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Medical Device Epidemiology Network (MDEpiNet)

Public-Private Partnership

Charter Proposal

Draft v. 09.01.14

1 Medical Device Epidemiology Network (MDEpiNet) Public-Private Partnership

(PPP)

1.1 Mission

The mission of the MDEpiNet PPP is to advance national and international infrastructure for patient-centered

regulatory science, surveillance and quantitative methods. By doing so, MDEpiNet will be able to optimize

evidence generation, appraisal and synthesis for medical device TPLC evaluation.

The service of this mission is intended to leverage knowledge, experience, resources and capabilities of

MDEpiNet’s public and private sector partners, and to engage and enhance patient and public confidence and

trust in medical devices that sustain and improve the public health.

The MDEpiNet PPP mission will be operationalized through the avenues delineated in the MDEpiNet Charter. The

Charter will be kept public, and will be modified over time to accommodate growth of the PPP and alignment with

other key initiatives such as the National Medical Device Planning Board and the National Registries Task Force,

and other efforts, and in conjunction with the principles and priorities of the National Medical Device Postmarket

Surveillance System and the 2014-2015 Strategic Priorities of the Center for Devices and Radiologic Health into

the future.

Principles central to the MDEpiNet PPP approach to its mission and deliverables will include:

1. Identification and implementation of predictable and sustainable applications linking relevant registry and

other related electronic information to eliminate infrastructure discontinuities as a means to more

efficient and informative clinical outcomes data collection, device identification and tracking.

2. Promotion of novel methodological approaches to outcomes data analysis and interpretation of safety

signals emerging from heterogeneous medical device data sources

3. Development of approaches to risk/benefit evaluation, pre-/post-market equipoise, better and more

efficient clinical trial and data structure in disease specific/device specific contexts that also produce

principles generalizable to other medical device applications.

4. Provision of a PPP organization that actively encourages intellectual, operational and leadership

participation to the broad range of stakeholders engaged in the medical device ecosystem.

5. Provision of a dynamic working environment focused on gaps in medical device evaluation and tasked to

barrier identification, barrier prioritization, development of novel solutions to key barriers, conduct of

proof-of-concept projects illustrating the benefit of such solutions, and re-assessment of the modified

innovation landscape for new barriers.

6. Promotion of intellectual and professional trust and frank communication, commensurate with and

supportive of the novel potential of a pre-competitive, collaborative effort across stakeholders.

The MDEpiNet Coordinating Center is proposed to facilitate the operational organization, transparency and activities of

public-private partnership (PPP) in support of the core Mission.

1.2 Executive Summary Contemporary medical device evaluation, especially for high risk and implantable devices, is associated with

multiple methodologic and interpretative challenges. No medical device is risk free, yet risk/benefit metrics

remain controversial. In part, such controversy reflects differences in stakeholder nomenclature and

expectations—what patients, doctors, manufacturers, regulators and payers consider the risks and the benefits

are importantly different. Many evaluative challenges change as medical devices move through different stages

of the product life cycle. Long term performance expectations, the impact of operator learning curves, technology

mal-distribution, differential effects in important sub-populations, rare but catastrophic safety issues, and robust

data related to the comparative effectiveness of alternative therapies all constitute critically important knowledge

gaps. Gaps in knowledge and variability in the definition of risk/benefit equipoise hamper all aspects of medical

device innovation, technical optimization, clinical best practice, uptake and adoption and even reimbursement

decisions, and have the potential to undermine both public confidence and public health.

Largely gaps in stakeholder perception of risk/benefit equipoise or critical device outcomes information are a

reflection of gaps between the information systems used to evaluate medical devices over the course of the

device life cycle. Information repositories accessed by manufacturers, professional societies, regulators, patients

and payers usually reside in silos, separated from one another. Clinical care health records and clinical research

records are often maintained separate from one another. Clinical trial databases are siloed from one another.

Historically both research and development programs and even regulatory authorities have fragmented the TPLC

into stages, each using dedicated teams, review processes, and data required at each step, rather than

constructing a system that ensures the overall and ongoing accrual of knowledge about a device, or a device

pipeline, as it moves from breakthrough technology to more mature product development. The gaps associated

with information and infrastructure fragmentation produce redundancy in human clinical trial efforts, slow the

evaluative processes, increase the cost of development, and, most importantly, undermine the true accrual of

knowledge about device safety and risk/benefit.

Recently, evaluation strategies that have included determinations of comparative effectiveness have been

recognized as having potential public health benefit by promoting a more integrated approach to regulatory and

reimbursement decisions. However application of these strategies may create new challenges. The current wide

range of gaps in scientific knowledge warrants novel approaches to systematic evidence evaluation, clinical data

collection infrastructure, and analytical approaches.

The Medical Device Epidemiology Network (MDEpiNet) initiative was launched to create pre-competitive

collaboration across stakeholders through the establishment of a transparent PPP with Food and Drug

Administration (FDA) experts. The work of this PPP is intended to develop infrastructure linking fragmented data

sources and related analytic methodologies for conducting efficient, robust and ongoing medical device

evaluation. In so doing, the MDEpiNet PPP mission prioritizes the advance of regulatory science applied

throughout the TPLC by creating infrastructure and analytic methods that link the stages of the TPLC as stages of

progressive knowledge accrual on device-related performance and outcomes, replacing the fragmented, siloed

approach that is the contemporary norm.

The expansion of MDEpiNet as a PPP was also motivated by the recognition that to successfully move medical

device innovation in this direction requires the resources and expertise of multiple stakeholders, eg. an

“ecosystem” approach. Such resources can be directed towards the development of infrastructure and the

application of appropriate methods to both study designs and surveillance necessary to evaluate medical devices.

While FDA has considerable expertise and analytic tools to evaluate device safety and effectiveness, collaboration

with methodological and clinical subject matter experts in medical device research, industry manufacturers and

other stakeholders is expected to result in both more efficient and more comprehensive understanding of device

safety and performance. Centers and stakeholder partners participating in the network will be expected to take

part in FDA-hosted and other related scientific workshops and selected disease-specific projects that address

methods for medical device comparative analyses, best practices and best design and analysis approaches. From

these meetings and projects the MDEpiNet PPP will produce public domain deliverables including, where

appropriate, think tanks, white papers, leveraged data sets, and selected research project proof of concept

models.

Thus the MDEpiNet partnership will focus on the collaborative leveraging of resources to improve and enhance

evaluation of device safety and related risk/benefit issues, with emphasis on adding efficiency and quality to such

evaluations through information accrual strategies that eliminate current gaps and fragmentation of efforts, data,

and knowledge. Through development and application of novel methodological techniques and synthesis of

knowledge about medical device evaluation processes, MDEpiNet PPP will collect, evaluate and share information

in ways that facilitate advances in regulatory science, as well as national and international device innovation, in

order to protect and promote public health. MDEpiNet deliverables will enable better, more informed and more

predictable regulatory and other related decision-making about medical devices by FDA, the Centers for Medicare

and Medicaid Services (CMS), the medical device industry, medical professionals and the American public.

Importantly, the MDEpiNet PPP approach to eliminating gaps is intended to promote the forging of linkages

among medical device data repositories that are capable of centrally supporting multiple risk/benefit metrics,

using a single source to accommodate the interests and priorities of specific stakeholders.

In addition to the knowledge gaps outlined above, the medical device community has identified many other

unmet needs. The PPP will establish processes that adjust its focus and expand its operations as its scope,

capacities and priorities mature and evolve—all of which, by organizational design, will undergo dynamic

reconsideration over time.

1.3 Background and Public Health Context The historically fragmented paradigm for acquiring and integrating clinical information predictive of real-world

settings warrants revision to more accurately and efficiently establish whether the benefits of a device outweigh

the risks. Randomized controlled trials (RCT) that serve as the basis for the approval of most new class III devices

are traditionally small, short-term, burdensome to conduct in the United States of America (USA), and

generalizable only to a small percentage of patients in actual clinical practice. Traditionally, post-market studies

have suffered from important design limitations and are also burdensome to conduct in the USA. These

limitations have become increasingly apparent over the last decade because medical device technology has

changed at an increasingly rapid pace, therapies are increasingly utilized outside their intended populations and

labeling, and broadly representative groups of patients are likely to include subgroups that respond differently to

the same therapy. Well-known criticisms of RCTs include the limited generalizability of study findings to real

world practice and patients. Recently, clinical trial investigators have attempted to broaden the inclusion criteria

for study populations. However, as the spectrum of study participants has broadened, variation of individual

treatment effects has increased. Heterogeneity of treatment effects occurs when the same treatment produces

different results in different patients. Sub-group analyses are often used to search for evidence of treatment

heterogeneity but this approach can result in additional difficulties. Most trials are not sufficiently powered for

sub-group testing; most sub-group analyses are undertaken on a post-hoc basis; the most appropriate methods

for making inferences about sub-groups are often not utilized; and sub-group results are often over-interpreted.

Even when sub-group analyses are depicted as hypothesis-generating only, confirmatory follow up studies are

rarely pursued due to logistical and cost considerations.

A complete evaluation of medical devices is thus limited by gaps in both scientific knowledge and research

infrastructure. Advances supporting the elimination of such gaps are challenging but profoundly transforming to

both the quality and efficiency of applied regulatory science throughout the TPLC. For any given disease-specific

device, implementation of identical nomenclature and definitions using global or national registry infrastructure

and the application of novel analytic methodologies support far more systematic evaluation of evidence and thus

the ongoing accrual of knowledge within that device TPLC pipeline.

The creation of the MDEpiNet PPP was motivated by the need to leverage the resources and expertise of many

stakeholders to develop and apply innovative methods to fill these scientific gaps using an ecosystem approach.

Such a broadly-based collaborative, pre-competitive partnership of multiple stakeholders from industry,

professional organizations, government entities, hospitals, patients, third-party payers, and others, will contribute

to the overall understanding of the risk/ benefit balance of medical devices through the development of a unique,

combined repository of expertise and experiences with the regulatory processes, development and use of medical

devices. FDA already has considerable internal expertise and analytic tools to evaluate device safety and

effectiveness. Collaboration with methodological and clinical subject matter experts in the field of medical device

research through the MDEpiNet PPP can produce more efficient and predictable processes for data collection and

accrual, more appropriate and informative application of statistical methods and study designs, and through this a

more robust and pragmatic regulatory science with more comprehensive understanding of device safety, risks and

benefits.

Specific projects implemented under the auspices of the MDEpiNet PPP will incorporate innovative statistical,

epidemiologic and clinical trial methods for studying medical devices. The introduction of these methods and

integration of this new knowledge with the Center for Devices and Radiologic Health (CDRH) will provide

regulators, researchers, clinicians, industry partners, patients and payers with the predictive and evaluative tools

they need to better understand the performance of devices and radiological products while promoting a more

efficient and predictable environment for device innovation. FDA will work with participating MDEpiNet partners

to develop and implement a wide range of tools to facilitate the linkage of existing data repositories or even

leverage the development of unique data repositories that facilitate evaluation of device performance and safety.

Such sources of data will include, but not be limited to, clinical trials, registries, electronic health records, claims

data, and data from outside the USA. In its development there will be active interest in pragmatic approaches to

international and global data linkage opportunities toward this same end, recognizing global fragmentation of

research and development and evolving corrective directions to eliminate those gaps as within the MDEpiNet PPP

medical device “ecosystem” scope. In conjunction with such work in specific device areas, general principles for

data linkage, access, governance, security and methodologies will also be crystallized. The MDEpiNet PPP will

focus on the pre-competitive, collaborative integration of resources to improve and enhance understanding of

device risks and benefits. Using the PPP modality of stakeholder collaboration will assist the development of

central data repositories constructed and positioned to deliver risk/benefit models that accommodate multiple

individual stakeholder variations in how medical device risks and benefits are defined and prioritized from a

single, central body of knowledge.

To support development and application of novel methodological techniques and synthesis of knowledge about

medical devices, MDEpiNet PPP will thus provide means to collect evaluate and share information to facilitate

device innovation and advance regulatory science to protect and promote the public health. These novel

methodological techniques, infrastructure development and application can be targeted to simultaneously serve

other key areas of public health or professional society applications, including but not limited to informing best

practice guidelines, appropriateness criteria, value-based purchasing and reimbursement decisions integral to the

overall comparative effectiveness metrics related to new devices approved for use in medical practice. This will

enable better decision-making about medical devices by FDA, CMS, the medical device industry, and by medical

professionals and the American public, concomitantly improving the reliability of the information base for such

decisions and the confidence in medical device products overall.

In addition to the emphasis on transparent, pre-competitive collaboration, the MDEpiNet PPP will prioritize

efforts with impactful deliverables that support the pragmatic advance of regulatory science relevant to medical

devices over the TPLC, with particular emphasis on the accrual of safety knowledge in pre-market studies through

ongoing postmarket risk identification. Such efforts may include, but not be limited to, pan-stakeholder think

tank meetings, topical white papers published in the public domain, development of data warehouses responsibly

accessible in the public domain, and research programs providing proof of concept advances in regulatory

processes and medical device surveillance and epidemiology.

1.4 Partnership Strategic Objectives

1.4.1 Strategic Objectives:

Improve how medical device information is utilized throughout the TPLC, with special emphasis on the accrual of knowledge through ongoing postmarket risk identification as it pertains to evaluation of device risk/benefit, pre-market approval decisions and post-market surveillance.

Identify elements of risk/benefit perception and priorities specific to individual stakeholders, to support interactive data platforms that accommodate different stakeholder constructs from a centralized data sources

Develop national and international infrastructure for more informative integration of data from pre-market clinical trials, post-approval observational studies, domestic and international registries, medical claims data, electronic health records, and published literature on medical device use and associated clinical outcomes throughout their life cycle, with particular emphasis on linking electronic data acquisition networks (such as registries) and related data repositories.

Develop unique methodologic and analytical approaches to enhance data quality assessment (including but not limited to data completeness, consistency and accuracy), synthesis and signal detection, discrimination, and analysis for medical devices

Develop a conceptual framework for comparative effectiveness that examines relationships between and among medical treatments, patient characteristics and outcomes, medical devices, including selected aspects of cost and reimbursement strategies supporting sustainable data accrual and infrastructure

Develop models for sustainable advances in data infrastructure and access tools such as strategically linked and queriable data repositories managed responsibly in the public domain to facilitate medical device evaluation, with particular regard to safety concerns that alter the risk/benefit balance

Advance regulatory science through the development of novel clinical trial designs and active postmarket risk identification utilizing the above for CDRH regulatory decision making throughout the TPLC.

Create a sustainable, transparent public-private partnership organization and structure focused on: o advancement of regulatory science o pre-competitive collaboration o broad stakeholder participation o transparent processes o dissemination of constructs and deliverables through public meetings and peer review publications.

1.4.2 Strategy Implementation:

Systematically evaluate gaps in existing processes related to integrating data sources and applying optimal analytic methods supporting the accrual of evidence of medical device risks and benefits pertinent to regulatory science and ongoing TPLC decision-making frameworks.

Collaborate with interested stakeholders with relevant expertise to further define and prioritize sources of evidence gaps, questions for study, datasets for use, and pertinent clinical perspectives.

Conduct think-tanks or other intellectual forums commensurate with the above

Support transparency with publication of white papers summarizing think-tank issues and discussion

Incorporate appropriate technical principles and technological strategies, study designs, analytical strategies, and regulatory and potentially reimbursement decision making to develop a framework for incorporating patient-centered outcomes in medical device studies and regulations.

Develop, test and disseminate innovative methodological approaches and study results in medical device research “proof of concept” projects that concomitantly provide disease-specific/device-specific and more generalizable principles of more seamless information accrual strategies

Leverage partner resources and expertise to create a sustainable infrastructure that stakeholders can use in an ongoing fashion to obtain or advance knowledge about medical devices.

Facilitate integration of the MDEpiNet infrastructure into CDRH decision making and the systematic evaluation of medical devices.

2 Organizational Structure of MDEpiNet PPP

2.1 Overview No single group possesses the expertise or bandwidth to create a functional medical device evaluation system

that spans all areas of medical care sub-specialties or that can recognize and overcome all of the barriers faced by

stakeholders. Each medical and surgical specialty has its own unique resources and challenges, including 1)

existing collaborative data sources and physician networks, and 2) specialty-specific medical devices with unique

risks and benefits, from manufacturing processes to operator expertise to clinical outcomes. To achieve the aims

of the CDRH, the MDEpiNet Initiative must successfully engage as wide an array as possible from stakeholders

including:

Academic, industry, government agencies, patient stakeholders who have a vested interest in creating a

functional medical device evaluation system, Individuals who possess the specialty-specific expertise to

map high priority areas for medical device research, Professional Societies, hospital systems, health

plans, and insurers that have invested in our nation’s existing data infrastructure.

The proposed structure for the MDEpiNet Initiative creates a matrixed organization in which the MDEpiNet

Infrastructure, Methodology, and Coordinating Centers support an array of Disease-based Working Groups.

Working Groups will concentrate the expertise necessary for advancing the current regulatory system of medical

device evaluation within each medical specialty.

The core functional operations of the Working Groups will be supported by the MDEpiNet Science and

Infrastructure Center (Cornell University), the Methodology Center (Harvard University), and the Coordinating

Center (Duke University). The organizational structures of the Science and Infrastructure Center and the

Methodology Center have been previously defined. The organizational structure of the Coordinating Center is

outlined here. It is expected that one of the first tasks of the Coordinating Center will be to develop a Charter

which describes in greater detail its mission, deliverables and structure.

Summarily, using processes to be determined in due time, the Coordinating Center will convene core

committees, each with a unique supportive role in the system, including, but not limited to: 1) the Stakeholder

Council, 2) the Executive Operations Committee, 3) the Stakeholder Engagement and Sustainability Committee, 4)

the Scientific Oversight Committee, 5) the Public Programs and Meetings Committee, and 6) the Publications

Committee. Formal charters will be developed for each committee.

2.2 Proposed Organizational Structure for the MDEpiNet PPP

For illustrating purposes only, we are including the flow diagram below to demonstrate the proposed working

structure of the MDEpiNet PPP. As each committee develops its own charter, and defines its duties and

responsibilities in a manner consistent with this charter, this flow chart may be adjusted to reflect the relationship

between the centers and committees.

In brief, the Stakeholder Council will provide strategic oversight, including high-level input from a wide range of

stakeholders; the Executive Operations Committee [EOC] will coordinate operational leadership across the three

MDEpiNet Centers and core committees; the Scientific Oversight Committee [SOC] will oversee, facilitate and

coordinate the proposals, progress and deliverables of the Disease-based Working Groups, and recommend

prioritization of resources to the EOC; the Public Programs and Meetings Committee [PPMC] will coordinate

facilities, agendas and related aspects such as CME accreditation as appropriate for think tank and other public

meetings; the Publications Committee will recommend topic selection priorities to the EOC, and subsequently

coordinate topic meetings and related programs, and co-authorships and related matters for white papers or

other cross-cutting publications that stem from the joint efforts of the collaboration; the Stakeholder

Engagement and Sustainability (SES) Committee will solicit feedback from the medical device community to

ensure broad stakeholder participation and input into development of a value-based plan for long term

MDEpiNet sustainability and growth. Disease-based Working Groups are the functional groups for the

collaboration. Membership will be open to all parties as per MDEpiNet governance document. . Working

Groups will be convened by the Scientific Oversight Committee (SOC) upon completion of a brief proposal during

which the need for and interest in a collaborative effort are demonstrated, its relevance to medical device

regulatory science and MDEpiNet Mission are established, and leadership for the project is assured. The

function, organization, and membership for each Working Group will vary based on the existing resources (data

infrastructure, finances, etc.) and stakeholders for the given disease-state. Working Group responsibilities will

broadly include: 1) landscape mapping, 2) roadmap creation, 3) needs assessment, and 4) implementation. They

will be supported through interactions with the Methodology Center and Science and Infrastructure Center, and

will report on programmatic progress, deliverables and timelines to the SOC. The mission, membership,

responsibilities, and deliverables of the Working Groups are detailed further, below. As with the entire

MDEpiNet PPP charter, it is expected that the National Registry Task Force and other similarly aligned partner

programs will provide key input into the priorities of these Working Groups.

2.3 Committee Overview

2.3.1 Stakeholder Council

The Stakeholder Council will be convened directly by the MDEpiNet Coordinating Center, with the purpose of

providing a “level playing field” and a range of senior expertise and involvement sufficient to both review and

evolve the strategic directions, operations and productivity of the overall MDEpiNet Initiative. The Stakeholder

Council will include (but, not be limited to) leadership from the MDEpiNet Centers, the PPP Executive

Committee, senior Industry representatives, regulatory officials, charitable foundation leadership, and other

stakeholders. The Stakeholder Council will meet both remotely and face to face on a regular basis, on a

schedule to be determined. The mission, membership, responsibilities, and deliverables of the Stakeholder

Council are detailed further, below.

2.3.2 Executive Operations Committee (EOC)

The EOC will be the central operations leadership committee. This committee will be tasked by its charter with

executing the MDEpiNet vision, with strategic direction provided through interaction with the Stakeholder

Council. EOC membership will include (but, not be limited to) leadership from the Science and Infrastructure,

Methodology, and Coordinating Centers, operational committee chairs, and the U.S. FDA. More details about

the mission, membership, responsibilities, and deliverables of the EOC are provided below.

2.3.3 Stakeholder Engagement and Sustainability (SES) Committee

The Stakeholder Engagement and Sustainability Committee (SES) will be chartered by the EOC to develop a

strategic planning document that outlines activities to facilitate broad and balanced participation by a wide

range of stakeholders. The SES will specifically compile and track a listing of medical device ecosystem

stakeholders currently engaged with the MDEpiNet PPP, and the primary values related to that involvement. In

parallel the SES will also identify key stakeholders who are not yet engaged with the PPP, and develop related

outreach strategies. In addition the SES will create a sustainability plan to ensure that MDEpiNet activities and

deliverables provide clear business value to engaged stakeholders. This will include definition of what

constitutes MDEpiNet PPP “member” status, rights and privileges. The initial MDEpiNet financial sustainability

plan will balance membership value with operational costs of maintaining the PPP. The plan is expected to

include membership funding options as well as development of contingencies for budget surpluses or deficits.

As the PPP matures and stakeholder involvement increases, the SES may split its responsibilities into those of a

Membership Committee and a Budget Committee to more effectively meet MDEpiNet objectives. The SES

Committee will not initially review or distribute grant funding. Should grant funding become part of the

MDEpiNet scope of operations, the roles of SOC and SES will be revisited as necessary. The SES Committee will

report directly to the Executive Operations Committee.

2.3.4 The Scientific Oversight Committee (SOC)

The SOC is the convening, oversight and facilitation body for the Disease-based Working Groups. The SOC will

report directly to the Executive Operations Committee. SOC membership will include a broad range of

individuals, representing the scientific community (from academia and industry) and regulatory agencies (U.S.

and International). The SOC will both facilitate and evaluate the progress of the individual Working Groups; it

will be chartered to consider key aspects of the Working Group implementation plans, including but not limited

to: 1) the alignment of objectives with the MDEpiNet mission; 2) the practicality of the implementation plan,

including access to resources, leadership, expertise and timelines for deliverables; and, 3) the impact of specific

proposed deliverables. The leadership of the SOC will be defined in the Committee Charter. The mission,

membership, responsibilities, and deliverables of the SOC are detailed further, below.

2.3.5 Publications Committee

The Publications Committee will be chartered to oversee the production (including authorship, timelines, and

journal submission) of white papers and other collaborative manuscripts originating within the MDEpiNet

Initiative. The details of these processes will be described in its charter. Publications will develop its directions

through interactions with the SOC and PPMC, to ensure that publications facilitating transparency and

dissemination of deliverables are aligned with priorities of Disease Specific Working Groups and production of

PPP. The Publications Committee will report directly to the Executive Operations Committee.

2.3.6 Public Programs and Meetings Committee (PPMC)

The PPMC will be chartered to facilitate topical think tanks and other meetings that will address cross-cutting

issues affecting the function of the Disease-based Working Groups. PPMC will receive direction from

interactions with the SOC and Publications Committees to ensure that programs are aligned with priorities of

Disease Specific Working Groups and production of PPP deliverables. PPMC will coordinate a broad group of

collaborators to identify leadership, agendas, faculty, calendar timing, location, financial planning and other

specifics related to the conduct of these meetings. PPMC will report directly to the Executive Operations

Committee.

3 Disease-based Working Groups

3.1 Mission Disease-based Working Groups are the cornerstone functional groups for the collaboration. Each Working Group

will be charged with development and implementation of a proposal-based program related to advancing

regulatory science related to device evaluation in the specific disease space. Working group chair and co-chair

will serve as ex-officio members of the SOC.

3.2 Membership Working Groups will be initiated following submission to and acceptance of a proposal by the Scientific Oversight

Committee. The SOC will identify the project leaders (chair and co-chair), topic and deliverables. On approval,

membership in the Working Group will be opened to interested volunteers from all stakeholder groups.

Membership in the Working Groups is intended to be inclusive of all individuals and organizations with a stake

and interest in both device evaluation and the particular disease state. Broadly, membership will include (but, not

be limited to):

1. Patient Representatives

2. Professional Societies

3. U.S. FDA

4. Medical Device Industry

5. Data Partners

6. Academia

7. Hospitals and health care systems

8. Medical claims payers

9. Other related Federal agencies and providers

3.3 Responsibilities Responsibilities of the Working Groups will include all of the activities necessary to produce the deliverables

specified in the SOC-approved project proposal. Working Groups will report to and respond to feedback from the

Scientific Oversight Committee. Examples of responsibilities will include (but, not be limited to):

1. Mapping the existing disease-specific device evaluation landscape with particular attention to:

a. Existing data resources, and

b. High risk medical devices relevant to the proposal

2. Creating a disease-specific project-based Roadmap to a functional, efficient device evaluation system,

including:

a. Needs assessment, and

b. Business plan

3. Operationalizing the Roadmap in collaboration with the Methodology, Science and Infrastructure, and

Coordinating Centers, as needed;

4. Soliciting and securing funds, data access, and analytic support for Working Group operations;

5. Reporting to the SOC on progress, obstacles encountered, and solutions identified when operationalizing

the disease-specific collaborative Roadmap;

3.4 Deliverables Deliverables and timelines for deliverables will be specific to each individual Working Group and will be outlined

in the project-based Roadmap.

Independent of the specific Working Group projects, deliverables will include (but, not be limited to):

1. Report to the SOC on the disease-specific landscape, horizons, and project-based Roadmap to a

functional, efficient medical device evaluation system;

2. Submission to the SOC and SES of a systematic needs assessment for accomplishing the disease-specific

project-based Roadmap;

3. Report on an annual basis to the SOC on the progress, obstacles encountered, and solutions identified

during implementation of the disease-specific project-based Roadmap.

4 Scientific Oversight Committee (SOC)

4.1 Mission The SOC is the convening and facilitation body for the Disease-based Working Groups. It is charged with 1)

reviewing and approving Disease-based Working Group proposals, 2) overseeing Working Group roadmap

implementation plans, and 3) and identifying strategic priorities for think tank and other collaborative meetings

and manuscript development.

4.2 Membership Membership (number of members to be determined) in the SOC will include a broad range of individuals,

representing the scientific community (from academia and industry) and regulatory agencies (U.S. and

International). By charter, leadership of the SOC will rotate among the membership, and individuals with conflicts

of interest will be recused in the review of specific proposals.

Membership will include (but, not be limited to):

1. MDEpiNet Methodology Center

2. MDEpiNet Science and Infrastructure Center

3. MDEpiNet Coordinating Center

4. MDEpiNet FDA CORE Program

5. Medical Device Industry

6. Data Partners

7. Professional Societies

8. Patient Representatives

9. Health Systems

10. Payers

11. Governmental Agencies

4.3 Responsibilities Scientific Oversight Committee responsibilities center around convening, facilitating and overseeing the Working

Groups. These responsibilities include (but, are not limited to) the following:

1. Review project proposals including review of the needs of and resources available in each field, and

convene Disease-based Working Groups for approved projects;

2. Review and provide feedback to each Working Group on its Roadmap and progress reports, with specific

attention to the alignment of objectives with the MDEpiNet mission, the practicality of the

implementation plan (including access to resources, leadership, expertise and timelines for deliverables),

and the expected impact of specific proposed deliverables;

3. Address Working Groups needs together with the EOC and Business and Finance Committee through

collaborative interaction across MDEpiNet Centers; collaboration with international partners; and

collaboration with stewards and owners of common sources of data;

4. Submit a quarterly advisory report to the Executive Operations Committee that addresses the common

strategic priorities, progress, obstacles, solutions, and needs of the Working Groups. This report will

include an assessment of the effectiveness of each Working Group, as well as recommendations regarding

high impact areas for public-private collaborative funding;

4.4 Deliverables 1. Annual feedback reports to the Working Groups, with specific suggestions for achieving strategic

priorities;

2. Quarterly advisory report for EOC regarding both the operations and needs of the Working Groups, as

well as their overall progress toward the strategic vision of the MDEpiNet collaboration.

5 Executive Operations Committee (EOC)

5.1 Mission The EOC is responsible for interfacing between the Scientific Operations Committee (SOC), the Stakeholder

Engagement and Sustainability (SES) Committee, and the Stakeholder Council. The EOC will facilitate the high

level strategic prioritization for common resources and directions for the MDEpiNet Initiative. By charter,

leadership of the EOC will rotate among the three MDEpiNet Centers.

5.2 Membership EOC membership will include (but, not be limited to):

1. Leadership from each of the three MDEpiNet Centers

2. Operational Committee Chairs

3. U.S. FDA CDRH Representative

5.3 Responsibilities The EOC will be responsible for the following specific tasks:

1. Interface with the Stakeholder Council;

2. Prioritization of strategic SOC needs;

3. Broad oversight of the financial planning of the Operational Committees and Working Groups.

5.4 Deliverables The EOC is responsible for summarizing on an annual basis the operations, specific progress, needs, and strategic

vision for the partnership

6 Stakeholder Council

6.1 Mission The Stakeholder Council (number of members to be determined) is a high-level convening organization of the

executive leadership of organizations with a stake in the system of medical device evaluation. This Council will be

convened directly by the MDEpiNet Coordinating Center, and like the existing Interim Stakeholder Council will be

charged with providing strategic guidance and aid for development of the medical device evaluation system. The

Council will meet remotely ad hoc as needed, but face to face at least once per year.

6.2 Membership The Stakeholder Council will engage the leadership from a broad range of organizations, including (but, not

limited to):

1. U.S. FDA CDRH Pre-Market Group

2. U.S. FDA CDRH Post-Market Group

3. Academia

4. Medical Device Industry

5. Interested Foundations and Trusts

6. Data Partners

7. Hospital Systems, Private, University and Federal

8. MDEpiNet Science and Infrastructure, Methodology, and Coordinating Centers

9. Patient Advocates

10. Medical claims payers

11. Professional medical societies

6.3 Responsibilities The Council will consider specific requests from the EOC regarding strategic prioritization, in-kind aid, and system

support. They will give guidance and assistance to the EOC as their means allow.

6.4 Deliverables The Stakeholder Council will have no direct standing deliverables.

7 MDEpiNet Coordinating Center

7.1 Mission The MDEpiNet Coordinating Center is charged with facilitating and overseeing the efficient operations of the 6

core Operational Committees and the Disease-based Working Groups.

7.2 Responsibilities The responsibilities of the Coordinating Center include (but, are not limited to) the following:

1. Operational Committees:

1. Support and coordinate the administrative functions of the Operational Committees;

2. Convening Function:

1. Convene bi-annual meetings of the Operational Committees, including one face-to-face meeting and one

off-cycle Teleconference for each;

2. Coordinate PPP and Working Group process initiation, advancement and oversight through the SOC,

PPMC and publications committees.

3. Convene think tank meetings, as necessary, to address cross-cutting Methodology and Science and

Infrastructure topics.

8 MDEpiNet Methodology Center

8.1 Mission The MDEpiNet Methodology Center is charged with developing and applying novel statistical and epidemiological

methods to monitor the safety and effectiveness of medical devices.

8.2 Responsibilities The responsibilities of the Methodology Center include (but, are not limited to) the following:

1. Select medical devices for post-market surveillance, develop, and illustrate methodology for inferring causal

effects of the selected medical devices, including synthesizing information from diverse data sources

2. Advance statistical methods to improve understanding of medical device vulnerabilities to chemical,

biological, radiological, chemical, or nuclear events in particular

3. To work with the Coordinating and Science & Infrastructure Center, as necessary, to address cross-cutting

topics

9 MDEpiNet Science and Infrastructure Center

9.1 Mission and Objectives

1. Create and advance a new conceptual framework for medical device innovation and evaluation complementing exiting efforts such FDA Total Product Life Cycle Approach.

2. Facilitate national system creation that will contain unique device identifiers (UDI) to address safety and effectiveness of priority implantable medical devices and devices enabling interventions.

a) Encourage development of national and regional registries and consortia that contain detailed device information.

b) Promote linkages between registries and routinely available data sources that allow adequate follow up for device evaluation

c) Advocate enhancement of routinely available electronic, discharge and claims data to address National Post-market Surveillance system needs for priority medical devices.

3. Facilitate and lead International registry consortia creation that will contain device identifiers that can address safety and effectiveness of priority implantable medical devices and devices enabling interventions.

4. Conduct comparative outcomes studies that determine advantages and demerits of different devices and surgical techniques regarding patient-centered outcomes. Apply studies to inform clinical and regulatory decision making.

5. Collaborate with partners and create forums for discussion, workshops and conferences to bring external stakeholders with relevant data and expertise to share best practices and build collaborations.

6. Collaborate with partners in developing peer-reviewed papers and white papers

7. Collaborate with Methodology center in development and testing of innovative methodological approaches such as use of distributed network analyses, propensity scores, instrumental variables, and other epidemiological methods.

10 Business Plan To ensure that the MDEpiNet is sustainable beyond the initial program planning period, monetary resources and in-kind

contributions will be needed to support Project Plans. The opportunity to advance both the quality and efficiency of

medical device regulatory science throughout the TPLC has humanistic, social, professional practice and outcomes, and

financial implications of enormous magnitude. Conducted in the collaborative, participatory and pre-competitive

environment of a PPP, this opportunity will constitute the primary leverage for participation and contribution of

resources from members, sponsors or granting organizations. In addition, this charter, the MDEpiNet PPP’s widely

accessible avenues for participation by stakeholders, and distribution of operational expenses over multiple participants

create opportunities at reduced cost to any single participant.

The Coordinating Center will commence work as soon as possible to secure funding for Project Plans approved by the

Stakeholder Council, as a Project Plan’s access to funds will be a contributing factor in Board approval decisions.

Several financial models will be developed and vetted. It is anticipated that a sustainable long-term financial model will

be selected during the initially funded program planning period of 3 years. During the first 3 years of the MDEpiNet

initiative, existing meetings (e.g. annual meeting) will be leveraged to maximize program activities and minimize costs.

Coordinating Center costs may include:

o Administrative Costs (including coordinating center staff)

o Implementation and operations of think tank and other meetings (including Stakeholder Council Meetings)

o Implementation and operations of the 6 Operational Committees

Within the first three years of operations, Coordinating Center will develop and implement a business plan that includes

definition of membership, membership categories and identifies funding sources. Federal agencies and/or their staff

shall not be involved in fundraising, the development and/or implementation of the business plan or pay membership

fees.

The selection and award of grants and/or contracts funded under MDEpiNet will be conducted in accordance to federal

law where applicable, and in such a manner as to ensure fairness, impartiality, and inclusiveness, as well as conformity

with all its policies.

11 Conflict of Interest Policy

No member of the MDEpiNet PPP Stakeholder Council may participate in the decision-making process on any matter in

which the Board member, or a Relative of such member, has any Interest. The terms “Relative” and “Conflict of

Interest” are defined as follows:

“Relative” means the spouse, parent(s), sibling(s), child(ren), and domestic partner(s) or any others sharing a

financial or household relationship to the Executive Committee member.

“Conflict of Interest” means any pecuniary or proprietary interest that would cause a board member or

company to not act in the best interest of the MDEpiNet PPP and its collective members.

Upon learning that MDEpiNet PPP is involved in a matter in which Board member believes a real or potential Conflict of

Interest may exist, the member shall notify the Board Chair and Vice-Chair and shall recuse him/herself from any further

consideration or discussion of the issue around which the conflict exists.

Additionally, each federal agency participating in the activities of the MDEpiNet PPP will implement and enforce all

federal rules governing conflicts of interest in relation to employee involvement in the MDEpiNet PPP, including in

addition to any agency-specific regulations the applicable criminal provisions of Title 18 of the U.S. Code (e.g., sections

208, 203, 205, 209) and Parts 2634 and 2635 of the Code of Federal Regulations.

Federal employees known by their employing agency to have any apparent or actual Conflict of Interest will not be

assigned to participate or will not be permitted to continue participation in the MDEpiNet PPP unless or until any

apparent or actual Conflict of Interest has been waived or resolved under federal law and regulation. In the event a

Conflict of Interest is waived for a federal employee to permit that employee’s participation in activities of the

MDEpiNet PPP, the federal agency will promptly notify the MDEpiNet PPP Coordinating Center that a waiver is in place

with respect to that employee.

12 Liability and Indemnification of Officers, Directors, Employees, and Agents

a) All entities or individuals participating in the MDEpiNet partnership shall hold harmless and assume any and all

liability against directors, officials, committee members, employees, and agents of any of the MDEpiNet

committees, or against any federal agency, director, employee or agent participating in the MDEpiNet

partnership, for any obligations or actions to third parties stemming from or directly arising from the

participation in any MDEpiNet committee, including without limitation judgments, fines, and penalties; and

reasonable expenses (including without limitation reasonable counsel fees and other reasonable related fees)

actually and necessarily incurred by or imposed on him or her, in connection with such Potential Indemnitee’s

defense against any claim, action, suit, or proceeding (whether actual or threatened, civil, criminal,

administrative, or investigative, including appeals) (each, a “Proceeding”) to which he or she may be or is made a

party to in connection with his/her participation in the PPP.

b) The indemnification provided by this article shall continue as to a person who has ceased to be a Director,

Officer, employee, or agent and shall inure to the benefit of the heirs, executors, and administrators of such a

person.

c) In lieu of providing the advancements or indemnification provided for herein, Duke may, at its own expense and

not to be reimbursed by the Potential Indemnitee, undertake the defense of any such Potential Indemnitee, in

which case the Board in its discretion may determine whether MDEpiNet shall reimburse such Potential

Indemnitee for any fees and expenses incurred as a result of his or her engagement of separate counsel,

whether through advancements or indemnification.

d) Except as otherwise provided herein, within fifteen (15) business days after the MDEpiNet’s receipt of a request

therefore, and of a written undertaking by the Potential Indemnitee to repay or to reimburse all such amounts if

it is determined that such Potential Indemnitee is not entitled to indemnification under this Article, the

MDEpiNet shall advance Indemnifiable Amounts to a Potential Indemnitee. The provisions of this Article shall be

applicable to Proceedings made or commenced after the adoption hereof, whether arising from acts or

omissions to act occurring before or after adoption hereof.

e) The indemnification and advancements provided by this Article shall not be deemed exclusive of any other

rights to which any Potential Indemnitee may be entitled under any applicable law.

f) There shall be no indemnification in relation to matters as to which the MDEpiNet Stakeholder Council finds that

the Potential Indemnitee acted or omitted to act, in either case in bad faith, or engaged in willful misconduct in

the performance of a duty to the PPP. Prior to making any such finding, the MDEpiNet Stakeholder Council shall

provide the Potential Indemnitee with at least ten (10) business days written notice of its intent to consider the

matter, within which time the Potential Indemnitee shall have the right to submit relevant written materials to

the Board for its consideration.

g) As a condition precedent to a Potential Indemnitee’s right to be indemnified or receive advancements

hereunder, he or she shall (i) give to the MDEpiNet notice in writing directed to the MDEpiNet’s Stakeholder

Council Chair (or to such other individual as the MDEpiNet may designate) as soon as practicable of any

Proceeding made against such Potential Indemnitee for which indemnity will or could be sought, and (ii) other

than in connection with a Proceeding by or in the right of the MDEpiNet, provide the MDEpiNet with such

information and cooperation as it may reasonably request.

h) Insurance. The Coordinating Center will purchase insurance on behalf of all MDEpiNet Directors and Officers

against any liability which may be asserted against or incurred by him or her that arises of the such person’s

status as an MDEpiNet Director, Officer or Committee member, or out of acts taken in such capacity, whether or

not the MDEpiNet would have the power to indemnify such person against that liability under law. To the extent

that any applicable insurance is available to respond to any proceeding addressed in this Article, such insurance

shall be exhausted before any payment is made pursuant to the advancement and indemnification provisions in

this Article.

13 Miscellaneous Provisions

Use of Electronic Mail/Communication. Any requirement in this charter that notices or other communications must be

in writing shall be satisfied by electronic communications or transmissions.

Voting procedures. The primary system for decision-making within the partnership shall be consensus. Nevertheless, in

the rare event that consensus cannot be reached, the decision-making for all matter of the partnership shall be

performed through a majority vote of the membership. What constitutes majority and membership shall be defined in a

subsequent governance document.

14 Charter Addendums and Amendments

This Charter is intended to provide a framework for the MDEpiNet PPP, and it recognizes the potential need to add

provisions as addendums. The primary system for decision-making within the partnership shall be consensus.

Nevertheless, in the rare event that consensus cannot be reached, any modification to this Charter shall require a Two-

Thirds (2/3) majority vote of the membership, as per membership definition in a subsequent governance document.