DEVELOPMENT OF Coordinated Registry NetworkS: BENEFITS to THE FDA MISSION Danica Marinac-Dabic, MD, PhD, MMSc, FISPE Director, Division of Epidemiology, FDA/Center for Devices and Radiological Health

Summary Contextual building blocks: Via “Nets” to NEST Coordinated Registry Networks (CRNs) and MDEpiNet’s CRN Community of Practice (COP) Vascular CRN: Example of partnership effort VISION/RAPID How these initiatives fit together?

FDA RWE Guidance 2010 2011 2012 2013 2014 2015 2016 2017 MDEpiNet THE VISION FOR NATIONAL SYSTEM LAUNCHED FDA 4- day Public Meeting Day 1. Launch of FDA strategy Day 2. MDEpiNet Annual Days 3-4. Registries Reports: Planning Board MDEpiNet Registry Task Force IMDRF FDA RWE Guidance International Consortia (e.g. ICOR, ICCR) MDEpiNet Launch 2010 2011 2012 2013 2014 2015 2016 2017 Develop and test drive novel methods and scientific infrastructure for device evidence generation synthesis and appraisal nationally and internationally MDEpiNet Methodology Center at Harvard MDEpNet Science and Infrastructure Center at Cornell MDEpiNet Launched CRN Community of Practice

VISION CRN 2010 2011 2012 2013 2014 2015 2016 2017 MDEpiNet Launched THE VISION FOR NATIONAL SYSTEM LAUNCHED FDA 4- day Public Meeting Day 1. Launch of FDA strategy Day 2. MDEpiNet Annual Days 3-4. Registries Reports: Planning Board MDEpiNet Registry Task Force IMDRF International Consortia (e.g. ICOR, ICCR) MDEpiNet Launch 2010 2011 2012 2013 2014 2015 2016 2017 VISION CRN Develop and test drive novel methods and scientific infrastructure for device evidence generation synthesis and appraisal nationally and internationally MDEpiNet Methodology Center at Harvard MDEpNet Science and Infrastructure Center at Cornell MDEpiNet Launched CRN Community of Practice

www.fda.gov

2015 Medical Device Registry Task Force recommendations to FDA Coordinated Registry Networks (CRN) Principles: Link complementary sustainable registries/e-repositories (Professional society registries, EHRs, Claims data) TPLC as a true continuum of structured “real world” evidence “Dual purpose” existing site-base work flow Krucoff MW, Normand SL et al, JAMA 2015 www.mdepinet.org

CRNs – The Key Concepts Data capture embedded in routine practice (better, faster , cheaper) Strategically coordinated/harmonized within the ecosystem Clinical core data sets (including PRO where possible) Informatics solutions (including UDI, SDC) Sustainability (value propositions, ROI, maturity models) Network Term was ” Coined” for registries - but applies beyond Include national and international/global opportunities

CRNs Build on International Models and Standards “Organized system that continuously and consistently collects relevant data in conjunction with routine clinical care, evaluates meaningful outcomes and comprehensively covers the population defined by exposure to particular device(s) at a reasonably generalizable scale (e.g. international, national, regional, and health system)’ with a primary aim to improve the quality of patient care”. The IMDRF definition of medical device registry approximates the definition of CRN.

Strategically Coordinated Registry Networks (CRNs) National International Ortho CRN Vascular CRN – VISION Cardiac CRN Neurology CRN – DAISI Gastrointestinal CRN – Obesity SPARED CRN – Prostate ablation Robotic Surgery CRN TMD/TMJ VANGUARD Women’s Health Technologies – Uterine Fibroids, Pelvic Floor Disorders, Sterilization Devices, Breast Implants - NBIR Abdominal Hernia CRN International Consortium Orthopedics Registries (ICOR) International Consortium Vascular Registries (ICVR) International Consortium of Cardiac Registries (ICCR) International Collaboration of Breast Registries Activities (I-COBRA) Development of 11 national CRNs is underway Four international consortia

In 2018 MDEpiNet has launched CRN Community of Practice To create a learning community where Coordinated Registry Networks (CRNs) can share lessons learned and best practices. CRN’s will continue to produce RWE to support regulatory decision making, essential for the next round of MDUFA negotiation Currently 15 CRN under development, which will cover the majority of implantable devices MDEpiNet is helping CRN mature (produce evidence to evaluate devices) through a Community of Practice (COP, national and international) Share lessons learned Develop maturity models Minimum core data sets Develop informatics underpinnings

RAPID/VISION: A Scalable Framework to Efficiently Conduct Real-world Enabled Vascular Clinical Trials   Two MDEpiNet projects VISION (led by Cornel) and RAPID (led by Duke) were launched to complement each other VISION - to develop National Vascular Implants Surveillance and Outcomes Network by linking VQI registry to claims and other data sources for longitudinal assessment RAPID - to developed a core data element (CDE) set informed by multiple registries, EHR systems, and stakeholders. Leveraging both efforts the SPEED pilot is now being designed to demonstrate how clinical trials sufficient to support regulatory decision-making can be efficiently implemented into existing healthcare systems for expanding the indications The SPEED trial that will involve 12600 patients from the VQI registry with (estimated 4200 prospective and 8400 retrospective patients data and 2940 patients with 1 year follow-up data available for developing Objective Performance Criteria – OPCs The projects leverage the GUDID Database to enable comparative effectiveness research of peripheral vascular technologies. It will involve data refinement and analyses to develop contemporary OPCs using RWE, data sharing with industry stakeholders for potential labeling modification (e.g., longer lesions, heavy calcified lesions, diabetic patients). The new paradigm is that industry will have access to the conglomerate of data plus their own data. Thus, if pre-specified statistical plan is met for a given subgroup analysis population as per examples above, a labeling modification could be requested/granted.

Evaluation of Medical Device Postmarket Landscape 2009-2014 ARRA, HITECH Acts. 125 million lives captured in mini-Sentinel. Establishment of MDEpiNet. Final Rule for UDI. 2014-2019 Evaluation of UDI within claims and EHR. Linkage of device registries with other healthcare data sources. Use of distributed data networks for surveillance. 2019-2024 Device registries and UDI fully integrated into patient healthcare dataset. Patient info able to be tracked across datasets via “hashing” or “fuzzy logic” linking. 2024-2029 Postmarket infrastructure allows most evaluation via automatic data collection. In rare instances where additional data needed, patient surveys and disease-based registries created. 2029-future Continue to innovate and utilize novel methodologies and new technologies to better understand performance and clinical outcomes of medical devices in the postmarket. Ongoing evaluation of postmarket landscape used to provide context for benefit-risk balance for newly developed devices. Medical Device Reports Enhanced Surveillance De Novo Data Collection Decreasing – Additional data sources available with advent of UDI, integration of registries into long-term data, and newly developed data linking capabilities De Novo Data Collection Sentinel Initiative – * Signal Refinement for identified potential public health concerns * Initially claims data, will also include electronic healthcare records Evaluation of Medical Device Postmarket Landscape Administrative and Claims Data Postmarket Infrastructure and Novel Methodologies Systematically Developed and Enhanced via MDEpiNet Electronic Healthcare Records Use of EHR and Claims Data – * Most data currently captured in registries is also captured by the facility at the time of the procedure. * Incorporation and utilization of this data from the EHR and claims data allows for better understanding of medical device use in the context of other healthcare utilization and provides additional data regarding patients outcomes. Alternative Data Collection for Registries – * Utility of registries increases with accurate and timely data collection. * Collecting data from EHRs or directly from patients will enhance the long-term capabilities while removing burden from healthcare facilities. Device-Based Registries International Consortium of Orthopedic Registries – * 3 million lives with orthopedic procedures captured globally * Follow-up and outcomes assessed via common data model Secondary analysis of previously collected data – e.g. meta-analysis, cross-design evidence synthesis Disease-Based Registries 2009 2014 2019 2024 2029 2034

Thank You! www.fda.gov