Thread by @azfaust

The world is on fire and the R01 deadline just passed so it's the perfect time to talk research strategy for an R01 application...

First, a disclaimer: this is how I do it. I have a PhD, I worked as a scientific writer for a while, and have been drafting grants for a decade. This is what works for me (most of the time). It's not an iron-clad rule of how it should be done. Feel free to ignore. Now...

First I pull up my Specific Aims page. Likely, it has been chewed over, torn apart, and stitched together. I am happy with it. Most importantly, the PI is happy with it. It's ready.

I do a page break and draft my aims and research strategy as a single document. So the document will be 1+12 pages plus references all together.

The traditional R01 has three major sections: significance, innovation, approach. Why, why now, and how.

I outline my sections. Then I outline my subsections. Include subsections that are important criteria for review: "rigor of prior research" for significance for example. I usually split innovation into intellectual and technical.

Then for approach I'll put in aims and I like to do "statistical analysis" "potential problems and alternative solutions" "expected outcomes." I've seen people do "scientific premise" for each aim and this can work well (that said, I haven't adopted this)

I don't generally do a "preliminary data" subsection. I sprinkle preliminary data where it makes sense: if it is necessary to set up the question or the hypothesis, then it goes in significance. If it demonstrates a novel technique or method, innovation.

If it demonstrates feasibility or experience with a certain technique, but does not directly inform the scientific question, then it goes in the approach when I am describing the experimental approach.

Now I go back to the significance. I copy the first two paragraphs of my aims and paste them in the significance section. These two paragraphs will be my guides for this section. They should inform the question and provide the rationale for the hypothesis.

I will bold the question and the hypothesis. These are my anchors. Now I break the paragraphs so that each sentence is on its own line. The goal is to now use these sentences and expand them into paragraphs.

I use each of these aims sentences as my starting topic sentence. Now below, I will provide the supporting information for that sentence by drawing on previous work. I support each of my statements with references.

A short interlude re references: make sure that whatever paper you are using for reference clearly and unambiguously supports the statement you are making. If you are referring to an obscure figure in a paper that is actually focused on something else, say that in the text.

"In Figure 5 of Smith, 2011, the authors demonstrated that X binds to phosophorylated Y" Some reviewers will just read the titles and abstracts and if it sounds like the paper is unrelated to your statement, they will think you made a mistake.

Back to the Research Strategy. As I mentioned, if the preliminary data supports my question and hypothesis, it goes in my significance. Published and unpublished data are fine. I have seen people put in figures from other lab's papers and I'll be honest, it makes me queasy.

I think there is this assumption (maybe just mine?) that whatever data is there was produced by the PI and collaborators. That said, when I've seen it done, it was always done with proper citations, which is important.

So the significance should be 1) question 2)hypothesis. This is my chance to explain why this is the most pressing question the study section will try to address today - and why this hypothesis is imperative to test right away.

I learned early to err on the side of boasting instead of humility.

Now for "rigor of prior research" - and this is new so I am drawing on what I used to do here. I always describe why, after all these folks who have worked on this problem for years and published on it, why we still don't know the answer.

I know that the text of the guidance reads like an invitation to criticize prior work. Resist this temptation! The goal isn't to say that what they did was wrong or insufficient, the goal is to build on the work that was done. But with big words, so it doesn't sound incremental.

"With the foundation built from prior studies and the new technical advances described in this proposal, our team has the necessary tools to address this critical question."

So, innovation. Again, I like to split into intellectual (hypothesis, pathway, mechanism) and technical (methods, techniques, instruments). I am ok with saying something is new or not done before, but you also have to explain why that's important to do in the first place.

Usually, you can build your proposal so that the significance offers the justification for the innovation. "We couldn't answer the question before because there was no technology that can capture the necessary measurements" "Here, we propose to use new technology that can"

Like that, but prettier.

Now for the approach. The first two sections are me describing why. The approach section is me describing how. *But I do try to echo the way at the beginning of each aim.

If there is a universal technique that will be used throughout the proposal, I will actually describe it before I get into the aims. The level of detail really depends on the PI. Super famous and established PI: general overview.

Brand new PI (especially if they have not published on the technique before): with as much detail as I would use to describe it to a 2nd year grad student. No, you don't need incubator temperature, but a general demonstration that you know what to do is important.

Now cite the aims verbatim as they are on the aims page. After the aim title, I explain how accomplishing this aim will help us answer the question. Then I go into experiments. I describe what they will do and how they will do it. Any feasibility data goes here.

Describe the stats (I go to a real stats person with this section) then potential problems. Describe what other methods/techniques can give you the information necessary to answer this part of the question. Then describe why these techniques are your second and not first choice.

*I learned early that money (saying something is too expensive) is never a valid reason in grant writing, but time and precision are. Use that as you wish.

Then end each aim with expected outcomes. Short sentence of the information you will have at the successful completion of each aim.

Repeat for each aim.

Some folks like to do one potential problems section at the end of the whole grant. I always feel like something is missing when folks do this. I prefer to address this for each aim in each aim.

I end the grant with an impact paragraph. Remember that impact paragraph from my aims page? The big picture one? I will copy it off my aims page and put it at the end of my grant. I will then expand a little bit on it, rewrite a few parts, but overall, the message will be same.

I know what you are saying - AZ, you forgot the timeline! Unless specifically required by the call, I stopped doing timelines. It was a lesson from one of the big name scientists I worked with who said they were useless and no one pays attention.

I do put them in if a call has deliverable or milestones or go/no go points. But otherwise 🤷‍♀️