Between 2009 and 2017 the wholesale price of a single vial of Humalog, the Eli Lilly and Co.-manufactured insulin, nearly tripled — rising from $92.70 to $274.70.

This article was first published on Tuesday, March 12 in Kaiser Health News.

By Bram Sable-Smith

When Erin Gilmer filled her insulin prescription at a Denver-area Walgreens in January, she paid $8.50. U.S. taxpayers paid another $280.51.

"It eats at me to know that taxpayer money is being wasted," said Gilmer, who has Medicare and was diagnosed with Type 1 diabetes while a sophomore at the University of Colorado in 2002.

The diagnosis meant that for the rest of her life she'd require daily insulin shots to stay alive. But the price of that insulin is skyrocketing.

Between 2009 and 2017 the wholesale price of a single vial of Humalog, the Eli Lilly and Co.-manufactured insulin Gilmer uses, nearly tripled — rising from $92.70 to $274.70, according to data from IBM Watson Health.

Six years ago, Gilmer qualified for Social Security Disability Insurance — and thus, Medicare — because of a range of health issues. At the time, the insulin she needed cost $167.70 per vial, according to IBM Watson Health.

"When it's taxpayer money paying for medication for someone like me, it makes it a national issue, not just a diabetic issue," Gilmer said.

Stories about people with Type 1 diabetes dying when they couldn’t afford insulin have made headlines. Patient activists like Gilmer have protested high prices outside Lilly’s headquarters in Indianapolis.

Last October in Minnesota, state Attorney General Lori Swanson sued insulin manufacturers, alleging price gouging. Pharmaceutical executives were grilled about high drug prices by the Senate Finance Committee on Feb. 26.

This is the backdrop for Lilly's announcement last week that it is rolling out a half-priced, generic version of Humalog called "insulin lispro" The list price: $137.35 per vial.

"Patients, doctors and policymakers are demanding lower list prices for medicines and lower patient costs at the pharmacy counter," Eli Lilly CEO David Ricks wrote in a blog post about the move. "You might be surprised to hear that we agree – it's time for change in our system and for consumer prices to come down."

No Panacea

When Lilly’s Humalog, the first short-acting insulin, came to market in 1996, the list price was about $21 per vial. The price didn’t reach $275 overnight, but yearly price increases added up.

In February 2009, for example, the wholesale price was $92.70, according to IBM Watson Health. It rose to $99.65 in December 2009, then to $107.60 in September 2010, $115.70 in May 2011, and so on.

"There's no justification for why prices should keep increasing at an average rate of 10% every year,” said Inmaculada Hernandez of the University of Pittsburgh School of Pharmacy, who was lead author of a January report in Health Affairs attributing the skyrocketing cost of prescription drugs to accumulated yearly price hikes.

"The public perception that we have in general is that drugs are so expensive because we need to pay for research and development, and that's true," Hernandez said. "However, usually research and development is paid for in the first years of life of a drug."

At $137.35 per vial, Lilly’s generic insulin is priced at about the same level as Humalog was in 2012, 16 years after it came to market.

"We want to recognize that this is not a panacea," said company spokesman Greg Kueterman. "This is an option that we hope can help people in the current system that we work with."

It's worth noting that Humalog is a rapid-acting insulin, but that’s only one of the two types of insulin most people with Type 1 diabetes use every day. The second kind is long-lasting. Lilly makes one called Basaglar. The most popular long-lasting insulin is Lantus, produced by Sanofi. Neither has a lower-cost alternative.

Still, Lilly's move on Humalog could put pressure on the other two big makers of insulin to act.

Novo Nordisk called Lilly's lower-priced generic insulin "an important development," in an emailed statement.

"Bringing affordable insulin to the market requires ideas from all stakeholders," Novo Nordisk's Ken Inchausti said in an email, which also listed steps the company has taken, such as a patient assistance program. The statement didn't say whether Novo Nordisk is considering offering a lower-priced version of its popular insulin Novolog, a rival of Humalog.

A statement from Sanofi, the third major insulin maker, also didn't say whether the company would offer lower-priced versions of its insulins.

"Sanofi supports any actions that increase access to insulins for patients living with diabetes at an affordable price," spokewoman Ashleigh Koss said in the email, which also touted the company’s patient assistance program.

A Different Kind Of Generic

One twist in this story is that Lilly's new insulin is just a repackaged version of Humalog, minus the brand name. It's called an "authorized generic."

"Whoever came up with the term 'authorized generic'?" Dr. Vincent Rajkumar said, laughing. Rajkumar is a hematologist at the Mayo Clinic in Rochester, Minn.

"It's the same exact drug" as the brand name, he continued.

Typically, Rajkumar said, authorized generics are introduced by brand-name drugmakers to compete with generic versions of their drugs made by rival companies.

But in the case of Humalog and other insulins, there are no generics made by competitors, as there are for, say, the cholesterol medicine Lipitor or even other diabetes drugs, such as metformin.

So when Lilly's authorized generic comes to market, the company will have both Humalog insulin and the authorized generic version of that medicine on the market.

Rajkumar said it's a public relations move.

"There's outrage over the price of insulin that is being discussed in Congress and elsewhere. And so the company basically says, 'Hey, we will make the identical product available at half price.' On the surface that sounds great," Rajkumar said.

"But you look at the problems and you think, 'OK, how crazy is this that someone is actually going to be buying the brand-name drug?'"

In fact, it's possible that Lilly could break even or profit off its authorized generic compared to the name-brand Humalog, according to University of Pittsburgh's Hernandez.

The profit margin would depend on the rebates paid by the company to insurers and pharmacy benefit managers. Rebates are getting a lot of attention these days as one factor that pushes drug prices higher. They're usually not disclosed and increase as a drug's price increases, providing an incentive to some companies to raise prices.

"Doing an authorized generic is nothing else than giving insurers two options," Hernandez said: pay the full list price for a brand-name drug and receive a higher rebate, or pay the lower price for the authorized generic and receive a presumably smaller rebate.

"What we really need to get insulin prices down is to get generics into the market, and we need more than one," Hernandez said, adding that previous research has shown that prices begin to go down when two or three generics are competing in the marketplace.

Even so, Lillly's Kueterman said the authorized generic insulin "is going to help hopefully move the system towards a more sustainable model."

"I can guarantee you the reason that we're doing this is to help people," Kueterman said, noting the company's Diabetes Solution Center has also helped "10,000 people each month pay significantly less for their insulin" since it opened in August.

For Erin Gilmer, the news about an authorized generic insulin from Lilly has left her mildly encouraged.

"It sounds really good, and it will help some people, which is great," Gilmer said. "It's Eli Lilly and pharma starting to understand that grassroots activism has to be taken seriously, and we are at a tipping point."

This story is part of a partnership that includes NPR and Kaiser Health News.

Bram Sable-Smith: @besables

The Department of Defense has reportedly drafted proposals to convert more than 17,000 medical positions into fighting and support positions — a 13% reduction in medical personnel.

This story was first published Monday, March 11, 2019, by Kaiser Health News.

By Jordan Rau

The U.S. military is devising major reductions in its medical corps, unnerving the system's advocates who fear the cuts will hobble the armed forces' ability to adequately care for health problems of military personnel at home and abroad.

The move inside the military coincides with efforts by the Trump administration to privatize care for veterans. The Department of Veterans Affairs last month proposed rules that would allow veterans to use private hospitals and clinics if government primary care facilities are not nearby or if they have to wait too long for an appointment.

Shrinking the medical corps within the armed forces is proving more contentious and complex. In 2017, a Republican-controlled Congress mandated changes in what a Senate Armed Services Committee report described as "an under-performing, disjointed health system" with "bloated medical headquarters staffs" and "inevitable turf wars." The directive sought a greater emphasis for military doctors on combat-related needs while transferring other care to civilian providers.

Details of reductions have yet to be finalized, a military spokeswoman said. But within the system and among alumni, trepidation has increased since Military.com, an online military and veterans organization, reported in January that the Department of Defense had drafted proposals to convert more than 17,000 medical positions into fighting and support positions — a 13% reduction in medical personnel.

"That would be a drastic first cut," said Dr. David Lane, a retired rear admiral and former director of the Walter Reed National Military Medical Center in Bethesda, Md.

At most risk in the current planning are positions that aren't considered essential to troops overseas, such as training spots for new doctors and jobs that can be outsourced to private physicians and hospitals — obstetricians and primary care doctors, for example. The reductions may also limit the military’s medical humanitarian assistance and relief for foreign natural disasters and disease outbreaks.

Even in war zones, Lane warned, it would be a mistake to downplay the importance of contributions by doctors who do not specialize in trauma. In the 1991 invasion of Kuwait, for instance, cases of diseases and non-battle injuries rather than combat injuries created the most medical work, he said.

Doctors who train in the military's highly regarded medical school — who have committed to serve in the armed forces after training— and those who do military residencies account for much of the staff serving troops overseas. A major deployment could leave the military flatfooted, said Dr. John Prescott, a former Army physician.

"The majority of folks in the military don't stay in for their whole career, they stay in for a few years," Prescott said. "I'm concerned there will be a very small cohort that will be available for deployment in the future."

The military health system is responsible for more than 1.4 million active-duty and 331,000 reserve personnel, with 54 hospitals and 377 military clinics around the world. Split among the Navy, Army and Air Force, each with its own doctors and hospitals, the service has been targeted for years for overhaul to reduce redundancies and save costs.

The department has already started moving administrative functions under one bureaucracy, called the Defense Health Agency, which is slated to take over the service branch hospitals in 2021.

The budget for the next fiscal year is still being developed and final decisions have not yet been made, a Department of Defense spokeswoman, Lt. Col. Carla Gleason, said in an email. "Any reforms that do result will be driven by the Department's efforts to ensure our medical personnel are ready to provide battlefield care in support of our forces, and to provide the outstanding medical benefits that Service members, retirees and their families deserve," she said.

For years, critics of the broad role of the military health services have argued that many medical corps services — such as maternity care and pediatrics on bases — could be provided more effectively by civilian doctors and hospitals.

But Lane said there is too much focus on the high-profile trauma cases on the battlefield "that at the end of the day are a small portion" of medical care. "When we're trying to put things back together that got broken during a war," he said, "that's what you need the most of — pediatricians, public health doctors, primary care doctors."

Some studies commissioned by the department have concluded private hospitals could deliver less costly care, in part because doctors at hospitals take care of more patients. But the Congressional Budget Office said savings were not at all certain and that military hospitals might be less expensive if the government arranged for greater use of them.

Brad Carson and Morgan Plummer, who held senior jobs in the Department of Defense during President Barack Obama's administration, argued in a 2016 essay that the military isn't the best training for surgeons because it doesn't provide them with a sufficient number of cases to develop expertise.

The military health system "has too much infrastructure, the wrong mix of providers, and predominantly serves the needs of beneficiaries who could easily have their healthcare needs satisfied by civilian providers at far less cost and with equal or better quality," they wrote.

The government this year is spending $50 billion on the military health system, including Tricare insurance for more than 9 million active-duty service members, veterans, families and survivors, according to Congress’ budget office. That is roughly a tenth of the military budget. The CBO projected costs are on track to increase to $63 billion in 2033.

Defenders of the system reject the idea that non-wartime jobs can be eliminated without it hurting that core mission.

"Military healthcare providers between deployments maintain their clinical skills by treating service members and millions of beneficiaries," Dr. Arthur Kellermann, dean of the school of medicine at the Uniformed Services University in Bethesda, wrote in a 2017 Health Affairs article. "Military hospitals provide valuable platforms for teaching the next generation of uniformed healthcare professionals and standby capacity for combat casualties."

Prescott, the former Army doctor, said that the military may have trouble turning to civilian doctors in some regions given physician shortages, which he said the military cuts would exacerbate.

"Most hospitals are already pretty full, most healthcare providers are pretty busy,” said Prescott, now chief academic officer at the Association of American Medical Colleges.

Doctor shortages would increase if the military cut the slots it now has to train doctors, because there wouldn't be new civilian residencies created to compensate. "Those positions basically disappear," he said.

Kathryn Beasley, a retired Navy captain who is director of government relations for health affairs at the Military Officers Association of America, said she was also concerned with unforeseen consequences of dramatic cuts.

"Everything's tied together, there’s a lot of interdependencies in these things," she said. "You pull a string on one and you might feel it in an area you don't expect."

Jordan Rau: jrau@kff.org, @JordanRau

The FDA has let medical device companies file reports of injuries and malfunctions outside a widely scrutinized public database, which leave doctors and medical sleuths in the dark.

This story was first published Thursday, March 7, 2019, by Kaiser Health News.

By Christina Jewett

Dr. Douglas Kwazneski was helping a Pittsburgh surgeon remove an appendix when something jarring happened. The surgical stapler meant to cut and seal the tissue around the appendix locked up.

Kwazneski later turned to the Food and Drug Administration's public database that tracks medical device failures and "there was nothing," he said. Yet when he surveyed leading surgeons on the matter, he discovered that more than two-thirds had experienced a stapler malfunction, or knew a peer who did. Such failures can have deadly consequences.

Kwazneski had no idea the FDA had quietly granted the makers of surgical staplers a special "exemption" allowing them to file reports of malfunctions in a database hidden from doctors and from public view.

"I don't want to sound overdramatic here, but it seemed like a cover-up," said Kwazneski, who practiced in Pasco County, Fla., from 2016 through earlier this year.

The FDA has built and expanded a vast and hidden repository of reports on device-related injuries and malfunctions, a Kaiser Health News investigation shows. Since 2016, at least 1.1 million incidents have flowed into the internal "alternative summary reporting" repository, instead of being described individually in the widely scrutinized public database known as MAUDE, which medical experts trust to identify problems that could put patients in jeopardy.

Deaths must still be reported in MAUDE. But the hidden database has included serious injury and malfunction reports for about 100 medical devices, according to the FDA, many implanted in patients or used in countless surgeries. They have included surgical staplers, balloon pumps snaked into vessels to improve circulation and mechanical breathing machines.

An FDA official said that the program is for issues that are "well-known and well-documented with the FDA" and that it was reformed in 2017 as a new voluntary summary reporting program was put in place for up to 5,600 devices.

Yet the program, in all its iterations, has been so obscure that it is unknown to many of the doctors and engineers dedicated to improving device safety. Even a former FDA commissioner said he knew nothing of the program.

KHN pored over reams of public records for oblique references to reporting exemptions. After months of questions to the FDA, the agency confirmed the existence of reporting-exemption programs and thousands of never-before-acknowledged instances of malfunctions or harm.

Amid the blackout in information about device risks, patients have been injured, hundreds of times in some cases, lawsuits and FDA records show.

"The public has a right to know about this," said Dr. S. Lori Brown, a former FDA official who accessed the data for her research. She said doctors relying just on the public reports — and unaware that many incidents may be omitted — can easily reach the wrong conclusion about the safety record of a particular device.

The FDA has also opened additional — and equally obscure — pathways for device makers to report thousands of injuries brought to light by lawsuits or even deaths that appear in private registries that medical societies use to track patients. Those exemptions apply to risky and controversial products, including pelvic mesh and devices implanted in the heart.

FDA spokeswoman Deborah Kotz confirmed that the "registry exemption" was created without any public notice or regulations. "Any device manufacturer can request an exemption from its reporting requirements," she said in an email.

Agency records provided to KHN show that more than 480,000 injuries or malfunctions were reported through the alternative summary reporting program in 2017 alone.

Alison Hunt, another FDA spokeswoman, said the majority of device makers' "exemptions" were revoked that year as a program took shape that requires a "placeholder" report to be filed publicly.

More than a million reports of malfunctions or harm spanning about 15 years remain in a database accessible only to the FDA. But with the agency's new transparency push, the public may find a public report and submit a Freedom of Information Act request to get information about incidents. A response can take up to two years.

The long-standing exemption program "has allowed the FDA to more efficiently review adverse events … and take action when warranted without sacrificing the quality of our review or the information we receive," Hunt said in an email.

To those outside the agency, though, the exceptions to the reporting rules are troubling. They strike Madris Tomes, a former FDA manager, as the agency surrendering some of the strongest oversight and transparency powers it wields.

"The FDA is basically giving away its authority over device manufacturers," said Tomes, who now runs Device Events, a website that makes FDA device data user-friendly. "If they've given that up, they've handed over their ability to oversee the safety and effectiveness of these devices."

Doctors, like Kwazneski, who have turned to the public data to gauge the risks of surgical staplers have seen little. He wrote about the "unacknowledged" problem of stapler malfunctions in a 2013 article in the journal Surgical Endoscopy. In 2016, while reports of 84 stapler injuries or malfunctions were openly submitted, nearly 10,000 malfunction reports were included in the hidden database, according to the FDA.

Device maker Medtronic, which owns stapler maker Covidien, has been described as the market leader in surgical staplers. A company spokesman said that the firm has used reporting exemptions to file stapler-related reports through July 2017. Ethicon, the other major stapler maker, said it has not.

The public database shows that Medtronic has reported more than 250 deaths related to staplers or staples since 2001.

Mark Levering, 62, nearly lost his life after a stapler malfunction early last year, according to a lawsuit filed by his family. His surgeon has testified that a surgical stapler misfired during his liver surgery at ProMedica Toledo Hospital in Ohio.

Staff performed CPR for 22 minutes while surgeons rushed to suture the severed vein. He emerged from a coma unable to walk or consistently recognize his wife and son. The surgeon, hospital and device maker Covidien have denied allegations of wrongdoing in an ongoing legal case.

Told of the reporting "exemption" for surgical staplers, his wife, Doris Levering, was incredulous.

"Why would this information not be made available to doctors? The true information — I mean the actual numbers …" she said. "People's lives are at stake. Mark's life will never be the same."

The Stapler Problem

The sheer number of malfunctions made surgical staplers an easy pick for the new alternative summary reporting program at its inception nearly 20 years ago, according to Larry Kessler, a former FDA official and now a University of Washington health services professor.

Surgical staplers have a unique ability to help — or harm — patients. The device is designed to cut and seal tissues or vessels quickly, often during minimally invasive surgeries. When it fails to seal a major blood vessel, medical staff can quickly shift into "code blue" mode to rescue a patient from bleeding to death.

The severity of some of the injuries caught former FDA official Brown's attention in the early years of its reporting exemption. Her 2004 article on stapler mishaps, published in the Journal of the American College of Surgeons, accounts for one of the few places in public records where an FDA authority mentions the "alternative summary" program. She found that in the first 28 months of filing to the hidden database, stapler makers filed more than 5,100 reports of malfunctions or injuries.

She also noted that the publicly reported 112 stapler-related deaths in patients aged 22 to 91 from 1994 to 2001 were a "reason for concern."

In the public data filed since, it would appear that the staplers rarely misfire. In 2011, only 18 injury or malfunction reports were filed publicly. Last year, the number was 79.

Lawsuits detail how quickly a stapler failure can turn a smooth surgery into a catastrophe.

In Michigan, Eugene Snook's surgeon was in the process of removing part of his lung when he cut but couldn't seal a major vessel due to a "stapler malfunction," the surgeon said in sworn court testimony. Snook, then 59, had no detectable blood pressure for four minutes during the 2012 surgery.

The damage to Snook’s artery was so great, his surgeon decided to remove his lung completely, medical records filed in court say. Snook sued stapler maker Covidien, which in court records said there was no proof the stapler was unsafe when it left Covidien's control and also that the surgeon used it improperly. The case reached a confidential settlement in 2017.

Another surgeon attempting to remove a benign liver growth from April Strange, 33, in 2013, testified that a stapler malfunction caused the woman to bleed to death. Strange, of central Illinois, left behind a husband and two daughters, then 6 and 8.

The stapler was thrown out after surgery, court records say. Covidien argued in court records that Ryan Strange couldn't prove that the stapler had a specific defect.

Covidien reached an agreement to settle the family’s claims for $250,000, part of a larger settlement in the case.

Doctors initially thought Mark Levering had liver cancer. So when the diagnosis came back as an abscess that needed to be surgically removed last February, it came as a relief to his wife, Doris.

That relief turned to dread the day of surgery. The procedure was supposed to last two hours, she said. But the surgery hit a snag when the stapler "misfired," according to the surgeon, causing so much bleeding that the minimally invasive procedure was converted to an open procedure so the doctor could suture the vein.

Levering underwent CPR for 22 minutes. A code blue was called, a nurse testified. Levering lost 3 quarts of blood — about half the blood in his body. He was put on life support and would remain in a coma for weeks.

After Levering reopened his eyes, it was clear that the man who used to tend to stray cats and enjoy dinner out with his family was gone. Levering could no longer walk, comb his hair or recognize the letters of the alphabet.

Doris and Mark Levering have sued the doctor, hospital and surgical stapler maker, alleging that the device caused Mark's bleeding and brain injury. The surgeon has acknowledged in sworn testimony that the stapler malfunctioned, but denied other wrongdoing. The hospital said in a legal filing that its actions were "prudent, proper" and "lawful."

Covidien denies any defect with the stapler or that it caused Levering's injuries. A spokesman for parent company Medtronic declined to comment further on any lawsuit but said that "we always make patient safety our top priority" and that the company complies with FDA requirements.

The company's reports of stapler problems in the public database remain relatively low. But in 2018, with the reporting exemption gone, a spike of reports emerged for Covidien's staples — not to be confused with staplers. While Medtronic reported 1,000 staple malfunctions or injuries in 2015, the number soared to 11,000 for 2018.

Rolling Out The Program

The alternative summary reporting program started two decades ago with a simple goal: to cut down on redundant paperwork, according to officials who were at the FDA at the time.

Kessler, the former FDA official, said the program took shape after scandals over under-reporting of device problems spurred changes allowing criminal penalties against device companies.

Soon, thousands of injury and malfunction reports poured into the agency each month, with about 15 staff members dedicated to reviewing them, Kessler said. Many reports were so similar that reviewing them individually was "mind-numbing." Kessler went to the FDA's legal department and to device manufacturers to propose a solution.

Device makers would be able to seek a special "exemption" to avoid reporting certain complications to the public database. The manufacturers would instead send the FDA a spreadsheet of injury or malfunctions each quarter, half-year or year.

That way, Kessler said, reviewers could quickly look for new problems or spikes in known issues. When the program launched in 2000, the list of exempted devices was made public and only a few devices were involved, Kessler said.

"I don't know why it's not [made public] now," he said. "I'm surprised about that."

Starting in September, KHN filed Freedom of Information Act requests for "exemption" agreements and reports for several medical devices. Health and Human Services officials denied an appeal to provide some of the records quickly, concluding there was no "compelling need" for haste. For one request, the records were estimated to arrive in 22 months.

The FDA declined to provide a complete list of "about 100" devices that have been granted reporting exemptions over the years, but confirmed that exemptions have been used for mechanical breathing machines and balloon pumps, known as intra-aortic balloon pumps, inserted in the vessels of people with circulation problems.

An FDA spokeswoman said "alternative summary" exemptions remain in place for pacemaker electrodes and implantable defibrillators.

Matthew Baretich, a biomedical engineer in the Denver area, said he helps several area health systems analyze device-related patient injuries and make equipment-purchasing decisions.

He said he regularly scans the FDA's public device-injury reports. Asked about "alternative summary" reports, he said, "I've got to tell you, that's a new term to me."

Bruce Barkalow, president of a Michigan-based biomedical engineering firm, said he's the guy government officials, attorneys or device makers call if someone gets a pacemaker and dies in the shower three days later.

In an interview, he said he was not aware of the reports, either. He said they may appear to the FDA to be a "nothing burger," but the data would be meaningful to his forensic investigations.

The ECRI Institute, a nonprofit leader in medical device safety, declined to provide an engineer for an interview. Educating hospital leaders and health providers, the institute issues an annual "Top 10" in medical technology hazards. Its tagline: "Separating fact from fiction in healthcare."

Among the institute's "top medical device subject matter experts," spokeswoman Laurie Menyo said in an email, "none of them had any familiarity with FDA's Alternative Summary Reporting Program."

Even Dr. Robert Califf, former FDA deputy commissioner and commissioner from 2015 to 2017, said in an interview that he was unaware of the program. "Never heard anything about it," he said. "It's interesting."

Companies that get the exemptions tend to be very "tight-lipped" about them, said Christine Posin, a former device firm manager and consultant to device companies.

The relative secrecy around the program can give them an advantage, she said. For instance, sales representatives can print out only the public reports of device problems, ignoring what's buried elsewhere.

That creates a business opportunity to persuade a doctor to try a different device. "'We have a good product that does the same thing,'" Posin said a sales representative might tell a physician.

Exemptions Multiply

The FDA has spent millions, convened experts and pledged to improve its work in device safety in recent years. All the while, it has quietly opened new avenues for the makers of controversial and risky devices to file injury and even death reports with little public review.

Pelvic mesh is one example. The fabric-like device has long been used to hold up pelvic organs in women experiencing organ prolapse. In 2011, the FDA issued a "safety communication" saying "serious complications" like pain or infection were "not rare."

The agency soon reclassified the device, ordered safety studies and saw most mesh makers remove the device from the market.

Behind closed doors, though, the agency has since granted pelvic mesh makers a special exemption from reporting injuries to the public, according to the FDA and mesh makers who were asked about the practices.

Under what the FDA calls the "litigation complaint summary reporting" exemption, device makers can file a single placeholder "injury" report. Attached to the summary report, device makers have sent the FDA a spreadsheet with as many as 1,175 reports of patient injuries, based on allegations in lawsuits. 

To someone tallying the overall number of injuries related to pelvic mesh, the report would appear as a single injury. It would take a sharp eye to find the summary report and a special request — taking up to two years to be filled — to get the details on the 1,175 cases submitted directly to the FDA.

According to the FDA, in 2017 alone, eight mesh makers used their exemptions to send nearly 12,000 injury reports to the FDA.

Dr. M. Tom Margolis, a urogynecologist in the San Francisco Bay Area and an expert medical witness for those who are suing mesh makers, said a program that might hinder doctors relying on open FDA data to assess the risks of mesh is "horrible" and "unethical."

"We need to know the good and the bad," said Margolis, who treats patients in his urogynecology practice. "If you're trying to hide complications from me, well that's … wrong, my God, it's heinous."

The FDA issued the same kind of exemption to the makers of da Vinci surgical robots months after Johns Hopkins University School of Medicine researchers pointed out that the company was filing a notably small number of injury reports in the public database. Johns Hopkins professor Dr. Marty Makary noted in 2013 that the handful of reports sent to the FDA at the time were signs of a "haphazard" system that is "not independent and not transparent."

Within months, the FDA allowed the makers of the robots to file a single report, noting that a spreadsheet sent straight to the FDA summarizes about 1,400 injuries alleged in lawsuits, with some injuries dating to 2004. Since then, the device maker has reported smaller batches of 99 and 130 injuries at a time.

"This is very frustrating," said Homa Alemzadeh, an assistant professor of computer engineering at the University of Virginia who is working with MAUDE data to create software to identify errors in real time or before they happen in surgeries performed by robots. She said she was not aware of the reporting exemption.

Under another reporting exemption, the FDA is allowing device makers to report hundreds of death cases in spreadsheets sent directly to the agency.

Under the "registry exemption," device makers can summarize what they learn from registries that tend to be held by specialty medical societies, and track the use of a certain kind of device, according to FDA spokeswoman Kotz. 

Kotz said the data in registries often falls short of the level of detail that the FDA seeks for the more thorough death reports that device makers are required to file.

Device makers filing such reports include Edwards Lifesciences, which makes the Sapien 3 valve that's snaked through a vessel and implanted in the heart. Some hail the device as a breakthrough for saving patients from the trauma of open-heart surgery to replace a valve. Others raise concerns over limited data showing how long the valve will last in the body.

The summary reports offer potential patients few answers. Such reports document as many as 297 deaths or 1,800 injuries in a single filing, with virtually no detail readily available to the public. In all, Edwards has filed more than 1,800 Sapien 3 valve patient deaths as summaries since 2016.

Edwards spokeswoman Sarah Huoh said in an email that the FDA mandated the tracking of every patient who has the valve in the registry to provide "comprehensive evidence for device safety."

"The approval of alternative reporting protects against duplicate reports coming from multiple sources," Huoh said.

Another device, the MitraClip, is used to attach two flaps in the heart that are allowing blood to flow backward. The device has been controversial, with some scientists saying it is crucial for a certain subset of patients, and others pointing to the harm it can cause to the heart.

The FDA has allowed Abbott Vascular, which makes the MitraClip, to report as many as 347 deaths or 1,000 injuries in a single filing, also shipping the details straight to the agency, FDA records show.

An Abbott spokesman said in an email that the company has done clinical trials with thousands of patients to establish the MitraClip's safety. He said the exemption was granted because data in the registry was stripped of patient identifiers, making it hard to know whether the company would be filing redundant reports to the FDA.

Last year, the FDA finalized regulations for yet another summary reporting program. Under the newest system, device makers do not have to seek an exemption or notify the FDA that they'll be filing a public summary report in MAUDE.

The FDA has deemed the makers of more than 5,600 types of devices eligible to file "voluntary malfunction summary reports." Among them are some of the riskiest devices the agency oversees, including cardiac stents, leadless pacemakers and mechanical heart valves.

The growing cadre of exceptions to the injury- and death-reporting rules strikes Dr. Michael Carome, director of the Public Citizen Health Research Group, as a retreat by the FDA from making crucial information available for researchers and patients.

"It's just another example of a flawed oversight system," he said, "bent toward making it easier for industry rather than making protection of public health the primary goal."

California Healthline reporter and producer Heidi de Marco contributed to this report.

Christina Jewett: ChristinaJ@kff.org, @by_cjewett

Heidi de Marco: heidid@kff.org, @Heidi_deMarco

A small but growing number of doctors prescribe drugs 'off-label' for their possible anti-aging effects, even though there is scant evidence that the practice works.

This story was first published Wednesday, March 6, 2019, by Kaiser Health News.

By Marisa Taylor

Dr. Alan Green's patients travel from around the country to his tiny practice in Queens, N.Y., lured by the prospect of longer lives.

Over the past two years, more than 200 patients have flocked to see Green after learning that two drugs he prescribes could possibly stave off aging. One 95-year-old was so intent on keeping her appointment that she asked her son to drive her from Maryland after a snowstorm had closed the schools.

Green is among a small but growing number of doctors who prescribe drugs "off-label" for their possible anti-aging effects. Metformin is typically prescribed for diabetes, and rapamycin prevents organ rejection after a transplant, but doctors can prescribe drugs off-label for other purposes — in this case, for "aging."

Rapamycin's anti-aging effects on animals and metformin's on people with diabetes have encouraged Green and his patients to experiment with them as anti-aging remedies, even though there's little evidence healthy people could benefit.

"Many of [my patients] have Ph.D.s," said Green, who is 76 and has taken the drugs for three years. "They have read the research and think it's worth a try."

In fact, it's easier for patients to experiment with the drugs — either legally off-label or illegally from a foreign supplier — than it is for researchers to launch clinical trials that would demonstrate they work in humans.

No rigorous large-scale clinical trials have been conducted aimed at aging. The FDA so far has not agreed that a treatment could be approved for delaying the onset of aging or age-related diseases, citing questions about whether research can demonstrate an overall effect on aging rather than just on a specific disease.

Given such reservations, pharmaceutical companies have little incentive to fund costly, large-scale trials. Also, both metformin and rapamycin are generic and relatively cheap.

"There's no profit," said Matt Kaeberlein, a professor of pathology at the University of Washington medical school whose team received a $15 million grant from the National Institutes of Health to study the effects of rapamycin in dogs, but has noted the lack of funds for studies in people. "Without profit, there's no incentive."

Supplements with purported anti-aging effects routinely enter the market with little scrutiny and less evidence.

Yet, late last year, the NIH rejected a $77 million grant proposal by a prominent group of researchers to determine whether metformin could target multiple age-related diseases at once. It was the second rejection of the ambitious but unorthodox bid.

"We’re going to keep trying," said a lead author of the metformin proposal, Stephen Kritchevsky, a co-director of the Sticht Center for Healthy Aging and Alzheimer's Prevention. "These things take time."

Less is known about rapamycin's anti-aging effects and its possible side effects in the general population, including the possibility it could lead to insulin resistance. Yet a litany of studies show that rapamycin extends animal life spans. It also has been shown in such studies to stave off age-related diseases, from cancer to cardiovascular diseases to cognitive diseases.

"There should have been a clinical trial for rapamycin and Alzheimer's disease years ago," said Kaeberlein, who has publicly urged NIH to use a historic boost in Alzheimer's funding to study the drug’s effects. "But the fact is, the clinical trials are really hard and expensive."

Alexander Fleming, a former FDA official and advocate for the metformin proposal, said he believed it was difficult for regulators and funders to grasp that aging can be tackled as a whole — not just one disease at a time.

In fact, NIH reviewers who rejected the metformin proposal cited problems with the project's aim of testing multiple age-related diseases at once. The researchers considered appealing the decision, asserting those reviewers were biased against studying aging as a whole. NIH, which declined to comment, discouraged the attempt.

Dr. Evan Hadley, director of the National Institute on Aging's division of geriatrics and clinical gerontology, told Kaiser Health News that NIH is not ruling out funding projects that target aging, saying such proposals are still "of interest."

The FDA also is open to considering such efforts "based on the scientific evidence presented to us," said FDA spokeswoman Amanda Turney.

Fleming, who oversaw the controversial FDA approval of metformin for Type 2 diabetes, said an argument could be made that it could approve a drug like metformin for preventing age-related diseases instead of just treating them. He points to now widely used statins, which were approved to prevent heart disease.

"There is some kind of belief that the FDA can't approve a therapy to reduce the progress of aging or age-related conditions," said Fleming, an endocrinologist. "It's just not true."

Given the lack of consensus, other researchers have moved ahead with clinical trials focused on specific age-related conditions.

Researchers have shown that a "cousin" of rapamycin boosts the effectiveness of flu shots and lowers the incidence of upper respiratory infections in seniors by up to 30%. This group, led by Dr. Joan Mannick, has licensed it from Novartis and is now working on getting approval to target Parkinson's disease.

"We're trying to be pragmatic," Mannick said of her team's approach.

Some doctors and patients have decided not to wait. At a recent scientific forum on aging, one of the researchers on the NIH proposal asked the 300 or so people in attendance to raise their hands if they were already taking metformin for aging.

"Half the audience raised their hands," recalled the researcher, Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, who said a pharmaceutical rep recently estimated that metformin sales are up 20%.

Barzilai is concerned about the off-label trend, although he sees metformin as promising. He contends that researchers in the longevity field first need to set up a framework for testing in clinical trials. Even if metformin doesn't pan out as the most effective drug, he asserts a model like the metformin proposal is needed for any major clinical trial to proceed. His group is now trying to secure about half the amount of funding it requested from NIH from a mix of nonprofit and private investment.

"Much of the aging field is charlatans," Barzilai said. "They tell you take this or that and you'll live forever. But you have to do a clinical trial that is placebo-controlled and only then can you say what it really is and whether it’s safe."

Green nonetheless said he plans to continue prescribing. He estimates about 5% of his patients are doctors themselves. Others have backgrounds in science or are in the upper-income bracket. According to his website, he charges $350 for an initial visit and does not accept insurance.

"They fly to see me on their own planes," he said.

But other doctors who are open to prescribing metformin are holding off on rapamycin, given side effects in higher doses in sick patients.

"I need to see more evidence," said Dr. Garth Denyer, a doctor in The Woodlands, a wealthy Houston suburb, who said he prescribed metformin to a small number of patients but is waiting on rapamycin. "I'm hoping to see more data on safety."

Michael Slattery, who has been HIV-positive since 1983, said he is taking both drugs because the virus is likely to shorten his life expectancy.

So far, he has not noticed any side effects or benefits. His partner, however, who is also HIV-positive, stopped taking rapamycin after getting kidney infections.

"I feel I have nothing left to lose," said Slattery, a retired biotech consultant.

Other patients remain hopeful, even though the evidence is unlikely to be definitive anytime soon.

Linda Mac Dougall, 70, of Port Hueneme, Calif., said she participated in a small study that did not have a placebo control. She’s uncertain whether it had any effect on her.

"I really haven't noticed anything, but that doesn't mean it didn’t work," said Mac Dougall, a massage therapist for seniors. She has slightly more confidence in the wide array of supplements she takes, she said: "If I live until I’m 110, we’ll know."

Marisa Taylor: mtaylor@kff.org, @marisaataylor