A new study published in the British Medical Journal is reigniting the debate over mammography as a screening tool. Lead author Dr. Phillipe Autier looked at historical data from 1980 to 2006 to determine the impact of screening mammography on breast cancer-related mortality in six European countries. The greatest decrease in mortality over this 26 year period was seen in women ages 40 to 49. However, there was not a correlation between decreases in mortality and the availability of screening mammography in these countries. Accordingly, the authors have concluded that there is no impact on breast cancer mortality as a result of screening mammography. Rather, the authors infer that improved treatments for breast cancer and efficiencies in healthcare are more likely responsible for this decrease.
This and other studies published on the efficacy of screening mammography seem at odds with new recommendations from the American College of Obstetrics and Gynecology (ACOG). This week, ACOG released updated guidelines recommending screening mammography annually for all women over 40. ACOG revised its earlier recommendations of annual screening at 50 due to new evidence that more aggressive tumors have shorter sojourn times (time from detection to symptoms) in women under 50, and that reductions in mortality due to screening are similar for women in their 40s and 50s. ACOG emphasizes the importance of communicating the risk of false positives to women receiving screening mammography as this risk increases with more frequent imaging. This high false positive rate is also referenced in the widely-discussed USPSTF guidelines from 2009 that recommend biennial screening at age 50.
This issue is likely to lead to increasing consumer confusion regarding the effectiveness in screening mammography at lowering the rate of mortality for breast cancer. Therefore, it is imperative that providers are open about the risk of false positive exams with patients. While many in the radiology community are concerned about the number of unnecessary exams, ACOG notes that many patients are aware of this risk and are well-adept at coping with anxiety that results from biopsies and other downstream procedures.
Alternatively, using more specific screening technology, such as tomosynthesis, may help to decrease breast cancer-related mortality. Some radiologists suggest using breast MRI to screen for all patients, though it is already plagued by a high false positive rate and will be prohibitively expensive for many providers (and payers). Tomosynthesis promises to improve on the recall rate from screening mammography though it is not yet clear if this will reduce the number of breast cancer related deaths over a long period of time.
As vendors release new products and upgrades to existing technology it will become increasingly difficult to determine the relative effectiveness of each product. Research cannot keep pace with innovation so it will be left to individual physicians and hospitals to determine the relative merits of each new tool.
Technology Insights is continuing to track the screening mammography pipeline to provide up-to-date guidance on right-fit investments in the ever-changing breast imaging market.
In light of recent incidences of excessive radiation exposure, the FDA has issued an advisory to medical imaging providers to discontinue use of the CardioGen-82 rubidium isotope generator for myocardial PET imaging studies. The CardioGen-82 rubidium chloride injection generator has since been voluntarily recalled by the vendor, Bracco Diagnostics.
This news comes on the heels of recent reports and a public advisory issued by the FDA regarding two incidences of patients receiving radiation exposures in excess of expected thresholds when using the CardioGen-82 generator for myocardial PET imaging studies. According to the FDA's announcements, and coverage in trade websites Health Imaging and AuntMinnie, the risks associated with the excessive exposure are expected to be minimal and on par with cumulative exposure from other cardiac imaging studies; the two patient exposures are estimated to be approximately 90 mSv - approximately 30 times the average exposure for CardioGen-82 myocardial PET imaging procedures. Given the FDA's determination the manufacturing procedures for the CardioGen-82 generator are not sufficient for ensuring the "reliable performance of the generator used to produce the Rb-82 chloride injection," the vendor, Bracco Diagnostics, has since voluntarily recalled the CardioGen-82 generator, and is actively working with the FDA and regulatory agencies to determine the exact cause of the excessive exposure. However, questions still linger regarding whether the excessive exposures are the result of a manufacturing flaw or appropriate quality control techniques at clinical sites using the Rb-82 chloride injection system. In the interim, providers are encouraged to use alternative isotopes or different cardiac imaging studies when clinically appropriate. In a July 15 advisory when the incidences were first identified, the FDA presents a detailed description of steps patients and providers should take in determining and mitigating potential risks associated with CardioGen-82 use.
This comes as a roadblock to the use of myocardial PET imaging for perfusion and viability imaging, which has received a considerable amount of attention over the past 18 months. Rubidium-82 is the principal radiotracer used to evaluate myocardial perfusion with PET. Evidence of superior clinical efficacy for obese patients relative to traditional cardiac nuclear imaging, as well as growing coverage for the use of cardiac PET following equivocal SPECT studies, has led to greater awareness of the value of cardiac PET imaging. But, interest and adoption in cardiac PET has been spurred by market factors, including declining reimbursement for cardiac nuclear imaging (particularly office-based procedures), the worldwide technetium radioisotope shortage, and greater desire to maximize the use of hospital-based PET/CT scanners.
Previously, cardiac PET imaging has been slow to develop given the entrenched practice patterns of cardiologists with standard cardiac nuclear imaging, fluctuating reimbursement, and the hefty price tags associated with monthly rental of the rubidium-82 generator - often upwards of $25,000 - rendering breakeven on the investment challenging. Further, adoption of cardiac PET can both generate new procedure volume and cannibalize from existing cardiac nuclear imaging studies, rendering it a strategic, programmatic investment for hospitals to support comprehensive cardiovascular services.
At this time, it is unclear when the FDA and Bracco Diagnostics will lift the recall of the CardioGen-82 generator system. Providers are encouraged to stay tuned to new developments and communications from the vendor and the FDA regarding future use for Rb-82 PET imaging.
After a unanimous panel vote, the Berlin Heart Excor Pediatric VAD is expected to receive humanitarian device exemption (HDE) from the FDA. This technology--a bridge-to-transplant, pneumatic blood pumping ventricular assist device intended for use in children with isolated left ventricular or biventricular dysfunction--is currently the only option for patients with severe heart failure (HF) who are awaiting transplant. The Berlin Heart can provide children with extended time before a needed heart transplant, thereby decreasing mortality rate and increasing survival rate.
In the device's trial, 48 patients age 16 or younger received either the Excor or extracorporeal membrane oxygenation (ECMO), the standard of care at present for pediatric patients awaiting a heart transplant. While ECMO patients demonstrated between 66 and 75 percent survival rates depending on cohort (as determined by body surface area), Excor patients showed survival rates between 86 and 92 percents. These dramatic differences between groups led panelists to vote in favor of the Berlin Heart VAD despite significant adverse event rates among these patients: adverse events such as bleeding incidents or infections occurred in 85 percent of study patients overall, and nearly 30 percent suffered a stroke.
Nevertheless, when compared to current therapy, FDA members agreed that these risks were worth the added benefit to survival. Devices such as the Berlin Heart Excor--the only option of their kind--can significantly improve pediatric cardiology treatment, given that the average wait for a heart transplant can exceed four months and the current ECMO survival timeframe is only two weeks. While further, targeted studies are needed for this technology, panelists are hopeful for its potential to impact pediatric survival and mortality.
GAITHERSBURG, Md.-- On Wednesday, July 20, the FDA's Circulatory System Devices Panel voted 9-0, with one abstention, that the FDA approve Edwards Lifesciences' Sapien valve, a first-in-class device offering inoperable patients with severe aortic stenosis, albeit well enough to benefit from valve replacement, a treatment alternative for the first time. Specific items on which the panel voted included: effectiveness (9-2 in favor), safety (7-3 in favor), and whether the procedure's benefits transcended its associated risks (9-0 in favor). The panel did not, however, have the opportunity to change their questions or re-vote as has been done in past panels. Nonetheless, the majority of the panel concluded that the Sapien heart valve displayed "reasonable assurance" of overall safety and effectiveness in this patient population.
This favorable recommendation for SAPIEN came after more than 10 hours of presentations, discussions, debate, and myriad questions, where a packed house of physicians, clinical experts, industry members, and consumers alike remained on the edge of their seats for the duration of the day. Top-of-mind topics for discussion included persistent concerns around stroke and vascular complications in the PARTNER trial, physician and site training protocols (e.g. the need for a multidisciplinary heart team), the need for a national data repository for all patients (e.g. a nationwide TAVI registry), as well as the importance of post-market surveillance for careful assessment of the device's safety and effectiveness in all patients. Off-label use and patient selection concerns were likewise identified and discussed as critical concerns relating to the device's commercial approval in the United States.
Particular controversy emerged over discussion of a subset of continued access patients who received TAVI following the conclusion of the trial. Questions from the panel focused on clearly defining mortality rates for this small subset population, in which deaths for patients receiving TAVI appeared to be higher than patients administered standard therapy. One panelist, Dr. John Somberg from Rush University Medical Center (Chicago, IL) cited this concern over data as the rationale for his abstention from voting in favor of recommending TAVI for FDA approval.
The debate over patient selection also took center stage in panel discussions, with committee members calling attention to the potential for widespread dissemination of the device in non-surgical patients deemed inappropriate for device implantation. Though lower than the mortality rate for standard therapy patients in the PARTNER trial, the mortality rate for TAVI patients raised the question of not only, "Can you?" implant the device for non-surgical patients, but, "Should you?" Structuring clearly defined patient selection criteria to set not only "the floor" but "the ceiling" for patients unable to receive traditional aortic valve surgery will be critical to successful patient outcomes, as one panelist pointed out.
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A new robot, the Amadeus system, may give Intuitive Surgical a run for its money in the near future. The Amadeus system, which is manufactured by Titan Medical Inc. (Toronto, Canada), would make an interesting addition to the robotics market, which has and continues to be dominated by Intuitive Surgical, the maker of the da Vinci robot.
Titan Medical recently posted on its website the first batch of concept designs for the Amadeus (see below).
Concept Design for the Amadeus surgical robot (Titan Medical Inc., Canada)
According to announcements made by the company at the end of Q1, initial testing of the robot's beta console were recently completed and its makers are happy with the testing's "encouraging results." The company has also disclosed that the Amadeus system will be using arms made by Kuka Robot Group, an international company based in Germany. Among the features of this lightweight arm (pictured below), which will weigh only 14 kg, is that it includes seven degrees of freedom (DOF). This is the same number of DOF as Intuitive's da Vinci.
Lightweight robotic arm (KUKA Robotic Group, Germany)
Despite all this progress, Titan Medical's Amadeus appears to be still several years away from complete development. Still, as far as competition for Intuitive's da Vinci is concerned, the Amadeus seems to be one of the more developed systems out there and may be the closest competitor da Vinci has for now.
Amid the great promise of new cutting-edge technologies comes the responsibility of introducing them appropriately to ensure the right patients receive the right care from the most qualified providers. Such is the perspective of the American College of Cardiology Foundation and Society of Thoracic Surgeons, who jointly released an expert consensus overview regarding the adoption of transcatheter valve therapy, in particular, transcatheter aortic-valve implantation (TAVI). This is especially important for not simply addressing the promise of the likely soon-to-be-approved technology, but instead to provide context for the core programmatic elements which need to be in place to succeed with the new technology.
Published in the June 27, 2011 edition of the Journal of the American College of Cardiology, authors Dr. David Holmes, president of ACC, and Dr. Michael Mack, president of STS, shed light upon the many fundamental components of TAVI use which will impact diffusion of the technology into clinical practice. According to the authors, and as described in a recent article from theheart.org, it is not common practice to release consensus papers before the technology has been granted commercial approval for sale and use. However, given the clinical promise and impact TAVI may have on certain patients with significant structural heart disease, the societies believed it appropriate to release the overview not to "answer all the unanswered questions associated with TAVI but to set out what those should be."
The authors detail seven necessary components for the successful introduction of transcatheter valve therapy, including:
- Specialized, regional heart centers with highly qualified and experienced multidisciplinary physicians and paramedical personnel
- The development of professional multidisciplinary "heart teams", consisting of primary cardiologists, cardiac surgeons, interventional cardiologists, cardiac imagers, and heart failure specialists, among many other support personnel
- Proper procedures, protocols, and facilities, including modified cardiac cath labs and "hybrid" operating suites
- The development and active participation on comprehensive databases and registries which can effectively, and seamlessly, like clinical and administrative data to assess long-term quality and cost-effectiveness
- The development and ongoing use of scientific literature to apply evidence-based practice to the use of TAVI for specific indications and patient types, with primary focus on determining candidates for the procedure relative to other, more established alternatives
- The creation and adherence to standardized protocols for patient management
- Appropriate ongoing personnel training to establish and maintain clinical competency
From the expert consensus document, it is highly apparent many of these responsibilities fall to both hospital and CV administrators, as well as the physicians themselves, in establishing and fostering a collaborative environment to succeed with catheter-based valve therapies, both with respect to patient management and technology implementation.
As previously reported, the FDA is set to review the first transcatheter valve on July 20, 2011. Technology Insights will continue to keep you abreast of any updates.
Last week, a group of spine specialists reported that the clinical research that has supported the widespread adoption of Medtronic's bone morphogenic protein product, InFuse, is misleading and biased. The main analysis, which was led by editors of the The Spine Journal, found a systematic failure to report serious complications with Infuse in 13 industry-sponsored studies. The researchers found complication rates that were 10 to 50 times greater than the estimated complication rates revealed in the peer-reviewed medical literature. Reported side effects include male sterility, infection, bone loss and unwanted bone growth.
The editors of The Spine Journal also charged that researchers with financial ties to Medtronic overstated the product's benefits with inadequate reporting of associated risks. Additionally, the authors claimed that conflicts of interest were either not reported or were unclear in the various studies. The 13 papers reviewed in The Spine Journal were co-authored by doctors who received a median of at least $12 million to $16 million per study from Medtronic, the journal reported.
In response to these findings, Medtronic chairman and CEO Omar Ishrak stated that he strongly continues to back the safety profile of Infuse. He states that while The Spine Journal questions the findings in peer-reviewed literature, the journal does not find faults in the data submitted to the FDA in 2002 for the approval of this product. To that end, Ishrak maintains that InFuse remains safe for use in the identified indications on the product's label.
The analyses in the current issue of The Spine Journal followed another investigation in late May which linked Infuse to retrograde ejaculation, a cause of infertility. According to FDA records, it was found that in the primary clinical trial which led to the approval of product in 2002, five of the 78 men treated with InFuse developed the retrograde ejaculation compared to 1 of 68 men who received the standard hip bone graft. The physicians involved in the study contended the sterility complication was caused by the surgical technique as opposed to InFuse, which is why the sterility data was not included in the published papers. However, other physicians accuse these researchers of "cherry-picking" the results and maintain that all serious complications should be listed in published papers, regardless of what is believed to be the cause.
Medtronic's InFuse remains the primary product in the BMP/biologics market to date and is estimated to be used in approximately one quarter of all spinal fusions performed in this country every year.
The latest news from The Spine Journal follows a slew of negative press Medtronic has received this year for its class of bone growth products. Despite receiving recommendations for approval last year, the FDA refused to approve Medtronic's Amplify rhBMP-2 Matrix, a bone graft product for use in posterolateral spinal fusions, earlier this year due to possible cancer risks associated with the product. With recent Department of Justice investigations on BMP, insurance pushback on overuse, and this recent data on InFuse, the impact on Medtronic and the market for bone growth products remains to be seen.