NIH All About Grants Podcast: Transcript

Am I Doing Human Subjects’ Research


>> Kosub:  Hello, and welcome to another 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're going to have the first of three conversations to help our investigators better understand how do we know you are actually doing Human Subjects Research.  And we have with us, Lyndi Lahl.  She is a Human Subjects Officer in the NIH's Office of Extramural Research, and I welcome you to the program. 


So to provide kind of a framework to this discussion, we're going to be talking about Human Subjects Research as it's defined in The Common Rule, and we'll jump into that ‑‑ a little bit of that later, but that's kind of the overarching assumption that we're working with today. 


So Lindy, can you start us off, just tell us a bit about what is human subjects’ research?


>> Lahl:  Yes, so I'm going to go from the standpoint that we know the activity is research and we're questioning whether or not human subjects are involved.  So the regulations provide a definition of human subjects, and that is a living individual about whom an investigator obtains either information or specimens through intervention or interaction with someone, and uses, studies or analyzes that information or specimen, or they obtain, use, study or analyze or generate identifiable private information or identifiable biospecimens.


>> Kosub:  Well, thanks for that.  Why is it important for me to know if I'm actually doing human subjects’ research?


>> Lahl:  Well, I would want an investigator to know that they're doing Human Subjects Research because I would want them to be conducting that research in accordance with ethical principles that were identified in the Belmont Report.  And those ‑‑ there's three principles.  One is respect for persons.  One is beneficence.  And one is justice. 


It's also important, not just the ethical reasons, but it's also so they can be compliant with the regulations, and those regulations are ‑‑ we'll talk about those a little bit more later.


>> Kosub:  Great.  And I raised it at the beginning, The Common Rule.  Can you tell us how this all fits in with The Common Rule?


>> Lahl:  Yeah.  So the Common Rule is called the Federal Policy for the Protection of Human Subjects, and it's the basic protections that need to be followed when an institution receives support for human subjects research from one of the Common Rule agencies.  There happen to be 20 different federal departments and agencies that have signed on to be part of The Common Rule. Those include entities like the Department of Homeland Security, Department of Defense, Department of Veterans Affairs, along with the Department of Health and Human Services. 


Now, The Common Rule was actually updated in 2017, and the updated regulations are known as The Revised Common Rule.  So the reason it's important for an investigator that's doing NIH‑supported or funded research is because NIH is an agency under HHS, so any time they're doing Human Subjects Research with HHS money, they would need to follow the HHS regulations at 45CFR46.


>> Kosub:  Great.  So let's jump into some of the process kind of questions.  Are there any resources that we can share with our listeners to help determine if they're doing Human Subjects Research?


>> Lahl:  Yeah, actually NIH and OHRP, who is the regulatory agency that makes sure people are in compliance with the HHS regulations, both have resources to help guide an investigator and their reviewing IRB to determine if the activity that's being proposed involves human subjects and is research.  So NIH has a decision tool called "am I doing human subjects research", and NIH also has two different infographs, one that's called "Human Subjects Research", and the other is called "Exempt Human Subjects Research". OHRP also has a lot of resources, and the one that would be relevant for this is the Human Subjects Regulations Decision Charts.


>> Kosub:  Just for clarification for our audience, OHRP, is HHS Office of Human Research Protections, and IRB is Institutional Review Boards, just to kind of spell out the acronyms. 


So along the lines of that tool, can we jump into kind of get a better understanding of when ‑‑ or what might be considered Human Subjects Research.  Let's say I had some blood or tissue samples that were from a previous experiment or previous study that are not directly involved with my current research project. Does that fit?


>> Lahl:  Oh, good question.  That is generally called secondary research.  It's when an investigator is doing research on information or specimens that were collected for another purpose.  So there's a lot of considerations when an investigator is going to be working with previously‑collected biospecimens such as what conditions were the samples obtained, have they been anonymized, meaning that there's no way you can see who is who, deidentified; or coded, meaning that original sample that had somebody's name and birth date has been anonymized so the samples are A, B or C; or will they have full identifiers. 


If the samples are coded, does the investigator or anyone on the research team have a key to the code, which would allow the investigator to identify who individual participants are?


And if the specimens were obtained under a different research study, did the informed consent from that other research study disclose plans for new research activities?


In other words, did the participant give permission for new research activities on that specimen that was going to be banked and used for something else?


And I also want to note that in general, the reviewing IRB or the institution is going to determine if that specimen activity involves human subjects research or if the human subjects research activity with the biospecimen is exempt from the regulation, or if it's not human subjects research at all.


>> Kosub:  All right.  Well, let's build further on this.  What if a sample came from deceased person? Is that considered human subjects’ research?


>> Lahl:  Well, no.  And as you might recall, I talked about the definition of human subjects a few minutes ago, and it's qualified by having the individual being a living person.  So under the regulation, a deceased individual would not be considered human subjects; however, there may be some other regulations that would apply to this research.


>> Kosub:  One more example, what about for epidemiological studies?


>> Lahl:  Well, in general, yes, epidemiology studies would be conducted using human populations to evaluate the distribution of disease and the factors that affect health, so, yes, they would generally be human subjects research.


>> Kosub:  All right, great, wonderful.  Kind of moving on to a slightly different part.  What if I'm putting together my project, I have my application already to go, but I accidentally don't recognize it as human subjects when it actually does involve them?


>> Lahl:  Well, if an applicant does not identify their project as including human subjects, then they are not going to include information that the reviewer is going to need, and unfortunately, this may result in poor scores and award delays.


>> Kosub:  So ‑‑ are there any other requirements that we should be thinking about?


>> Lahl:  Well, there's a lot of other requirements if an investigator is conducting Human Subjects Research.  And let me talk about four of these.  So the first one would be if the investigator is doing Human Subjects Research, that means that their institution is engaged in research and is going to need a federal-wide assurance, or FWA is what it's called for short.  And then secondly, the awardee, which the institution, will need to certify that the nonexempt Human Subjects Research was approved by the IRB.  Third, investigators and all key personnel ‑‑ and those would be people who are involved in the design of the conduct of NIH‑funded Human Subjects Research ‑‑ will need to fulfill an education requirement on human subjects, and then this would also be relevant if there is a new staff member that joins after the NIH award is made.  They would also need to do that education. And then fourth, I want to mention inclusion, so inclusion of children, women, and minorities needs to be adequate, and they'll need to track that.


>> Kosub:  So, I think you just mentioned nonexempt Human Subjects Research.  Can you give examples of what might be exempted?


>> Lahl:  Yeah, so there is research that is considered exempt.  The regulations actually have eight categories of research that have been identified as exempt research, and that could be anything from secondary research to research involving normal educational practices.  And the important things to know about exempt research are: The institution does not need a federal-wide assurance. 


There's no certification of IRB review required, since you don't have to have IRB review for exempt human subjects research, but the investigator will still need to do the inclusion tracking for all exempt research except for research which involves Exemption Category 4, and that is the secondary use of biospecimens or data.


>> Kosub:  Can the investigator make the decision on what is exempt?


>> Lahl:  Well, it's really interesting, because the regulations don't actually identify who should be making this determination, but in general, I would say the institution, or the IRB will have this responsibility to make the determination of whether or not something is exempt.  It should not be the investigator because the investigator is considered to have a potential conflict of interest.


>> Kosub:  And I guess one more point of clarification.  You were mentioning institutions that were engaged in research.  Can you clarify or discuss that a little bit further?


>> Lahl:  Sure.  So engagement is actually a term that is found in the regulations, and it says that each institution engaged in research that's covered by this policy ‑‑ and it goes on and on and on, saying that it will comply with the requirements of this policy, and it's going ‑‑ and that the institution will provide written assurance.  So I had mentioned the federal-wide assurance earlier, and that would be the written assurance that an engaged institution would have to provide to OHRP. 


So depending on what the institution's involvement is in the research, the institution may or may not be engaged, so if an institution's employees are obtaining data about the participant through intervention or interaction, if they're obtaining identifiable private information about the research participant, or obtaining informed consent from the participant, they would be found to be engaged in research.  It would need that federal-wide assurance.


>> Kosub:  Great, great, great.  So this is an opportunity before we close out that I always like to give our guests an opportunity to talk a little bit further, raise some important issues about the topic.  Are there any final thoughts you would like to leave with the audience about understanding Human Subjects Research?


>> Lahl: So this is not always a cut and dry, easy thing to figure out.  There's a lot of gray area, but know that there are a lot of resources available to investigators and institutions including personnel, a program officer, NIH, OHRP, that they are not alone, and certainly their IRB as well within their institution.


>> Kosub:  Great.  Wonderful.  Thank you, Lindy, for joining us virtually today, discussing our first in a series of three discussions on how do I know I'm doing Human Subjects Research.  And to reiterate one of the points she just raised, please be sure to check out the NIH grant sites on Human Subjects Research.  You will find information there, as well as the HHS Office of Human Research Protections, and don't hesitate to reach out to your program officials or here at the Office of Extramural Research for additional information.  And we look forward to having you joining us with future conversations on this topic where we'll actually be focused a lot more on the applications in our second conversation and the award in the third conversation. This has been David Kosub with the NIH's Office of Extramural Research.  Thank you very much.