The NIAID Clinical Trial Implementation Cooperative Agreement (U01 Clinical Trial Required), under funding opportunity number PAR-24-100, supports investigator-initiated, high-risk clinical trials, including mechanistic studies aimed at advancing the understanding of human diseases. These high-risk trials may involve non-routine interventions, unlicensed products, or licensed products used for unapproved indications. The program seeks to fund projects addressing high-priority areas relevant to NIAID’s mission, such as infectious, immunologic, and allergic diseases. Applicants are encouraged to propose trials that are hypothesis-driven and ready for implementation, with all planning activities completed prior to submission.

The award covers costs related to trial implementation, including personnel training, recruitment, data management, investigational product expenses, and regulatory activities. Applications can request funding for up to five years, with no specified budget limit, as long as the budget reflects the project's needs. For larger budgets (over $500,000 in direct costs in any year), applicants must consult with NIAID staff well before submission. Mechanistic studies, which investigate the biological mechanisms underlying disease, are particularly encouraged, especially for trials funded by the Division of Allergy, Immunology, and Transplantation.

Eligible applicants include U.S. and foreign institutions of higher education, non-profit and for-profit organizations, small businesses, local governments, and certain other entities. Proposals must be distinct and cannot overlap with other applications submitted for review. The application process involves detailed scientific and operational planning, including a complete clinical protocol, plans for data and safety monitoring, and strategies to address ethical considerations and trial logistics.

The review criteria focus on the significance, innovation, and approach of the proposed trial, as well as the qualifications of the investigators and the feasibility of the project timeline. The NIH peer review system will assess the likelihood of the project to significantly impact the field, with consideration of potential challenges and plans for overcoming them. After peer review, applications undergo a second level of evaluation by an advisory council before final funding decisions are made.