This Funding Opportunity Announcement (FOA) invites Small Business Innovation Research (SBIR) grant applications from small business concerns (SBCs) that propose to implement investigator-initiated clinical trials related to the research mission of the NIAID. This program will utilize the cooperative agreement mechanism (U44) to enable support for hypothesis-driven, milestone-driven clinical trials. Although clinical trials not considered high-risk may be proposed, this program encourages high-risk clinical studies. High-risk does not imply human subject or patient risk, but rather defines a study that contains one or more of the following unique features: involves non-routine interventions, administration of an unlicensed product, or administration of a licensed product for an unapproved indication. Mechanistic studies are also encouraged and can be proposed under this program. However, not more than one clinical trial should be proposed within each grant application. The NIAID has a robust infrastructure for conducting clinical studies that includes independently managed resources provided through grants and contracts, as well as resources that are integrated within existing NIAID-supported clinical trial networks. Proposed clinical trials may use NIAIDs independent infrastructure for clinical studies, however, support will not be provided for studies that propose to use dedicated resources that are part of a NIAID-supported clinical trial network. A Commercialization Plan must be included that details plans for promoting further commercialization of the intervention/product/technology to be derived from or associated with the proposed clinical trial, including plans for promoting and establishing partnerships between the SBIR Phase II awardee and third-party investors and/or strategic partners.