New CDRH Decision Methods Will Be Put To The Test, Starting With Stents
Full article reprinted from "The Gray Sheet" - September 29, 2008
Find out why defining a "new science" for post-market surveillance is a top priority for the FDA device center's post-market group.
Full article reprinted from "The Gray Sheet" - September 29, 2008
Defining a "new science" for post-market surveillance is a top priority for the FDA device center's post-market group, according to the program's new leader.
"Quantitative decision making for post-market safety and surveillance data is a critical focus of the [device center's] matrix organization," said Jonathan Sacker-Bernstein, associate director for post-market operations at CDRH.
On Sept. 2 Sackner-Bernstein became the first permanent director of the office, created as part of the device center's so-called "post-market transformation initiative," after acting heads Diane Mitchell and Don St. Pierre got the initiative off the ground (1"The Gray Sheet" Sept. 8, 2008, p. 19).
Sackner-Bernstein's job is to help develop CDRH's post-market policies and day-to-day strategies, and to lead its collaborative matrix organization, which will facilitate communication about product safety issues in the center.
Developing a brand-new "quantitative decision-making approach" within the center and piloting it in two product areas was one of the nine original priorities of the post-market transformation initiative (2"The Gray Sheet" July 9, 2007, p. 5).
"What we're coming down to is the need to define our science of post-market surveillance," Sackner-Bernstein said Sept. 22 at the AdvaMed 2008 MedTech Conference in Washington, D.C.
Carotid Stent Pilot Project
CDRH is almost a year into its first pilot project - on carotid stents - to see if quantitative decision making will actually work for device regulators. Though still early in the process, "it's got a lot of potential," said Larry Kessler, director of CDRH's Office of Science and Engineering Laboratories.
Kessler is working on the project with Telba Irony, a biostatistician in the Office of Surveillance and Biometrics, and David Chan, a CDRH fellow who is a physician from Brigham and Women's Hospital in Boston and a doctoral candidate in economics at the Massachusetts Institute of Technology.
All products carry risks and benefits, FDA acknowledges. The agency says it tries to weigh both before making decisions like whether to approve a product or recommend a recall, but the current decision-making system has been criticized as "ad hoc, informal and qualitative," Mitchell, now deputy associate director for post-market operations, said at the AdvaMed meeting.
The goal is to come up with a predictable, widely understood methodology for quantifying risks and benefits up front and throughout the life of a product.
Carotid stents are a good starting point because FDA has good, quantifiable data on the devices, Kessler said. Carotid stents are approved for patients at high risk for adverse events during carotid endarterectomy, though trials are under way to expand the indication to patients at lower risk (3"The Gray Sheet" Oct. 22, 2007, p. 12).
The pilot project will retrospectively evaluate pre-market data for all FDA-approved carotid stents. With the help of outside consultants and other experts, FDA will consider different methods of conceptualizing and quantifying risks and benefits.
Once a risk-benefit profile is established for a particular product, "when we get new risks in post-market, we can start saying, 'Does this change our balance?'" Kessler explained in an interview.
The process is more complicated than counting up the risks, counting up the benefits and ending up with "some magic number," he points out.
"We don't say death is worth a certain value in our decision making and life is worth X, Y and Z. But we do try and make sure that we have a good sense that the benefits outweigh the risks when the product is used as intended by the manufacturer and labeled correctly."
Kessler does not expect that, during the pilots, FDA will discover the benefits of an approved product don't outweigh the risks after all.
Next, the team will expand the pilot to other areas, such as spinal discs or other orthopedic devices, Irony said.
"We're going to try two or three pilot projects to learn, then sit down with center management and find out how broad they want to take it, which areas we might want to concentrate in," Kessler said.
Of course, FDA can't conduct this type of analysis for every device, or it would never get new products out the door, he said. Instead, in cases where there is controversy, where risks are particularly concerning, or where extra post-market surveillance is anticipated, "this will be a very valuable set of tools."
Lawyer Urges 'Smart, Careful' Trend Analysis
Changes in the risk-benefit balance "occur incessantly during the life cycle of a device," noted Beverly Lorell, senior medical and policy advisor at the law firm King & Spalding and former chief medical officer of Guidant.
The challenge for FDA and others will be determining whether a safety signal is "real" in the post-market world versus the well-controlled clinical trial environment, she said at the AdvaMed conference.
In clinical trials, confounding variables are mitigated, populations are well-monitored and device users are relatively expert. By contrast, the real world is varied, complex and "messy."
When FDA does begin to systematically analyze post-market information coming from multiple sources, it will need to decide when to act and notify others, whom to notify, and how much information to provide, Lorell said. Like CDRH's Sackner-Bernstein, she says there is no overwhelming regulatory or scientific consensus about the right way to confirm safety signals in the post-market environment.
"The issue of how to be smart and do quantitative and careful trend analysis is critical," Lorell concludes. "It's really the decision whether or not a low-frequency but very important safety signal is the play of chance, or is it likely to be both systemic and systematic and occur in a predictable way in future issues."
- Jessica Bylander
No one covers FDA/CDRH regulation of medical devices like "The Gray Sheet" - Sign up for your 30-day, risk-free trial today. Or call 1-800-332-2181.
