Humanitarian Use Devices/Humanitarian Device Exemptions in cardiovascular medicine

The Second Dartmouth Device Development Symposium held in October 2004 brought together leaders from the medical device community, including clinical investigators, senior representatives from the US Food and Drug Administration, large and small device manufacturers, and representatives from the financial community to examine difficult issues confronting device development. The role of the Humanitarian Use Device/Humanitarian Device Exemption (HUD/HDE) pathway in the development of new cardiovascular devices was discussed in this forum. The HUD/HDE pathway was created by Congress to facilitate the availability of medical devices for "orphan" indications, ie, those affecting <4000 individuals within the United States each year. The HUD/HDE pathway streamlines the approval process and permits less well-characterized devices to enter the market. HDE approval focuses primarily on issues of safety and scientific soundness and does not require demonstration of efficacy. In the 7 years since the first device was approved in 1997, a total of 35 HDEs have been granted (23 devices, 6 diagnostic tests). As the costs to gain regulatory approval for commonly used devices increase, companies often seek alternative ways to gain market access, including the HUD/HDE pathway. For a given device, there may be multiple legitimate and distinct indications, including indications that meet the HUD criteria. Companies must choose how and when to pursue each of these indications. The consensus of symposium participants was for the HUD/HDE pathway to be reserved for true orphan indications and not be viewed strategically as part of the clinical development plan to access a large market.     

Developing an Action Plan for Patient Radiation Safety in Adult Cardiovascular Medicine : Proceedings From the Duke University Clinical Research Institute/American College of Cardiology Foundation/American Heart Association Think Tank Held on February 28, 2011

Technological advances and increased utilization of medical testing and procedures have prompted greater attention to ensuring the patient safety of radiation use in the practice of adult cardiovascular medicine. In response, representatives from cardiovascular imaging societies, private payers, government and nongovernmental agencies, industry, medical physicists, and patient representatives met to develop goals and strategies toward this end; this report provides an overview of the discussions. This expert “think tank” reached consensus on several broad directions including: the need for broad collaboration across a large number of diverse stakeholders; clarification of the relationship between medical radiation and stochastic events; required education of ordering and providing physicians, and creation of a culture of safety; development of infrastructure to support robust dose assessment and longitudinal tracking; continued close attention to patient selection by balancing the benefit of cardiovascular testing and procedures against carefully minimized radiation exposures; collation, dissemination, and implementation of best practices; and robust education, not only across the healthcare community, but also to patients, the public, and media. Finally, because patient radiation safety in cardiovascular imaging is complex, any proposed actions need to be carefully vetted (and monitored) for possible unintended consequences.     

An outline for public registration of clinical trials evaluating medical devices.

Public registration of clinical trials is fundamentally important to the integrity of the medical device development process. In addition to fulfilling obligations to those study volunteers, a complete record of trial results provides the general public, clinical community, and medical device manufacturers with a more accurate understanding as to how a specific therapeutic should be used. Although the issues associated with public disclosure of clinical trials are similar to the pharmaceutical industries, the iterative nature of device development introduces differences in what type of information needs to be disclosed during development and commercialization. The Second Dartmouth Device Development Symposium (3D2) held in October 2004 brought together thought leaders representing many of the stakeholders associated with medical device development. This consensus document arising from the proceedings of the 3D2 is offered to provide background to these issues and recommend pathways to implementation of device trial registration.     

An outline for public registration of clinical trials evaluating medical devices

Public registration of clinical trials is fundamentally important to the integrity of the medical device development process. In addition to fulfilling obligations to those study volunteers, a complete record of trial results provides the general public, clinical community, and medical device manufacturers with a more accurate understanding as to how a specific therapeutic should be used. Although the issues associated with public disclosure of clinical trials are similar to the pharmaceutical industries, the iterative nature of device development introduces differences in what type of information needs to be disclosed during development and commercialization. The Second Dartmouth Device Development Symposium (3D2) held in October 2004 brought together thought leaders representing many of the stakeholders associated with medical device development. This consensus document arising from the proceedings of the 3D2 is offered to provide background to these issues and recommend pathways to implementation of device trial registration.     

Developing an action plan for patient radiation safety in adult cardiovascular medicine: proceedings from the Duke University Clinical Research Institute/American College of Cardiology Foundation/American Heart Association Think Tank held on February 28, 2011

Technological advances and increased utilization of medical testing and procedures have prompted greater attention to ensuring the patient safety of radiation use in the practice of adult cardiovascular medicine. In response, representatives from cardiovascular imaging societies, private payers, government and nongovernmental agencies, industry, medical physicists, and patient representatives met to develop goals and strategies toward this end; this report provides an overview of the discussions. This expert “think tank” reached consensus on several broad directions including: the need for broad collaboration across a large number of diverse stakeholders; clarification of the relationship between medical radiation and stochastic events; required education of ordering and providing physicians, and creation of a culture of safety; development of infrastructure to support robust dose assessment and longitudinal tracking; continued close attention to patient selection by balancing the benefit of cardiovascular testing and procedures against carefully minimized radiation exposures; collation, dissemination, and implementation of best practices; and robust education, not only across the healthcare community, but also to patients, the public, and media. Finally, because patient radiation safety in cardiovascular imaging is complex, any proposed actions need to be carefully vetted (and monitored) for possible unintended consequences.     

Developing an action plan for patient radiation safety in adult cardiovascular medicine. Proceedings from the Duke University Clinical Research Institute/American College of Cardiology Foundation/American Heart Association Think Tank Held on February 28, 2011

Technological advances and increased utilization of medical testing and procedures have prompted greater attention to ensuring the patient safety of radiation use in the practice of adult cardiovascular medicine. In response, representatives from cardiovascular imaging societies, private payers, government and nongovernmental agencies, industry, medical physicists, and patient representatives met to develop goals and strategies toward this end; this report provides an overview of the discussions. This expert "think tank" reached consensus on several broad directions including: the need for broad collaboration across a large number of diverse stakeholders; clarification of the relationship between medical radiation and stochastic events; required education of ordering and providing physicians, and creation of a culture of safety; development of infrastructure to support robust dose assessment and longitudinal tracking; continued close attention to patient selection by balancing the benefit of cardiovascular testing and procedures against carefully minimized radiation exposures; collation, dissemination, and implementation of best practices; and robust education, not only across the healthcare community but also to patients, the public, and media. Finally, because patient radiation safety in cardiovascular imaging is complex, any proposed actions need to be carefully vetted (and monitored) for possible unintended consequences.     

The corporate coauthor

Drug marketing techniques include the sponsorship of articles signed by academic physicians or researchers and submitted to peer-reviewed medical journals. Some of these articles are authored or coauthored by ghostwriters who work for pharmaceutical companies or medical education companies hired by pharmaceutical companies. Conflicts of interest may be difficult to detect in the subset of articles and presentations sponsored by pharmaceutical companies that never mention the targeted drug, but focus on stimulating the perceived need for the targeted drug or highlighting problems with competing drugs. The current voluntary standards for declaring conflicts of interest to readers of medical journals and audiences at medical conferences are inadequate. A public database that contains conflicts of interest of physicians and researchers would be useful.     

The role of industry in the implantation and follow-up of devices: a practitioner's perspective

Implantable cardiac rhythm management devices continue to get more technologically complex at a pace that is difficult for most clinicians to keep up with. We have come to rely heavily on industry representatives to provide technical expertise during device implantation and follow-up. Concern has been raised about the involvement of medical device industry representatives in the clinical environment. Guidelines have been published that acknowledge the importance of device industry representatives in providing technical expertise and assistance, while also clarifying the role these representatives should play in patient care. The main principles from published policy statements are summarized, emphasizing that the physician remains responsible for the patient's overall care as well as device function and programming.     

Proposed guidelines for housestaff interaction with pharmaceutical companies

The relationship between the medical profession and the pharmaceutical companies is complex, since industry depends on physicians for research and development, and for sales of its products. As a result, physician interactions with industry could undermine the patient-centered medical ethic, and jeopardize the physician-patient relationship. There is evidence that physicians are influenced by their encounters with the pharmaceutical industry. Particularly troubling is the increasing interaction of pharmaceutical companies and housestaff through detailing and educational support. Several studies have documented the pervasiveness of such relationships in training programs. Although professional bodies have developed criteria to help physicians in their dealings with the pharmaceutical industry, no principles have yet been formulated to address the unique aspects of resident contact with pharmaceutical companies. Guidelines designed to answer this need are proposed in this article.     

Economic Implications of Potential Changes to Regulatory and Reimbursement Policies for Medical Devices

Objective

To evaluate the impact of regulatory scenarios on the financial viability of medical device companies.

Design

We developed a model to calculate the expected net present value of a hypothetical product throughout preclinical development, clinical testing, regulatory approval, and postmarketing. We tested 3 scenarios: (1) the current regulatory environment; (2) a scenario in which medical devices are subject to the same evidence standards required for pharmaceuticals; and (3) a scenario consistent with the Coverage with Evidence Development: Coverage with Study Participation (CSP) policy proposed by the Centers for Medicare and Medicaid Services, whereby Medicare will pay for beneficiaries to receive new devices that are not currently determined to be “reasonable and necessary” if the patients participate in clinical studies or registries.

Measurements and Main results

When applying assumptions consistent with the implantable cardioverter-defibrillator market, the net present value at the start of development was an estimated $553 million in the current regulatory environment, $322 million in the pharmaceutical scenario, and $403 million in the CSP scenario. Sensitivity analyses showed that the device industry would likely be profitable in all 3 scenarios over a range of assumptions.

Conclusions

The environment in which the medical device industry operates is financially attractive. Furthermore, when compared with the alternative of applying the same evidence standards for pharmaceuticals to medical devices, the CSP policy offers improved financial incentives for medical device companies.

     

Biomedical Device-Associated Infections in Surgical-Critical Care Patients

ISSUE: Each year, over 8000 medical devices enter the U.S. market. A small number of these devices fall within the high-risk (class III) category, requiring careful FDA review. The explosive growth of the biomedical device industry has lead to several problematic issues for infection control practitioners, including implementation of appropriate surveillance strategies and development of effective interventional practices reducing the risk of infection.PROJECT: This project was developed as an educational exhibit, discussing the microbial etiology, pathogenesis, and risk factors associated with infection in biomedical devices. The exhibit would serve as a focus for discussion of device-related infections in both surgical and critical-care patients. In addition to identifying the scientific basis for infection, the exhibit was developed as a vehicle for reviewing specific evidence-based strategies for reducing device-associated infectious complications.RESULTS: The exhibit was presented at hospital-staff venues involving nursing and medical/surgical clinical practitioners. An effort was made to incorporate specific patient-care episodes within selected case discussions. Following review of this exhibit, the healthcare professionals were able to: 1) identify major microbial pathogens associated with biomedical device-associated infections in high-risk patients, 2) discuss the microbial pathogenesis and risk factors associated with device-associated infections and 3) identify strategies for prevention and management of biomedical device-associated infections.LESSONS LEARNED: The rapid increase in the development and implementation of new invasive biomedical technologies requires that infection control practitioners become familiar with these innovative devices, the risk factors predisposing infection, and appropriate interventional strategies to reduce the risk of infection in surgical/critical care patient populations.     

On the need for probity when physicians interact with industry

Physicians are expected to practice scientifically sound medicine, to be critical of industry claims, and to be immune from making clinical decisions biased by commercial sponsorship and marketing. The reality, as argued in this article, is that much of medical research, in its conduct and reporting, is distorted by commercial interests and that physician decision-making remains vulnerable to the effects of subliminal commercial promotion which has the potential to create conflicts of interest, or perceptions thereof, and undermine public trust. Research is presented that may encourage physicians to view recently revised Royal Australasian College of Physicians (RACP) guidelines on the ethical relationships between the medical profession and industry as an attempt to deal with such conflicts in protecting our authority and standing within the community.     

Trial registration for public trust: making the case for medical devices

Recently, several pharmaceutical companies have been shown to have withheld negative clinical trial results from the public. These incidents have resulted in a concerted global effort to register all trials at inception, so that all subsequent results can be tracked regardless of whether they are positive or negative. These trial registration policies have been driven in large part by concern about the pharmaceutical sector. The medical device industry is much smaller, and different from the pharmaceutical industry in some fundamental ways. This paper examines the issues surrounding registration of device trials and argues that these differences with pharmaceutical should not exempt device trials from registration.     

Remote Monitoring of Patients With Implanted Cardiac Devices

Three different types of implantable cardiac devices are now commonly used in clinical medicine: pacemakers (including cardiac resynchronization systems), cardiac defibrillators, and loop recorders. Although pacing specialists and electrophysiologists have traditionally been responsible for device follow‐up, the newest generation of implanted devices stores a wealth of information that can be useful to the clinical cardiologist. Important information, in addition to device function, such as incidence and type of arrhythmias, general clinical condition of the patient, and hemodynamic status can now be stored on large databases that are available via web access to all physicians caring for an individual patient. The advent of the remote monitoring capability of implanted devices has initiated a rapidly accelerating paradigm shift in device follow‐up that can potentially improve patient care at lower cost. Copyright © 2010 Wiley Periodicals, Inc.     

Hand-carried ultrasound improves the bedside cardiovascular examination

OBJECTIVES: We assessed the clinical utility of hand-carried cardiac ultrasound (HCU) devices to assist physicians in the diagnosis of cardiovascular disease. MATERIALS AND METHODS: We reviewed 42 articles published from 1978 to 2004. RESULTS: The capability and simplicity of the HCU device assist physicians in the diagnosis of cardiovascular disease at the initial patients contact. HCU is particularly useful in the setting of emergency or critical care, community screening, or in remote areas with limited access to health care. CONCLUSION: The inherent limitations of the physical examination as well as the reduced focus and training in physical diagnosis of current and recent medical school graduates has set the stage for the HCU device to modify traditional medical practices by complementing the physical examination with real-time cardiovascular imaging.     

Impact of expanding indications on the safety of pacemakers and defibrillators

The number of patients living with a pacemaker or implantable cardioverter defibrillator (ICD) increased markedly during the 1990's. Expanding device indications and increasing device sophistication has important implications for patient and device safety. While the FDA is responsible for assessing the safety and efficacy of medical devices, manufacturers, physicians, patients, medical professional societies, and legislators will all play a role in ensuring that medical device patients continue to receive safe, quality medical care.     

More than a device: today's medical technology companies provide value through service

When physicians implant cardiac rhythm management devices, they establish a long-term relationship with those devices and with the manufacturers of those devices. The therapeutic value that each device will provide to its patient is enhanced throughout the life of the device by the services that the manufacturer provides. Services are provided prior to, during and long after implantation. Services include physician and allied health professional training, quality assurance programs, therapy outreach initiatives, on site technical support during device implantation and follow-up, technical service expertise and customer service support. The costs of these services are substantial. When assessed on a per device basis, the service costs may actually exceed the costs of manufacture. Further, the costs of these services are rising. Over the past five years, the number of implanted cardiac rhythm management devices has doubled. Industry field forces have tripled in size. Clearly, industry is dedicated to providing service as a critical element in achieving excellent patient outcomes.     

Advances in remote monitoring of implantable pacemakers,cardioverter defibrillators and cardiac resynchronization therapy systems

Unlike the standard quarterly or semi-annual direct ambulatory device interrogations procedures, state-of-the-art implantable electronic cardiovascular devices (IECD) enable their wireless remote interrogation and monitoring, and automatically send reports and special alerts on a daily basis. This allows physicians to respond more proactively to changes in patient or device status, more appropriately triage patient care, and more efficiently perform the post-implant ambulatory follow-ups. This review presents the-state-of the-art technology of remote IECD monitoring and summarizes the main clinical observations published through June 2008. Cardiovascular remote monitoring systems made by several manufacturers are currently in various phases of development, clinical investigation, and medical applications. Data collected in several completed and ongoing studies strongly suggest that this new technology will make important contributions, particularly with respect to the facilitation of IECD follow-ups, enhancement of patient safety and quality of life, and lowering of medical costs. Further technological advances and a more clear understanding and appreciation of the clinical and economic benefits of telecardiology, will likely increase sharply the use of remote IECD monitoring in upcoming years.     

Physician-industry relations. Part 1: individual physicians

This is part 1 of a 2-part paper on ethics and physician-industry relationships. Part 1 offers advice to individual physicians; part 2 gives recommendations to medical education providers and medical professional societies. Physicians and industry have a shared interest in advancing medical knowledge. Nonetheless, the primary ethic of the physician is to promote the patient's best interests, while the primary ethic of industry is to promote profitability. Although partnerships between physicians and industry can result in impressive medical advances, they also create opportunities for bias and can result in unfavorable public perceptions. Many physicians and physicians-in-training think they are impervious to commercial influence. However, recent studies show that accepting industry hospitality and gifts, even drug samples, can compromise judgment about medical information and subsequent decisions about patient care. It is up to the physician to judge whether a gift is acceptable. A very general guideline is that it is ethical to accept modest gifts that advance medical practice. It is clearly unethical to accept gifts or services that obligate the physician to reciprocate. Conflicts of interest can arise from other financial ties between physicians and industry, whether to outside companies or self-owned businesses. Such ties include honorariums for speaking or writing about a company's product, payment for participating in clinic-based research, and referrals to medical resources. All of these relationships have the potential to influence a physician's attitudes and practices. This paper explores the ethical quandaries involved and offers guidelines for ethical business relationships.