The discussion of U.S. medical device regulation and the handling of postmarket device performance issues has undergone a substantial shift during the past year, but it remains to be seen what lasting changes will result.

In previous years, the topic of premarket application review time-lines, as governed by the Medical Device User Fee Modernization Act of 2002, was clearly the primary focus of most FDA discussions with stakeholders, with issues relating to device oversight after approval play-ing a secondary role.

But starting with the controversy surrounding Merck's market withdrawal of Vioxx in late 2004 - including allegations that the company should have advised FDA of the drug's potential adverse effects earlier - and continuing with revelations about failures of Guidant cardiac rhythm management products last summer, the conversation has moved from premarket efficiency to postmarket vigilance.

In the most recent development, CDRH announced Jan. 19 a new "Medical Device Postmarket Transformation Initiative," which could reshape the landscape of device postmarket surveillance and adverse event reporting.

"We are taking on something here, and really doing something, that we as a center have not done with this kind of comprehensive approach over the course of the 30 years we have been in existence," CDRH Director Dan Schultz said in an interview that day.

Going into 2005, there was already a movement toward making improvements on the postmarket side at the FDA device center.

The concept of the "total product lifecycle" was already well established at CDRH, and in December 2004 CDRH Director Dan Schultz told "The Gray Sheet": "It really behooves us to look at what we are doing to ensure safety of medical devices and to not wait for some major press event" (¹ 'The Gray Sheet Almanac' January 2005, p. 9).

The center had recently decided to switch responsibility for condition-of-approval studies from the Office of Device Evaluation to the Office of Surveillance & Biometrics and to develop a new tracking system - now in place - to strengthen the agency's oversight of mandated "condition-of-approval" postmarket data collection.

Guidant Recalls Put Spotlight On Device Safety Issues

The events that began May 23 - when Guidant sent a letter to physicians warning them of a rare defect that could cause a short-circuit in its Prizm 2 DR ICD and that was associated with the death of a 21-year-old college student - added new fuel to the fire.

Two days after Guidant's letter, the New York Times published the first in a series of stories criticizing the company for continuing to sell potentially flawed devices after learning of the short-circuiting problem.

Congress, already focusing its efforts on FDA's drug oversight in the wake of the Vioxx controversy, widened its inquiry to device matters. Senate Finance Chairman Senator Chuck Grassley (R-Iowa), in particular, picked up on the Guidant story and began probing FDA's handling of device safety issues in general (² Also see "Grassley Requests FDA Info On Guidant ICD Alerts Following NEJM Article" - Medtech Insight, 25 July, 2005., p. 5).

Grassley's office did not return calls for comments on the status of any investigations into device safety issues.

Schultz acknowledges that "external concern from various stakeholders" played an important role in realigning CDRH's priorities.

CDRH Offers Path Forward

The fallout for Guidant itself is starting to take shape. After issuing recalls on more than 20 cardiac rhythm management devices, its reputation and stock price took a significant hit last summer and fall. In December, FDA issued a warning letter to Guidant that calls for manufacturing quality system changes and restricts the firm's ability to export devices and gain marketing approval for new products. The firm is facing product liability suits on a large scale.

Ironically, on the business side, Guidant's regulatory woes have had a positive effect. By reducing the firm's perceived value and making it a more affordable takeover target, Guidant's troubles have contributed to a fierce bidding war between would-be acquirers Boston Scientific and Johnson & Johnson.

But the broader effects of the Guidant safety issues and the negative publicity surrounding them are still unfolding.

The most tangible hints of things to come are contained in CDRH's Jan. 19 "transformation initiative." In what may be an attempt to preempt congressional action, the initiative creates a "senior matrix execution team" of FDA staffers and outside experts to revamp the device postmarket safety program.

Schultz said that improving the program will involve consolidating all of the center's information in an electronic, searchable format. Currently, he acknowledges, the various sources of postmarket data - including adverse event reports submitted by device companies and hospitals, the results of manufacturing facility inspections, and data from postmarket studies - are not aggregated in a manner that allows the center to easily spot important patterns.

Attention will also go toward enhancing the quantity and quality of information FDA receives. The device center hopes to enhance collaborations with other agencies, such as CMS, and strengthen CDRH's MedSun program, which trains hospital staff to take a more active role in reporting device problems, among other things. At this point the center does not plan to request additional funding to make the improvements.

Heart Rhythm Society Brings Stakeholders Together

Schultz said that improving postmarket safety will require the cooperation of industry. This is particularly true when it comes to determining the best process and format for communicating potential risks to doctors and patients.

On this question, the Heart Rhythm Society, a professional organization for the electrophysiologists that implant pacemakers and ICDs, has taken a leading role, at least in the realm of cardiac rhythm management products.

HRS and FDA organized a public conference in September to address questions about when and how doctors and patients should be notified about device performance issues (³ Also see "Guidant Posts CRM Performance Data As Stakeholders Discuss Recall Notices" - Medtech Insight, 26 September, 2005., p. 3).

Since then, working groups at AdvaMed and FDA have been collaborating with an HRS physician task force formed in October to produce guidelines for communication between government, industry, doctors and patients. The guidelines will not be binding on companies or FDA but are nevertheless expected to have a significant effect on industry practices.

Much of the September conference centered on the debate over what threshold should be used to determine the appropriate timing to publicly report a potential problem with an ICD or pacemaker.

The discussion also focused on the amount of information that should be provided by companies and FDA, with some arguing that physicians need more than just raw data about failure rates to weigh the potential benefits and risks of explanting a device.

In a recent interview, the chair of HRS' task force, Mark Carlson, suggested the group's recommendations will lean towards giving physicians a smaller, more selective amount of information on ICD performance. "Too much data and information has the potential to obfuscate or camouflage problems that may be important, and we certainly don't want that to occur," Carlson said.

He also said that the task force guidelines, which are expected to be out in May, will try to encourage practitioners to more frequently return devices that may have malfunctioned to aid in company and FDA efforts to analyze events.

A first draft of recommendations still contains "gaping holes," Carlson said.

Another panel member, Dr. William Maisel of Harvard Medical School, said HRS is working with AdvaMed to try to standardize the details of how product performance is reported. "I think that individual companies should be required to report their individual failure rates, so that as a consumer I can choose a product that I think is best for my patient," Maisel said.

Equally important, he noted, is the need to re-evaluate the way FDA issues advisories on implantable devices. "I think ideally the term 'recall' wouldn't be used to describe implantable devices that do not require explanation," Maisel said. "The terminology is misleading, and I think in some cases results in physicians mismanaging the advisory or mismanaging the problem."

Changes of the type Maisel refers to could have applications beyond ICDs, and CDRH's new initiative may prove the mechanism by which the lessons are transferred to the rest of the device industry.

The center is planning a series of postmarket workshops, co-sponsored by AdvaMed, that could be a first step in this direction. The first is scheduled for Feb. 8-9.

- Matthew Perrone

Postmarket Takes Spotlight: Guidant Recalls Reshuffle FDA And Device Industry Objectives For 2006

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