ROCKVILLE, Md., April 7-An FDA analysis of thousands of pages of manufacturers' data on the safety of silicone gel-filled breast implants, prepared for an advisory committee meeting next week, has found little evidence to back an application to give the devices wider marketing permission.
Despite a review of the voluminous submission, the FDA said late this week it was not able to reach specific conclusions about the safety of silicone breast implants, adding that manufacturers may not have submitted enough data to warrant putting the devices back on the market without limitations.
Action Points
- Explain to patients that the FDA will be revisiting the question of whether silicone gel-filled breast implants should be allowed to have wider marketing again, by first asking expert advisers to weigh the data and give recommendations.
- Understand that the agency is considering a wealth of data, and that there is some disagreement between the manufacturers and the agency as to the true complication rates. Two published reports, unconfirmed, said the agency found that 75% or more of the implants for augmentation purposes might rupture at 10 years.
- Explain that saline-filled breast implants will not be the subject of the advisory panel meeting next week.
The FDA's General and Plastic Surgery Devices advisory panel will meet for three days starting on Monday to consider whether silicone implants, which have been severely restricted since 1992, should receive wider marketing approval.
A majority of panelists voted in October 2003 to back approval of silicone implants, but the committee chairman later wrote the FDA to say more safety data was needed.
The two main manufacturers, Inamed and Mentor, have been following 1,007 patients in a 10-year FDA-mandated study. The first patient was enrolled in 2000. So far, the agency says, only 74% of patients showed up or were able to be evaluated at the pivotal three-year point. It was these data the FDA had hoped to present to its advisers next week.
In the trial, 551 women received implants for augmentation, 251 for reconstruction, and 205 were included because they had revisions of a previous implant. The agency noted that so far 15% of the 551 augmentation patients had already had a revision at the three-year point, for various reasons that included rupture.
The agency paid particularly close attention to rupture rates. When a device ruptures, often the patient and the physician do not know. The gel leaks and may migrate into the breast area, the lymph nodes, or other locations. The health consequences of this gel leakage are still not clear, said the agency.
An exhaustive Institute of Medicine report concluded in 1999 that silicone gel leakage had not been definitively linked to any disease or condition.
According to its analysis of the latest data, the FDA said that rupture rates differed depending on what source was examined and how long the device had been implanted. For a group of patients who had regular MRIs at one and two years post-implantation, the rates at three years were 0.5% for augmentation, 0.8% for reconstruction, and 4.8% for revision.
The Associated Press and The New York Times both reported that the FDA said in one set of documents that as many as 75% of implants, and up to 93%, might rupture at 10 years. The source of those data was not clear in the thousands of pages of documents, but the published reports may have been referring to the Danish literature on ruptures, showing a rupture rate of 8.9 per 100 implants per year.
"The Danish literature data describes a rupture incidence rate for definite or possible ruptures of 8.9 ruptures per 100 implants per year (95% confidence interval 6.6 - 11.3)," said the FDA. There were about 250,000 augmentation patients voluntarily reported as having breast augmentation just in the year 2003. "Assuming that augmentation patients have bilateral implants at the incidence reported in 2003, that would be 500,000 augmentation implants per year. If half of the augmentation mammoplasties reported in 2003 would be with gel-filled implants if approved (this is probably an underestimation), there would be 250,000 silicone gel-filled augmentation implants per year. Of these 250,000 silicone gel-filled implants per year, using the Danish literature data (i.e., 9 ruptures per 100 implants per year), one could expect at least 22,500 implant ruptures per year in augmentation patients."
Inamed Corp. said it estimated the four-year risk of rupture at 1.6% to 1.7% for augmentation patients, 12.3% to 15.1% for reconstruction patients, and 6% to 7.7% for revision patients. The overall rupture rate at four years post-implantation was 5.2%, said Inamed in its briefing documents.
Mentor argued in its submission that a number of studies "do not support an association between ruptured silicone breast implants and systemic disease or symptoms." It said that rupture rates may be as low as 1% at three years, or as high as 5%.
The FDA looked at other safety issues, as well. On the basis of data submitted, the FDA calculated that the risk of capsular contracture at three years was 8.2% for augmentation patients and 8.8% for reconstruction patients.
Reoperation risk was high, as well -- at 26.3% for reconstruction patients and 15% for augmentation patients.
At the end of the three-day meeting, the FDA's advisers will vote on whether to approve the devices for wider marketing. The agency generally follows its panelists' advice, but not always.