On This Page:
- Definition of BESH
- Key Characteristics of BESH
- Answering the 4 Clinical Trial Questions for BESH
- Intervention vs. Measurement
- About BESH Funding Opportunities
- Policy Flexibilities for BESH Funding Opportunities
- Tips for BESH Investigators
All BESH meet the NIH definition of a clinical trial. But not all clinical trials are BESH.
Basic Experimental Studies involving Humans (BESH) are studies that fall within the NIH definition of a clinical trial and also meet the definition of basic research . Here are some key characteristics to help identify if your study fits within a BESH funding opportunity:
The study has the purpose of understanding fundamental aspects of phenomena without specific application towards processes or products in mind
We define “process or products” as the application of biomedical or behavioral products, procedures, or services intended to affect a health-related outcome either by better understanding the mechanism of action of an intervention or a measurable improvement in health. If the study does have specific applications toward processes or products in mind (e.g., Phase I drug or device study), then the application should be submitted under a clinical trial FOA, not a BESH FOA.
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)
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.
For more details, see Guidance for Determining if a Study Falls Within a BESH FOA
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.
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.
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.
A group of adolescents will participate in a longitudinal study examining changes in executive function over the course of a normal school year. Color naming performance on the standard version of the Stroop test will be obtained. All measures will be compared at multiple time points during the school year to examine changes in executive function. The purpose is to observe changes in executive function and to observe if differences exist in the Stroop effect over the course of the school year for these adolescents.
- Does the study involve human participants? Yes, adolescents will be enrolled in this study
- Are the participants prospectively assigned to an intervention? No, there is no intervention in this study and no independent variable manipulated. The adolescents are not prospectively assigned to an intervention, but instead the investigator will examine variables of interest (including the Stroop test) over time. The Stroop effect is used as a measurement of point-in-time data.
- Is the study designed to evaluate the effect of the intervention on the participants? N/A, there is no intervention. Performance on the Stroop test is a well-established measure of executive function and the test is not providing an independent variable of interest here. It is not being used to manipulate the participants or their environment. The purpose is simply to obtain a measure of executive function in adolescents over the course of the school year.
- Is the effect being evaluated a health-related biomedical or behavioral outcome? N/A. No effect of an intervention is being evaluated.
This study is not a BESH or a clinical trial.
A group of participants with social anxiety will perform an experimentally manipulated Stroop test. In this variant of the Stroop test, the stimuli presented are varied to include emotional and neutral facial expressions presented in different colors. Participants are instructed to name the colors of the faces presented, with the expectation that they will be slower to name the color of the emotional face than the neutral face. The purpose of the study is to examine the degree to which participants with social anxiety will be slower to process emotional faces than neutral faces.
- Does the study involve human participants? Yes, participants with social anxiety will be enrolled in this study.
- Are the participants prospectively assigned to an intervention? Yes, the participants will be prospectively assigned to perform a modified Stroop test using different colored emotional/neutral faces to explore emotional processing in people with social anxiety. Note that the independent variable is the presentation of emotional vs neutral faces.
- Is the study designed to evaluate the effect of the intervention on the participants? Yes, the study is designed to measure the effect of emotional valence (i.e. emotional faces) on participant response time to name the color. The purpose is to determine whether the response time to emotional faces is exaggerated for people with social anxiety as compared to neutral faces. Note that the response time to name the colors is the dependent variable in this study.
- Is the effect being evaluated a health-related biomedical or behavioral outcome? Yes, the processing of emotional information is a health-related biomedical outcome.
This study is a basic experimental study involving humans (BESH)
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.
NIH has issued a series of parent FOAs specifically designated as "Basic Experimental Studies with Humans Required" in the FOA title. Refer to our chart of FOA types by clinical trial allowability to determine what FOA 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 FOA and talk with a Program Officer to determine the most appropriate FOA for your application.
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, 2023.
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 FOA.
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 FOAs 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-21-088 for additional details.
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 announcement 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 FOAs: While BESH studies can be appropriately conducted under any “clinical trial required” or “clinical trial optional” FOA, the policy flexibilities for BESH studies are only applicable to BESH studies conducted under specific BESH FOAs. Therefore, it is recommended that BESH studies apply to BESH FOAs 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.