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

Statement of Diana Zuckerman, PhD, President of the National Research Center for Women & Families

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.

The FDA & Breast Implants: The First 50 Years

Breast implants were first sold in the U.S. in the 1960s, at a time when there was no government regulation of any medical devices, including breast implants. When a law was passed giving the FDA that authority in 1976, the agency was overwhelmed with an enormous backlog of devices that needed to be evaluated. Most devices were allowed to remain on the market until those reviews were completed, and breast implants were generally considered a much lower priority than potentially life-saving devices such as heart valves and shunts.

Scientists and physicians started expressing strong concerns about the safety of silicone breast implants in the late 1970’s, and their concerns were discussed at a 1978 FDA advisory committee meeting. By the early 1980’s, most of the risks that eventually led to the removal of silicone gel implants from the market were known or suspected, and included in a proposed rule in the Federal Register.[1]

Finally, in 1988 the FDA finalized the proposed rule. At an FDA advisory committee meeting, the warnings of earlier years had become more urgent, and a lawyer, a former Dow engineer, and other experts testified that they had seen protected court documents indicating that manufacturers were hiding safety information from FDA and the public. Several women described their own terrible experiences with implants.

The November 1988 FDA advisory panel on breast implants expressed considerable concerns about their safety. They recommended that the FDA establish a national registry of women who have breast implants.  FDA officials were opposed because of the expense, and because it could set a precedent for other implants that might cause problems for the agency. Moreover, the FDA thought a registry wasn’t viable because the American Society of Plastic and Reconstructive Surgeons did not support it.

The panel also recommended a mandatory program to inform the public of potential risks of breast implants, possibly including informed consent prior to surgery. However, it was decided that the regulations required for a mandatory program would be so strongly opposed by the plastic surgeons and manufacturers, that it was more practical to develop a voluntary program instead. At the January 1989 panel meeting, the FDA announced plans to develop a brochure and videotapes to educate women about the risks of implants prior to surgery.

The brochures and videotape were to be distributed voluntarily in the offices of plastic surgeons. The educational materials were to be developed by consensus by a diverse group of 23 individuals representing consumer organizations, manufacturers, and health professionals; each representative was given the authority to veto any decision. Because of disagreement within this group about what the materials should say, the brochures and videotapes were never completed.

By 1990, almost one million women in the U.S. had breast implants and the numbers were increasing substantially.  Congressman Ted Weiss (D-NY) chaired a Congressional oversight hearing to criticize the FDA for not yet requiring the manufacturers to evaluate the  safety of their breast implants, and the fact that no clinical trial data had been published regarding their effects on human health.

Silicone Gel-Filled Implants
In 1991, pressured by Rep. Weiss and media reports of illness and complications, the FDA finally required the manufacturers of silicone gel breast implants to submit safety studies. FDA scientists reviewing those studies pointed out that the research was inadequate — the studies included few women, the women had implants for very short periods of time, and many women were lost to follow-up. The law requires that products be proven safe and effective in order to be sold in the United States, but the FDA could not conclude whether the implants were safe or effective because of the shortcomings of the research. (There is no requirement that products be proven unsafe to keep them off the market.)

However, there was enormous pressure to keep breast implants on the market from manufacturers, plastic surgeons, and their Congressional representatives. In 1992, as a compromise, FDA allowed silicone gel breast implants to remain available as a “public health need,” but only for women participating in clinical trials, and primarily for women who had mastectomies, breast deformities, or wanted to replace a broken gel implant. Any woman who had implant surgery with silicone gel implants after 1992 was required to be regularly evaluated by her plastic surgeon as part of the study. Only a limited number of women could  receive gel implants for first-time augmentation as part of clinical trials.

In January, 2004, the FDA announced it would not approve silicone gel breast implants, because of the lack of long-term safety data. However, in April 2005, the FDA held a public meeting to once again consider approval of silicone gel breast implants, with almost the same data that they had rejected the year before. In November 2006, the FDA announced that they were approving silicone gel breast implants made by two manufacturers, Allegan and Mentor. However, the approval was on the condition that the implant makers each study 40,000 women with silicone gel implants for 10 years. In addition, the FDA stated that silicone breast implants were not approved for women under the age of 22.

Saline-Filled Breast Implants
In 2000, the FDA reviewed the safety of saline-filled breast implants for the first time. Saline implants have a silicone outer envelope and are filled with salt water. The FDA required studies of local complications, such as pain, infection, hardening, and the need for additional surgery. They did not require studies of diseases or other systemic health problems. Despite extremely high complication rates during the first three years (approximately three out of four reconstruction patients and almost half of first-time augmentation patients), the FDA approved saline implants. As part of the approval process, the FDA made information about the risks of breast implants more available. A consumer handbook and a brochure with photographs of common complications are available online here.

2011 Developments
In January 2011, the FDA announced that women with breast implants seem to be more likely to develop ALCL (anaplastic large cell lymphoma), a rare cancer of the immune system. The risk of developing ALCL is very low, but much higher in women with implants than it is in other women of the same age. ALCL is especially rare in the breast area, but for women with implants it has been found in fluid surrounding the implant and in the scar capsule, but not the breast tissue itself.  It seems that ALCL can develop in women with different types of breast implants, but the cause is unknown.[2] That is why the FDA requests  that healthcare providers notify the FDA of any cases of ALCL in women with breast implants, to determine how great the risk is compared to women without implants.

In June 2011, the FDA released the preliminary results of the long-term studies of silicone breast implants that were required as a condition of FDA approval in 2006. This included long-term follow-up of the two-year and three-year studies that were the basis of FDA approval for Mentor and Allergan silicone gel implants. It also includes each company’s study of more than 40,000 breast implant patients, that were started after the 2006 approval decision and that will be followed for 10 years.

The results indicated that complications were frequent and increased as the implants aged in the body. The most common complications were capsular contracture (hardening of the area around the implant), the need for additional surgeries to fix implant problems, and implant removal.

The FDA reported that three out of four women with Mentor implants that were enrolled in the Mentor study of 40,000 women had dropped out by the third year of the study, thus making the results meaningless. The Allergan study of augmentation patients was slightly better, with just over half of the patients still participating in the study after two years. The Allergan study of reconstruction patients was the only one of the large studies that could provide useful information, with more than 70% of those patients still enrolled after 2 years. For our summary of this report, click here. You can also read the FDA’s update on silicone breast implants (full report).

[1] The FDA’s Regulation of Silicone Breast Implants: Staff Report Prepared by the Human Resources and Intergovernmental Relations Subcommittee of the House Government Operations Committee, December 1992.

[2] Food and Drug Administration. Anaplastic Large Cell Lymphoma (ALCL) In Women with Breast Implants: Preliminary FDA Findings and Analyses.

2011 Update on Silicone Gel-Filled Breast Implants

• 2011 FDA Update on Silicone Gel Breast Implant Safety: Many Unanswered Questions (Our Analysis)

• FDA Update on the Safety of Silicone Gel-Filled Breast Implants (2011)

Selected Public Testimony at FDA Advisory Panel meeting on Breast Implants, August 2011

Margaret Dunkle

Dana Casciotti

For testimony of implant patients, read their testimony here.

FDA Materials

• Photographs of Breast Implant Complications

• FDA warning on ALCL and breast implants

Selected Public Testimony at FDA Advisory Panel meeting on Silicone Breast Implants, April 2005

Testimony of Diana Zuckerman, Ph.D.

Testimony of Ed Brent

Testimony of Dawn Miller

Testimony of Shannon Scott

Testimony of Linda MacDonald Glenn

Testimony of Audrey Sheppard

Testimony of Judy Norsigian

Testimony of Marcy Gross

Testimony of Claudia Miller, MD

Complete Transcript of FDA Advisory Panel meeting on Silicone Gel Breast Implants, April 2005

April 11, 2005 Transcript [Morning and Afternoon Public Comment] (Word)

April 11, 2005 Transcript [Evening Public Comment] (Word)

April 12, 2005 Transcript [Inamed Only] (Word)

April 13, 2005 Transcript [Mentor Only] (Word)

FDA summary of Inamed data for April 12, 2005 FDA advisory panel meeting
http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_tab-1_fda-Inamed Panel Memo.pdf

FDA summary of Mentor data for April 13, 2005 FDA advisory panel meeting
http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1_Tab-1_fda-Mentor Panel Memo.pdf

FDA PowerPoint presentation of data on Mentor and Inamed Silicone Breast Implants, April 2005
http://www.fda.gov/ohrms/dockets/ac/05/slides/2005-4101s1.htm

Additional information about Inamed and Mentor silicone gel breast implants from the April 11-13 FDA advisory panel meeting
http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4101b1.htm

Testimony Before the FDA in 2003

Testimony of Diana Zuckerman, Ph.D.
October 15, 2003

Testimony of Anne Kasper, Ph.D.
October 14, 2003

Testimony of Sherry Henderson
October 14, 2003

Testimony of Suzy Cunningham
October 14, 2003

Testimony of Marcy Gross
October 14, 2003

Testimony of Becky S.
October 15, 2003

Testimony of Susan Pope Helman, Ph.D.

October 15, 2003

FDA PowerPoint Slides of Inamed Complications with Silicone Breast Implants, October 14-15, 2003
http://www.fda.gov/ohrms/dockets/ac/03/slides/3989s1.ppt#49

Testimony Before the FDA in 2002:

Testimony of Diana Zuckerman, Ph.D.
July, 2002

Testimony of Jae Hong Lee, MD, MPH
July, 2002

Testimony of Cynthia Pearson
July, 2002

Research by FDA Scientists

• Click here for articles by FDA Scientists

Transcript of FDA March 2000 Meeting on Saline Implants
To read the exact transcript of the 3-day FDA Advisory Panel meeting on Saline Breast Implants, click the day you want to read first. It may take some time to view or download the file:

March 1, 2000

March 2, 2000

March 3, 2000

 

Public Health Implications of Differences in US and European Union Regulatory Policies for Breast Implants

Reproductive Health Matters, December 2012
By Diana Zuckerman, PhD, Nyedra Booker, PharmD, MPH, and Sonia Nagda, MD, MPH

Tens of thousands of defective silicone breast implants were recalled in Europe in 2011–12 soon after the FDA’s unrelated announcement that a rare cancer of the immune system was associated with all saline and silicone gel breast implants. These developments raised questions about whether U.S. and European regulations were protecting patients from unsafe medical implants.

In the US, breast implants are regulated as high-risk medical devices that must be proven reasonably safe and effective in clinical trials and subject to government inspection before they can be sold. In contrast, clinical trials and inspections have not been required for breast implants or other implanted devices in Europe. As a result of these differing standards, the PIP breast implants that were recalled across Europe had been removed from the market years earlier in the US. Nevertheless, the FDA track record on breast implants indicates that studies have provided limited information about safety.

The authors conclude that neither the European Union nor the US has used their regulatory authority to ensure the long-term safety of breast implants. However, in 2012 the EU announced regulatory changes that could improve that situation.

To see the official summary: http://www.ncbi.nlm.nih.gov/pubmed/23245415

Adolescents, Celebrity Worship, and Cosmetic Surgery

Journal of Adolescent Health, November 2011
Summary by Maura Duffy

A study shows that media portrayals of celebrities influence how adolescents feel about their looks and influence their decisions to undergo cosmetic surgery.  Dr. John Maltby and Dr. Liz Day studied 137 young adults between the ages of 18 and 23, using questionnaires to measure their attitudes toward celebrities whose body image they admired. The researchers followed up with the adolescents eight months later, and found that the women and men who showed intense “celebrity worship” were more likely to undergo elective invasive cosmetic procedures, even after controlling for other known predictors of cosmetic surgery, such as low self-esteem, greater preoccupation with body image, and previous cosmetic surgery. The study was published in the Journal of Adolescent Health in 2011, and did not include reconstructive surgeries such as correcting birth defects, or non-invasive procedures such as teeth whitening.  The most common procedures for these UK adolescents were breast augmentation, breast lift, liposuction, nose reshaping, laser skin resurfacing, Botox injections, and soft tissue fillers, which are also the most popular cosmetic procedures among adolescents in many Western countries. Although Botox injections and soft tissue fillers are not considered “surgery,” they are invasive procedures.

In a commentary by Dr. Anisha Abraham and Dr. Diana Zuckerman in the same journal, the two point out that the young adults in the study are not just mimicking the clothing and hairstyles of their favorite celebrities, but rather undergoing invasive procedures to feel better about how they look. This study has significant implications for the health and well-being of teenagers, as increasingly unrealistic expectations of what it means to be beautiful are perpetuated by TV shows, web sites, and advertisements featuring cosmetic surgery. The authors urge doctors to develop and use an effective screening process for adolescents who wish to undergo cosmetic procedures, which includes evaluating celebrity worship. Since self-concept improves and celebrity worship tends to decrease as adolescents mature, health professionals would do well to recommend that teenagers wait before undergoing cosmetic surgery. Guidelines for consent procedures that promote better screening and counseling for these young people could improve their decision process to get procedures that are invasive, expensive, and can result in serious medical complications. The authors conclude that the study indicates how crucial it is to encourage young people  to be more self-confident and accepting of their bodies, rather than comparing themselves to “perfect” celebrities.

To read Maltby and Day’s original article “Celebrity Worship and Incidence of Elective Cosmetic Surgery: Evidence of a Link Among Young Adults,” click here.

To read Dr. Diana Zuckerman’s editorial “Adolescents, Celebrity Worship, and Cosmetic Surgery,”  click here. Both appeared in the November 2011 publication of the Journal of Adolescent Health.

The Price of Beauty: Some Hidden Choices in Breast Reconstruction

This article was published in the New York Times, December 23, 2008
By Natasha Singer

For many cancer patients undergoing mastectomies, reconstructive breast surgery can seem like a first step to reclaiming their bodies.

But even as promising new operations are gaining traction at academic medical centers, plastic surgeons often fail to tell patients about them. One reason is that not all surgeons have trained to perform the latest procedures. Another reason is money: some complex surgeries are less profitable for doctors and hospitals, so they have less of an incentive to offer them, doctors say.

“It is clear that many reconstruction patients are not being given the full picture of their options,” said Diana Zuckerman, the president of the National Research Center for Women and Families, a nonprofit group in Washington.

One patient, Felicia Hodges, a 41-year-old magazine publisher in Newburgh, N.Y., chose a double mastectomy after she was found to have cancer of the right breast in 2004. She consulted a plastic surgeon, who offered her only reconstruction with breast implants, she said.

Ms. Hodges chose implants filled with saline, a procedure for which more than a third of reconstruction patients underwent a follow-up operation, studies show.

Ms. Hodges developed wound-healing problems that required her surgeon to remove her right implant, and she was left with a concave chest with a quarter-size hole in it, she said; she described the experience as “worse than the mastectomy.”

Then Ms. Hodges discovered a chat room on the patient-information Web site breastcancer.org, where women share detailed information about breast reconstruction beyond what they may have heard from their doctors.

Ms. Hodges learned of newer, more complex procedures that involve transplanting a wedge of fat and blood vessels from the abdomen or buttocks, which would be refashioned to form new breasts.

“It’s unfortunate that a lot of general surgeons, breast surgeons and plastic surgeons don’t mention it,” said Ms. Hodges, who underwent one of the surgeries, known as a GAP flap, last year. A lifelong athlete and a karate enthusiast, she is now back at her dojo.

To raise awareness of breast reconstruction and to market it to patients, the American Society of Plastic Surgeons has adopted the vocabulary of the movement to support a woman’s freedom to choose an abortion, adjusting it for women with breast cancer. Although women “don’t choose their diagnosis, they can choose to go ahead with reconstruction or not, and with the aid of a knowledgeable plastic surgeon they can choose what their options might be,” Dr. Linda G. Phillips, a plastic surgeon in Galveston, Tex., said in a telephone news conference organized by the plastic surgery society to mark Breast Cancer Awareness Month in October. “Then they have that much more power over their lives if they have that power to choose.”

But for many patients, the options may be limited because their doctors are not proficient in the latest procedures. Dr. Michael F. McGuire, the president-elect of the American Society of Plastic Surgeons, said it is not unusual for surgeons to omit telling patients about operations they do not perform. He compared the rise of more complex breast reconstruction to the advent in the late 1980s of minimally invasive laparoscopic surgery of the gallbladder.

“At the time, only a small percentage of surgeons were doing them and doing them well,” said Dr. McGuire, who is chief of plastic surgery at St. Johns Hospital in Santa Monica, Calif. “If you were not familiar with laparoscopic gallbladder surgery, you were still doing it the traditional way with an open great big scar across the abdomen.”

Uneven information about reconstructive options is a subset of a larger problem, said Dr. Amy K. Alderman, an assistant professor of plastic surgery at the University of Michigan Medical School in Ann Arbor. Only one third of women undergoing operations for breast cancer said their general surgeons had discussed reconstruction at all, according to a study by Dr. Alderman of 1,844 women in Los Angeles and Detroit that was published in February in the journal Cancer.

“In the big picture, it would be great if we could just get doctors to tell people they have an option of reconstruction,” Dr. Alderman said.

Once patients are so informed, she added, plastic surgeons should tell them of options beyond implants. “The next hurdle would be letting them know that using their own tissue is an option, because my guess is that they are not even getting that far in the discussion,” Dr. Alderman said.

About 66,000 women in the United States had mastectomies in 2006, the latest figures available, according to the federal government. And about 57,000 women had reconstructive breast surgery last year, according to estimates from the plastic surgery society.

For many of these women, the operations were more about feeling whole again than about restoring their appearance.

Implant surgery is the most popular reconstruction method in the United States. Often performed immediately after a mastectomy, it initially involves the least surgery ­ usually a short procedure to insert a temporary balloonlike device called an expander and the shortest recovery time.

But implants come with the likelihood of future operations. Within four years of implant reconstruction, more than one third of reconstruction patients in clinical studies had undergone a second operation, primarily to fix problems like ruptures and infections, and a few for cosmetic reasons, according to studies submitted by implant makers to the Food and Drug Administration. (Reconstructive patients are more likely to develop complications after implant surgery than cosmetic patients with healthy breast tissue.)

Complication rates for newer flap procedures like the one Ms. Hodges had have not been well studied, though many surgeons say they are less likely to require follow-up operations. The most common flap procedure, named a TRAM flap, for the rectus abdominis muscle, cuts away a portion of abdominal fat, as well as underlying muscle containing blood vessels, and uses the tissue to rebuild a breast. The vessels provide a blood supply for the new breast mound. The procedure promises a more lifelike look and feel, but it carries a risk of a weaker abdominal wall and hernia.

Another flap method, the DIEP free flap, is the newest and most intricate, named for the abdomen’s deep inferior epigastric perforator vessels. It involves moving abdominal fat and blood vessels, but no muscle. The DIEP flap theoretically holds out the promise of a reduced likelihood of abdominal problems. But Dr. Alderman cautioned that researchers have not yet conducted rigorous national studies that would establish a complication rate. Sometimes the flaps fail and need to be surgically removed.

All breast reconstructions involve a tradeoff, said Dr. Scott L. Spear, the chief of plastic surgery at Georgetown University Hospital in Washington. “The implants have a lower investment in the short term and a longer-term higher risk of having to redo it,” said Dr. Spear, who is a paid consultant to the implant maker Allergan. “The flaps have a bigger investment in the short run, but you are less likely to revise it in the long run.”

Dr. Spear said plastic surgeons sometimes fail to mention the flap options for the simple reason that implant surgery can be more profitable. “It’s really embarrassing to say so, but, from a purely selfish point of view, if you are looking at insurance reimbursement for TRAM and DIEP flaps, it’s a loss leader,” Dr. Spear said. “They really require so much time and effort that a surgeon thinks, ‘Man, I can’t afford to do this.’ ”

Nevertheless, Georgetown, long a center of expertise for implant reconstruction, recently hired a plastic surgeon who specializes in the more complicated tissue flaps.

A typical surgeon in Manhattan charges insurers about $7,000 for a one-hour implant reconstruction, but for a DIEP procedure that takes 6 to 12 hours, the going rate is $15,500.

Although health insurers are required by federal law to cover reconstructive breast surgery after mastectomies, the government does not set private insurance rates. Flap reconstruction typically requires a higher out-of-pocket co-payment than implant surgery.

“In certain geographical areas where it is badly reimbursed, it’s a disincentive for plastic surgeons even to do the work,” said Dr. Richard A. D’Amico, a past president of the American Society of Plastic Surgeons, speaking of the flap procedures.

Dr. Stephen R. Colen, the chairman of plastic surgery at Hackensack University Medical Center in New Jersey, said plastic surgeons might also not inform patients about the flap procedures because they lacked the advanced training in microvascular surgery needed to perform them.

“A lot of patients are offered implants because the surgeon does not know how to do the flap, and then the implant fails and they need the flap anyway,” Dr. Colen said.

To counter doctors who might routinely steer patients to implants, Dr. Colen started a program at his hospital in which women can meet directly with an impartial physician’s assistant, who goes over the benefits and drawbacks of reconstruction methods.

“We sort of wanted to take the flow of the patient out of the control of the physician and put it in the hands of a medical person who has no personal or financial interest,” Dr. Colen said.

Dotti Campbell, a retired nurse in Crossville, Tenn., said the plastic surgeon who performed her breast reconstruction after a mastectomy offered her only an implant. “That was his procedure,” said Ms. Campbell. Her first implant developed hardened scar tissue and required replacement. Her replacement implant ruptured. Now she is going to have an operation to replace the second implant, she said.

The DIEP flap was developed by Dr. Robert J. Allen, a plastic surgeon in New York, New Orleans and Charleston, S.C., in 1992. Now surgeons at hospitals including the University of Pennsylvania Health System in Philadelphia and Beth Israel Deaconess Medical Center in Boston specialize in the procedure.

Dr. Allen and Dr. Joshua L. Levine, who operate together in Manhattan, often recommend a prospective patient talk at length with patients of theirs who have had a successful flap procedure, like Ms. Hodges, the magazine publisher and karate student, as well as with those whose first flap reconstructions failed and required a second procedure.

“Patients should not necessarily accept the first thing they hear as the end-all, because that is not necessarily the full story,” Dr. Allen said.

In F.D.A. Files, Claims of Rush to Approve Devices

This article was published in the New York Times, January 13, 2009.

In F.D.A. Files, Claims of Rush to Approve Devices

By Gardiner Harris

An official at the Food and Drug Administration overruled front-line agency scientists and approved the sale of an imaging device for breast cancer after receiving a phone call from a Connecticut congressman, according to internal agency documents.

The legislator’s call and its effect on what is supposed to be a science-based approval process is only one of many of accusations in a trove of documents regarding disputes within the agency’s office of device evaluation.

Nine agency scientists complained in May to Andrew C. von Eschenbach, the F.D.A. commissioner, and the agency began an internal review. Dissatisfied with the pace and results of that review, the scientists wrote a letter to Congress in October pleading for an investigation, and the House Committee on Energy and Commerce announced in November that it would begin one. Last week, the scientists wrote a similar letter to President-elect Barack Obama’s transition team.

Agency documents that are part of the internal investigation, including e-mail messages, were provided to The New York Times. Details of the investigations have not previously been made public.

The documents show that front-line agency scientists, like many outside critics of the agency, believe that F.D.A. managers have become too lenient with the industry. In medical reviews and e-mail messages, the scientists criticize the process by which many medical devices gain approval without extensive testing. And in e-mail correspondence, they contend that an agency supervisor improperly forced them to alter reviews of the breast imaging device and others.

William McConagha, the agency’s assistant commissioner for integrity and accountability, said he was continuing to investigate the scientists’ claims. Mr. McConagha said that Dr. von Eschenbach had offered to meet with the nine scientists before Friday, his last day in office.

“We in the Office of Commissioner are extremely concerned about allegations like this,” Mr. McConagha said.

In the documents, Representative Christopher Shays, a Connecticut Republican who lost re-election in November, is described as having called an agency supervisor a year ago to express concern about the fate of a computer device that is supposed to help radiologists detect breast tumors.

The device, the iCAD SecondLook Digital Computer-Aided Detection System for Mammography, is used with screening equipment made by Fujifilm Medical Systems.

Fujifilm Medical is based in Stamford, Conn., the heart of Mr. Shays’s former district. In the documents, Mr. Shays is referred to as “Congressman Fuji.”

“I am the Fuji congressman because I represented that district,” Mr. Shays said in an interview Friday.

Mr. Shays said he had called the agency supervisor only to demand that the agency make a final decision, not that it approve the product.

He scoffed at suggestions in the documents that his call led the supervisor to overrule scientists and approve the device. “That would be idiotic for someone to approve something they don’t think should be approved,” he said.

A spokeswoman for Fujifilm Medical, Courtney A. Kraemer, said the company had called its “local Congressional offices to ask them to help us get clarification on the F.D.A. process.”

The dissenting scientists protested, according to the internal documents, that “iCAD never tested the device by the intended users (i.e. radiologists) under the intended conditions of use. This is the most basic and fundamental requirement of all F.D.A. submissions.”

An internal review said the risks of the iCAD device include missed cancers, “unnecessary biopsy or even surgery (by placing false positive marks) and unnecessary additional radiation.”

Ken Ferry, iCAD’s chief executive, said, “We have done all the appropriate testing to get the product approved.”

Mr. Ferry said that F.D.A. scientists were increasingly asking for more rigorous testing of devices, and that his company complied with those demands.

Diana Zuckerman, president of the National Research Center for Women and Families, said the Bush administration had “finally made the device approval process so meaningless that it’s intolerable to the scientists who work there.” Ms. Zuckermen, a longtime critic of the agency’s device approval process, particularly as it relates to breast implants, added, “Virtually everything gets approved, no matter what.”

The F.D.A. has a three-tiered approval process for medical devices that, depending on their newness or complexity, requires varying amounts of proof.

A growing chorus of critics contends that the agency requires few devices to complete the most rigorous of these reviews and instead allows most devices to be cleared with minimal oversight. In 2007, 41 devices went through the most rigorous process, compared with 3,052 that had abbreviated reviews.

According to internal documents, some scientists in the agency’s device division seem to agree with these critics. One extensive memorandum argued that F.D.A. managers had encouraged agency reviewers to use the abbreviated process even to approve devices that are so complex or novel that extensive clinical trials should be required.

For instance, Shina Systems, an Israeli company, applied for approval for AngioCt, a device that combines CT images with X-rays to help guide cardiac surgeons during angioplasty and stenting procedures. The company sought an abbreviated review, according to the documents.

An F.D.A. reviewer said the company should conduct a clinical trial to prove that the device works since it is novel and risky.

“Should the images be misleading,” Dr. Brian Lewis, an agency cardiologist, wrote in a memorandum, “F.D.A. could expect immediate misguidance of catheters and possibly puncture of coronary vessels or overaggressive, inappropriate or inadequate stent or balloon use.”

Nonetheless, an F.D.A. supervisor — after meeting with Shina representatives — pressed scientists to consider allowing an abbreviated review, according to the documents. The agency’s decision on the device is pending, according to the documents. Dr. John Smith, a lawyer for Shina, wrote in an e-mail message that he would not comment on “ongoing regulatory matters.”

FDA review indicates possible association between breast implants and a rare cancer

This news release was published on the FDA website January 26, 2011.

FDA review indicates possible association between breast implants and a rare cancer
Agency requesting health care professionals to report confirmed cases

The U.S. Food and Drug Administration today announced a possible association between saline and silicone gel-filled breast implants and anaplastic large cell lymphoma (ALCL), a very rare type of cancer. Data reviewed by the FDA suggest that patients with breast implants may have a very small but significant risk of ALCL in the scar capsule adjacent to the implant.

The FDA is requesting that health care professionals report any confirmed cases of ALCL in women with breast implants.

In an effort to ensure that patients receiving breast implants are informed of the possible risk, FDA will be working with breast implant manufacturers in the coming months to update their product labeling materials for patients and health care professionals.

“We need more data and are asking that health care professionals tell us about any confirmed cases they identify,” said William Maisel, M.D., M.P.H., chief scientist and deputy director for science in FDA’s Center for Devices and Radiological Health. “We are working with the American Society of Plastic Surgeons and other experts in the field to establish a breast implant patient registry, which should help us better understand the development of ALCL in women with breast implants.”

According to the National Cancer Institute, ALCL appears in different parts of the body including the lymph nodes and skin. Each year ALCL is diagnosed in about 1 out of 500,000 women in the United States. ALCL located in breast tissue is found in only about 3 out of every 100 million women nationwide without breast implants.

In total, the agency is aware of about 60 cases of ALCL in women with breast implants worldwide. This number is difficult to verify because not all cases were published in the scientific literature and some may be duplicate reports. An estimated 5 million to 10 million women worldwide have breast implants.

The FDA notification is based on a review of scientific literature published between January 1997 and May 2010 and information from other international regulators, scientists, and breast implant manufacturers. The literature review identified 34 unique cases of ALCL in women with both saline and silicone breast implants.

Most cases reviewed by the FDA were diagnosed when patients sought medical treatment for implant-related symptoms such as pain, lumps, swelling, or asymmetry that developed after their initial surgical sites were fully healed. These symptoms were due to collection of fluid (peri-implant seroma), hardening of breast area around the implant (capsular contracture), or masses surrounding the breast implant. Examination of the fluid and capsule surrounding the breast implant led to the ALCL diagnosis.

The FDA is recommending that health care professionals and women pay close attention to breast implants and do the following:

 

  • Health care professionals are requested to report all confirmed cases of ALCL in women with breast implants to Medwatch, the FDA’s safety information and adverse event reporting program. Report online or by calling 800-332-1088.
  • Health care professionals should consider the possibility of ALCL if a patient has late onset, persistent fluid around the implant (peri-implant seroma). In cases of implant seroma, send fresh seroma fluid for pathology tests to rule out ALCL.
  • There is no need for women with breast implants to change their routine medical care and follow-up. ALCL is very rare; it has occurred in only a very small number of the millions of women who have breast implants. Although not specific to ALCL, health care providers should follow standard medical recommendations.
  • Women should monitor their breast implants and contact their doctor if they notice any changes.
  • Women who are considering breast implant surgery should discuss the risks and benefits with their health care provider.

 

The FDA published its literature review in a document posted on FDA’s website site today titled “Anaplastic Large Cell Lymphoma (ALCL) in Women with Breast Implants: Preliminary FDA Findings and Analyses.”

The FDA also plans to provide an update on its review of silicone gel-filled breast implants in the spring of 2011. This update will include interim findings from ongoing post-approval studies for silicone gel-filled breast implants currently sold in the United States, adverse event reports submitted to the FDA, and a review of the scientific literature on these products.

Women’s health advocates question FDA about missing safety data on silicone breast implants

By Matthew Perrone, Associated Press
January 5, 2012

WASHINGTON — Consumer safety advocates are questioning the Food and Drug Administration about seemingly incomplete and erroneous data used to affirm the safety of silicone breast implants last year.

The FDA concluded last summer that the silicone-gel implants are basically safe as long as women understand they come with complications. More than one in five women who get implants for breast enhancement will need to have them replaced within five years, the agency’s report concluded.

In August, an outside panel of physicians affirmed the FDA’s decision that the devices should remain available for both breast enhancement and reconstruction.

But the National Research Center for Women and Families says the FDA did not present information that showed women reported lower emotional, mental and physical well-being after implantation. Additionally, the group questions why figures presented by the FDA appear to show implant complications declining over time. The implants are known to fail over time.

“This shows problems with the data, since the complication rates are reported to be cumulative and should therefore stay the same or increase over time,” states Diana Zuckerman, the group’s president, in a letter to the head of FDA’s medical device division.

Most of the FDA’s data on the safety and effectiveness of breast implants comes from long-term studies conducted by the two U.S. manufacturers of the devices, Allergan Inc. of Irvine, Calif., and Mentor, a unit of Johnson & Johnson, based in New Brunswick, N.J.

When the FDA reviewed the initial applications for the devices in 2005, women using Allergan’s implants scored lower on nine out of 12 quality-of-life measures, including mental, social and general health. Women did report higher scores on measures of sexual attractiveness-body esteem.

Women implanted with J&J’s implants also scored worse on measures of physical and mental health. In the 11-page letter, Zuckerman questions why that information was not presented at FDA’s public meeting in August.

“Breast implants are widely advertised and promoted as a way to increase women’s self-esteem and positive feelings about themselves,” said Zuckerman, in an interview with the Associated Press. “But the implant companies’ own data, which the FDA made public in 2005 but ignored last year, shows the opposite.”

Silicone gel breast implants have traveled a long, winding regulatory path at the FDA over the last 20 years. The FDA banned the silicone-gel type in 1992 amid fears they might cause cancer, lupus and other diseases. For more than a decade, only saline-filled implants were available. But when research ruled out most of the disease concern with silicone, regulators returned the implants to the market in 2006 — with the requirement that manufacturers continue studying patients to see how they fare long-term.

When the FDA revisited the devices’ safety last year they relied on eight and 10-year follow-up data from J&J and Allergan, respectively. This followed up on similar data submitted in 2005.

Breast implants are known to rupture and break down over time. But Zuckerman points out in her letter that the company data seem to defy this trend, with complication rates falling over time.

For instance, Allergan’s reported rate of swelling among patients fell from 23 percent in 2005 to 9 percent reported in 2011. Rates of scarring similarly fell from 8 percent to 4 percent.

“This again raises questions about the accuracy of reporting, and whether patients with complications were excluded from the 10-year sample,” writes Zuckerman.

FDA staffers did not immediately respond to a request for comment Thursday.

The questions about FDA’s review of breast implants come amid a wave of recalls and warnings over similar devices across Europe and South America. The implants from French company Poly Implant Prothese are being pulled from the market amid fears they could rupture and leak silicone into the body.

French investigators say the now-defunct company used cheap industrial silicone, not medical-grade silicone, and that more than 1,000 women in France have had one or two implants burst. French health officials have agreed to pay for an estimated 30,000 women in France with the implants have them removed.

Read Dr. Zuckerman’s letter to the head of FDA’s medical device division.

I have been diagnosed with breast cancer. What are my options so that I can still have breasts?

Q. I have been diagnosed with breast cancer. What are my options so that I can still have breasts?

A. We’re not doctors and we don’t provide medical advice, but I can tell you what we know based on research and from speaking with many experts and with women who have had breast implants.

If you have been diagnosed with early stage breast cancer (stage I, IIa, IIb, or IIIa) , you probably can keep your breasts, and have a lumpectomy rather than a mastectomy (which removes the entire breast). Early-stage breast cancer patients who undergo a lumpectomy (which removes only the cancer and a small area around it) that is followed by radiation will live just as long as women who have a mastectomy instead. The experts recommend a lumpectomy with radiation for most women because it is less traumatic physically and emotionally, and avoids the problems from reconstructing a breast. For more information about this, see a booklet printed by the National Cancer Institute, the NIH, AHRQ, and the National Center for Health Research at http://www.stopcancerfund.org/t-breast-cancer/a-booklet-for-patients-surgery-choices-for-women-with-early-stage-breast-cancer/ .

If you have been diagnosed with a pre-cancerous condition such as Stage 0 breast cancer, including ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS), it is very unlikely that you need a mastectomy. Women with LCIS do not have breast cancer and most will never get breast cancer. They do not need a mastectomy or even a lumpectomy, although they do need regular mammograms. Most women with DCIS can choose lumpectomy with radiation, rather than mastectomy. For more information, see http://www.stopcancerfund.org/in-the-news/free-patient-booklet-on-ductal-carcinoma-in-situ-dcis-2/

For women with breast cancer who want to have breasts, the preferred choice is usually to keep their breasts (rather than remove their breasts and create new ones). Although a lumpectomy can make the breast smaller or change the shape, it will still have the sensation of a natural breast. In contrast, a woman who has a mastectomy with reconstruction, either with implants or with tissue transferred from elsewhere in her body, will have “breast shapes” that do not have any feeling. They are numb. Reconstruction also requires at least two surgeries. Reconstructed breasts may look fuller or “younger” but when the options are explained to them, many women would prefer to have sensation in their breast (or breasts), and would prefer not to have to worry about complications and the need for additional surgery.

If a woman needs to have a mastectomy, because the DCIS has spread throughout the breast or the cancer is large, there are several choices for reconstruction: saline breast implants, silicone breast implants, and moving tissue to create a new breast, such as a TRAM flap (Transverse Rectus Abdominis Myocutaneous flap) or DIEP flap (Deep Inferior Epigastric Perforator flap).

Many plastic surgeons know how to reconstruct breasts using breast implants, but few are skilled at moving tissue (which is called autologous tissue transfer). That is one of the reasons why so many plastic surgeons recommend breast implants.

Saline or Silicone? Some surgeons prefer silicone gel breast implants to saline, because they feel more natural. However, saline breast implants are approved by the FDA as “reasonably safe” and silicone gel implants are not. That is why women getting silicone gel breast implants must agree to be in a study. The goal is to find out how many complications or problems arise in these women in order to decide whether they are safe enough to approve. You would be part of an experiment to find out if the implants are “safe enough” for other women.

One problem with silicone breast implants is that they can break without a patient knowing it. Although less embarrassing than an instant deflation (which is likely with saline), breakage without symptoms is a bad thing, not a good thing. If silicone gel breast implants break and leak, the silicone can get into lymph nodes and travel to the lungs, liver, and brain. No research has been done on those risks, but a study by scientists at the National Cancer Institute found that women with breast implants were twice as likely to die from brain cancer or lung cancer compared to other plastic surgery patients. More research is needed, but those findings are cause for concern.

If saline implants break they are usually easy to remove. If silicone implants break, they can leak and can be extremely difficult and expensive to remove carefully. For that reason, we believe that saline are safer than silicone, even though both have very high complication rates.

Risks. All breast implants, even saline implants, are enveloped in an outer shell made of silicone. The envelope also contains other chemicals and heavy metals, such as microscopic amounts of platinum or tin, which vary during the manufacturing process. Unfortunately, some women have a reaction to those substances. Although silicone is considered “biocompatible” and most people don’t have an immediate allergic or autoimmune response, some people do, and many more develop a response years later.

It’s impossible to predict who will have problems with breast implants, and who won’t. It’s important to know that all implants will eventually break, sometimes within a few months or years, and usually within 10 years. Sometimes women who have a mastectomy get breast implants to replace one breast and to make the other breast look more similar to the replaced breast. However, it’s important to know that either silicone or saline breast implants interfere with mammograms. They show up white on the film, hiding tumors that are above or below.

Alternatives to Implants. An alternative to breast implants is “autologous tissue transfer,” such as the TRAM flap and DIEP flap procedures. These procedures use a woman’s own fat and tissue is used to reconstruct the breast. Many women prefer it to implants because it feels more natural and apparently lasts for a very long time (possibly forever, although the procedure has mostly been done in the last 15 years so it’s impossible to say). However, both the TRAM flap and DIEP flap procedures are more expensive than implants, require an especially skilled surgeon for a good result, and the healing process usually takes at least several months and can be painful. Women are only able to get this surgery if they have enough body fat in their abdomen area or back to form breasts. And, like a breast implant reconstruction, the breast has no feeling. For a woman who has the tissue transferred from her abdomen area (in an operation that has been compared to a “tummy tuck”), there is some loss of muscle in that area. That can be a problem for athletic women, but many other women don’t mind.

The DIEP flap is a similar type of reconstruction but does not remove any muscle. Instead, for the DIEP flap, the surgeon only removes fat and other tissue and makes a small cut in the abdominal muscle. Since no part of the abdominal muscle is removed, patients are able to maintain abdominal strength, making this surgery a better option for most women, especially those who are physically active.

Fortunately, TRAM flaps and DIEP flaps are covered by some health insurance companies. These are complicated surgeries with long recovery times and you would need to find a physician who is very experienced doing these procedures, and we highly recommend asking the doctor to put you in touch with other patients who were happy with the reconstruction.

Latissimus Dorsi Flap Surgery. Reconstruction using the latissimus dorsi muscle usually combines a breast implant with autologous tissue from your own body.  In a way, this is the worst of all worlds: the risks, complications, and cost of autologous tissue surgery with the risks and replacement costs of breast implants.  Some surgeons offer it because they do not have the skills to do a DIEP.  If you want a natural, long-lasting reconstruction, we suggest you keep looking to find a surgeon who is experienced with DIEP.

In a latissimus dorsi flap procedure, an oval flap of skin, fat, muscle, and blood vessels from your upper back is used to reconstruct the breast. Keep in mind that the fat in that area feels stiffer than breast fat skin on your back usually has a slightly different color and texture than breast skin.  The surgery can cause a partial loss of strength or function that makes it hard to lift things and twist, and can affect your ability to swim, golf, or play tennis.

For more information about the risks, see here:  Latissimus Dorsi Flap Surgery Risks

The comments and statements of the National Research Center for Women & Families are believed and intended to be accurate, and where applicable, based on scientific literature. NRC’s statements do not constitute medical diagnoses, medical advice, plans of treatment, or legal opinion, and we are not responsible for the use or application of this information. All medical information should be reviewed with your health care practitioner.

We hope that the information we’ve provided is helpful. In order to maintain this free service to all women and their families, we invite your tax-deductible contributions to NRC (see http://center4research.org/contribute/)

My implants are making me sick. Can someone help pay for implant removal?

Q. My breast implants might be making me sick. Can someone help me afford medical care or help pay for implant removal?

A. We’re not doctors or lawyers and we don’t provide medical or legal advice, but we can tell you what we know based on speaking with many experts and with women who have had breast implants.

Lawsuits?

There are currently no class action suits for implants and individual suits are almost impossible. For more than 20 years, women have been asked to sign informed consent forms prior to implant surgery that are designed to protect the implant company and the physician.  Unfortunately, that means that most women who have gotten implants since then can’t sue unless the doctor committed malpractice.

There have been several class action legal settlements to provide compensation to women whose implants ruptured or caused medical problems; however, the deadlines for these settlements have passed.

Health Insurance?

Until recently, it was almost impossible to get health insurance companies to pay for removal of breast implants.  However, thanks to the Affordable Care Act (Obamacare), insurance companies can’t refuse to remove implants because the woman already had the implants when she got the insurance policy, for example.  We don’t know of any insurance companies that will replace breast implants for augmentation, but some companies will pay to remove implants that are leaking or causing serious medical problems. For more information on insurance coverage, click here.

If you would like help trying to get your insurance company to cover your breast implant removal, please fill out this very short survey, and we will try to help you: https://www.surveymonkey.com/s/KHCWGM8  We cannot guarantee that you will receive coverage, but we are here to help you with the process of trying to get coverage.

Financial Assitance Programs?

The Common Benefit Trust has established a program to provide financial assistance for explantation surgery on behalf of women who meet certain eligibility requirements.  This assistance is in the form of a direct payment of up to $5,000 to the plastic surgeon who performs the removal surgery.  There are eight requirements that must be met in order to be eligible for this assistance.  The first requirement is that you must have at least one silicone gel-filled or double lumen type breast implant in your body that was implanted before December 31, 2006.

In order to find out how the Explant Financial Assistance Program works, learn about the eligibility requirements, and express your interest in receiving this assistance, please visit www.explantassistance.com and www.oplc.org.  If you have any questions, feel free to contact the Program Administrator at jcondra@oplc.org, or (205)252-6784.

Want your Breast Implants Removed- (2)

The comments and statements of the National Center for Health Research are believed and intended to be accurate, and where applicable, based on scientific literature. NCHR’s statements do not constitute medical diagnoses, medical advice, plans of treatment, or legal opinion, and we are not responsible for the use or application of this information. All medical information should be reviewed with your health care practitioner.

We hope that the information we’ve provided is helpful. In order to maintain this free service to all women and their families, we invite your tax-deductible contributions to NCHR (see http://www.center4research.org/contribute.html)