R01s Versus R21s For New Investigators

Jan 29 2008 Published by under Careerism, Grantsmanship, NIH

You're a new investigator and you are trying to decide how best to get money to support your new lab. You may be weighing the relative risks and rewards of submitting as your first NIH research project grant application an R21 versus an R01. This is actually one of the easist decisions you will ever make as a new PI.


If we weigh the costs and benefits of an R01 versus an R21 grant application, you will see that only in very particular circumstances does it make sense for a new PI to spend any of her time writing R21s.

R01s have the following benefits over R21s: (1) Limited to five years instead of two years. (2) Modular budget limited to $250,000 per year for all five years, instead of only $137,500 per year for two years. (3) Competitive renewal permitted.

R21s have the following ostensible benefits over R01s: (1) 15 page application, instead of 25. (2) Although R21 Funding Opportunity Announcements differ in their exact focus, one commonality is that much less preliminary data than for an R01 is explicitly demanded. Are these benefits real?

Well, it takes nearly as much time to prepare an excellent R21 application as an R01, so the shorter page limit is of minimal relevance. And "less (actually 'no') preliminary data required", while theoretically fantastic for a new PI, is actually pretty close to bullshit. Unless the proposed studies are patently feasible (and, thus, probably boring and getting hit on significance), study sections almost certainly will ding the absence of preliminary data as a "feasibility" issue, but just without using the magic verboten words "preliminary data". When all is said and done, however, the sheer amount of preliminary data required to satisfy an R21 study section is somewhat less than that typically required for an R01.

Now, figure out which of the following two populations you are a member of:

Population #1: You have sufficient space and start-up resources to run your lab with two post-docs (or equivalent) and a technician (or post-graduate researcher) for at least three years without any grant income.

Population #2: You do not have sufficient space and start-up resources to run your lab with two post-docs (or equivalent) and a technician (or post-graduate researcher) for at least three years without any grant income.

If you are in population #1, you should focus your time and efforts solely on getting a first R01 funded, and forget about R21s. You should have enough start-up resources--if you plan and manage effectively--to generate preliminary data for at least two credible scientifically distinct R01 applications. An R21 application is too little money for too little duration in return for all that effort, and does not provide a competitively renewable long-term expected future flow of grant support that is essential for sustained viability of your independent career. This is essential for tenure, and if you look at success rates for competitive renewals you will see why a competitive renewal application has a greater expected future value than a new application. Since you have sufficient start-up resources to keep hammering experimentally on two distinct R01s for at least three years, you can afford the risk of both R01s requiring a second resubmission (i.e., reaching "A2" status) before one of them hits.

If you are in population #2, the decision becomes a little more tricky, and depends on how much start-up resources you can command. If you have essentially none, you are pretty much stuck with R21 applications, because you have no way to generate preliminary data sufficient for an R01. Once you manage to get an R21, that gives you the resources to leverage into an R01.
If you have only enough for two or three person years of experimental effort (about half of that required to place you in population #1), then it requires a quantitative weighing of risk and benefit. The danger of going for R01s only, is that you may end up running out of start-up resources before getting two distinct R01 applications to A2s, and getting one awarded. You might be fortunate enough to get one sooner, and thus be ok, but you would be taking a bigger risk than someone in population #1.

If you go for one R01 and one R21, on the other hand, you diversify your risk better, and the R21 gives you a shot of getting some substantial funding even in the absence of a pile of preliminary data sufficient for an R01. And then you can leverage the resources provided by an R21--essentially an extra infusion of start-up--into an R01 (or a second one if you are fortunate).

17 responses so far

  • juniorprof says:

    First off, thanks for revisiting this discussion. I ask for advice on this a lot and get a wide variety of answers. Yours is the best reasoned I have heard. The whole thing seems to hinge on preliminary data (at least for population 1) so what about the following scenario:
    Let's say you're a new PI in population 1. You have the outline for your first R01 submission together. You have three aims. You have strong preliminary support for aim 1 and 2. Support for aim 3 can be inferred from data for aim 1 and 2 but you have no direct evidence to support aim 3. You also have no proof you can do technique in aim 3 (but its nothing outlandish based on your expertise). Should this junior PI go ahead and submit first R01 application now or work toward preliminary data for aim 3? I suppose the questions comes down to, what is the bump for a new investigator on R01 submissions and is it enough to overcome a deficiency in preliminary data in an otherwise well written and well thought out proposal?

  • PhysioProf says:

    Should this junior PI go ahead and submit first R01 application now or work toward preliminary data for aim 3?

    SUBMIT NOW! The likelihood of a fundable score on the first submission is very small even if you have a massive fuckload of preliminary data. You need to get your grant in the pipeline ASAP.
    While it is in the system you will be working feverishly on more preliminary data. This will put you in the best possible position for an outstanding first resubmission ("A1") as soon as possible.

  • whimple says:

    Also important is that an R01 is generally required for tenure.
    Some other R21 advantages:
    1) Some institutes (FIC, NCCAM, NCI, NCMHD, NIGMS) do NOT accept unsolicited R21 applications. If you can match a PA at one of these institutes, your application is going to potentially be trying to swim in a much smaller pool with many less sharks than would an unsolicited R01 application.
    2) Study sections tend to view funding R01s as a zero-sum game. If they fund you, they don't get to fund one of their friends. This is much less true for R21s.
    3) In some fields, getting an R21 is considered "paying your dues". The expected progression now seems to be K99/R00, then R21/R03, then R01. If you skip the R21 step you're viewed as trying to jump the line.
    4) Translational studies and/or descriptive rather than mechanistic studies tend to get hammered as R01s. The R21 is considered "more appropriate" for either descriptive or exploratory/developmental studies.
    5) It's not that hard to write an R01, and then split it into smaller pieces, modify the pieces a bit and send them off as R21s / R03s to different study sections in order to give more people a chance to say "yes" to your work, without a tremendous amount of additional writing. That is, if you've written the R01 application, you don't need to start all over from scratch for the R21.

  • DrugMonkey says:

    The notion of what is "sufficient" preliminary data is in the eyes of the beholder reviewer. So it is always a tough balance.
    If you have what you think is strong support for two Aims, as a new investigator, I'd say it is time to get that R01 submitted. First reason is, as always, you have to assume that you are going to have to revise this thing at least once. Unless you have the most unbelievable 1%-ile first submission. And likely you do not. No offense, these are the odds. So why wait? Is it really that likely that what you can do with one more rounds' time is going to magically put you above the revision bias? No. So get it submitted.
    You may consider ditching Aim 3 if you think it is reviewer bait. Nothing wrong with reducing the scope and there is nothing magical about three Aims. Well there IS, but it isn't etched in stone. Perhaps Aim 3 is your R21 parallel submission that the PP was discussing?

  • DrugMonkey says:

    "2) Study sections tend to view funding R01s as a zero-sum game. If they fund you, they don't get to fund one of their friends. This is much less true for R21s."
    I take exception to whimple's tone here and in fact the data do not seem to support the implication. It is true that there is much OldBoy-ism in review, a frequent topic of this blog (new readers will have to refer to the WP archives for now). I try to make clear in my ranting however that this is an emergent property of certain human behaviors and study section traditions. It is not for the most part any sort of overt quid pro quo. I'm not saying it can't happen. Likely it does. I just don't see it on my section. Which I have no reason to believe is somehow all nicey-nice.
    The implication here that R21s will fare better because they are not in competition with R01s at the study section is exactly backwards. In my section (and I've heard similar from other sources) the problem is too much hammering on R21s. Putting the triage burden on the R21s disproportionately. Reviewing R21s "like" R01s in terms of preliminary data support.

  • whimple says:

    DM: I take exception to whimple's tone
    I didn't intend any tone. I was trying to point out that with funding levels where they are, each reviewer knows that of the pile of grants they get to review, only one (if that) is going to get funded.

  • PhysioProf says:

    The implication here that R21s will fare better because they are not in competition with R01s at the study section is exactly backwards. In my section (and I've heard similar from other sources) the problem is too much hammering on R21s. Putting the triage burden on the R21s disproportionately. Reviewing R21s "like" R01s in terms of preliminary data support.

    Yep. And the Program Announcement thing mentioned above is a red herring. Unless it is a Request for Applications or Program Announcement With Set-Asides, you are competing against all the "unsolicited" apps anyway; response to a PA doesn't really improve your chances substantially.

  • PhysioProf says:

    Oh, and as far as the "paying your dues by only seeking an R21", that is not something I have ever observed in any field or subfield that I have worked in.

  • DrugMonkey says:

    I had something on this before
    http://drugmonkey.wordpress.com/2007/06/27/new-investigator-dont-cut-yourself-off-at-the-knees/
    I think there is a pronounced tendency in some minds that new investigators shouldn't "get greedy" . should "prove themselves with a small project". etc. Program says this crap too.

  • PhysioProf says:

    I think there is a pronounced tendency in some minds that new investigators shouldn't "get greedy" . should "prove themselves with a small project". etc. Program says this crap too.

    PhysioProf says, "Fuck that noise!" If you give a study section cool enough science, they will eventually fund it, regardless of greed, proving oneself with a small project, or any of that other happy horseshit.

  • DrugMonkey says:

    right. my main point in that post was that despite this tendency, if you had R01 stuff you should go for it. Still, there is that tendency. And if that causes you to chop a couple of modules so you look small or drop a year so you look limited, well that can pay off. of course, when you get that fundable score you are going to kick yourself but that's a whole 'nother thing...

  • If you give a study section cool enough science, they will eventually fund it. . .
    Hey! Hasn't your SRO ever told you not to use the "F" word? "We're here to evaluate the relative quality of the science, not to make funding decisions - that is done at Program."
    But, yeah, yeah, I live in the real world - I also know that study section knows whereabouts the funding cutoff is likely to be.
    I believe that I am in a different research area from DM or PP but their observations are quite similar to those from my experiences. For my two cents, I share the sentiment that R21 applications are not worth the effort and will only get scored fairly once there are separate study sections for R21 and R03 apps. Having a batch of R21 apps thrown in the middle of panel that has spent the last day discussing R01s and will get back to them again tomorrow, R21s are too often judged as if they were R01s. Prelim data is not expected but I have yet to see one come in without it.
    If you're in Population #1, generate enough prelim data to get into the R01 queue as early as possible, take advantage of the opportunity to submit supplementary data prior to review and, if you really need more pilot funds, apply to some local foundations that have a smaller payout but usually demand far less effort and have a better probability of funding than an R21.

  • PhysioProf says:

    And if that causes you to chop a couple of modules so you look small or drop a year so you look limited, well that can pay off.

    I disagree strenuously. It is foolish to ever submit an R01 that is not requesting five years and full modules ($250,000 per year). If the proposed science doesn't have a broad enough scope to merit that, you should broaden the science.
    The reason for this is that you get minimal, if any, bump by the study section for having a modest budget. And the benefit to extra years and dollars per year is massive, especially when you consider that there are limits to the percent above the original grant budget that a competing renewal can request in most (all?) institutes.
    Many reviewers of R01s just assume that if you have three decent-scoped aims, then a full 5-year modular budget is just approved as being standard, and not assessed substantively.

    [I]f you really need more pilot funds, apply to some local foundations that have a smaller payout but usually demand far less effort and have a better probability of funding than an R21.

    This is hugely important for new PIs. You must apply for every single scholar award and foundation grant you are eligible for.

  • juniorprof says:

    I'm sending out scholar and foundation grants at a furious rate. Moreover, my dept and others with interest are informing me of opportunities I never knew existed. While I fully understand the importance of this money for supplementing the startup and beyond, does the ability to demonstrate fundability on a project have any further bearing on review of your R01. For example, if I get a small foundation grant with a similar title to my R01 submission will study section note this on my support page and will it have an impact (hey, they liked it and that makes us like it just a bit more)? Just curious...

  • writedit says:

    Gentlemen ... please, not everyone works with drug-addicted rats and little worms with Latin names. Not everyone falls neatly into the two populations described above, particularly those investigators who have to spend time with these pesky things called patients. Most important, as also alluded to above, not all ICs view R21s the same, even those who do fund them. I haven't talked with program officers about this in a while, but in the past, they (including one in particular from a basic sciences division at NCI) generally recommended against R21s as starter grants for several reasons, many of which you have rehashed here. In FY07, R21s had a success rate of 16.3% vs 19.2% for new R01s. Of course, there are no competing renewals for R21s ... Type 2 R01s applications enjoyed a 36.1% success rate. The lack of a renewal option is a huge reason to leave R21s for anything but genuinely exploratory research, including clinical pilot work (which could handle the smallish asymmetrical budget and would not need a renewal - full trial gets its own R01 or U01, sometimes preceded by an R34).
    On the other hand, an R01 does not need to be 5 years, so a sensible 3-4-year R01 to achieve Aims 1 & 2 in Juniorprof's example would work well. I just wrapped up a really elegant 3-year R01 that clearly has legs for competing renewals - once the PIs have achieved the initial 2 aims (they opted to drop their 3rd contingent aim, leaving them with a tight, well-justified proposal). Just remember not to short-change your budget at the same time: that is, cut years rather than modules since the Type 2 budget cap will be tied to the Type 1 award level. Otherwise you will likely be restricted to an increase of no more than 20% over your final Type 5/noncompeting award, which are only going up 1% in FY08 as it is.
    And at the risk of having PP use a naughty word against me, I'm going to politely disagree with the suggestion that responding to a program announcement (other than PAS or PAR) is like pissing in the ocean. A program announcement with priority topics, which derive from council-cleared concepts, is always a better bet than submitting to the parent PA. Still a lot of competition, but at least you know program is looking to support research addressing those topics and, if motivated, may pull yours from above the payline for funding ... a topic near & dear to DM's heart.

  • DrugMonkey says:

    juniorprof, it isn't really the "fundability of the project" that is important.
    First, of course, the money is good in and of itself to get some work done.
    Second, it provides the evidence your study section advocate needs to say "sure s/he's never had an R01 but s/he holds independent research support and is functioning as a PI". This gets you past one thing that verges on a StockCritique, i.e. "no evidence of running an independent research project"
    Third, hopefully you can claim that the award supported the collection of some of the Preliminary Data included. People like this because it shows a logical continuity of the project and of your career. or so I surmise, this not being a big thing for me when I'm reviewing...

  • PhysioProf says:

    One additional subtlety about junior-PI foundation grants: Some of them are intended only for PIs who have not yet secured an R01, and continued non-competing renewal can be explicitly tied to continued lack of an R01. In some cases, this can be finessed so as to be able to keep non-competitively renewing the foundation grant even though you have an R01.
    The trick is that the project funded by the foundation grant and R01 have to be arguably distinct enough that you could credibly assert to the foundation that--despite now having an R01--you will have to mothball the project they are funding if they cut you off now.

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