On April 28, the Office of Extramural Research (OER) released a new webpage that provides additional guidance to investigators conducting Basic Experimental Studies with Humans (BESH). The NIH definition of a clinical trial includes basic research manipulating an independent variable, resulting in some basic research studies being subject to NIH clinical trials policies.
Based on prior feedback from the research community, NIH provided temporary leniency to basic research applications subject to the clinical trials policies to allow flexibility on the platform used for registration and results reporting and on applications submitted to an incorrect FOA based on the study-type designation (NOT-OD-18-212). Soon after this notice, the NIH issued parent FOAs on Basic Experimental Studies With Humans (e.g., PA-19-091), and only submissions to these BESH FOAs have the continued registration and reporting leniency that now extends through September 24, 2023 (NOT-OD-21-088).
When the temporary leniency for application submitted to an incorrect FOA based on study-type designation ended in 2019, a number of grant applications submitted under Clinical Trials Not Allowed FOAs were determined to be BESH applications, indicating continued confusion regarding the distinction between basic studies that are not clinical trials and basic studies that are also clinical trials (BESH). To address this confusion, OER met with a number of NIH program officers with BESH portfolios and worked intensively with a subgroup of them over the past year to provide greater clarity about what is or is not a BESH study, culminating in this recently released webpage and revised case studies.
Much of the confusion stemmed from the term “intervention” in the NIH clinical trials definition. While some research fields narrowly define “intervention” to mean an applied treatment while other entities, such as the Office of Human Research Protections (OHRP), define “intervention” broadly to include essentially anything done to a research participant by the investigator. To clarify this term for NIH BESH, the new website makes clear that a BESH intervention “is often an experimental manipulation being used as a probe to understand a basic phenomenon, process, or the mechanism of action of the manipulation.” The only human studies that are appropriate for a Clinical Trials Not Allowed FOA are those studies in which an independent variable is not manipulated based on study protocol. If your study involves manipulating, controlling, or isolating an independent variable, then it is a clinical trial, and if that manipulation is not intended to change the health status of the research participants but instead to understand a basic phenomenon, process, or mechanism of action, then it is also a BESH.
The new website also provides information on the distinction between “measurement” and “intervention”. Many measurement approaches involve a within-subject manipulation. Examples include measuring orthostatic hypotension by assessing blood pressure sitting and standing, measuring implicit associations by assessing reaction times to various word pairing tasks, or measuring response inhibition via a Flanker Task. Such measurements can be part of an observational study and not be considered BESH provided that their purpose is not to manipulate the independent variable of the study.
NIH continues to work on meeting the goals of these policies while adapting them to the needs of specific research approaches. Clinicaltrials.gov continues to study how to address the unique needs of some BESH studies for registration and results reporting, and while NIH encourages all clinical trials studies to register and results report in clinicaltrials.gov, leniency of BESH studies to use an alternative registration and reporting platform continues through September 24, 2023.
We have benefited from the feedback of the research community as we work toward the shared goal of greater research transparency, and we welcome feedback to continue to improve the clarity of the new BESH webpage and revised case examples.