NIH All About Grants Podcast

Transcript: Human Subjects’ Research Protections and Monitoring Plans


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


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>> 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 having our second in a three‑part conversation on human subjects research.  As you may recall, in our first conversation we looked at how do you know you actually are doing human subjects research, and today we're focused on the applications, specifically the Human Subjects Protections and Monitoring Plan, and we have with us Dawn Corbett.  She is NIH's Inclusion Policy Officer, and will be happy to tell us everything we wanted to know about these areas.  Welcome to the show.


>> Corbett: Thanks, David.


>> Kosub: Sure.  So let's start with the basics.  What is the Human Subjects Protection and Monitoring Plan?


>> Corbett: The Human Subjects Protection and Monitoring Plans are part of an NIH Grant Application.  These plans are the section of the application where you describe how your research will involve human subjects, and discuss the study, risks and benefits, and any monitoring that will occur.


>> Kosub: And why are they important?


>> Corbett: Well, by regulation, NIH must evaluate all applications involving nonexempt human subjects research for four factors.  And these four factors that are in the regulation are risks to subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of knowledge to be gained. 


So at NIH we delegate this to peer review, and the peer reviewers assess how the section addresses each of these four factors.  And they consider if the involvement of participants is justified in terms of the scientific goals of the study and the research strategy proposed.  And they'll consider this assessment in the applications priority score.


>> Kosub:  So getting to the application itself, where might someone find these as part of the application?


>> Corbett:  This part of the application is founded in the PHS Human Subjects and Clinical Trials Information form.  This form was introduced a couple of years ago and it consolidates all of the Human Subjects Information in the grant application into one place. 


So it includes five sections, including inclusion enrollment information, clinical trial information, and the human subjects protection and monitoring plans can be found in section 3 of that form.


>> Kosub: And if I was putting together my application, what would you suggest I kind of spotlight or focus on while putting it together?


>> Corbett: Applicants that are proposing nonexempt human subjects research should make sure they adequately address each of those four factors that I mentioned before.  They should describe all potential risks to participants and their strategies to protect against risks and also discuss those risks in relation to the benefits of the study and the knowledge to be gained.  They should also describe how participants will be assigned to study groups.  Will folks be randomized or otherwise allocated to study groups, describe all procedures involving participants, where those procedures will be performed, how they will obtain any human material they may be using, such as cell samples or these kinds of things, and also describe who has links to any identifying information about participants.


And if there are vulnerable populations that are included in the study such as children or prisoners, you'll also want to include a justification for including those populations and describe any additional protections for those participants. 


And then finally, if you're doing research that is exempt from the regulation, then you'll need to provide a justification for that exemption in this section.


>> Kosub: I'd like to focus on the risks you mentioned in your last answer.  And what are the risks to the subjects that should be addressed?


>> Corbett: Any risks that are related to the study participation, including risks from all of the study interventions that are in their proposed research, and also considering not only physical risks, but also potential risks such as psychological, social, cultural, and financial or legal risks to the participants.  And you also want to consider risks to participant privacy or confidentiality.


>> Kosub:  How would we know that the risks are adequately addressed in an application?


>> Corbett: NIH peer review evaluates the plan to understand how the study team intends to minimize or mitigate risks.  So, for example, they're going to look at the methods for obtaining informed consent from the participants.  They will look at how you're protecting the privacy of the participants and their data.  And also, how you address incidental findings.  And they will consider all of that information in their evaluation of the application.  When appropriate, they'll look to see how the applicant will ensure necessary medical professional or medical intervention in the event of an adverse effect on the participant.


>> Kosub: I see.  I see.  So on the flip side, the benefit, can you talk a little bit about that? You mentioned benefits earlier as one of the core criteria.


>> Corbett: That's right.  So the applicant needs to address the potential benefit of the research, and to the participants, and also to other groups such as persons with a similar condition.  And this should be justified and explained why the risk is reasonable in relation to the anticipated benefits of the study.  Applicants should not list financial compensation in this section.  It's a common mistake that folks may make.  This is not considered a study benefit.


>> Kosub: And jumping back, also you mentioned the importance of the knowledge to be gained as one of those core criteria.  Is there anything else you would like to mention on that?


>> Corbett: The applicant should provide a justification explaining why the risks to the participants are reasonable in relation to the importance of the knowledge that's going to be gained in their proposed research.


>> Kosub: I see.  So jumping to something slightly different, so are there any differences if someone was proposing, say, a clinical trial in their application, versus clinical research more generally?


>> Corbett: Yes, clinical trials are going to require some additional information, so if you're proposing a clinical trial, you'll also need to include a data safety and monitoring plan, and indicate whether a data safety and monitoring board will be appointed.  The data and safety monitoring plan should be commensurate with the risk, the size and the complexity of the trial.  And the plan's going to specify who will provide the monitoring for the trial and provide some details such as the frequency of that monitoring and processes for adverse event reporting for example. 


One thing to note is that you may need to provide a data and safety monitoring plan even if you're not proposing a trial, so make sure you're familiar with IC requirements.  And then some trials such as multi‑site trials and NIH defined Phase III trials also require a data and safety monitoring board be appointed, and the applicant will specify this in Section 3.


>> Kosub: So throughout, you've been talking about what you should be thinking about putting in there.  I'm pretty sure you've seen some other things that have been included in an application that probably shouldn't be, like what kind of pitfalls have you noticed, I guess is what I'm trying to get at, that you can help someone correct?


>> Corbett: A common mistake that we find in applications is that the applicant fails to describe the potential risks of all interventions, so for example, if a study involves a focus group, a blood draw, and administration of study medication, the applicant may just describe the risks associated with the administration of The medication, but not address the risks of the blood draw to focus groups.  So it's important to make sure that you address the risks of all study interventions and also risks such as participant confidentiality and those data. 


Another common pitfall is failure to address incidental findings.  So, for example, if you're going to be doing an FMRI on participants and you find a brain tumor, what are you going to do? Are you going to communicate that to the participant? Who is going to be communicating that? What kind of expertise do they have? So you need to have a plan for that. 


And then another pitfall is failure to provide sufficient detail or clarity, so you'll want to avoid vague terminology such as, you know, claiming, you know, data or participants are deidentified or anonymized, you want to explain the details of that, so that peer review and NIH staff understand exactly how  you're going to be interacting with participants and their data.


>> Kosub:  If peer review came across any of these sorts of pitfalls, mistakes, what have you, would that cause the application to be poorly or not funded?


>> Corbett: Yes, it could, if the section is not adequately addressed.  The Protection of Human Subjects Plan and the Data and Safety Monitoring Plans are considered in the priority score of the application.  So an application that receives a poor score may not be funded.


>> Kosub: I see.  Would someone have the opportunity to address the concerns that may be arising during peer review?


>> Corbett: Applicants should really make sure that they include complete information in the application at the time of submission.  Peer review has concerns about involvement and the application will be funded.  The applicants may need to resolve any issues that are found with their IRB.  Every NIH study will require approval by the IRB.  So they need to be satisfied with the Human Subjects Protections before award.


>> Kosub: Wonderful.  This is the opportunity at the end of the conversation, I always like to give the guests a chance to kind of bring back an important point.  Is there anything that you would like to leave our audience regarding these portions of the application?


>> Corbett: When you're developing the protection of human subjects section, clarity and detail are really important.  Peer review and NIH staff should understand exactly the procedures in which participants will be involved, and that you've anticipated all risks and have plans to address them.  And if you have any questions, feel free to ask.  Your program officer and other NIH staff are here and available to help.


>> Kosub: Wonderful.  Thank you very much, Dawn.  Greatly appreciate this opportunity to hear more about the human subjects protections and monitoring plans part of an application.  We look forward to having everyone join us for our final conversation related to what we should do if you get the award.  This has been David Kosub with NIH's "All About Grants".  Thank you.