiastic, particularly when it comes to any potential changes to drug testing and approvals. If O’Neill still holds the views he has espoused over the years, that’s “worrisome,” says Diana Zuckerman, a health policy analyst and president of the National Center for Health Research, a nonprofit think tank in Washington, DC. 

“There’s nothing worse than getting a bunch of [early-stage unproven therapies] on the market,” she says. Those products might be dangerous and could make people sick while enriching those who develop or sell them. 

“Getting things on the market quickly means that everybody becomes a guinea pig,” Zuckerman says. “That’s not the way those of us who care about health care think.” 

The consumer advocacy group Public Citizen puts it far more bluntly, describing O’Neill as “one of Trump’s worst picks” and saying that he is “unfit to be the #2 US health-care leader.” His libertarian views are “antithetical to basic public health,” the organization’s co-president said in a statement. Neither O’Neill nor HHS responded to requests for comment.

“One of us”

As deputy secretary of HHS, O’Neill will oversee a number of agencies, including the National Institutes of Health, the world’s biggest funder of biomedical research; the Centers for Disease Control and Prevention, the country’s public health agency; and the Food and Drug Administration, which was created to ensure that drugs and medical devices are safe and effective.

“It can be a quite powerful position,” says Patricia Zettler, a legal scholar at Ohio State University who specializes in drug regulation and the FDA.

It is the most senior role O’Neill has held at HHS, though it’s not the first. He occupied various positions in the department over five years during the early 2000s, according to his LinkedIn profile. But it is what he did after that has helped him cultivate a reputation as an ally for longevity enthusiasts.

O’Neill appears to have had a close relationship with Thiel since at least the late 2000s. Thiel has heavily invested in longevity research and has said he does not believe that death is inevitable. In 2011 O’Neill referred to Thiel as his “friend and patron.” (A representative for Thiel did not respond to a request for comment.)

O’Neill also served as CEO of the Thiel Foundation between 2009 and 2012 and cofounded the Thiel Fellowship, which offers $200,000 to promising young people if they drop out of college and do other work. And he spent seven years as managing director of Mithril Capital Management, a “family of long-term venture capital funds” founded by Thiel, according to O’Neill’s LinkedIn profile.

O’Neill got further stitched into the longevity field when he spent more than a decade representing Thiel’s interests as a board member of the SENS Research Foundation (SRF), an organization dedicated to finding treatments for aging, to which Thiel was a significant donor.

[….]

Longevity science is a field that’s long courted controversy, owing largely to far-fetched promises of immortality and the ongoing marketing of creams, pills, intravenous infusions, and other so-called anti-aging treatments that are not supported by evidence. But the community includes people along a spectrum of beliefs (with the goals of adding a few years of healthy lifespan to the population at one end and immortality at the other), and serious doctors and scientists are working to bring legitimacy to the field.

Pretty much everyone in the field that I spoke with appears to be hopeful about what O’Neill will do now that he’s been confirmed. Namely, they hope he will use his new position to direct attention and funds to legitimate longevity research and the development of new drugs that might slow or reverse human aging.

[….]

Changing the rules

While plenty of treatments have been shown to slow aging in lab animals, none of them have been found to successfully slow or reverse human aging. And many longevity enthusiasts believe drug regulations are to blame.

O’Neill is one of them. He has long supported deregulation of new drugs and medical devices. During his first tour at HHS, for instance, he pushed back against regulations on the use of algorithms in medical devices. “FDA had to argue that an algorithm … is a medical device,” he said in a 2014 presentation at a meeting on “rejuvenation biotechnology.” “I managed to put a stop to that, at least while I was there.”

During the same presentation, O’Neill advocated lowering the bar for drug approvals in the US. “We should reform [the] FDA so that it is approving drugs after their sponsors have demonstrated safety and let people start using them at their own risk,” he said. “Let’s prove efficacy after they’ve been legalized.”

This sentiment appears to be shared by Robert F. Kennedy Jr. In a recent podcast interview with Gary Brecka, who describes himself as a “longevity expert,” Kennedy said that he wanted to expand access to experimental therapies. “If you want to take an experimental drug … you ought to be able to do that,” he said in the episode, which was published online in May.

But the idea is divisive. O’Neill was essentially suggesting that drugs be made available after the very first stage of clinical testing, which is designed to test whether a new treatment is safe. These tests are typically small and don’t reveal whether the drug actually works.

That’s an idea that concerns ethicists. “It’s just absurd to think that the regulatory agency that’s responsible for making sure that products are safe and effective before they’re made available to patients couldn’t protect patients from charlatans,” says Holly Fernandez Lynch, a professor of medical ethics and health policy at the University of Pennsylvania who is currently on sabbatical. “It’s just like a complete dereliction of duty.”

[….]

Ultimately, though, even if O’Neill does try to change things, Zettler points out that there is currently no lawful way for the FDA to approve drugs that aren’t shown to be effective. That requirement won’t change unless Congress acts on the matter, she says: “It remains to be seen how big of a role HHS leadership will have in FDA policy on that front.”

A longevity state

A major goal for a subset of longevity enthusiasts relates to another controversial idea: creating new geographic zones in which people can live by their own rules. The goal has taken various forms, including “network states” (which could start out as online social networks and evolve into territories that make use of cryptocurrency), “special economic zones,” and more recently “freedom cities.”

While specific details vary, the fundamental concept is creating a new society, beyond the limits of nations and governments, as a place to experiment with new approaches to rules and regulations.

In 2023, for instance, a group of longevity enthusiasts met at a temporary “pop-up city” in Montenegro to discuss plans to establish a “longevity state”—a geographic zone with a focus on extending human lifespan. Such a zone might encourage healthy behaviors and longevity research, as well as a fast-tracked system to approve promising-looking longevity drugs. They considered Rhode Island as the site but later changed their minds.

Some of those same longevity enthusiasts have set up shop in Próspera, Honduras—a “special economic zone” on the island of Roatán with a libertarian approach to governance, where residents are able to make their own suggestions for medical regulations. Another pop-up city, Vitalia, was set up there for two months in 2024, complete with its own biohacking lab; it also happened to be in close proximity to an established clinic selling an unproven longevity “gene therapy” for around $20,000. The people behind Vitalia referred to it as “a Los Alamos for longevity.” Another new project, Infinita City, is now underway in the former Vitalia location.

O’Neill has voiced support for this broad concept, too. He’s posted on X about his support for limiting the role of government, writing “Get government out of the way” and, in reference to bills to shrink what some politicians see as government overreach, “No reason to wait.” And more to the point, he wrote on X last November, “Build freedom cities,” reposting another message that said: “I love the idea and think we should put the first one on the former Alameda Naval Air Station on the San Francisco Bay.”

And up until March of last year, according to his financial disclosures, he served on the board of directors of the Seasteading Institute, an organization with the goal of creating “startup countries” at sea. “We are also negotiating with countries to establish a SeaZone (a specially designed economic zone where seasteading companies could build their platforms),” the organization explains on its website.

“The healthiest societies in 2030 will most likely be on the sea,” O’Neill told an audience at a Seasteading Institute conference in 2009. In that presentation, he talked up the benefits of a free market for health care, saying that seasteads could offer improved health care and serve as medical tourism hubs: “The last best hope for freedom is on the sea.”

Some in the longevity community see the ultimate goal as establishing a network state within the US. “That’s essentially what we’re doing in Montana,” says A4LI’s Livingston, referring to his successful lobbying efforts to create a hub for experimental medicine there. Over the last couple of years, the state has expanded Right to Try laws, which were originally designed to allow terminally ill individuals to access unproven treatments. Under new state laws, anyone can access such treatments, providing they have been through an initial phase I trial as a preliminary safety test.

“We’re doing a freedom city in Montana without calling it a freedom city,” says Livingston.

Patri Friedman, the libertarian founder of the Seasteading Institute, who calls O’Neill “a close friend,” explains that part of the idea of freedom cities is to create “specific industry clusters” on federal land in the US and win “regulatory carve-outs” that benefit those industries.

A freedom city for longevity biotech is “being discussed,” says Friedman, although he adds that those discussions are still in the very early stages. He says he’d possibly work with O’Neill on “changing regulations that are under HHS” but isn’t yet certain what that might involve: “We’re still trying to research and define the whole program and gather support for it.”

Will he deliver?

Some libertarians, including longevity enthusiasts, believe this is their moment to build a new experimental home.

Not only do they expect backing from O’Neill, but they believe President Trump has advocated for new economic zones, perhaps dedicated to the support of specific industries, that can set their own rules for governance.

[….]

“The notion around so-called freedom cities, with respect to biomedical innovation, just reflects deep misunderstandings of what drug development entails,” says Ohio State’s Zettler. “It’s not regulatory requirements that [slow down] drug development—it’s the scientific difficulty of assessing safety and effectiveness and of finding true therapies.”

Making matters even murkier, a lot of the research geared toward finding those therapies has been subject to drastic cuts.The NIH is the largest funder of biomedical research in the world and has supported major scientific discoveries, including those that benefit longevity research. But in late March, HHS announced a “dramatic restructuring” that would involve laying off 10,000 full-time employees. Since Trump took office, over a thousand NIH research grants have been ended and the administration has announced plans to slash funding for “indirect” research costs—a move that would cost individual research institutions millions of dollars. Research universities (notably Harvard) have been the target of policies to limit or revoke visas for international students, demands to change curricula, and threats to their funding and tax-exempt status.

The NIH also directly supports aging research. Notably, the Interventions Testing Program is a program run by the National Institutes of Aging (a branch of the NIH) to find drugs that make mice live longer. The idea is to understand the biology of aging and find candidates for human longevity drugs.

The ITP has tested around five to seven drugs a year for over 20 years, says Richard Miller, a professor of pathology at the University of Michigan, one of three institutes involved in the program. “We’ve published eight winners so far,” he adds.

The future of the ITP is uncertain, given recent actions of the Trump administration, he says. The cap on indirect costs alone would cost the University of Michigan around $181 million, the university’s interim vice president for research and innovation said in February. The proposals are subject to ongoing legal battles. But in the meantime, morale is low, says Miller. “In the worst-case scenario, all aging research [would be stopped],” he says.

The A4LI has also had to tailor its lobbying strategy given the current administration’s position on government-funded research. Alongside its efforts to change Montana state law to allow clinics to sell unproven treatments, the organization had been planning to push for an all-new NIH institute dedicated to aging and longevity research—an idea that O’Neill voiced support for last year. But current funding cuts under the new administration suggest that it’s “not the ideal political climate for this,” says Livingston.

Despite their enthusiasm for O’Neill’s confirmation, this has all left many members of the longevity community, particularly those with research backgrounds, concerned about what the cuts mean for the future of longevity science.

“Someone like [O’Neill], who’s an advocate for aging and longevity, would be fantastic to have at HHS,” says Matthew O’Connor, who spent over a decade at SRF and says he knows O’Neill “pretty well.” But he adds that “we shouldn’t be cutting the NIH.” Instead, he argues, the agency’s funding should be multiplied by 10.

“The solution to curing diseases isn’t to get rid of the organizations that are there to help us cure diseases,” adds O’Connor, who is currently co-CEO at Cyclarity Therapeutics, a company developing drugs for atherosclerosis and other age-related diseases.

[….]

RFK Jr.’s Planned Assault on Corporate Influence Is Clashing With Reality

In the News, News Stories & Editorials, We're In the News

Margaret Manto, NOTUS, June 26, 2025

Health Secretary Robert F. Kennedy Jr. has made ending “corporate capture” of the federal health agencies a key tenet of his plan to eradicate what the MAHA Commission Assessment describes as “threats to American childhood that have been exacerbated by perverse incentives.”

But health care lobbyists, regulatory experts and advocates for reduced industry involvement all told NOTUS the same thing: So far, Kennedy’s words don’t match his actions.

“The rhetoric is quite different, but it doesn’t seem like the reality is obviously different,” said Diana Zuckerman, president of the National Center for Health Research, who has criticized the Food and Drug Administration’s funding structure that relies on collecting fees from the companies whose products it regulates. “There’s all kinds of conflicts of interest that have been absolutely ignored by HHS and, as far as we can tell, still are.”

Since ascending to the top of the U.S. public health system, Kennedy has made grand gestures towards his supposed goal of clamping down on corporate influence at the Department of Health and Human Services. He’s held press conferences to tout agreements made with food producers to end the use of certain synthetic food dyes and with insurance companies to speed up the prior authorization process, both of which companies have lobbied against for years.

But these agreements have all been entirely voluntary. In the case of the food dye announcement, that was a direct result of industry influence, said one lobbyist granted anonymity to speak frankly.

“Their biggest win was not real,” the lobbyist said.

[….]

“Secretary Kennedy’s commitment to eliminating undue corporate influence and restoring public trust in health policy is backed by decisive action. Under the Secretary’s leadership, HHS has taken concrete steps to increase transparency, strengthen ethical standards, and prioritize the health and well-being of the American people over industry profits,” the spokesperson wrote.

But the MAHA report, which took aim at a range of public health interventions that the MAHA movement is suspicious of, including vaccines and ultraprocessed foods, was noticeably light on criticism of the agriculture industry and pesticide use — which Kennedy has pledged to reform.

In a hearing last month before a subcommittee of the Senate Committee on Appropriations, Kennedy assured senators that he would “not do anything to jeopardize that business model.”

Other than reworking their pitches to use new, more MAHA-friendly language, companies and the lobbyists who work for them haven’t had to do much to adapt to the new HHS leadership, the lobbyist said.

“I haven’t noticed anything different at all,” they said. “I don’t know anybody who’s had a problem getting a meeting.”

[….]

Since these meetings, HHS has embarked on policies that both advance the MAHA movement’s public health goals and provide potential benefits to industries deemed acceptable.

Earlier this month, STAT News reported that HHS put out a call for proposals for a “bold, edgy” public messaging campaign to “inspire and empower Americans to reclaim control over their health.” The request specifically asks for proposals that highlight health wearables as “cool, modern tools.”

“My vision is that every American is wearing a wearable within four years,” Kennedy said during a congressional hearing this week.

Other policy decisions seem poised to benefit not just certain niches of the health care industry, but key players within the MAHA movement. In early June, the Food and Drug Administration declined to contest a court ruling that overturned a 2024 FDA rule regulating laboratory-developed tests.

The agency had previously argued that increased regulation was necessary to “better protect the public health by helping to assure the safety and effectiveness” of tests that are manufactured and used by a single laboratory, as opposed to commercially available in-vitro diagnostics that are used by labs nationwide and which the FDA requires to be thoroughly verified and validated.

[….]

The FDA is the main arbiter of which drugs, medical devices and food additives are allowed to enter the U.S. market. It has long borne the brunt of Kennedy’s and other HHS critics’ “corporate capture” accusations thanks to its user-fee funding structure, where companies pay to have their products reviewed by the FDA and help supplement the agency’s congressionally allocated funds.

Corporate influence watchdogs are scrutinizing other recent FDA shifts, too.

While FDA commissioner Marty Makary promised “radical transparency” during his confirmation process, earlier this month he announced a nationwide “listening tour” where he will meet with pharmaceutical and biotech CEOs to solicit their input on “how the FDA can modernize its regulatory framework to better support innovation and patient access to safe and effective therapies.”

Companies are required to have an active drug or device application with the FDA in order to send a representative to meet with Makary.

“The listening tours usually actually involve listening to the public, not just listening to each other,” said Zuckerman. “In the past they’d have it at some university or medical center or something, a public meeting. Anybody could sign up to attend, anybody could sign up to ask questions or make comments.”

The HHS spokesperson said the listening tour is intended to “break through the bureaucratic echo chambers that have long hindered the FDA” and that “direct engagement with regulated industry is essential for real reform and accountability.”

Makary also recently announced a new “Commissioner’s National Priority Voucher” program that would speed up the FDA review process for companies whose products “enhance the health interests of Americans.”

Reshma Ramachandran, a professor of medicine at Yale University who studies the influence of pharmaceutical companies, said the new voucher would likely worsen the existing conflict of interest issues at the FDA. She pointed to the shorter review time and deep personnel cuts at the agency as issues that would increase the FDA’s reliance on what the companies themselves say about their products.

“Will FDA have enough capacity to even push back against companies?” Ramachandran said.

HHS’ spokesperson disputed this characterization, saying that the National Priority Review Voucher program is about urgency, not favoritism.

“Expediting reviews for high-impact products does not compromise scientific integrity — it enhances timely access to innovations that can save lives,” they wrote.

One industry expert said he felt that both could be true at the same time.

“The National Priorities Voucher initiative at FDA goes right to the top of my lists of things that make you go ‘hmmm,’” said Steve Grossman, a regulatory consultant and co-founder of the Alliance for a Stronger FDA. “I like the boldness in thinking about FDA’s contribution to public health, the clear commitment to quicker decisions by the agency and the good sense of starting with a pilot program. At the same time, I worry about diluting the focus on unmet medical needs, the subjectivity of who receives the vouchers and the potential manpower crunch.”

Makary also announced earlier this year that the FDA would limit industry representation on FDA committees to what was “statutorily allowed” — something that Zuckerman said has been “pretty much true for years.”

While changes to committee membership may get plenty of attention, “there’s a much bigger universe of ways in which industry interfaces with HHS and all its subsidiary agencies,” said Matthew McCoy, an assistant professor of Medical Ethics and Health Policy at the University of Pennsylvania who studies conflicts of interest.

“It’s not as if that’s the only way in which industry influences can shape the way that policy making happens within these health care agencies,” said McCoy.

—
Margaret Manto is a NOTUS reporter and an Allbritton Journalism Institute fellow.

CORRECTION: An earlier version of this story misstated Steve Grossman’s title. He is a regulatory consultant and co-founder of the Alliance for a Stronger FDA.

 

Trump’s diversity purge freezes hundreds of millions in medical research at universities across the country

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By Sarah Owermohle, May 8, 2025

Universities across the country are scrambling to comply with President Donald Trump’s anti-diversity push in an effort to hold on to hundreds of millions of dollars in federal grants that fund critical medical research in areas such as cancer and maternal health.

Last month, the Trump administration threatened to cancel medical research funds and to pull the accreditation for universities that have diversity and inclusion programs and that boycott Israeli companies.

The latest moves broaden the anti-DEI mandate that Trump signed just hours into his second term, declaring diversity, equity and inclusion efforts discriminatory.

The administration is locked in a legal battle with Harvard University that on Monday saw officials cut off future funding, escalating a total freeze on $2.2 billion in federal grants directed to Harvard. The university has sued to unlock those funds, a fight that will likely be expensive, and take months to resolve.

Most universities, particularly public and smaller institutions, lack the resources to take up the fight the way Harvard has. Dozens of schools across the country have publicly ended DEI programs and quietly taken down or rerouted websites referencing diversity and equity. Some have more openly acquiesced to the administration’s demands, banning the use of certain words and phrases such as “equality,” “gender” and “White supremacy,” and laying off dozens of university staff.

But those efforts haven’t spared them from mass funding cuts.

At Columbia University, some $250 million in health research grants remain in limbo even after the university made significant policy changes in late March to placate the administration. Leaders at Ohio State University, Vice President JD Vance’s alma mater, acted early to end DEI programs and eliminate 16 staff positions in February, citing Trump’s mandate and a state bill.

But in March, the administration still canceled 10 grants to Ohio State, clawing back $2.4 million in planned spending on HPV and Covid-19 vaccine uptake and separate studies on substance use, suicide risk and PrEP access among different LGBTQ populations.

Starting in February, the US National Institutes of Health terminated roughly 780 research grants that referenced equity, racial disparities, minority health, LGBTQ populations and Covid-19. The canceled grants spanned the country: Roughly 40% were to organizations in states Trump won in November, according to a KFF analysis.

Those have included cuts to research seemingly squarely in line with the stated goals of the Trump administration and US Health and Human Services Secretary Robert F. Kennedy Jr., such as studies on autism diagnoses, chronic disease improvements and environmental exposures’ intersection with health.

Besides the immediate impact of frozen research and staff layoffs, scientists and public health experts worry about a chilling effect for health care studies overall. The NIH is the world’s largest public funder of biomedical research, issuing roughly 60,000 grants a year to nearly 3,000 universities and hospitals. That accounts for more than 80% of the agency’s current $48 billion annual budget, although the administration aims to slash that spending by a third next year.

“People are frightened,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit group aimed at improving health care research. “One of the things that I’ve said to people is, you know, ‘how much can you do what you’ve been doing but just call it something else?’”

That can be a tricky prospect for research on health care issues that disproportionately affect certain populations.

Medical researcher: We should be sharing vaccines with developing world

For instance, the US reports persistently high rates of maternal and infant deaths compared with other high-income countries. There are stark disparities within those figures: Black women are three times more likely to die of pregnancy-related causes than White women.

Researchers and state medical boards attribute those statistics to a range of factors including racial bias, health care access, underlying health conditions and socioeconomic status.

That makes it extraordinary difficult to strip equity, race and risks for certain populations from questions about maternal health care and other research, experts say. Whether it’s new mothers’ postpartum survival, HIV prevention in LGBTQ populations or higher risk of aggressive breast cancer in Black women, many studies necessitate a focus on the people most affected, those experts say. The NIH cut research in all those areas.

“There’s real issues here that could be better understood and responded to, and lives could be saved, but only if you study them – and only if you understand what you’re studying,” Zuckerman said.

Beyond hundreds of grants citing words such as equity, disparities, gender, minority, LGBTQ populations or race, the NIH also canceled spending on Covid-19 outreach, vaccination and messaging.

“HHS grants will only go to the most qualified applicants and will not adhere to ideological requirements or discriminatory quotas,” an HHS spokesperson said in response to questions about the canceled grants.

The mass culling of NIH grants has even stoked concern among Republican leaders who argue that the US could slide in medical innovation and world leadership with the combined funding cuts, mass layoffs and agency shakeups.

“We must not lose sight at what is truly at stake here,” Sen. Susan Collins, a Maine Republican, said during a Senate Appropriations hearing last week. “If clinical trials are halted, research is stopped and laboratories are closed, effective treatments and cures for diseases like Alzheimer’s, type 1 diabetes, childhood cancers and Duchenne muscular dystrophy will be delayed or not discovered at all.”

Maternal health and the DEI battle

In 2023, the NIH launched a $168 million initiative across 10 universities to improve maternal health care.

In March, the agency canceled funding to two of them.

Columbia University, one of the 10 maternal health centers in the mass NIH project, was one of the first schools ensnared in grant freezes and a public battle with the Trump administration.

But the broad grant cancellations also caught the Morehouse School of Medicine, part of a historically Black university in Atlanta, Georgia, a state with some of the worst maternal mortality rates in the country.

Along with Georgia’s Emory University, Morehouse stood up a program focused on improving pregnancy and postpartum care for Black women. There was $1.6 million remaining in the $2.9 million grant when the NIH cut funding. Morehouse School of Medicine President Valerie Montgomery Rice stood fast against anti-DEI efforts in February, telling local radio station WABE that “diversity, equity and inclusion, as it relates to health, is not a political term.”

[….]

“The reason that we knew that we were having disparities in our maternal outcomes is because we started disaggregating the data. We started looking at the outcomes for Black women and White women and Hispanic women,” said one OB/GYN researcher focused on maternal mortality. “If we’re not measuring it, we won’t do anything to improve, because we won’t know. It’s almost like sticking our heads in the sand.”

The researcher asked that their name not be used because they are affiliated with one of the still-funded maternal health programs and are fearful that research could be cut next. Although many of the remaining universities in the program have publicly ended their DEI programs, none feel safe, the person said.

[….]

 

MAHA priorities amid NIH cuts

Dozens of the cancellations seemingly clash with Kennedy’s vision for a healthier America with fewer chronic illnesses, researchers said. Those include at least two research projects aimed at autism, two focused on diabetes and others on cancer research in rural and underserved areas, and disparities in long-term chronic disease outcomes. In most cases, the grants explicitly mentioned a minority population, equity or disparities in care.

Many of those researchers were years, and thousands to millions of dollars, into their projects: Some were ending soon anyway, and had just a fraction of their grants left to spend.

[….]

Ohio State’s 10 canceled grants include one focused on substance use and associated chronic illnesses across sexual minorities in urban and rural areas. Of the nearly $173,000 grant, just $538.11 was left to be disbursed, according to federal data. The grant was cancelled on March 21; it was scheduled to end 10 days later.

[….]

At the Tulane School of Medicine, the $16 million grant for the maternal health center was untouched in March funding cuts. However, the administration did axe the remaining funding, roughly $279,000, for a $4.2 million grant to study lupus progression in Black Americans. Tulane also lost funding for research on Covid-19 treatment in cancer patients.

The medical school has since quietly removed and rerouted diversity pages on its website. The psychiatry department’s page on equity, diversity and inclusion now says that the content is unavailable: “Some content is currently under review to ensure compliance with the latest federal guidelines and executive orders.”

The president of Tulane University announced in a message to students and faculty on March 13 that it would transition its DEI program into a new “Office of Academic Excellence and Opportunity” to comply with federal law. Diversity pages now reroute to that site.

[….]

Read original article here.

Tougher Approval Standards May Follow Vinay Prasad’s Appointment To Lead US FDA’s CBER 

Uncategorized

By Sarah Karlin-Smith, May 7, 2025

The US Food and Drug Administration’s announcement of Vinayak “Vinay” Prasad as the new director of the Center for Biologics Evaluation and Research may signal a major philosophical shift in the data required to approve medical products, particularly cell and gene therapies. 

FDA Commissioner Martin Makary announced the pick of Prasad, a hematologist and oncologist, in a 6 May email to staff obtained by Pink Sheet. Prasad most recently worked at the University of California, San Francisco, as a professor of epidemiology and biostatistics. 

Prasad will replace Peter Marks who resigned from FDA rather than be fired in late March

[….] 

Will Prasad Nix Makary’s ‘Provisional’ Pathway? 

Prasad also has a long track record of criticizing the agency for making it too easy to get drugs on the market, raising concerns about the accelerated approval pathway and recent gene therapy approvals, such as Sarepta’s Elevidys (delandistrogene moxeparvovec-rokl). 

He has supported randomized controlled studies with hard clinical outcomes even as the FDA, including Marks, embraced more flexible approaches, particularly for rare diseases. 

Whether Prasad’s views can align with Makary’s recent proposal for a new ‘plausible mechanism’ pathway for rare disease drugs is unclear. 

Prasad’s history, which includes criticism of the FDA and pharma’s close working relationship, worries industry. 

His appointment “seems counter,” to Makary’s discussions in recent weeks about reforming the drug approval process, particularly for rare diseases, said Nicole Paulk, CEO and Founder of Siren Biotechnology, which is developing gene therapies for cancer. 

“Based on [Prasad’s] books that he’s written and the tweets that he has shared, and podcast that he has been on and all of these various public forums, it would seem to be that his position, kind of broadly regardless of modality is pretty anti-FDA, fairly anti-innovation, fairly anti-accelerated anything,” Paulk told Pink Sheet. 

Investor Misunderstanding About CDER, CDER Product Oversight 

The news of Prasad’s appointment sent biotech stocks plummeting. 

A 6 May analyst note from William Blair suggested investors may be confused about the products regulated by CBER and the Center for Drug Evaluation and Research. The analysts said they do not believe there is a risk to the existing development path for most oncology drugs, which are overseen by CDER. 

For cell and gene therapies, “there are clearly outstanding questions and increased uncertainty now as we wait to see whether Dr. Makary or Dr. Prasad will have more impact on the guidelines and regulatory development requirements for these novel therapies, particularly in rare diseases,” the analysts wrote. “Dr. Makary has been vocal since being confirmed as commissioner for more accelerated approval opportunities in the cases of ultrarare diseases or therapies with overwhelming efficacy.” 

Prasad’s appointment also likely will add to the negative sentiment in the vaccine space, they added. 

A Triumph For Evidence Over Hope? 

Many critics of the FDA’s approval standards hope Prasad’s appointment will lead to tougher approval standards. 

“Like us, Vinay has led several impactful research projects raising concerns around surrogate markers and their lack of association with meaningful clinical outcomes, particularly in oncology,” said Reshma Ramachandran, co-director of the Yale Collaboration for Regulatory Rigor, Integrity and Transparency. “He also similarly expressed concerns around the previous CBER Director’s decision to override multiple scientific and technical review teams to approve Elevidys despite lack of evidence of its efficacy. Hopefully, this is a sign that in his new role, he will listen to his scientific review staff in making regulatory decisions.” 

“I think very highly of him,” said Diana Zuckerman, president of the National Center for Health Research. She suggested that Prasad’s track record suggests someone who would not allow products on the market simply because patients lack any treatment, unlike Marks. 

“I understand the desire to be responsive to patients’ needs and desire to have hope for a new treatment, but I think it does patients no favor to give them false hope by approving treatments that end up being extremely expensive and not only ineffective, but they don’t follow through with the required post-marketing testing,” Zuckerman said. “So for years they end up on the market with companies that make a lot of money off of them and patients who don’t benefit at all or are harmed financially, physically or both.” 

Ethan Perlstein, CEO Of Perlara, a biotech public benefit corporation developing treatments for rare genetic diseases, said the negative reaction to Prasad comes from “traditional bio” because they dislike a person as outspoken as Prasad who “can’t be controlled in some way or is not beholden to them or to anybody.” 

Perlstein said he understands why many in the industry see Prasad as a “chaos agent,” but added that he appreciates Prasad demonstrating that he is “not beholden to anybody except his principles,” and seems willing to evolve. 

Has Prasad Changed? 

Other medical experts who raised concerns about Prasad’s views on COVID-19 and other vaccine issues in recent years acknowledged that before 2020 they liked many of his stances, such as requiring more rigorous follow up on oncology drugs after accelerated approval. 

But they were not confident that Prasad still existed. 

[….]

“He started out criticizing the COVID vaccines and I think a lot of it is audience capture,” said David Gorski, a professor of surgery and oncology at Wayne State University and editor of the blog Science Based Medicine. “As he drifted into more contrarian positions, he got more likes, clicks praise, as a brave truth teller.” 

[….] 

Gorski suggested Prasad is a victim of what he calls “evidence-based medicine fundamentalism,” which is “if it isn’t a randomized placebo-controlled, double-blind clinical trial, it’s crap,” Gorski said. 

[….]

To read the entire article, click here

In Vague Announcement, FDA Says It Will Cut Ad Comm Conflicts

In the News, News Stories & Editorials, We're In the News

Jessica Karins and Maaisha Osman, Inside Health Policy News, April 17, 2025

FDA will not allow experts who are employed by regulated industry to serve on advisory committees, the agency said in an announcement Thursday (April 17), but though the statement was framed as a change in policy, one expert said it was similar to FDA’s existing policy and so vague as to be “an announcement of nothing.” Another researcher, however, said the move come signal an attempt to add voices to advisory committees who are less qualified but ideologically aligned with the Trump administration.

In its Thursday statement, FDA said it was announcing “a policy directive that limits individuals employed at companies regulated by the U.S. Food and Drug Administration, such as pharmaceutical companies, from serving as official members on FDA advisory committees, where statutorily allowed.” The statement also said FDA will “prioritize and elevate the role of patients and caregivers, strengthening the voices of their communities.”

“Industry employees are welcome to attend FDA advisory committee meetings, along with the rest of the American public, but having industry employees serve as official members of FDA advisory committee members represents a cozy relationship that is concerning to many Americans,” FDA Commissioner Marty Makary wrote. “In fact, the FDA has a history of being influenced unduly by corporate interests.”

The announcement said employees of regulated industry can still serve on advisory committees when required by statute, and that “exceptions can be made in rare circumstances (i.e., when the scientific expertise in an area is only available from an employee of an FDA-regulated company) provided that the official strictly complies with the applicable ethics requirements.”

To Diana Zuckerman, president of the National Center for Health Research — an organization that has been critical of FDA advisory committees–the new policy sounded much like the existing policy.

Zuckerman said she’d like to see less industry influence on advisory committees. “It would be great if this is a new day, but it’s just not clear,” she said.

FDA advisory panel members are typically not employees of regulated companies, with the exception of industry representatives, who do not vote. Most expert members are physicians and academics, and most panels include at least one patient, consumer or caregiver representative; these members typically do not vote.

[….]

Zuckerman said the impact of the policy will depend on multiple factors not made clear in the announcement, including whether FDA will also exclude from committees experts who have non-employment relationships with regulated companies. Those relationships, such as past consulting work, research funding or payments for licensed inventions, have been frequently criticized by Kennedy in the past.

At press time, HHS had not responded to Inside Health Policy’s questions on whether these relationships will be included.

Zuckerman also said the allowance for employees of regulated companies to serve on an advisory committee if deemed necessary makes the implications of the announcement more unclear.

Additionally, Zuckerman said, the announcement doesn’t mention other conflicts of interest FDA traditionally hasn’t recognized — such as cases in which a physician has prescribed a product in the past for which safety is now being reevaluated and is worried about being sued, or a physician whose livelihood depends in part on a medical product being examined, such as a plastic surgeon who frequently provides breast implants.

Patients can also have conflicts of interest, Zuckerman said, and the patients FDA typically hears from — whether as patient representatives, consumer representatives or speakers during public comment periods — tend not to be those who have been harmed by medical products.

Michael Abrams, a senior researcher at Public Citizen Health Research Group, said the shift from FDA is opaque but potentially dangerous.

“I think it may be a veiled pretext for RFK Jr. to dissolve existing advisory committees, regardless of membership conflicts, and replace them with individuals who are less scientifically accomplished and adept, but who share the new HHS Secretary’s . . . world view,” he told IHP.

[….]

Abrams also pointed to the practical implications of dismantling or overhauling the current committee system, especially amid recent FDA staffing and budget cuts.

[….]

— Jessica Karins (jkarins@iwpnews.com), Maaisha Osman (mosman@iwpnews.com

To read the entire article, click here.

Canadians could lose vital safety information amid deep cuts to the U.S. FDA, experts warn

In the News, News Stories & Editorials, We're In the News

Annie Burns-Pieper, CTV News, April 13, 2025

Canadian health experts warn the fallout from thousands of job cuts at the U.S. Food and Drug Administration on April 1 could disrupt the flow of safety information on drugs, medical devices, and food to Canada.

For years, Canadian agencies responsible for monitoring food and pharmaceutical safety have worked closely with regulators around the world. The U.S. Food and Drug Administration’s (FDA) vast resources and global influence have played a role in informing decisions in Canada on issues such as safety warnings and recalls of dangerous foods and drugs from the market.

However, sweeping changes to the FDA since U.S. President Donald Trump took office could impact the benefits Canada derives from this historic collaboration, reducing the quality and availability of information about harmful drugs and food products—potentially allowing serious health risks to go undetected and products to remain on the market longer.

The U.S. Department of Health and Human Services (HHS), now headed by Robert F. Kennedy Jr., laid off 10,000 workers as part of Elon Musk’s Department of Government Efficiency task force. The department plans to cut 3,500 jobs directly from the FDA.

A ‘huge problem’

While a memo on the restructuring claimed that layoffs wouldn’t affect reviewers or inspectors of drugs, medical devices, or food, reporting in the U.S. revealed that these areas are being impacted. Reported job losses include lab scientists who tested food for contaminants including deadly bacteria, scientists at drug safety labs, and staff in the drug inspections and investigations office, among many others.

“I think this is a huge, huge problem,” said Matthew Herder, a professor of law and medicine at Dalhousie University who specializes in regulation of pharmaceuticals. He told CTVNews.ca in an interview that Canada has long benefited from the FDA’s size and reach.

[….]

Canada has historically benefited from U.S. post-market surveillance—the ongoing monitoring of drugs and medical devices after they’ve been approved—to detect safety issues that may not have surfaced during clinical trials. “They just have vastly more resources,” said Herder. “The chances of us picking up something before the U.S. are very slim.”

For example, in 2017, Health Canada issued a safety review and letter to health professionals for commonly used antibiotics, fluoroquinolones, following a review by the FDA, warning of a potential risk of “disabling side effects” from tendonitis or nerve damage.

In 2019, Health Canada recalled surgical mesh for transvaginal repair of pelvic organ prolapse following a U.S. recall. Canadian women had reported debilitating side effects, including urinary problems, mobility challenges, emotional distress, and discomfort during sex associated with this medical device.

Diana Zuckerman, the president of The National Center for Health Research in Washington, D.C, called the staff cuts at the FDA a disaster: “you can’t cut 20% of their staff and think it’s not going to have a tremendous impact.”

She said in an interview with CTVNews.ca that post-market surveillance is already under-resourced and worries it will be weakened further by the cuts.

Herder said less surveillance of approved drugs is particularly concerning given the trend in recent years of letting more drugs into the market with less evidence. “If we’re losing the oversight that the FDA offers globally or losing even the percentage of it, that is really terrifying.”

CTVNews.ca asked Health Canada, responsible for drug and medical device safety, about the concerns raised by experts that a diminished FDA could pose risks to Canadians, but the agency declined to comment.

Canadian outbreaks could ‘go totally unnoticed’

Canada has also long collaborated with American agencies for food safety. Keith Warriner is a food safety professor in the Department of Food Science at the University of Guelph. Despite the Buy Canadian movement, he believes imports from the U.S. will continue to be a significant source of food in Canada.

He said American agencies, including the FDA, Centers for Disease Control and Prevention, and the United States Department of Agriculture, have been particularly good at surveillance, and Canadians have benefited from information sharing.

“When an outbreak occurs, they’re pretty hot on it. In Canada, we could get outbreaks that go totally unnoticed,” Warriner told CTVNews.ca. Often recalls and alerts originate with American products and are adopted in Canada, meaning that a delayed response in the U.S. could also impact Canadian consumers.

His biggest concern about the changes to the FDA is that the U.S. might reduce food safety surveillance, and “if they cut back on that, then it’d be outbreaks running rampant.” He suspects the deep cuts will lead to fewer recalls due to a decrease in outbreak detection.

[….]

Dr. Joel Lexchin is concerned that, given the climate of U.S.-Canada relations, pharmaceutical information sharing could be reduced. The retired emergency room doctor and a former professor at York University who has been researching pharmaceutical policy in Canada for more than 40 years told CTVNews.ca, “if the FDA keeps data to itself, unsafe products may remain on the Canadian market for longer than they currently do.”

He would like to know how the historically collaborative relationship between the FDA and Health Canada is currently operating and how Health Canada plans to fill in any gaps left by potential changes in information sharing.

[….]

To read the entire article in CTV News, click here https://www.ctvnews.ca/health/article/amid-deep-cuts-to-the-us-fda-experts-warn-canadians-could-lose-vital-safety-information/

CPTF Public Comment Regarding the FDA’s Draft Guidance for the Study of Sex Differences in the Clinical Evaluation of Medical Products

Uncategorized

April 7, 2025

[Docket No. FDA-2024-D-4245]

Thank you for the opportunity to comment on the FDA’s Draft Guidance for the Study of Sex Differences in the Clinical Evaluation of Medical Products. The National Center for Health Research has conducted research on this issue for decades and our comments today build on the findings of that research.

We strongly support most of the FDA’s proposed guidance, but we note that the agency has attempted to improve the representation of women, older Americans, and racial and ethnic minorities for many years but has fallen short. We have scrutinized this proposed guidance and are providing several suggestions that we respectfully encourage the FDA to implement.

Meaningful Representation of Males and Females and Major Demographic Subgroups

First and foremost, the agency should not focus entirely on increasing females but rather focus on ensuring males and females be substantially represented in all studies of medical products that will be used by males and females. Just as women have historically been underrepresented in studies of treatments for heart disease and several other illnesses, males have been underrepresented in studies of weight loss products and implants that are used by both males and females, for example. We therefore agree with the statement that “For diseases or conditions that can occur in both females and males but rarely occur in one of the sexes in actuality, avoid arbitrary exclusion criteria that prohibit participation based on sex.” It is not sufficient that males and females in the studies be represented in proportion to their likely use of the product; instead, meaningful representation requires that sufficient numbers of patients of the underrepresented sex (or demographic group) be included so that they can be statistically analyzed separately, and the statisticians can draw conclusions about safety and effectiveness for members of each sex.

We agree that sex differences should be the focus, rather than gender differences. We also agree with the importance of enrolling females and males of different ages, races, ethnicities, co-morbidities, and hormonal statuses. For example, when males or females are taking any form of sex hormones for whatever reason (birth control, menopausal symptoms, low testosterone, or due to gender preference), it may be necessary to analyze those groups separately to see if the hormonal treatments affect sex differences. If there are too few to analyze these subgroups separately, the indication on the product label should make it clear that the data may not apply to patients in those subgroups.

We agree with the proposed guidance that companies should analyze and interpret sex-specific data to hormonal and other changes with age, for products used by adults of all ages. Ideally, researchers should first analyze the data separately by sex to see if there are age differences in safety or effectiveness.

Encouraging Rather Than Requiring Meaningful Representation

Unlike other U.S. public health agencies, the FDA merely “encourages representation of females (or other demographic groups) in clinical trials submitted to the FDA” rather than requiring representation. As a result, major demographic groups have often been under-represented in clinical trials submitted to the FDA (Fox-Rawlings et al., 2018). The FDA has justified this lower standard by stating that the studies submitted to the FDA are paid for industry, rather than the U.S taxpayer. However, the U.S. taxpayer pays for the treatments that the FDA approves, even when those treatments are not studied on patients that meaningfully represent the U.S. population. Therefore, encouraging rather than requiring representation is potentially misleading and unsafe for the patients who are not meaningfully represented. At the very least, the FDA should improve the incentives for companies to comply with the recommendations by ensuring that labeling indicates which types of patients were not reliably studied, and limiting the indication to the sex (and age groups, etc.) for whom safety and effectiveness data are reliably provided. 

We support the FDA Draft Guidance statement that sponsors “must submit a diversity action plan with goals for study enrollment, disaggregated by sex, among other demographic characteristics.” Unfortunately, diversity action plans do not always result in achieving the goals intended. We agree with the FDA’s list of ways “to improve the recruitment, enrollment, and retention of females in clinical trials” but believe they are also suitable for improving recruitment of men of all ages as well.

Trial Design

We agree with the initial statement of the draft guidance regarding trial design: “For most drugs and devices, males and females should be included in clinical trials in numbers adequate to allow for reliable benefit-risk assessments and to understand any potential sex related differences in medical product response.” 

However, we strongly disagree with the Draft Guidance’s strong focus on determining if a product is safer or more effective for one sex than the other, because that does not matter to patients. What matters to patients is whether the product is statistically significantly safe and effective compared to placebo or other treatments. In other words, there is no reason why a woman would care if a product is more effective for men that for women as long as it is beneficial in a clinically meaningful way for females. Similarly, why would any man care if a product is safer for women than men, if its benefits outweigh the risks for both? Rather than analyze men and women together and separately and then determine if it is safe and effective for both, as the guidance suggests, it would introduce less bias to start with the smaller number of study participants in each sex and if each has statistically significant benefits that outweigh the risks, then it is not necessary to combine males and females. If those benefits are not statistically significant compared to placebo but suggest meaningful benefits, then the men and women can be combined to see if together the results are statistically significant or not. 

We disagree with the draft suggestion that only where sex differences “are anticipated, there should be sufficient numbers to inform reliable benefit-risk assessments in males and females.” Since, it is often unanticipated or unknown whether there will be sex differences, there should always be sufficient numbers of males and females to provide meaningful data. 

Statistical Concepts

We agree that “Analyzing sex differences in medical product performance is an important component of assessing product safety and effectiveness and can inform what goes in the product labeling to improve patient care.” We also agree that “Sex is [only] one of many potential demographic characteristics typically evaluated in subgroup analyses of a clinical trial or non-interventional study.’ We agree that when many subgroup analyses are performed, some will be statistically significant by chance, and that different effects between males and females may be due to other factors associated with sex, such as age and weight. These must be taken into consideration when multiple statistical analyses are performed.

Reporting Results of Analyses 

We support the requirement that sponsors “must include in their annual reports for drug and biological products conducted under an IND, the number of participants entered into the study to date tabulated by age group, sex, and race, and sponsors must present safety and effectiveness data in the clinical data section of an NDA by sex, age, and racial subgroups. Because the enrollment demographics of the clinical study may impact the generalizability of the conclusions, for clinical studies of devices, the FDA recommends that sponsors report the number and proportion of study participants by sex.” We also agree that “Any potential difference by sex should be investigated, explained, and discussed with the Agency.” 

We agree that the labeling should specify the safety and effectiveness of any product separately for males and females of different demographic subgroups when available, and we add that the labeling should specify when those subgroup analyses are not available.

Other General Considerations 

We reiterate that if a product is not proven safe and/or effective compared to placebo or a different treatment, that information should influence the indication. The Draft Guidance suggests that such differences “may potentially be further explored in a study after approval” and that the FDA can require a postmarketing study when applicable criteria are met.” We strongly disagree with this laissez-faire approach, because it can result in years of inappropriate or ineffective treatment for males or females when other treatments might be more beneficial. Therefore, when there is evidence that a product is not safe or not effective for females, or for males, additional research should be conducted before approval.

For example, in our study of high-risk medical devices, we examined publicly available documents for all 22 medical devices that the FDA designated “highest risk” or “novel,” that were reviewed through the premarket approval (PMA) pathway, and were scrutinized at the FDA public meetings from 2014 to 2017 (Fox-Rawlings et al., 2018).1 We evaluated patient demographics and subgroup analyses for all pivotal trials. Although 20 were intended for men and women, the number of patients in the minority gender was only 1 in one study and half the studies included less than 35% of the minority gender. Only 6 (33%) of the devices included subgroup analysis by sex for safety and 13 (72%) included subgroup analysis by sex for effectiveness. One of the devices, the Lutonix drug-coated balloon catheter used to reduce blockage in the leg, was effective for the total patient sample, but that was because it was effective for men. Women assigned to the Lutonix study arm had slightly worse outcomes than women in the control arm of the study; the artery remained sufficiently dilated a year after the procedure for just over half the women. Nevertheless, the FDA approved this high-risk device for women as well as men. The FDA required a post-market randomized study, but the sponsor said it was unable to enroll a sufficient number of patients. Subsequent data continued to indicate female Lutonix patients did not do as well as male patients, but no publicly available studies indicate if non-drug eluting catheters are superior to Lutonix using real life data. Lutonix continues to be approved for female as well as male patients.

Our study indicated that the frequent lack of subgroup analyses makes it impossible to inform patients or physicians as to whether many newly approved medical devices are safe and effective for specific demographic subgroups defined by gender, race, and age. However, even when the analyses indicated that the women did not benefit from a high-risk device, it was approved by the FDA for women and men anyway.

References

1 Fox-Rawlings, S. R., Gottschalk, L. B., Doamekpor, L. A., & Zuckerman, D. M. (2018). Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients?. The Milbank quarterly, 96(3), 499–529. https://doi.org/10.1111/1468-0009.12344

2 U.S. Food and Drug Administration. (n.d.). PAS 1 (Extended Follow-up Study) [Post-Approval Studies Database]. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm?c_id=&t_id=524729

3 Becton, Dickinson and Company. (n.d.). Lutonix™ Drug Coated Balloon PTA Catheters: Clinical Data. BD. Retrieved April 7, 2025, from https://www.bd.com/en-us/products-and-solutions/products/product-families/lutonix-drug-coated-balloon-pta-catheters#clinicaldata

RFK Jr. brings FDA under tighter control with HHS workforce cuts

In the News, News Stories & Editorials, We're In the News

Lizzy Lawrence, Sarah Todd, and Matthew Herper, STAT News, March 27, 2025

WASHINGTON — Around 3,500 employees are on the chopping block at the Food and Drug Administration, but they don’t yet know who they are.

The Health and Human Services Department on Thursday announced a sweeping plan to cut 10,000 jobs and consolidate operations across its sub-agencies. FDA drug, medical device, or food reviewers and inspectors will not be among those fired, according to an HHS fact sheet. Instead, the cuts will target employees working on policy, human resources, information technology, procurement, and communications. The administration will start sending notices to employees on Friday, with the terminations coming into effect on May 27.

The sparing of FDA reviewers may put some industry leaders at ease, but other FDA experts are concerned that firing the thousands of employees supporting their work will make it more difficult for the agency to promote innovation and protect public health. The layoffs will shrink the FDA by almost 20%.

“Even though the intent is not to affect product reviews or or inspections, inevitably, by cutting back on services, there will be an impact,” said Wayne Pines, former associate commissioner for public affairs for the FDA.

The cuts align with Elon Musk and the U.S. DOGE Service’s mission to trim the workforce. But they also represent HHS Secretary Robert F. Kennedy Jr.’s goal to exert more control over the sub-agencies he oversees. Even high-level FDA officials appear not to have been briefed on the cuts, sources told STAT, indicating a tightening of command within HHS. The power shift is clear on the media side, as STAT’s media requests continue to be redirected from FDA to the HHS press tea

[….]

This is not the administration’s first attempt to shrink HHS. In February, Musk laid off thousands of probationary workers, including people working on food safety, AI regulation, and preventing the spread of infectious diseases. After pushback from the device industry, the administration rehired some FDA reviewers a week later. A federal judge has since paused all the probationary layoffs. The administration has also offered civil servants $25,000 to leave their posts, and instated a strict work-in-office work policy that has alienated some employees.

Several employees at FDA have told STAT that morale is extremely low, particularly given the agency’s leadership vacuum. The Senate on Tuesday confirmed Marty Makary as FDA commissioner, but he hasn’t yet been sworn into the role. Lawmakers pressed Makary at his confirmation hearing about the DOGE cuts at the FDA, urging him to personally assess personnel before any major culling of the agency.

“If confirmed as commissioner, you have my commitment that I will do an assessment of the staffing and personnel at the agency,” Makary said. It is unclear if he will get the chance.

[….]

Pines noted that efforts to consolidate HHS and FDA are not new; as the former head of communications, he’s witnessed several reorganizations. But he said the level of consolidation is unprecedented, and could significantly impact the way FDA operates.

“The concept of consolidation, every secretary has had their point of view about that,” Pines said. “But there’s never been a change like this at FDA anywhere near this scale.”

The cuts seem “too big, too fast. I agree with RFK Jr., who says this is going to be painful, and I’m not sure what the rewards are going to be,” said Diana Zuckerman, a former congressional investigator for FDA approval standards and president of the nonprofit think tank National Center for Health Research. “These kinds of changes usually are extremely disruptive and not productive for at least a few years.”

Zuckerman wondered whether the cuts will ultimately impede Kennedy’s ambitions to reshape U.S. regulation of food. Kennedy has said he wants to focus on food labeling and fixing the “generally recognized as safe,” or GRAS, loophole in FDA review of food ingredients, as well as improving the quality and supply of infant formula. 

“I think those are important,” Zuckerman said. “Who’s going to do that?” Even if the people working on those specific issues are not affected by the cuts, “usually you’d need more people working on those kinds of issues.” 

Around 46% of the FDA’s total budget comes from “user fees” paid by industry to speed up product reviews. The FDA can use this money to fund employees who review medical product applications, conduct research to speed up regulatory decisions, inspect facilities, and evaluate products’ safety after they hit the market. The HHS reduction in force will likely spare most of these employees.

But the cuts won’t make their lives any easier. One FDA employee told STAT they are starting to lose access to medical journals they rely on for regulatory research. Gutting administrative personnel and cutting down on agency resources may slow down reviewers and worsen morale.

“Eliminating those people, it’s just going to be more difficult from a personnel perspective,” said Brian Ravitch, a regulatory consultant at Olsson Frank Weeda who worked for the FDA for 25 years.

To read the entire article, click here https://www.wsj.com/politics/policy/rfk-jr-plans-10-000-job-cuts-in-major-restructuring-of-health-department-bdec28b0

Public Comment Regarding Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway

Policy, Testimony & Briefings

March 10, 2025 — (Docket No. FDA-2024-D-3334)

The National Center for Health Research (NCHR) [and the Cancer Prevention and Treatment Fund] appreciate[s] the opportunity to comment on the FDA’s draft guidance on Accelerated Approval and Considerations for Determining Whether a Confirmatory Trial is Underway. We strongly support the FDA’s efforts to ensure timely completion of confirmatory trials; however, we have concerns regarding the vagueness of key criteria to be used to determine when a trial is considered “underway.” FDA’s clearly defined and specified regulatory expectations are needed to improve corporate achievements and public trust in the Accelerated Approval process.

Concerns About Imprecise Language & Lack of Specificity

As currently written, the guidance relies heavily on important terms such as “diligent and timely,” which are very vague and leave room for inconsistent interpretation by sponsors. Unfortunately, some companies’ definitions of diligent and timely will not be considered timely or diligent by regulators or public health experts and will not reduce the frequent delays in the completion of confirmatory trials. The lack of specific enrollment and timeline benchmarks will result in delays that expose patients to drugs without verified clinical benefit for many years.This is exactly the situation that the guidance is intended to correct. For that reason, we strongly recommend that the FDA replace ambiguous terms with clear, measurable criteria, including concrete benchmarks and milestones and clearly defined interim analyses to avoid delays.

Timeline for confirmatory trials. The draft guidance states that a confirmatory trial’s target completion date should be “consistent with diligent and timely conduct.” This language is too broad and subjective, resulting in a wide range of timelines for target completion dates, many of which will be lengthier than necessary. Since these are just the target completion dates, the actual completion dates are likely to be even later, and there are no specific warnings or penalties in the guidance of how the FDA plans to strengthen accountability. Instead of this vague wording, the FDA should specify that confirmatory trials should be completed within 1-3 years of accelerated approval, depending on how rare the disease is and how large and longitudinal the study is.That is consistent with a review of oncology drugs granted accelerated approval from December 11, 1992, to May 31, 2017.[1] Although 40% of the 93 indications had not yet completed confirmatory trials or verified benefit when the study was published in 2018,  those with confirmatory trials underway at the time of approval were verified after a median of 3.1 years. For the 9 indications without ongoing trials at the time of approval, those that were verified later were verified after a median of 5.5 years, ranging from 0.5 to 12.6 years. Additionally, 8 indications had remained on the market for more than 5 years without verifying their benefit, and 5 indications (5%) were withdrawn from the market. These findings confirm that a substantial percentage of confirmatory studies experience delays or remain incomplete for extended periods, highlighting the need for stronger regulatory oversight to ensure timely completion and protect patient safety.

Patient Enrollment Prior to Approval. The current guidance states that “enrollment of the confirmatory trial has been initiated.” This needs to be clarified. Does “enrollment has been initiated” mean that:

  • one or more patients were enrolled
  • or some number or percentage of patients have been identified as suitable but have not yet agreed to participate
  • or some number or percentage have started providing baseline data
  • or some number or percentage of patients have started treatment
  • or some number or percentage of patients have almost completed treatment?

A 2015 study found that 19% of clinical trials failed to meet accrual goals or were terminated early due to insufficient enrollment, with recruitment challenges cited as a major barrier to trial completion.[2] That is why it is essential that “enrollment has been initiated” be defined as a substantial number of patients (such as 25 patients or 25% of patients, whichever is larger) already have been in treatment long enough to determine if adverse events or other missing data are likely to be a problem.That would better ensure that the trial is feasible as designed.

We agree with the guidance that completion of a confirmatory trial will be compromised when a drug granted accelerated approval becomes available on the market. This is especially a concern when the trial is a randomized, blinded trial, but it is also important to ensure an appropriate comparison sample for any confirmatory study. For that reason, it is essential that all patients be enrolled for most of the planned length of the trial prior to granting accelerated approval or at least prior to making the newly approved drug available on the market. FDA should not permit researchers to break the blinding of an ongoing study or switch to open label as soon as a product has been approved, because it undermines the integrity of the study and makes any results inconclusive or potentially inaccurate. That is unfair to all the patients who enrolled in the study, whether in the experimental or control group, because the study becomes useless in terms of determining the safety and efficacy of the treatment compared to a control group.

We agree with the guidance that “to ensure the confirmatory trial enrolls and retains sufficient U.S. participants, the sponsor’s enrollment strategy should prioritize early U.S. recruitment.” Because of demographic differences, differences in health habits, and differences in medical care and medical systems, U.S. study participants should be considered the most important study population for confirmatory trials submitted to the FDA. However, we disagree with the guidance that implies it is sufficient for the U.S. recruitment “be closer to completion at the time of accelerated approval.” Instead, recruitment in the U.S. should be completed and the treatment of those U.S. study participants should be near completion.

Progress Reports. The 180-day progress reports need to be improved by requiring them to include recruitment rates, patient retention, adverse events and other safety concerns, and additional metrics that will help identify barriers to the timely completion of the study. FDA guidance should clarify what is acceptable and not acceptable if enrollment targets are not met or drop out rates or missing data undermine the integrity of the study.These reporting requirements will improve transparency and accountability and help ensure a level playing field among companies conducting confirmatory trials.

Concerns Regarding Rare Disease Trials. The FDA acknowledges the unique challenges of conducting randomized post-marketing confirmatory trials for certain rare diseases, particularly those with very small populations and high unmet need. As a result, the proposed guidance permits non-randomized post-marketing studies and, in some cases, does not require that a confirmatory trial be underway before granting accelerated approval—provided there is appropriate justification.

While we recognize the difficulties in patient recruitment and trial feasibility in rare disease settings, this plan is overly flexible and will inevitably result in patients, CMS,  and other healthcare entities spending millions of dollars on treatments that have not been proven to provide meaningful clinical benefits. An example of this is the case with Sarepta accelerated approval drugs for Duchenne Muscular Dystrophy.[3] Without a clear requirement that studies be underway, patients will not have the information they need to make informed treatment decisions for many years, and meanwhile other companies will have less incentive to develop new treatments and conduct their studies in a timely manner. Furthermore, the FDA guidance allowing confirmatory trials to be a continuation of the accelerated approval’s trial evaluating the same surrogate endpoint should not be considered to be a confirmatory trial, since many surrogates do not accurately predict a clinically meaningful outcome. However, continuing the initial study for a confirmatory trial that follows the study participants for a longer period of time to evaluate a meaningful clinical endpoint should be encouraged. We previously raised our objection to confirmatory trials that use unproven biomarkers and surrogate endpoints that are not clinically meaningful in our comment for the guidance entitled “Expedited Program for Serious Conditions—Accelerated Approval of Drugs and Biologics” [Docket No. FDA-2024-D-2033], which highlighted the need for stronger evidence.[4]

Patients with rare diseases are desperate for treatments, but deserve better efficacy evidence than has often been provided by the many expensive treatments approved by the FDA. Patients will not get the evidence they need unless the FDA requires specific enrollment milestones pre-approval and a clearly defined timeline for confirmatory trials, with FDA providing incentives to comply and penalties or disincentives for non-compliance. If studies take longer than promised, the FDA should require companies to allow patients to have free access to the drugs under the FDA’s expanded access program until the confirmatory trial is completed. This would balance the need for patient access with scientific rigor and patient safety.

Conclusions

We support the FDA’s efforts to improve the accelerated approval process, but the vague wording of this guidance is very unlikely to achieve that goal. The FDA needs to be more specific and less “flexible” to ensure that confirmatory trials are completed within a few years of accelerated approval and that the trials provide the clinically meaningful information that patients need to make informed decisions.

References

[1] Beaver, J. A., Howie, L. J., Pelosof, L., Kim, T., Liu, J., Goldberg, K. B., Sridhara, R., Blumenthal, G. M., Farrell, A. T., Keegan, P., Pazdur, R., & Kluetz, P. G. (2018). A 25-year experience of US Food and Drug Administration accelerated approval of malignant hematology and oncology drugs and biologics: A review. JAMA Oncology, 4(6), 849–856. https://doi.org/10.1001/jamaoncol.2017.5618

[2] Bull, J., Uhlenbrauck, G., Mahon, E., Furlong, P., & Roberts, J. (2015, September 3). Barriers to clinical trial recruitment and possible solutions: A stakeholder survey. Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/barriers-clinical-trial-recruitment-and-possible-solutions-stakeholder-survey

[3] Bendicksen, L., Zuckerman, D. M., Avorn, J., Phillips, S., & Kesselheim, A. S. (2023). The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence. Annals of internal medicine, 176(9), 1251–1256. https://doi.org/10.7326/M23-1073

[4] National Center for Health Research. (2025, February 4). Public comment on FDA draft guidance: Expedited program for serious conditions—Accelerated approval of drugs and biologics (Docket No. FDA-2024-D-2033). National Center for Health Research. https://www.center4research.org/nchr-comment-accelerated-approval-draft-guidance