Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional)

The NIH, through the National Institute of Neurological Disorders and Stroke (NINDS), is offering funding to support the clinical validation of candidate biomarkers for neurological and neuromuscular disorders through a cooperative agreement. This initiative (PAR-25-055) seeks to establish the clinical sensitivity and specificity of pre-identified biomarkers, which have already been analytically validated, for use in clinical populations aligned with FDA guidelines. The goal is to generate robust evidence for biomarkers that will advance therapeutic development, aid clinical decision-making, and improve trial design within NINDS’s mission scope. Funding is available to projects that meet the scientific, clinical, and regulatory requirements necessary for later-stage clinical trials or clinical applications. Applications must focus on validating biomarker measurements within one or two specified contexts of use (COUs), such as diagnostic, prognostic, or monitoring applications, which should be justified in terms of both clinical need and feasibility of implementation in clinical trials or practice. Proposed studies should provide sufficient preliminary data on biomarker performance, including clinical sensitivity and specificity, and describe an established detection method. This program uses a cooperative agreement model, emphasizing milestone-driven research with NIH’s active collaboration in shaping and reviewing the project’s progress. To qualify, applicants must demonstrate that their biomarker has been subject to initial testing with clinical sensitivity and specificity data available and that detection methods are robustly validated. Eligible applicants include U.S.-based institutions, nonprofit organizations, and government entities, with a strong preference for collaborations that involve multidisciplinary teams such as statisticians, clinical scientists, and regulatory experts. The application must include a Plan for Enhancing Diverse Perspectives (PEDP) to foster inclusivity, encompassing diverse scientific expertise, community engagement strategies, and recruitment efforts aimed at underrepresented populations. Applications must adhere to NIH’s standards on rigor and transparency, with emphasis on well-justified study design, appropriate statistical methodologies, clear participant inclusion criteria, and comprehensive project timelines with quantitative annual milestones. The budget for each award is flexible, based on the project’s actual needs, with the maximum project period set at five years. The NIH encourages the use of existing resources, such as the NINDS BioSEND repository for biospecimens, and expects applicants to develop a rigorous Data Management and Sharing Plan. Collaborative efforts, particularly those involving established clinical trial resources or biospecimens from ongoing studies, should include letters of support and evidence of intellectual property (IP) arrangements as applicable. Applications will be reviewed based on their potential impact, rigor, feasibility, and the expertise of the investigative team. Specific evaluation criteria include the biomarker’s anticipated utility in clinical settings, the strength of the study design, adherence to regulatory standards, and the feasibility of achieving project milestones within the designated timeline. Applicants must submit detailed protocols for biomarker validation, including clinical and statistical analyses, with clear go/no-go decision criteria to assess progress. In cases where single-site studies are proposed, a strong scientific justification is required. Submission deadlines occur twice annually, with the earliest due date on February 21, 2025. Letters of intent are encouraged 30 days prior to the due date, though they are not mandatory. Applications must be submitted through the ASSIST or Grants.gov platforms and include all required sections, including the PEDP and milestone plans, to avoid administrative withdrawal. Applicants seeking over $500,000 in annual direct costs must contact NIH staff at least six weeks prior to submission. Following submission, applications will undergo a multi-stage review, including both NIH peer review and advisory council evaluation, with funding decisions based on merit, alignment with NINDS priorities, and available resources.