The NIAMS Clinical Trial Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) is a phased award program designed to support investigator-initiated, single- or multi-site interventional clinical trials in the fields of arthritis, musculoskeletal, and skin diseases. This opportunity is provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The cooperative agreement mechanism involves two phases: the UG3 phase for final preparations to initiate a clinical trial and the UH3 phase for trial execution and data collection. This award ensures that trials are hypothesis-driven and aligned with NIAMS' mission to improve clinical care and health outcomes.

The UG3 phase, limited to one year with a budget cap of $250,000 in direct costs, supports necessary activities to prepare for the clinical trial launch. These include finalizing protocols, gaining regulatory approvals, developing data management systems, and establishing contracts and agreements with clinical sites. Successful completion of UG3 milestones, such as IRB and Data and Safety Monitoring Board (DSMB) approvals, is required for transition to the UH3 phase. The UH3 phase, which can last up to five years, involves trial enrollment, implementation, data collection, analysis, and reporting. Milestones must be proposed for both phases, including detailed recruitment targets, progress assessments, and dissemination plans for study results.

Applications must clearly articulate the significance, innovation, and feasibility of the proposed clinical trial. This includes the scientific rationale, study design, analysis plans, and contingency strategies for potential challenges. The research strategy should describe how the trial addresses an important research gap, its potential to influence clinical practice or health policy, and plans to engage people with lived experience, such as patients and caregivers, in all phases of the research process. Meaningful engagement of diverse populations and collaborators is strongly encouraged to ensure the trial’s relevance, inclusivity, and impact.

NIAMS encourages the use of innovative trial designs, such as adaptive designs or methods for futility analysis, to optimize study efficiency. Trials must adhere to NIH’s single Institutional Review Board (sIRB) policy for multi-site studies and ensure compliance with ClinicalTrials.gov registration and reporting requirements. A clinical monitoring plan and robust data management and sharing strategies must also be included in the application to ensure quality, transparency, and reproducibility.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, tribal governments, and local governments within the United States. Foreign institutions are not eligible; however, foreign components of U.S. organizations may participate. Applicants must register with necessary systems, including SAM.gov, Grants.gov, and eRA Commons, before submission. Multiple applications from the same organization are permitted if each proposal is scientifically distinct.

Applications are reviewed for scientific merit based on their significance, rigor, feasibility, and the expertise of the investigative team. Specific factors include the clarity and feasibility of UG3 milestones, the robustness of the trial design, and the adequacy of recruitment and retention plans. The program also evaluates the inclusion of people with lived experience and the trial's potential to address health disparities. Funding decisions are contingent upon scientific merit, NIAMS priorities, and availability of funds.

The first application deadline is March 4, 2025, with additional cycles occurring semi-annually through March 4, 2027. Applications must be submitted electronically via Grants.gov, and applicants are encouraged to consult with NIAMS program staff before submission. For inquiries, applicants may contact Charles Washabaugh for scientific and research questions or Kathy Salaita for peer review matters. Full details, including program requirements and review criteria, are provided in the funding announcement.