Blog #54 Andrew Siegel, M.D.
Medical devices are capable of saving lives and vastly improving the quality of our existences. Prosthetic valves for cardiac valve problems, artificial joints for severe arthritis, defibrillators for heart rhythm issues, urethral slings for stress incontinence, penile implants for erectile dysfunction, etc., can make a meaningful contribution to our health and well being. There are countless novel technologies that have been able to achieve unparalleled benefits for society. Sadly, despite enormous upside potential for improving our longevity and lives, medical devices can also maim, or on rare occasions, even kill us.
One of the greatest strengths of the USA is the wonderful culture of innovation that we thrive in, as well as a system of colleges and universities that is bested by no other country. As important as innovation is to ensure that we have access to lifesaving and lifestyle-improving devices, so is a system that is capable of guaranteeing safety and effectiveness. As devices have become more complicated, the current device-approval system has failed the task of assuring us that all implanted devices are safe and effective. The device-approval system currently in place is obsolete, having been designed in 1976, at a time when devices were fewer and far less complex.
The United States device regulatory process was initiated in 1938. In 1976, Congress passed the Medical Device Amendments, which established the foundation of the present system. Devices are triaged into three classes of risk:
Class I devices (low risk): e.g., tongue depressors
Class II devices (moderate risk): e.g., hard contact lenses
Class III devices (high risk): e.g., heart valves
There are two means of getting a new medical device on the market. The more stringent method is the PMA process (Pre Market Approval). This is mandated by the Food and Drug Administration (FDA) for class III devices and involves extensive clinical testing. A less stringent FDA process to gain clearance (note the use of the word clearance as opposed to approval) for a new medical device without the need for human testing is known as 510(k) clearance process, named for the statute from which it is derived. The 510(k) criterion of clearance of a new medical device is that it is “substantially equivalent to a predicate device”—in other words, that it is very similar to a device that is already on the market. No clinical data or clinical trials regarding safety and effectiveness are required with a 510(k) clearance. Every year, several thousand medical devices are cleared via the 510(K) process, representing approximately one third of all new devices.
The PMA standard for approval of class III devices is safety and effectiveness, while the standard for 510(k) clearance is substantial equivalence to a previously cleared “predicate” device. Unfortunately, the assumption that a device that is “equivalent” to a previous similar device will be as safe and effective as that device is often erroneous. Although the FDA may request preclinical or clinical data to support the claim of equivalence, a finding of equivalence is by no means a determination that a device is safe and effective.
An effective device approval system should be capable of balancing innovation and safety. The process should be sensible and efficient such that patients have expedient access to innovative medical devices. On the one hand, regulation should not be a burdensome process that stifles innovation and compels device manufacturers to go overseas. On the other hand, the regulation serves an important role in oversight, safeguarding us from risky and untested medical devices.
Mentor Obtape: My Involvement
Sub-urethral slings are small strips of material that are used to treat stress urinary incontinence (urinary leakage with exercise, sneezing, coughing, etc.) in women. They work by providing anatomical support to the urethra (the urinary channel leading from the bladder to the external opening). They are placed by a simple outpatient procedure and can dramatically improve the quality of life of women who suffer leakage with physical activities and exertion.
A few years back, I found myself enmeshed in a public health nightmare regarding a particular type of sling made by the Mentor Corporation called the ObTape, an abbreviation for obturator tape. This sling was cleared by the 510(k) process and had multiple predicates. In other words, this device was cleared because it was found to be substantially equivalent to an existing device that had previously been cleared, in turn, by being found substantially equivalent to another device!
In 1999, Mentor’s Porges division introduced the Obtape sling to the European market. What was unique was the means of sling placement—via the obturator area of the groin, as opposed to the original technique that placed the sling via the lower abdomen—avoiding the potential perils and hazards of abdominal procedures. Interestingly, the original European product was called Uratape, a synthetic material made of polypropylene with a central silicone coating. Because of a high incidence of vaginal extrusion associated with the Uratape, it was withdrawn from the market and replaced with the Obtape that had no silicone component. (Vaginal extrusion is a condition in which the sling does not incorporate properly into the body and is exposed and visible in the vagina.)
Beginning in 2003, over a 15-month period I implanted ObTape slings in 30 patients with stress incontinence. In follow-up, it was noted that many patients were having problems with sling integration, with the vaginal wall failing to heal properly and the sling extruded or exposed. When I came to realize that this adverse event was more than just an isolated occurrence, I stopped implanting the ObTape sling. Ultimately, six patients (20%) were found to have vaginal extrusion requiring removal of the sling material. This complication, in which the sling fails to integrate properly into the body, causes bloody vaginal discharge, pain, infections and the presence of exposed sling in the vagina.
I voiced my concerns to Mentor Corporation on several occasions regarding the integration problems that my patients were experiencing. Mentor’s representatives had the audacity to suggest that the problem was “on a technical basis secondary to inadequate vaginal closure technique.” I was advised to close the vagina in two layers as opposed to the typical one layer that is the standard. In other words, Mentor was blaming the problem on the physician (that being me), rather than the device. I rejected the Mentor response because of my significant experience with trans-vaginal sling procedures since completing a fellowship in incontinence and female urology in 1988, having always closed the vagina satisfactorily in one layer.
It was my judgment that the Mentor ObTape sling incurred an unacceptably high rate of defective vaginal wound healing and extrusion and should be considered inappropriate for use in sling surgery. I wrote up my findings based upon my thirty patients and in November 2005, an article entitled: “Vaginal Mesh Extrusion Associated With Use of the Mentor Trans-Obturator Sling” appeared in our Urology journal (The Gold Journal). My conclusions were that the sling material was the source of the problem: in short, the ObTape has micro-pores and is inelastic. Pore size is a critically important factor in sling surgery, allowing for tissue in-growth and hence integration. ObTape has small pores—approximately 50 microns in diameter—that are more apt to harbor bacteria and impair tissue in-growth and integration than larger-pored slings. Additionally, the inelasticnature of the sling impedes the ability of the sling to adhere to the contours of the urethra and underlying tissues; this predisposes the sling to lay immediately above the vaginal wall (versus lying directly under the urethra), another set up for poor integration and the potential for extrusion. The alternative slings at that time—those made by Gynecare, American Medical Systems and Boston Scientific—were more elastic and had macro-pores greater than 80 microns and did not have incorporation problems.
Subsequent to my publication, numerous other clinicians reported similar problems with vaginal extrusion and poor integration of the Mentor sling. Mentor eventually voluntarily withdrew the Obtape from the market, replacing it with an alternative macro-pored sling. The large number of complications resulting from the use of the Obtape sling engendered numerous lawsuits. Because my Urology article was the first to report the complication, I received calls from many attorneys across the nation requesting that I serve as a medical expert in numerous patients’ claims against Mentor Corporation. I was more than happy to participate in this capacity, because I knew firsthand the personal havoc wreaked by Mentor’s defective product. Ultimately, there was a major settlement between Mentor Corporation and the attorneys representing hundreds of injured women who had had the ObTape implanted.
The bottom line was that this sling was brought to market prematurely, before adequate human testing. As it ended up, the sling testing experience was done on the collective private patients of urologists and gynecologists throughout the nation. Furthermore, Mentor had European data that documented integration issues that was withheld from implanting surgeons when the sling became available in the USA. What the enthusiastic Mentor representatives did present to us was supporting data including 4 disks—one of an anatomical dissection, two disks showing surgical technique and one containing a PowerPoint presentation. On the surgical technique disk, a nationally renowned leader from a prominent American medical school fully endorsed the ObTape, stating that the ObTape “retains its advantage against the gold-standard TVT (Tension-free Vaginal Tape).” The narrator of one of the surgical technique disks stated that the ObTape monofilament polypropylene tape gives “excellent properties of incorporation and colonization.”
With entrepreneurial haste and aggressive salesmanship, this defective sling was foisted upon surgeons with misleading and incorrect supportive materials and data. Essentially, Mentor Corporation marketed an ill-designed product that did not have the properties necessary to achieve maximal biocompatibility, resulting in numerous patients with integration and incorporation issues. Pre-market testing received short shrift, and in Mentor’s zeal to release the first trans-obturator sling in the nation, many damaged patients were left in its wake. Data, published by myself and corroborated by MAUDE (Manufacturer and User Facility Device Experience) and numerous other physicians, unequivocally showed extrusion and incorporation issues. I, among many other surgeons, was mislead by Mentor Corporation, strongly persuaded by the Mentor sales force that the ObTape sling was not only effective and less invasive than alternative slings, but that it passed muster in terms of safety.
The ObTape was FDA cleared based upon it being a Class II device, and thus upon the 510(k) process of “substantial equivalence” to a predicate product. The predicate of the ObTape was the Johnson and Johnson Gynecare TVT sling. Mentor Corporation’s claim was as follows: “Mentor ObTape is substantially equivalent in material, performance, production, and design to the urethral support tapes for the manufacture produced and marketed by Johnson and Johnson.” This claim was flagrantly incorrect! Interestingly, the predicate device for the Johnson and Johnson Gynecare TVT was a Boston Scientific sling, the ProteGen sling. The ProteGen sling was made of polyester fabric coated with collagen. The ProteGen sling was a total disaster, incurring major integration issues and ultimately being withdrawn from the market in January 1999. So the child that failed—the Obtape sling—had as its parent a great sling—the TVT, but as its grandparent, a disaster sling—the ProteGen. The ProteGen was cleared in 1997 based on a substantial equivalence, since the polyester fabric coated with collagen was already in use for cardiovascular grafting.
What was the FDA thinking? Do we not entrust the FDA to safeguard us from devices that are unsafe? Shouldn’t the FDA approach devices with the same regulatory scrutiny accorded to drugs? If the ObTape sling had been classified as a class III device instead of a class II device, it would have demanded a much more stringent regulatory process prior to approval. In my opinion, despite shortcomings in the ability of the Food and Drug Administration to police drugs and devices, the ultimate responsibility for assurance of device safety and satisfactory pre-market testing falls upon the manufacturer.
The 510(k) device-approval system is clearly antiquated and needs to be replaced with a new system that will assure safe and effective devices and avoid the potential for tragic innovations like the ObTape. The predicate system is flawed and the shortcomings of the multiple predicate approach are even more profound. Physicians as well as the public want assurance that a device is safe and effective, not that it is “equivalent” to another device, and that its benefits outweigh its risks, assurances that the 510(k) cannot provide.
We need a system that adequately tests devices before they come to market, so that we have the surest guarantee possible that the new devices are beneficial and do no harm. Equally as important is a system that provides oversight after any new device is made available. Registries must be created to monitor and track every patient who undergoes a device implantation—this would provide a means of collecting data, analyzing it, and acting upon it. In this way, if a device comes to market with seemingly satisfactory safety/efficacy pre-market data that turns out to be erroneous with follow-up registry data revealing unanticipated complications, there would be a system in place to manage this. This system would benefit from a means of rapidly disseminating this information to the medical community as well as the public and furthermore demands a process by which flawed devices could be expediently recalled and banned from future use. In this way, physicians and patients could be best assured that available devices are sound and safe.
Link to N.Y. Times article on Mentor ObTape in which I am interviewed:
Andrew Siegel, M.D.
Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food
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