Biomaterials Science || Legal Aspects of Biomaterials

ChapTEr III.2.8 Legal Aspects of Biomaterials 1431

in vivo models that are relevant. These include, but are not limited to, sheep, pigs, calves, dogs, and non-human primates. Currently, there is no ideal model for preclini-cal assessment of heart valves, but existing models can be improved upon by incorporating additional outcomes, for example, including site-specific testing. Other poten-tial improvements include the increased use of focused screening models, such as isolated hearts, the use of risk analysis for determining not only the end points, but also the choice of controls and power of the study, and increased communication with regards to negative find-ings. Compliant preclinical assessment provides not only an accurate correlation of in vitro and in vivo perfor-mance of a device, but also provides a basis for clinical trials.

Once preclinical assessment has indicated that the new valve is suitable for use in human patients, clinical trials may be designed to evaluate the safety and efficacy with regard to toxicity, efficacy, and field conditions. Complete documentation must cover therapeutic indica-tions, contraindications, safety precautions, and safety information. Given the broad public health significance, it is critical for the clinical trial process and resultant data to conform to rigorous ethical standards. Therefore, investigators need to submit a study protocol for IRB review. This protocol will include a risk–benefit analysis, adequacy of informed consent, appropriate selection of subjects, ongoing monitoring of subjects, mechanisms to ensure confidentiality, examination of additional safe-guards, evaluation of incentives for participation, and plans for continuing review. The sponsor must also sub-mit an Investigational Device Exemption (IDE) to the FDA for approval. Subsequently, the clinical trial may be conducted according to the general principles described above. Often, during the development process, preclini-cal assessment, and clinical research, most cardiac valves

will have undergone only short-term safety and efficacy assessment in a limited number of carefully selected human subjects before being approved for marketing.

In contrast, post-marketing safety surveillance is uti-lized in an effort to detect rare or long-term adverse effects not easily recognized during preclinical testing by examining a much larger patient population over a pro-longed period of time. Although such events may be rare, their potentially catastrophic consequences cannot be ignored. With better documentation of such problems, future device iterations can be redesigned to attempt to eliminate failures.

BIBLIOGRAPHY

Code of Federal Regulations. (June 23, 2005). Title 45 Public Welfare, Part 46 Protection of Human subjects. Revised.

Guidelines for the Conduct of Research Involving Human Sub-jects at the National Institutes of Health. (August 2004). 5th printing.

International Conference on Harmonization. (1996). Good Clinical Practice: Consolidated Guidance. ICH Guidelines E6, 8–9.

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1979). The Belmont Report on Ethical Principles and Guidelines for the Protection of Human Subjects of Research, April 18.

UNDP/World Bank/WHO/TDR. (2000). Good Laboratory Prac-tice (GLP) Handbook: Quality practices for regulated non-clinical research and development.

US Government Printing Office. (1949). Trials of War Crimi-nals before the Nuremberg Military Tribunals under Control Council Law No. 10. (Vol. 2). Washington, DC: US Govern-ment Printing Office.

World Health Organization (1995). Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products. WHO Technical Report Series. No. 850, Annex 3.

World Medical Association (1964). World Medical Association (WMA) Declaration of Helsinki on Ethical Principles for Med-ical Research Involving Human Subjects. Helsinki, Finland: Adopted by the 18th WMA General Assembly. June 1964.

CHAPTER III.2.8 LEGAL ASPECTS OF BIOMATERIALS

Jay P. Mayesh and Angela R. VicariKaye Scholer, New York, USA

INTRODUCTION

Students of biomaterials engineering know that no prod-uct lasts forever, and that implantable medical devices have unwanted side-effects. In today’s litigious society, these factors often transform patients and device manu-facturers into warring parties in always unwelcome and sometimes financially disastrous products liability litiga-tion over the safety of medical devices. Products liabil-ity law imposes legal responsibility on manufacturers of products (ladders, cars, and medical devices, to name a few), as well as other companies involved in the “stream

of commerce,” such as wholesalers, distributors, and retailers, for injuries incurred by the consumer.

Products liability falls within the area of civil law called torts. A tort is simply a wrongful act that may give rise to a lawsuit, for example an auto negligence law-suit or professional malpractice claim against a doctor or lawyer. If the plaintiff is successful, a tort lawsuit results in an award of money to the plaintiff called damages.

Products liability plaintiffs typically rely on four theo-ries of liability. First, they claim that the manufacturer was negligent, meaning that the manufacturer failed to use reasonable care in designing and manufacturing the product. Second, plaintiffs claim that the manufacturer breached legally enforceable promises, called warran-ties, because the product did not meet recognized per-formance expectations or have the qualities expected of products of its type. Third, plaintiffs sue under strict liability, where a manufacturer is held responsible for a

1432 SECTION III.2 Voluntary Standards, Regulatory Compliance, and Non-Technical Issues

product that was unreasonably dangerous to the con-sumer or carried inadequate warnings, regardless of the degree of care exercised or any promises made by the manufacturer. Strict liability rests on two assumptions about law and economics – first, that imposing liabil-ity on a manufacturer, even without a showing of care-lessness on the manufacturer’s part, is fair because the manufacturer is best able to discover and correct defects in products before they cause harm, and second, that in the event of personal injury attributable to a product, the manufacturer can afford to compensate the injured party, add the cost of injury to the product and, if neces-sary, raise the price of the product to recover the cost. Finally, plaintiffs sue device manufacturers for consumer fraud, which involves a wide range of improper practices with respect to the advertising, marketing, and sale of medical devices. Many consumer fraud claims allege that a device is not performing in the way it was represented or advertised to perform (because of false advertising, product defects or other reasons). To avoid liability under each of these legal theories, device manufacturers must design, manufacture, and sell products that are rea-sonably safe, they must disclose written warnings to phy-sicians (and sometimes to patients) about risks associated with the products, and they must advertise, market, and sell products in a truthful manner.

This chapter describes “mass tort” products liability litigation involving implantable medical devices – that is, personal injury litigation implicating thousands of individ-uals making a claim for an injury as a result of an alleged failure of a medical device. Although the individual inju-ries vary, most if not all claims arise out of the same mode of failure, insufficient warning or a false claim. Faced with numbers of cases involving hundreds of millions of dol-lars, the parties often attempt to consolidate mass tort claims in order to streamline pretrial procedures, either by class action or by consolidated litigation, in which all cases are assigned to one judge. In the federal courts, such consolidated litigation is termed “multidistrict litigation” or “MDL.” Many states have their own analogs to MDL.

Although medical device mass torts raise complicated scientific and medical issues, in the United States legal system lay jurors, untrained in medical science, are the arbiters of reasonable safety, adequate disclosure, and causation. The vagaries of the jury system always create a degree of risk and uncertainty for litigants. That risk is compounded in medical device litigation when jurors are asked to discern which of many competing medical and scientific theories is more credible. Outcomes become even more unpredictable in cases involving unsettled or evolving areas of science.

To help illustrate the subtle and complex world of mass tort litigation, the six largest subjects of medical device litigation are described below, followed by a dis-cussion of some of the obstacles faced by litigants in prosecuting and defending these claims, including the problems posed by science in the courtroom.

INTRAUTERINE DEVICES

The first mass tort litigation involving a medical device arose out of injuries to women who received intrauter-ine devices (“IUDs”). In the early 1970s, the IUD was presented to the public as a safe, effective alternative to oral contraceptives. In the following decades, serious reproductive health risks associated with IUDs ensued, prompting women to sue the manufacturers.

A. H. Robins, the manufacturer of the Dalkon Shield, bore the brunt of IUD litigation. Because the Dalkon Shield predated the Medical Device Amendments of 1976 (see later discussion), no requirements for pre-market testing were in place. As described in the case Tetuan v. A. H. Robins Co. (241 Kan. 441 [1987]), A. H. Robins was anxious to make inroads in the mar-ket and stave off competitors, and thus began market-ing the device in 1971 having performed few safety and efficacy studies. While internal corporate documents reflected the company’s concern with the paucity of information on the product, A. H. Robins nevertheless publicly touted the benefits of the Dalkon Shield, dis-tributing product cards that claimed the Dalkon Shield was superior to other forms of contraception, and plac-ing advertisements in popular magazines. These efforts earned the Dalkon Shield a dominant position in the IUD market.

As further detailed in Tetuan v. A. H. Robins Co, shortly after the device came onto the market the manu-facturer began to receive adverse incident reports from doctors about health problems believed to have been induced by the Dalkon Shield, including septic abortions and an increased incidence of pelvic inflammatory dis-ease (“PID”). The Dalkon Shield, like other IUDs, has a string that descends through the cervix from the uterus to allow the user to ensure the device is in place. Before mar-keting the Dalkon Shield, the manufacturer had knowl-edge that the string had a “wicking” tendency, meaning it could transport fluid by capillary action into the uterus and introduce bacteria into an otherwise sterile environ-ment. The string was surrounded by a nylon-6 sheath, but the sheath biodegraded in the moist body environ-ment, permitting wicking. The wicking was alleged to be the cause of the comparatively high rate of infections and injuries in women who used the Dalkon Shield.

Between 1970 and 1974, approximately 2.2 million women in the United States used the Dalkon Shield (In re Northern Dist. of Cal., Dalkon Shield IUD Prods. Liability Litigation, 693 F.2d 847, 848 [9th Cir. 1982]). The device had been linked to 16 deaths and 25 miscar-riages by the middle of 1975 (H.R. Rep. No. 94-853, p. 8 [1976]). By the end of 1975, the lawsuits against A. H. Robins were sufficiently numerous that they were consolidated before a district court in Kansas for pre-trial purposes (In re A. H. Robins Co., Inc., “Dalkon Shield Products Liability Litigation,” 406 F. Supp. 540 [J.P.M.L. 1975]), and the number of lawsuits continued


to multiply. By early 1976, more than 500 lawsuits seek-ing compensatory and punitive damages totaling more than $400 million had been filed (H.R. Rep. No. 94-853, p. 8 [1976]). Although A. H. Robins was successful in early suits, once certain damaging corporate documents became public the tide turned, and plaintiffs began to win large verdicts. In May of 1985, in the pivotal Tetuan case, a Kansas jury awarded $9.25 million in damages. Shortly after the Tetuan verdict, A. H. Robins filed for bankruptcy reorganization (Vairo, 1992). Under the reorganization plan a trust fund of $2.475 billion was established to pay outstanding claims against the manu-facturer. The bulk of the fund came from another health-care company that agreed to make the contribution in order to acquire A. H. Robins (Vairo, 1992).

IUD plaintiffs have claimed injuries such as uterine perforations, infections, ectopic pregnancies, spontane-ous abortions, fetal injuries and birth defects, sterility, and hysterectomies (In re Northern Dist. of Cal., Dalkon Shield IUD Prods. Liability Litigation, 693 F.2d 847 [9th Cir. 1982]). The theories asserted included failure to warn, unsafe design, breach of warranty, and fraud. Plaintiffs prevailed at trial and were able to negotiate large settlements because the defenses that manufactur-ers typically rely on in medical device litigation were less likely to avail the IUD defendants. Sometimes medical device manufacturers argue that their device cannot be linked with the type of injuries suffered by the plaintiffs. In IUD cases, causation had been a less defensible issue as compared to other medical device litigation because medical experts generally agree on the type of injuries IUDs can produce (Vairo, 1992). Although an IUD manufacturer may successfully argue that the plaintiff’s injury had another cause, such as a sexually transmitted disease, the general causative correlation between IUDs and certain injuries is not in question.

In light of evidence that they were not sufficiently can-did about health problems associated with their devices, IUD manufacturers also had difficulty proving they sat-isfied their duty to warn physicians of the risks of IUD use. For instance, in Nelson v. Dalkon Shield Claimants Trust (1994 WL 255392 [D.N.H. June 8, 1994]) the court refused to dismiss the plaintiff’s claims because the evidence showed that A. H. Robins failed to issue pub-lic warnings about the risks associated with the Dalkon Shield’s string. Statutes of limitation, which provide an injured party with a fixed amount of time to file suit after an injury occurs, frequently have provided IUD manu-facturers with their strongest defense. Injuries caused by IUDs may not manifest themselves for many years, and an even greater amount of time may pass before the user becomes aware that the IUD may have caused the injury.

The Dalkon Shield was ultimately linked to “thou-sands of serious injuries to otherwise healthy women” (Vladeck, 2005). By October 1984, the manufacturer had settled or litigated approximately 7,700 Dalkon Shield cases (Sobol, 1991).

PEDICLE SCREWS

Pedicle screws are bone screws that are implanted in the pedicles of the spine and are used to anchor a vari-ety of stabilizing hardware. Litigation involving pedicle screws was sparked by a December 1993 exposé on the ABC news program, 20/20. The story publicized allega-tions that orthopedic screws, which had received FDA approval only for use in the long bones of the arms and legs, were being implanted in the pedicles, a procedure associated with a high rate of complications (Hoyle and Madeira, 2001). The story spawned a multitude of law-suits, which were consolidated before a Pennsylvania district court for all pretrial procedures (In re Orthope-dic Bone Screw Products Liability Litigation, 1998 WL 118060 [E.D. Pa. Jan. 12, 1988]).

Plaintiffs alleged several variants of device failure. They complained that bone screws implanted in their spines broke, loosened, corroded or were malposi-tioned, causing, among other injuries, pseudarthrosis, neurogenic bladder, and arachnoiditis. In addition to device failure, plaintiffs also alleged that manufacturers committed fraud-on-the-FDA by seeking FDA approval for orthopedic screw use only in the long bones of the arms and legs, but then promoting their use in spinal surgery. Ultimately, the United States Supreme Court rejected this theory of liability in a case called Buck-man v. Plaintiffs’ Legal Committee (531 U.S. 341 [2001]), in which it held that such fraud-on-the-FDA claims are not actionable by plaintiffs in product liabil-ity cases. The Supreme Court reasoned that if courts were permitted to find insufficient disclosures made by a manufacturer to the FDA, even though those same disclosures were deemed appropriate by the FDA, the FDAs ability to protect the public would be frustrated. Plaintiffs also attempted, unsuccessfully, to impose lia-bility on doctors and medical associations, alleging they conspired with manufacturers to commit fraud by con-ducting medical seminars that promoted bone screws for unapproved uses.

In addition, plaintiffs argued that manufacturers should be liable for failing to warn of the risks inherent in pedicle screws. Many failure-to-warn claims involv-ing pedicle screws were dismissed by courts under the “learned intermediary” doctrine, which provides that, in the case of most medical devices, a manufacturer has dis-charged its duty to warn once it has informed the medi-cal community (not the patient) of the risks associated with the device. Dismissals under this doctrine occur when the implanting surgeon testifies that he was aware of the risks through sources entirely independent of the manufacturer’s product literature.

In addition, plaintiffs claimed, usually without suc-cess, that the pedicle screws were defective. In Toll v. Smith & Nephew Richards, Inc., 1998 WL 398062 [E.D. La. July 14, 1998]), for instance, the court dismissed the case because the plaintiff could not make the required


showing that an alternative design capable of preventing the alleged injury existed. Courts have found that lack of FDA approval for use of orthopedic screws in the spine does not strengthen plaintiffs’ claims of defect, and that “off-label” use of a medical device (that is, use for a pur-pose other than which it is FDA-approved) is not prohib-ited. Finally, since spinal surgery can have complications regardless of the instrumentation used, plaintiffs’ claims have frequently failed because they could not show their injuries were not complications of surgery unrelated to the use of the screws.

As the discussion indicates, many claims against pedicle screw manufacturers were dismissed by courts prior to trial. However, a handful of cases reached juries, with mixed results. A Louisiana jury rendered a verdict against one manufacturer in the amount of $318,000 after finding the pedicle screw was unreasonably danger-ous (Anonymous, 1995a), and a Texas jury awarded the plaintiff $451,000 against one manufacturer for misrep-resenting the safe and effective use of its pedicle screws (Anonymous, 1998b). On the other hand, a Pennsylva-nia jury rendered a verdict for the defendant manufac-turer (Anonymous, 1995b), and a Tennessee trial ended with a hung jury (Anonymous, 1998c).

The financial strain of the massive litigation prompted one manufacturer, AcroMed, to settle and agree to con-tribute $100 million and the proceeds of its insurance pol-icies to a settlement fund. In exchange, the manufacturer, as well as its distributors and physicians and hospitals that used its products, were released from suit under any products liability theory (In re Orthopedic Bone Screw Products Liability Litigation, 176 F.R.D. 158 [E.D. Pa. 1997]). Approval of this $100 million settlement was based, in part, on an expert economist’s opinion that AcroMed had an estimated value of about $104 million, and that based on AcroMed’s financial condition, lim-ited insurance coverage, defense costs, and adverse ver-dict potential, the $100 million settlement was “at the outer boundary of what AcroMed can afford to pay” (In re Orthopedic Bone Screw Products Liability Litigation, 176 F.R.D. at 170). Interestingly, within a few weeks after the settlement was declared final, AcroMed was sold for $325 million, more than three times the expert’s estimated value of $104 million.

The death knell of the pedicle screw litigation came in July 1998 when the FDA approved bone screws as safe and effective for spinal surgery.

SILICONE BREAST IMPLANTS

Since the early 1960s, an estimated two million silicone breast implants have been implanted in women, for both breast augmentation and reconstruction. Silicone breast implants are made out of a poly(dimethyl silox-ane) (“PDMS”) elastomer shell, to which fumed amor-phous silica is added, encasing PDMS gel or saline (see Chapters I.2.2.B and II.5.18). Some implants have been

manufactured with a thin layer of polyurethane foam covering the elastomer shell; this was thought to decrease the formation of capsular contracture (hardening of the scar capsule surrounding the implant with resultant dis-figurement), one of the common local complications of breast implants.

Physicians have long recognized that silicone breast implants (including those filled with saline) occasionally cause local complications such as capsular contracture, and that implants can rupture, often necessitating surgery to remove and replace the implants. However, it was not until the early 1990s, spurred on by a television exposé and the publication of several case reports of women with implants who developed autoimmune diseases, that breast implants exploded into mass tort litigation. The FDA, having classified silicone breast implants as Class III devices that “present a potential unreasonable risk of illness or injury” in 1988, enforced the requirement that manufacturers collect and provide safety data on the devices. At this point there were no controlled epidemio-logical studies exploring the relationship between breast implants and systemic disease. Citing the lack of safety data, the FDA imposed a moratorium on the use of sili-cone breast implants, except in clinical studies.

Meanwhile, tens of thousands of implant recipi-ents sued the implant and raw material manufacturers, claiming that they had developed autoimmune diseases, such as lupus, scleroderma, and fibromyalgia. To estab-lish that the implants caused illness, plaintiffs’ lawyers relied on uncontrolled case reports of autoimmune dis-ease in women with implants, and on anecdotal testi-mony by treating physicians to persuade juries that the implants caused illness. They also relied on early case reports of autoimmune disease following direct injec-tions of silicone liquid and paraffin into the breasts of Japanese women. Although none of these sources of evidence scientifically established that breast implants cause autoimmune disease, several early plaintiffs won large verdicts.

After publication of the first well-controlled epidemi-ological studies refuting an association between implants and recognized autoimmune diseases, many plaintiffs modified their injury claims. They alleged that they had developed “atypical” autoimmune diseases with signs and symptoms that would not have been looked for in the studies that tracked the classic autoimmune diseases.

Plaintiffs premised liability on assertions that manu-facturers defectively designed the implants and failed to warn physicians and patients of health risks. A cen-tral allegation in plaintiffs’ lawsuits was that silicone has myriad ill effects on the immune system. Plaintiffs claimed that, as a result of rupture of the implants and “gel bleed” of low molecular weight PDMS through the elastomer shell, silicone microdroplets migrate to remote organs where the silicone causes a chronic inflammatory response and the development of silicone granulomas (Plaintiffs’ Submission and Proposed Findings, 1997).


Moreover, they claimed that silicone is an antigen capa-ble of eliciting an immunologic response in the body, and that silicone acts as an adjuvant, heightening the body’s immunologic response to other substances. Plaintiffs claimed that silicone, through these mechanisms, exac-erbates existing autoimmune diseases, and causes classic and atypical autoimmune diseases in exposed women.

In addition to citing gel bleed as a factor in causa-tion, plaintiffs offered several theories that implicate biodegradation of silicone. They alleged that silicone, migrating throughout the body, is picked up by phago-cytes and transformed into crystalline silica which, they claimed, was immunogenic and caused connective-tissue disorders. Moreover, they alleged that the silicone bio-degrades into silanols, relying on in vivo NMR spectros-copy studies that purported to identify silicone and its metabolic byproducts in the blood and livers of exposed women. Other scientists were unable to replicate these NMR findings (Macdonald et al., 1995; Mayesh and O’Hea, 1997).

In a medical science atmosphere of anecdotal case reports and uncertain elaborate scientific theories, even though no epidemiological studies supported causation, the industry was prepared to spend approximately $4 billion to settle claims globally. The plaintiffs demanded more money, and settlement fell apart. Faced with poten-tial liability and enormous defense costs, Dow Corning, the largest manufacturer of breast implants, was forced into bankruptcy.

Over time, scientific evidence began to mount against causation. Each epidemiology study from leading institu-tions such as the Mayo Clinic, Harvard Medical School, Johns Hopkins University, the University of Michigan, and the University of California failed to show any asso-ciation between silicone breast implants and any classic or atypical autoimmune disease. Nonetheless, occasion-ally manufacturers were still subjected to substantial jury verdicts.

In 1996, the coordinating MDL judge, before whom all lawsuits filed in federal court were consolidated for pretrial proceeding, appointed a National Science Panel of four impartial scientific experts. An immunol-ogist, epidemiologist, toxicologist, and rheumatologist were charged to evaluate the scientific data in relation to connective tissue diseases and immunologic dys-function (National Science Panel, 1998). These experts were instructed to “review and critique the scientific literature pertaining to the possibility of a causal asso-ciation between silicone breast implants and connec-tive tissue diseases, related signs and symptoms, and immune system dysfunction.”

On three occasions in 1996 and 1997, the panel of four court-appointed scientists heard testimony from expert witnesses chosen by the lawyers for plaintiffs and for the manufacturers. The panel received more than 2000 documents from counsel, and the panel mem-bers performed their own literature searches. The panel

concluded in November 1998 that available data did not support a connection between silicone breast implants and any defined connective tissue disease or other auto-immune or rheumatic condition (National Science Panel, 1998).

IMPLANTABLE CARDIAC DEFIBRILLATORS

Implantable cardiac defibrillators (“ICD”) are small, battery-powered devices used to treat a variety of poten-tially fatal cardiac arrhythmias by delivering electrical therapy to the heart. They do so through small wires called “leads” that on one end are attached to the ICD, and on the other end are attached directly to the patient’s heart muscle through a coronary vein. If electrodes on the leads detect that the patient’s heart is out of rhythm, the ICD sends an electric shock to the heart muscle through the leads in order to correct the problem (see Chapter II.5.3.C).

Since the first human use of an ICD was reported in 1980, use of these devices has expanded dramatically, and their design has undergone remarkable change. Modern ICDs are implanted transvenously, provide physiologic pacing in up to three cardiac chambers, per-form a number of automated functions and self-checks, and can deliver pacing or high voltage therapies to treat life-threatening arrhythmias. A pacemaker-dependent ICD patient will receive more than 100 million paced beats over the device’s lifetime.

As with many evolving technologies, advances brought with them new safety risks. The risks spawned two major products liability litigations involving ICDs, both of which centered on the manufacturer’s failure to warn of known problems with the product.

In February 2002, Guidant Corporation identified certain electrical flaws with one of its ICD products. As a result, the company made manufacturing changes to reduce the short circuit risk. However, the company did not notify physicians or patients of these failures or of the manufacturing changes. It continued to sell ICDs manufactured using the older process while it phased in the newer version. The company justified its decision to continue selling older devices and not notifying physi-cians of the new modifications on the grounds that the overall failure rate of the device, even including these events, was extremely low and because the device was performing better than its design specifications. It also concluded that the risk of explanting the device was greater than the risk of device malfunction.

The company eventually announced that there were problems with its ICD after the death of a 21-year-old college student with a genetic heart disease. Guidant acknowledged that the student’s ICD short-circuited, and subsequently told his doctors that it was aware of 25 other cases in which the ICD had been affected by the same flaw. Following this disclosure to the student’s


physicians, Guidant was contacted about a New York Times article that was set to run entitled “Maker of Heart Devices Kept Flaws from Doctors” (Meier, 2005). The company’s first public announcement came hours before the New York Times published its article – more than three years after it had allegedly become aware of the problem. By June 2005, there had been two deaths reported to the FDA suspected to be associated with this malfunction. By October 2005, there were 21 clinical failures, including three patient deaths, worldwide.

Over the next several months, Guidant announced several additional physician notifications covering a sig-nificant number of similar products. The company also began issuing a series of recalls for what amounted to over 100,000 devices in the United States. The company had different problems with different devices, some more serious than others, involving electrical shorts, as well as other defects, including memory errors and premature battery depletion.

A spate of personal injury lawsuits followed, and a multidistrict litigation commenced in November 2005. Unlike many of the other large mass torts discussed in this chapter, the parties settled the litigation soon after. In July 2007, the parties entered into an initial $195 mil-lion proposed settlement. After more individual settle-ment claims than anticipated were submitted, the parties commenced renegotiation, resulting in an increase in the settlement fund to $240 million. The agreement cov-ered 8550 patient claims, including all of those that had been consolidated in the multidistrict litigation, as well as other filed and unfiled claims throughout the United States.

Guidant was not the only ICD manufacturer to face lawsuits. In 2006, patients with ICDs utilizing Medtron-ic’s Sprint Fidelis leads as a component began to suffer painful shocks. An investigation by a physician at the Minneapolis Heart Institute concluded that the shocks were caused by fractures in the leads, and that the leads were failing at a significantly higher rate than other leads, a sentiment echoed by another physician at Cornell Uni-versity Medical Center in New York (In re Medtronic, Inc. Sprint Fidelis Leads Products Liability Litigation, 592 F. Supp. 2d 1147 [D. Minn. 2009]). Plaintiffs claim that upon being confronted with this information, Medtronic undertook a campaign to defend its leads, even though it knew that they were unsafe. As part of that campaign, Medtronic purportedly delayed filing “adverse event reports” with the FDA concerning fail-ures of the leads.

In May 2007, Medtronic filed a supplemental appli-cation to the FDA containing design and manufactur-ing changes to the Sprint Fidelis leads. According to plaintiffs, Medtronic filed this supplement in order to correct defects endemic to the leads. Yet, Medtronic did not advise the FDA that it was filing the premar-ket approval (“PMA”) supplement because of the lead failures, instead merely informing it that the proposed

changes were intended to make the leads more “robust.” The FDA approved Medtronic’s PMA supplement in July 2007, but previously manufactured (and allegedly defective) Sprint Fidelis leads continued to be shipped to hospitals and implanted into patients.

On September 10, 2007, Medtronic filed more than 120 adverse event reports concerning Sprint Fidelis leads. On October 7, 2007, Medtronic suspended sales of the leads but did not inform the FDA, doctors or the public of its decision, and they continued to be implanted into patients. On October 15, 2007, Medtronic recalled the Sprint Fidelis leads, and the FDA issued a “Class I” recall shortly thereafter, the most serious type of medical device recall. At the time of the recall, approximately 257,000 Sprint Fidelis leads remained implanted in patients.

Following the recall, plaintiffs across the country began to file actions against Medtronic alleging (among other things) claims for negligence, strict products liabil-ity, fraud, and breach of express and implied warranties. According to the plaintiffs, the leads were not adequately tested prior to seeking FDA approval, the method of manufacturing, which involved direct resistance spot welding of two different metals, was prone to damag-ing them, and Medtronic knew (but failed to disclose to the FDA) that this welding technique was likely to result in the leads failing. Finally, plaintiffs claimed that Medtronic failed to take adequate steps to ensure that the Sprint Fidelis leads were not damaged during produc-tion, including failing to perform adequate testing on the leads’ components, and failing to take corrective action to prevent lead failures.

Although a multidistrict litigation was commenced on February 21, 2008, in the United States District Court for the District of Minnesota, many of the claims were dismissed on the ground of preemption (In re Medtronic, Inc. Sprint Fidelis Leads Products Liability Litigation, 592 F. Supp. 2d 1147 [D. Minn. 2009]). As discussed further below, preemption is a powerful defense available to manufacturers in cases involving devices that were approved through the FDAs premarket approval process.

ARTIFICIAL HEART VALVES

Artificial heart valves are composed primarily of metal or carbon alloys, and are classified according to their structure as caged-ball, single tilting-disk or bileaflet tilting-disk valves (Vongpatanasin et al., 1996) (see Chapter II.5.3.A). All three types have been the subject of product liability litigation.

In the late 1970s, 15 suits were brought against a manufacturer of a caged-ball valve. Plaintiffs claimed that defects in the valve caused it to wear out prema-turely, resulting in major embolic complications, pre-mature open heart surgery to replace the valve, and catastrophic popet-ball escape from the valve cage. The theories of liability included negligence in the design, manufacture, and testing of the valve, breach of express


or implied warranties, and strict liability (In re Cutter Labs, Inc. “Braunwald-Cutter” Aortic Valve Products Liability Litigation, 465 F. Supp. 1295 [J.P.M.L. 1979]). The manufacturer incurred significant legal expenses, yet was only partially successful in defending the lawsuits (Lindsay v. Cutter Laboratories, Inc., 536 F. Supp. 799 [W.D. Wis. 1982]).

Beginning in the mid-1980s, a manufacturer of a tilting-disk valve, implanted in 50,000 to 100,000 patients between 1979 and 1986 (Bowling v. Pfizer, 143 F.R.D. 141 [S.D. Ohio 1992]), became the object of numerous lawsuits due to the valve’s potential to fracture. Plaintiffs alleged that even before the valve was marketed, the first instance of valve failure due to “strut fracture” occurred in clinical trials. The valve consists of a disk located inside a metal ring covered by a Teflon sewing ring, which is sutured to the heart. The disk opens and closes rhythmi-cally, allowing blood to pass through the heart. The disk is held in place by two wire holders, the inflow and out-flow struts. When the overflow strut fractures, the disk escapes from the ring, causing uncontrolled blood flow through the heart, usually resulting in death. According to a Congressional report on the valve, based in part on examination of the manufacturer’s internal documents, strut fracture was most likely caused or exacerbated by deficiencies in quality control procedures.

The number of lawsuits mounted, and eventually the manufacturer entered into a settlement with a class of plaintiffs implanted with its valve who had not yet expe-rienced fracture. Under the terms of the settlement, the manufacturer agreed to establish a $75 million Patient Benefit Fund for research and heart valve replacement surgery, and a Medical Compensation Fund of between $80 million and $130 million to provide cash payments to valve recipients. The settlement also guaranteed immediate cash payments in the event of a fracture, and provided for contribution of another $10 million for spouses of class members (Bowling v. Pfizer, 143 F.R.D. 141 [S.D. Ohio 1992]).

The issue of whether a plaintiff whose heart valve has not failed can make a legally valid claim against a manu-facturer has been addressed repeatedly. Generally, courts have demonstrated little willingness to entertain lawsuits based on a valve recipient’s fear of failure because either physical injury or an actual device failure is a prerequisite to imposing liability on a manufacturer. However, excep-tions to the general trend can be found. For instance, in a California case, Kahn v. Shiley, 217 Cal. App. 3d 848 [1990], the court allowed a plaintiff to proceed with her fraud claim because the court reasoned fraud does not challenge the safety or efficacy of the medical device. Because fraud allegations focus exclusively on the defen-dant’s conduct, the fact that the plaintiff’s valve had not failed was immaterial. In another case, Michael v. Shiley, Inc. (46 F.3d 1316 [2d Cir. 1995]), a court allowed a plaintiff to proceed to trial because, unlike most plain-tiffs asserting fear of future valve failure, she suffered a

tangible injury because she underwent surgery to replace her heart valve.

The most recent round of litigation concerning artifi-cial heart valves involves the Silzone heart valve, which has a patented silver elemental coating on the sewing cuff, the part of the valve that is sewn to the patient’s body. The purpose of the coating is to use silver’s antimi-crobial properties to help combat endocarditis, an infec-tion of heart tissues and a common cause of prosthetic valve failure. Although the silver-coated Silzone valve was approved for commercial distribution in 1998, the FDA prohibited the company from claiming that the sil-ver coating would reduce the risk of endocarditis.

Following FDA approval, the device manufacturer enrolled 792 patients in a multi-national clinical trial designed to study whether the silver-coated heart valve reduced the incidence of endocarditis in humans. The study was never completed, however, because the moni-toring board found that recipients of the Silzone valve were more likely than controls to experience a complica-tion called “paravalvular leak,” requiring the valve to be removed and replaced.

With these results, the manufacturer voluntarily recalled all of its unimplanted Silzone products. As part of the recall, the manufacturer immediately notified hos-pitals and physicians, instructing them not to use the valves. The company also sent letters regarding the care and management of patients with its implanted valves, and established a reimbursement program to pay for uninsured medical costs associated with the detection, diagnosis, and treatment of paravalvular leak.

These remedial measures, however, did not stop a tide of tort litigation by the patients who received the silver-coated Silzone valves. Some of these claimants alleged bodily injuries as a result of an explant or other com-plications, which they attributed to the Silzone product. Others, who had not had their valve explanted, and who were asymptomatic with no apparent clinical injury to date, sought compensation for past and future costs of medical monitoring.

A number of individual lawsuits were filed and consol-idated in a multidistrict litigation in a Minnesota federal court, which then consolidated various class action com-plaints consolidated into one class action. A class action is a form of lawsuit where a large group of people collec-tively bring their claims. The proposed class must consist of a group of individuals that have suffered a common injury, and in many cases, the party seeking certification must show that common issues between the class and the defendants will predominate the proceedings, as opposed to individual fact-specific conflicts between class mem-bers and the defendants.

Class actions alleging physical injury from defective medical devices often fail to meet these requirements, because such cases inevitably involve individual issues. In addition, nationwide classes are often not certified because there is no national body of product liability


law. Plaintiffs must sue under the law of a particular state, and differences in state law make class resolution of personal injury claims impracticable.

The Silzone consolidated class action was brought by five named plaintiffs on behalf of themselves and over 11,000 other Silzone valve recipients. The litiga-tion presents a sort of class action rollercoaster ride, as the case bounced between the district court and the Eighth Circuit Court of Appeals for five years. In 2004, the district court certified a nationwide class of plain-tiffs who had been implanted with the Silzone valve seeking injunctive relief in the form of medical moni-toring, as well as a consumer protection class under Minnesota’s consumer protection law. This decision was reversed by the Eighth Circuit Court of Appeals in 2005. The appellate court rejected the medical moni-toring class because the class presented “a myriad of individual issues making class certification improper” (In re St. Jude Med., Inc., 425 F.3d 1116, 1122 [8th Cir. 2005]). However, it remanded the case to the district court for it to reconsider the consumer class decision, because the lower court did not properly ana-lyze whether the law of Minnesota should apply to the claims of all of the potential members of the proposed nationwide class.

On remand, the district court determined that Min-nesota law should apply to all claims in the nationwide class, and recertified the consumer protection class (In re St. Jude Medical, Inc., 2006 WL 2943154 [D. Minn. 2006]). The manufacturer appealed again and won. In 2008, the Eighth Circuit held that the district court erred in certifying the consumer protection class, because there were material variations in the represen-tations made by the manufacturer concerning the valve, as well as material differences in the kind and degree of reliance on those representations by the potential class members. The Eighth Circuit recognized that trial would require physician-by-physician inquiry into each doctor’s sources of information about the valve, and held that the case was not suited for trial as a class action (In re St. Jude Medical, Inc., 522 F.3d 836 [8th Cir. 2008]).

Following the Eighth Circuit’s rejection of the con-sumer protection class action the plaintiffs continued to pursue their claims by trying to substitute “omissions” for affirmative misrepresentations in their allegations, but in light of the appellate court’s prior rulings, the district court refused to certify the class (In re St. Jude Medical, Inc., MDL No. 01-1396 (JRT/FLN), 2009 WL 1789376 [D. Minn. June 23, 2009]).

As of April 24, 2009, there were only three indi-vidual Silzone cases pending in federal court, and seven individual state court suits concerning Silzone. The plaintiffs in these cases were requesting damages between $10,000 to $100,000 and, in some cases, an unspecified amount (St. Jude Medical Form 10-Q [May 12, 2009]).

HIP/KNEE PROSTHESIS IMPLANTS

Prosthetic hip implants used in total hip replacements are made up of two components – a socket-like shell that is surgically inserted into the acetabulum of the pelvis, and a ball-like device to replace the femoral head (see Chapter II.5.6). The Inter-Op Shell manufactured by Sulzer Ortho-pedics was one such implant. It was constructed of an outer, porous titanium covered cup and an inner polyeth-ylene cup, and was designed to bond with the natural bone.

In September 2000, Sulzer began to receive adverse reports from surgeons complaining that patients were experiencing symptoms post-operatively that suggested a defect in the hip implant. There were reports of severe pain, loose implants, second surgeries, inability to bear weight or walk, and other health complications. Sulzer initiated an investigation, and after eight weeks, they identified the cause of the problem. During the manu-facturing process, a small amount of a mineral-based oil lubricant leaked into the machine coolant. Residual amounts of the lubricant remained on the surfaces of the shell, interfering with the bonding process between bone and shell. On December 8, 2000, Sulzer recalled many of its Inter-Op acetabular shells. According to the company, residue remained on the surface of the shells following the machining process which could prevent the implant from properly bonding with the bone.

Initially, Sulzer offered to pay for revision surgery, which cost between $20,000 and $70,000 per patient. Many patients, however, were frustrated with the fact that Sulzer did not offer to pay for pain and suffering associ-ated with revision surgery and rehabilitation. Also, many of the patients’ revision surgeries would be covered by Medicare, and so patients felt the offer was not genuine compensation for their surgery or for their pain. In 2001, patients began filing lawsuits against Sulzer, basing their claims on theories of strict liability for manufacturing a defective product, breach of warranty, negligence, and strict liability for failure to warn. Damages sought against Sulzer included: all pain and suffering associated with the recall implant; all past and potential future medical expenses associated with the defective hip implant; and all loss of earnings and/or earning capacity associated with the surgery. Many patients also sought punitive damages.

Around the same time, in early 2001, Sulzer began receiving adverse incident reports regarding its Natural Knee II Tibial Baseplate, an orthopedic knee implant. The Tibial Baseplate is one component of a system used for complete knee replacements. The Baseplate is inserted into the tibia or shin bone. While some implants are cemented into the bone, the Natural Knee II, like the Inter-Op Shell, was designed to allow the bone to grow into and around the implant. Again, surgeons reported that patients were experiencing poor recovery progress and ambulatory pain. X-rays showed radiolucencies under the baseplate, suggesting that the implant had separated from the bone. Sulzer discovered that the same


manufacturing problem that caused the hip implants to fail was causing the knee implants to fail to bond. In May 2001 Sulzer announced a recall of its knee implants, and informed surgeons who had implanted its Tibial Base-plates of the unanticipated adverse clinical outcomes.

As knee implant patients began to file suits, and hip implant patients continued to file suits, Sulzer realized that it would have a difficult time trying a case in which it had voluntarily discovered and already admitted responsibility for the cause of the defect. In attempts to settle the matter without going bankrupt, Sulzer opened its books up to plaintiffs’ attorneys and financial advi-sors who engaged in extensive discovery regarding the company’s liability insurance and financial condition. A $1 billion settlement was approved on May 8, 2002.

PREEMPTION

Prior to 1976, medical device manufacturers were not required to seek FDA approval for a new medical device. In that year, a new regulatory scheme was imple-mented under the Medical Device Amendments of 1976 (“MDA”). The new regulatory regime established vari-ous levels of oversight for medical devices, depending on the risks that they presented. Class I, which includes such devices as elastic bandages and examination gloves, is subject to the lowest level of oversight. Class II, which includes, for example, powered wheelchairs and surgical drapes, is subject to certain performance standards and postmarket surveillance measures. Most medical devices are considered Class II devices. The devices receiving the most federal oversight are those in Class III. These devices usually sustain or support life, are implanted or present potential serious risk of illness or injury.

The MDA also includes a “preemption” provision, Section 360k(a), which states that: “no State … may establish … any requirement (1) which is different from, or in addition to, any requirement applicable under this chapter, and (2) which relates to the safety and effective-ness of the device …” Device manufacturers frequently argue that the MDAs preemption provision precludes plaintiffs from bringing lawsuits under state tort law. The preemption defense succeeds if a court finds that Congress intended that the federal regulatory scheme govern the question of device safety to the exclusion of state tort law.

The extent to which state tort law claims are pre-empted is determined by the manner in which a medi-cal device is approved by the FDA. In 2008, in a case called Riegel v. Medtronic Inc. (128 S. Ct. 1999), the Supreme Court addressed preemption in the context of Class III medical devices. New Class III medical devices, such as the balloon catheter at issue in the Riegel case, must receive premarket approval (“PMA”) before they can be legally marketed. The PMA process is the “rigor-ous” process through which the FDA weighs any prob-able benefit to health from the use of the device against any probable risk of injury or illness. A manufacturer

must submit what is typically a multivolume application including, among other things, full reports of all studies and investigations of the device’s safety and effectiveness, a full statement of the device’s components, ingredients, and properties, and of the principle or principles of oper-ation, a full description of the methods used in, and the facilities and controls used for, the manufacture, process-ing, and a specimen of the proposed labeling. The FDA then spends an average of 1200 hours reviewing each application, and grants premarket approval only if it finds there is a reasonable assurance of the device’s safety and effectiveness. In Riegel, the Supreme Court held that PMA approval imposes “specific federal requirements” applicable to a particular device, and that state law tort claims impose requirements that “are different from, or in addition to” the requirements imposed by federal law. Thus, the Court found that the plaintiff’s claims against Medtronic under New York law based on strict liability, breach of implied warranty, and negligence in the design, inspection, distribution, labeling, marketing, and sale of the catheter were preempted by the MDA.

However, most medical devices are not approved through the PMA process; rather, they are marketed after receiving FDA approval through the less rigorous “premarket notification” process. Premarket notification facilitates the marketing of medical devices that are new to a company, but “substantially equivalent” to a device already on the market (known as a “predicate” device). Substantial equivalence means that the new device has the same intended use as the predicate, and is at least as safe and effective as the predicate device. In 2005, the FDA authorized the marketing of 3148 devices through the premarket notification process, and granted PMA approval to just 32 devices.

Unlike PMA-approved Class III medical devices, there is only a limited preemption defense available in litiga-tion involving devices that were approved through the premarket notification process. Whether state law tort claims are preempted depends on whether FDA regula-tion of these devices constitutes a specific “requirement” applicable to the particular device. Courts have held that certain non-PMA-approved medical devices, such as tampons (Papike v. Tambrands Inc., 107 F.3d 737 [9th Cir. 1997]), and contact lens solutions (Tuttle v. CIBA Vision Corp., 2007 WL 677134 [D. Utah March 1, 2007]), meet this threshold, because specific FDA regula-tions govern the labeling of such products.

Interestingly, Congress has chosen to subject medical devices and prescription drugs to different regulatory schemes. Despite its enactment of an express preemp-tion provision for medical devices in the MDA, Con-gress has not enacted such a provision for prescription drugs. Thus, in 2009, in a case called Wyeth v. Levine (129 S. Ct. 1187 [2009]), the Court held that the FDAs approval of prescription drug labeling does not preempt a plaintiff’s state law tort suit, alleging deficiencies in the approved label.


The disparity between the medical device and pre-scription drug regulatory schemes creates possible ten-sion regarding the scope of a preemption defense in a case involving a “combination” product that combines drugs, devices, and/or biological products, such as the Silzone artificial heart valve discussed above, a drug-eluting stent or a tapered metallic spinal fusion cage. At least one court has held that where the FDA regulates a combi-nation product as a medical device, express preemption under the MDA applies (Riley v. Cordis Corp., 2009 WL 1606650 [D. Minn. June 5, 2009]). However, in the Sil-zone heart valve MDL, the court questioned, although it did not decide, whether a combination product would be subject to the MDAs express preemption provision (In re St. Jude Medical, Inc. Silzone Heart Valves Prods. Liab. Litig., 2004 WL 45503 [D. Minn. 2004]).

SCIENCE IN THE COURTROOM

When medical device lawsuits reach the trial phase, the expert witness assumes a critical role. Whether an allegedly defective medical device caused the plaintiff’s injury is an issue deemed beyond the ken of the average juror, and courts therefore require the litigants to present scientific evidence in the form of expert opinions. The courtroom, however, is a forum ill-suited to discussion of scientific principles, and the scientific evidence com-municated to jurors often fails to meet the standards of reliability our judicial system envisions.

Laypersons who lack schooling in the fundamentals of scientific inquiry are prone to biases. For instance, a layperson would be more inclined to accept coincidence as proof. As Marcia Angell, the former editor of the New England Journal of Medicine, noted, many people might find a reasonable proposition that mere temporal rela-tionship, i.e., that health complications followed breast implantation, is sufficient proof that implants caused the injuries (Angell, 1996). A scientist, on the other hand, is trained to understand that association is not causa-tion, and anecdotal reports are no substitute for scien-tific data. Studies also show that laypersons are likely to ignore epidemiological evidence, and that they have a so-called “hindsight bias,” i.e., they tend to favor facts that are more consistent with the ultimate outcome (Haskel, 2007).

The gap between a layperson’s and a scientist’s under-standing of cause and effect yawns even wider in the courtroom, because both the goals and the methods of science and litigation are at odds (Mayesh and Ried, 1986). Litigation and science employ disparate standards of proof, as well as disparate measures of causation. Sci-ence examines causative correlations in the population at large, whereas litigation asks whether a particular device caused a particular plaintiff’s injury. Moreover, litiga-tion and scientific inquiry demand quantitatively differ-ent standards of proof. Scientific inquiry seeks to establish causal relationships to a 95% degree of certainty, whereas

judicial inquiry requires only a 51% probability of cor-rectness. Under these circumstances, it is easily imaginable that a jury could determine that a systemic disease was caused by exposure to an implanted device, while a scien-tist would find the same evidence merely sufficient to sug-gest an interesting hypothesis (Mayesh and Ried, 1986b).

As a practical matter, the judicial system’s goal of timely conflict resolution would not be well-served by imposing the standards of the scientific community on the courtroom. Lawsuits must be resolved in a few years. Questions of sci-ence typically take decades of testing and data accumula-tion before repeatability can be achieved and the question thereby answered. To resolve the tension, the judicial sys-tem has fashioned a compromise by allowing juries to hear only that scientific evidence deemed by the judge to be reliable and generally accepted within the scien-tific community. In modern federal practice, this is called the Daubert standard after the US Supreme Court decision, Daubert v. Merrell Dow (509 U.S. 579 [1993]). Federal trial judges are given wide discretion to admit or preclude evidence under this standard (Mayesh and Ramallo, 2007).

The saga of DNA identification is an example of how judges serve as the gatekeepers of whether scientific evidence is allowed before the jury. Until DNA typing became generally accepted as reliable, it was not allowed into the courtroom. Now that it has been established as accepted methodology, DNA proof may be put before the jury although, of course, subject to rigorous dispute over correct methodology. This model, however, does not always prove satisfactory.

Because litigants face admissibility hurdles over sci-entific evidence, litigation-driven science has become a growing phenomenon. Fortunately, the few courts that have confronted litigation science to date have generally been skeptical of the value of these studies. For example, in In re Breast Implant Litigation (11 F. Supp. 2d 1217 [D. Colo. 1998]), the court excluded the testimony and opinions of a plaintiff’s rheumatology expert, in part, because his patients were litigants who had been referred to him. The court also excluded the testimony of the plaintiff’s biomaterials expert, in part, because the vast majority of his business came from plaintiffs involved in breast implant litigation.

Because scientific inquiry is typically characterized by a degree of uncertainty, deft litigants may succeed in cast-ing doubt upon strong scientific proof. On the other side, experts for hire are sometimes allowed to spin unproven theories in order to strengthen the inclination of jurors to assume that anecdotes are the equal of data, and asso-ciation the correlate of cause. At the conclusion of the evidence, 12 laypersons, who have listened to experts express conflicting opinions, vote on which is more per-suasive. The opinions themselves need not be held with more than a “reasonable degree” of scientific certainty, which the giver of the opinion may define as “more prob-able than not.” Although the jurors usually need to be unanimous, their measure of confidence need only reach


“a fair preponderance of the credible evidence,” mean-ing 51%. Little wonder, then, that there is a disconnect between real science and courtroom science. As the great jurist, Learned Hand, observed in the beginning of the last century: “But how can the jury judge between two statements each founded upon an experience confessedly foreign in kind to their own? It is just because they are incompetent for such a task that the expert is necessary at all” (Hand, 1902).

BIOMATERIALS ACCESS INSURANCE ACT

Plaintiffs suing the manufacturer of an allegedly defective device sometimes also join as defendants the suppliers of its raw materials and component parts. The incentive to sue a raw material supplier is particularly strong if the supplier has significant financial resources and the medi-cal device manufacturer has limited assets. For instance, DuPont, a supplier of Teflon used in TMJ implants, spent $26 million litigating more than 650 lawsuits over implants used to treat TMJ after the small manufacturer of the implants went bankrupt (Murphy, 2000). Although bulk suppliers have consistently succeeded in having suits against them dismissed, the cost of litigation can none-theless be substantial. After weighing the risk of becom-ing embroiled in expensive litigation against tiny profits derived from the medical device market, bulk suppliers began to deny manufacturers access to their products, and the United States faced a serious biomaterials short-age in the 1990s.

To address the dwindling supply of biomaterials essential for the manufacture of implantable devices in 1998 Congress passed the Biomaterials Access Assurance Act (“BAAA”). The act shields suppliers of raw materials and component parts from liability, unless the supplier is also the manufacturer or seller of the device or furnished materials or components that did not comply with con-tractual requirements or certain other specifications. Under the act, a supplier named in a lawsuit is entitled to move for dismissal immediately. Once a motion to dis-miss is filed, the supplier is excused from participation in any “discovery,” the expensive and time-consuming process by which litigants seek information from each other before trial. Limited discovery is allowed only to determine whether a supplier failed to comply with con-tractual requirements or specifications.

After dismissal from the lawsuit, the supplier may still face liability in certain, limited circumstances. After a ver-dict against the device manufacturer, the plaintiff or manu-facturer can require the supplier to pay part of the judgment if the court determines that the supplier’s negligent or intentional conduct was a cause of the plaintiff’s injury. The plaintiff may utilize this procedure if the full amount of damages cannot be recovered from the manufacturer.

Although the BAAA was enacted in 1998, there appears to be only one reported decision concerning

the act or its interpretation. In 2008, the United States District Court for the District of Colorado dismissed claims brought against a company that manufactured the femoral hip head component of a hip replacement system, because the company was not the manufacturer of the implant, was not the seller of the implant, and did not furnish raw materials or component parts that failed to meet applicable contractual requirements or specifi-cations (Whaley v. Morgan Advanced Ceramics, Ltd., 2008 WL 901523 [D. Colo. March 31, 2008]).

LIABILITY OF THE DESIGN ENGINEER

For several reasons, an individual design engineer is an unlikely defendant in medical device cases. First, plain-tiffs know that manufacturers are more likely to have the financial resources to compensate them for their injuries. Second, a plaintiff gains a “David and Goliath” tactical advantage by suing only the manufacturer, and not the design engineer. A jury will be more inclined to sympa-thize with a plaintiff if the case is viewed as a confronta-tion between a single individual and a corporate giant.

If sued, a design engineer is theoretically not immune from liability. However, the theories available to plain-tiffs are less expansive when suing a design engineer as opposed to a manufacturer. For example, courts have recognized that the policy objectives underlying strict liability would not be furthered by applying the theory of strict liability to design engineers. Courts have rea-soned that design engineers provide a professional ser-vice, and do not occupy the same superior position that allows manufacturers to discover defects and spread economic losses. Although the law of strict liability is subject to some flux and uncertainty, the great weight of judicial precedent provides a good deal of assurance that a design engineer who develops a medical device will not be held liable.

That being said, design engineers may be liable under a theory of professional malpractice, which asks whether the design engineer has exercised the degree of care rea-sonably expected in the profession. Liability will only be imposed if the design engineer is found to be at fault for failing to live up to that standard.

In addition, a design engineer can be held criminally liable if he or she is also a corporate or compliance offi-cer. For example, in U.S. v. Caputo (517 F.3d 935 [7th Cir. 2008]), an appeals court upheld the criminal convic-tions of a device designer and his assistant. They were alleged to have marketed an unapproved medical device, known as an autoclave, which left a harmful blue-green residue on brass instruments employed for procedures in the eye. Their convictions were upheld because they wore multiple hats: the device designer was also the President and CEO of the manufacturer, and his assistant was also the Vice President of Regulatory Affairs and Chief Com-pliance Officer. As a practical matter, however, a design engineer is very rarely named as a defendant.


DEVICE MARKETING AND PROMOTION

With increasing frequency, plaintiffs suing medical device manufacturers allege that the manufacturer promoted the product in an improper manner. One type of improper promotion is known as “off-label” promotion, whereby a manufacturer promotes a medical device for some other indication than that for which it has been approved by the FDA. Once the FDA has approved a medical device for marketing, a physician may prescribe it for any use, even uses not approved by the FDA. Often, such off-label use of a medical device becomes the standard of care. Nonetheless, although off-label use of medical devices by physicians is accepted and occurs frequently, device manufacturers are prohibited from engaging in off-label promotion. A medical device that is labeled or promoted for a use that has not been approved or cleared by the FDA is considered to be misbranded by the FDA.

Government scrutiny of off-label promotion is on the rise. During calendar years 2003 through 2007, the FDA issued 42 regulatory letters in response to off-label promotions requesting companies to stop dissemina-tion of violative promotions. During that same time, the Department of Justice settled 11 civil and criminal cases that involved, at least partially, off-label promotion. The settlements in these cases were for staggering amounts (Table III.2.8.1). And, although they involved pharma-ceutical companies, medical device manufacturers are certainly not immune to such investigation.

DEFENSIVE MANUFACTURING AND MARKETING

Although little can be done to prevent a plaintiff from ini-tiating a lawsuit, the best defense to a products liability suit is having manufactured a safe, well-designed prod-uct with adequate warnings. In virtually every lawsuit alleging injury caused by a medical device, the plaintiff – and eventually jurors – will have access to the manufac-turer’s internal corporate documents. These include lot histories, manufacturing specifications, results of toxi-cology and safety tests, quality assurance documents,

FDA submissions and compliance reviews, adverse event incident reports, and intracorporate memos discussing all of these, whether paper or email. The majority of these documents will have been prepared many years prior to the lawsuit, often by personnel who are no lon-ger employed by the manufacturer at the time of trial.

If the manufacturer makes the proper investment up front in designing, manufacturing, and selling the prod-uct, these documents can be the best proof that the man-ufacturer performed all necessary safety testing, that the product conformed with all government and industry standards, that no manufacturing defects occurred, that warnings and instructions for use were legally appropri-ate, and that the manufacturer complied with all regu-latory requirements for device approval. Moreover, the documents should establish that the manufacturer took appropriate post-market safety surveillance, and had adequate quality assurance systems. This includes doc-umentation that it was responsive to complaints from doctors and patients, had a method of tracking such complaints as well as resolving them, and when appro-priate, took post-market action, such as product recall and issuing revised warnings.

CONCLUSION

Very few things are certain in either law or science. How-ever, when it comes to products liability, scientists and lawyers alike can safely bet that scientists will always test and expand the limits of current technology, creative plaintiffs’ counsel will constantly be developing novel theories of liability, and defendants will be equally cre-ative in trying to rebut those claims.

BIBLIOGRAPHY

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Anonymous. (1995a). Federal jury finds acromed device unreason-ably dangerous, awards $318,000 in Reeves. Mealey’s Litig. Rep. Pedicle Screws l(17).

TaBLE I I I .2.8.1 Department of Justice Settlements 2003–2007

Company product Date Settlement amount

Serono, S.A. Serostim October 2005 $704 millionThe Purdue Frederick Company OxyContin May 2007 $634 millionBristol-Myers Squibb Abilify September 2007 $500 millionSchering-Plough Corporation Temodar and Intron A August 2006 $435 millionPfizer Neurontin May 2004 $430 millionInterMune, Inc. Actimmune October 2006 $36.9 millionEli Lilly and Company Evista December 2005 $36 millionPfizer, Inc. Genotropin April 2007 $35 millionJazz Pharmaceuticals, Inc. Xyrem September 2007 $20 millionCell Therapeutics, Inc. Trisenox April 2007 $10.5 millionMedicis Loprox May 2007 $9.8 million

ChapTEr III.2.9 Clinical Trials for Medical Devices 1443

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CHAPTER III.2.9 CLINICAL TRIALS FOR MEDICAL DEVICES

Gary L. Grunkemeier,1 Ruyun Jin,1 Lian Wang,1 and Albert Starr2

1Medical Data Research Center, Providence Health & Services, Portland, Oregon, USA2Oregon Health & Science University, Portland, Oregon, USA

INTRODUCTION

The designation “Clinical Trial” is usually interpreted to mean “Randomized Clinical Trial” (RCT), and an RCT is usually considered to be the gold standard for biomedical studies. We take the position that random-ized controls are not necessary or even the best option for many medical device studies, and that the maligned historical controls, if used in carefully designed prospec-tive observational studies, will yield as good or better information regarding the safety and efficacy of a new medical device, with advantages in the areas of gener-alizability (external validity), speed, cost, and ethical considerations.

Our experience with clinical trials for valve replace-ment, the first life-supporting device in heart surgery, runs the gamut from first-in-man, to the rapid develop-ment and implantation with significant refinements, start-ing in small numbers of patients hoping for improved performance, and finally to large-scale distribution and long-term follow-up of all patients receiving the

device – all before the US Food and Drug Administra-tion (FDA) became involved in 1974, when the Bureau of Medical Devices and Diagnostic Products was cre-ated. The FDA had the benefit of looking back at this heart valve development experience for developing guidelines for future medical devices. Also, early on before the FDA or major medical societies provided guidelines, our group had experience with randomized clinical trials of coronary artery bypass surgery (CABG). This has given us insights into the process that provides a clear perspective for the evaluation of various clinical trial methodologies. From the very beginning, surgeons and cardiologists of our team at the Oregon Health and Sciences University were allied with in-house mathematicians and statisti-cians, providing a powerful tool in pushing forward the frontiers of cardiac surgery.

Since our experience is primarily with heart valve replacement devices, we will begin by giving a brief his-tory of heart valve development. Then we will critically assess the pinnacle position customarily assigned to randomized studies in the so-called “hierarchy of evi-dence,” discuss the pragmatic view being adopted by the FDA, and the consequent alternatives to RCTs that have been advocated and used successfully for medi-cal devices (especially heart valves). Then we mention some methods that have been proposed to improve observational studies, and to make comparative studies more adaptive, and conclude the heart valve story with the latest technological breakthrough – transcatheter implantation.

http://www.gao.gov/new.items/d08835.pdf

http://www.sulzerimplantsettlement.com

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