Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 Clinical Trial Optional) | PAR 21 059

Opportunity Information: Apply for PAR 21 059

The funding opportunity titled "Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 Clinical Trial Optional)" (PAR-21-059) is a National Institutes of Health (NIH) program announcement designed to push promising neurological and neuromuscular biomarkers from the "this looks encouraging" stage into rigorous, clinically grounded validation. The central aim is to support studies that test how well a biomarker actually performs in the real clinical population it is meant to serve, using validation practices that align with FDA expectations. In practical terms, the work supported under this announcement should generate strong evidence about a biomarker's clinical performance, especially its positive predictive value and negative predictive value, so that clinicians, researchers, and regulators can understand how accurately the biomarker identifies or rules out a condition (or a clinically meaningful state related to that condition) in the intended use setting.

This announcement is not meant for early discovery or basic feasibility work. It assumes that several key pieces are already in place before applying. First, the candidate biomarker itself must already have been identified, meaning there is a strong rationale and preliminary evidence supporting its relevance to a particular neurological or neuromuscular disease or condition. Second, the method used to detect or measure the biomarker must already exist and must have been analytically validated, which generally implies the assay or measurement technology has already been shown to be technically reliable (for example, demonstrating accuracy, precision, sensitivity, specificity, reproducibility, and appropriate quality controls). Third, the clinical or research need has to be clear, along with a plausible "context of use" describing how the biomarker would be used in practice (for example, diagnosis, prognosis, patient stratification, monitoring disease progression, or measuring response to treatment). The point of the program is to fund the clinical validation step that connects a technically sound measurement to demonstrated value and reliability in the target patient population.

The award mechanism is a U44 cooperative agreement, which signals a more hands-on partnership with NIH compared to a typical grant. Under cooperative agreements, NIH staff generally have substantial scientific and programmatic involvement during the project period, which can include coordinated milestone oversight, alignment with program goals, and active collaboration to keep the project focused on generating validation-grade evidence. The notice also states "Clinical Trial Optional," meaning applicants may propose a study that includes a clinical trial component if it is appropriate for the validation work, but they are not required to run a clinical trial to be eligible. The funding activity is categorized under health, and the opportunity is associated with CFDA number 93.853, reflecting NIH support for neurological research and related translational efforts.

Eligibility is focused on small businesses, which places this opportunity in the SBIR/STTR-style translational pipeline where companies can advance products or tools toward real-world adoption. Foreign institutions are not eligible to apply, and non-U.S. components of U.S. organizations are also not eligible. That said, "foreign components" as defined in the NIH Grants Policy Statement may be allowed, which typically means a U.S. applicant might be able to include certain limited, well-justified foreign activities or collaborations if they meet NIH policy requirements and are clearly necessary for the project.

Overall, the opportunity is best understood as a targeted bridge between a biomarker that already looks strong on paper and in the lab, and a biomarker that has been convincingly validated in the patient population where it is intended to be used. The expected deliverable is not simply another association study, but a rigorous, FDA-consistent demonstration of clinical predictive performance that can support downstream steps such as broader clinical adoption, integration into trials, or advancement toward regulatory qualification depending on the biomarker and intended use. The original closing date listed for this opportunity was 2023-08-07, and the program was created on 2020-11-19, indicating it was part of a multi-year effort to accelerate high-quality biomarker validation in neurology and neuromuscular disease.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 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 2020-11-19.
• Applicants must submit their applications by 2023-08-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: Small businesses.

Apply for PAR 21 059

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: