Efficacy trials test the potential success of an intervention in an ideal situation: full participant adherence and a high degree of control over testing conditions and other variables. Consequently, they can overestimate success rates and value to actual communities with diverse patient populations—this is particularly true among older people, minoritized groups, and women. Embedded pragmatic clinical trials (ePCTs), however, offer an important complement in the evidence generation ecosystem because they test how interventions work in routine care conditions within real-world populations. As such, investigators who write an ePCT grant application for the NIH or PCORI must ensure that their proposed sample is not merely based on convenience. Rather, they should be intentional from the outset and demonstrate a plan to include broad representation of populations affected by the condition of interest, even if it requires greater recruitment efforts and consideration of demographics, socioeconomic influences, cultural barriers, and existing healthcare systems.

These considerations result in more valuable real-world data, a better-served patient population, and potentially better relationships and interactions across the healthcare system for all.

Inclusion of women and members of minoritized groups as participants is compulsory for NIH-funded clinical research grants. Investigators are required to provide details about the patient population, including sex, race, and ethnicity, as those relate to the real-world impact of the study. If the proposed cohort skews toward a specific demographic or excludes others, investigators must justify this explicitly on scientific or ethical grounds consistent with desired research outcomes, disease pathology, or other factors.

Inclusion of participants across the lifespan has been compulsory for NIH-funded clinical research grants since 2019. Research findings should apply to the full age range potentially affected by the disease or condition being studied. Any exclusions or focus on specific age groups must be justified explicitly on scientific or ethical grounds consistent with desired research outcomes, disease pathology, or other factors.

PCORI considers health disparities a national priority and has developed Foundational Expectations for Partnerships in Research, which includes diversity and representation expectations and states, “Projects should include partners, organizations, researchers and other team members who reflect the diversity of patients and communities affected by the research topic.” Because of this fundamental expectation, studies are often powered above typical power for heterogeneity of treatment effect analyses to allow for subgroup analyses, recognizing that not every patient is the same and interventions may work well in one population but not another. It is mandatory that investigators provide targets for recruitment that reflect the diversity of those affected by the condition of interest.

Considerations for Recruitment of Diverse Participants in PCTs:

• Engage individuals with the same lived experience as prospective study participants in the planning of the research protocol
• and throughout the entire lifecyle of the study
• Work with community organizations to identify and address social and cultural influences that impact trustworthiness of healthcare providers and attitudes about healthcare
• Review opportunities for economic incentives for participants
• Consult national or global networks of investigators with greater success in recruiting and supporting representative populations
• Consider remote/virtual check-ins or other technology solutions that reduce participant burden, increase participant flexibility, and, potentially, generate more data and insights
• Address barriers to access in participation in trials such as transportation, the digital divide, and insurance
• Collaborate with established community partners to show investment in sustainability beyond the trial period

Additional Considerations for ePCT Investigators, Advisory Boards, and Collaborators:

• Consider community engagement studios (Scheffey et al 2022) in the development of the research protocol
• Ensure advisory and review boards are representative of the patient population and include members of trusted community organizations, social workers, and healthcare professionals
• Support development of representative research teams, beyond just recruitment, to grow perspectives in current and future studies
• Work with local communities to create dialogue and leave positive legacies, helping both patients and future clinical trial investigators
• Consider convenience, access, and standing within the community when selecting study sites (See Planning for Diversity - Stakeholder Engagement and Site Selection to Maximize Diversity)
• Discuss the study plans with an NIH program official, if appropriate, in case the institute has any specific guidance