1 

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FDA/CDRH Webinar

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Conference number: PW8996213
Leveraging Existing Clinical Data for 

Extrapolation to Pediatric Uses of 

Medical Devices: Final Guidance

Vasum Peiris, MD, MPH

Chief Medical Officer

Pediatrics and Special Populations

Food and Drug Administration (FDA)

Center for Devices and Radiological Health (CDRH)

August 2016
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Webinar Objectives

• Provide context for and overview of the 

Guidance 

• Describe the key changes from the draft 

guidance to the final guidance

• Answer clarifying questions about the 

concepts in the final guidance
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CONTEXT AND OVERVIEW
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Promote Pediatric Medical Device 

Development

• The FDA is dedicated to promoting timely access to safe and 

effective medical devices for all patients, and recognizes the 

unique needs of pediatric patients

• Despite a recognized need, relatively few medical devices have 

pediatric-specific indications and labeling

• The Final Guidance proposes a framework to leverage 

appropriate data for minimizing risk to pediatric patients while 

maximizing access to medical devices indicated for pediatric 

patients 

• The approach may stimulate growth in the number of devices 

indicated and labeled for pediatric patients
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Regulatory Background

• Regulatory authority allowing for extrapolation

– Title III of the Food and Drug Administration Amendments 

Act (FDAAA) is the Pediatric Medical Device Safety and 

Improvement Act (PMDSIA) of 2007 

– PMDSIA specifically authorized the use of adult data to 

demonstrate pediatric effectiveness

• CDRH believes extrapolation for safety is also appropriate 

in some circumstances
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What is Extrapolation?

In this guidance, “extrapolation" refers to the leveraging 

process where an indication in a new pediatric patient 

population can be supported by existing clinical data from a 

studied patient population.

• When existing data are relevant to a pediatric indication and determined to be 

valid scientific evidence, it may be appropriate to extrapolate such data for 

pediatric use. 
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Pediatric Definition

Age ranges for pediatric subpopulations: 

• Neonates: from birth to 1 month of age

• Infants: greater than 1 month to 2 years of age

• Children: greater than 2 to 12 years of age

• Adolescents: greater than 12 through 21 (up to but not including 

the 22nd birthday)

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuid

ance/GuidanceDocuments/ucm089740.htm 
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Challenges to support Pediatric Indications

• Small and diffusely scattered potential study populations

– May confound optimal trial size

• Enrollment and consent procedures 

– May increase trial time

• Increased variation in physiology, pathophysiology, anatomy, 

and human factors as compared to adults

– Challenges development of appropriate technologies 

Because of these challenges, adult devices are used off-label in 

pediatrics. 
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Why Consider Extrapolation? 

Leveraging relevant available clinical data when appropriate, may

• Lead to more devices being granted marketing authorization for 

pediatric indications

• Increase availability of medical devices with appropriate labeling 

to support safe and effective device use in pediatric patients

• Streamline the process for establishing a pediatric intended use 

claim

• Enhance and encourage pediatric device development programs
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Final Guidance Highlights

• Background 

– Regulatory History

– The purpose and potential benefits of extrapolation

• Extrapolation Decision Process

– Figure 1 provides complete decision tree

– Full vs. partial extrapolation

– Extrapolation for effectiveness vs. safety

• Examples and Statistical Methodology for Extrapolation

– Appendix

• Statistical guidance on potential methods 

• Six hypothetical and one actual example
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Objectives of Guidance

• Increase availability of safe and effective pediatric devices by 

providing a roadmap for leveraging relevant existing clinical data for 

use in premarket approval applications (PMAs), humanitarian device 

exemptions (HDEs), and de novo requests

• Explain the circumstances in which the FDA believes it may be 

appropriate to leverage existing clinical data to support pediatric 

device indications and labeling

• Outline the approach FDA uses to determine whether extrapolation 

is appropriate, and if so, to what extent the data can be leveraged 

• Describe suggested statistical methodology that may be used to 

leverage the data in a way that increases precision for pediatric 

inferences 
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Guiding Principles

• Fairly and responsibly serve the need of pediatric patients

– For devices with appropriate labeling to support safe and effective 

pediatric use

• Guidance does not change

– threshold for approval 

– need for valid scientific evidence 

• Appropriateness of extrapolation is considered 

– case by case, guided by the decision tree 

– separately for effectiveness and safety 
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Determination of Appropriateness of 

Extrapolation

Three factors:

1. Similarity 

– Of existing adult response data and/or population 

characteristics to the intended pediatric subpopulation

2. Quality

– Study design

– Data collection

– Measurement

3. Fair and responsible support of

– Reasonable assurance of safety and effectiveness 

(or probable benefit for HDEs)

– Valid scientific evidence
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Extrapolation Decision Tree

General Considerations

Relevance of Data

• Does the disease or condition occur in a pediatric (sub)population?

• Endpoint in data set relevant to intended pediatric (sub)population?

Similarity of response to intervention

• Device characteristics

• Disease characteristics

• Population characteristics

Quality of Data

• Is the adult/other population data of sufficient quality to demonstrate safety and 

effectiveness in pediatric (sub)population?

• If not, is data of sufficient quality for partial extrapolation?
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Possible Extrapolation Decisions

• Full extrapolation: existing clinical data are used directly (i.e., as 

a complete substitute) for prospective pediatric clinical data 

• Partial extrapolation: existing data are combined via a statistical 

model with pediatric data sources or prospective pediatric 

clinical data 

• Partial extrapolation permits utilization of existing clinical data to 

support demonstration of device safety or effectiveness for use in 

pediatric patients, with the expectation that some pediatric data are 

necessary 

• If not appropriate or insufficient to meet the threshold of valid 

scientific evidence, data will not be extrapolated
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Extrapolation Does not Imply Approval

• A conclusion that extrapolated data may be used does not 

necessarily mean the data will support an approval decision. 

• If extrapolation is deemed appropriate, the data would be 

considered in conjunction with the totality of evidence to either 

support or not support a reasonable assurance of safety and 

effectiveness (or probable benefit)
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KEY CHANGES
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Changes From Draft Guidance

• Clarifies and explains the following:

– the guidance applies to PMAs, HDEs and now de novo requests where a 

pediatric indication is sought

• PMDSIA states that extrapolated data may be used to support a “reasonable 

assurance of effectiveness (RASE)”

• Extrapolation for safety may be appropriate in some circumstances

– PMAs and de novo requests both require a demonstration of RASE

– HDEs require a demonstration of safety and probable benefit

• Extrapolated data may be particularly useful in HDEs given the rarity of the 

disease/condition addressed
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Changes From Draft Guidance contd.

• Clarifies the concept of “borrowing strength”

– Quantitative information provided by existing adult/population data may 

be incorporated in one of two ways:

• As a substitute for any potential pediatric data

• As a supplement to “new” pediatric data considered in the context 

of a statistical model
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• Clarifies how to determine “similarity in device effects”

– Both the direction and magnitude of the device effect should 

be considered

• By direction of device effect, we mean that if the device has a benefit 

for adults, it should also have a benefit for pediatrics

• The magnitude of benefit should also be similar between populations

Changes From Draft Guidance contd.
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Next Steps

Implementation

– CDRH will use pediatric expertise in the 

evaluation of any application in which 

extrapolation is considered

– CDRH is developing the PEDs (Pediatric 

Extrapolation for Devices) Team

• A centralized group with pediatric expertise 

• Available for consultation regarding extrapolation

• Enhanced consistency and standardization with 

respect to extrapolation decisions
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Concluding Remarks

• Despite a recognized need, relatively few medical devices have 

pediatric-specific indications and labeling

• The guidance proposes a framework for leveraging existing data 

to augment availability of medical devices indicated and labeled 

for pediatric patients

• The guidance provides clarity and predictability for device 

sponsors and enhances consistency within FDA regarding 

decisions involving extrapolation
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Thank You
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Questions?

Division of Industry and Consumer Education: 

DICE@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” (subsection- “Cross-Cutting 

Premarket Policy”)