Date: Fri, 16 Jun 2000 14:05:24 +1200

-----Original Message-----

From: USSW

Date: Friday, 24 July 1998 07:59

Subject: Summary of IOM Scientific Workshop

NATIONAL ACADEMY OF SCIENCES

INSTITUTE OF MEDICINE

COMMITTEE ON THE SAFETY OF SILICONE BREAST IMPLANTS

SCIENTIFIC WORKSHOP - JULY 22, 1988

NOTES ON THE PROCEEDINGS

DONALD J. SCHAEZLER, PH.D., P.E., CIH

EPIDEMIOLOGY AND OBSERVATIONAL STUDIES

The first panel were reports by Louise Brinton of the National Cancer Institute and Lori Brown of FDA.

The NCI is well into a large epi study of women with augmentation mammoplasty. The NCI study is designed to address weaknesses of some prior epi studies like Mayo, Harvard, Hennekens. These prior studies relied on records primarily, with some questionnaires administered by mail. There was no follow up, detailed evaluation of symptoms, or physician visit. Success rate was low.

The new study has 13,000 women who had BI augmentation (bilateral, non-cancer) and 4000 women who had other plastic surgery are in the control group. All the women are from the SE or Wash DC areas to avoid overlap with other studies and to avoid Texas, which has a very large amount of litigation ongoing. After identifying a large population of prospective women, a great deal of effort was spent locating them and then administering detailed questionnaires by phone. 18 plastic surgeons are doing individual follow up with patients. The success rate is over 70%.

The analysis of results with respect to diseases (cancer, connective tissue disease, etc.) and symptoms will be analyzed for external Standardized Incidence Rates (SIR) and for internal Relative Risk (RR). The first analysis will compare incidence of diseases to the recognized incidence in the general population. The second will compare the incidence of diseases and symptoms to those in the control population. They will also try to define the constellation of symptoms unique to this group of women. The studies will identify Confounding Factors, bias, role of implant type, etc. and will have "stratified" analysis of results viz-a-viz these factors.

Evaluation of cancer effects should be available fall 98. Connective tissue disease effects should be early 99.

SUMMARY: This is a well-designed, extensive study; it should remove many of the problems of older studies. The investigator seems very sensitive to women's issues. 

Brown's FDA study is using a subset of the NCI study for a special study on local complications, i.e. infections, pain, stromas, contracture, expulsion, igration, rupture, bleed. Brown recognizes that previous reports show migration, chronic infection, ulceration, pain, numbness, granulomas, etc.

This investigator is also sensitive to women's issues. She pointed out that FDA received 94,000 reports of problems with silicone implants and that 23% - 63% of implants have been reported to rupture.

FDA has picked 1247 women from Brintons Alabama group. The study will build on Brinton's survey and checkup results by doing MRIs and by reviewing surgery records. They will then analyze results for the local complications mentioned above. Results will be in early 99.

SUMMARY: This study is also well-designed and will use new MRI analyses to estimate rupture rates, making this a first study to have goo rupture rates on a non-problem-referred group of women.

The second panel had Dr. Duhamel from McGhan, who reported on McGhan's internal studies to be used for FDA regulatory requirements.

Studies segregated women into Augmentation, Reconstruction, and Revision categories. Separate studies have been or will be completed for silicone and saline, and will address Core and LST purposes (FDA definitions). The studies are preliminary at this time but will eventually extend for 10 years. The IDE has been submitted and FDA has given preliminary approval to begin PMA study. PMA expected in 2001, after 2 years of results. Preliminary results form a pre-Core study indicate:

1% infection rate

14% contracture at 5 yrs

4% rupture at 5 yrs (mostly the saline part of double lumens)

9% explanation at 5 yrs (38% for a pretty small population of Recon patients, which they dismissed as non-representative because of small numbers) high degree of satisfaction The presenter added an anecdotal observation that every polyurethane explant he has seen show evidence of biodegradation. [Note: Manufacturers may not be too happy with this comment.]

[Note: The 4% rupture at 5 years is actually consistent with results of Feng, Middleton (afternoon sessions) who went on to show very high rupture rates after 12 + years.]

SUMMARY: Not too remarkable; a lot is planned compared to what has actually been accomplished to date. The time period even for the pre-Core study is too short to make conclusions relative to other reports and studies. 

Dr. Leroy Young of U. Missouri gave an interesting report on evaluation of silicone and silica in capsule material. He spent considerable time trashing Shanklin's microscopic work and then explaining the intricacies of light microscope (including polarized light) strengths and weaknesses and features of birefringence, crossed polarization brightness, refractive index, etc. Apparently a number of materials appear as bright objects under light microscopy, including calcium carbonate, talc, starch, and silicone. Crystalline silica, in fact, will not show as well in a very thin section.

Young went onto describe a more sophisticated infrared procedure, Laser Raman Microprobe Spectroscopy (LRM), and pushed for its acceptance as the standard for pathological analysis of breast tissue.

He also spoke about a newer Solid State NMR procedure which is more suitable than the procedures used by Garrido several years ago, when he postulated the appearance of small amounts of crystalline silica from silicone degradation (a phenomenon not accepted by most). Young conducted two small studies with only a few subjects in which he sent slides of capsule material to Garrido for the newer NMR and to others for LRM. The studies identified silicone but no silica in the samples, by both analyses.

COMMENT: Small but good quality studies; need to hear Garrido's opinion of the relevance to his prior work. For one thing, his first study may have looked at other tissues than capsules. Young's comments on light microscopy are correct, I believe. His comments on NMR need confirmation by an expert, which he obviously is not.