Human Subjects Mechanistic and Minimal Risk Studies (R01 Clinical Trial Optional) | PA 18 351

Opportunity Information: Apply for PA 18 351

The Human Subjects Mechanistic and Minimal Risk Studies funding opportunity (R01; Clinical Trial Optional), PA-18-351, is a National Institutes of Health (NIH) grant program intended to advance research on the visual system. The central aim is to support well-justified studies in humans that deepen understanding of how vision works in normal conditions and in disease, or that test low-risk interventions related to vision. The announcement is run through NIH (with the National Eye Institute, NEI, as the relevant institute for vision-focused work), and it uses the R01 mechanism, which is typically designed for mature, hypothesis-driven projects with a clear scientific premise, a strong approach, and an experienced team.

A key feature of this opportunity is how it defines what kinds of human research it will and will not support. It accepts two broad categories of applications. First, it supports studies that involve human subjects but do not meet NIH’s definition of a clinical trial (as referenced in NOT-OD-15-015). These might include observational or experimental studies in humans where the design does not involve prospective assignment to an intervention with the goal of evaluating health-related biomedical or behavioral outcomes, depending on NIH’s clinical trial criteria. Second, it supports applications that are NIH-defined clinical trials, but only if they fall into one of two acceptable types: mechanistic clinical trials or minimal-risk intervention studies.

The FOA is especially focused on mechanistic work. In this context, a mechanistic trial is one designed to explain how something works rather than primarily to confirm clinical efficacy. That can include studies that probe biological or behavioral processes, clarify the pathophysiology of a visual disorder, or determine the mechanism of action of an intervention. The emphasis is on understanding underlying mechanisms in human vision, whether in health (for example, sensory processing, neural coding, perception, or visual development) or disease (for example, how specific retinal, optic nerve, or cortical disruptions alter function). Projects that use interventions as tools to reveal mechanisms can fit well, as long as the trial’s main purpose is mechanistic insight rather than large-scale efficacy testing.

The second eligible clinical trial category is minimal-risk intervention research. “Minimal risk” is defined using the standard human subjects benchmark: the probability and magnitude of harm or discomfort anticipated in the research are not greater than what people ordinarily encounter in daily life or during routine physical or psychological exams or tests. In practice, this means the FOA is aimed at studies where participant safety risks and burdens are low and well-controlled. It is not meant for trials involving substantial invasive procedures, high-risk treatments, intensive monitoring needs, or complex safety oversight requirements.

Just as important are the boundaries the FOA draws around what is not eligible. NIH-defined clinical trial applications that are neither mechanistic nor minimal risk are explicitly not allowed under this announcement. The FOA also discourages large-scale clinical trials and makes clear that complex, high resource, or higher safety-risk trials do not belong here. Examples specifically called out as inappropriate include human gene-transfer trials and stem cell therapy trials, along with other trials that would require heavy infrastructure or pose heightened safety concerns. In other words, this opportunity is meant for targeted, scientifically focused human studies that either illuminate mechanisms or test interventions that remain within minimal-risk parameters, not for major confirmatory efficacy trials or cutting-edge interventional studies with substantial clinical risk.

Because NIH’s definitions around “human subjects research” and “clinical trial” status can be nuanced, the FOA strongly encourages applicants to consult NEI program staff before submitting if the project includes human subjects. That early contact is meant to prevent applicants from spending time on an application that ends up in the wrong FOA or is deemed ineligible due to trial type, risk level, or overall scope. This is especially relevant for borderline cases where an intervention is used, outcomes are health-related, or the design involves prospective assignment, any of which can shift a study into NIH-defined clinical trial territory.

From an administrative standpoint, the opportunity is categorized as discretionary grant funding in the health area (CFDA/Assistance Listing 93.867). A wide range of applicant organizations are eligible. Beyond the usual academic and research institutions, eligibility extends to state, county, and local governments; special district governments; independent school districts; public housing authorities/Indian housing authorities; federally recognized tribal governments; and tribal organizations that are not federally recognized governments. Nonprofits (with or without 501(c)(3) status), private institutions of higher education, and for-profit organizations (including small businesses and other for-profits that are not small businesses) are also eligible. The FOA also highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian serving institutions, Asian American and Native American Pacific Islander serving institutions (AANAPISISs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and even non-U.S. (foreign) organizations, reflecting NIH’s broad eligibility framework when scientifically justified.

Overall, PA-18-351 is best understood as an R01 funding path for human vision research that stays tightly aligned with either mechanistic discovery or low-risk intervention testing. It is tailored to studies that can be conducted safely and efficiently, where the expected payoff is clearer understanding of visual function and dysfunction or carefully bounded evaluation of minimal-risk procedures. Projects that drift into large, resource-intensive clinical testing, involve gene or stem cell therapies, or carry higher participant risk are expected to seek other NIH funding routes that are designed for those trial types and oversight needs.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Human Subjects Mechanistic and Minimal Risk Studies (R01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.867.
• This funding opportunity was created on 2017-11-08.
• Applicants must submit their applications by 2021-01-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PA 18 351

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