FDA Resists Pressure to Tweak Vaccines to Stretch Supply
(Bloomberg) -- The top U.S. drug regulator is resisting calls to tinker with how Covid-19 vaccines are administered, sticking to the scientific evidence and its own procedures after being more flexible in the face of outside pressure earlier in the pandemic.
There have been increasing calls worldwide to experiment with dosing regimens to speed up inoculation efforts and arrest a worsening pandemic. However, the Food and Drug Administration’s leadership pledged in a statement late Monday “to make decisions based on data and science.”
Extending the length of time between shots, or cutting doses by half, hasn’t been studied in clinical trials and could put “public health at risk,” said FDA Commissioner Stephen Hahn and Peter Marks, director of the agency’s office that oversees vaccines, in the statement.
While the FDA has been criticized for its earlier stand on treatments touted by U.S. President Donald Trump, its statement this week is emblematic of how the agency has handled vaccine reviews. It has demanded safety data that rejected Trump’s push for a vaccine by the November election and insisting on a public airing of that data while Trump clamored for authorization.
On Wednesday, the FDA’s stand drew strong support from Francis Collins, the head of the National Institutes of Health, who said any changes in how the shots are given without more data on the effects could prove harmful. “Let’s not make stuff up,” he said during a Washington Post event.
“The FDA has acquitted itself really well with vaccines,” said Jason Schwartz, an assistant professor in the Department of Health Policy and Management at the Yale School of Public Health. “There’s a clear lesson learned.”
While the Trump Administration officials had forecast that 20 million people would get shots by the end of 2020, just 5.05 million were delivered as of Tuesday, according to Bloomberg’s vaccine tracker. That shortfall has spurred speculation by some researchers, politicians and academics on how to get more shots into arms more quickly.
On Sunday, Moncef Slaoui, Operation Warp Speed’s scientific adviser, said the U.S. government is considering cutting doses of the Moderna Inc. shot given to those age 18 to 55 by half. He said there is evidence showing the half-dose provides the same level of protection for that age group, but added that such a decision would be in the FDA’s purview.
“We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster,” Hahn and Marks wrote. “However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.”
Past criticism of the FDA has revolved around the agency’s authorization of treatments that were strongly pushed by Trump.
In March, the agency authorized the malaria treatment hydroxychloroquine for emergency use against Covid-19 after Trump repeatedly touted the drug, calling it a “game changer” even though clinical evidence of its efficacy was lacking. Research later showed the drug didn’t work against the virus and had dangerous side effects, leading the FDA to revoke the authorization in June.
Trump then began pushing the use of convalescent plasma from patients who recovered from the virus as a treatment that would “save countless lives.” The FDA authorized the therapy in August, but Hahn later had to walk back statements exaggerating its benefits. The commissioner has continued to back its use while clinical trials are underway.
This time the FDA finds itself not in opposition with Trump, but a strategy by the U.K. that aims to give one shot of the Pfizer Inc.-BioNTech SE vaccine to as many people as possible as early as possible. The U.K. government has said people can wait as long as 12 weeks to get a second dose rather than the three weeks found to be 95% effective in clinical trials.
Both the companies and the FDA have recommended against that change, saying it’s unclear how long protection from the first shot will last. U.S. health officials, meanwhile, have kept about half of available vaccine supplies in storage to ensure people get their second shot on time.
Advisers to the World Health Organization also warned that official dosing schedules should be maintained, but left wiggle room for countries to follow the U.K.’s example.
Countries facing “exceptional circumstances of vaccine supply constraints” can delay administration of the second dose of two-shot vaccines for a few weeks, according to a statement on Tuesday by Alejandro Cravioto, chairman of the Strategic Advisory Group of Experts on Immunization for WHO.
In the U.S., supply hasn’t yet been an issue. Instead, the drive to vaccinate most Americans has been hampered by ineffective coordination and a lack of federal support for states and health-care systems.
But Walid Gellad, an associate professor of medicine and health policy at the University of Pittsburgh who supports stretching out the time between shots, said this will soon change as states ramp up over the next week or two to reach people beyond front-line health-care workers.
In Pennsylvania, where Gellad lives, the department of health has said it will begin listing public vaccination sites as early as this week that will service the general public.
“The bottom line for me is we’re keeping dosages in the freezer while we’re running out of oxygen for patients in L.A.,” Gellad said. “Let’s not lose sight of that.”
Meanwhile, scientists at the NIH and Moderna, the maker of one of the vaccines authorized for emergency use, are analyzing research data to see whether the company’s doses are as effective if cut by half, the New York Times reported.
That research could take about two months, the Times was told by John Mascola, the director of the Vaccine Research Center at the NIH.
It may be that some states eventually make their own decisions about how to use vaccines.
However, Holly Fernandez Lynch, a University of Pennsylvania bioethicist, warned that the existing vaccines have been authorized only on an emergency basis, not with full approvals. That could muddy up doctors’ ability to use vaccines in ways that don’t conform with the instructions on the label.
While doctors can’t force drug or vaccine companies to produce evidence or share all their data, the FDA can, Fernandez Lynch said. “FDA plays a critical role in both forcing the production of evidence and evaluating evidence in a way that individual doctors simply cannot,” she said.
As it was pushed to speed its vaccine authorizations over the last few months, the FDA has emphasized that it looks deep into companies’ clinical trial data to confirm findings and understand how a product works.
“We find ourselves with two rigorously, carefully studied and evaluated vaccines that have shown high levels of efficacy and high levels of safety,” Yale’s Schwartz said. “My concern is we would essentially set aside all of that hard work, all of that good persuasive evidence, and improvise.”
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