www.fda.gov Guidance Snapshots are a communication tool and are not a substitute for the guidance 

document. To learn more about enhancing the diversity of clinical trials, read the guidance. 

Enhancing the Diversity of Clinical Trial Populations — 

Eligibility Criteria, Enrollment Practices, and Trial Designs 

Final Guidance 

Enrolling participants with a wide 

range of baseline characteristics may 

create a study population that more accurately reflects 

the patients likely to take the drug, if approved. It 

also may uncover differences by demographic and 

non-demographic characteristics that maybe important 

for safe and effective use of the investigational drug.

Why is clinical trial 

diversity important? 

What is recommended 

in the guidance? 

Guidance Snapshot 

This guidance discusses approaches 

that sponsors can take to increase 

enrollment of underrepresented populations in clinical 

trials that are intended to support a new drug application 

or a biologics license application. It also discusses 

representing demographic and non-demographic 

characteristics1

 in study populations. This guidance 

provides recommendations on the following: 

1. Broadening eligibility criteria and avoiding 

unnecessary exclusions in clinical trials to 

increase diversity in enrollment 

2. Designing trials that are accessible 

3. Adopting enrichment strategies 

4. Applying the recommendations for broadening 

eligibility criteria to clinical trials of drugs 

intended to treat rare diseases or conditions 

1

Demographic characteristics are considered characteristics such as sex, race, ethnicity, age, location of residency, while non-demographic characteristics are 

considered patients with organ dysfunction, comorbid conditions, disabilities, those at the extremes of the weight range, and populations with diseases or conditions 

with low prevalence. 
www.fda.gov Guidance Snapshots are a communication tool and are not a substitute for the guidance 

document. To learn more about enhancing the diversity of clinical trials, read the guidance. 

Broadening Eligbility Criteria to 

Increase Diversity in Enrollment 

How can sponsors make 

their clinical trials 

more inclusive? 

• Ensure, when developing clinical trial 

protocols, that eligibility criteria are 

representative of the population for 

whom the drug has been developed. 

• Examine each exclusion criterion and 

determine whether it is necessary to help 

assure the safety of trial participants or 

to achieve the study objectives. If it is not 

necessary, consider eliminating or modifying 

the criterion to expand the study population. 

• Consider whether exclusion criteria from 

phase 2 studies can be eliminated or 

modified for phase 3. 

• Consider characterizing the drug metabolism and 

clearance across populations that may 

metabolize or clear the drug differently early 

in clinical development. 

• Consider using an adaptive clinical trial design2 

that would allow for pre-specified trial design 

changes during the trial when data become 

available, including altering the trial population. 

• Consider creating a broader pediatric development 

program that does not arbitrarily limit the study 

population and unnecessarily delay development of 

medicines for children. including pharmacokinetic 

sampling to establish dosing in individuals who 

become pregnant during a trial. 

• Consider including a reasonable sample of 

marker-negative participants who have the 

disease but do not meet the enrichment criteria. 

How can sponsors 

make clinical trials 

less burdensome 

for participants? 

• Reduce the frequency of in-person 

study visits and consider flexibilities 

in visit times. 

• Enlist mobile medical professionals, 

such as nurses and phlebotomists, to 

visit participants instead of requiring 

participants to visit distant clinical trial sites. 

• Replace visits to clinical trial sites with 

electronic communication tools and 

devices, such as telephones/mobile 

phones, secured email, social 

media platforms, or digital 

health technologies, where 

appropriate. 

• Inform participants of possible 

reimbursements for travel, 

lodging, and costs associated 

with participation in trials. See 

the information sheet guidance 

for institutional review boards 

and clinical investigators 

Payment and Reimbursement 

to Research Subjects 

(January 2018).

3 

2

See the guidance for industry Adaptive Design Clinical Trials for Drugs and Biologics (November 2019). For the most recent version of a guidance, check the FDA guidance 

web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 

3

For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
www.fda.gov Guidance Snapshots are a communication tool and are not a substitute for the guidance 

document. To learn more about enhancing the diversity of clinical trials, read the guidance. 

How can sponsors improve their clinical trial enrollment and 

retention practices to enhance inclusiveness? 

ENROLLMENT Enroll participants who reflect the characteristics of clinically relevant populations 

regarding age, sex, race, and ethnicity. Consider having a diverse clinical trial staff 

to facilitate enrollment and retention of diverse participants. 

GENERAL 

ENGAGEMENT

 Educate participants about clinical trial participation. Industry, patient advocacy 

groups, medical associations, and other stakeholders can consider collaborating 

to educate participants about clinical trial participation. 

 Ask for patient feedback. For more information, see the guidance for industry, 

FDA staff, and other stakeholders Patient-Focused Drug Development: Collective 

Comprehensive and Representative Input (June 2020).4

 Engage medical societies, focus groups, community advisory boards, and disease 

registries to meet the needs of potential participants. More information is available 

at the National Institute on Minority Health and Health Disparities’ CommunityBased Participatory Research Program website.

Hold recruitment events frequently and offer them during evenings and weekends. 

 Consider holding the events in nonclinical but trusted locations, such as places of 

worship or community centers; social places of business, such as barbershops and 

beauty salons; and public events, such as cultural festivals, carnivals, and parades.

 Use online/social media recruitment strategies to identify participants for whom 

traditional referral centers are not accessible. 

CULTURAL

COMPETENCY

 Provide research staff with cultural competency and proficiency training 

to facilitate building of trust with participants.

Avoid the use of cultural generalizations and stereotypes.

 Share trial resources and documents in multiple languages and 

use multilingual research staff and/or interpreters.

 Remain engaged with communities after the clinical research ends 

and share trial updates to continue strengthening relationships 

with communities.
Guidance Recap Podcast - 

Hear Highlights Straight from FDA Staff 

Speakers: Jamie Gamerman, JD, Regulatory Counsel, Office of Medical Policy 

Click here to listen Click here to read transcript 

Guidance Snapshots are a communication tool and are not a substitute for the guidance 

document. To learn more about enhancing the diversity of clinical trials, read the guidance. 

To see additional Guidance Snapshots, check out the pilot program.

www.fda.gov 

How can sponsors improve diversity in clinical trials for 

rare diseases?

 Early in the drug or biologic development process, engage with patient advocacy groups, experts in 

the rare disease, and patients with the rare disease; ask for their suggestions on the design of trials, 

including trial procedures.

 Re-enroll participants from the early-phase trials into later-phase trials when medically appropriate 

and scientifically sound to ensure that participants continue to have access to the investigational drug 

or biologic based on tolerability and benefit.

 Refer to the following guidance: Rare Diseases: Common Issues in Drug Development (January 2019).4 

GEOGRAPHY

 Ensure that clinical trial sites include geographic locations with a higher 

concentration of racial and ethnic minority patients and indigenous populations, 

as well as locations within the neighborhoods where these populations receive 

their health care. 

TRIAL 

EFFICIENCY

 Consider using real-world data to promote more efficient recruitment of a diverse 

population by using, for example, claims data and electronic health records to 

identify potential sites and participants. 

 Consider using “electronic informed consent” to allow participants to read and 

sign necessary forms remotely instead of traveling to a clinical trial site, while 

ensuring that all potential participants, including those with literacy issues, 

understand all necessary information. 

4

For the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 

As a sponsor, where can I obtain more information? 

• Clinically Relevant Population - 

FDA Action Plan to Enhance the Collection 

and Availability of Demographic Subgroup Data 

• Older Adult Populations 

• Pregnant Women - 

Task Force on Research Specific to Pregnant 

Women and Lactating Women 

• Participants with Rare Diseases - 

Rare Diseases: Common Issues in Drug 

Development Guidance 

• FDA’s Office of Women’s Health web page 

• Oncology Center of Excellence’s Project Equity 

• FDA’s Consumer Updates web page 

• FDA’s Office of Minority Health 

and Health Equity web page 

• Office for Human Research Protections

(OHRP) web page 

• NIH Clinical Research Trials and You web page 

• Clinicaltrials.gov web page, a database of 

privately and publicly funded clinical studies 

conducted around the world 

• ResearchMatch, which connects researchers 

with people who are interested in participating 

in clinical trials