Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (R21 Clinical Trials Not Allowed) | PAR 20 168

Opportunity Information: Apply for PAR 20 168

The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (R21 Clinical Trials Not Allowed)" under Funding Opportunity Number PAR-20-168. This announcement supports investigator-initiated research aimed at improving scientific understanding of ME/CFS, with an emphasis on studies that explore the causes of the illness (etiology), improve or refine diagnosis, clarify underlying disease biology (pathophysiology), and document how ME/CFS presents and progresses in different people. A central theme is capturing ME/CFS in diverse populations and across the full lifespan, recognizing that risk, symptoms, severity, and outcomes may vary by age, sex, race and ethnicity, geography, and other social or biological factors.

The FOA is particularly focused on closing major knowledge gaps in ME/CFS. Priority areas include identifying environmental and biological risk factors that may contribute to disease onset or persistence, as well as understanding why the condition can look so different from one patient to another. Applicants are encouraged to study the determinants of heterogeneity, meaning the factors that drive different symptom patterns, functional impacts, trajectories, and comorbidities among individuals with ME/CFS. Another key goal is to uncover common mechanisms that may connect the many body systems affected in ME/CFS, supporting research that looks across organ systems rather than treating symptoms in isolation. In practical terms, this can include work to develop or validate biomarkers and to characterize physiologic or pathophysiologic responses in specific organ systems, especially when done in a way that integrates multiple disciplines and methods.

The NIH signals a strong preference for interdisciplinary research teams, reflecting the complexity of ME/CFS and the need for coordinated expertise across clinical medicine, immunology, neurology, endocrinology, metabolism, genetics, microbiome research, epidemiology, data science, and related fields. The announcement explicitly welcomes team-building approaches that can bring together complementary skill sets to tackle biomarker discovery and to map how ME/CFS affects different systems of the body. The larger intent is to generate evidence that can ultimately translate into better diagnostic tools, better-targeted treatments, and improved quality of life for people living with ME/CFS, even though this specific funding mechanism is not intended to directly run clinical trials.

This opportunity uses the NIH R21 mechanism, which is designed for exploratory and developmental research that is innovative and potentially high impact. The R21 is meant to support projects that either generate early pilot data to test feasibility, pursue higher-risk experiments that could open the door to breakthroughs, or demonstrate the feasibility of new technologies that could significantly advance ME/CFS research. The expectation is that proposed work should be bold and potentially transformative rather than incremental, with a clear rationale for why the approach could shift the field forward if successful. As the title states, clinical trials are not allowed under this FOA, so applications must be structured as non-trial research (for example, observational studies, mechanistic studies, biomarker development, or technology validation work that does not meet NIH's definition of a clinical trial).

Eligibility is broad and includes many types of institutions and organizations. Eligible applicants listed include state, county, city/township, and special district governments; independent school districts; public and state-controlled colleges and universities; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses); small businesses; and other applicant types. The FOA also highlights additional eligible groups such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISI). Faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, regional organizations, and non-U.S. entities (foreign organizations) are also included, reflecting an interest in inclusive participation and the potential value of international or multi-regional expertise.

Key administrative details provided include an agency sponsor of the National Institutes of Health, a grant funding instrument, and activity categories spanning education, environment, and health. The CFDA (assistance listing) numbers associated with this opportunity are 93.113, 93.121, 93.242, 93.273, 93.350, 93.846, 93.853, 93.855, and 93.879. The opportunity record shows an award ceiling of $200,000, a creation date of April 13, 2020, and an original closing date of May 7, 2023. Overall, the program is positioned as a way to spark novel, well-justified, and potentially field-changing ME/CFS research that clarifies disease mechanisms, supports better diagnostics through biomarkers or other tools, and lays groundwork for future advances in care without directly funding clinical trials under this specific announcement.

• The National Institutes of Health in the education, environment, health sector is offering a public funding opportunity titled "Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (R21 Clinical Trials 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, 93.242, 93.273, 93.350, 93.846, 93.853, 93.855, 93.879.
• This funding opportunity was created on 2020-04-13.
• Applicants must submit their applications by 2023-05-07. (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.

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