The **NIDCR Prospective Observational or Biomarker Validation Study Cooperative Agreement (U01 Clinical Trial Not Allowed)** supports investigator-initiated observational studies or biomarker validation studies that require prospective data and biospecimen collection or analysis of existing resources. This opportunity is issued by the **National Institute of Dental and Craniofacial Research (NIDCR)** under the U01 cooperative agreement mechanism, with substantial involvement from NIH program staff. Projects must address significant scientific or clinical questions related to dental, oral, or craniofacial diseases, focusing on robust observational or biomarker validation methodologies. Clinical trials are not supported under this funding announcement.

The purpose of this funding opportunity is to generate high-quality data to improve preventive, diagnostic, and therapeutic approaches for dental, oral, and craniofacial diseases. For prospective observational studies, supported designs include epidemiologic studies assessing disease risk factors, longitudinal cohort studies monitoring treatment outcomes, and studies exploring genetic or environmental mechanisms of disease progression. Biomarker validation studies should focus on advanced analytic and/or clinical validation of biomarkers to ensure reliability and utility in clinical diagnosis, prognosis, or treatment response. Proposed projects must demonstrate readiness for large-scale data and biospecimen collection or advanced analysis, supported by a rigorous study design and a qualified team, including statisticians and data managers.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, and tribal organizations, among others. Foreign institutions are not eligible; however, foreign components as part of U.S.-based projects are permitted. Projects can request budgets reflective of actual needs, with no pre-set budget limits, for a duration of up to five years. Applications must align with NIH guidelines, including compliance with the NIH Data Management and Sharing Policy, and are required to include a Quality Management Plan, a Data Management Plan, and, if applicable, a Schedule of Events for study participants.

Applications must follow the standard NIH submission processes through **Grants.gov** or **NIH ASSIST** and adhere to the SF424 (R&R) Application Guide. Letters of intent are encouraged 30 days prior to the application due date. Key application deadlines follow NIH standard due dates: **June 5**, **October 5**, and **February 5** annually, with subsequent reviews and award start dates based on NIH’s review and advisory council timelines. Projects requesting $500,000 or more in direct costs annually require pre-submission contact with NIDCR at least six weeks before the due date.

Applications will be reviewed for significance, innovation, approach, investigator qualifications, and overall feasibility. Reviewers will evaluate scientific rigor, the adequacy of data collection, statistical analysis plans, and the potential for studies to generate impactful findings. Biomarker validation proposals must demonstrate prior discovery work and robust plans for assay validation or clinical performance metrics. Awardees will work closely with NIDCR program staff, with NIH providing scientific oversight throughout the project lifecycle.

For additional guidance, applicants are encouraged to contact program officials, such as Dr. Lorena Baccaglini or Dr. Dena Fischer, well in advance of submission. Successful applicants must comply with NIH award policies, including protections for human subjects, resource sharing, and federal reporting requirements. The announcement will remain open for submissions until **January 8, 2025**, after which it will be reissued as PAR-25-239.