INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed) | RFA OD 20 004

Opportunity Information: Apply for RFA OD 20 004

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness opportunity (RFA-OD-20-004) is a National Institutes of Health (NIH) funding announcement that supports early-stage clinical research projects designed to make Down syndrome studies more ready for successful future clinical trials. It uses the NIH R21 mechanism and is explicitly "Clinical Trial Not Allowed," meaning the work should focus on preparatory steps that strengthen the field's ability to launch well-designed trials rather than testing an intervention for efficacy in a trial setting. The core purpose is to remove practical and scientific bottlenecks that slow progress from promising therapeutics or diagnostics to well-powered, feasible, and interpretable clinical trials for people with Down syndrome, including those experiencing co-occurring conditions across the lifespan.

The program is centered on clinical trial readiness needs that can materially improve the speed, efficiency, and success rate of later Down syndrome trials. Projects are expected to generate tools, data, and methods that trial teams can directly use when designing or running future studies. Examples of the kinds of activities the FOA is aiming to support include developing and testing biomarkers that can serve as indicators of disease state, progression, treatment response, or target engagement; creating or refining clinical outcome assessment measures that are meaningful, reliable, and appropriate for individuals with Down syndrome; and establishing or validating trial methods that reduce burden, improve data quality, and account for the unique clinical and developmental context of Down syndrome. The FOA also highlights the importance of recruitment and retention strategies, reflecting the reality that successful Down syndrome trials often depend on trust, accessibility, community engagement, and protocols that fit into real-world family and clinical settings.

A major emphasis is placed on understanding Down syndrome in the context of co-occurring conditions, because these conditions can shape symptoms, progression, and outcomes and can complicate trial design if they are not well characterized. The announcement encourages studies that define the presentation, natural history, and course of these co-occurring conditions in individuals with Down syndrome so that future clinical trials can be designed with appropriate eligibility criteria, stratification approaches, endpoints, and follow-up windows. In practice, this could mean generating longitudinal or cross-sectional clinical data that clarifies how a condition manifests differently in Down syndrome, how quickly it changes over time, what meaningful clinical milestones look like, and which measures are most sensitive to change. By clarifying these foundational clinical questions, the FOA aims to reduce the risk that later trials fail due to poorly matched endpoints, inadequate understanding of variability, or incomplete knowledge of baseline trajectories.

From an administrative standpoint, this is a discretionary NIH grant opportunity in the broad areas of health and social services, with multiple CFDA listings associated with NIH programs. The award ceiling is listed as $200,000, consistent with the R21 concept of supporting exploratory or developmental work that can quickly generate proof-of-concept evidence, feasibility data, or validation results. The original closing date in the source information is 2021-11-03, and the opportunity was created on 2019-12-13, which helps place it in the timeline of the INCLUDE initiative's early funding efforts.

Eligibility is broad and includes many organization types commonly able to apply for NIH grants: public and private institutions of higher education, state and local governments, federally recognized tribal governments, tribal organizations (including those not federally recognized), independent school districts, public housing authorities/Indian housing authorities, nonprofits with or without 501(c)(3) status, for-profit organizations (other than small businesses), and small businesses. The FOA also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions. On the non-U.S. side, the FOA draws an important distinction: non-domestic (non-U.S.) entities and non-domestic (non-U.S.) institutions are not eligible to apply as applicant organizations, but non-domestic components of U.S. organizations may participate, and foreign components (as defined by NIH policy) are allowed. In other words, the lead applicant organization must be U.S.-based, but the project may still include certain foreign activities or collaborations if they meet NIH definitions and requirements.

Overall, this opportunity is best understood as targeted infrastructure and methods funding for Down syndrome clinical research: it is meant to create the measurements, operational approaches, and clinical understanding that make future trials more feasible and more likely to produce clear, actionable answers. Instead of funding a trial itself, it supports the steps that prevent trials from failing for avoidable reasons, such as weak or inappropriate endpoints, lack of validated biomarkers, recruitment challenges, or incomplete characterization of co-occurring conditions that influence outcomes in people with Down syndrome.

• The National Institutes of Health in the education, environment, health, income security and social services sector is offering a public funding opportunity titled "INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.113, 93.121, 93.173, 93.233, 93.310, 93.361, 93.837, 93.838, 93.839, 93.840, 93.846, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2019-12-13.
• Applicants must submit their applications by 2021-11-03. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA OD 20 004

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