If it looks like a duck, swims like a duck, and quacks like a duck, then it's probably a duck. While that "duck test" may be true for fowl, determining how medical devices are used in patients is a trickier subject.
While medical devices are granted clearance or approval by FDA for a prescribed indication, off-label use is legal in many circumstances and is up to a doctor's discretion. The fact that it is legal, means that off-label promotion of medical products is commonplace, says Mike Drues, p?resident of Vascular Sciences (Boston).
Still, it can be a risky practice for medical device makers because it can lead to costly legal penalties under the False Claims Act if the non-indicated use was promoted. For instance, GlaxoSmithKline was ordered to spend $3 billion in 2012 to settle criminal claims related to off-label promotion, failure to disclose safety data, and a variety of civil complaints under the False Claims Act. Other pharmaceutical and medical device companies have also been ordered to pay billion- and million-dollar fines to settle similar allegations. For instance, in 2010, atrial fibrillation device maker Atricure (West Chester, OH) was ordered to pay $3.76 million to settle Medicare fraud and kickback allegations related to its surgical ablation devices. The Wall Street Journal had reported on the Cleveland Clinic's investment in AtriCure and the fact that the prestigious hospital had implanted more than 1200 of its patients.
The question of what something is and what it is not is a murky question in the world of medical devices. Patient safety, not to mention a whole host of ethical considerations and legal ramifications on the part of the actual device companies, hang in the balance.
Legal Marketing vs. Illegal Marketing vs. Off Labeling Marketing
The distinction between what constitutes legal marketing and what is fraudulent promotion can be contentious. The law makes permissible use of any legally marketed medical device by doctors under the practice of medicine doctrine. However, off-label promotion of legally marketed device for non-FDA approved uses is considered unlawful. Then the marketing of medical devices that have been altered through modifications or found to be in design constructs not consistent with the intended uses for which they were cleared or approved are adulterated and misbranded. The distribution of such devices is a prohibited act.
In the pharmaceutical realm, a number of executives have argued successfully that off-label promotion is protected by free speech. In the device realm, former Acclarent executives William Facteau and Patrick Fabian are making similar arguments in a lawsuit that could help establish boundaries regarding what constitutes legal and illegal promotion of medical devices.
Earlier this year, Medtronic was ordered to pay $2.8 million to the U.S. Justice Department to resolve off-label allegations that it paid physicians "tens of thousands of dollars' to encourage health providers to use [a neurostimulation device] off-label," reports the Star Tribune of Minneapolis. Another recent example of the potentially high cost of off label promotion is the Synthes bone cement debacle, which led to five patient deaths and the ultimate jailing of four Synthes executives.
FDA offers guidelines on the off-label use of drugs and devices and released a 2011 guidance document providing advice regarding unsolicited requests for off-label use of medical products. The FDA has other guidance documents related to the subject, which it continues to revise. At present, many people in the medical device industry aren't clear where the boundaries are between legal marketing and fraudulent off-label promotion. "Part of the lack of clarity around the issue relates to how you define the word 'advertise,'" Drues notes. And another consideration is when a device design appears to only work for a non-FDA approved or cleared use.
Modifications and New Intended Uses
When previously FDA-cleared or approved devices are modified in manners that may change the intended use, or indication, manufacturers are required to obtain a new application for premarket approval (PMA), premarket notification [(510(k)] or an exemption--the exception being if such modifications do not impact safety and effectiveness.
Questions around Orthopedic Devices
In the orthopedic device field, Amedica (Salt Lake City, UT) received a warning letter for marketing the Valeo-C VBR in 2009 for new intended uses. The device manufacture was found to have marketed the Valeo-C VBR for use in the cervical spine although it was only cleared for use below the neck, specifically for the thoracolumbar spine. "A trapezoidal spacer with a rectangular inner hole intended to be filled with bone grafting material." The letter adds the device is, " ... available in two sizes: small (16 x 12 mm) and medium (17 x 14 mm) with height ranges from 5-12 mm"--footprint sizes and heights designed for use as an intervertebral body disc replacement device in the cervical spine in the neck. Amedica was also found to be promoting the use of violative product for use with biologics.
Questions around Cardiovascular Devices
The Myxo ring was a device designed to treat degenerative myxomatous disease of the mitral valve--a new intended use never approved or cleared by FDA. Patients were first implanted with the novel device in 2006. The manufacturer, Edwards Lifesciences (Irvine, CA) claimed it could sell the device because it was substantially equivalent to other previously 510(k) cleared mitral valve replacement devices. FDA disagreed as it required Edwards to change the name of the device before granting an investigational device exemption (IDE)--all done after-the-fact. Even so, FDA still issued a warning letter referencing the Myxo under its new device name "dETlogix" deeming the device misbranded because the company had failed to report serious adverse events. Allegations of human experimentation and patient safety concerns prompted a Senate probe led by ranking Senate Judiciary chairman Hon. Chuck Grassley. Search of FDA's MAUDE database reveals 21 adverse events, including a patient death. Of those injured, nearly all patients required repeat open heart surgery to explant the Myxo device. Two additional injuries involved its use under the name dETlogix. The Myxo device was removed from U.S. hospital shelves, described as a "voluntary retrieval" in Edward's 2009 SEC 10-K filings. Nevertheless, the identical Myxo device is still sold in Europe, where safety regulations are more relaxed than those in the U.S.
The FDA employs in-house medical experts, biomechanical engineers, physicians, and also enlists outside panelists to advise the agency on matters of critical device evaluation, safety and effectiveness. In addition, manufacturers are required to tell the truth about how their devices work and what they're actually designed to do. Each 510(k) application requires that manufacturers submit a truth and accuracy statement, declaration of conformity, and provide risk assessment data supporting that the subject device is designed to do what the manufacturer claims it's actually suppose to do, and that the benefits of using the device outweigh the risks. Falsifying such reports or declarations of conformity is a prohibited act.
The orthopedic and cardiovascular devices mentioned herein, demonstrate inconsistencies on what constitutes a change in intended use and/or indication that impacts safety and effectiveness. These discrepancies, in part, led to FDA's 2014 final guidance documents regarding the agencies review of traditional 510(k) premarket notifications. But the 510(k) process itself has come under considerable scrutiny in recent years after several devices cleared via the pathway were linked to considerable numbers of adverse events and lawsuits.
Examples of controversial products cleared via the pathway include metal-on-metal hip implants, power morcellators, transvaginal mesh, the Myxo ring, and the ReGen Menaflex collagen scaffold device that was the subject of a 2009 FDA report titled "Review of the Regen Menaflex: Departures from Processes, Procedures, and Practices Leave the Basis for a Review Decision in Question." Between 2005-2009, 78% of medical devices recalled for life-threatening or very serious hazards were FDA-cleared using the less stringent 510(k) process or were considered so low risk that they were exempt from review.
A recent GAO report notes on postmarket studies explains that "between May 1, 2008, and February 24, 2015, about 94% of the postmarket surveillance studies ordered were for devices cleared through the 510(k) premarket notification process."
The 510(k) clearance process, which is used to clear some 90% of medical devices in the United States, has been at the heart of several prominent lawsuits, such as with the aforementioned Acclarent lawsuit and the federal government has been stepping up its efforts to clamp down on off-label promotion, as witnessed by the flurry of fraud lawsuits filed by the government to hold device companies personally accountable.
Historically, medical device companies have faced relatively minor penalties for such actions--a slap on the wrist by way of receiving an FDA warning letter with no further legal action. But the push to bring medical devices to market even faster is sure to test the very protections put into place to insure patient safety. Use of medical devices that have been modified or designed for non-FDA approved indications and intended uses are challenging interpretations of what constitutes the use of "test articles" as defined under provisions covering human subject clinical trials under 21 CFR part 50.
Confirmation Hearing for New FDA Commissioner
As the Senate HELP committee holds Full Committee Hearing session on Nov 17, 2015, one important question for the nomination for the next FDA commissioner Dr. Robert Califf's, who has largely built his career on industry-sponsored clinical testing, will be how he intends to enforce provisions designed to insure patient safety while addressing increasing pressure to relax regulatory controls that industry claims are overly burdensome and hampering innovation.
Learn more about medical technology trends at BIOMEDevice San Jose, December 2-3.