Exploring Human Potential

Medical Device Regulation – FDA’s Weakest Link

Posted on | January 22, 2018 | 1 Comment

Bjork-Shiley heart valve

Mike Magee

Most Americans remain unaware that in the eyes of the FDA not all therapies are considered equal when it comes to regulatory approval and oversight. Drugs are one thing, but medical devices are quite another.

As we’ve seen with drug approvals, over the 20th century, organized review and oversight of the efficacy and safety of America’s medicines tightened in response to tragedies like the infection of children from tetanus-tainted diphtheria vaccine in 1901, the poisoning death of over 100 children from sulfanilamide elixir in 1938, and the fetal deformities associated with thalidomide use in pregnant women in 1961.

In response to all of the above, a relatively stringent and formal review process, somewhat liberalized over time with “fast-tracks” and “abbreviated reviews”, created a level of confidence in American medicines. Most citizens assume that a similarly stringent process exists for approval and oversight of medical devices. But they assume this at their own risk.

In fact, even the most high-risk implantable devices are often approved after a single clinical research trial, and most of these are not randomized, controlled or blinded trials. Some 15% of approved devices created by this $150 billion dollar industry in the U.S. are eventually removed from the market, but often not removed from the patients in whom they were implanted. Unlike drugs, devices often remain for a lifetime, subjecting their subjects to continued risk and worry.

Such was dramatically the case with the Bjork-Shiley heart valve co-invented by American engineer Donald Shiley and Swedish heart surgeon Viking Bjorg in 1971. It’s basket design with metal carbon-coated disc held in place by two welded struts was seen as a technological improvement and implanted in 55,000 patients around the world from 1979 to 1986 before being pulled off the market. By then the company had been purchased by Pfizer in 1979.

The problem? A design defect led to the fracture of the anchoring struts releasing the discs from their housings in over 400 patients and  resulting in nearly 300 sudden deaths. This left behind some $500 million in liability for Pfizer to deal with, which was nothing compared to the remarkable burden for remaining patients and families left to weigh the risks versus the benefits of having their potentially deadly heart values replaced.

The FDA regulatory framework at the time for medical devices was still relatively new. Like other FDA regulation, it was the product of a tragedy. In 1970, Dr. Hugh J. Davis sold his invention, a small fish like implantable uterine device which dragged a porous multifilament string, to the A.H.Robins Company. In 1971, it went to market as an IUD that would be a safer alternative to birth control pills considered high-risk at the time. Called the Dalkon Shield, it was implanted in 2.8 million women. But within five years, its association with infection, septic abortions and death was irrefutably established and linked to its’ mutifilament tail. Within the decade, there were 300,000 lawsuits and A.H. Robins went bankrupt.

In response to the public outcry, Congress passed the 1976 Medical Device Amendments to the Food, Drug and Cosmetic Act, and for the first time required testing and approval of “medical devices.” The loose system they put in place had to deal with the fact that all the devices in use at the time had never been independently analyzed or approved. They were effectively grandfathered in.

All new products were placed in one of three classes. Class I included low risk devices like tongue depressors or forceps. Class II devices were “cousins” to other devices already in use like joint replacement devices and electrocardiographs. And Class III were new devices which appeared to carry some risk like pacemakers or heart replacement valves. Class I and II required quick and inexpensive premarket review, little extra documentation, and simple “premarket notification”. Product enhancements could be filed when they occurred or at annual reviews. Class III required that manufacturers provide some kind of evidence that the product was safe and effective, but this often came from scientific reviews that were less than rigorous and often anecdotal. In return the company received a “premarket approval.”

Liberalization of the process occurred in the years that followed with two tracts created for new product approval: 1) “premarket approval” requiring clinical testing and inspections, or 2) the 510(k) process requiring affirmation that the new device is essentially similar to a device already on the market. User fees range from around $200,000 for “premarket approval” versus around $4000 for the 510(k) tract.

Equivalency can be in the eye of the beholder. For example, the ObTape Vaginal Sling for operative repair of female stress continence sailed through on a 510(k) approval in 2003 based on the manufacturer’s contention that it was substantially equivalent to support tapes manufactured by J&J and American Medical Systems already in use. But when adverse reports of encapsulation and expelling of the material with infection began to surface in 2004, it became clear that the ObTape was made of a dense material poorly incorporated by biologic tissues while the comparators were porous materials that allowed for vessel in-growth. In 2006, the product was withdrawn. In a bizarre twist, the ObTape creators  had argued that the product was unique enough to support their patent application on the one hand, but essentially similar enough to existing products to allow 510(k) approval on the other hand.

As might be expected, the use of the less expensive and faster 510(k) route proliferated, and the FDA, poorly staffed and funded to support a rigorous regulatory process, did little to obstruct abuse. The net effect was that 113 approved devices had to be recalled between 2005 and 2009 because of serious complications or death. Roughly 4 out of 5 of these had avoided vigorous review. In 2010, 500 million individual devices were recalled nationwide, and a review by the Institute of Medicine  found the approval process ”flawed based on its legislative foundation” and that the FDA lacked a “integrated premarket and post-market regulatory framework.”

Historic problems from infection plagued duodenoscopes, to knee pad implants rejected thrice for 510(k) approval but pushed over the finish line after direct appeals by New Jersey’s two senators, to Cyberonics vagus nerve stimulators to treat severe epilepsy which failed to stop convulsions but killed patients by stopping their hearts, continued to occur. And legal redress “checks and balances” are limited. A Supreme Court ruling in 2008 extended pre-emption protection to manufacturers of high-risk devices that cleared the premarket approval process.

Critics claim that the situation is getting worse, not better. The 21st Century Cures Act, which dramatically drew the support of Joe Biden in the wake of his son Beau’s cancer death, was also loaded with FDA changes that further liberalized approval of medical devices including the use of “data summaries” and “real world observational studies” to support device approval.

New devices appeared in multitudes. Let’s take for example the case of pacemakers. Approximately 400,000 Americans have them implanted each year, with 80% over 65 and 20% over 80 years old. In 1984, there were 56 heart conditions for which the American College of Cardiology approved a pacemaker as treatment. Twenty-five years later, that list had bulged to 88 conditions. Only 5% of those indications were backed by double-blind studies. Some 60% of the approved indications were based on recommendations from a 17 member expert government panel. 11 of those 17 were on the payroll of medical device makers. 

One real world issue not covered by the 21st Century Cures Act legislation was the fact that medical devices are fundamentally different than pharmaceuticals in one important respect. If a drug is pulled from the market, a patient can stop the drug and it will eventually clear from the system in a relatively short period of time. In contrast, many devices either cannot be safely removed, or their removal comes at great risk.

When Pfizer finally settled its’ Shiley Heart Valve claims with a $500 million settlement, roughly 1/3 of that payment supported a fund that allowed patients to consult with their cardiologists and deliberate what to do next. Those who chose inaction accepted the uncertainty and lifelong dread that at any moment the struts on their valves might give way, and that sudden death would follow. This pressing reality – the potential irreversibility of harm – has been somewhat lost in the continuing debate over regulation of medical devices.


One Response to “Medical Device Regulation – FDA’s Weakest Link”

  1. BiopharmaVantage
    January 24th, 2018 @ 6:39 am

    Fantastic article Mike. This really creates a choke point in the efficient commercialisation of innovative medical devices as well. We advise and conduct commercial due diligence for the healthcare sector, and most investors prefer investing in the medical devices area. Not only with the FDA, the EMA’s working mode is similar. Once the issues are addressed, one can expect to see more capital and more investment flowing into the sector, which will ultimately benefit patients.

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