Hello, this is Toby Chai. I'm a professor of urology and the vice chair of research in the Department of Urology at Yale University School of Medicine. Today I want to talk about a certain part of your grant application facilities, resources section as well as human subjects and consortiums and subcontracts. Also we'll touch about preliminary data, timeline and budget. Let's go to the next slide. Why is it not advanced? There we go. So the facilities and resources portion of your grant basically entails you telling the grant reviewers what you have available to do the proposed project you have in the grant. And I think what you write down on the facilities and resources depends on whether your application is a basic versus a clinical investigation. And what the reviewers want to know is your physical setup that you have available that you can utilize to accomplish your specific aims. The resource page often includes where your academic office is relative to your clinical research subject if you're doing a clinical grant. They also want to know where the appropriate research staff such as the research coordinator or the data entry person, where are they located, where are research charts housed and also where research subjects will be seen. And it would be good to show a separation between the clinical practice side of the equation versus the research side to show that you do have a clear demarcation between research infrastructure and clinical infrastructure that sometimes reviewers will ding people on saying that, you know, there's no clear delineation between research and clinical. Now for basic laboratory investigations, you should describe your wet bench where you're doing your experiments. And often in these basic science proposals you will utilize core facilities at your institution and you should describe those fully. I just put some examples of what core facilities many academic health centers have, microscopy core, molecular biology core, animal surgery core, et cetera. And you also should describe any major equipment that you have at your disposal. So a segment for applications for early stage investigators, especially those who are writing career development awards, these are actually very important supporting text or supporting letters that you need to show that your institution is ready to commit to you resources to your career development. And the reason this was required in many of the career development awards is that it forces the person, the PI who's writing the grant to make sure he or she addresses longstanding problems with insufficient institutional support for an early stage investigator. And writing the section forces the PI to have to go to their chairman or their dean of research to say, hey, you need to write me a strong letter of commitment of institutional support. And often what is written in these institutional commitment letters or supporting sections within the grant is, you know, the level of the PI's current academic appointment. It looks good if the PI already has a tenure track appointment, but of course there's this catch-22 here is who can get a tenure track appointment if they don't already have a grant. And therefore many of these points in this institutional commitment becomes a similar catch-22 because it's like trying to get a job without job experience. But again, a strong institutional commitment letter from a chairman of a department or a dean of research is very, very helpful. Other items include institutional developmental startup, like what the department committed monetarily to the PI, especially if this departmental startup was used to obtain some data that was used in this particular application. Also, what the department has committed to research time for you, the PI. Specifically, this is only as good as that time that is being paid for by the department. There's a joke that I once heard is that a junior faculty says, oh, my department chair is so nice to me because he allowed me unlimited time to do research. But the problem was the chairman only allowed the junior faculty to do research after 8 p.m. every night and on weekends, meaning it was unsalaried time. So anyways, a commitment from a department is very strong if they say that, you know, we are paying for X percent of time of this junior faculty to do research. Research space, research equipment given to the PI. And then, of course, whatever the institution has in terms of formalized career development programs, whether it's these lecture series that a junior faculty may go to that supports the development of the career development of that junior faculty or any courses given to the junior faculty. Now, responsible and ethical conduct for research is done really in a separate section of the grant. But you could say it here as well. Every institution now has standardized – there were usually online modules that show that they are teaching and educating and re-educating and doing continuous medical education of the PI on responsible and ethical conduct for research. Other things to consider are facility resources. Other core facilities that could be highlighted. Does your academic institution, is it a CTSA? This is a – the NIH was looking across the national map. We're looking for institutions that can form core clinical trial centers that can offer services to all the faculty members of that institution. There's a, I don't know, maybe 40 or 50 of these CTSA sites. Maybe there's more. I can't remember the exact numbers. But if you have a NIH designated CTSA site, you might want to talk to the program director of the CTSA to see how you can sort of formally develop some sort of relationship to show that you realize that there's other NIH core facilities that are being supported. Also, other core facilities that are available at your institution involves data management or statistical resources. Those are important to highlight, like a biostatistical computing core. Of course, most of these are probably going to be, you know, what I call contractually based, meaning you use a core and you pay for it based on how early use. The human subjects section is important because it impacts overall score of the application. So pay attention to this section. If you do a shoddy job, it's going to lower your overall priority score. So there are several sections of human subjects that you have to discuss in your research. Risks to subjects. You have to identify all potential risks in your proposed study. Adequacy of protection against these risks. What steps will you take to protect the research subjects against these risks? What potential benefit would these subjects have by participating in your research? And then the importance of the knowledge to be gained in your proposal. All of these bullet points should be already things you have to acknowledge and answer in your local IRB presentation. So much of this is cut and paste, not something specific for the grant. Specifically in the NIH type of grant that you don't have to do at your local institution, I don't think, although I think many of the local institutions want gender descriptions. You have to talk about inclusion of the female gender or when you're going to purposely exclude one gender from the study. And if you're going to exclude either a male or female, you have to sort of say why the other gender would be inappropriate. Obviously if you're studying, you know, uterine problems, you're not going to have the male involved. But if you say you're going to study urinary incontinence, you know, obviously it flips both populations and you're going to have to explain why one gender may or may not be, why one gender may be excluded. Other reasons are the research question addressed as relevant only to one gender. Evidence for prior research strongly demonstrates no difference between genders or the sufficient data exists already with regards to outcomes of comparable studies in the excluded gender and duplication is not needed. And what's interesting is that reviewers have to code how well you, you know, write the section in your grant, whether gender representation in the grant is both and whether it's acceptable or unacceptable, whether only women are included, whether it's acceptable or unacceptable, or even unknown. I'm not sure why unknown would be acceptable because it means the reviewers confused that you don't know which gender you're studying. But in any case, these are coded by the reviewers. Also a minority section is required. You have to discuss minority individuals and how you're going to try to recruit these individuals into the trials. And you could, you know, exclude minorities if inclusion of these individuals would be inappropriate with respect to their health. You can also say you're only going to look at minorities if the research questions are only relevant to only one racial or ethnic group and you wouldn't look at anything else. And many of these are, for example, how African Americans have higher likelihood of high-risk prostate cancer. And you would only be looking at African Americans because you're looking at only high-risk prostate cancer, for example. Other things to consider is evidence of prior research strongly demonstrates no difference between racial or ethnic groups on the outcome variables. Or you're going to study only a single minority group to fulfill a research gap. Or that sufficient data exists only with regard to outcome of comparable studies in the particular minority group. So again, these are coded by the reviewer. When they read your grant, whether your grant proposal or the specific aims involve minorities and non-minorities, whether it's acceptable or unacceptable, whether it involves minorities only, if it's acceptable or unacceptable, if it's not minorities only, if it's acceptable or unacceptable, et cetera. I'm not quite sure what foreign means here, so I apologize for that. You also have to have an exception on children. I think most of us listening to this webinar do not do children-based research, but you'll have to say why you're not going to exclude children. And the rationale will be that the disease process that you're looking at usually afflicts that pediatric population. And I think if you look at the age cutoff, I think children is a little higher than what you and I would think of 18. I think there's some areas where I think the age range is 21. Let's see. So again, there's codes for whether including or excluding children is acceptable or unacceptable. Again, make sure you acknowledge that. So the concept of meeting a data and safety monitoring board is, I think, really for the large clinical trials. I mean, this is a decision tree I got from the NIH looking at whether you need a data safety monitoring board. On one hand, I did say it's probably for larger trials, but if you really want to be safe, you could just propose a data and safety monitoring board for any clinical trial that involves any patient. You don't have to have a data and safety monitoring board that's off-site, so to speak, or different people. You could have your colleagues, co-faculty members be on the data and safety monitoring board. But you can read what they're looking for in the data and safety monitoring plan. So it probably is more conservative if you just propose it. Now, we're going to talk about consortium costs as well as subcontracts. This is when you collaborate with other investigators at institutions that are not your own. The facilities and administrative rates, which is the indirect cost rates, this is where it's what I call double dipping on your grant. It's actually counted at your own grant budget as a direct cost. So your institution will take an indirect cost rate of the other institution's indirect cost rate up to a certain amount, but it still sort of decreases the effectiveness of using your budget when you have to go outside the institution. So again, there's usually a cap on the outside F&A rate. So the pros are you can include experts at other institutions to show collaborative effort, but the cons are this could be cost ineffective if you have multiple contractors or other PIs, I'm sorry, other co-investigators at other institutions. So if you have someone with the same expertise at your institution, it might be better to keep the grant quote-unquote in-house. So let's talk a little bit about preliminary data. I think this is a little bit confusing for some people, and I think reviewers, depending on what type of grant you're writing, may look at it differently when it comes to preliminary data. I think if you're writing, well, let's just talk about preliminary data in general. Any preliminary data that justifies your approach at specific aims, I think is preliminary data. It could be something you've done yourself that's published or unpublished, or it could be published literature. Either one of these can support your approach, but when I say what type of grant you're writing, if you are a junior investigator with limited amount of time getting your own preliminary aims, certainly you're not going to have a lot of your own published or unpublished data to show preliminary data to justify your aims. So you would have to rely on the literature. But if you become more senior and you develop more hypothesis-tested data or data that supports certain hypothesis, I think you're going to have to show some of your own data. Especially, I think, if you're doing a continuation, I'm sorry, a competitive renewal of your grant where every five years, what that competitive renewal means is reviewers are looking at what you've done, and your preliminary data is going to be published data to support that you've been effective in your previous five years to generate data that's been accepted for peer review. But preliminary data can't be published or unpublished. It can be yours or not yours, and it depends on what level of your training or your faculty position is to decide that. So the timeline is also important to present your grant. You want to show that you are going to cover your specific aims in an expedient within the timeframe of the grant that you are going to be able to keep this on schedule. A graph with a timeline is very helpful with the aims so the reviewers can visualize what you propose to do over a period of time. So there are some budgetary things you should be aware of. First of all, the good thing about the budget is it's never as part of the priority score. Reviewers cannot review you, score you down low if you've mis-budgeted. But what you propose for a specific aim obviously is very important because if you don't have money, you can't do those aims. So it does go hand in hand, and I've never quite understood why you can't think somebody up a wrong budgeted thing because you can propose to do a lot of aims if budget is very low and you can score highly because your aims are all appropriate. But really, I think if you're going to propose to do an aim, you should do it. If you don't have the right budget to do that aim, it will look really bad if you get the grant and you don't accomplish your specific aim. Obviously, there's always a limit to the budget and you can't design a perfect trial because there is no such thing as an unlimited budget. And so often the idea for a grant is purely restricted by the cap on a budget that a sponsor will propose. So the budget, unfortunately, does determine the type of science you can propose. And I've seen people who write within the body of the grant as they're proposing specific aims. They already know that somebody might ding them. Why didn't you propose a third aim? Because they're predicting the reviewer's thought process. And they'll say, we're not doing the third aim because of the budgetary constraint. So they're already trying to not get a science dinged with a lower priority score by saying it's because of the budget constraint. But be aware, budgets do not, cannot be cut as part of the score. So often what ends up happening is budgets are over-budgeted and reviewers will say to do these aims, you don't need that much money. We recommend a certain amount of reduction in the budget. And there's also another thing in the NIH called the administrative selection of the budget. Often you go through a review of your grant by the reviewer. They get a priority score. They go through the secondary review, which is called the Scientific Advisory Council Review, and they decide to fund your grant. You're all happy. Then there's automatic administrative cuts across institutions of like 15%. That is not based on the reviewer's comment about how to do your budget, but really an administrative cut. So that happens primarily because often Congress will not allocate enough money for every institute at NIH to do what they wanted to do. And you end up getting an administrative cut. So this is a complicated process and there are a lot of things, but unfortunately sometimes the money is not exactly what you think you're going to get. So this is just a thing about modular budgets. The NIH R01 budget follows a modular plan if you have a grant that is less than $250,000. But if it's greater than $250,000, you need a detailed budget, which means every little thing has to be described. But a modular budget is pretty easy. You don't have to break down all the details of animal costs, reagents, chemicals, et cetera. Now, between $250,000 to $500,000, you can propose a detailed budget and you don't have to get special permission from NIH. If you have a grant that's over $500,000, which is rare these days, you need special permission from the NIH. So that's all I have for my set of things I talked about. And I hope this was helpful to you all.

grant applications

urology

facilities and resources

institutional commitment letters

data safety monitoring board

modular budgets