Women's Implant Support Newsletter ~ January 1, 2000

Date: Sat, 1 Jan 2000 15:44:00 -0800

The first issue of the Women's Implant Support Newsletter of this Millennium! Letter: Core Study for Silicone Breast Implants This guidance was written prior to the February 27, 1997 implementation of FDA's Good Guidance Practices, GGP's. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP's.

Letter: Core Study for Silicone Breast Implants

January 11, 1996

To Whom It May Concern:

The Food and Drug Administration (FDA) is aware that your company may be interested in the opportunity to manufacture, distribute and/or market silicone gel-filled breast implants. The purpose of this letter is to inform you of the clinical data needed to submit a Premarket Approval Application (PMA).

The FDA requests that each company conduct a prospective "Core" clinical study (preceded by a small Pilot study) to assess the safety and effectiveness of their silicone breast implants. In an effort to facilitate your possible submission and FDA review, we have developed preliminary guidance for the design of the Core study protocol.

The Agency also expects applicants to provide retrospective data on the frequency and consequences of implant ruptures. This may be obtained through study of previously marketed implants, or by relating available data to the proposed product through appropriate in vito testing. Guidance for the design of this retrospective rupture study will be outlined in a subsequent letter.

FDA suggests that a Pilot study be conducted before the Core study protocol is finalized. We suggest it include at least 30 augmentation patients and 30 reconstruction patients. Advantages of performing such a Pilot study include: 1) an opportunity to validate specific study design/documentation details; 2) the estimation of short-term adverse event rate for your product to determine the specific sample size needed for the Core study; and 3) an opportunity to gain initial human experience with the final product. We encourage you to meet with FDA to discuss details of the pilot study design for your product.

The Agency anticipates the Core study will include:

Sufficient numbers of women to determine the rupture rate with reasonable precision, we suggest 500 women to be followed to the end of the study. Estimating a 40% drop out rate, we recommend recruitment of at least 850 subjects.

This will provide precision of +/- 4% at a rupture rate of 50% and +/- 1.9% at a rupture rate of 5%.

Separate tracking and evaluation of reconstruction patients (300-350) and augmentation patients (500-550) is recommended.

The Core study should include 18 month experience with 650-700 patients (including at least 25% reconstruction patients) prior to submission of the PMA, and two year experience prior to PMA approval. There should be at least 10 years of follow-up including both premarket and postmarket evaluations. The initial consent form should reflect the total length of the study follow-up.

Determination of infection, contracture, failure rates and other safety evaluations should occur periodically. We suggest collecting data at three months, six months, one year, 18 months and two years. After the two year follow-up, annual patient evaluations are recommended.

To support approval, we feel the Core study should determine the incidence, timing and clinical consequences of silent rupture. This could be accomplished through sequential screening of a subgroup of the study population using MRI or other imaging techniques.

Quality of Life assessments in a subset of the study population might be beneficial and should be considered.

A Connective Tissue Disease (CTD) screening questionnaire should be conducted after patient enrollment, but before implantation, and again during follow-up visits. Symptoms should be followed over time, with referral to a rheumatologist if appropriate, for diagnosis and treatment. This screening questionnaire will be used to document patients' pre-implantation CTD status and identify any patients who develop CTDs.

Determination of gel bleed potential may be made by pre-clinical assessment.

This represents our current thinking on the study design for silicone gel-filled breast implants. We welcome feedback or alternative suggestions. We recognize that testing may be tailored to the specific product, and encourage you to meet with FDA before finalizing a study protocol.

We are currently developing a more complete guidance document to aid manufacturers with the testing and submission of silicone, saline, and alternative breast implants. We hope to have this guidance available later this year.

I hope the information above will help you design and submit an effective protocol for assessment of silicone gel-filled breast implants. If you have any questions, please call Ms. Beth Nairn, Breast Implant Coordinator at (301) 594-3090.

Sincerely yours,

/S/

Kimber C. Richter, M.D.

Acting Director

Division of General and

Restorative Devices

Office of Device

Evaluation

Center for Devices and

Radiological Health

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Documenting the Neurological Impact of Exposure to Silicone Mark B. Hutton and Liz Dudley R.N.

Of this sample neuropsychologists assessed that 60.9% demonstrated neurocognitive deficits consistent, at least in part, with chronic solvent exposure, with only 3 of 69 (4.3%) strongly suspected of malingering. Several findings suggested that the right cerebral hemisphere was slightly compromised more than the left. Shoaib, et al (1994) reported that "Memory Problems" were one of the "Commonest Symptoms" and was reported at a frequency of 81%.5 Brown (1993) et al presented data on 15 breast implanted women with complaints of cognitive dysfunction in whom brain SPECT scans and psychological testing were performed. They found statistically significant decreases in the bilateral temporal regions of SPECT scans along with impaired memory.6 The pattern of cognitive dysfunction presented by symptomatic women with breast implants is similar to other connective tissue diseases, as documented in the article by Carbolte (1994):7

We have found that more than 25% of SLE patients,

irrespective of NP status, showed significant problems in areas such as verbal and non-verbal memory, visuographic skills and verbal productivity (word finding). As even larger proportion of patients with current or previous NP symptoms showed problems in psychomotor speed and cognitive flexibility, both sensitive indices of CNS compromise. A working hypothesis to explain the mechanism of cognitive dysfunction in SS (Sjogren's Syndrome) has been lymphocytic infiltration in the CNS; this has been supported by abnormal findings in the cerebral spinal fluid, reminiscent of multiple sclerosis (oligoclonal bands, increased IgG index) and the existence of behavioral abnormalities in MRL-1pr mice with disease which may represent a form of SS secondary to SLE. Pg. 1368.

The eosinophilia-myalgia syndrome (EMS) is a newly recognized multi-system rheumatic disorder described in 1989, occurring in association with the ingestion of L-tryptophan containing products in one report approximately one-half of the affected individuals reported difficulties in short-term memory and logical thought, while in the second, significant cognitive complaints reported initially and up to 25% of the patients, found to persist in most of them, now appear to anew in another 16%, despite considerable improvement in other symptoms. Pg. 1370. Marotta, Batich and Hardt (1996) documented the migration of silicone gel from ruptured breast implants into the brains of rabbits.8 Garrido, et al reported elevations in brain metabolites of implanted women versus controls.9 Vestibular and sensory losses have also been reported by Dr. R.J. Grimm10 who noted abnormal neurological exams in 43 out of 45 silicone implanted women. The neurological abnormalities consisted of a mild, distal sensory neuropathy in the hands and disequilibrium due to vestibular end organ deficits (laboratory confirmed in 32). Of interest, and consistent with other clinicians, was the fact that all had signs and symptoms of "ACTD" in addition to the neurological abnormalities.

Dr. F. O. Black has also reported on the vestibular and auditory function abnormalities in silicone implanted women.11 Auditory and vestibular function tests were obtained from 19 women with ruptured SBI and were compared to matched, asymptomatic SBI control group and with a published, age matched normal database. His results were as follows:

Sixty-seven percent of SBI subjects (SBIs) had abnormal positional nystagmus (32% of normals), 6% had abnormal Hallpike tests (2% of normals), and dynamic posturography sensory organization tests were abnormal in 100% (17% of normals). Vestibulo-ocular reflex function was comparable to that of normals. Sensorineural hearing loss was documented in 39% of SBIS (24% of normals). Based upon these findings, immune response to silicone compounds appears to be associated with pathologic changes in vestibular and auditory function. Dr. Sander Greenland, an eminent medical epidemiologist who gave a presentation to the MDL 926 Science panel in July, has also examined the association between silicone prostheses (non breast implants) and connective tissue disorders and neurologic diseases in a recent case control study utilizing an insurance claims database.12 The results were as follows:

All analyses exhibited positive associations between implants (both silicone and metal) and neurologic conditions, especially idiopathic progressive neuropathy and Meniere syndrome, as well as the expected associations with arthritic conditions....In conclusion, further studies of prosthetic implants and neurologic diseases appear warranted. Thus the "myth" of silicone-related neuropathy is dispelled by a review of the literature and clinician's reports. Some patients with silicone prostheses who have systemic signs and symptoms develop neurological abnormalities consisting primarily of peripheral neuropathies, cognitive dysfunction and vestibular/inner ear disorders. Some patients also develop a multiple sclerosis-like syndrome, which is different from the idiopathic form in that they also have coexisting signs and symptoms of "ACTD" (rheumatological /chronic inflammation systemic symptoms).

ENDNOTES

1. Whaley, K., et al, Sjogren's Syndrome, Textbook of Rheumatology, Eds. Kelley, Harris, et al., 3rd ed., pp 999-1019 (1989).

2. Woods, V., et al, Pathogenesis of Systemic Lupus Erythematosus, Textbook of Rheumatology, Eds. Kelley, Harris et al., 3rd Ed., pp 1077-1100 (1989).

3. Davis, John; Campagana, Joan, et al, UCSF of San Francisco, California; Clinical Characteristics of 343 patients with Breast Implants, Abstract presented at the American College of Rheumatology annual meeting, October 1985.

4. Prange, R., Boksenbaum, S.J., Erblich, J., Silverman, S.L., Cedar Sinai Medical Center and UCLA School of Medicine; Preliminary Neuropsychological Findings on a Subgroup of Silicone Breast Implanted Women, presented at the National Institutes of Health, 1995.

5. Shoaib, B.O.; Patten, B.; Calkins, D.; Adjuvant Breast Disease: An Evaluation of 100 Symptomatic Women with Breast Implants or Silicone Fluid Injections, Keio Journal of Medicine, Vol. 43, No. 2, pp 81, Table 1,(1994)

6. Brown, Stacy; Patten, B., et al; Silicone Breast Implants: Association with Abnormal SPECT Scans and Memory Defects, 15th World Congress of Neurology, Abstract Journal (09/93)

7. Carbolte, R., Denburg, S., et al; Cognitive Deficit Associated with Rheumatic Diseases: Neuropsychological Perspectives, Arthritis and Rheumatism, Vol. 38: 1363-1364 (1994)

8. Marotta, J.; LaTorre, G.; Batich, C.; Hardt, N.S.; Yu, L.; Measurement of Silicon in Tissue Sites both Adjacent to and Distant From Ruptured and Intact Silicone Breast Implants, Fifth World Biomaterials Congress, Abstract, May 29-June 2, 1996, Toronto, Canada.

9. Garrido, H.; MRS Brain Study of Women with Breast Implants, 5^th Scientific Meeting Abstract, Vancouver, Canada, April 12-18, 1997.

10. Grimm, R.J.; Vestibular and Sensory Losses in 46 Women with Silicone Breast Prosthesis: Preliminary Studies (1994), Poster presentation, 5^th Legacy Sci. Fair, (1994)

11. Black, F.O.; Vestibular and Auditory Function Abnormalities In Silicone Breast Implant Patients, Presented at the American Otological Society Combined Otolaryngological Spring Meetings, May 6-10, 1997,Scottsdale Arizona.

12. Greenland, Sander; Finkle, W.D.; A Case-Control Study of Prosthetic Implants and Selected Chronic Diseases, Ann. Epidemiol., Vol. 6: 530-540 (1996)

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CHECK THIS ONE OUT ~ VERY INTERESTING SITE

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When Pacemakers Break

Thank you Toni for sending our way!

Difficult to Sue Manufacturers of Medical Products

By Deborah Amos

ABCNEWS.com

W A S H I N G T O N, Dec. 27 - Lora Lohr had a dangerously rapid heart beat. A pacemaker solved the problem, but then, without warning, her pacemaker stopped.

"I completely blacked out, and then I'd come to," Lohr says. "And then I'd black out again." The lead wire sending the electronic impulses from her pacemaker to her heart was defective. "My heart actually stopped beating completely," Lohr says. After a series of surgeries, Lohr's legal battles began. She first contacted Medtronic, the pacemaker lead manufacturer to pay the medical bills.

"We got a letter back basically saying that if you want this, we'll see you in court," Lohr says.

"To all intents and purposes," says her attorney, Dan Shaugnessy, "this was a very typical products liability suit against a manufacturer for a defective product that had caused harm."

Lawsuit-Immune Manufacturers

But the judge denied her a day in court. He ruled that because the Food and Drug Administration had approved her pacemaker lead, the manufacturer could not be sued, even if the lead caused harm.

"I was shocked," Lohr says. "I mean, I feel like you can sue for bad brakes on a car if somebody gets hurt, but you can't for a medical device that's keeping me alive? That, to me, is unheard of."

Lohr decided to fight the ruling. She appealed all the way to the Supreme Court, winning her case in 1996, but the ruling was specific only to her case. This left the door open for medical device manufacturers to deny other injured people the right to sue.

Manufacturers with products from pesticides that harm people to air bags in cars have been immune from suits because the product as approved for use by a federal agency.

"Congress, when it passed consumer protective statutes in the first place were trying to protect consumers," says Brian Wolfman, a lawyer with Ralph Nader's Public Citizen. "It's absolutely essential that consumers get compensated."

For Lohr, victory came six long years after a defective pacemaker lead almost killed her, but others may not be so committed to fight for their right to sue.

New and Improved Pacemaker

For people having trouble with their pacemakers, there is some good news. It has always been very difficult to replace a pacemaker's "leads," the wires that connect the device to the heart. There is now a new way to handle the problem that could help hundreds of thousands of patients.

At The Cleveland Clinic, Tom Olsen is readied for a remarkable operation. A wire that sends electrical impulses from his pacemaker to his heart is defective. The problem is that the defective lead is now embedded in scar tissue.

Dr. Bruce Wilkoff is a pioneer in the latest technology to remove damaged pacemaker leads.

"We'll be using some laser technology that allows the scar tissue to melt away," Wilkoff says, "rather than have to peel or tear away the scar tissue."

The technology dramatically reduces the risk to patients.

Wilkoff makes a small incision so he can examine the lead. He remarks that the lead is shorted out. It will have to be replaced. "We're going to take this [laser] sheath," Wilkoff says, "and advance it over the lead.

"The red laser light hits the tissue," Wilkoff says. "It will melt through the tissue, and just millimeter by millimeter, will pass over the lead all the way down to the heart. And then when it gets all the way down to the heart, there will be no more scar tissue holding the lead in so the lead will slide back out."

It is now easy to slip in a new one.

This is a vast improvement over the old technique to remove a lead wire, which involved tugging it out and separating it from the tissue. Now the procedure takes fewer than 10 minutes.

"I feel a little dopey," Olsen says in the recovery room. "I'm aware that there's been some activity there, but it doesn't hurt." It was activity he hopes will get him back to a normal life in just a matter of days.

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ABSTRACT

Finnish women's experiences of silicone breast implants

Researcher Sirpa-Liisa Hovi Research group Elina Hemminki, Mirja Määttä, Ilmo Keskimäki; Lyly Teppo, Eero Pukkala, Cancer Registry; Sirpa Asko-Seljavaara, Helsinki University Central Hospital Financing STAKES, Ministry of Education, Cancer Registry, National Agency of Medicines

Timetable: 1994-2000

The purpose of this research is to find out the experiences Finnish women have had with silicone breast implants. The main study is finished, but a substudy investigating women's motivations for having cosmetic breast implant surgery is ongoing.

A new plan has been made to find out if there is any connection between silicone breast implants and women's and her offspring' subsequent health. A cohort of all the breast implantations in Finland will be collected and follow-up data will be collected from registers.

Keywords: breast, implant, silicone

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OTHER SILICONE RELATED RESOURCES ARE AVAILABLE THROUGH THE SILICONE WEBRING

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WHERE THERE'S SMOKE THERE'S FIRE ~ On The Net

The following websites have the "Where There's Smoke There's Fire" documents:

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FOR AOL MEMBERS OR OTHERS, WORKING WITH ON-LINE SERVICES NOT ASILY ACCOMMODATING THE FORMAT OF THESE NEWSLETTERS, YOU MAY ACCESS THEM FROM THE CANADIAN CONNECTION WEBSITE AT THE HYPERLINK BELOW. TONY & MICHELINE LAMBERT HAVE GRACIOUSLY ARCHIVED THEM FOR US.

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INSPIRATIONAL

IF I HAD MY LIFE TO LIVE OVER - by Erma Bombeck

I would have gone to bed when I was sick instead of pretending the earth would go into a holding pattern if I weren't there for the day.

I would have burned the pink candle sculpted like a rose before it melted in storage.

I would have talked less and listened more.

I would have invited friends over to dinner even if the carpet was stained, or the sofa faded.

I would have eaten the popcorn in the 'good' living room and worried much less about the dirt when someone wanted to light a fire in the fireplace.

I would have taken the time to listen to my grandfather ramble about his youth.

I would have shared more of the responsibility carried by my husband.

I would never have insisted the car windows be rolled up on a summer day because my hair had just been teased and sprayed.

I would have sat on the lawn with my children and not worried about grass stains.

I would have cried and laughed less while watching television - and more while watching life.

I would never have bought anything just because it was practical, ouldn't show soil, or was guaranteed to last a lifetime.

Instead of wishing away nine months of pregnancy, I'd have cherished every moment and realized that the wonderment growing inside me was the only chance in life to assist God in a miracle.

When my kids kissed me impetuously, I would never have said, "Later. Now go get washed up for dinner."

There would have been more "I love you's".. more "I'm sorry's" but mostly, given another shot at life, I would seize every minute look at it and really see it .. live it...and never give it back.

Stop sweating the small stuff. Don't worry about who doesn't like you, who has more, or who's doing what.

Instead, let's cherish the relationships we have with those who Do love us. Let's think about what God HAS blessed us with.

And what we are doing each day to promote ourselves mentally, physically, emotionally, as well as spiritually.

Life is too short to let it pass you by.

We only have one shot at this and then it's gone.

I hope you all have a blessed day.

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In memory of Erma Bombeck who lost her fight with cancer. Here is an angel sent to watch over you...