Significance – NIH style
The significance section of an R01 is probably the most misunderstood part of the entire NIH grant. Perhaps this should come as no surprise, as this section has been a bit of a moving target over the past several years. Another source of confusion may be that Webster’s definition of significance and the NIH’s definition are “significantly” different. A brief history lesson may shed some light on why the significance section is a bit murky and will put today’s directives in context.
A brief history of significance
Way back in the dark ages, when getting your NIH review in the mail as a “pink sheet”, the R01 proposal was 25 pages long. Significance was included with background, and given the overall length of the grant, background often expanded into a verbal upchuck of information about the topic at hand. In 2009, the powers that be decided to give the reviewers a break and the 25 page limit was reduced to 12. The background and significance section slimmed down and was intended to highlight key findings rather than review the world’s literature. In 2016, spurred on by the need for public accountability, NIH grants underwent a major overhaul and the significance section had a new set of instructions. Significance was to include the word premise, which was defined by the NIH as “the quality and strength of the prior research used as the basis for the proposed research question or project; this is distinct from the hypothesis or justification.” The significance section was also to describe the strengths and weaknesses of the prior research. Since these initial instructions, the word premise has been dropped and quality and strength of prior research is addressed as, wait for it…., rigor.
Webster defines significance as “the quality of being important”. Investigators must like this definition, as most significance sections that I have read include something about the importance of the work. However, the NIH forgot to check Webster’s, and if you only include statements about the importance of the work your significance section will miss the mark. The NIH assumes success of your specific aims and wants to know “how will your work, successfully carried out, impact the field?”. I put the word successfully in italics, because if your work is founded on weak preliminary data and/or a poor approach, successful completion of aims will not have a major impact on the field.
Significance today
Knowing the evolution of the significance section might explain the potential differences that you’ll see either as a reviewer or in reading examples of successful grants. Now let’s head back to the future. What are reviewers looking for in today’s version? The current significance section looks for impact based on the rigor of prior research. What is rigor of prior research you ask? Right from the horse’s orifice of choice, rigor of prior research is defined as “the quality and strength of the research being cited by the applicant as crucial to support the application; this is distinct from the hypothesis or justification.” It’s premise without the word premise.
As part of the rigor of prior research, the applicant is supposed to address the “strengths and weaknesses of the prior research used to support the application and describe how the proposed research will address weaknesses or gaps identified by the applicant. This may include the applicant’s own preliminary data, data published by the applicant, or data published by others.” Here is your opportunity to discuss the strengths of your preliminary data (for an R01) or published data (R21, R03) that are the foundation of your hypothesis. The weaknesses you will, of course, be addressing in the grant.
Structuring your significance section
Although the exact order isn’t critical, the elements described above must be included in your significance section. I suggest starting with a brief paragraph restating the critical need your proposal addresses and how successful completion of your proposal will change the field. Remember, this is the NIH definition of significance. If you have a surprising statistic that supports the need here’s the spot. In the next paragraph restate the hypothesis, followed by the strengths of your key supporting data. I don’t think it’s over the top to include a sub-header entitled “Rigor of prior research”. It’s hard for a reviewer to claim this wasn’t addressed when you have it written as a separate section. From there you discuss the weaknesses, which prepares the reviewer for the approach section where they will be addressed.
Here’s an example of a significance section, which is taken from a proposal using e-yarn as a way to detect lost socks. This example highlights my approach, but as the saying goes, there are many ways to skin a significance section.
Socks are the number one lost laundry item in the United States. Every household is, at some point, plagued by the problem of lost socks. Lost socks generate substantial psychological and financial burdens on many households, which escalate exponentially in families with 8 feet or more. Last year alone, replacement costs for lost socks reached 1.2 million dollars, and this cost is on the rise. Experts from the Simpson Family Foundation, a think tank focused on family issues, project that by 2040 the problem of lost socks will surpass health care as the number one drain on family budgets. New ways to find lost socks must be found now to avert this future financial catastrophe.
Rigor of prior research: We hypothesize that socks made with e-yarn will be detectable within an average size US home (2000 sq feet) using a barcode cell phone application. This hypothesis is built on strong data demonstrating that detectability of e-yarn is resistant to dye (Figure 1), water (Figure 2), and that 1 g of e-yarn is currently detectable up to 2000 feet (Figure 3). Based on these data, the proposal that follows will develop a unique, cost effective way to find lost socks. Successful completion of this proposal will represent a significant step towards eliminating the financial and psychological burden of lost socks. A side benefit of this approach is that, if desired, family members with similar sized feet can identify their own socks. Finally, this technology can be applied to other problematic clothing items such as cufflinks and earrings.
This proposal will address the following weaknesses in preliminary and published data. Our preliminary data shows that 1 g of e-yarn is detectable by RFID up to 2000 feet. However, we have not yet tested smaller amounts of e-yarn. Since it is not cost effective to make an entire sock of e-yarn, we will determine the smallest amount of e-yarn that can be woven into a sock and remain detectable. This question will be addressed in Aim I.
Many studies have taken a compensatory approach to the problem of lost socks rather than finding the sock itself, which is the goal of this proposal. Some studies, for example, suggest that purchasing a 6 pack of socks can address the lost sock problem.2-5 However, these studies have only used white athletic socks and do not take into account more expensive dress socks. Another approach, reported by Hanes, et al, was to wear mismatched socks.6 However, their study was limited to 15-25 year olds, who have been shown to enjoy wearing mismatched socks.7-9 A similar approach, wearing only one sock, was supported by findings of Scholl, et al.10 However, this study involved a more sedentary population. When tested in a younger, more active population, Adidas et al found that the one sock approach was not feasible due to foot sores and odor, particularly when studied in student athletes traveling together on buses.11,12
As outlined above, this example starts with a restatement of the problem, adding a little more detail than what was presented on the specific aims page. From there, I restate the hypothesis, so that it is fresh in the mind of the reviewer as he/she goes on read the key data supporting your hypothesis. These key data are the “strength” of the strength and weaknesses of supporting data. Make sure that you demonstrate the strength of your data with figure legends that support rigor and reproducibility (positive and negative controls, statistics, numbers of replicates and experiments/animals, etc). After listing the key supporting data, I describe what will happen upon successful completion of the proposal. Because this section focuses on the proposal, rather than the problem, the successful completion part flows nicely from here. I then finish by discussing the weaknesses/gaps that will be addressed.
Where’s the background?
Since the NIH got rid of the “background and significance” section it’s dealer’s choice as to where to the background. Do you even need a background section and if so, how much? Yes, you need some background information. I think of background as a “need to know” section. Include what the reviewer needs to know so that he/she understands your work and its context. Some investigators still put this information in the significance section, and others put it at the beginning of the approach. I do not recommend putting your background with the significance, because you risk reviewers missing the information the NIH asks for (and you are scored on) by getting caught up in background details.
If nothing else, remember that the significance is the impact of your proposal, if completed successfully, on the field. Reviewers are instructed to score grants with this idea in mind. Now time to do some laundry.
Additional Resources
Sell Your Specific Aims Using the PASTOR Method
Avoiding Barriers Between Your Work and Your Reviewer
Your Grant as Story – the Rogue Character
What the F? Reference Letter vs Letter of Support
Communicating to the reviewers your ability to succeed in science and the support you have around you to make that happen is a crucial component of a fellowship application. Often, your mentors, collaborators, or course instructors convey this via reference letters or letters of support. But what is the difference and how do you determine who to ask to write each type of letter?
Reference Letters
NRSA fellowship applications must include at least 3, but no more than 5, reference letters. Those asked to serve as a referee should be able to speak to your qualifications and potential to be a successful scientist as well as to the training program that will guide you to that goal. You may want to consider asking previous research mentors, current collaborators not listed as senior/key personnel in the application, or course instructors to write a letter. The mentor/co-mentor(s) listed in the application may not submit reference letters. They share their commentary on your qualifications, abilities, training, and future plans in the Sponsor/Co-Sponsor statement. In addition, any other senior/key personnel listed in the application may not serve as a reference.
Once you have developed a list of 3-5 reference letter writers, reach out to those individuals to ask them to write on your behalf 6-8 weeks prior to the application due date—earlier if possible. Once a referee agrees to write, send instructions on how to submit the letters, which are submitted directly to the NIH. In the instructions, you will need to provide your name as it appears in Commons, eRA username, and the number of the Funding Opportunity Announcement (FOA) to which you are applying. It is helpful to also include specific highlights you would like the writer to focus on regarding your abilities, potential, and training as a scientist. Providing an updated version of your biosketch or CV is helpful. Additionally, you could offer to write a draft of the letter. In that instance, be sure to leave humility at the door and boast about your accomplishments and abilities. Also, make sure each letter you write has a slightly different voice to it so they don’t seem like they were all written by the same person.
Applicants are not able to view reference letters but will receive an email and/or be able to log-in to the eRA Commons system to confirm each letter has been received. The list of reference letter writers should be listed in your cover letter with the writers’ names, titles, and affiliated departments and institutions included.
*Helpful Tip* Make sure the referees have the correct FOA. Fellowship FOAs update on an almost annual basis. It is helpful to confirm you still have the correct FOA a week or so prior to submission as there may have been an updated FOA released since you originally reached out to your letter writers. If a new FOA has been announced for the application cycle to which you are applying, you will need to update your referees. Without the correct FOA, submitted letters will not be associated with your application in eRA Commons. If letters are submitted under the wrong FOA, the eRA Commons help desk can assist in associating the letter with the correct FOA/application as long as the letter was submitted on time.
For additional guidance on reference letters, visit the NIH Reference Letter webpage.
Letters of Support
According to the NIH fellowship instructions (Forms F), letters of support should be submitted by those collaborators, consultants, or advisors who plan to contribute to the scientific development of the applicant or contribute in the execution of the applicant’s planned project and research training. A collaborator in a neighboring lab or at another institution, the director of a core institutional resource that will be used (i.e., mouse facility or biobank), or a scientist who may train you on a specific technique are examples of those you may want to request a letter of support from. The letter should include specific details on how the individual (or resource) will contribute to your project and/or training. It is often helpful and expedites the process if you draft the initial letter.
Letters of support are not a required component of an NRSA fellowship application. However, those who do plan to submit them may include up to 6 pages of letters of support which are compiled into one PDF and uploaded as a single application component.
Those planning a career in academia will continue to draft these types of letters for their future K, R, and a multitude of other grants, so no better time than now to get comfortable with the distinction between the two and how to write each. Best of luck!
Additional References from NIH
Difference Between Reference Letters and Letters of Support
NIAID Overview of Letters of Support
A Smorgasbord of Grant Writing Pointers with a Side of Wit
Edge blogger, Dr. Lucile Wrenshall, MD, PhD, Professor at Wright State University, has produced a prodigious series of blogs with practical and entertaining writing advice. Whether focused on your own writing, mentoring, or teaching scientific writing, it’s a treasure trove. Covering insights for grants, manuscripts, and plain language, she highlights style pointers and common mistakes. We’ve rounded up the posts so you can select from the full menu:
1. Beginner’s Eye for the Science Guy (or Gal)
The beginner’s eye is observing as if you’ve never seen something before. What if you reviewed the last several months of experiments as if you’ve never encountered them — with no a priori hypotheses, no preconceived ideas about meaning, just a clean slate and a basic understanding of the science (hey, that sounds like a reviewer!).
2. Your Grant as Story – the Rogue Character
Have you thought of a grant proposal as a story with a cast of characters? For a reviewer, even those in your field, getting a grip on your characters is like going to a family reunion where you don’t know most of the people. The onus is on you to set the stage for each of your characters. A sudden appearance of molecule “Janet” will confuse the reviewer and break the flow of the grant.
Today, NIH significance sections look for the impact of the proposal against the ‘rigor of prior research.’ Reviewers score significance based on how well a proposal, if successful, will address weaknesses and gaps in the field. (Bonus: discover an ingenious solution for finding lost socks.)
4. Sell Your Specific Aims Using the PASTOR Method
Beyond prayer and hoping for the best. Sell your aims with a ‘loving, caring, protective attitude towards your customer/reviewer.’
5. Building the Specific Aims in Three Parts
- Part I: Use the first paragraph to explain the scientific problem.
- Part II: The second paragraph describes your solution (a solution that needs the sponsor’s investment).
- Part III: The Aims conclude with the next logical conclusion, your hypothesis. What is a good hypothesis?
6. Writer’s Toolbox: Creating Sentences That Flow
Intentional writing forges a path for your intrepid but weary reader/reviewer. If words are cobblestones, then sentences are the way the stones are put together so that one can walk through the forest (grant) without getting lost.
7. Avoiding Barriers Between Your Work and Your Reviewer
Clarity is key to preventing a brilliant idea from being muffled (as words through a mask). Sneaking in definitions and reminders keeps the reviewer connected to your story. Selectively using abbreviations (or opting for long-hand) removes distractions for the reader.
Visit drlucywrenshall.com for more on grant writing, manuscripts, and 1:1 writing help.
Related Resources:
Ome Sweet Ome
The Scientist’s Adverb
What’s Your Water?
Big Words
Your Grant as Story – the Rogue Character
Humans are wired for story. Your grant, whether you realize it or not, has a cast of characters including a hero, villain, supporting characters, plots and subplots. If you think about your grant in these terms when you write, the ideas will flow better and your proposal will be easier for outside readers (code for reviewer) to understand.
Before I explain further, I have a confession to make. I review grants for a large government institution that funds human health-related research. I confess this because things that bug, annoy, peeve, confuse, or irritate me as I’m reading a grant might have the same impact on reviewers reading your grants. Reviewing grants is a great learning experience, and I’m here to share what I’m learning.
Today I’d like to talk about the rogue character. As mentioned above, your grant, just like a novel, has a cast of characters. Unlike a novel, however, you don’t have an unlimited amount of space and time to introduce your characters. You have one, dare I say specific, page to introduce your main characters. For the reader/reviewer, even those close to your field, getting a grip on your characters is a little like going to a family reunion where you don’t know most of the people. You’re “hanging on for dear life” to remember the name of your second cousin twice removed, who you were just introduced to a few minutes ago and is now heading towards you with his significant other.
Let’s look at an example. To maintain anonymity, I’ll stick with the reunion analogy. I was minding my own business, merrily reading a proposal, and taking notes to keep the relatives straight. I already met the problem, the drunk uncle, whose behavior has gotten out of hand. He needs an intervention. Along comes the young whippersnapper nephew, who has a special relationship with the uncle and is going to facilitate these interventions. The uncle has had this problem for a while, so he’ll need at least 3 different types of interventions. Now that I’ve met everyone, and I know the interventions, I’m settling in to see how the nephew is going to pull this off. All of a sudden, in walks Janet. Huh? Wait a minute, who in tarnation is Janet? Nobody knows her. Maybe she’s a “reunion crasher” just pretending to be a relative. I go back through the story/proposal to make sure I didn’t miss anything, and low and behold there she is. Her name is on a list of relatives, but I don’t know who she is or why she’s there. Turns out that Janet is going to play a major role in the first intervention, but since I don’t even know how she’s related, I’m a bit perplexed. In addition to being perplexed, the flow of the story is broken, and now I need a coke and some potato chips.
Needless to say, Janet’s arrival would have been a lot less confusing if I would have known ahead of time that she was coming. Maybe the author of this story thought it would take up too much space to tell me about Janet ahead of time, or maybe the author thought I was a mind reader. Reviewers get that a lot. However, just like the author of a good novel, the onus is on you as writer to properly set the stage for each of your characters.
I hope this analogy hasn’t been too much of a stretch, but sometimes it’s more fun to talk about books and relatives than signal transduction pathways. If a molecule/pathway/chemical, etc is a major part of an aim, the reviewer should be introduced and know the context prior to the aim itself. Otherwise, you run the risk of confusing your reviewer. In the world of grants, confusion = no. And on that happy note, I’m going back to the story. Turns out the drunk uncle was an American spy in Russia during the cold war. Might explain the vodka.
Related Resources:
How to Make Writing More Memorable and Persuasive
The Conversation: How To Get A Grant – Part 1
Tips for Scoring a VA Career Development Award
For those with a connection to the Veterans Health Administration, the VA CDA 2 can be a great way to propel your career. These awards are bigger than an NIH K, but come with unique requirements. Dr. Eric Tkaczyk recently received one of these grants, and he shares his tips for success below.
Benefits
A VA CDA gives you much more money than an NIH K, with some awards comparable in size to an R01. You receive five years’ salary at 75% effort with no salary cap. You’ll also receive enough money to pay for a postdoc, as well as bonus funding for filing patents.
At around 30% for most VA locations, the success rate is higher than many NIH institutes.
Drawbacks
The VA only gives you four opportunities to submit a CDA application in your life. Plan carefully.
You must receive approval of a letter of intent before you can apply.
You receive $30,000 for equipment, but it can take over a year to order and receive that equipment.
VA-specific Tips
Most, if not all, of the tips in our earlier series of posts for writing NIH K awards apply to VA CDAs. These are the quirks specific to the VA:
- It’s a much bigger application than a K. Most come in around 200 pages, with an 18-page research plan.
- Since you receive a lot more money, plan in advance how you’re going to use it. Dr. Tkaczyk recommends using it primarily for salaries and core resources.
- Unlike the NIH, where you can (and should) call your potential Program Officer directly, at the VA you never speak directly to your PO. Always go through your local Chief of Staff. (That said, your PO might email you.)
- Reviewers need multiple reminders that you can’t do full-time research during clinical training.
- Reviewers can become suspicious that your mentors won’t stick around for the full five years; prophylax against this in their letters.
- Given the increased length of the application, it’s more likely that reviewers will skim or miss things, so each page needs to stand alone.
- Use plenty of metrics and accepted standards, and show you meet them.
- If resubmitting, everything rides on the cover letter. Polish till it shines.
- You must capitalize “Veteran”! There are other nuances to writing for the VA; use NIH RePORTER to find awardees on your campus and seek their advice.
Visit the VA’s site for career development awards for more information.
More Resources
Not that Kind of Grant: Tales of Early Career Investigator Grants
More Things I Wish I’d Known Before I Wrote My K
Many colorful letters. Useful for concepts
Three more K awardees share the advice they wish they’d received before preparing career development awards. Writing your K? Listen up. (And read advice from prior K awardees.)
Prepare Early
Before you start writing, know which award and which institute you’re trying for, as this will influence how you shape your application.
Research NIH institutes’ paylines. Your work may fit, or could be lightly massaged to fit, at multiple institutes, so be aware of success rates.
Not all institutes allow the same number of years on a K. Some count time spent on a K12 toward your six-year maximum of career development award time. This will impact how many years of support you request.
Review videos from institute meetings and special events. You can learn quite a bit about where the institute is going and what they’re interested in funding from these panels, addresses, and symposias. (Here’s NHLBI’s list of past events, for example.)
Use NIH Matchmaker and NIH RePORTER to see what’s being funded in your research area.
Get permission from leadership to apply. Your department chair or division chief may not be able to spare 75% of you right now. Know this before you start writing.
If you can, use the Early Career Reviewer Program to sit on a study section and see how the sausage is made.
Start early. Our grant pacing guru recommends at least 16-20 weeks out.
Even the budget will take more time than you think. You can’t just do it the week before the due date—at least, not without making your grants manager VERY unhappy.
Writing the Application
“Training” doesn’t need to mean, or even include, going to class. At this point in your career, much of the training you need can be accomplished more quickly and easily by attending conferences, summer institutes, intensives, or workshops, and working with/learning from the right people. These people might be your mentors who are teaching you the finer points of your shared field; they might be folks at other institutions you visit for two weeks a year to learn a specific technique in their lab.
Use your mentor letter to cover ground you can’t fit into the body of the grant. (Yes, you will draft their letters.)
Everyone reads your biosketch, even reviewers not assigned to your grant. This is your best place for self-promotion, so craft your personal statement and contributions to science carefully.
For your resources and facilities section, only include those cores, resources, etc. that you will actually use. This means edit the boilerplate text your institution or department keeps, don’t just copy it in without any changes. End paragraphs by noting that this is the group or core you’ll be using to do x.
If you’re mostly using data from large, well-known repositories, ask for 3-4 years on your K. Reviewers know you won’t need to spend time collecting or cleaning the data, so showing that you realize this and understand your grant doesn’t need to be the max number of years makes you look good.
Allay Potential Skepticism
To allay fears you won’t be able to launch your proposed study, show reviewers you’ve already got it rolling. Include a timeline with a “T minus 1” year to show what you’ve already accomplished, whether that’s getting approval from review boards or owners of data sets or specimens you’d like to use, enrolling participants, or breeding mice. Cite your IRB and/or IACUC approval numbers in the text.
Generic personal statements in mentor or co-investigator biosketches imply they’re not committed to you. Ask for the Word document rather than a PDF and tweak the personal statement to reflect their support.
Consider editing the “contributions to science” section of mentor biosketches to emphasize work that is most applicable to your research and make it clear why you chose that person for your mentoring committee.
Technical Items Are Just as Important
Make sure you choose the right RFA. Different RFAs allow or disallow a clinical trial (and NIH has broadened their definition of clinical trials); you’ll get shot down if you respond to the wrong one.
You can update your publication info up to one month before review. This allows significant time to get more papers out; review committees meet approximately 4-5 months after each of the K due dates.
For resubmissions, don’t forget to update dates/other info in letters. Some study sections really care about this. Don’t let an easy fix hold you back.
Use the space you’re given. NIH allows 6 lines per inch, so a 10 inch page=60 lines per page. A standard Word document with .5” margins in 11pt Arial single space font will fit 55-56 lines. This means you can fit 4-5 more lines per page with the right hack. (Go to “Paragraph,” then under Line Spacing choose “Exactly” instead of “Single.”) Voila, more lines!
Get to know your program officer before you submit. POs who have seen you through earlier grants, like Loan Repayment or fellowships, are invested in you and want to see you succeed with your K. Even if you haven’t applied for NIH grants before, if the PO has spoken with you about your science he or she will have a face, or at least a voice, to put with your name.
You can ask to switch study sections if you were assigned to a less favorable one. Call the PO for the study section you want to ask if they’ll scoop up your application. Be aware this might not make you any friends.
To avoid headaches during the Just In Time (JIT) period, keep the same study name between your IRB application and your grant. One panelist found that a different study name between the two caused considerable confusion. If you’ve already submitted your K with a different study name, talk to your institution’s grants management office so they aren’t at a loss when asked to verify your IRB approval.
Thanks to panelists Derek Smith, DDS, PhD; Eric Tkaczyk, MD, PhD; and Ebele Umeukeje, MD, MPH, for their great advice.
Additional Resources
Not that Kind of Grant Application: Tales of Waiting for Career Development Awards
How a Jail-house Letter and Goat Research Can Get Your Grant Funded
What the F? Deciding When to Submit an NRSA Fellowship
In a previous “What the F?” post, I discussed the NRSA fellowship and why you should consider writing one. The next step in the fellowship application process is to decide when to apply. The usual answer is “as soon as possible”. The NIH wants to support your training, so it is best to apply as early in your training as you can. But what factors determine the best time for you?
Do I Need All the Data?
Applicants often worry that they need to be an expert in their area of research and have a mountain of data before they can apply. However, NRSA fellowships are designed to support your training as a scientist, not the science itself. Good science does need to be presented, but the training plan is the most important factor when reviewing fellowship applications. Reviewers should be confident that you have a basic understanding of your science and what question(s) you are trying to answer, but you need not be an expert on the topic prior to submitting. That’s what the training is for! When submitting a fellowship application, it is okay, and often expected, that you will use data and/or findings from a current or former lab mate’s work. Just be sure to give credit to the team.
When are Applications Accepted?
What else goes into determining when to begin the application process? NIH due dates are a great first start. Fellowship applications have three submission cycles with standard due dates on the 8th of April, August, and December. After submission, it takes an NIH institute 5-9 months to review an application and announce whether or not it will be funded (see table below). So, if you want your funding to start April 1st of next year, you must submit your application nine months prior on August 8th of this year.
How Much Time for Writing?
In addition to the 5 – 9 months needed for NIH review, you need to determine how much time to allocate to the writing process. In my experience, it takes an applicant 3-6 months to gather the information required to write, review, and edit a well-thought-out application. Questions to consider when determining how much time to schedule for writing include:
- What amount of time do coursework and research take in my week?
- Are there other regular commitments I need to devote time to such as lab meetings, journal clubs, etc.?
- Does my lab, collaborator, and/or institution have descriptive text available on equipment, facilities, animal use, etc. or do I need to create original text?
- How available is my PI (and collaborators) to provide feedback and edits? How far in advance do they need a draft to provide comments? How much time do I need to make the recommended edits?
- How much time do those I’d like to ask to write letters of recommendation need to do so? [Voice of Experience: Ask them at least 3 months in advance.]
When the 5-9 months it takes for the NIH to process a Notice of Award is added to the 3-6 months to write, you’ll find you need to begin writing a fellowship application 8-15 months prior to when you would like your fellowship funding support to begin (see graphic below). That is, of course, if your initial application is funded, which is never guaranteed.
How Do I Develop a Timeline?
I find it helps to start at the end and work backwards. In an ideal world, when would you want this funding to begin? It’s helpful to consider what funding sources are currently available to you. Are you on a training grant that ends in 10 months? Does your PI have dedicated funding on a research grant that must be expensed over the next 20 months? Once you determine that ideal start date and how much time you need to write, work backwards 8-15 months and that is when you should target starting your application.
Finally, here are a few additional unique items each population of biomedical trainees (doctoral candidates, dual degree students, and postdoctoral fellows) might also want to consider.
Doctoral Students
- F31 and F31-Diversity guidelines require that a doctoral student have passed their qualifying exam prior to when funding begins. You may submit prior to completing your qualifying exam, but you must have completed and passed it prior to beginning your award.
- Does your graduate program offer a grant writing course that will help guide you in the process? If yes, you may want to plan your submission date for after completion of this course.
- Doctoral students are eligible for up to 5 years of NRSA support, which is cumulative of time appointed to NRSA funded training grants (typically T32) and support from an individual fellowship. Does your institution/program typically fund a portion of your training via a T32 appointment? Does that impact when the ideal time for you to apply is?
MD/PhD (and other dual-degree seeking) Students
- F30 (Institution with MSTP or Institution without MSTP) guidelines require that MD/PhD students must apply within 48 months of matriculation to their dual-degree program. This is 48 months from the start date (typically orientation) of the earlier of the MD/PhD or MD program, if on different schedules. This policy may be slightly different for other dual degree programs (i.e. AUD/PhD, DDS/PhD, etc.).
- F30 guidelines also stipulate that at least 50% of time on fellowship support must be for training during the graduate years. If you are in a 2-4-2 program and would like the final two years of medical school training supported by your fellowship, you would need to apply no later than the first semester of your second year of graduate school so that funding could begin in your third year (remember the 8-15 months we discussed above to turn a grant around).
- Dual degree students are eligible for up to 6 years of NRSA funding, cumulative of NRSA T32 and fellowship support. The layout of your program may dictate the best time to apply and/or the number of years of support to request.
Postdoctoral Trainees
- For postdoctoral trainees, the answer to when to apply is simple. Now. The NRSA provides three years of funding for postdoc training, cumulative of both time you have been appointed to a T32 institutional training grant as a post-doc and time funded by your F32 postdoctoral fellowship. [Quick tip: The cumulative amount of time appointed to a NRSA funding source restarts after completion of pre-doc training.] On average a postdoc experience is 4-5 years and as stated above, it takes 8-15 months to write, submit and receive funding, so you will want to start writing as soon as possible in order to maximize the amount of funding available to you.
- A question to consider as a postdoc is when to submit your K-award post-F32 submission. Check out these blogs for more information on that topic.
Shark Tank for Scientists: NIH’s SBIR/STTR Grants
Have you ever searched for something in NIH RePORTER and seen some unusual grantee organizations in the results, maybe ones with “Inc.” or “LLC” in the name rather than “University” or “Medical Center”? If so, you’ve come across grants made to small businesses through the SBIR/STTR programs.
Go from idea to production with SBIR/STTR funding.
The federal government’s Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs grant over $1 billion per year to businesses in the private sector commercializing biomedical technologies, drugs, and devices. Five agencies participate: HHS (NIH), DOD, DOE, NSF, and NASA. Relevant to academic researchers is that the SBIR program encourages, and the STTR program requires, that these small businesses collaborate with a non-profit research institution. These mechanisms tend not to be first in most PIs’ minds, and as a result, at some institutes the paylines are fairly high. For example, in FY2017, the success rate for STTRs at NIMH was 48%. (Use NIH’s Data Book to view success rates for your institute.) Amount of funds per grant varies according to the science, but can be up to $1,710,531 over two years.
I sat down with Robert Freundlich, MD, who recently sat on two study sections for these grants. He told me what these grants are all about and why you might want to collaborate with a small business to apply for one.
What Kind of Science Do They Fund?
SBIR/STTR grants differ from traditional NIH research grants by having commercial potential. Rather than the publications and further grant applications that define success for R01s, the end goal for these grants is to bring a product to market. “Product” is broadly defined and can include devices like artificial joints or implantable monitors, clinical equipment like improved blood testing or imaging units, and drugs. The company that receives the grant can also market and sell the product, or the PIs can sell it to another commercial entity that will bring it to market.
NIH defines two phases for these grants. Phase I is more exploratory, including high-risk-high-reward aims. If you have an idea for a new device, but don’t know if it will work and need some funding to test it, you have a Phase I idea. Phase II projects have solid scientific foundations (i.e., the device definitely works) and now need to continue validation, scale up production, and/or request regulatory approval from the FDA or other agency. Phase II grants are only made to projects that have received a Phase I grant.
As with more familiar grants like R01s, NIH has topics they really want to spend SBIR/STTR money on. Right now, hot topics include opioid addiction and personalized medicine, among others. (NIH’s current medical research initiatives.) If your work fits into one of these initiatives or special focus areas, it may better your chance of getting funded.
Format
SBIR/STTR grants are structured and reviewed largely like R01s, with an overall impact score and scores for significance, investigator(s), innovation, approach, and environment. The business plan should be integrated with the research plan. For a Phase I application, this might mean a “future directions” or “planned Phase II” section explaining that upon completion of Phase I, you will move from prototype to production, request regulatory approval, or start selling the device. Phase II applications often include sections detailing methods of production, marketing plans, expected revenue stream, or other commercialization plans.
These grants allow for and encourage a much more diverse roster of collaborators than is typical for R01s. For SBIRs, the PI must be employed by a small business; for STTRs, the PI can be employed by a small business or the collaborating academic institution. (Other requirements for splitting the work between the collaborating entities.) For both types, applications are strengthened by including private sector investigators who understand how to commercialize a product. Also important is to clearly explain who is doing what with the project and how that person’s specific background has given him or her the ability to do their part. For example, if you’re an Assistant Professor with no experience in industry, describe how your co-investigator, the COO from your collaborating small business, who has brought several products to market, is going to guide the commercialization aspects of the grant.
Study Section
No standing study sections exist for these grants; all are ad hoc special emphasis panels. Reviewers range from researchers at academic institutions, to small biotech business CEOs, to federal regulators. Panel members work in a variety of areas from basic to translational or clinical to computer science, unlike study sections you may have encountered where all the members are, say, pulmonologists doing basic science in wet labs. One panel Dr. Freundlich sat on had only two physicians in the whole group.
When writing an application, keep in mind that while reviewers have some scientific background, it’s unlikely to be in your exact area, and they were invited to join the panel because of their expertise in bringing products to market or in federal regulations. Your science must be crystal clear and easy to follow for these people. By that same token, review panels include plenty of folks who will know if there’s a market for a device or drug like yours, and have experience bringing products to market, so your business plan should be solid too.
One way to learn a lot about these grants in a very short amount of time is to join a review panel through the Early Career Reviewer Program. If chosen to join a SBIR/STTR study section, you’ll see plenty of these grants and learn a lot about how they work and how they’re reviewed. It’s also a great opportunity to network with smart people outside of academia.
FURTHER READING
What the F? An Introduction to the NRSA Fellowship
In fiscal year 2020, NIH awarded approximately $180 million to support pre- and postdoctoral trainees through its National Research Service Awards (NRSA) individual fellowship programs.
What exactly is an NRSA individual fellowship and why should you apply for one? I’ve managed predoctoral fellowships for five years and have advised dozens of students at an R1 university with their submissions. Here’s an overview of these awards and my suggestions for why you should apply for one.
Fellowship awards provide financial support to students enrolled in doctoral programs and those who have recently graduated with a doctoral degree (PhD, MD, PharmD, DDS, etc.) who decide to further their scientific training through a mentored opportunity with a faculty sponsor in order to pursue an independent research career in academia.
NRSAs typically include funding for tuition, a stipend (living expenses), and an institutional allowance, which is often used to cover the costs of health insurance, student fees, travel to scientific conferences, and/or conducting research.
The NIH offers a variety of fellowship awards, but this post focuses on those intended for the singular pre- or postdoctoral experience. Those opportunities include the F30, F31, F31-Diversity, and F32.
NRSA Individual Fellowships for pre- and postdoctoral trainees
Click image for the funding announcements of NRSA fellowships
NRSA fellowships support the unique training pathway of an individual trainee. Unlike R01s or similar research grants awarded based on scientific merit, fellowship awards value the training plan as much as, if not more than, the scientific merit of a trainee’s research project. Good science needs to be presented, but a thoughtful and intentional training proposal that highlights your plans to engage in educational, professional, and scientific training activities is essential. A commitment from your mentor and institution stating how they will support your training is also required.
Some individuals apply for fellowships because the financial support is critical to them being able to complete their training. However, if you are in a fortunate situation where your training experience is fully funded by your mentor and/or training program, there are still benefits to applying for an individual fellowship.
Becoming an independent researcher means submitting grants. Lots of them. All the time. Writing a fellowship provides you with your first opportunity to learn how to read a funding announcement, pace your writing, write persuasively, and gather and incorporate feedback.
If you’re new to your research project (and if you’re a grad student or postdoc, you probably are), writing a fellowship application gives you the opportunity to read up on the background, synthesize the existing knowledge with your current work, and share where your preliminary data may lead. Even if your application doesn’t succeed, the process of writing it will lead to a better understanding of your science.
This is also an opportunity to refine your career goals and determine the additional training needed to obtain them. This may lead to a discussion with your mentor about what opportunities they are willing to support. How much time are they willing to let you be away from the lab to participate in career development training? Does your mentor have funds available for you to travel to professional conferences? How and where can your mentor provide you with networking opportunities?
Submitting a fellowship may be your first opportunity to develop a relationship with a Program Officer (PO) and/or Grants Management Specialist (GMS) at the NIH. A GMS once told me that they want to build relationships with trainees so they can invest in them and their science and, hopefully, follow them into their K and R01 funding.
If your fellowship isn’t funded, it’s an opportunity for you to gather feedback on your science and refine your writing style in a resubmission or in future grants. You can still list it on your CV to let future employers know you took the initiative to seek funding and gained skills in grant writing.
Prior success often indicates future success, and if your fellowship is awarded, it is a first step in demonstrating you can write an effective NIH grant application. Now go determine which opportunity best supports your training and start writing. Good luck!
More Resources
What the F? Reference Letter vs Letter of Support
What the F? Deciding When to Submit an NRSA Fellowship
What the F? Creating a Commons ID
What the F?: Childcare Costs Now Allowable
What the F? Advice for fellowship applicants from reviewers. Part 1
What the F? Advice for fellowship applicants from reviewers. Part 2
What the F? Advice for fellowship applicants from reviewers. Part 3
