Category Archives: Testimonies and Statements by NCHR

FDA Approves Silicone Breast Implants Despite Safety Concerns

Diana Zuckerman, PhD, National Center for Health Research: November 17, 2006

The FDA’s decision to approve silicone gel breast implants is a triumph of corporate lobbying and hype over sound science and women’s health.

The FDA’s standards for implants have reached a new low with this decision. It’s important for women to know that the FDA has not determined that silicone gel breast implants are safe – only that they are “reasonably safe.” What does that mean? In this case, it means that if a woman lives for 25 years after getting these implants, she will need to remove them at least once, probably twice, and possibly more than that. If she doesn’t, the implants are likely to break inside her body, and possibly leak silicone into her breasts, lungs, and other organs.

What do we know about the risks? Most women with silicone gel breast implants experienced at least one complication within the first three years of getting implants, including breasts that were hard or painful, oddly shaped, or had lost sensation, or the need for additional surgery to fix implant problems. The additional surgery is often very expensive, and almost never covered by health insurance. FDA scientists found that women with silicone breast implants for two years had a significant increase in several auto-immune symptoms, such as joint pain and chronic fatigue. Contrary to the hype, breast augmentation patients did not report a significant improvement in self-esteem and tended to report a lower quality of life after implants. Perhaps that is why scientists at the National Cancer Institute found that women with breast implants were twice as likely to kill themselves, compared to other plastic surgery patients.

The impact of silicone implants on breast milk is unknown. The long-term health risks (after three years) are unknown. Given the known risks and the unknown risks, silicone breast implants should be considered less “reasonably safe” than sky diving or other high-risk adventures. Most sky divers are not harmed, but some are harmed a little, and some die as a result. According to the information provided by implant manufacturers to the FDA, most women with silicone breast implants will be harmed. The harm after can be to her health, her mental health, her appearance, or to her pocketbook, or all four.

We support the FDA’s decision to require 10-year studies of 40,000 women. This clearly indicates that the FDA acknowledges the need for information about long-term risks. We will do all we can to make sure that the FDA enforces that research requirement, but we wonder what FDA will do if the companies do not complete those studies.

We support FDA’s recommendation that women have breast MRIs to check for leakage every two years, but we know that most women can’t afford the $2,000+ that breast MRIs cost.

We support the FDA’s age restriction, limiting augmentation with silicone gel breast implants to women ages 22 and over. We strongly encourage plastic surgeons to abide by those restrictions, since younger women are still developing physically and emotionally.

FDA’s announcement was made at 5:30 on the Friday before Thanksgiving, in an effort to reduce media coverage. Since FDA offices are normally closed at 5 pm, apparently even they are ashamed of their own decision.

The National Center for Health Research is a nonprofit research and education organization focused on health and safety issues. The Center is not opposed to silicone implants but is opposed to FDA approval of any implanted medical devices that are not proven safe for long-term use. For more information about breast implants and the personal stories of women with implants, see www.breastimplantinfo.org. For information about numerous other women’s health issues, see the Center’s website at www.center4research.org.

All articles are reviewed and approved by Diana Zuckerman, PhD, and other senior staff.

Statement of Diana Zuckerman Regarding FDA Legislation Before the Subcommittee on Energy and Commerce

Diana Zuckerman, Phd, National Center for Health Research: June 12, 2007

Thank you for the opportunity to testify about the Subcommittee’s discussion draft FDA legislation. I am Dr. Diana Zuckerman, president of the National Research Center for Women & Families, an independent think tank that analyzes and evaluates a wide range of health programs, policies, and agencies, including the FDA.

I am trained as an epidemiologist at Yale Medical School and for more than a dozen years I worked in Congress, the U.S. Department of Health and Human Services, and the White House, determining which health policies were working and which ones were not.

Our center is an active member of the Patient and Consumer Coalition, comprised of nonprofit organizations representing patients, consumers, public health researchers and advocates, and scientists. The Coalition is working to strengthen the FDA and to ensure that FDA approval once again represents the gold standard of safe and effective medical products. Our Center is also an active member of the FDA Alliance, which is a coalition of pharmaceutical companies, medical device companies, former FDA officials, and consumer and patient organizations that work together to support increased resources for the FDA. I am proud to serve on their Board of Directors.

In my testimony, I am speaking on behalf of the National Research Center for Women & Families, not on behalf of other organizations we work with. I will start my testimony by focusing on medical devices and MDUFA, but will also include a brief analysis of PDUFA and other issues that you are considering in your legislation.

Every American relies on medical devices — whether they use band-aids, contact lenses, or pacemakers. Baby boomers increasingly rely on implanted medical devices, whether hips, heart valves, or wrinkle fillers.

More than 5,000 medical devices were approved by the FDA last year. Almost all (98%) were cleared through a “quick and easy” process that usually does not require clinical trials to prove that these medical devices are safe or effective. As a result, some of these devices are neither safe nor effective.

Are medical devices “proven safe and effective”? Not usually.

The American public is very concerned about the FDA drug approval process, wondering how Vioxx, Avandia, and so many other drugs can be prescribed by physicians who are not given accurate information about the risks, and then sold to millions of patients who are unable to make informed decisions about their own medical care. For all its faults, however, the FDA approval process for prescription drugs is much more rigorous than the device approval process.

There are two ways that the Center for Devices and Radiological Health (CDRH) approves medical devices, and neither has the same criteria – to prove that the product is safe and effective – that the drug approval process requires. In a book published this year, FDA officials state, “The FDA is responsible for ensuring that there is reasonable assurance that a medical device will be useful while not posing unacceptable risks to patients.” That standard is certainly more vague and less stringent than the standard for prescription drugs, and yet medical devices are just as important for saving lives and protecting the quality of people’s lives.

The statement is an accurate reflection of the FDA approval process for medical devices. In fact, most medical devices – approximately 98% — are allowed to be sold after a review that does not usually require any clinical trials. Device companies don’t need to prove that their products are “safe and effective” – they only need to prove that they are “substantially equivalent” to a product that was on the market before 1976. This much less rigorous process is known as the 510(k) process.

The 510(k) process was intended to be a temporary alternative to a full review when the FDA first was given the authority to regulate medical devices in 1976. This authority was the result of thousands of women being harmed by the Dalkon Shield IUD (intra-uterine device), which was found to cause serious infections, permanent infertility, and even death.

When the FDA started regulating medical devices, there were thousands of different devices on the market that had never been proven safe or effective. Most were “grandfathered” — allowed to stay on the market — with the FDA requiring some companies to conduct and submit safety studies for the first time. At the same time, to be fair to companies that wanted to sell medical devices that were similar to untested devices that were already on the market, section 510(k) of the Food, Drug, and Cosmetics Act gave the FDA the authority to “clear a product for market” if it was deemed “substantially equivalent” to medical devices already being sold.

We think that decision made sense. If logic had prevailed, however, FDA would have eliminated or at least drastically reduced their use of the 510(k) process in the three decades since 1976. Instead, the process was continued, with the rationale that device manufacturers are constantly improving their products and that it would stifle innovation to require each small change to be reviewed by the FDA in the more careful premarket approval (PMA) process. The assumption has been that a medical device that has been modified very slightly does not need to be tested as carefully as a new product.

Unfortunately, over time the definition of “substantially equivalent” was changed to include almost any product for the same medical condition. The FDA is now using the 510k process for 98% of the medical devices that they review. As a result, new products, using new materials, or a new mechanism, made by a different manufacturer, are being reviewed as if they were a mere tinkering improvement over previously sold products. In fact, it doesn’t even matter if the previously sold product was subsequently found to be unsafe or ineffective and is no longer for sale. There are medical devices on the market today that were approved as “substantially equivalent” to products that were subsequently recalled for safety reasons.

Why Clinical Trials are Needed

Even small changes to a medical device can affect safety, and can be very dangerous. For example, when Bausch & Lomb added MoistureLoc to their contact lens solution, the new product was approved through the 510(k) process. No clinical trials were required. The result: severe eye infections causing blindness and the need for corneal transplant surgery.

Although the standard of “substantially equivalent” for devices sounds almost like the standard for a generic drug, the reality is completely different. Many medical devices approved by the FDA through the 510(k) process are not like any medical devices already on the market, and are instead made of different materials, used for different purposes, use a different technology, or are otherwise “new and different” rather than slightly improved.

A Few Examples of 510(k) Device Disasters

TMJ Implants: Vitek jaw implants were cleared as substantially equivalent to silicone sheeting, which was made from a different material that was not developed for use in a joint. The Teflon from the Vitek implants broke off into particles that caused bone degeneration in the jaw joint and skull. Some patients can no longer eat, others have holes in their skulls.

Bladder Slings: Boston Scientific won approval for a ProteGen bladder sling to treat stress incontinence. The sling, made of a new synthetic material coated with collagen, caused vaginal erosion.

Pacemakers and Defibrillators: Frequently reviewed with the 510(k) process, tens of thousands of pacemakers and defibrillators have been recalled in recent years. When these products are defective, patients can die.

ReNu with MoistureLoc Contact Lens Solution: Bausch & Lomb’s contact lens solution was found to be an excellent breeding ground for a fungus that caused severe eye infections. One-third of consumers who developed the eye infections needed to have their eyesight restored with corneal transplant surgery. The product was recalled in May 2006.

Complete MoisturePlus Contact Lens Solution: Advanced Medical Optics’ contact lens cleaning and storing solution was found to not protect against a different bacteria that can cause severe eye infections. It was recalled in May 2007.

Shelhigh heart valves and other implants: In April 2007, the FDA seized all implantable medical devices from Shelhigh, Inc., after finding deficiencies in manufacturing. The devices are used in open heart surgery in adults, children and infants, and to repair soft tissue during neurosurgery and abdominal, pelvic and thoracic surgery. “Critically ill patients and pediatric patients may be at greatest risk,” according to the FDA.

How does this affect the practice of medicine? According to Dr. Donald Ostergard, past president of the American Urogynocologic Society, many medical devices used to treat incontinence and other urological conditions were not required to conduct clinical trials before being sold. As a result, surgeons considering the use of a new device must rely on colleagues’ anecdotal experience or promotional information from the manufacturer. He points out that some have caused serious problems that were not identified until the device had been used on hundreds or even thousands of women. As a result, patients who started out with a minor health problem can end up with many surgeries and with permanent and debilitating health problems.

Part of the problem is the very loose definition of “substantial equivalence.” As long as a product is used for the same general purpose – such as the treatment of depression or cancer – and if its risk to benefit ratio seems to be similar, a product can be approved as “substantially equivalent.” Not to be glib, but this would be like saying that cheese is substantially equivalent to peanuts or bread because all three are food that provide nutrition, and each has risks and benefits for the general population. But, if you are allergic to peanuts, or sensitive to milk products, you know that there is a world of difference regarding how those foods will affect you, and the percentage of people who can be harmed by them. They are not interchangeable.

In addition to other safety concerns about the 510(k) process, current law permits manufacturers to hire a third party to review their devices, instead of the FDA. The goal is to speed up the review process and reduce the FDA workload. However, according to the FDA, the program has not reduced the FDA workload because of the use of FDA staff to administer the program. The benefit to device manufacturers is modest since the companies must pay the third parties and the review time is reduced by an average of less than two weeks.

Why are 98% of Medical Devices Reviewed Through the 510(k) Process?

CDRH has a modest budget and fewer resources than the Center for Drug Evaluation and Research (CDER). And yet, they have a greater workload in terms of number of devices submitted to them for review every year. It is not surprising that the FDA has increasingly relied on the less labor intensive 510(k) process to review the thousands of products submitted for review every year.

Under the current law, 80% of 510(k) reviews are completed within 90 days. This is a very short turnaround time, making it difficult for the more complicated applications to receive careful evaluations.

In speaking with physicians, scientists, and consumer advocates, we have developed several suggested changes in the 510(k) review. The goal is to increase useful information for physicians and improve safeguards for patients. These changes, supported by most members of the Patient and Consumer Coalition, include:

Excluding implanted medical devices from the 510(k) process;

Requiring clinical trials for all medical devices that could harm patients and consumers; and

The FDA needs to establish an appropriate definition of “substantial equivalence.” They should revert to the original intent of the 510(k) process: the review of products that are substantially equivalent in terms of intended treatment, form, what they are made of, mechanism, and function.

We know that device manufacturers believe that the 510(k) process is safe enough and necessary to get products to patients more quickly. From a policy point of view, however, many medical devices cleared for sale by the FDA under the 510(k) process are not reimbursable under Medicare or Medicaid, or by private insurance companies. The Center for Medicare and Medicaid Services (CMS) and insurance companies have higher standards for reimbursement than the FDA has for device approval. Although thousands of medical devices are cleared for market by the FDA through the 510(k) process every year, many Americans will not have access to all those products because insurance companies require published research to prove that the products are safe and effective. For many important products, the patient will not benefit at all until those studies are done.

If medical devices are not reimbursable until peer reviewed studies are published, then the 510(k) process is NOT getting many new, innovative products out to patients more quickly. Research will still need to be conducted. Wouldn’t it be better to make sure that the studies are evaluated by the FDA through the PMA process, to make sure that the analyses are not manipulated to minimize the risks?

We strongly support the Committee’s plan to require a study of the 510(k) process. Either the IOM or GAO could do a credible study and report, and we urge you to determine which can do the best job in the next 12-18 months.

The “Full Review” Premarket Approval Process

The more rigorous approval process, which is similar to the process for prescription drugs, is called the premarket approval (PMA) process. Drug companies and device companies must conduct clinical trials and other tests to determine that their products work well and are safe. However, the drug approval process requires that the products be “proven safe and effective.” The approval process for medical devices has a lower standard: the products must provide merely a “reasonably assurance of safety and effectiveness.”

That rather vague definition is not an appropriate standard. In our Center’s review of thousands of pages of FDA advisory committee transcripts, we found how dangerous this vague definition can be. For example, at an FDA advisory panel meeting on the Kremer LASIK device, a physician explained that she recommended approval “because I did not see from the data that this was totally unsafe or totally ineffective.” At a different FDA advisory panel meeting for a device to treat Alzheimer’s Disease, a neurosurgeon recommended approval after saying, “Only time will tell whether or not this will pan out to be helpful.” The FDA went along with advisory panel recommendations for approval almost every time. With standards like these, patients and their families will waste billions of dollars on products that are not proven safe and effective, do not benefit them, and that replace products that might have helped save their lives or improve the quality of their lives.

There is no logical reason why the standard for the PMA should be any different than the standard for prescription drugs. All medical products should be required to be proven safe and effective. That does not mean that the product has no risks, but it should mean that the benefits outweigh the risks for the people who will be using the product.

Post-market Studies, Surveillance, and Advertising

Since so many medical devices are approved through the 510(k) process, and the rest are approved on the basis of the vague criteria of “reasonably safety and effectiveness” it would make sense for CDRH to devote a great deal of resources to post-market surveillance. In fact, the CDRH often requires post-market studies be conducted, but they do not monitor those studies to make sure that they are done appropriately.

For example, in 2000 CDRH approved saline breast implants on the condition that 10-year post-market studies be conducted. Because of the enormous media attention and controversy, the CDRH required the implant makers to present their 5-year data at a public meeting in 2003. At the meeting, it was shown that one of the companies, Mentor Corporation, had lost track of 95% of their augmentation patients after 5 years.

Any epidemiologist will tell you that when you lose track of 95% of your patients, your study does not provide useful safety information. The FDA criticized the company, and encouraged them to re-contact more of the patients in their study. However, even with more extensive follow-up, more than two-thirds of the patients were missing from the post-market study at the six-year follow-up. And yet, the company continued to sell their product with no penalties. They even came back for approval of their more controversial silicone gel breast implants two years later, and those implants were approved on the basis of the company’s promise to study those women for 10 years. In other words, they made the same promise that they had previously broken, and the FDA approved their product anyway.

In a recent book, the director of CDRH wrote that “the premarket evaluation program alone cannot assure continued safety and effectiveness of marketed devices” and explained the need for post-market surveillance to determine the risks after a product is approved and widely used. Thus far, those efforts have been under-funded and ineffective. Registries for implanted medical devices and improvements to the adverse reporting systems would provide important information to doctors and patients about devices already on the market. The Energy & Commerce Discussion Draft of MDUFA authorizes additional funding that would make post-market surveillance possible, but does not require specific post-market surveillance activities.

Under current law, if an implanted device is recalled, it is unlikely that the men, women, or children who have that device in their bodies will be notified. Doctors and medical centers will be notified, but they may not be able to notify all – or even most – of their patients. Registries for implanted devices, using unique identifying numbers, are needed to help ensure that patients will be notified as quickly as possible if there is a defective implant inside their body.

MDUFA does not include any user fees for the review of direct-to-consumer (DTC) advertising, which has been increasing greatly for medical devices. For example, in the spring of 2007, Allergan Corporation has extensive DTC ad campaigns for three medical devices: gastric lap bands (which are surgically inserted for weight loss), Botox, and Juvederm; the latter two devices reduce wrinkles, and are injected by a physician. Allergan is currently preparing an ad campaign for silicone gel breast implants. The ads on their Web site and on TV feature enthusiastic patient testimonials with no meaningful risk information. According to the Allergan Web site, the patients receive free treatment, worth thousands of dollars, as compensation for their testimonials.

Speed and Safety

The MDUFA Discussion Draft would not speed up the 510(k) process, which is already very fast, reviewing 80% of the products within 90 days. That is a wise decision. It is important that the legislation focuses on decreasing the cost of user fees for the smaller companies, but does not reduce the already very inexpensive user fees for 510(k) reviews.

The decrease in funding for the PMA process seems reasonable, as long as the process is not required to speed up. The total funding, and the increase in appropriations authorized, would help ease the stress on CDRH staffing levels and improve their ability to conduct careful reviews.

Third Party Inspections

Rather than FDA conducting inspections of manufacturing facilities, device companies can directly pay a third party to do the inspection, and can negotiate the price of the inspection. The current law includes very modest restrictions on third party inspections of Class II and Class III medical devices, which are the most stringently regulated devices. The current law allows two consecutive third-party inspections, after which the FDA must conduct the next inspection (unless the FDA issues a waiver).

The MDUFA discussion draft wisely does not expand this program. Critics have compared third party inspections to allowing parents to select and pay a third party to determine school grades for students, or allowing employees to hire a third party to make salary and promotion decisions. According to 2007 FDA testimony, the agency has spent millions of dollars on this program, but it has very rarely been used. We urge the Committee to ask the GAO or IOM to evaluate whether this program is workable and cost-effective, or whether the funds should instead be used to hire more FDA inspectors.

Progress on PDUFA and Safety Issues for Drugs, Devices, and Biologics

The FDA discussion draft legislation includes many important provisions that will greatly improve the safety of drugs and potentially the safety of all medical products.

We strongly support the proposed addition of $225 million over five years in new safety money, and urge Congress to make sure that funding is used to improve resources to conduct post-market surveillance and modernize the FDA’s computer systems, including software for reporting and analyzing adverse reactions for drugs and devices. We also strongly support the provision that would include patient and consumer organization representatives in the negotiations for any PDUFA renewal and MDUFA renewal. The patient and consumer organizations represented should be full partners at the negotiations, and should not have financial ties to pharmaceutical or medical device companies.

The proposed legislation builds on the best REMS provisions in the Waxman-Markey bill (HR 1561), giving the FDA the authority it needs.

For drugs and medical devices, it is important that there be required registration of all Phase II thru IV trials. We agree with the discussion draft provision that the results of all these studies should be made publicly available, and that should apply to studies on medical devices as well as drugs.

In Section 5, the discussion draft includes the Senate bill’s section 201, which is based on a suggestion by former FDA Commissioner Dr. Mark McClellan and introduced in a bill by Senators Gregg, Burr, and Coburn (S. 1024). In combination with REMS, these databases from Medicare and elsewhere are very important because they can be used to detect short- and long-term safety problems in drugs and devices.

We support the discussion bill’s recognition that nothing in these FDA bills pre-empts state tort laws.

Additional Suggestions for Devices and Drugs

As a member of the Patient and Consumer Coalition, our Center strongly supports several recommendations to strengthen provisions in your discussion draft of PDUFA and other FDA legislation.

Although the conflicts of interest” provision is a clear improvement over the Senate bill, we believe that conflicts of interest should be eliminated in FDA advisory committees for drugs and devices, by excluding any members with stock, stock options, or other financial ties to companies that have stakes in the topic under discussion. The discussion draft includes a good provision on conflicts of interest, but it is essential that “conflicts of interest” be defined in the law as a financial relationship within the last 36 months. Otherwise, FDA advisory committees could include members who received million dollar honoraria from the company whose product is under review just 13 months prior to the committee meeting. And, since stock and stock options are so strongly affected by FDA decisions, either should always be unacceptable for advisory committee members.

Better consumer protections regarding DTC advertising is needed. The discussion draft section on DTC advertising is a good start, but needs to be strengthened by making pre-clearance of all DTC advertising for drugs and devices mandatory rather than voluntary. An effective system of civil monetary penalties is also needed, and those must be substantial to be an effective deterrent.

Strong whistle-blower protection provisions are needed, as well as a provision clarifying the right of FDA officers and employees to publish scientific articles, with proper disclaimers. The right to publish could have meant earlier warnings about the risks of Vioxx, Avandia, Actos, and other blockbuster drugs and devices, saving the lives and improving the quality of life of many Americans.

In addition to the provisions in the discussion drafts on making data available, we strongly urge that you consider the Senate provisions making FDA reviews, evaluations, and approval documents promptly available to the public, including dissents and disagreements. In addition, the FDA should be required to publish observational study results, in addition to clinical trial results.

We support legislation by Representatives Tierney, Emerson, and Stupak that would create a separate Center for Post-market Evaluation and Research with real clout within the agency, but strongly urge that the Center include devices as well as drugs and biologics.

In conclusion, thank you for the opportunity to testify and share our views about the discussion drafts. You have made important progress, and we appreciate your consideration of provisions that would strengthen this legislation to help ensure that safe and effective medical products are available to all Americans.

Statement of Dana Casciotti, MPH, PhD at the FDA on Breast Implants

Dana Casciotti, MPH, PhD, National Center for Health Research, August 2011

I am the public health research director of the Cancer Prevention and Treatment Fund, a nonprofit center that uses research findings to improve prevention and treatment strategies. Our nonprofit does not accept money from pharmaceutical or device companies so I have no conflicts of interest.

My perspective today is as someone trained in public health at Johns Hopkins and previously worked at the National Cancer Institute. I am very familiar with clinical trials and research methodology.

You have already discussed how poor the follow-up was on the implant studies. I was disappointed that an FDA official implied yesterday that most of the post-market studies were fine, and only a few were not.

I completely disagree. It was not just the Mentor large study that was so outrageous after only 3 years, and Allergan barely kept half their augmentation patients after only two years.

The Adjunct studies were even worse, only 16-23% of the women were still in the studies after 5 years. The Core Studies were slightly better, but Mentor had only 58% of their patients at 8 years, and that is not acceptable in any of the places where I have conducted research.

Our nonprofit has talked to many women who have had serious problems with their breast implants, and I am talking about recent patients, not patients from 20 years ago. But, many of these patients have already missed work because of their illness and couldn’t take the time to be here this week. Some told us that their kids are going back to school this week, and they need to be there. Others didn’t even hear about this meeting in advance, it wasn’t exactly highly publicized to the general public.

But history should be our guide. We know that most new breast implants seemed great at first. It isn’t until years later that it becomes obvious that the “newer safer breast implants” also break and leak and cause problems. So, it may take a few years to get a better idea about the safety of the “new cohesive gel implants” but we already know after yesterday’s testimony and from talking to many other patients that these new implants can bleed silicone into the scar capsule even when the implant is intact. And even the new implants can break.

I also want to correct some misconceptions that were reflected in yesterday’s panel discussion. The large studies done by Allergan and Mentor are not asking women to come to the plastic surgeon’s office every year. Most years, they are asking women to fill out a questionnaire, which they can do online at home. I have seen copies of these questionnaires and they are much too long. By the time women get to the questions about their symptoms on page 22 of the Allergan questionnaire, for example, they will have already answered questions about 20 connective tissue diseases, many of which they never heard of and can’t pronounce, such as eosinophilic fasciitis. They will also have answered the same 20 questions about each of their children. I have to assume that by the time they get to page 22 to answer questions about symptoms they might actually have, they are in no mood to answer the question about “dilated red blood vessels under the skin surface that appear as red marks, especially on the face, hands, and lips.” Given these questions, I think it is very unfair to blame the low response rate on the patients.

Similarly, Mentor patients have told us that the symptoms listed on their questionnaire were often confusing and difficult to answer.

I have one more thing to add. The first 2 years of the Allergan and Mentor Core studies showed that self-esteem on the Rosenberg Self-esteem scale went down in most patients with implants, and that symptoms of connective tissue diseases went up. Those data were reported at previous FDA Advisory Committee meetings. But, those data are missing from the analyses that the FDA has reported for the 8-year and 10-year Core study follow-ups. I ask the FDA to explain why.

Thank you for your time.

Testimony of Margaret Dunkle at the FDA on Silicone Gel Implant Studies

Margaret Dunkle, George Washington University, 2011

I am Margaret Dunkle, Senior Research Scientist at the Department of Health Policy of The George Washington University. I also direct the Early Identification and Intervention Collaborative for Los Angeles County. Among other awards, I have received the American Academy of Pediatrics’ Dale Richmond Award for outstanding achievement in the field of child development; and Vice President Al Gore’s “reinventing government” Hammer Award.

I have testified nine times before Congress on issues affecting women, children, and families and have authored more than 100 publications on these subjects.

I am here today solely because of my interest in ensuring that medical products for women be proven to be safe and effective. I am not representing any organization. I am not being paid or otherwise compensated.

The 2006 FDA approval of silicone gel breast implants was controversial because there were so many unanswered questions about the long-term safety of implants, including when they might break and leak inside a woman’s body, and what the consequences of such leakage might be.

“As conditions of approval,” the FDA required that the two implant companies (Allergan and Mentor) each study at least 40,000 women. The FDA also required that these studies be at least 10 years long since some serious adverse outcomes might not become obvious, or even be measurable, in just a few years. And it takes both time and a large sample to identify subpopulations of women who might be at greater risk for problems, such as autoimmune reactions, or reproductive or connective tissue concerns.

It is now five years later, when the studies should be close to half done. But the data for both the Allergan and Mentor studies are not what they need to be for a study of this importance.

Why do I say this? Because of the extraordinarily high “loss” of study participants, as the following table shows.

In just three years, Mentor (now a subsidiary of Johnson & Johnson) has somehow managed to “lose” four out of five of both the silicone-implant patients and the augmentation patients enrolled in its 10-year study. Their paltry overall enrollment rate, with only 21% to 29% of patients still in the study, makes their data virtually useless in terms of assessing either safety or effectiveness.

As you can see, Allergan’s rates are better, but still likely too low to meet the study’s goals. Simply put, when you lose half or more of your sample, you cannot assume that the data for the few left in the study also represent those who were “lost.”

The Mentor rates, especially, would be laughable, were it not for the seriousness of the issues. Let me put it this way. If I can easily find my antediluvian high school classmates with a few “advanced search” clicks on Google, how can it be that these well-resourced medical-device companies cannot keep track of much younger patients that they have already enrolled and consented into their clinical trials? If the will were there, there are many sound methodological ways to ensure high rates of ongoing participation in these studies.

So, what to do about this bad situation?

The FDA’s job is to protect public health by ensuring that such things as medical devices implanted into women are both safe and effective. My five recommendations are aimed at helping the Agency do just that job.

First, rescind approval for the Mentor implants. They did not uphold their part of the bargain for the post-approval study. If they can’t competently do this research to ensure their product’s safety, they should not be putting their product into the bodies of more than a hundred thousand women every year.

Second, do not restore approval of the Mentor implants until they have at least two years of credible data with 80% or more retention of clinical-trial recipients. They could accomplish this by re-enrolling or “finding” the thousands of women they have “lost to follow up.” To ensure credibility, Mentor would need to pay an independent entity to check the validity of their data.

Third, extend the duration of both the Mentor and Allergan studies to 15 years. The FDA’s own “Update” report indicates that 10 years may not be long enough to identify long-term problems from cancer to rarely diagnosed autoimmune diseases, or to detect populations especially susceptible to adverse outcomes.

Fourth, require ongoing transparency and disclosure of the data from these studies by making public meetings such as this, and the June 2011 “Update” report, the rule, rather than the exception.

Fifth, implement a broad FDA policy to put companies on notice that there will be consequences of not doing or incompetently doing FDA-required post-approval research. Consequences could include withdrawing a product from the market, or substantial financial penalties for doing a bad job of the research, and then using that “penalty money” to fund research controlled by AHQR or independent researchers.

In conclusion, with almost 400,000 women getting breast implants each year for augmentation or reconstruction these studies need to be done right. The current situation also provides a window for the FDA to improve the incentive system so that manufacturers do not again ignore post-approval research requirements to the detriment of the public’s health.

Thank you for this opportunity to comment. And I ask that my full written statement be inserted into the meeting record.

Invited Testimony of Diana Zuckerman, PhD, Before the Standing Committee on Health, Canadian Parliament, Ottawa, June 8, 2006

Diana Zuckerman, PhD, National Center for Health Research

I am Dr. Diana Zuckerman, President of the National Center for Health Research. 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.

I am speaking from the perspective of someone trained in psychology and epidemiology, who was a university faculty member and researcher at Harvard and Yale and taught courses in research methods before moving to Washington, DC to work on health issues in the U.S. Congress, U.S. Department of Health and Human Services, White House, and for nonprofit organizations.

I have read every published epidemiological study on breast implants and will briefly discuss what is known and not known, based on those studies. I will also tell you about a criminal investigation of one of the implant manufacturers, Mentor, and the many calls and emails we have received from women in Canada who are finding it impossible to have their leaking silicone gel breast implants removed in a timely manner.

Who conducts research on breast implants?

Clinical trials are a major source of information on the short-term risks of silicone breast implants. In clinical trials, the goal is to follow women prospectively to determine what complications and health problems occur, and to compare that to a control group. Although silicone implants have been on the market for 40 years, the only well-designed clinical trials have data for only 2-3 years and they do not include a control group. The clinical trials have been conducted by the implant companies as part of their effort to obtain approval to market the implants in Canada and the US.

Epidemiological studies are the major source of information about what actually happens to women who have breast implants for at least five years. Almost every published epidemiological study on breast implants has been paid for by companies that sell or sold breast implants. In fact, one company in the U.S. has received many millions of dollars from Dow Corning to conduct most of these studies, almost all of them in Europe, and every one of those studies has concluded that implants are safe. However, careful scrutiny of the results in the peer-reviewed articles indicates serious health problems among women with those implants. For example, one study reported that women with breast implants were significantly more likely to report breast pain and take anti-depressants, but still concluded that breast implants were safe.

More importantly, a small number of studies have been conducted by independent researchers, not using implant company funds or funds from plastic surgeons. These include government-funded researchers in Canada and the U.S. Their findings almost always indicate problems with implants that are in direct contradiction to the findings of the studies funded by implant companies. I will focus on their findings today.

What do we know about the health effects of ruptured silicone gel implants?

The FDA funded, designed, and conducted the best study on the health of women with ruptured silicone implants. FDA scientists concluded that most women with implants for 11 years or more have at least one ruptured implant, even if they don’t realize it. They also found that 21% of women with implants for at least 7 years have at least one implant that is leaking silicone outside the scar tissue, and that women with leaking implants were more likely to report fibromyalgia or several other painful and debilitating autoimmune diseases. The FDA study is superior to other studies because 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.

Most women who have had problems with rupture had implants for a long time — usually much longer than seven years.

Cosmetic Problems

More independently funded research is needed on the risks of ruptured silicone gel implants. Meanwhile, let’s look at some 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. 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. Inamed reported a 6% necrosis rate among reconstruction patients in their Core study.

Signs and Symptoms

Now that you have seen some of the cosmetic problems, let’s take a look at the women’s symptoms. In data presented to the FDA, Inamed and Mentor both found that women with implants for only two years had a significant increase in auto-immune symptoms such as joint pain and nervous system symptoms. FDA asked a statistician to determine if this was due to aging. It wasn’t. And, these findings are consistent with what we have heard from thousands of women with silicone breast implants. Most were happy with their implants for years and never suspected that their increasing problems with fatigue or aches and pains might be related to their implants. The women’s personal experiences are not conclusive evidence, but they indicate a pattern that needs to be considered — especially since they are consistent with Inamed and Mentor’s own data showing an increase in autoimmune symptoms over a period of only two years on a cohort of young augmentation patients.

What do we know about the health risks of silicone gel implants more generally?

Aleina Tweed, an epidemiologist at the British Columbia Centre of Excellence for Research on Women, conducted a study of breast augmentation patients in Canada, most of whom had implants for 10 years or longer. She found that the women with implants visited doctors and specialists more often, and were four times as likely to be hospitalized, compared to other women the same age from the same communities.

Why has that important Canadian study received so little attention? Probably because no one was paid to do PR on the study. In contrast, studies funded by Dow Corning, the maker of silicone, have received enormous publicity. You may have heard that hundreds of studies, including studies at Harvard and the Mayo Clinic and a report of the U.S. Institute of Medicine, provide clear proof that breast implants are safe. However, the Institute of Medicine report is outdated – completed in 1999 and based on studies conducted before that. And, it was based on the other studies that are so often quoted, such as the Mayo Clinic study and the Harvard study – studies that were all funded by Dow Corning and other implant makers.

Almost all the studies included in the Institute of Medicine report suffered from the same shortcomings: they were too small, and they lacked statistical power because they included women who had implants for too short a period of time. 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 U.S. government has also funded some important studies of breast implants, and like the Canadian study, they tend to report serious health problems for women who have implants for a long period of time. The National Cancer Institute study found a doubling of brain cancer, lung cancer, and suicide. It is an exceptionally well-designed study, because all the women in the study had breast implants for at least 12 years. Another major strength of the study is that it compared women with silicone implants to women who underwent other kinds of plastic surgery, such as liposuction. This is important because all plastic surgery patients tend to be above average in health and income, but also tend to smoke more than other women.

How do the many implant studies funded by Dow Corning compare to the government funded studies in Canada and the U.S.? Many of the Dow Corning studies focused on women with implants for a short period of time, and at least one on women with ruptures for a short period of time. Many measured illness in terms of hospitalization rather than diagnosis. Remember that most women getting breast augmentation are in their 20’s or 30s, with many in their teens. Think of how unlikely it is that a 30-year old woman will be hospitalized for rheumatoid arthritis.

Inamed and Mentor Research Quality and Integrity

Inamed and Mentor both started clinical trials to analyze the safety of silicone gel breast implants in 1990. Both companies lost track of almost all of their patients to follow-up within 5 years. If only they had done a good job on those studies, we would have great long-term data today. But they didn’t, and so we don’t.

The companies both were given the opportunity to test their silicone gel implants on thousands of patients in the Adjunct Studies that they conducted. They enrolled thousands of patients and then failed to follow-up on most of them, making those studies useless.

Last year, shortly after Inamed and Mentor silicone implants were considered by advisory committees in Canada and the U.S., I heard from several Mentor employees who expressed concerns about the accuracy of the data that Mentor provided to the FDA, and also informed me that the patch used on Mentor implants leaks silicone and should be fixed. I contacted the FDA and arranged for the Mentor employees to speak to FDA officials. As a result, the FDA started a criminal investigation, interviewing me and several former Mentor employees. I was told several weeks ago that the investigation is still underway. I would be glad to put those former Mentor employees in touch with officials at Health Canada as well.

What does approval matter?

Although there are restrictions on silicone gel breast implants in Canada and the U.S., tens of thousands of women have continued to get them. Many of those women were not breast cancer patients.

Even so, approval matters. If Health Canada approves silicone gel breast implants, it will send a clear message that it believes that the implants are safe, and more teenage girls and women will certainly choose silicone implants as a result.

The study by Aleina Tweed shows that in Canada, women with breast implants have more health problems and their efforts to get well are costly to the Canadian system. Most of the women had at least one surgery to fix an implant problem, and 17% had four or more additional surgeries. Tweed’s findings are especially striking to us because our Center hears from many Canadian women with breast implants who tell us that they can’t get help from most Canadian plastic surgeons. Many have discovered — often after years of symptoms – that their implants are leaking. They need a plastic surgeon to remove them, and often can’t afford to pay for the surgery. But the waiting list is very long. We know a patient who contacted Dr. Mitchell Brown’s office this spring, because she heard he is an excellent surgeon who knows how to remove leaking silicone implants. She was told she would need to wait until December 2006 just to see him for a consultation. She was told that if she needed surgery, that would have to wait until December 2007. My staff found that hard to believe, so we also contacted Dr. Brown’s office more than a week later and we were told the exact same thing. My staff asked if there was a shorter wait if she could pay for the surgery, and we were told that the wait was much shorter.

We know several patients who tried to arrange surgery with other Canadian plastic surgeons. They were told that silicone would likely leak during the surgery and that they could be left looking deformed, They were discouraged from removing their implants, and told that at least they should replace them with new implants.

If Health Canada approves silicone gel breast implants, the number of teenagers and women needing to have leaking silicone implants removed will increase dramatically. To allow that to happen in a country where few plastic surgeons know how to remove leaking silicone gel breast implants, and those that do have very long waiting lists is not ethical or appropriate. And, according to Aleina Tweed’s research, it will cost the Canadian healthcare system dearly.

The full transcript can be viewed here

All articles are reviewed and approved by Diana Zuckerman, PhD, and other senior staff.

Statement of Diana Zuckerman, PhD on FDA Approval of Breast Implants

Diana Zuckerman, PhD, National Center for Health Research, September 21, 2005

Today the Food and Drug Administration (FDA) issued an “approvable letter” to Inamed Corporation for their silicone gel breast implants. Inamed Corp. was granted this first step in the approval process based on a revised application that is missing most of its breast cancer patients. After their application was rejected by the FDA a few months ago, Inamed belatedly decided to eliminate a defective style of breast implant (Style 153) from their application for approval. Unfortunately, two-thirds of the breast cancer patients in their study had this defective style of implant, which had a tendency to break even during the first three years in the body. When the company resubmitted their application, they removed those women from their study, apparently leaving fewer than 30 breast cancer patients who underwent MRIs to determine if their implants had ruptured or were leaking silicone. Yet the agency had asked that at least 250 breast cancer survivors be studied. In August, the Mentor Corporation also received an approvable letter.

STATEMENT –

“It is absolutely unacceptable to approve a breast implant that hasn’t been carefully studied to make sure it is safe for breast cancer patients. Sadly, this isn’t the first time — rival implant maker Mentor’s long-term data included zero breast cancer patients.

“The approvable letter was sent despite FDA scientists’ scathing criticisms of the company’s data and a vote from FDA’s advisory panel recommending that the implants not be approved. This action by the FDA once again raises questions about whether the agency is making decisions based on scientific evidence.

“This sounds familiar. Just a few weeks ago, the FDA ignored their own scientists when they refused to approve the morning-after pill for over-the-counter sales. Once again, the FDA is ignoring the concerns of their own scientists, this time potentially endangering breast cancer survivors.

“Only scientific evidence and solid safety data can protect women. Wishful thinking should not be a basis for approval.”

Statement of Dr. Diana Zuckerman, President of the National Center for Health Research, Regarding the FDA Breast Implant Decision

Diana Zuckerman, PhD, National Center for Health Research: July 28, 2005

WASHINGTON, July 28 /PRNewswire –The Food and Drug Administration (FDA) has issued an “approvable letter” to Mentor regarding their silicone gel breast implants. This does not mean that these implants have been approved, but it is a warning sign that corporate pressure on the FDA has once again put women’s health at risk.

The FDA letter is a stumbling step in the wrong direction, amid mounting questions about FDA decision-making. Approval would be an embarrassment unless the Senate and the FDA give Mentor a “clean bill of health” after thoroughly investigating allegations that Mentor misrepresented the rupture rate of its implants.

A Senate investigation of the Mentor safety data and the FDA approval process is currently underway, and concerns are growing. Just before the FDA announcement today, key women members of the U.S. Senate sent a letter to the FDA Commissioner, expressing their strong concerns about the lack of safety data on silicone gel breast implants. And, as the public learns about defective pacemakers, recalls of defibrillators and the dangers of several other medical devices, questions still remain as to how safe these breast implants are.

Every week we hear from women with leaking breast implants, who can’t afford the surgery to have them removed. FDA needs to make sure that they don’t approve a product that adds to this frightening situation for so many women across the country.

The FDA needs to listen to its scientists and demand more long-term safety data before issuing any kind of decision. They also need to make sure that the data they are given are accurate. The credibility of the FDA is on the line, as is the health of millions of women.

Dr. Diana Zuckerman is the president of the National Center for Health Research, a nonprofit research and education organization that works to improve policies and programs that affect the health and safety of women, children, and families. Dr. Zuckerman is a nationally-recognized health policy expert with post-doctoral training in epidemiology from Yale Medical School. She was on the faculty of Vassar and Yale, and a researcher at Harvard, prior to becoming a Congressional investigator in the U.S. House of Representatives, where she initiated the first Congressional hearing on the lack of safety data on breast implants, held in 1990. She is widely quoted on a wide range of health issues, especially FDA and medical products. For more information about the Center’s work, click here.

All articles are reviewed and approved by Diana Zuckerman, PhD, and other senior staff.

Testimony of Diana Zuckerman, PhD at the FDA on Silicone Gel Breast Implants

Diana Zuckerman, PhD, National Research Center for Women and Families,  April 2005

I’m Diana Zuckerman. I am President of the National Research Center for Women and Families, and I’m very pleased to be here. I have no conflicts. I’m a psychologist and epidemiologist and president of a nonprofit center that scrutinizes research to see what the implications are for health and safety.

We’ve heard that implants are the most studied medical product in the United States, but in 1991 there were about a million women with breast implants. The number of empirical published studies at that time was zero.

And at that time when they submitted their PMA, Inamed had only studied 39 breast cancer patients. Thirty-nine. And in their augmentation sample they had lost 65 percent of their augmentation patients at three to six months, according to the FDA summary.

Now, it brings us to 2003. Things have changed a little. We’re looking at the two to three year data that was available in 2003. It showed very high complication rates, including a lot of reoperations. It showed an increase in auto-immune symptoms, just about all of them that were measured. And it also showed no improvement and some worsening in most self-esteem and self-concept measures.

Now we know that most of the people talking have said this product has improved the quality of their life. But as has been pointed out by Panel members, the data just don’t support it. There is some improvement on body image, but not on quality of life, not on all of these other measures that have been touted as the main advantage of implants.

It’s very worrisome that all the patients in these studies are white, just about all of them. And, yes, I understand that most people getting breast implants for augmentation are white, but that is certainly not true of reconstruction patients. There are many, many thousands of reconstruction patients in this country that are women of color, and yet just a handful — I thought it was six African-American women, and five Asian American women, but according to the data shown this morning, it’s actually even lower. And I don’t understand how it could possibly be acceptable to approve a product with no data.

The reason why it’s important to have racial diversity in these samples is because there are racial differences in scarring and in auto-immune disease. African-American women are more likely, more susceptible to auto-immune disease. So we’d want to know are they more at risk, and we can’t conclude that because not only weren’t they analyzed separately, there weren’t even enough women to analyze separately.

That brings us to 2005. I thought that we’d have additional year of data. I was very interested to see what would the new data show and how would it be different. So I thought there’d be more data on complications compared to last time, but no, there aren’t. And I thought that there’d be another year of data on auto-immune, and no, there aren’t. And I thought there’d be another year of data on self-esteem and quality of life, and no, there aren’t. There is rupture data, and that’s great. But it was really for the three-year MRI data. It’s called four-year data, but since MRIs were done in the third year, it doesn’t take us very far.

When Inamed compared ruptured and intact implants, they did not evaluate connective tissue disease symptoms for most women with ruptures. I say that based on the FDA’s scientific analysis in your package.

They did find a significant increase in muscle pain. They didn’t find too many increases, but they had a very, very small sample to work with, partly because it just wasn’t measured.

The Adjunct Study has, according to Inamed, included 25,000 paients, but they didn’t follow-up on them. This is very upsetting because this was such a great opportunity to provide really good data and longer term data. And let me say that the young woman who testified about her problems not being reported, whether she was in the Adjunct Study or the Core Study, her problems should have been reported. And it says something about the commitment of the sponsor that they seem to think as long as it was the Adjunct Study, it doesn’t matter. I think it does matter. They should be taking care of patients in their studies, and they should be reporting them regardless of which — I don’t know which study she was in, but whichever one it is, she should have been reported.

And also remember that Inamed started their studies in 1990. Had they followed those women, we’d have at least a dozen years of safety data, the data we want. But they didn’t do that.

The literature review that FDA did talked about the Danish registry, but the mean number of years of women, and that was less than four years –not long enough.

It talked about the Danish rupture study. Forty percent of the implants were tested with a faulty MRI, so that study was not helpful.

And basically the data that many of you talked about showing up to ten years of rupture is faulty data. And I hope that Dr. Blumenstein will say something more about that later.

The FDA study did have a 21 percent extracapsular leakage for implants that were seven years old or more, and they also found an increase in fibromyalgia, which has not really been discussed at this meeting.

Thank you.

NCHR Press Release on Inamed High Complication Rates for Breast Implant Patients

Diana Zuckerman, Phd, National Center for Health Research: October 16, 2003

In a split decision, an advisory committee to the FDA recommended approval for Inamed’s silicone gel breast implants on October 15th. “The news is not good for breast implant patients, especially those with breast cancer,” noted Dr. Diana Zuckerman, President of the National Center for Policy Research for Women & Families, a Washington-based think tank. “The company’s own research indicates high complication rates for the first three years, including the need for additional surgery for 46% of breast cancer patients. The long-term risks remain unknown.”

Inamed’s “core” study included 221 breast cancer reconstruction patients, 494 augmentation patients, and 225 revision (replacement) patients. According to the FDA, their complication rates are very high. For example, 46% of reconstruction patients underwent at least one re-operation within 3 years, 25% had removal or replacement, 6% had a diagnosed ruptured implant, 6% had breast pain, and 6% were diagnosed with necrosis, a painful and disfiguring condition where the skin or tissue dies. Complications were lower but still substantial for augmentation patients (for example, 21% with re-operations, and 1% diagnosed rupture) and revision patients (33% with re-operations and 4% diagnosed ruptures). The FDA assumed that the rupture rate was higher than reported, since three out of four ruptures would not be diagnosed unless a woman underwent an MRI.

The largest study, called the Adjunct Study, enrolled 15,465 reconstruction patients and 9,881 “revision” patients (who had replaced their previous breast implants with new Inamed silicone gel implants). The Adjunct Study was the compromise developed by the FDA to enable large numbers of mastectomy patients and women with broken gel implants to use silicone gel implants at a time when the company had not proven that their product was safe. Although women wanting silicone breast implants were required to participate in the Adjunct Study, the company apparently made little effort to comply with this requirement: barely half (54%) of the breast cancer patients who received Inamed implants stayed in the study for one year. Even fewer — 27% — stayed in the study for three years.

Women who wanted silicone gel implants to replace broken gel implants were also required to participate in the Adjunct Study, but they were even less likely to stay in the study than breast cancer patients. Less than half (44%) stayed in the study for one year and only one in five (20%) stayed for three years. “Most women did not stay in these studies for even one year, making the largest study useless in determining whether the implants are safe” explains Dr. Zuckerman. “Inamed was told that they were supposed to study the safety of implants as a condition of sale. The main concern about silicone implants is the health risks when they break, but the company did not study women long enough to find out what those risks are.”

Inamed also gathered data about health symptoms experienced by their patients. In the FDA review of Inamed’s data, FDA scientists noted the following:

  • Muscle pain, joint pain, hair loss, rashes, and fatigue all increased within two years of getting implants.
  • In terms of their quality of life, almost every measure of emotional and physical health, including social interactions and self-esteem, declined within two years of getting implants. The improvements were in self-reported sexual attractiveness.

In its description of the components of the implant shell, the FDA noted the presence of 24 potentially toxic metals, including arsenic, lead, mercury, and platinum. (FDA Review Team Memo, p. 9)

In its review of scientific studies conducted by other researchers, FDA scientists noted:

Cancer — “The finding of excesses in lung (or respiratory), cervical, vulvar, and leukemia have been reported in more than one study. These findings are difficult to interpret, and further research is needed to clarify this issue.” (FDA Review Team Memo, p. 35)

Mammography — “The possibility that implants may delay cancer detection is of concern.” ( p. 38)

Silicone Migration — “Cases of distant migration of gel to breasts, axillary lymph nodes, abdomen, groin, arm, and fingers have been reported, some with serious consequences and deformities…” (FDA Review Team Memo, p. 37)

Inamed also reported results from a 5-year study started in 1990, but it included only 29 reconstruction patients. The study started with 547 augmentation patients, but most were not studied for all five years. Since most of the patients dropped out of the study and most had breast implants that the company is no longer selling, results from this study were not useful.

“The findings show many areas of concerns and unanswered safety questions, and provide worrisome evidence that women with silicone gel implants will face numerous complications directly related to the implants, symptoms such as pain and fatigue, and declines in health and mental health,” concludes Dr. Zuckerman. “Although the rupture rate is low during the first two years, it is expected to increase every year, as it has in other studies.”

The FDA advisory panel held their public meeting on October 14-15 in Gaithersburg, MD to decide whether to recommend Inamed’s silicone gel breast implants for FDA approval. All the plastic surgeons on the panel recommended approval. Most of the other doctors and scientists on the panel voted against approval, including a toxicologist, epidemiologist, statistician, radiologist, dermatologist, and cancer surgeon. The pediatric surgeon who chaired the panel only votes to break a tie, but stated publicly that he would have voted against approval.

Silicone gel breast implants have been available under FDA-imposed restrictions since 1992 because implant makers did not provide adequate research evidence that they were safe. The FDA is expected to make a final decision about whether or not to approve the implants within a few months.

Testimony of Diana Zuckerman, PhD, at the FDA for Silicone Gel-Filled Breast Protheses

Diana Zuckerman, PhD, National Center for Health Research, October 15th, 2003

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:

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.

Cosmetic Problems

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.