ATDEPARTMENT OF HEALTH AND HUMAN SERVICES

> FOOD AND DRUG ADMINISTRATION
>
> CENTER FOR DEVICES AND RADIOLOGIC HEALTH
>
> **GENERAL AND PLASTIC SURGERY DEVICES PANEL**
>
> **OF THE MEDICAL DEVICES ADVISORY COMMITTEE**
>
> Wednesday, October 15, 2003
>
> 7:30 a.m.
>
> Gaithersburg Marriott Hotel
>
> 9751 Washington Blvd.
>
> Gaithersburg, Maryland
>
> P A R T I C I P A N T S
>
> Thomas V. Whalen, M.D., Acting Panel Chairperson
>
> David Krause, Ph.D., Executive Secretary
>
> VOTING MEMBERS:
>
> Brent A. Blumenstein, Ph.D.
>
> Phyllis Chang, M.D.
>
> Michael A. Choti, M.D.
>
> Ann Marilyn Leitch, M.D.
>
> Michael J. Miller, M.D.
>
> Amy E. Newburger, M.D.
>
> CONSUMER REPRESENTATIVE:
>
> Alisa M. Gilbert
>
> INDUSTRY REPRESENTATIVE:
>
> Debera M. Brown
>
> TEMPORARY VOTING MEMBERS:
>
> Benjamin O. Anderson, M.D.
>
> Dennis W. Boulware, M.D.
>
> Emily F. Conant, M.D.
>
> Nancy A. Dubler, LLB
>
> Ruth A. Lawrence, M.D.
>
> Stephen Li, Ph.D.
>
> Ellice S. Lieberman, M.D.
>
> Barbara R. Manno, Ph.D.
>
> Mary H. McGrath, M.D., MPH
>
> Michael J. Olding, M.D.
>
> Celia Witten, Ph.D., M.D., FDA
>
> [C O N T E N T S]{.underline}
>
> Call to Order and Introductions,
>
> Thomas V. Whalen, M.D. 5
>
> Open Public Comment:
>
> Virginia Silverman 11
>
> Dr. Marie Pletsch 13
>
> Dr. Philip C. Haeck 16
>
> Susan Schambeck 20
>
> Julie Godoy (read by J. Rosanna) 22
>
> Holly A. Feustel 27
>
> Dr. Elvin G. Zook 29
>
> Ruby Rahn 32
>
> Donna Sims (read by Nicole Rudick) 35
>
> Dr. Karen Becker 38
>
> Lale Goddard (read by Ruby Rahn) 41
>
> Teresa Hamilton (read by Erica Clare) 44
>
> Cheryl Robinson 47
>
> Linda Dintino (read by Stephanie Donny) 50
>
> Rebecca J. Smith-Miles 52
>
> Myrl Jeffcoat (read by Pam Dowd) 54
>
> Elaine Donnelly (read by Kathleen Witter) 57
>
> Rogene Schorer (read by Georgiana Hanson) 60
>
> Wanda Simison (read by Sibyl Goldrich) 63
>
> Lois A. Travis (read by Jan Erickson) 66
>
> Deborah Guillory (read by Jennifer Cook) 70
>
> Gerie A. Voss 71
>
> Susan Pope Helman 74
>
> David Helman 78
>
> [C O N T E N T S]{.underline} (Continued)
>
> [PAGE]{.underline}
>
> Open Public Comment: (Continued)
>
> Dr. Christopher Batich 79
>
> Marilyn Malnack 87
>
> Leslie A. Rumsey 90
>
> Nikki Dollie 92
>
> Mike Dollie 96
>
> Dr. Ernest Lykissa 96
>
> Audrey Sheppard 108
>
> Dr. Elizabeth Connell 110
>
> Dr. T. Wade Clegg, III (read by Erin Hemstra) 116
>
> Lynda Roth, Coalition of Silicone Survivors 118
>
> Dr. Jane Zones, Breast Cancer Action 123
>
> Cynthia Pearson, National Women\'s
>
> Health Network 128
>
> Mary Dickerson 133
>
> Joe Kelly, Dads and Daughters 134
>
> Jama K. Russano, Children Afflicted
>
> with Toxic Substances 141
>
> Rodney Hayton, National Silicone
>
> Implant Foundation 147
>
> Dr. Carolyn Kerrigan, Plastic Surgery
>
> Educational Foundation 150
>
> Dr. James H. Wells, American Society of
>
> Plastic Surgeons 158
>
> Mary McDonough, In the Know 169
>
> Dr. Diana Zuckerman, National Center for Policy
>
> and Research for Women and Families 172
>
> Open Panel Discussion 183
>
> Sponsor Summation, Scott Spear, M.D. 228
>
> Concluding Panel Deliberations and Vote 266
>
> [P]{.underline} [R]{.underline} [O]{.underline} [C]{.underline}
> [E]{.underline} [E]{.underline} [D]{.underline} [I]{.underline}
> [N]{.underline} [G]{.underline} [S]{.underline}
>
> **Call to Order and Introductions**
>
> DR. WHALEN: Welcome to the second day of the General and Plastic
> Surgery Devices Advisory Panel. I would like to ask the panel members
> to give a brief reintroduction of themselves with their area of
> particular expertise as it relates to this PMA, starting to my right
> with Dr. Choti.
>
> DR. CHOTI: Michael Choti. I am a general surgeon in surgical oncology
> at Johns Hopkins Hospital, and my interest is in clinical cancer
> surgery.
>
> DR. BLUMENSTEIN: Brent Blumenstein, biostatistician working
> independently.
>
> DR. CONANT: Emily Conant, Associate Professor of Radiology, University
> of Pennsylvania. I am a breast imager, chief of breast imaging there.
>
> DR. LIEBERMAN: Ellice Lieberman. I am an associate professor of
> obstetrics and gynecology, Harvard Medical School, and Associate
> Professor of Maternal and Child Health at the Harvard School of Public
> Health, and my expertise is in epidemiology.
>
> DR. MANNO: I am Dr. Barbara Manno, from the Louisiana State University
> Medical Center, in Shreveport, Louisiana. I am a professor in the
> Department of Psychiatry. My background is toxicology and my
> sub-specialty within toxicology these days is forensic toxicology.
>
> MS. BROWN: I am Debera Brown, the Vice President of Regulatory Affairs
> for Broncus Technologies. I am the industry representative for this
> panel, and I have had over 20 years of experience in medical device
> development.
>
> MS. GILBERT: I am Alisa Gilbert. I am the consumer representative. I
> am also a breast cancer survivor and founder of the Unbroken Circle in
> the Office of Native Cancer Survivorship.
>
> DR. WITTEN: I am Celia Witten. I am the Division Director of the
> Reviewing Division at FDA for these products.
>
> DR. MILLER: I am Michael Miller. I am Professor of Plastic Surgery at
> the University of Texas MD Anderson Cancer Center.
>
> DR. ANDERSON: Ben Anderson, breast cancer surgeon, surgical oncologist
> from the University of Washington in Seattle.
>
> DR. LI: Steve Li, President of Medical Device Testing and Innovations
> in Sarasota, Florida and my areas are biomaterials and biomechanics.
>
> PROF. DUBLER: Nancy Dubler. I am Director of the Division of Bioethics
> at Montefiore Medical Center, and a professor of Epidemiology and
> Population Health at the Albert Einstein College of Medicine.
>
> DR. NEWBURGER: I am Amy Newburger. I am in private practice in
> dermatology, in New York. I teach at St. Luke\'s Roosevelt Hospital
> Medical Consortium.
>
> DR. BOULWARE: I am Dennis Boulware, professor of medicine, University
> of Alabama, at Birmingham, and a rheumatologist.
>
> DR. LEITCH: I am Marilyn Leitch. I am a surgical oncologist and
> professor of surgery at the University of Texas Southwestern Medical
> Center, in Dallas.
>
> DR. CHANG: Good morning. I am Phyllis Chang, plastic surgeon and an
> associate professor in the Department of Surgery at the University of
> Iowa College of Medicine.
>
> DR. KRAUSE: My name is David Krause. I am the executive secretary of
> this panel and I am also in the branch that reviews these devices.
>
> DR. LAWRENCE: I am Ruth Lawrence, University of Rochester School of
> Medicine, Department of Pediatrics and Ob/Gyn. I am a pediatrician,
> clinical toxicologist, and my special interest is newborns and breast
> feeding.
>
> DR. WHALEN: Thank you. I am Tom Whalen. I am Professor of Surgery and
> Pediatrics at Robert Wood Johnson Medical School and the Acting Chair
> for this Panel.
>
> There are brief housekeeping attention details that probably need to
> be presented in a little while when more people come in. For those who
> did not stay until the end last night, the panel did conclude the
> scheduled day\'s business and did get through the FDA questions. I
> will very briefly go over the results of those deliberations as we
> begin this afternoon\'s activities before the panel has final
> deliberations and voting.
>
> What we are about this morning is further public testimony that will
> probably take up the entire morning until the lunch break, which will
> be about midday or perhaps slightly later. We will then have final
> summation and closing by FDA and then by sponsor and then the panel
> will deliberate.
>
> To reiterate something that I said yesterday, which apparently was not
> heard by many people, please either turn off your cell phones or place
> them on silent mode because it is extraordinarily rude to have them
> continuously going off when we are trying to hear people who have
> significant messages to give us from the podium, and the panel\'s
> deliberations as well.
>
> We now will proceed with today\'s open public comment session. All
> persons addressing the panel are asked to speak clearly into the
> microphone as the transcriptionist is dependent upon this means of
> providing an accurate record of this meeting. I would specifically now
> like to have the attention of all the individuals who are registered
> to speak to the panel today. You have all been given a number
> corresponding to your order of appearance. Please come to the podium
> area in advance so that we are not spending a great deal of time in
> transitions from speaker to speaker. Specifically, we would ask that
> the speaker who is next to speak be in the corridor between the
> chairs, towards the end of that corridor, as the person is speaking at
> the podium.
>
> I would also like to remind you that we will have a timer to help you
> remain on time. In view of the large volume of people who are going to
> speak to us today, it will need to be rigorously enforced and I
> apologize in advance for intrusions upon you if you extend beyond your
> allotted time. At the 30-second mark there will be a yellow continuous
> light that comes on in front of you, and then a red light at the
> conclusion of that time.
>
> I would finally like to address the issue of financial disclosure.
> Both the FDA and the public believe in a transparent process for
> information gathering and decision-making. To ensure such transparency
> at the open public hearing session of the advisory committee meeting,
> FDA believes that it is important to understand the context of an
> individual\'s presentation.
>
> For this reason, FDA encourages you, the open public hearing speaker,
> at the beginning of your written or oral statement to advise the
> committee of any financial relationship that you may have with the
> sponsor, its product and, if known, its direct competitors. For
> example, this financial interest information may include the
> sponsor\'s payment of your travel, lodging or other expenses in
> connection with your attendance at the meeting. Likewise, FDA
> encourages you at the beginning of your statement to advise the
> committee if you do not have any such financial relationships. If,
> however, you choose not to address this issue of financial
> relationships at the beginning of your statement, it will not preclude
> you from speaking.
>
> We will start with those individuals who have notified the FDA of
> their request to present in the open session. Speaker number one,
> please come to the podium.
>
> **Open Public Comment**
>
> MS. SILVERMAN: Good morning. My name is Ginger Silverman. I am from
> California, and Inamed provided me transportation and my
> accommodations for coming to the meeting.
>
> Twenty-four months ago I was diagnosed with ductal carcinoma in situ,
> breast cancer. That is the bad news. The good news is that I basically
> had breast cancer for about seven days. Because of my familiarity with
> the disease, all the statistics, my knowledge of the options that were
> available to me and the possible outcomes, I chose the most aggressive
> treatment available to me at the time. I had a double mastectomy two
> years ago, and that happened one week after my radiologist\'s phone
> call.
>
> As a result of my early diagnosis and my aggressive proactive choices,
> I now have silicone breast implants and did not need radiation or
> chemotherapy. The discovery of, and subsequent process of ridding my
> body of breast cancer held many miracles. Finding the right doctors is
> probably at the top of the list; embracing the love of my friends and
> family who gathered around to support me through the ordeal; and
> learning a lot about myself, my courage.
>
> Surprisingly, my ability to heal was facilitated in an unanticipated
> way, my selection of silicone breast implants. My plastic surgeon
> recommended them because I chose immediate breast reconstruction and I
> wanted to have the most natural look possible. I have no uncomfortable
> side effects and I could not be happier with the results. They have
> actually helped me in my process of recovering my life.
>
> I have a five-year old daughter. Her name is Eve, and she has just
> started kindergarten. She looks at life through very impressionable
> eyes and I made it my life\'s mission to be a healthy role model for
> her as I made it through the past two years. I wanted her to see that
> she had a choice in the way that she dealt with adversity, and choice
> is the operative word in that. Women who choose or need breast
> implants for any reason should be allowed to make an informed decision
> on the type of implant they choose. Silicone breast implants are
> available in many other countries outside of the United States but no
> woman should be forced to leave the country in order to satisfy her
> choice.
>
> Just as I teach Eve she can choose the way that she lives her life, I
> am asking you to please let American women have the choice of what
> implants to put into their own bodies. They have a right to make the
> recovery of their lives the best that it can possibly be. Thank you
> very much.
>
> DR. PLETSCH: Dr. Whalen, advisory panel, my name is Dr. Marie Pletsch.
> I am a board-certified plastic surgeon and have been in private
> practice in Santa Cruz and Monterey, California for the last 34 years.
> I took care of my own expenses to come to this meeting. My only
> connection with Inamed is that I have been an investigator in their
> core study for silicone gel breast implants, and I have also been an
> investigator for some of their competitors. I am not a witness nor a
> party in a pending lawsuit regrading these implants.
>
> I am grateful for having had silicone implants available to me when I
> was diagnosed with breast cancer in 1988 and underwent bilateral
> mastectomies and reconstruction. The original implants were replaced
> in 1991, using McGhan, now Inamed, anatomic or shaped implants, not
> because there was anything wrong with the first set of implants but
> because I was undergoing a revision of my reconstruction and I
> requested changing of the implants for a larger size and more
> anatomical shape. Please note, reoperation is not necessarily an
> indication that there is something wrong with the implant.
>
> I may be the only presenter before this panel that can boast a unique
> combination of having implanted approximately 1,000 women with
> silicone gel breast implants and over 200 of these have been since the
> restrictions in 1992. In addition to that, I have implanted
> approximately 500 women with saline implants. Added to this, I am a
> female plastic surgeon with implants myself and this gives me a more
> intimate view of the situation both from a patient\'s and a surgeon\'s
> viewpoint.
>
> When asked by my patients and the press, are these implants safe? I
> confidently answer yes. If they were not safe, do you believe that I
> would keep these implants and would not have them removed, and why
> would I continue to use them? I have implanted silicone gel breast
> implants since the mid-1960s and since 1992 I have used them every
> time the FDA protocol allows them to be used.
>
> What I believe is a tragedy is the harm that has come to American
> women in many ways because of these restrictions. I will list several
> of them. First, many women were falsely frightened about effects of
> silicone implants and many had unnecessary surgery to remove them.
> Some did not replace them with anything and were consequently
> deformed, causing physical and psychological damage. Others replaced
> them with saline implants, only to find out saline wrinkled and
> sometimes deflated. Some of these women then requested replacement
> implants with silicone again.
>
> Secondly, some women with various diseases have erroneously been led
> to believe that their illnesses were due to breast implants when, in
> fact, they were due to other causes.
>
> Thirdly, women who could afford it left the country to go to other
> countries that allow these implants.
>
> DR. WHALEN: Doctor, you need to conclude, please.
>
> DR. PLETSCH: American women apparently do not have the right to choose
> the type of implants. The rest of the world uses these 95 percent of
> the time. I was in Germany in 1998 at the ECWON meeting and they were
> shocked and horrified by the actions of the FDA. I ask you to look at
> the scientific facts and to encourage the FDA to lift the
> restrictions. Thank you.
>
> DR. HAECK: My name is Phil Haeck. I am a board-certified plastic
> surgeon, practicing in Seattle, Washington. I have been in practice
> for 18 years and I am a plastic surgeon without implants.
>
> I am the editor of [Plastic Surgery News]{.underline}, the monthly
> news magazine of the American Society of Plastic Surgeons. This
> organization has paid my travel expenses to be here today. I have no
> financial interest in any device manufacture or their subsidiaries of
> affiliates. Breast surgery accounts for approximately 20 percent of my
> practice.
>
> I am going to address the issue of reoperation in breast augmentation
> surgery since it has not been given an adequate airing here from the
> standpoint of the surgeon. Plastic surgeons dealing with the
> challenges of a practice in breast surgery are not at all surprised at
> the reoperation rates reported here yesterday.
>
> So, this is what I tell my patients who have decided to undergo a
> breast augmentation procedure: You are about to begin on a road to
> satisfaction. To get there may mean more than just the one surgery,
> the one you and I have planned.
>
> There are only two reasons for immediately going back to the operating
> room in the first few days after breast surgery. Severe bleeding is
> extremely rare but if it is severe and results in a collection of
> blood around the implant a hematoma may occur. Most of those will need
> to be drained in a short second operation.
>
> Likewise, an infection around the implant will need a short operation
> to drain the liquids off and possibly remove the implant for a week or
> more. It can then safely be replaced. Both of these are extremely rare
> problems that happen in less than one percent of cases.
>
> All other reasons for reoperation happen later, over the time period
> of three to twelve months after the operation, or rarely, even years
> later when an implant fails.
>
> Capsular contracture can and does occur. You should expect that it
> could occur anywhere from three to ten percent of my patients, but if
> it happens to you and you need reoperation, then it will feel more
> like it is 100 percent, and it may be painful both before and after
> reoperation.
>
> After this, the reasons relate to just two categories: My skills in
> correcting your preexisting asymmetry of your breasts, or the way in
> which your body healed or didn\'t heal correctly after the surgery.
>
> It is a rare patient that arrives in my office requesting breast
> surgery who feels she has a perfect match between her left and right
> breasts. Many have quite a different appearance from side to side. You
> are probably expecting perfection and it is my intention to give that
> to you, but there is always the chance that what seemed like adequate
> correction at the time of surgery may not prove later to be to your or
> my liking.
>
> I tend to prefer to err on the conservative side since that is always
> easier to adjust later. Complex intraoperative decisions about the
> modification of the infra-mammary fold, release of the pectoral
> muscle, re-positioning of a drooping nipple, and differential sizing
> of the implants may not turn out in the healing phase to have been
> exactly what was needed to provide a mirror image.
>
> The more extreme the preoperative differences from side to side, the
> greater the likelihood that a second operation will be needed.
> Nevertheless, these secondary surgeries are not drastic operations and
> frequently can be performed with local anesthesia. The patient usually
> returns to her normal routine within 48 hours or less, and I do not
> charge the patient a professional fee for these surgeries.
>
> The difficulty here, in my opinion, is that we look at any reoperation
> as a statistic. But breast augmentation surgery is a unique situation
> in the realm of all surgical procedures. Lumping and minor scar
> revision go into data that also holds statistics for implant failures
> and reoperations for ruptures\--
>
> DR. WHALEN: Doctor, you need to conclude.
>
> DR. HAECK: \--which gives a dangerously over-jaded look into this
> situation. We are in a unique predicament here that does not have the
> morbidity precedent in another area of surgery. As long as both the
> surgeon and the patient expect perfection from this operation, there
> will always be another patient on tomorrow\'s surgery schedule
> somewhere who is not undergoing her first surgery. Thank you.
>
> MS. SCHAMBECK: Good morning. My name is Susan Schambeck. I am the
> recipient of gel implants made by Inamed Corporation. Inamed has
> provided my travel and lodging expenses here.
>
> I would like to share my story with the panel. I decided to have
> breast surgery in 1995. I feel that my decision was well thought out,
> and my research led me to Dr. Pletsch, in Santa Cruz, California. I
> was 36 years old and the mother of a two-year old son, Norton. I had
> nursed him for a little more than a year and felt confident that
> giving him that kind of healthy start in life was a gift. I felt
> complete with having one child to leave my legacy to and it was time
> to give myself a gift. Since I have always been athletic and outgoing,
> I saw an opportunity to get my body back into balance. Dr. Pletsch was
> very helpful in that process. I knew that I was a good candidate for
> breast augmentation. I knew that it would be a significant boost for
> my self-esteem and personal image. These are the best years of my life
> and it is very important to have choices.
>
> I had my surgery in February of 1995. My only choices were to have
> saline implants or live with the effects of nursing my son. I chose
> the saline implants. The end result of that procedure was that I had
> severely wrinkled implants that looked and felt unnatural. In July of
> 1999 one of the implants ruptured. After discussing my options with
> Dr. Pletsch and my family, I was able to choose an upgrade to silicone
> gel implants.
>
> I realized the difference in the look and feel of the silicone gel
> immediately. It was far superior to the saline. I am convinced that if
> I had had a choice, I would have chosen the silicone gel over the
> saline. I didn\'t like the feeling of wrinkled water bags in my body.
> They caused me to feel self-conscious. With the silicone gel implants
> I feel that I have a very balanced and natural shape. Nothing about
> the silicone gel feels unnatural. The consistency is as close to the
> real thing as it gets and I am very happy with the result.
>
> I sincerely wish that every woman who is considering an enhancement or
> reconstructive surgery could some day have real choices from the
> beginning of her journey. I personally feel honored to assist in that
> process. It doesn\'t seem fair to me to require two surgeries in order
> to achieve a choice. I am very happy and healthy with the gel
> implants. It is difficult for me to reflect back on the emotional and
> financial burden that I have survived simply because I didn\'t have a
> choice in the beginning. Please allow us to have choices. Thank you. I
> have copies for the panel.
>
> DR. WHALEN: Please go ahead.
>
> MS. GODOY: Yes, my name is Julie Godoy. I am a U.S. citizen, married
> to a Norwegian, living in Norway. I paid my own expenses. I am not a
> professional speaker.
>
> DR. WHALEN: Ma\'am, and for everyone, the microphones are very
> directional. So, if everybody, when they come up, would just make sure
> that they are speaking directly into the mike, it would help us.
>
> MS. GODOY: Shall I repeat?
>
> DR. WHALEN: You can just continue; that is fine.
>
> MS. GODOY: Someone is going to read by speech, Jama Rosanna. I am
> having some eye problems.
>
> MS. ROSANNA: This is Julie Godoy. She is a citizen, married to a
> Norwegian, currently living in Norway. She is a breast cancer patient,
> implanted with silicone breast implants in 1980. Immediately following
> her surgery, she suffered from an adverse reaction from the implants.
> Monday morning, on CBS the President of the American Plastic Surgeons
> Society stated that the implant seeking approval has been used in
> Europe for ten years. Tuesday, we were told that the implant has been
> used for 25 years in the U.S.A. Obviously they are speaking about the
> old implants. What is new?
>
> Europe has united their efforts to protecting their citizens against
> adverse and debilitated effects of failed breast prostheses on their
> women and children. I flew here to see what new developments are
> pending with regards to the implant problem, only to find that there
> is no new device.
>
> There is nothing more than a facade\--the same device, old product,
> new name. I am having difficulty reading, sorry. Recently, Inamed
> Mentor and McGhan breast implant manufacturers submitted new patents
> on breast implants, outer breast prostheses, shells and breast implant
> fillers. In their own words, each patent identifies the failure of the
> design of the silicone sacs, migration of silicone oil outside of the
> implant and the toxicity of the silicone oil to human tissue, along
> with the medical literature documenting the failure of the prior
> devices. In fact, all 73 breast implants from 1958 to 2003 have
> identified in great detail, with medical documentation, the adverse
> severe problems. All previous breast implant patents document the high
> failure rate.
>
> For an example, in 1995 the Payman second breast Implant patent
> claimed that the Avalon breast prosthesis was porous so that it would
> absorb blood and other body fluids and become invaded by blood vessels
> and living body tissue, with the result that a sponge implant
> surrounding the body tissue became so interwoven as to permanently
> retain the position in the body. Also, because of the infiltration of
> germs directly into the sponge, the fibers became more absorbent.
>
> Dr. Frank Gerro, in 1987, wrote in detail, severe adverse reactions to
> silicone breast implants identified human adjuvant disease comparing a
> ruptured implant to free silicone injections. Additionally, escape of
> the silicone gel from the envelope of the prosthesis is associated
> with other adverse consequences in satelliting of the gel into various
> parts of the soft tissue around the prosthesis pocket down or into the
> arm.
>
> Recent data also suggests that the risk of infection in the
> surrounding prosthesis is increased following its rupture and free
> silicone gel in the prosthetic pocket. He was the first to also
> identify death from a breast implant.
>
> In 2001, McGhan Medical Corporation filed for a patent for a filler
> material for a surgically implanted prosthesis such as breast
> implants\--
>
> DR. WHALEN: You need to draw to a conclusion, please.
>
> MS. ROSANNA: \--whiiich have conventionally used silicone gel.
> Moreover, adverse consequences have recently become associated with
> silicone implants because it has been discovered that the silicone oil
> can migrate through the implant shell, and silicone oil is not
> biocompatible with the other human tissue. Therefore, the use of
> silicone-based filler materials have been discontinued in the
> industry. Those are their words.
>
> Dr. David Kessler discovered the addictive\--
>
> DR. WHALEN: Excuse me, you will need to end your comments, please. You
> are over time.
>
> MS. ROSANNA: Well, can I just finish the sentence?
>
> DR. WHALEN: The very last sentence.
>
> MS. ROSANNA: Dr. David Kessler found in the patents the addictive
> tobacco through the manufacturers\' patents. To date, we need to know
> what implant we are dealing with.
>
> DR. WHALEN: I just need to reemphasize to everybody, in view of the
> first few speakers, we very much want to hear everybody who signed up.
> Over the two days, we have about 110 such individuals. The only way we
> can do that within the time constraints that I think have generously
> been set up for the public testimony, is to have everybody fulfill the
> time requirements that have been set for them. So, please, if we could
> do so? Thank you.
>
> MS. FEUSTEL Good morning. I am Holly Feustel. I am receiving no
> compensation for speaking here today.
>
> Just over two years ago I had both of my breasts removed during simple
> mastectomies. While the initial surgery and reconstruction were
> terrifying, the process was not new to me. At the time of my surgery,
> two of my older sisters had already had the procedure. Unfortunately,
> my family is intimately familiar with breast cancer. The disease has
> taken my maternal grandmother, my mother, her sister and my cousin.
>
> While I have spent the majority of my childhood watching women die of
> breast cancer, my mother\'s and cousin\'s death have had the greatest
> impact on me. I spent years of my childhood watching my mother
> experience the slow, painful death of fighting breast cancer. When she
> died she was just 42 years old and I was nine. I spent a year of my
> adult life watching my cousin and her battle with breast cancer. At
> the time of her death she was just 36 years old and I had turned 21.
>
> You may be thinking that while my experiences are tragic, how are they
> relevant to you? Well, my experiences are relevant because they are
> about choice. At the time I had my mastectomies I was not diagnosed
> with breast cancer. It was an elective surgery, my choice as the
> result of watching others die of breast cancer and discovering that my
> two older sisters and I possess the genetic mutation BRCA1.
>
> When faced with the results of my genetic testing, I chose to have a
> mastectomy. I chose to have reconstruction following and I chose
> silicone breast implants. I assure you that a lot of thought went into
> each of these decisions. Perhaps the toughest choice was silicone
> versus saline implants. Fortunately, when the time came to make that
> choice I had a wonderful plastic surgeon, years of sound research and
> the personal experience gained from two older sisters who already had
> the procedure. One chose saline implants and the other chose silicone.
>
> I firmly believe that choosing silicone implants was the right
> decision for me. I have no medical problems from my implants and I am
> pleased with the natural feel and shape of my breasts.
>
> I have come here today at great personal expense. My husband serves
> our country in the U.S. Army and is currently away. I have four school
> age children and I have traveled a great distance to be here for just
> three minutes. My motivations are simple and selfless. I want other
> women and my four young daughters to have the same options and choices
> that I had, and I thank you for your time.
>
> DR. ZOOK: Good morning. I am Elvin Zook. I have been Professor of
> Surgery and Chairman of Plastic Surgery at Southern Illinois
> University School of Medicine for the past 30 years. I am
> board-certified in plastic surgery. I have no affiliations or
> conflicts of interest with the implant device manufacturers, and I
> have paid my own travel expenses to present at this hearing.
>
> In my practice of plastic surgery, I use breast implants in performing
> both breast reconstruction and breast augmentation surgery, and I
> derive a portion of my income from this type of surgery.
>
> Prior to the 1992 decision by the FDA, I actively used silicone gel
> breast implants for cosmetic augmentation of the breast, and since
> then I have used them for breast reconstruction, as permitted by the
> FDA under clinical studies.
>
> One of the sharpest criticisms leveled at surgeons during the 1991 and
> 1992 FDA hearings, and still today, is the perceived lack of adequate
> information given to the women before surgery regarding the safety of
> silicone gel breast implants.
>
> When using silicone gel breast implants in my own practice, I make
> every effort to inform patients about what is known about the safety
> of the implants, as well as the risks of potential complications that
> could occur. I have found it is helpful to have sample implants
> available for women to see and feel during their consultation. I
> believe this effort has been responsible for my not being threatened
> with any breast-related lawsuits. I personally think patients should
> be educated as fully as possible on surgical procedures and materials.
> They can then be free to make their own choice for surgery.
>
> Nearly one year ago I was asked by the American Society of Plastic
> Surgeons to chair a team to develop a patient information document to
> provide women with information on the risks and potential
> complications of silicone gel breast implant surgery. A number of
> patient information documents were studied before we created this
> document.
>
> The group worked diligently to create what is now an online brochure,
> which you have, covering what is known about silicone gel breast
> implants, expectations of breast implant surgery, risks and potential
> complications. Options for surgical placement of the implant are
> explained, as well as financial issues related to treatment of
> complications.
>
> The brochure includes color patient photos to visually illustrate some
> local complications. It is followed by a series of questions to
> evaluate understanding of the effectiveness of the information and its
> validation. We have tried to be comprehensive in our approach,
> recognizing that no procedure is totally without risk. In fact, we all
> could agree that nothing in life is totally without risk.
>
> We believe that women who read and understand this information and ask
> questions should be adequately educated to make their own choice. The
> brochure is available on the website of the American Society of
> Plastic Surgeons. It is available to members of the American Society
> of Plastic Surgeons with the recommendation that they use it to inform
> women about breast implant surgery. Thank you.
>
> MS. RAHN: Good morning. My name is Ruby Rahn. I received breast
> implants after being diagnosed with fibrocystic and micromastia
> disease. I have a similar story to many women who have made statements
> here. I got breast implants. After ten years I got very sick and once
> my implants were removed my health improved. When I got sick I wanted
> to find out what happened to me. I wanted to take responsibility for
> my health so it seemed reasonable to start to look for answers.
>
> I have spent the last decade trying to find answers. In my search I
> came across an advertisement for silicone in an issue of [Plastic and
> Reconstructive Surgery]{.underline} in which they talked about the
> wonders of silicone products. It showed pictures of breast implants
> and other medical devices made of silicone, and I wondered if other
> products had problems too and I discovered they do.
>
> Wear debris is a well-known and documented complication of a long list
> of medical devices, including breast implants. Wear debris occurs when
> implants age and degrade inside the body. As implants degrade they
> start to break down into small particles. They can travel to the
> lymphatic and vascular system into regional and distant parts of the
> body.
>
> To illustrate wear debris, I have included some photographs of breast
> implants that were removed from a friend of mine. One implant is still
> intact, while the other shell has broken down and disintegrated. These
> breast implants were removed en bloc where the implant and capsules
> were removed in one piece. While the scar capsules held much of the
> silicone gel inside the elastomer, the elastomer shell broke down
> inside the capsules and is no longer visible. What happened to it?
> Where did it go? And, what are the long-term effects of having an
> elastomer shell break down and migrate inside the body?
>
> When our immune system detects these particles, it responds by
> creating a chronic inflammatory foreign body reaction. A similar
> foreign body reaction can occur when a splinter gets in your hand or
> foot, only in this case the inflammation isn\'t visible on the outside
> of your skin; the process happens internally. Compound this reaction
> by having multiple implants over the period of 10 or 20 years and
> there is no question that you will develop a chronic inflammatory
> syndrome from countless splinter-like shell particles or wear debris.
>
> It is important to note that once the immune system becomes
> chronically activated, it leads to an ever-increasing attempt to
> destroy a foreign object that cannot be destroyed by the weapons our
> immunity has in its arsenal. Our immune system is designed for
> destroying biological entities, not indigestible, man-made chemical
> composites like silicone elastomer. In an attempt and failure to
> destroy these particles, our immune system chronically activates
> macrophages that produce destructive cytokines. Cytokines and the
> chemical cascade they produce are implicated in a long list of serious
> health concerns, including depression, and may be the leading reason
> why so many women who have had breast implants have committed suicide.
>
> I strongly urge this committee to recommend to the Food and Drug
> Administration to further require long-term studies to investigate
> whether a cellular response to particulate debris is causing the
> health problems that hundreds of thousands of women, who have already
> had breast implants, are currently experiencing. I think those are
> important questions to ask and understand before making breast
> implants available.
>
> Thank you for giving me this opportunity to make a statement.
>
> DR. WHALEN: Ma\'am, before you leave the podium, are you also going to
> be reading a subsequent statement?
>
> MS. RAHN: Yes, I am.
>
> DR. WHALEN: Do you have that with you now?
>
> MS. RAHN: No.
>
> DR. WHALEN: Okay, fine.
>
> MS. RUDICK: Good morning. My name is Nicole Rudick, and I am reading
> testimony for Donna Sims because she was too sick to be here today.
>
> My life with and without silicone breast implants: I am a 47-year old
> woman with no conflicts of interest. I had silicone breast implants
> put in, in 1983. In 1998, 15 years after implantation, I felt that my
> breasts were getting hard and painful so I had a mammogram done both
> in 1999 and 2001. Both mammograms indicated very dense, fibroglandular
> breast tissue present. The mammograms were so painful, they hurt so
> bad that if my breasts weren\'t stuck in the machine I would have been
> on my knees.
>
> I knew then that there was something really wrong with my implants,
> and I tried in every way I know how to find someone who believed me.
> Finally, I found a plastic surgeon who is very reputable and took my
> problem seriously. My plastic surgeon said that I had capsular
> contracture, grade IV, and I needed to get my implants removed as soon
> as possible.
>
> This is where the real problem starts. My husband and I live on a low
> fixed income and I have no insurance. We tried everything to get the
> money together for my surgery. Finally my family came through with the
> money I needed for explantation.
>
> The surgery was scheduled for New Year\'s Eve, 2001. The surgery was
> very painful and I was slow to heal. The surgeon said that both
> implants were completely ruptured. I had drains in for over a week.
>
> In October, 2002, ten months after explantation, I found two lumps in
> my left breast. They were very painful and growing larger every week.
> Again, I had to try to find the money before yet another surgery and,
> again, my family had to come up with the money to pay for my surgery.
>
> I had surgery in October, 2002. The hard lumps turned out to be left
> over silicone from my explant surgery that had migrated throughout my
> breast. Since then I have found two more lumps on my right side. I
> can\'t afford another surgery. I don\'t have any insurance and my
> husband and I are so far in debt I don\'t think we will ever see the
> daylight again.
>
> With my having silicone breast implants, I have not been able to find
> an insurance company that will insure me because of my implants. I
> have tried to get help from my state government welfare program but I
> have been turned down several times because my husband and I own our
> own home.
>
> My hair has been falling out. I have skin problems, dental problems
> and vision problems. My entire body aches with pain and inflammation
> of my joints and muscles. My memory is awful. I have been diagnosed
> with fibromyalgia, polyarthritis, Sjogren\'s syndrome and silica. I
> just don\'t know what is next. The bills for all these tests just keep
> climbing and so do the illnesses. Will this ever end?
>
> DR. BECKER: Good morning. My name is Dr. Karn Becker. I am the
> president of a scientific consulting firm here, in Washington. I have
> 15 years of experience in the development and clinical evaluation of
> innovative medical devices. I have not been compensated for my
> professional time or expenses today.
>
> I came here because I was, as a woman and a scientist, alarmed at the
> misinformation being put forward in the popular press regarding these
> devices.
>
> Over the years I have contributed to the design and approval of many
> original PMAs and, in 1991, I prepared one of the breast implant PMAs
> considered by this committee. My knowledge of the science and clinical
> experience with breast implants is extensive. I have spent
> approximately 20 percent of my professional time over the last 13
> years on one breast implant project or another. As a result, I have
> personally reviewed thousands of studies\--chemistry, manufacturing,
> preclinical, clinical and epidemiology.
>
> The past decade of research on this device has been productive and has
> considerably narrowed the focus of our questions regarding the
> performance or silicone gel-filled breast implants for reconstruction
> and augmentation. Clearly, the product can be reliably and
> consistently manufactured. The materials of which this device is
> comprised are biocompatible. The short-term complication rates at two
> and three years have been reliably estimated. The concern that these
> devices may pose a risk of long-term systemic toxicity or reproductive
> toxicity has been resolved by affirmative evidence from numerous
> well-controlled studies. This data and information comprises valid
> scientific evidence sufficient to provide a reasonable assurance of
> safety and effectiveness for this device when marketed with adequate
> instructions for use.
>
> The premarketing clinical data provided in this application you are
> considering today, with three-year follow-up, is more extensive than
> that typically required for an implanted device.
>
> The data on the long-term performance of this device is, however,
> limited. Premarketing studies do not provide data on rare or uncommon
> complications, nor on the long-term performance of implanted devices.
> This committee is aware that questions of long-term performance are
> evaluated in the postmarketing setting. Postmarketing studies for
> innovative implanted devices, although not required, provide the
> opportunity to study the performance of the device in a broader
> patient population, in larger numbers of patients, and over a longer
> period of time. This information is essential for continued safe use
> and for continued product improvement. For the silicone gel-filled
> breast implants under consideration today, the sponsor has proposed
> postmarketing research to assess long-term performance.
>
> I respectfully submit that this committee consider the approval of
> this product be accompanied by a risk management program to include
> three elements, number one, a mandatory informed consent; number two,
> a postmarketing study to provide clinical data on long-term
> performance, in particular, the incidence and prevalence of
> complications and device failure over time.
>
> DR. WHALEN: Conclude, please, doctor.
>
> DR. BECKER: And, third, a device retrieval program to study the
> changes that occur in the product itself over time, and systematically
> investigate the failure modes for this device. Thank you for the
> opportunity to comment.
>
> PROF. DUBLER: Dr. Whalen, may I pose a question for a moment?
>
> DR. WHALEN: Yes, Prof. Dubler?
>
> PROF. DUBLER: We have heard that there is a new application and new
> patents that have been submitted by the sponsor. In your work, have
> you worked on these patent applications?
>
> DR. BECKER: I have worked on some but I don\'t know the ones that you
> are referring to, not for this sponsor.
>
> PROF. DUBLER: We have been told by the sponsor that the product under
> consideration by this panel is precisely the same product that was
> discussed in \'91 and \'92. But there is also the implication that a
> new product is being developed. Have you worked on this new product?
>
> DR. BECKER: With this particular PMA, I am only familiar with the
> publicly available information. So, I couldn\'t say, myself, whether
> it is exactly the same as the submission made in 1991.
>
> PROF. DUBLER: Thank you.
>
> MS. RAHN: My name is Ruby Rahn and I am reading for Lale Goddard, who
> is too sick to be here today.
>
> My name is Lale Goddard and I have no financial ties with anyone.
>
> In 1997, my breasts were augmented with silicone gel-filled breast
> implants. In the mid-1980s, I started having joint pains and
> depression with thoughts of suicide. I was diagnosed with bipolar
> disorder.
>
> In 1987, my rheumatologist diagnosed me with definite asymmetrical
> inflammatory arthritis or possible rheumatoid arthritis with atypical
> presentation, with poly arthralgia but with little joint swelling. My
> bone scans showed signs of inflammation and my bilateral hand and
> wrist x-rays showed non-specific bone irregularities.
>
> In 1988, my bleeding sediment rate went up to 85 and X-rays of my
> hands and feet showed multiple bone erosions. I was also diagnosed
> with fibromyalgia, anemia and seropositive rheumatoid arthritis.
>
> In 1989 I had my breast implants removed and both implants had
> ruptured and the elastomer shells had deteriorated, and my left breast
> was deformed. I have joint contractures, ligament ruptures and severe
> osteoporosis and my right hand is deformed.
>
> Silicone elastomer used in solid or bulk form is biocompatible.
> However, transformation of silicone elastomer of an intact silicone
> gel-filled breast implant, into particulate debris and the capacity of
> the particles to induce excessive inflammatory cytokine synthesis by
> macrophages and other cells, could cause particle-activated arthritis
> that mimics rheumatoid arthritis. Unlike silicones, inflammatory and
> anti-inflammatory cytokines are biologically active proteins.
>
> Orthopedic surgeons refer to bone destruction due to macrophage
> activation by particles as a cellular response or particle disease.
> They do not refer to it as immune response or autoimmune disease.
> Scientific literature states that elevated inflammatory cytokines can
> contribute to the induction of depression and depression can lead to
> suicide.
>
> The FDA has recognized, [in vivo]{.underline} and [in
> vitro]{.underline}, testing standards of biological responses to
> particles and both standards state the following: It is well
> recognized that the biological responses to particles could be
> different from those to solid materials. The interaction of the
> particles with cells in the tissue, notably macrophages and other
> phagocytic cells, is the key to the final biological response.
>
> Please recommend to the FDA to require Inamed Corporation to do
> preclinical testing for biological responses to elastomer particles,
> less than 10 microns in size, prior to the approval of the PMA because
> it is relevant to women\'s health.
>
> If you have any questions, call me anytime at area code 916.444.1967
> or send me an e-mail at lalegoddard@msn.com. For a copy of my
> statement, go to my website at www.lalegoddard.com. Thank you very
> much for your time.
>
> MS. CLARE: Hello, my name is Erica Clare. I am reading for Teresa
> Hamilton, who is too ill to be here today.
>
> My name is Teresa Hamilton, and I am from California. I have no
> conflicts of interest.
>
> In 1986 I was diagnosed with breast cancer at the age of 29. My left
> breast was removed because of cancer, and a month later my right
> breast was removed since I was told I had a one in three chance of
> getting cancer in that breast prior to menopause.
>
> After radiation treatments, I had expanders put in to stretch my skin
> out so I could have implants. These were removed and temporary
> implants were put in a few months later, in 1987. I still had problems
> with scar tissue so stronger implants, made by McGhan, now Inamed,
> were used to replace the other implants. I looked and felt great for
> maybe two years.
>
> After that, I started to get allergies to nickel in jewelry and
> allergies to pollen and penicillin. I also had repeated yeast
> infections and seemed to get more and more colds. Being a single
> parent, it was getting harder to take care of my elementary
> school-aged daughter. She would have to stay at my parents\' house
> while I would try to recuperate.
>
> A few years later I noticed my right implant was getting harder. The
> infections and allergies seemed to get worse. Soon I was housebound
> and stayed that way for over five years. Still, I was told my implants
> were safe. By this time, my daughter was living with my parents most
> of the time since I was too sick to care for her.
>
> In 1999 I thought I had better have my implants removed. The left
> implant was weak but still intact. The right implant had dissolved
> completely, shell and all, into a gooey mess.
>
> I have since had a hysterectomy due to numerous fibroid tumors. I now
> have a lowered immune system, fibromyalgia, a low thyroid. I am
> constantly tired despite medication to help my fatigue, asthma, and
> foggy thinking. I am 45 years old now. I am slowly detoxing but I am
> still so ill I can\'t work except when I feel up to it, just a few
> hours a week. Consequently, my parents, who are in their 70s, are
> having to take care of me and pay for most of my medication bills and
> all of my living expenses.
>
> I was in the Dow Corning settlement but I have only seen \$725 for
> years of pain and suffering. My chest is scarred and disfigured as a
> result of all the surgeries I had to have to put in the implants in
> the first place. I don\'t believe that I will ever get the justice I
> deserve from all the pain, suffering and expenses that implants have
> caused me and my family.
>
> I have been cancer free for over 14 years now but I am still
> chronically ill from my silicone/saline implants and the right one
> rupturing and dissolving into my body. I never had any of these health
> problems before having breast implants, but I am sure that having
> these implants has not only lowered my immune system but will also
> lower my life expectancy as well. After all, they have been slowly
> killing me for years. Thanks for letting me speak my mind, Teresa
> Hamilton.
>
> MS. ROBINSON: Good morning, ladies and gentlemen. My name is Cheryl
> Robinson and I live in the Damascus, Maryland area. Due to the
> enormity of this issue and the fact that the safety and quality of
> women\'s lives are at stake, I am obligated and compelled to share my
> story.
>
> I have no financial relationships with Inamed or any other of its
> competitors. My decision to choose silicone augmentation was
> cosmetically motivated. Initially I was very happy with my decision.
> My breast implants enhanced my self-esteem and promoted my confidence.
>
> It wasn\'t until ten years after implantation when I began to suffer
> with complications. I noticed that my right breast began to harden,
> exhibiting signs of capsular contracture. I also began to notice my
> left breast was getting smaller. I now realize that was an early
> indication that my implants were leaking silicone from my chest into
> my bloodstream and tissues.
>
> Over the years I became very ill, presenting with a host of physical
> and neurological symptoms, for example, the inability to concentrate;
> profound confusion; and short-term memory impairment. Eventually it
> became impossible to resume my family responsibilities and I was
> unable to support our lifestyle, and had only my husband\'s salary and
> mounting medical bills. Keep in mind that before all of these symptoms
> surfaced I was very physically active; actually one of the few female
> jockeys in my early 20s and continuing to maintain my active lifestyle
> through middle age.
>
> When I was explanted both implants were found to be ruptured and had
> probably been so for a long time, though there is no way to predict
> exactly when the ruptures occurred. My implants were considerably
> lighter than when originally implanted and the silicone that couldn\'t
> be removed during my en bloc procedure is still migrating throughout
> my body.
>
> I have been diagnosed with fibromyalgia, chronic fatigue, Hashimoto\'s
> thyroiditis and autoimmune related thyroid disease, and degenerative
> disc disease. At the age of 49, I am left with the fears and
> uncertainties of what diseases or conditions may continue to surface.
> For me, there is no doubt had I not made the decision to be explanted,
> I would not be personally delivering this short speech to you today. I
> am absolutely, unequivocally sure that my implants were the direct
> cause of my declining health. Of course, I suffer with depression as I
> live my life in chronic pain and am forced to accept the fact that
> there is no proven or definitive way to rid my body of the silicone
> that has migrated from my chest, ravaging and polluting my body on a
> systemic level.
>
> The data being presented on behalf of Inamed to market silicone breast
> implants does not reflect the long-term studies that are necessary to
> assess the possible safety and health risks that these implants may
> impose. Silicone breast implants do not offer women a choice but,
> rather, offer women a chance to play Russian roulette with their
> health.
>
> I respectfully ask you, members of the panel, would you allow or
> encourage your loved one to be the recipient of such a ticking time
> bomb? I hope the answer to this question is a resounding no. Thank you
> for your time and attention.
>
> MS. DONNY: My name is Stephanie Donny. I am reading for Linda Dintino,
> who is too ill to be here this morning.
>
> My name is Linda Dintino. I had one set of silicone breast implants,
> implanted in 1980, at the age of 27, when my breasts were removed due
> to fibrocystic disease. Silicone breast implants were in my body for
> 13 years, until I was explanted in 1994.
>
> Within two months of implantation I developed migraine headaches.
> Every day of my life for the last 23 years I wake with a headache that
> does not go away. I was a healthy woman in 1980. I had two beautiful,
> healthy children without any problems. I was athletic even after
> implantation. I was a very active mother of two boys, a Cub Scout
> leader and a secretary of the PTA.
>
> In 1987 I was forced to give these activities up, along with enjoying
> my children growing up. You see, I was just too tired and hurt too
> badly to do these activities any longer. I could not lift my arms
> above my head, the pain was too great, and I had slowly been losing
> upper body strength for years. I literally had to sleep with pillows
> tucked in between my breasts while sleeping on my side because of the
> burning hot pain involved.
>
> When the implants were removed from my body, I learned that my right
> implant was ruptured. I was left with a big gaping hole in my right
> chest wall. My body would not heal properly. I walked around with this
> hole in my chest for four months. My scars were open on both sides and
> would not close. Even the drainage holes where the drainage tubes were
> took longer than they should have to heal. I dressed these holes in my
> body twice daily for four months, while green oozing slime came from
> them.
>
> I am only one woman in a sea of thousands, all experiencing the same
> problems, and the only common denominator between us is the fact that
> we all had silicone breast implants.
>
> Studies that are being touted as proving that implants are safe have
> been bought and paid for by the very manufacturers that produce them.
> These manufacturers are not studying what we have going on in our
> bodies, the very women that were affected.
>
> We need real research. We need for this panel to take a stand and
> demand that thorough research be done, not just a short-term study
> aimed at putting money in the pockets of the manufacturer. Thank you.
>
> MS. SMITH-MILES: Good morning. My name is Becky. I am from northern
> Michigan. I have not been paid or reimbursed, nor have any conflicts
> of interest.
>
> I had silicone implants put in over ten years ago. I developed
> capsular contracture within two years and had intense pain. I wanted
> to be more beautiful with implants. Instead, my breasts became
> scarred, hard and ugly. I hid my breasts from my husband. I could not
> jog, walk fast or jiggle my implants without experiencing intense
> pain.
>
> Within eight years I was diagnosed with a neurological disease. I went
> from being a very athletic, active person to being physically
> inactive. I was a registered nurse. I worked daily prior to my
> implants. I have had fatigue, aches, spasticity with numbness and
> tingling in my calves, toes and fingers. My headaches are severe and
> every day. I started to stumble while jogging. With the intense pain
> and general ugliness of my breasts, I became depressed.
>
> A mammogram confirmed I had ruptured. I don\'t know for how long. My
> skin developed rashes and reactions to different substances. I started
> to have blister-like eruptions on my fingers. These were intensely
> painful, with burning and itching. I would scratch, and scratch, and
> scratch until the top layer of my skin would come off. Then I found
> that if I used my teeth and bit into them, I could feel a little
> crystal on my tongue. As soon as I got that crystal out, it healed and
> it stopped burning and itching.
>
> My gynecologist noted my depression and he ordered the MRI which
> diagnosed me with an autoimmune neurological disease. My implants and
> capsules were removed. My histology has shown giant cell incursions
> around my capsule. My blood work has tested positive three times for
> ANA. I developed partial facial paralysis and extreme gait
> disturbances. I have had silicone leakage in my chest, in my axillary
> lymph nodes and down my arms.
>
> For the last five years I have been having silicone eruptions
> surgically removed and they keep popping up all over. My life since
> getting implants has changed totally and forever.
>
> I lost my job and became disabled. I suffer periods of being
> bed-ridden for days. I can no longer jog, ski, exercise or even walk
> without the assistance of a cane. I can\'t help my son\'s soccer team
> or his football team. I can\'t ride my horses any longer, which was
> one of my big passions. I can\'t shop or go for a walk in the
> woods\--that is totally out of the question, or even pick up my
> grandchildren.
>
> I have lost most of my friends and all of my social life activities. I
> beg you to think about my limited life when you make this important
> decision. Thank you for your time.
>
> MS. DOWD: Good morning, members of the panel. My name is Pam Dowd and
> I am reading the story of my friend, Myrl Jeffcoat, from Sacramento,
> California.
>
> Hello, my name is Myrl Jeffcoat, Sacramento, California. My purpose
> for writing this statement is to tell this panel a little of my
> experiences regarding silicone gel breast implants.
>
> On December 7, 1994 I was implanted with MgGhan 3M silicone implants.
> I was very pleased at that time with the cosmetic outcome. But in
> mid-1998 I began experiencing health issues that were diagnosed and
> tested for, subsequently being put on propranolol, a beta blocker, for
> severe daily headaches, gait problems, extremely low blood pressure
> and heart rhythm problems. I also had developed an involuntary head
> tremor. Propranolol has been a wonder drug in containing many of these
> symptoms but not the daily headaches, which I continue having to this
> date.
>
> Later that year I developed thyroid problems and was put on thyroxine,
> and I was diagnosed with cervical uterine cancer and was given a
> hysterectomy in early in 1989.
>
> In the early \'90s I began a severe bout with chronic fatigue and
> fibromyalgia. My hair began falling out and became thin. I still have
> fibromyalgia symptoms often and the persistent daily headaches. On my
> visits and testing with my medical professionals during the late \'80s
> and early \'90s implants were never mentioned as being a suspected
> cause of my health issues.
>
> In \'92 or \'93 I read articles written about my health symptoms and
> illnesses being associated with breast implants. The medical community
> simply doesn\'t want to go there with our illnesses with breast
> implant association. They continue to this day to be in total denial
> of it.
>
> In about 1994 I was seen by Dr. Eric Gershwin, of the University of
> California at Davis, and he classified me as a category B on the old
> global settlement grid. It has been approximately nine years now that
> myself and nearly 440,000 women in this country have been corralled in
> this travesty of justice, some of us having been paid pittances from
> what we were originally promised; others not being paid at all; and
> some that will never see a dime for the pain and suffering they have
> endured.
>
> Our medical bills, sent to the MDA, are being hidden in a shroud of
> secrecy while cloaked in an exemption of the Freedom of Information
> Act. Yet, in all of that the silicone manufacturers continue to
> believe they can turn a profit selling these harmful products to the
> women of this country and other areas of the globe.
>
> For 40 years there has been no FDA approval of these products. There
> has only been a long and endless trail of meaningless studies while
> manufacturers continue, with FDA\'s blessing, to put human life and
> health at risk. The reason for my comment here is to implore the FDA
> to perform the job the American taxpayers pay them to do. I request
> that they perform their own studies and tests on silicone implants and
> not rely on the biased studies of manufacturers who stand to gain
> financially while putting human beings at risk. Thank you for your
> time.
>
> MS. DONNELLY: Good morning. My name is Kathleen Witter, and I am going
> to be reading testimony from Elaine Donnelly, who is too ill to be
> here. She has no financial interest in Inamed, nor any other
> competitors, nor is being paid to submit her testimony.
>
> My name is Elaine Donnelly. I am 44 years of age, and I reside in
> Louisiana.
>
> I was augmented with silicone gel implants at the age of 19. I was a
> healthy young woman who worked effortlessly as a health and exercise
> counselor and attended a local university. I loved the look and feel
> of my implants and I felt, although expensive for me especially on a
> college student\'s budget, it was something I deserved and that I had
> earned.
>
> After my implantation I began to experience capsular contraction. I
> returned to my plastic surgeon and a revision was performed. Again
> within a few months, capsular contraction occurred but I didn\'t have
> any health problems.
>
> Nine years later I began having severe health problems that my doctors
> could not diagnose. They believed that I had some sort of autoimmune
> disease developing. I spent a total of 27 months in the hospital over
> five years, having tests performed and repeated, yet no treatment or
> cure could relieve the symptoms I was experiencing.
>
> In February, 1994 I suspected my implants were leaking since my
> breasts looked noticeably smaller each day. I was told to have a
> mammogram done to see if there were any abnormalities to my breasts.
> That is when I found out that both of my implants had ruptured.
>
> One week later I had my implants removed. Much of the gel was gone
> from each breast implant and cannot be retrieved from my chest cavity.
> Any breast tissue that was contaminated with the sticky, unstable gel
> had to be removed surgically. As a result, I lost all my breast tissue
> in both breasts.
>
> My breasts are now deformed in appearance, and I am not among those
> who are fortunate to have had their health restored after
> explantation. Perhaps because of all the silicone in my body, my
> health has continued to spiral out of control and I have become
> homebound. Many days I am to ill to even get out of bed.
>
> As a result of having been augmented with silicone gel breast
> implants, my health has been destroyed and my body has been deformed.
> It is imperative that breast implants be studied at least a decade,
> not only a few years. Most women who might have problems will not
> begin to show their problems for at least seven to ten years.
>
> In addition, since some women who might have problems will not be able
> to obtain health care through the private health care industry because
> many health insurers will not cover a woman with implants even if she
> is in fine health, they might become dependent on Medicaid and
> Medicare programs. That is why our government has successfully sued
> several breast implant manufacturers for tens of millions of dollars
> to reimburse Medicare for the cost of care of women who became ill
> because of their breast implants.
>
> I implore you to vote against the request made by Inamed to approve
> their silicone breast implant based on such a short research study. In
> addition, I have much faith that some day you will have safe implants
> and I look forward to that day. If we can put a man on the moon, we
> can put out a safe implant and women deserve that choice, but we will
> only have a safe implant once that implant has been studied thoroughly
> and researched for at least ten years. Thank you so much for your
> time.
>
> MS. HANSON: Good morning. My name is Georgiana Hanson and I am reading
> for Rogene Schorer, who can\'t be here today because she is too ill.
>
> My health took a downturn within weeks of getting silicone gel breast
> implants, beginning with chemical sensitivity. It wasn\'t until 15
> years later that I realized that my implants might have anything to do
> with my scleroderma, my fibromyalgia and my cognitive problems.
>
> Ten years after having my implants removed, most of my health problems
> have been reversed and, as long as I am mindful and follow a fairly
> strict health program, I feel well.
>
> I have been an activist in the implant issue from the time I attended
> my first support meeting. It was there that I watched a group of young
> mothers learn for the first time that the health problems their
> children were experiencing were shared by the children of other
> implanted women. That awful moment, seeing the shock, guilt and horror
> on the faces of those young mothers, has been my driving force since
> then.
>
> After all these years, I ask why is there still no definitive study on
> the effects of breast implants on unborn and nursing children. Over
> the years I have communicated with thousands of women looking for
> information and support. One thing we all have in common is a pattern
> of symptoms that are destroying our lives. These women are from all
> walks of life. They could be your daughters, your sisters, wives and
> mothers, maybe even your sweet little granddaughter some day.
>
> The women are often desperate. Some see suicide as the only solution.
> They are sick but don\'t understand why. They feel, as I did, that
> they are dying without knowing why. They are frequently in pain,
> experiencing cognitive problems, mood swings, allergies, digestive
> problems and neurological problems but the doctors can seldom define
> their illnesses. Many doctors, especially their implanting surgeons,
> have been rude and dismissive.
>
> In the meantime, women often lose their jobs, medical insurance,
> savings, and sometimes their home and family. Many of them end up
> struggling to survive on welfare and Medicaid. Of course, those
> numbers will increase if silicone gel implants are approved.
>
> The marking of breast implants usually targets young women, often
> before they have children, before they are mature enough to understand
> how much their decision could cost over their lifetime. The costs are
> not only in dollars, but in health, careers, insurance and
> relationships.
>
> Few women will visit the FDA\'s very informative website to learn
> about the risks before getting breast implants. This company has not
> proven that silicone gel implants are safe, and so they should not be
> approved. However, if women are allowed to use them as part of
> clinical trials, as has been the case for ten years, a third party
> should counsel them on all aspects of the study.
>
> In closing, each new generation of implants promises to be new and
> improved but, to date, all have failed to be safe in the long term.
> There is a huge population of women who have already received breast
> implants. Before subjecting more women to studies for new and improved
> implants, we need to study what has happened to those who already have
> them. This disaster has been going on too long. Do you have the
> fortitude to stop it? Thank you.
>
> DR. WHALEN: As the next speaker is coming up, just so everybody knows,
> each individual speaker has three minutes. People who speak for
> organizations have greater periods of time. For anybody who has yet to
> speak who is anticipating that they will have more than that amount of
> time\--that will be only if somebody else has yielded time to you. So,
> if you come up and you have more than three minutes, you could perhaps
> just tell us whose time has been yielded to you to allow you that
> extra amount of time. Thank you.
>
> MS. GOLDRICH: Good morning. My name is Sibyl Goldrich and I am
> speaking on behalf of Wanda Simison, who is too ill to attend.
>
> I was diagnosed with a precancerous tumor in 1987 and, after a
> mastectomy, I used McGhan, now Inamed, gel implants.
>
> I developed aches and pains, eye problems and a general feeling of
> unwellness within two years, and was diagnosed with fibromyalgia in
> 1992.
>
> I saw over 60 medical doctors in North Carolina, Florida, Texas,
> Connecticut and New Jersey who could not give me a definite diagnosis
> for my illness.
>
> I became blind in my left eye and my health rapidly deteriorated. I
> have been bedridden with dozens of symptoms since June of 1993. I have
> been diagnosed with MS and lupus. I was hospitalized for ten days at
> St. Mary\'s Hospital, in Connecticut, where they found lesions on
> brain and spinal cord, and an ANA of 180.
>
> I was then transferred to a different hospital where I spent another
> 53 days getting stabilized and prepared for explantation. My implants
> were removed in 1993, and the right implant was leaking. I was
> hospitalized for a total of 180 days within a one-year period due to
> illness and toxicity from breast implants. I was explanted on my
> birthday, September 22, 1993, and felt better within 24 hours.
>
> I spent \$300,000 on treatments not covered by insurance, and
> relocation to Houston, Texas for 18 months. Gradually my health has
> improved and most of my blood work is back to normal. I have not
> developed new lesions on brain or spinal cord. My brain fog improved
> greatly after explantation, but depression is still a huge factor. I
> can\'t handle stress of any kind; my diagnosis of fibromyalgia was
> taken away.
>
> It is the FDA\'s job to approve medical implants that are safe and
> effective. I understand that cancer patients need some form of
> reconstruction, but it should be safe, not almost safe.
>
> Meanwhile, the United States Department of Health and Human Services
> is suing breast implant manufacturers for Medicare costs of ill breast
> implanted women. Where is the logic? What information that the company
> provided would convince that breast implants are now safe?
>
> Wanda has asked that I take the remaining time that she has. Last
> night there were a few questions that came up about gel migration and
> I would like to read to you from the panel memorandum, page 37: Cases
> of distant migration of gel to breast axillary lymph nodes, abdomen,
> groin, arms and fingers have been reported, some with serious
> consequences and deformities, for example, extensive migratory
> granuloma, formation of contracture, and scarring from gel extrusion
> and ulcerations described as a result of gel migration.
>
> Inamed also reported on the results of a physician survey in which
> five cases of migration were reported out of 114. I just wanted to
> point out the location of that to you.
>
> I also wanted to mention to you that this is really a matter of common
> sense. We are asking for ten years of study. Breast implants are
> available. Women can get them. Nobody is being denied the product. But
> we are being denied the appropriate studies to prove that this product
> is safe. I implore you to give us the ten years. This company will
> survive. They are selling their implants. Please, ten years of study.
> Thank you.
>
> MS. ERICKSON: Good morning. My name is Jan Erickson. I have been asked
> to present the testimony of Lois Travis, who is not able to be with us
> today. Lois lives in Houston, Texas.
>
> Her testimony reads, I was happily married and the mother of two
> beautiful girls, working part-time in the hospital as a registered
> nurse. After mastectomies in 1965 and 1971, I was encouraged to have
> reconstruction surgery will silicone implants.
>
> Four months after implantation I began having vision problems and was
> told that I had cerebral edema, cause unknown. My physical strength
> and endurance declined and I could not continue my active lifestyle of
> cross-country skiing, mountain hiking and tennis because of muscle
> problems. I did try to play tennis but it was difficult because of
> muscles cramping up and shortness of breath, and I would have to stop
> the game to catch my breath.
>
> In 1976, a rheumatoid workup was done and the results mentioned
> possible early connective tissue disease. I lost half my hair and was
> told I would possibly have to wear a wig. I also lost some of my
> smaller nails and my entire body peeled. To this day, I have very thin
> hair.
>
> The implants were changing and I would notice slight differences in
> the shape and then tightening around them that started to cause
> limitations in my reach and range of motion in my arms. If I reached
> too high it was a sharp, burning pain and if I lifted something, like
> patients, it was sore for days. The contractures around the implants
> became very hard, painful, asymmetrical and distressing to me,
> especially when trying to choose clothing.
>
> In 1987, because of the pain and limitations, I sought medical advice
> and was told I needed to have the implants removed and replaced. I
> foolishly agreed to be re-implanted with double-lumen implants. After
> surgery, I was told that the ones that were removed were taken out in
> pieces because they had ruptured.
>
> I later suffered suicidal thoughts and was hospitalized. I was
> dysfunctional, mentally dull, unable to care for my business affairs
> and unable to read and comprehend what I had read. I still have
> difficulty following instructions, reading and writing my thoughts.
>
> In 1994, I was explanted after seeing a rheumatologist. If I had known
> the damage silicone would cause to my body I would never have agreed
> to have the first ones put in, let alone the second ones.
>
> I am somewhat better since my second explant but I am still plagued
> with muscle pains, headaches, depression, burning pain in my hands and
> feet, stabbing pains in the deep muscles of my legs, arms and hips and
> last, but very important, severe chemical sensitivity. If I start to
> enter an elevator and it has just been cleaned it triggers my asthma.
> Strong odors and most perfumes will trigger an asthma attack. I must
> have my inhaler with me at all times.
>
> Now I know that there was not sufficient research done to back the
> claims of safety of silicone breast implants, and the new Inamed
> research shows that there is still not enough research to prove that
> they are safe for the long term. I hope my story helps you understand
> what those statistics mean; what it is like to live with breast pain
> and pain throughout your entire body; what it is like to have your
> quality of life decline year after year.
>
> Thank you for your attention, and I hope you will give great thought
> to our testimonies before you allow other women to possibly be
> burdened with this kind of history. It is no fun.
>
> Additionally, I would like to\--
>
> DR. WHALEN: You need to conclude.
>
> MS. ERICKSON: Excuse me?
>
> DR. WHALEN: You need to conclude, please.
>
> MS. ERICKSON: All right. I am also handing a letter over to the
> members of the panel that is co-signed by a number of national
> organizations.
>
> MS. COOK: My name is Jennifer Cook and I am here on behalf of Deborah
> Guillory.
>
> My name is Deborah Guillory and I had silicone gel implants inserted
> into my body at the age of 19. I was fine at first, but years later I
> could no longer walk a straight line and my concentration and memory
> were very impaired. I also suffered from fibromyalgia-type pain.
>
> I had the implants removed in March of 1992, and at that time the left
> implant was only half the size of the right implant, half the size it
> had originally been. This meant that a great deal of leakage had
> occurred over the 22-year period that I had my implants.
>
> I am glad to say that my ability to think and concentrate has improved
> after the implants were removed and I can now walk in a straight line.
>
> I have had to take antidepressants since 1992 because of low-grade
> depression, which is consistent with the three recently published
> studies of high levels of suicide among women with implants. A
> forensics pathologist found that I have large levels of platinum in my
> body. The pathologist explained that this platinum was contained in
> the silicone gel implants. I still experience fibromyalgia-type pains,
> like the women in the FDA\'s study of leaking implants, and I have
> been disabled and unable to work in ten years.
>
> The silicone implants with the thicker gel were not expected to ever
> leak. Current implants are made with thinner gel. But perhaps most
> important, you can\'t tell what will happen to someone\'s health until
> at least ten years later.
>
> I am now going through a divorce, and attribute this largely to the
> fact that I am unable to lead a life of normal activity level and my
> husband would no longer tolerate this deficiency that I must live
> with. Silicone gel implants ruined my life. Sincerely, Deborah
> Guillory.
>
> MS. VOSS: Good morning. My name is Gerie and I am 29 years old. I have
> come to address this panel today to explain why I believe the
> restrictions against silicone implants should be looked at based on my
> own positive experiences with them.
>
> I began my painful struggle with breast lumps and eventually breast
> cancer at the age of 20 after six years of having breast surgeries to
> remove these lumps, and fortunately learning they were benign
> fibroids. I was not so lucky in the year 2001. That year I learned
> that I had severe atypical hyperplasia in my left breast and ductal
> carcinoma in situ in my right breast.
>
> As a result, at the same time that I was planning my upcoming wedding
> for the following year, I was exploring medical options with breast
> surgeons, medical oncologists, radiation oncologists and plastic
> surgeons. I eventually decided to have a nipple-sparing bilateral
> mastectomy with immediate reconstruction, a decision that would change
> my life, and certainly for the better.
>
> During my recovery period I had several saline expander injections
> into my breast between October 2001, my initial surgery, and February,
> 2002, my follow-up cosmetic surgery. I was surprised to see that the
> saline expanders were quite visible beneath my skin showing folds,
> creases and dimples. My research explained, and my plastic surgeon
> confirmed that such an appearance was common using a saline-filled
> implant.
>
> When it came time to order my new implants for my follow-up cosmetic
> surgery I was a little nervous. Like many women, I had heard that
> silicone breast implants may be harmful to my health. However, upon
> further research I learned that there was actually no evidence that
> silicone implants were directly responsible for causing cancer
> occurrence. I am so glad that I did that extra research and I was able
> to learn the truth about silicone implants. It was a huge difference
> in my recovery process.
>
> In a couple of weeks after follow-up surgery I was back to work,
> cancer free and feeling better than I had before the surgery. I took
> the liberty of taking a slightly bigger cup size and, with the help of
> my plastic surgeon, got two perfectly shaped breasts, much better than
> after my earlier surgical biopsies. As a result, I was able to get
> married in the wedding gown of my choice; danced all night long and
> have a wonderful honeymoon, not ever wondering whether everyone
> thought that my breasts might not be real.
>
> I realize that not all women are as fortunate as I am to have caught
> my cancer so early; have active professional doctors and the freedom
> to carefully consider my treatment options.
>
> While I know that these options did not totally eliminate my risk for
> recurrence, it gives me the best possible chance to not ever have to
> worry again about those fibroids and hear the words \"you have breast
> cancer\" again. It also did something else, it was extremely important
> to my overall recovery. It helped me to restore the confidence that I
> had lost during the whole process. I am proud of how I look again.
>
> Hopefully, not every woman will have to go through what I have gone
> through, but I strongly believe we need to allow women who want or
> need implants the choice to decide which is best for them. While the
> appearance of the saline implants may be fine for some women, it is
> not fine for all women, especially those of us diagnosed with breast
> cancer in our 20s and 30s.
>
> Please let us make informed decisions as to what we want to do with
> our bodies. Silicone implants were the right choice for me and they
> may be the right choice for other women like me.
>
> DR. HELMAN: Good morning. I am Susan Pope Helman. I have no conflict
> of interest.
>
> As I speak, please pretend I am your wife or someone you love very
> much. A little over 13 years ago I was normal. I had two children and
> took care of my mother who had Alzheimer\'s disease. I had two jobs
> and put myself through college. I was a productive tax-paying mom who
> enjoyed golfing, swimming, bicycling and long walks on the beach and
> in the mountains. I never missed a day of work.
>
> Then, September 6, 1990, I made the biggest mistake of my life. I
> trusted my plastic surgeon who stated that silicone breast implants
> were safe and they would last me a lifetime and I would go to my grave
> with them. I assumed the FDA had determined they were safe or they
> wouldn\'t be available. Boy, how wrong that was!
>
> Within about six months I started getting horrible headaches. I
> couldn\'t think right and noticed that I was dizzy and nauseated an
> awful lot of the time. I would lose my balance and feel like I was
> going to fall over. I couldn\'t figure out why.
>
> During the second year all of my hair fell out. I was diagnosed with
> fibromyalgia. I couldn\'t concentrate and I seemed to be in a fog most
> of the time. When the pain would come I would thrash back and forth in
> bed and I couldn\'t see; I couldn\'t focus; I couldn\'t get up. My
> life was destroyed. I lost a wonderful job. I lost my car, my salary,
> my home, my productivity and my sense of well being as a person.
>
> The illnesses began with a vengeance around 1997. Both breasts burned
> like they were on fire and they throbbed with pain. I had sores,
> blisters in my mouth and on my hands that would bleed, as well as on
> my bottom all of the time, and I wondered why I felt so bad and
> couldn\'t figure it out.
>
> I had the implants removed in 1992. The implants were only in my body
> less than two years. In 2001 I found out the reason. The capsules
> which contained bacteria and T cells and silicone were still left
> inside my body and continued to make me sicker.
>
> I also found out both implants had ruptured and all of the silicone
> was never accounted for. Testing revealed that silicone had migrated
> throughout my entire body. I have had brain scans that show lesions. I
> was told that I have the brain of an old lady. Other tests showed
> other neurological problems.
>
> Two years ago a plastic surgeon removed the remaining capsules and the
> silicone that had spilled out into my chest. She said she couldn\'t
> get it all and I had to live the rest of my life this way.
>
> I was treated like a guinea pig in a horrible experience that never
> should have been allowed to happen. Without the grace of God and my
> husband, there is no way I could have made it through this.
>
> If the FDA approves these silicone gel implants, we know that women
> will be told that the FDA has decided that silicone breast implants
> are completely safe. I really want this panel to seriously consider
> the experiences of women like me. My hopes are that you will make it
> clear that a company that wants to sell breast implants needs to
> provide at least ten years of good data before expecting their
> implants to be sold and approved by the FDA. Thank you.
>
> DR. ANDERSON: May I ask the speaker a question? Ma\'am, a number of
> people like you have testified about the serious and terrible
> experience that you have had and then said we want ten years of data.
> My question to you is if they came up with ten years of data that did
> not show a connection between the silicone implants and the illness
> that you are experiencing, would you accept it as being that, no,
> there really is no connection, or is your belief that there is no
> question that these two, regardless of the data, are connected?
>
> DR. HELMAN: First of all, my belief is the guidelines for safety in
> any situation, and particularly for the FDA, are \"do no harm.\" My
> feelings are if they are proved safe beyond any reasonable doubt, then
> I believe they should be available. Thank you.
>
> MR. HELMAN: I don\'t have any problem pretending that I love her; she
> is a loved one. She is my wife. I am Craig Helman. I am angry about
> all the things that she doesn\'t and does talk about, and have to take
> all the drugs that she takes with the hope of just staying alive. I
> lay there at night, watching her in bed, jumping around, jerking
> uncontrollably with pain, and watch her face when she is grabbing her
> chest because she is in pain. I have lived each day of this and enough
> of that.
>
> With all the modern technology, I think that the manufacturers could
> invent something that is safe. It seems to me like, no matter what
> they do with silicone, it is still migrating through these people.
> Maybe they will make a better wrapper and it can\'t get out. I don\'t
> know what they have to do, but they need to do something. Until
> silicone implants have been proven completely safe\--I don\'t know
> what to say. I would like to see more independent long-term studies
> before the FDA can make any decision. That is it.
>
> DR. BATICH: My name is Chris Batich. I am a professor of material
> science and engineering, and also biomedical engineering in University
> of Florida. In the past I have served as an expert witness for
> plaintiffs and defendants in the breast implant area. I only work with
> plaintiff attorneys part time.
>
> The National Organization of Women has paid for my room last night. I
> am up here for an NIH study section so they paid for my travel.
>
> I would also like to thank the panel for having such an inclusive
> meeting in covering this information, and I would also like to thank
> Mary McDonough for the three minutes that she has provided for me to
> expand to six minutes.
>
> DR. WHALEN: Doctor, what was that name? That yielded to you?
>
> DR. BATICH: Mary McDonough.
>
> DR. WHALEN: Just to clarify, I have taken the time off and you will
> have whatever time was allotted to you. She has given you three
> minutes or her entire time since she was representing her
> organization.
>
> DR. BATICH: My apologies for running through this very quickly. Of
> course, there is not a lot of time for a technical presentation.
>
> \[Slide\]
>
> I am going to talk about the chemical composition, the uncertainties
> in that, and the changes in the chemical composition of the breast
> implants and what should be known about it.
>
> \[Slide\]
>
> If you are going to put something in someone\'s body that is going to
> continuously release material during its entire lifetime by gel bleed
> or, occasionally, by rupture as a bolus you want to know some things
> about it.
>
> First of all, what is being released? This is highly variable. It
> depends on manufacturing changes and it is frequently not documented.
>
> You would like to know how much is released. This is highly variable,
> depending on the women. For one thing, the type of surgery\--it is not
> a well controlled parameter right now for both implant reasons and for
> physiological reasons and biological response.
>
> You would like to know where the material goes. There are major
> uncertainties about where the material is distributed through the
> body, and some good radiolabeled studies would resolve a lot of these
> issues. Some of them are starting to be done now.
>
> You would like to know whether it undergoes any chemical changes.
> Silicone is a really complex material. It is highly stable. It is used
> in transformers because of its chemical stability, but part of that
> stability is because it has a reversible hydrolysis. In a non-aqueous
> environment it reheals itself. In an aqueous environment you are going
> to generate small molecules, low molecular weight molecules,
> continuously. Because of this equilibrium, you can never extract them
> all out. There is some concern, for instance, that there is a new
> shell that is being introduced, a fennel-based siloxane. There is a
> real question about what its small molecules will do. As far as I
> know, these have been very little tested, except perhaps internally by
> Dow Corning.
>
> So, you would like to understand the chemical changes and then you
> would like to know what kind of responses you might expect from those
> types of chemical changes. Then, with that kind of data you can start
> making some reasonable estimates of the kinds of things you would look
> for. It is obvious that this is not a very straightforward problem but
> it is clear that there are some very active species coming out.
>
> \[Slide\]
>
> If you look at this slide, this is from a book on immunology of
> silicone. There was a symposium at NIH in 1995. I presented one of the
> introductory papers on degradation reactions right after Dow Corning
> got up and talked about background of silicone. There were a lot of
> papers on immunology presented.
>
> If you just look at this schematic diagram, you don\'t have a solid
> fibrous capsule. You have a synovial type cellular layer, histiocytic.
> Those things pick up the silicone that comes out through bleed. They
> pass into the tissue. So, at the very least, you have a part of the
> immune system that is picking up these tiny particles, carrying them
> somewhere, doing something, and a lot of that is not tracked, not
> known.
>
> \[Slide\]
>
> One example of the changes\--this is a picture of the cover of the
> book and this is a histology slide. So, it is processed in xylene and,
> yet, you see residual gel. The residual gel indicates some
> cross-linking has probably taken place to allow that gel to stay in
> the slides. The gels have been linked to adjuvant type reactions, and
> all, so it is interesting, provocative but it has not been followed up
> on as to what happens here. Also, very tiny amounts, when they are
> distributed to very tiny particles, can create tens of square meters
> of surface area and that also has not been related to dose response.
>
> \[Slide\]
>
> If you look at this slide, particles of gel, even from oil when there
> is no rupture, also show that they become a gel.
>
> \[Slide\]
>
> One of the postulated mechanism is you could have oxidation. It is
> well-known that lysosomes can produce things like hydroxyl radical or
> other reactive species which are known to oxidize silicone. There are
> hydrolysis reactions that are well-known.
>
> \[Slide\]
>
> I tried to look over a little bit of the mass of volume of technical
> literature that came out. D4 is one of the most interesting molecules.
> I only found studies from D5 on up. Again, there has been no
> discussion of what phenyl-containing coupling agents do, and there are
> silanols which are known to be very biologically active.
>
> \[Slide\]
>
> Here are summary points. I see my red light flashing and I will just
> try to finish very briefly. There are a lot of things that could be
> studied that are not being studied. You need some independent
> investigators funded by organizations like NIH to get in here and look
> at some of these things. I think you definitely need to keep looking
> at the data and try to do a better technology analysis before these
> things are approved for non-regulated use.
>
> DR. MILLER: Dr. Whalen, can I ask a question of this presenter? I
> wonder what you would suggest to us in terms of how to address all
> these questions and the relevance of all these questions, given the
> fact that there has been no evidence that has linked the implants to
> disorders. I mean, you can raise lots of questions, and I share your
> concern about wanting to understand, as detailed as possible,
> everything that happens with the implants, but the quandary that I
> find myself in is are we going to find something in answer to these
> questions that will make us discover that there are health problems
> associated with it?
>
> DR. BATICH: Well, one of the ways to miss important information is to
> put it in a lot of different situations. In other words, there are
> very many different types of implants out there, very many different
> kinds of materials are releasing at many different rates. If you put
> some good data in a lot of mixed bad data, you are not going to see
> certain relationships. Sometimes it looks like there are no problems
> at all; there are very positive responses from implants. Other times
> there seem to be a consistent\--I don\'t know\--group of symptoms.
>
> A lot of plastic surgeons I have talked to say they think there is
> something really there but they don\'t know what it is. I think it
> behooves us to try to identify the kinds of things that could be
> coming out, and then you can study and see if there is a dose
> response. The immune system is involved somehow because of the
> macrophages, but what it is doing I certainly don\'t know. That is not
> really an answer but it is not a simple problem and there isn\'t good
> data to resolve it I think.
>
> DR. MILLER: Thank you.
>
> MS. GILBERT: I have a question. Alisa Gilbert. On your slide number
> seven you are asking the question what materials are released and you
> mentioned D4. What is it about D4 that you think should be looked at?
>
> DR. BATICH: Well, D4 is the monomer that silicone gel is made from.
> So, when you make the shell and the gel there is frequently D4
> present. It is removed in different ways but it is a stable molecule
> in the sense that it is reformed again at very low rates by the gel
> itself and by the shell. So, if you extract it completely and wait a
> while, especially in the presence of any kind of catalyst like sodium
> chloride or something like that, it will slowly reform. So, there are
> a number of toxicological studies of D4 that have been published by
> other people. D3 is more reactive and it is also interesting.
>
> MS. MALNACK: Good morning. I am Marilyn Malnack, from Gilbert,
> Arizona. I am here to tell you about a successful surgery, and 25
> years after I can say I am still satisfied with my implants.
>
> I had them in 1978, and the reason I wanted to have implants was to
> make my body a little more symmetrical. I have nice hips and a nice
> waist but I was totally flat in my breast area. I found a surgeon that
> did a wonderful job. He told me about all of the risks that were
> associated with having a foreign substance introduced into your body.
> I listened carefully and took a few months to think about it, and my
> husband agreed that it would be a great thing to have.
>
> So, I went in and had gelicone\--gelicone!\--silicone gel implants
> inserted in 1978. I am still as active as I was then. I am a healthy
> woman of 54. I am very happy that I had them inserted.
>
> I don\'t know what else to say, except every person\'s body is
> different. Your body is never static; it is always changing and when
> you make the decision to have this stuff done, you really need to look
> at all of the risks that are associated and decide whether you want to
> take those chances or not.
>
> Implants are a totally optional surgery. Nobody has to have it. Women
> seem to want to have these things done because we feel like we need to
> be more perfect than we are. So, I think that is why a lot of women
> have it done. Everybody has their own reasons.
>
> But I saw in the newspaper a small article by Inamed, that they were
> coming here, in front of the panel, to try to get silicone approved.
> So, I e-mailed them and let them know that I had them for 25 years,
> and they called me back and asked me if I would like to testify, and I
> am doing that for my own self and for all the other women that have
> had successful implants and are happy with all of the results. Inamed
> did pay for my travel expenses but that is all. Are there any
> questions?
>
> DR. WHALEN: I think gelicone is a great word and you ought to get on
> the web and trademark that right now before somebody else does!
>
> \[Laughter\]
>
> DR. CHOTI: A question for you, how are you following up? Are you
> concerned about leakage or rupture at this point, or what is your
> plastic surgeon telling you?
>
> MS. MALNACK: You know, I haven\'t gone back to see my plastic surgeon
> because I had it done in Washington. I am very aware of my body. I am
> always looking at it, checking it and I think I would know if anything
> was leaking. Some people are more in tune with their bodies and
> really, if you are going to have a foreign substance introduced, you
> really have to pay attention. Even though it has been 25 years, I know
> that I can change and I am changing, and you always just need to pay
> attention to what is going on. You can\'t just put them in and forget
> about it and go along with your life.
>
> DR. CHOTI: What about mammograms? Are you concerned at all about
> getting mammograms?
>
> MS. MALNACK: Yes, I have had two mammograms and everything is normal.
>
> DR. CHOTI: But it doesn\'t bother you about compression or worry about
> damage to the implants with the mammogram?
>
> MS. MALNACK: No, but it does kind of hurt. Ouch! Of course, it does
> for all women. It is not a pleasant procedure.
>
> MS. RUMSEY: Hi. My name is Leslie Rumsey. I am from Pennsylvania. I
> have no financial interest in this issuel; I have a very passionate
> interest in it though. I had a little speech written but I sort of
> wanted to speak from my heart a little bit more.
>
> I was diagnosed with stage 0, non-invasive ductal and lobular
> carcinoma in situ in November of 2001. Very delusionally, I thought at
> the most I would need was a lumpectomy and I would move on with my
> life. I was told, however, that I needed a bilateral mastectomy and my
> world just came crashing down.
>
> I didn\'t even know how to deal with it. I had two young children, two
> younger step-children, and there was no choice, breasts are removed
> and you go on from there.
>
> I researched on the Internet, talked to doctors, talked to nurses,
> talked to survivors about my choices for reconstruction. They sort of
> dangle that out there for you, like everything else is minor\--you are
> going to look great immediately after surgery. I researched it all,
> and sort of wavered between saline and silicone implants until I had
> the expanders, and they were just very difficult for me to deal with.
> They felt hard; unnatural. My children couldn\'t nestle up to me. I
> was used to them nestling up to me. So, I made the decision to go with
> silicone implants.
>
> I had that done in June of 2002 and I have never regretted that
> decision. They feel natural. They look natural. My children can lay
> against me. It is just the most wonderful feeling.
>
> When you have seen yourself with breasts removed, and scars and the
> impact that has on you, it takes an hour just to get undressed for a
> shower, and in a short period of time, to look the way I look now, I
> can\'t describe in words how wonderful that is\--to be able to show my
> daughter that you can have breast cancer and you don\'t have to fear
> it the way I feared it when I was growing up. The movie of the
> week\--you wake up; no breasts; your husband leaves you. She doesn\'t
> have to face that. She looks at me and she doesn\'t even see anything
> different about me. So, that is something I really treasure.
>
> I have so much compassion when I hear what the women who have had
> negative results feel. I listen to that and I would still make the
> same choice, and I would go through it, knowing that I am responsible;
> that I would need to go back to my doctor; I would need to know what
> is going on and take responsibility for my own physical health. But it
> is something where I would still make the same choice for and go ahead
> with.
>
> In 2001 I was a victim of breast cancer. When I had my bilateral
> mastectomy I became a survivor of breast cancer. But I feel with all
> my heart that when I had the implants installed I became a thriver of
> breast cancer, and that is something I wouldn\'t change. Thank you.
>
> MS. DOLLIE: Good morning. My name is Nikki Dollie and I am a silicone
> survivor. I have no financial affiliations with anyone, except the
> next speaker that is my husband. He drove 30 hours to get us here as
> it is that important for us to ask you to vote no to silicone.
>
> I have heard much talk of silent ruptures and that is a grave concern,
> but I talk of silicone gel as my personal, silent killer. I was
> implanted in 1992 with silicone gel. Had you observed me one year
> later or eight years later, you would have been observing a healthy,
> active, happy, trial attorney.
>
> I have developed a plethora of symptoms over a very short time span,
> and I was in a wheelchair with many symptoms identical to those
> experienced by what I call my silicone sisters.
>
> After explantation and removal of lymph nodes in my armpit and over my
> lungs in the year 2001, approximately six months after I first
> developed symptoms, I was out of the wheelchair within 72 hours of
> explantation. I began immediate improvement in other areas as well.
>
> As a result of my gel bleed, my lymph nodes were saturated with
> silicone. That is the pathologist\'s report. No rupture. My life was
> destroyed. That is me, my victim\'s report.
>
> Today I am a shut-in, sharing many of the same diseases with which my
> silicone sisters suffer. My life is a nightmare of illnesses and
> surgery after surgery. Yes, that is one quick sentence but it is about
> the end of my life as I knew it. This is the story of a gel bleed,
> ladies and gentlemen, and the devastation of my life and countless
> lives, my fellow implant survivors.
>
> I moderate an international support group for my wonderful women who
> can\'t be here:
>
> From Joyce in Pennsylvania\--she asked me to tell you please do not
> approve the manufacturing of implants to kill the next generation as
> it is killing ours.
>
> From Kay in Oklahoma, we are the studies; the sisters. I ask you to
> look at our bodies and consider the mail you have received about our
> pain and tell me how you can even consider placing a toxic killer back
> on the market. From Rosanna in Florida, there is not enough research
> on these implants. I have personally been very ill following a
> rupture. I have worked with thousands of women over the last ten years
> that are sick and dying from the very same symptoms and diseases. Why
> not study us? I am the evidence. We are the evidence, the women.
>
> From Colea in Washington, no one should receive silicone implants
> without being tested for sensitivity to silicone.
>
> From Susan in Texas, it is important for you to realize that despite
> suffering the ill effects of silicone, we represent someone\'s mother,
> child, sister, spouse, friend, etc. We are important people and
> something horrible has been done to us with our exposure to silicone.
>
> From Michelle in Louisiana, please do not allow silicone to be the
> silent killer of the next generation as well.
>
> From Linda in Texas, having breast cancer at 29 was devastating.
> Getting reconstruction surgery, recommended by my plastic surgeon,
> with implants\--
>
> DR. WHALEN: Ms. Dollie, you need to conclude, please. Could you
> conclude, please?
>
> MS. DOLLIE: Yes. I just have two more.
>
> DR. WHALEN: I am sorry, you need to come to your concluding sentence.
>
> MS. DOLLIE: Ladies and gentlemen, based on what I have experienced
> with what was determined to be just a silicone bleed\--and I say just
> a silicone bleed\--very seriously, I ask you to vote no to silicone
> gel. It was determined I had no rupture. My pathologist\'s report
> showed that removal of the silicone in my lymph nodes is what allowed
> me to start breathing again. I have had silicone removed, or about to
> be removed from my hands and my feet. I don\'t believe this is a
> normal process of aging, and it took almost nine years for the first
> symptom to present. Prior to that I was a happy, healthy, working
> attorney. Had I known this would happen, had I been warned, I
> wouldn\'t be here today and I implore you to vote no. Thank you.
>
> MR. DOLLIE: Good morning. I am Mike Dollie. That was my wife, Nikki. I
> have no financial affiliation with anyone.
>
> I don\'t have a clue what I am going to tell you. I just want to speak
> from my heart here for a minute. I have watched my wife go from a very
> athletic, very professional, vibrant attorney to a woman who is held
> captive in her own home, who can\'t get out of bed in the mornings
> until I bring her her pain meds. Then, she is still there for a couple
> of hours till they take effect. I have watched her go from somebody
> who is a published author to not being able to concentrate enough to
> read the newspaper. I have watched her go from a woman who helped
> everybody do everything to somebody who now has to have someone help
> her. It breaks my heart to see what has happened to her. Everybody who
> knows her, knows what she used to be and what she is now.
>
> So, we ask jointly, as a couple, that you vote no in this situation.
> Thank you.
>
> DR. LYKISSA: Good morning. My name is Ernest Lykissa. I have been
> involved in the last\--oh, since the years \'89, \'90 with silicone
> breast implant research. Presently, I am involved in forensic and
> clinical toxicology in the city of Houston.
>
> When I was affiliated as a professor of clinical and forensic
> toxicology with Baylor College of Medicine in Houston, I was able to
> do extensive research with these particular devices.
>
> Oh, I forgot\--my affiliations are that the National Organization of
> Women paid my ticket to fly up here and also paid for my stay last
> night in this hotel.
>
> In this Power Point that I present for you, I just summarize in the
> first four pages some research that was performed with mice at Baylor
> College of Medicine. In order to remind you, this particular work was
> done at the time when we were told that silicone was inert, that there
> was no toxicity associated with it. We were able to prove that there
> is an LD-50 associated with cyclosiloxanes. We were able to prove, in
> our paper in [Analytical Chemistry]{.underline}, that both the
> silicone and the platinum catalyst that is included in the low
> molecular weight silicone oil in order to polymerize that mixture and
> make it a good fill for the envelope so that it can be implanted in a
> human being, that material was passively leaking out of the porous
> envelope. We were also able to show that there were toxic effects in
> the mice to the point where we also had death due to fatal hepatic and
> liver complications\--hepatic and liver, I am sorry, I mean hepatic
> and pulmonary complications with the mice.
>
> As I said, in the second paper that I have there, we are showing also
> that platinum was being released in a very significant manner from
> those implants. What we were saying was that the devices were
> depolymerizing with aging. Remember, we worked not with brand-new,
> shiny implants. We worked with devices that had been explanted from
> women after they had been in situ for a period of up to ten years,
> sometimes more.
>
> It seems that these devices, when they were manufactured, had
> convinced the manufacturers that they were a good device. And, I agree
> with them. They were looking at something very shiny, off the show
> room. The problem is once you put it in a human body, once you subject
> it to the rigors that those ladies that were being implanted were
> subjecting them to, those devices were coming very quickly to a very
> high failure rate.
>
> I am not talking about ruptures now. I am talking about where
> optically you can look at the device and you see nothing wrong with
> it. Of course, you see some small tears. If you put it under the
> microscope you see a lot of different things happening. The fact that
> the capsule is formed by the body shows you a very strong reaction of
> the body. It is rejecting it like a cyst. It is encapsulating it like
> it was a cyst.
>
> So, we know that from day one that the body is not reacting very well.
> In the old days the plastic surgeons were known to literally hit the
> women in the breast with a two by four literally to break the capsule
> because they would get hard. Women obviously didn\'t want their
> breasts to be hard.
>
> After Baylor College of Medicine, in the laboratory, was able to test
> women that had been implanted and had been explanted, we were able to
> test their blood, their urine, hairs, nails, sweat and so on and so
> forth, and what we found was that there was still silicone. Obviously,
> the silicone that had migrated in their body, in small foci throughout
> their body, was still releasing D4s, D3s, D5s, D6s, D7s, and so on and
> so forth. These are the low molecular weights that get polymerized
> with the introduction of the catalyst of platinum and put in a gel
> form from the oil.
>
> So, once we had that situation, we found that these materials were
> still present in their bodies. Some of them were worse than others.
> Let\'s don\'t forget that it is not one breast implant out there,
> there are a lot of models. There are a lot of batches. When they were
> manufacturing them, if the batch did not gel properly according to the
> formulation, they went in and sprinkled a little more
> hexachloroplatinic acid or whatever else they needed.
>
> So, we are talking about a little bit of alchemy here. We are not
> talking about chemistry; we are not talking about a controlled
> science. Remember, these devices were not produced under strict
> controls. I am talking about the early days. Slowly, as we saw the
> symptoms being developed, as we saw women complaining, they went back
> and they used that as quality control.
>
> Of course, they attacked everything the scientists were trying to do
> by saying we have financial\--you know, obviously I am not a
> millionaire and I am not going to make my living doing this, but what
> I am here to tell you is that my research has shown that these
> particular devices, with time they are like tires. They have enough
> mileage on them and once they get enough mileage on them they will
> fail.
>
> So, I implore you, in your decision-making that you take that into
> consideration\--that you ask the manufacturers to provide you with
> data that they have done stress testing on these devices. I implore
> you, like you do with aspirin and like you do with vitamin pills, put
> an expiration date on these devices. Demand that the manufacturer puts
> an expiration date on these things. Just tell them, based on their
> studies, based on your decisions, I implore you that you do that
> because, if you don\'t do that, your names will be known to many of
> these women and somebody will be testifying against you. Remember
> that. You are handling here human lives. I took an oath to cause no
> harm\--I don\'t know about you\--and I uphold that.
>
> In the last conclusive evidence that I am going to give you here so I
> can let other people talk to you about more important things, I think
> the recipients of these devices should be forewarned of the increased
> risk of the systemic toxicity with prolonged implantation past those
> expiration\--
>
> DR. WHALEN: Doctor, would you conclude, please?
>
> DR. LYKISSA: I am done, sir.
>
> MS. GILBERT: I have a question. You don\'t have page numbers, but in
> the platinum in samples of women with silicone gel or silicone saline
> implants and their children, how long out did you do your studies? I
> mean, how far away were the women from implantation and what about
> children?
>
> DR. LYKISSA: As I said, you have to remember that these were not every
> case that we tested. At the time we tested it, it was a custom case. I
> mean, it was not like some type of\--to answer your question, I will
> say that we tested these women with their implants, we tested them for
> a period of about two months to three months [in vitro]{.underline} in
> order to see what they were releasing in our laboratory under the
> conditions that simulated the human body. When we tested them, as I
> said, with the saline implant we did not find any toxicity to talk
> about that was, you know, very significant. But with silicone breast
> implants, I can guarantee you.
>
> The Germans have confirmed our research. So, I can stand up here and
> tell you that our research is valid and you can look at it with
> scientific criteria that has been published in [Environmental Health
> Perspectives]{.underline}, [American Journal of
> Pathology]{.underline}, [Analytical Chemistry]{.underline}. So, we are
> not talking here about, you know, something that came out of
> somebody\'s closet.
>
> DR. MILLER: Can I ask you a question also? Could you tell me about
> ExperTox? How long has ExperTox, Inc. been a company?
>
> DR. LYKISSA: ExperTox, as I said, is a clinical and toxicology
> laboratory and has been in practice now since the year 2000.
>
> DR. MILLER: What percentage of your studies are done related to
> silicone problems?
>
> DR. LYKISSA: I would say less than five percent.
>
> DR. MILLER: So, you do toxicology testing\--
>
> DR. LYKISSA: We just do toxicology, sir. We just have ICPMs, DCMs,
> LCMs, all the best technology. You give me the samples; I give you
> answers.
>
> DR. MILLER: And one other question, you know, you list a lot of toxic
> appearing things and you say that the longer the implant is in, the
> increased is the risk of toxic, you know, systemic effects. Yet, we
> have no epidemiologic data that suggests there is a linkage between
> systemic illness and the implants. So, how do you square these
> epidemiologic studies and the questions raised by this kind of
> information?
>
> DR. LYKISSA: Well, the epidemiologic studies were not our concern. We
> were testing patients, individual patients. Obviously, the patients
> that had problems came to us. The patients that did not have problems,
> they had no use for ExperTox. The people that I see in my laboratory,
> sir, they are all suffering from some kind of toxicity most of the
> time. The best news you can get out of my laboratory is that I found
> nothing and that happens very rarely, unfortunately.
>
> In these particular cases, the patients that I tested, they had been
> seen by rheumatologists, dermatologists. They were suffering from
> silicone deformities. They had sores on their bodies. I mean, a very
> obvious disease state had established itself in their bodies for a
> long time.
>
> So, how do I square it off? Believe me, I have seen enough people and
> enough sickness to tell you that I am so convinced of this, and I am
> very hard to convince, I promise you that\--the people that I have
> seen have been sick, and I know that the fact that we have
> hexachloroplatinic acid release from those devices, which is an
> alchemist\'s product\--it is platinum treated with aqua regia, for
> crying aloud, from the 1400s. You know, we have this material released
> from the body. I know that is the reason for the sensitizations and I
> know that the silicone, when it starts being released in the body,
> just adds to the burden and that is what breaks the camel\'s back.
>
> DR. MILLER: Thank you.
>
> DR. LIEBERMAN: I have a question. You clearly have this data and
> clearly there is a lot of variation in the symptoms\--
>
> DR. LYKISSA: Oh, yes.
>
> DR. LIEBERMAN: So, I wondered if you could help us to think about what
> factors might influence whether a woman has symptoms or not.
>
> DR. LYKISSA: Okay, I will start by telling you that since all my
> graduate work up in Montreal, in medical school and following my
> graduate work with a Ph.D. and all these other things, what I learned
> was let\'s not forget the DNA. Let\'s not forget the genetics here.
> So, we have predispositions from the genetic factors.
>
> Number two, which makes it very complicated for any one of us in this
> room to have a clear understanding of what is going on, there were
> multiple models of breast implants. There were the Dow Corning; there
> were the McGhan; there were this; there were that. There were batch
> variabilities. We went in and we tried to make ends meet. So, this is
> another factor, what is the device you are talking about?
>
> We are all standing up here like, you know, the monkeys in 2001,
> trying to tell you that we know what the fact is. We don\'t know what
> it is. These are devices that were manufactured under different
> conditions. So, these are the factors you want to look at.
>
> Then, number three, and very important, is the life of the woman. What
> is she going to do with her body? Where is she going to live? Is she
> going to live in a cold climate? We found out that as you turn the
> temperature up these materials depolymerize a lot faster. So, if she
> is going to live in Florida with her breast implants versus Upstate
> New York, we are going to have different factors there.
>
> Also, we found out that lipophilicity\--you know, the pores on the
> envelopes seem to allow this migration and depolymerization in the
> presence of stearic acid, for example, which is the human adipose
> tissue. Also, unsaturated fatty acids seem to help that material.
>
> So, I can stand up here and tell you that I know but, you know what, I
> really don\'t know. I wouldn\'t want your job. Thank you.
>
> DR. LIEBERMAN: I have one more question.
>
> DR. WHALEN: I am afraid that is all we have time for right now. We
> will try to maybe come back to it if we can, because we have multiple
> other speakers that are coming.
>
> I do want to let the audience know, especially the people who have
> spoken who wonder why different people get different periods of time,
> we have tried to make that announcement in advance but we weren\'t
> able to at that particular time. But one of the subsequent speakers
> did donate five minutes of their time to the doctor.
>
> MS. SHEPPARD: Good morning. My name is Audrey Sheppard. I live locally
> and have no conflicts.
>
> I headed the FDA Office of Women\'s Health for four years, from 1996
> through \'99. Regarding silicone gel implants, these years produced an
> action-packed time. My office worked closely with the Center for
> Devices to meet repeatedly with industry and women advocates to revise
> the breast implant booklet and place it on the web, and to sponsor
> FDA\'s rupture study and more.
>
> I left the FDA nearly four years ago. Perhaps distance creates
> perspective. So, let me summarize what I see as key considerations as
> you mull this critically important decision, whether to recommend that
> FDA approve the devices for widespread augmentation as well as
> reconstruction, releasing them into the bustle of the marketplace.
>
> One, as we have heard, over time silicone implants rupture and cause
> other significant local complications. If approved for augmentation,
> considering the increased popularity of them, ultimately millions of
> young and middle-aged women are each likely to face a number of
> additional surgeries. Based on the duration of the data submitted, it
> is certainly impossible to conclude this will not happen with the
> devices you are considering.
>
> Two, we are told various neurological diseases, perhaps atypical
> syndromes, can\'t be ruled out in a subgroup of implant recipients.
> Here we have met and heard the personal stories of some of these women
> and their illnesses. I would suggest that FDA has the responsibility
> to them and future women to apply a high standard for establishing
> reasonable safety.
>
> Three, FDA approval is the gold standard. Should there be approval,
> consumers and physicians will take this as a clear indication of
> out-and-out safety. You are well aware that augmentation is not a
> medical necessity which would justify a high degree of risk.
>
> Last, if FDA were to condition approval on rigorous post-approval
> requirements, this would be well intentioned but could not be
> successfully enforced.
>
> I see my time is getting short. Inamed\'s proposed postmarket
> surveillance by mail seems less than stringent. Placing much stock in
> hopes of meaningful postmarket data down the road is no substitute for
> a hard up or down decision now.
>
> I have been immensely impressed with the seriousness of these
> deliberations. The health of millions of women rest in your hands.
> Thank you.
>
> DR. CONNELL: Good morning. I am Dr. Elizabeth Connell. I have been
> kindly yielded some time from Susan Lynch Hunt.
>
> I am currently Professor Emeritus in the Department of Gynecology and
> Obstetrics at Emory University School of Medicine, in Atlanta. I
> appreciate this opportunity to present my experiences and views to
> this panel. I have no financial relationship with Inamed and I have
> received no compensation or reimbursement for my appearance today.
>
> For more than 50 years I have had the privilege of practicing medicine
> and providing health care to women. I began as a general practitioner
> in rural Maine, following which I received training in OB/GYN. I then
> went into practice and also developed clinics for women in Spanish
> Harlem and at Columbia University in New York City.
>
> In addition to being a health care provider during these years, I also
> had the opportunity to conduct numerous research projects. I have
> published over 200 scientific peer reviewed papers. I also served five
> years as Associate Director of Health at the Rockefeller Foundation,
> and worked with the U.S. AID as a member of the agency\'s research
> advisory committee.
>
> I have also had a long involvement, starting in 1970, with this
> particular agency. I have served on seven different advisory
> committees. I have chaired three of them, including the first one
> dealing with silicone breast implants.
>
> To go back more than a decade now, I was invited to chair this panel
> when it was convened in November of 1991. We were given two major
> charges by the then Commissioner, David Kessler. First, we were to
> evaluate the PMAs of four companies who had submitted data on their
> breast implant products. Then, we were to advise the FDA as to whether
> or not the PMAs were adequate for approval.
>
> Second, we were asked to determine if there was a public health need
> for silicone gel-filled breast implants. In this context, we were to
> decide whether particular groups of patients, specifically those who
> had undergone major breast surgery mainly for breast cancer or for
> significant deformities, should be viewed as distinct from the larger
> group of women who were receiving implants for augmentation.
>
> Following three arduous days of hearings from dozens of witnesses, our
> panel deliberated and determined that the data from the four
> manufacturers were not complete enough to warrant approval at that
> time.
>
> However, I think it is critical to note that this was in no way a
> statement that we found these devices unsafe. Nor did we determine
> that they posed a health threat to women who had received them. Had we
> determined at that time that this was the case, we would have
> recommended that they immediately be removed from the marketplace.
>
> As to the second mandate, whether they met a public health need, we
> agreed there was ample evidence that they held a significant
> importance for both reconstruction and augmentation patients.
>
> Early in the following year, February of 1992, I again chaired this
> panel. Before the follow-up meeting occurred, the FDA had asked for a
> voluntary moratorium on silicone breast implants pending evaluation of
> new evidence that potentially linked implants with autoimmune disease.
> This time also Dr. Kessler gave us a mandate. We were not to revisit
> the decisions regarding the PMAs that we had made at the previous
> meeting. Because of the new information, he asked us to consider two
> questions.
>
> First, given several concerns, including leakage and rupture of the
> implants, what information should be given to women who already had
> them? Second, given the new information, should these devices be
> allowed to be used in the future and, if so, under what conditions?
>
> After three more intense days of testimony and deliberation, we
> concluded again that although more research was necessary, there
> continued to be a public health need for these devices. We recommended
> that women always receive the best available scientific information
> before using these devices. We also concluded that there were no
> scientific data indicating that silicone implants posed a significant
> health threat to women, especially in the area of connective tissue or
> autoimmune disease.
>
> In summary, we determined that silicone breast implants should
> continue to be available, but that more study was needed to answer the
> remaining safety questions. The panel also recommended that these
> implants be made available to all individuals who needed them for
> reconstruction, most particularly women who had breast cancer.
>
> Additionally, the panel recommended that some women be allowed to have
> these implants for breast augmentation so long as their surgery was
> conducted under clinical protocols, designed by appropriate agencies
> and organizations such as the FDA, NIH, plastic surgeons and other
> relevant groups.
>
> Over the past decade, I have continued to review the growing body of
> scientific evidence regarding the safety of silicone breast implants.
> There, as you know, have been numerous studies, both here and
> internationally, carried out by recognized professionals seeking
> evidence-based information on this issue. They have been conducted by
> such prestigious institutions as the Mayo Clinic, Harvard Medical
> School, the University of Michigan and Johns Hopkins, and the United
> Kingdom Independent Review Group, among others. It is now 2003 and I
> believe that today there is sufficient valid evidence to answer the
> questions that we posed more than a decade ago.
>
> To put this issue into proper perspective, I believe that all of us
> have a stake in this matter. We need to have confidence that medical
> and health policy decisions will be grounded in legitimate science.
>
> In conclusion, I believe that you are fortunate to have more than a
> decade of new research to consider, information that, unfortunately,
> was not available to us during our earlier meetings. I continue to
> believe there is no evidence for significant health risks to women and
> that for many women the benefits will outweigh whatever risks there
> exist. I think it is critical, and we said this very clearly in 1992,
> that women need to be given the best available evidence at the time
> that they are considering the use\--
>
> DR. WHALEN: Can you conclude, please, doctor?
>
> DR. CONNELL: I am. Also, I think we would be well advised to continue
> to monitor the situations, as we had recommended, in line with the
> current FDA protocol. Thank you.
>
> DR. WHALEN: Seeing no questions, we are on track to be a little bit
> ahead right now. I can\'t reconcile that with yesterday, but we are. I
> would hope that FDA and the sponsor will be prepared to make their
> final summations and comments prior to lunch, with the schedule we are
> presently on rather than after lunch as was originally designed. We
> will take a 15-minute break and reconvene at 10:15.
>
> \[Brief recess\]
>
> DR. WHALEN: We will have further open public comment. We are left at
> this juncture with such comments coming from members representing
> various societies. So, if the first of those speakers would, please,
> proceed to the microphone?
>
> MS. HEMSTRA: Good morning. My name is Erin Hemstra, and I am here to
> read the testimony of Wade Clegg, from Panama City, Florida, who could
> not be with us today. Neither of us have any conflict of interest.
>
> Silicone gel breast implants break and leak. When that happens,
> implants can cause pain and debilitating illness. If FDA were to
> return this inherently debilitating device to the market it would be a
> very sad day in government oversight.
>
> Silicone gel implants allow for years of debilitation. For healthy
> women, electing augmentation often assures that no insurance coverage
> will be provided to assist when problems occur. The history of these
> devices clearly shows that any conclusions about safety need to be
> based on long-term testing of no less than ten, but preferably 15,
> years.
>
> The real question is have the risks and complications that have been
> seen in previous gel implants been eliminated by Inamed silicone
> breast implants? Judging from the lack of long-term research data, the
> answer seems to be we don\'t know.
>
> If you recommend approval another group of teenage and young women
> face a future of debilitation. Have any risks and complications been
> avoided by the implants that you are reviewing here today? If the
> manufacturer claims that their product is better than previous gel
> implants, there is only one way to prove that\--to study women who
> have had the implants for a long enough time to find out what happens
> when the implants break.
>
> It is not until the implants are in women\'s bodies for several years
> that it is possible to learn if they will break, leak or cause health
> problems. Two years of research or even three, four or five years is
> not enough. Thousands of women have had their lives diminished because
> they believed breast implants were safe.
>
> I hope that you will not repeat this fraud. I plead for this FDA
> advisory committee to extend this process and continue to restrict
> access to gel implants while research continues, rather than approving
> implants which have not been proven safe for the long-term use. Thank
> you. Wade Clegg.
>
> MS. ROTH: Good morning. My name is Lynda Roth. I am founder and
> director of the Coalition of Silicone Survivors, a group of over
> 10,000 breast implant survivors.
>
> I paid my own way here. I received some help from friends and other
> implant survivors toward additional expenses.
>
> In 1990 I was diagnosed with breast cancer. Understandably, I was in
> shock. When presented information on silicone breast implants, I
> trusted that what my highly respected plastic surgeon and other
> doctors were telling me was true.
>
> I soon found out there were many risks that were not disclosed. My
> implant hardened immediately, resulting in a great deal of pain and a
> very misshapen breast. It spontaneously and silently ruptured within a
> few months.
>
> It was removed shortly thereafter, but much of the silicone gel was
> not. I had a second implant removed a year after the first, and it was
> already sagging a great deal. I had lost a lot of silicone. My surgeon
> told me that silicone gel was inert and would not harm me. I can
> assure you that my concern for having silicone implants was truly
> uninformed. The pain and disfigurement that I suffered was immense.
>
> Within a year I was having problems with extreme fatigue, balance,
> memory, concentration, visual disturbances, fibromyalgia, etc., etc.,
> etc. In \'94 I was diagnosed with lupus. There is no family history of
> this or other related autoimmune problems. Was it just a coincidence?
>
> It was certainly not a coincidence that I had small, hardened, rubbery
> lumps of silicone come out of my forehead for three years, or that I
> had silicone granulomas on my arm and leg.
>
> I still have neurological problems. By the way, both neurologists who
> diagnosed this in \'92 had never seen a silicone patient and both put
> in their notes that they thought silicone toxicity caused my problems.
>
> I have a masters in social work. I lost my job because of my health
> problems. I also lost my health insurance. I am basically uninsurable.
>
> Women who want implants today are told they must waive the right to
> sue the manufacturer. If the implant makers are so sure their product
> is so safe, why would they do this? It may be acceptable to some that
> an implant can harden; that it can move; that their body may reject
> it; and an amount of pain may be acceptable to some.
>
> But please remember that silicone injections in the breast were banned
> by the FDA because women had serious health problems and died from
> injections. A ruptured silicone implant is no more nor no less than a
> massive silicone injection. All silicone implants will rupture in
> time.
>
> I believe many women could evaluate the risk of these devices if they
> had enough time and enough information. Unfortunately, women who are
> told they have a life-threatening disease, such as cancer, are not in
> any objective shape to make these choices, especially when they are
> told by their plastic surgeon that these devices are safe, as I was.
>
> Reports to our group still show very few women are truly informed of
> the risks prior to these devices. The studies that have been conducted
> by the manufacturers, supposedly monitored by FDA, are not run the way
> clinical trials are expected to run. Many women report to groups like
> mine that they have never been contacted for follow-up in these
> studies.
>
> What good are these follow-up safety studies if many of the women are
> not contacted to see if they are problem-free and healthy? I have been
> a group leader since 1991. I am astounded at the fact that hundreds of
> thousands of women that registered and claimed injury from silicone
> implants in these lawsuits\--that the rosy picture painted by Inamed
> and other people is not accurate.
>
> Studies that covered two years or five years inevitably will not find
> the kinds of problems that group leaders like myself have seen and
> heard about. We all know from asbestos, dioxin, radioactivity,
> mercury, PCB, DVT and others take 20 to 30 years to manifest. Why
> would silicone be different?
>
> If you now approve implants based on two years of data, while allowing
> eight more years to collect more, hundreds of thousands of women more
> will be exposed to these toxins before more evidence is in. And, you
> have no way to enforce that the studies are done properly.
>
> Women receiving implants today may not be ill for 10 to 25 years. What
> kind of future are we guaranteeing to them? And, do we want 17-year
> old women to have these implants? Is that a responsible decision for
> this committee to make?
>
> DR. WHALEN: You need to conclude, please.
>
> MS. ROTH: You have a very important decision. I hope you will consider
> all the women who have been harmed by their silicone gel implants
> before you make your recommendations. Thank you.
>
> MS. GILBERT: Excuse me, can I ask you one question?
>
> MS. ROTH: Sure.
>
> MS. GILBERT: Are you the director?
>
> MS. ROTH: Founder and director of the Coalition of Silicone Survivors.
>
> MS. GILBERT: Do you guys actively\--are you participating in any kind
> of research? Are you collecting information on all these survivors?
>
> MS. ROTH: You know, we would love to see a retrospective study of the
> people who really have had the problems but the manufacturers will
> never do that because there is too damned much evidence.
>
> DR. ZONES: Good morning. My name is Jane Zones. I am a medical
> sociologist and I am here as a member of the Board of Directors of
> Breast Cancer Action.
>
> Breast Cancer Action is the first national breast cancer organization
> to refuse donations from any organization that would represent a
> conflict of interest and I have no conflict of interest here.
>
> Twenty years ago I sat on this panel as a consumer representative when
> FDA was considering whether or not manufacturers should be required to
> submit evidence of safety of silicone breast implants. At that time,
> the only other woman in the room was the transcriber of the hearings.
>
> Things have gotten a lot more sophisticated since that time, but the
> one thing that hasn\'t advanced appreciably is our understanding of
> the long-term safety of silicone breast implants. Twenty to thirty
> percent of women who have mastectomies choose to undergo
> reconstructive procedures with clear psychological and perceived
> appearance benefits, at least in the short run. Many of these women
> are encouraged by their surgeons to have additional surgery on the
> unaffected breast in order to provide a better match. Women with high
> genetic risk of developing breast cancer also have been encouraged in
> many cases to undergo prophylactic double mastectomy, followed by
> reconstructive surgery.
>
> We have seen at these meetings that women who have reconstruction with
> implants after mastectomy experience much more complications than
> women who receive implants for breast augmentation. Many women still
> do not receive detailed information about complications as part of the
> informed consent process.
>
> While the Institute of Medicine did an admirable job of compiling the
> accumulated evidence regarding the effects of silicone breast
> implants, they seem to have accepted the literature at face value. To
> take a single example, one of the best and largest studies of silicone
> breast implants which shows no association of the devices to
> connective tissue disease, the Nurses Study, reveals considerable
> conflict of interest.
>
> Much of the research on implants is sponsored and carried out by those
> with a vested interest in the results, which is known to bias outcomes
> compared to independently sponsored studies. Authors, including the
> lead and corresponding authors of the Nurses Study, variously received
> grants from manufacturers or payments from law firms representing
> manufacturers. Two major investigators resigned from the project
> because of the appearance of conflict of interest, though one remained
> an author in the study.
>
> There are other concerns with the Nurses Study which were not
> addressed by the IOM committee. The researchers report a mean
> follow-up after surgery of 9.9 years, with a range of one month to
> 40.5 years. It is not clear how this was calculated since silicone
> breast implants have only been used since 1963, fewer than 30 years
> before the study cut-off. Including even a small number of cases
> extending to over 30 years could inflate the mean follow-up
> substantially.
>
> Reported health problems of women with their breast implants occur
> with greater frequency as implants age in the body. Long-term
> follow-up is a crucial variable in examining breast implant safety.
>
> As with other major studies of connective tissue diseases, the Nurses
> Study used only diagnosable diseases as outcomes and did not examine
> signs and symptoms. Finally, although the sample size was very large,
> over 86,000 women, the prevalence of connective tissue disease in the
> population is very small, and the number of those with both connective
> tissue disease and breast implants, if randomly distributed, is
> extremely small. The sample would have to be tremendously large, over
> 60,000 women with breast implants and twice that many controls,
> followed for ten years each, to have enough power to detect a doubling
> of relative risk of scleroderma, for example.
>
> The authors themselves conclude that because of the infrequency of
> occurrence of connective tissue disease, the study cannot be
> considered definitely negative.
>
> Recently, established medical perspective on two breast cancer related
> issues has been shown through randomized clinical trials to be
> completely wrong. Doctors massively opposed randomization of their
> patients to control groups because they so thoroughly believed in the
> safety and efficacy of HRT and high-dose chemotherapy. Tens of
> thousands of women were unnecessarily harmed because these beliefs
> were not true.
>
> It is unlikely that we will ever again get the opportunity we had 20
> years ago to conduct sound and independent trials with long enough
> follow-up to answer the questions we continue to have about silicone
> breast implants. We urge the panel to not recommend approval of this
> device which has still unknown long-term physical consequences. Thank
> you.
>
> DR. ANDERSON: May I ask a question? First, in the study that you
> cited, I happen to have the abstract, and the issue about 40.5 years
> follow-up, what they are saying is that they had up to 40.5 years
> follow-up for the entire cohort. They were looking at the connective
> tissue disease patients. So, I don\'t think that that is an issue.
>
> But I think you made a very serious allegation against the authors of
> this study where you suggested that in the Nurses Study they were
> biased because of funding from private companies. Do you have any data
> that they received funding prior to the publication of the study, as
> opposed to being\--
>
> DR. ZONES: Oh, it was in the disclaimer.
>
> DR. ANDERSON: In the disclaimer of the Nurses Study?
>
> DR. ZONES: Yes, the article is Sanchez Guerrero, in [The New England
> Journal]{.underline}.
>
> DR. ANDERSON: Okay.
>
> DR. ZONES: Yes.
>
> MS. PEARSON: I am Cynthia Pearson, Executive Director of the National
> Women\'s Health Network, an independent member-supported organization
> dedicated to safeguarding women\'s health rights. We have no conflict
> of interest.
>
> We have reviewed the data that the FDA made available on its website
> on Friday. We have listened to the sponsor\'s presentation yesterday,
> the FDA\'s review, and listened carefully to the panel\'s discussion
> last night. Based on that information, I would like to use our time
> this morning to respond to four important points that I believe the
> panel has expressed over the last day.
>
> These points are that at least some panel members articulated very
> clearly that they believe that the large body of evidence looking at
> the health of women with implants, in general, is conclusive and is
> enough, and shows that long-term risks don\'t need to be worried about
> because of this literature.
>
> Two, I have heard some members of the panel say that the short-term
> increase in chronic tissue disease symptoms that were documented by
> the Inamed study is either not clinically meaningful or not clinically
> interpretable.
>
> Three, we have heard panel members say that they believe that it is
> important and possible to get more information after the approval of
> these devices, if they are approved.
>
> Four, some panel members have said that consent may make it all okay,
> good informed consent that lays out all the information, then
> appropriately allows a woman to make her own choice.
>
> I believe there are problems with each of those assumptions and would
> like to address them. First, the issue of chronic tissue disease
> symptoms, there were questions, legitimate questions, in the absence
> of a control group, about to what extent are these increases in the
> symptoms, as we all saw posted yesterday, just a sign of normal aging,
> and as the night wore on to midnight there were jokes about maybe it
> is just a sign of normal fatigue because we would all score high on
> these now.
>
> We understand the problems with comparing to another study, but I
> would just like to point out that there are other studies that started
> with healthy women, that followed them over a period of years, that
> did not see these increases. I will just take the Women\'s Health
> Initiative, which was a very large study that enrolled healthy women
> that were, on average, 30 years older than the average age of
> augmentation patients and, as reported in the last year, over a 4.2
> year follow-up there was no worsening in mental health, general
> health, bodily pain, energy or fatigue. I emphasize fatigue because to
> compare to the two-year follow-up in women at median age 34 years,
> that doubled in two years.
>
> So, we are concerned that these increases are at least worrying. They
> certainly aren\'t conclusive because of the study design.
>
> Second, we disagree with the people on the panel who articulated that
> the literature gives us assurance that we don\'t need to really worry
> about silent rupture. It would be nice to know why implants rupture;
> it would be nice to know how much of the silicone gets outside the
> capsule, but in the end we don\'t really need to worry because all
> these studies show that there is no conclusive cause and effect
> relationship between implants and harm to women\'s health in the long
> term.
>
> I just want to repeat what one panel member said yesterday. If you
> look for a needle in a haystack by throwing the hay up and you don\'t
> find it, that doesn\'t mean that if you used a metal detector you
> wouldn\'t find that needle. What that means in these women\'s lives is
> to do studies of long-term users with the power to find an effect.
> Those studies have started to come out since the IOM review. They have
> shown some troubling associations between suicide and other types of
> cancer. They are not conclusive but they are troubling and post hoc
> speculation doesn\'t make suicide risk go away when it is shown
> repeatedly in three of these studies that have the power to find it.
>
> Third, we heard some panel members say that the need for more data
> will be remedied by what comes in post-approval, if the devices are
> approved. The data that have been heard yesterday are from one to
> three years of a ten-year plan.
>
> I want to just remind the panel that while in this case the study from
> which you are hoping to get data post-approval was designed and begun
> pre-approval, I believe it is really crucial for you all to remember
> that the FDA\'s enforcement power to require post-approval data is
> very limited. As far as we know, the FDA has never taken action
> against a product because of a sponsor\'s failure to complete
> post-approval studies. If you believe that we need more data, you had
> better ask for it now, pre-approval.
>
> To respond to the fourth issue, the panel believes that women have the
> right to choose after excellent informed consent. So do we. But if
> important information does not yet exist, informed consent is
> inadequate no matter how long and detailed the patient information
> brochure is. We believe that the right to choose is an illusion
> without the information to support a fully informed choice that has a
> full explanation of important and relevant risks and benefits.
>
> So, to conclude my remarks, I want to say that 12 years ago the FDA
> said there wasn\'t yet enough data to adequately evaluate the balance
> between risks and benefits. Twelve years later we still don\'t have
> answers to women\'s important questions about the long-term effects of
> Inamed silicone gel-filled implants and women are counting on the FDA
> to take the right action to get those questions answered. Thank you.
>
> MS. DICKERSON: Good morning. My name is Mary Dickerson. In 1994 I was
> diagnosed with breast cancer. Three weeks after my diagnosis I went in
> for a mastectomy. I did have reconstruction. My doctor used a tissue
> expander and about six months after that I had a saline implant put
> in. I had that for six years.
>
> Three years ago, in December, I had a silicone implant put in and I
> just want to tell you a little bit about the differences. I feel
> better with the silicone. I look better with the silicone. It is more
> natural. It has a more natural feeling. I can wear clothes better. I
> just feel more comfortable with it.
>
> Having a saline implant inside of my breast was like having a tennis
> ball. I couldn\'t wear a button-down shirt like this. There were
> obvious differences, although we tried to make my other breast my
> reconstructed breast.
>
> I was 36 years old at the time and I knew I had no other choice but
> reconstruction. My doctor worked very closely with me on what would be
> best for me. I just want to say that for the past three years, with my
> silicone implant, my labs have all been fine. I see my oncologist
> diligently. I see my plastic surgeon diligently. And, I am just here
> to ask you to give the women the right to choose. Thank you.
>
> MR. KELLY: Good morning. My name is Joe Kelly. I am from Minnesota. I
> am president of the national, non-profit Dads and Daughters. My
> organization paid for my trip here. I have no conflict of interests.
>
> Everyone knows that silicone implants have risks. You have to decide
> whether the benefits outweigh the risks. I have never testified at an
> FDA meeting before but I am here today because of our very great
> concern about the growing use of implants among girls, and the
> unchecked cultural pressure on girls and boys to value how a girl
> looks more than who a girl is, and a woman also. This pressure is
> toxic and too often fatal for our daughters.
>
> Under current FDA restrictions, teens under 18 cannot get elective
> silicone implants. If you approve these implants, regardless of the
> restrictions you ask for, they will be available for off-label use,
> just like saline implants are today.
>
> Teenage girls in this culture are dissatisfied with their bodies and
> some will do anything to fit our culture\'s narrow, unrealistic
> genetic heritage-defying definition of beauty. They will smoke to lose
> weight; use alcohol to numb the pain of not measuring up; spiral into
> depression and other mental illness; abuse a laxative and induce
> self-vomiting; and they will choose elective plastic surgery
> regardless of the risks.
>
> Girls\' responses to the toxic beauty myth of our culture have
> serious, sometimes fatal health consequences. And, that doesn\'t even
> touch on the social harm emanating from valuing appearance over
> substance in human beings. We have a word for that phenomenon,
> bigotry.
>
> Perhaps most disturbing is the incredible number of people actively
> exacerbating this situation and selling our children\'s well being
> down the river to make money. According to news reports, the most
> popular high school graduation gift this year in the U.S., in order of
> popularity, is cash, plastic surgery, cars. The number of breast
> augmentations in girls 18 and younger has more than doubled since
> 1986. Research shows that teenagers are the most likely age group to
> be dissatisfied with their appearance, especially features that do not
> meet culturally determined stereotypes emphasized in mass media, but
> that dissatisfactions lessens with age, as any parent with common
> sense knows.
>
> Although the FDA approved saline implants only for women 18 and older,
> there are no restrictions on the procedure so doctors perform on
> patients under 18 but medical associations, such as ASPS, apparently
> have no official position on teen surgery. Breast implants have to be
> replaced when they break. That is surgery that young women may not be
> able to afford and which may harm their health.
>
> Perhaps most outrageous to me as a father is the way that implants
> interfere with mammography, obscuring breast tumors.
>
> Finally, is it appropriate to perform cosmetic surgery on patients
> whose bodies are still maturing? Unfortunately, no one has conducted
> studies or clinical trials on the safety and long-term risks of breast
> implants in patients under 18 or, if they have, the results have not
> been revealed.
>
> I think denying approval is your only reasonable response, though my
> argument might be a bit different than most that you will hear. Even
> if it was the case, which it isn\'t, that no physical harm ever
> results from breast implants, your approval would endorse capitulation
> to an \"appearance first\" cultural standard that is dangerous and
> health-threatening to our daughters and, I might add, to our sons.
> After all, would you tell your son that the size of a woman\'s
> cleavage is more important than the size of her heart? Not unless you
> wanted to set him up for failure in life-long relationships.
>
> These \"appearance first\" cultural pressures have concrete negative
> consequences and I ask you to imagine your daughter\'s or your
> granddaughter\'s face in the story I am about to tell. When we started
> Dads and Daughters we hired an immensely talented, committed young
> woman, named Heather Henderson, as our deputy director. One morning,
> in September 2000, she did not come to work, which was very unlike
> her.
>
> I eventually went up to her house where I found Heather laying face
> down on the kitchen floor, dead of a heart attack at age 27, after an
> 11-year battle with bulimia. It is obscenely ironic that Heather died
> of the very \"appearance first\" insanity she spent her life fighting.
> But I think she died because there are not enough others of us out
> here, raising bloody hell about the waste of obsession with appearance
> that leads to deadly eating disorders; the waste of obsession with
> appearance that leads girls to smoke in order to lose weight and then
> develop breast and lung cancer as a result; the waste of obsession
> with appearance that leads girls to fall for elective breast
> enhancement and a lifetime of health risks, surgery and providing
> elective profits to implant providers.
>
> This is where you get to take your stand. Please put your children\'s
> face in the picture and do what you know is best for everyone\'s
> health and say no. Thank you.
>
> DR. WHALEN: Mr. Kelly, can I ask you a question? Your passion and the
> cogency of your argument is extremely well conveyed but, since you
> asked us as panel members to visualize your daughter, can I ask you a
> question in return?
>
> MR. KELLY: Please, sir.
>
> DR. WHALEN: If you visualize your daughter, or your wife or your
> sister a few years from now with breast cancer, does your argument
> change at all in terms of the reconstructive argument? Or, is your
> off-labeling concern sufficient to even limit for that population of
> people not having silicone breast implants?
>
> MR. KELLY: Well, first, thank you for your compliment about my age; I
> have adult daughters. I have to say that, you know, my feelings are
> probably not quite as strong when it comes to reconstruction but they
> are not much less strong either. I was talking about this, this
> morning with someone. I have a mother who had severe polio when she
> was a young person. It damaged her appearance. It damaged her ability
> to get around. It never bothered her; she went on with her life; she
> dealt with the imperfections of her experience and made amazing
> contributions to her family and to the world. It is a challenge for
> all of us to deal with our imperfections and our disabilities and the
> struggles that we face. I don\'t think it is worth endangering our
> future health to deal with something that is ultimately an internal
> struggle and decision that we have to make about how we live our
> lives.
>
> DR. WHALEN: Dr. Miller?
>
> DR. MILLER: Can I also ask a question? I appreciate also all your
> perspectives. I wonder, given your perspectives, do you feel that
> there is any amount of safety information which could be generated
> about the implants which would make them suitable as a procedure? Or,
> is the mere principle of putting in an implant something which you
> oppose as a baseline?
>
> MR. KELLY: No, I wouldn\'t oppose an absolutely risk-free implant, no.
> But this certainly doesn\'t look or sound like a risk-free implant.
>
> DR. MILLER: Just as a conjecture, if the implants could be proven
> absolutely with no risk whatsoever, zero risk, would the risk/benefit
> of the implants be suitable in your mind at that point to make them
> freely available?
>
> MR. KELLY: You know, if I had my druthers I would say let\'s make them
> available to people who need them for reconstructive purposes. I think
> the whole emotion of elective, trying to change our bodies from what
> they are genetically wired to be, is absurd and it is part of a larger
> cultural problem that is really harmful to all of us, and especially
> to our children. I think it is important to see it in that context,
> that we are harming our children, and I think particularly marketers
> and people who are making money off our children\'s insecurities are
> hammering at our children with the notion that how they look is more
> important than who they are and what they can do. And, that is just
> wrong. No parent would tell their child that. And, I don\'t think we
> should do things and make public policy that reinforces that negative
> message, that message that is, at its face, a lie, that someone\'s
> appearance is more important than who they are.
>
> DR. MILLER: Thank you.
>
> MR. KELLY: Thank you, sir.
>
> MS. RUSSANO: My name is Jama Russano, and I am the founder of children
> Afflicted by Toxic Substances. I was a child at 14 that received a
> silicone breast implant, in 1972. I was born with a hemangioma tumor
> on my right breast and I never developed fully. My left side was a
> little bit larger than my right. I grew up in the \'70s and I wanted
> to look like everybody else. So, my mom, at age 14, took me to a
> plastic surgeon and he put in a silicone breast implant and said, you
> know what, the only reason that you would have to take this out is
> because you might develop a little bit larger on your left side than
> your right but, other than that, it will last you a lifetime.
>
> Six months later my right breast was like a baseball. I went back to
> the plastic surgeon and they told me, you know what, that is just
> normal. There is nothing wrong. Just massage it a little bit; you will
> be fine.
>
> At 16 I started getting headaches. I started having problems. That
> breast implant remained in my body for 19 years. I went to doctors. I
> couldn\'t understand what was wrong with me. I was finally diagnosed
> with systemic sclerosis.
>
> In 1989 I went to a plastic surgeon and I asked is there any way that
> this implant could be due to my health problems? Oh, no; no, no, I
> don\'t think so. I was diagnosed with systemic sclerosis. I will give
> you a new, better implant, a new better silicone implant.
>
> I had the surgery. Within months the implant fell into my armpit. I
> got worse. My health deteriorated. I lost a high-paying job. I
> couldn\'t take care of my kids. My kids couldn\'t come up and hug me
> because of the scars.
>
> With all of those issues of dealing with young children, on top of all
> of that, I realized when the silicone issues started coming out what
> about my children? Where are these studies? The safety of silicone and
> breast feeding and pregnancy? Are our children just anecdotal studies?
> There are thousands.
>
> I decided that, you know what, this question needed to be answered. I
> came from a manufacturing background. Why weren\'t these questions
> answered? They had 20 years to do this and they didn\'t.
>
> We started Children Afflicted by Toxic Substances and we had several
> main concerns. One was a young girl getting implants. We testified at
> saline hearings at FDA and we asked that young girls\--if they were
> going to approve them, that they not be used under the age of 18. A
> young girl cannot understand or comprehend this type of data. Most
> normal adults can\'t understand it, and the data is not even half
> there. They don\'t understand that when they have an implant put in
> they might lose sensation of their nipple; that they might not be able
> to breast feed later because their nerve endings were cut. How do you
> tell that to an 18 or a 19-year old? How do they understand that? They
> don\'t.
>
> When it comes to reproductive issues, we have had many, many women who
> have complained and sent in questionnaires about infertility problems;
> about miscarriages. And, when they got their implants taken out their
> problems got better. They were able to have children. Anecdotal? Yes,
> you could say that.
>
> The ability for women to breast feed a child\--in one study by the
> Hertz report, up to 64 percent of 42 women with implants were unable
> to breast feed compared to 7 percent of 42 women without implants.
> This is the highest reported range in the literature, that having an
> implant may significantly affect the ability to breast feed.
>
> The health effects on children born to mothers with implants,
> concerning silicones and secondary chemicals, the catalysts, the
> benzine, the phalates, are we looking at that?
>
> It is so important that we understand and get MedWatch forms out. We
> have tried. We have collected thousands. We have submitted many
> hundreds of MedWatch forms to the FDA and so far only 136 are reported
> by the FDA. I know that number can\'t be right.
>
> As the director of CATS, we worked on a questionnaire with the FDA
> many years ago and, unfortunately, we didn\'t have the funds to be
> able to submit it to pediatric doctors or OB/GYN doctors. We couldn\'t
> get funding. Who is going to fund a children\'s foundation? Our
> children are sick.
>
> I know I only have eight seconds, but this is a very important issue
> and I ask the Commissioner if I could just have another minute to be
> able to talk about the kids.
>
> DR. WHALEN: That, unfortunately, is unfair to everybody else who
> wishes to speak so, I am afraid, you will need to sum up.
>
> MS. GILBERT: Excuse me, I would really like to hear her testimony when
> it comes to children. If we could just take one more minute?
>
> DR. WHALEN: Are there any of the succeeding speakers who are willing
> to yield their time? We will allow you 30 seconds and that is all we
> can allow.
>
> MS. RUSSANO: I am going to quickly show some slides. We had a number
> of children go to a doctor or specialist, an orthopedic specialist in
> the Midwest. Each mother took their child and ask the pediatrician if
> their breast implants could be a cause of this rare bone deformity and
> the doctor told them no. He did not report these to the MedWatch. He
> didn\'t report it to the FDA. He didn\'t write it in their health
> reports for the children.
>
> These children are one in two million, one in three million, and they
> have not been looked at. They have not been studied. I ask you, for
> the sake of our children, for the sake of our next generation, for the
> sake of your child, would you want to think about your child and what
> would happen to that child being exposed to this device that is
> leaking through your body?
>
> We need more studies. We need fair studies. We need studies by the
> NIH. We need studies that are not manufacturer funded. We need to come
> together as a group, as a society and take care of these kids. They
> can\'t get health insurance. Mothers are afraid to go to the doctors
> and say anything because their insurance company will drop them.
>
> I wish I had more time, but there are many, many children out there
> and there is plenty of evidence. You know what, I have two boys. My
> two boys have severe problems. My young son had a bone cyst removed on
> his head, and I have about ten other kids that have the same thing.
> So, I beg you, do not put these implants back on the market.
>
> MR. HAYTON: I am Rodney Hayton. I am the CFO of the National Silicone
> Implant Foundation. I have paid for the complete expenses of this trip
> out of my own pocket.
>
> I know that Inamed says silicone implants don\'t cause disease. That
> depends on your definition. However, the impact of silicone implants
> varies from person to person according to leakage rate and personal
> immune system threshold. Silicone overloads and damages the immune
> system. Silicone allows a variety of atypical disease symptoms to
> develop.
>
> Silicone implants can harm infants because silicone crosses the
> placental barrier and goes into mother\'s milk, proven by what is
> referred to as the Scandinavian studies, funded by Dow well over
> quarter of a century ago, report number 39-89 Dow Corning research
> department, 1972. I have provided a copy to the panel.
>
> In March, 1994, the FDA advised the Human Milk Making Association to
> screen for women who have or have had silicone implants. The body
> tries to remove silicone with macrophages, nibbling off bits of the
> polymer chain. Silicone is moved all over the body. Wherever the
> macrophage is when it expires is where the silicone is deposited at
> these locations. The body, through its wondrous chemistry,
> demethylizes the silicone which results in grains of sand all over the
> body.
>
> What has happened to some of these women with implants the SPCA
> wouldn\'t allow to be done to your dog. A five-year old child does not
> need epidemiological studies to figure out \"don\'t touch the hot
> stove.\" They do not have to understand how and why.
>
> Actuaries for insurance companies know about silicone implants. That
> is why Blue Cross and Blue Shield in Texas and other states will not
> provide insurance coverage to women with implants. The Canadian FDA
> knows about silicone implants since Canada has socialized medicine and
> their actuaries know that silicone implant patients have a
> disproportionately higher morbidity and mortality rate as compared to
> similar women without implants. United States centers of Medicare and
> Medicaid actuaries know the statistics because of women\'s health care
> and disability claims.
>
> Mme. Curie died of the effects of radiation toxicity from her
> experiments with pitchblende. She discovered and separated uranium and
> radium from pitchblende. This was back in the time when we did not
> know the dangers of radiation in the human body. She died just the
> same.
>
> There have been silicone implants where the removed the shell was
> completely disintegrated. What happens to these women? We do not know
> because it has never been studied and researched. It is illegal to
> inject silicone gel. So, what is the difference between an injection
> and leakage?
>
> The manufacturers\' own data shows a 35 and 45 percent complication
> rate after four years. I have seen the complications first hand. Not
> being a doctor, but being part of a support group, women have been
> fairly free to show what has happened to them. Some of them just show
> pictures and that is downright disgusting. How many lives have been
> lost or ruined from silicone in the body? How many more before the FDA
> will step up to the plate to do the right thing without regard to
> financial gain?
>
> For those who plan to do so, I applaud you. For those who do not,
> please step up to the plate also. We need more longer, in-depth
> studies and a better product before approval so we do not ruin any
> more women\'s lives that may be mothers, daughters, sisters, wives,
> granddaughters. I would hate to have eye surgery with a complication
> rate such as this. The results are more devastating than to be blind
> but I would not even think about it. Thank you.
>
> DR. KERRIGAN: Good morning. I would like to thank the General and
> Plastic Surgery Devices Panel for the opportunity to present today. My
> name is Dr. Carolyn Kerrigan. I am an officer of the Plastic Surgery
> Educational Foundation, and I am here today speaking for that
> organization.
>
> I am a Professor of Surgery at Dartmouth Medical School and Section
> Chief and Residency Program Director for Plastic Surgery at
> Dartmouth-Hitchcock Medical Center.
>
> In 1989 I wrote a report on polyurethane breast implants for the
> Ministry of Health of Canada, and in 1991 I testified for Surgitek at
> the FDA hearings on polyurethane covered silicone gel breast implants.
> I have no current affiliations or conflicts of interest with any
> implant manufacturer, and the Foundation has paid for my travel to
> present at this hearing.
>
> In my full-time academic practice of plastic surgery, I am a salaried
> physician. I do perform breast implant surgery, both for
> reconstructive and cosmetic reasons, and this surgery generates
> practice revenue for my multi-specialty clinic.
>
> The Plastic Surgery Educational Foundation represents the education,
> research and service arm of the American Society of Plastic Surgeons.
> The Foundation, founded in 1948, has three main core purposes:
> Education, research funding and international outreach and service.
>
> Critical to improving patient safety is continuing medical education
> of physicians. The Foundation sponsors instructional courses and
> several annual symposia to provide in-depth review of safety and
> outcomes related to breast reconstruction and breast augmentation.
> Learning opportunities in this arena have intensified since 1991. The
> Foundation has also developed an innovative web-based outcomes data
> collection tool allowing for national benchmarking and comparison of
> an individual surgeon\'s outcomes against that benchmark.
>
> Our organization also monitors the scientific literature on breast
> implants. This information is used to guide directed research projects
> in areas of identified concern and to support ongoing education of its
> membership. A document summarizing the current literature has been
> submitted to the panel.
>
> Research, as sponsored by the Educational Foundation, includes both
> non-directed and directed research. Over the past 13 years, the
> Educational Foundation has funded more than two million dollars in
> grants. Many of these projects are related to aesthetic and
> reconstructive breast procedures.
>
> Our directed research studies are an important component of the
> Foundation\'s activities. Our directed research policy does not allow
> any individual organization or corporate entity to direct or influence
> the selection, funding or design of any Foundation-administered study.
>
> In 1991, the FDA\'s call for the manufacturer\'s PMA for silicone
> gel-filled implants clearly identified the need for additional
> clinical research. Consequently, the Foundation established a three
> million dollar breast implant research fund. This focused effort,
> starting in 1991 and continuing to this date, has included 18 very
> specific projects to investigate multiple aspects of breast implants
> including autoimmune disorders, biochemistry of silicone gel implants,
> quality of life, device integrity, local complications, explantation
> and implant rupture.
>
> Eleven of the original 18 projects were acknowledged by the Institute
> of Medicine of the National Academy of Sciences in its 2000 report,
> \"Safety of Silicone Breast Implants.\" The IOM found, as most of you
> know, that women with silicone breast implants were no more likely
> than the rest of the population to develop cancer, immunologic
> diseases or neurologic problems.
>
> Building on members\' positive response to directed research funding,
> the Educational Foundation took a giant step forward in 1994 and
> established the specialty-wide National Endowment for Plastic Surgery.
> The goal was to create a perpetual funding source for research
> projects relevant to clinical practice and unanswered clinical
> questions. One such project so far sponsored includes support of the
> Center for Implant Retrieval and Analysis, which determined and
> demonstrated the types of scientific analysis needed for each type of
> implantable device used by plastic surgeons.
>
> In 2000, the Foundation developed the National Breast Implant Registry
> for data collection on all implant types and procedures. This has now
> evolved to a robust web-based data tool, with participation from more
> than 75 practices and over 5,000 women.
>
> Ten months ago the European Union mandated that its member countries
> implement breast implant registries by 2004. Several countries have
> selected our National Breast Implant Registry as the model of choice.
> The International Breast Implant Registry was thus formed to allow
> collaborative data collection and analysis between the U.S., European,
> South American and Australian organized plastic surgery.
>
> In conclusion, our specialty has remained at the forefront of
> reconstructive and aesthetic surgery based on its commitment to
> education, innovation and sound clinical and basic science research.
> The Plastic Surgery Educational Foundation is funding breast implant
> research to educate its membership, to ensure patient safety and
> improve patient outcomes. The Foundation has been proactive in
> establishing the National Breast Implant Registry and has established
> significant international collaborations. The Foundation believes that
> breast implants and informed choice offer health-related quality of
> life benefits for many women. Thank you.
>
> DR. WHALEN: Doctor, can I ask you a question? You mentioned, midway
> through your presentation, that the corporations do not direct or
> influence what research the Foundation does. Are you aware of any
> dollar amount contributions that Inamed may have made to the
> Foundation since 1992?
>
> DR. KERRIGAN: I don\'t have any numbers at my fingertips. Certainly,
> the substantial proportion of contributions to the saline implant
> research was through membership contributions.
>
> DR. WHALEN: Are there corporate contributions?
>
> DR. KERRIGAN: There are some, yes.
>
> DR. LI: Dr. Whalen, I have a question for the speaker\--Steve Li. You
> mentioned that you support the Center for Implant Retrieval and
> Analysis. Has this Center published any of their results anywhere?
>
> DR. KERRIGAN: I believe they have. We can get you those references.
>
> DR. LI: Thank you.
>
> DR. MCGRATH: Dr. Kerrigan, we were talking yesterday briefly about a
> registry. Can you tell us a little bit about where you see this
> National Breast Implant Registry going, what this is, how it may grow
> or whether you intend to have it grow?
>
> DR. KERRIGAN: We certainly intend to have it grow and develop in many
> avenues. Right now the Registry is basically physicians reporting
> details of their surgery; types of implants they use. As the numbers
> grow and we get more data, we will then be able to do an analysis and
> reflect. It is very easy to add particular data fields so if there is
> a specific issue that we need to address, we can add that to the
> database. Obviously, long-term we want to expand this so that women
> who go through this surgery have a chance to report on their outcomes
> and also their baseline health status before participating in this
> type of surgery. I mean, it has huge potential. It will take many
> years to grow but there is lots that we envision for it.
>
> DR. MCGRATH: Are there any measures in place to protect the patients\'
> privacy?
>
> DR. KERRIGAN: It certainly would be HIPAA compliant.
>
> DR. CONANT: May I ask a quick question? What is the incentive to
> register your patient if there is a benchmarking that is a
> requirement?
>
> DR. KERRIGAN: It is not currently a requirement. It is currently
> voluntary. But the development of this database and other web-based
> collection tools are very closely tied to some of the ongoing work by
> the American Board of Plastic Surgery which certifies plastic
> surgeons. As many of you are aware, there is an initiative in place to
> bring on board maintenance of certification so that surgeons would
> have to continue to maintain some degree of certification, and this
> would be an obligatory participation, logging of all surgical cases
> you do which, obviously, then would include a subset of breast implant
> cases.
>
> DR. CONANT: Any kind of auditing of one surgeon relative to the
> benchmark?
>
> DR. KERRIGAN: Yes, I mean the tool is designed so that individual
> surgeons can reflect on their practice relevant to national
> benchmarks. A group such as the American Board of Plastic Surgery
> would monitor how folks are doing, and if there are outliers, would
> have the capability to audit the practice. This is what we hope is
> coming over the next five to ten years. It is not there yet but that
> is part of what we envision.
>
> MS. GILBERT: So, for the 5,000 patients you mentioned, is it
> accessible to patients?
>
> DR. KERRIGAN: The Registry is currently not open to patients. Those
> are some of the issues that we are addressing and would like to see it
> evolve to that.
>
> DR. WELLS: Good morning. My name is Dr. James Wells. I am
> board-certified plastic surgeon and I practice in Long Beach,
> California.
>
> I am President of the American Society of Plastic Surgeons, the
> largest organization of plastic surgeons in the world. On behalf of
> the 5,000 member surgeons, I want to thank you for the opportunity to
> present the perspectives of our organization.
>
> I have no affiliations or conflicts of interest with any implant
> manufacturer. The Society has paid my travel. I perform breast implant
> surgery as part of my practice.
>
> Breast reconstruction and breast augmentation are procedures that
> significantly improve the quality of life for many patients. Both
> procedures give women a sense of normalcy.
>
> As a result of previous discussions with the FDA, the need for a
> document with photos which will fully inform the patient about risks
> and possible complications of surgery using silicone breast implants
> has been developed by ASPS, in cooperation with our sister society,
> the American Society for Aesthetic Plastic Surgery. This is an example
> of such a document, and I believe you have it in front of you. It
> includes a short quiz to validate the patient\'s understanding of the
> procedure which includes the risks and benefits.
>
> The choice of elective or reconstructive breast surgery has always
> been an individual choice for women. Consultations may take 30 minutes
> to one hour to complete. Most surgeons will continue to follow their
> patients indefinitely. However, the satisfied patient without any
> problems is reluctant to return for routine follow-up. This may
> account for the failure to obtain a higher percentage of follow-up
> sought by this panel. Even the periodic manufacturer\'s payment to
> patients for follow-up is not a consistent inducement for patients to
> return in the absence of any obvious problems.
>
> Plastic surgery is often a series of progressive operations, following
> one another at intervals. Breast reconstruction may require two or
> three procedures over a period of a year. Are these reoperations?
> Breast implant patients, other than reconstructive patients, may
> require some minor adjustments to achieve the perfection that they
> expect and the plastic surgeon hopes to achieve. Many of these minor
> procedures are done under local anesthesia, at no charge to the
> patient with the expense absorbed by the physician. In most cases,
> patients return to their normal activities in a very short time. Are
> these reoperations?
>
> As plastic surgeons, we recognize that the public has come to expect
> perfect outcomes virtually all of the time. How often do families
> insist that the plastic surgeon be called to the emergency room to sew
> up the simple lacerations, clearly within the capabilities of our
> emergency physician colleagues? The breast surgery we perform is not
> different. Patients and the public have come to expect perfection.
>
> Following this expectation of perfect, are we expecting or demanding
> that the breast implant achieve that same level of perfection? Could
> it ever achieve that designation of being the perfect implant? Or, is
> it reasonable to accept that, like all medical devices, it has its
> limitations, associated failures, needs for reoperations and, in some
> cases, is not indicated for all patients.
>
> ASPS believes that continued monitoring and tracking of these patients
> and devices should be part of the process. An earlier presentation by
> Dr. Bruce Cunningham and Dr. Kerrigan outlined a concept and plan from
> an existing registry to accomplish this and we are prepared to work
> with the FDA and manufacturers to accomplish this, if this is the
> recommendation of the panel. We are also interested in linking our new
> patient information document to the web-based registry and adding the
> follow-up patient satisfaction survey as a third component.
>
> The emotion of body image and its importance to all patients is what
> drives much of the demand for plastic surgery. This includes the use
> of breast implants. Every patient has a vision of themselves that may
> not be the same as others see them. Once considered the domain of only
> the wealthy, aesthetic surgical choices are now available to all
> women.
>
> Unfortunately, the occurrence of breast cancer is age indiscriminate.
> I can remember a 26-year old woman, faced with breast cancer, recently
> married, who was told she had to have a mastectomy. She was devastated
> when she came to my office. We agreed on a mastectomy, tissue expander
> and a gel implant. That was almost 20 years ago.
>
> After her surgery, she was faced with a decision to have a child or
> not. She consulted with me about that and, with encouragement, she and
> her husband had that child. She was concerned she would not be here to
> see her child grow up. She had the child. She beat the cancer. She
> still has the same gel implant of almost 20 years ago, and I receive
> an annual Christmas card update.
>
> Should she have been denied a gel implant which helped her with a
> serious life decision? The young woman with a totally male physique
> receives breast implants. What emerges is a young woman, at a critical
> social time in her life, who now feels and looks like a young woman.
> Was it wrong to give her gel implants after a long and detailed
> discussion?
>
> The picture I have tried to create for you is that of the typical
> plastic surgeon, consulting with patients, using implants which make a
> positive difference in their lives. It is not a perfect device. They
> all know it will have to be replaced at sometime in the future but, in
> spite of that, they make a choice which alters their life.
>
> During the implant terror of the early \'90s, I answered the telephone
> on an 800 bank of phones with other plastic surgeons, answering
> questions of patients not understanding the decision reached then.
> Many of these women were terrified regarding that decision. I don\'t
> want to have to repeat that scene.
>
> The scientific process is a continuum. What we learn today will be
> replaced by new technology and information in a matter of years. It
> has become the responsibility of this panel to determine the safety
> threshold which the implant must achieve to make it available for
> general use by all women. The tracking of outcomes, the use of
> evidence-based medicine, the follow-up and presentation of ongoing
> research would all be part of this discussion.
>
> On behalf of the members of ASPS, our current patients and future
> patients, we recognize your challenge and responsibilities. We will
> continue to care for our patients regardless of the panel\'s
> recommendation. We remain committed to scientific evaluation, the
> availability of a safe implant, and the patient\'s ability to choose
> the device she prefers. Thank you.
>
> MS. GILBERT: I have a question. Is this the document you were talking
> about?
>
> DR. WELLS: Yes.
>
> DR. ANDERSON: I have a question\--Ben Anderson. You speak for a very
> large group. We are not reviewing today all silicone implants; we are
> reviewing this one company\'s implant and the panel was quite
> surprised at the number of ruptures that occurred in a very brief
> follow-up period. Do you individually, or speaking for your group,
> consider the rupture rate acceptable?
>
> DR. WELLS: I am not sure that we have sat down to analyze that in any
> great detail. We heard the numbers today, same as you. Rupture rates
> are hard to evaluate. Patients come to us with silent ruptures, as we
> heard about earlier today. I have had patients personally who know
> they have had it for two years. They are satisfied with the appearance
> but, under urging that this is not the way the device is intended, it
> is replaced at some point in time.
>
> I think you can do breast examination. I think you heard from Dr.
> Spear that the breast has a different consistency and feel in the
> patient who has a ruptured implant. If the physician does his job and
> continues to examine his patient who comes back on a regular
> basis\--and that is always difficult to determine\--I think you can
> detect it and take appropriate action. Do we know the real number? I
> don\'t think we do.
>
> DR. ANDERSON: My question was, in your opinion, are these implants
> rupturing too frequently?
>
> DR. WELLS: No.
>
> DR. LI: Dr. Whalen\--
>
> DR. WHALEN: Yes?
>
> DR. LI: This is Steve Li. You mentioned your patient that has 20 years
> with her gel implant. Knowing that there seems to be increase of the
> possibility of bad events as time goes on, what advice are you giving
> this patient? Are you recommending that she replace her implants,
> knowing that the chance of rupture is going up with every year that
> goes by?
>
> DR. WELLS: Well, you know, it is that old story of \"if it ain\'t
> broke, don\'t fix it.\" I think if you maintain contact with your
> patient and you see that there is an issue, that the breast
> examination changes, then removing a device at that point of time is a
> relatively straightforward procedure. It can be done under local
> anesthetic. The device is pretty much contained in that pocket, in my
> experience, and removing it and replacing it is a relatively
> straightforward procedure.
>
> DR. LI: Thank you.
>
> DR. MCGRATH: One of the speakers before, making a fine presentation
> about surgery in youngsters, mentioned that the American Society of
> Plastic Surgeons doesn\'t have an opinion about that. Is that the
> case?
>
> DR. WELLS: No, we don\'t encourage surgery in patients under 18. There
> are situations where there will be some cases where a young woman has
> a congenital absence of a breast. She is developing; she is living
> with her peers. You can see dramatic changes in that patient if you
> afford them an implant after a long discussion with the parents and
> the patient. The presumption that the parent should not be involved in
> these decisions is a wrong decision. You have to have parental support
> in this kind of a thing.
>
> If you present that to the patient and suggest what if this device
> breaks, and you see the response from the patient, then the surgeon
> has an obligation at that time to say, no, you don\'t tell everybody
> yes because you have the tool in your box to fix the problem. It
> doesn\'t fit for everybody. At some point in time you are going to
> have to tell the patient the same thing\--you have had a negative
> outcome; you have had a reoperation. This implant is not designed for
> you; we are not going to put another one back in. At some point you
> have to draw the line. We are interested in a safe device; safe
> outcomes for patients. It doesn\'t stand to reason to think that we
> are going to use a device that is going to put our patients in harm\'s
> way.
>
> DR. CONANT: Just a quick question, I am still very interested in the
> concept of silent rupture and your ability to detect this by physical
> exam. I understand that when the capsule has ruptured there is
> extracapsular silicone, potentially nodules or even softening of the
> implant as the capsule ruptures that can be detected by physical exam.
> But I am wondering if you are aware of any study that compares
> physical exam with contained rupture.
>
> DR. WELLS: I am not.
>
> DR. CONANT: What do you feel your sensitivity is in detecting that on
> physical exam?
>
> DR. WELLS: Well, again, it depends on the amount of capsule. If you
> have a relatively soft breast\--and it is interesting how many of them
> continue to be soft\--there is a doughy feel to the breast instead of
> the kind of rebound phenomenon that the intact implants have. I think
> you can detect that on physical examination. You have to do the exam.
>
> DR. CONANT: And do you feel that there is a continuum between
> intracapsular and extracapsular\--
>
> DR. WELLS: It can be very similar. Again, it depends on the mechanism
> for the extracapsular. If it is under trauma, sudden deceleration, if
> you will, of the implant, it may be a different situation. Thank you.
>
> MS. MCDONOUGH: Good morning. My name is Mary McDonough. I have no
> financial tie to Inamed. I paid my own way here from California.
>
> I am here today as a survivor of silicone gel breast implants. My
> story is very similar to the stories that you have heard over the last
> 24 hours.
>
> At first I was very happy with my implants, but after about five years
> I developed complications and symptoms. When an MRI and a mammogram
> failed to detect a rupture, yet my symptoms progressed, I decided to
> have my implants removed. It was only then that I learned that the
> shells of both of my implants had completely disintegrated. I have
> been diagnosed with lupus, fibromyalgia and Sjogren\'s syndrome.
>
> I share the panel\'s frustration that despite 11 years of opportunity
> for research, Inamed has presented only one or two years of clinical
> data. However, I feel that some members of the panel may believe that
> postmarket surveillance is the solution to this dilemma and in a
> perfect world the manufacturers would continue to diligently and
> thoroughly follow the patients, both in the clinical trial stage and
> in the postmarket surveillance phase of the research. But the reality
> of the situation, and also listening to yesterday\'s data, leads me to
> doubt the ability of a postmarket study to answer any of the
> outstanding questions about safety that you and I have.
>
> Dr. Brown made a point last night that postmarket surveillance is not
> equivalent to a clinical trial. Furthermore, the members of this panel
> have concluded that the adjunct study, which could have provided for
> at least five years of data on approximately 25,000 women, had such a
> low follow-up rate that it cannot be considered reliable. So, the
> members of this panel should not be comforted by promises that
> postmarket surveillance will adequately answer the remaining questions
> of safety.
>
> In conclusion, the panel yesterday had a question about whether there
> were any published studies of degradation and breakdown of the implant
> shell [in vivo]{.underline}. I do want to point out that there is such
> a study, and it was given in the handout by Dr. Batich earlier today.
> The study states, quote, exposure to the [in vivo]{.underline}
> environment weakens silicone gel breast implants over time.
>
> Thank you very much for your time and consideration to this very
> important issue. Thank you.
>
> MS. BROWN: I just wanted to clarify, from a manufacturer\'s point of
> view, that there is a difference between post-approval monitoring of
> your commercial population as opposed to an obligation that the
> sponsor has to follow a clinical study, such as the core clinical
> study, out through ten years. This particular sponsor manufacturer was
> complimented on its follow-up activities with respect to their
> population. So, I actually have confidence in the sponsor\'s ability
> not only to monitor the adverse events in the commercial population
> but, in addition, specifically if they have an obligation to do
> follow-up for their core study population, they will, in fact, do that
> because they are legally obligated to do so.
>
> The second thing I wanted to mention is that I have heard a lot of
> comments about why is there so little follow-up at this point in time
> and, having gone through the product development process myself, I
> know that for companies doing validation it takes at least a year to
> do that. It probably took one or two years to negotiate the study
> protocol with the FDA. It probably took two years to enroll patients
> and another three years to do follow-up, and then another year to put
> the report together and get to this panel meeting. So, if you add
> those numbers up, from the time you decide what your device is and set
> the design, it probably took nine or ten years to get here today.
>
> DR. ZUCKERMAN: I paid my way here. I am donating my time and I have no
> conflicts of interest.
>
> I am Dr. Diana Zuckerman. I am president of the National Center for
> Policy and Research for Women and Families. Our independent,
> non-profit organization is a think tank that gathers research
> information and uses it to improve the health and safety of women,
> children and families.
>
> It is hard to testify as the last public comment, although I am sure
> you are happy to have one that is last. I will try to make this a
> grand finale. Since you already discussed the key questions last
> night, I wonder how I can say anything that you haven\'t heard or
> might want to hear or might be willing to hear.
>
> I will express my admiration for all the hard work that you have done,
> and my sympathy for your very hard hours here, and just let you know
> that I didn\'t get home until one o\'clock last night and then I had
> to rewrite all my testimony. So, I may have actually stayed up even
> later than you did.
>
> I am speaking from the perspective of someone trained in psychology
> and epidemiology who is a university faculty member and researcher and
> taught courses in research methodology before moving to Washington
> where I worked in the U.S. Department of Health and Human Services,
> the White House Science Office and for non-profit organizations.
>
> As a researcher, I studied depression, women\'s self-esteem and body
> image so I find myself in familiar territory here. I have read every
> published epidemiological study on breast implants and would like to
> very briefly discuss the Inamed studies in the context of those other
> studies.
>
> What do we know about the health effects of ruptured silicone gel
> implants? The FDA study, described by Dr. Brown yesterday, is the best
> designed study ever conducted on this topic. One reason for its
> superiority is that it was limited to women who had breast implants
> for at least six or seven years. There are other studies that had
> women who had implants for an average of six or seven years. That is
> very different from having studies where everybody had their implants
> for at least six or seven years.
>
> We know from hearing testimony of the women yesterday and today that
> many of these women were very happy with their implants, but then they
> had a rupture. Often that rupture occurred well after seven years. We
> also know that when epidemiologists try to figure out what is going on
> with what looks like some kind of new syndrome or disease, they do two
> things, they ask questions; they talk to people and they look at
> research. Both of those things are very important. You find your
> patterns when you talk to the people and then you look for your
> research to explain it and understand it.
>
> What do we know about the health risks of silicone implants more
> generally? I have heard the Institute of Medicine report, the Mayo
> Clinic study, the Harvard Nurses Study, and the meta-analysis all
> cited here. One thing I wanted to make clear, they are all about the
> same thing. The 17 epidemiological studies in the Institute of
> Medicine report are the same ones that are in the meta-analysis and
> they lean very heavily on the Mayo Clinic study and the Harvard Nurses
> Study. So, when you are talking about these as if they are
> independent, different proof of safety, they are not; they are
> actually quite the same thing.
>
> I would like to very briefly describe the shortcomings of some of the
> studies. I think it was said yesterday, in the context of the panel
> describing the safety research on the Inamed study\--I hope I didn\'t
> misunderstand, you said it was too small; too short. That is exactly
> what is true of many of these studies. They had rather small samples
> and they studied women who had implants for a short period of time. I
> will give just one example.
>
> The Mayo Clinic study, one of the best studies, included only 749
> women with breast implants; only 125 of them were breast cancer
> survivors. To be in the study, women had to have had implants for at
> least a couple of months\--months. On average, they had implants for
> seven and a half years. So, that means there were only about 375 women
> who had implants for more than seven years.
>
> Since diseases like rheumatoid arthritis and scleroderma take years to
> develop, there is no latency there; no time for them to develop. Since
> rheumatoid arthritis is not very common in women in their 30s and 20s,
> as these augmentation patients were, you are really looking at a very
> small sample and there is no statistical power to find out whether
> there is a significant increase. You don\'t have to take my word for
> it. Just read the study. The authors point that out themselves.
>
> So, while I agree that the Institute of Medicine report doesn\'t have
> sufficient evidence that there is a link between implants and disease,
> you can\'t conclude that there isn\'t, based on that report.
>
> In contrast to that study, the National Cancer Institute study also
> looked at women who had implants for at least eight years, another
> study that was really far superior to any other study, and they found
> women twice as likely to die from brain cancer; three times as likely
> to die from lung cancer; and four times as likely to commit suicide. I
> was on the scientific advisory panel on that study and I know it
> really well and would be happy to answer any questions.
>
> I have some descriptions of the studies that I have talked about since
> I don\'t have time to go into it, which I will give to the panel.
>
> Now I want to talk about signs and symptoms. Let\'s take another look
> at the signs and symptoms in the Inamed study. Think about the
> testimony you heard from the women. It took years for them to develop
> diseases but first they had symptoms that they didn\'t take very
> seriously. We all feel fatigue\--well, maybe it is because I am not
> getting enough sleep. Maybe I am working too hard; maybe I am getting
> older. There are a lot of good reasons. But I also want to emphasize
> that there are a lot of women who couldn\'t come today who would have
> loved to tell their story, but they couldn\'t afford to get here; they
> couldn\'t even afford \$150 to stay in this hotel.
>
> I now want to briefly talk about the cosmetic problems because I think
> that is one of the things that is most obvious, that when a woman has
> cosmetic results that are disastrous as a result of her implants, it
> is clear what is causing it. I have some photographs that I want to
> share with you.
>
> Here is a photograph of a 29-year old woman who had her implants
> removed after seven years. She had capsular contracture that was so
> painful she just had to have here implants taken out. This photograph
> is from the FDA website. That is obviously not a good outcome.
>
> Here is another woman that wasn\'t so lucky, Sharyn Noakes; you saw
> her photo yesterday. Her ruptured implant had leaked into her healthy
> breasts and when the silicone was removed that is all that was left of
> her breasts.
>
> This last one is Cathy Nye, a breast cancer survivor who suffered from
> necrosis and her implant extruded through her skin. We haven\'t talked
> very much about the complication rate in the Inamed study. Six percent
> necrosis among breast cancer patients\--six percent necrosis and that
> is a pretty serious thing to be worried about.
>
> Now very briefly, I will talk about the Inamed research and the
> quality of it. I applaud Inamed\'s excellent response rate in their
> core study, as many of you did. But, like Dr. Whalen and Prof. Dubler,
> I share your amazement of how little research the company has done in
> the last ten years. Look at their 1990 study, 29 breast cancer
> patients and even then they couldn\'t keep hold of them so they
> didn\'t follow them up. Several hundred augmentation patients
> disappeared into thin air; no follow-up. That is the research that
> could have given us ten years of study. It started in 1990 but they
> didn\'t follow up.
>
> Let\'s look at the adjunct study. That was the opportunity to study
> thousands of women but they lost them all to follow-up. Those data are
> gone and they could have been very, very valuable and helpful.
>
> One more thing, the core study is almost entirely white women. Women
> of color might get breast cancer but only six African American women
> and five Asian American women are in that study even though we know
> that both groups have more problems with scarring and that African
> American women are more susceptible to autoimmune disease.
>
> What does approval mean? If Inamed silicone gel implants are approved
> the company might be required to conduct research for another seven or
> eight years, but the FDA cannot enforce that. They do not have the
> authority to make sure that those studies are done. If they are
> approved, the FDA can try to enforce informed consent but they can\'t
> actually enforce it; they don\'t have that authority. If they are
> approved, the women ages 18 and older, 17 and 16-year old girls, will
> still have access to them, just as they do to saline breast implants.
>
> Finally, most important, FDA approval is the seal of approval. It
> sends a message, it says we think this implant is safe. So, if it is
> approved, even if you talk about all your concerns, it will still be
> seen as an approval. It will still be seen as a statement of safety.
>
> So, in closing, I agree that the FDA should have asked for more than
> two years but they didn\'t. But that still does not excuse the company
> from not doing the research that they knew would really help us
> understand what the long-term safety is. Thank you.
>
> MS. GILBERT: Can I go ahead? Dr. Zuckerman, I have some questions
> about some of the related cancer rates that you were talking about.
> Can you just tell us a little bit about that?
>
> DR. ZUCKERMAN: Sure. The National Cancer Institute study was really
> important because it compared women with breast implants to other
> plastic surgery patients, and that is a very good control group
> because they are very similar in terms of their affluence, social
> class and lifestyle choices. In this study where all the women had
> breast implants for at least eight years or the comparison group that
> had had plastic surgery without silicone, a different kind of plastic
> surgery eight years ago, what they found is that the implant patients
> were twice as likely to die from brain cancer; three times as likely
> to die from lung cancer or respiratory diseases; and four times as
> likely to kill themselves.
>
> They tried to control for smoking and they didn\'t have perfect data,
> but there were no differences among smokers in plastic surgery
> patients and breast implant patients. They are equally likely to
> smoke. So, there was no reason to think that smoking was the
> explanation for that.
>
> DR. ANDERSON: Thank you. That was a very helpful, interesting
> analysis. You cited in the studies, the Harvard study and the Mayo
> study and that you can\'t conclude that this group doesn\'t exist, the
> women who would have these adverse effects, because the study is not
> large enough. That is a type II error. You can estimate, however,
> based upon the statistics that you got, how large that group could be.
> Maybe Dr. Blumenstein could comment on this, but we know it is not 100
> percent that have it and the hypothesis is it is not zero. So, is it
> two percent? Is it five percent? Is it ten percent, based upon the
> data we do have?
>
> DR. ZUCKERMAN: Yes, let me say that I think from the data you can
> conclude that the vast majority of women do not get sick quickly. That
> is absolutely clear. But because there weren\'t very many women who
> had implants for a long enough period of time to develop these
> diseases, I think it is really hard to make any kind of judgment about
> what might happen in the future. You can make a judgment, you know,
> based on an average of seven years, or whatever, but it is very
> difficult.
>
> Just for example, if a woman smokes four packs a day of cigarettes and
> she has been doing that for eight years, she is not going to have lung
> cancer. You have to study her for a longer period of time. Lung cancer
> doesn\'t develop that quickly. And, we don\'t know how long it takes
> to develop scleroderma but we know it doesn\'t develop in two or three
> years. In fact, I would argue if a woman got scleroderma six months
> after her breast implants, it wasn\'t caused by the breast implants so
> you don\'t even want to look at those women. That is why you want to
> focus on those who had implants for a longer period of time.
> Personally, I think focusing on women with ruptured implants is really
> a very good way to study this, and cost effective.
>
> **Open Panel Discussion**
>
> DR. WHALEN: Other questions? If not, on behalf of the panel, I would
> like to acknowledge all of the last day and a half\'s public
> discussants. I would like to reassure them, as I did yesterday, that
> the panel, indeed, has heard each and every one of them and does not
> disregard the information that has been portrayed to us. So, we
> appreciate all of that. I think it is appropriate at this juncture to
> also acknowledge the yeoman\'s job that
>
> Ann Marie Williams, from FDA does, in trying to corral 110 smart,
> passionate people up to the microphone in the way that she does.
>
> Before we proceed with the scripted activities, because of the subject
> at hand and because the moon was high in the sky when we had our
> deliberations last night, we are going to open up for a brief period
> of time to the panel if there are any glaring or exceptional issues
> that anybody would like to discuss at this particular juncture. This
> is for discussion and not for questions at this particular point in
> time. But if anybody wishes to do so, keeping in mind this horrible
> configuration where we are sitting at where I can\'t see 60 percent of
> you, try to get my attention and I will recognize you for discussion.
> Brent?
>
> DR. BLUMENSTEIN: Will we have a chance to make comments later?
>
> DR. WHALEN: The last sequence of information exchange before a motion
> would be entertained and a vote would be taken upon would be that of
> the sponsor, following FDA having an opportunity to do so. There will
> be some time at that juncture, following the time allotted to Inamed,
> for some questions and answers. But if we are talking about comments
> per se, the only time that you will be making comments per se after
> this, if you choose not to do so, would be the justification for your
> vote as it was cast. Prof. Dubler?
>
> PROF. DUBLER: Dr. Whalen, I, at least, would argue that there are
> substantial issues to be discussed among the panel members, given
> their different expertise, before I would be comfortable voting,
> though I am not sure how to deal with that.
>
> DR. WHALEN: That is what we are about right now.
>
> PROF. DUBLER: Well, let me pose my questions and see if panel members
> have any response. I am extraordinarily conflicted after all of the
> testimony and the data that we have heard and the passionate pleas
> between my concern that the data of one or two years is simply
> inadequate for us to determine safety, on the one hand, and the notion
> that there are certain women who clearly do want access to silicone
> breast implants.
>
> I think there is another tension that concerns me and that is, as I
> mentioned last night, between the notion of do no harm, which is the
> physician ethic, and the notion of buyer beware, which is the market
> ethic. Every time I see advertisements in the newspapers and in
> women\'s magazines for breast augmentation it makes me suspicious that
> the people who will engage in the discussions with women will not be
> unbiased, which brings me to the notion that has been floated a number
> of times that a robust process of informed consent can, in some way,
> cure the defects in data and presentation that we have discussed.
>
> I would like to argue that that is not possible for numbers of
> reasons. One, because I think of the physician perspective, and we
> have had a lot of physicians who have testified that they are in
> full-time salaried practice and\--bravo, right?\--I think that the
> impact on their group is unlikely to affect their judgment. But if you
> are out there selling breast implants, I think that may affect your
> judgment.
>
> So, the process of informed consent begins on a tainted platform.
> Moreover, the data on informed consent, unfortunately both in the
> clinical and the research literature, show it doesn\'t work, that,
> indeed, there is something called the therapeutic fallacy that says my
> doctor is telling me to do this; it must be for my benefit. But there
> are serious structural problems with this notion of informed consent.
>
> So, I am faced with a problem, to which I would like other panel
> members to respond, that to approve something which doesn\'t have the
> data to support its safety seems to me to be irresponsible, but not to
> expand access seems, to me, to be mean to the women who want access.
> So, a compromise, in the sloppy business of reaching compromise, might
> be to expand access substantially but leave it under the aegis of a
> clear protocol to ensure that we get the data. So, I don\'t know how
> people with expertise would respond to that suggestion.
>
> DR. WHALEN: If I could jump in and maybe ask Dr. Witten to correct me
> when I say something wrong here, I would simplistically abstract what
> you have just said, Professor, into what form of motion you might wish
> to bring forward post lunch when we do it. To me, you are suggesting
> that that would be a motion to not approve because you feel that
> further study would need to be done before it is approved. Am I
> misinterpreting that?
>
> PROF. DUBLER: That would be my motion but I would be very interested,
> before I made that motion, in hearing whether those members of the
> panel who have greater expertise in research methodology and data
> analysis than I do are comfortable with the data that have been
> presented.
>
> DR. BLUMENSTEIN: If I might go ahead\--Brent Blumenstein\--one of the
> comments that I wanted to make because it occurred to me as all of
> these presentations were made, and so forth, was on the utility of
> registries. What I wanted to do is remind people that registries are
> not a replacement for randomized clinical trials or carefully
> conducted longitudinal studies.
>
> Registries do have utility, especially administrative utility, but
> registries are generally based on convenience sampling. That is an
> insult in statistical terms, in case you don\'t recognize it. And,
> convenience sampling doesn\'t lead to accurate estimates of incidence
> or outcome rates, especially when follow-up is also subject to
> volunteering to follow-up.
>
> Also, the lack of randomization and intervention assignment prohibits
> the valid comparison of outcomes with respect to interventions.
> Therefore, you cannot use registries to compare interventions.
>
> As I have been sitting here, I have been thinking about other studies
> that could be done, that are really necessary that came up in all of
> this. Some of these are in the form of questions that might be
> answered in the sponsor\'s comments and some of these might be ideas
> for studies that maybe somebody might want to consider. Especially
> when one considers all the resources being put into planning and
> implementing registries, I personally would prefer some of those
> resources diverted into good clinical studies, rather than registries.
>
> So, let me just forge ahead. One of the things that I wondered about
> was whether an analysis of the Inamed data included looking at
> outcomes, say reoperation or just time to bad things, by surgeon. One
> of the things that came up here is how good are the surgeons; how much
> variability is there in the surgeon\'s performance. And, you have an
> excellent opportunity here to explore that I think.
>
> Another question I wanted to pose was whether there were experiments
> with implants in large animals, large mammals as opposed to small
> rodents. The idea here is that the physical characteristics of these
> larger mammals would more closely mimic the physical characteristics
> of an adult human or teenage human, as the case may be.
>
> Another example of a needed study that I saw was to evaluate the
> diagnostic performance of the physical examination for a silent
> rupture as compared to, say, MRI. There was an assertion that maybe
> good, close follow-up by the surgeon with a physical examination might
> be sufficient. Well, we need to know that, and here is an example of
> the kind of research that might not be sponsored by the sponsor, might
> not be funded by the sponsor but is certainly needed in order to carry
> forward with this. That is all I wanted to say.
>
> DR. WHALEN: Brent, in terms of how good are the surgeons, it is
> rumored that Denton Cooley was once asked to name the three greatest
> heart surgeons of all time and he could not think of the other two
> names!
>
> \[Laughter\]
>
> DR. LEITCH: I guess the question I would ask is what kind of study are
> we saying would be sufficient to answer the questions that I think
> have been raised by the public that has spoken? Are we asking for a
> randomized trial of saline versus silicone implants? Are we asking for
> a study that would have follow-up of 20 years of a particular device?
> You know, I think we have heard this theme over and over again about
> the long-term issues of follow-up and that some of these side effects
> that people are reporting appear late. So, you are asking for a study
> with at least ten years of follow-up and maybe beyond that as the way
> of sorting out if this is okay.
>
> So, if you say that is the case, then, you know, you take an implant
> that is proposed at this time that would be implanted over a period of
> five years maybe, then you need the data collected on those patients
> for ten years beyond that. What happens in that interval for research
> and development for implants that are better if the manufacturers
> anticipate that their way to get that to market is that they must
> produce a 15-year or 10-year follow-up experience before it comes to
> approval? So, I think we have to say what kind of study are we saying
> we have to have to say it is okay. I think that is one thing we need
> to know, and how could that be designed.
>
> DR. WHALEN: We will go to Dr. McGrath and then to Ms. Brown.
>
> DR. MCGRATH: I am a little out of sequence here because my response
> really isn\'t a scientific, technical one. I really wanted to speak
> back to Ms. Dubler\'s questions when she mentioned her conflicts
> because some of those really revolve around questions of the ethics of
> the plastic surgeons involved in this and the researchers, and also
> the issue of self-enhancement which you actually brought up twice.
>
> I think we probably should look at those head on. One of my other hats
> is I have served since 1982 on the committee of ethics for the
> American College of Surgeons, and I also chaired the ethics committee
> for the American Society of Plastic Surgeons, and these are issues
> that we talk about all the time. Every physician is paid for their
> services when you do something for a patient and, yet, there is a
> concept of professional beneficence which we regard as the behavior of
> the physician that puts the good of the patient over the good of the
> physician. This is something that we take very seriously and is
> practiced by, I think, the vast, vast majority of physicians in the
> United States.
>
> Obviously, there is a tension since physicians do get paid for what
> they do, but the goal is to always have that payment only secondary to
> doing the correct thing for the patient. In this particular case, I
> don\'t think this is really such a pressing issue, to tell you the
> truth, because right now having this product available will have very
> little financial impact on plastic surgeons\' practices. We have
> saline implants available. We use them for breast reconstruction and
> for breast augmentation. So, I don\'t see this as a major issue.
> Therefore, I wouldn\'t call into question, as you did, the testimony
> of the physicians before us today or the researchers before us today.
>
> The second issue that you brought up is self-enhancement and sort of
> you having a struggle with this. You know as well as I that this is
> ancient and pervasive, the whole concept of self-enhancement. I would
> ask everyone in the audience how many of their children have had
> orthodontia. Orthodontia is a right of passage for teenagers nowadays.
>
> The breast surgery I do on teenagers, interestingly, is all on boys. I
> see a large number of young males who come in with feminization of
> their breasts. It is called gynecomastia. Even as I was leaving San
> Francisco the other day, there was a 15-year old boy who essentially
> had D-cup breasts. This is cosmetic surgery. This is not covered by
> insurance. I can do a procedure where I put this young boy under
> general anesthesia, with its attendant risks, and with a combination
> of liposuction and excision take away this feminization. Is this
> trivial to him? Is this something that I shouldn\'t do? It has no
> functional effect on him. There is nothing wrong with him hormonally.
> He is simply embarrassed by the fact that he has girl-like breasts and
> he doesn\'t like to take his shirt off in the gym. Somehow we don\'t
> have a problem with saying that that is okay, to correct that
> feminization for that boy but, yet, we struggle with saying it is okay
> to make a girl with a flat chest have A or B cup breasts with an
> implant.
>
> I think we really need to think about where our own acceptance of
> these procedures comes into play here. Those are really my comments.
>
> DR. WHALEN: Ms. Brown?
>
> MS. BROWN: With respect, at this moment in time, to advising the
> sponsor to conduct a new randomized clinical study, a bigger study, a
> better study, a new study, as a manufacturer, I would ask what is a
> manufacturer to do who wants to get one of these devices approved?
> They started this work back in\--what?\--1992, 1994, and they had to
> have embarked on a discussion with FDA on what was an appropriate IDE.
>
> The FDA never guarantees that when you conduct an IDE they are going
> to get approval from the data because you can\'t predict what the data
> are going to look like, but you do negotiate a protocol that you hope
> will lead to approval. In this case the company was additionally
> guided by this guidance document that I printed off the Internet. I
> don\'t know if it was in our packages. It is called \"Guidance for
> Saline, Silicone Gel and Alternative Breast Implants, Guidance for
> Industry and FDA.\" It was recently updated, February 11, 2003 and it
> supersedes a document from August 13, 2001, and I don\'t know if there
> is a previous version of it. But in this is a description of the
> preclinical and clinical testing that should occur in order to get to
> this point.
>
> Once again, it doesn\'t say what are the appropriate safety data that
> you absolutely need but I can tell you that the size of the study, the
> nature of the study, the nature of the analysis that have been done
> are extremely consistent with this document. It also goes on to say
> FDA believes that a PMA may be filed with a minimum of two years of
> patient follow-up on a sufficient cohort of patients to evaluate the
> safety and effectiveness of the product. Then it goes on to say that a
> total of a minimum of ten years prospective patient follow-up should
> be required.
>
> The company, I will say, has already demonstrated that if a PMA were
> to be approved they certainly would do ten years worth of follow-up. I
> believe that they would do adequate patient follow-up and compliance
> because they have demonstrated they can do that already with saline
> implants that are on the market. So, those are my comments.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: The concern that I have with that is that what we are
> learning is that the concerns don\'t really fit with this guidance
> document. There is no precedent for asking longer than two years. But
> we are concerned that there are delayed effects, delayed rupture, the
> performance issues that defy the recommendations of typical devices,
> at least this is what I am grappling with.
>
> I am having trouble coming up with a feasible study that would really
> answer the concerns that we have on these delayed problems. So, I
> agree that it is a problem for the sponsor to tackle or to answer our
> concerns, but that still doesn\'t necessarily obviate the fact that
> these problems are there.
>
> MS. BROWN: I hear you, and I heard this morning somebody suggesting
> that we might need a treatment group of 60,000 patients and a control
> group of 60,000 patients. If one were to need studies of that size,
> you might as well kiss the breast implant business goodbye. I am not
> sure anybody will be able to do the study.
>
> DR. WHALEN: But could I just interject, I couldn\'t get to sleep last
> night because, you know, that word \"safety\" keeps flashing in front
> of my eyes. If that is, indeed, the case we can\'t say, well, you
> know, from a pragmatic point of view the study would be too difficult
> to do so to hell with it; we will approve it even though we haven\'t
> demonstrated its safety.
>
> I think the charge to the panel is to disregard the pragmatism and
> disregard the logistics of whatever the study would be to accomplish
> the goal; that the goal is, is it safe or isn\'t? Dr. Miller?
>
> DR. MILLER: I have tried for so long to understand why this is such a
> difficult topic, and why I can discuss controversial medical things
> with my colleagues and others and it is just a discussion about a
> disagreement but in this one, if I encounter somebody I disagree with
> my morality is questioned; my ability to think clearly is questioned.
> I mean, it becomes a very personal thing. Now, why is that? I mean,
> what is happening with this problem?
>
> One thing we haven\'t discussed in all of our deliberations, and we
> had a unanimous opinion last night, was the effectiveness of the
> device. I mean, our charge is to determine safety and effectiveness.
> Effectiveness is universally agreed upon, that this thing changes the
> shape of the breast by making it larger or creating a simulation of a
> breast when there wasn\'t one there. Nobody argues the effectiveness;
> that is a closed book.
>
> We are talking about the safety, the safety is a problem because it is
> a ratio of the benefit versus the risk. The reason why we have such a
> difficult time describing acceptable risks is because we have such a
> different view of the benefits. So, that ratio is different in
> everybody\'s mind. We have had testimony here, in this hearing, from
> every part of the spectrum, from somebody who feels so strongly
> against the morality of enhancement surgery that a perfect safety
> record would be unacceptable because, by principle, there is no
> benefit but, in fact, there is only damage from these devices. So, by
> definition, you could never have a safe device, given that
> perspective.
>
> There are different grades of the benefit. What we have to avoid is
> getting into the business of deciding for people what the benefit is
> because the individual who wants this surgery has to go through this
> risk/benefit exercise in their own mind, and it is going to be
> different for every person. There are those who perceive such an
> enormous benefit from having these devices that they would face
> enormous risk to have them.
>
> Now, there is a limit to what we should permit in terms of somebody
> doing that, but I don\'t know if we have hit that limit. I don\'t
> think we are there. I think that a large amount of latitude needs to
> be given to people to weigh for themselves the benefit and risk, and
> that is what is going to define safety for them.
>
> I think that is why we have such difficulty with deciding if these are
> safe. It is not because we are not sure what the risks are. I think
> the risks are really pretty clear. I mean, we know the short-term
> complication rates. We know what has to be done for those. We know the
> long-term risks in terms of systemic diseases. We haven\'t
> demonstrated a link with systemic diseases. That is not to say they
> are not there but we haven\'t demonstrated it.
>
> Now, I have heard a lot of analogy to the needle in the haystack and I
> like that. If I could try and attempt to use that for a moment, we
> have this giant haystack. We know that needle is getting stuck\--that
> needle is a bad thing, and we have had numerous examples of how bad it
> is to get stuck by the needle. If there is a needle in that haystack,
> I want to know if it is there. Okay? But the needle is so small, is it
> appropriate to restrict any access to the hay because you might stick
> yourself with the needle that we don\'t even know is there?
>
> I mean, we have to have perspective on this. I mean, if somebody says
> I am so afraid of being stuck by the needle that there is no way
> anybody should be stuck by a needle and I am not going to touch the
> hay if I can\'t be assured there is no needle there, that would
> require exhaustive knowledge of the haystack, which is impossible. So,
> you could never say it is a safe device.
>
> But if somebody says, look, the needle may be there or may not be
> there. My chances of getting stuck by the needle are so enormously
> small because it is a needle in a haystack, I am going to take some
> hay and take my chances. They have weighed this risk/benefit thing in
> their mind.
>
> I don\'t think we should stand in the way of that. I think we should
> permit them to weigh that in their mind. Based upon the evidence I
> have seen, I am comfortable that, given the definition of safety and
> given the ability of the person to have the freedom to weigh this
> benefit/risk ratio in their mind, the risks are well defined, small;
> the benefit, the patient can decide. My job is to inform them what the
> risks are and let them make the decision. That is sort of how I would
> analyze it. Thank you.
>
> DR. WHALEN: I think it makes a difference whether you are the farmer
> or the horse. Dr. Leitch?
>
> \[Laughter\]
>
> DR. LEITCH: Again with respect to the study issue and how that would
> occur, whether a study would occur before market approval or would
> occur after market approval, I think one of the questions being raised
> by speakers to the podium and also on this panel is if the panel were
> to approve the product with conditions, what is the authority of the
> FDA to confirm that those conditions are lived up to and if, in the
> performance of those conditions, there is found to be a significant
> adverse issue what is the authority of the FDA to then bring that
> product back for reconsideration? I think that is some of the concern
> that has been raised. If you let it go, then it is gone and you can\'t
> do anything about it.
>
> DR. WHALEN: Dr. Witten, would you like to answer that question?
>
> DR. WITTEN: Well, I think what someone commented on previously is
> true, which is that we haven\'t pulled one of these products from the
> market because of something seen in the post-approval study. But
> typically what we do is work with the manufacturer to make sure that
> that information, from that post-approval, becomes public and is made
> a part of the labeling, that the information is available to the
> physicians and the patients so that they can enhance their ability to
> make a choice as to their use of the product. So, you know, that would
> be what we would do, whether it is adverse information or information
> that confirms longer-term durability or sheds some other light on the
> longer-term performance of the product.
>
> DR. LEITCH: What about the idea that if you make the condition that
> they have do deliver on it? You know, if you approve with a condition?
>
> DR. WITTEN: Our ability to enforce that is limited. We do work with
> sponsors to make sure that we get the information that we need but I
> think it would be accurate to say that it is limited.
>
> DR. WHALEN: To extend that perhaps to what I would think might be an
> extreme example, if the panel were to stipulate and FDA were to accept
> the recommendation that the sponsor must continue the data acquisition
> with the same degree of rigor that has been done to this point in
> time, and if in a year the sponsor decided, well, we aren\'t going to
> do our mail-out surveys that we originally proposed; we don\'t really
> need to do that, what recourse would FDA have in that case?
>
> DR. WITTEN: Well, I just say we hope it wouldn\'t come to that. We
> would work hard with the sponsors to try to avoid that situation. It
> is really hard for me to speculate on what action we could or would be
> able to take in that case.
>
> DR. WHALEN: I hate to press you\--maybe you won\'t ask me back and
> that is okay\--
>
> \[Laughter\]
>
> \--but, to your knowledge, in the Code of Federal Regulations what
> power is vested in FDA when posed with a circumstance such as that?
> Make it generic, when a sponsor largely completely disregards the
> stipulations that have been made as part of the approval process, what
> power do you have to do something about that?
>
> DR. WITTEN: I think it would be very difficult for us to do take
> action with respect to the application.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: I would like to speak a little bit about the biomaterials,
> biomechanics of this device. I think the things that we are worried
> about here, short or long term to different degrees, is the fact that
> these implants rupture and that there is some silicone that makes it
> either intra- or extracapsular.
>
> From the materials mechanics standpoint, I find that it is amazing to
> me that we are still discussing this. The preclinical testing is
> essentially irrelevant to those two questions, has been irrelevant for
> over ten years. If you know that some percentage\--we have been
> discussing what that percentage is but it is certainly something above
> zero and could be some alarmingly high number\--you know some
> percentage is going to happen, if you have a laboratory test to show
> that none of them break, that laboratory test has no clinical
> significance.
>
> Worse than that, not only can we not assess this device, hopefully,
> some other company will come with a device that is touted to be more
> rupture resistant. But in the absence of a clinical test to
> demonstrate that, how will we ever believe the next implant will, in
> fact, be more rupture resistant?
>
> So, as near as I can tell, there has been no data that has been
> presented or that I have seen in the literature that even makes kind
> of a passing attempt to try to mimic the clinical failures of rupture
> and gel migration. In fact, we are still discussing just exactly what
> that gel is because a gel with a high molecular weight certainly is
> not going to migrate anywhere but, certainly if it is a D4 version of
> a silicone it is going to migrate somewhere. We have no idea what
> percentage is coming out. We have no idea where it is going. And, a
> lot of these are essentially very basic\--if I may take the liberty of
> saying that\--basic biomaterials questions that neither the sponsor
> nor the industry seems to have directly addressed.
>
> I think retrieval studies are crucial to this understanding but I
> think what we have seen from this application is that a retrieval
> study will not get us there if the approach to getting that retrieval
> is not scientifically based or unbiased to essentially to assign blame
> as to why the implant fails. It has to have the more basic failure
> mode approach to it that has been demonstrated in retrievals of other
> medical devices.
>
> So, my quandary is that the data that is presented for the mechanics
> and materials is absolutely no help to me to assess what the
> performance of this device is going to be. I think that underpins our
> question in all these clinical studies. If it is 15,000 or 60,000 some
> percentage is going to break and we are not going to know why.
>
> So, it is a little tough to me to describe how big a clinical study
> has to be if one of the things we are really worried about is rupture
> and we have no fundamental understanding of where that rupture comes
> from. For as long as these devices have been around, I am shocked and
> I don\'t know what to do about it.
>
> DR. ANDERSON: The argument was made by a number of people that if the
> FDA endorses the product the public will just accept this as, well,
> then it is without risk. I want to challenge that idea. I deal mostly
> with women who have breast health or breast cancer problems who, I
> must say, is a very educated crowd. So, I may be biased by that. But I
> think we may be selling the public short when we assume that proper
> informed consent cannot be performed.
>
> That being said, I think the question for the panel is do we have
> enough data that we can tell the patients what the risks are, because
> there are risks to everything that we do and this is not an exception.
> If the answer is, yes, we can describe what the risks are, then I
> don\'t see why we, in a paternalistic way, would say, well, then you
> can\'t have the product, because there are risks that we do to
> everything we do in life. If we cannot define what the risks are, if
> we don\'t really know what the worst-case scenarios are or the
> percentage likelihoods of these are, then that is the reason we need
> the study.
>
> I don\'t think we need further study to prove that this is a device
> without risk. We need further study to clarify what that risk is so
> that we can really know what they are getting into.
>
> DR. WHALEN: Is there anyone else on the panel who has any further
> comment at this stage? Yes, Ms. Brown?
>
> MS. BROWN: Once again as a manufacturer, I was actually unaware that
> post-approval requirements are unenforceable. Most companies that get
> those letters from FDA take them really seriously and the regulatory
> people inside a company walk around to hammer people over the head for
> the entire year to get the data in to FDA. Reputable companies, and I
> believe Inamed is a reputable company, take letters that they get from
> FDA extremely seriously. We try to comply 110 percent. So, even though
> there may not be apparent enforcement teeth to these letters,
> companies do take them seriously and the panel probably could make a
> requirement that those data get presented to this panel on some
> periodic basis.
>
> DR. WHALEN: Ms. Gilbert, did you have something?
>
> DR. LI: Dr. Whalen, just one other comment, if I may?
>
> DR. WHALEN: Ms. Gilbert had something. We will get back to you.
>
> DR. LI: Sorry.
>
> MS. GILBERT: Well, first I just want to thank everybody for their
> public testimony. I am tremendously affected by what I have heard. I
> just have this to add, if this product fails one woman it is not
> safe\--one woman and it is not safe.
>
> \[Applause\]
>
> We can do so much better\--we can do so much better. I am not
> convinced that we have an explanation on long-term issues, side
> effects. I know that when it comes to how doctors explain the
> complications and the cleanup of a mess from a rupture, it is varied.
> When you are going in and you are discussing about personal choice,
> me, myself as a consumer, I don\'t think that that was really\--I
> wasn\'t educated on the facts and I went through this surgery twice as
> a breast cancer survivor.
>
> You know, I am appalled when I hear this situation and how some of
> these circumstances women are going to have to live their life dealing
> with. It is horrifying; it is horrifying. And, I think if more women
> knew honestly what their choices were I think that they might choose
> something else. I think it is our responsibility to make sure that we
> are giving them that option.
>
> It is not just the women who go through the surgeries but, also
> something I didn\'t think about before we actually made it here on
> this panel, are the children and the second generation exposure to
> this. This is something that didn\'t even occur to me and it is so
> much bigger than what we are. We have a responsibility to look into
> that and I don\'t think we have really gotten any indication of what
> some of those side effects are; what some of the long-term
> ramifications are. I have children. I had children after I had
> implants. I am concerned. I just wanted to bring that up.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: I just want to add one other thing, and I don\'t mean to
> lecture my clinician colleagues but I don\'t think that we should
> accept the rupture rate that you have got even if the fix is something
> that is clinically easy to fix. I think the rupture rate is higher
> than I would like it to be. It seems well within our materials and
> engineering knowledge to improve upon that rupture rate, to lower that
> rupture rate. So, I think we need to think in terms of why is the
> rupture rate something that we are questioning after this point and
> are worried about\--obviously because we are concerned that it is too
> high.
>
> So, I wouldn\'t be satisfied with just being able to maintain our
> current level of performance. I think there is large room for
> significant improvement in that and I think we should aim for that
> somehow.
>
> DR. WHALEN: Dr. Miller?
>
> DR. MILLER: I could just say a word to that. I agree\--
>
> DR. WHALEN: You are not going to extend the hay analogy, are you?
>
> DR. MILLER: No, I would like to know why they fail. It bothers me that
> the mechanical testing preclinically does not reflect what happens [in
> vivo]{.underline}. I mean that tells me there is a real problem with
> the preclinical testing. I agree with that completely. I may be naive
> but it would seem to me that you could contrive a test that would
> simulate what the implant experience is [in vivo]{.underline} and try
> to refine that test until you begin to match the failure rate that we
> see. I mean, it would help you make a better implant. I mean, that
> needs to happen.
>
> That would make a better implant but we still have the safety of the
> current devices. I mean, it doesn\'t necessarily change the question
> about current device safety. We may not know the rupture rate but
> there are silent ruptures because they are asymptomatic and they
> don\'t seem to cause any problem. I mean, if there was a problem
> caused by the rupture rate we would probably have known years ago why
> they rupture and at what rate they rupture, but because they rupture
> and they don\'t generally produce any symptoms or any harm and women
> sometimes don\'t even want to change, tells you something about that
> there may not be a clinical relevance to the fact that it ruptures. I
> am uncomfortable with that but, again, I don\'t want to let my
> discomfort with the aesthetics of a ruptured implant just make me not
> want to have data that it actually harms people. So, I want to avoid
> that temptation.
>
> We need to find answers to these things but I don\'t know if it is
> appropriate to make these things contingent upon releasing these to
> wider use given the criteria of safety and effectiveness that we have
> to work with. I think it is holding the devices to a very high
> standard. I heard applause for the idea that any failure is
> unacceptable. That is a standard that is unachievable. So, we have to
> have a balanced view on this I think.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: Just one point, I think one way to kind of think about it
> for the panel is, based on the data we heard, what is the concern
> about rupture, about free gel, intracapsular and extracapsular? That
> is one way to distill the data. I do think the performance of this
> device in regards to rupture is quite poor and the recommendations are
> basically to leave it until there is evidence of rupture. So, one can
> then say, unless it is changed for other reasons, 100 percent of women
> will have a ruptured implant, who have them put in, basically.
>
> The question that you mentioned and that we are grappling with is how
> bad is free gel in the capsule? Similarly, how bad is extracapsular
> extravasation? That is something that we don\'t have good data on from
> the study but it is really an issue of how you look at the literature;
> how good is the literature that there is harm, both local and
> systemic, with free gel.
>
> DR. MILLER: I like that. I would like to know the answer to that. I am
> not sure that requiring an answer to that is necessary to maintain a
> restriction on the use of the device. I mean, I would like to know the
> answer and we need to find the answer but that is a pursuit that we
> will have for many, many years to come. In the meantime, there are
> many women who don\'t have the devices available because of the
> restrictions. So, some compromise has to be made here I think.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: I would just like to echo that thought. I think, for me,
> it is disturbing and I have said this already, the rate of rupture.
> The endpoint of that is failure. But the endpoint of the other medical
> devices is failure as well. A perfect example is knee replacement.
> They will not last forever. The endpoint will be failure of the
> device. The question is not will the device fail or really what
> percentage will will fail because sooner or later there theoretically
> will be 100 percent rupture. The question is will that result in some
> short-term or long-term problem. We know that, in fact, there are
> some/many short-term problems. We at least have a fairly good idea
> from the data, the literature, that the long-term problems, if they
> exist, are small. I think we need to remember that while we are
> thinking about these percentage rates.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: If I haven\'t done it already, I would like to kind of hammer
> home again another reason why we need to understand how these ruptures
> happen, and this is because if we don\'t know the mechanism of how
> these ruptures happen we are kind of at the mercy of the materials and
> design of the manufacturer through no fault of their own. For
> instance, we heard that the device now is substantially the same as it
> was ten years ago and they have made some small changes to, they hope,
> toughen the material.
>
> Well, in the orthopedic world our history is littered by improvements
> that people have done that were logical and in time turned out not to
> be logical because we did not understand the mode of failure. For
> instance, the simple example I gave the other day is that one would
> think that thicker would be better. But thicker may not, in fact, be
> better if you don\'t know the mechanism of its failure. So, the
> nightmarish thing that keeps me awake sometimes is suppose\--I am not
> saying the sponsor is going to do this but this is a generic thing, if
> the sponsor decides, for instance, to change their sterilization
> method, if they change to a different gel, if they change some
> relatively small manufacturing detail that changes the material
> properties somehow, in the absence of understanding the connection
> between material properties and structure they could inadvertently put
> themselves in a place where they don\'t have to be.
>
> An example of this is a French company that makes ceramics for femoral
> heads in orthopedics. The company has been in business\--I don\'t
> know, 15 years or more and never had a problem, and they brought in
> new ovens, a new type of oven. The first few batches in the new oven,
> which they swore would be faster, better, cheaper because of the
> temperature control in that oven\--the first few batches of that
> resulted in so many failures that it was temporarily recalled by the
> government because we didn\'t really understand the subtleties of that
> particular step. So, if we don\'t understand where the rupture comes
> from, in the nightmarish scenario, everything the manufacturer does to
> produce that implant potentially has an effect on the outcome.
>
> DR. WHALEN: Does anyone else have comments at this juncture?
>
> DR. MILLER: Can I say one more thing?
>
> DR. WHALEN: As long as it is not about the hay.
>
> DR. MILLER: I am sorry, I can\'t help myself. I just have to say one
> more thing. You know, part of the problem I think with why the device
> has not been improved so much, say, over the last ten years is an
> artifact in a way of what has happened with the regulation of the
> device. I mean, before the decisions in the early \'90s there were a
> dozen companies. Now, competition basically has been destroyed amongst
> the companies and all the companies have just been trying to answer
> some legitimate questions about the devices but there is not much
> discretionary time and energy and resource for improving in that
> environment.
>
> I think one thing which we may see if we lighten it up a little
> bit\--and I don\'t know, I have to ask if it is an all or none thing,
> do we say they are safe and then it is all over, or we restrict it at
> the current level, or can we do an in between sort of thing where we
> continue to monitor, and all of that? We can discuss that I guess. But
> I think a little liberalization to availability of implants and a
> little pressure off the companies will perhaps lead to better devices.
> I could see that happening.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: I just want to go on public record saying that I don\'t
> agree with you, Dr. Miller, on that at all.
>
> \[Applause\]
>
> We are talking about using these devices in patients and I don\'t
> think we need to cut anybody any slack. We want safe devices before we
> put them in people.
>
> DR. WHALEN: Dr. Newburger?
>
> DR. NEWBURGER: The device failure rate, I recall, is similar to the
> saline implant rupture rate that we discussed a couple of years ago
> when we were getting the follow-up on those devices, their
> post-approval progress report. But when a saline implant ruptures the
> patient knows it immediately, obviously. I mean, she wakes up one
> morning and it is just not there anymore. So, she is going to replace
> that quickly. With the silicone it is a different situation. The gel
> is slow to extravasate. So, it would be hard for the patient to detect
> if she has no symptoms, and if she has no symptoms she may not want to
> replace it.
>
> Since the silicone rate right now seems to be forever and it is not
> biodegradable\--I have listed to the people who have given testimony
> and the silicone chemistry really isn\'t well worked out\--it seems
> pretty clear to me that there is a small subset of individuals who
> have adverse reactions of one type or another to this. Prospective
> studies really are the gold standard and the size of the current study
> means that we are going to be missing the 1/1,000, 1/10,000 events,
> and I really think that we have to hold this to a different standard
> than other devices by the nature of the filler.
>
> DR. WHALEN: All right, I have once again masterfully mismanaged time
> so that my promise that we would have the FDA and sponsor before lunch
> was a complete bare-faced lie, for which I apologize. We will adjourn
> for lunch and reconvene at 1:30.
>
> \[Whereupon, at 12:45 p.m., the proceedings were recessed for lunch,
> to reconvene at 1:40 p.m.\]
>
> [A F T E R N O O N P R O C E E D I N G S]{.underline}
>
> DR. WHALEN: Some who were here yesterday may recall that there was
> some discussion about the pronouncement or position of the American
> College of Rheumatology, and our subject expert in that matter, Dr.
> Boulware, has done some further investigation and has some comment.
>
> DR. BOULWARE: The reason this was an issue for me yesterday is that in
> reviewing our conflict of interest with the FDA, we had to submit
> whether we had any financial interest which was obvious, but also
> whether we belong to any type of organization or professional society
> that has official policy statements about this. I serve on the board
> of directors on the American College of Rheumatology and queried them
> directly about this. I was given reassurance from them directly they
> did not have an official policy and, thus, I was a little distressed
> yesterday that maybe I either had wrong information or they had wrong
> information.
>
> I contacted them last night after the meeting, was able to get in
> touch with them and received a faxed letter from them today, which I
> will turn in to the panel but I will read to you briefly.
>
> The statement on silicone breast implants and the updated silicone
> breast implants statement\--and there was one in July, 1996 which we
> were not provided and I have that up here\--are not formal position
> statements of the College. Rather, they are statements that were
> developed in response to media inquiries. In addition, it is ACR
> policy that statements which are not reviewed and renewed within three
> years are automatically sunsetted. Therefore, the ACR currently has no
> active official statement on the issue. To clarify an issue I raised,
> the statement cited research studies that were completed at the time
> of this statement. The College did not conduct any research nor has
> looked at the research available since July, 1996. I submit this to
> the Chair.
>
> DR. WHALEN: Thank you, Dr. Boulware. At this time, I am going to
> attempt to very briefly summarize the panel discussions on the
> questions from last night to update individuals in the audience who
> may not have been able to be with us at the time that we went through
> them.
>
> For those who are M.D.s, I am sure you know how internists do this.
> You are about to get a surgeon\'s discharge summary on the questions
> last night, but the entire discussion is, of course, a matter of
> public record that will be published.
>
> The first of the draft panel questions had to do with judging whether
> or not there is adequacy of information to determine the safety of the
> product as regards asymptomatic rupture. There was consensus of the
> panel, overwhelming consensus of the panel that such was established
> for the short term, just one to two years, as was required by FDA but
> that long term that had not been established.
>
> The second question looked into the use of the historical published
> literature and asked whether or not that provided adequate
> justification to determine safety of the product with respect to
> long-term general health effects, and also the preclinical testing in
> that regard.
>
> Looking at the preclinical testing first, there was some persistent
> disquietude, among particularly the clinical panel members that may or
> may not represent a disconnect between the chemists and the actual
> testing that is involved, but the preponderance of opinion was that
> that preclinical testing did not translate in the way that one would
> like to an actual [in vivo]{.underline} situation.
>
> There was a higher degree of assurance, however, by the majority of
> the panel members that there is long-term literature that judges
> general health safety.
>
> The third and fourth questions, although we ended up discussing them
> separately, had a very similar pattern to them and asked us to
> consider, respectively for the augmentation and the reconstruction
> groups, whether or not there is reasonable assurance of safety, taking
> into account core study, adjunct study and AR90 study, local
> complication rates, the asymptomatic silent rupture information in the
> core study and published historical literature.
>
> There was some considerable divergence of opinion among the panels
> members and really no consensus could be reached on either of these.
> Although initially I, as the Chair, thought there would be a similar
> view in the augmentation and reconstruction groups, clearly there was
> some divergence of opinions, and there was also a particular concern
> raised in the augmentation groups as to the impact of implants upon
> patient attitude towards mammography and the potential effect that
> that might have in terms of screening for future neoplasia.
>
> The fifth question, shifted from safety to effectiveness and, as Dr.
> Miller and others alluded to this morning, there was fairly widespread
> agreement upon effectiveness having been demonstrated. It asked if the
> instruments that were used in judging patient satisfaction and health
> status, quality of life, such as the SF-36, Body Esteem Scale, etc.,
> were adequate.
>
> The consensus of the panel was that, yes, there was establishment of
> that, however, the caveat needs to be made that, once again, there is,
> just because of the imposed methodology, some question about whether
> or not that will remain so long term because there is a degradation in
> satisfaction with time, in part as might be anticipated, but also a
> trend that is as yet not fully plotted out.
>
> The sixth question had two arms to it. Going back to the safety
> questions that were raised in question number one, we were asked, in
> respect to labeling for this device, how often and how we would
> recommend that there be screening for asymptomatic rupture. Following
> from that, or at least attached to it, to comment upon the
> recommendations for the necessity of explantation of asymptomatic
> implant ruptures.
>
> As regards to that question, again there was no strong uniformity of
> opinion. The preponderance of people felt that mere screening
> examinations\--mere is not a word I should use; that is
> editorial\--that screening examinations would be sufficient but there
> was a significant element that felt that more sophisticated screening
> should be utilized, and the most predominant one that was raised was
> magnetic resonance imaging. The frequency of intervals of exam ranged
> from six months to two to three years, with a preponderance falling
> upon annual examinations.
>
> As to whether or not those asymptomatic ruptures should be explanted,
> there were seven of the panel members indicating they should; three
> indicating they should not; and three uncertain as to those who
> registered their opinions.
>
> The final question had to do with the outlined post-approval study. In
> the PMA the post-approval study was outlined to be a two phase, one-
> to five-year, six- to ten-year, follow-up study which would be
> mail-out surveys. There was a strong preponderance of opinion that
> that should be drawn to at least ten years, and at least a minority
> element felt that it should be beyond the ten years, and that a
> mail-out survey would be insufficient and there should be face-to-face
> contact, hopefully, with a physician, and also that the MRI study
> should be drawn out to ten years or more.
>
> As to specific endpoints which might be captured in a longer-term
> study, there were several that were mentioned, including the rupture
> rate, explantation rate, studies, if possible, histologically,
> biochemically and otherwise of the capsule and the extracapsular
> tissue, systemic problems being significantly and rigorously tracked,
> what other surgeries were performed, and the impact upon both
> pregnancy and offspring of those who have had implants.
>
> Now that I have finished it, it was more internal medicine than
> surgery. I got on a roll; I apologize. But, Dr. Witten, does that
> synopsis adequately, to FDA\'s regard, characterize our answering of
> the questions?
>
> DR. WITTEN: Yes, thank you.
>
> DR. WHALEN: Very well. At this time, is there anyone from the FDA
> panel or from the FDA who feels they need to give any synopsis or
> closing information?
>
> DR. WITTEN: Dr. Whalen, I don\'t think that we need to do so.
>
> DR. WHALEN: Thank you. We will then go to the closing comments from
> the sponsor. I serve at the pleasure of the panel that I represent
> here as to whether or not you feel, before they go into their formal
> 20 minutes\--we have, in view of everything that came up yesterday,
> extended the normal time from ten to 15 minutes to 20 minutes so that
> they may close. But short of that actual formal closure, are there
> significant questions of the sponsor, hopefully focused questions
> towards one answering entity from sponsor that anybody needs to raise?
> I am not going to preclude subsequent questions after their
> presentation as well by soliciting these questions.
>
> \[No response\]
>
> Then, if you would proceed, sir?
>
> **Sponsor Summation**
>
> DR, EHMSEN: Thank you, Mr. Chairman. Again, I am Ron Ehmsen, Senior
> Vice President of Clinical and Regulatory Affairs for Inamed
> Corporation. The sponsor\'s summation will be presented today by Dr.
> Scott Spear, who is our principal medical consultant. Again, Dr. Spear
> is Professor and Chairman of the Division of Plastic Surgery at
> Georgetown University Medical Center, in Washington, D.C. Dr. Spear?
>
> DR. SPEAR: Thank you. I almost get the last word in these hearings. I
> am Scott Spear, and it is my privilege to deliver this summation
> statement on behalf of Inamed.
>
> To begin with, I want to thank each of you on the panel for your
> extraordinary efforts over the last two days. Certainly the debate and
> discussion have been lively and informed, and all interested parties
> have had a fair opportunity to express their views.
>
> It is now my responsibility to summarize and, more importantly, to
> clarify Inamed\'s presentation. First, I want to say to the panel that
> yesterday afternoon many of you asked some very important and
> difficult questions and, candidly, we don\'t believe all of our
> answers were as complete or as responsive as they should have been.
> This was, frankly, unintentional, of course, and probably attributable
> to the pressures of the moment. Nevertheless, we realize that we may
> have created some uncertainties, some questions, and I would like to
> use my time to address some of those outstanding issues.
>
> To begin with, a question was raised regarding the length of the study
> we conducted on silicone gel-filled breast implants. Let us be clear
> about this. The agency outlined in their guidance document the filing
> criteria for a ten-year study, designed for submission after two
> years, which the company closely followed.
>
> Inamed conducted the study with rigor, accumulated the data and filed
> the information in a modular fashion, as requested in the agency\'s
> guidance. We remain confident in our data and of the timeliness for
> the study. As you may recall, the company filed two-year data for its
> saline implants and received approval. We believe that the two- to
> three-year data we presented over the last two days, coupled with the
> vast epidemiologic information from multiple studies that has been
> conducted over the past decade, has fulfilled the agency\'s guidance.
>
> Another important issue that was discussed, and this came up several
> times, was the question on whether we improved the quality of the
> product under consideration.
>
> We believe that confusion arose yesterday when questions came to us
> about whether this was the same product or not. We answered that it
> was the same product because it is still a silicone shell and still
> filled with a silicone gel. But there are crucial differences in the
> manufacturing specifications, and they are significant with regard to
> the device\'s safety and effectiveness.
>
> The difference is that the quality has improved in three important
> areas: An increased minimum shell thickness, almost doubling in
> thickness; a change in the specification to increase the cohesiveness.
> It is the same chemical composition, but the cross-linking increases
> the gel\'s consistency. Third, a more consistent, predictable
> manufacturing process with tighter tolerances of quality assurance
> based on stricter validation standards.
>
> Next, many panel members had concerns about local complications,
> particularly reoperation. Of the many possible local complications
> studied by the sponsor, the two most important that are implant
> related and are not cosmetic are capsular contracture and implant
> rupture.
>
> \[Slide\]
>
> Capsule contracture is shown on this overhead which, unfortunately,
> none of you can see. It occurred in 8.3 percent of 494 augmentation
> patients, similar to the rate of saline implants. It occurred in 16
> percent of reconstruction patients, lower than the rate for saline
> implants. You will note, those of you who can see on the projected
> graph, that the Kaplan-Meyer risk curve for capsular contracture is
> reasonably flat, particularly so for augmentation and revision.
>
> Complications such as asymmetry, malposition, bruising, scarring,
> hematoma, swelling, etc., are not implant related but surgery related
> complications. These same complications occur at similar or even
> higher rates with saline implants, and occur in other breast
> operations even without implants, including mastopexy, breast
> reduction, mastectomy and even breast biopsies.
>
> While data was collected on reoperations, removals and replacements,
> these are actually not complications but are, in fat, simply a
> description of events that are a response to either a complication or,
> more likely, some other indication.
>
> As mentioned last night by one of the panel members, plastic surgery
> is different than other surgical specialties. It is a process. Some
> members of the panel were concerned that 20 percent of augmentations
> and 45 percent of reconstructions had a reoperation. Well, it is
> widely known and accepted by plastic surgeons and their patients that
> 20 percent of rhinoplasties have a reoperation; most cleft lip repairs
> have a revision; the vast majority of flap breast reconstructions have
> a second operation; and any reconstructive or cosmetic procedure, if
> followed long enough, could benefit from a revision. Reoperation and
> revision is part of what distinguishes plastic surgery from other
> fields of surgery.
>
> Looking at the primary reason for reoperations for breast
> augmentation, only one was for rupture, representing 0.2 percent of
> all patients, and 35 were for capsular contracture, representing 7
> percent of all patients. Less than 10 percent of augmentation
> reoperations were for these implant-related complications.
>
> Of the reoperations for breast reconstruction, 6 were for rupture,
> representing only 2.5 percent of reconstruction patients, and 15 were
> for capsular contracture, representing 6 percent of all reconstruction
> patients. On the other hand, 71 were for surgery-related problems or
> cosmetic indications. So, of the 127 reoperations in the
> reconstruction patients, 15 percent were device related but 85 percent
> were not device related.
>
> A fourth issue that came up yesterday was the European experience with
> silicone filled breast implants. It is important to remember that in
> most countries in the European Union silicone gel-filled breast
> implants were never\--and I repeat never taken off the market. This
> gives these medical devices a 30-year or more track record in markets
> such as Italy, Germany and the United Kingdom.
>
> There were questions yesterday on whether there was any reliable data
> from Europe, but before I address that I would like to mention that
> the Europeans use silicone gel-filled breast implants over saline
> breast implants in a better than 9:1 ratio.
>
> To our knowledge, and I believe to the FDA\'s knowledge, there has
> been no cohort of women and no ministry of health to emerge and relate
> any serious health care issues concerning silicone gel-filled breast
> implants.
>
> All serious epidemiologic studies of the health outcomes of long-term
> silicone gel-filled implant use have come from the European countries,
> in particular in Scandinavia with their unique care and data registry
> systems. The literature to date has addressed every health concern of
> the FDA. Since 1994, these long-term studies have consistently shown
> that there is no evidence of silicone gel-filled implants having any
> long-term adverse health consequences.
>
> Now turning to probably the most talked about and most serious issue
> of yesterday is the issue regarding rupture and silicone gel-filled
> breast implants. Let me clarify one point that was not clear to the
> panel yesterday. Since our core study began in 1999, 318 patients,
> totaling nearly 600 implants, had had one MRI. An additional 86
> patients, totaling 170 implants, had a second MRI at a two-year
> interval. Our estimated Kaplan-Meyer risk at three years of silent
> rupture is 2.7 percent based upon that data.
>
> The rate of rupture of silicone gel-filled breast implants overall in
> our core study, projected over a three-year period, was collectively
> 3.4 percent. This result is consistent with a recently published,
> historic, prospective two-year randomized MRI-based rupture study. For
> silicone gel-filled breast implants similar to the Inamed implants
> under review, the failure rate between three and five years was
> approximately one percent per year.
>
> If you extrapolate the data from our MRI study and the Danish study I
> just quoted, the rate of rupture for a five-year period would be
> expected to be no more than five percent and for a ten-year period we
> would expect it to be 10-15 percent.
>
> But what is the significance when a silicone implant ruptures? In our
> data, with 26 reported ruptures with Inamed devices, there was no
> extracapsular silicone found either by physical examination or by MRI.
> Historically, with standard, substantially inferior earlier generation
> devices, approximately 20 percent of ruptured implants were associated
> with extracapsular silicone, which includes an era when closed
> capsulotomies were commonly performed, which were a known cause of
> extravasation of silicone.
>
> On the question of are patients with ruptured silicone gel-filled
> implants at risk of disease, the best way to answer that question is
> not in a small clinical study such as ours but, rather, in a large
> epidemiological study or studies. As has been shown in study after
> study, including a large scale recent Scandinavian study of over 8,000
> patients, there are three key findings that the panel needs to be
> aware of: There is no convincing epidemiologic evidence of systemic
> illness caused by silicone gel-filled implants, period. Finally there
> is no convincing epidemiologic evidence of systemic illness caused by
> extracapsular rupture of silicone gel-filled breast implants. There is
> no evidence for any of these concerns.
>
> Why do silicone gel-filled breast implants rupture? While nobody knows
> for certain why silicone gel-filled breast implants rupture, it is
> certainly the opinion of many experienced surgeons and many
> bioengineers that long-term ruptures are related to repetitive folding
> and tears created by creases from that repetitive folding.
>
> A question was raised this morning concerning a patent for a Trilucent
> soybean oil-filled breast implant. This patent was originally filed in
> 1994 by three individuals, not affiliated with Inamed, who were
> seeking a competitive alternative to silicone gel-filled breast
> implants. That patent was subsequently acquired by two different
> companies before being acquired by the Collagen Corporation in 1998.
>
> In 1999, Inamed acquired Collagen Corporation for its facial
> aesthetics business. In the course of that transaction, more than 600
> pieces of intellectual property became the property of Inamed,
> including the soybean oil patent. Clearly, Inamed would not state in a
> patent application that the use of silicone-based materials has been
> discontinued by the industry. Clearly, this would have been a false
> statement at the time it was made.
>
> I trust that we have addressed the issues that were on your minds
> yesterday, at least many of those issues. Now, what would Inamed do as
> a responsible company moving forward if the panel and FDA recommend
> approval of these devices for commercial use?
>
> Nancy Dubler gave us the correct formulation yesterday morning, one
> where we have an equal ethical responsibility with everyone else here
> today. It is our responsibility to protect the public with the safest
> possible product and maintain a patient\'s right of choice. In that
> process of choice, physicians and patients must have full access to an
> informed consent process that is reasonable and understandable. In
> addition to safety and efficacy, we agree that it is medicine and not
> the marketplace that should guide the decision to use this product.
>
> It is the obligation of Inamed to continually pursue a better product
> and this is what we propose to help meet our obligation, the
> following: Inamed agrees that a thorough informed consent form for the
> patient is essential. We would ask that a small group of the panel
> members help develop such a consent form, along with the FDA.
>
> Inamed would develop and distribute a patient education booklet on
> breast implants. This pamphlet will be built from the informed consent
> form and will be written for the woman who uses Inamed products. We
> will utilize focus groups to develop such a book. We want to make sure
> that every woman considering breast implants is as informed as
> possible.
>
> Next, we support this panel\'s opinion and will recommend to FDA that
> the patients should be followed up to ten years via physical
> examinations and MRIs at five, seven and nine years, and even longer
> if the panel so recommends. We understand from legal counsel that the
> FDA has every bit of the authority to enforce this requirement.
>
> Next, as a condition of approval, Inamed will supply to FDA and this
> panel annual reports on the post-approval study, and have an
> independent third-party, on annual basis, audit that study. Inamed
> will pay particular attention to any relationship between outcomes and
> rupture status.
>
> The company further agrees to conduct a device retrieval program to
> study the changes that occur in the product over time, and
> systematically investigate in a more aggressive fashion the failure
> modes for this device. We agree that if this independent third party
> finds that the study is not in compliance with these conditions,
> Inamed will agree that our PMA will be withdrawn.
>
> Fifth, we recommend any patient with silicone gel-filled breast
> implants have regular physician follow-up as long as the woman has the
> device in place.
>
> Sixth, Inamed will produce a guide and establish a toll-free telephone
> number for women regarding how to monitor their breasts after
> implantation with a silicone gel-filled implant.
>
> Seven, Inamed is developing a surgeon education and certification
> program to train surgeons in this particular area of surgery using
> silicone gel-filled breast implants.
>
> Eight, an Inamed patient registry that exists today will continue to
> track patients who use breast implants.
>
> In closing, Inamed feels strongly that we have conscientiously met the
> FDA criteria for safety and efficacy as outlined in their guidance and
> consistent with longstanding standards for implantable devices.
>
> In addition, these devices meet or exceed the safety data for the
> FDA-approved saline breast implants.
>
> The evidence for the long-term safety for these devices is the reason
> why they are widely available around the world, approved in over 60
> countries other than the United States.
>
> I personally feel strongly that these devices should be available to
> women who choose to have breast implants because they would be the
> best devices that would be available for women in the United States at
> the present time. I encourage you to approve this PMA in light of the
> above conditions that Inamed has proposed.
>
> Finally on a personal note, let me thank the panel members for their
> attention, their obvious hard work and their personal sacrifice to
> take part in these proceedings. Thank you.
>
> DR. WHALEN: Thank you. Are there questions of Dr. Spear while he is up
> at the microphone?
>
> DR. ANDERSON: I have a question. At the beginning of your summary and
> at the end you referred to FDA-approved saline breast implants. I was
> not on the panel two to three years ago, but my understanding was that
> it actually wasn\'t approved without restrictions; it was approved
> under conditions. Can you tell us what those conditions were, and what
> has the follow-up been? Do we actually know that the track of Inamed
> is that it follows through on conditions when they are provided?
>
> DR. WHALEN: Before you answer that question, let me just state to
> Inamed that we are going to have as many questions as the panel may
> have of you. Although it has been my experience that FDA sort of
> guards this table zealously from sponsors, I think it might actually
> facilitate things if you want to identify the most probable answerers
> of your questions to come to this table so that you don\'t leave your
> plastic surgeon floundering alone at the podium.
>
> DR. SPEAR: Poor plastic surgeon! I can begin to answer that question
> but, obviously, a regulatory person would be better equipped. Usually
> with approval comes labeling and conditions. Now, there was labeling
> associated with the saline approval which I don\'t think is really
> that critical. I think the conditions included long-term data
> collection. For example, the PMA was approved in May of 2000 and I
> think in 2002 the panel was reconvened for follow-up data on saline. I
> don\'t know how long that review continues out but I do know there
> were some conditions. JoAnn, do you want to answer that?
>
> DR. KUHNE: Yes, JoAnn Kuhne for Inamed Corporation. Yes, the
> conditions of approval were to follow those patients out to ten years.
> Six through ten years was with a mail survey; one through five years
> was with physician visits. We are currently in our seventh year of
> follow-up. We did present last year, in July, on those conditions of
> approval, identifying where we stood with those patients.
>
> Our follow-up was very good. We captured capsular contracture,
> reoperations, standard types of complications that we would look at in
> the clinical trial to begin with, as well as patient satisfaction.
> Those numbers, continuing out to five and six years, were consistent
> with what we had found earlier in the studies.
>
> Also, conditions of approval were a retrieval study, which we
> concluded last year and also presented in July on those implants as
> well as, as Dr. Spear mentioned, labeling. We did a focus group to get
> lay persons\' perspective on our patient brochure, making an informed
> decision for women for saline-filled breast implants to make sure that
> that information was readable and understandable to women. We got
> various feedback from women, basically on having glossaries in that
> patient brochure, as well as having data segregated in terms of
> reconstruction in one area and augmentation information in another
> area because women having surgery for those separate indications
> didn\'t want to see all of the data combined. They wanted to just
> focus on the data that was particular to their situation. As well, we
> had follow-up fatigue testing that we also presented last July.
>
> DR. WHALEN: Does that answer your question?
>
> DR. ANDERSON: Is the data that you are describing available on your
> website or easily available to the public?
>
> DR. KUHNE: The information that we presented to FDA last year was
> available on the website. We did update our labeling. I don\'t recall
> if the information is still available but we obviously could make that
> publicly available again. We will be continuing to follow these
> patients up through ten years. I don\'t know if FDA will require us to
> present to the panel again annually but, you know, we certainly are
> willing to do that and present that information publicly.
>
> DR. WHALEN: Other questions?
>
> DR. LAWRENCE: May I ask how you plan to follow the offspring, the
> women who were implanted and gave birth?
>
> DR. SPEAR: Here I am giving personal opinions in part, but offspring,
> in my opinion, should be followed not by a small study of 900
> patients. Most of these women are just ending or past their
> childbearing ages. That would need to be a much larger epidemiological
> study, looking at women who had implants and comparing them to a
> control group. So, it would have to be an epidemiological study, not
> in a group of 900 patients.
>
> DR. KUHNE: JoAnn Kuhne for Inamed. I would also like to point out that
> we did do extensive animal testing in terms of reproductive issues and
> teratology. If the panel wishes, we could have Dr. James Lamb, who is
> a toxicologist who was heavily involved in these studies, discuss that
> further. Dr. Lamb?
>
> DR. LAMB: I am James Lamb. I am a paid consultant to Inamed, with BBL
> Sciences.
>
> As part of the submission, there were both literature studies and
> studies done specifically on the elastomer gel, two generation
> reproductive study. In that case, they pulverized the gel elastomer,
> implanted it into the animals, mated those animals. Then, the
> offspring were kept long enough to implant in them and mate the
> offspring. So, you had an evaluation of not just the offspring early
> in life and also their potential exposure through lactation, but also
> then their own reproduction and development of their offspring.
>
> In all those studies they saw no difference in litter size; no
> difference in fertility; no difference in growth. They did
> histological evaluations to address some of the issues that have been
> raised before about the potential estrogenicity of certain components
> in the silicone for example.
>
> DR. LAWRENCE: Yes, I did read that material and I noted that in some
> of the experiments you actually sacrificed the animals before they
> were breast fed, and so forth. I was speaking of human information
> because it is different.
>
> DR. LAMB: Just to be clear, I am addressing just the preclinical
> animal toxicology studies.
>
> DR. WHALEN: Other questions? Dr. Li?
>
> DR. LI: First, I think your improvement on the retrieval studies, as
> Dr. Spears described, is excellent. I didn\'t see a commitment, if you
> will, to try to understand where the ruptures actually come from. The
> retrievals are one way to access those mechanisms, but I didn\'t see a
> commitment to either develop or fund the development of more
> clinically relevant failure modes of the device. Would the company
> care to comment on that?
>
> DR. SPEAR: Can I start off commenting? I have spoken to the
> bioengineers about this previously and within the last 24 hours. To be
> frank, I think this is a subject that has frustrated not just this
> company\'s bioengineers of this device but other companies because the
> preclinical testing has not, as we have seen, been a great test of
> clinical conditions. I think what they have committed to and, in fact,
> are excited about, frankly, is working harder to see if they can come
> up with something that better predicts behavior in humans versus in
> the lab. It is a hard model to produce for a lot of reasons, a lot of
> biological variables, but I think they are committed to come up with a
> better model.
>
> DR. WHALEN: Dr. Chang?
>
> DR. CHANG: Dr. Spears, thank you for clarifying some of the issues
> raised last evening. I would like to ask you to give me some advice
> since we have had so much public comment. If one of the women who had
> problems related to a diagnosis of fibromyalgia came to my office
> seven years after having augmentation with silicone gel, sat in my
> office and was so convinced that these changes came after the implant,
> seven years after, what advice can you give me in terms of how I would
> counsel them?
>
> DR. SPEAR: I guess I would give you the advice I would give the
> patient. The advice I give patients like that\--I mean, that is a
> clinical experience most of us have had\--is to say the literature
> does not support causation between silicone gel implants and
> fibromyalgia. It is a disease that is difficult to diagnose; it is
> difficult to get your hands around, but that a patient has options and
> if they feel strongly personally that they are linked, they have the
> option of removing the device totally or replacing it with a saline
> implant. And, different women make different decisions with that
> information. The minority, interestingly, remove the device. Probably
> most would leave it and a significant number would switch to a saline
> implant which still, of course, has a silicone elastomer.
>
> DR. WHALEN: Dr. Anderson?
>
> DR. ANDERSON: One of the questions that was raised is if you do a
> cosmetic augmentation that a woman is paying out of pocket to do, and
> then she has a rupture, say it is a premature rupture, she is then
> obliged to come up with more funds, which she may not have, to pay for
> this. How would the company in a responsible way handle this? Is there
> a warranty that comes with your product? Is there a period of time?
> Or, is this the \"buyer beware\" approach?
>
> DR. WHALEN: Could I please just interject, the transcriptionist
> requests that when all of us, but when Inamed is making responses, you
> start each time with your name.
>
> DR. SPEAR: We include it each time?
>
> DR. WHALEN: I am afraid so.
>
> DR. SPEAR: This is Dr. Spear responding. Inamed does have a warranty
> program for both silicone and saline implants, the precise details of
> which I am not aware but I know that it pays for a certain amount of
> dollars towards reoperation for a certain number of years, plus I
> believe it is a lifetime replacement of the device as long as the
> patient is alive. So, there is some warranty process. I don\'t think
> it totally obviates any expense.
>
> But interestingly, for many patients, fortunately, insurance takes the
> position that for whatever reason you got the implant, now that you
> have it, if you have a problem with it, insurance will pay, not in
> every case but in many cases. I have an analogy. You know, insurance
> companies, when you have an accident on your motorcycle, don\'t say we
> aren\'t going to cover it because you were stupid to get a motorcycle.
> I mean, the fact is if you get an injury, regardless of the cause, if
> you have insurance it usually does cover it.
>
> So, there is a warranty program and in many cases if a patient does
> have a significant problem with an implant, it is often covered by
> their insurance. Not inserting a new one. I charge patients after many
> years for putting a new implant in, but insurance usually covers the
> removal, or whatever else is required.
>
> DR. KUHNE: Excuse me, this is JoAnn Kuhne from Inamed. I just wanted
> to expand on what Dr. Spear said. The program that Inamed has is
> called the \"Confidence Plus Program\" and it does provide for up to
> \$2,400 of financial assistance in addition to the replacement
> implants, as well as a contralateral replacement if that is needed in
> a situation. These are both for our silicone gel-filled and our
> saline-filled breast implants.
>
> DR. WHALEN: Debera?
>
> MS. BROWN: I just wanted to bring up sort of a point of historical
> context. There are testicular prostheses available that have been
> recommended for approval by another panel. There are saline-filled
> testicular implants that were approved in July, 2002 based on one-year
> data. There are also silicone gel-filled testicular implants that have
> been approved on two-year data. Just so this panel is aware\--they are
> probably smaller; I have never seen one\--but there are similar type
> devices that are on the market that have been approved.
>
> DR. WHALEN: I would hope they are smaller, or maybe that is just me!
>
> MS. BROWN: No comment!
>
> \[Laughter\]
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: I have a couple of questions about item number seven in
> your proposals. The first question is, is this a recent idea that you
> are just putting out or is this a preexisting program, this idea of
> surgeon education, certification?
>
> Second question, would this be a required thing that would be a
> condition of purchase?
>
> Third thing, do you really mean certification? As you know, it is very
> difficult for any medical body to provide certification, which is a
> statement of competence and incompetence about the individual\'s
> performance of the technical process. It is one of the things we
> struggle with because it requires an examination process, and a
> proctoring and monitoring process while an individual is doing that
> surgery. So, I would like you to elaborate a bit on what you mean by
> that word \"certification.\"
>
> DR. SPEAR: I can answer two of those. I am not sure I can answer the
> middle one. But it is not a new concept actually. It has been in
> development for about six to nine months, the idea that if these
> products were approved, because they have been off the market in the
> United Sates for 12 years, there would need to be a reeducation
> program for surgeons to make sure, frankly, that we didn\'t go through
> what we did in the 1980s where people, who were not necessarily
> familiar with these implants, would be using them without proper
> training. So, that has been in the works. In fact, the first program
> was scheduled to occur in November, in Los Angeles, if there was an
> approval.
>
> Regarding certification, you can certify people. I don\'t know what
> certification will get you. I mean, the company could certify that
> somebody has had the program and has passed the training. It is
> certainly not required to have a license in any given state. The thing
> I can\'t answer is whether the company would require somebody to go
> through this program in order to be able to use the devices, and I am
> not sure that has been thought about. Do we have a decision on that?
> No. I don\'t think the company has made a decision about that.
>
> DR. MCGRATH: I think that would be a very important issue for us to
> have fleshed out before we accept this as one of the conditions.
>
> DR. WHALEN: Brent?
>
> DR. BLUMENSTEIN: Have you done an analysis by surgeon and on outcome
> to see how much variability there is between the surgeons that
> participated in your studies?
>
> DR. SPEAR: I don\'t believe we have, although I am dying to do it.
>
> DR. WHALEN: Let me follow that up though just from a practical
> standpoint, if you were going to do that, I would hope you would
> disclose the fact that you were going to do that. If, indeed, you were
> going to do that, how might it impact upon surgeon participation in
> your studies, in your opinion?
>
> DR. SPEAR: You are talking about analysis of the surgeons that
> performed?
>
> DR. WHALEN: Yes, if you were going to, surgeon by surgeon, look at
> results, which physicians in general and probably surgeons in
> particular are not necessarily wildly enthusiastic about having done,
> might that impact upon your ability to have surgeons participate in
> your study?
>
> DR. SPEAR: This is Scott Spear answering again. It is sort of a new
> territory for us to address but, frankly, it would be in everybody\'s
> interest, including the surgeon\'s, that if that did occur it would
> involve retraining of the surgeon. The surgeon, in the long-run, would
> be better off, having fewer problems, if he was identified as having a
> higher incidence of problems so that he would have fewer problems in
> the future. So, I think it would even be in the surgeon\'s best
> interest, not to mention the public\'s best interest and the
> company\'s best interest.
>
> DR. BLUMENSTEIN: This is Brent Blumenstein. I just wanted to make it
> clear that my interest in this analysis isn\'t to identify particular
> surgeons but, rather, to estimate the variability across surgeons,
> which would give you a lot of information about how intense you need
> to be about training.
>
> DR. SPEAR: Of course.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: Yes, Michael Choti. You mentioned that the device was
> improved in the last decade, the thickness and so forth. We still
> don\'t have clinically relevant criteria for determining whether those
> changes really improve the product. For example, what about the
> rupture rate? Any information that rupture is less with the new device
> than the older device? I mean, just to show that these mechanical
> properties may be different, or the thickness may be greater, or the
> cross-linking may be different\--how is the product any better?
>
> DR. SPEAR: This is Scott Spear answering again. What we are seeing is
> the maturation of the data that is going to give you that answer. The
> study I referred to in Scandinavia, looking at patients who have had
> what we call a third generation or the same type of device as this one
> but available in Europe, are showing a significantly lower rupture
> rate at five and ten years as compared to data from the \'80s, looking
> at the previous generation of devices.
>
> DR. CHOTI: But it may be capsulotomy and other factors that are
> related to that and not the device performance itself.
>
> DR. SPEAR: It could be but the fact that the rupture rate is lower is
> such good news that I wouldn\'t want to, you know, turn down good
> news. Whether it is the surgical practice that has gotten better as
> well as the device\--I mean, the device is being manufactured to much
> tighter specifications than it was. That alone should mean that you
> would have less problems, less failures.
>
> The MRI data that the sponsor presented, with 600 MRIs at one year and
> 200 at the second interval, is actually good data. The extrapolation
> of that data from the Scandinavian study gives you about the one
> percent rupture rate per year which, although it is higher than I
> would like, is not the doomsday scenario that people would have you
> believe.
>
> DR. BROOK: Could I just pick up on that? This is Michael Brook. One of
> the issues that came up was this question of the compatibility before
> and after. I think it wasn\'t mentioned this morning but, in fact, if
> you do the same mechanical tests on the explanted materials the
> mechanical properties had not changed. They were within the
> specifications of the materials before. This gets back to the question
> of the source of the rupture but those tests were done to show that
> the mechanical strength is there.
>
> DR. CHANG: May I ask how old were these explants that were tested?
>
> DR. BROOK: These were within the two-year study.
>
> DR. WHALEN: Dr. Miller?
>
> DR. KUHNE: JoAnn Kuhne. I just wanted to clarify that the retrieval
> study included devices that were out to an average age of 6.8 years.
>
> DR. MILLER: I have a question about how you would envision the
> education and certification program being conducted, and whether you
> think it would be appropriate to put in some criteria about what types
> of physicians would be permitted to go through this training program,
> where that is appropriate, and then there is going to be required some
> cooperation on the part of the practicing surgeon to deliver the
> devices back if they fail for a retrieval study and to follow-up
> patients and to register the devices. Do you have a plan to enforce
> compliance on the part of the practitioner with these programs?
>
> DR. SPEAR: I can answer some of that. I may need some help with some
> of the other questions, but in terms of how the sponsor would go about
> putting this program together, the plan is to do these at local sites,
> such as Los Angeles, Dallas, New York, Washington in the vicinity of
> major national regional meetings, before and after.
>
> Regarding putting teeth into surgeon compliance, we all know, the
> surgeons on this panel or not on this panel, that that is a harder
> issue. But, for example, the warranty program could be tied into
> surgeon compliance. I suppose shipment of devices could be tied into
> surgeon compliance. Am I going to get some help here?
>
> DR. CROTTEAU: Crotteau, from Inamed Corporation. In our \"Confidence
> Plus Program\" the patient or the doctor is not awarded the monetary
> remuneration until the explanted device is returned to us. So, by
> associating the return of the device with the payment of the program
> we try to facilitate the return of devices so that we can perform
> analysis.
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: Yes, do you think the company would be willing to
> consider making attendance at an education program and certification a
> pre-condition for receiving the implant to use?
>
> DR. SPEAR: This is Dr. Spear. I saw the appropriate nod from the
> responsible party of the company.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: I think, before we go too much further with talking about
> that, we had probably better step back a step and think about whether
> we really want to put all of these teeth in having physicians who use
> a product go through some sort of a mandatory process as a contingency
> for taking care of their patients and getting remuneration for their
> patients, not for themselves, because I am not quite sure that the
> best place to have the education and the \"ascertainment\" of
> competence is in the hands of a device manufacturer. This gives a
> certain amount of control over access to the device that might prove
> in the long run to not be the best thing for the physician and for
> patients.
>
> So, before we go too much further with that, I would stop and really
> want to hear what we are talking about here. Right now, it is a one
> sentence that seems to me very \"loosey\" and I would like to hear a
> lot more about this before we say that is a good thing to endorse.
>
> But my question really was on item two, your patient education
> booklet; item four, your discussion of the device retrieval program;
> item eight, the patient registry\--I mean, all of these are things
> that you are also borrowing from the presentations that were made
> today by the professional organizations. Do you see yourself
> interfacing with these non-industry groups that are already working in
> this direction?
>
> DR. SPEAR: This is Dr. Spear answering. I saw a nod from the
> responsible part from the corporation so I guess the answer to all
> those questions is yes. But with respect to your question about
> industry education, I know there is precedent for this. Certainly,
> there is precedent, for example, with the Midas Rex Drill. That was a
> very powerful tool for craniofacial surgery and you could only use it
> if you were trained by the company to use that drill. So, I am not
> sure it is necessarily a bad thing but there is a precedent for it.
>
> DR. WHALEN: Dr. Leitch, did you have a question?
>
> DR. LEITCH: Again on the education issue, I wonder if you have thought
> about education in terms of conduct of clinical trials because I think
> maybe some of your issues of maintaining follow-up of the patients and
> some of the violations, protocol violations that you had in the
> beginning of the study may be related to unfamiliarity of physicians
> or surgeons performing in a clinical trial, particularly if they are
> only admitting three or four patients into that trial. I think what
> you are hearing is that this panel would be interested in rigorous
> follow-up, and the way to ensure that that happens is that your
> \"investigators\" are well educated about their responsibilities and
> how they are able to maintain follow-up of their patients, and that it
> is their obligation.
>
> DR. SPEAR: This is Dr. Spear responding again. I have two responses to
> that. First of all, I think the FDA recognizes that the compliance in
> this trial, as in the saline trial that preceded it, was very good. I
> think, in fact, the sponsor deserves to be congratulated, from my
> perspective, for the good compliance.
>
> The Catch-22 for the manufacturer in terms of the surgeons who are
> involved in the trial is that I think there was an effort made to hit
> the broad section of surgeons who would actually be using the devices
> which, by definition, is not always surgeon scientists. So, you are
> trying to get real surgeons who are using these devices to report on
> their experience, which meant that you had to use people who were not
> necessarily academicians\--in fact, I am not sure even a majority were
> academicians.
>
> DR. LEITCH: And that is to be applauded. I support that because they
> are ultimately the people who are delivering the majority of the care,
> and we are experiencing that in some of the other clinical trials, if
> they are using surgeons who, you know, have not previously had
> experience, they do need some education. I think it would be a good
> idea to make sure that that happens.
>
> DR. SPEAR: And let me add\--this is Dr. Spear again\--that the sponsor
> has had a very, very robust regulatory compliance program which audits
> all the sites at least once, if not twice, a year, reviewing all the
> data; trying to contact the patients. They have been very proactive in
> this study, as in their other studies.
>
> DR. KUHNE: JoAnn Kuhne, for Inamed. I just want to comment to you that
> that is a point well taken, and we do refresher courses and have found
> that to be very useful, especially in our adjunct study where we are
> really trying to go after those sites and make sure that they complete
> their paperwork so that we get that paperwork and have more data and
> our compliance increases.
>
> DR. WHALEN: Dr. Miller?
>
> DR. MILLER: I have another question. It has been suggested that if the
> FDA labels these as now safe, it will become a free-for-all out in the
> world and these will be used in everybody for indiscriminate reasons,
> and this sort of thing, because now they are safe. Do you propose any
> steps\--I mean, do you think the steps you have proposed are
> sufficient to prevent that sort of behavior?
>
> DR. SPEAR: This is Dr. Spear answering that question. I have
> personally struggled with the decision made by the FDA in 1992
> regarding who could and who could not have these devices. I still feel
> that it under-estimated women and was overly paternalistic. I think a
> combination of labeling and conditions for approval should give people
> enough information that they can make a rational decision.
>
> For example, I have family members who have taken Accutane. Anybody
> who has taken Accutane and read the disclaimers for Accutane should
> think three times before taking Accutane. It has a lot of risks
> associated with it but it has benefits. I think between labeling and
> public information this could be handled perfectly appropriately.
>
> The idea that there would suddenly be a windfall of silicone
> implants\--as Dr. McGrath said earlier, women already have access to
> breast implants. What we are trying to provide them is a better breast
> implant.
>
> **Concluding Panel Deliberations and Vote**
>
> DR. WHALEN: I would like to thank Inamed and ask that they perhaps
> retreat, and I then ask our Executive Secretary, Dr. David Krause, to
> read to us the voting instructions.
>
> DR. KRAUSE: Please listen carefully. These are the options for panel
> recommendation for premarket approval applications.
>
> Medical Device Amendments to the Federal Food, Drug and Cosmetic Act,
> as amended, allow the Food and Drug Administration to obtain a
> recommendation from an expert advisory panel on designated medical
> device premarket approval applications that are filed with the agency.
> The PMA must stand on its own merits and your recommendation must be
> supported by safety and effectiveness data in the application or by
> applicable publicly available information.
>
> Safety is defined in the Act as reasonable assurance, based on valid
> scientific evidence, that the probable benefits to health, under
> conditions of intended use, outweigh any probable risk.
>
> Effectiveness is defined as reasonable assurance that in a significant
> portion of the population the use of the device for its intended uses
> and conditions of use, when labeled, will provide clinically
> significant results.
>
> Your recommendation options for the vote are as follows: The first
> option is approval if there are no conditions attached.
>
> The second option is approvable with conditions. The panel may
> recommend that the PMA be found approvable subject to specified
> conditions, for example, physician or patient education; labeling
> changes; full analysis of existing data. Prior to voting, all of the
> conditions should be discussed by the panel.
>
> The third option is not approvable. The panel may recommend that the
> PMA is not approvable if the data do not provide a reasonable
> assurance that the device is safe or if a reasonable assurance has not
> been given that the device is effective under the conditions of use
> prescribed, recommended or suggested in the proposed labeling.
>
> Following the voting, the Chair will ask each panel member to present
> a brief statement outlining the reasons for their vote. Thank you.
>
> DR. WHALEN: Is there a motion?
>
> DR. BOULWARE: Mr. Chairman?
>
> DR. WHALEN: Dr. Boulware?
>
> DR. BOULWARE: Based on the information we have had so far and the
> instructions, I move approval with conditions.
>
> DR. WHALEN: It has been moved that there be approval with conditions.
> Is there a second to that motion?
>
> DR. CHANG: Second.
>
> DR. WHALEN: Seconded by Dr. Chang. Is there a condition that is moved?
> Dr. Anderson?
>
> DR. ANDERSON: I move as a beginning point that what was laid out in
> the sponsor\'s presentation just now be adopted as conditions subject
> to discussion and modification.
>
> DR. WHALEN: Sorry, can you be more specific about what you mean about
> what they outlined?
>
> DR. ANDERSON: I move that the eight points that were laid out by Dr.
> Spear be the conditions for approval subject to our discussion and
> modification thereof.
>
> DR. WHALEN: Looking towards my FDA conscience who is ignoring me, is
> it appropriate to take those eight collectively or do we need to take
> the eight individually? Okay, they may be taken collectively. Is there
> then a second that those eight points be a condition?
>
> DR. BOULWARE: Second\--Dr. Boulware.
>
> DR. WHALEN: It has been moved and seconded that the eight conditions,
> as outlined on pages four and five of the Inamed statement, be
> conditions. That is open to discussion. Would you care to start that
> off, Dr. Anderson?
>
> DR. ANDERSON: I would like to discuss the informed consent form. The
> proposition is that a small group of panel members, along with the
> FDA, help to develop a consent. I would like to discuss how we would
> do that. Is there any precedent to in FDA about how we might
> facilitate a proper consent development?
>
> DR. WHALEN: Dr. Witten, would you address that?
>
> DR. WITTEN: Yes, I am not sure what is referred to in this condition.
> We do work on patient education booklets with sponsors, which is
> number two here, and we have asked panel members for input on that.
> So, as far as informed consent, I am assuming what is meant here is
> surgical informed consent. Is that what you all\--
>
> DR. WHALEN: Yes, right.
>
> DR. WITTEN: Although we haven\'t done that in the past, I don\'t
> really see why we couldn\'t. You are talking about having a model
> informed consent that would be part of the material that the sponsor
> would distribute to surgeons with the labeling? Is that the idea? I am
> just trying to understand what is being proposed.
>
> DR. WHALEN: If I could interject, it would have to be a model consent
> form since even FDA, with all of its power, is not going to have the
> authority to tell every practitioner at every institution\--
>
> DR. WITTEN: Right.
>
> DR. WHALEN: \--what consent form they must use.
>
> DR. WITTEN: Exactly. Thank you for making that point. I was going to
> explain that. That is what it would be. So, yes, I think that we could
> certainly\--you know, the sponsor could certainly propose something
> and we could work with the panel to get input. I mean, it isn\'t
> something we have done before but it doesn\'t look to me to be outside
> of the realm of something that we could do in conjunction with the
> sponsor and members of the panel prior to approval. I think we would
> have to work out exactly how to do that.
>
> PROF. DUBLER: Dr. Whalen?
>
> DR. WHALEN: I will get to you in just a moment, Prof. Dubler. Dr.
> Blumenstein and then Prof. Dubler.
>
> DR. BLUMENSTEIN: Perhaps some of the people who testified in the
> public open meeting part of this activity would also have something to
> say about the informed consent.
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: I am of that generation that needs something to hold in
> my hand that I read. But it is clear that that is not the most
> effective way of communicating, and there have been some recent
> studies in [The New England Journal of Medicine]{.underline} that
> demonstrate how woefully inadequate the written word is in
> communicating risks and benefits to patients. This is a real
> opportunity, I would argue, to experiment with videos that would give
> all the voices an opportunity to be heard and, indeed, to be seen, and
> you might produce some patient education that really could incorporate
> some of the dialogue that took place at this panel.
>
> DR. WHALEN: Other discussion on these eight conditions? Dr. Olding?
>
> DR. OLDING: I just wanted to make a comment about that. There, in
> fact, are patient education videos made now by ASPS, and I would think
> that type of thing would serve well for what you have requested.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: Steve Li. I think I would just like to perhaps add a little
> bit to number four, the retrieval program, as Mr. Krause suggested
> that we could do. I think one of the things I would like them to do in
> addition to continuing the retrieval program is to perhaps work with
> the FDA and essentially reexamine the retrievals they have got
> already. They have a substantial collection of retrieved devices and
> there quite possibly could be a lot of valuable information there
> perhaps if they extended the things they measured and examined. I
> would want them to establish, as they suggest, perhaps a third-party
> consultant group that would ensure that the retrieval program would,
> hopefully, lead us to some conclusion as to where these ruptures come
> from.
>
> DR. WHALEN: I would suggest that that may be substantive enough that
> it probably should be an additional condition that we will consider
> shortly, after dealing with these eight conditions, whether or not
> they are approved as conditions.
>
> PROF. DUBLER: Dr. Whalen?
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: There has been some discussion today especially about
> the visual examination of the field to see if silicone, in fact,
> exists outside the elastomer space. Even the MRI might not be
> sufficient. But someone suggested this morning that what is needed is
> a biopsy when the implant is taken out. Now, I think this would be
> another condition and I am in over my head, for those clinicians who
> might like to rescue me, but is that something that we would like to
> see happen?
>
> DR. WHALEN: As you, yourself pointed out, Nancy, that would be an
> additional condition, which is certainly going to be in order but is
> not presently. So, if we could focus on condition number one, which is
> these eight conditions, for further discussion upon these? Dr.
> McGrath?
>
> DR. MCGRATH: Condition number five talks about recommending that the
> patient have regular physician follow-ups. I assume that this is
> related to the detection of rupture as one of the reasons to have
> regular physician follow-ups. I think this is the point of the
> correlation with the MRIs that you are doing, and that whole question
> the has so aptly been brought up by someone on the panel that there
> needs to be more information about the efficacy of physical
> examination in a ruptured gel implant and get some data on how that
> does correlate with your MRI findings at five, seven and ten
> years\--nine years. I would build that in as a condition, that that
> would have to be actually a piece of research that would be
> accomplished as part of that item five.
>
> DR. WHALEN: Perhaps I am being subjective but I would incorporate that
> as a friendly amendment so that we could encompass it in the present
> discussion. Dennis?
>
> DR. BOULWARE: For that same number five, have we assigned a time
> period? Annual or five years? Can we strengthen that to say regular
> annual physical follow-up?
>
> DR. WHALEN: I think while substantive, it is editorial to the changes
> at hand. So, you are proposing that it be annual?
>
> DR. BOULWARE: Yes.
>
> DR. LIEBERMAN: Dr. Whalen, for number five, one of the things that is
> not done here, and I don\'t know if this is a separate condition, is
> to follow-up the women who have explants because these are the women
> with rupture and if we stop following them once they are explanted,
> then we don\'t find out their health outcomes.
>
> DR. WHALEN: So, you would actually be proposing that there be deletion
> on number five past \"follow-ups\" and delete \"as long as they have
> the device.\"
>
> DR. LIEBERMAN: Yes.
>
> DR. WHALEN: Would you have a suggestion as to how long that explanted
> population should be followed?
>
> DR. LIEBERMAN: I think that that population should be followed for the
> length of the study, as long as they are following those women. I
> think that that is the population that we are concerned about in terms
> of the effects of silicone that has been extracapsular and may cause a
> problem. It doesn\'t necessarily have to be the same type of
> follow-up; we could work on that. But I think we need to get the
> health status of those women and find out what has happened to them.
>
> DR. WHALEN: Okay. Dr. Miller?
>
> DR. MILLER: On that same question number five, I agree with the point
> that was just made about needing to follow women. Once they get the
> device, whether they have the device or not, they are followed for
> \"forever\" as possible. Yearly I think is a good idea.
>
> I would like to have some mechanism to ensure compliance with this. I
> mean, in the current study, of course, there is very intense
> compliance where you have to send reports and everything. I think some
> kind of compliance could be ensured here where perhaps the physician
> could send in e-mail or send in a report of some kind that they have
> seen the patient. What do you think of that? I would like to see some
> way of enforcing it, even though I know how difficult it is. I don\'t
> just want to have this become something that is very casual and is
> ignored.
>
> DR. WHALEN: Do you have a concrete suggestion in that regard?
>
> DR. MILLER: How about\--I am just picking an idea, I don\'t know if it
> has ever been done before, but perhaps mandating some sort of form be
> returned to the company, either by e-mail or by mail, that needs to
> appear at the company\'s door every year, or something. If it is not
> there, then the physician is contacted and if some explanation isn\'t
> made that physician is disqualified from receiving any more implants.
>
> DR. WHALEN: Is there any more discussion on that? Dr. Leitch?
>
> DR. LEITCH: So, how many patients that would turn out to be?
>
> DR. MILLER: I think it would depend on the surgeon. I think some
> surgeons implant\--
>
> DR. LEITCH: But overall what would the company expect to receive?
>
> DR. MILLER: In terms of follow-ups?
>
> DR. LEITCH: Yes.
>
> DR. MILLER: Oh, probably hundreds and hundreds.
>
> DR. LEITCH: Thousands, wouldn\'t it be?
>
> DR. MILLER: Yes, it would be a big job but I think that, you know,
> there is precedent with this for other devices. Again, the thing that
> comes to my mind are things like pacemakers. These are very heavily
> monitored and tracked. You know, so much concern has been raised over
> the breast implants that I think an extra effort needs to be made to
> keep track of the patients, those who have received one of these
> devices, and some mechanism needs to be created to do that.
>
> DR. WHALEN: Dr. Manno?
>
> DR. MANNO: With reference to your tracking comments, I don\'t think
> the whole blame\--usually I am hacking on physicians but this time I
> am not. I think that not all the blame for lack of information should
> rest on the physician because there will be a component of women who
> will not, if they are not sick, go in for a checkup. It would appear
> to me that it needs to be impressed on the women that this is equally
> as important as a yearly mammogram.
>
> Now, you realize that it has been an education process to get women to
> admit that they are vulnerable and go for their yearly mammograms. We
> also have the problem of extending the age group downward rather than
> upward, and the young women are not used to having to go for these
> yearly exams as we older people are. I think there is going to have to
> be some education of the patient, and I am thinking especially of the
> augmentation patient. If you are sick you will go to the doctor. If
> you are not sick you are not going to take the time.
>
> DR. CONANT: I would just question who is going to pay for those
> visits.
>
> DR. WHALEN: Sorry, can you say that again?
>
> DR. CONANT: I would just question who is going to pay for those
> visits. The young implanted patient isn\'t going to be paying for
> those visits unless they are not charged by the surgeon, and I wonder
> how many surgeons are going to no-charge an office visit.
>
> DR. WHALEN: I see no further discussion right now. Is there any
> further point to be brought up on condition number one, which subsumes
> the eight conditions with some changes that we have already made? I
> will read these before we vote. Is there any further discussion?
>
> PROF. DUBLER: I didn\'t think we quite finished that last discussion.
> I think that is a very hard issue. Young women will need to go back
> for an annual visit. That is expensive. They probably haven\'t
> budgeted for it. Some of them won\'t have health insurance. I do think
> it is going to be very hard to get asymptomatic young women, who are
> not used to going for mammography, to come in and get checked and I
> just don\'t know what to do about that, and I don\'t think it is fair
> to make that a responsibility of the surgeons. I think this is going
> to be a very difficult group to monitor. So be it.
>
> DR. WHALEN: Further discussion?
>
> DR. MILLER: It is difficult in a forum like this to create a
> mechanism. Could we just say that one of the things that has to be
> worked out with the FDA and perhaps the panel members is a practical
> mechanism to ensure follow-up?
>
> PROF. DUBLER: Encourage.
>
> DR. MILLER: Yes, encourage follow-up perhaps.
>
> DR. WHALEN: I mean, you are basically asking can you stipulate a
> condition and the answer is obviously yes. So, the reason we are here
> as resource experts to the FDA is to stipulate those conditions we
> feel are appropriate and to vote them up or down.
>
> DR. MILLER: I would add that to number five, that there be some
> mechanism worked out to increase the rate of compliance with the
> follow-up.
>
> DR. WHALEN: Further discussion?
>
> DR. BLUMENSTEIN: Brent Blumenstein. I am just going to blurt this out,
> but maybe the gynecologists could help in this.
>
> DR. WHALEN: Phyllis?
>
> DR. CHANG: A practical friendly amendment, rather than saying annual,
> knowing that this is going to be so difficult, the visits so far are
> one, three and five years. Why not make it seven and nine years so
> that it may be achievable? And the effort is education for women who
> don\'t have symptoms, and this is data collection that they have
> enrolled in a clinical trial so that they are assisting in
> establishing long-term safety records by showing up. Given that
> education, I believe many participants would come back. I don\'t know
> what kind of incentive program\--I don\'t think we were privy to that
> three years ago in terms of how the sponsor was able to achieve a very
> excellent follow-up. So, a similar model perhaps could be extended
> beyond the fifth year to nine years.
>
> DR. WHALEN: I am sorry, just so I know what you are phrasing, for
> number five you are stating instead of annual that it be one, three,
> five, seven, nine?
>
> DR. CHANG: Right, and that these details, I am going to also suggest,
> be worked out between FDA and the sponsor in continued discussion.
>
> DR. WITTEN: Can I just clarify? I had understood number five to be
> referring to any patient who was implanted with one of these products.
> But are you talking about that, Dr. Chang, or are you talking about
> patients who were in the study?
>
> DR. CHANG: These conditions are for patients in the study.
>
> DR. WHALEN: No, these are conditions for any patient who gets an
> implant.
>
> DR. WITTEN: Just for clarification, the study is annual. The MRI
> cohort only gets MRIs on odd numbered years.
>
> DR. LAWRENCE: Item number three does specify five, seven, nine years
> and longer if necessary for physical and MRI. So, three and five are
> probably compatible.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: Probably we need to clarify with the sponsor if number
> three refers to the planned study group patients versus this idea of
> follow-up of all patients. Again, I think the requirements that we
> have on follow-up for all patients would be different in terms of the
> requirement to the sponsor than would be the study requirements, which
> I think would need to be stringent about and there is specific
> performance that is required of the sponsor on that part. If you are
> asking them to be responsible for the monitoring of every single
> patient every year or one, three, seven and nine, then, of course,
> that is a much higher degree of responsibility in terms of the number
> of patients and the cost thereto. So, I think those two points are
> separate.
>
> The point I would make about seven, as part of the patient
> education\--I mean, we have talked about this idea of long-term
> follow-up of patients and, certainly, we heard from patients their
> concerns of long-term issues. So, I think that is what needs to be
> expressed to patients in terms of motivating them for follow-up, that,
> in fact, they are receiving a service in the sense of coming for
> follow-up to assess for complications or problems which they,
> themselves, may be unaware of at the time of presentation, and that
> they would then potentially be benefited, as the MRI data matures, as
> to whether that should become a part the screening mechanism that
> would be undertaken as some degree of routine. So, I do think we need
> to separate what we are talking about in those two groups.
>
> MS. GILBERT: Alisa Gilbert. I just want to say something about the
> recruitment or retention of the participants in the study group. There
> has to be more work done in making sure that the women are following
> through and really tracking these women. Can that be added somewhere
> within the eight, that there would be a motion for retention and
> recruitment?
>
> DR. WHALEN: I am just trying to clarify what you mean since we are
> making conditions for all implants, when you say retention and
> recruitment, do you mean into the physician\'s practice who has
> implanted it, since this is no longer a study but, rather, a practice
> standard?
>
> MS. GILBERT: Well, for the women who are in the study\--I guess that
> is where I want to be clear about this too, is this just for the
> follow-up\--
>
> DR. WHALEN: This is for the entire population of patients who would be
> utilizing this device, were it to be approved.
>
> MS. GILBERT: But there still will be an ongoing study, right, for the
> ten years?
>
> DR. WHALEN: For the ten years there will be, yes.
>
> MS. GILBERT: And there still needs to be more work done in getting
> more women to be actively recruited into the study to get accurate
> data.
>
> DR. WHALEN: Well, are they going to be recruiting further patients or
> simply following patients\--
>
> MS. GILBERT: Following them better, yes.
>
> MS. BROWN: You want adequate follow-up for study patients.
>
> MS. GILBERT: Yes.
>
> DR. WHALEN: So, you would like to have an additional recommendation
> that there be\--help me here.
>
> MS. GILBERT: More work to retain the patients that are actively
> enrolled in the study. Because what are the numbers right now that we
> are looking at? How many people are actively enrolled and what is the
> dropout rate and, you know, the loss of some of the women that were
> involved in the beginning but they then have kind of fallen out of the
> study?
>
> DR. WHALEN: Just again to further clarify it, I would imagine, in
> terms of the study, it is almost always going to be the goal of those
> conducting the study to have as high a retention of the study
> population as possible. So, if we are simply encouraging them to do
> what we already anticipate they will be doing, it doesn\'t take on a
> very strong dimension. Do you feel that there need to be some teeth
> put into that?
>
> MS. GILBERT: I don\'t know.
>
> DR. CHANG: Dr. Whalen, can I ask the sponsor or Dr. Spears to clarify
> something?
>
> DR. WHALEN: If it is a very focused question, yes.
>
> DR. CHANG: The very focused question is for your proposals for
> follow-up on item three, is it your intent that \"we support this
> panel\'s opinion and will recommend to FDA\"\--is it study patients be
> followed up for ten years via physical examinations? It is study
> patients that should have MRIs at five, seven and nine years?
>
> DR. WHALEN: If I could just interject, Scott, you were talking about
> what we talked about yesterday, that it be all patients.
>
> DR. SPEAR: I apologize for the confusion. I sincerely do apologize for
> the confusion, but number three refers specifically to the study
> patients. The discussion was whether the mail-in would be a
> replacement for physical examination and whether the MRI is necessary
> for the five, seven and nine years. All the others refer to all
> patients but number three is specific to study patients.
>
> DR. WHALEN: Okay.
>
> DR. CONANT: Dr. Whalen, I am not sure if this is an addition to or an
> amendment so correct me if I am at the wrong time here. For number
> seven, the surgeon education, I would also like to see the sponsor
> develop an algorithm for surgeon evaluation by physical exam and then
> a system, if there is concern about rupture, for what the next step
> is\--MRI evaluation if there is rupture; whether explantation is
> recommended. I don\'t know if that is wrapped in number seven. So,
> like a paradigm for how you deal with these patients and that part of
> the surgeon education.
>
> DR. WHALEN: I think we need to take that separately so I will get back
> to you. What I am going to do now is recognize Dr. Witten.
>
> DR. WITTEN: Thank you. Before you get to the vote on this, I just want
> some clarification from the panel on what their expectation would be
> for number eight. In other words, what is the objective for number
> eight in the panel\'s mind?
>
> DR. WHALEN: The subject of expectations of the registry is open for
> discussion. Dr. McGrath?
>
> DR. MCGRATH: I will go back to that, Dr. Witten, because I mentioned
> before that I thought number two, the patient education brochure,
> number four, the device retrieval program and the registry should all
> be done in coordination with a third non-registry party. Such a group
> could be a university or a professional organization. Certainly, those
> initiatives are under way out there. But I would like to see
> partnerships with non-involved parties on those efforts. I agree that
> it needs to be fleshed out.
>
> DR. WHALEN: What I am going to do now is make my best attempt, with
> some of the changes we have just been discussing and changing some of
> the language to make it more appropriate, to go through each of these
> eight and ask the assistance of my fellow panel members to correct me
> when I goof up on any of them.
>
> Number one, Inamed will, in conjunction with FDA and any panel members
> they would deem appropriate, develop a model consent form.
>
> Number two, Inamed will develop and distribute a patient education
> booklet on breast implants. This pamphlet will be built from the model
> informed consent form and will be written for women who use their
> products. Inamed will utilize focus groups to develop such a book.
> Inamed will make sure that every woman considering this product is as
> informed as possible. Brent?
>
> DR. BLUMENSTEIN: Can I suggest using the word \"media\" instead of
> \"book\" so they can do a videotape as well?
>
> DR. GILBERT: I agree with that, media or packet. A packet that would
> have a booklet, video and/or CD ROM.
>
> DR. MCGRATH: Tom, before you leave that, you are either deliberately
> or inadvertently omitting my friendly amendment that this be done in
> conjunction with\--
>
> DR. WHALEN: That is why we are doing it this way, Mary, so you can
> keep me honest If you could just rephrase that for us?
>
> DR. MCGRATH: Well, it was just a codicil on the last sentence.
>
> DR. WHALEN: I am sorry, say that one more time.
>
> DR. MCGRATH: It was an addition to the last sentence or final sentence
> on that paragraph. We are talking about number two, the patient
> education booklet\--
>
> DR. WHALEN: Correct.
>
> DR. MCGRATH: The final sentence of this would be partner with other
> organizations such as professional organizations.
>
> DR. WHALEN: So, Inamed will assure that every woman considering this
> product, in conjunction with partnered professional organizations\--
>
> DR. MCGRATH: Well, it would probably go up to the focus group. We will
> utilize focus groups, partner professional organizations, and so
> forth, to help develop such a book.
>
> DR. WHALEN: I assure you it wasn\'t intentional. Number three, Inamed
> recommends to FDA that study patients should be followed up for ten
> years via physical examinations and MRIs at five, seven and nine
> years, and longer if deemed necessary.
>
> DR. LIEBERMAN: I think that the recommendation about following
> explanted patients belongs there and not in number five.
>
> DR. WHALEN: So, you would want to incorporate the MRI suggestions into
> the explanted patients?
>
> DR. LIEBERMAN: I think we need to have the follow-up of the explanted
> patients as part of the study protocol, which it isn\'t currently.
>
> DR. LEITCH: I would not suggest that the MRIs continue once they are
> explanted. You know, if they are of the age to have mammography, they
> should have mammography at annual intervals but I would not say to
> continue MRI once they are explanted if they are not reimplanted.
>
> DR. WHALEN: Would it subsume, both of what you are saying, to have it
> as I worded it but then to continue on to say that explanted patients
> will continue to be followed in the study at five, seven and nine
> years, not necessarily having the MRI part in it?
>
> DR. LEITCH: No, I wasn\'t implying they should have MRIs.
>
> DR. WHALEN: Mary?
>
> DR. MCGRATH: A question, at this point we are talking about the study
> patients and their follow-up with physical exam and MRI. Are we going
> to talk now or later on about other things that we might like to ask
> about those patients, ask them to look for in those patients besides
> doing a physical exam?
>
> DR. WHALEN: I think that is dealer\'s choice but since I hold the
> deck, why don\'t we just make that a separate one and we will deal
> with it?
>
> DR. MCGRATH: Thank you.
>
> DR. WHALEN: Number four, Inamed will supply to FDA and, if deemed
> appropriate by the FDA the panel, annual reports on the post-approval
> study and have an independent third-party on an annual basis audit
> that study. Inamed will pay particular attention to any relationship
> between outcomes and rupture status. They agree to conduct a device
> retrieval program to study the changes that occur in the product over
> time and systematically investigate the failure modes for the device.
> Inamed agrees that if the independent third party finds the study is
> not in compliance with these conditions that they will withdraw the
> PMA.
>
> Steven, was there anything further you wanted to put in there or do
> you just want to wait and add it to the discussion?
>
> DR. LI: I will wait and add it to the next condition.
>
> DR. WHALEN: Thank you. Bear with me a second on number five\--any
> patient with a silicone gel-filled breast implant will have annual
> physician follow-ups and there will be a mechanism to assure
> compliance with follow-ups.
>
> DR. CHANG: I have a friendly amendment because I don\'t think that is
> a sustainable condition because it reads that Inamed recommends that
> any patient who has a silicone gel-filled breast implant have regular
> physician follow-ups. Now, that can be specified, annually as long as
> they have the device but that is a recommendation and I don\'t believe
> it is a practical, achievable goal to say that Inamed will be
> responsible\--
>
> DR. WHALEN: Well, that is why I deleted \"Inamed\" and stated \"any
> patient.\" The context of Dr. Miller\'s suggestion was that it be
> annual on this particular item. Clearly, that is why we are going
> through these and discussing them. We can modify it any way that we
> want, but I deleted the Inamed part from this because this is what we
> are hoping FDA is going to recommend be a practice standard in terms
> of this device.
>
> DR. NEWBURGER: Question, I am concerned about this, that if current
> trends are to continue within three years or so, this will be one
> million more women with breast implants and I find that a very
> unwieldy number. Since part of the purpose of this I think is to also
> have access to this information on a more informal basis as well, I am
> wondering how those numbers would be managed. Of course, yearly exams
> for a million people in three years is financially very difficult. Is
> it fair to ask people to assume that burden, and is it fair to try to
> put that onto insurance companies to cover this? So, I have a lot of
> trouble with number five.
>
> DR. WHALEN: In view of what you just stated, would have a follow-up
> suggestion on what the frequency should be, or do you feel that we
> should not be stipulating that follow-up be part of this?
>
> DR. NEWBURGER: I would like to see the follow-up less than once a year
> and perhaps every other year, and I would like to have some informal
> tracking mechanism for reports on these people.
>
> DR. CHOTI: Another comment, first of all, a recommendation without any
> method\--just putting it in as a guideline, it is unlikely to happen.
> Second, regular physician follow-up doesn\'t specify that that is the
> plastic surgeon and, therefore, the gynecologist or the regular
> physician isn\'t going to be\--if the goal is to detect rupture, and I
> assume that is the goal, and we have no other mechanism for doing it,
> no other imaging studies, then it needs to be a physician that is
> trained at detecting rupture. So, this thing has no teeth. I mean, we
> just want these women to be followed, not just to have these things
> put in and lost to follow-up. But this is really not going to solve
> any problem.
>
> DR. WHALEN: Do you have a counter proposal?
>
> DR. CHOTI: Perhaps that the surgeon, the plastic surgeon putting it
> in\--the recommendation should be that they should be the one to
> follow-up. Then I don\'t know, as Dr. Miller suggested, how we can put
> a little compliance into that thing. I don\'t know how to do that. I
> don\'t think women will be followed up, many of them won\'t be.
>
> DR. WHALEN: As it stands, I think we have three open issues on this
> particular item, frequency of follow-up, by whom, and the question of
> a mechanism for ensuring compliance, along with Dr. Newburger\'s
> concern about reporting data for all these patients. Since that opens
> so many things, I think for this item we are going to have to go
> around the table. So, we are going to start with Dr. Miller and ask
> how you would come on each of those items.
>
> DR. MILLER: Do we have to resolve this at this panel or is this
> something we can leave to the work subsequent to the panel meeting
> that is going to go on with the educational material and informed
> consent? Why don\'t we add this to that work?
>
> DR. WHALEN: Well, it would be my contention that since we are
> stipulating a condition of approval, for this genre of stipulation we
> have to come in with some specificity to it. Is there a particular
> type of specialist who needs to be involved, how often should it be,
> and the like? So, I don\'t think we can simply say the condition would
> be FDA will work on some form of follow-up.
>
> DR. MILLER: Okay. I agree with the comments made about one-year
> follow-up. Perhaps every two to three years is practical. I think it
> should be examined by a person who is in the pool of surgeons who are
> certified to perform these procedures. It may not be the same surgeon
> because people do move around, especially these younger patient
> populations, but there should be some effort to have that patient be
> linked to another surgeon who can do the examinations and is competent
> to do that.
>
> Then the enforcement part of it, that is a very difficult thing. Yes,
> Mary?
>
> DR. WHALEN: We are going to go around the table, Mary, and ask
> everybody to chime in with what they feel about this.
>
> DR. MILLER: I think some sort of accountability mechanism, either just
> a mailed in piece of paper\--even if a surgeon can\'t track the
> patient, just a statement from the surgeon that he has made an effort
> and this patient has now disappeared, some sign-off by the surgeon
> that he made a good-faith effort to follow these patients, maybe as
> simple as a mail-in thing.
>
> DR. WHALEN: I am asking this as a question in regard to that last
> issue of a mechanism to ensure compliance, how is what you are
> suggesting different from a patient registry, or is it?
>
> DR. MILLER: I don\'t think it necessarily is. I think they both are
> coupled together. You populate the registry by the follow-up from
> these physicians so they both go hand-in-hand I think.
>
> DR. WHALEN: Dr. Anderson?
>
> DR. ANDERSON: I see recommendations five and eight as being linked.
> Number eight is the Inamed patient registry. I would suggest that
> there is a recommendation made by the company and the FDA for annual
> follow-up, and we recognize that when we make a recommendation
> patients will have the option of following that or not following that.
> Remember, we do have a study group that is being followed out to ten
> years. So, it is not that we are devoid of data. We have a selected
> subgroup that we are extracting data from. I would suggest that we
> roll this into number eight, the registry, and this is a relationship
> between the company and the patient because patients move. I think it
> is unrealistic to expect that the surgeons would track these folks. It
> won\'t happen. But if you make that relationship, there is a registry
> that is available and the patient understands this, and there is an
> annual card that is sent out, \"how are you doing?\" We do this in
> epidemiological studies and that is how the registry data would be
> populated.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: I will generally defer to my clinical colleagues on the
> practicality of this, but as someone who might be interested in
> looking at that data to try to assess implant performance, it seems to
> me that you would have to know what information you want to be
> getting. In other words, I don\'t know what I would do as a materials
> person to have a card that says this patient is doing fine. So, I
> think if we are going to collect the data it has to be for a certain
> purpose, and if you aren\'t going to meet that purpose I am not really
> sure why all the effort and the expense is going to be put into that
> effort.
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: Patients have authority and autonomy but they also have
> responsibility, and I think that number five gives us the opportunity
> to emphasize the patient\'s responsibility with physician best
> practice. So, in the certification and training for plastic surgeons,
> I think that the notion that yearly follow-up is a part of the process
> should be an element.
>
> I think in the informed consent materials the notion that yearly
> follow-up is part of the process has to be an element. Beyond that, I
> just don\'t think there is a lot we can do. With one final note, which
> is that the cost of this is, of course, an issue and insurance
> companies should be encouraged to cover the cost of this yearly
> follow-up and physicians should be encouraged to make it financially
> available.
>
> DR. WHALEN: Dr. Newburger?
>
> DR. NEWBURGER: I think the purpose of this expanded registry then
> would be to detect the events that would occur in 1/1,000 cases,
> 1/10,000 cases, 1/50,000 cases, and without it we are not going to be
> able to see these. I think one way that we can get higher compliance
> is to offer a financial incentive to patients who have received the
> implants. The company has done that in the case of certain fillers. I
> think that attracts more people to the process.
>
> DR. WHALEN: We are looking here at all patients who receive implants.
> Are you proposing that the manufacturer be providing financial
> incentives for all patients who receive implants?
>
> DR. NEWBURGER: Perhaps with each card that would be sent to a patient,
> a reminder to see your physician for a follow-up. If you do, here is a
> partial rebate. I don\'t think it is appropriate for our insurance
> premiums to pay for covering the cost for an elective cosmetic
> procedure for other subscribers.
>
> DR. WHALEN: Dr. Boulware?
>
> DR. BOULWARE: Can you remind me again what the question is?
>
> \[Laughter\]
>
> DR. WHALEN: We are trying to find a needle in a haystack.
>
> \[Laughter\]
>
> We are looking to see how often we are recommending, in number five,
> that patients are going to be followed; is there a specific breed of
> practitioner who is going to be following them; and are we going to
> propose that there be some compliance mechanism?
>
> DR. BOULWARE: I guess my thoughts are that number five really is
> subsumed in number eight and for the patient registry we can come back
> with another condition to include the data we would like to have in
> that, which may include an annual physical exam and/or historical
> medical data that can be provided.
>
> DR. WHALEN: So, you would say annual?
>
> DR. BOULWARE: Yes.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: With regard to number five\--before when I got all
> excited and was rising my hand out of turn, I was going to also
> suggest incentivizing with the manufacturer\'s rebate for these
> examinations for the patients. However, I want to mention one other
> thing, if we are linking this, as I think three panelists have
> already, to number eight, the registry, again, I just want to comment
> that we are back to the same thing and I think the registry should be
> something that is managed by an independent party. Ultimately, if we
> have a patient registry for breast implants we want something that can
> include implants from other manufacturers. We want to have something
> that will live into perpetuity if companies change hands, and so
> forth, I think that this registry should be managed by an independent
> third party.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: I would favor an annual follow-up with the idea because if
> you advise people for wider intervals they are, you know, likely to
> forget. If you give them a two-year interval the chance is that they
> will do this in three years rather than two years. So, I favor annual
> although I would defer to my plastic surgery colleagues in terms of
> some of the physical exam evaluations if they feel that every two
> years would be sufficient for that.
>
> In terms of how you get patients to do that, I also agree that there
> is some responsibility on the patient\'s part to have follow-up. I
> mean, the patients here have told us that they may have long-term
> issues. So, the way to address that and be certain that their surgeon
> is aware of that is that they have regular follow-up.
>
> While I think incentivization may be appropriate for the study
> patients, I think for the routine follow-up of patients it is not
> necessarily the responsibility of the sponsor to do that, unless they
> particularly wanted to do it. But I think this is education of the
> patient that we have to focus on, that they do need to have some
> follow-up so that if they have issues they have a potential to be
> recognized.
>
> DR. WHALEN: Dr. Chang?
>
> DR. CHANG: I am going to be recommending that the sentence in item
> five that we are redoing be placed at the end of the patient
> information brochure, just as a general guideline.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: Well, as I said before, I think that the main goal of the
> regular follow-up is detection of rupture. So, I think it needs to be
> a trained plastic surgeon with experience in identifying rupture. That
> is part of the education of the surgeon, or certification perhaps. So,
> that needs to be specified. I don\'t think any physician, perhaps
> including myself\--I wouldn\'t be able to detect easily what rupture
> would look like.
>
> I don\'t think it is the same as the registry. I think the registry
> can track follow-up and can track issues such as rupture or any other
> problems. So, I think the registry is linked to the follow-up to
> monitor follow-up, but it is distinct. I think annual is probably
> reasonable for the reasons mentioned.
>
> DR. WHALEN: Dr. Blumenstein?
>
> DR. BLUMENSTEIN: No comment.
>
> DR. CONANT: Just a comment, I think our trouble with number five boils
> down to the lack of long-term follow-up on this implant and we are
> trying to create that. It bothers me that we will be doing that by
> this method. However, I like the idea of the registry monitored by an
> independent group, but I think that the follow-up\--it is incredibly
> unfeasible to think that young women with implants are going to be
> followed yearly by any physician, and they are going to be lost. So, I
> think it is a combination of patient responsibility and I would love
> for physicians to feel some responsibility as well, but I would think
> that patients could answer quite a few questions regarding their
> implants. They could be prompted potentially from a registry of some
> sort. So, things like symptomatology, shape of implant, softening of
> implant, hardening of implant, things like that. So, I think it might
> be a combination of patient response with and without physician exam.
>
> DR. WHALEN: Dr. Lawrence?
>
> DR. LAWRENCE: I would agree with those remarks and other comments as
> far as this stage of the recommendation is concerned.
>
> DR. WHALEN: Dr. Lieberman?
>
> DR. LIEBERMAN: I would like to echo Dr. Conant\'s comment. I think
> that our angst with this has to do with our discomfort at the level of
> follow-up and feeling that there is this lack of information. If we
> are considering this, I think we need to be realistic about the
> follow-up. I think with all of those problems\--financial\--they are
> probably not going to be followed up regularly even if we recommend it
> and we should build into the registry some kind of regular mail
> follow-up that gets us at least symptomatology and serious outcomes.
>
> DR. WHALEN: Dr. Manno?
>
> DR. MANNO: I pretty much agree with what has been said, but I heard
> two things that troubled me. One was that the company should consider
> offering some sort of incentive for follow-up in the general group of
> patients. I question whether that is really ethical in today\'s
> climate. That can perhaps be addressed by Dr. Dubler.
>
> The other thing that I heard that bothered me is that if there is a
> registry, as pointed out in number eight, which states an Inamed
> registry, they should not have to bear the burden of the other
> implants that I heard stated by a panel member. I think that is over
> and above\--beyond the call of duty.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: I also agree that patients should be examined on an annual
> basis by one of the certified\--if that is how you want to refer to
> them\--plastic surgeons. I also agree that there should not be a
> financial enticement for the patients to do that. Finally, I certainly
> agree with Dr. McGrath that there should be a third-party participant,
> some professional organization, who monitors this or participates with
> this group, if for no other reason than to add a certain air of
> validity to it.
>
> DR. WHALEN: Ms. Brown?
>
> MS. BROWN: I have no further comments on this.
>
> DR. WHALEN: Ms. Gilbert?
>
> MS. GILBERT: I agree with what Dr. Olding just said, and I would
> encourage the patients to take the responsibility in getting annual
> examinations. I think it is really important because of the rupture
> rate and because of the failure rate of this device for them to take
> the responsibility.
>
> DR. WHALEN: In view of what I think all the panel members were
> contributing to this, I am going to give a shot at verbalizing the
> opinions that have been expressed and state that for number five it is
> very strongly encouraged that any patient with a silicone gel-filled
> breast implant have follow-up at least one- to two-year intervals by
> appropriate physicians conversant with the implants.
>
> The silence is deafening so we will go on to number six. Inamed will
> produce a guide and establish a toll-free telephone number for
> patients regarding how to monitor their breasts after implantation
> with a silicone gel-filled breast implant.
>
> Number seven, Inamed will develop a surgeon education and
> certification program to train surgeons in this particular area of
> surgery using silicone gel-filled breast implants.
>
> DR. MCGRATH: A simple wording change, Inamed will develop, with a
> professional educational organization, a surgeon education and
> verification program, and so forth. I add that because I think a
> professional educational organization knows how to apply standards for
> physician training, also how to verify and test for some level of
> having acquired those skills, and also, if needed, to set up a
> proctoring program.
>
> DR. WHALEN: Dr. Anderson?
>
> DR. ANDERSON: That was the point.
>
> DR. WHALEN: Dr. Manno?
>
> DR. MANNO: Along with what has been said on seven, it might be
> feasible for the company, the company or the society doing the
> educating and certifying to keep a list of the currently certified
> physicians on their website so that, with the mobility of the
> patients, they can always have access to their nearest plastic
> surgeon.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: I just would suggest perhaps a slight addition of a few
> words at the end of that, that would be as a requirement for
> utilization of the implants.
>
> DR. WHALEN: We have three substantive changes. I just want to try to
> recapitulate and ask if they are agreeable. Dr. McGrath suggested that
> this be Inamed along with appropriate professional associations and
> that, instead of certification it be a verification program.
>
> Dr. Olding has suggested that it be as a requirement for utilization
> of these implants. Brent?
>
> DR. BLUMENSTEIN: It is really a physician registry, and then you can
> link the outcome to the physicians.
>
> DR. WHALEN: Thanks!
>
> \[Laughter\]
>
> Very well. We have already touched upon number eight a bit but I think
> we need to have some further discussion about this, as it reads, and
> it is verbatim from the sheet in front of you, an Inamed patient
> registry that exists today will continue to track patients who use the
> products. Someone has suggested that it should be independent of the
> sponsor. Comments and discussion upon this point? Dr. McGrath?
>
> DR. MCGRATH: Independently sponsored with, obviously, Inamed
> participating and joining into this also.
>
> DR. ANDERSON: And I would suggest that the registry needs to
> explicitly track data regarding rupture, intracapsular and
> extracapsular.
>
> DR. CHOTI: That is part of it. I don\'t think that needs to be
> specified but one thing that can be emphasized is something like \"for
> life.\" It says patients who use the product so I assume that means
> forever. Right?
>
> DR. WHALEN: Well, I would differ. I think you would have to actually
> stipulate that because \"use the products\" could mean till
> explantation. Are you talking about life of the patient or life of the
> product?
>
> DR. CHOTI: Life of the patient. I think that is important,
> particularly the ones where there is rupture, but for all of them I
> think it is an important point and in the registry they need to be
> tracked beyond the time it is explanted or changed.
>
> DR. WHALEN: So, it perhaps then should read that a patient registry
> that exists today will continue to track patients for the duration of
> their lifetime.
>
> DR. ANDERSON: And there was one other point about a mail-in card type
> follow-up. The registry can\'t just exist with no data filled into it.
> There needs to be a good-faith effort to follow-up on patients, just
> as we would do in an epidemiological study.
>
> DR. WHALEN: So, perhaps a patient registry that exists today will
> continue to track patients throughout their natural lifetime and
> strong efforts will be made to assure the highest accrual of data to
> that registry.
>
> DR. ANDERSON: Yes, that is good.
>
> PROF. DUBLER: I am just puzzled. We want this to be an independent
> registry. I agree it should be, but we want Inamed to fund it because
> I don\'t see any other funders stepping up to the line.
>
> DR. MCGRATH: That is not true. There is already a registry that exists
> in one of the professional organizations that has other
> manufacturers\' implants already involved.
>
> PROF. DUBLER: Oh, so there is one that exists that could be expanded
> to meet this purpose?
>
> DR. MCGRATH: Well, we heard a presentation about that today. I don\'t
> know the details. I mean, I don\'t know about it but I heard them
> present that material, yes. Dr. Kerrigan presented it.
>
> DR. WHALEN: Dr. Witten?
>
> DR. WITTEN: Yes, I just want to clarify something. These are
> conditions on the sponsor, right? These aren\'t conditions on another
> party? Is that what we are talking about? I just want to understand
> the relationship, if number eight is recommendation of another party,
> how is it a condition on Inamed?
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: Let me respond, Dr. Witten. I think, Dr. Witten, what we
> had before is this number eight and the question was do we support
> number eight or not. My answer is no, I don\'t support number eight as
> it is written. I do support Inamed participating in a patient registry
> process, but I don\'t think the patient registry process should be an
> in-house thing in their house. I think it should be an independent
> registry, administered by a professional organization of some sort and
> eventually that might include other manufacturers, and so forth and so
> on. I think this is for everybody\'s safety because manufacturers
> change and companies change, and so forth, and it is safer to have
> this in independent hands.
>
> DR. WHALEN: Very well. We are now at a point where we can look upon
> our first conditions, which is these now modified eight
> sub-stipulations of condition number one. When I ask for a hand vote
> on this, I will ask you to please keep your hands up for a little
> while because it is difficult for me to see everybody and I will be
> ducking and darting a little bit to see that.
>
> All those in favor of condition number one, please indicate by raising
> your hands.
>
> \[Show of hands\]
>
> DR. WITTEN: Just to clarify, who is voting? Who votes on this?
>
> DR. WHALEN: Everybody except the consumer and industry reps. I only
> vote in case of a tie. Dr. Krause does not vote and you do not vote
> either. So, as I see it, it is unanimous. Everybody is in favor of
> this condition number one.
>
> Very well, taking it in step-wise fashion, I believe we have
> consideration for potential four more conditions, at least. As I
> recorded them, the first would be Dr. Li to talk about explants.
>
> DR. LI: I guess this is a new condition because what I would like them
> to do, perhaps after they have worked with a third party in
> establishing what data to collect on retrieved implants, is that they
> reinvestigate the current implants they have in hand to see how much
> information they can glean from actually already a substantial number
> of retrievals.
>
> DR. WHALEN: Further discussion? You couldn\'t hear him? I am sorry,
> would you repeat it, Dr. Li?
>
> DR. LI: I was looking behind me, sorry. My condition was that after
> the FDA and a third party has worked with Inamed to establish how they
> should collect and what type of data they should collect in their
> ongoing retrieval program, that those same criteria be applied to
> their existing 339 retrievals that they have in hand because it is a
> very difficult collection of implants to get and I don\'t want to miss
> that information.
>
> DR. WITTEN: Just for clarification, I am assuming, since this is a
> condition of approval motion, that your recommendation is that they
> apply those criteria to those retrieval specimens after approval and
> you are not suggesting necessarily that we complete that and look at
> the data prior to approval, or am I wrong? Because it makes a
> difference as to whether it is a condition or whether you are asking
> for new data prior to approval. So, I just want to understand what you
> are recommending.
>
> DR. LI: Good question. Actually, in this particular case I think I
> would make it a condition for approval in the event that on
> reexamination of the 339 retrieved components they perhaps would find
> a factor that would leave to rupture. So, I would hate to find that
> out after the fact.
>
> DR. WHALEN: The only question I would have on that one is since this
> is really short-term sort of data that you are looking at in terms of
> these explants, and their short-term rupture rate was not as
> high\--our concerns are really more with the long-term rupture
> rate\--do we need to stipulate that as a pre-approval condition rather
> than a post-approval condition?
>
> DR. LI: I suppose I could live with it either way but if I personally
> had my druthers, I would make it a condition for approval.
>
> DR. WITTEN: Let me just say that looking at new data is not a
> condition for approval. I mean, if you feel that you need to do that
> before approval, then that would be a not approvable recommendation,
> with the recommendation that they need to do that to put it in an
> approvable form. If you think you can live with it after approval, it
> can be a post-approval condition.
>
> DR. LI: I guess then I would vote for after approval.
>
> DR. WHALEN: Dr. Leitch and then Dr. Anderson.
>
> DR. LEITCH: I guess the question I would have is if these implants
> have already been analyzed in some way, are they susceptible and
> available to be analyzed again in a different way? Or, have they been
> compromised in some way with the analysis they have already had and
> trying to apply a different set of criteria wouldn\'t work out? I
> guess that is something the sponsor would have to answer.
>
> DR. WHALEN: That is a specific question to the sponsor, so if you
> could give us a concise answer to that? Are they still in a condition
> where they are analyzable, or are they beyond hope?
>
> DR. CROTTEAU: These devices are available. They have gone through
> standard analysis and may have been tested to some extent but are
> available for further testing.
>
> DR. WHALEN: Thank you. Dr. Anderson?
>
> DR. ANDERSON: I do not feel that testing needs to be done prior to
> approval, the reason being that whatever information is gleaned from
> this in terms of whey these are rupturing, the company would like to
> know this too because they would like to come out with a model that
> doesn\'t rupture. So, I don\'t think we have to be concerned that they
> wouldn\'t actively try to seek it. I think that was an excellent
> recommendation that we made to try to answer the question that is so
> important.
>
> DR. WHALEN: Dr. Miller?
>
> DR. MILLER: Does this sort of fall underneath stipulation number four
> that we already voted on, where they will diligently investigate
> further modes?
>
> DR. WHALEN: The Chair had exercised the prerogative to make it
> separate. Obviously, they are tied together but number four, as we
> reworded it, was already approved as condition number one. So, this is
> a separate condition although it is somewhat linked.
>
> DR. MILLER: Could I suggest as well that a test be developed by the
> manufacturer, which goes beyond the ASTM tests that are done, that
> reproduces the fold flaw question, reproduces what happens to wall of
> the implant [in vivo]{.underline}. It is going to require a new test
> that hasn\'t been described yet but I think that needs to be a part of
> investigating the failure modes.
>
> DR. WHALEN: The gist of the discussion that I captured in the past 36
> hours is that they very much would like to find that Holy Grail of
> testing but it hasn\'t yet appeared. So, if you are going to stipulate
> that that is a condition, it is not presently, as I understand it, an
> achievable condition.
>
> DR. MILLER: I guess I will have to defer to the bioengineering experts
> here as to how achievable that is, but I would like for it to be
> pursued.
>
> DR. WHALEN: Steven, can you comment upon that?
>
> DR. LI: It is difficult for me to say if the development of the test
> would be easy or hard seeing as how the device has been around for a
> while and the test doesn\'t exist. I think it would be difficult to
> strap anyone with the responsibility to develop a test in a certain
> time period that demonstrates clinical significance. Can it be done in
> general? I think the answer is yes. Can it be done in six months? I
> don\'t know. A year? I don\'t know. Maybe it will take a couple. You
> know, without knowing the mechanism of the failure, it is a little
> difficult for me to tell you how to simulate the failure. So, I would
> have made this clearly a condition if I knew how to word it in some
> practical fashion but I can\'t think of how to do it.
>
> DR. MILLER: I will just assume that what I am describing falls under
> the category of investigating the failure modes and just leave it at
> that.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: Steve, help me on this, but I think you could even
> broaden it a little bit. It seems to me that what we are really
> talking about is that we want more material analysis, and we want to
> see more about long-term performance, not just in terms of rupture but
> also gel bleed and everything else. So, what we are really asking for
> is additional studies over a period of time, in a more representative
> environment, that will give us this long-term materials analysis. Am I
> saying that right, and can you word that better, Steve?
>
> DR. LI: Actually, you said it quite well. I think that is kind of a
> two-parter though, in my mind. I think there are things we can glean
> out of the retrieval program but that might not, for instance, give us
> meaningful data for gel bleed as a for instance. So, that would be
> like a separate area. So, my current suggestion for a condition is
> that I basically would like them to reinvestigate their current
> collection of retrieved implants, with perhaps a new set of data to
> collect on them to see if we can\'t get a better fundamental
> understanding of the information they already have. That would be in
> addition to item number four of the condition we just passed.
>
> DR. WHALEN: Since you just reworded it for us or restated it for us
> because I stepped on my parliamentary left foot, that was a motion for
> condition number two which we should not have discussed until it was
> seconded. Is there someone that will second it?
>
> DR. MCGRATH: Second.
>
> DR. WHALEN: Thanks a lot. Anything else, Steven?
>
> DR. LI: No.
>
> DR. WHALEN: Is there any further discussion on this second stipulated
> condition that we are discussing right now? Dr. McGrath?
>
> DR. MCGRATH: Just procedurally then, I would like to break it into two
> parts, the part that Dr. Li is mentioning should be the analysis of
> the ruptured implants and particles to look at the rupture cause, but
> also some other long-term performance parameters that would be looked
> at.
>
> DR. WHALEN: I am sorry, when you say split the two parts, you want to
> split this into two conditions or are you willing to contain it as
> one? Okay.
>
> Will all those in favor of this condition please indicate by raising
> your hand, and keep it raised? All the voting members?
>
> \[Show of hands\]
>
> It is unanimously approved. The next in sequence that I had jotted
> down as a possible condition would be Prof. Dubler in terms of the
> capsule.
>
> PROF. DUBLER: Well, I would look for help to the clinicians and
> researchers, but there were a number of times over the last two days
> when certain of the people presenting testimony indicated they didn\'t
> think that a gross examination of the field told us enough when we
> explanted a device and that perhaps even the MRI did not tell us
> enough. If that were to be the case, then I would think it would be
> incumbent to set up a study which attempted to get patient agreement
> to do a biopsy at the time of explant. Now, that may make no sense
> but, if it is a possibility, I would like to hear the clinicians
> comment.
>
> DR. WHALEN: I don\'t think we have yet reached the stage of a motion
> on that so I am not yet going to ask for a second. So, is there any
> clinician help in terms of the phraseology of how this would be done?
> Dennis?
>
> DR. BOULWARE: I would like to move that we include in the retrieval
> mechanism biopsies in dependent and random areas within the capsule.
>
> DR. WHALEN: Is there a second for that? Dr. McGrath seconds. Dr.
> Anderson?
>
> DR. ANDERSON: What we are really talking about is creating a tissue
> bank of capsules, which actually is a very interesting idea. In fact,
> you might find that there would be information that could be gleaned
> about why people get capsular contracture. So, I think it is a
> valuable idea. It is important to understand that tissue banks are not
> a minor issue. They are a big deal to create. You have to decide if it
> is fresh tissue or fixed tissue, and the biggest problem that we have
> right now is that it is not hypothesis driven. You are just collecting
> the tissues just sort of hoping that some day you will come up with
> the hypothesis.
>
> It would not be a shock to see that there are minute amounts of
> silicone on the all of the capsule. So, my concern with this is that
> just showing the presence of that doesn\'t necessarily tell us
> anything. I am not discrediting the idea because actually it wouldn\'t
> even be a bad idea for the company if they could find something that
> didn\'t make such tough capsules and capsular contracture.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: Yes, I think it is an excellent idea but in orthopedics this
> is actually a ripe area for NIH grants. This is a very scientific, not
> straightforward type of analysis. For instance, we don\'t know exactly
> how much is there. We don\'t know the species that is there. And, the
> analytical techniques to analyze for silicone actually don\'t exist at
> the moment. So, it is a little difficult for me to figure out how you
> would make this a condition for a company to be approved. I think it
> is a great idea and needs to be done, I just don\'t see us
> approving\--but I see Dr. Newburger with a question.
>
> DR. WHALEN: Dr. Leitch and then Dr. Choti and then Dr. Newburger.
>
> DR. LEITCH: This is sort of a great study question but then, as was
> mentioned, you have to know what you are going to look for, what you
> are going to analyze, how you are going to retrieve the tissue. Do you
> just want a microscopic exam? I think one of the concerns that Dr.
> Dubler had was is there extracapsular silicone. So, what she is really
> asking for I think is a biopsy of the tissue that is outside of the
> capsule, not the capsule itself. The problem with that potentially is
> a sampling error. You know, if you take a sample from wherever the
> surgeon makes the incision to remove the implant, that might not be
> the spot where there would be extravasated silicone. So, you might be
> misled by the results. If you found something, you could say something
> about that but that would be the problem.
>
> I think what we have heard in discussions over the last two days are a
> lot of good ideas for research, but whether that is reasonable to have
> the sponsor do that, unless they were highly motivated and if they
> thought it would make a big difference for them and they had a
> hypothesis, then they could say this is how we want to receive the
> tissue\--we want fresh; we want formalin fixed, whatever it is they
> want. Fresh tissue, though, is a big problem and almost all the
> clinical trials that have tried to do fresh tissue collection perceive
> it as a big problem in implementation. So, again, you have to be
> prepared for the repercussions of that, and are we prepared to require
> that at this moment?
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: Yes, I agree. I mean, it is interesting but I don\'t see
> any reason to make this a condition of the sponsor for approval.
>
> DR. WHALEN: Dr. Newburger?
>
> DR. NEWBURGER: My belief is that the Department of Environmental and
> Toxicologic Pathology at the Armed Forces Institute of Pathology has
> the ability to do Raman spectroscopy and Fourier infrared
> microspectroscopy, and they keep a registry there. So, I think any
> issues in terms of handling tissue could be addressed by them in a
> very efficient manner.
>
> DR. LI: Excuse me, as a response for that, it is my understanding that
> with that particular method though they will be able to say yes or no
> for silicone as an element, is it there or not, but they won\'t be
> able to tell you the form of the silicone or what molecule it is
> necessarily part of, or whether or not it makes any difference that
> you can find silicone. So, it is not so much a matter of we don\'t
> have a way to detect silicone in a location, but it is the nature of
> the silicone and its chemical environment, and those kinds of things
> that I was referring to.
>
> DR. NEWBURGER: Indeed, but the AIFP does have coincident
> histopathology done by more standard techniques so that you can get a
> real sense of what the reaction pattern is where it is found.
>
> DR. WHALEN: Just remember down there, please, when you talk to one
> another, talk directly into the microphone so the rest of us can hear
> you. The ones that are aimed at the angle of your mandible don\'t help
> too much either. Dr. Choti and then Prof. Dubler.
>
> DR. CHOTI: Again, we don\'t even know what we are going to study with
> this. Why not look at serum samples? I mean there is no evidence to
> suggest that capsular biopsy is any more valid or more informative
> than any other sample.
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: This discussion did exactly what I hoped it would do. It
> convinced me this is a bad idea.
>
> \[Laughter\]
>
> DR. WHALEN: With that in mind, since it was a motion as a condition,
> we do need to take a vote upon it. All those in favor, please indicate
> so by raising your hand. It has already been seconded so I think it
> would be a better process to take a vote on it.
>
> \[One hand raised\]
>
> One. Dr. Newburger votes in favor. All those opposed?
>
> \[Show of hands\]
>
> Everybody else votes against it. The next that I had written down I
> believe was Dr. Conant\'s, in terms of a potential condition.
>
> DR. CONANT: Yes, I was interested in adding on an educational
> component for the surgeons in terms of follow-up and recommendations
> for management of patients about to have rupture, based on physical
> exam, some kind of paradigm for this evaluation. What I would imagine,
> on exam if rupture was suspected\--these are out of study
> patients\--and MRI would be recommended and then the sponsor would
> state in their labeling or I guess in their data that if there was
> rupture, it would be recommended that the implant be removed, to take
> a stand on that.
>
> DR. WHALEN: So, if I am getting it right, there are three components
> to this. You feel that there needs to be an educational program so
> that surgeons are brought up to speed on clinical recognition\--
>
> DR. CONANT: Yes.
>
> DR. WHALEN: \--of potential extrusion of silicone.
>
> DR. CHOTI: Yes.
>
> DR. WHALEN: That an MRI be done if there is clinical suspicion and
> that, furthermore\--you want to wrap all this into it\--if there is
> silent rupture, the recommendation be made to remove the implant.
>
> DR. CONANT: Yes.
>
> DR. WHALEN: Have I got it right? Is there a second to that motion?
>
> DR. ANDERSON: I would suggest a modification to that. I am going to
> defer to my plastic surgery colleagues, but I don\'t think requiring
> an MRI\--if it is something that is clinically obvious\--
>
> DR. WHALEN: I am sorry. I have already gotten chastised once. I think
> this discussion would follow a seconding and we haven\'t yet had a
> seconding, if that is okay with you.
>
> DR. ANDERSON: Sorry.
>
> DR. WHALEN: Is there a second to this condition?
>
> DR. MILLER: I will second it.
>
> DR. WHALEN: Dr. Miller seconds. I am sorry, Dr. Anderson. Please
> continue.
>
> DR. ANDERSON: I apologize. Requiring an MRI I don\'t think is
> necessary. Recommending and MRI is appropriate. But if you don\'t need
> it, you don\'t have to get it.
>
> DR. CONANT: Actually, I think that is a valid recommendation. However,
> my concern, and the reason I do say MRIs, is that I think there is
> sometimes a difficulty establishing whether it is a contained rupture;
> whether there is actually flattening and softening of the implant; and
> whether there are actually small areas of extracapsular rupture. I
> would think, and again I will leave this to my plastic surgery
> colleagues, that if there were extracapsular rupture you would like to
> know where it is; you would like to map that out, and the MRI has that
> more global capability for doing that. So, removal could attempt to
> take out at least the localized free silicone. That is my thought
> process.
>
> DR. WHALEN: What about the recommendation for removal of silent
> ruptures? Is there any discussion on that?
>
> DR. MILLER: Was that a part of the recommendation?
>
> DR. WHALEN: The motion was made that there be provision of clinical
> education and recognition of rupture; that there be a recommendation
> for MRI if rupture is suspected; and that, if rupture is confirmed,
> the implant be removed. The recommendation is made that the implant be
> removed. Dr. Chang and then Dr. McGrath.
>
> DR. CHANG: Just in response to the last comment, if, indeed, on
> clinical examination I were positive by history and physical that a
> rupture had occurred, an MRI would not add substantive information to
> change the treatment. I would look with due diligence for any areas of
> palpable silicone. So, I don\'t believe that the cost would outweigh
> the benefit gained of additional information, and would not change my
> treatment plan. So, I don\'t think it would be wise to require MRI as
> an algorithm.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. CONANT: Can I just comment on that?
>
> DR. WHALEN: Dr. McGrath and then we will get back to you.
>
> DR. MCGRATH: I think your motion is a bit broad. Can we just take part
> one, about the education of physicians and the recognition of rupture,
> and perhaps could even include that in what we already voted on before
> because it is really very close to it. We talked about surgeon
> education and verification in this area of surgery using silicone
> gel-filled implants. Certainly, the recognition of a ruptured one
> would go with that.
>
> I think it is a totally different issue to bring up\--I don\'t think
> we are ready to educate people about the use of MRI for explantation
> because, if I remember our voting and discussion from last night, we
> really hadn\'t gotten to a consensus yet about whether there is a
> utility for MRI or explantation.
>
> DR. CHOTI: I think the consensus was, although the data is limited,
> there is a benefit and that we should recommend explant if there is
> evidence of a leak. Is that not the consensus of the group?
>
> DR. WHALEN: No, seven, three and three was the opinion registered,
> seven to take it out; three not to take it out; three on the fence.
> So, it was a majority but not an overwhelming one.
>
> Other discussion? If not, let me ask the pleasure of the panel. Dr.
> McGrath has suggested that we divide this question and take the first
> part of it, which is the component of education of the implanting
> surgeons as to the subsequent recognition of rupture, and incorporate
> that back into the education program, which we have already stipulated
> as a condition and voted upon. Is it the will of the panel to divide
> that out? Is there any further discussion upon incorporating that
> aspect to the education program, into the overall education program
> that is being developed? Seeing none, all those in favor, please
> signify by raising your hands.
>
> \[Show of hands\]
>
> Even Brent got his hand up so I know we approved it unanimously. Good.
> Very well.
>
> The divided question then leaves us with, in the face of clinical
> recognition of rupture, that there be a recommendation for MRI and
> that confirmation of rupture lead to explantation. Any further
> discussion on that motion?
>
> DR. CONANT: I am certainly willing to soften that to \"consider\" MRI.
> My only concern about the MRI is, again, that free silicone isn\'t
> necessarily palpable nor is it visible. Again, I would ask for plastic
> surgeons to comment on this. In removing a ruptured implant with
> extracapsular extravasation, my impression was that it is ideal to
> remove as much of the silicone as possible. So, I would like some
> comment on that. I think \"consider\" MRI if indicated is fine.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: Wouldn\'t it be the case though that with a mammogram,
> which is cheaper, you could see gross extravasation of silicone and
> that would be another way of mapping?
>
> DR. CONANT: Actually, unfortunately, mammography doesn\'t always show
> the extent of disease because the silicone has such a high optical
> density. If the area is superimposed over the implant you will not see
> additional areas of silicone. You may see it tracking superiorly along
> the pectoralis or inferiorly, but you really don\'t have a
> three-dimensional mapping of it. So, I don\'t think mammography is
> adequate.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: Practically speaking, at the time of explantation\--it
> sounds like you are potentially even talking microscopic. The only
> practical part that we would remove would be the part that we could
> palpate or see. So, although I would agree that an MRI would certainly
> be helpful, I don\'t think it should be required.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: When we discussed this last night, you know, we felt that
> a decision about whether to recommend a screening MRI and decision
> about explantation has to be data driven. We don\'t yet have the data
> to make a clean recommendation on this. Therefore, maybe what we
> really should do is turn this into another item and make that item a
> real hard plan, developing a plan for looking at this issue as a part
> of the post-approval study plan.
>
> DR. WHALEN: Dr. Miller?
>
> DR. MILLER: I think I have nothing to add to my comments that is
> relevant at this point.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: Well, you do have the MRI follow-up study and I think that
> is an opportunity to generate the data to answer this question. So, we
> can add that on as a clear goal of that study, to assess the value of
> that as a screening study. Then, presumably, there will be outcomes
> for people in that study who identified they had a rupture and some of
> them are going to have the implants removed and some probably won\'t.
> So, there will be data from those patients. It won\'t be in a
> randomized fashion, as Dr. Blumenstein was suggesting, but it will
> exist as some data that could be evaluated, and that should certainly
> be an outcome that would be requested from that particular study.
>
> DR. WHALEN: Dr. Anderson, did you have something?
>
> DR. ANDERSON: Last evening we had this discussion about the removal of
> implants. I think that we need to have it again here to make a
> decision whether we can decide or not. I would like to make a proposal
> that the recommendation be when a ruptured implant is discovered, it
> is recommended to the patient that it be removed.
>
> DR. WHALEN: Maybe I am just going to ask you what the difference is.
> As it was worded, we said that the recommendation would be that it be
> removed if we find that it is ruptured. Certainly, we can\'t require
> that. That is a matter of informed consent and a decision between the
> surgeon and the patient. So, I am not sure\--
>
> DR. ANDERSON: I am sorry, I didn\'t understand what our discussion was
> then. Can I comment on that? If we are not unanimous, because I heard
> some of my colleagues saying that they are not convinced of this, I
> think that in the absence of data showing the safety of ruptured
> implants, we have to recommend their removal. A randomized trial or
> data demonstrating safety, until that is there, it seems to me that
> should be the position of the FDA.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: I guess it is a little like number five on the first
> condition, this would be a condition of the sponsor to recommend that
> in the literature? That would be their position, to recommend removal?
> Is that it?
>
> DR. WHALEN: Basically, Dr. Witten, I would assume if this comes as a
> recommendation as a condition, it would be a labeling issue. So, that
> translates to a sponsor recommendation.
>
> DR. WITTEN: That is what we would assume.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: I am still struggling with this. If we don\'t have a
> consensus among ourselves about whether it is appropriate to explant
> it just because it is ruptured, then how can we ask the manufacturer
> to put in educational materials that that would be a stipulation for
> their post-market approval. I think we have to go back even further
> and make it one of the items that has to be part of a post-approval
> study plan. That is, to start looking at patients with ruptured
> implants and to continue to gather this data in a formalized way so
> that we have a sense about what happens with these individuals.
>
> DR. WHALEN: My read on that, Dr. McGrath, would be that, contrary to
> the way we have been voting today, rarely do you see necessarily
> unanimous votes on any of these recommendations. Since this is a
> motion on the table, we will come to a vote on it. As is FDA
> procedure, if it is a divided vote, we will read for the record those
> who favor and those who do not favor that particular stipulation of
> approval, which is an element of FDA subsequent consideration of what
> are only recommendations on our part if they are going to go forward
> with it.
>
> As to studying it going forward, I would entertain that as potentially
> yet a separate condition of approval. Dr. Chang?
>
> DR. CHANG: I will just make the comment that item one that was passed
> incorporated bullet four, where the sponsor said we will pay
> particular attention to any relationship between outcomes and rupture
> status.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: As one of the panel members who disagreed with the
> treatment alternative when there is a verified rupture, intracapsular
> rupture, I would certainly be in favor of your statement if it said
> extracapsular rupture because we certainly have the data to recommend
> that. But it would be difficult for me to agree with the intracapsular
> rupture.
>
> DR. WHALEN: Before we advance to voting on this condition, let me read
> for the record and announce that Dr. Lawrence, one of our panel
> members, had to leave us and there are, therefore, now 15 voting
> members remaining, although if there is an abstention and a tie
> breakdown among those 15, I become a voting member to break the tie.
>
> What I believe we are about to vote on, and correct me if I am wrong,
> is a recommendation as a condition of approval that in the face of
> clinical suspicion of rupture, there be consideration of performance
> of an MRI examination, and that, by whatever means, if rupture is
> confirmed that there be explantation\--a recommendation of
> explantation.
>
> Before we get to the actual vote, have I articulated that condition
> correctly or does anybody object to how I just stated that? Seeing
> none, on that condition of approval, would those who are in favor
> please signify by raising your hands?
>
> \[Show of hands\]
>
> For the record, Dr. Miller, Dr. Anderson, Dr. Li, Prof. Dubler, Dr.
> Newburger, Dr. Leitch, Dr. Chang, Dr. Choti, Dr. Conant, Dr. Lieberman
> and Dr. Manno have voted in approval.
>
> Would those who are opposed, please signify, and abstention is
> allowable.
>
> \[Show of hands\]
>
> Dr. Blumenstein opposes this, as does Dr. Olding. Those who abstain?
>
> \[Show of hands\]
>
> Dr. Boulware and Dr. McGrath. Thank you. The next in order of
> potential conditions of approval was an issue raised by Dr. McGrath. I
> am sorry, I only wrote down your name and not exactly what the issue
> was.
>
> \[Laughter\]
>
> DR. MCGRATH: Tom, I am disappointed! As the next condition of
> postmarket approval, that the manufacturers be charged with evaluating
> the patients with ruptured implants, and monitoring the effects of
> this rupture both locally and systemically in these persons.
>
> DR. WHALEN: Is there a second for that condition?
>
> DR. LIEBERMAN: Second.
>
> DR. WHALEN: There is a second by Dr. Lieberman. Is there any issue,
> Dr. Witten, in terms of that?
>
> DR. WITTEN: No, was that just in general or in the study, because that
> is already part of the study?
>
> DR. MCGRATH: In the study.
>
> DR. WITTEN: Pardon me? In the study? That is already part of what they
> are proposing. So, I am just wondering what else you are suggesting.
>
> DR. MCGRATH: It is number four, I believe, that you are referring to,
> where it says we will pay particular attention to any relationship
> between outcomes and rupture status. I didn\'t know what \"particular
> attention\" meant and I would like this to be a formal study protocol.
>
> DR. WHALEN: It has been moved and seconded. Further discussion upon
> that?
>
> DR. CHANG: Dr. McGrath, could you just clarify \"formal study
> protocol?\" Do you mean incorporate these patients who are found to
> have ruptured implants?
>
> DR. MCGRATH: Dr. Chang, I don\'t really want to rate the protocol
> right now but I can think of a lot of ways that these patients really
> need to be looked at very closely, and I am sure that can be written
> up.
>
> DR. WHALEN: Seeing no further discussion on the motion as a condition
> of approval that the sponsor, in study patients, evaluate them for
> ruptured implants and monitor effects thereby, both locally and
> systemically, would all those who are in favor of that, please
> indicate by raising your hands?
>
> \[Show of hands\]
>
> It does pass unanimously. That is the sequence that I jotted down
> during our discussion of the first condition of approval of other
> conditions of approval. I will now entertain any further conditions of
> approval that anybody would like to make. Dr. McGrath?
>
> DR. MCGRATH: Last night when we were talking, when we got to question
> 7(b), it was please describe any other specific endpoints which should
> be captured as part of the post-approval study. We talked about a
> number of those and we had a fair list. Is this the right time to
> resurface those and now bring them up as formal items?
>
> DR. WHALEN: If you feel that they rise to the degree of conditions of
> approval, indeed, yes.
>
> DR. MCGRATH: Since you are the only one who wrote them down, Dr.
> Whalen, would you read them to us?
>
> DR. WHALEN: That presupposes that I can actually find where I wrote
> them down, so if you will bear with me for a moment, I will try.
>
> The conditions that I noted last night were that there be tracking of
> rupture rates; explantation rates; that there be investigation into
> the capsular tissue itself and extracapsular tissue; that there be
> rigorous recording of systemic problems; tracking of other surgeries
> that are being performed; and tracking of patients with implants as to
> pregnancy data and complications of pregnancy, as well as tracking of
> their children as to their subsequent health and development. Dr.
> McGrath?
>
> DR. MCGRATH: Two others that I had written down were tracking with
> continuing the health status questionnaire, quality of life
> questionnaires because of the peculiarity of the two-year data that
> was reported, and also continuing to track or looking at some other
> way of asking patients about fibromyalgia because of the issues that
> had arisen with the self-reported fibromyalgia systemic symptoms that
> had seemed very prevalent.
>
> DR. WHALEN: This, again, is in the study population. Did we second
> that one? I need a second for that.
>
> DR. ANDERSON: I will second it.
>
> DR. WHALEN: Thank you. Any discussion?
>
> DR. ANDERSON: I heard the capsule tissue being on that list. We should
> take it off since we already discussed it and decided not to.
>
> DR. WHALEN: Barring objection, okay.
>
> DR MILLER: Point of clarification, are we entertaining adopting all of
> that list? Is that what the proposal is?
>
> DR. WHALEN: Barring objection, we would do it globally. As we just
> did, we can pick something out if we don\'t want to do it.
>
> DR. MILLER: It seems like many of those things we have sort of
> discussed indirectly with some of the other things that we talked
> about. It seems like we have covered a lot of that, except for
> tracking the children. I think it is a good idea to track the children
> of implanted patients and I haven\'t heard that discussed.
>
> DR. WHALEN: They can\'t hear.
>
> DR. MILLER: I am sorry. In that list you just read, as best I can
> recall, we discussed most of it indirectly in the other things we
> talked about, with the exception of tracking the children. So, maybe
> we should become more formal about how we are going to track the
> children of people who get implanted.
>
> DR. WHALEN: So, would you like to extract that and make it a
> subsequent motion?
>
> DR. MILLER: Yes.
>
> DR. WHALEN: Okay, barring objection? Very well, further discussion?
>
> DR. CONANT: Further discussion on children?
>
> DR. WHALEN: No, actually that is going to become a subsequent item.
> Seeing no other discussion, all those in favor, please indicate by
> raising your hand.
>
> \[Show of hands\]
>
> That is again unanimous. I would entertain, Dr. Miller, a motion.
>
> DR MILLER: I would move that we formalize a tracking method for
> monitoring how the children of implanted patients do over the years
> after implantation.
>
> DR. WHALEN: Is there a second for that?
>
> \[The motion was duly seconded\]
>
> We have a second. Discussion is open.
>
> DR. CONANT: Can we expand that, please, to pregnancy and lactation?
> Pregnancy, lactation and offspring, kind of like one package deal?
>
> DR. MILLER: Sure.
>
> DR. CONANT: Thanks.
>
> DR. WHALEN: Further discussion on this then?
>
> DR. CHOTI: Monitor for what?
>
> DR. MILLER: For the adverse health outcomes that have been discussed
> in the course of our discussions over several days.
>
> DR. WHALEN: I am doing my best to make sure we hit the Beltway at the
> worst possible time so I would like a little bit more discussion.
>
> \[Laughter\]
>
> Dr. Leitch?
>
> DR. LEITCH: Well, I think maybe phrasing it as \"tracking the
> children\" may be unrealistic. I mean, you can ask questions of the
> patient about congenital deformities in their children or specific
> disease states in children, but the idea that you would, you know,
> \"track\" the children per se\--I don\'t know that I would phrase it
> in quite that way because that implies essentially a whole other study
> and level of consent, and that sort of thing, for tracking of the
> children.
>
> DR. WHALEN: So, gather data on health problems of children?
>
> DR. LEITCH: Yes, that would be reasonable.
>
> DR. NEWBURGER: I need some more information about how this tracking
> can be done because you are looking at millions of people. When you
> have a three percent spontaneous birth defect rate and then there are
> other health issues that are encountered, I don\'t see how those
> babies can be managed.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: I thought maybe we could ask Dr. Blumenstein, given the
> patient population that we are dealing with in the study group, are
> there enough patients in that study group to answer questions about
> the offspring if the events are rare?
>
> DR. BLUMENSTEIN: I have no idea.
>
> DR. LEITCH: You are supposed to help us on these things!
>
> DR. BLUMENSTEIN: Well, I figure I am helping because what is going on
> here is that we are loading this stuff out so much that the sponsor is
> not going to want approval.
>
> DR. LIEBERMAN: I think there are probably going to be some issues with
> getting an adequate number since many of the women are past their
> childbearing years when they have their breast implants. I think it
> would be important, through some venue, to at least get some
> information on pregnancy and lactation and major health problems, and
> maybe that could be incorporated into the registry if we are going to
> be sending questionnaires. It could just be hooked on the end as a few
> extra questions rather than making it an independent mechanism.
>
> DR. WHALEN: I would just follow-up on what Dr. Blumenstein said,
> perhaps only partially tongue in cheek. We are not dealing with a
> 501C3 corporation here that is looking to give away stuff. They are a
> business at the end of the day and we have to keep that in mind. We
> are trying to come up, if we are going to approve this, with
> conditions that maximize to the degree possible a guarantee of safety.
> That could rise to the level where it is no longer a feasible business
> venture to do it. So be it, if that is the case. But I would not use
> that as criteria for judging whether or not something should be
> approved. The criteria for approving it is whether it impacts on
> safety or efficacy. Dr. Manno?
>
> DR. MANNO: I am the one who brought that up last night, and I think
> when I brought it up I limited it to the women of childbearing age in
> order to cut the number of people that they would have to screen.
>
> DR. WHALEN: I am sorry, I am not sure I understand what you are
> saying.
>
> DR. MANNO: I was the one that brought the tracking of the children up
> last night. I proposed that it only be done in women of childbearing
> age, and it be asked in the routine checkup whether they have had a
> pregnancy since the last checkup.
>
> DR. WHALEN: Maybe I was having a little trouble understanding you
> because, as I understood it, if we are going to be tracking offspring
> of patients with implants that would sort of be part of the process\--
>
> DR. MANNO: Well, you are certainly not going to take a 65-year old
> woman who has reconstructive surgery after breast cancer. It wouldn\'t
> be relevant. If she has had the breast work done at 65, her kids are
> grown and gone.
>
> DR. WHALEN: No, I understood where you are coming from. I mean, like
> we haven\'t stipulated in here that it be in females either. That sort
> of comes with the territory, you know?
>
> DR. ANDERSON: I don\'t think it is realistic to collect data on unborn
> people. Indeed, I don\'t think that at my institution, if I said I
> wanted to create a database of individuals that I can\'t consent
> because they haven\'t been born yet\--I don\'t think that that would
> pass HIPAA rules.
>
> DR. WHALEN: Mike?
>
> DR. MILLER: My motivation is to get at some idea to answer some of the
> concerns that have been raised about the impact on second generation
> implant people. I think perhaps a simple question included in the data
> that is gathered from the patient, from the primary patient\--have you
> had a child? Is the child normal? Maybe that is enough just to create
> some red flags about something that is happening. I guess I just
> don\'t want that to be neglected in the data points that are gathered
> on these patients.
>
> DR. WHALEN: That is fine. I was dealing with a not so minor logistical
> issue here. You know, last night our rally call was \"we\'ll stay up
> until we get the business done\" and then \"torpedoes full speed
> ahead.\" I have been informed that at 1700 hours, which is about 33
> minutes from now, we will be formally ejected from this room. So,
> unfortunately, with that time constraint in mind, we have to focus
> upon the business at hand. Is there any more important discussion that
> we have to have upon the issue of tracking health outcomes of children
> of women with implants? Ms. Brown?
>
> MS. BROWN: Michael, following up on your idea, if a woman answered
> yes, there has been an issue, it would be important for the company
> then to understand what her genetic history was, what her family
> history was in order to try and understand that situation. So, you
> know, the simple yes/no is going to involve a lot more at the back
> end. I don\'t know\--if there are 800 patients and you take it down to
> women of childbearing age which is maybe 500 patients, and then the
> incidence of defects in the normal population is three percent\--I
> don\'t even know what that number is but, from a statistical
> perspective, we will be trying to understand the difference between
> that natural incidence and whatever happens here.
>
> DR. MILLER: I guess I wasn\'t looking for an exhaustive analysis, and
> if it would be of no value to even just gather an indication of how
> many of these implant patients get pregnant and how many have
> problems, we can find another way to do it, other than this process.
>
> DR. WHALEN: Dr. Chang?
>
> DR. CHANG: Is there a way to satisfy the concerns about lack of
> information by having labeling that there is a lack of information,
> rather than trying to have the sponsor embark on a daunting study on a
> limited number of involved study patients, or an amorphous follow-up
> of a large number of patients, to try to satisfy the concerns that we
> have about the unknown by stipulating, as postmarket approval,
> specific labeling to register reservations about what the unsettling
> portions of the unknown are?
>
> DR. WHALEN: Dr. Anderson?
>
> DR. ANDERSON: I agree with that point. I think that this is a labeling
> issue. The consumer needs to be made aware that we don\'t have
> adequate data about childbearing and we do have some data to suggest
> that breast feeding may be less successful after augmentation.
>
> DR. WHALEN: Any further comment? The motion, as it was made and
> seconded, was that we track healthcare outcomes of children of
> patients who have implants. Will all those who are in favor of that,
> please indicate by raising their hands?
>
> \[Show of hands\]
>
> Dr. Blumenstein, Dr. Conant, Dr. Lieberman voted in favor.
>
> Will all those who are against that, please indicate by raising your
> hands?
>
> \[Show of hands\]
>
> Dr. Choti, are you abstaining? All right. Those who abstain, raise
> your hands.
>
> \[Show of hands\]
>
> Dr. Newburger, Dr. Li, Dr. Choti and Dr. Olding abstain and the rest
> are against.
>
> Is there a follow-up motion in terms of labeling? I am told that is
> already in the labeling.
>
> DR. ANDERSON: Is it already in the labeling?
>
> DR. WHALEN: Since this is a new product going forward, we will be
> designing labeling. Is there a motion about labeling as regards the
> subject of nursing and children?
>
> DR. ANDERSON: I make a motion that labeling indicate that we do not
> have adequate information about childbearing after placement of
> implants and that we have data to suggest that breast feeding is less
> likely to be successful after placement of implants.
>
> DR. WHALEN: Is there a second for that?
>
> \[The motion was duly seconded\]
>
> Is there further discussion on that? Seeing none, all those in favor,
> please signify by raising your hands.
>
> \[Show of hands\]
>
> All right, Dr. Miller, Dr. Anderson, Dr. Li, Prof. Dubler, Dr.
> Newburger, Dr. Chang, Dr. Choti, Dr. Blumenstein, Dr. Conant, Dr.
> Lieberman, Dr. Olding and Prof. Manno are in favor.
>
> Those who are opposed?
>
> \[No response\]
>
> And abstentions?
>
> \[Show of hands\]
>
> Three abstentions. Are there further stipulations of conditions of
> approval to be made?
>
> PROF. DUBLER: I think I have one final one that I can make brief. I
> think it is plain that there are some teenagers for whom breast
> implant is totally appropriate. But someone yesterday said that in
> some places the word has been \"give your daughter a lovely present
> for her high school graduation; get her implants.\" So, I would just
> like some statement, perhaps in best practice, perhaps in labeling,
> that these should be available to adult women, with exceptions made
> for teenagers who have congenital deformities. I am not sure what the
> list should be but I would like it to be flagged that these are not
> appropriate high school graduation presents.
>
> DR. WHALEN: The motion I think is in terms of the labeling.
>
> PROF. DUBLER: In labeling.
>
> DR. WHALEN: Is there a second to that labeling recommendation?
>
> DR. ANDERSON: I will second it.
>
> DR. WHALEN: Dr. Anderson seconds. Is there further discussion upon
> that?
>
> \[No response\]
>
> So, the motion has been made that these be utilized in adult female
> patients and that they only be used in adolescent patients with
> congenital deformities\--was that your phrase?
>
> PROF. DUBLER: I wouldn\'t like to list them all out but for special
> indications.
>
> DR. WHALEN: That they only be used in adolescent patients for special
> indications, and this is in the labeling. Dr. McGrath?
>
> DR. MCGRATH: I think on this the wording becomes very important and I
> don\'t think Dr. Dubler said \"but only.\" I think she said that they
> were most appropriate in adult persons and in youngsters with
> deformities and perhaps some other exceptions, but I wouldn\'t make it
> as Draconian as saying \"but only\" because I think that changes her
> intent and certainly would change perhaps others\' intent too.
>
> PROF. DUBLER: I would agree with that.
>
> DR. WHALEN: So, deletion of the word \"only\" is what you are seeking?
> I just want to get the phraseology, that they be used in adult
> patients and in adolescent patients with special indications. All of
> those in favor of that, please indicate by raising your hand.
>
> \[Show of hands\]
>
> I believe that is unanimous. Further stipulations on conditions of
> approval will be entertained. Conditions of approval can only be made
> by voting members of the panel.
>
> Seeing none, returning to the primary motion, the motion has been made
> and seconded that the premarket approval application for McGhan
> silicone gel-filled breast implants from Inamed Corporation be
> recommended to the FDA for approval with the conditions that we have
> just voted upon.
>
> Will all those who are in favor of that, please indicate by raising
> your hand and keeping it up?
>
> \[Show of hands\]
>
> I am going to have to read names so please keep your hand up for a
> moment. In favor of that is Dr. Miller, Dr. Anderson, Dr. Li, Prof.
> Dubler, Dr. Newburger, Dr. Boulware, Dr. McGrath, Dr. Leitch, Dr.
> Chang and Dr. Olding. I am sorry, somebody did not raise their hand.
> Dr. Newburger did not raise her hand so Dr. Newburger was not in favor
> of approval.
>
> Would all those who are opposed, please raise their hands?
>
> \[Show of hands\]
>
> Dr. Newburger, Dr. Choti, Dr. Blumenstein, Dr. Conant, Dr. Lieberman,
> Dr. Manno. I don\'t believe there are any abstentions, correct? That
> has accounted for everybody.
>
> The motion then carries for approval with conditions as stipulated.
>
> We need to go around the table and, I would ask in a relatively
> concise fashion, have each member, starting with Dr. Miller, explain
> why they voted as they did.
>
> DR. MILLER: I think, based upon the evidence that was presented at the
> meeting, the effectiveness of the device was demonstrated and the
> safety was adequately demonstrated based upon the benefit/risk
> assessment, and given the conditions of approval that were agreed
> upon, I am comfortable with approving the PMA.
>
> DR. WHALEN: Thank you. Dr. Anderson?
>
> DR. ANDERSON: I would just say to the audience this was unbelievably
> difficult, much more difficult than I had ever anticipated.
> Ultimately, I believe in the right to choice and informed consent.
>
> DR. WHALEN: Dr. Li?
>
> DR. LI: I echo Dr. Anderson\'s feeling that this was difficult. I was
> on the panel that approved the saline implant a few years ago, as were
> several of my colleagues, and this was a much more difficult decision.
> I am not sure if I would have been comfortable either way but, at the
> end of the day, I think that despite my lack of information about some
> of the basic information about how it fails, at least the preliminary
> data seem sufficient and it seems like there are benefits of this
> device over the saline one.
>
> DR. WHALEN: Prof. Dubler?
>
> PROF. DUBLER: I came back from lunch prepared to vote no. I thought
> the company\'s ability to recognize the problems that the panel was
> facing and to come forward with a very active suggestion for
> monitoring those elements, at least for me, made all the difference in
> the context of the fact that there are women who want access to these
> implants.
>
> DR. WHALEN: Dr. Newburger?
>
> DR. NEWBURGER: I agree that the sponsor has responded very, very well
> and certainly has conducted a very good essentially two-year study. My
> problem with voting for approval is that this is the short-term data.
> We have a certain incidence of device failure. The long-term data\--I
> am really relying on what is in the literature. The European community
> doesn\'t have the same reporting mechanisms that we have. I am not
> comfortable with the silence from across the Atlantic Ocean and I am
> not comfortable with the retrospective studies which are essentially
> from the literature. I think the gold standard is prospective, and I
> am not comfortable with the amount of data that is available for the
> longer-term issues.
>
> DR. WHALEN: Dr. Boulware:
>
> DR. BOULWARE: This was a very difficult issue. But charged with what
> we were from the FDA in terms of definitions of effectiveness and
> safety, the data we were provided and the charge that the decision had
> to be science-driven, I am comfortable with my vote.
>
> DR. WHALEN: Dr. McGrath?
>
> DR. MCGRATH: Not just as a panel member but as a physician and surgeon
> using these implants on my patients, I came here looking for
> evidence-based data and I thought that there was an accumulative
> amount sufficient to show that these devices are safe, but I do think
> that we needed to put in these post-approval conditions for them. I
> certainly, and my patients, will want more information about ruptures,
> causality, detection and the effects locally over time. We have some
> glimmerings of the frequency of it in the very early years but we need
> a lot more. I want more information on reoperation data. I think if
> the manufacturer goes forward with all these post-approval conditions
> with the FDA we will have made a good decision.
>
> DR. WHALEN: Dr. Leitch?
>
> DR. LEITCH: I agree with the other panelists that this has been a very
> difficult conclusion to arrive at for all of us, and we all were
> looking for the information to be able to come to a decision we would
> feel comfortable with.
>
> I think, as was said earlier today, since the last panel meeting we do
> have more data about some of the very concerning issues that women had
> regarding breast implants and their outcomes so I think that data has
> satisfied a lot of our safety concerns regarding systemic symptoms.
>
> Our concerns relative to the local problems of breast implants and the
> complications thereto are being addressed I think very clearly with
> the stipulations that are placed in the conditions upon which the
> approval is being recommended. So, I think we will address these
> issues and have made it clear, and I think the sponsor has promised in
> good faith to do that and has demonstrated with their saline implants
> that they will follow through on those conditions.
>
> I think, clearly, the efficacy is there for patients. As a cancer
> surgeon, I want for my patients to have all the options available for
> them to consider for reconstruction. If they come for a choice for
> silicone implants, I expect them to be well informed about what they
> can expect over time. Similarly, I expect those patients who have
> saline implants to be well informed. Thank you.
>
> DR. WHALEN: Dr. Chang?
>
> DR. CHANG: Again I reiterate what other the panel members said about
> the difficulty of making a decision on the vote. I did not make up my
> mind until this afternoon, post lunch, with the presentation and some
> answers and suggestions for answering some of the remaining questions
> that we have about long-term follow-up. The issue is availability and
> also choice, as well as education.
>
> So, this is moving forward. I have been impressed with the integrity
> of the sponsor in following through with previous requests for
> additional information regarding saline implants and the quality of
> the data, as well as the quality of the data in this study, short term
> as it is, two years when we all are searching for further answers and
> definitions. So, that is why I voted as I did.
>
> DR. WHALEN: Dr. Choti?
>
> DR. CHOTI: I do not think that we have sufficient information to
> provide reasonable assurance of long-term safety. I think that we did
> see short-term safety. We have some evidence in the literature but I
> think, particularly in the subset of patients who develop ruptures
> which will be a significant portion of these women, I cannot feel
> confident that we have reasonable assurance of long-term safety, both
> local and systemic.
>
> I think the post-approval stipulations are really a manifestation of
> this panel\'s concern about the lack of long-term safety. I think part
> of this laundry list of conditions and attempted conditions emphasizes
> the fact that many of us still have a lot of concerns regarding
> long-term safety. Even the recommendation that all implants that
> rupture should be removed implies that we have concerns that ruptured
> implants cause long-term effects; that it is not inert and these all
> go to rupture at some point.
>
> I think the consent process is also difficult. When we are not even
> clear about what the risks are, it is very difficult, indeed, to
> provide real, true informed consent. So, those are my reasons for
> voting non-approval.
>
> DR. WHALEN: Dr. Blumenstein?
>
> DR. BLUMENSTEIN: I found this much less than a perfect device, as
> evidenced by the ruptures, and I was particularly concerned about the
> silent ruptures and the possible under-ascertainment of even those. I
> am also concerned about the changes in symptoms related to the CTDs.
>
> I also was unconvinced about the use of literature because analyzing
> for diagnoses is not the same thing as analyzing for changes in
> symptoms. So, I found it very difficult to feel comfortable that there
> aren\'t some kind of long-term effects.
>
> DR. WHALEN: Dr. Conant?
>
> DR. CONANT: I also found this extremely difficult. I find that they
> have certainly proven the effectiveness of the implants and there
> certainly is a severe public health need for a better implant than we
> have right now. But my concern echoes Dr. Choti\'s in that I really
> don\'t feel that we have long-term data and I was frustrated by the
> comparison, for example, to the rupture rate of saline implants and
> this is not the same at all. There is silent rupture where we don\'t
> know the impact of the silicone, and I just needed more long-term data
> so I voted not approvable.
>
> DR. WHALEN: Dr. Lieberman?
>
> DR. LIEBERMAN: As most members of the panel, I found this an
> extraordinarily difficult decision and I think all of us were thinking
> long and hard about balancing choice and benefits of the gel implants
> with the risks. In the end, I think that we did not have enough
> long-term data about rupture or about systemic systems to assure
> safety. So, I couldn\'t approve the motion.
>
> DR. WHALEN: Dr. Manno?
>
> DR. MANNO: I didn\'t have any problem with the obvious effectiveness
> of the idea of the implant that is being presented. I understood all
> of that. However, I thought that we did not have sufficient safety
> information as to where the silicone really is going on a long-term
> basis. It is lack of that long-term data that gave me a problem.
>
> DR. WHALEN: Dr. Olding?
>
> DR. OLDING: We were charged to both consider the safety and efficacy
> of these implants and, like the rest of the panel members, I felt that
> the effectiveness of the implants is certainly well presented and I
> really have no problem with that whatsoever.
>
> I did have some problems with the rupture rate with the safety per se,
> as I think everyone did, and that is part of the reason that we are
> now going to look into those explants.
>
> The sponsor\'s summary statement, as well as the post-approval
> conditions, however, have at least put at rest for me the majority of
> the safety issues, and knowing that we are going to continue to look
> closely at these women and their problems and long-term follow-up
> makes me much more comfortable, and I am comfortable with our
> decision.
>
> DR. WHALEN: Any concluding remarks, Dr. Witten?
>
> DR. WITTEN: No, I would just like to thank the public who participated
> over the last two days, the panel who really spent an enormous amount
> of time and thought over what was obviously a difficult discussion for
> them and, most particularly, I would like to recognize the FDA review
> staff and David Krause for all the hard work that went into preparing
> for this meeting.
>
> DR. WHALEN: Thank you. Although not voting, I am asked to see if the
> consumer rep and the industry rep would like to make any closing
> comments, Ms. Brown and Ms. Gilbert?
>
> MS. BROWN: Actually, I have no comments.
>
> DR. WHALEN: Ms. Gilbert?
>
> MS. GILBERT: I just have a comment on the long-term follow-up and the
> safety issues. You know, there are going to be a lot more women
> getting implants and there are going to be a lot more concerns raised
> and I really hope that Inamed stands by their product and that the
> warranty is extended to every woman who has a problem with these
> issues. It was a very tough decision. I want to thank the panel for my
> opportunity to be a participant here.
>
> DR. WHALEN: I would also like to thank my fellow panel members, as
> well as the audience and the FDA, and declare that this meeting is
> adjourned, and ask everybody to please take conversations outside the
> room because they really need to turn this room over immediately.
> Thank you.
>
> \[Whereupon, at 4:50 p.m., the proceedings were adjourned.\]
>
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