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Real-world data (RWD) and real-world evidence (RWE) are becoming essential tools for informing regulatory decision making in health care and offer an opportunity for all stakeholders in the healthcare ecosystem to evaluate medical products throughout their lifecycle. Although considerable interest has been given to regulatory decisions supported by RWE for treatment authorization, especially in rare diseases, less attention has been given to RWD/RWE related to in vitro diagnostic (IVD) products and clinical decision support systems (CDSS). This review examines current regulatory practices in relation to IVD product development and discusses the use of CDSS in assisting clinicians to retrieve, filter, and analyze patient data in support of complex decisions regarding diagnosis and treatment. The review then explores how utilizing RWD could augment regulatory body understanding of test performance, clinical outcomes, and benefit-risk profiles, and how RWD could be leveraged to augment CDSS and improve safety, quality, and efficiency of healthcare practices. Whereas we present examples of RWD assisting in the regulation of IVDs and CDSS, we also highlight key challenges within the current healthcare system which are impeding the potential of RWE to be fully realized. These challenges include issues such as data availability, reliability, accessibility, harmonization, and interoperability, often for reasons specific to diagnostics. Finally, we review ways that these challenges are actively being addressed and discuss how private-public collaborations and the implementation of standardized language and protocols are working toward producing more robust RWD and RWE to support regulatory decision making.

This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled “The Role of Endpoint Adjudication in Medical Device Clinical Trials”. The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence.

The Interregional New Technologies Committee (INTC) is one evaluation route for new medical technologies or technologies with expanded indications within Kaiser Permanente (KP). The primary focus of the INTC is to consider all available published evidence on a particular technology, surgical technique, or implantable device for a specific clinical indication and provide a recommendation on the sufficiency of the evidence for determining net medical benefit to Permanente Medical Group leaders and Kaiser Foundation Health Plan management throughout KP Regions. This iterative process provides an objective, evidence-based assessment to inform decision making by physicians and support the most appropriate care for KP members. This overview illustrates the INTC process and how it supports clinical decision making using implantation of laparoscopic adjustable gastric bands (LAGBs) as an example. In February 2011, the US Food and Drug Administration (FDA) approved lowering the acceptable body mass index for the Lap-Band from 35 to 30 kg/m(2) for patients with at least one comorbid condition. It is difficult to find published studies on medical technologies that have been recently approved by the FDA. The manufacturer often submits clinical data to the FDA, but details are frequently not publicly available at the time of approval. The LAGB example demonstrates the complex issues addressed by the INTC, particularly when there is some evidence of short-term improvement in outcomes with a medical device but little if any confirmation of long-term safety or effectiveness.

For several years, the Southern California Chiefs of Radiology explored various technology options to improve the efficiency of after-hours services. Until 2002, on-call radiologists at each of the 11 medical centers provided after-hours radiology services for their local Emergency Departments (ED) in Kaiser Permanente Southern California (KPSC). This process had been in place for many years and reflected the medical group's political structure (essentially 11 separate groups of radiologists). The time lag between when a radiologist received a page and when s/he arrived at the medical center produced inevitable delays in providing radiology consultations to EDs. In most cases, the radiologist was needed only to provide image interpretation, not to perform the exam. The Chiefs discussed a variety of options, including providing each on-call radiologist with the ability to view exams and transmit interpretations from home. This and other potential solutions did not prove to be feasible for various reasons, including: concern over the quality of images viewed on home computers, the challenge of remotely supporting a variety of home systems and the Southern California Permanente Medical Group compensation structure. After much discussion, the Chiefs, with the support of administration, elected to implement a teleradiology system that would station a radiologist in a central location to provide image interpretation for CT, MRI and ultrasound exams from 7:00 pm to 7:00 am seven days a week for all KP Southern California medical centers. “Wet read” reports would be communicated via fax to the referring ED. However, when working out the final details of the implementation, two important changes were made. First, the single central location plan was abandoned. The radiologists strongly preferred an alternative option that provided the ability to access the teleradiology studies from any of KPSC's 11 medical centers. This alternative permitted each teleradiologist to work from his/her home medical center, or another if more convenient. This change was made due to concerns about the willingness of radiologists interested in working a teleradiology shift to travel to a central location (for example radiologists who normally worked in San Diego to travel more than 125 miles to Pasadena). Doing so offered the advantage of having the teleradiologist work in a familiar setting, using familiar equipment and traveling no more than for a typical workday. Second, the plan to communicate the teleradiologist's findings via fax was replaced by a Web application that would provide the ability to track a request for teleradiology services throughout the entire process, as well as communicate the findings to the referring site.

This article describes our initial experience with intraoperative infusion of the fibrinolytic agent streptokinase. Five patients with various complications of atherosclerosis manifested by limb-threatening ischemia were treated by balloon-catheter thromboembolectomy followed by intra-arterial streptokinase infusion. In each patient viability of the involved extremity was questionable after removal of all thrombus accessible to the balloon catheter. Fibrinolytic therapy was used when operative arteriography showed residual thrombus distal to the popliteal artery. All patients were systemically heparinized during the operation, and three patients were maintained on anticoagulants during the initial postoperative period. A streptokinase solution containing 750 U/ml was infused intra-arterially proximal to the residual thrombus. The total dosage ranged from 20,000 to 100,000 units per patient. This treatment was considered successful in all five patients, as documented by return of palpable pulses, audible Doppler flow signals where none was present prior to infusion, and operative arteriography. There were no complications related to intraoperative streptokinase infusion. We conclude that intraoperative fibrinolytic therapy is a safe adjunct to catheter thromboembolectomy. The observed improvement in limb perfusion can be attributed to lysis of thrombus in the distal arteries that could not be retrieved with the balloon catheter. Laboratory studies are in progress to establish precise indications for intraoperative streptokinase and to determine the most effective dosage and rate of administration (J VASC SURG 1985;2:319-26.)