Regulatory Framework for Clinical Decision Support Software: Present Uncertainty and Prospective Proposition

US regulators have been slow to provide meaningful guidance to industry participants on the issue of clinical decision support (CDS) software. It is crucial that regulators soon clarify the differences between regulated medical devices and unregulated health management software that nevertheless has the potential to affect patient care. Future CDS regulation in the United States should aim to reduce ambiguity by establishing detailed and simple criteria for manufacturers to use in deciding if a CDS product will be regulated. Clear standards will help ensure the safety of CDS that is brought to market. In addition, clarification will facilitate technological innovation, delivering clinical benefits to needy patients. To this end, the regulatory framework implemented in the United States with respect to CDS should consider the “substantial dependence” standard.     

Regulatory and reimbursement challenges for molecular imaging

Molecular imaging is being hailed as the next great advance for imaging. Since molecular imaging typically involves the use of specific imaging probes that are treated like drugs, they will require regulatory approval. As with any drug, molecular imaging probes and techniques will also require thorough assessment in clinical trials to show safety and efficacy. The timeline for the regulatory approval will be long and potentially problematic because of the mounting costs of obtaining final regulatory approval. The current article is a detailed review of the regulatory and reimbursement process that will be required for molecular imaging probes and techniques to become a widespread clinical reality. The role of molecular imaging in the therapeutic drug discovery process will also be reviewed, as this is where these exciting new techniques have the potential to revolutionize the drug discovery and development process and, it is hoped, make it less costly. [(18)F]fluoro-2-deoxy-2-D-glucose positron emission tomography, one of the first molecular imaging techniques to be widely used, will be used as an example to illustrate the process of obtaining eventual reimbursement for widespread clinical use.     

Impact of the European Clinical Trials Directive on academic clinical research

With the adoption of the Clinical Trials Directive it was Europe's intention to make the performance of multi-national clinical trials in Europe easier through the harmonization of the regulatory procedures. As the Directive was mainly conceived to facilitate the performance of multi-national clinical trials to develop new drugs, it is to be determined to what extent academic clinical trials will be concerned by the Directive and more importantly what will be its impact on daily academic clinical research. Contrary to several national regulations the scope of the Directive is very large only excluding non-interventional trials. This implies that most of the academic clinical trials will be concerned by the Directive. Besides the handling of the regulatory procedures in the different countries, issues related to insurance, labeling requirements and provision of the investigational medical products will expose the academic sponsor to additional administrative and financial challenges that will have to be handled appropriately, as the academic sponsors will be controlled by Inspectors regarding their compliance with the new regulations to come.     

Use of personal digital assistants for retrieval of medical images and data on high-resolution flat panel displays.

For its new acute care hospital, the University of California at Los Angeles is evaluating innovative technology involving high-resolution flat panel display devices configured as "network appliances" that can be wall mounted for use in the retrieval and display of medical images and data. Physicians and healthcare providers can log on with wireless handheld computers, which can serve as an identification device as well as a navigational tool for selecting patient records and data. These data are displayed and manipulated on the flat panel display without the need for a keyboard or mouse. A prototype was developed with commercially available image display software, which was modified to allow the remote control of software functions from a handheld device through an infrared communication port. The system also allows navigation through the patient data in a World Wide Web-based electronic patient record. This prototype illustrates the evolution of radiologic facilities toward "shareable" high-quality display devices that allow more convenient and cost-effective access to medical images and related data in complex clinical environments, resulting in a paradigm shift in data navigation and accessibility. Copyright RSNA, 2003.     

(68)Ga-labeled peptides for clinical trials - production according to the German Drug Act: the Göttingen experience

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials. AIM, METHODS: As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission. RESULTS: During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection. CONCLUSIONS: The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.     

Regulation of medical devices in radiology: current standards and future opportunities

Today's radiology community depends heavily on cutting-edge diagnostic and therapeutic medical devices to serve patients. These products are regulated by the U.S. Food and Drug Administration (FDA) under a system that grants marketing approval for only those indications for which the safety and effectiveness have been established. Although this complex system is the result of a societal decision to ensure device safety and effectiveness, it has the potential to delay product marketing and impede innovation. Medical device regulation recently has undergone major changes with the enactment of the Food and Drug Administration Modernization Act of 1997 (FDAMA), legislation that is intended to increase system efficiency while retaining the requirement of safety and effectiveness. However, many of the envisioned improvements cannot occur without cooperative interaction between stakeholders in the device development process, including the FDA and the clinical medicine community. The radiology field must continue to build on its strong history of productive dialogue with the FDA to transform the legislative vision of FDAMA into regulatory reality. Such action will ensure timely access to the new device technologies that are necessary for the growth of our specialty and the effective care of our patients.     

An introduction to the food and drug administration and how it evaluates new devices: Establishing safety and efficacy

Most physicians, and certainly the lay public, have only limited knowledge of the responsibilities and limits of the Food and Drug Administration (FDA) of the United States of America. Although laws as early as 1902 protected the public from unrestricted sale of unsafe drugs, it was not until 1976 that devices came under regulation. An obvious difference existed between regulatory control of drugs vs devices. The drug-based approach for evaluation was rejected in favor of a new system based on device class and its degrees of risk. The premarket notification process (510K), and the premarket approval application (PMAA) became the regulatory pathway for device approval. The investigational device exemption (IDE) became the mechanism for established safety and efficacy. Occasionally conflicts exist between industry and the FDA. Submission of poorly planned studies wastes FDA resources whereas prolonged approval times can be devastating to the small single product business that creates the majority of our new devices. A compromise is obviously necessary if we are to maintain our premier identity as a new device entrepreneurial center and avoid industry’s migration to countries where the regulatory standards might be less rigid     

Off-label use of contrast agents

When contrast agents are approved, the label describes the approved indications and particular circumstances of use such as age, organ function or pregnancy. The use of contrast agents outside their labelled indications is increasing, namely with contrast agents used for MRI. The aim of this paper is to improve the knowledge about this topic. The basis for off-label use is the physician’s prerogative, which finds its basis in the “Declaration of Helsinki”. Off-label use is allowed under special conditions and might be even the medical state of the art. The necessity for off-label use will continue to increase for MR-contrast agents, as the regulatory requirements for approval of new indications continuously increase, and clinical trials for registration purposes are quite costly and time consuming. As a consequence, manufacturers will concentrate on clinical studies for the essential indications.     

穿戴式健康监测设备的现状与未来

智能手机与移动通信技术的迅速发展,为穿戴式健康监测提供了发展机遇。穿戴式健康设备能够监测用户的重要生理信号,通过手机接入移动通信网或互联网进行数据远程传送或共享,从而实现医学监护并降低医疗成本。本文概述了穿戴式健康设备的发展现状,指出穿戴式医疗发展机遇与风险挑战并存,并展望了其发展趋势。     

Lasers and light sources for PDT: past, present and future

The more recent use of Photodynamic therapy in Oncology dates to the early 1970’s, when Dr. Thomas J. Dougherty, began his investigations into the mechanisms and clinical uses hematoporphyrin derivative (HpD). Since then the therapy has found its way through the regulatory process in numerous countries throughout the world. In many of these locales as it was in the United States, this was the first drug device approval, for oncology, that had been undertaken and ultimately approved, by the regulatory agencies in the respective countries. Throughout this time changes occurred in the formulation of HpD as well as the development of other photosensitizers. The more difficult aspect, however, of this modality has been the availability of reliable, affordable and appropriate devices for the production and delivery of light to the targeted areas. In the last 10 years, however, there has been a slow yet improving landscape in the development of devices for PDT that ultimately will provide the impetus for greater acceptance of PDT in the medical community.     

Radiologic diagnosis and management of complications related to central venous access

Central venous access is an important aspect of medical treatment. There are different designs of access devices for different purposes. In essence, they can be classified as short- and long-term devices. Insertion procedures vary for different devices. There is a risk for both acute and delayed complications. Radiology plays a central role both in placement and in device management. Image-guided insertion increases technical success and reduces the rate of acute complications. The diagnostic approach to long-term complications includes radiography, fluoroscopy, CT, and ultrasound. Treatment by interventional procedures is possible for a number of these conditions. These interventions increase device lifespan and reduce the number of necessary reinsertions.     

Unified reconstruction framework for multi-modal medical imaging

Various types of advanced imaging technologies have significantly improved the quality of medical care available to patients. Corresponding medical image reconstruction algorithms, especially 3D reconstruction, play an important role in disease diagnosis and treatment assessment. However, these increasing reconstruction methods are not implemented in a unified software framework, which brings along lots of disadvantages such as breaking connection of different modalities, lack of module reuse and inconvenience to method comparison. This paper discusses reconstruction process from the viewpoint of data flow and implements a free, accelerated, extensible Unified Reconstruction Software Framework (URSF). The software framework is an abstract solution that supports multi-modal image reconstruction. The goal of this framework is to capture the common processing work flow for different modalities and different methods, make the development of reconstruction for new devices much easier, and implement a set of popular reconstruction algorithms, so that it is convenient for researchers to compare against. The overall design and certain key technologies are introduced in detail. Presented experiment examples and practical applications commendably demonstrate the validity of this framework.     

Barriers and facilitators to conducting radiotherapy clinical trials: Findings from a UK survey

IntroductionAs an essential component of service delivery, radiotherapy clinical trials were championed within the NHS England service specifications. A call for a 15% increase in research and clinical trial activity, alongside a demand for equity of access for patients with cancer subsequently ensued. National understanding of current radiotherapy clinical trials operational practices is absent, but essential to help establish the current provision required to support the development of a strategic plan for implementation of NHS England's specifications.MethodsA cross-sectional survey was developed by a multi-disciplinary team and distributed to therapeutic radiography clinical trial leads across the UK to ascertain the current provision of radiotherapy clinical trials only, including workforce resources and the trials management processes to establish a benchmark and identify potential barriers, enablers, and opportunities to increase access to clinical trials.ResultsThirty-two complete responses were obtained equating to 49% of the total UK NHS departments and 74% of those departments invited. Four key findings were identified: 1) research strategy and systems, 2) participation and activity in radiotherapy clinical trials, 3) access to clinical trials at alternative departments and 4) facilitators & barriers. Overarchingly a lack of radiotherapy clinical trials strategy or supported processes were apparent across the UK, aggravating existing barriers to trial activity.ConclusionIt is essential for radiotherapy clinical trials to be embedded in to departmental and Trust strategy, this will help to ensure the processes and resources required for trial delivery are not only in place, but also recognised as imperative and important for patients with cancer as radiotherapy treatment delivery.Implications for practiceFailure to address the barriers or build upon the facilitators may result in UK radiotherapy departments facing challenges in achieving the 15% increase in radiotherapy clinical trial activity.     

Medical workstations for applied imaging and graphics research

We present a medical workstation for the efficient implementation of research ideas related to image processing and computer graphics. Based on standard hardware platforms the software system encompasses two major components: A turnkey application system provides a functionality kernel for a broad community of clinical users working with digital imaging devices, including methods of noise suppression, interactive and automatic segmentation, 3D surface reconstruction and multi-modal registration. A development toolbox allows new algorithms and applications to be efficiently implemented and consistently integrated with the common framework of the turnkey system. The platform is based on an elaborate object class structure describing objects for image processing, computer graphics, study handling and user interface control. Thus expertise of computer scientists familiar with this application domain is brought into the hospital and can be readily used by clinical researchers.     

Endovascular coiling of cerebral aneurysms using "bioactive" or coated-coil technologies: a systematic review of the literature

SUMMARY: Second-generation coils have been available since 2002. We wanted to assess their performance and appraise available evidence. Therefore we performed a systematic review of the literature from 2002 to 2007. There were 27 studies with a total of 2390 patients that met pre-specified inclusion criteria. All studies were classed as having a high risk of bias. There were no randomized trials and for most studies results were not independently assessed and follow-up periods were short (mean 7 months). There were large differences in demographic and aneurysm characteristics, making comparisons between coil cohorts difficult. Procedure-related morbidity and mortality were similar for all coil types. Hemorrhagic events during follow-up were few, in the range of 1%/year for all coil types. The available literature is of poor quality and clinical series provide very little evidence in favor of second-generation coils. Positive randomized trial results are needed to justify routine clinical use. This systematic review illustrates the failure of the industry, the regulatory authorities, and the neurointerventional community combined to provide a reliable and prudent approach to the introduction of new devices.     

Regulatory compliance associated with contrast media

A basic understanding of the role of regulatory agencies in governing the healthcare environment and their influence over contrast media use is required of radiographers and imaging administrators to meet the many standards of compliance. In addition, radiology management teams must consider cost effectiveness, departmental efficiency, workplace safety, and compliance in choosing to implement new products. Regulatory agencies may be classified into 2 groups, voluntary and involuntary. Involuntary agencies are governmental agencies mandating regulatory compliance by local, state, or federal laws. Voluntary agencies are precisely that, those agencies an institution voluntarily chooses to participate with, to demonstrate the quality of care they provide. Failure to follow involuntary regulatory guidelines or to participate in voluntary best practice standards jeopardizes patient safety and the quality of care provided, and exposes the institution and the individual to liability risks. Severe penalties may result from a failure to maintain regulatory compliance, including the possibility of large fines, criminal indictments, and loss of third-party reimbursement. Achieving regulatory compliance is never an easy venture with the number of regulatory agencies and standards needing to be addressed. Combining regulatory compliance with the effects of doing business provides quite a challenge for today's imaging departments. A solid knowledge base in regulatory standards along with continuous investigation of new standards will allow departments to evaluate their own processes involved in providing patient care. Recognition of areas of high risk/high volume, including contrast media use, will assist in directing the departments' focus appropriately. A thorough evaluation of the products used and their respective handing and administration, in regard to patient and workplace safety, and appropriate documentation of workplace injuries due to contrast media packaging, will assist in maintaining a high level of compliance.     

Embolic protection in carotid artery stenting: new options

Carotid artery stenting (CAS) has emerged as an attractive alternative to carotid endarterectomy (CEA) in patients with carotid disease who are at high risk for CEA. With increasing experience and improved technique, results in CAS patients have improved consistently over time in several clinical trials. Carotid stenting is clearly not inferior to CEA in appropriately selected high-CEA-risk patients treated by experienced operators. With improving results, CAS now has the potential to be considered "front-line therapy" even in standard-risk CEA patients, as demonstrated in CREST and as being studied in ongoing trials, such as the ACT I trial. Successful, low-risk CAS can only be performed if distal embolization is minimized during this procedure. This can be accomplished only with appropriate patient and case selection, adequate operator training and experience, and meticulous attention to procedural detail. Embolic protection devices (EPDs) are an important cornerstone of low-risk CAS. There are well-established, study-validated embolic protection systems available for CAS. Four new EPD options have been introduced in the United States over the past 3 years. Results with these newer devices appear to be extremely promising, with low event rates seen in high-risk clinical patients. This article will offer a practical review of techniques to decrease distal embolization during CAS. We will review patient selection and provide a "cookbook" approach to procedural technique, emphasizing techniques unique to each of the various EPD systems currently available. We will also introduce the newer options in EPDs, provide practical tips on their use, and contrast their use and results with that of the existing EPD systems. We will provide practical procedural techniques that incorporate the use of various EPDs into strategies that will reduce distal embolization during CAS and also provide pertinent data referencing results of these devices seen in clinical trials.     

Molecular imaging research in the outcomes era: measuring outcomes for individualized cancer therapy

Advances in molecular imaging, combined with the goal of personalized cancer therapy, call for new approaches to clinical study design for trials testing imaging to guide therapy. The role of cancer imaging must expand and move beyond tumor detection and localization to incorporate quantitative evaluation of regional tumor phenotype. Imaging study design and outcome analysis must move beyond metrics designed to measure the performance for detection to include measures of prognosis, prediction of therapeutic success, and early therapy response. This implies a need for different approaches to cancer imaging clinical trials and changes in their regulatory oversight. Demonstration that a biochemical or molecular imaging method correctly and accurately measures a specific biologic feature should be sufficient for approval for clinical trials. It may be possible that a combination of imaging procedures known to accurately depict tumor phenotype may be prognostic, even if the individual study cannot be directly validated against patient outcomes. Therefore, it will be important to be able to apply a range of possible imaging studies to different targeted cancer therapy trials. Academia and industry must work together with regulatory agencies and payers to facilitate well designed clinical studies, with appropriate outcome measures, to test the effectiveness of imaging in helping to direct cancer therapy. These will ensure the appropriate use of imaging to direct treatment and make an important step towards individualized cancer therapy.     

The Air Medical Leadership Congress: setting the health care agenda for the air medical community

BACKGROUND: Emergency air medical transport provides the means for critically ill or injured patients to rapidly access sophisticated medical flight teams and medical centers. However, issues such as surging emergency medical services helicopter accidents, expected pilot and nurse shortages, falling reimbursements, and new compliance regulations are now threatening these important but expensive transport services. Unless an industry strategy can be developed to address these and other threats, many medical flight programs may be forced to curtail the availability of these lifesaving services. PURPOSE: On September 4-6, 2003, air medical leaders, experts, program managers, providers, and users of emergency air medical services gathered in Salt Lake City, Utah, to discuss and formulate recommendations to address the top issues that threaten the future of air medical transport services. This congress was open to anyone engaged in the field of air medical transport. This historic meeting resulted in a plan to enhance transport safety, foster appropriate utilization, improve in-flight medical care, maximize cost and reimbursement effectiveness, and develop strategies to reduce the adverse effects of new regulatory and compliance mandates. OBJECTIVES: This article describes the significance of the Air Medical Leadership Congress and the 10-Point Plan method used to develop it.     

A searchable medical implant database for safety in the medical resonance environment

Implanted medical devices can present significant, life-threatening hazards in the magnetic resonance environment. Ascertaining the specific hazards of individual devices when a patient presents for investigation can be time consuming. Ready access to the results of previous searches for information is therefore valuable in a busy department. Data on 352 implantable devices have been collated over more than 10 years and incorporated into a searchable database. Issues surrounding sharing this data are discussed.