Announcer: From the National Institutes of Health in Bethesda, Maryland this is All About Grants.
Megan: Welcome to another edition of All About Grants. This is Megan Columbus from the National Institutes of Health Office of Extramural Research. Today we’ll be talking about addressing human subject research in your NIH grant application. I have with me Maria Stagnitto and Dr. Ann Hardy from the NIH Office of Extramural Research. Maria and Ann are Human Research Protection Officers here at the NIH. They help ensure that grants that NIH fund provide appropriate protections to research participants. How about if we start today with talking about what types of research NIH actually considers to be human subjects research. Could you address that Maria?
Maria: Sure, We actually need to start a little bit before that because we follow the regulations from Health & Human Services. And it has a fancy name: it’s 45CFR46, which stands for Code of Federal Regulations. And that’s the regulations we have to follow. Here at NIH we then take that information and have put information into our guide notices and into our applications regarding human subjects and what needs to be included in it.
Megan: It seems like it would be obvious what’s a human subject in a grant application, but what about when you get to things like autopsy specimens or coded data received from a researcher’s ongoing clinical trial?
Maria: It is very confusing, and we do spend time reviewing grants, so it’s okay if people are a little bit confused. But a human subject is a living individual about whom an investigator, and it can be a professional investigator or it can be a student, is conducting research. If they’re obtaining data through intervention or interaction with the individual, or if they’re obtaining identifiable private information, it’s considered a human subject.
Ann: So to answer your specific questions. So, if you’re doing research with autopsy specimens, because those aren’t coming from living individuals, it’s not going to meet the definition of human subjects research. There may be state and local laws that would apply, but as far as NIH and federal regulations are concerned that would not be considered human subjects research. Using specimens that were collected for another reason is going to depend on that second part of the definition, whether it’s identifiable. So it’s going to depends on whether the researchers doing research on those existing specimens have access to identifiers.
Maria: The Office of Human Research Protection, which you will hear called OHRP, has decision trees, and very specific guidance for you to follow.
Megan: And the NIH application guide provides a link to that decision tree?
Maria: Yes it does.
Megan: So I hear a lot about research being exempt or considered exempt. What exactly does that mean?
Ann: Well, the regulations outline certain types of research that does meet that basic definition that we just went over, but is so low risk that they have decided to make it exempt from having to follow all the regulations. So the types of things/activities that are considered exempt would be studies in educational settings of different approaches to teaching, is one thing that’s exempt. Studies of taste in food quality would be considered exempt. Studies that only involve observation of public behavior or doing interviews or surveys, in some instances, may be considered exempt.
Maria: Now even within that, some of them do not apply to children. So you need to make sure you’re referring back to the 45CFR46 that I mentioned earlier, and the subpart that talks about children. They might look at the exemptions and say, “Okay, great, my research, my grant is exempt,” but if they’re studying children it might not be exempt. So that’s one thing we run into a lot.
Ann: This is Ann. Let me add done other point that most of the IRBs at the institutions where the investigators are have people who are very familiar with the exemptions and can help the investigators determine whether it is exempt. So if someone is doing an application and thinks the research may be exempt but isn’t sure, they probably have some resources right within their institution.
Megan: Talking about institutional review boards, can you tell us briefly how the NIH review process differs from what the institutional review boards look at when they review the grant application?
Ann: Yes. A couple things to keep in mind. The NIH review process is going to focus on scientific and technical merit and part of that is going to include, for the applications that are proposing human subjects research, looking at what the investigators have outlined in their application about how they’re going to protect human subjects. We ask the peer reviewers to do that as part of their review for scientific and technical merit. However, on top of that, each of the institutions have to have institutional review boards that are going to look at the protocols in detail, look at the consent forms in detail, factor in local requirements, local issues.
Megan: How should an applicant put together the human subject section of the grant application? Do you have specific tips for actually writing the application that might be useful?
Ann: I think what’s important is for the investigators to have some awareness of what’s required in the human subject section, make sure they allow enough time to do it. I think a lot of times the focus is on the research plan and putting all that together, but just making sure they allow enough time to adequately address all these issues in their grant because again the reviewers are going to factor this in to their overall evaluation of it.
Megan: Is there a page limit for the human subjects section of the application?
Ann: No, the human subjects section does not have a page limitation, so that particularly in cases of very complex or risky research that the investigators proposed approach to all of those issues can be laid out well. Let me also mention that for research that doesn’t meet the definition of human subjects, but involves the use of human specimens or human-level data, should be clear in the application why that research does not meet the definition of human subjects. As I said, this often depends on whether the specimens or data are identifiable, and if there’s nowhere in the application where that is stated, but it’s clear that human specimens are going to be used or it’s not clear how they’re being obtained, that’s going to be a problem for the reviewer.
Maria: Ann already said it but there is no page limit and make it as long as you need to so that your reader understands what you’re doing, how you’re protecting people or how you’re protecting the information, privacy.
Megan: At the same time, I could imagine that you have reviewers who are busy who need to get through the applications. And so while there is no page limits, I can imagine that being careful how you put together the information so it’s not just a laundry list, but it’s synthesized into a coherent story would be important.
Ann: Yes, I think that’s true for any part of the application. I think we force that issue a little bit more in the research plan perhaps because it’s limited in pages, but yes if you follow the instructions and all the information required and stick to that, it should outline again a nice protection of who’s involved, what are we doing to them, what are we collecting, what are the risks from that, and what is the researcher doing to reduce those risks as much as possible. So again, we leave space, but it should move as concisely as possible through all this.
Megan: What about clinical trials, are there any special requirements if this is going to be research involving clinical trials?
Ann: Yes, there are. NIH has a few additional requirements for the application for those cases. First, let me start off with a definition of clinical trial. And NIH considers a study to involve a clinical trial if it includes prospective research designed to answer questions about biomedical or behavioral interventions. That would be considered a clinical trial. And if an application is proposing a clinical trial it should also address data safety monitoring – how they’re going to monitor the safety of subjects in that trial. And in some cases, if it’s a multi-site trial or it’s greater than minimal risk, or if what we call a phase III clinical trial, it’s also going to have to address having a data safety monitoring board, an independent group that’s going to help oversee the monitoring for that trial. Another requirement for applications that are proposing human subjects research is that they also address inclusion of women, children and minorities and include what we call a targeted enrollment table to show what the numbers they projects to enroll in those demographic categories.
Megan: In fact, we’ll be having another podcast to follow this along in another couple of weeks on that topic, and so listeners can look forward to that, as well.
Megan: Once NIH thinks it’s likely to fund an application that involves human subjects research, is there other information that the applicant is going to have to provide just-in-time for award?
Ann: Yes, there are a few things that are going to be required that are not required at the application stage, but are going to be required at the just-in-time process before the grants are awarded. One is they’re going to have to show that they have appropriate assurance, what we call federal-wide assurance with OHRP, the Office of Human Research Protection that Maria mentioned, that is really responsible for compliance with federal regulations for human subjects protection and research. So the institution is going to have to show that they have that. They are going to have to get their institutional review board, their IRB to approve it, they’re going to have to document that that was done. They’re going to have to document that each of the key personnel involved in the research have gotten or taken appropriate human subjects education.
Megan: That’s actually probably an important thing to mention because we do have an online education component that can be used for that.
Maria: Yes, we have the Protecting Research Participants in English, and we have it in Spanish, as well. And I would recommend you, if you haven’t watched it, to participate.
Megan: In summary, identify early in the application process whether you will be using human subjects, engage your institution and your IRB as needed, and then read and follow the application instructions thoroughly to prepare the best possible human subjects section of your application. For NIH and OER, this is Megan Columbus.
Announcer: For regulations, policies, guidance and training, click on “Research Involving Human Subjects” on the OER homepage at grants.nih.gov. For information on obtaining an institutional assurance, visit the OHRP homepage at www.hhs.gov/ohrp.