July 2002

This month, we will focus on the process of preparing a grant application. Obviously, the quality of science is critical. However, bad writing can kill good ideas. Although grant applications to different funding agencies may differ in their details, there are several characteristics that seem to be true of most, if not all, successful grant applications. I have tried to cover them in this column. My sources include successful, well-established investigators, as well as online and print resources, many of which are listed below. The idea is to give you a place to get started and make it easier for you to find and take advantage of resources in your own geographic/scientific area.

Proposal Preparation

1. Start Early. You will hear this over and over again. A good research proposal is like a novel in that you need to tell a convincing story and hold the reader's interest. And like a novel, a good research proposal takes time to prepare. Six months ahead of deadline is not too early to begin preparing your R01 or K award application. By developing your objective and specific aims early, you have time to acquire preliminary data to strengthen your application. This will also enable you to identify potential collaborators and request letters of support and recommendation in a timely fashion.
2. Contact the funding agency for advice. Before you call, have a prepared, concise overview (2-3 minute long) of your proposed idea, why it is important and your approach. Some suggested questions are: (1) When and how to apply. The NIH typically has three funding cycles per year but the dates for specific awards, RFAs and PAs can vary. (2) Does your idea fit in with any ongoing target area of research? Can it be made more appealing? (3) If you have program guidelines in hand, check their date to determine if they are the most current. PHS 398 forms were most recently revised on 1/25/2002. (4) Is there anything you need to know that is NOT in the guidelines? (see question 2) (5) Ask specific questions about procedures. (6) Question what fatal flaws they have seen in other proposals that you should try to avoid in yours! (7) Ask for information about their website. (e.g., the NIH (http://www.nih.gov) [ see last month's column] and the American Heart Association (http://www.americanheart.org/research) have very comprehensive websites that include application instructions/forms as well as information about the awards they have funded in the past.)
3. Read the instructions. I cannot stress this enough. The PHS398 form currently contains 116 pages of instructions (http://ftp.grants.nih.gov/forms/phs398.pdf) regarding everything from eligibility to budget limits to the font size and number of lines on a page. Yes, they will reject applications without reviewing them if your font size is too small or if you squeeze a few extra lines on a page. **Tip: K awards have separate instructions embedded within the PHS 398. Know the funding cycle dates for your institute and award.
4. Get to know your contracts and grants officer. Most academic institutions have an office that facilitates research in various ways, from helping to identify funding sources, assisting in proposal development and review, to helping interpret guidelines and promoting compliance. Here at UCSD, the Office of Contracts and Grants assigns each of the NIH institutes to an individual staff member. Your grants-processing organization may have internal deadlines 2 or more weeks in advance of the actual agency deadline. Often, you will need to have your budget and administrative pages finished (see #5) while you finalize your research proposal. Otherwise, you may find yourself running around frantically trying to get signatures and chasing down the FedEx truck! **Tip: Many contracts and grants offices have excellent websites with information about grant preparation as well as downloadable applications with prefilled-out areas (e.g., institutional contact information) that can make your life a lot easier.
5. Start Early. Writing takes time. Lots of time. Start thinking of ideas 6-12 months ahead of the deadline. When you are finished writing the application, put it aside for a few days, then look it over with a "fresh" eye. It may surprise you how many mistakes you can find. Remember, the person reviewing your application is (hopefully) going to be your advocate at the study section. Think about how you would feel reading an application filled with typos or not well organized. How do you know when it is ready? Critically assess your proposal using these five criteria: significance, approach, innovation, investigator and environment. These are the mandated criteria used by NIH reviewers in analyzing your application. **Tip: Start preparing your application one grant cycle early. Look at successful proposals from colleagues in your field.
6. Get critiques. Consider having someone more expert, preferably with study section experience, look over your objective and specific aims before you get too far along in writing your proposal. Then, be prepared to hand over a "finished" copy to trusted colleagues/advisors to get their input. Choose an insider (expert in your field) as well as an outsider. Again, people with study section experience are valuable. This should be your best draft! You are asking a big favor in terms of their time and input. Don't waste their time by having them pick up typos. Give them at least two weeks for look it over. Then allow another two weeks to think about their suggestions and decide about whetheror not to incorporate them.
7. Start early. Don't wait until the last minute to fill out the administrative pages. Read the instructions. Does your application require letters of support/recommendation? Get your requests out early. Start working on your budget. Does your application require biohazard approval? Animal safety approval? If you are not studying human subjects or animals, it's still a good idea to include a section for each, noting that the section is "not applicable." For applicants conducting research on humans or animals, state how you are protecting them in your research plan and show either IRB or IACUC approval. Also, make sure certifications are in place with OHRP or OLAW. For human subjects, your research plan must include plans for data and safety monitoring; inclusion, exclusion, analysis and outreach for women, children and minorities; and analyses, including those to detect differences in the intervention effect for women and minorities for NIH-defined phase III clinical trials.
8. Once your grant is in the mail. Your work isn't over yet! Put special effort into doing experiments that address weaknesses in the grant. You can either submit a few bits of key additional data before the grant is reviewed or at least substantially improve their chances for funding on the off chance you don't get funded the first time.

ANATOMY OF A PROPOSAL

1. Write clearly. Concise, logical, clearly written English is one universally cited hallmark of a successful proposal. Remember, your reviewer may have 50 other proposals to read and typically will only read your proposal once. Avoid long sentences. Avoid jargon. Use an easy-to-read typeface. Check carefully for spelling and grammatical errors. Make sure figures are clear and clearly labeled. Use bold and italicized text judiciously to help readers pick out important text without "yelling" at them. Leave spaces after headings and between paragraphs to organize your proposal's layout and increase readability. Repeat key words and concepts. If you are not meticulous about preparing your proposal, this may create the impression that you will not perform careful science as well. State the research question early and clearly. Remember: significance, approach, innovation, investigator and environment. **Tips: Make sure your hypothesis/question is clearly stated. Do you have the expertise to perform the experiments? If not, you will need to find collaborators. Do you have preliminary data demonstrating their feasibility?Make sure your experiments test various predictions of your hypothesis from multiple angles or can help you distinguish among different possibilities
2. ABSTRACT and SPECIFIC AIMS. These two are absolutely linked and are critical to a successful proposal. Everyone in the study section will have at least read these two parts. In the abstract you will provide an overview of your project, including one to two lines of background to orient the nonspecialist. A concise hypothesis or statement of the question should then be followed by the specific aims or questions and the techniques you will be using to answer these questions. This is important in helping study sections assign reviewers to your grant. Convey how these experiments combine to form a story/picture that will significantly advance your field.
3. BACKGROUND AND SIGNIFICANCE. Remember, you are writing for a diverse audience, one that is not necessarily intimately familiar with your field. You need to be explicit and include basic information that helps to clarify your project's goals. Demonstrate that you are familiar with the literature, that you have carefully examined the issues and point out what still needs to be addressed or has not yet been answered. Credit other people in the field where appropriate. Prepare a concise yet inclusive reference list that features works from different laboratories/points of view. Importantly, point out how your proposal addresses current knowledge deficits in the field or will help resolve important issues.
4. PRELIMINARY RESULTS. In this section, you demonstrate that you have the expertise to perform the proposed experiments, that you are capable of designing logical, focused, well-controlled experiments and can explain your results clearly without overstating them. Spend time on producing good, easy-to-read, well-labeled figures. As a new principal investigator without a proven track record, you will need to demonstrate your ability to perform any proposed techniques that are difficult, especially if they are new (to you or the field in general).
5. BUDGET. Don't ask for too much money; don't ask for too little money. This simple concept seems obvious but can be difficult to achieve in practice. The NIH currently uses the modular grant approach. Modular grant applications were intended to reduce the paperwork burden of submitting a grant and to expedite the approval process. Investigators use an abbreviated application form to request funds in modules of $25,000 up to a maximum of $250,000. Hopefully, this process will enable reviewers to focus on the innovativeness and potential scientific impact of the proposal rather than the specifics of its budget. However, many other agencies still require an itemized list of supplies divided into broad categories of use. In addition, you need to be able to justify salary support for both you and possibly technical support.
   
   Science is expensive but you want to appear reasonable and be able to justify your request for supplies in terms of the number of proposed experiments. Do you know how much a carton of pipettes cost and how many cartons you will need in a year? Learn what the big ticket items are (e.g., kits for molecular biology). In terms of salary support: Your grant should pay for the portion of time you devote to the project. If you plan to spend one-fourth of your time on it, you should include one-fourth of your salary in the budget. For beginning investigators, think carefully before putting down less than 25% of your time. People whose time is overly fragmented usually cannot do a good job on any of their responsibilities. Also, Career Development awards (e.g., NIH K awards) often require a minimum amount of time to be spent on the project. In terms of requesting technical support, you need to justify both the amount of time that a technician will be spending on your project and the level of expertise that this person will need. In other words, what techniques/skills will this position require? What and how many assays/experiments will this person be responsible for each week? Will this person be required to perform any supervisory duties? **Tips: Your contracts/grants officer should be able to assist you with this and calculating fringe benefits. Let them know early that you will be applying. They can work on the budget pages while you work on the narrative! Check with your human resources department to learn the definitions for the varying levels of technical positions available within your institution.
6. EXPERIMENTAL METHODS. This is where you get to discuss the design and the underlying logic of the proposed experiments. There are a couple of ways to approach this. Some people divide each specific aim into rationale (why you want to do this experiment and the logic behind the experimental design), method (the actual procedures involved) and anticipated significance/potential problems. Others use a two section approach in which the first section describes the protocol for each specific aim followed by a materials/methods section at the end in which they spell out the details of any proposed techniques/procedures. You need to demonstrate that you not only know how to perform the techniques involved, but also understand their limitations and how to account for them, (i.e., provide alternative methods). If you do not have experience with the proposed techniques, then find collaborators.
7. ANTICIPATED RESULTS/SIGNIFICANCE. Save precious space for this section. This is perhaps the hardest to write. Never assume that your hypotheses are correct. That is why you are testing them. Discuss potential results in the context of your hypothesis and how it will help support it or suggest alternative possibilities. If so, how will you pursue these? Anticipate "what if?" questions. Discuss potential pitfalls in a manner that doesn't make your proposed approach seem undoable and provide contingency plans. Significance: put your immediate results in the context of the "Big Picture." Emphasize why and how your work will expand our knowledge. Remember, you are telling a story and need to make the reader care about the ending! **Tips: Make sure the methods section matches up 1:1 with the specific aims. Don't get bogged down in experimental detail! For example, unless you're describing a brand-new technique, buffer concentrations are usually not required and may detract from the overall flow of the proposal. Finally, make sure you include power calculations to establish and justify the number of studies/animals/humans needed to produce significant results.

PROPOSAL PREPARATION WEBSITES

1. Finding funding sources
   OGSR - Community of Science (COS): http://www.cos.com
   Grantsnet (part of the Science's Nextwave website, this free service is sponsored by the HHMI and AAAS): http://www.grantsnet.com/
   The Federal Trough and The Toolkit:
   http://nextwave.sciencemag.org/feature/careercenter.shtml/
   Links to private foundations and international sources: http://nextwave.sciencemag.org/cgi/content/full/2000/09/21/10
2. Grantwriting resources on the web
   NIH website: http://grants1.nih.gov/grants/grant_tips.htm
   The Toolkit: http://nextwave.sciencemag.org/feature/careercenter.shtml/
   The Grantdoctor: http://chroma.med.miami.edu/research/Ellens_how_to.html (Nice overview.)
   Grantwriting "library" with links to other sites: http://research.unc.edu/grantsource/grantwriting.html