Understanding the US Health Care Industry as a Commercial Determinant of Health
Who Employs Your Doctor? Increasingly, a Private Equity Firm.
A new study finds that private equity firms own more than half of all specialists in certain U.S. markets.
by Reed Abelson and Margot Sanger-Katz
n recent years, private equity firms have been gobbling up physician practices to form powerful medical groups across the country, according to a new report released Monday.
In more than a quarter of local markets — in places like Tucson, Ariz.; Columbus, Ohio; and Providence, R.I. — a single private equity firm owned more than 30 percent of practices in a given specialty in 2021. In 13 percent of the markets, the firms owned groups employing more than half the local specialists.
The medical groups were associated with higher prices in their respective markets, particularly when they controlled a dominant share, according to a paper by researchers at the Petris Center at the University of California, Berkeley, and the Washington Center for Equitable Growth, a progressive think tank in Washington, D.C. When a firm controlled more than 30 percent of the market, the cost of care in three specialties — gastroenterology, dermatology, and obstetrics and gynecology — increased by double digits.
Average price of gastroenterology visit
The paper, published by the American Antitrust Institute, documented substantial private equity purchases across multiple medical specialties over the last decade. Urology, ophthalmology, cardiology, oncology, radiology and orthopedics have also been major targets for such deals.
“It’s shocking when you look at it,” said Laura Alexander, director of markets and competition policy for the Washington Center, who said private equity firms dominated only a handful of markets a decade ago. By looking at individual markets, the researchers were able to document the local impact. “National rates mask this much more acute problem in local markets,” she said.
The higher prices paid by private insurers contribute to high insurance premiums, and may increase out-of-pocket costs for patients.
Private equity firms, which pool funds from institutional investors and individuals to form investment funds, tend to purchase companies using debt, with an eye to reselling them in a few years. The industry has turned to health care fairly recently, but it has begun purchasing doctors’ practices at a steady clip, combining smaller practices to form larger companies.
When a private equity arm of a Canadian pension fund, OMERS Private Equity, bought Gastro Health, a large gastroenterology medical group, in 2021, it proceeded to acquire nearly a dozen smaller practices, according to the researchers, who say the group is now dominant in markets including the Miami area. The company now operates in seven states, employing over 390 doctors. The researchers saw similar patterns in other markets, where a firm would buy one large practice, then increase its market share by adding nearby smaller practices in the same medical specialty.
Historically, doctors’ practices have been relatively small, and owned by doctors themselves. But that model has been rapidly declining as the business of medicine has become more complex and the insurance companies that negotiate with doctors over prices have become bigger. Nearly 70 percent of all doctors were employed by either a hospital or a corporation in 2021, according to a recent analysis from the Physicians Advocacy Institute.
“We’re seeing a fundamental change in how medicine is being practiced in the U.S.,” said Richard Scheffler, a professor of health economics and public policy at Berkeley and director of the Petris Center.
Hospitals and insurance companies have also bought out many independent physicians’ practices. Optum, an arm of the publicly traded UnitedHealth Group, which also owns one of the nation’s largest insurers, employs roughly 70,000 physicians. Studies have shown that these types of concentrated ownership of doctors in a given market are also associated with higher prices.
Private equity is often viewed by physicians as an attractive alternative to having their practice bought by a hospital. In part, the doctors are “getting more scale and gaining efficiencies,” including help with office administration and technology, said Lisa Walkush, a national managing principal for the professional services firm Grant Thornton. “It can be a really good thing, but the private equity firms have to keep their promises and be held accountable,” she said.
Michael Kroin, the founder and chief executive of Physician Growth Partners, a Chicago firm that advises independent practices, said the private equity firms “provide scale to allow independent practice groups to survive and maintain their autonomy.” If they could, given their rising costs and how squeezed they feel by insurers, “every independent group would want to increase its fees,” he said.
The private equity industry has begun to attract particular scrutiny from researchers and policymakers. Lawmakers in the House are considering legislation to require more reporting when the firms buy health care companies. Currently, the acquisitions can be difficult to track. The authors of the new paper relied on data on deals from a company called PitchBook, which they then matched with doctors in a health care claims database to measure payments from private health insurers.
The researchers couldn’t be sure whether the payment increases they measured happened because doctors were performing more complex procedures or just negotiating higher prices, but they suspected the prices explained most of the effect.
Previous studies of private equity-acquired hospitals and physician practices from Zirui Song, an associate professor of health policy and medicine at Harvard Medical School, have also documented increasing revenue associated with the purchases. In an interview, Dr. Song said he expected the industry would continue to buy doctors’ practices in the coming years. “We still have a lot of small physician-owned specialty practices,” he said. “That’s an opportunity for consolidation. It’s an easy opportunity.”
Critics of the industry, including Professor Scheffler, have also raised concerns about the medical care delivered by private equity-owned health care companies, arguing that the industry’s emphasis on profits could cause patient harm. Research on private equity ownership of nursing homes has shown evidence of lower staffing levels and higher rates of prescriptions for antipsychotic medicines.
But little rigorous research has been published on patient care in the office-based medical specialties that the new paper focuses on.
How the change in ownership and independence affects doctors and how they treat patients “has been very severely understudied,” said Barak Richman, a professor of law and business administration at Duke University, who reviewed the paper. But he said there is evidence that these firms are skilled at exploiting loopholes in existing regulations to maximize their profits.
“Private equity is like the system on steroids,” said Sherry Glied, the dean of the Wagner School of Public Service at New York University. “Every time there’s an opportunity for making money, P.E. is going to move faster than everyone else. And consolidation is the way to do that.”
While federal regulators are contemplating changes to how they oversee these deals, researchers say the report underscores the need to pay attention to what happens when a company makes a series of seemingly modest acquisitions. “This builds the case for strong antitrust tools for these incrementally small but collectively larger consolidation trends,” said Erin Fuse Brown, the director of the Center for Law, Health and Society at Georgia State University.
Profiting From Risky Atherectomies That Can Lead to Amputations
Kelly Hanna’s leg was amputated on a summer day in 2020, after a Michigan doctor who called himself the “leg saver” had damaged her arteries by snaking metal wires through them to clear away plaque.
It started with a festering wound on her left foot. Her podiatrist referred Ms. Hanna to Dr. Jihad Mustapha. Over 18 months, he performed at least that many artery-opening procedures on Ms. Hanna’s legs, telling her they would improve blood flow and prevent amputations.
They didn’t — for Ms. Hanna or many of his other patients. Surgeons at nearby hospitals had seen so many of his patients with amputations and other problems that they complained to Michigan’s medical board about his conduct. An insurance company told state authorities that 45 people had lost limbs after treatment at his clinics in the past four years.
Dr. Mustapha is no back-alley operator working in the shadows of the medical establishment, an investigation by The New York Times has found. With the financial backing of medical device manufacturers, he has become a leader of a booming cottage industry that peddles risky procedures to millions of Americans — enriching doctors and device companies and sometimes costing patients their limbs.
The industry targets the roughly 12 million Americans with peripheral artery disease, in which plaque, a sticky slurry of fat, calcium and other materials, accumulates in the arteries of the legs. For a tiny portion of patients, the plaque can choke off blood flow, leading to amputations or death.
But more than a decade of medical research has shown that the vast majority of people with peripheral artery disease have mild or no symptoms and don’t require treatment, aside from getting more exercise and taking medication. Experts said even those who do have severe symptoms, like Ms. Hanna, shouldn’t undergo repeated procedures in a short period of time.
Many people with peripheral artery disease also have heart disease or diabetes, which present serious risks. Such patients, already anxious about their health, are susceptible to warnings from doctors that, absent intrusive medical procedures, they could lose their legs.
Some doctors insert metal stents or nylon balloons to push plaque to the sides of arteries. Others perform atherectomies, in which a wire armed with a tiny blade or laser is deployed inside arteries to blast away plaque. Rigorous medical research has found that atherectomies are especially risky: Patients with peripheral artery disease who undergo the procedures are more likely to have amputations than those who do not.
The volume of these vascular procedures has been surging. The use of atherectomies, in particular, has soared — by one measure, more than doubling in the past decade, according to a Times analysis of Medicare payment data.
There are two reasons. First, the government changed how it pays doctors for these procedures. In 2008, Medicare created incentives for doctors to perform all sorts of procedures outside of hospitals, part of an effort to curb medical costs. A few years later, it began paying doctors for outpatient atherectomies, transforming the procedure into a surefire moneymaker. Doctors rushed to capitalize on the opportunity by opening their own outpatient clinics, where by 2021 they were billing $10,000 or more per atherectomy.
The second reason: Companies that make equipment for vascular procedures pumped resources into a fledgling field of medicine to build a lucrative market.
When doctors open their own vascular clinics, major players like Abbott Laboratories and Boston Scientific are there to help with training and billing tips. The electronics giant Philips works with a finance company to offer loans for equipment and dangles discounts to clinics that do more procedures.
The Times searched a database of state loan filings for the 200 doctors who have billed Medicare the most for atherectomies since 2017. At least three-quarters either received loans from the device industry or work at clinics that have. Some loans have gone to doctors with well-documented histories of endangering patients.
The device industry rewards high-volume doctors with lucrative consulting and teaching opportunities. And it sponsors medical conferences and academic journals to bolster a niche medical field that favors aggressive interventions.
This self-sustaining ecosystem is worth $2 billion a year, analysts estimate. Insurers pay doctors per procedure. And because new equipment is needed each time, the companies also profit from repeat customers.
Dr. Mustapha declined to comment on Ms. Hanna’s case, citing health care privacy law. But he strongly defended his treatment of the seriously ill patients who form the bulk of his practice. He said his clinics have “very low” rates of complications, including 1.3 percent of patients having “major amputations” within 30 days of treatment.
“The vast majority of the patients we serve have had exceptional outcomes,” Dr. Mustapha said. “We have saved countless limbs — and lives.”
Representatives of Philips, Abbott and Boston Scientific stood by their work with outpatient clinics, which they said cut costs and were better for patients. The Philips spokesman said it was standard practice across industries to provide loans to finance large purchases.
The vascular industry faces minimal regulation. Many medical devices sail through the Food and Drug Administration’s clearance process without much data showing they work. The clinics are not subject to the same safety regulations as hospitals. Even when regulators determine that doctors have performed unnecessary procedures, they generally impose paltry fines and let them continue practicing.
Fifteen surgeons told The Times they were frequently called in to fix problems caused by doctors in vascular clinics.
“Someone who cuts or inserts something into a patient for unnecessary work is the same as someone stabbing you in the street and taking your wallet,” said Dr. Russell Samson, a vascular surgeon in Florida.
‘A Clear Business Motive’
Medicare’s decision to reimburse doctors for procedures performed outside hospitals led to a proliferation of outpatient clinics specializing in everything from orthopedics to dermatology.
The policy also motivated doctors to perform more procedures, in part because private insurers tend to follow the federal agency’s lead. Before, doctors working in a hospital pocketed only a slice of what insurers paid, with the hospital getting the rest to cover overhead costs. Doctors who owned clinics could now collect the entire payment.
A decade ago, there were virtually no clinics to treat peripheral artery disease. Today, there are about 800, according to an industry trade group.
Atherectomy devices were first developed in the 1980s to clear blockages in arteries. Even then, they were controversial. Studies cast doubt on their safety and effectiveness in the heart.
In the ensuing decades, several companies began selling the devices to treat blockages in the legs. The F.D.A. sets a low bar for authorizing atherectomy tools and other medical devices: Companies just have to convince the agency that their devices are similar to existing products.
The turning point came in 2011, when Medicare began paying for outpatient atherectomies. That year, Medicare reimbursed doctors $86 million for the procedures, according to the Times analysis of Medicare data. By 2021, the most recent year for which data is available, the figure was $612 million.
The amount spent on atherectomies is far higher. Private insurers covered roughly three times as many procedures as Medicare did, according to Definitive Healthcare, a health analytics firm.
Yet a wide body of scientific research has found that for about 90 percent of people with peripheral artery disease — including those who experience the most common symptom, pain while walking, or have no symptoms — the recommended treatments are blood-thinning medications and lifestyle changes like getting more exercise or quitting smoking.
For some people with advanced forms of peripheral artery disease, atherectomies can be useful. But even for them, studies have found that atherectomies do not work better than less expensive methods of clearing blockages and restoring blood flow. Others have found that because atherectomies can further inflame patients’ arteries, they can lead to higher rates of amputations. And atherectomies tend to beget more atherectomies.
Some doctors who own their own clinics push patients to undergo screenings to catch peripheral artery disease in its early, asymptomatic stages. Doctors often encourage patients to get repeat procedures, weeks apart.
“There is a clear business motive for treating people with no symptoms,” said Dr. Caitlin Hicks, an associate professor of surgery at Johns Hopkins University School of Medicine who has studied the overuse of atherectomies.
Many of the doctors who do the most vascular procedures receive payments — for consulting, speeches and other services — from the device industry that profits from their work.
For example, the top provider of Medicare-financed atherectomies in Louisiana, Dr. David Allie, received $2.8 million from drug and device makers between 2013, when the federal government began collecting such data, and 2022. He didn’t respond to requests for comment.
In addition to those payments, device companies have lent money to 153 of the 200 doctors or their clinics to finance the purchase of medical equipment, according to a Times review of loan filings.
At least one company, Philips, allows doctors to reduce or eliminate their monthly payments if they use the company’s equipment to perform a minimum number of procedures, according to current and former Philips employees.
The Philips spokesman, Ken Peters, said the loans are issued by Philips Medical Capital, which Philips owns with a finance company. He said Philips Medical Capital made independent decisions about which doctors get loans.
Eva Gunasekera, who was the top lawyer in a health care fraud unit at the Justice Department from 2008 to 2017, said such incentives were problematic because they can prompt doctors to say, “Let’s use this procedure more.”
Some of the doctors who received the Philips loans had troubling professional histories.
Among them is Dr. Ralph Brookshire, a vascular surgeon in Texas. The state medical board found in 2016 that he had been abusing his medical license to prescribe himself opioids. The board said he was using the drugs during the same period that he performed a procedure that triggered hemorrhaging in a patient. (Dr. Brookshire said he was taking an opioid at night for migraines, not while he was treating patients. He is now in good standing with the board.)
In 2020, Dr. Brookshire opened his own outpatient clinic in the Rio Grande Valley. He needed at least $600,000. He approached lenders, which demanded high interest rates. He also balked at the terms offered by a venture capital firm.
So Dr. Brookshire turned to Philips, which lent him the funds to get his clinic running. Philips “can offer advantageous financing through this difficult hurdle in the process,” he said in a 2021 promotional brochure, “From Passion to Possible,” on the company’s website.
Philips Medical Capital also lent money to Dr. James McGuckin, a Pennsylvania radiologist, and the chain of clinics where he was chief executive, according to loan filings.
Dr. McGuckin has been among the most prolific providers of atherectomies, earning $4 million from Medicare for the procedures in 2021 alone.
Philips has featured Dr. McGuckin on its website. In a 2016 testimonial, he said Philips helped him procure imaging equipment across his multiple clinics, a “huge benefit and advantage.”
Yet authorities were publicly cracking down on Dr. McGuckin. The year before the testimonial, regulators in Washington State found that he had created an “unreasonable risk of harm” when he performed an unproven vascular procedure on patients with multiple sclerosis.
Dr. McGuckin paid a $17,500 fine but was allowed to keep practicing. Regulators in other states issued their own fines.
George Bochetto, a lawyer for Dr. McGuckin, said he “has saved literally thousands of patient limbs and lives.” He said no patients complained about Dr. McGuckin’s treatment, which was part of a clinical trial.
In 2018, Dr. McGuckin’s company agreed to pay $3.8 million to resolve federal allegations that the company defrauded Medicare by billing for unnecessary procedures on dialysis patients. Mr. Bochetto said the government “uncovered no evidence implicating Dr. McGuckin personally.”
In May, the Justice Department sued Dr. McGuckin for performing what the government said were more than 500 unnecessary procedures on patients with peripheral artery disease, including many that used Philips equipment. Mr. Bochetto predicted the lawsuit will be “deemed to have no merit.”
After receiving questions from The Times, Philips removed the testimonials of Dr. Brookshire and Dr. McGuckin from its website.
“We take any allegations relating to patient safety extremely seriously,” said Mr. Peters, the Philips spokesman.
Assembly Line
Of the 200 doctors who performed the most atherectomies, Dr. Mustapha stands out — both for the harm that patients and doctors say he has caused and for the support he has received from the device industry.
Dr. Mustapha’s ascent through vascular medicine is a rags-to-riches story that he has told frequently, including in promotional materials produced by G.E. Healthcare, which makes equipment used in vascular clinics. Born in Lebanon, he fled the war there and arrived in the United States in the 1980s as a teenager. He said he initially sold umbrellas on the streets of New York. After medical school, he eventually landed a job at Metro Health Hospital in Grand Rapids, Mich.
Dr. Mustapha’s website said he performed his first “limb-salvage treatment” more than a dozen years ago, “preventing the amputation of the leg of a 52-year-old woman.” Of all of his professional titles, the website says, he is proudest of “the Leg Saver.”
In 2018, he and his nephew, Dr. Fadi Saab, opened their first vascular clinic in Grand Rapids. Later that year, they opened another in Lansing. The business was called Advanced Cardiac & Vascular Centers for Amputation Prevention.
From 2013 to 2017, while Dr. Mustapha worked for Metro Health, he performed 358 atherectomies. In the next four years, he billed Medicare for more than 1,500. Dr. Saab billed the agency for 1,150 more.
Those atherectomies earned their clinics nearly $18 million from Medicare alone. That doesn’t include any procedures covered by private insurance.
Dr. Mustapha’s clinics at times felt like an assembly line, according to three former employees who requested anonymity because they still work in health care. Sometimes, they said, he performed procedures on two patients simultaneously.
Dr. Mustapha said that “procedures are scheduled with enough time so patients can be treated safely, kindly and respectfully.”
Dr. Ron VanderLaan, a cardiologist who briefly merged his practice with Dr. Mustapha’s in 2020, said he and his staff were pressured to refer as many patients as possible for vascular procedures at Dr. Mustapha’s clinics.
“They kept telling us we weren’t getting enough,” Dr. VanderLaan recalled.
Dr. Mustapha suggested Dr. VanderLaan was unreliable. He sued Dr. Mustapha’s clinic over his employment contract. And in 2019, Dr. VanderLaan was convicted of a misdemeanor, though it had no bearing on his medical license.
Rushed to the Hospital
Atherectomies and other procedures on Kelly Hanna’s veins and arteries started in February 2019.
That August, Ms. Hanna’s right baby toe had to be amputated.
Just over a year after the first procedure, she had undergone more than a dozen.
When she went to the hospital in July 2020, her right foot was purple and cold to the touch. A vascular surgeon at the hospital, Dr. Judith Lin, said in an interview that she had no choice but to amputate above the knee.
By then, Dr. Lin had already treated several of Dr. Mustapha’s former patients. Some required amputations. Others needed leftover wires extracted from their legs. Like Ms. McAdams’s surgeon, Dr. Lin complained to Michigan’s licensing board. The complaint described severe complications that Dr. Mustapha’s treatments had caused in multiple patients.
The patients recalled to Dr. Lin how Dr. Mustapha had warned them that atherectomies were needed to save their legs, she said in an interview.
“They would cry and say they can’t believe this is happening to them,” Dr. Lin said.
Dr. Mustapha questioned Dr. Lin’s expertise but declined to comment on what she said about his patients. He also raised the possibility of Dr. Lin having competing interests, because Michigan State University, her employer, is opening a vascular clinic in Lansing. Dr. Lin said that had nothing to do with her complaints, which long predated the new clinic.
Starting in 2020, the medical licensing board investigated her complaint and referred it to Michigan’s attorney general, who brought a disciplinary action against Dr. Mustapha. An expert hired by the state to review eight patient cases concluded that his practice “was characterized by overtreatment and poor documentation.” The expert found that in some cases, including Ms. Hanna’s, unnecessary procedures hastened amputations.
The state’s expert also cited the case of Traves Louch as another example of someone who underwent “a concerning number” of unnecessary procedures — four in less than three weeks.
After the last one, blood stopped flowing to Mr. Louch’s left foot. Ten days later, his lower leg was amputated.
“What the signs say on his offices is to prevent and help prevent amputations,” said Mr. Louch, 50. “And here I am with half my leg gone.”
Dr. Mustapha declined to comment on individual patients.
In April, he reached a settlement with the Michigan attorney general, agreeing to pay $25,000 and to take medical education courses. He did not acknowledge wrongdoing.
Dr. Mustapha said the state could have imposed a tougher punishment and the fact that it didn’t “speaks for itself.” He also said that members of the medical board lacked his experience in treating patients with advanced peripheral artery disease.
The state board is also investigating complaints that Blue Cross Blue Shield of Michigan filed last year against Dr. Mustapha and Dr. Saab. In its complaints, which The Times obtained through a public records request, the insurer said it had found that between 2017 and 2021, the doctors performed procedures on the same patients over and over, sometimes “within days of each other.”
Forty-five Blue Cross patients needed amputations after the doctors treated them, the insurer said.
“In each case, we made the treatment decision best suited to the patient’s condition,” Dr. Saab said. “No medical procedure is 100 percent efficacious in every circumstance. Some patients require multiple treatments, and some limbs cannot be saved despite our best efforts.”
Dr. Mustapha referred The Times to a handful of patients who raved about his treatment. Two said in interviews that Dr. Mustapha saved their limbs.
Another said he began seeing Dr. Mustapha at his doctor’s advice, even though he had no pain in his legs and was physically active. The man said Dr. Mustapha had been performing procedures on him for 14 years. In 2021, his lower leg was amputated.
A Symbiotic Relationship
Dr. Mustapha owes his rise in part to the companies whose devices and equipment he uses.
In a testimonial on the Philips website, Dr. Mustapha said that “from site identification to capital financing, Philips assisted every step of the way” when he and Dr. Saab opened their first vascular clinic.
Philips removed the testimonial following questions from The Times. Dr. Mustapha told The Times that the testimonial was mistaken and Philips did not help him select a site.
Philips and more than a dozen other device manufacturers have paid him about $2.6 million for speeches, consulting and other services since 2013. For example, Bard, which makes catheters and angioplasty balloons, paid him more than $467,000.
Troy Kirkpatrick, a spokesman for Becton, Dickinson & Company, which bought Bard in 2017, said collaboration between device companies and doctors is valuable. He described Dr. Mustapha as a leading expert on peripheral artery disease, whose work “aligns with our own ‘Love Your Limbs’ initiative in preventing amputations and improving patients’ lives.”
Dr. Mustapha made the most money — $633,200 — from Cardiovascular Systems International, known as C.S.I. Dr. Saab also received hundreds of thousands of dollars.
Dr. Mustapha said the payments were for teaching and consulting “so that I can spread the word and raise awareness” about treatment for peripheral artery disease.
Dr. Saab said, “All the medical decisions I make are motivated solely by what’s in the best interest of my patients.”
C.S.I. has a history of paying doctors to get them to use the company’s atherectomy devices. In 2016, the company agreed to pay $8 million to settle federal allegations that it had given illegal kickbacks.
According to a former C.S.I. executive, the company also contributed $100,000 to the CLI Global Society. The group was co-founded by Dr. Mustapha to advance the “common business interest” of doctors focused on severe artery disease. The society publishes a journal that frequently runs industry-sponsored studies that support the regular use of atherectomies and other procedures.
Dr. Barry Katzen, the president of the society, said the group was financed by its members as well as grants from companies.
A spokesman for Abbott, which bought C.S.I. this year, declined to comment on the company.
This year, Dr. Saab registered a business in Traverse City, Mich., using the same name as his and Dr. Mustapha’s other clinics. It is in a building with a podiatry clinic, whose website says it screens for peripheral artery disease. In May, Dr. Saab’s new business received a loan from Philips Medical Capital.
https://www.nytimes.com/2023/07/15/health/atherectomy-peripheral-artery-disease.html
Alzheimer’s drug trials target older Californians. Do they understand what they’re signing up for?
by Melody Peterson - LA Times - July 10, 2023
For those fearing their memories are fading, the ads provide hope.
“Early diagnosis extends quality of life,” says an ad by Dung Trinh, an Orange County physician, on the website of a program for seniors at Mount of Olives Church in Mission Viejo.
Trinh offers free memory tests and personalized recommendations based on the results. He gives scores of lectures a year at assisted living homes, senior centers, churches and Rotary Clubs in Southern California, telling audiences how they can keep their memories sharp. He describes himself as a medical missionary and “healthy brain” expert.
All this helps in his job of recruiting patients for a private company’s clinical trials of experimental drugs for Alzheimer’s disease.
The studies Trinh is recruiting for are part of a new gold rush in pharmaceutical research that was sparked when federal regulators approved two new drugs for Alzheimer’s. Trials of those two drugs have shown at best modest results in slowing cognitive decline.
The Food and Drug Administration’s controversial approval of the two drugs — Aduhelm and Leqembi — came as the country struggles with caring for a fast-rising number of Alzheimer’s patients with no cures to help them. More than 6 million Americans have Alzheimer’s — a total expected to double in the next 25 years.
After the manufacturers priced the first two medicines at more than $26,000 for a year of treatment, other companies sped up their efforts to complete clinical trials of their experimental drugs. More than 57,000 research subjects are needed for the planned trials of more than 140 experimental drugs for Alzheimer’s disease, according to a study published in May. A drug that meaningfully improved memory function could extend the quality of life for millions of people while saving billions of dollars in healthcare costs.
All this helps in his job of recruiting patients for a private company’s clinical trials of experimental drugs for Alzheimer’s disease.
The studies Trinh is recruiting for are part of a new gold rush in pharmaceutical research that was sparked when federal regulators approved two new drugs for Alzheimer’s. Trials of those two drugs have shown at best modest results in slowing cognitive decline.
The Food and Drug Administration’s controversial approval of the two drugs — Aduhelm and Leqembi — came as the country struggles with caring for a fast-rising number of Alzheimer’s patients with no cures to help them. More than 6 million Americans have Alzheimer’s — a total expected to double in the next 25 years.
After the manufacturers priced the first two medicines at more than $26,000 for a year of treatment, other companies sped up their efforts to complete clinical trials of their experimental drugs. More than 57,000 research subjects are needed for the planned trials of more than 140 experimental drugs for Alzheimer’s disease, according to a study published in May. A drug that meaningfully improved memory function could extend the quality of life for millions of people while saving billions of dollars in healthcare costs.
The increasing sums spent to recruit older people with memory problems to these experiments gives some doctors pause. They say that people with dementia can confuse the helpfulness of clinical trial recruiters with actual medical care from doctors, an outcome that scientists call a “therapeutic misconception.” The purpose of a clinical trial is to test an experimental drug, these doctors point out, and not to provide medical care.
And the trials have been the subject of intense debate. More than 95% of the studies of dementia drugs have failed to show the therapy slows memory decline. Plus, the drugs come with adverse effects, sometimes serious. At least three people participating in trials of Leqembi died, although its maker has questioned whether the drug was the cause, saying the number of deaths was similar to the rate in the placebo group.
The two new drugs and many of the others being studied are monoclonal antibodies that are designed to clear amyloid, a protein that can build up in the brain. They are given by intravenous infusion and come with a risk of bleeding or swelling in the brain. In the trials of Aduhelm, 40% of participants suffered from brain bleeding or swelling.
Aaron Kesselheim, professor of medicine at Harvard Medical School, said scientists performing the studies need to make sure patients with memory problems understand the risks.
“This is a population that may not fully understand the consent process,” Kesselheim said. “The investigator needs to be very careful to make sure people know what they are getting involved with.”
Peter Whitehouse, professor of neurology at Case Western Reserve University, said trial investigators can “earn phenomenal amounts” for the patients they recruit.
“There’s a bias for them to want to get people into these studies,” said Whitehouse, who has studied the financial conflicts of interest in Alzheimer’s research. In some cases, he has found, “they overpromise the likely results of these trials and create false hope.”
Trinh is an executive at privately held Irvine Clinical Research, which says it “is the leading independent site” for Alzheimer’s drug trials in California. The company has long focused its recruitment efforts in Orange County, with its large retirement communities, including Laguna Woods Village, which has 18,500 residents.
Late last year, Trinh expanded the company’s reach by setting up an office in Long Beach called the Healthy Brain Clinic, where he said he hoped to reach more Black patients and other minorities.
He holds “lunch and learns” where people can get a free meal while hearing his health tips. All his services are free to the patients, he explained in a February podcast. Pharmaceutical companies eager for new study volunteers are picking up the tab, he said.
His assistant assured the podcast audience that there was “absolutely” no danger for volunteers. “The patient’s health is our No. 1 priority,” she said.
In September, an 84-year-old grandmother from Lake Forest signed herself up for a trial at Irvine Clinical Research. The woman’s daughter said she did not learn of the clinical trial until weeks later when her mother suffered a sudden decline, acting confused and unable to remember what day it was. The family took her to the doctor, who ordered an MRI, which showed she had suffered a stroke.
The daughter asked that the family not be named so she could speak openly about her mother’s medical condition and treatment. The daughter said her mother had been worried about her memory but had not been diagnosed with Alzheimer’s.
She allowed The Times to review documents from the trial of the experimental drug called remternetug, which is owned by Eli Lilly, as well as the woman’s medical records confirming the stroke.
The woman signed a 21-page consent form, which listed risks of the drug.
Her daughter said her mother had recently struggled to make sense of her monthly electric bill.
“How was it even possible for her to consent to this study?” her daughter asked.
Federal regulations say that a person without the mental capacity to understand the consent form in a trial may not be enrolled unless a legally authorized representative consents on the subject’s behalf.
The FDA recommends that scientists running the study consider having an independent monitor such as a clinician unaffiliated with the trial’s sponsor determine whether patients have the mental capacity to know the risks in the consent form.
“From an ethical perspective, you want to make sure that people understand information that’s given to them,” said Emily Largent, a bioethicist at the University of Pennsylvania.
“Even well-intentioned investigators can sometimes have a conflict of interest,” she said. “It can help to have somebody who’s looking at the situation a little bit more dispassionately to maximize protections for individuals.”
In October, the woman received the first drug infusion in the trial. When she didn’t show up for later visits, Irvine Clinical Research repeatedly sent Ubers to pick her up at her mobile home park, her daughter said, which the family sent away.
The Times spoke to the woman this month. She said she did not remember going to Irvine Clinical Research or any of the visits described in the documents. “When did I go there?” she asked.
Ralph Lee, chief executive of Irvine Clinical Research, declined to answer questions, including how his company had ensured elderly patients had the capacity to understand the consent form and whether it used an independent expert. “We keep information about clinical trial participation strictly confidential, so we cannot answer your request,” he wrote in an email.
Trinh did not respond to repeated voicemail and email messages.
Irvine Clinical Research has performed other research for Eli Lilly. The trial company’s executives wrote on LinkedIn that they had enrolled more people into studies of donanemab, Lilly’s other experimental drug for Alzheimer’s, than any other trial site in the world.
Tarsis Lopez, an Eli Lilly spokesperson, said that the drug company’s research is subject to review by an independent institutional review board, which must approve trial protocols and consent documents.
The protocol for remternetug required participants to have Alzheimer’s disease that “has not progressed beyond the mild dementia stage,” he said.
“Lilly takes the safety and well-being of our valued clinical trial participants very seriously,” he said. “We are saddened to hear when anyone participating in a clinical trial experiences challenging medical issues, but we cannot comment on the specific circumstances of individual participants in ongoing clinical trials.”
Advarra, the private-equity-backed, for-profit institutional review board that Lilly hired to oversee the trial, declined to comment.
Performing clinical trials can be a lucrative business. A study of 225 clinical trials performed between 2015 and 2017 found that it cost pharmaceutical companies an average of more than $40,000, and as much as $75,000, for each test subject completing a trial.
Trials of Alzheimer’s drugs are especially expensive, according to USC researchers, because of the difficulty in recruiting patients and the extensive testing required of each participant. Drug companies typically pay the recruiting company $600 for a cognitive test, $2,400 for an MRI and up to $8,000 for a PET scan, the researchers said. Volunteers are often compensated as well.
Pharmaceutical companies are willing to pay those sums because a drug that wins approval can bring in many billions of dollars. Eisai, the Japanese company that sells Leqembi, one of the two drugs conditionally approved by the FDA, expects worldwide annual sales of the drug to reach $7 billion by 2030, the company’s executives said in March.
The FDA initially approved Leqembi and Aduhelm under accelerated approval rules that are used for drugs greatly needed by patients but not yet backed by studies proving their potential benefits.
On July 6, the agency granted Leqembi full approval based on an Eisai study that showed the drug slowed the rate of cognitive decline by 27%. Some doctors question whether that figure, which represents less than a half-point on an 18-point scale of cognitive function, constitutes a meaningful improvement for patients.
Irvine Clinical Research is just one of dozens of for-profit companies recruiting Alzheimer’s patients in California and across the country. The pharmaceutical companies also pay universities to recruit patients, but they often turn to the private research sites where there can be less bureaucracy to navigate.
“Drug companies have found that academic institutions can be difficult to deal with,” Whitehouse said. “So they like these private operators, who basically set up their own system to do trials and can be much more efficient at enrolling patients.”
Of the 76 sites recruiting patients for Lilly’s remternetug trial, one is a university.
Parexel, a trial operator owned by two private equity funds, including one controlled by Goldman Sachs, recruits patients using a method similar to Irvine Clinical Research’s. It created what it calls “a community memory clinic” on the campus of Glendale Adventist Medical Center.
In a medical journal article about the clinic, Parexel staff explained the company was recruiting patients for the earliest human trials of experimental drugs, including Phase 1. Such trials often involve small numbers of people because little is known about the experimental drug’s effect in humans. The employees wrote it was difficult to get people to sign up for these trials because they come with higher risks and require complex invasive procedures such as lumbar punctures.
The Parexel employees wrote that they had “significantly increased” the number of people referred to the company’s clinical trials by hosting lectures for seniors and then asking audience members a series of questions on their cognitive abilities. Those who appear to suffer from memory problems are invited to the memory clinic for a battery of neurological tests, they wrote.
If the staff concludes the person has mild cognitive impairment or Alzheimer’s disease, the article said, the person and their family are given recommendations and told about available clinical trials for which they could volunteer.
Parexel told The Times in a statement that the doctors and staff operating the memory clinic were separate from those performing the clinical drug trials. “The memory clinic does not manage clinical trials, it does not administer investigational drugs,” it said.
If the clinic finds a person has cognitive decline, the company said, the results are provided to the participant’s primary care physician for a diagnosis.
“Patient safety is always the highest priority,” Parexel said.
The company said that a physician running the trial makes sure participants are competent to understand the study risks by quizzing both them and their family members about the information in the consent form. It said the physician is employed by a medical group not owned by Parexel.
Since Parexel’s memory clinic opened in 2016, more than 400 people have had cognitive evaluations, the company said, but less than 3% were deemed eligible to participate in a clinical trial.
When pharmaceutical companies pay for the clinical trials, they control what information gets released.
Eli Lilly began testing remternetug in 2018 but decided to stop the Phase 1 trial after enrolling 36 healthy adults. The company did not release the results.
Six months after the Lake Forest woman entered the trial at Irvine Clinical Research, Lilly released data on 41 participants in a second Phase 1 trial.
The company said the drug had led to “rapid and robust amyloid plaque reduction” in the subjects’ brains and that the results supported its continuing research.
A close look at the data shows that 24% of the subjects suffered brain swelling and 17% had bleeding in the brain, according to the study. One of the 41 volunteers had both brain bleeding and swelling and attempted suicide.
David Knopman, a professor of neurology at the Mayo Clinic in Minnesota, reviewed the data for The Times and noted that the cases of brain swelling and bleeding increased as test subjects were given higher doses. He described the case of the participant who attempted suicide as a “serious symptomatic adverse event.”
The question, he said, is if investigators used the same dose in 200 people, how many of them would suffer similar complications. “And then the next question is, what’s the limit for where it becomes unacceptable?”
Knopman said that while the data showed the drug reduced levels of amyloid plaque, scientists don’t know whether that leads to improvement in cognitive abilities. “They removed amyloid, but you don’t know if that had any clinical benefit,” he said. That question is still being studied.
FDA guidelines say that recruiters trying to enroll people into studies should not imply that the experimental drug is safe or effective. Recruiters also should not promise free medical treatment, the agency said.
In a May 2022 webinar for residents of the Covington, an assisted living facility in Aliso Viejo, and other senior residences owned by ECS, Trinh told the audience they could get free tests to look for amyloid plaque in their brains at his office.
“Just give a call whenever today, tomorrow,” said Trinh, after giving the audience his email address and phone number.
“If we scan your brain or if we draw your blood and we see plaque, then we have medications in clinical trials that are designed to remove the plaque,” he said. “Our goal is plaque removal before there’s significant damage because that’s where prevention comes in.”
No comments:
Post a Comment