Travelling through the NETs of the NEST: Toward Collective, Collaborative Intelligence via Continuum of Evidence Generation Developing the DAISI (Devices for Acute Ischemic Stroke Intervention) Coordinated Registry Network: A NEST Development Project Murray Sheldon, MD; Carlos Peña, PhD Center for Devices and Radiological Health U.S. Food and Drug Administration MDEpiNet Annual Meeting 2017 White Oak, Maryland October 20, 2017
Why Acute Ischemic Stroke? Burden of Stroke Approximately 795,000 Americans suffer a new or recurrent stroke each year and stroke kills nearly 129,000 people a year. Introduction of Neurothrombectomy devices Neurothrombectomy devices (primarily stent retrievers and aspiration catheters) have been cleared for revascularization by removal of thrombus in AIS patients who are ineligible or who failed IV t-pa (drug therapy). Limited opportunities to collect additional clinical evidence Data needed for expanded indications and other uses may be difficult to obtain for marketed devices that have become standard of care Challenging study designs in some circumstances where new device development and new clinical studies are needed Study design and evaluation of outcomes are complicated due to complexity of the neurovasculature While RCT studies may still be needed to answer some questions, the cost can be burdensome to industry and in some cases, may be answered through RWE 2
Historical Perspective 1996 CDER approves IV t-pa for AIS (<3 hours) 2004 CDRH clears Merci Retriever [510(k)] for contraindications to or failure of t-pa Current marketed mechanical thrombectomy devices cleared with a revascularization indication for use: Merci Retriever Penumbra system Solitaire Revascularization Device Trevo Retriever Capture Revascularization Device 3
Current Device Examples Stent Retrievers Solitaire Trevo Aspiration Devices Penumbra Aspiration System 4
The Ah-Ha Moment! (2015) Publications of five prospective randomized trials Marketed mechanical thrombectomy devices Endovascular Therapy (ET) in combination with pharmacotherapy IV tpa within 3-4.5 hours from symptom onset proximal large vessel occlusion (LVO) stroke in the anterior circulation (M1 Middle Cerebral Artery (MCA) segment with or without concomitant Internal Carotid Artery (ICA) occlusion) All studies showed superior clinical outcomes in the ET treatment arm compared to patients who only received best medical management, typically IV t-pa alone. Based on this data, the American Heart Association- American Stroke Association added ET using stentretrievers as a first-line treatment to its clinical guidelines for the early management of patients with acute ischemic stroke. 5
Regulatory Pathway September 2016 FDA granted a de novo classification request to allow marketing of the Concentric Medical Inc. Trevo Pro Vue Retrievers based on clinical data. FDA established a new classification regulation (21 CFR 882.5600) with product code, POL for neurovascular mechanical thrombectomy devices intended for acute ischemic stroke treatment with mandatory special controls. These special controls include performance data to demonstrate improvement in clinical outcomes of reduction in disability. 6
DAISI Coordinated Registry Network: Devices for Acute Ischemic Stroke Intervention Partnering with Stakeholders for Success The Beginning, February 2, 2017
Professional Societies American Association of Neurological Surgeons American Heart Association Congress of Neurological Surgeons Neuropoint Alliance Society of NeuroInterventional Surgery Society of Vascular and Interventional Neurology Contract Research Organizations The Emmes Corporation Boston Biomedical Associates Stakeholder Attendees Industry Boston Scientific Cardinal Health Codman Neuro Cook Medical Johnson & Johnson Medtronic MicroVention, Inc. MIVI Neuroscience Neuravi Limited WL Gore & Associates Penumbra Inc. Pulse Therapeutics Stryker Neurovascular Other (MDIC) Hospital Corporation of America Academia Cleveland Clinic Columbia University Dartmouth-Hitchoock Medical Center Duke-Margolis Center for Health Policy George Washington University Oklahoma State University UCLA University at Buffalo, Jacobs Institute Weill Cornell Medicine Government FDA NIH National Library Medicine AHRQ 8
Clinical Working Groups Core data element Common definitions Informatics and Methodology Central vs. distributed model Data sharing structure and interoperability Sustainability and Value Governance structure to assure value Funding structure Data use agreements 9
Current Stroke Registries in US NeuroVascular Quality Initiative (NVQI) Society of Neurointerventional Surgeons Get with the Guidelines-Stroke Database American Stroke Association/ American Heart Association Paul Coverdell National Acute Stroke Registry CDC INterventional Stroke Therapy Outcomes Registry (INSTOR) 10
What s Next? Capture data on Real World use of these devices A few potential examples Core infarct volume Imaging criteria for patient selection for treatment Use with other interventional devices during the surgical procedure Use in additional areas of the vasculature Coordinate Registry Networks as an infrastructure for additional data capture 11