On January 29, the National Institutes of Health (NIH) issued a notice of great interest to and relief for behavioral and brain scientists: Basic Experimental Studies in Humans (BESH) Will No Longer Be Considered Clinical Trials by the NIH (NOT-OD-26-032). This announcement follows years of advocacy, education, and ongoing efforts to reduce administrative burden.
Back in 2014, in an effort to increase transparency, accountability, and precision in tracking research, the NIH revised its definition of clinical trials. The new, expanded definition — 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 — suddenly included basic behavioral and brain sciences. The expanded definition triggered serious challenges for FABBS scientists trying to comply with related registration and reporting requirements designed for clinical trials as defined by Section 801 of the Food and Drug Administration Amendments Act.
To address the unintended consequences, NIH created a new classification Basic Experimental Studies Involving Humans (BESH). However, this was an imperfect solution that led to considerable confusion and inconsistencies across NIH institutes.
According to the announcement, “NIH now considers a health-related biomedical or behavioral outcome as having the potential for direct advancement of health. Although BESH research, which produces fundamental information about biology or behavior, might eventually inform advances in health, it is not conducted with the express intent of changing clinical practice or health but rather aims to understand fundamental aspects of phenomena without immediate clinical applications.”
This change is effective for applications submitted to due dates on or after May 25, 2026.
Currently funded BESH studies should follow their established Terms and Conditions of Award as well as NOT-OD-25-134 (Flexibilities for Registration and Results Reporting of Prospective Basic Experimental Studies with Human Participants).
Going forward, BESH researchers will not need to follow requirements for clinical trials, including registration and reporting in ClinicalTrials.gov. BESH researchers must continue to follow all other applicable clinical research laws, regulations, and policies, including, but not limited to, human subjects protections and the NIH Data Management and Sharing Policy. Accordingly, BESH researchers now can respond to Notices of Funding Opportunities (NOFOs) labeled “Clinical Trials Not Allowed.” NIH anticipates terminating all BESH-specific NOFOs for due dates on or after May 25, 2026.
Our argument has been that preregistration and prompt reporting of results are excellent goals for all research, not just human subject research. The problem was that trying to insert the round peg of discovery science into the square hole of classical clinical trial reporting was just never going to be a good fit. We are glad the NIH has come around to that conclusion.
Jeremy M. Wolfe, PhD, Past President of FABBS
See previous FABBS coverage below:
NIH Indefinitely Extends Reporting Flexibilities for BESH ( July 2025)
NIH Extends Registration Flexibility for Clinical Trials (March 2021)
NIH Taking Steps to Build a Better System for BESH Registration and Reporting (December 2020)
Clinical Trial Definition Continues to Cause Confusion (February 2020)
See other reporting:
NIH redefines ‘clinical trials,’ dividing researchers (Stat News)
NIH scraps policy that classified basic research in people as clinical trials (The Transmitter)
NIH rolls back red tape on some experiments — spurring excitement and concern (Nature)
