Pesentation, October 19th, 2021: What’s Next in RWE for Medical Devices: The Art of the Possible. Presented by Paul Coplan, ScD, MBA, FISPE, Vice President, Med Device Epidemiology and RWD Sciences, Johnson & Johnson; Adjunct Professor, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine; Fellow of the International Society of Pharmacoepidemiology - Why RWE is Important for Medical Devices: Challenges with Clinical Trials of Medical Devices (Blinding, Surgeon skill/technique, Hospital process, Product modifications, Long term Follow up, Enrolment challenges) - Types of Real-World Data Sources (Complaints like MAUDE, Eudramed and Company Databases, Hospital Databases, Electronic Health Records, Claims, Registries, Patient surveys, Surgeon surveys, PROs, Patient Preferences, wearables, sensors, social media, Surgical videos, device generated data, radiographic images) - FDA CDRH Report on RWE Examples for Regulatory Decisions - J&J Med Device Epidemiology & Real-World Data Sciences - US National Evaluation System for Health Technology (NEST) - RWE for Safety Assessments: Cobalt in Implants and at Work and Risk of Cancer - Summary of Cobalt Exposure and All-Site Cancer Risk, by Study Type - Comparative Effectiveness Studies Using RWE - Summary a. Use of RWE is important to benefit patients globally and enhance the safety and innovation of medical devices b. Regulators are interested in using RWE for regulatory decisions but data quality and evidence needs to be regulatory grade c. NEST has been a useful forum to advance the use of RWE for regulatory decisions in the US d. RWE can be used for safety assessments, regulatory decisions, comparative effectiveness research, and R&D of products

1. What’s Next in RWE for Medical Devices: The Art of the
Possible
Paul Coplan, ScD, MBA, FISPE
Vice President, Med Device Epidemiology and RWD Sciences, Johnson & Johnson
Adjunct Professor, Department of Biostatistics, Epidemiology and Informatics
University of Pennsylvania Perelman School of Medicine
Fellow of the International Society of Pharmacoepidemiology

2. Opinions expressed are those of
an individual employee of
Johnson & Johnson, not those
of Johnson & Johnson
2
Disclosure

3. Why RWE is Important for Medical Devices:
Challenges with Clinical Trials of Medical Devices
Source: Johnston S et al. Value & Outcomes Spotlight 2019
Drummond MF Value in Health 2009
Blinding
Difficulty blinding patients and
doctors
Surgeon skill/technique
Strong confounder of outcomes;
learning curve with experience
Hospital process
Hospital processes
influence outcome
Product modifications
Innovation cycle of 3-5 years for
MD vs 10-14 years for drugs
Long term Follow up
High loss to follow up as patients
come to tertiary hospitals for surgery
Enrolment challenges
Small patient pools

4. 4
Types of Real-World Data Sources
Complaints: MAUDE, Eudramed and Company Databases
Hospital Databases
Electronic Health Records
Claims
Registries
Registries linked to claims/EHR
Patient surveys, Surgeon surveys, PROs, Patient Preferences, wearables, sensors, social media
Surgical videos, device generated data, radiographic images

5. 5
FDA CDRH Report on RWE Examples for Regulatory Decisions
Insights
• RWE studies led to highest number of regulatory decisions in
2017
• Before FDA RWE guidance released, PMA supplement and PMA
are most common regulatory actions
• RWE supporting 14 De Novo decisions
FDA identified 90 examples where RWD/RWE was an
“essential” component of the regulatory decision
• Includes products across the total product life cycle (i.e., premarket and
postmarket) and all the review divisions
Examples of Real- World Evidence
(RWE) Used in Medical Device
Regulatory Decisions
Selected examples with file summaries,
details on real-world data source, population,
and descriptions of use
Center for Devices and Radiological Health
Link to the report: https://www.fda.gov/news-events/fda-voices/leveraging-real-world-evidence-regulatory-submissions-medical-devices

6. Deliver evidence for
regulatory decisions
Publish Scientific Evidence to
support Claims and Market
Access
Leverage RWE to conduct
safety assessments
Medical Device Innovation Consortium
National Evaluation System for health
Technology Coordinating Center
(NESTcc)
Mercy Health System EHR Partnership
Pioneer use of RWE for
label expansions and
commitments through
NEST and FDA
collaboration
Applies clinical and scientific
expertise to generate published
evidence from complex data on
clinical and cost benefits of new
technology targeted at payers
and surgeons
Transforms complex
big data sets to RWE to
answer safety questions
previously deemed
unanswerable
Links digital data of device use
during surgery with patient
outcomes in EHR to develop
guidance on safe and effective
use of digital platforms
Apply Machine Learning models
to enhance patient outcomes
Shaping the global environment for using Real World Evidence
We leverage clinical and real-world data to further the safety and understanding of our products
J&J Med Device Epidemiology & Real-World Data Sciences
OUR MISSION • Develop and conduct patient-centric, scientifically robust and influential RWE studies for J&J medical devices
• Shape the environment through regulator interactions, journal publications and conference presentations
Strategic
Pillars
Value
Leading
Industry
Partnerships
6

7. US National Evaluation System for Health Technology (NEST)
NEST:
Public-private partnership funded by FDA to accelerate
development of new and safe health technologies using
RWE and innovative research
Goal
• Mature the use of RWE to support
regulatory decisions
• Collaborate with FDA and academic healthcare researchers on
developing RWE through NEST
• Conduct 4 studies of J&J products with
leading medical centers funded by FDA
- Duke, Mayo, Yale, Weill-Cornell, Pediatric Children’s Hospitals
Status
• NEST selected 21 test cases for funding, 4 proposed by J&J
• Applying learnings for label extensions and safety surveillance
Test Cases of RWE for
Safety Surveillance
Spinal Fusion
intervertebral
fusion devices
Pediatric craniomaxillary
facial distractors
Cardiac Ablation:
ThermoCool catheter label
extension to persistent AFib
and ventricular tachycardia
Liver Tumor Ablation:
NueWave MWA for nonresectable liver
tumor ablation
Test Cases of RWE for
Label Extensions
7

8. RWE for Safety Assessments:
Cobalt in Implants and at Work and Risk of Cancer
• European Chemicals Agency Committee proposed up-classification of metallic cobalt to
Carcinogenicity Classification of Category 1B based on animal toxicology studies
• Did not evaluate relevance of classification for patients exposed to Co-containing alloys
in medical devices
“Presumed to have carcinogenic potential for humans”
• Cobalt is ubiquitous in medical devices because cobalt alloys are biocompatible
materials with a unique combination of properties including strength, durability, and
long history of safe use that make them suited for use in a wide-range of medical
devices.
• We undertook a comprehensive summary of literature and meta-analysis leveraging
data and scientific expertise from 17 companies and external experts
Background

9. Summary of Cobalt Exposure and All-Site Cancer Risk, by Study Type
Cancer rate higher in
comparator
Cancer rate higher in cobalt-exposed
Average follow-up 9.7 years (range: 2.7 – 31.1)

10. Comparative effectiveness of powered staples for bariatric surgery
• Stapler 1 compared to Stapler 2
• 1,964 matched (1:1) patients undergoing laparoscopic sleeve gastrectomy for
obesity
• Patients using Stapler 1 had fewer hemostasis-related complications
• 0.61% vs. 2.24%, p=0.0012
• Reference: Rawlins L, Johnson B, Johnston S, et al. Medical Devices:
Evidence and Research 2020:13 195–204
0.61%
2.24%
0.0%
1.0%
2.0%
3.0%
GST Signia
Stapler Hemorrhagic
complications
Comparative effectiveness of ablation catheters for atrial fibrillation
• Catheter 1 compared to Catheter 2
• 1,720 Afib patients with Catheter 1 and 1,295 with Catheter 2, propensity score
matched
• Catheter 1 group had significantly:
• 54% lower odds of post-procedure rehospitalization for CV disease
(1.8% vs 3.4%)
• 17% lower total ablation cost ($23,096 vs $27,682, p ≤ 0.0001)
• 27% lower supply cost ($10,208 vs $13,816)
• Reference: Costea A, et al. BMJ Open 2020 ;10:e035499. doi:10.1136/bmjopen-2019-035499
48 journal articles since January 2020
Comparative Effectiveness
Studies Using RWE
10
%
of
Treated
Patients
%
of
Treated
Patients
$20,000
$22,000
$24,000
$26,000
$28,000
$30,000
0.0%
1.0%
2.0%
3.0%
4.0%
Catheter 1 Catheter 2
Rehospitalization for CV disease
Total ablation cost
Post-Ablation for Atrial Fibrillation: Rehospitalization for CV disease
p=0.0012
Stapler 1 Stapler 2

11. 11
Summary
Use of RWE is
important to
benefit patients
globally and
enhance the
safety and
innovation of
medical devices
Regulators are
interested in using
RWE for
regulatory
decisions but data
quality and
evidence needs to
be regulatory
grade
NEST has been a
useful forum to
advance the use
of RWE for
regulatory
decisions in the
US
RWE can be used
for safety
assessments,
regulatory
decisions,
comparative
effectiveness
research, and
R&D of products

12. Thank You!
Contact for questions: pcoplan@its.jnj.com