December 4, 2014, NIAID Funding News

Read this full issue online at http://www.niaid.nih.gov/researchfunding/newsletter/2014/Pages/1204.aspx

December 4, 2014

Feature Articles

Preliminary Research: Don’t Stop ’Til You Get Enough

Opportunities and Resources

In The News

Advice Corner

Become a Search Superhero
Reader Questions
- Why doesn't NIAID post paylines for all grant types?
- Could you clarify what kind of IRB certification you need for just-in-time? Would the IRB approval letter be enough?

New Funding Opportunities

See the list

Preliminary Research: Don’t Stop ’Til You Get Enough

Your preliminary research may be the difference between your application scoring within or short of NIAID’s paylines. For R01s, the thoroughness of your preliminary research can be just as important for impressing peer reviewers as the Specific Aims it supports.

Sometimes investigators feel frustrated by the perceived need to provide so much preliminary data that it feels as if a good portion of the project is completed before the project is ever funded. On the other hand, peer reviewers need to see that key proof-of-principle experiments have been done to demonstrate the feasibility and potential impact of the project. It’s a difficult balance to achieve.

Here, we’ll answer a few common questions, including how to gauge how much is enough when it comes to preliminary results and the catch-22 of needing them to apply for funding to do preliminary research.

Why Should I Include Preliminary Research?

Strong preliminary research helps your application in two ways: it demonstrates that your proposed research is promising and that your ability to carry it out is credible.

There is no checklist of how much preliminary research is adequate. In general, the more surprising your findings, the more data you’ll need (in terms of replications and statistical significance) to convince reviewers the results are real. For complex or multiproject applications, you should include preliminary research relevant to each component. The more paradigm-shifting your hypothesis, the higher the quality your data must be.

You must also assess whether or not your preliminary data are sufficient to convince reviewers that your proposal has a high likelihood of success. Reviewers use your work to evaluate both the merit of your Specific Aims and your skills as a scientist.

Which Grant Mechanisms Require Preliminary Research?

The investigator-initiated R01 does, as do several fellowship grants.

Small grants (R03) and exploratory/developmental grants (R21) are tricky. By rule, they do not require preliminary research. But, as we tell you in Know the Importance of Preliminary Data, most applicants include preliminary research in their R21 applications, and those who do enjoy greater success rates.

As a rule of thumb, if you have preliminary research that is rigorous and justifies your proposed work, include it. But remember, any preliminary research that you do include will be judged and scored.

Requests for applications (RFAs) and program announcements reviewed at an institute (PARs) vary on whether or not preliminary research is required, so for those you will need to read the individual funding opportunity announcement (FOA). Still, the same rule of thumb applies—include any evidence that justifies your proposed research.

Must I Personally Generate the Research?

Generally, you should rely on data that you have generated, but you can certainly include data generated by your project collaborators if they show that your team is capable of carrying out the experiments you propose. More broadly, anytime you have a collaborator who fills a gap in your expertise, you should include evidence that your collaborator does in fact fill the gap.

For research results that are already published, know that there is no requirement for reviewers to read any papers cited in your references section or follow any Web links (URLs) you include in your application. Put any information that is critical for justifying your Specific Aims directly into the application.

But again, if the preliminary research is not your own, you must be mindful of finding other ways to demonstrate your capabilities, since you will likely be competing with researchers who have. For example, you might use a literature review to support one of your Specific Aims—if so, your review needs to be an original, thoughtful analysis, not merely a list of references.

Does the Preliminary Research Need to Be Data?

People often take data to mean quantitative data, but qualitative data is equally important.

For example, you may include a figure that verifies your ability to perform a new technique you’ll use in your proposed research. Demonstrating the sensitivity, specificity, and reproducibility of the technique is an important part of preliminary research, and should be included.

Data is also useful because it allows peer reviewers to assess your interpretation of it. But data is often only as valuable as the methodology that generates it. So find a way to show off your research skills. Especially for early-stage investigators, thoughtful interpretation of data is critical because it shows reviewers how you think.

You don’t need to convince reviewers that your hypotheses are true in the application itself—that work is what the grant is designed to support—but you do need to show them that you have a viable plan to answer the research questions you pose (and a viable back-up plan should you need it).

How Can I Generate Preliminary Research if I Don’t Already Have Funding?

Network! Find other scientists interested in working on the same topic as you. Consider writing a multi-PI application if you are conducting multidisciplinary research or team science. If you are an early-stage investigator, you should search especially for collaborative opportunities that allow you to hone the methodologies relevant to your area of research.

You might also consider the following as sources of funding:

Startup funds or other institutional support
Foundations, professional societies, and advocacy groups
Transitional and career development grants
Small and exploratory research grants

Keep in mind, the R03 and R21 activity codes are not meant to be stepping stones for new PIs to reach their first R01. Instead, we encourage new investigators to apply for an R01 directly if they have sufficient data to support the proposed work, since NIAID has a separate R01 payline for new PIs. Alternatively, you may be eligible to apply for an Academic Research Enhancement Award (AREA, R15) grant to help get you started. That caveat aside, R03s and R21s are ideal grant activity codes to explore novel avenues of research.

Preliminary research is not required for the R03 and R21, but if you do not have any, you must still show reviewers that your proposal is impactful and that you are likely to accomplish it fully. Make critical assessments of other research, explaining where and why additional research is needed. Early-stage investigators should find experienced collaborators whose strengths complement theirs.

Pay attention to RFAs and PARs as well, which sometimes do not require extensive preliminary research. You will still need to show that you are a capable researcher and demonstrate why your proposal is relevant within the FOA’s broader aims. Remember, you can check Concepts: Potential Opportunities to review Council-approved topics.

How Should I Write My Application?

In the application itself, you should present your past research to show rigorous methodology, insightful and unbiased interpretation, and applicability to your Specific Aims.

You can put your preliminary data anywhere in the Research Strategy that you feel is appropriate; just make sure your reviewers will be able to distinguish your original work from other evidence you cite in support of your Specific Aims. Alternatively, you can create a separate section with its own header. In our experience, strong applications mix preliminary findings into each Specific Aim, using the data as justification along the way. You can even indicate in the figure legend or in the text describing the preliminary data which Specific Aim that data supports.

Do not paste preliminary research into your application without adequate explanation and/or a figure legend, and then leave it for your reviewers to decode. If using a table or figure from a publication, make sure to update the legend so that everything needed is in the application. Show how the implications of your preliminary research are relevant to the research you propose. Do not neglect the statistics—reviewers will want to know if your findings are significant.

Make reading your application easy for reviewers. Keep your figures simple. Label all axes and units. If you embed a figure in the text, place it so that your reader doesn't have to flip back and forth to refer to it. Double check your footnotes. If you fail to adequately polish your application, you risk alienating the reviewers.

Don’t make the reviewer give you the benefit of the doubt—you are responsible for relating your preliminary research to your proposed methodology and Specific Aims. Speak to any limitations of the previous work and how you plan to overcome them.

Check out our Sample Applications and Summary Statements to see how other investigators successfully presented preliminary research in their applications.

Finally, talk to a program officer. They are scientists experienced in assessing whether an application has provided sufficient preliminary research. They can tell you if more preliminary research is needed to justify your Specific Aims.

FOA Seeks New Approaches to Host-Directed TB Therapy

A high priority in global health is to improve treatment for both drug-sensitive and multidrug-resistant tuberculosis (TB). The question is, how? One possible way: adjunctive therapy with immunomodulators, more commonly called host-directed therapy or HDT agents.

HDT is the focus of a recent funding opportunity announcement (FOA) that will support projects proposing limited preclinical work and planning activities needed to advance HDT strategies as adjuvant therapies for TB. Such strategies should also be applicable to HIV/TB coinfection, and by the end of the project, be sufficiently developed to evaluate in subsequent proof-of-concept (POC) clinical trials.

The types of agents (or combinations of agents) that investigators may study include small-molecule agents that, as therapeutic adjuvants, have various functions, e.g., modulate destructive immune-mediated inflammatory responses, allow host immune cells to prevent or inhibit cell entry and/or survival of TB through reversal of functional defects.

We are particularly interested in agents that are effective as adjuvants for TB treatment and may also have therapeutic activity against HIV, either directly or by enhancing immunologic reactions.

The Activity Code and Your Application

Keep in mind two key points about the UH2/UH3 activity code that this FOA uses.

One: It's a phased award

That means the results of the milestones you'll propose for the UH2 phase must be sufficiently promising before you can get a UH3 award to implement the POC clinical trial during the last three years of the grant.

You'll address both phases in the Research Strategy of your application, with a section for each phase.

UH2

This phase includes funding for preclinical investigations to study candidate HDT agents, identify the optimal dosing regimen, and provide any other data needed for performing a POC clinical trial of an HDT agent.

In the UH2 section of the application, include items such as a detailed description of the planned preclinical research; a description of, and rationale for, choosing the proposed HDT agent(s); activities that will be carried out during the POC clinical trial planning period; and specific, measureable, and scientifically justified milestones.

UH3

This phase is for implementing the POC clinical trial. The Research Strategy section for the UH3 should cover how the trial will be organized and managed, including the plans to identify and select additional collaborators, if applicable; the organizational and coordination activities required for conducting the POC trial; and protocol-specific milestones.

For more information on what to address for each phase, go to Section IV. Application and Submission Information of the FOA.

Two: It's a cooperative agreement

That means NIAID anticipates substantial programmatic involvement with awardees during the performance of the activities. While Institute staff may share some tasks and activities, the PDs/PIs have primary responsibility for the project as a whole.

Go to Section VI. Award Administration Information to learn more about roles and responsibilities.

Deadlines and Other Details

Optional letters of intent are due by February 25, 2015. The deadline for applications is March 25, 2015.

Find complete details about this opportunity in the November 13, 2014, Guide notice.

New Funding Opportunities Target Eosinophils and Eosinophil-Associated Disorders

Take a look at two new funding opportunity announcements (FOAs) seeking your proposals for research to develop predictive biomarkers, identify therapeutic targets, create new animal models, or investigate the cellular and molecular mechanisms related to rare eosinophil-associated disorders.

NIAID developed these FOAs with input from patient advocacy groups to address gaps in our understanding of eosinophil pathophysiology.

You have two choices: an R21 for two-year, early-stage or conceptual research projects, or an R01 for full-fledged investigations of up to five years.

You can also apply for both opportunities—as long as applications for the same review cycle cover substantively different research questions.

Whatever you decide, talk to a program officer before you develop your application.

We're partnering with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), so you'll want to make sure your application finds the right institute and study section, which you can do by making a request in your cover letter.

Read the October 31, 2014, R01 and R21 Guide announcements for more information, including application instructions, scientific contacts, and research areas of interest.

Related Links

Mark Your Calendar for 2015 Small Business Conferences

Save the date—actually, save several—for the following 2015 small business conferences. NIAID staff will be available for one-on-ones at each of these events:

National SBIR/STTR Conference , June 14 to 17, Washington, D.C.
BIO International Convention , June 15 to 18, Philadelphia, Pennsylvania
AdvaMed 2015 MedTech Conference , October 5 to 7, San Diego, California
17th Annual SBIR/STTR NIH Conference, October (date TBD), Seattle, Washington

Check NIAID Small Business Program regularly for other key dates and information.

News Briefs

Reminder: Annual Reports to OLAW Due Next Month. You have until January 31, 2015, to submit your annual report to NIH'sOffice of Laboratory Animal Welfare (OLAW). To see what your report should include and how to submit it, read the November 21, 2014, Guide notice.

Comment on Policy for Reporting Clinical Trial Results. NIH is soliciting feedback on a draft policy meant to improve dissemination of clinical trial outcomes. Under the proposal, all NIH-funded clinical trials will be required to register with and report results to ClinicalTrials.gov. See the November 19, 2014, Guide notice for more information. The deadline to respond is February 19, 2015.

Reissue of Administrative Supplements FOA. NIH has reissued the Administrative Supplements for Research on Sex/Gender Differences funding opportunity announcement. Read the November 14, 2014, Guide notice for application instructions. Applications are due January 12, 2015.

Registering a Clinical Trial? Include Your NIH Grant Number. When registering a clinical trial in ClinicalTrials.gov, you will complete a field called Study Identification. In doing so, be sure to enter both your unique protocol ID and the secondary ID that includes the NIH grant number. If more than one grant is supporting the trial, be sure to include (or ask the responsible party to include) those grant numbers as well.

Our system will then automatically affiliate the grant with its clinical trials in RePORT, which you can verify in the "Clinical Studies" tab within Project Information in RePORTER. For additional information, see ClinicalTrials.gov Protocol Data Element Definitionsand How should NIH support be indicated in the ClinicalTrials.gov record?

Become a Search Superhero

When searching on the NIAID or NIH Web sites, sometimes using the navigation feels too slow. Save some time with these search strategies.

Choose Your Search Scope

For NIH, decide how to focus your search:

NIH site: use the default search box on the top right.
NIH Guide: use the Advanced Funding Opportunities and Notices Search.
Office of Extramural Research: use the Advanced OER Web Search.
PubMed: use the PubMed Advanced Search Builder.

For NIAID, you have two options:

Use the default search box shown at the top right of all NIAID pages.
Get more specific with NIAID's Advanced Search.

To search both NIAID and NIH at once–along with the rest of the Web–we suggest Google

or the Google Advanced Search

Use Advanced Search Commands

Try Google's advanced search commands to refine your searches. Most of these also work for NIAID and NIH search fields. Here's a summary of helpful search options.

Search Command	What It Does	Example Search	Result of Search
Quotation marksaround the term	Lets you search for an exact phrase.	"transmission rates"	Pages that use the quoted words together, in order, as shown.
Minus sign before the term	Excludes that term from the search.	transmission -engine -car -music	Pages that mention transmission but not engine, car, or music.
site:domain.ext	Shows results only from the site in the blank.	site:www.cdc.gov "transmission rates"	Pages at www.cdc.gov that use the phrase "transmission rates."
related:domain.ext	Other sites like the one in the blank.	related:www.cdc.gov	Pages of WHO, NIH, and other similar organizations.
asterisk (*)	Behaves as a blank in your search string.	"to * or not to *"	Pages containing the famous quote "to be or not to be," plus variations on it.

Find more at Google's Punctuation, symbols, and operators in search

Use Control-F to Save the Day

If you think you've found the right page but you can't spot your term, there's a way to save the day. Use the Control-F (Win) orCommand-F (Mac) key combination. This command works in most modern browsers and is easy to use. Just type a word or phrase in the search box to see all the instances of the term you want to find.

You can also check our indexes at NIAID's Find It! A-Z list, Standard Operating Procedures, Questions and Answers, and portals onGrants topics. Still having trouble finding your favorite resource? Email us at deaweb@niaid.nih.gov.

Feel free to send us a question at deaweb@niaid.nih.gov. After responding to you, we may ask your permission to include your question in the newsletter, incorporate it into the NIAID Research Funding site, or both.

"Why doesn't NIAID post paylines for all grant types?"—anonymous reader

We post NIAID Paylines for the activity codes that make up the largest pools of applications. For activity codes that result in fewer applications, the Institute prefers the flexibility of not setting a payline. Also, applications for some activity codes are only in response to requests for applications (RFAs) or program announcements with set-aside funds (PASs). Even without a payline, we usually fund applications in overall impact/priority score order.

To learn more about paylines, read Paylines Are a Conservative Funding Cutoff Point and NIAID Funding Decisions questions and answers.

“Could you clarify what kind of IRB certification you need for just-in-time? Would the IRB approval letter be enough?”—Patti Young, University of New Mexico

At NIAID, grants management staff typically request only the date of institutional review board (IRB) approval. We don’t need a copy of the letter, and there’s no separate certification needed.

The approval date must be less than a year old when it’s time for award. If not, the IRB will need to approve your project again. You would enter the new date in the Just-in-Time module of the eRA Commons.