NIH All About Grants Podcast � Basic Experimental Studies with Humans (BESH)

>> From the National Institutes of Health, in Bethesda, Maryland, this is "All About Grants".

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>> Kosub: Hello, and welcome to another virtual edition of NIH's "All About Grants" podcast.� I'm your host, David Kosub, with the NIH's Office of Extramural Research. And today we'll be talking about a topic that's important to ensuring the stewardship, the transparency, the reproducibility of our clinical research, and that's Basic Experimental Studies in Humans or BESH, and we have with us Dr. Pam Kearney.� She directs the Division of Human Subjects Research within the Office of Extramural Research and is going to tell us everything we need to know about BESH.� So welcome to the show, Pam.

>> Kearney: Thanks, David.� Thanks for having me.

>> Kosub: Great.� So let's just jump right in.� What is BESH?

>> Kearney: BESH, B‑E‑S‑H, is Basic Experimental Study in Humans.� And a BESH is a type of study that meets both the definition of basic science and it is also an NIH‑defined clinical trial.� And basic science is a study that is aimed at understanding fundamental aspects of phenomenon or observable facts, and they don't have a specific application toward processes or products in mind.� In other words, they're not efficacy studies, et cetera. An NIH defined clinical trial has four parts: Number one, it has human subjects. Number two, those human subjects are prospectively assigned to one or more interventions. Number three, the study is designed to evaluate the effect of those interventions on the participants. And then Number four, the effects are health related by a medical or behavioral outcome.

>> Kosub: Great.� Thanks for that.� You kind of hit on some of these, but are there any other key characteristics that define what BESH studies are?

>> Kearney: Yeah, pretty much.� I mean, a BESH, as I mentioned, has the purpose of understanding a phenomenon without any sort of specific application towards a process or product.� And these studies, the interventions are often experimental manipulations, if you will.� And those ‑‑ they're using these experimental manipulations to understand a basic phenomenon. So they have an intervention and they're measuring effects, but they're just doing it for a different purpose.� And the intervention, or the experimental manipulation, isn't intended to change the health status of the participant in any way.

>> Kosub: I see.� I see.� So kind of give some general groundwork, some framework as to what BESH studies are, and what they may not be, do you have like a favorite example, like maybe one thing ‑‑ one example of like a real‑world BESH study that you can share?

>> Kearney: BESH studies are really diverse.� I can think of a couple of examples.� One example, which is a very classic type of BESH study, is a study that ‑‑ where the investigator is aiming to characterize the neural activation in the frontal cortex during response inhibition. This could be done as an FMRI study, where the healthy volunteers would be asked to undergo a go‑no‑go task during MRI.� And when you look at this one, obviously, they're human subjects.� In this case, the go‑no‑go task is the intervention; it's being used as a manipulation, and the effect of the go‑no‑go task on the neural activation in the frontal cortex is being measured, so you're measuring the effect of the intervention. And this phenomenon, the activation in the frontal cortex during response inhibition, is a health‑related biomedical outcome.� So this is a classic BESH.� There are others that we could talk about that's very diverse.

>> Great, thanks.� Actually, jumping back to the policy, are there ‑‑ like what are the requirements for BESH studies that, you know, maybe as it compares to a traditional clinical trial?

>> Kearney: Actually, David, there really are no different requirements for BESH compared to other traditional clinical trials, because they are clinical trials.� They have all the same requirements, for example, they're going to have to fill out all the clinical trial‑related parts of the application.� The studies are subject to Good Clinical Practice or GCP training requirements. These studies will have to post informed consent forms per the Common Rule Requirement to do so.� And they also have to register the study within 21 calendar days of the enrollment of the first participant.� And they also have to report the results no later than one year after the primary completion date.� So it's the same as all the other clinical trials.

>> Kosub: So jumping off that, if everything is the same, are there ‑‑ I guess, are there any flexibilities that BESH studies ‑‑ or BESH investigators are afforded?

>> Kearney: Yes.� Yes, there are, actually.� If a BESH investigator has responded to a BESH funding opportunity announcement, they will temporarily have the flexibility to do the registration and results reporting in a platform other than clinicaltrials.gov.� So they can use an alternative publicly‑available platform.� They don't have to use clinicaltrials.gov, like the other clinical trials will have to do. This flexibility runs through September 24 of 2023, and keep in mind, it's only available to those studies that have ‑‑ that were responsive to a BESH FOA. BESH can come in under any clinical trial FOA, they can come in under clinical trial required, clinical trial optional, but only those that use the BESH FOA can exercise this registration recording alternative. If an investigator chooses to exercise this option, they're going to want to describe it at the time of application in the dissemination plan attachment, and then in the annual progress report, they're going to provide the unique identifier signed by that alternative platform if it's available, and also a link to the report, like the page of the record in that alternative platform.

>> Kosub: I see.� I see.� So you mentioned some BESH Funding Opportunity Announcements.� I assume one can probably find a lot of these Funding Opportunity Announcements and all this other information on ‑‑ resources online.� Can you ‑‑ can you share some more about the resources that are made available to our investigators out there interested in doing BESH studies?

>> Kearney: Oh, yeah, yeah.� Actually, we're very excited about a ‑‑ our new BESH website.� People can find this website off of the grants and funding page.� This website was put together by a number of program officials within NIH that has BESH in their portfolio, so they really understand the BESH investigators, and some of them have done BESH research themself. This website goes over the definition of BESH.� It outlines the key characteristics of these studies.� And one thing I really, really like about this website is that it goes through the four clinical trial questions and answers them from a BESH investigator perspective. It also has a paragraph outlining the difference between intervention and measurement, which can be very sticky sometimes in BESH studies, because oftentimes the intervention in other studies could be used as a measurement.� So there's some confusion about is it a measurement? Is it being used as an intervention? And sometimes the same thing can be used as either one or the other.� So I really like that paragraph in the website. It also has information ‑‑ a lot of the information that we're talking about here.� It goes into the BESH funding opportunities.� It talks about the policy flexibilities.� And then it goes into some tips for BESH investigators.� And in addition, there are a couple of new BESH Clinical Trial Case studies that were added that you can find on that website as well.� I would encourage people to take a look.

>> Kosub: Oh, I do.� I encourage it as well.� You mentioned something that intrigues me about the four clinical trials answered in a BESH perspective.� I think that was your wording.� Can you tell us more about what that means?

>> Kearney: Yeah.� Yeah.� BESH, as we've been discussing, are not typical applied clinical trials.� So the intervention in these studies looks very different than one would expect in a classic clinical trial. And the website walks the reader through the thinking of those four clinical trial questions from a BESH‑eye view, if you will. For example, the website talks about how it's useful for BESH investigators to think of the intervention and BESH studies as the independent variable, which the investigators then change or control.� The intervention, or the independent variable, will have a direct effect on the participant which can be measured. In other words, it directly affects a dependent variable which is then tested and measured in the experiment.� This thinking I think resonates more with folks who do this type of research and helps one to kind of think about, you know, what an intervention would look like in a BESH study.

>> Kosub: Thanks for that.� This has been very helpful.� I always like to give the opportunity for a guest to leave with some final thoughts.� Are there any kind of brief comments you would like to share with our audience about BESH?

>> Kearney: Sure.� I would really strongly encourage BESH investigators to talk to a program official before they submit their application.� These folks are very knowledgeable.� They know the different funding opportunities.� And they can help guide you to determine which one of those would be best for your study. And if you're unsure of the right program official, NIH has a really cool tool called the Match Maker Tool which is off of Reporter, and it can help folks kind of match up program officials that have certain types of studies in their portfolio so that you can reach out to them. I'd also encourage folks to take a look at the BESH clinical trial case studies which are in the clinical trial case studies off of the funding website.� There's a filter there.� You can actually filter for BESH and pull up the BESH studies. And also, if you go on to the website, which I mentioned earlier, there's also a link to those BESH studies as well.� A direct link to them, so you don't have to use the filter; it's already pre‑filtered.� And I would encourage folks to consider using one of the BESH FOAs.

>> Kosub: Very cool.� Very cool.� Thank you very much, Pam, for this opportunity to hear more about BESH, and I strongly encourage folks to check out the new BESH website as well.� A wealth of information there.� And there's ways to contact us, if you have any questions, so please do not hesitate to reach out.� We're here to help.� This has been David Kosub with NIH's "All About Grants". Thank you very much.