The NIH Directors Transformative Research Award Program supports individual scientists or groups of scientists proposing groundbreaking, exceptionally innovative, original, and/or unconventional research with the potential to create new scientific paradigms, establish entirely new and improved clinical approaches, or develop transformative technologies. For the program to support the best possible researchers and research, applications are sought which reflect the full diversity of the nations research workforce. Individuals from diverse backgrounds, including those from underrepresented groups (see, Notice of NIH's Interest in Diversity, NOT-OD-20-031) are strongly encouraged to apply to this Funding Opportunity Announcement. In addition, applications are welcome from the full spectrum of eligible institutions in all geographic locations and in all topic areas relevant to the broad mission of NIH, including, but not limited to, behavioral, social, biomedical, applied, and formal sciences and topics that may involve basic, translational, or clinical research. No preliminary data are required. Projects must clearly demonstrate, based on the strength of the logic, a compelling potential to produce a major impact in a broad area of relevance to the NIH. The NIH Directors Transformative Research Award is a component of the High-Risk, High-Reward Research program of the NIH Common Fund. Towards the objective of funding the best possible science, the Office of Strategic Coordination and the Center for Scientific Review are piloting a process for initial peer review of applications received in response to this FOA in which the identity of the investigators and institutions are withheld until the last phase of review. Instructions for anonymizing components of the application are given in Section IV and must be carefully followed. A description of the review process is given in Section V.