The MDEpiNet Coordinating Center is responsible for the advancement of novel infrastructure approaches and partnerships including strategically Coordinated Registry Networks (CRNs) and international registry consortiums, and the coordination of all MDEpiNet governance committees and project development activities. The Center collaborates with partners and creates forums for discussion. It engages external stakeholders, relevant data owners and experts to share best practices and build collaborations. The Center conducts comparative outcomes studies and applies the results to inform clinical and regulatory decision-making.
I.Coordinated Registry Network Development
MDEpiNet Coordinating Center provides registry development support for pilot projects and ongoing studies using CRN data. The Center facilitates subcontracting and legal support including data use agreements, data purchase, hosting, and access. The Center plays a crucial role in the methodology and analytics (e.g. data management and cleaning), statistical analysis, dataset linkage, objective performance criteria analysis, and others discussed further below.
One of the main MDEpiNet methodological advancements has been to conduct linkages between registry data and routinely available data sources (e.g. claims and administrative data). The Center has been successfully developing and refining anonymous linkage algorithms to harness data resources including registries, claims data, and electronic health records. Data linkage with indirect identifiers is reliable with high sensitivity and accuracy. It is the most cost-effective way to obtain long-term outcomes and has positive implications for long-term device surveillance. linkage between registries and Medicare claims data; three-way linkage between registry, Medicare, and clinical data; linkage between registry and statewide discharge data; and linkage between registry and New York City Clinical Data Research Network data.
The Center is also building medical device information libraries, which include information like catalogue numbers and manufacturer names, to enhance the capacity of the FDA’s GUDID for research and surveillance. The International Consortium of Orthopedic Registries (ICOR), again, has a great example of a device library. The ICOR implant library is supported by the Coordinating Center to develop a global, standardized classification system of hip and knee implantable devices, and includes all their clinical attributes and characteristics to advance the implementation of unique device identifiers and FDA post-market surveillance.
Distributed Analysis for International Registries
The Center has developed methodologies that have enabled the distributed analysis of international data. One great example of this work is in the ICOR in which data is being collected from over 30 registries across the world that can be used to conduct more large-scale studies. In this approach, a standardized data extraction is implemented by ICOR and distributed to participating registries. Each registry then completes the analyses of their own registry and completely de-identified data summaries are sent back to the coordinating center. Data are then combined using multivariable hierarchical models to evaluate comparative outcomes of devices regarding the main patient-centered outcomes (e.g. revision surgery after initial device implantation).
Natural Language Processing
Another important initiative of the Center is to develop natural language processing methods to extract information from text data. Ongoing work includes the development of methods to extract patient and device events and other information from device adverse event reports in the FDA Manufacturer and Use Facility Device Experience (MAUDE) database. These events and information can then be used to analyze patient and device events related to reintervention and patterns in adverse event reporting.
The Center is also developing objective performance criteria (OPC) to leverage routinely available electronic, discharge and claims data to advance national post-market surveillance. An OPC is a target performance that was derived from historical data from clinical studies and/or registries, which may be used to compare safety or effectiveness endpoints for medical devices. OPCs can be utilized in pre-market and post-market clinical studies, such as single-arm trials, to improve the assessment of new and existing devices when having a control group is not feasible. OPCs may also be used toward evidence for labeling change of existing devices. OPC methodology has been used to evaluate the clinical performance of prosthetic heart valves and in other settings. The Center is currently working with Orthopedics CRN in developing OPC for outcomes following hip and knee replacements.
II.Delphi Processes To Establish Core Minimum Data
The Coordinating Center supports the CRNs by convening stakeholders and leading a Delphi process to facilitate consensus on important aspects of registry advancement, such as the development of a core minimum dataset. Undergoing a Delphi process is a preferred method for reaching concordance about a core minimum dataset as there are many challenges to the traditional consensus panel approaches, such as the impact of a single person with a strong personality or the lack of anonymity, which may introduce bias. As a result, the Delphi process was developed to achieve consensus while minimizing bias inherent in group dynamics and face-to-face responses.
The below figure shows the working process of the Delphi method:
During a Delphi process, the first series of questionnaires are sent to the panel and answered by each expert anonymously and individually. From the questionnaires, experts have an opportunity to introduce new options and suggestions between rounds. Results are analyzed to identify responses with strong consensus (e.g. >50%). Data elements that lack consensus are automatically dropped (<50%) This process is repeated 2-3 times until a group consensus is reached.
MDEpiNet utilizes this process in various CRN efforts like National Breast Implant Registry (NBIR), Robotic-Assisted Surgical Devices (RASD), Study of Prostate Ablation Related Energy Devices (SPARED), Temporomandibular Joint (TMJ), International Consortium of Vascular Registries (ICVR), and Women’s Health Technologies (WHT). The WHT-CRN’s clinical working groups (sterilization/long acting reversible contraceptives, pelvic organ prolapse, and uterine fibroids) have made substantial progress to include additional stakeholders (e.g., patient partners) by using the Delphi method to create core minimum datasets from the initial list of clinical elements identified.
III.Stakeholder Alignment and Governance
MDEpiNet Coordinating Center supports stakeholder alignment and governance by identifying important stakeholders for each CRN and facilitating communications and meetings among parties. The Center helps establish a CRN governance structure, including a steering committee and various subcommittees; holds think tank meetings with stakeholders and manages annual meetings at the FDA; and coordinating periodic conference calls as well as providing regular management support. The Center manages various committees and stakeholder participation in executive operations, scientific oversight, development of international chapters, and manuscript and publications. The Center engages providers and clinicians, health system executives, device industry, policy makers, researchers, community boards, as well as patient advocates and organizations including patient partners.
MDEpiNet Coordinating Center actively helps to facilitate patient engagement efforts. Patients are an important part of MDEpiNet and a critical voice on many of its projects. Patient partners work alongside clinicians, researchers, device manufacturers, the FDA, and other federal agency staff to develop and improve real-world data collection and analyses in a variety of clinical areas. They bring the knowledge, experience and perspective of the patient community to MDEpiNet projects, advice to working groups on the needs and interests of the patient community and help develop the real-world data infrastructure that collects and communicates clinical evidence and outcomes that are of interest to patients.
The MDEpiNet Coordinating Center has implemented two different models for engaging patients:
Model 1 – patient partner recruitment by specific clinical areas
This effort engages patients in clinical areas of various CRNs. In this model, patients are recruited by each clinical working group through website announcements and an application process, are selected based on their interests, motivation, and experience being a patient or a caregiver in a specific clinical domain. Example: WHT pilot projects engaged patients in clinical areas such as stress urinary incontinence (SUI), uterine fibroids (UF), pelvic organ prolapse (POP), and long acting reversible contraceptives (LARC)/sterilization. Patient partners participate in an orientation to become familiarized with the project and activities; attend monthly meetings and calls with clinical working groups of their interest; provide feedback to the development of core minimum datasets to ensure that the registries collect patient-reported data; and are essential participants in answering research questions of fundamental interest to the patient community.
Model 2 – patient led roundtable with major stakeholders
This effort primarily engages patients in round-table meetings that bring patients together with agencies such as National Institue of Health, academics, device manufacturers and others to assess the current state of evidence relating to their field of medical devices. Example: TMJ piloted the model in TMJ replacement devices. Patients share their stories and concerns about the urgent need for interdisciplinary research and a paradigm shift in TMJ treatment; participate as Steering Committee members, working group co-chairs, working group participants, and co-investigators in the project; identify gaps and next steps to support working groups and establish a roadmap to achieve high-quality real-world data. They also highlight patients’ needs as they too often continue to receive less than adequate guidance and treatment and suffer physically, socially, and economically.
IV.MDEpiNet - High-Performance Integrated Virtual environment (HIVE)
MDEpiNet-HIVE is a technology that provides a secure healthcare biomedical data archival ecosystem. MDEpiNet-HIVE maintains a standardization and harmonization framework, high performance analytics, and an integrator platform. Dr. Vahan Simonyan is the lead instructor of HIVE efforts.
The recent implementation of HIVE hardware and software at the FDA presents a great opportunity for exploring new ways of analyzing vast amounts of data and deriving evidence that is more comprehensive to characterize a medical product.
HIVE is a distributed storage and computation environment and a multicomponent cloud infrastructure, which provides secure web access for authorized users to deposit, retrieve, annotate, and compute on biomedical big data. Importantly, it also allows users to analyze the outcomes using web interface visual environments appropriately built in collaboration with internal and external end users.
In addition to the initial HIVE applications to next generation sequencing, the current universe of HIVE projects covers tailor-made applications involving dimensionality analysis, federated and integrated data mapping, modeling and simulations that are applicable to basic research, biostatistics, epidemiology, clinical studies, post-market evaluation, manufacturing consistency, environmental metagenomics, outbreak detection, etc.
MDEpiNet Coordinating Center currently supports various HIVE pilot projects in women’s health technologies and cancer settings. Patient and physician registry platforms are being developed as well as infrastructure for hosting registry and claims data and conducting data linkages that are distributed and centralized to support national and international collaborations.
Pilot approaches are set to develop a customized FHIR app for projects such as POP and SUI. These are being tested on mobile and connected devices through work with clinical teams to finalize the data elements for terminology and refine the app with feedback on usability.
V.MDEpiNet and Weill Cornell Medicine Claims Based Research Initiative (CBRI)
The Center coordinates research within this program to evaluate current and innovative devices and device-based interventions in medicine. Collaborating with clinical departments at Weill Cornell Medicine, the project aims to provide information and evidence for physicians and patients to facilitate informed clinical decision-making. The scope of the CBRI initiative includes the evaluation of device or procedure safety and efficacy and assessment of the impact of provider characteristics on patient and device outcomes. The program has access to a number of datasets including Medicare, New York State comprehensive discharge data, SEER-Medicare data for various cancer surgeries, and National Surgical Quality Improvement Program data, as well as international registry data for various surgical procedures. The program has expanded with the formal development of the Institute for Health Technologies and Interventions at Weill Cornell Medicine, which collaborates with various clinical departments, depicted below:
Major Research Areas
Research in radiology focuses on procedures and devices used in interventional radiology. These procedures and devices, such as liver tumor ablation, kidney tumor ablation, and inferior vena cava, may be used for cancer and non-cancer treatment.
Research in colorectal surgery focuses on interventions and devices related to the treatment of colorectal cancer and benign conditions with a major focus on assessing safety, efficacy, and effectiveness of these technologies and interventions using big data and primary clinical data sources.
Research in vascular surgery focuses on both traditional open and minimally invasive procedures in cardiovascular practice, and patient-centered surgical outcomes and provider level factors in the areas of valve replacement or repair abdominal aortic aneurysm, peripheral vascular disease, carotid stenosis, and cerebral aneurysm.
Research in urology focuses on interventions and devices related to treatment of urologic cancers and benign urologic diseases, and comparative studies and patient-centered approaches that are used to assess the safety and efficacy of urologic procedures.
Research in cardio-thoracic surgery is conducted on various topics including pulmonary resection, treatment of lung cancer, cardiac valve replacement or repair etc.
Research in neurosurgery focuses on interventions and devices related to the treatment of brain tumors.
The MDEpiNet Coordinating Center advances the infrastructure and frameworks for medical device innovation and evaluation. Several FDA white papers guide the overall approach of the Center, including the following: