WASHINGTON — When the Food and Drug Administration allowed unproven coronavirus antibody tests to go to market in March, without validating their accuracy first, Regina Barrell worried about the consequences to the credibility of the agency where she had spent her career.
Consumer safety experts such as Barrell, a former FDA official who worked at the agency for 30 years, watched as over a dozen different tests reached the public only to produce flawed, unreliable results.
As defects in the serology tests were discovered throughout April, another concern emerged. Hydroxychloroquine, a malaria drug pushed by President Donald Trump as a potential “miracle” treatment for those critically ill with COVID-19 and authorized by the FDA for emergency use, was proving harmful to the oldest, most vulnerable victims of the growing pandemic.
The FDA reversed course on both decisions in recent days. Last week, the agency warned doctors against the use of hydroxychloroquine on coronavirus patients, and on Monday it demanded companies that produce antibody tests prove their effectiveness.
But career public health officials saw these early developments as warning signs that a greased regulatory framework, put in place in the heat of an unprecedented crisis, could become a slippery slope inflicting long-term damage on the agency’s credibility.
As the FDA uses emergency powers to fast-track antibody testing, drug treatments and vaccine trials during the pandemic — circumventing regulations that have been honed for decades by public health officials — medical experts are asking if there is any going back.
“The question of false positives and false negatives goes to the heart of why these regulations are needed,” said Barrell. “We were always considered the gold standard in the world for health agencies — if you passed FDA muster, you got a gold star. For the agency to be impacted negatively one way or another would be a tremendous detriment not just to our country but to the world.”
Since the coronavirus outbreak became apparent in the United States, Trump and Vice President Mike Pence have called on the FDA to cut red tape obstructing diagnostic and serological tests, drug treatments and vaccine trials over half a dozen times from the White House podium.
But to the extent the Trump administration has acted with speed, it has primarily relied on emergency powers that were signed into law by former President George W. Bush in 2004 — motivated then by fears of a potential biological terrorist attack — and expanded upon during the Obama administration in 2013 with bipartisan support from Congress.
Those powers were designed to allow the FDA, housed in the Department of Health and Human Services, to quickly authorize the use of medical equipment, drugs, tests and gear in the event of a public health emergency — medical devices that had yet to secure approval under normal circumstances.
Public health officials say that, without those emergency authorities, the Trump administration would likely have relaxed FDA regulations in response to the crisis. That would have left the FDA without a framework in place to restore its pre-pandemic standards once the crisis ends.
“Obviously that was put in place to protect against backpedaling — ideally that’s the way things will be applied,” said Richard Frank, a Harvard professor who served as assistant secretary for planning and evaluation at the Department of Health and Human Services in the Obama administration. “But given that the devil is in implementation, how we go back to, in a sense, regular law if you will, is going to be very important. We want to go back to a world that prioritizes evidence-based treatment.”
Trump, who campaigns and governs as a businessman intent on cutting red tape across federal agencies, has repeatedly cited the removal of “unnecessary” bureaucratic hurdles as a top accomplishment of his administration in its response to the pandemic. And that is raising questions over whether he plans to allow those regulatory standards to return.
“We’ve launched an unprecedented effort to develop new treatments and therapies to battle the plague,” Trump said last month, hailing FDA Commissioner Stephen Hahn for the pace of his work.
“This extraordinary program is slashing red tape to speed in development,” Trump said. “If you look at what we’re doing in terms of the speed, it’s unrivaled. It’s totally unrivaled. There’s never been anything like it.”
In a statement to McClatchy, Hahn said that steps the FDA has taken using its emergency authorities have “been based on a careful, science-based balancing of the risks and benefits of making unapproved medical products or unapproved uses of approved medical products available to combat the pandemic.”
“The agency will continue to evolve its approaches both during and after this public health emergency,” the FDA commissioner said, “with a focus on efficiently using the full breadth of our authorities to ensure the safety, quality and supply of FDA-regulated products and provide the industries we regulate with the tools and flexibility to do the same.”
FDA officials who spoke with McClatchy note that, while the emergency use authorizations are meant to be temporary, there are no timetables built into the law that strictly limit their use. They can last for however long the secretary of the Department of Health and Human Services deems them necessary — possibly for years in the case of the COVID-19 pandemic, if the crisis drags on.
That prospect concerns public health officials, who worry that early FDA missteps on antibody testing and hydroxychloroquine have already compromised a fragile public trust.
“We’ve seen a bit of a whipsaw in the last couple months,” said Daniel Carpenter, author of “Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA,” and a Harvard professor. “It was a departure from the FDA’s modus operandi over the long haul, and I think what you’re seeing now is kind of in part a reaction to the pressure, and in part — I would have to guess — concern with their own credibility.”
One FDA official defended the agency’s initial guidance on antibody tests, telling McClatchy that “a higher level of flexibility was appropriate for antibody tests than for molecular tests that detect the presence of the virus” so that scientists could begin collecting large sets of data on the prevalence of COVID-19 early in the pandemic.
“The careful balancing of risks and benefits has shifted,” the official said.
Carpenter expressed confidence that the standards governing most of the FDA’s work — which regulate roughly 25% of all consumer spending in the United States — would remain unaffected by the pandemic fallout. But he predicted “a new normal” for testing and infectious disease research going forward.
“At some level, when you’ve got a lot of products coming out to the market, and people are saying, ‘many of them don’t work,’ that is a sign of the FDA not working,” Carpenter said. “They need to provide a floor for our beliefs.”
It is not only tests for antibodies — which determine whether an individual has recovered from COVID-19, the disease caused by the coronavirus — that have proved flawed. One rapid diagnostic test approved by the FDA, which debuted in the White House Rose Garden and was taken by the president himself, was recently found to produce false negative results roughly 15% of the time.
“It’s very un-FDA like to let these flimsy diagnostic tests get through — it reflects to me great pressure,” said Michael Kinch, associate vice chancellor at Washington University in St. Louis and the founder of its Centers for Research Innovation in Biotechnology and Drug Development.
Out of 18,000 employees at the FDA, only a handful are political appointees — a rare agency structure designed to insulate its workforce from political influence. Hahn has been the lone FDA representative at White House coronavirus task force news conferences throughout the crisis, offering the public caution while echoing Trump’s praise of agency staff for working at record speeds.
FDA officials, including Hahn, reject the notion that political pressures have interfered in the agency’s operations, insisting that an urgent sense of public duty has motivated its work to quickly identify tools that can combat the pandemic.
But some worry political pressures could soon come to bear on agency leadership over approving a vaccine, the most important decision the FDA could make over the course of the pandemic.
“I give the president credit for being America’s optimist in chief. There’s enough doom and gloom out there,” said Peter Pitts, former associate commissioner of the FDA under the Bush administration. “But I don’t know where the president’s getting his information on the timeline for a vaccine.”
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said the agency would ensure that any vaccine that emerges “meets our high standard for safety and efficacy.”
“Nobody’s looking to skip any of the parts of the development program to lead to a safe and effective vaccine,” Marks said in a virtual event with Axios on Monday. “That said, in this particular crisis, we need to try to move very quickly to get there, working meticulously, because there is just so much at stake here.”
On Sunday, Trump said he is “very confident” his administration will identify, approve and distribute a vaccine by the end of the year.
“All of this talk about not just a vaccine being identified and approved in a year, but being rolled out to 350 million Americans, is irrational exuberance,” Kinch said. “And it’s not benign, meaning that we being scientists and the FDA have only a finite amount of credibility. If we start to make broad claims and statements that we can’t back up, that credibility starts to shrink.”
Career FDA officials expect their internal debate over approving a coronavirus vaccine to be loud and rancorous, given its consequences both for the agency and for the public.
Scientists at the agency carry with them the weight of its past failures, controversies and legacy moments, such as the recall of Vioxx over its linkage to increased heart attack and strokes, the debate over the efficacy of Exondys in treating muscular dystrophy, and the lessons of Frances Oldham Kelsey, a former FDA reviewer credited for standing up against the approval of the drug thalidomide, which later proved toxic for pregnant women.
But even when the agency, under intense public scrutiny, weighed the careful balance of risks and benefits in approving cancer medications in the 1970s and HIV/AIDS treatments in the 1980s, it did not face the concentrated pressures of a global focus and the president’s undivided attention.
“I can’t say that politics won’t try and push it through,” Barrell said, on the political push for a vaccine before the November election.
“But I think if it does, there would be a lot of people screaming,” she said. “It would be obvious that something’s going on. You’ll hear their voices that something’s not right.”
———
©2020 McClatchy Washington Bureau
Visit the McClatchy Washington Bureau at www.mcclatchydc.com
Distributed by Tribune Content Agency, LLC.