Welcome to today’s 

FDA/CDRH Webinar

Thank you for your patience while we register all of today’s 

participants.

If you have not connected to the audio portion of 

the webinar, please do so now:

Dial: 800-779-8625:

International: 1-210-234-0098 

Passcode: 7388850 

Conference number: PWXW5328003
Use of Real-World Evidence to 

Support Regulatory DecisionMaking for Medical Devices

Josh Chetta- Biomedical Engineer, Office of Device 

Evaluation

Yuzhi (Alex) Hu- Medical Device Epidemiologist, 

Office of Surveillance and Biostatistics

Center for Devices and Radiological Health
3 

Agenda

• Background 

• Differences between draft and final version

• Regulatory framework

• Highlights and scope of final guidance 

– Overview of selected sections

– Examples

• Questions 
4 

Context for RWE Guidance

FDA Reauthorization Act (FDARA) including MDUFA IV commitment to 

use of real-world evidence to support device pre/postmarket decisions

National Evaluation System for health Technology (NEST)

2016-2017 CDRH Strategic Priorities 

Guidance issued to clarify how RWE may be used to support 

regulatory decisions
5 

Definitions from the Guidance

Real-World Data (RWD) 

Data relating to patient 

health status and/or the 

delivery of health care 

routinely collected from 

a variety of sources

Real-World Evidence (RWE)

Clinical evidence regarding 

the usage and potential 

benefits or risks of a 

medical product derived 

from analysis of RWD
6 

Turning Data into Evidence

Real-World Data (RWD) 

Data relating to patient 

health status and/or the 

delivery of health care 

routinely collected from 

a variety of sources

Real-World Evidence (RWE)

Clinical evidence regarding 

the usage and potential 

benefits or risks of a 

medical product derived 

from analysis of RWD

RWD RWE Analysis 

Guidance addresses issues related to processes of:

• Generation and collection of RWD

• Analysis of RWD

• When results might be considered valid scientific evidence

Collection Use 
7 

Structure of the Guidance

• Scope and Definitions

• Background and Context

• General Considerations for use of RWE

• Investigational Device Exemption (IDE) 

Requirements 

• Data Quality – Relevance and Reliability

• Examples
8 

Scope of the Guidance

Guidance Discusses:

• How FDA will evaluate whether RWE is of sufficient quality 

to inform regulatory decisions for medical devices.

• Some of the potential uses of RWD.

Outside the Scope of the Guidance:

• Use of non-clinical data, adverse event reports, secondary 

use of clinical trial data, or systematic literature reviews. 

• Specific methodological approaches to study design/conduct 

or analytical methodologies.

 
9 

Evidence in Regulatory Decisions

Pre-Clinical 

Testing

+ 

Investigational

Device Exemption

Clinical 

Study Post-Market Pre-Market

Application

Real-World Device Use

Physician and Patient 

Experience

Hypothesis Generation

Device Innovation

Traditional Regulatory Pathway

Non-Traditional Clinical Data Generation

Informed Clinical 

Decision Making

Claims

Databases

Laboratory

Tests

Pharmacy

Data

Patient

Reported

Outcomes

Social

Media

Registries

Electronic 

Health

Records

Hospital

Visits

Healthcare 

Information
10

Guidance Publication Timeline

Guidance drafted

Draft published 

July 27, 2016

Final version issued 

August 31, 2017 

RWE Guidance 

Webinar

Public comments 

received, incorporated 

into final guidance
11

Responses to Stakeholder Feedback

• Clarify the scope of the guidance regarding devices types.

– Reiterated that this guidance applies to all devices as 

defined in 201(h) of the FD&C Act.

• Is there a deterministic score sheet for RWE applicability?

– No such uniform score sheet is possible. We further 

clarified the factors we will consider.

• Does RWE lower data requirements?

– No. The evidentiary standard—reasonable assurance that a 

device is safe and effective—is unchanged. 

• Clarify IDE and Human Subject Protections for RWE.

– Included additional information for when an IDE is needed. 
12

Data Quality
13

Valid Scientific Evidence

• 21 CFR 860.7(c)(1)

– Although the manufacturer may submit any form of 

evidence to the Food and Drug Administration in an 

attempt to substantiate the safety and effectiveness 

of a device, the agency relies upon only valid 

scientific evidence to determine whether there is 

reasonable assurance that the device is safe and 

effective.
14

What is Acceptable?

• 21 CFR 860.7(c)(2)

Valid scientific evidence is evidence from

– Well-controlled investigations,

– Partially controlled studies, 

– Studies and objective trials without matched controls, 

– Well-documented case histories conducted by qualified 

experts, 

– Reports of significant human experience with a 

marketed device from which it can fairly and 

responsibly be concluded by qualified experts that 

there is reasonable assurance of the safety and 

effectiveness of a device under its conditions of use. 
15

What is Not Acceptable?

• 21 CFR 860.7(c)(2) continued

...isolated case reports, random experience, reports 

lacking sufficient details to permit scientific evaluation, 

and unsubstantiated opinions are not regarded as valid 

scientific evidence to show safety or effectiveness. Such 

information may be considered, however, in identifying 

a device the safety and effectiveness of which is 

questionable. 
16

Data Quality

Benefit

Relevant & Reliable

Risk

Safety

Are there reasonable assurances, 

based on valid scientific evidence 

that probable benefits to health 

from use of the device outweigh 

any probable risks? [860.7(d)(1)]

Effectiveness 

Is there reasonable assurance, based 

on valid scientific evidence that the 

use of the device in the target 

population will provide clinically 

significant results? [860.7(e)(1)]

‘Fit for Purpose’ 

Data should be assessed for completeness, consistency, accuracy, 

and whether it contains all critical data elements needed to evaluate 

a medical device and its claims. 
17

Characteristics for RWE Evaluation

– Relevance – 

The data adequately addresses the applicable regulatory 

question or requirement.

• Examples of factors to be evaluated:

– Appropriate variables collected, e.g. device exposure.

– Endpoint definitions consistent and meaningful.

– Assessment schedule captures endpoints of interest.

– Population is appropriate and representative.

– Study protocol and/or analysis plan appropriate for 

question. 
18

Reliability includes factors related to overall data quality

• RWD data reliability is assessed using characteristics of:

– Data Accrual

– Data Assurance 

– Quality Control

Characteristics for RWE Evaluation

– Reliability – 
19

Aspects of data collection to consider:

– Pre-specification of:

• Standardized common data elements (CDE) to be collected

• Unambiguous CDE definitions

• Structured data formats for CDE population

• Methods for CDE aggregation and documentation

• Timeframe for data element collection

– Data sources and technical data capture methods. 

– Patient selection to maximize real-world population 

representation and minimize bias.

– Patient protections. 

RWE Reliability Evaluation

– Data Accrual – 
20

Reliability includes factors related to overall data quality

• RWD data reliability is assessed using characteristics of:

– Data Accrual

– Data Assurance - Quality Control

Characteristics for RWE Evaluation

– Reliability – 
21

People and processes in place during data collection and 

analysis to minimize errors and ensure integrity.

• Includes consideration of aspects such as: 

– How data elements were populated. 

– Data source verification procedures.

– Data completeness including of confounding factors.

– Data consistency across sites over time.

– Evaluation of on-going training programs.

RWE Reliability Evaluation

Data Assurance - Quality Control
22

Investigational Device Exemption (IDE) 

Process 

and Real-World Evidence (RWE)
23

• Whether collection of RWD requires an IDE depends on 

if the device is used in the normal course of medical 

practice or a clinical investigation. 

• Under section 1006 of the FD&C act, the FDA does not 

regulate health care practitioners in the use of legally 

marketed devices within a legitimate health care 

practitioner-patient relationship.

– May include use of legally marketed devices for uncleared or 

unapproved uses. 

• If found to be of sufficient quality, RWD collected during 

the routine care of patients may be used to support 

regulatory decisions.

RWD and IDE
24

Patient Protections

• Legal framework for patient protection includes:

– 21 CFR parts 50, 56, and 812

– Common Rule 45 CFR 46

– Health Information Privacy and Portability Act (HIPPA) 

– Other federal and local regulations

• RWE Guidance does not address all issues related to 

patient protection. The focus is on IDE process. 
25

IDE and Informed Consent

• The FDA regulations 21 CFR 50, 56, and 812 apply to all 

clinical investigations of devices to determine safety 

and effectiveness, with limited exceptions.

• If the device is used in the normal course of medical 

practice, an IDE would likely not be required.

• An IDE may be required when RWD collection that is 

intended to determine safety and effectiveness of a 

medical device influences patient treatment decisions.
26

Examples
27

Labeling Expansion 

Registry data regarding safety 

and effectiveness of unapproved 

use may support expansion of 

FDA-approved indications for use

Control Group 

Concurrent control group 

derived from RWD to support 

premarket decision

Post-Approval Surveillance 

Earlier device approval made 

possible by the use of RWE

.

Supplementary Data 

RWE Use Examples

RWE supplemented IDE helps FDA 

come to appropriate regulatory 

decisions faster 
28

• An existing national registry 

collecting clinical data on this and 

similar devices identified by the 

sponsor and the FDA.

• A Class III device was 

approved based on 

traditional clinical trials.

• Limited clinical study data 

available to support a 

reasonable assurance of 

safety and effectiveness for 

the new use.

• Safety and effectiveness information 

collected for all patients; link with 

administrative claims for long-term 

outcomes.

Labeling Expansion 

Registry data regarding safety 

and effectiveness of unapproved 

use may support expansion of 

FDA-approved indications for use

RWE Use Exam

• Widely used outside of 

the approved indications 

for use.
29

• Patients received investigational device were 

enrolled under an approved IDE.

• Clinical evidence needed to 

support substantial device 

changes.

• Ongoing registry identified 

collecting patient data 

treated with approved 

devices with similar 

intended use during routine 

medical care.

• Clinical study designed to compare:

o The use of new device

o Non-randomized concurrent control group 

derived from the registry

• After quality evaluation conducted by the 

sponsor and FDA, the registry was found to 

provide sufficiently relevant and reliable RWD 

on the control population. 

• Concurrent control group were not considered 

a part of the IDE.

Control Group 

Concurrent control group 

derived from RWD to support 

premarket decision

RWE Use Exam
30

• FDA was able to come to an appropriate

regulatory decision faster.

• PMA review for a new 

indication.

• Limited data from 

prospective clinical trial:

− Limited follow-up

− Inadequate data from 

 control group

• A pre-existing data source was already 

collecting and reporting RWD on the control 

therapies.

• Registry data supplemented and helped 

interpret the IDE results; additional clinical 

trial would have been required without the 

availability of RWD.

Supplementary Data 

RWE supplemented IDE helps FDA 

come to appropriate regulatory 

decisions faster 

mples

• Difficulty in interpreting 

results.
31

• New registry was created to generate RWD 

that could meet FDA’s data requirements.

• A breakthrough Class III 

medical device was 

approved based on 

randomized clinical trial.

• Earlier device approval conditioned on RWD 

collection and reporting postmarket was 

made possible by the early construction of 

the registry.

• Collecting data on other devices with similar 

design and Indications for Use (IFU) and has 

been used for

o Surveillance

o Analysis of all uses of device to expand IFU

o Embedded IDE trials for new devices

Post-Approval Surveillance 

Earlier device approval made 

possible by the use of RWE

.

mples

• Sponsor and FDA decided to 

use data generated from 

routine clinical care to 

support postapproval

commitments, in lieu of 

stand-alone clinical trials.
32

Conclusions/Requests

• CDRH believes that there is opportunity for greater use of 

RWD/RWE in regulatory decision making for devices.

• This guidance is designed to provide framework to help stakeholders 

assess relevance and reliability of RWE. 

• CDRH is supporting several efforts to facilitate the development of 

infrastructure and tools to better access and use RWE for regulatory 

decision making, including the development of National Evaluation 

System for health Technology (NEST).

• Please contact us via pre-submission or directly to let us know how 

we can help you.

 
Questions? 

Division of Industry and Consumer Education: DICE@fda.hhs.gov

RWE Policy Questions:

CDRHClinicalEvidence@fda.hhs.gov

OIR-Policy@fda.hhs.gov 

Slide Presentation, Transcript and Webinar Recording will be 

available at:

http://www.fda.gov/training/cdrhlearn Under the Heading: How to 

Study and Market Your Device; Sub-heading: Cross-Cutting 

Premarket Policy

Please complete a short survey about your FDA CDRH webinar 

experience. The survey can be found at www.fda.gov/CDRHWebinar

immediately following the conclusion of the live webinar.