FDA Advisory Committee On Saline Filled Breast Implants - Hearings Of March 1-3, 2000

SALINE-FILLED BREAST IMPLANTS - A CONTINUING AREA OF CONCERN

P. Blais, INNOVAL, 496 Westminster Avenue, Ottawa, Ontario K2A 2V1 Canada

Innoval has conducted studies on saline inflatable breast prostheses for nearly ten years, continuing work initiated by Canadian researchers in the early-eighties. Problems with these devices were discovered early and motivated proposals to amend the Canadian Medical Devices Regulations. The work was the object of publications which have not been widely disseminated.

Control of commerce in breast implants has been difficult and costly. Early efforts are credited to the FDA in the mid-seventies culminating in recommendations for better mechanisms of approval and upgraded post-market follow-up as early as 1978. Saline inflatable breast implants were areas of concern then and remain central today. The need for mandatory filing of pre-market approval applications (PMA) and updated Notices of Completion of a Product Development Protocol (PDP) for this class of product is clearly demonstrated and urgent in the light of continuing performance shortfalls and alarming patterns of adverse reaction.

Field reports on failures and adverse reactions from saline inflatable prostheses are not comprehensive. There is a history of under-reporting which has worsened significantly since 1990. Field report data do not realistically assess the extent or severity of complications. Promotion of the technology is at an all time high and shows no sign of abating.

Published information on the realities of the technology is sparse and incomplete. There is suppression of information regarding untoward events and service failure of the items. Any committee engaged in review of safety and efficacy of saline inflatable prostheses will not have access to all data. Publicly mandated committees will not be able to derive informed conclusions and policies without access to implant retrieval programs and independent laboratory studies. Epidemiology studies are distorted by a background of natural morbidity involving the disease prone female breast. The situation is significantly worsened by heavy industry sponsorship of university research, lobbying and conflicts of interest with many key researchers and clinicians presented as independent intervenants.

Amongst all commercially made saline inflatable prostheses, there is not one currently in use which could be construed as being substantially equivalent to a product made before May 28, 1976, the watershed date for U.S.F.D.A. medical device regulations. The products have undergone drastic changes at regular intervals as product design fashions, production machinery and raw material vendors changed. This view is confirmed in manufacturers' advertisements and promotional material to physicians and the public where the products are claimed to be novel and significantly improved from what was made previously. To date, there has been no perceptible change in the lackluster performance of the products.

Breast implants are flexible plastic shells fitted with filling ports and filled with water-based fluids. They have been described in publications and patents for more than forty years. Commercially made items appeared during the sixties. Since then, more than eighteen manufacturers have made such products. About seven remain active. Current devices have not significantly evolved since the seventies and problems of product quality and durability remain. Adverse reactions continue unabated. Promotion and de-emphasis of risks are stronger than ever with new generations of users swelling an existing pool of injured users.

Saline inflatable breast implants are widely promoted for cosmetic augmentation. In the early seventies, they represented less than 10% of the total breast prosthesis market. Many products were withdrawn in the eighties following pandemic failures and lawsuits. By 1984, the salines had nearly vanished. In 1992, the year when the FDA imposed a Moratorium on gel-filled breast implants, the number of new saline users in the U.S. increased by about 30,000 women. In 1997, new implantations were about 122,000. In 1998, about 132,000 women received saline implants for the first time. Worldwide, an increase of about 210,000 new users appeared in 1999, mostly in North America. The number of new implant users is growing at a compound rate of about 15% per year with Mexico, Latin America, Eastern Europe and the Far East reporting the most rapid rise.

Less than 5% of new users are breast cancer patients, nearly unchanged for the last two decades. The dominant part of the user population consists of cosmetic surgery clients seeking to augment breast size. About 9-10% of current users are replacement patients who had earlier implants that failed and left them disfigured. This number is rising, reflecting maturation, failures and 'wear out' of poorly made saline inflatable devices inserted in the mid-nineties.

The primary saline implant manufacturers are currently McGhan Medical Corporation (Inamed), Silimed S.A., Mentor H/S Corporation, NovaMed Inc., Poly Implant Protheses (PIP) S.A. and Progress Mankind Technology (PMT) GmbH. The U.S. is dominated by Mentor and McGhan who share the market. Secondary distributors include Hutchinson International and Sierra Medical Technologies Inc. There is an influx of unsanctioned foreign products imported and inserted in U.S. users at offshore clinics which advertise within the continental U.S.

All salines use basically the same concepts, components and materials. Dominant suppliers of silicone intermediates include McGhan Nusil Corporation (Inamed), Applied Silicone Corporation (Rhodia) and Dow Corning Corporation. Stock parts for some valved devices are supplied as commodities from U.S.-based corporations.

Lack of durability, fluid leakage, frequent replacements, adverse reactions and litigation have surrounded this technology from the outset. Late-nineties saline inflatable implants still have short service lives. They reflect antiquated designs and low quality. Many show serious fabrication defects. Implants that do not deflate noticeably at first become progressively less satisfactory with the onset of pain and deformity over time. Users inevitably must undergo more surgery with worsening cosmetic results and increased discomfort. In spite of rising problems of safety and durability, severe injury potential and large public health care costs, usage continues to rise, driven by misleading promotion.

Risks from these products are unacceptable in the light of the benefits they provide by any standard of measurement. If there was forthright disclosure of the side effects, few women would be willing to assume the risks of saline inflatable technology. Cultural and fashion pressures operating in an environment where the public is compelled by media to believe in medical miracles presents a regulatory dilemma with respect to the breast implant trades. Only agencies with long established credibility with the public, such as the FDA, are in a position to offset what has become outrageous promotion of the medically absurd.

Saline breast implants gradually lose the saline filling charge because of filling port failure, shell perforation, creasing and material deterioration. They are ephemeral devices. As the implants age, their shells become porous and valves incompetent. This not only causes outflow of the filling fluid but allows blood products and occasional micro-organisms to enter the filling charge. This process sets in insidiously well before deflation is noticed. Growth of bacteria, fungi and algae then takes place stimulated by decaying blood and proteins from the host. The growing organisms often reach florid quantities several year after insertion in the user. The shells ultimately fail releasing grossly contaminated fluid into the host.

According to prevailing views on infection control, micro-organisms in implants that leak fluid are perceived as incubation reservoirs and sources of infective fluids. Low grade infections around implants and their debilitating sequelae are common. They are regarded in some quarters as "normal" and users are subjected to chronic treatment with antibiotics and anti inflammatories. Because of fluid leakage, the organisms spread to the space around the implants and promote symptoms. The users re-enter the health care system with common complaints. Antibiotics may be prescribed to resolve the problems but symptoms recur with time. Diagnosis is difficult as symptoms appear unrelated to the faulty implants. In more severe cases, the space around the implant and the upper chest becomes filled with infectious fluid and the device may extrude through the skin. Such situations are frequently life threatening.

Incidents of grossly contaminated saline implants were reported in the seventies and eighties in widely read periodicals. On balance of probability, more articles were written in the nineties but were not published because editors feared loss of advertizing revenues or litigation by promoters. Litigation threats have been used by manufacturers to suppress information about defective and hazardous products. Litigation is an effective tool for publication control because authors and publishers do not have the resources, energy and motivation to defend these suits. Most prefer to avoid the issue by deferring publications or rejecting unfavorable manuscripts.

Health care technology assessment agencies and professional associations responsible for safety and efficacy of health care products remain non-committal and frequently take promotional stances. Some disclaim deflation and dismiss serious health risks posed by saline breast implants as imaginary, infrequent or benign. Development of realistic guidelines and public disclosure of saline implant risks have not taken place. Mounting public health care costs and third party insurer disbursements associated with use of the devices remain unaddressed.

Promotion of plastic surgery services increased dramatically in the nineties reflecting a growing number of surgeons offering 'lifestyle' medical services. The task has been facilitated by saturation of news media with reports of spectacular research advances in the biosciences. This environment has left the public expectating miracles; it has fostered a generation of individuals unprepared to accept that breast implant technology is antiquated and ill-conceived.

The key role of promotion in the spread of non-essential medical technologies devoid of scientific or clinical merit is a demonstrated fact. As before, a fashion conscious clientele with disposable income is targeted. Implantations are performed in ever greater numbers until new users crests after about 5-7 years. Morbidity and disenchantment rises as clients realize belatedly that claims were exaggerated and risks hidden. Implantations plummet, reaching a nadir after about 2-3 more years to be followed by a flood of adverse publicity. In the meantime, alternate cosmetic surgery procedures are promoted and re-do surgery of clients who received faulty implants provide a stop-gap income source for cosmetic surgery providers.

After a lull, a new generation largely unaware of past breast implant crises emerges and the cycle repeats.. Procedures using low cost implants which demand minimal surgical skills have always proven ideal in this context. This explains, in part, why breast implant crises take place at intervals of about 10-12 years. Following a comparatively quiescent period, breast augmentation, is once again popular, driven by aggressive advertising sometimes disguised as 'medical news'. As a result, implantation of new subjects has risen rapidly and, as expected, so have adverse reactions. Paradoxically, the implants have not improved.

Promotion of breast augmentation to new candidates is essential for success in the breast implant trades. An ever-growing base population is needed to provide momentum and cash flow. The process has features similar to pyramid schemes.

Other classes of patients such as individuals with resected tumors or deformed by implant misadventures are the least suited to the technology and most prone to adverse events. They may have the greatest need for implants and reconstruction but, in the eyes of promoters, they require far better implants, much more specialized surgical skill and long term follow-up. They rarely have a satisfactory outcome for more than a few years and are perceived by the implant trades as a challenging, accident prone patients class. Further, they do not constitutes a sufficiently large market to maintain profitability even when their ranks are swollen by a continuous stream of augmentation patients afflicted with implant problems.

As before, the implants are at the root of the problems. Old concepts, erratic production methods and spotty quality assurance practices prevail. Deep discounting, changing implant fashions, liquidation and other off-color trade practices remain. The once reviled saline-filled implants which failed in the past are again represented as innovations of great merit. The electronic media, magazines and newspapers are once more replete with promotional material thinly disguised as medical research and 'discoveries'. Yet, there is no significant research and development in breast augmentation technology. Such work has not been carried out since the sixties. Only promotion has become more sophisticated in a well orchestrated and generally successful campaign to override natural misgivings of a more weary and skeptical society.

Explanted saline inflatable prostheses were examined at Innoval as part of an implant performance investigation during the period 1990 to 1999. They included items with diaphragm valves, leaf valves and filling tubes. Many were ruptured. This part of the study c ncerned appraisal of valve reliability. Another part attempted to evaluate the amount and the quality of the residual filling medium. The valve reliability study was initially restricted to diaphragm valve systems because of the uniformity of this design across the industry. The filling medium evaluation could only be performed on devices which had retained shell and valve integrity. Basic medical records were available for all of the specimens comprised in the cohort.

Principal parameters were determined with the aid of simple micrometers, dial gauges and calibrated cylinders plug gauges) for measurement of shell and valve orifice. Valve quality was appraised using optical microscopes with illumination either from below or from a steep incident angle. The presence of contamination was ascertained initially with the eye unaided. Information on the morphology of the solids and micro-organisms was obtained by direct viewing through the shell using transillumination and a long working-distance microscope.

242 total number of saline implants available for study

74 with anterior diaphragm valves from 42 users with dwell times of 0.3 to

24 years

6 users reported significant pre-removal deflation

11 users claimed local or systemic complications prior to explantation

3 users were involved in litigation

12items predating 1976 made by Heyer Schulte or American Heyer Schulte

with the older style "Jenny" valve

62 items with the current miniature version of the diaphragm or apex valve

included:

- 22 by American Heyer Schulte

- 18 by 3M/McGhan, First American Corporation or Inamed

- 5 by Cox Uphoff or Cox Uphoff/Inamed

- 17 by the Mentor Corporation

The devices were examined for shell integrity, visible internal fluid contamination and security of valve closure. Results are shown below:

8items with frank ruptures, leak sites or iatrogenic cuts (unsuited for evaluation of residual content but still allowed reliable appraisal of the valve mechanism) 70items without rupture or perforation with protected fluid charge but showing grossly visible internal contamination in the form of flocculent suspended material of microbiological origin; more than half showed florid colonization and included:

- 12 with the early "Jenny" valves with securely held caps

- 57 with the miniature valve showing dislodged valve caps

- 1 with the miniature valve with the valve cap securely in place

The newer devices all had undersize cap diameters which spontaneously self-ejected when pushed-back in their orifice. Some exhibited large differences between the orifice diameter and the cap such that the cap was undersize with reference to the orifice and could not be retained.

The study demonstrated that diaphragm valve saline-filled breast prostheses nearly always became colonized with large quantities of micro-organisms. The more disturbing finding was that all of the recent implants with the small anterior diaphragm valves, including most of the types currently sold, had improperly fabricated valves including gross underdimensioning of the cap. The relative diameter of the valve cap to the valve orifice was mismatched and precluded secure closure indicating major problems at the production facilities.

Saline inflatable prostheses, including the ones presently in commerce, have similar anterior diaphragm valves which originate from the same vendor. The cap plugs are devoid of retention features such as ridges. They are slightly tapered and have rounded ends which further facilitate avulsion and slippage. Most of the caps examined to date are grossly undersize with respect to the valve aperture. For some items, there is tension on the cap support strap which facilitates spontaneous avulsion.

Some of the examined devices showed undersizing of the cap by as much as 0.005". These devices had no possibility of retaining the cap at the valve orifice. Tissue pannus and capsular material formed in the exposed parts of the valve system, frequently extending within the gap created by the undersized cap. Tissue from the capsule bound the cap strap to the capsule wall thus providing a fixation feature which ensured cap extraction during movement, even if closure was initially obtained. Such observations do not reflect random variations due to production vagaries. They suggest careless fabrication and erratic quality assurance. The problems are not limited to a single maker but affect the totality of products manufactured by the industry including foreign manufacturers who use the same stock parts. Yet, such valves have been in commerce for more than twenty years and there is no published report of the problem.

The most frequently discussed complication of saline inflatables is capsular contracture. The phenomenon is presented as benign. Some physicians consider contracture as 'normal' and unworthy of special mention in the context of adverse reaction reporting. This distorts the perceived risk of the product as contracture is as much a complication as it is a symptom of more serious underlying problems.

Saline inflatable implants incorporate filling valves which have been at the center of controversy in FDA classification panels and review committees since the late-seventies. Security of these valves and reliability of closure are key problems unresolved to this day. Whereas such a gap in the technology could be perceived as 'accidental' or the result of insufficient research and development, there is emerging evidence that valve leakage was intentionally sought so as to support tenuous claims of control of capsular contracture.

This issue appears in the literature and in patents.A non-secure filling valve allows unpredictable bidirectional fluid flow in a permanently implanted saline-filled device. This is a major safety concern. Egress of fluid leads to loss of volume and eventual deflation requiring replacement. Users are therefore compelled to undergo additional surgeries with major attendant risks. Ingress of body fluids within the implant causes accumulation of denatured proteins and adventitious micro-organisms within the filling charge. The unreliable valve subsequently discharges the contaminated fluid exposing users to these substances. The leakage of fluids containing denatured autologous proteins and viable micro-organisms which coexist in the mixture has predictable systemic consequences.

Long term saline inflatable implant use is associated with mineralization of the surrounding tissue. The problem affects at least 30% of users within ten years, assuming the device remains in situ that long. The mineralization frequently takes the form of sharp, abrasive structures which mechanically excoriate the shell causing it to leak grossly. In the late part, calcification phenomena affect the elastomeric material which is penetrated, swollen and rendered porous by the process. This has been noted in saline inflatable prostheses for more than twenty years. The mechanism is related to base-initiated hydrolysis of the silicone elastomer at an elevated intracapsular pH which prevails in long term users with calcific deposits.

Mineralization or calcification of tissue around such devices is a fundamental and unavoidable process caused by a combination of trauma from continuous movement of the prosthesis against the surrounding tissue. It is exacerbated by chronic denaturation of intracapsular substances. The effect is progressive and may affect all users of the technology. Pathology studies on mineralization of tissue surrounding prostheses, in particular saline inflatables, confirm not only secondary interstitial mineralization of tissue but frank metaplastic bone formation which culminates in gross anatomic alterations of the periprosthetic area including damage to the rib cage. These problems add to compressive deformation and indentation of ribs directly adjacent to the prostheses. Necrosis of pectoral and intercostal muscle tissue initiated by prosthetic debris impart supplemental damage with implications on respiration processes.

Formation of abrasive material at the interface between tissue and implant is noted widely. Excoriation of the shell against the mineralized tissue leads invariably to perforation, leakage and spallation of fine, inflammatory, fibrotic silica-rich debris. These are not risks - they are certainties and the magnitude of the effects increases in severity with dwell time.

Erosive action by calcified capsules and through friction of shell material at folds in the envelope produces fine particles of silica-rich elastomer with exposed activated silica rich surfaces. This debris is analogous to that produced by disintegrating Swanson type joint implants. Fine particles with systemic inflammatory properties disperse in the implanted area and eventually spread throughout the lymphatic chains initiating systemic phenomena, as noted for the finger joint prosthesis (21 CFR 888.3230). This problem is central to adverse reactions surrounding spallating joint implants such as the Vitek/Proplast temporo mandibular joints (TMJ), objects of other FDA regulatory actions in the early-nineties.

On the basis of Innoval's explant studies, currently manufactured saline inflatable prostheses show a large number of items with serious manufacturing defects. The defects are obvious and would have been unavoidably noted by competent Quality Assurance services. Widely encountered defects include improperly dimensioned valves which do not mate and where closure is not possible. Such valves are generic commodities fitted to different types of saline inflatable implants. The same valve defects are encountered in many types of implants made by different manufacturing facilities.

Perforated or leaky implants deflate and refill gradually with fluid and biological material from the user. Microbiological contamination of the fluid is inevitable within several weeks. The protected environment with nutrients makes the fluid ideal for colonization. Thus, a deflated implant is not a minor setback to be corrected at leisure. It is a clear and present danger. Prompt surgical removal of such an entity must be addressed in the context of user safety. It is not a cosmetic or elective issue.

Product Inserts on adverse effects are misleading. Adverse effects are presented as rare and random occurrences. Studies on explanted devices reveal otherwise. They confirm that complications result largely from manufacturing defects, design inadequacies and time dependent changes in constituent materials. With time, serious adverse events are inevitable. The short service life of some saline inflatable prostheses is therefore predictable. The inevitability of removal and/or replacement as well as risks from a retained deflated implant must be acknowledged.

Rupture followed by deflation is not the prevailing mechanism of failure. Instead, it is the slow deterioration of the shell followed by rapid or progressive unprovoked leakage which may initially appear benign to the user. Medical attention is likely to be delayed, exposing the user to greater yet more subtle risks such as infective phenomena from the release of colonized saline.

Material intended for distribution to prospective users and frequently incorporated in promotional brochures describe the aqueous filling medium as a harmless substance which will not adversely affect the user should leakage occur. Such claims are misleading. Sterilization processes used by the implant industry do not support claims that there can be no viable entities within saline inflatable prostheses at the outset. Even if absolute sterility is achieved fortuitously, subsequent handling and intrasurgical filling would lead inevitably to inoculation by viable entities from the surgical field rendering the aqueous medium septic.

Instructions for use allow filling of a device in situ via a cannula-bearing tube. Manual closure of the valve completes the filling procedure. This manipulation is performed within a blood infiltrated surgical field where there can be no reliable control on sterility. Blood and plasma proteins become entrapped within the valve mechanism during decoupling of the filling tube providing nutrients for viable entities. Most valve mechanisms are incompetent from the outset. Many have no capacity to seal. They rely on bidirectional 'pumping action' to maintain the volume of the prosthesis. These features ensure the presence of inoculae and nutrients in large quantities within the saline charge.

Private plastic surgery clinics with only basic infection control are the usual environment where saline inflatable prostheses are inserted. There is no capacity to achieve the required level of microbiological safety in such an environment. Reliance on antibiotic cover explains the comparative paucity of infective episodes at these facilities when surgeries do not involve implants. However, antibiotics are not well suited to control infective processes where encapsulated implants are concerned. They are totally ineffective against micro-organisms dispersed within the protected saline charge in an inflatable.

Extemporaneous use of pharmaceuticals in saline-bearing prostheses continues unabated, antibiotics and anti- inflammatories being the preferred additives. Product Inserts are silent or non-committal on this issue. In peripheral documentation, the practice is presented as a benign risk to shell integrity. Hazards associated with denatured pharmaceuticals colonized by adventitious micro-organisms are not discussed. The practice of 'medicating' the saline charge is neither safe nor effective. It is contrary to basic concepts of pharmacology and drug use.

There is a basis to explicitly contraindicate breast feeding for all saline inflatable implant users. The recommendation is strongly supported by observations that nearly all explanted devices of this kind show colonization of the saline charge after as little as one year of dwell time. With knowledge that valves are incompetent or leaky by design, it is reasoned that users will suffer sustained low level infections. In turn, the ongoing silent infective processes and colonization of the breast tissue will contribute to drastic diminution of quality of the breast milk. Risk of mastitis will be enhanced and may require supplemental medical treatment.

Risks to infants from breast milk contaminated by low level infective prosthetic effluents are not well documented. It is contrary to common logic to assume safety of human breast milk derived from bearers of leaky saline inflatable prostheses with colonized aqueous fluids. Breast engorgement followed by lactation has disruptive effects, even on non-augmented breasts. For an unstable augmented breast where severed ligaments and reattached muscles are often present, there are strong risks that the cosmetic effect for which the procedure was done will be lost thus motivating the user to undergo more corrective surgery with attendant risks.

Radiographic assessment of augmented breasts for tumor detection is subject to false negatives and is of minimal diagnostic value except for users with palpable, highly calcified tumors which would not require the radiographic diagnostic procedure in the first place. Radiodense structural elements of saline prostheses and peculiarities of the capsules that develop around such structures introduce artifacts, reduce contrast and often shield otherwise radiodiscernible tumors. These problems are widely acknowledged and are part of what would be termed false negatives or obscuration of malignancies. However, phenomena introduced by the prosthesis and its surroundings have comparable probability of mimicking tumors and thus give rise to false positives. The converse phenomenon is not widely acknowledged.

Calcification of the periprosthetic space after a dwell time of 5-7 years introduces periprosthetic artifacts which can mimic tumors with punctuate or stellated microcalcifications. Thus, the value of radiographic studies for tumor detection is compromised both by false positives and false negatives. Special techniques such as the displacement and compression (Eklund) technique introduce risks of their own. The processes may cause avulsion of valve closures or introduce sufficient stress to propagate shell defects at pleats.

The hazards of saline inflatable prostheses result partly from poor manufacturing practices and disclaimed yet obvious adverse phenomena. The mechanisms of injury are predictable upon considering basic principles of human anatomy and physiology. Some problems are easily understood from simple mechanical considerations. However, these issues are overshadowed by fundamental microbiological considerations which are obvious to any reasonable observer. Chronic degenerative impact of the devices on surrounding breast tissue and on underlying upper chest structures are also obvious to the casual observer.

In simple terms, the environment created by saline inflatable prostheses is analogous to that of large volume abscesses. Studies regarding the impact of chronic abscesses predate World War II. Such risks are widely acknowledged by the mainstream medical community but have been hidden and denied for more than thirty years by the breast implant trades. To a consumer, the risks associated with proliferation of atypical micro-organisms within large intracorporeal fluid-filled cavities subject to rapid discharge ought to be immediately apparent. If this information was presented to prospective users, no reasonable individual should be willing to accept such a product. Those who, for whatever consideration, are prepared to undertake such risks, must be compelled to accept inevitable consequences from the product including long term degenerative diseases.

Third party insurers and public health insurance programs must be fully briefed regarding the financial burden that the breast implant trades inflict on the public. Once implanted, breast implant users embark on an essentially irreversible path which culminates in ever-worsening damage with each procedure undertaken. Whereas the initial implantation may be deemed to be a matter of "free choice", and totally at the user's expense, the unavoidable sequelae are not. The costs of treating sequelae revert to the public either directly or through third party insurers who must increase insurance premiums for all their insured clients to compensate for increased costs associated with implant users.

Simple calculations confirm that long term sequelae cost far more than implantation. An option would be to charge the premium for insuring treatment of inevitable implant sequelae on implant users and promoters of the products. Thus, manufacturers and professional associations engaged in the breast implant trades would bear an appropriate share of the costs they engender. In some respects, there is a parallel between tobacco promotion and breast implant usage. Both are freedom of choice and lifestyle issues related to personal decisions but such decisions entail enormous long range health care costs to the public. There is an important difference between smoking and breast implant use. Whereas it is possible for a smoker to quit smoking without requiring a risky and disfiguring surgical procedure, a breast implant user has no such option.

Regulatory agencies such as the FDA and the Public Health Service have multiple responsibilities. They must protect the public's health from unreasonable risks posed by non essential technologies. They must ensure that such technologies are not the object of misleading promotion. Lastly, they must ensure that all costs engendered by faulty technologies do not dissipate resources allocated to public health. More importantly, they must ensure that the general public does not bear health care costs associated with consequences from faulty technologies promoted by the breast implant trades.

Forty years of haphazard breast implant promotion illustrate that the financial outlay and the health care resources consumed are staggering and are still increasing. Promotion costs alone, paid by the breast implant trades, are at par with budget allocations for some state-subsidized medical care programs. Saline inflatable breast implants are now central to this paradox.

The foregoing information and the Attachment containing some recommendations may assist the FDA and its associated agencies in the development of PMA guidelines. The leadership role of the FDA in the regulation of health care products is a global concern. The FDA is by much the best funded and the most able of any public agency mandated to protect the public from faulty health care technology. It has always been, and still is, a role model for every regulatory agency worldwide with a similar mandate. Thus, residents of all industrialized countries have a stake in the FDA. It decisions and recommendations on health care products affect regulatory policies on public health far beyond U.S. borders.

It is urgent to publish requirements for saline inflatable prostheses that may remain in commerce and determine if any are in compliance. It is equally urgent to advise potential users of the hazards that the items pose even if they are deemed to satisfy requirements. Current and prospective users must be made aware of the severe limitations and the insidious risks that the devices pose. Efforts must be devoted to ensure forthrightness of information presented in PMA submissions, clinical trial results and adverse reaction reports by the breast implant trades.

Innoval and the author are not involved in breast implant commerce, health care or diagnostic services or the provision of plastic and cosmetic surgery services. No support from industry, government or other agency is received. Research which forms the basis of this presentation is self-supported. The author, P. Blais, is a former Canadian government researcher and Senior Scientific Advisor then associated with development of medical device safety policies. He has consulted at different times for the breast implant industry, for plaintiffs' attorneys, for defense attorneys, for state Medical Examiners, for provincial Coroners, for official government agencies, for third party health insurers and has provided official court testimony in the context of trials, Congressional Hearings (U.S.), FDA hearings as well as foreign investigative committees on health care technology, including safety of breast implants.

*He is presently a witness in a Royal Canadian Mounted Police (RCMP) criminal investigation of the Department of National Health (Canada). The matter relates to alleged malfeasance by Department officials in

connection with safety and efficacy evaluation of medical devices entering Canadian commerce.

_________________________________________________________________

Added to final manuscript copy provided to Committee Chairman on March 1,

2000.

Requirements for PMA of Saline-Filled Breast Implants (21 CFR Part 878):

The FDA must take the initiative in providing realistic consumer education with respect to saline inflatable prostheses to offset misleading promotion and control widespread abuses. Recommendations are listed below:

Disclosure requirements for implants must be embedded in formal PMA guidelines, standardized informed consent documents and Product Inserts. Separable patient-oriented material must included and appropriate compliance mechanisms must be created to ensure that surgeons provide this material to prospective user-patients.

PMA submissions must provide realistic guidelines on durability expectations and the inevitability of removal with possible replacement in the context of cosmetically penalizing surgery and possible long term disabilities. Informed consent material must reflect reality in plain language to forestall evasion of the requirements by promoters. Product Inserts must provide expected durability statements, recommended countermeasures to adverse events and clear differentiation between risks and certainties. Injury mechanisms must be stated. Some injury mechanisms are discussed in Appendix A.

Post-market surveillance must be upgraded to resolve hiding of serious problems. There must be public disclosure of known problems affecting specific saline inflatables, in particular devices withdrawn from commerce in the past because of safety and efficacy concerns but still borne by some users. The disclosures must extend to pre-Moratorium devices with saline compartments such as gel-salines and bi-lumen implants subject to the same problems as saline inflatables.

Users of saline inflatables must be made aware that they are at significant risk for well defined, medically obvious but difficultly-treated systemic diseases, which worsen with time.

Problems of saline implants that undergo spallation of the surfaces in abrasive environments must be acknowledged as capable of initiating phenomena similar to that encountered with Swanson joint prostheses (21

CFR 888.3230) and Vitek/Proplast temporo mandibular joints implants (TMJ). Accordingly, users of saline implants must be forewarned of possible adverse reactions similar to Swanson and TMJ implants which were the object of FDA regulatory actions and Talk Papers in the early-nineties. Device batches which, through implant recovery studies, are demonstrated to undergo material deterioration and spallation of the surface, must be identified publicly through a 'Dear Doctor' letter. Such devices are clearly defective in terms of material formulation and processing. They are a source of disseminated silica-rich inflammatory particles with documented risks of long range systemic health effects.

A 'Dear Doctor' letter addressing the incompetent valve problems associated with leaf-style valves ("MLV") and late issue anterior or "Apex Diaphragm" valves must be issued to limit further implantations of these products and forewarn users of imminent complications.

Guidelines on documentation intended for distribution to prospective users and promotional material must specifically forbid the description of the aqueous filling material as a harmless substance should leakage occur.

Such claims are misleading. The devices can no longer be considered as filled with aqueous saline after several years in situ. Instead, they contain a microbiologically hazardous substance with a capacity to enter the bloodstream.

Rupture followed by immediate deflation is not a common mechanism of failure. Slow and unprovoked late leakage is the normal end-stage. The process occurs insidiously and with concurrent contamination of the saline charge. Both phenomena imply a poor prognosis for users. Product inserts must emphasize that medical attention cannot be delayed when deflation is noted. Prompt surgical removal of implants known to be leaky or deflated must be emphasized in a 'Dear Doctor' letter in the context of user safety for current and prospective users. It is not a cosmetic or elective surgery issue.

Product inserts must specifically forbid re-sterilization. Existing product inserts nearly all condone re-sterilization of prostheses deemed to be contaminated or having compromised sterility. Most provide re-sterilization procedures. Given the crucial importance of sterility of the interior compartment, there is no known process that would enable restoration of the original microbiological safety level of the product if contamination took place.

Product inserts must forbid in situ filling of saline inflatables ('Birnbaum Procedure'). Filling cannot be performed within the implant pocket without gross contamination of the saline charge incidental to manual closure of the valve system in a blood-infiltrated surgical field.

Guidelines on implantation facilities must be developed. Private plastic surgery clinics, the usual breast implantation setting, have only basic infection control and no capacity to achieve the required level of microbiological safety. Reliance on antibiotics to control infective processes affecting implant sites is unrealistic and hazardous.

Extemporaneous use of pharmaceuticals in saline-bearing prostheses must be contraindicated on the basis of inefficacy and intrinsic risks from toxins created from denaturation of pharmaceuticals incorporated within the saline charge. The instillation of pharmaceuticals within such closed environments is contrary to basic concepts of drug safety and compromises the microbiological status of the saline charge (Appendix B).

It is urgent and long overdue to explicitly contraindicate breast feeding for all saline inflatable implant users. Inevitable and time-dependent colonization of the saline charge followed by progressive and unpredictable leakage makes users ideally suited as delivery vehicles for microbiological vectors of unknown long term consequences. Ongoing silent intracapsular infective processes and colonization of the periprosthetic breast tissue constitute a clear and present danger to infants. Appendix C provides additional information on this topic.

Product inserts must contraindicate breast feeding for additional reasons unrelated to the health of infants. Breast engorgement and lactation disrupt the breast structure. For an unstable augmented breast, there are strong risks that the cosmetic effect for which the procedure was done in the first place will be lost thus motivating the user to undergo more surgery with attendant risks to correct for secondary breast involution.

The applicability of radiographic tumor detection techniques with breast prostheses of any kind in situ is undemonstrated. This is evident even to an unsophisticated observer examining a small number of state-of-the-art mammographic plates. Product inserts and consent documents should include a statement that augmented breasts are subject to false positives and false negatives with reference to malignancies.

Cautionary statements regarding the radiographic presentation dilemma of any implant user, with or without a prosthesis in situ, must be addressed. Radiodense structural elements of a saline prosthesis and peculiarities of the capsule that surrounds the device introduce artifacts, reduce contrast and may shield otherwise radiodiscernible tumors. The removal of the prostheses without ablation of pericapsular tissue may not restore the user to her original state. Her radiographic presentation may mimic the presence of anomalies similar to tumors. Residual calcified, involuted periprosthetic tissue may appear as stellated calcified areas, criteria relied upon by the radiology community for diagnosis of malignancies.

Recommendations must be provided to agencies responsible for public health insurance programs and third party insurers to control costs engendered by the breast implant trades and related activities. Cost studies and guideline documents should be prepared within the framework of a formally mandated Technology Assessment Program. The FDA and its associated agencies should rely on independent studies to perform this task as the published literature is not consistent with laboratory findings. This issue is further discussed in Appendix D.

APPENDIX A

The insertion of ill-conceived implants in a disease-prone area has a potential for injury which rises with the dwell time of the product. Implants cause structural, physiologic and biochemical changes in the chest environment. Some implants undergo degradation of the shell materials with dispersal of inflammatory debris. The devices act as release systems for pharmacologically active compounds produced through fermentation of the contaminated filling medium. Leaky valves contribute to the problem by providing entrapped micro-organisms with nutrients and allowing escape of inoculae. It is essential for users to understand the mechanisms by which the devices affect their health and comfort, including the microbiological implications of having improperly sealed devices within large stagnant tissue pockets.

Saline inflatables become reservoirs for decaying proteins and blood products in which microbiological entities proliferate. The mixture is contained as long as the shell has integrity and if the valve seal is maintained. Nearly all saline inflatable devices examined to date show deficiencies with respect to integrity of the shell and valve reliability ab initio and with time.

Microbiological entities surviving the sterilization cycle and introduced intraoperatively account for the parent inoculae. They are supplemented by micro-organisms in filling solutions. The faulty filling procedures and valve leakage provide initial nutrients from the user's extracellular fluids. Colonization takes place with enrichment of the population by hardy species as time passes. Leaky valves allow inoculae from the interior to leak into the intracapsular space causing initially silent low grade infective phenomena.

When shells perforate, the space originally filled with saline solution fills with tissue debris and body fluids. Movement from the user causes a pumping action which drives out decaying biological fluids. Systemic symptoms later become apparent as the capsule space becomes colonized. Protected intracapsular infections accelerate capsular fibrosis. The micro-organisms within dense capsules are not accessible to antibiotics. With large colonies, there is formation of pharmacologically significant quantities of toxic fermentation by-products, thus accounting for some disturbances reported by long term users.

Capsule problems are common in prosthetic patients but are worse for users that show baseline colonization of the capsule with bacterial and fungal entities. Removing the implants does not resolve problems unless the capsules are also removed. Otherwise, the capsular spaces refill with fluid and evolve into classical abscesses that can be seen radiographically as irregularly calcified masses. Late capsular mineralization (calcification), with or without implants in situ, is primarily a consequence of tissue necrosis. It affects more than 50% of implant users with dwell times in excess of 10 years and is unlike naturally occurring dystrophic calcification. It is a severe and injurious phenomenon which culminates in development of sharp, abrasive structures that traumatize tissue, cause focal bleeding with accumulation of blood products in closed spaces. In extreme cases hematomas develop, even if the area is sterile. In summary, prosthetic injuries in saline breast implant users can be attributed to at least six major mechanisms:

(1)Expected surgical trauma from deliberate severance of milk ducts, vasculature and muscles; unintended surgical misadventures resulting in collateral damage to functional or sensorial parts of the breast gland, the chest muscles and the upper limbs; cumulative effects of repeated surgery including loss of tissue, contractile fibrosis, neuromas and adhesions;

(2) Chronic biomechanical effects induced by the presence of foreign objects that cause compressive trauma, excoriation, distention, atrophy and restrictive adhesion between normally independent tissues planes or compressive and occlusive ischemia of the vasculature and the lymphatic system within the pectoral-axillary area;

(3) Acute and chronic locally injurious biochemical effects from reactive prosthetic substances that induce fibrotic, inflammatory and necrotic tissue changes;

(4) Long term tissue remodelling and deviant repair processes leading to hyperplasia, densification, mineralization and dehydration of the implant site;

(5) Implant-capsule interactions leading to tissue degeneration and denaturation of proteins in extracellular fluids to produce host tissue-derived antigens that elicit host-directed antibodies; devices with degradable materials that revert to silica-rich particles perform in such ways and are associated with autoimmune disturbances and focal tissue reactions;

(6) Pathologic effects from bacterial, viral or fungal colonization of the capsule space leading to low grade chronic infections and toxic phenomena from microbiological metabolites.

PHARMACEUTICALS IN SALINE-CONTAINING IMPLANTS

The instillation of pharmaceuticals added extemporaneously to filling media in saline implants started in the early-seventies. By the late-seventies, several publications were advocating the procedure. Initially promoted by plastic surgeons, the procedure met with strong objections from pharmacologists and drug manufacturers. The use of assorted antibiotic and bacteriostatic pharmaceuticals was predicated on the basis that they would prevent growth of micro- organisms inside or outside the shell. Anti-inflammatories and other drugs were expected to mitigate capsular contracture by slowly diffusing through the permeable implant wall.

Any individual skilled in the art would have been knowledgeable regarding the risks of contamination of the saline charge and the possibility of leakage for a contaminated saline inflatable. Studies had documented the rapid growth of micro-organisms within such devices. Through experience, the surgical community as a whole feared infection and growth of bacteria and fungi within liquid-filled implants. The instillation of pharmaceuticals designed for oral or intravenous use via improvised intrasurgical procedures would enhance the risk of microbiological contamination and would present unknown supplemental hazards from the deteriorating pharmaceuticals. Therefore, logic and conventional wisdom would have compelled clinicians and manufacturers to rigorously contraindicate the procedure. Paradoxically, popularity increased in the eighties and continues today in some quarters.

There are obvious negative aspects to the use of pharmaceuticals in saline inflatables. Current product inserts are misleading. They do not disclose the risks and consequences of the practice. The primary risks are not associated with physico-chemical damage imparted by the pharmaceuticals to the shell material. Instead, they have to do with insult to surrounding tissue by degradation and fermentation products. These form in complex mixtures of substances populated by micro-organisms and supplemented by extracellular fluids and tissue from the host. The contaminant-rich medium cannot be contained by the prostheses as they are designed.

Additives are ineffective and, in some instances, transparently hazardous. Studies on the use of steroidal anti-inflammatories for prevention of capsular contracture demonstrate the inefficacy of the approach unless the concentration is very elevated. Publications of the eighties forewarned of tissue resorption and implant extrusion in the context of steroidal use within aqueous media-filled implants and illustrated the undesirability of the practice. Antibiotics are no better. They are not stable for more than several weeks in closed implant environments. They become nutrients favoring growth of atypical micro-organisms that resist antibiotics. In a closed environment, enrichment of the flora by hardy entities of this kind would be the expectation and provide a particularly fearful prospect for the user.

Drug manufacturers never condoned the use of extemporaneously added pharmaceuticals in implants. Implant manufacturers initially supported the practice but dissembled when product inserts had to address the issue. The

problem remains with current product inserts where the use of such additives is left largely to the discretion of surgeons and where incorrect rationales are stated for contraindications. It is essential that saline implants be provided with definitive product inserts containing explicit prohibition of the practice of extemporaneous addition of drugs to saline filling media.

APPENDIX C

Breast prostheses have been implanted in large numbers for more than forty years and users have ranged from late adolescence to individuals of advanced age. The socio-economic profile of this cohort is tilted towards individuals with an age range of 25-40 and is rapidly dropping as promotion targets an even younger, image conscious population. Fertility and lactation concerns for such a group may not be at the forefront when a decision is made to undergo implantation. However, the issue resurfaces several years post-implantation as pregnancies develop in a significant fraction of users. Nearly all consumer oriented material as well as surgeons' reinforce the view that breast feeding is not only possible but desirable even for implanted patients. Implanted mothers therefore expect to retain their capacity to safely breast feed.

Such an expectation is illogical. Implantation of a foreign object in the breast irreversibly modifies the breast structure. Even with removal of the prosthesis, the structure and physiology of the gland are not restored to their original state. The very act of inserting such an object in the breast has lasting and irreversible consequences, all of which militate strongly against safe breast feeding. The changes greatly increase the probability of complications to the user as the breast engorges and tissue is strained. Concurrent physiologic and chemical changes in the breast area impact adversely on the amount and quality of milk produced by lactating mothers where insertion of a foreign object and extensive surgery has been performed.

The belief that breast feeding is possible and safe for implant users is novel thinking. In the sixties and seventies, breast feeding was not deemed desirable for implant users. Some physicians did not even regard it as possible. Their views were based on clinical, biomechanical, biochemical and physiologic considerations. Prostheses had mechanically damaging features known to modify the breast eventually damaging the vasculature and the lactation apparatus over the long term. The high impurity levels associated with implants, in particular oils similar to what had been used in connection with injected silicone augmentation, were known to impact adversely on lactation. The experience of oil-injected patients produced sufficient information to support the view that prosthetically modified breasts were unsuited for breast feeding.

In the following years, the issue remained dormant and no major investigation was performed. Instead, hearsay and fiction surrounded the issue and it became accepted amongst the lay public and some general practitioners that cosmetically augmented mothers could breast feed without problems. Specialists in surgery of the breast, and in particular plastic surgeons, knew otherwise but the information was not shared.

European publications of the seventies contraindicated breast feeding based on empirical data gathered from users of the previous decade. The advice against breast feeding was more a matter of cosmetic and comfort as opposed to risk to infants. It was reasoned that avoidance of breast feeding would minimize post-lactation ptosis, breast involution and connective tissue distention within the cosmetically modified breast. Microbiological issues were considered but not given prominence but it was recognized that colonization of the implant site and intracapsular mastitis would be factors that could spread to the lactation apparatus with time. Collapse of the lactation system is a logical expectation from surgical damage incidental to implant insertion and gross contamination of the breast by dispersible reactive debris. Similar results are expected from the introduction of implants that exert continuous pressure on the breast gland and the vasculature. Chronic, uncontrollable fibrosis further complicate the situation. Combination of these factors with recurrent low level infective processes will alter the gland over time and severe discomfort is expected upon engorgement prior to lactation.

Anatomic, biomechanical and physiologic considerations of the prosthetically modified breast clearly demonstrate why breast feeding is impractical and destructive. The use of a retromammary implant eventually causes pressure atrophy of the breast gland and collapse of the ducts which convey fluid to the nipple. This is known within some circles who have noted that there is chronic swelling of the nipple areolar complex in augmented patients. The phenomenon persists for many years until necrotic processes drastically diminish the fluid transport within the anterior of the breast. It is rare when atrophy is not present in surgically augmented breasts after implants have been in situ for 2-4 years. Irrigation within the critical area is reduced and large prominent veins appear in the periphery of the breast implant, usually close to the skin. Compression causes focal ischemia and oxygen depletion. These factors militate towards failure of the milk-producing system.

Upon cessation of breast feeding, the breast returns to its initial augmented volume but tissues and ligaments are stretched and the patient re-encounters ptosis and involution of the gland, further reducing the breast volume. Thus, the cosmetic benefits of the augmentation may be lost and re-do surgery to regain the esthetic effect may be undertaken.

Formal fertility and lactation studies have never been conducted rigorously by opponents or proponents of breast feeding. Only superficial surveys and anecdotal claims of successful breast feeding by individuals who had recently received implants appear in the literature. The work is oriented at reassuring prospective unsophisticated implant candidates as opposed to documenting the impact of breast feeding on existing implant users and infants.

Breast prostheses are not conventional medical products. Throughout the years they have been a heterogeneous mixture of low quality products with high levels of impurities and features which made their users vulnerable to chronic adverse processes. They induce infections that can remain dormant for many years, producing destructive local effects and high quantities of microbiological metabolites. The capsule around the implant does not impede dissemination of prosthetic debris. It only delays release. Capsules deteriorate and remodel with time to eventually release their content. Even popular contracture treatments foster infective complications by releasing entities captive within the intracapsular space thus spreading the effect of colonization to distal parts of the breasts. Evidence of necrosis and tissue degeneration surrounding implants is found in nearly all users with implant dwell times exceeding three years. This is seen in mammographic studies where large quantities of calcific debris are shown associated with tissue deterioration and fat necrosis. Such effects strongly militate against breast feeding.

Parenthood and breast feeding promotion organizations maintain that lactation in implanted mothers is feasible, desirable and safe. They support the practice on the strength of opinions that are devoid of clinical, physiologic and biochemical basis. To this day, there is no scientific basis to assume safety for lactating mothers with implants or for their offspring. On the contrary, established thinking based on the physiology of the breast strongly supports an elevated probability of adverse effects. Preliminary studies conducted on children from saline implanted mothers note adverse effects and should be a strong deterrent to breast feeding for any individual who either has or who has had a breast prosthesis in her lifetime, as would be the case for individuals with a history of frequent mastitis.

In the light of present knowledge, a firm contraindication on breast feeding is justified for all individuals with implants in situ. The contraindication is as important for the implant user as it is for the infant. For individuals who have had implants which have been subsequently removed as a result of complications, the recommendation is equally valid. Infective sequelae are frequently followed by long lasting manifestations which may produce large quantities of micro organisms and their by-products may enter the ductal system to ultimately alter the quality of the milk and possibly affect the infant. Individuals with a history of problems or with evidence of hematomas, seromas or nipple discharge abound amongst implant users. Such events should serve to reinforce the recommendation against breast feeding. Further, the risk may be greater to the offspring than to the mother.

APPENDIX D

Publications play a major role in the evolution and success of commercial products in medical technology sectors. Journals are the visible part of what is presented to the public as the advancing frontiers of knowledge. They constitute powerful promotional material. Professionals and the public alike assume that such publications are forthright and are subjected to rigorous evaluation with respect to content and accuracy. This is not necessarily true. There have been numerous aberrations in connection with publications pertaining to breast implants.

Publications are perceived as 'disclosures' of information believed to be uninfluenced by parties likely to derive material or professional gains from the publications. This is a fallacy. Recent policy changes by major journals have addressed this issue with limited success.

It is interesting to examine mechanisms whereby manuscripts are selected for publication. It is even more interesting to study how meritorious manuscripts and valuable information can be systematically excluded from

publication. Overt abuses of editorial mandate, unethical manuscript review practices and conflicts of interest amongst editors and editorial boards afflict most fields at some point in time. Instances where influential authors failed to disclose major personal advantages from promotion of certain products and technologies are known. Such aberrations have been noted widely in plastic and reconstructive surgery. Most abuses have taken place in clinical sectors involving clinicians and manufacturers, frequently in positions of influence as medical directors, chairmen of government-mandated committees, business leaders or administrators of health care facilities and university departments.

There are other mechanisms to control public and professional perception of commercial products or medico-surgical procedures. Some involve the restriction of information pertinent to adverse reactions or other unfavorable information. Public perception of medical technology is strongly influenced by public media and trade magazines. The public believes that professional thinking is shaped by specialized journals. This is not true for most scientific areas, least of all for the health sectors. Review type and newspaper style technical publications directed at professionals are much more influential because of their wide circulation. All of these publication vehicles are subject to complex editorial policies and are sometimes afflicted by illogical content selection mechanisms motivated by fads.

Most of these publications are strongly dependent on advertisements and funding from commercial sources. Their editorial boards are comprised mostly of established clinicians and commercial promoters who depend on product sales, university grants and clinical investigation contracts. Publications of a promotional nature are widespread in these media. They are often masked as "scientific news" or clinical study papers.

Predictably, adverse information on products and procedures is extremely difficult to publish via such routes. This is because of control by editorial boards. Even in the absence of conflicts of interest within the publication process, there are still obstacles to the release of negative information.

Control can be even more direct and invidious through threats of litigation-related tangles with third parties involved in the promotion and marketing of medical products. Such overt and implicit threats have been widely used to suppress publication of unfavorable information or the printing of articles that are discordant with ongoing promotional campaigns. The use of law suits structured along the aims of Strategic Litigation Against Public Participation (SLAPP) is prevalent against authors whose views are unfavorable to commercial activity. This form of suit is effective in silencing authors who hold dissenting views and has been, and is continuing to be, widely used in the context of breast implants.

Other reasons to suppress publications have to do with avoiding controversy because it is a destabilizing factor, even for a large, well-financed scientific publisher. The operation of a journal requires stability and editors of prominent journals are chosen because of their ability to stabilize organizations through negotiation, compromise and arbitration. Most editors represent mainstream views and generally function in insecure politico-professional climates. They are vulnerable to pressure of all types. Personal pecuniary issues, commercial consulting contracts, intra and extramural institutional feuds as well as university funding problems and interprofessional quarrels further complicate matters.

Popular or professional scientific publications do not always reflect the real world. More often they lag by many years the discovery of adverse reactions. Mostly, they tend to reinforce existing views and beliefs. The publication review processes facilitate that. They are imperfect mechanisms for selection of manuscripts containing new knowledge, in particular adverse reaction information pertinent to large populations. They are also unsuited to review papers that could alter prevailing practices or manuscripts that buck existing commercial trends. Overt and covert stakeholder participation in the process further distorts reality. Thus, the scientist's "Duty to Publish" and "The Public's Right to Know" are more often utopian hopes as opposed to practical realities.

The peer review process does not look favorably on dissenting manuscripts that bring sobering reality when there has been implementation of medical practices that have become surrounded by morbidity. This seems true even if early studies neglected to follow-up on adverse effects. It is ill-suited to adjudicate works that challenge established views reinforced by years of unquestioned clinical practice. The review process is even less reliable when manuscripts expose self -evident truths with unpalatable but predictable conclusions. Especially voided are articles showing that earlier studies were sloppy, biased or fraudulent and that elite professional groups were fooled by coarse commercial promoters or self-aggrandizing bureaucrats.