Safety Issues Involving Medical Devices: Title and subTitle BreakImplications of Recent Implantable Cardioverter-Defibrillator Malfunctions

This past spring, Joshua Oukrop, a 21-year old Minnesota college student with familial hypertrophic cardiomyopathy, died of cardiac arrest when his implantable cardioverter-defibrillator (ICD) short-circuited and failed to resuscitate him.¹ Guidant Corporation (Indianapolis, Ind), the maker of his ICD, was aware of the potential for this type of malfunction, having observed 26 similar failures out of 37 000 devices.^{1 - 2} The company, however, decided not to notify physicians of the flaw for more than 3 years after first detecting it.^{1 - 2} As implantations of complex electrophysiological devices become increasingly commonplace, the number of patients affected by defective devices can be expected to increase. Understanding the history of medical device regulation, the benefits and limitations of technology, the obligations of manufacturers, the expectations of physicians and patients, and the responsibilities of national physician and industry organizations can provide a framework for improving the medical device reporting and notification systems.

Prompted by a number of fatalities due to contaminated elixir of sulfanilamide, Congress enacted the Federal Food, Drug, and Cosmetic Act of 1938.³ This legislation charged the US Food and Drug Administration (FDA) with the task of establishing the safety of new drugs prior to their general distribution.⁴ The law required medical devices to bear accurate labeling and sufficient instructions for proper use but gave the FDA no authority to review devices before they were released to the market.⁴ FDA regulation of medical devices, therefore, was after-the-fact and required intervention primarily via the courts with injunctions, criminal actions, and civil seizures of product.⁴ Isolated efforts by the FDA to regulate some devices as drugs, which had more stringent controls, were time-consuming and ineffective.⁴

By the mid-1960s, close to 1300 medical device manufacturers shipped products with a total value that exceeded $1 billion.^{4 - 5} President Lyndon Baines Johnson’s administration introduced proposed legislation called the Medical Device Act of 1967, but it was not until almost a decade later, after several high-profile medical device safety questions arose, that Congress finally acted.⁴ Theodore Cooper, MD, PhD, then director of the National Heart and Lung Institute, chaired a committee that released a 1970 report documenting over 10 000 injuries attributable to medical devices, including 731 deaths.^{6 - 7} In 1974, the Dalkon Shield intrauterine device (A.H. Robins Co, Richmond, Va) was withdrawn from the market after reports of 209 second-trimester septic abortions and 11 maternal deaths.^{5 ,8}

Ultimately, Congress enacted the Medical Device Amendments of 1976 to better enable the FDA to establish the safety and effectiveness of medical devices.⁵ The legislation was based on the concept that the degree of device regulation should correlate with device complexity and perceived risk.⁵ During the 1980s, however, manufacturers were criticized for inadequate reporting of adverse events to the FDA, and for failing to report or conduct recalls.⁵ As further evidence of inadequate postmarket surveillance, some cited the withdrawal of the mechanical Bjork-Shiley convexo-concave heart valve from the market due to premature strut failure that ultimately affected 633 patients and was fatal in two thirds of those cases.^{9 - 10}

In response, Congress enacted the Safe Medical Devices Act of 1990, and the Medical Device Amendments of 1992.⁵ Postmarket surveillance was strengthened by requiring health care facilities to report device-related serious injuries or deaths, by establishing tracking of certain high-risk devices, and by giving the FDA authority to require tracking for any other device.⁵ Manufacturers were required to report to the FDA any device malfunction that causes, or could cause, significant injury to a patient.⁵ As a result of this legislation, the FDA has received numerous device-related adverse event reports, including approximately 160 487 reports submitted in 2004 alone.¹¹ The vast majority of the reports are directly from manufacturers.¹¹

The first human use of an ICD was reported in 1980.¹² Subsequently, a number of well-conducted randomized clinical trials conclusively demonstrated that ICDs improve survival in select populations at high risk for sudden cardiac death.^{13 - 15} Today, ICDs are a multibillion-dollar industry with approximately 125 000 new patient implants annually in the United States.¹⁶

Like many technologies, ICDs have undergone remarkable changes in the 2 decades since initial FDA approval. Random access memory has increased 50-fold while device size has decreased by a factor of 8.¹⁷ Modern ICDs are implanted transvenously, provide physiologic pacing in up to 3 cardiac chambers, perform a number of automated functions and self-checks, and can deliver pacing or high-voltage therapies to treat life-threatening arrhythmias. A pacemaker-dependent ICD patient will receive more than 100 million paced beats over the device lifetime, a truly remarkable technological accomplishment.

Given the complexity of ICDs, it is not surprising that they occasionally malfunction. Several database registries have monitored the performance of ICDs in the past and have reported hundreds of device malfunctions affecting dozens of models.¹⁸ In addition, approximately 29 FDA safety alerts and recalls (collectively referred to as advisories) affecting nearly 337 000 ICDs have been issued since 1990.^{2 ,18 - 19} In June 2005 alone, Guidant reported additional ICD-related safety problems that resulted in the voluntary recall of approximately 62 000 ICDs.^{2 ,20} Malfunctions involving ICDs, however, are not unique to Guidant. Medtronic Inc (Minneapolis, Minn), St Jude Medical Inc (St Paul, Minn), Biotronik Inc (Oswego, Ore), and ELA Medical LLC (Plymouth, Minn) have also issued advisories and/or physician notification letters in 2005 involving close to 141 000 ICDs.^{19 ,21 - 22}

These recent events highlight a number of shortcomings in the current device malfunction reporting and notification system and suggest a need for several important changes.

Manufacturers Should Annually Publish Detailed Data on Device Reliability. Remarkably, despite millions of ICD implants worldwide, public reporting of the number, type, and rates of malfunction have never been required of manufacturers. Previous calls to publicly report these data have gone unheeded.^{23 - 24} Product performance reports are provided by manufacturers^{25 - 27} but these publications do not include specific information regarding type, number, rate, or seriousness of device malfunctions. In addition, all malfunctions are not the same. A distinction should be made between a major malfunction that may preclude delivery of life-sustaining therapy, and a minor malfunction where the observed abnormality does not jeopardize life.

Detailed public reporting of medical device malfunctions and device reliability should be required by law to allow consumers, including physicians and patients, to make educated decisions about which product to choose. Public reporting would make safety a market force. Physicians and patients could choose products that have been documented as safe and reliable and avoid those that are less dependable. To maintain or increase market share, manufacturers would be forced to develop safer, more reliable devices. Ironically, consumers can learn more about the safety of the car they intend to purchase than they can about the reliability of their potentially life-saving ICD. Improved public device reliability reporting should remedy this inconsistency.

Manufacturers Should Publicly Report Every Confirmed Device Malfunction. Manufacturers are required to report to the FDA any device malfunction that causes or could cause significant injury.⁵ The decision for a manufacturer, however, of whether or not to notify physicians, patients, or the public about an observed malfunction is less straightforward. Historically, judgments have been made on a case-by-case basis by considering factors such as rate of malfunction, likelihood of patient injury, cause of device failure, and potential to mitigate the problem with an intervention. Because of the enormous financial consequences of the manufacturer’s decision, there is an inherent conflict of interest.

Some physicians argue that notification about every malfunction is too burdensome and results in significant physician liability. This argument, however, ignores the physician’s responsibility to act in the patient’s best interest. Public reporting does not necessarily need to be in the form of a direct physician or patient letter. Updated malfunction information, for example, could be provided on the manufacturer’s Web site. Direct physician notification, FDA advisories, and manufacturer press releases would be warranted for particularly important safety issues, such as observation of a recurrent malfunction, or identification of a product that does not meet expectations for reliability.

Physicians and Patients Should Be Educated to Have a More Realistic Expectation of Device Reliability. Accurate reporting of device malfunction rates would provide physicians and patients with a more realistic expectation of device reliability. Nearly one third of surveyed Heart Rhythm Society physicians reported that they would replace an ICD if the device had a 1 in 10 000 chance of failing.²⁸ Yet, according to Guidant, a 1 in 10 000 failure rate exceeds the reliability of all known ICDs.²⁹ This paradox is typical of the misperception of device reliability among physicians and patients.

Complicating matters further is the fact that it is often difficult for a manufacturer to estimate the true incidence of an observed malfunction.⁵ St Jude Medical, for example, issued an advisory in 2000 after a microprocessor anomaly was observed in 20 out of 144 000 Trilogy pacemakers.³⁰ In response to this notification, an additional 350 problem devices were identified.³⁰ The observed device failure rate will always be an underestimate of the true malfunction rate due to underreporting and patient deaths from unrecognized malfunction.

Patients Should Be Directly Notified About Safety Issues. If a patient’s medical device is recalled, the patient is not directly notified about the malfunction—the physician is. This contrasts with consumer product recalls, such as those affecting automobiles or children’s car seats, where the product owner is directly notified by the manufacturer. The outdated medical device notification system is rooted in the concept that medical information contained in a recall notice is too complex for a patient to understand. However, modern patients are knowledgeable, informed, and proactive, and they have the right to know about malfunctions or potential defects affecting their implantable device. Physician notification should remain in place and patients should be advised to seek the counsel of their physician when deciding on the clinical management of their recalled device. Ideally, a staged notification system would be initiated, whereby physicians are notified first and are given the opportunity to contact their patients. Patients would then be contacted directly to ensure that all those affected are notified.

National Physician and Medical Device Organizations Must Provide Guidance to Physicians, Patients, Regulators, and Industry. Even though an estimated 1 million pacemaker and ICD patients have been affected by device advisories in the past 15 years,^{2 ,18 - 19} no uniform standards for reporting and managing advisories have been developed.

The clinical decision of whether or not to replace a potentially defective device is a challenging one. The benefits of device replacement must be weighed carefully against the risks of replacement. In some cases, close follow-up without device replacement may be the best strategy. For example, the Telectronics Accufix pacing electrode was prone to fracture.³¹ On rare occasions, the lead fractured, perforated the heart or aorta, and caused death.³¹ Many patients underwent pacemaker lead extraction, although ultimately more patients were harmed by lead extraction than by the lead failure itself.³¹

In addition, expert physicians diverge on their clinical recommendations for many common advisory scenarios and do not always make the right choices.²⁹ Evidence-based guidelines should be developed by the Heart Rhythm Society to assist physicians and patients in the clinical management of safety alerts and recalls. The Heart Rhythm Society has formed a task force on device performance and plans to convene a policy conference in the September 2005 to bring industry, regulators, clinicians, patient advocates, and the public together to develop guidelines for clinicians and industry. Other industry organizations, such as the Advanced Medical Technology Association (AdvaMed), the world’s largest medical technology association, will play critical roles in developing guidance for industry to ensure the prompt and effective notification of physicians, patients, and the public when malfunctions do occur.³²

History teaches that device regulation and malfunction reporting experience recurrent growing pains as technologies evolve. Indeed, ICDs are a complex, life-sustaining technology and they are not unique in their potential to malfunction. It is inevitable that other complex implantable devices, such as left ventricular assist devices and total artificial hearts, will experience flaws that may result in device failure, patient morbidity, and mortality. Device safety issues will undoubtedly become more prevalent as physicians and patients increasingly rely on technological advances to treat medical conditions and prolong life. With expanding patient populations, more device implants, and increasing device complexity, it will be critical to ensure that continued advances do not come at the expense of decreased device reliability. The solution is not to refrain from developing these important products but rather to monitor device performance carefully, to report device malfunctions publicly, and to demand improvements in reliability as technologies mature.