Category Archives: Testimonies and Statements by NCHR

NCHR Public Comment to FDA on Breast Implant Safety

National Center for Health Research, April 26, 2019


National Center for Health Research Public Comment on General and Plastic Surgery
Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting [FDA-2019-N-0426].

Thank you for the opportunity to provide comments on FDA’s General and Plastic Surgery
Devices Panel of the Medical Devices Advisory Committee meeting on breast implants. The
National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts focused on research, programs, services, and policies that affect public health. Our Center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from companies that make medical products, so we have no conflicts of interest.

Our Program to Help Women Seeking Insurance Coverage for Implant Removal

Since its founding in 1999, our Center has heard from thousands of women who told us that their breast implants have caused serious health problems. In 2015, we began to offer a program that helps women navigate their health insurance policies so that they can get coverage when the removal of breast implants is medically necessary. In the past 3 years, more than 6,000 women have contacted us, and the number continues to grow dramatically. Some weeks we are contacted by more than 200 new women seeking our help to get their breast implants removed because of serious medical problems. Their reasons for needing their implants removed include leaking and ruptured breast implants, chronic pain from capsular contracture or from implants that are too large, autoimmune or connective tissue symptoms or diseases (referred to as “breast implant illness”), and ALCL. Some women contact us after recently developing symptoms from their breast implants, while others have been living with chronic health issues for years but either did not know they might be related to their breast implants or did not have the financial resources to have their implants removed. Prior to passage of the Affordable Care Act, breast implants were considered a “pre-existing condition” and explant surgery was almost never covered by health insurance.

Most women tell us that had they known that breast implants might cause these serious health problems, they never would have gotten them. We hear every day how women trusted their doctors when they were told that breast implants were safe and that complications were rare.

Recent research on 123,255 Israeli women by Watad et al. concluded that breast implants
significantly increase the chances of a woman being diagnosed with several autoimmune
diseases, such as rheumatoid arthritis and Sjogren’s Syndrome. However, because the FDA has repeatedly denied a link between autoimmune or connective tissue symptoms and breast implants, insurance companies will rarely pay for the removal of implants for women with symptoms of breast implant illness, such as joint or muscle pain, chronic fatigue, mental confusion, rashes, hair loss, and persistent flu-like symptoms. Of the thousands of women who seek assistance from our organization, only about 20% are able to get their implants removed. Even fewer get insurance coverage for their medically necessary explant surgery. The rest have to empty their savings, rely on credit cards or loans, or borrow money from friends and family. Unfortunately, most women who are unable to get insurance coverage for their breast implant removal are also unable to afford to pay out-of-pocket for explant surgery, which is why so many live with debilitating symptoms and escalating health problems for years. What might start as gradual increases in symptoms become so debilitating that many of the women lose their jobs (and with it, often their insurance), their ability to care for themselves or their families, and sometimes their spouses.

Implications for the Registries

The PROFILE Registry is intended to gather information about patients with BIA-ALCL, but not other health problems. The National Breast Implant Registry is designed to include as many Board-Certified plastic surgeons and their patients as possible, and therefore focuses only on re-operations – information that is relatively easy for physicians to document. It does not include information about the range of life-changing symptoms that thousands of women have reported, and also fails to include the thousands of women who need to have their implants removed, but are financially unable to do so. As we have found in our program assisting women who desperately seek insurance coverage for explant surgery, the number of women who have their implants removed and not replaced is only a small percentage of the number of women who want explant surgery because of medical problems. The registry needs to be substantially improved by including information about the autoimmune and connective tissue disease diagnoses as well as the moderate to severe symptoms that women refer to as breast implant illness. In addition, registries need to include information from primary care physicians and non-surgical specialists who are often conducting medical tests in an effort to determine the cause of the women’s symptoms. Most women who experience autoimmune or other symptoms from their breast implants are making appointments with primary care physicians, rheumatologists, neurologists, and other specialists; they rarely return to their plastic surgeons because those symptoms aren’t clearly related to their implants. Moreover, they tell us that when they go to a plastic surgeon because they have heard from other patients that the symptoms may be related to their implants, most surgeons tell them they are mistaken.

Another major shortcoming of the current Registry is that the data from the Registry is not
available to researchers or the public unless the ASPS Foundation chooses to make it public. Since the FDA considers registries an important aspect of post-market surveillance, it is essential that the data be available to anyone who wants to analyze it.

If Implants Can Cause Serious Symptoms, Will Removal Improve Health?

Our Center recently conducted a study of 449 women who had sought our help and succeeded in having their implants removed in 2016, 2017, or 2018. Fifty-seven percent of the women filled out our online questionnaire, all between November 2018 and January 2019. All of the women who we contacted had provided medical information to us when we had previously tried to help them obtain insurance coverage for explant surgery. Fifty-nine percent of the women in the study had symptoms for more than 5 years before they had their breast implants removed and 25% reported having symptoms for more than 10 years before explant surgery. These findings are consistent with patients’ testimony at the FDA meeting and with what thousands of patients have told us over the years: Many women have had debilitating symptoms for years, but did not know they were linked to their breast implants. So, instead of removing their implants when they first noticed health problems, they waited years, and sometimes decades, to seek explant surgery without replacement. Whether because of lack of money or lack of information that their symptoms were caused by their implants, our findings suggest that a short, easy-to-understand booklet and informed consent checklist could help warn women with limited financial resources about the risks of breast implants and also help women recognize their symptoms and consider explant surgery as an option before their health deteriorates.

We asked about family and personal health history and found that 69% of the women in our study reported a family history of autoimmune disease, 3% reported a personal history of autoimmune symptoms prior to getting implants, and 51% of the women reported that they were newly diagnosed with an autoimmune disease after getting breast implants.

Using a Likert scale with responses ranging from “much worse” to “much better,’ 61% of the women reported that their symptoms were much better since getting their implants removed and an additional 29% reported that their symptoms were somewhat better after having their breast implants removed. After performing a logistic regression to determine the factors that independently predicted health improvement after explant surgery, having explant surgery that removed as much capsule as possible predicted improvement after explant, as did not having a family history of autoimmune disease.

Implications for Informed Consent

Although all implant companies have patient booklets, in our experience most women report never seeing those booklets. In addition, the booklets are much too long and technical; they range in length from 55 to 180 pages, and include a great deal of information that is difficult to understand or promotional rather than informational. Nevertheless, the patient booklets include important information, such as the warning that breast implants were not studied on women with a history of autoimmune disease and therefore the safety of implants is not established for those women. However, there is so much information in these lengthy booklets that these types of important warnings are unlikely to be noticed by either doctors or patients that read them.

Although all patients sign an “informed consent” document, many are too technical for the
average patient to understand and include information that may be vague or confusing. They are often signed without having been carefully read. Informed consent is supposed to be a process, not just a piece of paper. Patients tell us that regardless of what the informed consent forms stated, their plastic surgeons were very reassuring about how safe implants are, rather than being candid about the risks. At the FDA Advisory Committee meeting on March 25-26, many plastic surgeons spoke about how carefully they provide informed consent to their patients, but those claims were undermined by the fact that many of those same surgeons stated that their patients are very happy with their implants, that ALCL is very rare and ‘not a big deal’ if caught early, and that the symptoms of breast implant illness are the same symptoms that all women tend to have. It is obvious that these physicians are unable to provide objective, informed consent about risks if they think the risks are minimal or non-existent.

Improving Informed Consent

Women need better informed consent in terms of written material and in terms of what their physicians tell them. Patient booklets specific to each company and implant model should be no longer than 20 pages and written at an 8th grade reading level, which is the reading level recommended by health educators. They should include easy-to-understand information about complications and risks, including information about BIA-ALCL and symptoms of breast implant illness. They should also include information from studies indicating that many women with breast implant illness experience significant improvement when their implants and scar capsules are removed. The writing of these booklets should require consensus among a group of experts that includes patients harmed by implants and their physicians, Board-certified plastic surgeons who put in breast implants and Board-certified plastic surgeons who primarily explant, the relevant implant manufacturer, and health educators.

In addition, there should be a required checklist, no longer than 3-4 pages, that is similar to the one that the FDA required for Essure, that provides information about the potential risks of all breast implants including BIA-ALCL and breast implant illness. These should be read and signed by patients and their doctors prior to any nonrefundable deposits for surgery. The checklist should include a black box warning regarding BIA-ALCL and breast implant illness, and information about the potential improvement in health for women who have their implants removed and not replaced.

In conclusion, we urge the FDA to require an informed consent checklist that specifically and succinctly warns of the symptoms and disease development risks that the patients at this meeting have reported. We ask that the FDA require manufacturers to complete the large, long-term studies that evaluate systemic symptoms. And finally, we urge the FDA to develop a national registry that includes symptoms as well as re-operations.

Thank you for the opportunity to comment on this important issue.

For more information, please contact Diana Zuckerman, PhD, at dz@center4research.org.

Public Comments by Women’s Health Experts on General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee Meeting


National Center for Health Research Public Comment on General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting.

Thank you for the opportunity to provide comments on FDA’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting.

We are writing on behalf of five nonprofit health organizations that have examined issues pertaining to women’s health for decades and have considerable expertise concerning breast implant safety issues. None of these organizations have financial or professional conflicts of interest pertaining to breast implant devices or surgery:

  • Breast Cancer Action is a national nonprofit grassroots membership organization with members across the country who are challenging the status quo and working to address and end the breast cancer epidemic.
  • The Jacobs Institute of Women’s Health identifies and studies aspects of healthcare and public health, including legal and policy issues, that affect women’s health at different life stages.
  • The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety.
  • The National Women’s Health Network (NWHN) is a non-profit advocacy organization that works to improve the health of all women by supporting informed consumer decision-making.
  • Our Bodies Ourselves is a nonprofit educational and advocacy organization that has advanced the health and human rights for girls and women for almost 50 years.

As a follow-up to the FDA’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee Meeting on breast implants, we are writing to express our views and concerns about the current status of information about breast implants and the role of the FDA in regulating the devices.

1. There is insufficient research to determine the long-term safety of breast implants. The clinical trials submitted to the FDA have numerous shortcomings:

  1. They excluded women with a history of autoimmune disease.
  2. They had an unacceptably high “loss to follow-up.” At the FDA meeting, FDA scientists presented data from studies that had lost up to 85% of the patients to follow-up, even in the revised studies that had already eliminated the 95% of patients who had dropped out. Those revised studies were already hopelessly biased, and presenting the data as if it were meaningful was unacceptable. And, the numbers of patients were also unacceptably small in many cases, with several reconstruction and revision patient groups represented by less than a dozen patients. Accurate information on the safety of breast implants cannot be gleaned from studies with such inadequacies.

The studies of autoimmune and connective tissue disease funded by industry and plastic surgeons had a different set of problems:

  1. Many included small number of patients, some of whom had breast implants for short periods of time, ranging from one month to just a few years. This is not relevant to long-term safety issues, since implants tend to deteriorate and rupture over time.
  2. They evaluated the number of women with diagnoses of rare diseases, but did not include women with symptoms of those diseases, nor did they have the statistical power to evaluate significant differences between women with implants and women without implants.
  3. Many evaluated the number of women hospitalized with those rare diseases or whose medical records specified those diseases, but the studies included women who had implants for such a short time that it was unlikely that the women had yet been diagnosed or hospitalized.

2. Most women do not receive objective informed consent regarding the risks of breast implants during the decision-making process. When the FDA approved breast implants, the agency required that plastic surgeons share information about the risks in a patient booklet. Unfortunately, most women say that they do not receive these booklets prior to surgery, and the booklets themselves are too long and complicated to provide useful information to patients. For example, although the patient booklets warn that the safety of breast implants have not been studied in women with a history of autoimmune disease, that information is difficult to find in these 44-202 page patient booklets.

3. To improve informed consent, women considering breast implants need a shorter, easy to understand patient booklet, which harmed patients should help to write. These booklets should include quantitative data on risks of the company’s implants for augmentation patients and reconstruction patients that are easy to understand. As experts in educating women on health issues, we would be glad to participate in writing these booklets as well. In addition, we strongly urge that the FDA require a short, user- friendly check list that provides balanced information about the risks, similar to the 3- page check list that the FDA required doctors and their patients to sign to inform them of the possible risks of Essure. The current informed consent checklists provided by some implant companies are vague consent forms rather than specific information acknowledging the risks. Informed consent checklists should explain all of the associated risks, encourage informed and shared decision making by the patient, and ultimately prevent long-term harm. It should clearly and succinctly state the risks that can occur with breast implants, including BIA-ALCL, the possibility of autoimmune symptoms, the need to remove the implants as they age and rupture, and the cost of MRI screening for silent rupture. The checklist should include a black box warning about BIA-ALCL and breast implant illness. The checklist should also include information based on studies indicating that women with breast implant illness are significantly more likely to improve after their implants and capsules are removed.

4. Since almost all cases of BIA-ALCL are associated with textured breast implants, implant companies that make textured implants should be required to conduct large retrospective studies to evaluate if the implants have any benefits compared to smooth implants. Some plastic surgeons believe that textured implants are less likely to cause capsular contracture and some other problems, but the FDA has not vetted any data to support those claims. Similarly, the use of mesh in breast reconstruction has not been scientifically studied to determine risks or benefits, and FDA should add warnings to the label and the FDA website about that off label use. In the meantime, textured breast implants should carry a black box warning about BIA-ALCL and that information should be provided orally and in writing to all women considering implants.

5. The newly designed breast implant registry tracks only the rates of reoperation, not other complications or health problems of women with breast implants. In addition, the National Breast Implant Registry misses the thousands of women who need to have their implants removed, but are financially unable to do so. To provide useful information, the registry should include information about important, debilitating autoimmune and connective tissue disease symptoms associated with implants. Registries should include relevant medical information from physicians other than plastic surgeons. In addition, the data from the registry are not available to the public unless the plastic surgeons chose to publish information. To improve transparency and informed decision- making by physicians and patients, data from the registries should be made available for free to the FDA, independent researchers, and the public to be analyzed and published.

6. We strongly urge the FDA to require manufacturers to complete large, long-term studies that evaluate the serious symptoms that patients described at the FDA Advisory Committee meeting. Well-designed studies were required as a condition of approval more than a dozen years ago, but those studies were not properly completed, due to enormous loss to follow-up. The FDA should require such studies now, and this time the research requirements should be enforced and implants taken off the market if the studies are not completed as promised.

In summary, the lack of good data, the lack of informed consent, and the lack of unbiased information for women who have become seriously ill from their breast implants are major shortcomings that FDA can help to remedy. We would be glad to share our expertise with you. Please feel free to contact the leaders of our organizations for additional information: Ms. Karuna Jaggar, Dr. Susan Wood, Dr. Diana Zuckerman, Ms. Cynthia Pearson, and Ms. Judy Norsigian.

NCHR Comment on FDA’s 510(k) Third Party Review Program Draft Guidance

National Center for Health Research: December 13, 2018


Comment of the National Center for Health Research Regarding the
510(k) Third Party Review Program:
Draft Guidance for Industry, FDA Staff, and Third Party Review Organizations.
OMB Control Number 0910-0375

The National Center for Health Research (NCHR) is a non-profit organization which conducts original research to better inform policy makers, health professionals, and patients.   NCHR accepts no funding from any entity which manufactures or distributes medical products.

We appreciate the opportunity to comment on this draft guidance.  We note that this draft guidance applies to low-to-medium risk medical devices, which concerns us because many Class II devices are permanent implants that have the potential to cause permanent harm to patients.  In fact, our research indicates that even Class I devices have been subjected to high-risk recalls by the FDA due to the potential for causing death or permanent harm.1 2 3

We have several serious concerns about the draft guidance.  First, Original Equipment Manufacturers (OEM) are accountable for the efficacy and safety of their medical devices.  FDA standards require that devices manufactured by OEM’s comply with relevant regulatory standards.  OEMs are required to track, monitor, and report product issues to FDA.  Overseeing the OEMs and their reporting are FDA’s responsibility to ensure patient safety.

Second, in the past FDA has had the opportunity to review the work of any third party reviewer, and reject it if deemed inadequate or shoddy.  In fact, the agency has often found problems with the third party reviews.  The proposed guidance would sharply reduce the agency’s oversight of third party reviews, which will clearly compromise safety.  Even if certified as qualified, third party review companies have an inherent conflict of interest: If their standards are too high, no device company will hire them and they will go out of business.  The system is similar to the EU regulation of medical devices, which has resulted in very harmful decisions, such as the clearance of the PIP breast implants that were found to use non-medical grade silicone.4  In addition, investigative reporters recently obtained CE clearance for a “surgical” mesh that was made out of a plastic mesh bag used for oranges.

Transparency is also a crucial factor.  Currently, third party review companies are not required to clearly label an OEM device indicating that a critical repair has been completed by someone other than the OEM.  Once that repair is made, the device is no longer the same device that was approved or cleared by FDA.  It is important that this chain of accountability is not broken or interrupted.

While we understand the desire of FDA officials to reduce medical device review times and reduce the burden on FDA staff and industry, the 510(k) program already is a quick way to get devices to market and the device industry has clearly benefitted from it.  The 510(k) pathway has been widely criticized by the Institute of Medicine, physicians, patients, and the media for its lack of clinical trials and lack of scientific evidence.5  Despite its weaknesses, the 510(k) pathway is considered superior to the EU regulatory system, however.  By reducing the “burden” for FDA staff and industry, the proposed guidance increases the burden on patients and doctors to figure out which devices are safe and which are not.  This would clearly put U.S. patients at greater risk.

FDA has not demonstrated that its proposed changes to the third party review pathway of Class I and Class II devices will benefit patients.  By definition, 510(k) devices only rarely are substantially superior to recent predicates.  Speeding up the process of clearance is not demonstrated to benefit patients.  Moreover, with registries, NEST, and other planned efforts to improve post-market surveillance still far from effectively implemented, any loosening of 510(k) regulations is very premature.

Finally, we note that Commissioner Gottlieb responded to recent media criticism of CDRH regulations by promising improvements to the 510(k) pathway to ensure patient safety.  The third party review program clearly moves in the opposite direction, reducing patient safety, rather than protecting patients from potentially harmful devices.   We strongly oppose it for that reason.

 

References

  1. Zuckerman, D.M., Brown, P, and Nissen, S.E.  (2011) Medical Device Recalls and the FDA Approval Process, Archives of Internal Medicine, 117, 1006-11.
  2. Zuckerman D.M., Brown P., Nissen S.E. (2011). In Reply, Archives of Internal Medicine, 171(11), 1045.
  3. Zuckerman D.M., Brown P., Nissen S.E. (2011). In Reply, Archives of Internal Medicine, 171(21), 1963.
  4. Zuckerman, D., Booker, N, and Nagda, S. (2012) Public Health Implications of Difference in US and European Union Regulatory Policies for Breast Implants, Reproductive Health Matters, 20 (40),102-111.
  5. Zuckerman D.M., Brown P. & Das A. (2014) Lack of Publicly Available Scientific Evidence on the Safety and Effectiveness of Implanted Medical Devices,  JAMA Internal Medicine, 174(11): 1781-1787.

 

Statement of Dr. Diana Zuckerman, President of the National Center for Health Research, Regarding the New Study of 100,000 Women with Breast Implants

Diana Zuckerman, PhD, National Center for Health Research: September 17, 2018.

In the largest study ever conducted of long-term health risks for patients with breast implants, researchers at The University of Texas MD Anderson Cancer Center have reported that women with silicone implants are more likely to be diagnosed with several rare diseases, autoimmune disorders, and other conditions.  These results are consistent with numerous previously published studies, but contradict the conclusions of studies funded by implant manufacturers or plastic surgery medical societies.

The study, published in the September issue of the medical journal Annals of Surgery, is by researchers in MD Anderson’s Department of Plastic Surgery and is based on analyses of almost 100,000 patients with either saline or silicone implants. The information was derived from the FDA’s database dating back to 2005.  When the FDA approved silicone gel breast implants made by two manufacturers in 2006, the agency required that each of the manufacturers study at least 40,000 women for 10 years.  Those studies were started but never completed, making it impossible to determine the long-term risks of breast implants.  In the absence of such crucial studies, patients report that they were not warned about the risks when they decided to get breast implants.

We thank Mark W. Clemens, M.D., associate professor, Plastic Surgery, the senior investigator of this very important study.  The findings are consistent with what thousands of women with breast implants have reported in Facebook groups and other social media, and directly challenge the FDA’s claims that breast implants do not cause such diseases.  We urge the FDA to be more patient-centered and finally require independent studies be conducted of women before and after their breast implants are removed.  Many women have reported that their debilitating autoimmune symptoms decreased or disappeared after their breast implants were removed, but scientific data is needed to establish the rate of recovery.

Statement of Dr. Diana Zuckerman, President, National Center for Health Research, Regarding the American Health Care Act

Diana Zuckerman, PhD, National Center for Health Research: March 9, 2017

The goal of the American Health Care Act is to replace the Affordable Care Act (ACA) with something better, but instead it represents a giant step backward for health care for all Americans. This proposed plan will cover far fewer Americans than the Affordable Care Act (ACA), and insurance will pay for less and cost more. The proposed tax credits and Health Savings Accounts (HSAs) will not begin to provide adequate health insurance for Americans covered under the ACA, particularly low-income patients.

A substantial number of people who had health insurance for the first time under ACA will lose it. The proposed 30% surcharge for those who let their insurance lapse is an insufficient incentive for healthy people to purchase insurance. Since the surcharge is the same for patients whose insurance lapses for 2 months or 20 years, it actually discourages healthy patients from buying health insurance until they have substantial medical expenses. The lack of healthy patients in the insurance pool means higher premiums and deductibles for all of us. And, as more uninsured patients end up in hospitals needing expensive medical care for cancer, heart disease, or other serious illnesses, that uncompensated care means higher hospital costs for all of us.

The very obvious shortcomings of the proposed TrumpCare bill are the reasons why hospital organizations, the American Medical Association (AMA), AARP, and many insurers are all against this legislation. It would disrupt the marketplace, create confusion and uncertainty, and reduce or strip health care coverage from millions of Americans.

Meanwhile, the bill would provide tax breaks for the wealthy at the expense of those losing health coverage. The legislation also would serve to severely reduce Medicaid benefits over time, by eventually turning the Medicaid coverage now provided into block grants to states, many of which might spend the funds on issues other than health care.

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

Statement of Dr. Diana Zuckerman on FDA Approval of New Silicone-Gel Breast Implant Natrelle 410

Diana Zuckerman, PhD, National Center for Health Research: February 21, 2013

Yesterday the FDA quietly approved yet another questionable style of breast implants, the Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Gel Filled Breast Implant made by Allergan, Inc.

The FDA based its approval on data from 941 women, which is a very small sample. The FDA reports that the complications from these implants are similar to those for other breast implants: pain and hardness caused by scar tissue (capsular contracture), the need for additional operations to fix implant problems, the need to remove the breast implants because of problems, uneven appearance (asymmetry), and infection.  The studies also found cracks in the gel of some Natrelle 410 implants, which has not been found in other breast implants.

Unlike other breast implant approvals, the FDA did not hold a public Advisory Committee Meeting to discuss the data, nor did they make the study data public for these new breast implants.  What are they afraid of?  It seems likely that the FDA decided it was better to hide this information than to make it public at a meeting where implant patients could talk about the health problems that have been caused by these implants.

The silicone gel in the Natrelle 410 implant contains more cross-linking compared to the silicone gel used in Allergan’s previously approved Natrelle implant. This increased cross-linking results in a silicone gel that’s firmer. Cross-linking refers to the bonds that link one silicone chain to another. Some physicians believe this will make the implant last longer, but there is no evidence to support that because these implants have only been studied for 7 years.

The FDA admits that Allergan’s studies did not compare the safety and effectiveness of the Natrelle 410 implant to other previously approved silicone gel-filled breast implants on the market.

As a condition of approval for the Natrelle 410 breast implants, Allergan must:

  •  Continue to follow, for an additional five years, approximately 3,500 women who received the Natrelle 410 implants as part of the company’s continued access study;
  • Conduct a 10-year study of more than 2,000 women receiving Natrelle 410 silicone gel-filled implants post-approval to collect information on long-term local complications (e.g., capsular contracture, reoperation, removal of implant, implant rupture) and less common potential disease outcomes (e.g., rheumatoid arthritis, breast and lung cancer, reproductive complications);
  • Conduct five case-control studies to evaluate whether women with Natrelle 410 implants, or other silicone gel-filled breast implants, are more likely to develop rare connective tissue disease, neurological disease, brain cancer, cervical/vulvar cancer and lymphoma;
  • Evaluate women’s perceptions of the patient labeling; and
  • Analyze the Natrelle 410 implants that are removed from patients and returned to the manufacturer.

Unfortunately, Allergan has not done a good job of doing post-market studies once their implants have been approved.  And, even if they do these studies, by the time these studies are done to find out what the risks are, hundreds of thousands of women could have these inadequately studied devices in their bodies, and could have been harmed by them.

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

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.