Safety and Benefits of Inamed Silicone Breast Implants From the April 2005 FDA Analysis and Meeting
Marcy Oppenheimer, M.D.
In January, 2004, Inamed’s application for approval of silicone breast implants was turned down by the FDA. In rejecting the application, the FDA noted the lack of safety data and requested better information about the rupture rate over the lifetime of the implants and the health consequences of implant rupture. Inamed’s 2005 data do not answer these essential safety questions, and in fact contains alarming data on the frequency and risks of implant rupture.
Inamed fails to provide rate of implant rupture
The FDA specifically asked Inamed to provide data from its Core Study with a “follow-up of sufficient duration . . . to measure or reasonably estimate how the shape of the curve” of implant rupture “changes over the lifetime of the device.” [1]
Inamed failed to do so. FDA’s summary of Inamed’s 2005 submission states that, “it is difficult to reasonably predict the probability of rupture through year 10 with the available data” from Inamed’s Core Study. [2]
Inamed fails to provide information on health consequences of rupture
FDA also requested that Inamed’s Core Study be extended sufficiently “to characterize the potential local health consequences of ruptured implants.” [3]
Inamed has failed to do this as well. With respect to assessing the health consequences of implant rupture, the FDA concludes that the Core Study data in the current application “is of limited value” and that the published articles referred to by Inamed “do not completely address all the health consequences of rupture.” Further, Inamed’s Adjunct Study, which the FDA had suggested could provide information on the health consequences of rupture, was also deemed to be “of limited value” in providing the necessary data, because of “under-ascertainment of rupture and inadequate patient follow-up.” [4]
FDA predicts high rupture rates as implants age
The table below presents the rupture rate in the Inamed Core Study among the implant patients who received MRIs. Almost all ruptures were detected by MRIs. Although some patients were followed for 4 years, this is essentially a 3-year rupture study because MRIs were performed in the first and third year, but not during the 4th year. Thus, any rupture occurring after third year are not likely to be detected until year 5.
| Type of Patient | Women with Ruptures in First 3 Years |
|---|---|
| Augmentation | 3% |
| Reconstruction | 20% |
| Revision | 11% |
The FDA concluded that Inamed had submitted insufficient information to calculate a longer-term rupture rate. However, the FDA did determine that the risk of rupture would most likely increase exponentially, so that the rupture rate at 10 years would be much higher than percentage reported after three or four years. [5]
Signs and Symptoms of Connective Tissue Disease
The FDA presented slides indicating an increase in several signs and symptoms of connective tissue disease, such as joint pain and fatigue, for women who have had implants for two years, compared to prior to getting breast implants. The analysis was conducted on all women in Inamed’s Core Study, not just those with a ruptured implant. [6] Although not provided by the FDA, an analysis presented by Advisory Panel member Dr. Brent Blumenstein indicates that these differences are maintained even when the impact of aging is statistically controlled.
Safety of Ruptured Implants
No one knows the health consequences of implant rupture and silicone leakage, and one aim of the Inamed Core Study is to examine this question. The table below compares local complications among patients with confirmed ruptured implants to patients with confirmed intact implants.
| Complication | Confirmed Ruptured Implants (17 patients) | Confirmed Intact Implants (79 patients) |
|---|---|---|
| No Complication | 47% | 47% |
| Asymmetry | 0% | 7% |
| Breast Pain | 12% | 14% |
| Bruising | 6% | 8% |
| Capsular Contracture | 12% | 14% |
| Infection | 18% | 3% |
| Lymphadenopathy (swollen lymph nodes) | 6% | 3% |
| Redness | 24% | 10% |
| Seroma (collection of fluid around implant) | 12% | 5% |
| Skin Rash | 6% | 1% |
It is clear from the table that patients with confirmed ruptures have higher rates of infection, lymphadenopathy, redness, seroma, and skin rash, which are shown shaded above. These symptoms are generally associated with an inflammatory reaction and/or with infection. While these data are based on a small number of patients (only 17 in the confirmed rupture group), they point to the conclusion that implant rupture may cause an inflammatory process in the body. (The much larger Adjunct Study does not provide reliable rupture data because of its low follow-up rate and the lack of MRIs, which are the most reliable way to determine if an implant that is still inside the body has ruptured.
Danish data submitted by the implant manufacturers show that women with ruptured implants are twice as likely to report non-serious pain in the affected breast that women with intact implants and are six times more likely to report breast hardness. In addition, women with extra-capsular rupture are 3 times more likely to report a connective tissue disease, 2 times more likely to report pleuritis, and 1.7 times more likely to report than women with intact implants, though these numbers were not statistically significant.
The next table presents Inamed data on the symptoms of connective tissue disease experienced by women with ruptured and intact implants. The number of patients is small since only 11 women in the study with confirmed rupture completed the questionnaire. However, the data show a higher percentage of reports of new gastro-intestinal, general, muscle, and skin complaints among the women with ruptured implants.
| New Symptoms | Confirmed Ruptured Implants (11 patients) | Confirmed Intact Implants (79 patients) |
|---|---|---|
| Joint | 0% | 20% |
| Urinary | 0% | 7% |
| Othern | 18% | 19% |
| Neurological | 9% | 21% |
| Gastrointestinal | 27% | 24% |
| General | 18% | 14% |
| Muscle | 45% | 17% |
| Skin | 27% | 18% |
Benefits
In addition to evaluating the risks of implants, the companies were required to evaluate the benefits as well. It is clear that breast implants increase breast size, but plastic surgeons and implant makers also claim that breast implants help women feel better about themselves and their lives. For that reason, the FDA required implant makers to use objective measures of emotional health, comparing women before they had implants and two years later.
Inamed data show that most patients say they are satisfied with their implants after three years. However, their answers to several scientifically developed scales and questionnaires shows that overall, their quality of life remained the same or declined two years after receiving implants. The table below summarizes these results. The “MOS-20” scale assesses six important health concepts including physical functioning, social functioning, mental health, and current health perceptions. In the table, a change that was not statistically significant is listed as “no change.”
| Assessment Tool | Augumentation | Reconstruction | Revision |
|---|---|---|---|
| SF-36 Role Emotional | Worse | No change | Worse |
| SF-36 Role Physical | Worse | Better | No change |
| SF-36 General Health | Worse | No change | Worse |
| SF-36 Pain | No change | No change | No change |
| SF-36 Social | Worse | No change | Worse |
| SF-36 Physical | No change | No change | No change |
| SF-36 Vitality | Worse | No change | Worse |
| SF-36 Mental Health | Worse | No change | Worse |
| MOS-20 Health Perceptions | Worse | No change | Worse |
| MOS-20 Physical Functioning | No change | Better | No change |
| MOS-20 Social Functioning | No change | No change | No change |
| MOS-20 Mental Health | Worse | No change | Worse |
| Tennessee Self-Concept Scale | Better | No change | Worse |
| Rosenberg Self-Esteem Scale | No change | No change | Worse |
| Body Esteem Scale – Total Score | Better | No change | No change |
| Body Esteem Scale – Sexual Attractiveness | Better | No change | No change |
| Body Esteem Scale – Weight Concern | No change | No change | No change |
| Body Esteem Scale – Physical Condition | Worse | No change | Worse |
In summary, neither the evidence presented by industry, nor the published literature, support the claim that Inamed silicone gel breast implants improve a women’s self-esteem or mental health, and on average augmentation patients feel worse about their physical and emotional health and vitality. Augmentation patients report some improvements in feelings of physical attractiveness.
[1] FDA Summary Memorandum, Inamed PMA Review Team, March 2, 2005, p.12 (“ISM”€)
[2] ISM, p. 40
[3] ISM, p. 12
[4] ISM, p. 40
[5] ISM, p. 37
[6] http://www.fda.gov/ohrms/dockets/ac/03/slides/3989s1_02-update_files/frame.htm, slides 45 and 55.