Aug. 31, 2011 — After two days of testimony on what the FDA should do about troubled long-term safety studies of silicone-gel breast implants, agency officials said the studies would continue.
“The current post-approval studies will continue,” said William Maisel, MD, MPH, chief scientist in the FDA’s Center for Devices and Radiological Health, in remarks after the meeting. “The FDA is committed to seeing them completed and making sure the follow-up rates improve.”
The safety studies in question, of nearly 100,000 women with breast implants, which the FDA said were the largest ever required of manufacturers after their devices were marketed to the public, have lost track of up to 79% of the women they enrolled just three years into planned 10-year efforts.
As a result, FDA epidemiologists testified yesterday, the studies had lost the ability to find rare complications, including connective tissue diseases, that they were designed to look for.
Save or Scrap Troubled Studies?
In a second day of testimony, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to the FDA heard plenty of opinions about what should happen with the studies.
Some panelists felt the companies should be compelled by the FDA to finish the studies they had agreed to complete as a condition of the approval of their devices. They asked FDA officials what regulatory powers the agency could wield to do that.
“If you do not meet the conditions of approval the FDA does have regulatory authority to either impose civil penalties or other regulatory actions,” said Mark N. Melkerson, director of the Division of Surgical, Orthopedic and Restorative Devices at the FDA’s Center for Devices and Radiological Health.
The agency said it was not considering taking silicone breast implants off the market.
Some consumer advocates thought that option ought to be on the table, however.
“It has now been 25 years since FDA declared silicone breast implants a class III device, and in that period, only weak attempts have been made to assess the safety of these implants,” said Kate Ryan, of the nonprofit Breast Cancer Action, which is based in San Francisco.
“Follow-up rates on the two large studies are dismal,” Ryan said in testimony. “Given that these studies were a condition of approval, Mentor should have done much more to ensure it had the technical skills to locate women and provide women with incentives to participate in this important research.”
Manufacturers fired back against the notion that they weren’t doing enough to complete the studies.
“To imply that patient safety is not first on our radar is simply inaccurate,” said Caroline Van Hove, a spokeswoman for Allergan. She said the company hoped that the meeting would give the FDA an opportunity to more fully appreciate the complexity of the required studies.
“In general, we are highly committed to collecting quality data in a way that is possible for them and possible for us,” she said.
Ideas for Improving Study Follow-Up
In other testimony, panelists heard from plastic surgeons like Dennis Hammond, MD, of Cedar Rapids, Mich., who participated in the clinical trials of Mentor’s Memory Gel implants.
In contrast to the 21% of patients retained overall by one of the Mentor studies, Hammond said he’d kept track of about 76% of the women he was following.
Panelists asked him how he did it.
“You’ve got to have dedicated surgeons that are really interested in making this study work,” Hammond said. He said he had one staff member devoted to follow-up with women in the clinical trial and that he allocated about half a day of clinical time each week to seeing women in the study for follow-up visits.
Additionally, “A really compelling part would be if the patient had some sort of compensation. It doesn’t have to be wild, really, just something they get back to compensate for the drive in.”
Allergan, the maker of Natrelle implants, which had a 60% follow-up rate with patients after two years, said they paid women a small amount of money for filling out annual questionnaires and coming back to scheduled office visits. Mentor did not.
“While it was certainly admirable to try to get 40,000 patients [in each study] to come back, that just wasn’t going to happen,” Hammond said.
Perspective of Surgeons
The American Society of Plastic Surgeons (ASPS) agreed, and it urged the FDA to consider other data sources, besides the troubled studies, if the agency still felt the need for continued safety monitoring.
“There has been shown to be no relationship between silicone breast implants and connective tissue disorders, which was the main reason these studies were agreed to on the release of these products,” said Phil Haeck, MD, president of the ASPS, in testimony to the panel. “This issue has been settled with the post-approval study data as it already stands now.”
Haeck said sources like the FDA’s own surveillance system, the Manufacture and User Facility Device Experience (MAUDE), which relies on clinicians to report instances of adverse events associated with devices, case reports, patient registries in the U.S. and Europe, and reviews of medical studies, could be relied on to spot any rare events that might arise.
Consumer advocates, like Dana Casciotti, PhD, the public health research director at the Cancer Prevention and Treatment Fund, said annual, 27-page questionnaires women were asked to complete should be shortened and simplified.
“I’ve seen copies of these questionnaires, and they are much too long” and technical, she said.
Panel members seemed to agree, and some suggested that future questionnaires might yield better data if they focused on symptoms rather than diagnosed diseases, since many connective tissue diseases, like lupus, are difficult to diagnose.
Patients who took time off work and paid their way to testify at the meeting urged the FDA to keep trying to answer questions about the long-term and rare complications of breast implants.
“Not everyone gets sick, but those who do, we pay dearly,” said Sharon Schwengler of Phoenix.