October 14, 2003
Statement by Sidney M. Wolfe, M.D.
Director, Public Citizen’s Health Research Group
FDA Hearing on Silicone Gel Breast Implants
Both the FDA approval standard for medical devices, “reasonable assurance of safety,” and the validity of informed consent/informed choice are legitimate only if studies are long enough in duration and comprehensive enough to answer existing questions about safety. Instead of reasonable assurance of safety, there is more accurately “reasonable assurance of ignorance” and therefore reasonable concern about safety. If the decision is to approve now, women will not get the information they need for truly informed consent before deciding whether to undergo silicone gel breast implant surgery.
It is ironic that the clear evidence of certain dangers such as local and regional complications, often from rupture, and remaining questions about other risks that led to the 11.5 year-old moratorium on silicone gel breast implantation (excluding post-mastectomy) were based on much longer exposures than now exist for the implants being seriously considered for approval today.
Despite these deficiencies in the duration of data being considered by the FDA, (only the first three years of a planned 10-year study) there are many red-flag warning signals within the thousands of pages of documents put up on the internet last week, more than enough to justify a decision to wait at least five more years to collect more information on the thousands of women who already have had implants, rather than precipitously approving these unsafe devices for marketing to hundreds of thousands of women a year who will, once they are told by the government the devices have “reasonable assurance of safety,” opt for the surgery to insert them and thereby participate in a massive experiment.
The chart below shows that the complication rates of the three year data in the 1990 Inamed study and the current “Core” study are quite similar, examining only the data on those implants in the 1990 study for which Inamed is now seeking approval.
The chart below compares the data from three years with that of five years in the 1990 study and shows the striking increases in the risk of various complications occurring between years three and five. For example, the risk of removal/replacement increased from 6.3% to 11.5% in just two years. Similarly, the increases in capsular contracture were from 9.5 to 14.9%. The cumulative risk of breast pain, not provided at three years in these data was 25.8% and loss of nipple sensation was 17.2% at five years. Since the five-year follow-up in the 1990 study was not as great as it could have been, it is not unreasonable to hypothesize that in the current core study, when the five-year data are collected, the risks will be as high or even higher than those found in the 1990 study.
The charts below show the increasing risk of various complications with time:
The following charts are derived from data in the unpublished SEER study, funded by Inamed and Mentor, using NCI surveillance data of breast cancer patients. The most striking finding is that based on 181 implant removals, the Kaplan-Meier risk of removal, 21% at five years after implantation for silicone gel breast implants, had risen to 50.5% by ten years – more than doubling. In other words, by 10 years more than half of these women had their implants removed. This compares with 40.7% for those women getting saline implants. This is the only population-based study, with the advantages of better ascertainment, to examine the problem of implant removal. It is noteworthy that of the 6563 women with breast cancer in the geographic areas covered by the study, only 1159 (17.7%) had breast implants, and in the study there are details for 1012 of these 1159 women (87%).
In addition to the primary deficiency of only having three years of data in the ten- year core study, according to the FDA “In the reconstruction study, only 59% of patients have reached the 3-year follow-up visit. Worse, the follow-up in the adjunct reconstruction group was only 53.8% at one year and 27% at three years.
Other problems noted by FDA reviewers were that in addition to 92 protocol violations in the core study, many involving a lack of informed consent, the adjunct study had even more egregious violations including 211 patients in whom informed consent was not obtained before surgery, 86 patients implanted at a facility without ethical review board approval and 25 patients implanted by a non-authorized investigator.
According to the FDA medical officer reviewing the Inamed application, “Given these limitations in the ascertainment of asymptomatic rupture [most patients did not have an MRI], there is concern regarding the determination of both asymptomatic ruptures and the total rupture rate.” This concern is greatly heightened by the findings of other FDA scientists, who studied the use of MRI in the U.S. on 344 randomly chosen women (average age 51) who had had silcone gel breast implants. Sixty eight percent of the women had at least one ruptured breast implant, median age of implant at rupture was 10.8 years, and 21% had silicone gel outside of the fibrous capsule in at least one breast.
Despite the concern about implant rupture and spread of silicone around the body, FDA stated that “Inamed provided no discussion of the significance of implant rupture… Cases of distant migration of gel to breast, axillary lymph nodes, abdomen, groin… have been reported [in the published literature].”
Although the 1999 Institute of Medicine Study review on breast implants focused mainly on questions of systemic disease and there is considerable new information since the conclusion of that review – it did conclude that local and regional complications were the main safety issues and that they had not been well studied. Like the FDA then, they further concluded that information on these complications is crucial for women deciding whether or not they want silicone gel breast implant surgery.
In a review of 35 different studies that encompass more than 8000 explanted silicone gel breast implants, failure was found to be 30% at 5 years, 50% at 10 years, and 70% at 17 years. The only studies that were used were ones that reported implant duration, the total number of silicone gel breast implants explanted, and the number of silicone implants for which shell rupture or failure (“not intact”) was confirmed upon surgical removal.
This year marks Sybil Goldrich’s 20th anniversary since her battle with breast cancer. But that was only the beginning of her fight on behalf of women. After undergoing a bilateral mastectomy in 1983, Sybil received silicone gel breast implants. Within 2 years, she underwent 7 operations, 2 mastectomies, for a total of 4 sets of implants. During this time she experienced excessive pain, capsular contracture, migration of gel to her uterus, ovary and liver, extrusion, necrosis and rupture. Finally, she chose to have a tram flap procedure. In 1998, Sybil co-founded Command Trust Network, a national clearinghouse dedicated to providing thorough and unbiased information about breast implants. Since then, she has worked tirelessly to ensure government and corporate accountability with regard to breast implants. Her goal is to ensure a safe implant is available to all women. She does not think that the short-term data submitted for FDA approval begins to approach such a goal.
A final irony can be found in the section entitled “Preclinical-Shelf life in one of the FDA documents. The document states:
“Based on all shelf life data provided, Inamed supported a 2.5-year expiration date on their package label.” (Tests included gel cohesion, shell ultimate break force, shell tensile set and shell elongation.) Even though many women are led to believe that these implants will last at least ten years if not a lifetime, this 2.5 years “expiration date” is a further insult.
The apparent unwillingness of the FDA to require silicone breast implant manufacturers to provide longer-term data as a prerequisite to approval of such devices raises serious questions about whether the agency is enforcing the 1976 Medical Device law to protect patients. The major precipitating event leading to passage of that law was the disaster concerning the Dalkon Shield intrauterine device (IUD). Seventeen women died and thousands of women were rendered sterile because of the increased uterine infections caused by this device. Requiring adequate pre-approval testing for permanently implantable devices such as breast implants was a major principle underlying the passage of the 1976 law but the agency appears poised to negate this principle as they consider the approval of silicone gel breast implants.
 FDA Summary Panel Memorandum, Sept. 12, 2003, page 33.
 FDA Clinical Summary Memorandum, Sahar MK. Dawisha, MD., page 64.
 FDA Clinical Summary Memorandum, Sahar MK. Dawisha, MD., pages 9-10
 FDA Clinical Summary Memorandum, Sahar MK. Dawisha, MD., page 75.
 Brown SL et al. Prevalence of rupture of silicone gel breast implants revealed on MR imaging in a population of women in Birmingham, Alabama. Am J Roentgenol. 2000;175:1057-64.
 FDA Summary Panel Memorandum, Sept. 12, 2003, page 37.
 Marotta et al. Silicone gel breast implant failure and frequency of additional surgeries: analysis of 35 studies reporting examination of more than 8,000 explants. J Biomed Mater Res. 1999;48(3):354-64.
 FDA Summary Panel Memorandum, Sept. 12, 2003, page 29.