The National Institutes of Health (NIH) seeks applications for high-risk, multi-center observational studies under the NIDDK High Risk Multi-Center Clinical Study Cooperative Agreement (U01). This funding opportunity promotes investigator-initiated studies targeting diseases aligned with the NIDDK’s mission, including diabetes and related conditions. Applicants must complete a planning phase before applying for the U01 award and provide a Plan for Enhancing Diverse Perspectives (PEDP) that promotes inclusivity throughout the study. The application process emphasizes rigorous study design and adherence to NIH data management policies. Key dates include application submissions from January 5, 2024, to November 5, 2026, with rigorous review criteria focused on scientific significance, innovation, and the applicant's ability to conduct the research. Eligible institutions include higher education entities, non-profits, and government organizations. NIH aims to address health disparities by encouraging studies involving underrepresented groups and fostering community engagement. Applications that do not align with these guidelines or lack necessary documentation will be deemed incomplete. This initiative reflects the NIH's commitment to advancing clinical research within its designated health domains while enhancing diversity and equity in healthcare research.