Basic Experimental Studies Involving Humans (BESH)

Basic Research
A systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena and of observable facts without specific applications towards processes or products in mind. (32 CFR 272.3)

Clinical Trial
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.

The study uses an experimental manipulation/intervention to understand a basic phenomenon
Basic research uses a range of probes or experimental manipulations to perturb a physiological process (including cognitive and perceptual processes) . Under the NIH definition of a clinical trial, most experimental manipulations involving humans are considered to be interventions.

The intervention/experimental manipulation is not intended to change the health status of the participants 
The NIH definition of clinical trial defines intervention as “ a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.”

This definition is not limited to manipulations that improve health-related endpoints in a long-term fashion. Many experimental manipulations are considered to be interventions even if the manipulation is being used to study the normal function of a physiological system and the effects are short-lived, reversible, and/or benign.

Answering the 4 Clinical Trial Questions for BESH

There are 4 key questions that determine if a study meets the NIH definition of a clinical trial. Here are some specific things to consider when answering these questions in the context of basic research studies.

1. Does the study involve human participants? 

By definition, BESH involve human participants. According to 45 CFR 46 , a human subject is a living individual about whom an investigator (whether professional or student) conducting research:

• Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or
• Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.

For further information about whether your study qualifies as human subjects research, see 45 CFR 46 .

2.  Are the participants prospectively assigned to an intervention?

Prospective assignment is not limited to random assignment to a manipulation or condition. “Prospectively assigned” means the experimental manipulation (intervention) is assigned per a predefined protocol. The method of prospective assignment also does not matter. Neither does the number of conditions.

For more about interventions, see question #3 below.

For BESH, the “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. Interventions are manipulations of the subject or the subject’s environment that are performed for research purposes. For BESH, interventions include a wide range of probes, tasks, or other procedures to control, isolate, and/or manipulate a study variable (typically the independent variable).

For example, evaluating the effect of the intervention on the participants in BESH often takes the form of observing the effect of the manipulation on a physiological, psychological, or social process (including cognitive and perceptual processes).

It is useful for BESH investigators to think of an experimental intervention as an independent variable, which the investigator changes or controls. The intervention (ie, independent variable) will have a direct effect on a participant which can be measured (i.e., directly effects a dependent variable which is tested and measured in an experiment). In contrast to BESH, researchers conducting observational studies do not control an independent variable. They observe and measure variables of interest (in some cases, over time) and look for relationships between them. The variables are measured, but not manipulated.

For help distinguishing an intervention vs. a measurement, see below.

Intervention vs. Measurement

It is possible that the same specific task or test could represent either an “intervention” or a “measurement” depending on how it is used, what is being measured, and why. Because of this, there cannot be a list of tests that are always measurements, or always interventions. 

If the task or test is being used to purposefully change or manipulate something about the participant and is being used to explore a concept – the task or test is probably an intervention. Think of the intervention as the independent variable in a study.

The two cases below use the Stroop Effect, an established measure of executive function in which a person’s response time to name the color of a words presented is measured. In the standard version of  the task, the colors of words presented can be the same or different from the meaning of the word itself.  The Stroop Effect is the slowing in color naming time for incongruent word presentations. Sometimes investigators modify the design, for example to study the effect of emotional content of the words (i.e. the independent variable) on the Stroop Effect.  As such, depending on how the Stroop task is employed, it may or may not be considered an intervention. 

As these examples show, the context of how a task is used is important in determining whether it is being used as an intervention or a measurement.

About BESH Funding Opportunities

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NIH has issued a series of parent funding opportunities specifically designated as "Basic Experimental Studies with Humans Required" in the funding opportunity's title. Refer to our chart of funding opportunity types by clinical trial allowability to determine what funding opportunity may fit you best.

Participation in BESH funding opportunities will vary by NIH Institute and Center (IC). Be sure to check the participating organizations section of the funding opportunity and talk with a Program Officer to determine the most appropriate funding opportunity for your application.

Policy Flexibilities for BESH Funding Opportunities

BESH studies are subject to the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information. However, NIH recognizes that registering and reporting results in ClinicalTrials.gov may pose a challenge for some types of BESH. To allow the necessary time to fully understand the challenges for dissemination of information about BESH, NIH has delayed the enforcement for ClinicalTrials.gov registration and results reporting through September 24, 2024.

This delayed enforcement is only applicable to BESH studies submitted to funding opportunities designated as “basic experimental studies with humans” in the title. It does not apply to applications submitted under a clinical trials required or clinical trials optional funding opportunity.

During this period of delayed enforcement, NIH continues to expect registration and results reporting for studies submitted to BESH funding opportunities, but with the additional flexibility to register and report results on alternative publicly available platforms.

Plans for meeting the NIH reporting expectations using an alternative platform should be described at the time of application in the Dissemination Plan attachment. Funded awardees for applications submitted to BESH-specific funding opportunities who are not using ClinicalTrials.gov to meet the policy expectation should provide in their annual progress reports the unique identifier assigned by the alternative platform, if available, and a link to the report (e.g., page or record) in the alternative platform

NIH also continues to expect Good Clinical Practice (GCP) training for all personnel involved in the conduct, oversight, or management of Basic Experimental Studies involving Humans (BESH). Additionally, all such applications continue to require completion of the full PHS Human Subjects and Clinical Trials Information form, and will be evaluated using the clinical trial review criteria.

See NOT-OD-22-205 for additional details.

Tips for BESH Investigators

Talk to a Program Official: All applicants are strongly encouraged to talk with a Program Official before submitting an application. Program Officials can help determine the right funding opportunity for your specific research. If you are unsure who the right Program Official is, try out our Matchmaker Tool!

Review BESH Case Studies: Check out the BESH case studies  to help understand what type of studies meet the criteria for a BESH funding opportunity.

Consider the Funding Opportunities: While BESH studies can be appropriately conducted under any “clinical trial required” or “clinical trial optional” funding opportunity, the policy flexibilities for BESH studies are only applicable to BESH studies conducted under specific BESH funding opportunities. Therefore, it is recommended that BESH studies apply to BESH funding opportunities when feasible.

Get to know the Human Subjects & Clinical Trial Information Form: Take a video tour of the application form to familiarize yourself with how this information is collected.