Research Project Grant (Parent R01 Clinical Trial Required) (PA-20-183)

Ellen Liberman, PhD
National Eye Institute (NEI)
Telephone: 301- 451-2020      
Email: ellenliberman@nei.nih.gov

NEI accepts clinical trial applications submitted under PA-20-183 that include human subjects prospectively assigned to one or more interventions that are minimal risk as defined by 45 CFR 46. Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. As part of the review process, the application must include a clear, detailed plan for monitoring safety that is commensurate with the risks to study participants. In addition to the minimal risk designation from the Institutional Review Board, other reporting to the NEI may be required and will be outlined in the Notice of Award Terms and Conditions.

Applications proposing mechanistic studies with human subjects must be submitted under the Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required) PA-20-184: /grants/guide/pa-files/PA-20-184.html

Applicants who wish to submit complex, large-scale, high resource- or safety-risk clinical trials that propose to test efficacy, effectiveness or safety should not submit to this FOA. Instead, these clinical trials must be submitted to one of the Clinical Research cooperative agreement FOAs listed here: https://www.nei.nih.gov/grants-and-training/funding-opportunities/current-funding-opportunities

Applicants are strongly advised to consult with NEI program staff prior to submitting an application with human subjects to determine the appropriate funding opportunity announcement

• mechanistic studies that meet NIH’s definition of a clinical trial and that have the primary goal of understanding how an intervention works. Mechanistic studies are designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (the goal must not be to evaluate safety, pharmacokinetics or pharmacodynamics, efficacy, or clinical trial feasibility)
• fundamental or basic experimental studies involving humans (BESH) that do not have specific processes or products in mind
• “hybrid” applications, i.e., applications that propose non-interventional fundamental science aims along with the mechanistic or BESH clinical trial(s)
• Studies using surrogate or clinical outcomes for the purpose of providing preliminary proof of an expected effect (these must not be efficacy studies, see next section) of the proposed mechanistic and fundamental or basic experimental study

• provision of a non-routine intervention, that is, an intervention or non-routine use of an intervention that would not otherwise be provided for the condition under study in the local facility where the study is being conducted;
• administration of an unlicensed product; or
• administration of a licensed product for an unapproved indication.

As announced in NOT-GM-22-027, NIGMS will accept applications in response applications to the NIH Parent (R01 Clinical Trial Required) FOA that propose:

• Studies that meet NIH’s definition of a clinical trial AND are mechanistic in nature. The primary objective of the trial should be to provide mechanistic understanding of the biology underlying one or more of the NIGMS clinical research areas. Studies focusing on mechanism of action of an intervention in these clinical areas are also potentially acceptable, subject to the limitations stated below. NIH provides examples of mechanistic clinical trials in NOT-OD-18-010. A strong evidence base of fundamental biological and clinical information supporting a robust, mechanistic hypothesis for the trial should already exist in peer-reviewed literature.
• Studies that meet the definition of Basic Experimental Studies Involving Humans (BESH). These clinical trials aim to understand fundamental aspects of phenomena without specific application towards processes or products in mind. Although NIGMS does not participate in R01 PA-20-184, the Institute will accept these applications under the Research Project Grant (Parent R01 Clinical Trial Required), consistent with its basic research mission.
• “Hybrid” applications, i.e., applications that propose non-interventional fundamental science aims along with the clinical trial(s) described above.

Please refer to NOT-GM-22-027 for additional information.