Implementation of Changes for Basic Experimental Studies with Humans

Implementation of Changes for Basic Experimental Studies with Humans Notice Number: NOT-OD-26-067

Key Dates

Release Date: April 06, 2026

Related Announcements

NOT-OD-26-032 - Basic Experimental Studies With Humans (BESH) Will No Longer Be Considered Clinical Trials by the NIH

NOT-OD-25-134 - Flexibilities for Registration and Results Reporting of Prospective Basic Experimental Studies With Human Participants

NOT-OD-18-212 - Delayed Enforcement and Short-Term Flexibilities for Some Requirements Affecting Prospective Basic Science Studies Involving Human Participants

Issued by

NATIONAL INSTITUTES OF HEALTH (NIH)

Purpose

This Guide Notice provides implementation details to the extramural research community for applications and proposals including Basic Experimental Studies Involving Humans (BESH).

Background

NIH announced in NOT-OD-26-032 that it will no longer characterize BESH as clinical trials, effective for competing applications submitted for due dates on or after May 25, 2026. As a result, BESH will no longer be subject to NIH clinical trial requirements (e.g. registration and results reporting in ClinicalTrials.gov). BESH must continue to follow all other applicable laws, regulations, and policies (e.g., human subjects protections and the NIH Data Management and Sharing Policy).

Scope and Applicability

This notice applies to competing NIH grant applications submitted for due dates on or after May 25, 2026, and contract solicitations issued on or after that date.

For applications submitted for due dates on or before May 24, 2026, and contract solicitations issued prior to that date, BESH will continue to be treated as a clinical trial. Applicants and offerors should continue to follow the instructions and requirements in the Notice of Funding Opportunity (NOFO) or contract solicitation.

Currently funded BESH studies should continue to follow the established terms and conditions of their respective grant or contract award and guidance as noted in NOT-OD-25-134.

Key Changes

NIH is implementing the following changes for applications submitted for due dates on or after May 25, 2026, and contract solicitations issued on or after that date:

Choosing the Correct NOFO for an NIH Grant Application

NIH will no longer characterize BESH as clinical trials. Therefore, the appropriate NOFO designation depends on whether the application includes any separate study(ies) that meet the NIH definition of a clinical trial, as described below.

Clinical Trial Not Allowed NOFOs

Applications proposing BESH (and not proposing a separate NIH-defined clinical trial) may be submitted to Clinical Trial Not Allowed NOFOs, unless otherwise specified in the NOFO.

If the application includes one or more studies that meet the NIH definition of a clinical trial the application must be submitted to a NOFO that permits clinical trials.

Clinical Trial Optional NOFOs

Applications proposing BESH may continue to be submitted to Clinical Trial Optional NOFOs, unless otherwise specified in the NOFO.

Clinical Trial Required NOFOs

Applications proposing BESH may not be submitted to Clinical Trial Required NOFOs unless they are proposing a separate clinical trial. When attempting to submit an application without a clinical trial study record to these NOFOs, eRA system-enforced validations will generate an error that will stop the application from processing through to NIH.

Basic Experimental Studies with Humans Required NOFOs

NIH anticipates expiring all NOFOs designated as Basic Experimental Studies with Humans Required with application due dates on or after May 25, 2026. Applicants are encouraged to work with the scientific research contact listed in the NOFO to determine an alternate NOFO in Grants.gov.

Completing the PHS Human Subjects and Clinical Trials Information Form for NIH Grants and Contracts

Applicants/offerors should answer the PHS Human Subjects and Clinical Trials Information Form Clinical Trial Questionnaire (1.4) based on the proposed study design. NIH now considers a health-related biomedical or behavioral outcome as having the potential for the direct advancement of health.  NIH expects the typical response pattern for BESH to be:

1.4.a. Does the study involve human participants?  YES

1.4.b. Are the participants prospectively assigned to an intervention? YES

1.4.c. Is the study designed to evaluate the effect of the intervention on the participants?  YES

1.4.d. Is the effect being evaluated as a health-related biomedical or behavioral outcome?  NO

Applicants/offerors should not provide clinical trial-specific information for BESH study records (e.g., protocol synopsis and other clinical trial-specific fields) unless otherwise specified in the NOFO or contract solicitation. Applicants/offerors must continue to provide all other required human subjects information consistent with the instructions in the NIH Application Guide and NOFO or contract solicitation.

Notable changes between applications and proposals proposing BESH submitted on or before May 24, 2026 and on or after May 25, 2026:

| | Due Dates on or Before May 24, 2026 | Due Dates on or After May 25, 2026 |
| Appropriate NOFO Types for BESH-Only Applications | Submit to NOFO designated as BESH, Clinical Trial Required, or Clinical Trial Optional | Submit to NOFO designated as Clinical Trial Not Allowed or Clinical Trial Optional |
| Typical Responses to PHS Human Subjects and Clinical Trials Information Form Clinical Trial Questionnaire (1.4) | Yes/Yes/Yes/Yes | Yes/Yes/Yes/No |
| Other PHS Human Subjects and Clinical Trials Information Form Responses | Complete clinical trial-specific fields/attachments as instructed in the NOFO (e.g., protocol synopsis, dissemination plan) or contract solicitation. | Do not complete clinical trial-specific fields/attachments for BESH study records, unless otherwise required by the NOFO or contract solicitation. |
| Clinicaltrials.gov Registration and Reporting | Flexibilities apply as specified in NOT-OD-25-134 | Not required |
| Other Clinical-Trial Specific Requirements (e.g. GCP training, Data and Safety Monitoring) | Required as specified in the terms and conditions of the grant or contract award. | Not required unless otherwise specified in the NOFO or contract solicitation and/or terms and conditions of the grant or contract award.  Consult the ICO Data and Safety Monitoring webpage to verify Data and Safety Monitoring requirements. BESH must continue to follow all other applicable laws, regulations, and policies (e.g., Section 801 of Food and Drug Administration Amendments Act of 2007 (FDAAA 801), 45 CFR 46, and the NIH Data Management and Sharing Policy) |

Resources:

See the Clinical Trials/BESH/Observational Webpage for additional information, case studies, and tips for BESH investigators.

Inquiries

Please direct all inquiries to:

NIH Office of Policy for Extramural Research Administration (OPERA)
Division of Grants Policy
[email protected]

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