Clinical Trial Readiness for Functional Neurological Disorders (U01 Clinical Trial Optional) | PAR 22 053

Opportunity Information: Apply for PAR 22 053

The NIH funding opportunity "Clinical Trial Readiness for Functional Neurological Disorders (U01 Clinical Trial Optional)" (PAR-22-053) is a discretionary grant program using a cooperative agreement mechanism (U01) to push the field of Functional Neurological Disorders (FNDs) toward being genuinely ready for rigorous, informative clinical trials. The program is framed around a practical problem: FNDs are common, disabling, and costly, yet progress in developing and testing treatments at a high evidence level has been slowed by gaps in diagnosis, measurement, and prediction of treatment response. NIH is essentially signaling that before the next wave of large, definitive treatment trials can succeed, the community needs better tools and shared standards for identifying participants, measuring change, and interpreting outcomes.

FNDs are described in the announcement as conditions involving altered voluntary motor or sensory function where clinical findings show incompatibility with recognized neurological or medical diseases. They sit at the overlap of neurology and psychiatry, but patients most often enter care through neurology, and their management frequently requires interdisciplinary approaches. The FOA highlights that FNDs are linked not only to major morbidity and high health care utilization, but also to mortality, and that the societal costs include lost productivity. Because effective therapeutic intervention is viewed as an underused opportunity, NIH characterizes the current state of care and evidence generation as a kind of healthcare crisis that could be improved with better clinical research infrastructure.

A major theme of the opportunity is that diagnosis and management remain difficult in routine practice and in research settings. Although diagnostic criteria exist, they are not universally accepted, and different FND subtypes vary in how straightforward they are to diagnose. While diagnosis is based on positive clinical signs, it can also be supported by laboratory or ancillary testing; importantly, the FOA emphasizes that laboratory-supported diagnosis is possible and that biomarkers could be developed, but that much more research is needed to make these tools reliable and clinically useful. This matters for trials because unclear diagnostic boundaries and inconsistent classification can lead to heterogeneous samples, noisier data, and weaker conclusions about whether an intervention truly works.

The FOA is targeted at "clinical trial readiness" work, meaning prospective clinical projects that create or validate the foundational elements needed for strong future trials. NIH specifically calls out projects that validate biomarkers, endpoints, and clinical outcome assessments (COAs) that are "fit-for-purpose" and include a defined context of use in clinical trials. In practice, this points to studies designed to show that a given measure is reliable, sensitive to change, clinically meaningful, and feasible across sites and populations, rather than early-stage exploratory work with unclear application. It also responds to the current barrier that, even when therapies exist or show promise in certain groups, the field struggles to generate high-level evidence because outcome measures can be inconsistent, poorly validated, or not well aligned with what trials need to detect treatment effects.

Another issue the announcement foregrounds is variability in treatment response. The FOA notes that differential responses have been observed, which makes it difficult to predict overall (aggregate) response in clinical studies. That variability increases the importance of better biomarkers, better stratification approaches, and stronger endpoints that can capture meaningful improvement across diverse patient presentations. By supporting projects that tighten these tools, NIH is aiming to reduce uncertainty in trial results and improve the ability to identify which patients benefit from which interventions.

Administratively, this opportunity is run by the National Institutes of Health under CFDA 93.853, and it uses a cooperative agreement structure, which typically means NIH program staff will have substantial involvement in the project compared to a standard investigator-initiated grant. The "clinical trial optional" language indicates applicants may propose projects that do or do not include a clinical trial component, as long as the work directly supports readiness for future trials through validation of biomarkers or outcome measures and other fit-for-purpose trial infrastructure elements. The original closing date listed is 2024-11-05, and the opportunity was created on 2021-11-02.

Eligibility is broad and includes many types of U.S. organizations and certain non-U.S. entities. Eligible applicants include state, county, and local governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); small businesses; and other entities. The FOA also explicitly encourages participation from organizations such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and foreign organizations.

Overall, the grant is best understood as a field-building effort focused on the measurement science and validation work that makes later therapeutic trials in FNDs credible and interpretable. Rather than primarily funding new treatments outright, it prioritizes the tools and standards that allow treatments to be tested properly: clearer diagnostic support where possible, stronger biomarkers, well-justified endpoints, and COAs that can capture meaningful change with a defined role in the trial setting.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clinical Trial Readiness for Functional Neurological Disorders (U01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853.
• This funding opportunity was created on 2021-11-02.
• Applicants must submit their applications by 2024-11-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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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