NIH has released Notice NOT-OD-26-032 to inform the research community of a significant policy change: Basic Experimental Studies Involving Humans (BESH) will no longer be subject to the requirements under the NIH Clinical Trial Definition.
This change is intended to reduce administrative burden and reflects NIH’s current interpretation of what qualifies as a “clinical trial,” particularly with respect to whether a study’s outcomes are intended to directly advance health.
Why This Matters: A Major Shift in NIH Classification
For years, BESH studies have been treated as clinical trials under NIH policy. That classification triggered a number of administrative requirements—most notably the expectation that these studies follow clinical trial-specific processes, such as registration and results reporting in ClinicalTrials.gov. Under this new notice, that will change.
NIH is now formally stating that BESH studies do not meet the NIH definition of a clinical trial, and therefore will not be required to follow NIH clinical trial requirements going forward.
More guidance and examples are expected from NIH to help the community navigate this updated classification approach.
Background: The 2014 NIH Clinical Trial Definition
NIH explains that in 2014, it revised its clinical trial definition to improve:
- Transparency
- Accountability
- Precision in tracking research
NIH’s definition describes a clinical trial as “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”
NIH notes that this definition revision was part of a broader stewardship effort. The goal was to ensure that all NIH-supported research involving human participants would meet rigorous standards and that results would be rapidly disseminated—even if the study did not qualify as an Applicable Clinical Trial under Section 801 of the FDA Amendments Act.
As part of this 2014 effort, NIH expanded its definition of a clinical trial to include Basic Experimental Studies Involving Humans (BESH).
What NIH Is Changing Now—and Why
NIH states that policies related to results dissemination have changed since 2014. As part of ongoing efforts to reduce administrative burden, NIH is now taking a new approach.
Effective for applications submitted on or after May 25, will no longer characterize BESH as clinical trials.
NIH also clarifies how it is interpreting the phrase “health-related biomedical or behavioral outcome.” NIH now considers this to mean an outcome that has “the potential for direct advancement of health.”
NIH explains that BESH research produces fundamental information about biology or behavior. While that work may eventually inform health advances, NIH emphasizes that BESH studies:
- Are not conducted with the express intent of changing clinical practice or health.
- Aim to understand fundamental aspects of phenomena.
- Typically do not have immediate clinical applications.
Because of this, NIH concludes that BESH studies no longer meet NIH’s clinical trial definition.
Applicability: When This Takes Effect
NIH states clearly that this change applies to applications submitted to due dates on or after May 25, 2026. For those applications, BESH studies will no longer be considered clinical trials by NIH.
What Changes for Researchers?
Once the change takes effect, NIH states that BESH studies will no longer have to follow NIH clinical trial requirements, including:
- Registration in ClinicalTrials.gov
- Results reporting in ClinicalTrials.gov
That is one of the most direct impacts of the notice.
What Does Not Change
Even though BESH studies will no longer be considered clinical trials, NIH emphasizes that BESH research must still follow all other applicable clinical research requirements, including but not limited to:
NIH also states that currently funded BESH studies should continue following:
- Their existing Terms and Conditions of Award
- NIH Notice NOT-OD-25-134 (Flexibilities for Registration and Results Reporting of Prospective Basic Experimental Studies with Human Participants)
More Guidance and NOFO Updates Are Coming
NIH states that it will provide further guidance and examples to help researchers assess whether a study should be classified as BESH, a clinical trial, or an observational study involving humans. NIH is actively reviewing current instructions and system validations and will release detailed guidance in a forthcoming Guide Notice describing any necessary instruction or system updates to reflect this change.
In addition, NIH anticipates expiring all BESH-specific NOFOs for due dates on or after May 25, 2026. NIH explains this is because BESH research can now be accepted through the Clinical Trials Not Allowed companion versions of these NOFOs.
Bottom Line
NIH Notice NOT-OD-26-032 signals a major shift. BESH studies will no longer be classified as NIH clinical trials for applications submitted on or after May 25, 2026.
This means BESH studies will no longer be subject to NIH clinical trial requirements, such as ClinicalTrials.gov registration and reporting, while remaining subject to other applicable research regulations and NIH policies.
More guidance and examples are expected from NIH to help the community navigate this updated classification approach.
