The NIH’s "Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders" (U44) provides funding through the Small Business Innovation Research (SBIR) cooperative agreement to support small businesses in the clinical validation of candidate biomarkers. This funding opportunity aims to ensure that previously identified and analytically validated biomarkers can demonstrate clinical sensitivity and specificity within a specified context of use, enabling use in clinical trials or as diagnostic tools in practice. The biomarker must be fully developed and shown to address a defined clinical need, with clinical data suggesting its potential value in patient stratification or therapeutic evaluation.

This grant requires applicants to prepare a Plan for Enhancing Diverse Perspectives (PEDP), emphasizing inclusivity and diversity within research teams and collaboration among institutions. Applicants must also include multidisciplinary teams with clinical scientists, statisticians, and those experienced in clinical trial design, as well as secure partnerships with consultants or industry experts in regulatory processes. Awardees are expected to leverage existing resources such as NINDS’ Human Biospecimen and Data Repository (BioSEND) or other data repositories to enhance reproducibility and scalability of the study.

The funding structure includes a maximum budget of $700,000 per year for Phase I projects (up to 2 years) and $1.5 million per year for Phase II (up to 3 years). Projects must outline metrics like sensitivity, specificity, predictive values, and a method for establishing biomarker thresholds or ranges for effective clinical decision-making. The budget can incorporate costs associated with PEDP implementation, data sharing, and potential IP management. The program uses a cooperative agreement model, allowing NIH staff to collaborate closely with awardees on study design, milestone setting, and regulatory guidance. A clearly defined milestone plan is required, specifying quantitative metrics and go/no-go decision points to help evaluate progress and feasibility.

Eligibility is limited to U.S.-based small businesses, with provisions for multi-institutional collaborations, but foreign organizations or foreign components are ineligible. Applicants are also required to demonstrate compliance with SBIR-specific transition benchmarks from Phase I to Phase II and commercialization milestones, especially if previously awarded SBIR/STTR funding. The program strongly encourages early consultations with NINDS staff to discuss the project's alignment with NIH goals, funding policies, and application preparation to ensure high-quality submissions.

The clinical validation studies are intended to generate data that may contribute to FDA submissions or regulatory qualifications, such as through the FDA’s Biomarker Qualification Program, aligning biomarkers with regulatory standards for broader use. The funding mechanism emphasizes NIH’s commitment to rigorous and reproducible science, requiring transparency in data collection and validation and encouraging the sharing of analytic tools, models, and datasets. The application deadlines begin on March 22, 2024, and occur semi-annually, with the funding opportunity closing in June 2026.