FDA Report

FDA ACTION PLAN TO ENHANCE THE 

COLLECTION AND AVAILABILITY OF 

DEMOGRAPHIC SUBGROUP DATA

August 2014 
Table of Contents

Introduction and Background............................................................................................................ 1

FDA Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data ............. 4

Priority One: Improve the Completeness and Quality of Demographic Subgroup Data (Quality)....................4

Priority Two: Identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage 

greater participation (Participation) .........................................................................................................11

Priority Three: Making demographic subgroup data more available and transparent (Transparency).........14

CONCLUSION ..................................................................................................................................17

APPENDIX A: FDA Action Plan at a Glance........................................................................................18

APPENDIX B: Building the Necessary Knowledge Base .....................................................................22

APPENDIX C: Statutory Language, Section 907 of FDASIA................................................................. 26

APPENDIX D: Relevant FDA Regulations/Guidance to Industry on Collection, Analysis, and Availability 

of Subgroup Data............................................................................................................................27
Message from Margaret A. Hamburg, M.D.,

Commissioner of Food and Drugs 

One of the core tenets of rigorous biomedical research, as well as a 

guiding principle of the FDA’s goal to meet the health needs of 

patients across the demographic spectrum, is the importance of 

encouraging diversity in clinical trials.

When a more diverse population participates in clinical trials, we 

increase the potential to know more about the extent to which 

different subgroups—males and females, young and old, people of 

various racial and ethnic backgrounds, and patients with differing 

comorbid diseases and conditions—might respond to a medical 

product. And when subgroup data are analyzed, we have available 

more information about the product that can be communicated to 

the public. The result is greater assurance in the safety and 

effectiveness of the medical products used by a diverse population.

FDA has been addressing these issues since the 1980s, when we first released guidance about the importance of 

studying the effects of drugs in elderly patients. In the 1990s, we issued a “Guideline for the Study and 

Evaluation of Gender Differences in the Clinical Evaluation of Drugs” and established the Office of Women’s 

Health. As a result, women today are far more adequately represented in the majority of clinical trials that are 

the basis for safety and effectiveness decisions about FDA-approved products. Moreover, analysis for sex 

differences in clinical drug trials, required by regulation since 1998, is now routinely done in new drug 

applications. More recently, we’ve been looking at ways to encourage greater inclusion of women in medical 

device trials. In 2011, we issued draft guidance outlining our expectations for sex-specific data analysis and 

reporting of medical device clinical study information, as well as recommending strategies for enrollment of 

women in clinical studies, and we have now issued a final version of that guidance.

Advances in science are also playing an increasingly important role in deepening our understanding of how 

patients within various subgroups respond to medical products. For example, information from areas such as 

pharmacogenomics is now being incorporated into product development and regulatory review to further 

address subgroup characteristics and population needs, helping to overcome the challenges of the “one-size-fits 

all” model of patient treatment. Ultimately, this is steering us towards the goal of tailoring treatments to 

individuals or subgroups of patients through personalized medicine—including patients in underserved and 

underrepresented populations.

But for all the progress we have made, there are still areas of concern, particularly involving 

underrepresentation of racial and ethnic minorities. That’s why it was important that in 2010, as part of the 

Affordable Care Act, we were able to establish FDA’s Office of Minority Health to advise FDA on ways to reduce 

health disparities among racial and ethnic subgroups. 

In Section 907 of the 2012 Food and Drug Administration Safety and Innovation Act, Congress directed us to take 

a closer look at the inclusion and analysis of demographic subgroups in applications for drugs, biologics and 

devices—including by sex, race and ethnicity, and age—and report on our findings. A cross-agency task force 

analyzed 72 applications for drugs, biologics and devices approved in 2011. Our report, published in August 
2013, found that the agency’s statutes, regulations and policies generally give product sponsors a solid 

framework for providing data in their applications on the inclusion and analysis of demographic subgroups; in 

general, sponsors describe the demographic profiles of their clinical trial participants; and the majority of 

applications submitted to FDA include demographic subset analyses that the FDA shares with the public in a 

variety of ways.

But in that report, we also concluded that we could do better, and Section 907 gave us a vehicle for considering 

improvements. It directed that one year after the issuance of the Section 907 report we publish and provide to 

Congress an action plan outlining “recommendations for improving the completeness and quality of analyses of 

data on demographic subgroups in summaries of product safety and effectiveness data and in labeling; on the 

inclusion of such data, or the lack of availability of such data, in labeling; and on improving the public availability 

of such data to patients, health care providers, and researchers.”

Today, after extensive consultation with stakeholders, FDA is delivering its Action Plan to Enhance the Collection 

and Availability of Subgroup Data. It includes 27 responsive and pragmatic actions, which are divided into three 

overarching priorities: improving the completeness and quality of demographic subgroup data collection, 

reporting and analysis (quality); identifying barriers to subgroup enrollment in clinical trials and employing 

strategies to encourage greater participation (participation); and making demographic subgroup data more 

available and transparent (transparency).

Some of the action items can be accomplished quickly while others will take longer to achieve and require 

additional resources. But once the plan is put fully in effect, I believe it will provide additional information to 

help health care providers and patients make decisions about the medical products they use. 

Addressing the three priorities of quality, participation and transparency will require a multifaceted approach 

and the active participation of both FDA and our many stakeholders. We look forward to working with them as 

we implement this action plan.

Sincerely,

Margaret A. Hamburg, M.D.

Commissioner of Food and Drugs
1

FDA Action Plan to Enhance the Collection and 

Availability of Demographic Subgroup Data

Introduction and Background

Section 907 of the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA)1 directed the Food 

and Drug Administration (FDA or the Agency) to publish and provide to Congress a report “addressing the extent 

to which clinical trial participation and the inclusion of safety and effectiveness data by demographic subgroups, 

including sex, age, race, and ethnicity, is included in applications submitted to the Food and Drug 

Administration.” Section 907 also directed FDA to publish and provide to Congress an action plan outlining

“recommendations for improving the completeness and quality of analyses of data on demographic subgroups 

in summaries of product safety and effectiveness data and in labeling; on the inclusion of such data, or the lack 

of availability of such data, in labeling; and on improving the public availability of such data to patients, health 

care providers, and researchers” and to indicate the applicability of these recommendations to the types of 

medical products addressed in Section 907. Congress also directed that the action plan be issued one year after 

the publication of the Section 907 report.

To fulfill these directives, an FDA-wide working group with representatives from the FDA’s Center for Biologics 

Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), the Center for Devices and 

Radiological Health (CDRH), and the Office of Commissioner undertook a detailed assessment of 72 applications 

for drugs, biologics and medical devices approved in 2011. In August 2013, FDA issued a report on the group’s

findings, Collection, Analysis, and Availability of Demographic Subgroup Data for FDA-Approved Medical 

Products.

2 The report concluded that the statutes, regulations and policies currently in place generally give 

sponsors a solid framework for providing data on the inclusion and analysis of demographic subgroups in their 

product applications and that FDA communicates this information in a variety of ways. It also concluded that the 

extent to which demographic subset data were analyzed varied across medical product types (drugs, biologics 

and medical devices) because of differences in regulatory requirements (drugs and biologic applications must, 

by regulation, include demographic subgroup analyses of effectiveness and safety). All of the biologics and drug

applications included in FDA’s assessment and a majority of the medical device applications provided the 

composition of clinical study participants by age, race and sex. Participants’ sex was the most consistently 

reported in the medical product applications. For approved drugs and biologics, the extent to which patients 

were represented in clinical trials by age and sex tended to reflect the disease indication studied. For devices, 

patient participation by age and sex varied by product type. Ethnicity (as defined by the Office of Management 

 

1 Food and Drug Administration Safety and Innovation Act of 2012, P.L. 112-144, July 9, 2012.

2 FDA Report. Collection, Analysis, and Availability of Demographic Subgroup Data for FDA-Approved Medical Products. 

http://www.fda.gov/downloads/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAm

endmentstotheFDCAct/FDASIA/UCM365544.pdf. 

Neither the Section 907 report nor this action plan address pediatric age groups as this is largely addressed in Sections 501-

511 of FDASIA and is subject to separate reporting. 
2

and Budget data standards as “Hispanic or Latino” and “Not Hispanic or Latino”) was not consistently reported in 

clinical studies across medical product types. The report noted that including participants from different 

subgroups in clinical trials did not necessarily mean that sufficient data are collected on those subgroups for 

meaningful analysis or to allow detection of relevant subgroup differences. 

As we3 began developing the action plan, we felt it was crucial to reach out to our stakeholders to hear their 

perspective, identify any concerns and listen to their recommendations about demographic subgroup 

representation, outcome analysis and public communications around this topic. Consequently, we opened a 

public docket from August 20, 2013, until May 16, 2014; held a public hearing on April 1, 2014; and had many 

other small group meetings with stakeholders. 

Among the comments we heard:

• Some patient advocacy groups and health professional groups believe that the proportion of women,

minorities and elderly patients in industry-sponsored clinical trials is not consistent with the prevalence 

of the disease in the underlying population. Some patient advocacy groups said that they believe health 

professionals and patients do not have sufficient demographic information to make well-informed 

treatment and diagnostic decisions. It was also noted that achieving racial and ethnic participation and 

relevance to U.S. subgroups can be a particular problem when foreign data is used.

• Some industry representatives said they believe there is a general lack of awareness about, and limited 

physical access to, clinical trials among some demographic subgroups. They also stated that in today’s 

global medical product market they sometimes conduct clinical trials in geographic regions with a racial 

and ethnic representation that is substantially different from the U.S. population. 

The public comments and our many interactions with stakeholders made it very clear that FDA shares a common 

goal with patients, health professionals, researchers and the biomedical industry: safe and effective medical 

products must be available to the broad range of patients who need them. When participants in a clinical trial

for a medical product reflect a diverse, real-world population (males and females, young and old, various racial 

and ethnic backgrounds, and patients with differing comorbid diseases and conditions) and when the subgroup 

data from the trial are appropriately analyzed, much more information can be known about the product and 

more meaningful clinical data can be communicated to the public. 

With all of this in mind, FDA developed an action plan that we believe is both responsive and pragmatic, and, 

most critically, has the potential to contribute to the health of the American public. The plan is divided into 

three overarching priorities—quality, participation and transparency. 

Priority One: Improve the completeness and quality of demographic subgroup data collection, reporting and 

analysis (Quality). 

Priority Two: Identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage 

greater participation (Participation). 

Priority Three: Make demographic subgroup data more available and transparent (Transparency).

 

3 Throughout this report, the use of the word “we” refers to FDA as a whole. Action items that refer to “we” will be 

addressed across centers and offices. 
3

What follows is a list of 27 specific actions divided up within the three priorities that FDA plans to implement, 

along with a projected timeframe for completion: short-term (within one year), intermediate-term (within 1 to 3 

years) or long-term (within 3 to 5 years). Many of these actions will have a broad impact on the work of FDA’s 

medical product centers and will require thoughtful implementation based on current evidence and available 

resources.

FDA’s Action Plan to Enhance the Collection and Availability of Demographic Subgroup Data reflects the Agency’s

commitment to encouraging the inclusion of a diverse patient population (with reference to sex, age, race and 

ethnicity) in biomedical research that supports applications for FDA-regulated medical products. Increasing 

representation is a multifaceted challenge that requires a multifaceted approach and the collaboration of our 

federal partners, industry, health care providers, patients and patient advocacy groups, academicians and 

community groups. 

A consistent and recurring comment from all of our stakeholders was the desire to continue a dialogue with FDA 

on this important topic. We share that desire. Thus, we are reopening a docket to solicit public comments on the 

action plan and will plan additional opportunities for the members of the public to provide their input on various 

action items in the plan. Updates and progress on the action items will be posted to the Section 907 Web page 

on FDA’s Web site, FDA.gov, on a regular basis.
4

FDA Action Plan to Enhance the Collection and 

Availability of Demographic Subgroup Data

The actions we are taking can be grouped into three main areas of emphasis and align with the mandate 

provided by Congress. Our actions seek to:

1) Improve the completeness and quality of demographic subgroup data collection, reporting and analysis 

(Quality); 

2) Identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater 

participation (Participation); and

3) Make demographic subgroup data more available and transparent (Transparency). 

Some actions will help enhance the quality and consistency of the demographic data and analyses that sponsors 

submit to FDA. This enhanced quality and consistency will better enable identification of clinically meaningful

knowledge gaps and differences across subgroups. Some actions are intended to remind sponsors to increase 

the diversity of clinical trial participants, taking into account the disease prevalence in demographic subgroups in 

the United States. Other actions involve FDA refining its policies and staff training to support more consistent 

and transparent collection, analysis and communication of demographic subgroup data across FDA review 

divisions. And finally, by engaging and communicating with the public, including with health professionals, about 

the importance of diversity in clinical research, we will encourage greater participation of diverse populations in 

clinical trials. 

These actions may involve multiple approaches; may involve FDA staff alone; or may involve FDA in concert with 

other government stakeholders, research investigators and healthcare professionals, medical product industry 

sponsors and members of the public, including those in patient advocacy groups. The interactions within FDA 

and with external stakeholders are vital to successfully accomplish the common goals in this plan.

Each action outlined and detailed below also is captured in a summary chart (see Appendix A), which will be 

posted on FDA’s Web site and updated as actions are completed. 

Priority One: Improve the Completeness and Quality of Demographic Subgroup Data (Quality)

We plan to improve the completeness and quality of demographic subgroup data collection, reporting, and 

analysis by:

1.1. Reviewing and developing a work-plan for updating, and/or finalizing, relevant guidance on 

demographic subgroup data, including FDA staff training and outreach to external stakeholders, as 

needed, for implementation; 

1.2. Working with sponsors to revise medical product applications to enhance information on

demographic subgroups in medical product applications; 

1.3. Strengthening FDA reviewer training by adding education/training around demographic inclusion, 

analysis, and communication of clinical data; 

1.4. Enhancing FDA’s systems for collecting, analyzing, and communicating diverse clinical information 

to optimize safe and effective use of medical products in diverse populations over the total product 

life cycle; and,
5

1.5. Conducting research on specific areas of public health concern related to demographic subgroups.

FDA’s August 2013 report demonstrated that FDA’s statutory and regulatory requirements, guidance 

documents, policies, and procedures generally inform sponsors and Agency staff about how demographic data 

should be collected and analyzed. Nevertheless, we intend to further enhance the quality and consistency of 

these efforts. It is important to provide industry with clear guidance about our expectations around the 

demographic data and analysis they submit. We will explore ways to standardize data fields so as to simplify the 

pooling of data across clinical studies and make it easier to identify trends regarding specific demographic 

subgroups or product areas. 

1.1 Reviewing and developing a work-plan for updating, and/or finalizing, relevant guidance on 

demographic subgroup data, including FDA staff training and outreach to external stakeholders, as 

needed, for implementation (Short-term and intermediate-term completion goal) 

FDA regulations and policies currently in place give product sponsors a solid framework for providing 

data in their applications on the inclusion and analysis of demographic subgroups studied. Nevertheless, 

we believe more improvements can be made. 

Action Items:

 CDER and CBER plan to review—and update and/or finalize, as needed—relevant industry 

guidance and internal FDA good review practice documents to encourage greater demographic 

subgroup representation in clinical trials, subgroup analysis and communication of results. We 

welcome public input on new evidence or best practices that could inform revision of our 

existing guidance including:

4

• Guideline for the Study and Evaluation of Gender Differences in the Clinical 

Evaluation of Drugs

• Collection of Race and Ethnicity Data in Clinical Trials

• ICH E7 Studies in Support of Special Populations: Geriatrics, both the original 

document and an amendment in 2012 with relevant questions and answers5

 We plan to incorporate recommendations from the recent guidance Evaluation of Sex-Specific 

Data in Medical Device Clinical Studies into reviewer templates, as appropriate, to provide staff 

training. We also plan to develop and offer an external webinar about how to use the guidance.

 

4 All FDA guidance discussed in this report can be accessed on FDA’s web site at 

http://www.fda.gov/ForIndustry/FDABasicsforIndustry/ucm234622.htm. 

5 ICH is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 

Human Use, a collaboration of regulatory authorities and the pharmaceutical industry in Europe, Japan and the United 

States that discusses scientific and technical aspects of drug registration. More information is available at 

http://www.ich.org. ICH E-7 specifically urged inclusion of patients older than 75, a point not made in the original ICH 

guidance. The impact of this change would be anticipated in future years. 
6

This guidance, finalized in August 2014, outlines FDA’s expectations and intent to improve the 

quality and consistency of available data on how well a medical device performs in both sexes. 

The final guidance includes recommendations on encouraging appropriate representation by sex 

in clinical studies of devices and explains that data from such studies should be appropriately 

analyzed by sex. 

 We plan to begin drafting a guidance document on analysis and reporting of ethnicity, race and 

age in medical device clinical studies. In doing so, FDA plans to explore key barriers and 

limitations to meaningful data analysis.

1.2 Working with sponsors to revise medical product applications to enhance information on 

demographic subgroups in medical product applications (Intermediate-term completion goal) 

FDA currently has frequent communications with sponsors during the product development process. These 

provide opportunities to remind sponsors to consider the diversity of target populations early in the 

development of their clinical trials and, later on, to consider whether subgroup diversity is represented in 

enrollment or conduct of multiple trials and at various time points throughout the product’s life cycle. A recent 

Good Review Practices (GRP) document, available to all CDER and CBER staff, pays particular attention to the 

need to examine study protocols for unwarranted exclusions (e.g., people over a certain age or with 

concomitant illnesses). 

Different product centers have processes in place to communicate the importance of collecting information on 

diverse populations for specific indications and products. For example, in the case of medical devices, CDRH 

currently includes standard advisory language in investigational device exemption (IDE) letters that encourages 

sponsors to collect clinical trial data for racial and ethnic minorities in accordance with the 2005 FDA-wide final 

Guidance on Collection of Race and Ethnicity Data in Clinical Trials and to enroll patients who reflect the 

demographics of the affected population with regard to age, sex, race and ethnicity. The advisory language also 

recommends that in the study protocol sponsors provide contextual information to FDA on disease prevalence, 

diagnosis and treatment patterns, and plans to address any factors identified or suggested that could explain 

any potential for under-representation of women and minorities. 

For drugs and biologics, current regulations require that, as part of the investigational new drug application 

(IND) process, annual reports be submitted to FDA that tabulate participants by sex, age and race. This provides 

an opportunity for review staff to monitor the adequacy of study-population diversity during product 

development and, together with the new Good Review Practice document, can serve as a basis for discussions

about inclusion of diverse subgroups in clinical trials during the sponsor meetings that take place at various 

points in a company’s development program. 

Action Item:

 CDER and CBER plan to revise the guidance on the Integrated Summary of Effectiveness (ISE) 

sections of new drug applications (NDA), and biologics license applications (BLA), with particular 

attention to the importance of demographic and other subgroup analyses. Consideration is also 

being given to developing guidance on the Integrated Summary of Safety (ISS). 

The ISS and ISE sections are critical components of the clinical safety and efficacy portions of a 

marketing application and are based on integrated analyses, specifically including subgroup 
7

analyses, of the data, once data collection is complete. The revised guidance should improve the 

quality of these analyses. When products are approved, the data in ISS and ISE sections, 

including subgroup data, can be reported to the public.

1.3 Strengthening FDA reviewer training by adding education/training around demographic inclusion,

analysis, and communication of clinical data (Intermediate-term completion goal) 

An integral and critical component of medical product development and FDA application review is our

assessment of patient or population characteristics that may be relevant to the safety or effectiveness of the 

product. FDA reviewers—physicians, biomedical engineers, clinical pharmacologists, toxicologists, statisticians 

and other scientists—are constantly engaged with medical product sponsors throughout the life cycle of their 

products in evaluating these characteristics. During drug development, for example, beginning with initial animal 

studies and continuing with studies looking at pharmacokinetic data and effects in healthy populations, with

studies in populations with the disease, and finally with the postmarket setting when a product is typically 

widely available for use by patients, we examine safety and effectiveness in the overall study population and in 

demographic subgroups. Each of these phases provides an opportunity for our review staff to discuss with 

sponsors the safety and effectiveness of their medical products in specific demographic groups.

Another training opportunity is available from FDA’s Office of Women’s Health (OWH), which jointly developed

three continuing education courses on sex and gender differences with the NIH Office of Research on Women’s 

Health. The online series6

is free of charge and open the public. Doctors, pharmacists and registered nurses, 

including FDA staffers, can receive continuing medical education credit for taking the course.

Action Items:

 We plan to require training for new clinical trial reviewers on the importance of demographic 

subgroup data inclusion, analysis and communication. 

 We plan to offer additional education and training courses for experienced reviewers to better 

clarify FDA’s expectations for data collection and analysis related to demographic subgroups. 

This provision of information will help ensure that FDA staff is knowledgeable and can 

consistently implement our policies and guidance in their interactions with sponsors and their 

review of subgroup data in applications. 

1.4 Enhancing FDA’s systems for collecting, analyzing, and communicating diverse clinical information to 

optimize safe and effective use of medical products in diverse populations over the total product life 

cycle (Intermediate-term to long-term completion goal)

A pragmatic and effective solution for improving public availability of demographic data to patients, health care 

providers and researchers is to use a two-pronged approach that enables greater availability of diverse clinical 

evidence. Our approach would involve (1) identifying ways to better leverage existing clinical data and (2) 

strengthening systems to make better use of data that may be collected once medical products are available on 

 

6 https://sexandgendercourse.od.nih.gov/index.aspx
8

the U.S. market. As resources become available, FDA would be able to enhance existing systems for collecting, 

analyzing, and communicating information to optimize safe and effective use of medical products in diverse 

populations. 

We realized more clearly as we compiled the Section 907 report that additional clarification is needed about the 

collection of race and ethnicity data as recommended by FDA’s guidance Collection of Race and Ethnicity in 

Clinical Trials. Stakeholders commented to the public docket that there are issues concerning the validity, both 

scientifically and clinically, of patient identification by race (phenotype) or ethnicity (a socio-cultural quality), 

rather than ancestry or genetic make-up, where appropriate. 

Updating current thinking about standardized age categories (e.g., grouping older patients in more discrete 

categories for analysis (65 to 74 years old, or 75 to 84 years old, rather than younger than 65 years old or simply 

using birth year), was another recurring recommendation to both the docket and at public meetings. It was also 

specifically recommended in the 2012 Q & A addition to ICH E7.

Such updates in our current data collection procedures, including updating definitions of subgroups that may be 

clinically informative, can lead to more standardized data collection and can also enhance our understanding of 

clinical outcomes and trends in specific patient populations. To redefine these standards also requires updating 

the tools we use for data collection and analysis to hone our understanding on a more complex level. It has 

become increasingly important to have consistent approaches for collecting data for all medical product 

submissions. 

Action Items: 

 We plan to work, to the extent possible, towards better standardization of data collection 

categories for age, racial and ethnic groups in submitted applications to facilitate harmonized 

data collection and analysis of subgroup outcome trends.

Data standardization with regard to demographic subgroups is an important, yet difficult, issue 

to address, and one that FDA cannot tackle alone. We are prepared to work with stakeholders, 

such as the Clinical Data Interchange Standards Consortium (CDISC), advocacy groups, industry, 

our federal partners, and our international regulatory partners, in exploring how to approach 

data standardization and examining how this information can contribute to greater scientific 

and clinical knowledge about demographic subgroups. As those broader discussions occur, we 

are interested in moving forward to achieve greater consistency and standardization in current 

submissions of this demographic information, given available resources. Some of this work will 

be addressed as part of our review of guidance under Action Item 1.1. 

 We plan to revise our MedWatch forms to enable a standardized collection of demographic 

information on possible adverse events that occur after medical products are broadly available 

on the U.S. market.

Because not all differences in safety or effectiveness for medical products can be anticipated or 

discovered during the premarket setting, it is vital to have robust postmarket surveillance 

systems in place. FDA’s Adverse Event Reporting System (FAERS) collects information on drugs

and biologics (except for vaccines); the Vaccine Adverse Event Reporting System (VAERS)

collects information on vaccines, and the Medical Device Adverse Event Database (MAUDE) 

collects information on medical devices. CBER, CDER and CDRH are currently assessing these 
9

systems for opportunities to improve demographic category standardization to make reporting 

more user-friendly for health professionals, patients and others. For example, race may be 

reported as free text instead of in limited drop-down categories on MedWatch forms used to 

report adverse events. The MedWatch form is currently going through re-review and 

reauthorization by the Office of Management and Budget. As part of that process, FDA plans to

develop a more standardized approach. 

 We plan to strengthen systems and infrastructure for making better use of data once products 

are broadly available on the U.S. market. 

The Mini-Sentinel pilot7 is part of the Sentinel Initiative, launched in 2008. Mini-Sentinel is 

enabling FDA to work with partners who can access pre-existing electronic health care data from 

multiple data sources, including major health networks, to identify and better understand safety 

signals in 150 million people, including demographic subgroups, in response to queries FDA 

poses for analysis.

CDRH’s proposed National Medical Device Postmarket Surveillance System is designed to meet 

the challenges of rapidly evolving medical devices, health care delivery and information 

technology. This is built on a variety of initiatives, including CDRH’s Unique Device Identifier 

(UDI) Rule which will require that most devices carry a UDI, a unique numeric or alphanumeric 

code that identifies the product, its lot or batch, when it was made and its expiration date. 

When implemented and incorporated into registries, electronic health records, administrative 

claims data and other sources, it will increase the potential to gather information about a 

specific devices use in larger and typically more diverse patient populations. UDI 

implementation is a key component of a robust National Medical Device Postmarket 

Surveillance System, which we envision will enable quick identification of potential safety signals 

from a variety of privacy-protected sources, while reducing the burden and cost associated with 

surveillance as well as approval/clearance of new devices and existing devices for new uses or 

patient groups. The timeline for completion of the National System will depend on available 

resources. 

1.5 Conducting research on specific areas of public health concern related to demographic subgroups

(Ongoing and Intermediate-term completion goal)

FDA has implemented a variety of policy and programmatic improvements over the years to enhance the 

representation of relevant demographic subgroups in clinical trials and the analysis of subgroup data. We also 

have supported research on issues such as sex differences and health disparities that affect demographic 

subgroups.

For example, since 1994, OWH has funded more than 300 research projects examining sex differences in FDAregulated products and diseases unique to, or predominantly experienced by, women. Information gleaned in 

these research projects has facilitated regulatory decision-making.8 OWH has also partnered with the NIH Office 

 

7 For more on Mini-Sentinel, see http://mini-sentinel.org/. 8 For more on research support by FDA’s Office of Women’s Health, see FDA’s web page at 

http://www.fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/default.htm. 
10

of Research on Women’s Health to support research through the Specialized Centers of Research (SCOR) on Sex 

and Gender Factors Affecting Women’s Health.

9

 

More recently, FDA’s Office of Minority Health (OMH), established in 2011, has funded research projects with 

FDA’s medical product centers and with the University of Maryland and Georgetown Centers of Excellence in 

Regulatory Science and Innovation (CERSI).10 OMH also collaborates with the National Institutes of Health 

(National Institute of Minority Health and Health Disparities, the National Human Genome Research Institute 

and the National Cancer Institute Center for the Reduction of Cancer Health Disparities) and with established

research projects at academic centers, all of which support advancing FDA’s understanding of health disparities. 

However, additional research is needed to better understand issues surrounding recruitment, participation and 

outcome analysis of demographic subgroup populations, focusing on certain disease areas where significant 

outcome differences may be anticipated. 

Action Items: 

 OWH plans to develop a new women’s health research roadmap that will help to better 

coordinate research across the Agency and target OWH funding to projects that answer specific 

regulatory research questions and emerging priorities from the product review centers. 

 OMH plans to develop research projects leading to better understanding of medical product 

clinical outcomes in racial/ethnic demographic subgroups. This work will serve to identify and 

address aspects of clinical trials in therapeutic areas impacted by low inclusion, ranging from 

participation to outcome analysis of demographic subgroup populations.

 OMH plans to collaborate with NIH’s National Human Genome Research Institute in research 

into the role of genetics and genomics in health disparities. Findings from this collaboration are 

expected to clarify how the collection of data on race and ethnicity aligns with the evolving 

knowledge base for ancestry and genomics.

 As resources allow, we plan to develop a program of directed research in which FDA 

investigators could select a certain disease category and conduct an in-depth look at the data 

contained in relevant applications submitted over a specified time period (i.e., 5-10 years). 

Some stakeholders have told us they believe some demographic subgroups don’t respond as 

well to treatments for certain disease categories such as cardiovascular disease and diabetes

The assessment will be designed to examine the data for trends; identify the adequacy of 

demographic subgroup representation in trials; assess the content and quality of subgroup 

 

9 http://orwh.od.nih.gov/sexinscience/researchtrainingresources/scor.asp

10 For more on FDA’s OMH CERSI partnerships, see http://www.cersi.umd.edu/research and 

http://regulatoryscience.georgetown.edu/cersi

See also areas of research supported by the Office of Minority Health at 

http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm349115.htm. 
11

analyses for safety and effectiveness; and assess the adequacy of the analyses to determine 

potential differences in subgroups

FDA plans to share results of FDA-funded research publicly, as appropriate. This sharing of information is 

illustrated by the recently-published meta-analysis of sex differences in cardiac resynchronization therapy 

(CRT).11

Priority Two: Identify barriers to subgroup enrollment in clinical trials and employ strategies to 

encourage greater participation (Participation) 

We plan to identify barriers to subgroup participation in U.S.-based clinical trials and employ strategies to 

encourage greater participation by: 

2.1 Seeking further clarity about barriers to subgroup participation rates; 

2.2 Implementing efforts to enhance appropriate use of enrollment criteria in clinical trial protocols; 

2.3 Collaborating with NIH, industry and other interested stakeholders to broaden diverse participation in 

clinical research; and,

2.4 Using FDA’s communication channels to encourage clinical trial participation by demographic 

subgroups. 

 

Dialogue at the public hearing and past workshops along with FDA’s findings in the August 2013 report all

highlight that certain subgroups in the United States are less likely to be enrolled in clinical trials than the 

population as a whole. This is particularly noticeable among Blacks, Hispanics, U.S. Asians, and patients over the 

age of 75. 

Participation in clinical trials is voluntary, so in order to have clinical trials with diversity among participants, a 

diverse population of people has to be willing to participate. Many barriers to participation by underrepresented 

subgroups in the United States have been cited: limited numbers of investigators who can help enroll 

underrepresented subgroups or who have access to a broader range of patient subgroups; patients and families 

with negative attitudes about medical research and concerns about risk; patient inconvenience; availability of 

transportation; geographic location; and insurance status. Lower participation by those patients over the age of 

75 is thought to reflect protocol exclusions. Observations since the 1980s have shown that, for most drugs, 

gender participation is appropriate to dosage.

With regard to balanced representation in clinical trials, we believe—and our own data demonstrate—that for 

approved drugs and biologics, the extent to which patients were represented in clinical trials by age and sex 

tended to reflect the disease indication studied, noting again the deficit of people over 75. For devices, patient 

participation by age and sex varied by product area. FDA fully supports efforts to encourage participation of

underrepresented ethnic and racial subgroups participating in clinical trials in applications for all FDA-regulated 

medical products, so that knowledge about the safety and effectiveness of these products is informative to 

patients who may use the products. 

 

11 Zusterzeel R, Selzman KA, Sanders WE, et al. Cardiac Resynchronization Therapy in Women: US Food and Drug

Administration Meta-analysis of Patient-Level Data. JAMA Intern Med. 2014;174(8):1340-1348.

doi:10.1001/jamainternmed.2014.2717
12

Clearly, this is a multifaceted problem that requires a multifaceted approach. FDA is committed to encouraging 

clinical trial participation by diverse demographic subgroups. FDA will need to work in concert with the National 

Institutes of Health (NIH), advocacy groups, and industry to raise awareness and identify best practices for how 

to improve the inclusion of demographic subgroups in biomedical research.

 

 

2.1 Seeking further clarity about barriers to subgroup participation rates (Short-term completion goal) 

FDA has sought to better understand potential barriers to participation in clinical trials. Last year, FDA’s OMH 

funded a study with the University of Maryland’s Center of Excellence in Regulatory Science and Innovation 

(CERSI) that surveyed researchers both in and out of FDA. Researchers found that although minorities may be 

less likely to participate in FDA-regulated research, the issue is not one of race and ethnicity alone. A myriad of 

other factors influence an individual’s likelihood of participating in FDA-regulated research, including access to 

trials and healthcare, both of which may be largely driven by socioeconomic status; the disease being studied; 

and the research design. Surveys such as this can be used to educate and engage researchers.

Action Item:

 Working with the Institute of Medicine, OMH plans to convene a meeting of experts in 2015 to 

better understand contemporary barriers to participation by minorities in clinical trials.

OMH plans to collaborate with the Department of Health and Human Service’s Office of 

Minority Health, the National Institutes of Health and others in preparations for the meeting.

We expect that participants will include those with expertise in minority health, clinical trials 

research, public health policy and other relevant disciplines.

2.2 Implementing efforts to enhance appropriate use of enrollment criteria in clinical trial protocols 

(Short-term completion goal)

Enrollment criteria define the study population for whom the researchers hope the benefits of a medical 

product will outweigh its risks while reasonably reflecting those populations who are likely to use the product 

once it is available on the market. Study enrollment criteria may unintentionally exclude certain demographic 

groups, thereby limiting useful information about product performance in diverse populations. We regularly 

encourage sponsors to incorporate meaningful inclusion of demographic subgroups in clinical studies so that the 

study participants reasonably reflect the populations who will be using the products if they are approved. The 

public may not be aware that these interactions take place between FDA and industry because such premarket 

meetings are confidential. 

Action Item: 

 We plan to work with industry to help ensure appropriate use of exclusion criteria in clinical trial 

protocols.

To better ensure that medical products are studied in the range of patients who will ultimately 

use them, FDA medical product centers are launching efforts to work more closely with industry 

to help ensure appropriate use of enrollment criteria in clinical trial protocols. As noted, older 
13

patients (those over the age of 65) may have been excluded from clinical studies in diseases or 

conditions that affect them. An age limit of 65 years can lead to disproportionate exclusion of 

women in cardiovascular trials, yet women typically develop heart disease at an older age than 

men. CDER recently issued a Good Review Practice manual of policies and procedures (MAPP) 

that draws attention to such exclusion and other types of unnecessary exclusions. Such 

exclusions can also affect patients with disabilities or with multiple comorbid conditions. This 

initiative will further educate FDA reviewers and industry about methods to address the 

identification of and removal of unnecessary exclusions, with the goal of leading to trials that 

assess safety and effectiveness in a more representative segment of the intended use 

population. 

2.3 Collaborating with NIH, industry, and other interested stakeholders to broaden diverse participation 

in clinical research (Short-term and intermediate-term completion goal)

We are encouraged by recent efforts on the part of industry to improve clinical trial participation—especially as 

it relates to minority and elderly patients—through partnerships with advocacy groups, consortia and a greater 

focus on community-based participatory research. FDA aims to support these broader efforts through a formal 

collaboration with NIH and other federal partners, as well as working with advocacy groups, medical 

associations, industry, and other stakeholders to increase the awareness of patients, specifically women, racial 

and ethnic minorities and the elderly, about the value of participating in clinical research and its role in moving 

safe and effective products to market. 

Action Items:

 We plan to establish a joint working group with the National Institutes of Health Inclusion Policy 

Officer to establish a framework of collaboration and information exchange on inclusion 

policies, practices and challenges. This new working group will explore educational tools and 

outreach mechanisms to more broadly engage subgroups that consistently have low 

participation rates in clinical trials. 

 OWH plans to collaborate with the NIH Office of Research on Women’s Health (ORWH) on a 

national campaign to educate and promote the importance of clinical trial participation, 

focusing on women. The two government organizations intend to develop partnerships with 

national organizations for outreach to their membership. 

 We plan to work with industry to develop and share best practices related to recruiting a broad 

representation of patients for clinical research supporting FDA medical product applications. 

We heard from a variety of companies developing medical products, as well as clinical research 

organizations, about successful strategies for recruiting a range of patients for biomedical 

research. Ideas to be explored include the development of plans in the early stages of medical 

product development to address the intended population and to share with FDA in early 

interaction meetings. 
14

2.4 Using FDA’s communication channels to encourage clinical trial participation by demographic 

subgroups (Short-term completion goal) 

FDA communicates to the public, including demographic subgroups, through a variety of channels including 

email, Twitter, Facebook, FDA Consumer Updates (which are similar in content to news articles) and the FDA 

Voice Blog, and by distributing various educational materials to our stakeholders. In addition, both OMH and 

OWH provide targeted outreach to stakeholders and make available a wealth of content on their own Web 

pages and on the dedicated Web page for Section 907.

. 

Action Items:

 We plan to explore various ways to communicate to demographic subgroups about clinical trial 

participation. We envision that steps will include updating information about clinical trial 

participation on FDA’s website and distributing a new patient brochure. 

 We plan to issue an FDA Consumer Update on clinical trial participation by demographic 

subgroups and distribute it to FDA’s subscriber list (approximately 140,000 subscribers) and to 

our targeted media list in both English and Spanish versions. 

Priority Three: Making demographic subgroup data more available and transparent (Transparency)

We will aim to make demographic data more available and transparent by: 

3.1 Posting demographic composition and analysis by subgroup in pivotal clinical studies for FDAapproved medical products; 

3.2 Identifying potential methods to consistently communicate meaningful information on demographic 

subgroups in medical product labeling; 

3.3 Implementing communication strategies that are sensitive to the needs of underrepresented 

subpopulations, with a focus on language access and health literacy; and

3.4 Establishing an internal FDA steering committee to oversee and track implementation of the action 

plan and serve as planning group for an FDA workshop on the action plan. 

Stakeholders repeatedly told us that information about demographic subgroups is not easily accessible, nor is it 

in a format that could be readily understood by patients or health professionals when making treatment 

decisions.

We agree that FDA needs to do more to improve public understanding about how the agency assesses 

information about such data and how it relates to public health. Because much of this information already 

exists, but is buried within medical product reviews on FDA’s Web site, we will be taking significant steps to 

extract the data and make it readily available to the public. We are also considering how to consistently 

communicate meaningful information on demographic subgroups in medical product labeling, as applicable. 

FDA is forming an internal working group to oversee this effort and all of the action items in this plan. In an

effort to be transparent, the working group will regularly report its progress to the public. We also plan to 

convene a workshop within 18 months after the release of this action plan to review progress and obtain 

stakeholder input. 
15

3.1 Posting demographic composition and analysis by subgroup in pivotal clinical studies for FDAapproved medical products (Short-term and intermediate-term completion goal) 

Researchers, health professionals, and patients want access to data describing demographic subgroups included 

in clinical research and subgroup analyses, and want to know whether these analyses have resulted in clinically 

relevant findings.

Although the demographic composition and subgroup analyses are already included in medical product reviews 

located on FDA’s Web site, they can be difficult to locate. In response to public feedback and in an effort to be 

more transparent, FDA is considering how to make this information more accessible.

Action Items: 

 CDER and CBER plan to post demographic information from pivotal clinical studies for newlyapproved drugs and biologics, such as New Molecular Entities and Biologics License Applications. 

We expect that this information will be excerpted from the medical product reviews or provided 

through hyperlinks to specific information in the medical product reviews and made available on 

a special Web page.

 FDA plans to explore approaches for public user-friendly ways of posting demographic 

information from medical device pivotal studies and completed post-approval and postmarket 

surveillance studies.

3.2 Identifying potential methods to consistently communicate information on demographic subgroups in 

medical product labeling (Intermediate-term completion goal) 

Although we believe publishing demographic data collection and analyses on our Web site is an expeditious, 

simple and cost-effective way to share information, we acknowledge that stakeholders are also interested in 

how the labeling for medical products reflects this information. Current practice for labeling focuses on 

communicating as concisely as possible the information needed to safely and effectively use a medical product

while minimizing extraneous information that may not be meaningful to guide clinical care or patient decisionmaking. The public has provided feedback that patients and health care providers also want information about 

the clinical trial population and the analysis of subgroups (e.g., if demographic analyses were performed; 

whether there were differences found among subgroups; and whether subgroup analyses were inconclusive due 

to limitations of sample size or missing data). 

. 

Action Items:

 We intend to work with industry, advocacy groups, risk communicators (including FDA’s Risk 

Communication Advisory Committee) and other stakeholders to explore potential methods for 

communicating meaningful information on demographic analyses to the public. 

For example, a standard set of concise statements could be developed for labeling. 
16

As discussed at the public hearing, it will also be important to assess unintended consequences12

that could result, for example, when data are inconclusive regarding a demographic subgroup. 

 CDRH plans to conduct a study with health care professionals to improve usability and 

understanding of medical device labeling and product instructions for use. 

Drawing on the test results, we envision that future guidance documents will contain a section 

that includes a discussion of the importance of meaningful information on demographics. 

We envision that this section of guidance would address not only what is considered the 

standard demographics of age, gender, ethnicity and race, but also demographics that should be 

addressed in the design and testing of a device that are important to safe device use (e.g., 

cultural backgrounds of the intended patients and how they understand graphics, pictures and 

symbols; health literacy including languages; morbidities and co-morbidities of the user; physical 

capabilities and disabilities of the user; and cognitive abilities). 

3.3 Implementing communication strategies that are sensitive to the language and health literacy needs 

of underrepresented subpopulations (Short-term and intermediate-term completion goal) 

 

FDA recognizes that many subpopulations may have limited English proficiency and thus be unaware of 

certain health warnings. FDA has been working hard to make more of its written materials available to 

non-English-speaking consumers or to those for whom English is a second language. For example, press 

releases, FDA Consumer Updates, and drug safety communications considered of interest to the Latino 

community are routinely translated into Spanish. FDA translates materials into other languages on a 

case-by-case base, depending on the issue, although these are often limited due to resource constraints.

FDA is interested in identifying more effective ways to communicate so that patients and consumers, 

including those with low health literacy and limited English proficiency are better able to use medical 

products safely and effectively.

Action Item:

 We plan to implement communication strategies that are sensitive to the needs of 

underrepresented subpopulations, with a focus on language access and health literacy. FDA first 

addressed this subject in a report in response to Section 1138 of FDASIA. 

 

12 An example of an unintended consequence might be that a patient decides to stop taking a critical medical product 

based on incomplete information. Patients should always consult their health care professionals before stopping a 

medication. 
17

3.4 Establishing an internal FDA steering committee to oversee and track implementation of the action 

plan (Short-term completion goal)

To be successful, we need leadership going forward to implement this action plan. Thus, we are 

establishing a new internal steering committee led by the Office of the Commissioner that will be given 

the responsibility for overseeing the plan’s implementation. 

Action Items: 

 We plan to establish an agency-wide steering committee to oversee implementation of the

action plan. The committee is expected to consider details for implementing the 27 action items 

as well as possible metrics for measuring progress, information that will be reported on a 

regular basis on the Section 907 Web page. 

 We envision that the steering committee will also begin planning for a public workshop to be 

held within 18 months of the publication of the action plan where both FDA and the public can 

discuss what progress has been made in implementing the plan.

CONCLUSION

The FDA Action Plan to Enhance the Collection and Understanding of Demographic Subgroup Data reflects our 

continuing commitment to encouraging the inclusion of a diverse subject population in biomedical research 

used to support marketing applications for FDA-regulated medical products. It is clear that when diverse 

populations of subjects are involved in clinical research, we all benefit from a more complete knowledge base 

about the safety and effectiveness of medical products. 

FDA agrees that greater representation of diverse populations in applications for FDA-regulated medical 

products is beneficial. By improving data quality, encouraging greater participation in clinical trials, and making 

demographic subgroup data more available and transparent, we can help to ensure that researchers, health 

professionals and consumers will have easy access to meaningful clinical information about medical products 

that will help them make informed decisions. FDA also acknowledges that the inclusion of diverse populations, 

obtaining better data, and communicating information to the public is a multifaceted problem that requires a 

multifaceted approach and the active participation of multiple stakeholders. FDA is committed to working with 

our many interested stakeholders on these important issues. This action plan is the first step in this process.
18

 

APPENDIX A: FDA Action Plan at a Glance

The action plan reflects FDA’s commitment to encourage the inclusion of a diverse patient population with regard to sex, age, race 

and ethnicity in biomedical research used in marketing applications for FDA-regulated medical products.

Priority One: Quality—improving the completeness 

and quality of demographic subgroup data 

Actions Time frame

1.1 Reviewing and developing a work-plan for updating, 

and/or finalizing, relevant guidance on demographic 

subgroup data, including FDA staff training and outreach 

to external stakeholders, as needed, for implementation

-CBER and CDER plan to review, update, and/or finalize, as 

needed, relevant industry guidance and internal FDA good 

review practice documents to encourage greater demographic 

subgroup representation in clinical trials, subgroup analysis and 

communication of results. 

-FDA plans to incorporate recommendations from the Evaluation 

of Sex-Specific Data guidance into reviewer templates, to 

provide staff training and develop and offer an external webinar 

on use of the guidance.

-FDA plans to begin drafting a guidance document on analysis 

and reporting of ethnicity, race, and age in medical device 

clinical studies. 

Short-term and

intermediateterm

completion 

goal

1.2 Working with sponsors to revise medical product 

applications to enhance information on demographic 

subgroups in medical product applications

-CDER and CBER plan to revise the guidance on the Integrated 

Summary of Effectiveness sections of NDAs and BLAs. 

Intermediateterm 

completion 

goal

1.3 Strengthening FDA reviewer training by adding 

education/training around demographic inclusion, 

analysis and communication of clinical data

-FDA plans to require training for new clinical trial reviewers on 

the importance of demographic subgroup data inclusion, 

analysis, and communication. 

 

-FDA plans to offer additional education and training courses for 

experienced reviewers and other staff to better clarify FDA’s 

data collection and analysis expectations related to 

demographic subgroups. 

Intermediateterm

completion 

goal

1.4 Enhancing FDA’s systems for collecting, analyzing and 

communicating diverse clinical information to optimize safe and 

-FDA plans to work, to the extent possible, towards better 

standardization of data collection categories for age, racial and 

Intermediateterm to long-
19

effective use of medical products in diverse populations over the 

total product life cycle

ethnic groups in submitted applications to facilitate harmonized 

data collection and analysis of subgroup outcome trends. 

-FDA plans to revise MedWatch forms to enable a standardized 

collection of demographic information on possible adverse 

events that occur after medical products are broadly available 

on the U.S. market. 

-FDA plans to strengthen systems and infrastructure for making 

better use of data once products are broadly available on the 

U.S. market. 

term 

completion 

goal

1.5 Conducting research on specific areas of public health concern 

related to demographic subgroups

-Office of Women’s Health (OWH) plans to develop a new 

women’s health research roadmap that will help to better 

coordinate research across the agency and target OWH funding 

to projects that answer specific regulatory research questions 

and emerging priorities from the product review centers.

-Office of Minority Health (OMH) plans to develop research 

projects leading to better understanding of medical product 

clinical outcomes in racial/ethnic demographic subgroups.

-OMH plans to collaborate with NIH’s National Human Genome 

Research Institute in research into the role of genetics and 

genomics in health disparities.

-As resources allow, FDA plans to develop a program of directed 

research in which FDA investigators could select a certain 

disease category and conduct an in-depth look at the data 

contained in relevant applications submitted over a specified 

time period (i.e., 5 to 10 years).

Intermediateterm completion 

goal

Priority Two: Participation—identifying barriers to 

subgroup enrollment in clinical trials and 

employing strategies to encourage greater 

participation 

Actions Time frame

2.1 Seeking further clarity about barriers to subgroup 

participation rates

-OMH plans to convene a meeting of experts in 2015 to better 

understand contemporary barriers to participation of minorities 

in clinical trials.

Short-term

completion goal
20

2.2 Implementing efforts to enhance appropriate use of 

enrollment criteria in clinical trial protocols

-FDA plans to work with industry to try to ensure appropriate 

use of enrollment criteria in clinical trial protocols.

Short-term 

completion goal

2.3 Collaborating with NIH, industry and other interested 

stakeholders to broaden diverse participation in clinical 

research

-FDA plans to establish a joint working group with the National 

Institutes of Health Inclusion Policy Officer to establish a 

framework of collaboration and information exchange on 

inclusion policies, practices and challenges. 

-OWH plans to collaborate with NIH Office of Research on 

Women’s Health on a national campaign to educate and 

promote the importance of clinical trial participation, focusing 

on women.

-FDA plans to work with industry to develop and share best 

practices related to recruiting a broad representation of patients 

for clinical research supporting FDA medical product 

applications. 

Short-term and 

Intermediateterm completion 

goal

2.4 Using FDA’s communication channels to encourage clinical 

trial participation by demographic subgroups

-FDA plans to explore various ways to communicate to 

demographic subgroups about clinical trial participation. 

-FDA plans to issue an FDA Consumer Update on clinical trial 

participation by demographic subgroups and distribute it in both 

English and Spanish versions to FDA’s subscriber list 

(approximately 140,000 subscribers) and to our targeted media 

list.

Short-term 

completion goal

Priority Three: Transparency—making demographic 

subgroup data more available and transparent

Actions Time frame

3.1 Posting demographic composition and analysis by

subgroup in pivotal clinical studies for FDA-approved

medical products

-CDER and CBER plan to post demographic information from 

pivotal clinical studies for newly-approved medical products 

such as New Molecular Entities and Biologics License 

Applications. 

-FDA plans to explore approaches for public user-friendly ways 

of posting demographic information from medical device pivotal 

studies and completed post-approval and postmarket 

surveillance studies.

Short-term and 

Intermediateterm completion 

goal
21

3.2 Identifying potential methods to consistently

communicate information on demographic subgroups in

medical product labeling

-FDA intends to work with industry, advocacy groups, risk 

communicators (including FDA’s Risk Communication Advisory 

Committee), and other stakeholders to explore potential 

methods for communicating meaningful information on 

demographic analyses to the public. 

-CDRH plans to conduct a study with health care professionals to 

improve usability and understanding of medical device labeling 

and product instructions for use.

Intermediateterm completion 

goal

3.3 Implementing communication strategies that are sensitive

to the language and health literacy needs of

underrepresented populations

-FDA plans to implement communication strategies that are 

sensitive to the needs of underrepresented subpopulations, with 

a focus on language access and health literacy.

Short-term and 

Intermediateterm completion 

goal

3.4 Establishing an internal FDA steering committee to

oversee and track implementation of the action plan

-FDA plans to establish an agency-wide steering committee to 

oversee implementation of the action plan. 

-FDA envisions that the Steering Committee will begin planning 

for a public workshop to be held within 18 months of the 

publication of the action plan. 

Short-term 

completion goal
22

APPENDIX B: Building the Necessary Knowledge Base 

Understanding the Assessment of Patient or Population Characteristics in 

Medical Product Applications

An integral component of medical product development and application review is the assessment of patient or 

population characteristics that are relevant to the safety or effectiveness of a product. FDA reviewers—

physicians, pharmacists, biomedical engineers, statisticians and other scientists—are constantly engaged with 

sponsors throughout the lifecycle of a product to evaluate these characteristics. From initial animal studies, to 

studies looking at pharmacokinetic (PK) data and the intervention in healthy populations, to studies in 

populations with the disease, and finally, in the postmarket setting, FDA looks at safety and effectiveness data 

for the overall population included in clinical trials and from other sources, and also by demographic subgroup. 

Based on these assessments, FDA may decide that further study is needed. 

Because there are different regulatory authorities and approaches for drugs, biologics and devices, the 

collection; review and analysis; and communication of demographic subgroup information differs from FDA 

center to center. Outlined below is a brief description of how drugs, biologics and medical devices are assessed 

for patient or population characteristics.

A. Drugs/Biologics

Peoples’ responses to pharmaceuticals are extremely variable. Common factors causing different responses may 

include body mass, kidney or liver function or how the body absorbs or metabolizes a drug. However, often the 

source of variability is not understood. (For example, why only a few patients in some cases experience a certain 

side effect.) During drug development, many studies are carried out with the goal of sorting out what factors 

may be leading to a lower treatment response or increasing the risk of a specific side effect. 

Broadly speaking, differences in response to a treatment among individuals can be based on differences in 

pharmacokinetics (differences in blood levels of the drug) or pharmacodynamics (differences in how a patient 

responds to the same blood level) of a drug. PK differences are easily identified in drug studies because it is 

generally easy to measure blood levels and to examine the effect on blood levels of such factors as:

 Body size

 Kidney function

 Liver function

 Enzymes in the body that metabolize the drug, which can differ from patient to patient

 The effect of other drugs a patient may be taking that could be altering the absorption metabolism, or 

excretion of the study drug

 Age or gender

It is now standard practice in drug development to test, in targeted studies, how a drug is removed from the 

body (excreted in urine) or metabolized to an inactive substance (excreted in bile). It is also standard practice to 

identify other drugs that could interfere with these processes. This understanding makes it possible for a doctor 

to adjust the dose of a drug to a specific individual, thus reducing or eliminating the effects of PK characteristics 
23

or drug-drug interactions. It is also usual today to measure blood levels in patients (population 

pharmacokinetics), enabling discovery of other, unexpected effects on the pharmacokinetics of a drug.

What is generally more difficult to discover and characterize are differences in pharmacodynamic (PD) response 

among patients; that is, why different patients respond differently to the same drug. In some cases, these 

clinical differences can be anticipated based on mechanistic considerations. For example, a patient whose 

elevated blood pressure is caused by high renin levels will respond better to certain antihypertensives than will a 

patient with low renin hypertension—and renin status can be related to race. However, in many cases, the 

reasons for response differences are not known. One way to detect such differences is to determine whether 

they are associated with certain recognized patient characteristics, including the demographic characteristics of 

age, sex and race, as well as other factors, such as concomitant illness, or disease severity.

FDA regulations13 require sponsors to include in their marketing applications analyses of effectiveness and 

safety by age, gender, and race and any other pertinent characteristics. As FDA documented in its Section 907 

Report, sponsors almost always carry out these analyses, and FDA reviewers are closely attentive to such 

analyses. In some cases, critical differences from subgroup to subgroup have been detected. Some examples 

are: 

1. Females are more likely to experience torsades de pointes than men. 

2. The antihypertensive drug amlodipine caused increases in several dose-related adverse effects, and 

women had markedly higher rates of these adverse effects, as described in amlodipine’s labeling. (This 

finding led to a difference in recommended dosages for men and women.) 

Amlodipine Placebo

Adverse Event Male (%)

N = 1218

Female 

(%)

N = 512

Male (%)

N = 914

Female (%)

N = 336

Edema

Flushing

Palpitations

Somnolence

5.6

1.8

1.4

1.3

14.6

4.8

3.3

1.6

1.4

0.3

0.9

0.8

5.1

0.9

0.9

0.3

3. In two early, well-controlled trials in the Veterans Health Administration system, BiDil, a combination of 

isosorbide dinitrate and hydralazine, appeared very effective in self-identified Blacks for the treatment 

of heart failure, but had a far smaller effect in Whites. The definitive study of BiDil, A-HEFT was carried 

out in the Black population and showed an over 40% reduction in mortality when BiDil was added to 

standard therapy. The drug product was labeled for use in self-identified Blacks. 

4. Guidances developed by FDA and by ICH on studies in the elderly identify the elderly as potentially more 

sensitive to sedative-hypnotics. Developers for hypnotic drugs carry out separate studies in the elderly, 

 

13 See 21 CFR 314.50.
24

and both PK and PD differences have been identified, generally leading to lower recommended doses in 

elderly patients.

When safety and/or effectiveness differences emerge from one subgroup of patients to another, it is critical to 

explain them. In some cases, a genetic difference has been shown to affect a person’s metabolism, leading to an 

increase of a drug in blood levels or a failure to form an active metabolite. When additional testing and analysis 

can explain such differences, this information is added to the knowledge base for that therapy, and it may even 

become possible to individualize or personalize treatment using the therapy. Increasingly, drugs are being 

developed to treat a specific subgroup of patients, for example, patients with tumors having specific genetic 

characteristics or patients with particular genetic variants of other diseases, such as cystic fibrosis or Hepatitis C. 

B. Medical Devices

The legal framework for medical device regulation is a risk-based standard for a broad range of technologies, 

which underscores the importance of nonclinical as well as clinical data in assessing medical device 

performance, and which adheres to least burdensome principles.14 

A medical device can range from something as simple as a tongue depressor to something as complex as robotic 

surgery systems and from single-use to permanently-implanted heart valves. Technological advancements have 

led to a proliferation of minimally invasive device alternatives to surgical procedures, implantable stimulator 

device alternatives to long-term drug therapy, devices that step in for failing organs, lost limbs, and more. With 

early clinical experience, manufacturers often find ways to modify and improve a device, to make it smaller, 

more flexible and more durable, to enable use in a broader range of patients. Thus, medical device evaluation 

presents unique regulatory challenges related to greater diversity of medical devices, rapid technological 

advances, and the iterative nature of product development. 

For higher risk devices, manufacturers provide FDA with clinical trial data as a component of the valid scientific 

evidence required to demonstrate a reasonable assurance of safety and effectiveness for its conditions of use. 

Lower risk devices in many cases do not require clinical data. Many attributes of a medical device can play a 

major role in the performance, safety, or effectiveness of the device. These attributes are routinely assessed via 

engineering tests. For example, for some implants, highly informative evidence about long-term performance 

comes from engineering tests that are able to challenge the device under worst-case conditions, test the device 

to failure, and simulate many years of use. 

Clinical study populations for medical devices often reflect conditions of use that are limited to certain 

subpopulations, in part due to device eligibility constraints (e.g., surgical, anatomical or size limitations). Some 

studies evaluate a medical procedure only in patients who do not respond to available drugs or other 

treatments. In such groups, reliable information on incidence or prevalence of disease may not exist. 

 

14 Most original PMAs and some supplements require clinical data to meet the statutory threshold for approval. Where 

clinical outcome can be reliably predicted from non-clinical data, however, well-designed bench and/or animal testing can 

be the basis for approval of the PMA. The cases when non-clinical data can meet the threshold for approval typically involve 

devices or modifications of approved devices for which scientifically valid information is available in the public domain. If

clinical data are needed, FDA and industry will consider alternatives to randomized, controlled clinical trials, especially 

when potential bias associated with alternative controls can be eliminated. 
25

Because many aspects of device performance can be evaluated with non-clinical testing, FDA can only impose 

the least burdensome data requirements.

15 Moreover, because of their nature, many medical device clinical 

studies enroll fewer patients than drug trials. Therefore, it is often difficult to ensure that all demographic 

groups are represented in premarket studies—in many cases, to have broad demographic representation would 

require larger clinical studies. If the size of device clinical trials were required to be larger, trials would last much 

longer and cost much more. This could lead to fewer important devices being marketed in the United States. A 

more pragmatic and effective approach would be to enhance FDA’s systems for collecting, analyzing and 

communicating information across the product life cycle. This approach can optimize safe and effective use of 

medical devices in diverse populations. 

C. Identifying Trends

When premarket or postmarket differences or trends emerge in different subgroups of patients and when these 

differences can be explained through additional scientific examination and analysis, they add to the foundation 

of knowledge that is leading to personalized medicine. When a signal in a clinical trial is first detected indicating 

that variability exists between two subgroups of patients, this signal leads to further assessments and questions. 

Questions could include: Is there a genetic reason why certain patients react differently to the treatment? Is 

there a biomarker that could help predict which patients are more likely to have a certain response? 

D. Personalized Medicine

Advances in science are driving the development of innovative medical products that are being used to treat 

small subsets of patients. For example, important discoveries about the role of cell growth and oncogenes in

cancer set the stage for the development and approval in 1998 of trastuzumab (Herceptin), the first genetically 

guided therapy for the treatment of HER2-positive metastatic breast cancers.16 Personalized medicine generally 

involves the use of two medical products—typically, a diagnostic device and a therapeutic product—that work 

together to improve patient outcomes. These products are helping overcome the challenges of the one-size-fitsall model of patient treatment. Increasingly, a diagnostic device can be used to target a therapy to just the right 

patient, or subgroup of patients, in such a way that the benefits greatly outweigh the risks of treatment. 

In a 2013 report, Paving the Way for Personalized Medicine, FDA’s Role in a New Era of Medical Product 

Development,

17 FDA describes the ways in which FDA has worked to respond to, anticipate, and help drive 

scientific developments in personalized therapeutics and diagnostics. The report provides a compendium of 

FDA’s many recent efforts to advance regulatory standards, methods, and tools in support of personalized 

medicine and to further refine critical regulatory processes and policies to bring about personalized medical 

product development. Making sure that different demographic subgroups are sufficiently represented in clinical 

trials and enhancing the analyses and public availability of subgroup data will contribute to development of a 

 

15 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085994.htm

16 In just the last three years, FDA approved four cancer drugs for use in patients whose tumors have specific genetic 

characteristics that are identified by a companion diagnostic test. In 2012, FDA approved a new therapy for use in 

certain cystic fibrosis patients with a specific genetic mutation. In 2013, three-dimensional (3D) printing was used to 

create a bioresorbable tracheal splint for treating a critically-ill infant.

17 This report is available on FDA’s Web site at 

http://www.fda.gov/downloads/scienceresearch/specialtopics/personalizedmedicine/ucm372421.pdf, accessed July 3, 

2014. 
26

sound knowledge base as we move toward a time when all stages of patient care - from prevention to diagnosis 

to treatment to follow-up—are truly personalized.

APPENDIX C: Statutory Language, Section 907 of FDASIA

SEC. 907. REPORTING OF INCLUSION OF DEMOGRAPHIC SUBGROUPS IN CLINICAL TRIALS AND DATA ANALYSIS IN 

APPLICATIONS FOR DRUGS, BIOLOGICS, AND DEVICES.

(a) REPORT.— 

(1) IN GENERAL.—Not later than 1 year after the date of enactment of this Act, the Secretary, acting through the

Commissioner, shall publish on the Internet web site of the Food and Drug Administration a report, consistent with the 

regulations of the Food and Drug Administration pertaining to the protection of sponsors’ confidential commercial 

information as of the date of enactment of this Act, addressing the extent to which clinical trial participation and the 

inclusion of safety and effectiveness data by demographic subgroups including sex, age, race, and ethnicity, is included in 

applications submitted to the Food and Drug Administration, and shall provide such publication to Congress.

(2) CONTENTS OF REPORT.—The report described in paragraph (1) shall contain the following:

(A) A description of existing tools to ensure that data to support demographic analyses are submitted in applications for 

drugs, biological products, and devices, and that these analyses are conducted by applicants consistent with applicable 

Food and Drug Administration requirements and Guidance for Industry. The report shall address how the Food and Drug 

Administration makes available information about differences in safety and effectiveness of medical products according to 

demographic subgroups, such as sex, age, racial, and ethnic subgroups, to health care providers, researchers, and patients.

(B) An analysis of the extent to which demographic data subset analyses on sex, age, race and ethnicity is presented in 

applications for new drug applications for new molecular entities under section 505 of the Federal Food, Drug, and 

Cosmetic Act (21 U.S.C. 355), in biologics license applications under section 351 of the Public Health Service Act (42 U.S.C.

262), and in premarket approval applications under section 515 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 

360e) for products approved or licensed by the Food and Drug Administration, consistent with applicable requirements and 

Guidance for Industry, and consistent with the regulations of the Food and Drug Administration pertaining to the protection 

of sponsors’ confidential commercial information as of the date of enactment of this Act.

(C) An analysis of the extent to which demographic subgroups, including sex, age, racial, and ethnic subgroups, are 

represented in clinical studies to support applications for approved or licensed new molecular entities, biological

products, and devices.

(D) An analysis of the extent to which a summary of product safety and effectiveness data by demographic subgroups 

including sex, age, race, and ethnicity is readily available to the public in a timely manner by means of the product labeling 

or the Food and Drug Administration’s Internet web site.

(b) ACTION PLAN.— 

(1) IN GENERAL.—Not later than 1 year after the publication of the report described in subsection (a), the Secretary, acting 

through the Commissioner, shall publish an action plan on the Internet web site of the Food and Drug Administration, and 

provide such publication to Congress.

(2) CONTENT OF ACTION PLAN.—The plan described in paragraph

(1) shall include— 

(A) recommendations, as appropriate, to improve the completeness and quality of analyses of data on demographic 

subgroups in summaries of product safety and effectiveness data and in labeling;

(B) recommendations, as appropriate, on the inclusion of such data, or the lack of availability of such data in labeling;

(C) recommendations, as appropriate, to otherwise improve the public availability of such data to patients, health care 

providers, and researchers; and 

(D) a determination with respect to each recommendation identified in subparagraphs (A) through (C) that distinguishes 

between product types referenced in subsection (a)(2)(B) insofar as the applicability of each such recommendation to each 

type of product.
27

APPENDIX D: Relevant FDA Regulations/Guidance to Industry on Collection, 

Analysis, and Availability of Subgroup Data18

TABLE 1. DESCRIPTION OF STATUES AND REGULATIONS BY CENTER

YEAR CENTER FDA REGULATION DIRECTION

1985 CDER Content and Format of a 

New Drug Application. 

21 CFR 314.50 [1] 

Requires effectiveness data be presented by gender, age and 

racial subgroups and dosage modifications be identified for 

specific subgroups. Also requires safety data be presented by 

gender, age and racial subgroups; and that safety data from 

other subgroups of the populations of patients treated be 

presented, as appropriate.

1997 CDER/CBER Food and Drug 

Administration 

Modernization Act 

(FDAMA) Sec. 115 

Clinical Investigations (b) 

Women and 

Minorities—Sec. 

505(b)(1;);) 21 U.S.C 355 

(b) (1) [2]

Requires that FDA and the National Institutes of Health (NIH),

along with representatives of the drug manufacturing 

industry, review and develop guidance on inclusion of women 

and minorities in clinical trials.

1998 CBER/CDER Investigational New 

Drug Applications. 21 

CFR 312.33 [3] 

Requires that investigational new drug (IND) data regarding 

participation in clinical trials be presented in annual reports by 

sex, age, and race. 

2002 Agency-Wide Best Pharmaceuticals for 

Children Act [4] 

Provides mechanisms for studying on- and off-patent drugs in 

children; seeks to improve the level of information in scientific 

publications and/or the label about pharmaceuticals used to 

treat children. Reauthorized in 2007, permanent 

reauthorization under FDASIA 2012.

2003 CBER/CDER Pediatric Research 

Equity Act [5] 

Requires that NDAs and biologics license applications (BLAs) 

for a new active ingredient, new indication, new dosage form, 

new dosing regimen, or new route of administration contain a 

pediatric assessment, unless the applicant has obtained a 

waiver or deferral. Reauthorized in 2007, permanent 

reauthorization under FDASIA 2012.

2007 Agency-Wide Food and Drug 

Administration 

Amendments Act, Pub. 

L. no 110-85 [6] 

Expanded clinical trials database; provided FDA authorities 

and resources for premarket and postmarket drug safety, 

including the authority to require postmarket studies and 

clinical trials, safety labeling changes and Risk Evaluation and 

Mitigation Strategies (REMS). 

 

18 As of July 1, 2014
28

TABLE 1. DESCRIPTION OF STATUES AND REGULATIONS BY CENTER

YEAR CENTER FDA REGULATION DIRECTION

2007 CBER/CDER Requirements on 

Content and Format of 

Labeling for Human 

Prescription Drug and 

Biological Products. 21 

CFR 201.56 [7]

Requires prescription drug products (including biological 

products that are regulated as drugs) to contain specific 

information about use in specific populations in the contents 

of drug labeling.

2012 CDRH Labeling for In Vitro 

Diagnostics Products. 21 

CFR 809.10 [8] 

Recommends that sponsors include information about the 

demographics of study populations in labeling.

2013 CDRH Medical Devices; 

Pediatric Uses of 

Devices; Requirement 

for Submission of 

Information on Pediatric 

Subpopulations That 

Suffer From a Disease or 

Condition That a Device 

Is Intended To Treat, 

Diagnose, or Cure. 21 

CFR 814 [9]

Amends the regulations on premarket approval of medical 

devices to include requirements relating to the submission of 

information on pediatric subpopulations that suffer from the 

disease or condition that a device is intended to treat, 

diagnose or cure. 

CFR: CODE OF FEDERAL REGULATIONS
29

TABLE 2. FDA GUIDANCE DOCUMENTS BY CENTER

YEAR CENTER GUIDANCE19 DIRECTION

1988 CDER Guideline for the Format 

and Content of the Clinical 

and Statistical Sections of 

an Application [10]

Recommends data analysis of safety, effectiveness and clinical 

pharmacology studies by sex, race and age.

1989 CDER Guidance for industry:

Study of Drugs Likely to be 

Used in the Elderly [11]

Recommends pharmacokinetic screen of Phase II/III trials and 

data analysis by age and sex.

1993 CDER Guidance for industry:

Study and Evaluation of 

Gender Differences in the 

Clinical Evaluation of 

Drugs [12]

Recommends pharmacokinetics and pharmacodynamics in 

women, pharmacokinetic screen as a tool to detect differences, 

analysis of safety and efficacy by sex.

1996 CBER/CDER Guidance for industry:

E6 Good Clinical Practice: 

Consolidated Guidance 

[13]

Provides a unified standard for the European Union (EU), Japan 

and the United States to facilitate mutual acceptance of clinical 

data by regulatory authorities. Guidance addresses 

pharmacokinetics, product metabolism, safety and 

effectiveness in population subgroups as appropriate (see 

Section 7.3.6). 

1998 CBER/CDER Guidance for industry: 

Providing Clinical Evidence 

of

Effectiveness for Human 

Drug and

Biological Products [14]

Provides guidance to applicants planning to file NDAs, BLAs, or 

applications for supplemental indications on the evidence to be 

provided to demonstrate effectiveness. Guidance addresses 

studies of effectiveness in demographic subsets (see Section C 

(2)(c)). 

1998 CBER/CDER Guidance for industry: 

General Considerations 

for Pediatric 

Pharmacokinetic Studies 

for Drugs and Biological 

Products [15]

Intended to assist applicants planning to conduct 

pharmacokinetic studies in pediatric populations. The guidance 

addresses general considerations for conducting such studies so 

that drug and biological products can be labeled for pediatric 

use.

1999 CBER/CDER Guidance for industry:

Population 

Pharmacokinetics [16]

Recommends use of population pharmacokinetics to help

identify differences in drug safety and effectiveness among 

population subgroups.

2000 CBER/CDER Guidance for industry:

E11 Clinical Investigation 

of Medicinal Products

in the Pediatric Population 

[17]

Intended to encourage and facilitate timely pediatric medicinal 

product development internationally. The guidance provides an 

outline of critical issues in pediatric drug development and 

approaches to the safe, efficient, and ethical study of medicinal 

products in the pediatric population.

2001 CBER/CDER Guidance for industry: 

Content and Format for 

Geriatric Labeling [18]

Provides industry with information on submitting geriatric 

labeling of human prescription drug and biological products.

 

19 All guidance documents are available at: http://www.fda.gov/regulatoryinformation/guidances/default.htm
30

TABLE 2. FDA GUIDANCE DOCUMENTS BY CENTER

YEAR CENTER GUIDANCE19 DIRECTION

2005 Agency-Wide Guidance for industry: 

Collection of Race and 

Ethnicity Data in Clinical 

Trials for FDA Regulated 

Products [19]

Recommends format for obtaining race and ethnicity 

information for U.S. and international clinical trials to be 

submitted for regulatory review to the FDA.

2005 CBER/CDER Guidance for industry: 

How to Comply with the 

Pediatric Research Equity 

Act [20]

Provides recommendations on how to interpret the pediatric 

study requirements of the Pediatric Research Equity Act and 

addresses the pediatric assessment, the pediatric plan, waivers 

and deferrals, compliance issues, and pediatric exclusivity 

provisions.

2006 CBER/CDER Guidance for industry: 

Clinical Studies Section of 

Labeling for Human 

Prescription Drug and 

Biological Products - 

Content and Format [21]

Assists applicants in deciding (1) what studies should be 

included in the CLINICAL STUDIES section of prescription drug 

labeling, (2) how to describe individual studies, and (3) how to 

present study data, including presentation of data in graphs and 

tables. Guidance is intended to make the CLINICAL STUDIES 

section of labeling, as described in the final rule amending the 

requirements for the content and format of labeling for human 

prescription drug and biological products (21 CFR 201.56 and 

201.57), more useful and to promote consistency in the content 

and format of the section across drug product classes and 

within drug classes and indications.

2006 CBER Guidance for industry: 

Considerations for 

Developmental Toxicity 

Studies for Preventive and 

Therapeutic Vaccines for 

Infectious Disease 

Indications [22]

Provides recommendations on the conduct of developmental 

toxicity studies for investigational preventive and therapeutic 

vaccines for infectious disease indications. Guidance pertains to 

the assessment of the developmental toxicity potential of 

preventive and therapeutic vaccines for infectious diseases 

indicated for females of childbearing potential and pregnant 

individuals.

2008 Agency-Wide Guidance for industry: 

Providing Regulatory 

Submissions in Electronic 

Format: Human 

Pharmaceutical Product 

Applications and Related 

Submissions Using the 

eCTD Specifications [23]

This is one in a series of guidance documents intended to assist 

applicants making regulatory submissions to FDA in electronic 

format using the electronic common technical document 

(eCTD) specifications. The eCTD guidance recommends 

application data, including demographic subgroup data 

information, be submitted in standardized electronic format.

2011 CDRH Guidance for Industry and 

Food and Drug 

Administration Staff: 

Evaluation of Sex 

Differences in Medical 

Device Clinical Studies 

(draft) [24]

Provides guidance on the study and evaluation of sex 

differences in medical device clinical studies and outlines 

CDRH’s expectations regarding sex-specific patient enrollment, 

data analysis and reporting of study information.
31

TABLE 2. FDA GUIDANCE DOCUMENTS BY CENTER

YEAR CENTER GUIDANCE19 DIRECTION

2011 CBER/CDRH Guidance for industry 

Clinical Investigators, and 

Food and Drug 

Administration Staff: 

Design Considerations for 

Pivotal Clinical 

Investigations for Medical 

Devices (draft) [25]

Provides guidance to those involved in designing clinical studies 

intended to support premarket submissions for medical 

devices. This guidance addresses subject selection and 

recommends sponsor discussion of potential issues with FDA in 

regards to clinical study involving vulnerable populations, such 

as pregnant women, in advance of study (See Section 6.4). 

Recommends stratified selection of subjects (e.g. by sex) for 

clinical study (see Section 6.5) and that study sites include 

subjects who reflect epidemiological distribution of the disease 

being treated with regard to variables such as sex (see Section 

6.6) . 
32

TABLE 3. FDA TOOLS FOR REVIEWERS

CENTER TYPE OF TOOL TOOL DESCRIPTION

CBER Standard 

Operating Policies 

and Procedures 

(SOPP)

SOPP 8412 Review 

of Product 

Labeling [26]

Outlines the general operating procedures for CBER staff in

processing draft and final product labeling submissions.

CBER Standard 

Operating Policies 

and Procedures 

(SOPP)

SOPP 8401.7 

Action Package for 

Posting [27]

Serves as a guide for staff for the development and assembly 

of action packages for posting, pursuant to Section 916 of the 

Food and Drug Administration Amendments Act (FDAAA) of 

2007.

CBER Review Template CBER Clinical 

Review Template 

(internal)

The clinical review template is intended to assist reviewers 

conducting the primary clinical review as part of the new 

biologics license application (BLA) or BLA supplement review 

process. The template is also meant to establish 

standardization and consistency in the format and content of 

primary clinical reviews and to ensure that critical 

presentations and analyses will not be inadvertently omitted. 

The standardized structure enables subsequent reviewers and 

other readers to readily locate specific information. Reviewers 

are instructed to discuss the results of analyses in special 

populations (e.g., pediatric patients, premature infants, the 

elderly and persons at exceptional risk for the health-related 

condition of interest). 

CDRH Review Checklist Summary of Safety

and Effectiveness 

(SSED) Clinical 

Section Checklist 

[28]

Intended to present a reasoned, objective and balanced 

summary of the scientific evidence, both positive and 

negative, that served as the basis of the decision to approve 

or deny the premarket approval application (PMA). This 

document discusses demographic subgroup data and analysis, 

including study population demographics and baseline 

parameters. 

CDRH Review Template Premarket 

Approval (PMA) 

Application 

Statistical Review 

Assessment [29]

Used to standardize the structure of statistical review memos 

and ensure review quality in an in-depth review of a PMA for 

therapeutic devices or diagnostics. This document discusses 

demographic subgroup data and analysis, including whether 

important subgroups are identified and their planned analyses 

described. 

CDRH Review Template Investigational 

Device Exemptions 

(IDE) Statistical 

Quality Review 

Assessment

(Internal)

Used to standardize the structure of statistical review memos 

and ensure review quality in an in-depth review of an IDE for 

therapeutic devices or diagnostics. This document discusses 

demographic subgroup data and analysis, including whether 

baseline covariates that include demographic information and 

time-dependent covariates to be measured on subjects are 

clearly identified; and whether important subgroups are 

identified and their planned analyses described.

CDRH Review Template Medical Officer 

Review Template 

(Internal)

Used to standardize the structure of clinical review memos 

and ensure review quality in an in-depth review of an IDE for 

therapeutic devices or diagnostics. This document discusses 

demographic subgroup data and analysis, including whether 

important subgroups will be enrolled in the clinical study.
33

TABLE 3. FDA TOOLS FOR REVIEWERS

CENTER TYPE OF TOOL TOOL DESCRIPTION

CDRH Summary Form Pivotal 

Investigational 

Device Exemption 

Descriptive 

Summary Form 

[30]

Completed by FDA reviewers as part of the IDE review process 

for pivotal trials to provide an accessible summary of the 

major trial design elements. This Summary helps CDRH 

achieve consistency in ensuring that an analysis plan is in 

place to evaluate sex differences in primary safety and 

effectiveness endpoints. It also aids CDRH in developing 

mechanisms to prospectively add and analyze current and 

future clinical trial metrics related to demographics. 

CDRH Review Template Post-Approval 

Studies (PAS) 

(Internal)

Requires reviewers to evaluate if the sponsors have submitted 

study enrollment data by sex/gender, age groups and 

race/ethnicity. Depending on the study planned analysis, 

reviewers are also required to evaluate if subgroup analyses 

are submitted. 

CDER Quality 

Assessment Tool

CDER 21st Century 

Review Process 

Desk Reference 

Guide [31]

Intended for use by both the applicant and members of 

CDER’s review team and designed to guide them through the 

pertinent sections of an application and to assist in assessing 

the content of the NDA/BLA submission as well as the overall 

review process

CDER Review Checklist Clinical Filing 

Checklist for 

NDA/BLA

(Internal)

Used to determine if a submission is fileable (i.e., will be 

accepted for full review) and considers whether all data 

required by the regulations are included, specifically listing 

applicability of foreign data to the U.S. population.

CDER Review Template Clinical Review 

Good Review 

Practice Policy and 

Procedure 

(Manual of Policy 

and Procedures 

(MAPP) 6010.3)

[32]

A structured outline and annotated table of contents used in 

the preparation of a clinical review, which outlines the 

organization of content, promotes consistency in the 

documentation of elements, and provides for ready retrieval 

of information. The template includes a sample table for 

demographic profile and the following review sections: 

 Efficacy demographics

 Efficacy subpopulations

 Analysis of clinical information relevant to dosing

 Overall exposure at appropriate doses/duration & 

demographics of target populations

 Drug-demographic interactions

 Special safety studies

 Pediatrics
34

TABLE 3. FDA TOOLS FOR REVIEWERS

CENTER TYPE OF TOOL TOOL DESCRIPTION

CDER MAPP Clinical 

Pharmacology and 

Biopharmaceutics 

Review Policy and 

Procedure (MAPP 

4000.4) [33]

States that the Clinical Pharmacology and Biopharmaceutics 

Review Template is to be used by all reviewers to document 

primary reviews of all original new drug application (NDAs) 

and supplemental NDAs (sNDAs) and establishes an outline 

for reviews of original NDAs and sNDAs. The template 

includes: 

 Elderly 

 Pediatric patients 

 Gender 

 Race, in particular differences in exposure and/or 

response in Caucasians, African-Americans and/or 

Asians 

CDER Review Checklist Statistics Filing 

Checklist for an 

Original NDA/BLA

(Internal)

Ascertains whether safety and efficacy were investigated for 

gender, racial and geriatric subgroups prior to application 

acceptance filing for full review.
35

TABLE 3. FDA TOOLS FOR REVIEWERS

CENTER TYPE OF TOOL TOOL DESCRIPTION

CDER Review Template Statistical Review 

and Evaluation 

Template 

(Internal)

Describes the content of an NDA/BLA statistical review 

relevant to demographic data. In the Findings in 

Special/Subgroup Populations section the reviewer describes 

efficacy (safety) results across subgroups defined by gender, 

race, age, and geographic region. Other subgroups such as 

those based on baseline characteristics may be included, 

depending on their relevance, representation in the clinical 

studies or on the disease being reviewed. In the subsection 

entitled, Gender, Race, Age, and Geographic Region, the 

reviewer describes efficacy (safety) results across subgroups 

defined by gender, race, age (e.g., less than 65 versus greater 

than or equal to 65 years), and geographic region (e.g., U.S. 

vs. non-U.S.). The reviewer also includes descriptive statistics 

for the defined subgroups and inferential statistics such as the 

results of tests for treatment by subgroup interactions that 

may also be included. Significant interaction test results are 

fully explained, e.g., by including graphics depicting the 

results, and the reviewer exercises caution when synthesizing 

the data across studies. 

Scientifically valid methods are employed when drawing 

inferences from pooled data, and the impact of a subgroup 

difference may be briefly addressed here and more fully 

explained in a subsequent section, or vice versa. Mention is 

made if no conclusions can be drawn due to lack of 

representation, limited sample size, etc. If, for example, the 

studies were conducted in one gender only, a brief statement 

is indicated that gender analysis was not applicable. In the 

subsection entitled, Other Special/Subgroup Populations,

other subgroups may be defined by baseline characteristics 

and are to be included depending on their relevance, on their 

representation in the clinical studies, or on the disease being 

reviewed. If no subgroups other than those in the previous 

sub-section are reviewed, the reviewer indicates here that no 

other subgroups were analyzed.