Innovation in Health Care: Time for a Gut Check

Skin in the Game: An Analysis of Venture Capital Investment in Dermatology from 2002 to 2021

Engaging Early-Career Physicians in Medical Device Innovation and Entrepreneurship.

Bringing New Technologies to Market: Hurdles and Solutions

The past 60 years have witnessed fundamental advances in our understanding and treatment of cardiovascular disease, prolonging and improving patients' lives. Central to these improvements has been the introduction of medical devices, including mechanical and biological heart valves, heart rhythm devices, and balloon angioplasty and stents. The introduction of these technologies has been dependent on an entrepreneurial medical device sector, coupled with an equally robust infrastructure to clinically develop and evaluate these new technologies. After approval and commercialization, continued study of device performance under “real world” conditions is crucial to ensure that the clinical potential is being realized. Central to a healthy medial device “ecosystem” is a robust regulatory system. Regulators must ensure that a device performs reliably and is adequately characterized, allowing physicians and patients to use it appropriately. Determining if/when a device is appropriate for approval is difficult and challenging and requires balancing its safety-efficacy profile. The technical sophistication required to make these determinations has grown as device complexity has grown. The stakes are very high, as illustrated by the recent Fidelis AICD lead recall, affecting 268 000 patients worldwide.1 These safety concerns must be balanced by the harm inflicted by withholding beneficial technology from patients. There is wide variation in how devices are regulated among countries with well-developed health care delivery systems, for example, the United States and Europe as well as Japan and Canada. The recent Food and Drug Administration (FDA) approval of the Sapien Transcatheter Heart Valve has brought these differences into sharp focus. In this commentary, we review the differences between the US and European Regulatory systems and how they have affected the investigational and approval process. ### Sapien Transcatheter Heart Valve: A Case Study On November 2, 2011, the Sapien Transcatheter Heart Valve (TAVR), manufactured by Edwards Lifesciences, was approved by the US FDA.2 The approval of the Sapien …

The development and introduction of new medical devices have radically changed the practice of medicine. No area of medicine has been affected more than cardiology, with new devices facilitating the effective treatment of coronary artery disease (percutaneous coronary interventions [PCIs]/stents), valvular heart disease (mechanical and bioprosthetic valves), and electrophysiological disorders (pacemakers and automatic implantable cardiodefibrillators). In addition to fueling the growth of the medical device industry, this explosion of technology has driven the development of new medical subspecialties, eg, interventional cardiology and electrophysiology. Other areas of medicine, including orthopedics and general surgery, have witnessed similar transformations. The current regulatory pathway for a significant-risk first-in-class medical device is typically a long, expensive, and risky process, culminating in a pivotal trial designed to demonstrate safety and efficacy. The pivotal trial phase is typically the most time-consuming and costly phase of the process. In the United States, medical devices are regulated by the Center for Devices and Radiological Health at the Food and Drug Administration (FDA), which has been charged by Congress to seek the “least burdensome means” when determining the scope of data required to evaluate the safety and efficacy necessary for device approval.1 Thus, pivotal trials by intention are designed to select patient cohorts most likely to demonstrate procedural benefit while limiting patient/study subject risk within the shortest time frame that can provide meaningful data. The realities of logistics, time, and resources limit the size and duration of most new device trials to 800 to 1500 patients, limiting the power of these trials to detect events with an occurrence rate of <1%. Furthermore, pivotal trials are conducted by the most experienced physician operators at medical centers with sufficient patient volume and research infrastructure to recruit and conduct clinical studies. Some have questioned whether results obtained under these settings from such …

ObjectiveMedical device industry payments to healthcare organisations (HCOs) can create conflicts of interest which can undermine patient care. One way of addressing this concern is by enhancing transparency of industry financial support to HCOs. MedTech Europe, a medical device trade body, operate a system of disclosure of education payments to European HCOs. This study aimed to characterise payments reported in this database and to evaluate the disclosure system. MethodsAn observational study of education-related payments to HCOs reported by the medical device industry in Europe was conducted. Data was manually extracted from transparentmedtech.eu. The primary outcome variable is the value of the payments, overall, and for each year, payment type, and country. The accessibility, availability and quality of the database was also analysed, using a proforma with 15 measures. ResultsOverall, 116 medical device companies reported education-related payments in 53 European and non-European countries, valuing over €425 million between 2017 and 2019, increasing in value between 2017 and 2019, from €93,798,419 to €175,414,302. Ten countries accounted for 94% of all payments and ten companies accounted for 80% of all payments. The accessibility, availability and quality of the database rated low for six measures, medium for six measures, and high for three measures. ConclusionThere is a large amount of education-related payments from medical device companies to European HCOs, creating substantial potential for conflicts of interest. MedTech Europe's disclosure system has many shortcomings. A European-wide publicly mandated disclosure system for both the medical device and pharmaceutical industries should be introduced. Public interest summaryThe medical device industry pay healthcare organisations (e.g. hospitals) large amounts of money. Industry states that this money is to help pay for healthcare professionals’ education. However, these payments can have a negative impact on healthcare professionals’ decision-making. This study sought to examine a website run by MedTech Europe, a representative body for the medical device industry, which outlines details of some of these payments (www.transparentmedtech.eu). Our analysis found that between 2017 and 2019 the medical device industry made ‘education’ payments valuing €425 million to healthcare organisations in Europe. We also assessed how comprehensive and user-friendly the database was and found a range of issues. For example, the database is not downloadable and some other important types of payments, such as payments for consultancy, are not included. We concluded that a mandatory database for both the medical device and pharmaceutical industry run by the European Union, would significantly improve transparency.

A surgeon’s perspective regarding the regulatory, compliance, and legal issues involved with physician-modified devices

Translational medicine and the National Institutes of Health road map: Steep grades and tortuous curves

The brave new world of artificial intelligence: dawn of a new era

The combination of medicine and engineering is a new interdisciplinary subject, which is a mode of cross integration and collaborative innovation between medical science and engineering. The combination and collaborative innovation of medicine and industry means more about the improvement, innovation and R&D of medical devices. However, the combination of traditional industry with biomedical engineering, modern medical imaging technology, electronic information technology and other high-tech in medical device industry is a reflection of the manufacturing industry and high-tech level of a country. The development mode of medical industry integration and collaborative innovation in China is mainly to merge medical colleges and universities with science and engineering colleges, promote the cross of different departments, and set up biomedical engineering specialty under the support of a series of relevant national policies, relying on large-scale comprehensive hospitals and research institutes, establish numerous research centers of translational medicine, thus achieving a series of achievements. Our team has made some explorations in the practice of the combination of medicine and engineering, including the utility model patent "reusable simple anal expander" and "incision protective cover of transanal multi-channel endoscopic surgery operation platform", which have been authorized by the State Intellectual Property Office, meanwhile the ultra-fine laparoscope, intragastric gasbag and other projects have been demonstrated by relevant research and development teams and are to be transformed into production. On January 10, 2020, with the approval of Guangdong Pharmaceutical Association, the Medical Innovation and Transformation Expert Committee of Guangdong Pharmaceutical Association was established jointly with the representatives of medical colleagues, scientific research institutions and enterprises, who are interested in the combination of medical industry and collaborative innovation. This Committee provides a platform for the exchange of medical colleagues, scientific research institutions and enterprises. We realize that clinical practice is the source of the combination of medical workers and collaborative innovation, and clinicians are the driving force of the combination of medical workers and collaborative innovation. At present, the main problems faced by the development of medical industry integration in China are as follows: insufficient integration of medical industry integration disciplines in the basic research stage; less interaction of clinical application needs in the application research stage; difficult transformation of scientific research achievements; the unconnected whole chain of "production, learning, research and application". If we can increase the investment in scientific research and policy incentives, strengthen the communication and interaction with enterprises, pay more attentions to the social and economic benefits of the promotion of achievements, open the whole process of the combination of medicine and industry, and improve the evaluation mechanism of the innovation ability of such combination, combination of medicine and engineering and collaborative innovation in China will enter the golden period of rapid development.

The high cost of capital for firms conducting medical research and development (R&D) has been partly attributed to the government risk facing investors in medical innovation. This risk slows down medical innovation because investors must be compensated for it. We propose new and simple financial instruments, Food and Drug Administration (FDA) hedges, to allow medical R&D investors to better share the pipeline risk associated with FDA approval with broader capital markets. Using historical FDA approval data, we discuss the pricing of FDA hedges and mechanisms under which they can be traded and estimate issuer returns from offering them. Using various unique data sources, we find that FDA approval risk has a low correlation across drug classes as well as with other assets and the overall market. We argue that this zero-beta property of scientific FDA risk could be a main source of gains from trade between issuers of FDA hedges looking for diversified investments and developers looking to offload the FDA approval risk. We offer proof of concept of the feasibility of trading this type of pipeline risk by examining related securities issued around mergers and acquisitions activity in the drug industry. Overall, our argument is that, by allowing better risk sharing between those investing in medical innovation and capital markets more generally, FDA hedges could ultimately spur medical innovation and improve the health of patients.

The high cost of capital for firms conducting medical research and development (R&D) has been partly attributed to the government risk facing investors in medical innovation. This risk slows down medical innovation because investors must be compensated for it. We analyze new and simple financial instruments, Food and Drug Administration (FDA) hedges, to allow medical R&D investors to better share the pipeline risk associated with FDA approval with broader capital markets. Using historical FDA approval data, we discuss the pricing of FDA hedges and mechanisms under which they can be traded and estimate issuer returns from offering them. Using various unique data sources, we find that FDA approval risk has a low correlation across drug classes as well as with other assets and the overall market. We argue that this zero-beta property of scientific FDA risk could be a main source of gains from trade between issuers of FDA hedges looking for diversified investments and developers looking to offload the FDA approval risk. We offer proof of concept of the feasibility of trading this type of pipeline risk by examining related securities issued around mergers and acquisitions activity in the drug industry. Overall, our argument is that, by allowing better risk sharing between those investing in medical innovation and capital markets more generally, FDA hedges could ultimately spur medical innovation and improve the health of patients.

Evaluating consumer and clinical sleep technologies: an American Academy of Sleep Medicine update

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Background Biopharmaceutical products have become an important sector of the pharmaceutical industry in the United States (U.S.). This fast-growing sector is in a critical position in which therapeutic biological products represent over a third of all new drugs in clinical trials or awaiting approval from the U.S. Food and Drug Administration (FDA) (International Trade Administration, n.d.). The development and review of a new therapeutic biological product is a complex process that requires considerable monetary and time investment. This process takes, on average, twelve years, and the estimated average cost of taking a new drug from concept to market exceeds $1 billion (Van Norman, 2016a). After the significant expenditure of manufacturer time and resources, many drugs fail to achieve FDA approval late in the process. Criticism has arisen from the fact that the increasingly complex regulatory environment and expense associated with drug development have caused a lag in the release of new pharmaceuticals to the drug market. Advocacy groups and experts in the area are demanding a more rapid approval and release of new products because they consider the current process to be risk averse, slow, and inefficient (Ty Williams, 2016; Van Norman, 2016a). The FDA has created programs to expedite the approval of drugs and biological products (FDA, 2018). Despite all of these efforts, FDA scrutiny remains a long, costly, and risky process. The goal of this work is the exploration of the factors and gaps relevant to the FDA review and approval process which contribute to process inefficiencies, as well as proposed methods and solutions to address such gaps. Review Findings Researchers who investigated the FDA review and approval operations have identified challenges and constraints in the process (e.g. Baylor, 2014; Conner et al., 2014; Kinch, 2016; Ty Williams, 2016; Van Norman, 2016a, 2016b). Van Norman (2016a) and Ty Williams (2016) emphasizes that the main challenges for the pharmaceuticals are in terms of cost and time. Complexities in the flow of information and the communications network have been identified due to the fact that the process involves multiple FDA resources and constant communication with the applicant. Additionally, complexities could arise from the review team not only having to deal with the flow of new submissions but also with the flow of resubmitted applications, which puts a strain on FDA normal operations by having to share resources between both types of submissions. Other relevant challenges are in terms of bias due to the user fees collected from sponsors and drug manufacturers to support the drug approval process (Ty Williams, 2016) and lack of transparency of non-published drug trial data (Van Norman, 2016b). The review of methods and solutions to address such challenges and constraints has identified a lack of research activity in studying the approval process from the regulatory agency point of view (i.e. from FDA internal operations). Most research efforts are directed toward the incorporation of modeling tools to the drugs development and production practices (e.g. Gernaey &amp; Gani, 2010; Horner, Joshi, &amp; Waghmare, 2017). Reform models to the current FDA review and approval process have been published with the purpose of providing flexible approaches to change the way medical products are brought to market (Thierer &amp; Wilt, 2016; Williams, Joffe, &amp; Slonim, 2016; Klein &amp; Tabarrok, 2016; Conko &amp; Madden, 2000; Gulfo, Briggeman, &amp; Roberts, 2016). The implementation of any of these reform models may imply a shift in the responsibilities of the FDA and therefore may change the organizational structure of the regulatory agency – something that must be addressed and measured for effectiveness. Conclusions Suggesting changes to the review and approval of therapeutic biological products is a challenging task. To the best of our knowledge, none of the academic articles identified in this scoping review have modeled the FDA review and approval process to address issues related to the robustness, reliability and efficiency of its operations from an internal point of view. The reform models identified in the literature are limited in several aspects. For example, there is a general lack of application of scientific methodologies and modeling techniques in understanding FDA as a complex sociotechnical system. In addition, tools and methods to assess their efficacy before implementation are largely absent. Findings from this scoping review suggest an opportunity to employ Model-Based Systems Engineering (MBSE) approaches to provide a systems-oriented descriptive model of the FDA approval process for therapeutic biological products as a service network, with the objective of providing a method to support individual, team, and organizational decision-making to balance the process structure in terms of enforcement and in-formation. This holistic approach will serve several investigative purposes: (1) identify influential sources of variability that cause major delays including individual, team, and organiza-tional decision-making, (2) identify the human-system bottle-necks, (3) identify areas of opportunity for design-driven im-provements, (4) study the effect of induced changes in the sys-tem, and (5) assess the robustness of the structure of the FDA approval process in terms of enforcement and information sym-metry.