BB&T Staff Writer and Staff Reports

The latest round in an ongoing dispute between Boston Scientific (Natick, Massachusetts) and Cordis (Miami Lakes, Florida), a Johnson & Johnson (J&J; New Brunswick, New Jersey) company, could put the so-called stent wars to rest – for a while at least. Cordis reported the companies reached a settlement and that Boston Scientific was slated to pay $1.73 billion to J&J.

This particular set of stent disputes date back nearly seven years ago and covers Boston Scientific's Jang patent and J&J's Palmaz and Gray patents. Under the agreement, Boston Scientific paid out $1 billion by the close of business on Feb. 1, with the remainder to be paid by Jan. 3, 2011. Nearly $800 million of this would come from cash on hand and another $200 million would come from Boston Scientific's credit facilities, according to an article in the Wall Street Journal.

The settlement could turn out to be one of the largest in recent med-tech history, said Larry Haimovitch, president of Haimovitch Medical Technology Consultants (Mill Valley, California) and a regular contributor to BB&T. But he stressed that he wasn't sure whether this was in fact the largest patent litigation settlement.

“I'd be surprised if there was [a larger settlement] Haimovitch,“ told BB&T. “Clearly this is going to have a negative effect on [Boston Scientific's] ability to do acquisitions in the future.“

Haimovitch noted that the company was just beginning to get back on the acquisitions trail after a brief hiatus. He said J&J generated $13 billion in free cash flow and paid out $5 billion in dividends in fiscal 2009, and that cash on hand for the company is at $15 billion while the company has $8 billion in debt.

“So the net cash is $7 billion,“ Haimovitch told BB&T. “That puts this settlement into a little more perspective.“

Some analysts have surmised that J&J would use the settlement to acquire new companies. A spokesperson for the company contacted by BB&T would not speak to those rumors. “[The settlement] is going to add to our net cash position,“ Carol Goodrich, a spokeswoman for J&J told BB&T.

In a statement Boston Scientific President/CEO Ray Elliot called the settlement “substantial“ but necessary. “It resolves major litigation without exposing Boston Scientific to the uncertainties of a jury trial and a potential damages award that was impossible to predict,“ Elliot said in the release. “In the past year, we have significantly reduced the volume of outstanding litigation, having now settled 17 lawsuits with J&J, as well as disputes with other competitors and the government.“

The settlement comes nearly two weeks after Boston Scientific won its own round in another long-running dispute, when a federal judge declared four of the J&J patents invalid. And last fall, Boston Scientific agreed to pay J&J $716 million to settle a little more than a dozen other patent infringement suits.

There are several stent patent cases still pending between med-tech companies. Between Jan. 1, 2004, and Aug. 13, 2008 there were more than 20 lawsuits involving Medtronic (Minneapolis), all of which deal with patents. Boston Scientific has also been named as part of more than 20 patent lawsuits in that time. Of that number for Boston Scientific, eight were filed in the first eight months of 2008, according to Justia.com, a database of legal news. Boston Scientific recently settled patent claims with Medtronic, and last year, Medtronic said it would pay $400 million to Abbott (Abbott Park, Illinois) to settle patent litigation over stents.

FDA eyes huber design after Class I recall

The voluntary January recall of GlucoPro glucose needles and syringes by Nipro Medical (Miami) wasn't the only bad news the manufacturer received in the first month of 2010. FDA and the firm unveiled a potentially bigger concern with the announcement that Nipro and distributor Exelint International (Los Angeles) are withdrawing two million huber needle kits made by Nipro in an action that FDA has hinted calls into question the design of this type of device.

According to an FDA statement, the non-coring huber needle made by Nipro has demonstrated a marked propensity to slice cores out of intravenous ports upon insertion, said to have occurred at a rate of 60%-72% in tests conducted at the firm's plant in Japan. The problem is thought to affect huber needle sets made by other manufacturers as well, even though agency spokespersons declined to state which other firms' products might have shown a similar tendency to produce cores.

Mary Brooks, a senior regulatory specialist at the Office of Surveillance and Biometrics at the Center for Devices and Radiological Health, said on a conference call that the huber design has been in play for nearly three decades. “They started being manufactured and cleared“ by FDA starting in 1983, she said, although another FDAer on the call noted that the design was patented in 1946.

Despite the urgency of the recall, FDA staff on the conference call acknowledged that they are unaware of any injuries that can be directly attributed to the problem. This marks the second time in recent weeks that FDA has announced a full market withdrawal of a device despite lack of information of adverse events that could be directly tied to the device in question. The first of these was the pullback of the SS1 sterilizer made by Steris (Mentor, Ohio), a sterilizer that was said to have incorporated substantive changes to the design without FDA clearance. In that instance, FDA forced Steris to withdraw even those units with the original cleared configuration.

Tim Ulatowski, director of the Office of Compliance at CDRH, said when FDA “became aware of the results of the [Nipro] testing, we held meetings with several manufactures of the huber needles,“ to find out if the coring problem was widespread. FDA asked 20 manufacturers, whom Ulatowski did not name, to respond to a set of questions regarding manufacturing and testing processes. Several other manufacturers' designs were said to have incurred coring, although Ulatowski declined to elaborate. Nipro is said to have contacted FDA about the issue.

Brooks said the MAUDE database includes more than 800 reports regarding incidents involving huber sets, a list which includes reports of leakage of infusion fluids and five reports related to damage to the septum of the intravenous port. Brooks said there are no reports of foreign bodies entering a patient's body as a consequence of coring, but the agency also hypothesizes that potential problems include inadequate drug delivery.

“Currently we do not have any studies that can validate our research,“ Brooks acknowledged, but part of FDA's concern is the potential for “a tremendous amount of under-reporting“ of such events.

NIH pushes for colorectal cancer screening

There is no such thing as a good cancer, but the epidemiology of colorectal cancer (CRC) suggests that it should be high on the list of diseases slated for a targeted attack. Hence, the National Institutes of Health published a report last week recommending a set of measures to improve screening for CRC, although the paper acknowledges that capacity is an issue.

The NIH paper reminds the reader that 150,000 Americans are diagnosed annually and that one third that number lose their lives each year. Screening rates for the population of interest – those aged 50 and older at average risk for the disease – rose sharply between 1997 and 2008, but the increase from 20%-30% at the beginning of that period to nearly 55% two years ago is seen as a positive trend in need of encouragement.

NIH asserts that screening for CRC is underused, but also argues that a registry is needed to evaluate the appropriate use of screening in general and the various modes for performing CRC check-ups. The NIH paper recommends that financial barriers – such as co-pays and other cost-sharing mechanisms – be eliminated and that studies be conducted to evaluate the various strategies for prompting screenings. However, the current capacity for the various modalties will support screening for those over the age of 50 only if fecal occult blood testing is the primary method for performing those checks.

The fecal occult blood test (FOBT) is perhaps the easiest way to screen, given the low invasiveness and current guidelines suggest annual screening via this method. Despite this, the NIH report states that colonoscopy is now “the most widely used screening test“ despite recommendations that it be used only every five years, thanks in part to a coverage decision rendered by the Centers for Medicare & Medicaid Services in 2001. Prior to then, the NIH paper notes, FOBT and flexible sigmoid colonoscopy were the two dominant approaches, but the popularity of the latter was diminished by the CMS coverage decision regarding colonoscopy. NIH also notes that the double-contrast barium enema “has fallen out of favor“ since 2001 as well.

CT colonography is technologically ready for prime time, but CMS recently concluded that extant data do not support this technology's use as a screening tool, a decision that generated mixed reviews. All the same, this modality is recommended for performance at five-year intervals after the age of 50, a frequency matching that for sigmoidoscopy and double-contrast barium enemas.

The guidelines for colonoscopy call for such an exam once per decade, according to the American Cancer Society-U.S. Multi-Society Task Force. The U.S. Preventive Services Task Force (USPSTF) currently offers no recommendations for CT colonography or double-contrast enema, but essentially agrees with the ACS-led group on the other recommendations. USPSTF offers no recommendation fecal DNA exams, which the other group offers only a limited suggestion of testing at no specific intervals after the age of 50.

As for the capacity question, the NIH paper states that even if FOBT were more widely used, any positive results would have to be checked with colonoscopy, an observation that applies to the other first-line approaches as well. The document observes that there is “substantial uncertainty that current colonoscopy capacity would be sufficient“ if the current screening guidelines were widely observed. By some accounts, this deficit could be made up within a decade, although sigmoidoscopy could largely fill the gap in the interim.

NIH recommends an effort to track screening via “an infrastructure for capturing information,“ which could be modeled on the Breast Cancer Surveillance Consortium. The paper also suggests that research go toward establishing which factors are most effective at prompting patients and doctors to prescribe and obtain a screening, and recommends that capacity be addressed with studies of demand and capacity “across geographic areas“ as well as “research assessing various options for expanding the supply of providers.“

Modalities may benefit from radiation scrutiny

As is widely known, FDA has unveiled an initiative to reduce excess exposure to radiation, but at least some physicians are of the view that the general concern about overexposure is overblown. Still, the agency's new emphasis on safety may hold a silver lining for makers of imaging equipment that do not rely on ionizing radiation to produce diagnostic images.

FDA announced the new emphasis in early February, which was fueled by reports of burns during CT brain perfusion scans conducted at Cedars Sinai Medical Center (Los Angeles), a situation that may have resulted in patients getting up to eight times the recommended dosage. According to the agency's Feb. 9 statement, the initiative is focused on CT scans, X-ray fluoroscopy, and procedures that depend on the use of radioactive dyes.

The agency states that these procedures “are the greatest contributors to total radiation exposure within the U.S. population and use much higher radiation doses than other radiographic procedures,“ a list that includes standard medical and dental X-rays and routine mammography procedures. According to FDA, a CT scan of the abdomen incurs “the dose from approximately 400 chest X-rays.“

The physician community is clearly not united behind the idea that ionizing radiation is exerting a profound or large-scale effect on the health of Americans. For example, several physicians who spoke at last year's edition of Transcatheter Cardiovascular Therapeutics are of the view that whatever the risk of such imaging, the benefits are far greater and that there is little in the way of data to suggest a systemic problem.

Jeffrey Shuren, MD, director of the Center for Devices and Radiological Health, remarked in the agency's statement, “the amount of radiation Americans are exposed to from medical imaging has dramatically increased over the past 20 years“ and said the agency's objective “is to support the benefits associated with medical imaging while minimizing the risks.“ The statement acknowledges “some disagreement over the extent of the cancer risk associated with exposure to radiation from medical imaging,“ but nonetheless makes the argument that there is “broad agreement that steps can and should be taken to reduce unnecessary radiation exposure.“

The FDA document notes that managing the risks of imaging procedures “depends on two principles of radiation protection,“ described as “appropriate justification for ordering and performing each procedure, and careful optimization of the radiation dose used during each procedure.“

FDA wants manufacturers “to incorporate important safeguards into the design of their machines, to develop safer technologies and to provide appropriate training to support safe use by practitioners.“ Examples of this include dose alerts, and data systems that record and transmit total dosage to the patient's electronic health record and to a national registry. The agency also announced a two-day public meeting on March 30-31, “to solicit input on what requirements to establish.“

The agency states that it and the Centers for Medicare and Medicaid Services “are collaborating to incorporate key quality assurance practices“ into accreditation requirements for imaging facilities and hospitals, intended to “improve the quality of oversight and promote the safe use of advanced imaging technologies in those facilities.“

In an e-mailed statement, Michael Graham, MD, President of the Society for Nuclear Medicine (Reston, Virginia), told BB&T that the association's members are “concerned about overdosing with radiation,“ which he said is one of the reasons why “we insist on quality across all diagnostic imaging procedures.“ He also said that SNM, along with several other organizations, seek to “create national standards for certification and licensure of all nuclear medicine professionals, including physicians and technologists.“

Graham also said the issue “emphasizes the urgency for Congress to pass the CARE (Consistency, Accuracy, Responsibility and Excellence in Medical Imaging and Radiation Therapy) bill, which would ensure that patients receive the same level of care at all accredited facilities nationally.“