FDA’s Center for Devices and Radiological Health’s State of the Union 2017 Jeff Shuren, MD, JD Center for Devices and Radiological Health U.S. Food and Drug Administration www.fda.gov

Disclosure Statement of Financial Interest I, Jeffrey Shuren, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. www.fda.gov

In 2009, industry argued that FDA regulation hindered innovation and contributed to the growing number of device companies seeking marketing authorization for their devices abroad before introducing them in the United States and the increasing gap between when a device is approved in another country and when it is approved in the US. This reality, its adverse impact on patients, plus CDRH’s own awareness of our declining performance over almost a decade, led CDRH to implement new programmatic changes. These changes, along with increased user fee funding and changes in federal law, have helped us to change course, strengthen our performance, and better address the rapidly evolving field of medical device innovation. To c www.fda.gov

Novel Device Approvals www.fda.gov

Examples Early Feasibility Studies for Transcatheter Mitral Valve Replacement Devices: Study approvals are on par with other countries Edwards Lifesciences SAPIEN XT/3 for Intermediate Risk Patients: From > 4 years for first generation device to 18 days plus “automatic” CMS coverage for new indication Medtronic 670G hybrid closed loop system for people with type 1 diabetes (first generation “artificial pancreas”): First in the world www.fda.gov

Vision We face a critical public health challenge The U.S. regulatory standard for market approval protects patients by setting a high public health bar but imposes costs that make the U.S. marketplace less attractive for innovators thereby delaying patient access to important technologies The solution is to reduce the time and cost of the total product life cycle… device development, assessment, review, manufacturing, monitoring, and reimbursement – without compromising the reasonable assurance of safety and effectiveness standard Vision “Patients in the U.S. have access to high-quality, safe and effective medical devices of public health importance first in the world.” www.fda.gov

Doing Business Better Since late 2009, CDRH has continuously improved the way we do business through a series of culture, policy and process changes www.fda.gov

Lower-Risk “Me-Too” Devices (510(k)s) www.fda.gov

High-Risk Devices (PMAs) www.fda.gov

Lower-Risk Innovative Devices (De Novos) www.fda.gov

Clinical Trials (IDEs) www.fda.gov

Doing Business Different Since late 2009, CDRH has been transforming the way we do business through a series of culture, policy and process changes www.fda.gov

Patient-Centered, TPLC Approach Benefit-Risk Tradeoffs Flexible Regulatory Paradigms Applied Across the Total Product Life Cycle CDRH Vision Patient-Centered, TPLC Approach Benefit-Risk Tradeoffs PMA, De Novo Benefit-Risk Determination Framework Guidance (2012) Postmarket Benefit-Risk Guidance (2016) Evidence Generation Premarket-Postmarket Balance Science of Patient Input Clinical Trials Regulatory Science Real-World Evidence Early Feasibility Study Paradigm Guidance (2013) Bayesian Statistics (2010), Adaptive Trial Design (2016) Guidances RWE Draft Guidance (2016) Expedited Access Pathway Program (2015) Patient Preference Information Guidance (2016) IDE Benefit-Risk Determination Framework Guidance (2017) Unique Device Identification Final Rule (2013) Balancing Premarket and Postmarket Data Collection Guidance (2015) Medical Device Innovation Consortium (MDIC) Patient Centered Benefit-Risk Project MDDT Pilot Program www.fda.gov NEST MDIC

The Value Proposition for NEST Patients would have more timely access to safer, more effective devices and better information to make decisions Clinicians would have better information about the use of a given device in practice Hospitals, clinical practices, and integrated health systems would benefit from improved quality, reliable assurances of safety, and, possibly, relief from multiple reporting requirements Payers would benefit from access to high-quality evidence on device performance in clinical practice, either alone or compared with other therapies www.fda.gov

The Value Proposition for NEST Device manufacturers would be able to provide high-quality evidence at lower cost and in less time to support premarket approval, clearance, and payer coverage, coverage with evidence development and reimbursement decisions and to meet or reduce the need for postmarket study and adverse event reporting requirements In cases where the potential public health value of the device is high, some data that would otherwise be collected in the premarket setting could be responsibly collected after market entry instead, owing to strong assurances that additional postmarket data would be generated The system may obviate the need for FDA premarket review of some device modifications because more timely and informative evaluations of the impact of those changes would occur in the course of routine data collection www.fda.gov

Key Features of NEST Purpose: To drive down the time and cost and increase the value and use of real-world data to meet the needs of medical device ecosystem stakeholders through a market-driven, collective buying power approach and using a neural network data model: Independent Coordinating Center responsible for driving standardization of core data elements, data quality, use of common definitions, linkages between data sources, development of advanced analytics, and creating data use agreements as conditions of data sources participating in NEST Overseen by a Governing Board comprised of representatives of ecosystem stakeholders that is responsible for establishing NEST’s policies and procedures, setting strategic direction and priorities, and directing investments by the Coordinating Center Business Model: Base funding from private and public sector sources NEST users pay for access to and analysis of data from participating NEST data sources Success requires demonstrating ROI, e.g., less expensive, more timely to use NEST “Minimally Viable Product” by December 31, 2019 www.fda.gov

Historical model of clinical research: Many recruitment sites and a coordinating center Hub & spoke model Top-down decision-making Sites operated independently 17 www.fda.gov

Neural Network Share Sites and Data Node Nodes are clusters of data that we are accessing www.fda.gov

Neural Network Share Sites and Data NEST Coordinating Center

Proof of Concept Premarket Examples Data from the Society of Thoracic Surgeons and American College of Cardiology’s Transcatheter Valve Therapy Registry used to support approval of an expanded indication for transcatheter aortic valve replacement devices Data from a company’s registry and the Society for Vascular Surgery’s registry used to support approval of a new indication for a drug-coated balloon for in-stent restenosis Use of registry data as a control arm for pivotal clinical studies Left ventricular assist devices Stent grafts Surgical mesh Use of database data to demonstrate clinical validity Next generation sequencing tests for cystic fibrosis www.fda.gov

Proof of Concept Postmarket Examples Post-approval study of TEVAR devices using the Vascular Quality Initiative Registry enrolled patients twice as fast as expected Nesting of required postmarket studies in registries 40% to 60% cost savings Pilot on using registry data in lieu of submitting Medical Device Reports for on-label adverse events www.fda.gov

Where Do We Go From Here? www.fda.gov

Thank You www.fda.gov