Mar 20 2009 Published by physioprof under Grantsmanship

Reposted by request of a dear friend of the blog.
One of the most important skills a PI in the biomedical sciences must master is writing grant applications. As we allude to constantly, the basic grant award that is the sine qua non of a successful self-sustaining research program is the NIH R01. The R01 is generally awarded for 4 or 5 years, with an annual direct budget of ~$250,000. This is sufficient to support a small research program of about four or five people, including the PI.
In this series, we will discuss how to structure the Research Plan of a new R01 application (competitive renewals are a different beast), taking each section in turn: Specific Aims, Background and Significance, Preliminary Studies, and Research Design and Methods. (Note: NIH has asserted that in the near future, the R01 applications will be reduced in length from 25 single-spaced pages to 12. It remains to be seen how applicants and study sections will adjust their expectations to this new length.)
We start with the Specific Aims.
The Specific Aims section of the R01 Research Plan is the first page, and it should absolutely without exception fit on that one page. Not one page plus one or two lines, but one single page. This has to be the tightest, most structured part of the application, as many of the study section members who will be scoring your application will only read this section, if they read any of the application at all. The goal of this page is to encapsulate the basic gist of the proposed research and get the reviewer excited. If the reviewer is not excited after reading this page, you are toast.
The first paragraph of the Specific Aims page should, itself, be a self-contained complete overview of the project. The first sentence of this paragraph states in the broadest possible terms the long-term goal of the research project. The next sentence or two describes, again in very broad terms, the approach(es) to be deployed in service of that goal. The final sentence states the specific hypothesis to be tested or other particular purpose of the project that will be addressed using the approach(es).
The next paragraph or two summarizes the background/significance and preliminary studies. The goal here is to (1) justify the importance of the research question and the relevance/utility of the model system chosen to address that question and (2) demonstrate that the selected approach(es) are feasible and will definitely succeed in allowing the specific hypothesis to be tested or other particular purpose of the project to be achieved.
Next is a short transition paragraph that leads into the specific aims themselves. Mine are always two sentences. The first sentence restates the main technical and substantive conclusions of the preliminary studies. The next sentence introduces the specific aims. For example:

The following three Specific Aims are intended to test the hypothesis that blah, blah, blah.

Now comes the enumeration of the specific aims themselves. For an application for 4-5 years $250,000 budget, there should almost always be three specific aims. Each aim should be headed in bold type as follows:

Specific Aim #1: Identify blah basis for blah in the blah

The header for each aim should always fit on a single line of the page. I always present each aim as a verb phrase: identify blah, determine blah, test blah, etc.
After the header, the aim should be described in two or three sentences. The first sentence or two recites what experiments will be performed. The last sentence states what will be revealed by those experiments.
In relation to the nature of the aims themselves, one important consideration is that the aims should be posed in such a way that each aim is at least partially independent of the others. This is because a typical reviewer knee-capper is “If aim #1 is not successful, then none of the other aims can proceed”. My practice, when possible, is to have at least 75% of the experimental goals of aim #1 already complete and in the preliminary studies. Aim #2 can be not at all done, so long as the approaches are well-established and pretty-much guaranteed to work. Aim #3 is an opportunity to get a little more speculative and wide-ranging.
After enumerating and describing the specific aims themselves, the Specific Aims section ends with a single paragraph that reiterates the importance of the proposed research in light of what is already known in the field and what will be vua the proposed studies. The last sentence of this paragraph then pulls back into a very broad perspective on where the proposed research might lead in the long term, and why that will be very important.
Here is a redacted version of a Specific Aims page that embodies this structure: