Category Archives: News Stories & Editorials

FDA Recommends “Modernizing” Review of Devices in Wake of Global Investigation

Jeanne Lenzer, The British Medical Journal: November 27, 2018


The US Food and Drug Administration is making changes to how medical devices are cleared for sale after a scathing investigation into the industry.

The global investigation into the medical device industry by journalists from 36 countries, including The BMJ, BBC Panorama, and the Guardian and led by the International Consortium of Investigative Journalists, unearthed thousands of documents to reveal rising numbers of malfunctions and injuries.

Scott Gottlieb, FDA commissioner, and Jeff Shuren, director of the Center of Devices and Radiological Health, said in a statement that there would be changes to the 510(k) pathway that is used to clear four in every five devices for sale. The pathway approves devices not on the basis of testing in humans but on how similar devices are to previous devices, called “predicates,” some of which were approved decades ago.

Gottlieb and Shuren said that … they were “encouraging” manufacturers to “use more modern predicates,” [….]

However, the reform didn’t go far enough, said Diana Zuckerman, epidemiologist and president of the National Center for Health Research in Washington, DC. She told The BMJ that using more “modern” predicates says nothing about safety or effectiveness. She said that “newer doesn’t mean better” and that “since less than 5% of 510(k) devices undergo any type of clinical trials, there’s no assurance that any devices cleared through that pathway are safe or effective.”

In 1996 the US Supreme Court concluded that “since the 510(k) process is focused on equivalence, not safety . . . if the earlier device poses a severe risk or is ineffective, then the later device may also be risky or ineffective.”

A recent study found that 16% of mesh clearances were based on recalled devices. When the FDA was asked why it cleared mesh implants on the basis of predicate devices that had been withdrawn because of safety concerns, the agency said that it didn’t evaluate the performance of predicate devices when clearing devices for sale.

A study of high risk implanted cardiac devices found that only 5% underwent clinical testing that even partly approximated the testing required for drug approvals.

Nor is safety surveillance reliable. A Government Accountability Office analysis found that 99% of device related “adverse events” were never reported to the FDA and that the “more serious the event, the less likely it was to be reported.”

Read the original article here.

Here’s What We Know About Breast Implants and This Rare Type of Cancer

Daisy Melamed Sanders, Survivornet: November 2018.

A series of new stories are examining the potential health risks that both silicone- and saline-filled breast implants may carry. The most serious of these is the possibility of developing a type of blood cancer. What’s not yet clear is if the evidence is significant enough for the government to issue a warning.

The blood cancer that implants may cause, called Breast Implant-Associated Anaplastic Large Cell Lymphoma or BIA-ALCL, is a type of non-Hodgkins lymphoma that is not breast cancer. It is rare, and symptoms include pain, redness and swelling around the implant or breast area.

And while getting breast implants certainly does not definitively mean you’ll definitely get this type of lymphoma, it’s a dangerous illness for those who do get it. “ALCL is rare, but for those who get ALCL from their breast implants, it is very frightening and potentially fatal,” says Diana Zuckerman, PhD, President of the National Center for Health Research.

Here’s what we do know: The Food and Drug Administration—responsible for regulating medications and medical devices—has acknowledged that it has known of a potential relationship between breast implants and increased risk of ALCL since 2011. The risk involves both textured and smooth implants but the FDA’s position is that the textured kind may have a higher likelihood of causing the disease. The FDA also notes that incomplete or inefficient monitoring of, and reporting on, these health issues on a national level has meant that many women do not know all the facts when choosing to have implants for either cosmetic or reconstructive reasons.

According to the FDA, “In most cases, BIA-ALCL is found in the scar tissue and fluid near the implant, but in some cases, it can spread throughout the body. Precise risks are difficult to determine due to lack of information about how many patients have received breast implants in the US and worldwide.”

In an interview conducted prior to recent news, Dr. Andrea Pusic, Chief of Plastic Surgery at Brigham and Women’s Hospital, told SurvivorNet that breast implants are generally considered safe—but they do require monitoring by a doctor. The FDA also states that breast implants are “not lifetime devices,” and that the longer a patient has them, the more likely they are to rupture or experience other complications.

With regards to the safety of implants, Dr. Darrick Antell, a private practice plastic surgeon in New York City, cites the rarity of these instances as part of the reason implants are not excessively dangerous. “Textured surface implants have rarely been noted to develop ALCL, at a rate of 1 in 30,000—I would even recommend them to a family member,” he says. “Multiple leading institutions from around the world have shown them to be safe.”

But, as Dr. Zuckerman urges, it’s important to discuss the risk with your doctor before getting implants, because some women felt blindsided and uninformed about the disease possibility. “We know women who, when they developed ALCL, felt betrayed because their doctors hadn’t warned them of the risks.”

Breast implants also have the possibility of causing other health or physical issues. These issues have not been fully studied, but Zuckerman and the NCHR recently released a paper that discusses some of the possible side effects.

The risks that come with implants are real for all women, Dr. Zuckerman tells SurvivorNet, but these risks increase with a personal or family history of autoimmune or connective tissue symptoms or diseases. They can happen soon after getting implants or years later, and are especially likely when a silicone gel implant breaks—most likely after three years. Another issue is that leaking silicone can migrate into the lymph nodes, and, “from there, the silicone can get into the lungs, liver, or other organs.” Broken saline implants, she continues, offer less risk when they leak, but can cause health issues from the silicone shell, other chemicals, as well as from bacteria, fungus and mold issues that develop over time.

This isn’t the first time instance of concern regarding breast implants and potential health risks. Throughout the 1980’s and early 1990’s, a company called Dow Corning was named in a number of class-action lawsuits claiming that their breast implants were the cause of a number of health issues.

In 1992, the FDA mandated that silicone implants be removed from the market, but they were re-introduced in 2006 following stricter regulations around tracking patients for at least 10 years after their surgeries. However, because monitoring the implants and patients with them is not always thorough nor properly reported, it is difficult to know for sure what side effects implants are having in the long term.

The best idea, as always, is to discuss all the possible risks and benefits of implants with your doctor before any procedures, and be on alert for any symptoms that indicate a medical issue, suggests Dr. Zuckerman. “If a woman with implants starts to have any of the autoimmune symptoms that we’ve described in our report, she should consider having her implants removed.”

See the original story here.

Medical Device Dangers: FDA Facing Criticism Over Missed Signs

Today News: November 26, 2018.


Americans undergo hundreds of thousands of surgeries involving medical devices every year – but does the system that regulates the devices put patients at risk? An NBC News investigation, in conjunction with the International Consortium of Investigative Journalists, takes a closer look at one type of hip device that caused a world of pain for patients, including former Olympic gymnast Mary Lou Retton. NBC’s Stephanie Gosk reports for TODAY. NCHR’s Jack Mitchell explains to the Today Show why metal on metal hip replacements were used in US after warnings were released in other countries.

See the original story here.

Breast Implant Injuries Hidden as Patients’ Questions Mount

Meghan Hoyer, Associated Press: November, 26 2018.


WASHINGTON (AP) — To all the world, it looked like breast implants were safe. From 2008 to 2015, the U.S. Food and Drug Administration publicly reported 200 or so complaints annually — a tiny fraction of the hundreds of thousands of implant surgeries performed each year.

Then last fall, something strange happened: Thousands of problems with breast implants flooded the FDA’s system. More than 4,000 injury reports filed in the last half of 2017. Another 8,000 in the first six months of 2018.

Suddenly, women like Jamee Cook had evidence suggesting their suffering might be linked to their breast implants. An emergency room paramedic, Cook had quit her job because of a vague but persistent array of health problems that stretched over a decade, including exhaustion, migraines, trouble focusing and an autoimmune disorder diagnosis.

Why had it taken so long for complaints like hers to see the light of day?

Makers of breast implants were required to track patients and their health. But for more than a decade, manufacturers with high numbers of recurring problems — in the case of implants, ruptures that required surgery to remove — were allowed to report issues in bulk, with one report standing in for thousands of individual cases and no way for the public to discern the true volume of incidents.

That agreement stood even as the FDA began closely monitoring a rare type of cancer and acknowledged in 2011 that it might be linked to breast implants.

“It looked like these devices had become safer, but they hadn’t,” Cook told The Associated Press. “The data was hidden. It’s a deceptive practice.”

Once Cook’s textured saline implants were removed, she said the majority of her symptoms disappeared. Her experiences prompted her to become a patient safety advocate, lobbying lawmakers and organizing groups of women online who have concerns about breast implants.

Public health advocates who’ve watched the debate over breast implant safety rage for nearly three decades say summary reporting is yet another way that information about the devices has been elusive for patients.

“They were told those devices were safe — the FDA would go back and say ‘We only have this many reports,’” said Madris Tomes, a former FDA staffer who founded a company to analyze medical device reports. “But data was coming in another way that wasn’t public. It leaves the patients demoralized — they don’t understand how many other people are suffering.”

The data came to light after the FDA instructed manufacturers in mid-2017 to go back and file individual reports in each case of patient injury, in response to a lawyer’s discovery that reports from his clients weren’t represented in the agency’s data. Patient advocates took up the issue, complaining about a lack of transparency and voicing concerns about a host of autoimmune problems they believed stemmed from their implants.

But even as the FDA was dealing with the problems of how breast implant manufacturers had used summary reporting, the agency was moving to expand device makers’ flexibility in how they report problems, saying it was trying to reduce the industry’s paperwork requirements.

This August, the agency began allowing roughly 90 percent of all medical devices — including all breast implants and more than 160 types of other high-risk implanted devices like artificial hips and replacement heart valves — to report malfunctions in a quarterly tally, instead of individually. They will not be able to report cases involving deaths or injuries that way, however.

The FDA rejected claims that expanding summary reporting could harm public health by making problems with devices less transparent, saying the plan “will also yield benefits . such as helping FDA process malfunction reports more efficiently and helping both FDA and the public more readily identify malfunction trends.”

FDA officials also said that the agency has closely monitored the breast implant industry in the past decade and issued updates about potential risks.

Two of the largest breast implant manufacturers, Mentor and Allergan, said they stood behind the safety of their products, citing years of studies that have led to inconclusive evidence that autoimmune problems are linked to breast implants.

“Our medical devices undergo extensive laboratory testing before they are submitted to government health experts for a science-based review,” Mentor spokeswoman Mindy Tinsley said. “Many of our devices undergo careful reviews by not just one, but multiple regulatory bodies around the world.”

Still, it can be hard for breast implant patients and advocates to track problems that do arise.

Insurance claims make no mention of the specific device or model implanted in a patient, and patients’ electronic health records aren’t required to record that either. In addition, products sold overseas can be renamed or carry a different model number, making international recalls or tracking across borders nearly impossible.

Meanwhile, the FDA’s main database on medical device problems, which requires manufacturers to report patient deaths and serious injuries to the government within 30 days, relies on hand-typed entries from a variety of people — from patients to device manufacturers — to help track troubled products. That can lead to underreporting, along with missing and flawed data.

Tomes said accurate, complete and publicly accessible data is crucial to identifying problems quickly and making sure devices are safe. The FDA numbers, she said, offer the lowest possible count of reports about problems with breast implants.

“You can assume that the numbers are probably much, much higher,” she said.

A Duke University report funded by the FDA in 2016 found that even though the agency collected data on device malfunctions for more than two decades, “reliably and efficiently tracking the medical device safety and effectiveness outcomes of most interest to patients remains a generally unfulfilled promise” that “significantly affects the public health.”

Insurers, auto buyers and regulators all use a car’s VIN number to track a vehicle’s history, down to the line it was manufactured on at a specific factory, and the FDA’s own pharmaceutical drug oversight works similarly. But medical devices didn’t have a similar unique identifier until 2015, and many of the least-risky devices won’t put an ID into use until 2020. On top of that, experts say it could be years before their use is required in patient records, on insurance claims and in the FDA’s own data.

What are the most common makes and models of breast implants reported as having caused injury? The FDA’s answer is still quite often “Unknown.”

___

The FDA requires manufacturers and medical facilities to file a report when any kind of medical device causes serious injury, death or malfunctions.

The resulting database — called MAUDE, for Manufacturer and User Facility Device Experience — is available online to the public, so consumers can search for a device type, manufacturer, the details of an incident and the date on which it occurred. That is, if the forms are filled out properly.

But categories often are left blank, with no indication of the model or who submitted the report. And device names and manufacturers also are often misspelled, making it nearly impossible for users to find all the reports of problems with a specific device or company. For example, the data contains roughly 2,000 variations of the name Medtronic plc, one of the world’s largest medical device manufacturers.

Overall, the MAUDE data contains reports of more than 1.7 million injuries and nearly 83,000 deaths over the past 10 years for all types of medical devices, according to an analysis of FDA data by the International Consortium of Investigative Journalists, which collaborated with the AP on a global investigation of medical device safety.

But in looking at problems with the MAUDE data, the investigation found an additional 2,100 cases in the past five years where people died but their deaths were misclassified as “malfunctions” or “injuries.” Of those, 220 deaths could be directly linked to medical device failure; the other reports did not include enough information to determine conclusively if the device played a role.

Beyond the misclassified data, FDA inspections at 17 hospitals in 2015 and 2016 found that only a fraction of “adverse events” were even being reported anyway. The review —which included major facilities in Los Angeles, New York, Boston and Chicago — found more than half failed to report deaths of patients with medical devices, as required by the agency’s rules. Jeffrey Shuren, the head of the FDA’s device division, said at the time that underreporting problems from hospitals was widespread. The agency enhanced compliance training for hospital employees nationwide as a result.

Part of the problem, advocates say, is that the FDA’s guidelines for reporting problem devices is vague — the agency states that reports are required from manufacturers within 30 days of an event when evidence “reasonably suggests” that a device was involved, allowing companies to make their own judgments.

S. Lori Brown, now a retired FDA senior researcher, used MAUDE for years in her studies of breast implants, ruptures and possible links to rare forms of cancer and a host of autoimmune disorders.

“It’s a difficult database to use, because there’s no good way to confirm what’s reported, and there’s no denominator — you don’t know how many people have received breast implants,” Brown said. “The MAUDE database was just not very helpful in finding out how frequently things happened or how severe the impact was.”

Where it was helpful, she said, was in gathering patient stories and seeing general trends. In the 1990s, even as manufacturers claimed breast implants were durable enough to be run over by a car without breaking, MAUDE showed silicone implants leaking gel into thousands of women’s bodies.

“As a signal, it was a burning bush, for sure,” Brown said. “Because there were so many reports of ruptured implants from every manufacturer.”

After the FDA removed silicone breast implants from the market in 1992, the public attention around ruptures and leaks resulted in a huge spike in the number reports about problems. During the 1990s, silicone implants represented the third-highest number of adverse events reports in MAUDE. At the time, the data show patients also complained about other symptoms, with hundreds of reports about chronic fatigue, headaches, autoimmune problems and fibromyalgia.

In 2006, silicone implants returned to the market, under the requirement that companies track patients for at least a decade. Although more than half the women dropped out of the studies within the first two years, researchers at the University of Texas MD Anderson Cancer Center in Houston released a study this September using the data the companies did collect and found that certain rare health problems — including immune system and connective tissue disorders — might be more common with silicone gel implants. The FDA, which mandated the original data collection, later criticized the study, citing “inconsistencies in the data.”

Last year, the FDA did confirm a link between breast implants, particularly textured saline or silicone models, and anaplastic large cell lymphoma — a rare cancer documented in only a few hundred cases.

On its website, the FDA also noted more common problems with implants, such as ruptures, which can send silicone gel throughout the body. And the agency warned that implants “are not lifetime devices,” but will likely need to be removed or replaced at some point.

The return of silicone implants, which advocates say feel more natural, has fueled a surge in surgeries. The American Society of Plastic Surgeons reported 400,000 procedures took place in 2017, up nearly 40 percent since 2000.

More than three-quarters of the implant surgeries were for cosmetic, not reconstructive, reasons. And there were about 20 percent fewer removals compared to 2000, the data show.

The increase in implants worries Diana Zuckerman, a medical researcher who was a congressional staffer during the earliest contentious House hearings on breast implant safety. She said poorly performed studies, research funded directly by manufacturers and the lack of data have left most women in the dark about the risks involved.

“Somehow, it’s the most studied device and we have almost no useful information about it,” said Zuckerman, the president of the National Center for Health Research, a nonprofit think tank that performs its own research, assesses the quality of others’ research and works with patients.

Zuckerman’s center reviewed more than 20 studies it says has been used by the industry to claim there is no evidence breast implants cause connective tissue problems and other long-term illnesses. She said almost all the studies were too small to detect rare diseases and conditions, only one required that participants have a medical exam and most didn’t focus on patients who had implants long enough for problems to develop.

In September, Cook and 19 other breast implant patients-turned-health-advocates visited Washington to lobby the FDA for more stringent regulation, testing and reporting on breast implants. Among their requests — that all types of textured implants, which are more closely associated with lymphoma, be banned from the market, and that manufacturers be required to disclose the chemicals in silicone implants’ shell and gel filling, which the makers claim is a trade secret.

The FDA has scheduled an advisory committee hearing for early 2019 on breast implant safety to address some of the U.S. group’s concerns and determine whether additional actions are needed to protect public health. The agency did not rule out the possibility of including a “black box warning,” the notification it puts on its most dangerous devices to draw attention to serious risks.

However, the FDA said in a statement: “The agency continues to believe that the weight of the currently available scientific evidence does not conclusively demonstrate an association between breast implants and connective tissue diseases.”

Cook, who leads several breast implant groups on Facebook from her home near Dallas, said she chose to get her implants, but did so with almost no information on the potential dangers.

“If you had sat down with me and said ‘this is the list of chemicals you’re about to put in your body and you could get lymphoma,’ no way in hell I would have done it,” she said.

Her implants, a textured saline model made by Poly Implant Prothese of France, were used in the U.S. for four years before the FDA implemented more stringent standards for breast implant approval in 2000. Under the new rules, the FDA denied the company’s application to sell implants in the U.S. after officials toured the company’s French plant and cited 11 major deficiencies in quality control and manufacturing practices.

Poly Implant went bankrupt in 2010 after doctors in France noted abnormally high rupture rates of the implants, which were found to be filled with industrial-grade gel. The company’s president was found guilty of aggravated fraud, and French authorities advised tens of thousands of women to get their implants removed as a precautionary measure.

Cook, 41, said she and others who already had the saline implants never were warned of the FDA’s actions.

“I’m not going to sit back and be embarrassed about my decision when I can try to change the way that the future is going to occur for women younger than me,” she said. “We need to make sure we’re giving that patient the most safe device we possibly can. And above that, we need to make sure she understands what the risks are before she makes that choice.”

___

The FDA may now require an identifying number on medical devices, but Zuckerman and other advocates note one big issue with the code associated with breast implants: The number is not actually stamped on the implant itself, but on the packaging.

“For the most part, these devices don’t cause immediate problems — they cause problems later,” Zuckerman said. “What good does it do to have these numbers if they’re not in your medical records and they aren’t on the implant itself?”

The unique device identifier, or UDI, is intended to help standardize device names and manufacturer information and make it easier to track devices to help in recall efforts and analyses of problems.

But that doesn’t work if the codes aren’t in the FDA’s own database. Tomes, whose company Device Events analyzes MAUDE data, said UDIs are still rarely included in adverse event reports and, even when they are, often are removed from the public data so they can’t be used to identify specific devices.

“The whole point of having a UDI is so that hospitals and providers and insurance companies and anyone else would be able to say ‘I’m seeing a pattern, it’s all this serial number,’” Tomes said. “But it’s redacted.”

Similarly, Tomes and others say the FDA’s expansion of summary reporting and its use of device registries — databases funded and maintained by outside organizations to track a singular specific device — may ultimately make less data available to consumers.

This fall, the agency announced a breast implant registry run through the Plastic Surgery Foundation that will collect patient and device data — including UDI numbers for breast implants — and allow surgeons to track patients’ medical history, complications and follow-up surgeries.

The participation of plastic surgeons in the registry is voluntary, and patients also can opt out. Doctors and researchers will have access to the collected data, but the public will not.

As the FDA weighed its expansion of the summary reporting program earlier this year, Cook and a dozen other patients with medical device problems, along with the patient-advocacy group Public Citizen, urged the agency to rethink its plan.

But the FDA sided with manufacturers and industry organizations, which had asked for easier reporting requirements for malfunctions, freeing them in some cases from filing tens of thousands of individual reports a year. Under the new rules now in place, roughly 90 percent of devices can report malfunctions quarterly.

“Thousands on thousands of consumers are harmed every single year by medical devices and we are discussing making it easier to hide the information that we need to make an informed decision,” Cook wrote in her dissent to the plan.

“While the goal is not to ‘hide’ the data,” she wrote, “in essence that is what is happening.”

 

See the original story here.

Concerns That Public Hearings on Breast Implants Will Favor Implant Manufacturers

Kris Pickel, CBS News: October 4, 2018.


PHOENIX (3TV/CBS 5) — The Food and Drug Administration has agreed to hold a public hearing on Breast Implant Illness. It’s a victory for women who petitioned the FDA but CBS 5 is investigating concerns the hearings will be stacked to favor implant manufacturers.

Breast Implant Illness (BII) is not recognized as a medical condition.

It is a term used by thousands of women to describe a wide range of unexplained symptoms experienced by women who believe their implants made them sick.

Symptoms of Implant Illness

 

 

 

 

 

 

 

 

 

 

CBS 5 has been investigating BII for almost two years and has seen the number of women coming forward increase by the tens of thousands.

When our first investigation aired, the Facebook group Breast Implant Illness and Healing with Nicole, had 17,000 members. It now has more than 51,000.

News reports and social media are connecting women who believe they suffer from BII.

They are finding strength in numbers.

More than 21,000 women signed an online petition demanding the FDA hold public hearings.

The FDA agreed to meet privately with a small group of women who believe they suffer from BII.

Among the women who traveled to the District of Columbia for the September meeting at FDA headquarters were breast cancer survivors, women who believe implants made them sick, experts on breast implants and women who recently played a role in having the birth-control device Essure pulled off the market.

Women in the group say the FDA set the terms for the meeting: No cameras, no recording, no reporters allowed.

Following the September meeting, the FDA released a statementdisputing a study linking implants to illnesses.

Buried at the end of the statement, the FDA announced they would hold a public hearing on breast implants next year.

Nicole Daruda founded the website HealingBreastImplantIllness.com and the closed Facebook group Breast Implant Illness and Healing with Nicole.

Daruda say some of the issues they want to address include taking textured implants the FDA has said might be linked to the potential for a rare cancer off the market, comprehensive studies and requiring surgeons to give women a checklist of potential risks at least a week before surgery.

In the FDA’s public hearing, an advisory panel will hear from industry representatives, experts, women who believe their implants made them sick and members from the public.

Following the public hearing, that advisory panel will vote on recommendations to make to the FDA. The panel does not have the power to make changes. It will only make recommendations.

Dr. Diana Zuckerman on CBS News

Dr. Diana Zuckerman is president of the National Center for Health Research in D.C. and is responsible for a dozen Congressional investigations on a various health issues.

Zuckerman says in the past, the FDA has stacked the panels with plastic surgeons who have a financial interest in protecting breast implants. 

“Having surgeons whose entire livelihood, or almost entire livelihood, is based on breast surgery, with breast implants, can’t possibly be objective,” Zuckerman said.

She says she has witnessed multiple times where plastic surgeons advocate for implants and dominate the hearings.

“I’ve seen situations where a statistician, for example, says, ‘Look at how unsafe these products are,’ and the plastic surgeon says, ‘No. No. No. We put these in all the time and they are very safe.'”

We contacted the FDA a several times during this investigation and asked if they would be looking at the panel to eliminate possible conflicts of interest.

They responded with a link to their application for panel members, which includes a section that addresses conflict of interest.

Conflict of Interest

The FDA website lists the core group of eight voting members on the advisory panel.

CBS 5 was able to confirm at least two of the doctors perform breast implant surgeries and a regulatory expert who previously worked for Johnson & Johnson, which owns implant manufacturer Mentor.

Zuckerman says in the interest of ensuring an unbiased panel, people should contact their elected officials in Washington and ask them to  pressure the FDA to make sure no one with financial ties to the implant industry sits on the advisory panel.

One Woman’s Story

Robin Towt shares her story

Cancer survivor Robyn Towt was in the group of women who met with the FDA.

When diagnosed with breast cancer, Towt immediately opted for a double mastectomy.

She says her health issues, including anxiety and insomnia, started the day her implants were put in.

Having survived cancer before, radiation was not an option.

Towt chose not to do chemotherapy, leaving no explanation as to why she was getting sicker.

“I have been never been that miserable in my entire life and in that dark a place,” she said. “I feel horrible because my family suffered. My husband suffered. I was not a happy person. I was not a healthy person. I had no quality of life. I was desperate. I was sleep deprived.”

Towt says a friend in a cancer support group suggested she look into her implants as a source for her health problems.

After connecting with women on social media, Towt had her implants removed just four months after having them put in.

She says her symptoms disappeared within 48 hours.

CBS 5 Investigates has uncovered that while implant manufacturers are required to publish informational booklets that include warnings on potential risks of implants, plastic surgeons are not required to give the booklets to women.

Towt says after her implants were removed, she went back and asked her surgeon for the booklet so she could compare the warnings to the consent forms she signed.

Towt says the warnings in the booklet were stronger when it came to certain risks, including cancer associated with breast implants.

“I kind of felt duped when I was comparing them because if I had read the information in that booklet to start with, I would have never ever considered it,” she said.

Towt’s plastic surgeon did not return calls to CBS 5 inquiring when the booklets are provided to patients.

A date for the FDA’s public hearing has not been set.

The FDA says it will happen sometime in 2019.

 

Read the original article and watch the news segment here.

F.D.A. Targets Vaping, Alarmed by Teenage Use

Sheila Kaplan and Jan Hoffman, The New York Times: September 12, 2018.


WASHINGTON — The Food and Drug Administration on Wednesday declared that teenage use of electronic cigarettes has reached “an epidemic proportion,” and it put makers of the most popular devices on notice that they have just 60 days to prove they can keep their devices away from minors.

The order was part of a sweeping government action that targeted both makers and sellers of e-cigarettes. If Juul Labs and four other major manufacturers fail to halt sales to minors, the agency said, it could remove their flavored products from the market. It also raised the possibility of civil or criminal charges if companies are allowing bulk sales through their websites.

The agency said it was sending warning letters to 1,100 retailers — including 7-Eleven stores, Walgreens, Circle K convenience shops and Shell gas stations — and issued another 131 fines, ranging from $279 to $11,182, for selling e-cigarettes to minors.

Federal law prohibits selling e-cigarettes to anyone under 18. In a briefing with reporters, the F.D.A. commissioner, Dr. Scott Gottlieb, said that more than two million middle and high school students were regular users of e-cigarettes last year.

The government’s tactics underscore a dilemma in the public health community: In addressing one public health problem — cigarette smoking, which kills 480,000 people in the United States each year — e-cigarettes are creating another — hooking teenagers who have never smoked on nicotine.

E-cigarette users inhale far fewer toxic chemicals than do smokers of traditional cigarettes. But they can take in higher levels of nicotine, which is addictive.

“The developing adolescent brain is particularly vulnerable to addiction,” the F.D.A. said in its statement announcing the actions.

In particular, the agency has been watching the wildly popular Juul, which offers especially potent nicotine hits. Juul Labs launched the sleek device, which looks like a flash drive, in 2015. It comes with “pods” in eight flavors, among them mango, menthol and creme. In a short time, Juul has become the dominant seller of e-cigarettes and a fad among students. According to Nielsen data, Juul controls 72 percent of the market, and is valued by investors at $16 billion.

In an emailed statement, a Juul spokeswoman said: “Juul Labs will work proactively with F.D.A. in response to its request. We are committed to preventing underage use of our product, and we want to be part of the solution in keeping e-cigarettes out of the hands of young people.”

Dr. Gottlieb said the F.D.A. would look closely at whether Juul and the other manufacturers were allowing bulk purchases of products through their own websites — a practice where the buyer could then sell to minors.

If such “straw sales” are happening, it should be readily apparent to the manufacturers, he said. “If the companies don’t know, or if they don’t want to know, we’ll now be helping to identify it for them.”

The other four products facing the 60-day deadline are RJR Vapor Co.’s Vuse, Imperial Brands’ blu and devices made by Logic. They said they were working with the F.D.A. as well.

RJR, Imperial and Altria are all major tobacco companies. As smoking rates have declined, the industry sees e-cigarettes as an important piece of its survival, a fact that makes some in public health mistrustful.

“They say they’ve changed from the days of Joe Camel,” Dr. Gottlieb said. “But look at what’s happening right now, on our watch and on their watch. They must demonstrate that they’re truly committed to keeping these new products out of the hands of kids.”

Dr. Gottlieb has said many times he believes that e-cigarettes and similar products known as electronic nicotine delivery systems may be effective options for adults who want to stop smoking but still crave nicotine. But he said teenage vaping has become so concerning that regulators may have to curb the availability of the devices to keep them out of the hands of youths.

“Inevitably what we are going to have to contemplate are actions that may narrow the off-ramp for adults who see e-cigarettes as a viable alternative to combustible tobacco in order to close the on ramp for kids,” Dr. Gottlieb said. “It’s an unfortunate trade-off.”

Dr. Gottlieb’s aggressive approach against private industry is unusual for an official in the business-friendly Trump administration which has sought to roll back numerous environmental and health regulations. But critics said that his decision last summer to extend a deadline for e-cigarette manufacturers to demonstrate that their products comply with public health concerns helped perpetuate the current problem.

“It’s nice they want to do something but realistically, what are they going to accomplish this way when they could be so much more effective by following the regulatory plan that had been ready to put into place and that the commissioner postponed?” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit health policy group.

She also pointed to the popularity of vaping among young adults. Researchers generally believe that the adolescent brain continues to develop through age 26. “It’s a big epidemic among people ages 18 to 30, too,” she said.

And while the F.D.A.’s announcement struck many as tough, legal experts said the agency could face a protracted legal fight if it follows through on its threats to ban flavors and curtail marketing.

Marc J. Scheineson, a health care lawyer and a former associate F.D.A. commissioner, said that the agency was relying on public opinion and its own bully pulpit to push the targeted manufacturers into “voluntary compliance.”

Some antismoking groups, while encouraged by the F.D.A.’s actions, expressed caution: “Asking the tobacco industry to come up with solutions is the proverbial case of asking the fox to guard the hen house,” said Robin Koval, the president and chief executive of Truth Initiative. “After decades, there is no evidence that the tobacco industry is able to regulate itself.” […]

A Juul spokeswoman, Victoria Davis, said recently that the company had already stepped up its own patrol of retailers who advertise to youths or who don’t enforce age requirements, as well as social media posts. But it’s not always easy.

From Jan. 1 through July 28, Ms. Davis said, Juul asked Instagram to remove over 5,500 posts, and the social media company complied on 4,562. Facebook Marketplace was less agreeable. The company agreed to remove 45 of 144 posts. Amazon took down 13 of 33.

Dr. Gottlieb said he was not impressed by the measures Juul and the other companies have taken.

“It didn’t have the intended impact or I wouldn’t be viewing the statistics I’m now seeing,” he said.

 

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FDA Rarely Uses Its Power to Recall Dangerous Medical Devices. Why Not?

Meg Bryant, MedTech Dive: August 31, 2018.


The FDA has the authority to recall dangerous and risky medical devices, but it has rarely done so, largely relying on manufacturers to take necessary actions when a product defect or spike in serious adverse incidents occurs.

Since Congress passed the medical device amendments to the Food, Drug & Cosmetics Act in 1976, the agency has used its 518(e) mandatory recall authority just a handful of times. In 1991, the FDA ordered Medline to recall its Dynafeed enteral pump due to design flaws and failure to comply with good manufacturing practices. The agency issued three mandatory recall notices the following year and in 2008, recalled Nebion’s MRI device, citing lack of FDA approval and safety and effectiveness data, as well as noncompliance with GMPs.

There have been some recalls under federal consent orders, and the FDA has in four cases taken the unusual step of banning a medical device. The first time was in 1983 when it banned prosthetic hair fibers used to treat baldness because of serious risks including infections. Then in 2016, the agency simultaneously banned powdered surgeon gloves, powdered patient examination gloves and absorbable power used for lubricating surgeons’ gloves. The danger: Residue from the powder could be left behind in the body cavity, causing inflammation and scarring that could lead to complications later on. In addition, bits of latex from the gloves could bind the powder and be inhaled, putting people with latex allergies at risk.

Given Bayer’s recent decision to stop selling the Essure birth control device, following years of unmitigated safety concerns and mounting patient lawsuits, and the release of the Netflix documentary, The Bleeding Edge, many are questioning why the FDA seems so reluctant to wield its recall authority.

“The FDA has not taken them off the market, has not rescinded approval for specific uses, has not done a mandatory recall and has tried to put out [a] warning that the agency knows is not going to be effective,” said Diana Zuckerman, president of the National Center for Health Research. “They do that all the time.”

‘Insurmountable threshold’

“Once products are on the market, it’s almost an insurmountable threshold to get the agency to take action to pull them from the market,” said Michael Carome, director of Public Citizen’s Health Research Group. “In the case of [Bayer’s] Essure, had the company not voluntarily acted, I suspect FDA would not have pushed them to pull it from the market, based on statements they made over the last few years in the face of concerns.”

Approved in 2002, Essure was associated with serious risks including persistent pain, perforation of the uterus and fallopian tubes and migration of the device into the pelvis or abdomen. The FDA required the addition of a boxed warning and patient decision checklist to the product’s labeling and in April restricted sales of Essure, but did not call for its withdrawal from the market.

That’s not unusual, says Jodi Scott, partner in Hogan Lovells’ Denver office and former FDA counsel. “By and large companies are pretty responsive to a very direct FDA request to take action,” she tol MedTech Dive. “And while I’m sure it doesn’t work in 100% of the cases, I will tell you it probably works 99% of the time.”

Mandatory recalls are also costly for FDA to take. According to the agency, the estimated annual reporting burden associated with section 518 actions is 1,098 hours.

As a last resort, FDA will order a recall, but it’s a lot easier to “look the company in the eye and tell them we think you need to do a recall and have them do it voluntarily,” Scott said. “And it happens much faster. To go to court and get an order takes a lot of time.”

It can also take time to sort out signals detected through the agency’s MDR reporting and Sentinel systems. If officials think there is an imminent risk of harm, they will do an analysis to determine whether the company needs to take some field action, which may or may not involve a recall. “You have to balance the risk and benefits,” Scott said, noting implants are often left in place and monitored when issues arise because of the risks associated with taking them out.

Still, she insists FDA “is not shy” about telling companies when reparative actions fall short and they need to do more. “But it’s all sort of informal, not invoking the mandatory recall authority,” she added.

Problem begins in premarket process

Critics say the real problem precedes FDA’s failure to act once a device is on the market and lies with the process used to bring most moderate and high-risk devices to market. Under the 510(k) premarket notification, companies need only to demonstrate that a device is substantially similar to another product in the market in terms of its intended uses and technological features. In most cases, no clinical trials are required.

Even when clinical trials are required for novel devices subject to premarket approval, they aren’t always randomized. And in cases where devices are given conditional approval and required to undergo postmark testing, the FDA is often lax about seeing that companies complete studies in a timely manner, they argue.

“They allow these studies to drag on for years and years and years, and by the time the studies are done, or if they are ever done, nobody needs the information anyway anymore because the product’s not on the market anymore or the product has changed so much that the information you have about the product that was being sold three years ago is not relevant to the product being sold today,” Zuckerman said.

Zuckerman pointed to the case of breast implants. The FDA approved two silicone gel-filled breast implants in 2006, with the proviso the manufacturers — Johnson & Johnson’s Mentor and Allergan — each would study 40,000 women for 10 years. Neither completed the studies, which involved cumbersome online questionnaires and did not provide any incentives for women to complete them. 

Too close to industry?

“Ultimately, the agency is too industry-friendly,” Carome told MedTech Dive. “They view the industry as a partner rather than a regulated entity.” He believes the adoption of user fees has made the situation worse by allowing industry to negotiate benchmarks for FDA product reviews and other activities in return for payments for reviewing product submissions and other services.

Meanwhile, a 2016 proposal to ban electrical stimulation devices intended to treat people with mental or behavioral disorder that who exhibit self-injurious or aggressive behavior has yet to be finalized.

At the time of the proposed ban, only one facility in the U.S. was using the devices: the Judge Rotenberg Educational Center in Canton, Massachusetts. “Our primary concern is the safety and well-being of the individuals who are exposed to these devices,” William Maisel, chief scientist and deputy director science at CDRH, said at the time. “These devices are dangerous and a risk to the public health — and we believe they should not be used.”

No one is arguing the FDA should recall or ban every device that poses an imminent risk of harm, Zuckerman said. But in cases where FDA opts to keep a product on the market despite well-known risks, it should use the powers it has to require timely and well-designed studies that demonstrate safety and effectiveness versus available alternatives. The agency should “use the teeth it has,” she argued. […]

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New Drugs So Pricey They Need New Payment Plans

Sarah Owermogle, Politico: August 13, 2018.


[…] FDA LOOKS TO MODERNIZE CANCER TRIALS — The FDA issued guidance on Friday intended to speed up certain early and mid-stage clinical trials for oncology drugs by merging elements typically found in phase 1 and phase 2 trials. Studying multiple patient groups separately for criteria like safety and efficacy has the potential to lower costs and add efficiency, Commissioner Scott Gottlieb said in a statement.

Initial reviews were positive: “There is no tablet that got handed down from God to Moses that said drug trials must be conducted in three conventional phases,” said Dana-Farber’s George Demetri, who chairs the American Association for Cancer Research’s government affairs committee. The new approach, known as expanded cohort trials, could allow researchers to be more nimble, Demetri said — more easily spotting a drug’s effect on specific cancers or realizing earlier that it isn’t working.

Vanessa Lucey said the Cancer Research Institute, where she directs the venture fund and clinical accelerator, has itself moved toward these kinds of studies.

The costs: But while the proposed changes could streamline certain cancer trials — the guidance is limited to cases in which a drug’s benefits justify an increased risk, like for cancers that have no cure — there still could be additional costs. In the guidance, the FDA warned that trial sponsors would need to streamline logistics and data collection, and incorporate plans to assess data in real time.

“What’s important about this guidance is it’s trying to come to some kind of political compromise,” said Diana Zuckerman, president of the National Center for Health Research. “It’s trying to do two things that usually conflict — speed and safety don’t go together, usually.” She added: “It’s OK to say they’re going to do this to speed up drug development, but some patients are definitely going to get harmed.” […]

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The Human Tragedy of Poorly Regulated Medical Devices Gets the Spotlight in a Netflix Film

Amy Martyn, Consumer Affairs: July 27, 2018.


The motel where Ana Fuentes arrives one evening with her young daughters charges $110 for a single night and doesn’t offer weekly discounts. Fuentes asks the cashier for a moment so she can think about it.

Outside, the camera captures an anguished look on her face. It’s clear she can’t afford the expense. She books the room anyway. “Do you like it?” she asks her girls as they excitedly unpack their bags.

The family used to have an apartment, but Fuentes had to visit the emergency room so often that she lost her job, her daughters explain on camera.

Such situations aren’t rare in the United States, where experts have repeatedly warned that millions of Americans have almost nothing in savings and are a single medical disaster away from financial ruin. The problem is compounded nationwide by costly healthcare, lack of access to paid sick leave in the workforce, or a combination of the two.

But Fuentes’ story, like dozens of others featured in an upcoming expose about the medical device industry, has a particularly cruel twist. She says in the film that she was healthy until a doctor convinced her to undergo what was supposed to be a routine, non-surgical medical procedure — getting small birth control implants permanently embedded into her fallopian tubes.

The $155 billion medical device industry has mostly avoided the type of scrutiny that drug companies and health insurers sometimes face from elected officials and others. On Friday, a documentary about the device industry and patients like Fuentes called The Bleeding Edge is set to go live on Netflix, bringing what advocates hope will be widespread attention to an industry increasingly characterized by lax safety standards, enormous power in the operating room, and horrific side effects.

“If you’re going to have something implanted in your body for potentially the rest of your life, wouldn’t you like it to be really well-tested beforehand? Is that really too much to ask?” says Dr. Diana Zuckerman, a health policy analyst who has worked in the White House and as a staffer in Congress.

The current president of the National Center for Health Research, Zuckerman and the other researchers at her non-profit are among the few to have taken interest in faulty medical devices.  

Diving into the medical device industry

Hollywood directors Kirby Dick and Amy Ziering knew they wanted to make a documentary film about preventable medical injuries, Dick tells ConsumerAffairs, but that was about it.

Sitting in on one patient advocacy meeting for research, they caught a presentation that Zuckerman gave about the medical device industry and the ease with which questionable products get on the market. They decided that they had found their story.

The team interviewed approximately 70 patients to make their film, Dick tells ConsumerAffairs. The film also includes interviews with numerous whistleblowers, such as doctors, former Food and Drug Administration (FDA) researchers, and one medical device sales rep who requested anonymity in exchange for speaking on camera.

Dick and Ziering were previously nominated for an Oscar for The Hunting Ground, their documentary about sexual assault on college campuses. Another earlier film, The Invisible War, is an expose about sexual assault in the military.

But persuading people to speak out against the device industry made for the most challenging interviews they’ve done, Dick tells ConsumerAffairs. (A medical device industry lobbyist touts in one scene that the industry is more powerful than some national governments.)

The “E-sisters”

As the film and the research it is based on shows, the problem is bigger than any single device. The Bleeding Edge captures the story by focusing  on four implants — three of which were used exclusively women’s reproductive organs.

The narrative is driven forward by the story of the “E-sisters,” or the activists who say that they suffered debilitating side effects after receiving the permanent birth control implant Essure.

For years, the “E-sisters” have organized a grassroots campaign to convince regulators to ban Essure from doctors’ offices. That goal seemed like an uphill battle until last week, when Bayer suddenly released an announcement that Essure will no longer be sold in the United States by the end of the year.

Bayer frames the move as a “business decision.” The announcement came one week before the Netflix documentary was scheduled for release.

“I’m very glad that these issues are getting this kind of attention, and I hope that Bayer’s decision to take Essure off the market won’t take away from the bigger message of the film,” says Zuckerman, “which is the whole process for devices that makes no sense at all.”

“Why in the world would you want to have a regulatory agency in our government, the FDA, having much lower standards for devices than they do for prescription drugs?”

Essure implants

The story of Essure, in particular, only saw the light-of-day thanks to the “E-sisters,” who count 30,000 people in their Essure Problems Facebook group and have convinced numerous elected officials, doctors, and even early clinical trial participants to join their cause.

“One of the things that is disturbing to me is that these issues only came to light because of the work of victims,” former Representative Mike  Fitzpatrick (R-Pa.) said in an interview several years ago.

Women who agreed to participate in clinical trials for Essure in the late 90s have said that they there were sold on a pitch to get a free, non-hormonal, and permanent birth control that was already proven safe.

A nickel coil, the size of a ballpoint pen, would be placed in each fallopian tube. That was designed to create an inflammatory response so that the coils would become permanently encased in the resulting scar tissue.

Regulators with the FDA approved the device in 2002, despite admitting that they knew little about the long-term side effects of such a procedure, as footage that the E-sisters had obtained captures. What’s more, numerous clinical trial participants later said that their painful side effects were not included in the company’s official data.

Doctors not long after began using the devices without questioning potential risks. “For some reason we did that to women. And I did that, too,” Dr. Shawn Tassone, an Austin-based gynecologist, tells ConsumerAffairs.

Insurance and profit margins

The sales representatives who taught doctors how to place the devices — something that Bayer has defended as a common industry practice — offered no instructions on how the device should be removed if there were side effects.

“We were just told from the very beginning that even if they’re misplaced, you don’t have to remove them,” Tassone remembers.

The role that insurance coverage may have played isn’t examined specifically in The Bleeding Edge, but testimony from patients and doctors suggests that getting insurers to cover Essure proved much easier than getting them to cover removal.

Tassone remembers that both private plans and Medicaid paid fairly generously for the Essure procedure, especially considering that inserting Essure was much cheaper and less labor-intensive than tubal surgery, the older sterilization procedure.

“If you think about a tubal ligation where you go to the operating room, it’s $400 [in profit] give or take,” he say. “Essure in the office, after you subtract the amount of the device, it’s probably $1100.”

Treating any resulting side effects proved impossible for women navigating unfamiliar territory. Angie Firmalino, the New York City mail carrier who founded the E-sisters network, initially seeked help from a doctor who morcellated the coils into small pieces — sending the nickel elsewhere in her body.

Connecting patients with doctors who are willing and able to properly remove the devices, as well who are able to code it correctly so that insurance will pay, has since become one of the E-sister’s major tasks.

Tassone, for his part, implanted his last Essure device in 2013. He says it was a call from another doctor who convinced him not to perform the procedure anymore; a woman with Essure apparently had gotten pregnant, he was told, which can be extremely dangerous for both the baby and the mother. One researcher has counted 303 fetal deaths linked to the device.

Tassone has since switched sides, counseling the E-sisters online and in the operating room. He estimates that he has conducted 600 Essure removal surgeries.

Trust remains despite ban

In recent years, the advocates have convinced the FDA to add a black box warning to Essure. Later on, they were able to help pass a rule which requires doctors to give patients more detailed warnings about the product.

But that didn’t appear to stop most doctors from trusting the device. The American College of Obstetricians and Gynecologists continues to say on its website that lasting pain from the procedure is “rare.” By contrast, nearly 27,000 reports have been filed to the FDA’s “adverse event” report database describing health problems caused by Essure and 16,000 lawsuits have been filed here. An estimated 750,000 women worldwide have undergone the procedure.

Now that Essure is off the market, doctors may be more willing to attempt removal surgery, Tassone says, something he thinks is necessary but frightening

“They’re going to think its not a big deal to take out,” he worries. (More detailed advice about removal surgeries is offered on the Essure Problems page).

Generally, before any major surgery involving a permanent implant, researchers advise patients to press doctors on the specific devices that will be used. Zuckerman, the health policy analyst who helped inspire the Netflix film, recalls that even she struggled to get specific answers when she asked a doctor what brand of hip he would choose for her own surgery.

The procedure ultimately went well, she says, but trying to search for good data comparing brands beforehand was nearly impossible.

“In the vast majority of cases, the surgeons are still quoting the company data,” Zuckerman says. “The company’s data on humans is nonexistent —  at least publicly.”

FDA Expedited Approval Process Raises Concerns About Risks

Roxanne Nelson, Medscape: July, 20, 2018


The Breakthrough Therapy designation created by the US Food and Drug Administration (FDA) expedites the approval of drugs intended to treat serious or life-threatening conditions, thus allowing patients quicker access to therapies. But the shorter approval process leads to great uncertainty about safety and efficacy. Are the risks greater than the benefits?

These concerns have been raised again in a new study published online July 17 in JAMA and in an accompanying commentary in the JAMA Forum.

The findings from this study “suggest that the FDA’s expedited review programs may invite greater risks than benefits,” writes Austin B. Frakt, PhD, director of the Partnered Evidence-based Policy Resource Center, Veterans Health Administration, Boston, Massachusetts, in the commentary.

“The idea that doing something more quickly means it is not done as well has considerable face validity,” he comments.

Shorter Trials Lacking Controls  

The new study reviewed all FDA approvals given Breakthrough Therapy designation from 2012 through 2017 and found that the pivotal trials used as a basis for these approvals more often than not lacked randomization, double-blinding, and control groups. They also tended to use surrogate markers as primary endpoints and had small patient cohorts.

In addition, over half of the approvals were based on the results of a single trial.

This leads to greater uncertainty, say the authors, led by Joseph S. Ross, MD, MHS, an associate professor of medicine at Yale University School of Medicine, New Haven, Connecticut.

It is not known whether the effect observed in the single small trial will be observed in a larger population or replicated in another trial, or whether the effect observed over the short term will persist over the longer term.

“There is also uncertainty over whether the effect observed on the outcomes used in these shorter trials, such as surrogate markers of disease, will be confirmed by eventual demonstration of benefit and safety based on clinical outcomes like improved mortality or improved symptoms,” Ross told Medscape Medical News.

Ross said that the FDA “is doing everything it can to expedite the development and review of drugs that treat serious and life-threatening conditions.”

“My expectation is that this is what the public and clinicians — and Congress — want,” he told Medscape Medical News. “More novel therapies coming to market as quickly as is reasonably possible, while still assuring drug safety and efficacy.”

But their research suggests that FDA approval of these breakthrough therapies is generally based on shorter and smaller clinical trials than those that support FDA approval of non–breakthrough therapy drugs.

If this “trade off” is going to be made, with novel drugs entering the market on the basis of evidence that is generally accompanied by greater uncertainty, “we must be committed as a clinical and scientific community to ensuring that high-quality, rigorous postmarket trials are conducted within a reasonable period of time,” he added. “This will resolve some of this uncertainty and ensure that the drugs are associated with the benefit/safety profile that we expect based on the initial clinical studies, allowing clinicians and patients to make fully informed decisions about whether to use these novel treatments.”

Minimal Evidence

In this study, Ross and colleagues reviewed all new FDA approvals that had been granted Breakthrough Therapy designation, looking at the pivotal clinical trials that serve as the basis for approval as well as pre-market development and review times.

They identified 46 agents that had received Breakthrough Therapy designation between 2012 and 2017, based on 89 pivotal trials. Of these, more than half were for oncologic indications (n = 25 [54.3%]), followed by infectious disease (n = 8 [17.4%]); just over half the drugs (n = 25 [54.3%]) were considered to be first in class.

In addition, nearly two thirds of these agents were designated as orphan products (n = 30 [65.2%]) and qualified for Fast Track review (n = 24 [52.2%]) and Accelerated Approval (n = 18 [39.1%]).

Many of these drugs had only one clinical trial (median, 1; interquartile range [IQR], 1 – 2), while the median number of patients enrolled in these trials was 222 (IQR, 124 – 796). Roughly half of all approvals were made on the basis of a randomized trial (n = 27 [58.7%]), while 21 studies used double-blind allocation (45.7%), 25 had an active comparator or placebo control group (54.3%), and 10 had a clinical primary endpoint (21.7%).

Clinical trials that supported breakthrough approvals with Accelerated Approval status were less likely to be randomized than those without Accelerated Approval (3 trials with Accelerated Approval [16.7%] vs 24 trials without Accelerated Approval [85.7%]; P <  .001).

The median time to FDA approval was 4.9 years (IQR, 2.7 – 7.6 years), and all eight agents (100%) that received accelerated approval had at least one clinical safety or efficacy-focused postmarketing requirement, as did 18 (64.3%) without Accelerated Approval designation.

Information Lost

Approached for comment, Diana Zuckerman, PhD, president of the National Center for Health Research, noted that historically, the FDA required two clinical trials with clinically meaningful endpoints, and for cancer, that was survival.

“That was the standard, and it did result in complaints,” she told Medscape Medical News. “There were complaints that trials take too long and are too expensive, and complaints from patients and physicians that the drugs weren’t available.”

“This research letter in JAMA is important, as it is a very well done reminder what you lose when you speed things up,” Zuckerman added.

The FDA required two studies because the second study shows replication of the results, and that is the keystone to research. “You need to replicate the results,” Zuckerman commented.

“This paper also shows that we have lost double-blinding and active comparators and placebo groups half of the time,” she said. In addition, “very few trials had a clinical endpoint.”

“We lost a lot of information, and this means that patients are using drugs that may not be as effective as older treatments, but yet are much more expensive,” she said.

Zuckerman pointed to a study that she coauthored in 2016, which found that many new cancer drugs approved on the basis of surrogate endpoints retain their approval status and remain available to prescribing physicians even though postmarketing studies show no survival or quality-of-life (QoL) benefit compared with placebo or observation groups.

Of 36 drugs that were approved between 2008 and 2012, 18 did not significantly prolong overall survival in postmarket studies. QoL information was available for 7 drugs, and compared with placebo or observation groups, 2 drugs demonstrated worse effects on QoL, 4 drugs showed no statistical difference, and 1 drug had mixed results. In addition, 1 drug reduced overall survival and 6 offered no survival benefit compared with placebo or observation groups.

“These drugs are very expensive,” Zuckerman explained, noting that they ranged in price from $20,237 to $169,836 per year. “There is no relationship between cost and evidence.”

The FDA does allow access to experimental drugs, and with the Right to Try law, it is now easier for patients to gain access, she said. “At least patients know that they are getting an experimental treatment, and that long-term safety and efficacy are unknown. But with expedited approval, they believe they are getting something backed by evidence.”

Right now, the model is “unsustainable,” she said.

Zuckerman also added that the FDA is not responding to these concerns by enforcing requirements for postmarketing studies, and those that are completed are not giving useful results.

Greater Risks Than Benefits?

In the related commentary, Frakt says the findings suggest that the FDA’s expedited review programs may invite greater risks than benefits.

He notes that most of the new drugs are approved even though information concerning long-term outcomes is limited, and more than two thirds are approved on the basis of clinical trials lasting under 6 months.

In addition, the median approval for cancer drugs in the expedited process is 6 months, which is much quicker than in Europe and Canada.

However, it remains an “empirical question” as to whether the drugs that receive an expedited approval have a worse or better benefit/risk balance compared with drugs that receive standard approval.

Frakt points out that over time, safety concerns may arise for drugs with expedited approval. “Drugs subject to less FDA scrutiny are more likely to exhibit safety problems, be withdrawn from the market, or carry black box warnings,” he says. “We should therefore continue to monitor these drugs and update the performance of expedited approval programs as more information is available.”

But another concern, he adds, is that from 2009 through 2013, only a minority of drugs with expedited approval had their efficacy tested in a postmarket trial within 3 years, as previously reported by Medscape Medical News.

Accepting greater risks may be “reasonable and consistent” with patient preferences, as the expedited review programs are for new agents designed to treat serious conditions and address unmet medical needs. But because many of these new drugs are quite costly and are paid for with public funding through Medicare, Medicaid, and other programs, Frakt notes that “the patients’ point of view is not the only one of relevance. A consideration of cost is also reasonable from the point of view of taxpayers.” […]

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