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New genetic research points to Wuhan animal market as origin of COVID pandemic, study says

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New genetic research points to Wuhan animal market as origin of COVID pandemic, study says

A new analysis of genetic material gathered from a live-animal market in Wuhan in the early weeks of the COVID-19 pandemic strengthens the case that the outbreak originated there when the coronavirus jumped from infected animals to humans, scientists said.

The findings, reported the journal Cell, do not identify any specific infected animal that brought the SARS-CoV-2 virus to a Chinese city inhabited by more than 11 million people. Nor do they definitively prove that the Huanan Seafood Wholesale Market was Ground Zero for a pandemic that has resulted in more than 7 million deaths.

But the genetic evidence shows the market met the conditions necessary to spark an outbreak and makes it increasingly difficult to explain how the coronavirus could have emerged from a laboratory, a farm or even from another of the city’s four live-animal markets, the study authors said.

“It’s like if a gorilla virus emerged in San Diego and first hit people who worked at the San Diego Zoo and lived nearby, then spread later more widely,” said Michael Worobey, an evolutionary biologist at the University of Arizona who worked on the study. “It would not be difficult to reason that it very likely came from the gorillas at the zoo.”

The root cause of the pandemic has been hotly debated since its early days. Wuhan is home to a government laboratory where scientists study coronaviruses similar to SARS-CoV-2, a fact that prompted politicians, national security experts, late-night talk show hosts and many scientists — including Worobey — to question whether the virus had leaked from the lab.

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Compelling though the argument may be, hard evidence to support the leak hypothesis has been lacking. Meanwhile, more information has come to light that has persuaded scientists with expertise in relevant fields that the virus that causes COVID-19 originated in animals, just like the viruses that cause SARS, MERS and influenza.

The new results continue that trend, said Dr. Dominic Dwyer, a member of the international task force that investigated the pandemic’s origins for the World Health Organization.

“You put all of these origin hypotheses on the table, and then some of them become stronger as you get evidence,” said Dwyer, a medical virologist at the University of Sydney and Westmead Hospital in Australia who wasn’t involved in the latest work. “This paper has more evidence that supports the animal origin through the Huanan market.”

The analysis published Thursday was based on genetic data gleaned from hundreds of samples gathered in and around the Huanan market collected by researchers from the Chinese Center for Disease Control and Prevention soon after the market was shut down on Jan. 1, 2020. The Chinese team detected the coronavirus in 74 of the environmental samples they tested, according to their report last year in the journal Nature.

Worobey and his colleagues dug deeper into that data. Using two distinct gene-sequencing techniques, they looked for pieces of SARS-CoV-2 as well as for DNA from animals and people.

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Then they plotted what they found on a map of the sprawling market, allowing the team to reconstruct how a few initial infections could have ballooned into a global health emergency.

Among 585 samples gathered in early January 2020, the ones that contained the coronavirus were clustered in the southwestern section of the market. That happened to be the area where wild animals were held in cages for sale.

“The market covers a couple of acres, and this comes down to one corner of the market, and to a couple of stalls,” Dwyer said. “That fits with an animal origin. If it was coming from people wandering around the market, you’d find it everywhere.”

One market stall “stood out,” the study authors wrote. It had evidence of SARS-CoV-2 in multiple places: on at least one cart, on an iron container, on the ground, and on a machine used to remove hair and feathers. The researchers dubbed it “wildlife stall A.”

Another 60 samples were taken from the market’s drainage system at the end of January 2020. The researchers found genetic evidence of the coronavirus in four of them, including one in front of wildlife stall A.

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That drain was still testing positive for SARS-CoV-2 in mid-February. So were two drains downstream from it that could have been contaminated by runoff from wildlife stall A, the researchers wrote.

The samples from the stall that contained the coronavirus also contained DNA from a variety of animals, including dogs, rabbits, hoary bamboo rats, Malayan porcupines and masked palm civets. The most abundant DNA was from raccoon dogs, and some was detected in a nearby garbage cart that also tested positive for the virus.

The closest-known relatives to SARS-CoV-2 that exist in the wild are coronaviruses that circulate in horseshoe bats in southern China, Laos and Vietnam and in pangolins from southern China. But no DNA from bats or pangolins turned up in any of the Huanan market samples.

Raccoon dogs, masked palm civets, hoary bamboo rats and Malayan porcupines have transmitted bat coronaviruses before, the study authors noted. Could they have done so in Wuhan, they wondered?

Security guards stand in front of the closed Huanan Seafood Wholesale Market in Wuhan on Jan. 11, 2020.

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(Noel Celis / AFP via Getty Images)

It is unclear whether bamboo rats or Malayan porcupines can be infected with SARS-CoV-2, the study authors wrote. There is no hard evidence that masked palm civets can catch the virus, but cell lines from the animals were susceptible in laboratory experiments.

Raccoon dogs, on the other hand, are known to catch and transmit SARS-CoV-2. And they were the most abundant animal in wildlife stall A.

The researchers dug into the raccoon dog DNA to see if they could have come from southern China, where they might have crossed paths with bats. They couldn’t tell, but they were able to rule out a connection to raccoon dogs that lived on fur farms in northern China.

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Worobey and his colleagues also studied non-SARS-CoV-2 animal viruses that were detected in wildlife stalls to see if they offered clues about where the infected animals had come from.

A kobuvirus that infected civets in the Huanan market was closely related to a virus detected in animals sold in Sichuan and Guangxi provinces, which are closer to the territory of horseshoe bats and pangolins. And a betacoronavirus that infected bamboo rats had a close relative on a bamboo rat farm in Guangxi, one of two southern provinces where market vendors were known to have sourced the animals.

“These findings suggest some movement of infected animals from southern China to Wuhan, a trade conduit that could have also led to the emergence of SARS-CoV-2,” the study authors wrote.

Nailing this down will require more sleuthing, including field work to collect samples from animals in China, said Florence Débarre, an evolutionary biologist at the French National Centre for Scientific Research in Paris and the study’s senior author. Worobey said he plans to continue this line of inquiry.

Dwyer praised the effort to determine where the animals in the market had come from — and by extension, how the virus could have gotten to the market.

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A second line of evidence also supports the hypothesis that the pandemic had a so-called zoonotic origin, scientists said.

Among the samples collected at the Huanan market on Jan. 1, 2020, the researchers were able to identify four nearly complete SARS-CoV-2 genomes. One of them was from so-called lineage A, and the other three were from the closely related lineage B.

The researchers weren’t able to tell whether those viruses were shed by animals or people, but the lineage A sample came from a stall where a worker sought medical attention in mid-December 2019. Although that was weeks before COVID-19 had been recognized as a disease, a report from the World Health Organization later described the worker as a suspected early patient.

Confirming the presence of both lineages in the market allowed the team to compare their genomes and work backward to figure out when the two strains diverged, and what their most recent common ancestor looked like. They came up with six candidates, some of them more plausible than others.

There was a 99% probability that one of the four most likely candidates was correct, and those four all had something important in common: They were “equivalent or identical” to the most recent common ancestor for the pandemic as a whole, said study leader Alexander Crits-Christoph, an independent computational microbiologist.

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That’s what they would expect to find if the outbreak began at the Huanan market, the study authors said. In that scenario, an animal or animals infected with the virus arrived at the market in November or early December. The virus then spread among animals held in close quarters indoors, as well as to their human handlers. Those conditions would have given the virus the multiple chances it needed to establish itself in people and begin spreading among its new hosts in a densely populated city.

On the other hand, it’s getting more difficult to fit all of this evidence into a coherent story that has the coronavirus entering China via imported frozen food (as the Chinese government has claimed) or escaping from a virology lab with lax biosecurity protocols (as some members of the U.S. intelligence community have proposed), Dwyer said.

“We’ve had nothing added to support the lab leak or the frozen food theories,” he said. “It just continues to strengthen the animal and market hypothesis.”

Considering that the pandemic began in a city with a virology lab where scientists study coronaviruses, it makes sense to ask whether that’s more than a coincidence and to wonder whether incriminating evidence is being covered up, DéBarre said.

“Many of us were extremely open to this idea,” she said. “But then data have accumulated, and they all go in the same direction — they all point to the market.”

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“In science you very rarely have final answers,” she added. “You say, ‘Given all the data we have, this looks like the most likely interpretation.’”

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Senators Press Marty Makary on Abortion Pills and Vaccines

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Senators Press Marty Makary on Abortion Pills and Vaccines

At a confirmation hearing for Dr. Marty Makary on Thursday, senators focused heavily on the safety of the abortion pill, with Republican lawmakers urging him to restrict access and Democratic lawmakers demanding that he maintain its current availability.

Dr. Makary, President Trump’s nominee to lead the Food and Drug Administration, signaled that he shared Republicans’ concerns about the current policy, issued during the Biden administration, which expanded access by allowing people to obtain the pills without an in-person medical appointment.

Several Democrats pointed to volumes of studies showing that the drugs are safe. Dr. Makary told members of the Senate health committee, which held the hearing, that he would review the pill’s safety and the policy at issue.

He said he would “take a solid, hard look at the data and to meet with the professional career scientists who have reviewed the data at the F.D.A. and to build an expert coalition to review the ongoing data, which is required to be collected.”

The hearing also touched on vaccines, with several lawmakers, including the committee chairman, Senator Bill Cassidy, Republican of Louisiana, questioning why an advisory committee meeting on next year’s flu vaccine had been canceled in recent weeks and asking whether it would be held later. He and others stressed that the flu panel met annually, and some reminded Dr. Makary that Robert F. Kennedy Jr., who oversees the F.D.A. as health secretary, had pledged transparency in agency decision-making.

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Senator Patty Murray, Democrat of Washington, called the cancellation “unprecedented and dangerous” after decades of annual meetings.

Dr. Makary repeatedly reminded senators that he was not responsible for scrapping the meeting. He also suggested there was a need for a broader review of the role of vaccine committees that convene experts to advise the F.D.A. He shot back at criticism, saying there is a “huge difference” between “requiring every 12-year-old girl to get an eighth Covid booster” and “rubber stamping” the vaccine chosen by a global health panel that had targeted dominant influenza strains.

He offered no details about any school or entity that requires children to have annual Covid boosters.

He also was questioned about the measles vaccine in light of the current outbreak in Texas, where one child has died and 22 people were hospitalized.

“Vaccines save lives,” Dr. Makary said. “I do believe that any child who dies of a vaccine-preventable illness is a tragedy in the modern era.”

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But he did not take the bait lobbed by Senator John Hickenlooper, Democrat of Colorado, who criticized Mr. Kennedy’s endorsement of vitamin A and cod liver oil as remedies for measles. Dr. Makary responded by saying that supplements can improve conditions like malnutrition, which is associated with poor outcomes in measles outbreaks.

Lawmakers also warned about staff cuts and hiring freezes the Trump administration has ordered and how they could affect workers who inspect the safety of the food supply, and urged Dr. Makary to review the layoffs among those staff members whose salaries are backed by industry fees.

They also touched on work related to chemicals like dyes in the food supply, an area Dr. Makary agreed to study, invoking European products with fewer additives as an area for review.

Among other issues raised during the hearing, the vexing problem of illegal vape products from China with unknown ingredients was stressed by Senator Ashley Moody, Republican of Florida.

The vapes tend to have high levels of nicotine, advertise thousands of puffs and come in flavors like strawberry lemonade that are appealing to adolescents.

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Ms. Moody said it was concerning that the products were banned within China.

“Whoever comes in as the head of F.D.A., this is one of your problems you have to address immediately,” said Ms. Moody, who was previously Florida’s attorney general.

Blocking the flow of the unauthorized vapes has been a priority for major tobacco companies that have followed F.D.A. rules and marketed vapes in tobacco or menthol flavors in the United States. It’s a priority public health groups also share. Dr. Makary said he would address the problem with the F.D.A.’s law enforcement division and the Justice Department.

Throughout the hearing, several senators returned to the abortion pill and the F.D.A.’s oversight of policy changes during the lengthy history of medication abortion over more than two decades.

Mifepristone — part of the standard two-drug medication regimen now used in nearly two-thirds of abortions — has become a focal point of anti-abortion efforts since the Supreme Court overturned the national right to abortion in 2022.

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In a lawsuit filed against the F.D.A. and other efforts, abortion opponents have demanded that the agency either withdraw approval for mifepristone or roll back regulations to prevent abortion pills from being prescribed by telemedicine and mailed to patients.

The Biden administration waived the in-person dispensing requirement in 2021. Senator Maggie Hassan, Democrat of New Hampshire, said that she was concerned that Dr. Makary would “unilaterally overrule the data that currently exists for political purposes and for political reasons.”

Dr. Makary repeated that he had no preconceived notions and would examine the data. “I wish you were hedging a little bit less today,” Ms. Hassan shot back.

Mifepristone, which blocks progesterone, a hormone necessary for pregnancy to develop, has long been regulated by the F.D.A. under an especially strict program that applies to only a small number of drugs.

For years after its approval in 2000, mifepristone could be prescribed only by a doctor and patients were required to attend three in-person doctor visits to obtain and take the medication. In 2016 and 2021, based on updated scientific evidence, the agency made several changes, including that nurse practitioners and some other health care providers could prescribe mifepristone and that patients did not have to pick up the medication in person.

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Senator Josh Hawley, Republican of Missouri, argued that the policy change to drop the requirement for in-person appointments was made in anticipation of the Supreme Court decision that overturned Roe v. Wade.

Reproductive health experts and organizations, however, had long argued that the requirement was unnecessary for safety and noted that the F.D.A. had already allowed women to take the medication at home without being supervised by a doctor. The Covid pandemic increased the importance of allowing people to obtain the pill by mail because many patients were not able to visit clinics or abortion providers.

Pressed further by Mr. Hawley, Dr. Makary signaled that he shared the concerns of some abortion opponents and said that he knew doctors who preferred to give the drug in their office: “I think their concern there is that if this drug is in the wrong hands, it could be used for coercion,” he said.

Mr. Cassidy closed the hearing with a direct request: to change the policy back to what it was in the first Trump administration and require an in-person visit.

The F.D.A. has a staff of about 18,000 and a budget of about $7.2 billion. The agency has vast regulatory authority over products that include prescription and over-the-counter drugs, medical devices, tobacco and about 80 percent of the food supply. It also regulates artificial intelligence software used to scan medical images, an area where the agency has been dismissed as too permissive in its approvals.

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If confirmed, Dr. Makary would first encounter tensions among staff members, who have been whipsawed by the Trump administration’s aggressive measures to reshape the federal bureaucracy in recent weeks.

The staff endured an initial round of about 700 layoffs, decimating some product-review teams that ensure the safety of medical devices such as surgical robots and systems that deliver insulin to people with diabetes. Those firings were followed by some job reinstatements, though many of those in the tobacco division who review the safety of new products and lost their positions, were not called back.

Asked about the layoffs, Dr. Makary said he supported efforts to increase efficiency and that he would review recent personnel decisions.

Pam Belluck contributed reporting.

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Contributor: How federally funded research saved my son's sight — and his life — from a rare cancer

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Contributor: How federally funded research saved my son's sight — and his life — from a rare cancer

If you want to make this country great, imagine the strength of a nation whose children have been fought for and know they have been fought for.

Last month, my son reached two years in remission from a rare, malignant cancer that almost took his eye and his life. He is alive, well and enjoying 20/20 vision because of a groundbreaking treatment that was pioneered by National Institutes of Health researchers, among others, and funded by the government grants the Trump administration is blocking and threatening to cut. If the president continues on this course, children diagnosed during and after this administration will needlessly fare worse than those who came before.

My son Jack was diagnosed in 2022 with retinoblastoma, a malignant childhood cancer of the central nervous system that originates and grows in the eye. If left untreated, it typically migrates through the optic nerve to the brain, eventually metastasizing and taking the life of the child.

Because the cancer usually attacks children under the age of 3, its victims are often unable to report the symptoms of a mass blocking their vision until it’s too late to treat with procedures that can salvage the eye. That’s when enucleation — removal of the eye — is required.

This is why pediatricians developed standard screening for retinoblastoma starting at birth. This now-routine preventative care has enabled medical professionals to find and treat most cases without a loss of vision or life. Because of these developments and others, retinoblastoma has a very high survival rate in 21st century America.

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Jack’s was one of very few documented diagnoses with retinoblastoma after the age of 8. His oncologist suggested his tumor had been hiding in a dark corner of his retina for years, out of his vision and that of physicians; other doctors thought it had “self-arrested” or presented late and grew rapidly. We discovered it only because it burst from the impact of a belly flop at the neighborhood pool, spewing cancer cells in a constellation of poison floating inside his still-intact eyeball, visible to Jack as spots that didn’t go away.

It took weeks for doctors to nail down the diagnosis. When we walked out of that appointment on a day that was so windy I had to hold onto my dress, I put Jack in the car, turned the radio on for him, closed the passenger door and walked about 30 feet away to scream in the parking lot. “My baby!” I wailed through the phone to my mother.

It was an advanced-stage tumor, complicated by the release of cancer cells inside his eye. They could now attach and grow anywhere within — including the optic nerve, with its direct connection to his brain — if we didn’t act quickly. We might have just days before it was too late.

“We could remove his eye,” our oncologist offered at first, “and even that might not be enough.”

Medical researchers from universities and the National Institutes of Health rally near the Health and Human Services Department’s headquarters in Washington.

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(John McDonnell / Associated Press)

Then he explained that we could try to save his eye with a highly advanced procedure called intra-arterial chemotherapy, or IAC. It involves threading a catheter through the thigh’s femoral artery, behind the heart through the carotid artery and into the skull. An interventional radiologist, guided by MRI, releases the chemotherapy agent directly into the artery feeding the retina. This allows doctors to deliver more aggressive and targeted medicine to the diseased cells and limit damage to the healthy ones.

Our oncologist explained that IAC is still a very new technology but one with extraordinary promise whose benefits far outweighed the risks for Jack.

My son underwent six rounds of intra-arterial chemotherapy and seven rounds of intravitreal chemotherapy, in which the medicine is injected directly into the eye. He went under anesthesia 13 times in six months, required monthly breathing treatments that made him spit gray foam, and lost most of the brow and all the lashes around the affected eye. His list of drugs included ketamine, propofol, hydromorphone, melphalan, fentanyl, topotecan, pentamidine, albuterol, prednisolone and aldosterone. At one point, he needed epinephrine because he nearly went into cardiac arrest. Toward the end of his treatment, he received cryotherapy to kill the base of the tumor and woke up from surgery in so much pain that he gritted his teeth to the point of cracking one.

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At every turn, my family was reminded of our privilege — to live in a country that was scientifically advanced enough to have developed such miracle treatments, to live in a city (Denver) with such good hospitals, to have good health insurance through my husband’s employer. If we had lived without such access to care, in a country lacking our resources or just 15 years earlier, our story would have ended differently. Instead, nine months after his diagnosis, thanks to the advanced research our country has supported socially, academically and financially, my son’s cancer was in remission.

My family recently attended a gathering with other retinoblastoma survivors, from toddlers to adults who had conquered the disease decades earlier. As each survivor entered the conference, it became evident that this was once primarily a disease of blindness: The price of survival was generally a loss of sight and eyes. Some of the older survivors had facial abnormalities from radiation or enucleation. Some had canes or family members to guide them. When we told the group that Jack’s body, vision and dream of becoming a pilot were all still intact, many gasped in awe that the science had advanced so far.

But now the Trump administration’s lack of empathy threatens other children and families facing such horrific diagnoses. Continuing research on intra-arterial chemotherapy and other treatments at the University of Colorado’s Anschutz Medical Campus, where Jack was treated, is paid for by programs in the administration’s crosshairs. “These cuts to NIH funding jeopardize the foundation of our life-saving research,” a university spokeswoman told Chalkbeat Colorado. “Reduced research capacity means fewer scientific discoveries, job losses and delayed advancements on therapies and cures that could improve — and save — lives.”

I wonder whether our hospital will be able to continue offering groundbreaking treatments should Jack face a recurrence. And will the newly diagnosed have the same access to care that we did? What greatness can be celebrated when a mother fears she will lose her child’s access to lifesaving treatment?

My son’s recovery was a direct result of the greatness of our country and its past leaders, who had the foresight to pursue progress and excellence in science and refuse to accept losing children without a fight. Because of it, I believe my son will someday fly planes. And I can only hope the next child who faces a dire disease will get the same chance he did.

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Dayna Copeland is a writer and teacher in Colorado.

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Florida Seeks Drug Prescription Data With Names of Patients and Doctors

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Florida Seeks Drug Prescription Data With Names of Patients and Doctors

Florida’s insurance regulator has demanded an unusually intrusive trove of data on millions of prescription drugs filled in the state last year, including the names of patients taking the medications, their dates of birth and doctors they’ve seen.

The Florida Office of Insurance Regulation in January sought this information from pharmacy benefit managers like UnitedHealth’s Optum Rx and CVS Health’s Caremark, companies that oversee prescription drugs for employers and government programs.

It remained unclear why the state was ordering the submission of so much data. In a letter to one benefit manager reviewed by The New York Times, the regulator said the state required the data to review whether the benefit managers, known as P.B.M.s, were compliant with a 2023 state law aimed at lowering drug prices and reining in the managers.

But the demand is sparking concerns about government overreach and patient privacy.

“You don’t need such granular patient information for purposes of oversight,” said Sharona Hoffman, a health law and privacy expert at Case Western Reserve University. She added: “You have to worry: Is the government actually trying to get information about reproductive care or transgender care or mental health care?”

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Florida’s six-week abortion ban, enacted by Gov. Ron DeSantis, a Republican, and the state’s Republican-dominated legislature, requires that doctors who prescribe abortion pills dispense them in person, not through the mail. Another Florida law banned transgender transition care for minors and made it harder for adults to seek such care. Last year, a judge struck down key parts of that law, though it is still being enforced while the legal fight makes its way through the courts.

The data requested by the state could, in theory, be used to determine whether physicians are complying with those laws.

It was also unclear whether any of the benefit managers had complied and turned over the information to the state.

Some benefit managers and the employers that hire them to handle prescription drug benefits for their workers have also criticized the state’s demand.

A group of large employers, the American Benefits Council, is asking the Florida regulator to withdraw its order to turn over the information. In a letter to the state, the council’s lawyers wrote that the “demand impermissibly violates the health privacy and security of millions of Floridians,” and that the state had not clearly outlined its authority or reasons for the action.

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“We have a duty to employees and their data,” Katy Johnson, the president of the council, said in an interview.

Shiloh Elliott, a spokeswoman for Florida’s insurance regulator, said that objections to the state’s data request “are clearly from those who do not want to be regulated or have any oversight in their industry.” She said the office “will continue to request data in the best interest to protect consumers.”

Rosa Novo, the administrative benefits director for Miami-Dade County Public Schools, which provides health coverage to about 45,000 people, said in an interview that while she appreciated the state’s efforts to address drug prices, it was unclear why it would need this level of detailed information about patients and their medications.

“My doctor is the only one who should know that,” Ms. Novo said.

Federal privacy law allows benefit managers to hand over limited data about individual patients in certain circumstances, such as when regulators are conducting an audit. But, according to experts, Florida’s data request could violate the law because it is so broad and may go beyond what the regulator needs to conduct its review.

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Experts said that another concern with Florida’s request is that when sensitive patient data is in multiple hands, it raises the risk of a breach in which the information may be stolen.

Ms. Elliott, the spokeswoman for the regulator, said those concerns “should be addressed to the actual health care insurance companies that have had countless data breaches exposing millions of Americans’ sensitive information.”

Florida’s data order was first reported by Bloomberg.

Like other states, Florida already has access to some of the data it is seeking, such as detailed information about prescriptions that are paid through Medicaid. But that data is generally strictly walled off, accessible only to staff members whose jobs require it.

Benefit managers often field requests from government regulators asking for slices of data to conduct audits or investigations. Such requests typically ask benefit managers to strip out patient names, and other identifying details, or ask for a small sample of patient claims.

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By comparison, Florida’s data request was “pretty expansive and unprecedented,” said Joseph Shields, the president of a group of smaller benefit managers, Transparency-Rx.

Florida sought data not only on Florida residents, but also on patients who may have filled a prescription while visiting the state. Its request included patients covered through the federal Medicare program and commercial plans through employers that are regulated under federal law rather than state law, according to the regulator’s letter to one benefit manager reviewed by The Times.

The Prescription Drug Reform Act, the Florida law the regulator used to justify the data request, imposed new reporting requirements on the benefit managers but said nothing about a mandate requiring them to turn over such detailed patient information. Benefit managers have fiercely fought efforts to scrutinize their business practices.

Patricia Mazzei contributed reporting from Florida.

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