To the General and Plastic Surgery Devices Panel Center for Devices and Radiological Health Food and Drug Administration Regarding Premarket Approval Application for Silicone Gel-Filled Breast Prostheses
October 15, 2003
I am Dr. Diana Zuckerman, President of the National Center for Policy Research for Women & Families. Our independent, nonprofit organization is a think tank that gathers and explains research information and uses it to improve the health and safety of women, children, and families.
It’s very difficult to testify as the last public comment. Since you already discussed the key questions last night, I wonder how I can say anything you haven’t heard and might want to hear or be willing to hear. I will express my sympathy to you for the very difficult work you have put in, and let you know that after I left this meeting very late last night, I had to rewrite this testimony. So, I may have been up even later than you all were.
Let me start by saying I am speaking from the perspective of someone trained in psychology and epidemiology, who was a university faculty member and researcher and taught courses in research methods before moving to Washington to work in the Congress, U.S. Department of Health and Human Services, and for nonprofit organizations.
I have read every published epidemiological study on breast implants and would like to briefly discuss the Inamed studies in the context of those other studies.
What do we know about the health effects of ruptured silicone gel implants?
The FDA’s study, described by Dr. Lori Brown yesterday, is the best designed study ever conducted on the topic. One reason for its superiority is that it focused on women who were basically happy with their implants, and who had implants for at least 7 years. That length of time is key. Other studies have included women who had implants for an average of 7 years — but not at least 7 years.
You know from hearing testimony from women yesterday and today that most women who have had problems with rupture had implants for a long time — usually much longer than seven years.
What do we know about the health risks of silicone gel implants more generally?
I have heard the Institute of Medicine report, the Mayo Clinic Study, the Harvard Nurses study, and the meta analysis all cited as clear proof that breast implants are safe. First of all, its important to note that they are pretty much all the same thing. The Institute of Medicine report was based on the same studies as the meta analysis, and they both included the Mayo Clinic study and the Harvard Nurses study as key components.
Almost all the studies included in the Institute of Medicine report suffered from the same shortcomings that many panel members described for the Inamed safety research: too small, and too short. For example, the Mayo Clinic study included only 749 women with breast implants, only 125 of whom were reconstruction patients. To be in the study, women had to have implants for at least one month. The average length of time was about 7.5 years, which means that only about 375 women had implants for more than 8 years. Since diseases like lupus, scleroderma, and rheumatoid arthritis are not very common among women in their 20’s and 30’s, this study doesn’t have the power to detect most of the diseases it measured. The authors themselves acknowledged that major shortcoming.
So, while I agree with the Institute of Medicine that there is not sufficient evidence to conclude that implants cause autoimmune disease, the report can’t be considered conclusive proof that implants don’t cause autoimmune disease.
The National Cancer Institute study finding a doubling of brain cancer, tripling of lung cancer, and quadrupling of suicide is also an exceptionally well-designed study, because all the women in the study had breast implants for at least 8 years. Again, other studies included women who had implants for an average of 8 years, but not a minimum of 8 years. And again, that means that other studies included women who were not exposed for a long enough time to develop a disease and be diagnosed.
Most of the Scandinavian studies were funded by Dow Corning, and had some shortcomings such as measuring illness in terms of hospitalization rather than diagnosis. Again, think of how unlikely it is that a 30 year old woman will be hospitalized for rheumatoid arthritis.
Signs and Symptoms
Now that you know some of the shortcomings of the research literature on systemic disease, let’s take another look at the signs and symptoms. Think about the testimony you heard from the women, many of whom were happy with their implants and never suspected that their problems with fatigue or aches and pains might be related to their implants. This is not conclusive evidence, but it is a pattern that needs to be considered — especially with data showing an increase in every symptom over a period of only two years on a cohort of young augmentation patients.
Even if the data on systemic illness and signs and symptoms are not conclusive, let’s look again at some of the photos you have seen of the cosmetic results of silicone gel implant problems.
Here is a 29-year old woman who had her implants removed after 7 years. Her capsular contracture was so painful that she apparently preferred getting her implants out to keeping them in. This photograph is from the FDA’s website.
That is obviously not a good outcome, but here is a woman who wasn’t so lucky — Sharyn Noakes. You saw her photo yesterday. Her ruptured implant had leaked into her healthy breasts. When the silicone was removed, this is all that was left of her breasts.
And this is Kathy Nye, a breast cancer survivor who suffered from necrosis and her implant extruded through her skin. Little attention was given to the 6% necrosis rate among reconstruction patients in the Inamed Core study.
Inamed Research Quality
Like many of you, I applaud Inamed’s excellent response rate in their Core study.
But like Dr. Whelan and Professor Dubler, I share your amazement about the lack of long-term research.
The company started to analyze the safety of silicone gel breast implants in 1990. It was terrible that they included only 29 breast cancer patients. But, they also lost most of their patients to follow-up before ending the study after 5 years.
The company was given the opportunity to test their silicone gel implants on thousands of patients in the Adjunct study. They enrolled thousands of patients and then failed to follow-up on most of them, making that study useless.
And, the core study is almost entirely White women. Women of color get breast cancer, for example, but only 6 African American women and only 5 Asian American women are in the reconstruction sample. And, of course both groups are more likely to have scarring problems, and African Americans are more susceptible to autoimmune diseases.
What does approval mean?
If Inamed silicone gel implants are approved, and the company is required to continue research for 7 or even 10 more years, consider the company’s track record so far.
You need to know that the FDA can’t truly enforce any requirement of post-market research. The FDA has leverage before a product is approved, since the company will comply in order to get their product approved. It has no real leverage after approval.
If Inamed silicone gel implants are approved, the FDA can try to improve informed consent. But again, it can’t enforce that.
If Inamed silicone gel implants are approved, the FDA can specify that it is approved for women ages 18 and older. But physicians will be free to use these implants on 17-year olds or younger girls — just as they do now, with saline implants.
If Inamed silicone gel implants are approved and you try to require women to get MRI’s, that can’t be enforced either. Even in the Inamed study, where the MRI’s were presumably free, many of the women did not comply.
Perhaps most important, approval is the seal of approval. We live in a sound bite world. If you recommend that silicone gel implants be approved, despite all the members who said last night that long-term safety is unknown, the message will be: “silicone gel implants are safe.” That will be your legacy. If you’re not sure that they truly are safe, then you should vote against approval.
A final word about the inadequacy of the 1-year, 2-year, and 3-year data. I agree with those who questioned why in the world the FDA issued a guidance asking for only 2 years of safety data, for a product whose main concerns are long-term safety. It doesn’t seem quite fair to then change their mind. On the other hand, the company has not exactly done everything they could do, in their 1990 study or their Adjunct study, to collect safety data. Is it really unfair to expect that a company would try to improve their product in the last 10 years, or try to evaluate the safety of their product. Better guidance would have been helpful, but the real responsibility is with the sponsor.