The NIH-R15, Part 2 – Taking your best shot

CurChem features funding! In this second of a two-parter on the NIH-R15, awardee and hockey enthusiast Dr. Joseph Provost walks us through critical elements of a competitive submission. For the first half – go here.


What does it take to be successful getting NIH R15 funding as a PUI with the current competition (I talked a lot about that competition in this post)?  I will let you know in a couple of months when I get my score from this week’s submission!  In truth, you are striking a balance between being innovative, without being “too ambitious.” If we go back to hockey…(did we ever really leave?) You need strong, well-defined aims, but you can’t be too far ahead of the puck .  Finding the balance between an incremental and an ambitious proposal is critical, and then…you have to sell it to the reviewers.

The Big Picture

nih-r15-twitterThree meaty aims or four smaller aims are usually enough to create an interesting proposal.  You are doing research with undergraduates, so finding a “safe harbor” for your project is essential. A “safe harbor” is a meaningful area that won’t be overrun by another larger lab.  If you are proposing the same basic research that others in research-intensive labs are working on, the reviewers will recognize the slower rate of work (possible) at a PUI….and, you get the picture. It can be a negative factor.

You should also look at the roster of NIH study sections to see your audience. Remember, the competition for R15’s also includes many larger schools with graduate students. Talking to the appropriate AREA contact (i.e. Program officer) before writing is also helpful. Hey, NIH-R15 is even on Twitter!

How much should you say about the undergrads?

Focusing on educational components are important, but be judicious in how much space and attention you give.  Let the reviewers know that students are involved in the project, that your project can be done at your institution with the resources at hand, and if portions of the work are done off campus, how students can still be involved to meet the educational goal of the program.  Describing in a half of page about how students are involved in your project is often good enough for most reviewers.

Describing in a half of page about how students are involved in your project is often good enough for most reviewers.

One of the best pieces of advice I have received was to get the reviewers to thing “I would like my son or daughter to work in this person’s lab”.  This information shouldn’t detract from the science or take up space needed for the project description

Convince them you can do it

Controls, proof-of-concept and preliminary evidence are critical for a competitive R15 proposal, even though the program announcement states that preliminary data is not required.  Don’t even try to submit without several convincing pieces of data along with a string of strong published evidence supporting your hypothesis and project goals.  If you are proposing something that is a particularly challenging approach or technique including some data showing you can do the work and if needed a description of collaborator or consultants for the specific technique will help.  The good news is we don’t have to have near the level of data needed by R01 proposals (often what seems like one or two papers already to submit).  Another hint: Pay close attention to describing controls and experimental variables for your project.  This is more important for PUI applicants than established big name labs.

Pay close attention to describing controls and experimental variables for your project.  This is more important for PUI applicants than established big name labs.

Nothing stays the same

Does anything stay the same? Reducing the page limits of the R15 research plan from 15 to 12 several years ago was painful for many of us.  Now there are additional requirements that have to fit into that same space – making the task of explaining your amazing research that much more difficult.

Reducing the page limits of the R15 research plan from 15 to 12 several years ago was painful for many of us.  Now there are additional requirements that have to fit into that same space…

Some changes like the biosketch and reference requirements are not too difficult and will not impact the 12 pages.  However, learning how to adjust and create these documents will take time, and you should factor in that time when planning to write your proposal.

There are other changes that impact the space in the research plan. One new element, “rigor and transparency” is required for proposals submitted on or after May 25 2016.  Reviewers are now asked to specifically address the following points: the scientific premise forming the basis of the proposed research, the rigorous experimental design for robust and unbiased results, and the consideration of relevant biological variables, and authentication of key biological and or chemical resources.  A great table summarizing the changes with helpful links is found here.

NEW: Scientific Premise

A new feature of the R15 application the required section labeled “scientific premise” in the Research Strategy portion of the Significance Section.  The scientific premise section is to explain how biological variables such as sex, are factored into research design and analysis.  This also needs to reflect the strength of the cited literature and preliminary data your project is based upon.  The NIH Extramural Nexus online publication “Open Mike” from Deputy Director for Extramural Research does a good job discussing this topic.  Dr Lauer explains a way to approach is to …”describe the scientific premise for the proposed project, including consideration of the strengths and weaknesses of published research or preliminary data crucial to the support of your application. Weaknesses in scientific rigor or gaps in transparency that preclude the assessment of scientific rigor should be acknowledged. If such weaknesses are identified, the applicant should consider whether or not to include this data in support of the application and how the proposed research will address the weaknesses”. 

The scientific premise section is to explain how biological variables such as sex, are factored into research design and analysis.

Some will have a separate section in the research plan to address this, others will indicate how to address this question integrated into each aim.

NEW: Rigor and Reproducibility

The Approach section of your Research Strategy (i.e. plan) should now include space for how your project includes Scientific Rigor and Biological Variables.  A project in Chemical biology vs. a project in microbiology are going to handle rigor and reproducibility differently.  Rigor is about how your experimental plan uses appropriate size studies and analysis to eliminate bias.  My interpretation of this requirement is to demonstrate how you will design and interpret your results in a transparent way.  The terms “robust and unbiased” mean that your methods should have multiple recordings, assessments, etc.  Defining sample sizes using power analysis, the appropriate evaluation (simple T tests and ANOVA without additional information will likely not be enough).  NIH provides examples for rigor here.  In order to address biological variables in the approach section, one should consider how variables like sex, age etc are factored into the research plan. If you are using mice or conducting human studies, you especially need to consider how to address this new requirement.

Other NEW stuff that doesn’t have to fit in the 12 page Research Strategy (Plan)

At least this new element doesn’t have to fit into your 12 pages. The Authentication of key biological and/or chemical resources requirements is an appendix item that has to address how you will ensure the unique and non-standard reagents are what you say they are.  How the cell lines and mutations you plan to use or create are really those cells.  This is a one or so page that describes your method to authenticate resources.

The Biosketch changes have been around for a little more than a year.  Now the biosketch includes a personal statement that describes how you are appropriate for the proposed work, and how your publications / works have contributed to science.

References – if you reference one of your publications in the proposal that included NIH funding, this needs to have a PMID or other reference identifier in the reference section.

And finally a new package with all forms (appropriately called Forms D) is new this year. This is the new applications guide and has changed considerably from the past format.  There is a “How to Apply” webpage describing the Forms D and application changes here.

What if you’re declined?

Getting turned down is frustrating.  Getting triaged is horrible.  But there is good news. There used to be a rule which capped the number of attempts per investigator to TWO – but that rule has been retired. This change helps PUI faculty who are more likely to need extra time to create preliminary and proof-of-concept evidence when compared to research-intensive PIs.  A proposal (“application” in NIH speak) can be resubmitted as an A1 (once called amended applications) only once for each new, unfunded application. You even get a single page to explain the resubmission. If that A1 is denied, you can adjust and modify your proposal again, but as a NEW submission.  You lose the extra page allowed for a resubmission on the “third try”. While a proposal can be turned in more than twice now (I have had one funded on the third try) the “third-try” has to be more than just a small change or minor tweak.  How much of the proposal to revise and evolve is one of the more difficult challenges in a resubmission.  I’ve had a proposal fall just outside the payline, so my resubmission was only “fine-tuned” with minimal changes, but the score on that resubmission was much worse than the initial submitted proposal! Go figure!

How much of the proposal to revise and evolve is one of the more difficult challenges in a resubmission.

In this most recent submission, we removed our fourth aim hoping address reviewer comments about the work being too ambitious (even dangerous!)  If we are not funded this round, then it is time to look elsewhere for funding to support this idea and come up with a new project to submit to NIH-R15.  We’ll keep shooting at the goal.

Why do it?

Being awarded an NIH R15 is not impossible, but it isn’t easy either.  Over the years, I’ve coached hockey for 23 different teams, from first-year boys and girls to high-school-aged kids for USAH and adult novice camps.  The sweetest wins were the come-from-behind kind… against teams who were clearly better than we were.

The sweetest wins were the come-from-behind kind…against teams who were clearly better than we were.

Knowing who your competition is should not stop anyone from applying.  Instead, as I’ve told my hockey players, if you are defeated to start with, you have no chance; instead, focus on what you can do well and play to that strength. I’ve been lucky to be funded several times, and I am hungry for more.  What drives me to submit/resubmit is the science that should be investigated, the spark of an idea, and bringing resources to support the next generation of scientists in the best possible place, our laboratories. One person who I highly respected admitted that she likes the creative part of writing the grant and the intellectual challenge to convince others her work is worthy of funding.  I agree.  Get in the game and go get it!


639~Dr. Joseph Provost is a Professor and Associate Chair of Chemistry and Biochemistry at the University of San Diego where he teaches a wide range of chemistry and biochemistry courses. Provost has been involved with a number of organizations involved to enrich the experience of undergraduates including: the American Society for Biochemistry and Molecular Biology, Council on Undergraduate Research and Project Kaleidoscope.  Provost ‘s research involves focuses the role transport protein plays in directed cell motility and tumor progression and how these membrane proteins regulate other critical mammalian cell functions.

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