Hey! New PI! Submit That R01 NOW!! (UPDATED)

As a new PI, your single most important task (by quite a margin) in the first three years of your faculty appointment is to obtain an R01 research project grant. Getting that first R01 is essential to the ongoing viability and productivity of your lab, and is also the single most important factor (for research-focused faculty appointments) in performance assessments generated in relation to promotion and tenure both internally and by outside letter-writers.
In light of this fact, PhysioProf has recently been discussing with some colleagues exactly when a newly independent PI should submit her first R01 application. Apparently, there is a lot of contradictory advice floating around out there, emanating from a variety of sources: senior colleagues, Program Officers, and fellow junior faculty.
The first step in assessing this advice is to consider its sources, and PhysioProf is going to be very frank here. Your senior colleagues are in denial about what is really happening right now as a result of severe budget problems, and are stuck in old ways of strategic and tactical thinking that just don’t work any more. Program Officers are shell-shocked right now, spending the overwhelmingly vast amount of their time over the last four years talking to investigators whose careers are dying because they can’t get funding. Under these extreme conditions, the only things a Program Officer has to tell you that are of use to you are (1) her impressions of the discussion of your grant at study section and (2) whether you are getting funded. (You do, however, need to at least pretend to take everything else they say very, very seriously as well.)
You can find out who to listen to, and what those people are likely to tell you below the fold.

The people who you should be listening to are those who are no more than a couple years ahead of you, and have been highly successful at getting R01s funded. These colleagues have figured out, through trial and error, what worked. And, just to be very clear, there are certainly multiple distinguishable tactics and strategies that can be effective. And what is effective surely differs to at least some extent between fields. The key is to listen to a bunch of different successful colleagues, and look for the common elements, as well as the elements that are specifically relevant to yor field.
Accordingly, you need to know that PhysioProf is speaking out of experience obtaining R01s in a very interdisciplinary collection of basic science fields amalgamated out of methodological and conceptual framewroks that address physiological function at all levels from genes, cells, tissues, organs, and, ultimately, intact organisms. Grant applications in this broad area are typically reviewed by the more cellular-and-molecular-focused study sections–specific for particular organ systems: brain, kidney, heart, eyes, etc–and assigned for funding to Institutes based on organ system.
So, what about some of the bad advice being promulgated by many Program Officers and senior colleagues? One thing I hear all the time is that new PIs are being told to submit only for R21s and R03s (much smaller, non-remewable grants than R01s) at first, in part because study sections will not want to give an R01 to a new PI until that PI successfully obtains and completes a smaller grant.
This is insaaaaane. The fact that a new PI has not completed any grants is totally irrelevant. Completing small NIH grants is not relevant to a study section’s assessment of a new PI R01. They want to know that you are truly independent–i.e., not some super-post-doc in a big lab–but your PI faculty status with space, start-up, and institutional support, and the fact that you are no longer at the same institution as your post-doc advisor, establish this.
Furthermore, and even more important, R03s and R21s do not benefit from substantially looser paylines applied to new PI R01s. For example, the National Institute of Allergy and Infection Disease new investigator R01 payline is currently 14.0 %ile, while the regular payline is 10.0 %ile. R03 and R21 paylines are the same for new and established PIs. Those extra 4 %ile points are huge. New Investigator Applications also usually get their annual budgets cut less, and usually get the full duration requested, rather than a cut of one year or more.
(On a side note, new PIs should be applying for every possible private foundation and scholar award grant that you qualify for. This is very important for keeping the cash flow reasonable, and getting one or more of these awarded to you definitely will definitely be helpful with the study section.)
Another thing PhysioProf has heard is that new PIs are being told to seek out colleagues with more of a track record to collaborate with on a multiple PI R01. What are the possible benefits, and accompanying costs, to adopting this strategy?
NIH recently altered their grant system that an R01 can have more than one completely co-equal PIs, with the idea of encouraging more collaborative projects, as the allocation of street cred for possessing an R01 only to a single PI created a disincentive for collaborative projects. The only possible advantage to submitting a multiple-PI R01 would be a better score from study section, if it perceives that the two PIs together have a much better chance of making the proposed studies work than with you alone as PI, such as if they each contribute some special skill set to the project, both of which will be heavily relied on. Whether having multiple PIs would help increase the likelihood of funding depends on your own biosketch and the biosketch of the other PI.
A new PI might, however, fruitfully think more along the lines of getting someone more senior to play an advisory/consulting role on application. This can be helpful with study section in feasibility assessment, but such a person should be play a non-PI consultant role on the application, not list any person months of effort in the budget, and make it clear in their Letter of Consultancy that they would simply be providing occasional advice/guidance as needed, but that you, the PI, would be truly running the research project. This person should *not* be your former post-doc mentor.
How about disadvantages to multiple-PI grants?
(1) Only if *both* PIs are new investigators is the application considered a “New Investigator Application”, thereby receiving both special consideration at study section (this is not so helpful in practice) and, most importantly, special consideration for funding by the assigned Institute, as described above.
(2) You need as much money as possible for your lab. The maximum modular budget you can request is $250,000 for five years. So long as you have two or three substantial aims, study sections do not pay any attention to budgets equal to or less than a maximal modular. They know it is almost certainly going to be administratively cut substantially (up to 45% over the 4-5 year life of the grant) and consider a full modular budget to be “standard”.
Don’t even think of not asking for a full modular budget. If your aims seem to narrow to support a full budget, add some science. You need *all* of that budget for *you* and *your* lab. You do not want to share any of this money with another PI and her lab.
(3) You need to establish clearly that you are, indeed, a successful independent PI as soon as you possibly can. One of the key ways to do this is by successfully competing for an R01. If you only have successfully competed for a multiple-PI R01, it could raise the issue of how independent you truly are with people who will be reviewing other grants of yours, as well as assessing you in letters of recommendation for promotion and tenure.
The upshot here is that it is only under very rare circumstances that the benefit for a new PI of submitting a multiple-PI R01 application outweighs the costs.
So what should the new PI be doing? You should be submitting your first R01 application as soon as is administratively possible. Those people telling you, for whatever reason, to wait, wait, wait: ignore them. If you are an assistant professor, with your own lab and start-up, and you have published in a related area as a post-doc, then waiting is nonsense.
You need to get your R01 in line with those of the rest of the new investigators. As it goes through the review process–almost certainly more than once–you will have plenty of time to produce a lot more preliminary data and refine your specific aims in resubmissions.
PhysioProf even wrote his first R01 at the very end of his post-doc, before he even opened the doors to his lab. The preliminary data was almost all figures from shit he published as a post-doc. It got triaged (not discussed at study section or given a priority score), but the practice writing an R01 (even a shitty one) and the insight into the review process provided by the summary statement were hugely valuable even though PhysioProf never even resubmitted that grant.
Bottom Line: Your single most important goal (by a substantial margin) as a new PI is to obtain a single-PI R01, as soon as possible, as this is the minimum standard for a self-sustaining truly independent research program. This is both for purely fiscal reasons–paying for personnel salaries and research expenses–and for building a reputation sufficient to support promotion and tenure. NIH understands this, and has a system in place to do everything possible to help new PIs get that first single-PI R01, including, most importantly, dramatically looser paylines. You should be doing everything in your power to exploit that system.
UPDATE: DrugMonkey has reminded me that R01 applications of new investigators that are not scored highly enough for award, may be converted into a one-to-two-year R56 bridge award to help the new PI generate more preliminary data, refine her specific aims, and resubmit a more meritorious application. This only applies to R01s, yet another reason that the new PI should be focused on R01s, not R03s or R21s.