Denise Grady and Roni Caryn Rabin, New York Times: March 19, 2019.

David Lim, Medtech: March 6, 2019.

Under Gottlieb’s tenure FDA rolled out a number of medical device initiatives, some mandated by the landmark 21st Century Cures Act, such as guidances on breakthrough devices, CLIA waiver improvements and least burdensome device review.

Other policies, such as the agency’s proposal to examine limiting manufacturer reliance on 510(k) predicate devices older than 10 years came in the midst of criticism the agency is too lax in its regulatory oversight.

But Gottlieb often left device decision making to Shuren, a sign he trusted the career staffer to run the show.

“At CDRH, really what he was doing was letting Jeff Shuren do his thing. It was Jeff driving it and Gottlieb giving him permission to do so,” Brad Thompson, a digital software attorney at Epstein Becker & Green, told MedTech Dive.  “I don’t mean to minimize that. There are some commissioners who would have said no, just saying yes to Shuren was significant.”

But Gottlieb was not hands off either. He regularly jointly announced medtech initiatives with Shuren including efforts to stand up a Pre-Cert Program for software as a medical device, which “at least created the impression that Dr. Gottlieb was very involved and proactive” in the device space, according to Jeffrey Shapiro, a device attorney at Hyman, Phelps & McNamara.

“I didn’t see an initiative from the device center that it hadn’t been working on to some extent in the last few years,” Shapiro said. “I don’t see a big change unless the new commissioner somehow has a different set of priorities or ideas about device regulation.”

President of the National Center for Health Research Diana Zuckerman agreed, telling MedTech Dive the true impact of Gottlieb’s exit on the device center will depend on if his replacement “will continue to let Jeff Shuren run the show or want to make changes.”

It’s unclear who will take Gottlieb’s place, but some in industry fear a less conventional, more typical Trump administration candidate. During the last FDA chief search, the rumored nomination of Peter Thiel associate Jim O’Neill, who advocated against mandating companies prove the effectiveness of new products, spooked some.

Bakul Patel, FDA associate center director for digital health, is another CDRH leader who shepherded the Pre-Cert Program from conception to its current proposal. His presence will maintain additional normalcy at CDRH, according to Thompson.

The agency is in the process of collecting feedback on the latest working model for the Pre-Cert Program, which has drawn fire from Democrats and some in industry for potentially overstepping FDA’s statutory authority.

Gottlieb and Shuren also worked together to stand up the National Evaluation System for health Technology (NEST), a real world evidence collection initiative tied to a postmarket surveillance push denoted in the Medical Device Safety Action Plan.

Transparency via social media may also take a hit with exit of Gottlieb, widely considered an effective communicator for FDA with his robust presence on Twitter. ​Twitter-less Shuren has kept a relatively low public profile compared to the commissioner.

“The most immediate change at FDA will no doubt be a radical slow-down in the news flow. Gottlieb is a genius at offering a constant stream of newsy updates, packaging almost any FDA guidance or workshop into a larger more gripping narrative,” Cowen Washington Research Group’s Rick Weissenstein said in a note. “In the absence of the constant, agency-directed messaging, those outside groups could start to reshape the narrative.”

Shuren, who has served as director of CDRH since 2010, has been the source of many of the center’s novel ideas over the past decade. For example, ​he recently co-authored a JAMA Viewpoint article advocating continuing to leverage RWE.

“We anticipate that decentralized network models, such as PCORnet and NEST, although still in their infancy, will emerge as appropriate models to harness the breadth of electronic data generated in health systems,” Shuren jointly wrote.

Abernethy, if appointed, will likely be supportive of the effort, according to Thompson.

Another potential downside for FDA will be a lack of a cheerleader to Congress. Senate HELP Committee Chairman Lamar Alexander, R-Tenn., praised Gottlieb’s time at the agency, noting he has worked closely with Congress and implemented Cures provisions aimed at bringing more medical devices to market faster. Rebecca Wood, who served as FDA chief counsel under Gottlieb, echoed the sentiment to MedTech Dive.

Gottlieb secured a nearly $50 million boost in appropriations for a spate of device and radiological health programs FDA recently received in the February package.

“He was one of the most politically astute commissioners. He knew how to get Congress on his side much more successfully than most FDA commissioners are able to do,” Zuckerman added. “It’s really actually unlikely that his successor will be as good at that.”

See the original story here.

Rebecca Ellis, NPR: February 26, 2019.

Surgeons are known for their busy schedules — so busy that they don’t just book surgeries back to back. Sometimes they’ll double-book, so one operation overlaps the next. A lead surgeon will perform the key elements, then move to the next room — leaving other, often junior surgeons, to open the procedure and finish it up.

A large study published Tuesday in JAMA suggests that this practice of overlapping surgeries is safe for most patients, with those undergoing overlapping surgeries fairing the same as those who are the sole object of their surgeon’s attention.

But the study also identified a subset of vulnerable patients who might be bad candidates; the practice of double-booking the lead surgeon’s time seemed to put these patients at significantly higher risk of post-op complications, such as infections, pneumonia, heart attack or death.

Researchers say Tuesday’s study by a multidisciplinary research team from several universities is the most comprehensive analysis of the practice to date, delving into the outcomes of more than 60,000 knee, hip, spine, brain or heart surgeries among patients ages 18 to 90 at eight medical centers. The study compared the outcomes of procedures done in isolation with those that were scheduled to overlap by an hour or more.

Dr. Anupam Jena, a physician and health economist on the faculty of Harvard Medical School and senior author of the study, says his research team found overlapping surgeries to be “generally safe.” Overlapping surgeries were not significantly associated with difference in rates of death or post-op complications.

These findings, says Jena, are in line with all but one of several such studies conducted since 2015, when an investigative team at the Boston Globe first turned searing attention on Harvard’s Massachusetts General Hospital. There, at one of the nation’s premier teaching hospitals, reporters highlighted a practice that at that point was little-studied and not widely discussed outside hospitals. In extreme cases, the surgeries were essentially concurrent, with the multi-tasking lead surgeon moving back and forth between ORs.

Within a year, the Senate Finance Committee jumped in with a report detailing lawmakers’ safety concerns about little-studied practice. And the American College of Surgeons updated its guidelines, adding that juggling “critical” parts of a surgery was “inappropriate.”

However, the less extreme practice of letting the beginning and end of surgeries overlap is still viewed by hospitals as an efficient means of deploying the skillful hands of their top surgeons. Mass General, which has continued the practice, is in the company of teaching hospitals nationwide. Overlapping surgeries in this way “offers greater and more timely access to certain surgical specialties,” Mass General says in an FAQ on the topic, “many of them high-demand, high-volume elective procedures.”

Jena says this is the first study to show that certain types of patients might particularly be at risk.

“This is the only [study] that breaks out and finds in certain high-risk groups, we might have worse outcomes”— namely, in older patients, those with pre-existing medical conditions, and those undergoing coronary artery bypass graft surgery, where blood flow is restored to the heart.

When the researchers homed in on these high-risk patients, they found slightly higher mortality rates among the patients who had undergone overlapping surgeries and were older or had underlying medical conditions — 5.8 percent compared with 4.7 percent for patients who had the lead surgeon’s full attention.

The scientists found a similar discrepancy in complication rates — 29.2 percent of high-risk patients experienced post-surgical complications when subject to overlapping surgery, compared to 27 percent of patients whose procedure was done in isolation. (The “complications” recorded in the study ranged from minor infections at the surgical site to heart attack or stroke.)

This discrepancy, says Jena, “could occur because a surgeon is separating their mental effort between two cases or [from] literally being [in] two places at once. Those kinds of problems would have a measurable effect on high-risk patients.”

The study also found that surgeries booked to overlap lasted a half-hour longer, on average, than those done in isolation.

Dr. Robert Harbaugh, former president of the American Association of Neurological Surgeons and current chair of the department of neurosurgery at Penn State’s Milton S. Hershey Medical Center, was not involved in the study, but says he was not surprised to see the findings show a “modest but real” risk posed to high-risk patients.

“In my practice, if I know someone is a very high-risk patient, you’re much less likely to (schedule) that patient for an overlapping surgery,” says Harbaugh. Surgical patients who have multiple underlying conditions, such as diabetes or hypertension, he says, require his full attention.

This study, he says, supports his sense that there is “a specific group of patients that probably has to be moderated more closely.”

However, Harbaugh says, overlapping surgeries are crucial “to make the operating room run more efficiently.” Surgeons are fully booked two or three months in advance in his department at Penn State, he says. Allowing four surgeries a day lets patients be treated that much sooner — as well as providing “the next generation of surgeons” much-needed training time.

The leading surgeon is always scrubbed-in for the “dangerous part of the surgery,” Harbaugh notes, and only leaves the patient with residents who are “competent to open or close a case.”

“If you’re finishing an operation and you tell your resident, ‘you can you go ahead and close the incision,’ they’re more than competent enough to do that,” he says. “Then you leave, go to another room where a [surgical] fellow has started a case. That’s an efficient use of time.” Harbaugh estimates 15 percent of the surgeries done by doctors in his department overlap.

Harbaugh also notes that his surgical department at Penn State requires surgeons to explain to patients when they sign the consent form that that they will be stepping out for parts of the surgery. But he doubts that policy of transparency is universal, he says.

Jena says there is “little information about what patients know” when it comes to the practice of overlapping surgeries. A 2017 study found few people had ever heard of the practice.

He says he and the study’s lead author, Dr. Eric Sun, an anesthesiologist and assistant professor at Stanford University, “both would agree that doctors should be telling patients about this practice.” Jena recommends patients ask, ahead of the operation, if their surgeon will be dividing their time.

If they don’t like the answer, Jena says, “At any point, the patient could say, “I don’t want care provided to me.”

Diana Zuckerman, a policy analyst and president of the National Center for Health Research, is doubtful many such conversations are likely to occur. “Most patients wouldn’t know to ask,” she says.

“The good news is, for an an individual patient, they shouldn’t worry,” Zuckerman says, pointing to the fact that the study found no significant increase in post-op problems or deaths overall.

However, she says, questions linger over whether patients should be informed about a surgeon’s other commitments, even if the risks of complications are low.

“I think it’s safe to say if patients were told, nobody would like it,” Zuckerman says. “Nobody wants to feel like the doctor is going in and out their surgery.”

See full article here.

Ronnie Cohen, Undark: February 4, 2019.

Dr. Samir Grover was taken aback when, early in his gastroenterology career, he saw one physician speak two times and present contradictory conclusions about the same medication. Each time, the speaker presented identical data on a drug used to treat inflammatory bowel disease. First, he recommended the pharmaceutical. A week later, he deemed it ineffective. “How could this exact same data be spun in two very different ways?” asked Grover, a professor at the University of Toronto. One fact did change — the drug manufacturer that sponsored and paid for the lecture.

It’s no secret that drug makers pay doctors to hype their products to other doctors. But few outside the halls of hospitals witness physicians bending a single set of facts in opposing ways. After watching similar acts of statistical wizardry throughout his nine years of medical practice, Grover set out to investigate a more sweeping question about conflicts of interest. Do they infect clinical practice guidelines? Professional societies produce thousands of these documents every year. They steer the decisions of health care professionals and insurance companies about how to prevent and treat an ever-widening range of conditions — from diabetes, hypertension, and heart disease to arthritis, hepatitis, cancer, and depression.

Grover and his colleagues’ paper and a companion study recently published in JAMA Internal Medicine suggest that simply following clinical practice guidelines could lead doctors — even those who shun all industry gifts — to unwittingly dispense financially tainted medicine. More than half of the authors of guidelines examined in the two studies had financial conflicts of interest. In many cases, the doctors who wrote the guidelines were paid by the same companies that produced the drugs they recommended. In addition, a significant portion of the doctors who took pharmaceutical money failed to disclose the payments, many of which amounted to $10,000 or more.

The consequences of financial entanglements can be profound, warned Dr. John P.A. Ioannidis, a professor at the Stanford University School of Medicine. “Writing guidelines is like prescribing something to millions of people,” he said. For their part, medical societies acknowledge the need for impartiality in the guideline-development process. Yet many view the task of disentangling industry from clinical practice guidelines as challenging, maybe impossible. Grover believes that panels can do better, particularly when it comes to disclosing conflicts. Still, he said, “it would be very hard to find experts, particularly for high-grossing medicines, to be completely devoid of conflict.”

Grover’s study examined financial conflicts of interest for the authors of 18 clinical practice guidelines that provided recommendations for the 10 highest grossing medications of 2016. The blockbuster drugs included treatments for hepatitis C, rheumatoid arthritis, and Crohn’s disease. Nearly one third of the authors declared receiving payments from companies marketing one or more of the top-revenue medications. A separate study underscored Grover’s findings. It examined industry payments received by the authors of 15 gastroenterology guidelines published from 2014 to 2016. More than half of the gastroenterology guideline authors received money from industry. In both studies, the payments could be funds for clinical trials, or they could be for travel, honoraria, or speaking fees.

The payments could bias guideline authors’ votes on prescription recommendations, and they could also prompt guideline authors to try to sway the votes of other committee members, said Matt Vassar, the study’s senior author and a professor at Oklahoma State University Center for Health Sciences in Tulsa. Prior research suggests that doctors who receive pharmaceutical money and gifts have different prescribing patterns than their peers who don’t. A 2016 study of nearly 280,000 doctors showed that those who attended a single industry-sponsored meal, with an average value of less than $20, were more likely to prescribe a brand-name medication promoted at the event than alternatives within its class.

“Doctors who take money from companies tend to prescribe drugs from these companies more — quite a bit more,” said Diana Zuckerman, president of the National Center for Health Research, a Washington, D.C. think tank. “We have to assume the same for doctors on guidelines teams.”

Especially worrisome to Vassar was his finding that the vast majority of the gastroenterology guideline authors failed to disclose industry payments that were reported in a federal database. Grover, too, discovered a lack of disclosure among guideline authors in his study — more than a quarter with conflicts failed to report payments they took from companies marketing one of the top 10 drugs. The undisclosed payments ranged from $1,638 to $102,309. For Grover, “the issue is not the conflict,” he said. “The issue is the transparency and adequately and appropriately noting conflicts.”

For Dr. Daniel Brauner, a professor of medicine at the University of Chicago, simply disclosing conflicts isn’t a cure-all. A geriatrician, he regularly sees patients suffering from what he believes are the consequences of specialists with conflicts writing clinical practice guidelines. “It’s over-prescription and a lack of really looking out for patients,” he said. When doctors adhere to multiple clinical practice guidelines, “older patients end up being on ridiculous numbers of drugs that will interact with each other and cause harm.” Yet doctors feel compelled to follow the guidelines, Zuckerman said. If they don’t, and their patients fare poorly, they can be sued for malpractice.

Ioannidis argues for a barrier blocking industry’s participation in clinical practice. “It’s fine to do research with industry funds,” he said. But then someone else should write the clinical guidelines. How can you be objective, he asks, “when every sentence you write may affect your own revenue, your own success, your own reputation?”[…]

See the original story here.

Liz Szabo, Kaiser Health News: January 8, 2019.

Spending on health care marketing nearly doubled from 1997 to 2016, soaring to at least $30 billion a year, according to a study published Tuesday in JAMA.

Jeanne Lenzer and Shannon Brownlee, Washington Post: January 4, 2019.

Ten years ago, Kathleen Yaremchuk raced to the bedside of a patient inexplicably gasping for breath. Chair of the department of otorhinolaryngology (ear, nose and throat) at Henry Ford Hospital in Detroit, Yaremchuk performed an emergency tracheotomy on the woman, cutting a hole in her windpipe, inserting a breathing tube and saving her life. When Yaremchuk began getting more calls over the following months for mysterious cases of respiratory distress, she launched a study to figure out what was going on.

All these patients, it turned out, had a small device implanted in the top of their spines to relieve pain. The object, used to hold a protein that stimulates bone growth, was cleared for sale by the Food and Drug Administration in 2003 without clinical testing in humans. When Yaremchuk and her colleagues reviewed the records of all 260 patients implanted with the device at Henry Ford Hospital between 2004 and 2009, they found that a significant number developed airway obstruction, trouble swallowing and respiratory failure, in some cases leading to death.

The neck implant is just one of the products associated over the past decade with 1.7 million injuries and more than 80,000 deaths. A searing global investigation last year by the International Consortium of Investigative Journalists places much of the blame on significant failings in the FDA’s oversight. The agency’s laissez faire attitude has resulted in artificial hips that cause cobalt poisoning (which can damage the heart and brain); surgical mesh that cuts through flesh and organs, causing infections and hemorrhage; and defibrillators that repeatedly shock patients beyond human endurance. Safety problems have led to recalls of devices implanted in hundreds of thousands of people. And the devices can be difficult or impossible to remove if they go bad. No wonder many patient advocates cheered when the FDA announced in November that it planned to make “transformative” changes in the way more than 80 percent of medical devices are cleared for sale in the United States. Some 32 million Americans walk around with such products in their bodies.

But the promised transformation is mere window dressing. Two key loopholes still exist, allowing most products to be approved for sale without clinical trials in humans. Although the FDA insists that high-risk devices undergo “stringent” testing to win approval, few actually do. A recent study, for example, found that only 5 percent of the highest-risk implantable cardiac devices were subjected to clinical trials on par with the testing required for drug approval.

In 1976, when medical devices first came under the regulatory control of the FDA, the agency simply grandfathered in all devices that were already on the market. Under this provision, known as the 510(k) pathway, new artificial joints, cataract lens implants and thousands of other devices developed after 1976 can win approval for sale (or “clearance” in FDA parlance) if the product is shown to have “substantial equivalence” to a previously cleared “predicate” device.” Four out of five devices are cleared for sale this way. Of those, at least 95 percent were cleared without clinical studies, according to research by Diana Zuckerman and her colleagues at the National Center for Health Research.

For some devices, that makes sense. You don’t need a clinical trial to test a new tongue depressor or hospital stretcher. But the agency also lets higher-risk devices through based on predicate devices, some of which have been recalled for safety problems. A recent study by researchers at the University of Oxford discovered that 16 percent of surgical meshes cleared for sale in the United States between 2013 and 2015 were based on products previously removed from the market because of serious complications. When one of us asked the FDA how this could happen, officials answered that the agency doesn’t evaluate the performance of the predicate when clearing devices for sale, just that there is (or was) a predicate.

According to the FDA, the “most impactful” change it is considering is recommending (not mandating) that companies cite predicate devices no older than 10 years. Yet device-makers could still cite predicates that were themselves based on earlier devices that may date back well past 10 years, something the FDA acknowledged in an email to us, stating that “devices cleared under a 510(k), regardless of how long the predicate has been on the market, have met the 510(k) regulatory review standard.”

The second loophole is the supplement pathway, which applies to new versions of the highest-risk devices, such as artificial hips, deep brain stimulators and spine implants. This process allows manufacturers to inform the FDA that they want to market an updated version of a device with minor changes — once again, allowing them to circumvent clinical trials. Researchers at Harvard found that 99 percent (5,829 of 5,906) of implanted cardiac devices, such as pacemakers and defibrillators, were approved through the supplement pathway from 1979 to 2012.

The supplement pathway has led to a number of disasters, such as one involving Medtronic’s Sprint Fidelis defibrillators, which are implanted in the chest to shock the heart if it goes into a deadly rhythm known as ventricular fibrillation. The company told the FDA in 2003 that it had updated the device to use thinner electrical leads into the heart. But the new wires were prone to fracture, hitting some patients repeatedly with shocks when their hearts were fine, and not delivering shocks to others who needed them. Doctors put the Sprint Fidelis into Bridget Robb, a patient from Pennsylvania in her early 30s. It shocked her 31 times in a span of minutes in 2007. She said in congressional testimony that it felt like being shot in the chest by a cannon at close range.

By the time Medtronic recalled the defibrillator in 2007, about a quarter-million were in circulation worldwide. Individuals implanted with it live under a sword of Damocles: They risk electrocution and possible death if they leave the Sprint Fidelis alone — and they risk death if their heart stops and the product fails. If they choose to have it removed, they face a 12 to 16 percent rate of serious complications or death from the surgery, according to a study published in 2010 in the journal Circulation.

Cases like these have received widespread coverage in the press but have had virtually no effect on FDA policy. Even a damning 2011 report by the Institute of Medicine (requested by the FDA), which deemed the agency’s 501(k) pathway so flawed it should be thrown out, fell on deaf ears.

Part of the problem lies in whom the agency believes it serves. At a recent meeting in Utah, the FDA’s device director repeatedly referred to manufacturers as the agency’s “customers” and showed a slide proclaiming “90 percent customer satisfaction.” Another slide documented the agency’s shorter and shorter approval times over the past eight years. These might not be the priorities of patients and taxpayers if they knew how often devices go on to harm people.

The FDA has become a captive agency. In 2007, Congress passed the Medical Device User Fee Amendments (MDUFA), which requires manufacturers to pay for device approvals. (Similar legislation, the Prescription Drug User Fee Act, directs money from drug companies to the FDA.) By 2018, 35 percent of the FDA’s budget for regulating devices came directly from the companies that make them. Zuckerman says that to continue collecting user fees under the MDUFA, the agency has to meet “performance goals” for faster approvals — leaving less time to evaluate products before they go on the market. It’s an inherent conflict of interest exacerbated by the revolving door of directors and commissioners who come from industry to the FDA and then go back. Before being appointed by President Trump to head the agency, Scott Gottlieb was paid millions of dollars for consultancies, directorships and other ties with some 20 health-care companies. He is a vocal supporter of Trump’s deregulation drive, arguing in 2013 that “the FDA’s caution is hazardous to our health.”

This is not a new problem. Before Gottlieb, President Barack Obama appointed Margaret Hamburg, who was then a director of Henry Schein, a leading medical-device distributor, to head the FDA. And in 2005, President George W. Bush named Lester Crawford, who abruptly resigned after just two months and came under criminal investigation for making false statements to Congress concealing his ties to companies the FDA regulates.

The relationship between the agency and the device industry is so cozy that in 2015, Rob Califf, then the FDA commissioner, met secretly with the Advanced Medical Technology Association (AdvaMed), the industry trade organization, to help craft the 21st Century Cures Act, which lowered the bar of evidence needed to approve devices even further.

Last fall, the FDA and AdvaMed were aware of the planned release of the Implant Files, the report by the investigative journalists’ consortium. AdvaMed executives were so concerned that they held a meeting to discuss strategies for dealing with the anticipated stories, which made headlines around the world in November. The executives promised their member companies that they would “hit back and hit back hard.” One day after the first reports were published, the FDA issued its “transformative” changes to the 510(k) pathway.

If Americans want devices that are safe and effective, they’ll need a new kind of regulation. First, the FDA should recategorize any implanted device as a high-risk or Class III product, which would subject it to rigorous clinical trials. Data from these studies should be made publicly available, or the manufacturer would forfeit the right to sell its product. And implanted devices should be entered into registries that track outcomes; patients should be given access to a website where they can immediately report problems and receive updates.

Lawmakers should also revive the congressional Office of Technology Assessment, which the House of Representatives killed in 1995, during a fit of anti-regulation insanity inspired by Newt Gingrich’s Contract With America. The office provided an invaluable service by independently assessing evidence for a wide range of technologies.

Finally, the FDA commissioner should be a civil servant without financial conflicts, not a political appointee (a practice started under Richard Nixon).

To do all of this, the FDA needs to overcome the constant threat of losing funding if it goes against the wishes of the industry it is supposed to regulate. Congress should repeal the MDUFA (and the prescription-drug equivalent) and fully fund the agency. Until the FDA requires clinical testing of implanted devices, as it does for drug approval, we simply won’t have the evidence to prove that a device is safe or effective.

See the original article here.