As data is captured through electronic health records, registries and unique device identifiers, the generation of evidence based on this data is expected to play a crucial role in informing orthopedic manufacturers’ decisions before and after regulatory approval. While regulators, payors, hospitals and manufacturers support this shift, they acknowledge that gaps remain in its optimal execution. Priority considerations include how to generate evidence to expedite regulatory market decisions, device indication expansion, postmarket studies, postmarket surveillance and reimbursement decisions. The National Evaluation System for health Technology Coordinating Center (NESTcc), an initiative of the Medical Device Innovation Consortium (MDIC), is leading the conversation with various stakeholders, including FDA and orthopedic device companies to support the sustainable generation of Real-World Evidence (RWE) using Real-World Data (RWD).

2. Rachel R. Rath, MBA, MPH
Chief of Staff, NESTcc
Wednesday, June 12, 2019
Real-World Evidence: The Future of Data
Generation and Usage through NESTcc

3. 2www.nestcc.org@NESTccMedTech
MDIC RECEIVED INITIAL FUNDING FOR NESTcc IN 2016
MDIC is a public-private partnership that facilitates programs and
activities to advance the medical device regulatory process for patient
benefit. These programs are housed within four core initiatives of MDIC.
HEALTH
ECONOMICS AND
PATIENT ACCESS
CLINICAL SCIENCE DATA SCIENCE AND
TECHNOLOGY
- Case for Quality (CfQ)
- Computational Modeling
and Simulation (CM&S)
- External Evidence Methods
- Cybersecurity
NATIONAL EVALUATION
SYSTEM FOR HEALTH
TECHNOLOGY
COORDINATING CENTER
(NESTcc)

4. 3www.nestcc.org@NESTccMedTech
Regulators
Health
Systems
Patient
Groups
Clinician
Groups
PayersIndustry
NESTcc
NESTcc’s MISSION & VISION
Mission
To accelerate the development and translation of new and
safe health technologies, leveraging Real-World Evidence
(RWE), and innovative research.
Vision
To be the leading organization within the health technology
and medical device ecosystem for conducting efficient and
timely high-quality Real-World Evidence (RWE) studies
throughout the Total Product Life Cycle (TPLC).

5. 4www.nestcc.org@NESTccMedTech
NESTcc DEVELOPMENT BEGAN IN 2012
4
201520162017
NESTcc envisioned as a voluntary data network of collaborators by Planning Board
FDA awarded funding for NESTcc to Medical Device Innovation Consortium (MDIC)
NESTcc Executive Director named and Governing Committee selected
NESTcc Strategic and Operational Plan developed
Initial NESTcc Data Network formed and testing initiated through Round 1 Test-Cases
2018
NESTcc Data Quality and Methods Subcommittees formed
2012
FDA proposed the development of a national system
20192022
Concept
Building
Capacity
Network
Development
Utilization
& Expansion
Interim and Final Results from Round 1 and Round 2 Test-Cases
NEST Version 1.0 is operational
NESTcc fully launched and operational

6. 5www.nestcc.org@NESTccMedTech
MULTI-STAKEHOLDER GOVERNING COMMITTEE ADVISES NESTcc
Trade Association Nominees
NAOMI ARONSON
Blue Cross Blue Shield Association (BCBSA)
KATHLEEN BLAKE
American Medical Association (AMA)
MARK DEEM – MDMA Nominee
The Foundry, LLC
PAMELA GOLDBERG
Medical Device Innovation Consortium (MDIC)
BILL HANLON – ACLA Nominee
LabCorp/Covance
ADRIAN HERNANDEZ
Governing Committee Vice Chair
Duke Clinical Research Institute (DCRI)
HARLAN KRUMHOLZ
Yale University
JENNIFER LURAY
Research!America
MICHELLE MCMURRY-HEATH –
AdvaMed Nominee
Governing Committee Chair
Johnson & Johnson Medical Devices
VANCE MOORE
Governing Committee Treasurer
Mercy Health
JEFFREY SHUREN
CDRH, FDA
SHARON TERRY
Genetic Alliance
DIANE WURZBURGER – MITA Nominee
GE Healthcare
MARC BOUTIN
National Health Council
TAMARA SYREK JENSEN
Center for Clinical Standards and Quality, CMS

7. 6www.nestcc.org@NESTccMedTech
FRAMEWORK STRATEGY TO ACHIEVE ESTABLISHED GOALS
To achieve success, NESTcc has four strategic priority areas for 2019:
1 2 3
Establish NESTcc
Governance
Develop NESTcc’s
Data Network
Establish NESTcc’s
Sustainability
Ensure NESTcc
Stakeholder
Engagement
Ensure NESTcc
Stakeholder
Engagement
4
Ensure NESTcc
Stakeholder
Engagement

8. Establishing the NESTcc Data Network

9. 8www.nestcc.org@NESTccMedTech
REAL-WORLD DATA & REAL-WORLD EVIDENCE
Real-World Evidence (RWE)
Insights gleaned from Real-World Data (RWD) that have the potential to inform and
empower patients, accelerate medical device innovation, and improve health care
outcomes.
Real-World Data (RWD)
Data generated in the routine course of care, rather than during pre-market research
or clinical trials, that takes into account real patient experiences.

10. 9www.nestcc.org@NESTccMedTech
NESTcc has established relationships with 12 Network Collaborators to
advance evaluation and use of high-quality RWD from various sources.
Profiles of each Network Collaborator can be found on NESTcc’s website.
ESTABLISHING THE NESTcc DATA NETWORK

11. 10www.nestcc.org@NESTccMedTech
BUILDING NESTcc’S DATA NETWORK
NESTcc surveyed its Network Collaborators to determine current
capabilities, gaps, and priority areas.
12
Duke University Health System
• HealthCore • Lahey Clinic
• Mayo Clinic • MDEpiNet • Mercy
• NYC-CDRN • OneFlorida
• PEDSnet • STAR
• Vanderbilt University
• Yale New Haven Health System
Network Collaborators represent
Hospitals
195 Outpatient
Clinics
Network Collaborators report
regular data refreshes
4 Quarterly
3 Mixed Rates
3 Monthly
2 Daily
Most cited expertise
 Cardiovascular and Cardiac Surgery
 Women’s Health
 Neurosurgery
 Gastroenterology
 Orthopedic
Patient
Records
494M+*
Patient data represents
Network
Collaborators
Common data models
 I2b2
 OMOP
 PCORnet
 Sentinel
*Does not account for duplicate records
Numbers reflect data as of February 2018

12. 11www.nestcc.org@NESTccMedTech
The collaborators comprising the NESTcc Data Network have access to a
range of available data sources, including those listed below.
ACCESS TO A RANGE OF RWD SOURCES
EHR
Public Claims
Pharmacies
Registries*
Private Claims
Patient-Generated
Data
*Registries Include (but are not limited to):
• Anesthesia Quality Institute’s National Anesthesia Clinical Outcomes
• Cardiac Catheterization
• Cardiogenic Shock
• Immunization
• Implant registries
• Integrated tumor
• International Consortium Lower-GI
• American College of Surgeons National Surgical Quality Improvement
Program
• Oncology
• Pediatric Cardiomyopathy
• Prostate Ablation‐Related Energy Devices
• Robotic Surgery
• Society of Thoracic Surgeons National Database
• Society for Vascular Surgery
• Thalassemia Clinical Research Network - Thalassemia Registry
• Vital Records (Birth and Death)
UDI
0 12# collaborators
0 12# collaborators
0 12# collaborators
0 12# collaborators
0 12# collaborators
0 12# collaborators
0 12# collaborators incorporating fully or
demonstrated capability
Available Data Sources UDI Implementation

13. Utilizing the NESTcc Data Network

14. 13www.nestcc.org@NESTccMedTech
PROGRESSIVE EXPANSION OF THE NESTcc CAPABILITIES AND USES
Since 2018, NESTcc has been progressively developing the capabilities
of the NESTcc Data Network through Test-Cases with the NESTcc
Network Collaborators.
ADDRESS
RETROSPECTIVE
RESEARCH
QUESTIONS FROM
MEDICAL DEVICE
MANUFACTURERS
ADDRESS QUESTIONS
FROM STAKEHOLDERS,
INCORPORATING
PATIENT-GENERATED
DATA (PGD) FOR
PROSPECTIVE
RESEARCH QUESTIONS
UTILIZE THE NETWORK
TO ADDRESS ACTIVE
SURVEILLANCE SAFEY
SIGNAL REFINEMENT
UTILIZE THE NETWORK TO
DETECT SAFETY SIGNALS
2018
2019
2019
2020

15. 14www.nestcc.org@NESTccMedTech
TWO ROUNDS OF TEST-CASES ARE UNDERWAY
The following process outlines the Test-Case process:
Organization
submits
question
Network
Collaborators
opt-in
NESTcc matches
manufacturer and
collaborators
Project is executed
Lessons and gaps
are sent to NESTcc
Collaborators
submit project
short forms
Collaborators
submit full
project proposal
NESTcc awards
funding
Call for
submissions
posted
1. FDA and MDIC staff
review
2. Preliminary Selection
Team approval
1. Final Selection Team
project-level approval
2. GC slate approval
3. MDIC Board slate
approval
4. FDA project-level
approval
ROUND 1 & 2 ARE HERE
START HERE

16. 15www.nestcc.org@NESTccMedTech
SELECTED TEST-CASES SUPPORT THE TOTAL PRODUCT LIFE CYCLE
NESTcc Test-Cases are intended to explore the Network Collaborators’ ability
to capture the data needed to support a range of studies and analyses.
NESTcc Test-Cases Advance Across the Medical Device Total Product Life Cycle (TPLC)
Pre-
Market
Label
Expansion
Post-
Market
Surveillance Coverage

17. 16www.nestcc.org@NESTccMedTech
NESTcc TEST-CASES ADDRESS A RANGE OF DEVICE QUESTIONS
NESTcc’s Round 1 Test-Cases span a wide range of devices classes,
regulatory pathways, TPLC stages, data sources, and disease areas.
Device Classes
Class I
Class II
Class III
Regulatory Pathway
510(k)
PMA
TPLC Alignment
Pre-Market
Label Expansion
Post-Market
Active
Surveillance
Data Sources
Claims
Electronic
Health Records
(EHRs)
Registries
Disease Area
Cardiology
Dermatology
Orthopedics
Surgery
Vascular

18. 17www.nestcc.org@NESTccMedTech
Eight Test-Cases were selected in the initial round of Test-Cases:
NESTcc ROUND 1 TEST-CASES
TOTAL-PRODUCT LIFE
CYCLE (TPLC)
ALIGNMENT
REGULATORY
PATHWAY
PRODUCT(S)
PARTICIPATING
NETWORK
COLLABORATORS (n)
DISEASE AREA
Pre-market Submission 510(k) Wound Closure Devices (topical skin
adhesives, staples, sutures)
2 Dermatology
Label Expansion PMA Endovascular stent 3 Vascular
Label Expansion PMA Catheters used in Rx of Cardiac
Arrhythmias
3 Cardiology
Label Expansion PMA Mechanical Aortic Heart Valves 2 Cardiology
Label from General to
Specific Indication
510(k) Microwave Ablation Device 4 Surgery
Post-market Surveillance 510(k) Total Knee Arthroplasty 2 Orthopedics
Post-market Surveillance 510(k) Craniomaxillofacial Bone Distractors 1 Orthopedics
Post-market Surveillance 510(k) Intervertebral Lumbar Body Fusion
Devices
2 Orthopedics

19. 18www.nestcc.org@NESTccMedTech
ORTHOPEDIC TEST-CASE – TOTAL KNEE ARTHROPLASTY
Project Title Testing the Feasibility of Registry and Claims Data Linkages
Data Sources Electronic Health Records, Public Claims, Private Claims, Pharmacies, Registries
Project Duration 12 months
Disease Area Orthopedic
Technology of Interest Total Joint Arthroplasty (TJA); Primary Total Knee Arthroplasty
Project Aims
• This project aims to conduct anonymous data linkages of Registry data with Real-World Data (RWD)
sources, including private claims databases within the NESTcc Network Collaborators, from Mayo
Clinic (Optum Labs) and HealthCore.
• The specific aim is to conduct a descriptive study to evaluate the clinical outcomes of total knee
arthroplasty (TKA) implant survivorship, mortality, revision/reoperation, readmission, and Emergency
Department visit following TKA 2012-2017 for private health plan members.
Pre-
Market
Label
Expansion
Post-Market
Participating Network Collaborators
Surveillance
Coverage
TotalProductLifeCycle(TPLC)Alignment
Regulatory Pathway
510(k)

20. 19www.nestcc.org@NESTccMedTech
ORTHOPEDIC/ENT TEST-CASE – CRANIOMAXILLOFACIAL DISTRACTORS
Project Title Developing Capacity to Conduct Proactive Post Marketing Safety Surveillance
of Craniomaxillofacial Distractors Using Electronic Health Record Data
Data Sources Electronic Health Records, Registries
Project Duration 9 months
Disease Area Orthopedic/ENT
Technology of Interest Craniomaxillofacial Distractors
Project Aims
• This test-case will assess the feasibility of using Real-World Data (RWD) captured through the NESTcc
Data Network to conduct proactive post-market surveillance for safety with devices used in pediatric
populations.
• This test-case seeks to determine the feasibility of using RWD captured through PEDSnet, a NESTcc
Data Network Collaborator, to conduct proactive post-market surveillance for safety and effectiveness
for CMF distractors.
Pre-
Market
Label
Expansion
Participating Network Collaborators
Surveillance
Coverage
TotalProductLifeCycle(TPLC)Alignment
Regulatory Pathway
510(k)
Post-Market

21. 20www.nestcc.org@NESTccMedTech
ORTHOPEDIC TEST-CASE – INTERVERTEBRAL LUMBAR BODY FUSION DEVICES
Project Title Developing Capacity to Conduct Proactive Post Marketing Safety Surveillance
of Intervertebral Body Fusion Devices Using Electronic Health Record Data
Data Sources Electronic Health Records, Registries
Project Duration 9 months
Disease Area Orthopedic
Technology of Interest Intervertebral Body Fusion Devices
Project Aims
• This test-case will assess the feasibility of using Real-World Data (RWD) captured through the NESTcc
Data Network to conduct proactive post-market surveillance for safety for class II medical devices.
• Specifically, this test-case will conduct proactive post-market surveillance for safety and effectiveness
of lumbar interbody systems captured within Lahey Hospital and Medical Center (Lahey), a NESTcc
Data Network Collaborator.
Pre-
Market
Label
Expansion
Participating Network Collaborators
Surveillance
Coverage
TotalProductLifeCycle(TPLC)Alignment
Regulatory Pathway
510(k)
Post-Market

22. 21www.nestcc.org@NESTccMedTech
ROUND 2 TEST-CASES SHOWED AN INCREASE IN SUBMISSIONS
The second round of Test-Cases, announced in June 2019, included a
more diverse set of concept submissions from multiple stakeholders.
Announcements
Submissions
• Round 2 included the first targeted Test-Case announcement and multiple announcements posted together.
• First announcement to specifically target patient-generated data (PGD).
• Round 2 received more than 4 times as many submissions as Round 1.
• 40 submissions were received in Round 2 from 26 organizations.
• Submissions were received from a diverse set of organizations—health systems, government entities, non-
profits including patient advocacy organizations, and industry.
• More than twice as many industry groups submitted concepts in Round 2 compared to Round 1.

23. 22www.nestcc.org@NESTccMedTech
NESTcc TEST-CASE WEBSITE DESCRIPTIONS
Round 1 and Round 2 Test-Cases are outlined on NESTcc’s Test-Case webpage,
including information on project titles, duration, and abstracts, as well as
technology of interest, disease area, and participating network collaborators.

24. 23www.nestcc.org@NESTccMedTech
LAUNCHING ACTIVE SURVEILLANCE ACTIVITIES
NESTcc received $3m in targeted funding from FDA and formed a Task Force
which will establish a Roadmap for advancing NESTcc’s active surveillance work
• Multi-stakeholder Task Force announced late 2018.
• Roadmap under development and issued for public commitment in Fall 2019.
Task Force Members
Name Perspective Institution
Kathy Blake NESTcc Governing Committee/Providers American Medical Association
Owen Faris FDA FDA
Kevin Haynes Network Collaborators/Payers HealthCore
Harlan Krumholz NESTcc Governing Committee/Network
Collaborators
Yale
Brad Malin Network Collaborators/Privacy Vanderbilt
Michelle McMurry-
Heath
NESTcc Governing Committee/Industry Johnson & Johnson
Bray Patrick-Lake Patients DCRI
Fred Resnic Network Collaborators/Integrated Health System Lahey

25. 24www.nestcc.org@NESTccMedTech
The NESTcc Active Surveillance Roadmap will be developed to lay out the high-
level foundation for Version 1.0 of Active Surveillance activities. Items will include:
o Initial users (FDA and medical device manufacturers)
o Products and services (signal detection and signal discernment)
o User experience
o Infrastructure and operations
o Data quality and methodology aspects
o Future directions (future users, products and services)
NESTcc ACTIVE SURVEILLANCE ROADMAP
The Task Force is working on a Roadmap that will undergo public
comment.

26. LAUNCHING NEST 1.0

27. 26www.nestcc.org@NESTccMedTech
1. ENGAGE
2. LAUNCH
3. EXECUTE
4. COMPLETE
Engage with NESTcc to develop a project and gain access to:
Data Network Assets
Pricing Structures
Terms and Conditions
Launch through collaborations with identified Network
Collaborators:
Execute required agreements
Communicate with the FDA point of contact
Execute the project through collaboration with the project team of
Network Collaborators while engaging with NESTcc to ensure project
progress
Complete the engagement with NESTcc through the receipt of the
final report, while participating in:
Publications and dissemination opportunities
Engaging directly with regulators and coverage providers for
product-specific discussions and submissions
NEST IS PREPARING FOR A PUBLIC LAUNCH
By the end of 2019, NESTcc will be operationally capable of intaking unsolicited projects from
external stakeholders to utilize the capabilities of the NESTcc Data Network.

28. Ensuring High-Quality Data & Analysis Methods

29. 28www.nestcc.org@NESTccMedTech
ADVANCING DATA QUALITY & METHODS
In 2018, NESTcc established multi-stakeholder subcommittees to support its
efforts to conduct real-world evidence studies for medical devices,
leveraging ongoing initiatives including expertise from MDEpiNet, PCORnet,
and Sentinel.
DATA QUALITY
SUBCOMMITTEE
• Chaired by Dr. Lesley Curtis, Duke University
School of Medicine
• 12-person subcommittee includes
representation from:
• 6 health systems, including Network
Collaborators
• 3 medical device manufacturers
• FDA
• Chaired by Dr. Sharon-Lise Normand, Harvard
Medical School
• 9-person subcommittee includes
representation from:
• 3 health systems, including Network
Collaborators
• 4 medical device manufacturers
• FDA
METHODS
SUBCOMMITTEE

30. 29www.nestcc.org@NESTccMedTech
DATA QUALITY SUBCOMMITTEE & FRAMEWORK
Charge & Vision
• Develop Data Quality Framework for NESTcc Network Collaborators
• Design a process by which NESTcc Network Collaborators can demonstrate
their aptitude with the NESTcc Data Quality Framework
• Develop first, simple, pragmatic, iteration of NESTcc Data Quality Framework
that will apply to a “first wave” of NESTcc Network Collaborators
Data Quality Framework Overview
• Initial version lays out the foundation for the capture and use of high-quality
data for post-market evaluation of medical devices
• Grounded in the use of real-world data (RWD) gleaned from the clinical care
setting and the electronic health record (EHR)
• Data Quality Framework will evolve for a “second wave” of data vendors or
similar collaborators with large de-identified datasets
Framework Organization
1. Governance
2. Characteristics of Data
3. Data Capture & Transformation
4. Data Curation
5. NESTcc Data Quality Maturity Model

31. 30www.nestcc.org@NESTccMedTech
METHODS SUBCOMMITTEE & FRAMEWORK
Framework Organization
1. Background: Disease, Available Therapies,
and Device Risk
2. Device Description
3. Study Specific Objectives
4. Target Population and Patient Selection
5. Outcomes: Primary, Secondary, Procedural,
and Device
6. Device Exposure
7. Study Design
7.1 Specific Design
7.2 Blinding (Masking)
7.3 Units of Randomization and Observation
7.4 Mechanism of Treatment Assignment
7.5 Other Covariates
8. Study Procedures
8.1 Patient Consent
8.2 Randomization
8.3 Protocol Deviation Handling
9. Required Sample Size
10. Study Registration
11. Monitoring Plan
12. Statistical Analysis Plan
Charge & Vision
• Develop a “living” Methods Protocol Framework for NESTcc addressing
device-specific considerations in benefit/risk studies and safety signal
detection.
• Develop a research agenda identifying critical issues in Methods for device,
imaging, and other diagnostic technologies studies across the TPLC
• Consult on an ad hoc basis to NESTcc to ensure that NESTcc activities
employ the most appropriate and rigorous methods of analysis
Methods Framework Overview
• Develop a methodological framework to include device-specific
considerations
• A single protocol is being utilized for both randomized trials and
observational studies

32. 31www.nestcc.org@NESTccMedTech
LAUNCHING THE SUBCOMMITTEE FRAMEWORKS
NESTcc Data Quality & Methods Subcommittee framework development
will include a public comment period before the first iterations are released.
July 2019
Version 1 of NESTcc
Frameworks Released
June 2019
Public Comment Period
Closes
May 2019
Public Comment Period
Opens
Implementation
and Iteration
NESTcc Frameworks
Utilized to Inform Test-
Cases and Active
Surveillance

33. Engage with NESTcc

34. 33www.nestcc.org@NESTccMedTech
NESTcc QUARTERLY NEWSLETTER
The NESTcc Quarterly Newsletter is distributed on the first Tuesday of
each quarter.
• The Newsletter is in response to
feedback from NESTcc stakeholders for
a high-level update on NESTcc
activities.
• The Newsletter contains upcoming
dates and links to news items and
publications from the previous
quarter.
• The newsletter is available to the
public and can be subscribed to here.

35. 34www.nestcc.org@NESTccMedTech
CONNECT WITH NESTcc
Explore opportunities to connect with NESTcc online with the
following resources:

36. 35
www.nestcc.org
@NESTccMedTech
@RachelRRath