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Submitting Your Best-Possible R01 Application

Grant writing has always presented challenges for new faculty members, but the current funding squeeze at the National Institutes of Health (NIH) has researchers especially worried. Many current investigators were trained in labs that that ran entirely (or almost entirely) on R01 funding. Scientists worked hard, and the month before the R01 due date was really busy, says Anne Churchland, an assistant professor of neuroscience at Cold Spring Harbor Laboratory in New York. But, “If you did good work and wrote grants carefully and published regularly, you could be thoroughly confident that you could fund your lab through NIH,” she says.

Those days seem to be over, Churchland says. Today, only a fraction of emerging scientists will manage to sustain their labs with NIH funding alone. That raises the grant-writing stakes considerably.

Scientific rigor and relevance are the main things but writing matters, too.

CREDIT: Constance Brukin, Cold Spring Harbor Laboratory
Anne Churchland

On a warm and sunny day in March at Cold Spring Harbor Laboratory, more than 200 neuroscience faculty and postdocs, NIH officials, and study section participants gathered to discuss the NIH funding process and how early-career investigators can improve their chances of obtaining an R01 grant. (You can view PDFs of some of the conference presentations here.)

Speakers at the event pointed out that even as the contest was becoming more competitive, the application process was changing. Within the last 3 years, the grant format has become shorter, at 12 pages instead of the previous 25. Investigators now get just two chances to submit a grant application for review, instead of the previous three.

Given these changes—and with paylines near record lows—it’s more important than ever to write your best R01 application: one that includes your best ideas and a clear, concise, realistic plan for carrying them out. (See Science Careers' "NIH R01 Toolkit" for more on NIH grantsmanship.)

Collected here are some tips the experts at this panel recommended. While this panel was aimed at neuroscientists, almost all of these lessons apply just as much to other NIH-funded fields.

Making the most of early-career status

Investigators just starting up their laboratories have less grant-writing experience than their senior colleagues and less opportunity to accumulate preliminary data. NIH recognizes these disadvantages and makes accommodation via two special investigator categories: A "New Investigator" is an applicant who hasn't received an R01 (or similar) grant from NIH, and an "Early-Stage Investigator" is someone who, in addition, is no more than 10 years past a terminal degree.

Groups of grant applications from these categories are typically reviewed together, and study sections are tasked with judging them differently than those from experienced researchers. When dealing with new and early-stage investigator proposals, reviewers put less emphasis on preliminary data and publications and more emphasis on a researcher's training and experience: Does she or he have what it takes to make the project succeed?

New-investigator proposals might receive a second look when NIH institutes make their final funding decisions, and strong proposals from early-career investigators are likely to be reconsidered. The National Institute of Neurological Disorders and Stroke (NINDS), for example, had a guaranteed payline at the 15th percentile last year for all investigators, says Story Landis, director of NINDS. But the institute took a second look at applications from early-stage investigators who scored within 10 percentile points of the payline. In examining these proposals, Landis says, she is looking at two critical questions: Are these investigators truly independent, with research autonomy and laboratory space? And is there a fatal flaw in the proposal that the principal investigator hasn’t addressed? If the investigator seems truly independent and the proposal is free of serious flaws, the application might be funded after all. Early-stage status also has another advantage: It qualifies you to apply for the NIH Director’s New Innovator Award.

Story Landis

If your Ph.D. is more than a decade old, you can petition to have your early-stage status reinstated. If, for example, you spent time away for family duty or sought extra postdoctoral training in order to change fields, NIH might be willing to extend your early-stage investigator status.

Be warned: You can only use your new or early-stage investigator status once. So use your status wisely, advises microbiologist Ruth Ley of Cornell University. “You don’t want to throw it away on somebody else’s grant,” she says. A few years ago, a colleague approached her with an invitation to be co–principal investigator on an R01 application. She declined, asking to be listed as a collaborator instead. That decision allowed Ley to keep her early-stage investigator status and apply for NIH’s New Innovator Award, which she received in 2010.

Avoiding those fatal flaws

Scientific reviewers are looking for innovative ideas and a research plan that is feasible. At the Cold Spring Harbor meeting, grant reviewers and program officers noted that preliminary data were less important for new investigators than for established researchers. Include any promising preliminary data you have, but leave out inferior data. Poor or inconclusive preliminary data will hurt your chances for success.

Another important issue for your study section is feasibility. Does your plan make sense? Do you have the skills and specialized equipment needed to carry it out? Churchland, whose laboratory uses rodent models to study how different sensory signals integrate within the brain, submitted her first R01 application earlier this year. During her training, she worked solely with primates. She knew reviewers would question her experience with and expertise in working with rodents. But she recently published a paper in The Journal of Neuroscience documenting experiments that used rodents, so she thinks she'll be OK.

Because you now have only two shots—and because the process is so competitive—it's more important than ever to make your submission as good as you can make it. “It’s not good enough to be ‘very good,’ ” says Ley, who won her first R01 funding last fall. “The whole thing has to be perfect all the way through.”

Scientific rigor and relevance are the main things but writing matters, too. The application needs to be tightly written in a consistent style, with clear and communicative figures and careful attention to details such as references. Ley advises using auxiliary documents strategically to present essential information that doesn't fit under the 12-page maximum.

Good applications take time

An R01 application isn’t built in a day, or even weeks. Ley got the idea for her grant at a Gordon Research Conference in early 2008. She submitted the resulting R01 application 3 years later. In the interim, she applied for seed money from Cornell to do initial experiments and built up a team of collaborators.

Mentors and other seasoned investigators can give you feedback and advice on how to structure your ideas and arguments. To make the most of those opportunities, you need to start early and put together a very solid draft months ahead of NIH's deadline. That will give your colleagues time to read your application thoroughly and offer feedback, and you'll have time to think hard about how to improve the proposal. No one will feel harried and your valuable advisers and mentors won't feel exploited. “Don’t give it to them the day before you need to send it off. Give time for them to read it and then for you to make the appropriate changes,” Landis says.

Churchland set a deadline for herself 2 months before NIH's deadline. She sent the draft to her Ph.D. thesis adviser and postdoctoral mentor, asking for thorough critiques. She got a lot of helpful advice. Her early start was helpful for another reason, too: “A lot of good ideas take time to develop,” she says.

Understanding the review process

Program officers at the various NIH institutes can provide specific advice and help you think through a grant application. If you have questions about the best funding mechanism for a particular idea, the appropriate study section to review your proposal, or the best institute to support your work, program officers are good people to ask. Program officers often attend major scientific conferences in their fields, so these are good places to connect and talk informally. During one of these conversations, a program director told Ley, “Don’t even bother to send your [R01] grant without preliminary data.”

A very good way for junior faculty members to learn more about what study sections and reviewers are looking for is to participate in study sections themselves. NIH recently created an Early Career Reviewer program, which is intended to increase diversity among reviewers and encourage participation by investigators from institutions that don’t typically receive R01 grants. Hector Biliran of Xavier University of Louisiana in New Orleans participated in the program last October, reviewing three R01 grants in depth and contributing to the discussion of several others. It gave him an inside look at what makes a proposal stand out and how experienced investigators write proposals. “It’s more of a hands-on experience,” he says. Recently funded by an R15 grant for his work on cancer biology, Biliran is thinking about how he might develop a competitive R01 application.

Program officers can’t talk with you with about an application that is under review, but they do sit in on the study section discussions and can talk later. So once you receive your scores and the summary statement, give the program officer a call. He or she can help you interpret comments and weigh their importance.

Funding decisions aren't always made promptly. Even after you get your scores and comments, delayed federal budgets can stall decisions. If you think your initial scores might fall within the payline, talk with your program officer about reviewers’ comments and address them. Your prompt attention could make a difference between being funded and narrowly losing out. If your application is not scored, or is scored outside the payline, your program officer can talk with you about your options and whether it makes sense to revise and resubmit.

Retooling after rejection

No one likes criticism or rejection, but it happens to everyone. Critiques aren’t personal and can serve as a guide for reframing and refocusing work.

Before Ley submitted her recent R01 proposal, she received “grueling feedback” on a related NIH submission. The combination of learning from those critiques and collaborating with an experienced investigator—Cornell geneticist Andrew Clark—on the new application proved crucial to her success.

If reviewers point out flaws in the first submission of an R01, take them seriously in preparing a resubmission. Sometimes small revisions and clarifications might satisfy the study section. Other times, you may need to completely rethink the idea or your methods. The comments will help you decide.

Once you have been rejected twice, you have to start over, but you don't have to throw out everything you've been working on. Your next attempt must have a new idea at its core, but just how new it needs to be is open to interpretation. Maybe you can use the same tools to look at a different system or look at different questions within the same system, Landis says.

There's no formula for deciding whether a new idea is new enough—but there is a computer program. NIH is using text checking software, and similar wording could raise questions about whether your application isn’t sufficiently new, even if you have made substantial changes. So don't copy language from the old proposal into the new one.

When in doubt, consult a program officer.

Follow your passion

In a tight funding environment, you might be tempted to cram yourself into a niche and build your grant applications around the topics you think are most fundable. At the Cold Spring Harbor meeting, Robert Finkelstein, NINDS’s director of the Division of Extramural Research, advised against this strategy. “Follow your bliss,” he said. Your application will be stronger if you’re passionate about and committed to the ideas that you’re pursuing.

That reminder was welcome, says Churchland, who noted how easy it is for young investigators to feel constrained by funding challenges. “It was kind of encouraging to hear somebody say that the things that brought us into in the field in the first place, a love of science and a passion for doing research, are the things that will help us at this new stage of our careers,” she adds. “I hope he’s right.”

More NIH funding tips from the new neuroscience faculty meeting at Cold Spring Harbor Laboratory

• Join NIH’s listserv for a weekly list of requests for application (RFAs) and other funding updates. This is one of the fastest ways to find out about new funding opportunities.

• You can apply for a grant in response to a specific RFA and then, if your application fails, resubmit an investigator-initiated proposal. Your RFA submission doesn't count as one of your two strikes, so this way you get three chances instead of two.

• If your work fits into the priorities of more than one NIH institute, propose a second (or even third) institute on your application. Paylines and funding priorities differ across institutes, so a grant that misses the mark at one institute might be funded by another.

Sarah Webb writes about science, health, and technology from Brooklyn, New York.


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