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CDRH Final Guidance:

Evaluation and Reporting of Age-, 

Race-, and Ethnicity-Specific Data in 

Medical Device Clinical Studies

Kathryn O’Callaghan

Assistant Director for Strategic Programs, CDRH

& 

Katherine Kim, M.P.H.

BIMO Reviewer, Bioresearch Compliance Branch I 

Center for Devices & Radiological Health

Office of Compliance

Division of Bioresearch Monitoring

U.S. Food and Drug Administration

October 31, 2017
3 

OUTLINE

• Background & Origins of the Guidance

• Scope & Objectives

• Terminology

• Key Recommendations by Section
4 

BACKGROUND

• In 2012, Section 907 of the Food and Drug Administration Safety and 

Innovation Act directed the FDA to examine participation of diverse 

subgroups and corresponding data in medical product submissions, 

and availability of this information to the public.

• In 2014, the FDA issued an Action Plan to improve participation, 

quality and transparency of medical product performance in ARE 

subgroups. 

• The Age, Race, and Ethnicity (ARE) Guidance was a commitment by 

CDRH under this Action Plan.

• The FDA sought input from experts, stakeholders and the public via 

numerous fora, including a 2015 Institute of Medicine workshop.

• Draft guidance was issued June 20, 2016, for public comment. Final 

guidance issued and went to effect on September 12, 2017.
5 

Food and Drug Administration 

Safety & Innovation Act (FDASIA)

Section 907

FDASIA

(2012)

Report

(2013)

Action Plan

(2014)
6 

FDASIA 907 Report

• Reviewed 37 original Premarket 

approval (PMA) applications 

approved in 2011:

– 46 pivotal clinical studies 

• Demographic data variables:

– Sex, Age, Race, Ethnicity

• Documents reviewed: 

– PMA applications submitted by industry

– Final labeling (industry public info)

– FDA internal review documentation 

– SSED: Summaries of Safety & Effectiveness Data 

(FDA public decision summaries)
7 

Need for Improved Consistency in 

Analysis & Public Transparency

Sex

• 88% of PMAs analyzed

• 63% presented publicly

Age

• 70% of PMAs analyzed

• 57% presented publicly

Race & 

Ethnicity 

• 27% of PMAs analyzed

• 16% presented publicly
8 

Participation by Age Range

• Lack of consistency 

in the type of 

descriptive statistics 

on age reported in 

the PMAs. 

• Age range was most 

commonly 

reported. 
9 

Participation by Race

• For some indications, 

racial composition was 

consistent with disease 

prevalence. 

• For other indications, 

racial composition did 

not appear to represent 

disease prevalence in 

the U.S. population. 
10

Participation by Ethnicity
11

ARE Guidance: Commitment 

Under FDASIA 907 Action Plan

Quality

Transparency 

Participation
12

WHY CONSIDER A-R-E 

SPECIFIC DIFFERENCES

• Differences in biology, environment and interactions 

between them which could affect health, disease, and 

response to medical devices.

– Pediatric patients are more sensitive to ionizing radiation 

exposure 

• Benefit-risk profile and other important aspects of device 

performance may differ across ARE subgroups. 

– Certain dermatology devices may have different 

considerations for use in a specific racial or ethnic population

– Certain orthopedic devices may have different considerations 

for use in specific age subgroups
13

IMPORTANCE OF DIVERSE 

PARTICIPATION IN CLINICAL TRIALS

• Historical lack of diverse enrollment in clinical studies 

lack of available data re: risks and benefits of medical 

device use in ARE subgroups. 

• Clinical trials should aim to include diverse populations 

that reflect the intended population whenever possible 

and appropriate.

• Recognizing the practical challenges in doing so, the 

guidance includes recommendations for overcoming 

common barriers, to balance with least burdensome 

principles.
14

Guidance Objectives

• Diverse Participation. Encourage the collection 

and consideration during the study design stage 

of relevant ARE and associated covariates 

• Consistent Analysis. Outline recommended 

analyses of study subgroup data with a 

framework for considering demographic data 

when interpreting overall study outcomes

• Transparency. Specify expectations for 

reporting ARE-specific information in 

summaries and labeling 
15

Scope of the Guidance

• To improve the quality, consistency, and 

transparency of data regarding the device 

performance within ARE-specific subgroups

• Applies to devices that include clinical information 

in support of a marketing submission (510(k), De 

Novo request, PMA, HDE)

• Also applies to post-approval study submissions 

and postmarket surveillance studies

• Extends the policy set forth in the Sex-Specific 

Guidance to include age, race, and ethnicity (ARE)
16

TERMINOLOGY

SEX AGE

RACE ETHNICITY
17

TERMINOLOGY: AGE

• Trial participants should be grouped into 

categories appropriate for the disease/condition

• Pediatric population is defined in device 

regulations as less than 22 years of age

• Geriatric or elderly population is not defined
18

TERMINOLOGY: RACE & ETHNICITY

• Participants self-report on both race and ethnicity

• Preferred method is separate collection of race and 

ethnicity (i.e., two-question format)

Other considerations:

• Disease/condition may warrant more granular race 

data

• Categories may not be appropriate outside the U.S.

– Methodology should be defined in the study protocol

See FDA’s Guidance for Industry: Collection of Race and Ethnicity Data in Clinical Trials
19

RACE & ETHNICITY TWOQUESTION FORMAT

• Question 1 (answer first): Do you consider yourself 

Hispanic/Latino or not Hispanic Latino?

• Question 2 (answer second): Which of the 

following five racial designations best describes 

you? More than one choice is acceptable:

– American Indian or Alaskan Native

– Asian or Pacific Islander

– Black 

– Hispanic 

– White 

Per OMB Policy Directive 15
20

Enroll Diverse 

Patients:

Section IV

Analyze & Interpret 

Study Data:

Section V

Submit & Report 

ARE Data:

Section VI
21

Recommendations Grouped By 

Stage of Development

Study Design, Early Enrollment 

Premarket Submission Stage

Postmarket Submission Stage
22

RECOMMENDATIONS BY 

SECTIONS

IV: Enrolling 

Diverse 

Patients

V: Analysis & 

Interpretation 

of Study Data

VI: Submit & 

Report ARE 

Data
23

Planning for Diverse Enrollment

• Ideally plan to enroll a representative proportion of 

ARE subgroups consistent with the intended use 

population of the device.*

• Consider:

– Disease incidence or prevalence in subgroups

– Diagnosis and treatment patterns in subgroups

– Proportions of subgroups included in past studies for 

target indication

– Clinically meaningful subgroup differences in safety, 

effectiveness, or overall benefit-risk profile

*See pg. 13 for Enrollment Resources
24

To Enhance Diverse Enrollment

• Include investigational sites with access to ARE 

subgroups

• Alternative communication strategies for study 

materials

• Consider broader enrollment criteria 

• Investigate reasons for no or low inclusion of ARE 

subgroups

• Involve community providers and patient advocacy 

groups in recruitment

• Compensation for transportation costs

• Flexible scheduling and child care and elder care

*See pg. 13 for Enrollment Resources
25

To Enhance Retention

Sponsors

• Develop follow-up plan 

including proxy contact info 

and actions to take when 

patient misses a visit

• Closely monitor follow-up 

rates so problems can be 

addressed quickly

• Report accountability of 

participants in study report

Investigators

• Stress the importance of 

follow-up at time of informed 

consent and subsequent visits

• Reminder calls for upcoming 

visits 

• Attempt to locate patients lost 

to follow-up

• Record reasons for patient 

withdrawals

• Maintain continued interest in 

patients with post-op and 

follow-up visit calls

*See pg. 19 for approaches to minimize loss-to-follow-up
26

RECOMMENDATIONS BY 

SECTIONS

IV: Enrolling 

Diverse 

Patients

V: Analysis & 

Interpretation 

of Study Data

VI: Submit & 

Report ARE 

Data
27

Statistical Recommendations – 

All Studies

• Statistical Analysis Plan (SAP) in the study 

protocol should: 

– Pre-specify assessment of heterogeneity across 

relevant demographic subgroups (may include 

interaction testing or other approaches)

– Pre-specify reporting by demographic subgroup

*Refer to FDA Guidance: Evaluation of Sex-Specific Data in Medical Device Clinical 

Studies for additional statistical recommendations
28

• Consider proper study design, sufficient enrollment of 

subgroups to allow meaningful analysis, and 

potentially controlling for multiple comparisons

• May consider subgroup-specific objective performance 

criteria (OPC) or performance goal (PG)

• May consider powering for subgroup-specific claims

• May consider demographic subgroups as stratification 

variables in randomization process when appropriate

*Refer to FDA Guidance: Evaluation of Sex-Specific Data in Medical Device Clinical 

Studies for additional statistical recommendations

Subgroup Differences 

Anticipated?
29

Recommendations for Demographic 

Subgroup-Specific Statistical Design
30

Recommendations for Demographic SubgroupSpecific Statistical Analysis for One-Arm Studies 
31

Recommendations for Demographic SubgroupSpecific Statistical Analysis for Comparative Studies 
32

RECOMMENDATIONS FOR 

ANALYZING SUBGROUP DATA

• FDA submissions should include analysis of the 

following for clinically meaningful ARE-specific 

differences:

– Primary effectiveness endpoints

– Primary safety endpoints

– Key secondary endpoints

• Regardless of the potentially limited statistical 

power of these subgroup analyses
33

OTHER CONSIDERATIONS OF 

SUBGROUP ANALYSIS

• Inadequate sample size and unplanned subgroup 

analyses are generally not considered adequate for 

statements in labeling

• Sometimes effect can be statistically significant but 

not clinically meaningful and vice versa

• Observed heterogeneity can sometimes be 

explained by other covariates 

• Hypotheses for exploratory analyses should be 

consistent with the literature (natural history, 

subgroups, known pathophysiology). 
34

INTERPRETATION OF ARE 

SPECIFIC DATA

• Clinically meaningful and/or statistically 

significant differences observed? Discuss with 

FDA.

• Describe how these contribute to overall 

benefit-risk profile in certain subpopulations.

• Limitations with small data sets or larger studies 

with underrepresentation of diverse subgroups 

 Discuss with FDA.
35

RECOMMENDATIONS BY 

SECTIONS

IV: Enrolling 

Diverse 

Patients

V: Analysis & 

Interpretation 

of Study Data

VI: Submit & 

Report ARE 

Data
36

RECOMMENDATIONS FOR 

SUBMITTING & REPORTING 

SUBGROUP DATA

The term “submit” refers to information submitted 

to the FDA for analysis.

Submit

The term “report” refers to information that should 

be included in publicly available documents 

(i.e., labeling, FDA review summaries).

Report
37

RECOMMENDATIONS FOR 

SUBMITTING & REPORTING 

SUBGROUP DATA

Submit to FDA Publicly Report 

Enrollment demographics for ARE subgroups

Differences in relevant baseline 

characteristics & co-morbidities

Any disproportionate loss to follow-up

Outcome differences Clinically meaningful and statistically 

significant outcome differences

Discuss generalizability of results when 

enrollment is substantially different 

than prevalence

How such differences affect overall 

benefit-risk profile for certain 

subgroups

Results of pre-specified subgroup analyses to support subgroup-specific 

labeling
38

Sample Reporting Format – Race 
39
Questions?

For general questions, please contact the Division of Industry and 

Consumer Education: DICE@fda.hhs.gov

For questions related to the guidance document:

CDRHPatientDiversity@fda.hhs.gov

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