Medical Device Daily Washington Editor

BOSTON – The first day of the Heart Rhythm Society (HRS; Washington) conference in Boston included a “town hall meeting” on the subject of the association's draft recommendations on device performance reporting for pacemakers and implantable cardioverter defibrillators (ICDs). The HRS task force published its recommendations April 26 in a 22-page volume that addressed a range of issues, not all of which industry is in a hurry to embrace.

The task force that assembled the recommendations convened after a meeting last September during which HRS concluded that “recommendations and guidelines were necessary to address concerns about the safety, effectiveness and postmarketing surveillance of cardiac devices,” according to Mark Carlson, MD, the chair of the task force. Carlson is an assistant professor in the department of surgery at the University of Nebraska Medical Center (Lincoln).

The obvious subtext for the session was the continued product problems encountered by Guidant (Indianapolis), which recently mailed letters to physicians in connection with a bad capacitor that was installed in nearly 1,000 defibrillators, 30 of which have been explanted. Forty six other implicated units are still operating in patients.

William Maisel, MD, director of the pacemaker and device service at Beth Deaconess Medical Center (Boston) and the chair of the HRS task force's surveillance committee, said that the guiding principal for any standard of reporting is transparency, and that many of the HRS recommendations are “certainly done to a certain degree already” for battery function. However, these standards should apply to all components, he argued.

He also noted that HRS called for device performance reports that are more frequent than yearly.

On the subject of how device malfunctions are defined, Maisel said that the HRS guidelines offered more specific guidelines than current FDA regulations require. The proposed guidelines suggest that failure be defined as device malfunction with compromised therapy, without compromised therapy, and induced malfunction. This last category would include but would not be limited to malfunctions induced by hazards described in product labeling.

At present, the FDA's definition of the term “malfunction” is “the failure of a device to meet its performance specifications or otherwise perform as intended. Performance specifications include all claims made in the labeling for the device.” This description appears in 21 CFR 803.3.

Maisel pointed out that “a number of companies are already” making some such changes to their reporting systems, including Guidant, which listed its approach to device reporting at its web site. According to a report by the independent panel assembled by Guidant in response to its recent problems, which is dated March 20, the definition of malfunction is a “deviation from the intended function or a response to a clinical event that the device is intended to provide.”

Maisel stated that the HRS draft recommended an independent panel of experts, some of whom would be physicians, engineers and statisticians, to review device performance.

Tim Samsel, CRM vice president of regulatory affairs at Medtronic (Minneapolis), remarked after Maisel's presentation that the “typical ICD malfunction rate is less than 1%,” and that pacemakers malfunction at an even lower rate. He argued that Maisel's analysis was deficient in that it failed to acknowledge that most of the reported problems with this class of devices are associated with deviations from battery charging intervals, most of which had no impact on device function.

Samsel stated that he was not in favor of the proposal to include non-Medicare populations in the National Cardiovascular Data Registry because the recommendation fails to account for differences in population subsets. Samsel pointed out that FDA advisories clarify issues connected to patient sub-population differences.

As for notification procedures and standards, Maisel acknowledged that one of the more controversial recommendations would be to advise patients directly of device failures due in part to the prospect of changes of providers.

“It is critically important,” he commented, “to advise patients shortly after advising doctors.” The HRS recommendations further include that physicians should be apprised of every report filed in connection with a device.

Samsel answered that not all such information would be “useful to clinicians,” but suggested that clinicians would be amenable to not getting reports on every performance deviation so long as “a robust system is in place” to analyze incoming data.

Eric Prystowski, MD, the director of the clinical electrophysiology lab at The Care Group (Indianapolis), described the recommendations for physicians managing device advisory notices. The summary for this section of the HRS draft guidance notes that public health notifications “regarding pacemakers, ICDs or leads do not necessarily translate into an immediate need” for explantation. The draft also points out that “the risk . . . is [also] associated with the experience of the implanter.”

Thus it was that Prystowski observed that the question of how to deal with advisories is relevant at the level of the institution, each of which “should know your own numbers” in order to properly advise patients.

Prystowski said that physicians consider alternatives to explantation of ICDs and pacemakers if the rate of malfunction is less than one in 1,000. He also suggested that physicians bear in mind that co-morbidities might argue against explantation “even when the risk of device malfunction or patient harm is substantial.”

Two studies presented at Heart Rhythm 2006 addressed this very question. A review of 732 ICD replacements at the Mayo Clinic (Rochester, Minnesota) between 2000 and 2005 disclosed nine complications (1.24%), including infection and hematoma. Of the 732, electives accounted for 570 and 162 were due to advisories and recalls. A similar review of 533 reimplantations by the Canadian Heart Rhythm Society Device Advisory Working Group disclosed complications in 43 out of 533 (8.1%), 31 of which required further surgical intervention. Ten of that 31 were re-explantations, two of which resulted in death.

Wyn Davies, MD, a consultant cardiologist at St. Mary's Hospital (London), offered a brief international perspective on medical device reports for cardiac devices. Davies pointed out that while “95% of such implants are made by” companies in the U.S., many of these devices are implanted in overseas patients.

This fact, he opined, fairly demands an international standard for reporting.

Davies commented that not only are reporting standards different from one nation to another, but that “health economy systems themselves” vary widely, even between adjacent nations that otherwise exhibit similar economic and health characteristics. He noted that many countries have minimal reporting requirements while some have no requirements at all.

On the other hand, the rate of implantation of cardiac devices in the U.S. outstrips that of most other nations, including Japan and European nations, “by a factor of 10,” according to Davies.

Davies informed the audience that the Global Harmonization Task Force (GHTF) was looking into this subject. “It's a laudable organization,” he remarked, “but it has a long way to go” to establish a universal reporting standard. GHTF is a group of representatives from regulatory bodies and industry formed in 1992 to examine a number of issues facing the development and regulation of medical devices.

GHTF has issued several documents in this pursuit. In its 2005 summary of requirements of regulatory bodies that require reports on adverse events, the document points out that many firms have to report some events to more than one nation's regulatory apparatus because “some regulatory authorities require reports to be submitted irrespective of the geographical location of the event.”

As is well known, the FDA requires American manufacturers to report events “without regard to the location of the event,” but the report also describes the Australian government's requirements, which apparently do not cover events taking place outside Australia. EU requirements include that “the report should be made to the competent authority in the country of occurrence of the incident,” as well as the country in which the device was implanted if the country in question is “a member state.”

In a further demonstration of the wild disparity of reporting requirements in states with extensive regulatory mechanisms, the report also states that in Japan, “manufacturers and importers of medical devices shall submit a Fuguai (AE) report to the Japanese government, but that “no other entity, organization or body can receive a Fuguai report directly in Japan” and that “foreign organizations can't receive Fuguai reports either."