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F.D.A.’s Accelerated Drug Approvals Come Under Scrutiny

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F.D.A.’s Accelerated Drug Approvals Come Under Scrutiny

By the point Brittany Bonds gave beginning to her third son behind an ambulance 10 weeks earlier than he was due, she not trusted the drug Makena.

The drug was meant to forestall preterm beginning and enhance the well being of a child. However it didn’t work for Mrs. Bonds, whose son Phoenix ended up in a NICU for 83 days. At 2, he nonetheless has a number of well being issues.

Makena is one other instance — just like the controversial Alzheimer’s drug Aduhelm — of a drugs fast-tracked by the Meals and Drug Administration onto the market though appreciable doubt remained about whether or not it labored.

The persevering with debate over Aduhelm’s approval has renewed consideration on the expedited pathway for medication to achieve the market. A invoice sponsored by one Republican in Congress would make it even simpler for a corporation to get a drug authorized and hold it obtainable. A proposal by a number one Democrat would give the F.D.A. extra authority to get definitive solutions about fast-tracked medication and to take away them from the market in the event that they fall quick.

However any efforts to impose limits on the fast-track course of is probably going to attract the ire of the highly effective pharmaceutical business, which was the highest U.S. sector in lobbying expenditures final 12 months and spends closely on political campaigns.

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“I believe there’s going to be great resistance from the pharmaceutical business” to tightening the foundations on accelerated approvals, mentioned Dr. Michael Carome, a director at Public Citizen, a nonprofit client advocacy group.

Questions had lingered about Makena for a decade earlier than a big research confirmed the drug had the identical impact as a placebo. The F.D.A. proposed taking the drug off the market greater than a 12 months in the past. It plans to carry a listening to on Makena’s destiny that can focus scrutiny on what some critics declare is a speed-over-science drug approval course of.

Mrs. Bonds is certainly one of 13 plaintiffs in a lawsuit towards the drug’s earlier proprietor, AMAG Prescribed drugs, and desires the drug taken off the market. “It didn’t work for me and I do know it didn’t work for different folks,” she mentioned.

Covis Pharma, which now owns the drug, plans to oppose the company’s choice on the upcoming listening to, arguing that Makena is really efficient for the ladies it had initially helped: African American girls, who face a few of the highest preterm birthrates within the developed world.

Untimely infants additionally face elevated dangers of being born lifeless or disabled. “Quite a lot of emotion will get concerned on this,” mentioned Dr. Washington Hill, a Black maternal-fetal medication specialist in Sarasota, Fla. He has prescribed the drug for many years to at-risk girls and was paid $1,200 in consulting charges when he testified in its favor in 2019. “I felt this drug was efficient within the sufferers I labored with,” he mentioned in an interview.

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All through the lifetime of the accelerated approval program that started 30 years in the past, the F.D.A. has needed to weigh passionate, generally determined pleas for entry to medication towards the obtainable science-based proof.

Throughout these a long time, the company issued 278 approvals underneath this system as of December. The approvals don’t show {that a} drug extends survival or improves high quality of life. As an alternative, medication might be put available on the market based mostly on a single research with a optimistic discovering — like tumor shrinkage — and saved available on the market if a follow-up research proves a profit.

This pathway, meant for critical situations and unmet medical wants, has given sufferers earlier entry to lifesaving medication, a degree of delight for business teams like BIO, the Biotechnology Innovation Group. A BIO consultant informed lawmakers final week that he supported a pending plan for drugmakers to make use of real-world proof to extra rapidly show that an accelerated approval drug works. PhRMA, which additionally represents drugmakers, mentioned it supported this system in its present type.

But critics and watchdog teams contend that Medicare has spent billions on accelerated approval medication, at the same time as drugmakers drag their toes to finish the required follow-up research which, if unfavorable, can result in withdrawal of the drug. In some circumstances, fast-tracked medication that confirmed little profit stayed available on the market anyway.

Rushing up science has lengthy been fraught: The F.D.A. was closely criticized for its actions on Vioxx, a ache drug that had been authorized underneath expedited assessment that was later withdrawn in 2004 over findings that it elevated coronary heart assaults and strokes. Much more avenues for expedited critiques had been granted underneath the twenty first Century Cures Act in 2016.

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On the heels of the Aduhelm approval debate, the F.D.A. faces one other spherical of scrutiny subsequent week when its advisory panel critiques a brand new drug, Amylyx, for amyotrophic lateral sclerosis, a deadly neurological dysfunction. Whereas the drug meets one bar for accelerated approval — the addressing a critical illness with unmet wants — its maker is looking for conventional approval.

As for the present state of accelerated approvals, April Grant, a spokeswoman for the F.D.A., mentioned the company was working to make sure that drugmakers accomplished follow-up research of the medication in a well timed method. If it finds gaps in its authority, “then the company will work with Congress to shut these gaps,” Ms. Grant mentioned.

The accelerated program traces its historical past to a raucous 1988 protest on the F.D.A.’s entrance steps, when AIDS activists stormed the company headquarters, enraged that it had performed so little as 1000’s of younger males had been dying.

They outlined one another’s our bodies with sidewalk chalk. The police cuffed them in zip ties and dragged them away.

Mark Harrington, who helped set up the 1988 demonstration, is government director of the Therapy Motion Group, which advocates entry to medical therapies. He mentioned the rowdy protest led to discussions for expediting entry to new medication.

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Whereas medication that originally appeared promising fell quick, by the mid-90s, protease inhibitors slashed virus ranges and delivered a medical miracle.

“So the underside line is that the accelerated approval rules labored,” Mr. Harrington mentioned. “They helped draw extra corporations into the area. They led to the invention of efficient therapies.”

But Mr. Harrington and others have watched with concern as researchers have recognized accelerated approval medication that delivered minimal, if any, positive factors for sufferers.

Of the 253 medication approved underneath accelerated approval since 1992, almost half — 112 — haven’t been confirmed to increase survival or enhance high quality of life, in line with an investigation within the The BMJ printed final 12 months. Two dozen of the medication had been available on the market for 5 years or extra.

One other research confirmed that 20 p.c of 93 most cancers drug therapies cleared since 1992 had been confirmed to increase total survival, whereas others remained available on the market after follow-up research confirmed extra modest positive factors, like delaying tumor development. The F.D.A. mentioned total survival enchancment might be exhausting to evaluate, because it takes years to realize.

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That research reported that one drug, Avastin, bought accelerated approval to deal with glioblastoma, a mind most cancers. Despite the fact that a follow-up research didn’t present prolonged survival or improved high quality of life, Avastin nonetheless acquired full approval for that use in 2017.

The identical drug was used to deal with breast most cancers and is the one instance of the F.D.A. revoking accelerated approval for one use of a drug — regardless of emotional pleas to permit it for most cancers sufferers in 2011.

In 2010, the F.D.A. backed off its choice to withdraw Midodrine for sufferers with dangerously low blood stress, only a month after telling the drugmaker it had “not been capable of present proof of the drug’s profit.”

Actually, the makers of Makena cited that precedent in arguing that their preterm-birth drug ought to stay obtainable. The company altered course on the blood stress drug “prompted by the outpouring of help for the drug and concern over dropping entry,” Makena’s maker reminded the F.D.A.

Covis, the drug’s present proprietor, funded a affected person group referred to as the Preterm Beginning Prevention Alliance, whose members could testify on the listening to over the drug’s destiny.

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The story of Makena begins with a medical thriller: Scientists aren’t sure what triggers the method of giving beginning in people. A clue to forestalling it appeared to emerge in 2003 with the outcomes of a research on the drug’s energetic ingredient, a type of the hormone progesterone.

The research, which included many high-risk Black girls, confirmed that these on the medicine noticed a 34 p.c discount of their danger of getting a preterm beginning in contrast with these in a management group.

An F.D.A. statistical assessment of the research concluded that the information does “not present convincing proof” of effectiveness. Of principal concern, the report mentioned, was that the drug appeared simplest when began at or earlier than 18 weeks of the being pregnant, when the charges of fetal or new child loss of life was additionally “most pronounced.”

Nonetheless, the F.D.A. granted the drug accelerated approval in 2011, and it stays the one authorized drug meant to scale back the chance of recurrent preterm beginning. High medical societies, which have accepted funding from the drug’s maker, endorsed its use, and Makena grew to become so routinely prescribed that it was tough to check in the USA.

By 2019, although, outcomes of a big research performed principally in Europe had been in. They instructed that the drug had no impact: The share of ladies who gave beginning preterm whereas on the drug was about the identical as these given a placebo.

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The F.D.A. examined the information to see if there was a subgroup of sufferers in the USA, together with 113 Black girls, who benefited. It couldn’t discover one. In October 2020, the F.D.A. introduced it wished to discontinue use of the drug.

The drug’s maker, then AMAG Prescribed drugs, requested for a listening to, arguing partly that the research left open the query of whether or not their drug benefited high-risk Black girls. “Our view is that given the outcomes of each of those trials, extra analysis is merited,” mentioned Francesco Tallarico, normal counsel for Covis Pharma.

It’s a priority shared by others who haven’t any monetary stake, together with Dr. Michael Greene, a professor emeritus at Harvard’s medical college. He and colleagues mentioned the second research was “underpowered” as a result of it included few Black girls.

“Is it actually truthful and equitable to yank the labeled indication for a drug that’s useful to a minority, simply because it’s not useful to the bulk?” mentioned Dr. Greene, who’s an affiliate editor of the New England Journal of Medication. “That didn’t actually appear truthful to us.”

Debate over the drug has divided the maternal-fetal medical care group, Dr. Hill, the maternal-fetal specialist in Sarasota, mentioned. He desires the drug to stay authorized, however is unsure that can occur. “My intestine response can be it’s going to take a variety of convincing.”

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Even those that are skeptical of the drug need to know extra. “I believe there must be extra research,” mentioned Olivette Bennett, a pregnant Baltimore girl, who’s Black, who lately stopped taking the drug as a result of she didn’t suppose it was working. “The place is the voice for the African American girls who mentioned it labored for them?”

Within the federal lawsuit towards AMAG Prescribed drugs, Mrs. Bonds of Missouri, who’s white, and different plaintiffs declare the corporate leaders did periodic critiques of the 2019 research, however continued to market the drug as one thing that would assist girls. AMAG mentioned the lawsuit must be dismissed, arguing it amounted to an assault on a drugmaker’s proper to promote an F.D.A.-approved drug.

In an interview, Mrs. Bonds mentioned she started taking Makena throughout every of three pregnancies after a stillbirth in 2011. Her first two sons had been born at 36 weeks, a number of weeks wanting full-term.

She mentioned she reluctantly took the drug whereas pregnant along with her third son. She was dispirited that his beginning got here earliest of all. She mentioned the drug ought to have been studied extra earlier than approval. “I believe it will have helped stop a variety of false hope,” Mrs. Bonds mentioned.

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Hospitals that pursue patients for unpaid bills will have to tell L.A. County

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Hospitals that pursue patients for unpaid bills will have to tell L.A. County

Hospitals must promptly report to the Los Angeles County Department of Public Health every time they try to collect medical debt from patients, under an ordinance backed Tuesday by county supervisors.

The ordinance, which requires a second vote to be adopted, requires hospitals to tell the county within a month or two of initiating debt collection, which can include making phone calls or mailing letters to seek payment more than 180 days after the initial billing, selling the debt to a collections agency, garnishing wages, seizing a bank account or informing a consumer reporting agency.

The new rules would also require hospitals to report up to four times annually on the medical debt amassed in recent months by their patients and what financial assistance they have offered them. If they fail to do so, they could face fines and legal action.

Public health officials said the rules would help shed light on hospital practices and address a crucial question: Where are the missed opportunities for hospitals to provide financial assistance?

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Hospitals are supposed to provide financial aid to patients in need, but “the rub is the implementation,” said Dr. Anish Mahajan, chief deputy director of the L.A. County Department of Public Health. In a survey by the national nonprofit Dollar For, less than 30% of patients saddled with hospital bills they couldn’t afford said they had applied for and ultimately received financial assistance.

Many hospitals make good efforts to offer aid, Mahajan said, but data show “there is just so much medical debt — and that debt is disproportionately carried by poor people.”

Los Angeles County officials estimate that medical debt totaled more than $2.9 billion in the county in 2022, burdening 1 in 10 adults.

The public health department has launched an initiative to quash medical debt, including buying up and forgiving existing debt. In June, it set aside $5 million for a planned agreement with a nonprofit that erases such debts, which county officials estimated could eliminate $500 million of debt for 150,000 residents.

But the county has stressed that it also wants to prevent patients from incurring medical debt in the first place. Mahajan said that by pulling together information under the new ordinance, “we can then understand how hospitals are doing … in having their patients who should get financial assistance actually receive it.”

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For instance, the county said it could match up data about patients whose medical bills were sent to collections to see if they might have been eligible for assistance, then reach out to hospitals about their findings.

“The goal is to help hospitals do better,” Mahajan said.

The figures could also help shed light on whether financial assistance is failing to reach particular groups of L.A. County residents, which could help guide future outreach and public education about the aid.

For instance, Mahajan suggested that in some cases, hospitals might have good policies on financial assistance, but some patients may fear seeking such aid amid worries about their immigration status.

Tackling such concerns could involve not just hospitals but other members of the county coalition that has sought to address medical debt, including legal aid and consumer groups, he said.

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The mandatory reports could also give health facilities a sense of whether their financial assistance and debt collection practices fall outside the norm, compared with other hospitals in the area. Public health officials reported that hospitals across L.A. County provided more than $600 million in financial assistance in 2021, but more than half of it was from just four facilities — those run by the county itself.

Those safety net hospitals “can’t cover the entire county, and they’re doing the bulk of the financial assistance,” said Dr. Naman Shah, director of the division of medical and dental affairs at L.A. County Public Health. “The reason for this ordinance is that we can do better.”

Dr. Elaine Batchlor, chief executive of MLK Community Healthcare, told the county board that her Willowbrook hospital proactively takes steps to assess whether patients need aid, using software and other tools to check whether they are likely able to afford copays, then writing off the debt if their finances appear shaky.

Such financial tools “are widely available, and they’re not difficult to use,” Batchlor said Tuesday.

L.A. County will also put up a website where the public can peruse aggregate data about medical debt at local hospitals, although it is still determining exactly what information will be posted, Mahajan said.

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The Hospital Assn. of Southern California said its members are deeply concerned about medical debt as an issue, but that the organization remains worried about some aspects of the county requirements.

In reaction to hospital concerns, the county has eased some rules surrounding how often reports must be provided, but “there still remain concerns about how voluminous” the data requirements will ultimately be, said Adena Tessler, the hospital association’s regional vice president for Los Angeles County.

For example, Tessler said that in some cases, hospitals might not be able to provide information because it hasn’t been provided by patients themselves. In addition, “the focus on hospitals remains a concern, because it’s just a piece of the medical debt issue.”

Public Health Director Barbara Ferrer said Tuesday that hospitals are a reasonable place to focus initially because “hospital bills comprise the majority of the debt and the largest bills.” Supervisor Janice Hahn added that “the work won’t stop here today” and that the county will be exploring how other entities — including insurance companies and private provider groups — play a role.

“Hospitals are not the sole cause of medical debt,” she said, “but starting there will help us develop a plan.”

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Stanford University professor of economics Neale Mahoney applauded the effort, saying he hoped it would expand to other jurisdictions. “Medical debt is a dark corner in the U.S. healthcare system,” he said, and shining a light on it can be “a strong disinfectant.”

The L.A. County requirements would apply only to a small number of hospitals in unincorporated areas — county officials estimated the number at seven, including MLK Community Hospital — but local cities could adopt them to cover their jurisdictions as well. Hospitals will have roughly six months after the L.A. County ordinance goes into effect before failing to turn in the reports becomes a violation.

Tessler, of the hospital association, said that because the rules will be rolled out first in the unincorporated areas, her hope is that government officials will take the time to make sure that the reporting requirements make sense before expanding such rules to other parts of L.A. County.

Ferrer said her department would reassess the burdens of collecting such data in a year. In light of concerns about patient information, she said the portal that hospitals will use to provide information when they try to collect debt from individual patients is compliant with federal law on protecting patient privacy.

Batchlor, in her remarks Tuesday, described helping an uninsured friend diagnosed with cancer get the care she needed, only to recently learn that the woman was again uninsured because “she can now afford to either pay down her medical debt or pay the premiums for her health insurance — she can’t afford to do both.”

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The hospital executive said that the “root cause of medical debt is the high cost of healthcare and the failure of health insurance to cover those costs.”

To solve the problem, she said, “we will ultimately need to address these root causes.”

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How do Olympic skateboarders catch serious airtime? Physicists crunched the numbers

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How do Olympic skateboarders catch serious airtime? Physicists crunched the numbers

Skateboarders call it “pumping,” and it’s a skill that both Olympic medalists and aspiring thrashers use to build launch speed from what seems like thin air.

But what separates the steeziest pro from the sketchiest beginner is the years’ worth of practice it takes to develop the know-how to execute the cleanest pump — or at least that was the case until now.

In a paper published Monday in the journal Physical Review Research, scientists have revealed the secret of achieving serious airtime.

A skateboarder rides the bowls at Etnies skatepark in Lake Forest. (Allen J. Schaben / Los Angeles Times)

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With a bit of coding, researchers were able to describe the optimal technique for pumping — a tactic where skateboarders crouch down low momentarily and then push their body upright on inclines. To get the highest jump, they need to do it once as they descend into the bowl, and then again as they shoot back up toward the sky.

The trick is knowing when and where to execute the maneuver.

“Pumping is the foundation of skateboarding in skate parks,” said professional skater Haden McKenna, during a morning session at the Venice Beach Skatepark. “You build off of that and learn tricks. Then the pumping just becomes something in the back of your brain.”

However, the likeliest users of the researchers’ perfect pump equation are non-humans.

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After skateboarding’s Olympic debut at the Tokyo Games, a research arm of the Japanese government reached out to Shigeru Shinomoto, a scientist at the Advanced Telecommunications Research Institute International in Japan. The organization had wondered if it was possible to build a skateboarding robot that could compete in the X Games.

The robot is still a ways off — right now it’s more like a toy that rides back and forth on a mini half-pipe — but the researchers discovered that the mechanics for good skateboarding technique can be surprisingly simple (well, at least compared to the complex fluid dynamics and neuroscience that they’re normally working on).

Kokona Hiraki of Japan crouches on her board before popping upright to pump at the Tokyo Olympics.

(Associated Press)

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“It’s just this cute little project which became much bigger than we expected,” said Florian Kogelbauer, an author on the paper and a mechanical engineering professor at the public university ETH Zürich. “People like it — it’s a fun topic. It’s easy to explain, but some serious math and computational work went into it.”

To test their calculations, study authors recruited an expert skater with over a decade of experience, and a novice with just two years under their belt. They told the skaters to catch as much air as possible on a half-pipe erected in a research lab.

The result: The pro much more closely matched their calculated optimal motion than the amateur. (Ideally the skater would pop up instantaneously, but the researchers conceded that humans lack the unlimited muscle strength to do this — plus it would send the skater flying off their board.)

“The experiment seems to agree well,” said Frank Feng, a mechanical engineering professor at the University of Missouri who was not involved with the paper, but studied similar motions in half-pipe snowboarding.

Feng said the simple physics model gets researchers most of the way there, then the computer optimization is able to account for complexities that the physics equations can’t handle.

While the study was mostly just for fun, it snowballed into a fairly big project, and ended up getting published in one of the world’s premier physics journals. Part of the reason is that it may have some serious implications for how to get robots to move effectively without face-planting all the time.

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It could help human skateboarders, too. Feng said the results could be used as a straightforward guide to help skateboarders train.

However, some question whether skaters would be able to use the information in the moment.

“This graph, showing the mass going up, is very helpful for somebody that can understand that,” said pro skater McKenna, who was not involved in the research. “But when you’re teaching kids and you’re trying to teach somebody that’s focused in the moment of skateboarding, they’re not going to be able to bring math into the equation.”

Also, out in the complex terrain of the park, the technique gets a bit more nuanced than a simple model the physicists developed. You need to flow as “one with the wall,” said McKenna. “Like what Bruce Lee says, ‘Be like water.’”

A skateboard descends a steep ramp.

Skateboarder Greyson Godfrey, 20, of Rancho Santa Margarita drops into the bowl at Etnies Skate Park Lake Forest.

(Allen J. Schaben / Los Angeles Times)

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While the researchers’ optimal solution may not always be the best suited for real-world conditions, it does help to illustrate the physics behind the technique.

Studio Gutierrez, who teaches skateboarding as a sports instructor to middle schoolers in the Los Angeles Unified School District, finds understanding the science helpful for new skaters. “I explain it to them in physics motions,” he said. “The more motion, the faster you go, the higher you get.”

The physics works similarly to how ice skaters increase the speed of their spinning in the Winter Olympics, said Kogelbauer. They start out spinning slow with their limbs extended outward. Then, they tuck their arms and legs in, causing them to spin faster.

Skateboarders also gain speed by using this technique on curved surfaces.

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When a skateboarder hits the circular section of the half-pipe, they start crouched down, positioning their center of mass further from the center of rotation above their head. As they climb the curved ramp, they pop up and bring their center of mass closer to the center of rotation, and they speed up.

While the pumping paper is one of the first to capture the physics of pumping, its authors aren’t the only ones studying the motion of skateboarding.

Google has also taken a stab at a more complex understanding with its Project Skate. It’s using AI to identify different tricks and motions — but AI requires a lot of computing power that many researchers who aren’t Google don’t have access to.

“They have [essentially] unlimited resources. If they want to, they can take a new server farm and then run trajectories as much as they want.” said Kogelbauer. “That’s what Google does. We’re not Google.”

If you’d like to study pumping physics on your own, you can tune in to the Paris Olympics. The women skateboarders are scheduled to compete in the park event (as opposed to the street event, which has fewer curved surfaces for pumping) Tuesday morning. The men are scheduled for Wednesday.

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McKenna has always seen skating more as an art form and community than a sport, but he’s stoked to watch nonetheless. “When I was a kid, which doesn’t seem that long ago, skateboarding was a crime, literally,” he said. “Now we’re winning gold medals in the Olympics.”

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Olympic boxing controversy sparks fierce debate over inclusivity in women's sports

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Olympic boxing controversy sparks fierce debate over inclusivity in women's sports

A Summer Olympics that hoped to champion inclusivity — choosing “Games Wide Open” as its slogan — has become embroiled in loud, angry debates over who should and should not be allowed to compete as a woman.

The dispute has triggered conflicting official statements, pointed comments and unhinged social media posts, all whirling around two athletes in the women’s boxing competition at Arena Paris Nord.

This isn’t about how Imane Khelif of Algeria and Lin Yu Ting of Taiwan identify. By all accounts, they were born as women but appear to have unusual body chemistry that triggered gender tests and caused them to be disqualified from last year’s world championships.

The Olympics, however, have broader eligibility rules.

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“I think we all have a responsibility to dial down this and not turn it into some kind of witch hunt,” International Olympic Committee spokesman Mark Adams told reporters. “These are regular athletes who have competed for many years in boxing, they are entirely eligible and they are women on their passports.”

His plea has been overshadowed by a Thursday afternoon bout in which Khelif punched an opponent hard enough to make her quit after 46 seconds. Paris has been lumped in the same category as previous controversies involving South African runner Caster Semenya and U.S. collegiate swimmer Lia Thomas.

This case might be more incendiary because, instead of running or swimming fast, Khelif and Lin are delivering potentially lethal blows. Italian boxer Angela Carini said she conceded to Khelif because “I had to safeguard my life.”

Experts wonder if the sports world has reached an inflection point.

“We really have not come up with a consensus on how we define sex,” said Jaime Schultz, author of a new book titled “Regulating Bodies: Elite Sport Policies and Their Unintended Consequences.” “People have to learn how to talk about this.”

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Over the last 24 hours, much of the public discourse has inaccurately described Khelif and Lin as transgender. Former President Donald Trump posted on Truth Social: “I WILL KEEP MEN OUT OF WOMEN’S SPORTS!”

Taipei’s Lin Yu Ting, red, takes a punch from Uzbekistan’s Sitora Turdibekova in the Women’s 57kg boxing match.

(Wally Skalij/Los Angeles Times)

There is no evidence that either boxer is transgender or has chromosomal abnormalities. Though purposefully vague, officials have described what appear to be “differences of sex development,” a designation that applies to women who are androgen-sensitive or have naturally occurring testosterone levels in the male range.

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The international track federation used this standard to demand that 800-meter star Semenya either take medication to alter her body chemistry or race against men. She fought the decision, losing in the Federal Supreme Court of Switzerland.

Sports have a long and troubled history with gender testing.

Early on, female athletes were forced to disrobe for physical inspections. Chromosome tests came into fashion for a while but were successfully challenged by Spanish runner Maria Jose Martinez-Patino in the 1980s because they could not account for rare conditions.

Though testosterone is now a common measure, there is continued disagreement over its validity.

Italy's Angela Carini, left, cries after her loss to Algeria's Imane Khelif at the Paris Olympics on Thursday.

Italy’s Angela Carini, left, cries after her loss to Algeria’s Imane Khelif at the Paris Olympics on Thursday.

(John Locher / Associated Press)

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“These criteria keep folding under the weight of closer scrutiny,” said Schultz, who is also a kinesiology professor at Penn State. “None of them have held up over time.”

Veterans on the amateur scene, Khelif finished fifth in the 60 kilogram event and Lin finished ninth at 57 kilograms in the Tokyo Olympics in 2021. The Algerian won silver at the International Boxing Assn.’s 2022 world championships. The Taiwanese athlete earned gold at that tournament in 2018 and 2022.

But last year, the IBA took action against both women.

Khelif was disqualified shortly before her gold-medal bout and Lin after her bronze-medal victory. The IBA stated the boxers did not “undergo a testosterone examination but were subject to a separate and recognized test, whereby the specifics remain confidential.”

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The situation grew more complicated when the IOC suspended its recognition of the IBA after years of dispute between the organizations. With the IOC temporarily in control of boxing at the Games, Khelif and Lin have had their eligibility restored.

It came as no surprise when Khelif’s bout on Thursday prompted dueling responses.

First the IBA condemned Olympic officials for letting Khelif and Lin compete, stating: “We absolutely do not understand why any organization would put a boxer at risk with what could bring a potential serious injury.”

The IOC fired back by saying: “Every person has the right to practice sport without discrimination.” It further noted the IBA disqualifications were “based entirely on this arbitrary decision, which was taken without any proper procedure.”

Algeria's Imane Khelif, right, walks beside Italy's Angela Carini after their women's 66kg preliminary boxing match.

Algeria’s Imane Khelif, right, walks beside Italy’s Angela Carini after their women’s 66kg preliminary boxing match.

(John Locher / Associated Press)

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On Friday morning, when questioned about the Olympics’ apparent struggle with gender rules, Adams said: “There is still neither scientific nor political consensus on this issue. It’s not a black and white issue. And we at the IOC would be very interested to hear of such a solution, such a consensus on this, and we would be the first to act on this should a common understanding be reached.”

Hours later, the media descended on a bout between Lin and Sitora Turdibekova of Uzbekistan. No devastating blows were landed during Lin’s victory, by unanimous decision, after which both athletes walked through the mixed zone without responding to questions.

Khelif’s next bout — against Anna Luca Hamori of Hungary — figures to attract similar attention on Saturday. The Hungarian Boxing Assn. has reportedly protested Khelif’s participation but Hamori did not seem as concerned. “I am not scared,” the boxer said. “If she or he is a man, it will be a bigger victory for me if I win. So let’s do it.”

Even Carini, who fell to her knees and cried after losing to Khelif, has been magnanimous. Her comments reflect the complexity of the issue.

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“I am not in the position of saying this is right or wrong,” she told reporters. “I did my job as a boxer, entering the ring and fighting.”

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