Every year, approximately 795,000 Americans suffer a new or recurrent stroke and nearly 140,000 people die from strokes of which 87% are ischemic 5. Stroke is a leading cause of disability and treatment costs exceed 70 billion in the USA. Endovascular mechanical stroke thrombectomy is one of the few devices approved for specific indication of stroke treatment and only limited real-world data is available to study device specific performance. Ccomplexity of the neurovasculature makes it challenging for industry and the FDA to conduct clinical studies for these devices. However, the FDA is committed to supporting the sustainable generation and use of robust RWE in the course of clinical care by patients, providers, and payers, for the purpose of enhancing regulatory and other decision-making.
The network for Devices used for Acute Ischemic Stroke Intervention (DAISI) was developed with a focus on acute ischemic stroke that allows the capture of data from actual patient encounters with medical devices and was launched by the FDA on November 9, 2017. Since its initiation, DAISI has held annual meetings to finalize common data elements, imaging data elements in neurothrombectomy trials to assess revascularization, and capabilities of imaging. The focus of the meetings has also been in aligning methodology and infrastructure in considering the recommendations of registry owners and the FDA, finalizing data use models of inflow and access to data from the CRN, and initiating the DUAs for industry trials and society registries to advance the development of the DAISI CRN.
The objectives of DAISI are to establish a nationwide and international CRN using RWE and develop methodology and infrastructure to support the CRN. DAISI CRN will provide support to establish evidence needed for clinical and regulatory decision-making, building from existing data infrastructure. Through the CRN, real-world practice data and evidence will be accumulated with the potential for post-market device surveillance, expanded indications, and future prospective trials for pre-market approvals.
DAISI CRN is a collaborative effort initiated by FDA and facilitated by the MDEpiNet Coordinating Center with partners from professional medical societies, neurointerventional device companies, and various government agencies.
The DAISI CRN is led by three clinical co-chairs: Adnan Siddiqui (University of Buffalo), Sameer Ansari (Northwestern), and David Liebeskind (UCLA). The FDA representation is led by Avena Russell and Carlos Pena. The governance council includes stakeholders who coordinate, plan, implement, and execute critical infrastructure controls by providing oversight of the CRN. This includes assisting with development, implementation and sustainability plans. The Governance Council includes members from the FDA, physician specialty societies, industry, MDEpiNet Coordinating Center, and other non-voting participants. The DAISI oversight and data use committees are to be identified to ensure no head-to-head comparisons of competitor devices, including by researchers.
DAISI CRN is governed by specific DUAs between M2S, MDEpiNet Coordinating Center at Weill Cornell Medicine, participating registries, and participating medical device companies. The professional medical society-supported registry data are stored on a secure server at M2S. CMS DUA is established to conduct for data linkages. Projects are approved by the DAISI Governance Council. All three DAISI CRN co-chairs have an established MOU with the MDEpiNet Coordinating Center to join the CRN COP and are members of the MDEpiNet Executive Operations Committee (EOC).
Initial focus of DAISI CRN includes patients with acute ischemic stroke who underwent endovascular mechanical stroke thrombectomy for basilar artery occlusions. Data from professional medical societies’ registries and industry sponsored registries are considered for the initial data capture, as well as data from clinical trials including high quality prospective data.
Professional medical societies such as the American Association of Neurological Surgeons, Society of Neurointernational Surgery and Society of Vascular and Interventional Neurology are working towards one combined registry for endovascular neurosurgeons, interventional neuroradiologists, interventional neurologists, among others and are in the process of combining data elements with a single vendor partner for data collection (M2S). The data elements come from NeuroVascular Quality Initiative, Quality outcome Database, Get with the Guidelines-Stroke Database, Paul Coverdell National Acute Stroke Registry, Interventional Stroke Therapy Outcomes Registry, and StrokeNet. The American Heart Association (AHA) also plans to contribute to DAISI CRN data infrastructure.
Industry Data: Industry partners, including Cerenovus (J&J), Medtronic, Penumbra, and Stryker Neurovascular, contribute to this CRN. The industry partners provide data on the following devices: Solitaire (stent retriever), Trevo (stent retriever), Embotrap (stent retriever), and Penumbra Aspiration System (aspiration device).
Current Projects and Plans
Basilar artery occlusions (BAO) pilot study: The current project of DAISI CRN is to evaluate the safety and efficacy of FDA-approved thrombectomy devices in the real world setting of posterior circulation stroke secondary to BAO. The data can be used to support a regulatory application to expand FDA labeling of stent retriever and/or aspiration thrombectomy devices for this indication.
This project is based on the retrospective collection of data from the DAISI CRN collaboration and will be conducted using the MDEpiNet infrastructure. Initial data capture will be limited to industry-sponsored registries and clinical trials with higher quality due to prospective data entry and adjudicated outcomes in comparison to self-reporting physician/society registries. For this project, DUA with industry partners have been initiated. Primary clinical outcome measures are planned to be captured accurately with modified Rankin Scale (mRS) at 90 days and secondary procedural and safety outcomes have been defined analogous to the previous stroke intervention trials. Common data elements are also approved for the project.
The DAISI mission is to establish a nationwide and international Coordinated Registry Network (CRN) using Real World Evidence (RWE) generated in the course of clinical care by patients, physicians, providers, and payers, for the purposes of improving care and enhancing regulatory and other clinical decision-making. This CRN will include national and international database(s) that will be used to capture information from actual patient encounters with medical devices used to treat acute ischemic stroke. The RWE will support the advancement of acute ischemic stroke clinical trials and when and where appropriate, capture data necessary to support regulatory, reimbursement/coverage, and physician and patient decision-making.
There are new device-based interventions to treat acute ischemic stroke that have been researched and developed by Sponsors, Investigators, and the clinical community, and approved by FDA. As technology continues to proliferate rapidly, the legacy approaches to evidence generation (randomized clinical trials ([RCT]) are becoming increasingly burdensome and have a potential to become obsolete by the time of completion. In addition, RWE needs to be taken into account for technologies that are well established or have become the standard of clinical care. Many decisions about use of these devices might be better made by using RWE instead of expensive, and often difficult to implement one-off studies.
The FDA is committed to supporting the sustainable generation and use of robust RWE throughout the medical device lifecycle, using Real World Data (RWD) generated in the course of clinical care by patients, providers, and payers, for the purpose of enhancing regulatory and other decision-making. Several of FDA’s ongoing strategic efforts align with FDA’s broader engagement under the National Evaluation Systems for health Technologies (NEST). This CRN, focused on acute ischemic stroke, will allow the capture of data from actual patient encounters with medical devices. The RWD will support the development of RWE that describes the outcomes of acute ischemic stroke treatments under different treatment conditions and when and where appropriate, captures data necessary to support regulatory, reimbursement/coverage, and physician and patient decision-making.