Full article reprinted from "The Gray Sheet" - July 7, 2008
In a letter in the July 3 New England Journal of Medicine, CDRH Director Dan Schultz defends FDA's approval of some devices based only on bench testing data.
The letter is a response to William Maisel, M.D.'s March 6 editorial in NEJM harshly criticizing the agency's and industry's approach to device safety in general and FDA's response to recent safety problems with Medtronic's Sprint Fidelis implantable defibrillator lead in particular.
FDA approval of modified devices like Sprint Fidelis based only on bench testing is not uncommon and "is not an inherently unsafe approach, as Maisel implies," Schultz asserts in the letter to the editor.
The agency's evaluation of a modified device begins with analysis of the proposed modification and a determination of the potential types of failure. The agency can require clinical data collection, but "in many cases, our questions are best answered by performing appropriate engineering analyses," Schultz explains.
"To require that these modified devices undergo clinical trials across the board as a condition of FDA approval would limit the availability of improved products," the CDRH chief maintains. "Also, most of these trials would have insufficient power to detect small but clinically meaningful differences in performance."
In an "Author's Response" to Schultz' letter, Maisel counters that bench-testing alone cannot be relied upon for some types of devices. "It is challenging to predict the long-term performance of implanted devices on the basis of bench testing or premarketing clinical trials of short duration. Thus, for selected life-sustaining products, postmarketing studies of sufficient size and duration must be required of manufacturers," he argues.
In an interview with "The Gray Sheet," Maisel explained that approving a device without pre-market clinical trials is not necessarily a problem, if the approval is followed by appropriate, proactive post-market surveillance. The Sprint Fidelis case was a "double whammy," because neither the pre-market nor post-market data was adequate to detect the safety problem, he explained.
Maisel directs the Medical Device Safety Institute at Beth Israel Deaconess Medical Center, Boston, and has published several studies on device safety and physicians' responses to FDA recalls. He is the former chairman of FDA's Circulatory System Devices advisory panel.
Medtronic removed the Sprint Fidelis ICD leads from hospitals in October 2007 after a review of 25,000 patients showed the 30-month fracture rate of pre-modification Sprint Fidelis leads was 2.3%.
The company had first learned of a limited number of device fractures the previous March, but did not recall the devices at the time because, prior to the completion of the 25,000-patient review, the Fidelis fracture rate appeared to be about the same as that of other Medtronic leads, about 1.1%.
But Maisel argued in his editorial that Medtronic's determination that the fracture rates were comparable to that of other devices was based on limited data. The postmarket study the company was conducting on Fidelis was "grossly underpowered" to measure the true failure rate, enrolling fewer than100 patients followed for two years.
"Adverse event reports are simply not of sufficient quality or scientific enough to tell you about a device's performance," Maisel told "The Gray Sheet."
"Unfortunately, when questions first arose about the performance of the Medtronic Sprint Fidelis ICD lead, the available postmarketing data were insufficient to allow an accurate evaluation of the device's performance," Maisel explains in his response to Schultz' letter.
The failure to collect adequate postmarket data on the device is particularly regrettable given that, by the time the fracture problems began to arise, the device had already been implanted in hundreds of thousands of patients, according to Maisel.
In the interview, Maisel explained that the specifics of an appropriate post-market study must be worked out between FDA and the manufacturer, but in general the study should be designed to enroll enough patients and follow them for enough time to measure the frequency of any particular safety problem.
Patients Should Know About Safety Reviews - Maisel
Maisel objects to Medtronic's and FDA's decision to keep Fidelis on the market as the comprehensive review was ongoing without telling doctors or patients that the company was investigating a possible safety problem.
In May 2007, Medtronic submitted an application to FDA to modify Fidelis to reduce the fracture risk. Even after the modification was approved two months later, the older version of the device remained in hospital inventories and continued to be implanted.
"There is nothing inherently wrong with [keeping an older model in circulation] unless the older models pose an undue health risk," Schultz maintains. "The continued marketing of Fidelis leads occurred when available data indicated that the fracture rate was similar to that of other leads. When continued monitoring of the situation showed otherwise, the lead was recalled and existing stocks were promptly called back."
Maisel's original editorial "didn't say that it was bad that it stayed on the market," he told "The Gray Sheet." "My point simply is that patients have a right to that information."
Optimism For The Future Of Lead Monitoring
Maisel and Robert Hauser, M.D., Minneapolis Heart Institute, are co-chairing a Heart Rhythm Society task force that is developing recommendations for FDA and industry on lead surveillance, failure thresholds, adverse event data collection and how industry, government and physicians can better communicate about lead performance issues (1"The Gray Sheet" May 26, 2008, p. 10).
Maisel says he is optimistic that the task force, which is modeled after a 2006 HRS task force that wrote recommendations on implantable defibrillator safety, will produce recommendations by the first quarter of 2009.
Collection of post-market data on leads will also be aided by the national ICD registry. That registry's board of directors recently voted to begin collecting information on lead performance.
- Reed Miller
Published weekly, "The Gray Sheet" provides in-depth specialized coverage of the medical device, diagnostic and instrumentation industries. Areas of coverage include regulatory and legislative activities, product development, marketing and promotion, and industry developments. Safety and efficacy decisions by FDA and reimbursement and technology assessment determinations by The Centers for Medicare and Medicaid Services are key elements. Plus, you'll get daily news coverage of medical device and diagnostics industries from Health News Daily on the Web at no extra charge. Start your 30-day, risk-free trial now!
