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I’ve written lots of grants. Some of them even got funded! Here are some things I learned in my journey from foundation grants to K08 to R01.

Grants beget grants

I was fortunate to have a T32 fellowship during my post-doc, after my clinical training. This helped me gain additional skills in experimental design and statistics. Unfortunately, though, my primary project had a negative phenotype in vivo. I pivoted my research to studying cell-free hemoglobin in lung injury and needed to build a dataset to serve as the foundation for my K08 application. Based on advice from my mentors, I started small and applied for one-year grants from research foundations. These applications are usually more straightforward to put together and can sometimes need less data to be competitive. My first application for a research grant from the American Thoracic Society was successful, which allowed me to hire a research assistant. The extra hands helped me get the preliminary data I needed and strengthen my upcoming career development award applications. Based on the success of my ATS-funded work, I applied and was awarded a Parker B. Francis Fellowship. At that point, I had successfully competed for at least three grants;  although small, this bolstered my credibility and experience as I started to prepare my K.

Take advantage of grant writing resources

The first big grant is the hardest. I hadn’t seen many specific examples of funded grants and was overwhelmed by the number of documents it required. My mentors and near-peer colleagues were willing to share their grants. I also looked at several K08 applications from the funded grants library at my institution, and I enrolled in a grant writing workshop at my institution geared at planning for a K application. This gave me a step-by-step process for crafting a strong and unified application and helped me pace out the work over several months. These institutional resources and network connections were incredibly helpful and made getting my first big grant out the door much more feasible.

Grants require strategy

If you read my last post, you know I have two amazing mentors, Drs. Lorraine Ware and Julie Bastarache. While I consider them equally important to my career, at the time, Julie didn’t yet have major R01 funding, so we decided to have Lorraine serve as my primary K08 mentor with Julie in a co-mentor role. I initially felt terrible about this, because I worried that Julie wouldn’t get credit as my primary mentor, but both assured me that this strategy was essential to turning in the best grant that I could. We worked together to craft an application with strong sections on candidate accomplishments, career development planning, and discovery research. I had specific roles for each member of my advisory committee too.

As I started to plan my first R01 application, it was great to really dig into the mechanistic science. I had so many ideas and too many Aims to include. It was a struggle to decide what the final draft would be. I hadn’t quite realized how important it was to work out the science earlier in the grant writing process. The budget is usually due two weeks before the grant goes in. You have to turn in subcontract budgets two or three weeks before that. It turns out that you can’t write a budget if you haven’t settled on the science. Your budget also affects how much science you can do and who you can do it with, so you need to understand the details early on. Money matters and a realistic budget is key to the success of a project.

Understand the grant review process

After my K, I had some experience with the numerous components of a training grant. I worked over the next several years to develop a project to lead to my first R and was working on selling my science. I was selected to participate in the NIH’s Early Career Reviewer program. Not only is it fun to read other people’s science—they’re doing cool stuff and you learn a lot—but it’s really helpful to see other styles of grant writing. I found that grantsmanship really affected how well reviewers could summarize a grant. As you may know, three reviewers are assigned to each grant and read the whole thing. These three scores determine whether your grant gets discussed or not. The other 25 or so people in the room listen to the discussion, look at the figures and bolded words, and their scores get you funded.

(Shocking, right? But true.)

This experience taught me to really focus on the audience for your grant proposal. Consider what you can do as a writer to make the reviewers’ job easier. The more you can repeat key information across the grant, the easier it is for Reviewer 1 to present it to the rest of the study section so they understand what you want to do, get excited about it, and ultimately want to fund it.

Seize opportunity, but do so smartly

Towards the end of my K08, my research was mostly ARDS focused and my clinical work was dedicated to lung transplant. I was hoping to merge these interests with future grants. Then, I learned that a company was planning a longitudinal study of transplant patients that would require biospecimens and clinical data uploading. I jumped at the chance to participate, knowing that this would facilitate transplant-related sample collection that I could use (and reuse) in the future. Even better, the company paid for my time and my study coordinator’s time!

I felt like I was starting to get the hang of this physician-scientist pathway. Then, there was an NIH RFA for a series of U01 grants to develop a Lung Transplant Consortium. This was perfect! An opportunity to network with leaders in lung transplantation and a big grant. However, the U01 mechanism meant splitting the money among institutions. While it would pay for the study, it wouldn’t be sufficient to support my lab or my non-human research. If funded, this would prevent me from using my Early Stage Investigator status for a traditional R01. I talked with my mentors (remember my last post on how fantastic they are?) and we decided that I should be a co-I on the U01 proposal with Dr. Ware as the site PI. This was the perfect balance of Lorraine’s expertise, our shared science, and keeping doors open for my other grant considerations. The grant was funded and it turned out to be a fantastic career opportunity for me.

Follow your passion

You need grants to fund your lab or group. But you also need to really love what you study. I love studying injured lungs. But I really love studying lung transplantation. For various reasons, I’ve mostly studied lung transplant-adjacent fields, through which I gained valuable skills and knowledge, but my dream was to have my clinical and science worlds collide. In late 2020, the Katz R01 mechanism was announced. This grant is for investigators who’ve never had an R01 and are studying something new to them, and it doesn’t allow preliminary data. This was my opportunity to write my dream grant – half human studies, half animal modeling, all on donor lung injury. Although some people around me cautioned against submitting—it would be a lot of work and these grants are unpredictable—I decided to turn it in anyway. If it didn’t get funded, I could get the preliminary data and put it in as a regular R01. I took the (calculated) risk…and then it paid off with a funded R01 (thank you Dr. Katz!).

Don’t get discouraged

I’ve been very fortunate with my early career grant funding. I haven’t told you about the proposals that weren’t funded. Shortly after my first R01 application had a non-fundable score, I was discouraged. I had a meeting with a very senior mentor from my institution who shared with me that they also had a recent grant given a similar unfunded score. We all put in grants that don’t get funded. We all get negative reviews. Most grants need resubmission and many ideas take years to refine into funded projects. It’s the nature of the game, and we can’t take it personally. Always try to find the silver lining in the critiques. I promise you it’s there if you look for it. Get the scores, look at the comments, laugh a little, then put your head down and get back to work.

I’m far from a grant writing expert. It’s still hard and I still need tons of advice. The journey has been fun so far. I have some money to help my lab group continue our discoveries and I’m now learning about managing grants. Every day is an adventure…stay tuned for my next post on advice for an early career scientist.

Read More

Lessons Learned While Building a Career: Mentoring Matters

Fighting Rejection, Reggae Style: Three Little Birds

Friendly Advice from Your NIH Grant Reviewer

I just finished an NIH study section and noted that more than half of the applications discussed did not adequately address sex as a biological variable (SABV). This is a relatively new (for some grant types) component of your grant, and while it may seem relatively minor, it is actually an important part of your grant (and your science!).

SABV is a scored component for peer review of Fellowship (F), Career Development (K), and Research (R) grants. This means that not getting the section right is an automatic weakness and will result in a lower score. Beyond the requirements for your grant proposal, numerous studies have shown that analyzing males and females separately in your study could uncover important biological differences.

I’m here to tell you that SABV is easy to “get right” in your application.

In your application, the NIH requires:

• Explanation of how relevant biological variables, such as sex, are factored into research designs and analyses.
  • Read: mention SABV explicitly in your Research Plan. It can be in the Approach, Study Design, Data Management, or Statistical Analyses sections, but it has to be stated explicitly.
• Animal Studies: Include a description of how you will use both male and female animals in the Vertebrate Animals section.
• Human Participants: Include descriptions of recruitment of both men and women across the lifespan.

At Study Section, the reviewers are instructed to answer the following question: Has the applicant presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? There is actually a separate section on the Critique Template for SABV and reviewers are instructed to factor this section into their score.

How can you get this right in your application?

It is not enough to study both male and female animals or humans. In fact, this is the most common “error” I see on applications in my study section. Rather, each sex needs to be analyzed independently for sex-specific differences. Make sure you state this in your Research Plan. Ask your mentor and your institution for examples of grant text that is relevant to your specific type of research.

SABV is an easy thing to “get right” on your application and may uncover something unexpected in your research – maybe even a new direction for another grant proposal!

More on the rationale of the policy is described on the NIH Office of Research on Women’s Health page.

Let’s talk about Training in the Responsible Conduct of Research (RCR) – you know, that one-page, required piece of an NIH grant application that could use a little attention.  NIH released new guidance (effective September 25, 2022) that does not substantially change prior guidelines, but serves as a good prompt to revisit the requirement.

While RCR is not a scored review element, it is required and will be evaluated as “acceptable” or “unacceptable.” Grants receiving an overall fundable score will need to amend an “unacceptable” plan before a grant is fully funded. Likewise, continuation funding can be withheld if an acceptable RCR update is not included in your annual progress report.

So…what is the expectation and how can you get it right?

NIH dictates five instructional components. For F-awards, especially, outlining your RCR plan in this same format is wise. You’ll make the reviewers’ job very easy if they can see at a glance that all components are addressed. Think of this list as a checklist the next time you prepare an RCR plan.

1. Format: Will the experience be face-to-face? Coursework? Discussion groups? Online or video conference instruction is acceptable, but cannot be the sole format. Think about all the things you are already doing that can count as learning or teaching RCR.
2. Subject Matter: Early career stages need a plan for broad coverage of NIH-recommended subject areas (think: ethics course during graduate school or day-long workshop during faculty/fellowship onboarding). Later-stage researchers can begin to concentrate on areas most closely related to scientific expertise. NIH’s current areas include:
   1. Conflict of interest & conflict of commitment (time, effort)
   2. Policies regarding human subjects, vertebrate animals, lab safety
   3. Mentor/mentee responsibilities & relationships
   4. Safe research environments (free from discrimination, harassment)
   5. Collaborative research (domestic, international, industry)
   6. Peer review (confidentiality, security)
   7. Data acquisition & analysis; lab tools (including digital images); recordkeeping (including e-notebooks)
   8. Secure & ethical data use (confidentiality, management, sharing, ownership)
   9. Research misconduct
   10. Responsible authorship & publication
   11. Scientist as a responsible member of society; contemporary ethical issues; societal impact of research
3. Faculty Participation: Which faculty are involved in instruction? Especially name your mentor(s) or program faculty who lead instruction and specify the roles they will play. Are you providing instruction to others?
4. Duration of Instruction: Describe the total number of contact hours of instruction, taking into consideration the duration of your grant. Does your institution/department have a required number of hours each year? Likely, you’ll be expected to meet or exceed the NIH recommendation of eight contact hours (minimum) for a single training plan.
5. Frequency & Timing of Instruction: Instruction must occur during each career stage (translation: as a graduate student, again as a postdoc, again as an assistant professor) and at least once every four years. Describe any prior training during your current career stage, including the dates instruction was last completed. Consider that training may need to be repeated during the proposed grant period if four years elapses.

Career Stage Considerations

As a K-award applicant, you’ll have more leniency in formatting this section due to the advanced career stage.  You’ll want to start by describing your most recent, prior RCR training.

• Did you already complete a broad RCR training course in the last four years? Perhaps your home institution offers one for every new research faculty hire. If so, describe that prior instruction, including the date instruction was completed.
• Was your prior instruction during a prior career stage (e.g., as a postdoc)? If so, additionally describe the initial training you will receive in this new career stage.

Second, propose plans to receive instruction and/or provide instruction (e.g., to participate as a course lecturer). Consider the Frequency & Timing section, above: if your grant is for five years, you will need to plan to refresh your training at least once to meet the “every four years” requirement. Propose activities that will enhance your understanding of ethical issues related to your specific research activities and the societal impact of that research. Propose activities that actually interest you – independent scholarly activities are permitted – or activities that are already part of your academic duties (e.g., writing case studies, moderating graduate courses, attending seminars, discussions with mentees). Also describe the role(s) your mentors will play in your instruction.

For Annual Progress Reports

Ok, you got the grant. Yay! Each year, you’ll submit a progress report, which needs to include a description of your RCR training (formal and informal) over the past year. The intent is for RCR to be a continual and integrated part of research and career development. Keep in mind that next year’s grant dollars can be withheld if the RCR section of the progress report is not complete.

• Formal Instruction: Did you complete the annual IACUC/IRB training this year? Did you complete the full RCR course offered by your program or institution this year (because it’s been 4 years, or you changed career levels, or the course was previously unavailable)? Did you act as an instructor or moderator in a formal RCR course? Be sure to include completion dates and align your description with the five components above.
• Informal Instruction: How have you stayed connected to good research practice this past year? Conversations with your mentor about your research? Training a graduate student in your lab? Journal club conversations about cases of misconduct? Writing RCR case studies? Attended or presented seminars on RCR topics? In the case of seminars, consider listing the date, title, and presenter.
• Individualization: Particularly for K-awardees, ongoing RCR activities can be uniquely tailored to your career stage or area of scientific expertise. This could include creating an independent study, publishing case studies, developing course content. In your description, include the role your mentor(s) play in your plans.

All the tech speak lives in the NIH Grants Policy Statement

• F Fellowships: NIH Grants Policy Statement, Section 11.2.3.4: Responsible Conduct of Research
• K Awards: NIH Grants Policy Statement, Section 12.4.1.4: Training in the Responsible Conduct of Research

More Resources

5 Ways to Improve the RCR Section of Your K

Counting What Counts in Responsible Conduct of Research

Game On: Join Kaizen

In this round-up are building blocks for key grant sections gathered from Edge for Scholars blogs. Some sections are specific to NIH, while others generalize to many sponsors.

A Blueprint for Execution: Like any builder, you’ll benefit from a solid plan. Check out this overview for pacing your grant writing to completion.

Specific Aims: Capture the reviewers’ attention and get them to turn the page.

• At this time, figures are permitted in Specific Aims. However, figures will soon be disallowed in abstracts.
• Consider yourself a salesperson:
  • Structure Aims using the Problem-Amplify-Story/Solution-Transformation/Testimony-Offer-Response (PASTOR) method.
  • Or dress your aims in peacoats PICOTS (Population-Intervention/Exposure-Comparator-Outcome-Timing-Setting).
• Proposing an observational study? Ace your aims with these protips.

Research Strategy: These three sections are the meat of major research proposals. Of these, data show the Approach drives reviewer scores.

1. Significance:  Begin with stating the critical problem in the field and how you’ll address it, then briefly summarize the “rigor of prior research” to address Significance, NIH-style.

2. Innovation: Treat this section like a marketing pitch. Using fresh ideas like bullets, quotes, and vignettes prevent it from becoming dense text.

3. Approach: A sound approach is required for a smooth landing. This checklist provides a glidepath so you won’t crash on approach.

Clinical Trials & Human Subjects Participant Research: Definitions and requirements changed in 2018. Edge for Scholars summarized the major considerations. Also double-check your RFA designation regarding clinical trials (“optional”, “required”) and use the checklist tools to confirm how NIH will view your proposal.

• Am I doing human subjects research?
• Does your human subjects research study meet definition of clinical trial?

Responsible Conduct of Research: Career development awards require a page about the candidate’s intended training in the responsible conduct of research. Also, refer to NIH’s RCR page (K awards, F awards) for key verbiage and elements to include.

• You can probably count much of what you already do.
• You need not include an exhaustive grocery list of every possible opportunity.

Rigor, Reproducibility, & Transparency: A newer requirement that you may be encountering for the first time. This also includes validation of biological samples. See also NIH’s RRT descriptions.

• There is some overlap with RCR activities and Approach checklist items
• Benefits for you: activities you are already doing may satisfy more than one are requirement, e.g., seminars, mentor meetings, validation of research materials.
• Benefits for the reviewer: thoughtfully repeat (or reference the earlier mentions) the qualifying activities in each section to help reviewers find items they are required to find.

Additional resources specific to grantsmanship:

Three (Grant) Peeves in a Pod: Write Better
Three (Grant) Peeves in a Pod: Appearance Matters
Avoiding a Mismatch: How To Work with a Writer or Editor

Additional resources specific to career development awards:

What I Wish I’d Known Before I Wrote My K
More Things I Wish I’d Known Before I Wrote My K
Not that Kind of Grant Application: Tales of Career Development Awards
Tips for Scoring a VA Career Development Award

The top 20% of grants in any given cycle at any study section are largely impossible to rank in terms of objective quality. Assuming paylines won’t allow all to get funded—which they won’t—funding individual grants in that 20% becomes a lottery, with subjective criteria often affecting reviewers’ scores.

Because reviewers are human beings, one of those subjective criteria is often whether they think well of you and your research. This is why you’re told to travel: To get to know these people and get them familiar with your work. Is it unfair? Possibly. Does it matter? Yes.

Pro tip: Look at the roster for the study section(s) your grants will go to. Find these people.

It’s important to remember that you should not discuss the specific grant under review when you are interacting with study section members.

You can:

Invite them to speak at your institution. Interact with them in person and show them your exciting science. Do this twice a year, and after four years, you’ve met with 20% of your study section’s roster (with fudge room for members rotating off after 4-6 years).

When you get invited to give a talk somewhere, if someone on your study section roster works there, see if you can meet with him or her.

Volunteer to moderate a panel at your national meeting and invite study section members to speak. You’ve done them a solid, and you likely get to chat with them. Everyone walks away happy.

Introduce yourself at meetings.

Connect with them on social media; if they are active on Twitter/etc., follow them and comment on their tweets or posts.

This strategy works just as well for likely reviewers at journals you submit to.

Related tip: If the top 20% of grants in study section are a lottery, it works in your favor to have as many balls in that tumbler as possible. Submit often. This will get easier as you become more senior and write more grants; you’ll have a bigger library of grant text to pull from.

Human nature can work in your favor if you put the right elements in place.

More Resources

Which Study Section Should I Pick? Try the Assisted Referral Tool!

How Study Section Works (And Why You Need to Know)

A Peek Inside Study Section: The Riff Raff Edition

As Mary Poppins says, let’s start at the very beginning. What is your hypothesis? Since the entire grant revolves around this one statement, it’s important that put some thought into generating a good one. What is a good hypothesis? One that is clear, testable, provable, and supported by rationale (aka your preliminary data). We’ll go into the specifics of how to write a good hypothesis in part 2 of this post, for now I want to make sure you have one. Chances are, if this is your first grant, or first grant on this topic, you haven’t written a hypothesis yet. We have vague hypotheses in our heads as we do experiments, but usually we don’t write these down. Now’s the time to get those visions of sugarplums out of your head and onto paper.

Let’s go through a couple examples of hypotheses to get a better sense of what I’m talking about. This morning when I woke up, the last piece of chocolate cake was gone. There was a plate and fork with cake crumbs in the sink. My son was in bed when I went to sleep but my husband was up watching TV. My husband really likes chocolate cake. In addition, my son is a teenager, and once asleep he does not get up (sometimes for days). Based on my husband’s love of chocolate cake, the fact that he was awake when I went to bed, and my son’s sleeping habits, I hypothesize that my husband ate the cake. When questioned, he denies it, saying the dishes were in the sink when he went to bed. Fingerprinting of the fork and plate revealed all 3 family members plus the dog had touched the fork and plate. In the end, hard to prove that my husband ate the cake. Criminal lawyers face this challenge daily. My hypothesis was clear, testable, and supported by rationale. However, it was not provable.

Here’s another one. My dog is super skinny. He’s always been thin but he’s lost more weight recently. In addition to his weight loss, there are these weird bits of stuff that look like rice surrounding his favorite dog bed. Google informs me that dried pieces of flat, rice-like looking stuff might be dried tape worm segments. Based on the rice-like segments and his weight loss, I hypothesize that my dog has tapeworms. This hypothesis is testable and provable. His stool can be examined for worms (yay) or the rice-like bits can be taken to the vet for assessment. I’m kind of cheap, so I’ll just skip all that diagnostic stuff and treat him but that’s another story.

The “hourglass” of your hypothesis.

The hypothesis is analogous to the neck of an hourglass. You sift through your preliminary data and choose the data (rationale) that best support your hypothesis. This is the data that will go into your grant. Data most important to supporting your hypothesis approaches the neck of this hourglass – this data go on the specific aims page. If there is data missing, now’s the time to get it. Developing your hypothesis sooner rather than later will ensure that you have the preliminary data necessary to support it.

Flowing out from your hypothesis is the approach. Your specific aims, sub-aims, etc. At the expense of sounding like Captain Obvious, it’s important that your aims truly address your hypothesis. We’ll go into this in more detail in the next post. Once you have your aims, think about how you’ll carry out each aim. What techniques will you use? Do you need a collaborator or consultant? New equipment? Thinking about your approach ahead of time will make sure you fill in the gap between what you can do and what you can’t. The best approach will fall short if reviewers don’t believe that you can do the work. The convincing is on you. Planning your approach early will make sure you have time to contact potential collaborators/co-investigators who have expertise in a field or technique new to you. If the technique is one your lab can do but has not done yet, a pilot experiment demonstrating this technique is “up and running” in your lab will show reviewers that you can do the work. Let me give you an example. I recently wrote a grant that required using immunoprecipitation. For those not familiar with this technique, it involves using an antibody to capture a protein of interest from cell or tissue preparations. This technique is not difficult, but not all antibodies are good for immunoprecipitating. Plus, it’s one of those techniques that is mechanistically easy but can require the sacrifice of a small chicken to get it to work. Because I had a specific antibody that I wanted to use for immunoprecipitating, it was important to demonstrate that the technique worked with this antibody. In addition, it was good to show that our lab had experience with this technique. I didn’t have a lot of time (clearly not following my own advice) so I bought a kit and after a few tries got the immunoprecipitation to work. I added the figure a few days before the grant went out. I was lucky, though, and was close to not having this data. The moral of this story is don’t do as I do, but do as I say – plan ahead.

On that note, plan ahead to read part 2 of this post on generating a testable hypothesis.

 Further reading:

Part I of the SA page series, setting up the problem (paragraph 1)

https://edgeforscholars.org/specific-aims-part-1-the-problem/

Part II of the SA page series, presenting your solution (paragraph 2)

https://edgeforscholars.org/specific-aims-part-ii-the-solution/

Writing for Science by Josh Schimel, especially Chapter 14 which includes fuzzy hypotheses

https://www.amazon.com/Writing-Science-Papers-Proposals-Funded/dp/0199760241/ref=sr_1_3?crid=ZA70FLW7RI5S&keywords=schimel+writing+science&qid=1637515803&sprefix=schimel%2Caps%2C323&sr=8-3