‘The Bleeding Edge’ Documentary, Tackling Medical Device Regulation, Spurs Diverse Cardiology Reactions

A new Netflix documentary looking at how medical devices are approved and regulated in the United States has piqued the interest of cardiologists, with some saying it’s time for more stringent device clearance in the United States and others maintaining that the agency is, for the most part, operating as it was designed.

The Bleeding Edge, which premiered on the online streaming site last month, follows the stories of patients, physicians, and activists dealing with safety scandals related to vaginal mesh, Essure (Bayer), metal-on-metal hip replacements, and robotic surgery. The film explores the two major pathways by which the US Food and Drug Administration (FDA) approves medical devices—the traditional premarket approval (PMA) process that has been in place since 1976, requiring at least one trial, and the less stringent 510(k) pathway that was created shortly thereafter, allowing manufacturers to have devices “cleared” by demonstrating that their device is "substantially equivalent" to devices that are already marketed for the same use.

A full 98% of medical devices today are regulated under the 510(k) pathway. According to the FDA, between January and July of 2018, 1,787 devices have been approved under the 510(k) pathway and only 20 have been approved through a PMA. This imbalance, as well as the tragic stories shared by patients affected by faulty devices, inform the film’s central message: federal regulation of medical devices in the United States is in dire need of an update.

The Netflix documentary did not look in depth at any cardiovascular devices, but cardiologists have nevertheless taken to Twitter for an informal film review. TCTMD reached out to several cardiologists to hear more of what they thought after watching.

“My initial reaction to this documentary was one of surprise,” William Suh, MD (David Geffen School of Medicine at UCLA, Los Angeles, CA), told TCTMD in an email. “As an interventional cardiologist, I am performing procedures that involve various medical devices on a daily basis. Most of the devices used in interventional cardiology are rigorously tested, and I assumed that most medical devices outside of cardiology are also tested properly for safety and efficacy. But then I began to realize that even within cardiology, there are instances in which a medical device has been brought to market without such rigor. This documentary brings to light some of the problems encountered today with the medical device industry and the FDA.”

Similarly, Luai Tabaza, MD, who is completing his fellowship in interventional cardiology at Albert Einstein Medical Center (Philadelphia, PA), called the documentary an “eye-opener,” in an interview with TCTMD. “As physicians we always care to practice evidence-based medicine, and when a device or a medication is introduced or on the market, we often or always ask about the data,” he said. “One thing I noticed that I personally never asked about was what type of approval or clearance did this device receive from the FDA, and that's something that I learned, that there are different pathways.”

Though he knew about both FDA pathways for device approval, Suh admitted that he assumed most were regulated through PMA. In that vein, “this film’s message of caution relating to medical devices can be applied to our specialty as well,” he said.

For example, Suh observed that the Lariat device (SentreHEART) for left atrial appendage closure “was approved under the 510(k) pathway for soft tissue approximation and ligation, but was not tested in a randomized controlled trial for stroke prevention in atrial fibrillation.” Also, the da Vinci system (Intuitive Surgical), which was profiled in the film, is used for robotic-assisted mitral valve repair, yet “to the best of my knowledge, robotic-assisted cardiac surgery has not been studied in a randomized trial to prove its safety and efficacy,” Suh said. “So yes, within cardiology and cardiac surgery, we need to be mindful of how our devices are approved and marketed to ensure that what we are doing is in our patients’ best interest.”

Within cardiology and cardiac surgery, we need to be mindful of how our devices are approved and marketed to ensure that what we are doing is in our patients’ best interest. William Suh

Sunil Rao, MD (Duke University Medical Center, Durham, NC), said that while the film was “interesting and I had a lot of empathy for the patients who were affected adversely,” it was clear that it, like most documentaries, had an agenda.“The issue is balance—how do we develop a system that allows for innovative beneficial technologies to be brought into clinical practice in a timely fashion and at the same time ensure public safety?” he asked in an email to TCTMD. “I don’t know the answer to that. To paraphrase Churchill, . . . I would say that the US system is the worst system except for all of the other systems out there.”

Longtime innovator Juan Granada, MD (Cardiovascular Research Foundation, New York, NY), said he found the film’s message at odds with common opinion within the field of cardiology.

“For cardiovascular devices, I don't think that anybody can really say the FDA is weak, mediocre, or easy to go through,” he commented to TCTMD. “By the contrary, the FDA is praised as the most strict agency [worldwide], thoughtful, and . . . aggressive, in making sure that these devices are properly, tested, validated, and approved. So I was kind of shocked to see that people in the documentary were saying, ‘Oh, the FDA is approving devices right and left.’ That has not been our experience.”

Granada’s biggest criticism of The Bleeding Edge is that it did not delve into the magnitude of the device complications explored. “Are we talking about 1%, are we talking about 0.5%, or are we talking about 50%?” he asked. “I am extremely sensitive to the fact that one complication in a million is still a complication and is a very sad event, but I think it's important that you put things into perspective. People seek treatment and physicians offer treatment because the patients are suffering—either there is a pain, disability, or a risk of death—and obviously some of these devices are not really treating critical conditions, but are trying to improve something. So, the reality is nothing in life is [completely] safe.”

Innovation vs Regulation

At one point in The Bleeding Edge, the filmmakers interviewed Rita Redberg, MD (University of California, San Francisco), a cardiologist and outspoken critic of the FDA’s device approval processes. “Just because you have a new technology doesn’t mean it’s innovation,” she says in the documentary. “I think too often I hear people say, ‘Oh, you’re going to stifle innovation.’ They’re not talking about stifling innovation, they are talking about stifling putting untested devices on the market. That’s not innovative.”

Rao responded that “there is definitely some truth to that. I think we all have to be careful and circumspect about new drugs or devices. But again, it’s about balance. The US was behind Europe in getting TAVR technology. It is possible, and likely, that some patients died waiting for that technology to be approved and commercially available here.” Yet conversely, many devices have real safety issues that should be rectified, he added.

Suh also used the example of TAVR as a new device-driven procedure that has proven its benefit in randomized controlled trials several times over. “I can confidently say that TAVR is new and innovative,” he said. “On the other hand, an example of an ‘innovative’ product failing to deliver on its promise was the first-generation bioabsorbable stent, which was taken off the market last year due to increased risk of stent thrombosis compared to metallic DES. I think Dr. Redberg’s point with that statement is that new devices first need to be properly studied to prove that [they are] an innovation and not to automatically equate new and innovation without data.”

Also citing TAVR as an example, Granada called the 510(k) pathway “reasonable.” If US physicians had had access right off the bat to smaller and thinner valves that were easier to implant, as were prevalent in Europe at the time, vascular access complications might not have been so prevalent in the US, he said.

Tabaza said innovation is “developing the technology and taking it from one step to another. If you want to take it literally, new does not mean innovative. New can be different but not innovative. But everything innovative should be new.” For cardiologists, randomized trial data serve as an “internal checkpoint to what is acceptable innovation. [A device] has to be effective, it has to be safe, and it has to be potentially also available on a large scale so you can actually help patients with it,” he explained.

David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), had watched half of The Bleeding Edge at the time he spoke to TCTMD and said he intended to finish it. Kandzari, who has served as an employee of the FDA and now sits on its Circulatory System Devices Panel, said a more conservative FDA “certainly would stifle the introduction of innovative therapies to the United States if sponsors and manufacturers of new drugs and devices knew that the cost of development to satisfy the FDA would be so prohibitive that the cost would exceed any potential merits for the company over a long term.” However, he told TCTMD, “it perhaps wouldn't stifle innovation per se. People may continue to develop drugs and devices, but they would be doing it with the intent on applying them to the practice of medicine in other countries and other geographies, rather than to the United States.”

The FDA’s intent, Kandzari emphasized, is “not to dictate a clinical practice of medicine, but rather to ensure the safety and efficacy of the device for the approved indications. In other words, FDA is never going to say to somebody, ‘You can't use that drug-eluting stent for an unstudied indication.’ That's not their purpose. Their purpose is to say, ‘We have at least full assurance of safety and efficacy for its use in the people who were studied.’”

Granada, who also took issue with Redberg’s comments, argued that “neglecting access to the latest technologies to people is also dangerous.” He acknowledged, however, that regulators will always need to balance risk and benefit because “as long as we actually have the unpredictability of science and humans are reviewing data, I think we are always going to be exposed to human error and human perception.”

What Should Happen at the FDA?

Going forward, Suh suggested that the FDA potentially “abolish” the 510(k) pathway and instead “all new medical devices should go through the PMA pathway. Yes, this will be more expensive for the medical device companies, but this is what is necessary to best assess safety and efficacy of a new device.” 

Others argue that making all devices go through PMA is a step too far. “It is quite obvious that the regulatory hurdles in some ways are quite high here in the US,” Rao said. “On the other hand, every system is subject to some degree of gaming, and I’m sure that happens with the 510(k) pathway. I don’t believe that either extreme—blanket deregulation or complete elimination of the 510(k) pathway—is the right answer.” Some change at the FDA is already occurring, he added, citing examples of MDEpiNet and NEST as “likely steps in the right direction.”

Kandzari said that the FDA “is very aware, too, that there was a time period where 510(k)s had such leniency in terms of new device approval that in all practical purposes a new technology could leverage a 510(k) pathway but really have nothing similar to the initial predicate device. It really took a life of its own and [then] the boundaries of what was similar to a predicate device, those lines became blurred over time.

“At present there is a plan that 510(k) technologies that are in use now for a large part do now require additional data to support a PMA application,” he continued, mentioning the regulatory process of Impella (Abiomed), which achieved 510(k) approval about 10 years ago, as an example. At the time, many debated whether the technology really deserved to be approved based upon the available evidence. In recent years, Impella has received PMA for various indications including high-risk PCI and acute MI cardiogenic shock, among others.

“The FDA has challenged that there are technologies [for which] the data are imperfect, but there's a need to provide therapies that may be potentially lifesaving or fulfill an unmet need,” he said, adding that they mandated an FDA panel meeting which concluded that some of the devices be either reclassified or held to a PMA process. “They then had to do additional clinical study to satisfy those PMA approvals, which they have, and now they've achieved that,” Kandzari said.

Ultimately, he said, people need to understand that “making change within FDA is not simply flipping a switch. It's more turning a large ship, and it's not something that happens overnight.”

Granada argued that based on his experiences with the FDA, he thinks the agency is “doing a very good job.”

He continued: “They have a group that is really thoughtful, that is trying to create the new wave of clinical trials to validate technologies. I think they are trying to do their best to balance risk, safety, and access to technologies for the patients in the United States. I mean, there is always room for improvement, but I have to tell you, I really believe the FDA is the best regulatory body in the world.”

If he had to pick one thing to change, Granada would suggest that the agency bring “more science to the regulatory process.” For example, the documentary shows that some patients who had the Essure coils implanted in their fallopian tubes ended up suffering from reactions to the nickel titanium, also known as nitinol, in the devices. Yet, CoreValve (Medtronic) and other self-expanding aortic devices are made of the metal alloy. “I don't know if it's the same material or same composition, but I was asking, so how come we have these side effects in these tiny devices in areas that are not in contact with blood, and we don't have patients with [self-expanding cardiovascular devices] coming in intoxicated with nickel titanium?”

Perhaps the FDA should work more in concert with the US National Institutes of Health to look into questions related to device complications like that, Granada suggested. The government may feel that it is the responsibility of manufacturers to look into these questions, but “medical device companies will never put money in research that is not actually aimed at passing the regulatory process, because in reality it's not their interest. They are not actually here for academic interest. They are here to build a safe and effective device, but going beyond that point, I don't think they are going to do it.”

For cardiologists, “it’s hard to know how much influence we can have on specific FDA policy,” Rao continued. “What we can do, and should do, is debate the risks and benefits of device studies, and really make sure that we are familiar with the indications and risks of a specific device. We also should strive for proficiency at using them. At the end of the day, it’s the clinician who makes the decision to use a device.”

Tabaza agreed that physicians need to be aware of the various FDA approval pathways and ask questions before procedures. “When you are being presented with a new device, always show interest in knowing what the FDA approval process was like and what kind of studies were done,” he said. “That also might motivate those device companies to go through the right pathway that would be more convincing for the physician and would show better data and better safety and efficacy evidence.”

Physician Reporting

Tabaza also urged physicians to do more complete reporting of complications, noting that it is mandatory for industry, but should be more strongly encouraged for doctors. The FDA’s MAUDE (Manufacturer and User Facility Device Experience) database, for example, exists for mandatory reporters (manufacturers, importers, and device user facilities) but also for voluntary reporters, namely doctors, nurses, patients, and consumers.

“We sit down and document things for hours a day, so a few clicks in the interest of patient safety will not be something that we can't do,” Tabaza said.

Suh said he has never reported any adverse device outcomes to the FDA through MAUDE, and Rao noted that he has only ever reported one device complication. “I haven’t reported any more because, one, device malfunctions are rare, and two, because of their rarity we forget to report them,” he said. “We do send the devices back to the company. At that point, it’s unclear whether it ever gets reported.”

Kandzari said he has reported a device complication to MAUDE and even wrote a book chapter about the database when he worked for the FDA. However, “the MAUDE database reporting is number one, very much dependent on the individuals reporting the event, and it's secondly quite limited with regard to further detail,” he cautioned. “It provides a very broad level survey of potential adverse events with a device, in which you're really looking for certain signals or warning flags associated with the use of a particular device.”

“When you have a complication, there is a combination of factors—patient characteristics, device malfunction, or actually physician procedural skills,” Granada added. “When it is an intrinsic, gross device failure, I think that actually physicians are good at recognizing it and reporting it. The problem is that if there is a complication that in a way is related to procedural conduct [or] judgement, or a complication that is related to the procedure itself that may be identified as a potential skill failure, what are you going to report?”

Regulation vs Obstruction

Given that the number of implantable devices available within the cardiology field seems to be growing every day, Tabaza believes balance is needed. “Too much regulation would lead to obstruction, and too little regulation would lead to chaos, or basically disorganization,” he said. “The question in my mind is: do we need to revise the regulations as a nation here and make it more difficult for devices to pass through when they are not qualified, and maybe easier for devices to pass through the approval process when they did their due diligence and they are safe?”

Tabaza also emphasized that “it's not the industry's fault that they want to try and get these things to us, but we need to make sure that they follow the rules and that everything is transparent when it comes to people's lives.”

“Many of us can be critical of the FDA either for being too slow and too conservative or in this case for being . . . too careless in their decision-making, but I don't think that many of us understand the challenges and the inner complexities of working at the FDA,” Kandzari concluded. “I know that for the FDA to see this [documentary], there are many elements that they would be criticized for, but much of this too is in hindsight for them. My hope though is that it doesn't hamper their endeavors to move forward with the progress they're making now with regard to internal revisions and evolving to at least a more open program that they're trying to achieve.”